abstract,articleTypes,authors,doi,firstAuthor,fullJournalName,issn,issue,journal,language,lastAuthor,meshTerms,pages,paperId,pmcId,pubDate,pubYear,pubmedUrl,title,volume,_run_id,_dataset_id
"Archaeological, osteological and genetic evidence suggests that Neanderthals lived in small groups1,2; however, less is known about whether these groups were part of isolated communities or belonged to larger, well-connected populations3. The dense concentration of broadly contemporaneous Neanderthal sites in the Meuse Basin, Belgium4, provides a rare opportunity to study regional populations at high resolution. Here we generated genetic data from 27 Neanderthals who lived less than approximately 52,500 years ago from ten archaeological sites in Belgium and France, including a high-coverage genome from a 45,000-year-old individual from Goyet, Belgium. We show that most of these individuals are more closely related to one another than to other contemporaneous late Neanderthals in Europe. Further, some of these individuals carry DNA from a Neanderthal lineage predating the split of late Neanderthals. Although these Neanderthals overlapped temporally with early modern humans in northwestern Europe from around 47,000 years ago, we find no evidence of recent gene flow from modern humans. They also do not show the genetic signatures of mating among close relatives found in Altai Neanderthals, suggesting that they lived in larger or better-connected groups. Moreover, genetic load did not accumulate over time, arguing against progressive genetic deterioration as a driver of Neanderthal extinction.","[""Journal Article""]","[""Bossoms Mesa A"", ""Essel E"", ""Peyrégne S"", ""Sümer AP"", ""Iasi LNM"", ""Heide C"", ""Popli D"", ""de Filippo C"", ""Gansauge MT"", ""Gerullat L"", ""Lippik L"", ""Nagel S"", ""Nickel B"", ""Schellbach B"", ""Schmidt A"", ""Visagie J"", ""Weihmann A"", ""Zeberg H"", ""Zorn J"", ""Rougier H"", ""Crevecoeur I"", ""Semal P"", ""Abrams G"", ""Devièse T"", ""Pirson S"", ""Di Modica K"", ""Cattelain P"", ""Draily C"", ""Toussaint M"", ""De Groote I"", ""Welker F"", ""Posth C"", ""Soressi M"", ""Hublin JJ"", ""Krause J"", ""Pääbo S"", ""Meyer M"", ""Kelso J"", ""Peter BM"", ""Hajdinjak M""]",10.1038/s41586-026-10625-1,Bossoms Mesa A,Nature,0028-0836,8122,Nature,eng,Hajdinjak M,"[""Animals"", ""Female"", ""Humans"", ""Male"", ""Belgium"", ""France"", ""Gene Flow"", ""Genetic Variation"", ""History, Ancient"", ""Neanderthals"", ""Phylogeny""]",409-417,42343123,pmc-id: PMC13345965;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42343123/,Genetic diversity of late Neanderthals in northwestern Europe,655,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"N-acetyltransferase 1 (NAT1) is an enzyme that acetylates certain drugs and carcinogens and is involved in folate metabolism. Some NAT1 variants are associated with susceptibility to cancer and birth defects. We show that while nearly all present-day humans carry a valine residue at position 149 and a serine residue at position 214, some carry the ancestral amino acids isoleucine and alanine at these positions because of gene flow from Neanderthals. Neither substitution affects enzymatic activity. However, replacing the serine residue, a known phosphorylation site, with a phosphomimetic aspartate reduces NAT1 activity by ~60%. Phosphorylation at this site may allow NAT1 to be down-regulated during pregnancy to reduce birth defect risk, while maintaining high activity in adults for xenobiotic clearance. This regulatory site is a molecular feature that differs between modern humans and Neanderthals.","[""Journal Article""]","[""Fast L"", ""Alberro ML"", ""Rakava E"", ""Ågren R"", ""Riesenberg S"", ""Huttner WB"", ""Kelso J"", ""Pääbo S"", ""Zeberg H""]",10.1126/sciadv.ady1666,Fast L,Science advances,2375-2548,23,Sci Adv,eng,Zeberg H,"[""Humans"", ""Phosphorylation"", ""Animals"", ""Arylamine N-Acetyltransferase"", ""Isoenzymes"", ""Neanderthals"", ""Female""]",eady1666,42247510,pmc-id: PMC13240207;,2026 Jun 5,2026,https://pubmed.ncbi.nlm.nih.gov/42247510/,Regulation of NAT1 activity in modern humans by a novel phosphorylation site,12,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"We present a genome sequenced to ~37-fold genomic coverage from an approximately 110,000-y-old male Neandertal from Denisova Cave in the Altai Mountains and analyze it together with previously published Neandertal genomes of high quality. We show that he belonged to a population more closely related to a ~120,000-y-old Neandertal from Denisova Cave than to Neandertals in Europe or to a ~80,000-y-old Neandertal from Chagyrskaya Cave in the Altai Mountains. Both Neandertals from Denisova Cave show evidence of gene flow from Denisovans, a pattern not seen in later Neandertals from the Altai region or from Western Europe. The extent of chromosomal regions of homozygosity in Neandertals from the Altai region between 120,000 and 80,000 y ago indicates that they lived in smaller and more isolated groups than later Neandertals in Europe (54,000 to 40,000 y ago). We estimate the extent of allele frequency differentiation among Neandertal populations and find that the older Eastern Neandertals in the Altai region and younger Western Neandertals in Europe were as differentiated as the most differentiated present-day human populations worldwide.","[""Journal Article""]","[""Massilani D"", ""Peyrégne S"", ""Iasi LNM"", ""de Filippo C"", ""Mafessoni F"", ""Bossoms Mesa A"", ""Sümer AP"", ""Swiel Y"", ""Popli D"", ""Silverman S"", ""Boyle MJ"", ""Kozlikin MB"", ""Shunkov MV"", ""Derevianko AP"", ""Higham T"", ""Douka K"", ""Meyer M"", ""Zeberg H"", ""Kelso J"", ""Pääbo S""]",10.1073/pnas.2534576123,Massilani D,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,13,Proc Natl Acad Sci U S A,eng,Pääbo S,"[""Animals"", ""Neanderthals"", ""Male"", ""Gene Flow"", ""Genome"", ""Humans"", ""Gene Frequency"", ""Genetics, Population""]",e2534576123,41871248,pmc-id: PMC13037865;,2026 Mar 31,2026,https://pubmed.ncbi.nlm.nih.gov/41871248/,A high-coverage Neandertal genome from the Altai Mountains reveals population structure among Neandertals,123,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Gene regulatory changes are considered major drivers of evolutionary innovations, including the cerebellum's expansion during human evolution, yet they remain largely unexplored. In this study, we combined single-nucleus measurements of gene expression and chromatin accessibility from six mammals (human, bonobo, macaque, marmoset, mouse, and opossum) to uncover conserved and diverged regulatory networks in cerebellum development. We identified core regulators of cell identity and developed sequence-based models that revealed conserved regulatory codes. By predicting chromatin accessibility across 240 mammalian species, we reconstructed the evolutionary histories of human cis-regulatory elements, identifying sets associated with positive selection and gene expression changes, including the recent gain of THRB expression in cerebellar progenitor cells. Collectively, our work reveals the shared and mammalian lineage-specific regulatory programs governing cerebellum development.","[""Journal Article""]","[""Sarropoulos I"", ""Sepp M"", ""Yamada T"", ""Schäfer PSL"", ""Trost N"", ""Schmidt J"", ""Schneider C"", ""Drummer C"", ""Mißbach S"", ""Taskiran II"", ""Hecker N"", ""Bravo González-Blas C"", ""Frömel R"", ""Joshi P"", ""Leushkin E"", ""Arnskötter F"", ""Leiss K"", ""Okonechnikov K"", ""Lisgo S"", ""Palkovits M"", ""Pääbo S"", ""Cardoso-Moreira M"", ""Kutscher LM"", ""Behr R"", ""Pfister SM"", ""Aerts S"", ""Kaessmann H""]",10.1126/science.adw9154,Sarropoulos I,"Science (New York, N.Y.)",0036-8075,6784,Science,eng,Kaessmann H,"[""Animals"", ""Cerebellum"", ""Humans"", ""Mice"", ""Gene Expression Regulation, Developmental"", ""Gene Regulatory Networks"", ""Evolution, Molecular"", ""Chromatin"", ""Mammals"", ""Biological Evolution""]",eadw9154,41610256,pmc-id: PMC7618896;manuscript-id: EMS212840;,2026 Jan 29,2026,https://pubmed.ncbi.nlm.nih.gov/41610256/,The evolution of gene regulation in mammalian cerebellum development,391,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"The selection of cells that have acquired a desired gene edit is often done by the introduction of additional genes that confer drug resistance or encode fluorophores. However, such marker genes can have unintended physiological effects and are not compatible with editing of single nucleotides. Here, we present SNIPE, a method that allows the marker-free selection of edited cells based on single nucleotide differences to unedited cells. SNIPE drastically enriches for cells, which have been precisely edited (median 7-fold). We validate the approach for 42 different edits using Cas9 or Cas12a in different cell types and species. We use it to enrich for combinations of substitutions that change missense mutations carried by all people today back to the ancestral state seen in Neandertals and Denisovans. We also show that it can be used to kill cultured tumor cells with aberrant genotypes and to repair heterozygous tumorigenic mutations.","[""Journal Article""]","[""Fast L"", ""Omar M"", ""Kanis P"", ""Schaffer T"", ""Chowdhury D"", ""Rakava E"", ""Pääbo S"", ""Riesenberg S""]",10.1038/s41467-025-66896-1,Fast L,Nature communications,2041-1723,1,Nat Commun,eng,Riesenberg S,"[""Gene Editing"", ""Humans"", ""Animals"", ""CRISPR-Cas Systems"", ""Neanderthals"", ""Mutation, Missense"", ""CRISPR-Associated Protein 9"", ""Base Sequence"", ""Cell Line, Tumor""]",10985,41361167,pmc-id: PMC12689631;,2025 Dec 8,2025,https://pubmed.ncbi.nlm.nih.gov/41361167/,Search-and-remove genome editing allows selection of cells by DNA sequence,16,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Denisovans have yet to be directly associated with a hominin cranium, limiting our understanding of their morphology and geographical distribution. We have attempted to retrieve DNA from a nearly complete Middle Pleistocene cranium from Harbin (>146 ka), northeastern China. Although no DNA could be retrieved from a tooth or the petrous bone, mitochondrial DNA (mtDNA) could be isolated from dental calculus. The mtDNA falls within Denisovan mtDNA variation and is related to an mtDNA branch carried by early Denisovan individuals in southern Siberia, previously observed in Denisova Cave. This suggests that Denisovans inhabited a large geographical range in Asia in the Middle Pleistocene. The association of Denisovan mtDNA with the Harbin cranium allows a better understanding of the morphological relationships between Denisovans and other East Asian Middle Pleistocene fossils. Furthermore, the retrieval of host DNA from dental calculus opens new possibilities for genetic research on Middle Pleistocene hominins.","[""Journal Article""]","[""Fu Q"", ""Cao P"", ""Dai Q"", ""Bennett EA"", ""Feng X"", ""Yang MA"", ""Ping W"", ""Pääbo S"", ""Ji Q""]",10.1016/j.cell.2025.05.040,Fu Q,Cell,0092-8674,15,Cell,eng,Ji Q,"[""DNA, Mitochondrial"", ""Dental Calculus"", ""Animals"", ""Fossils"", ""Hominidae"", ""Skull"", ""China"", ""Phylogeny"", ""DNA, Ancient"", ""Humans""]",3919-3926.e9,40920634,,2025 Jul 24,2025,https://pubmed.ncbi.nlm.nih.gov/40920634/,"Denisovan mitochondrial DNA from dental calculus of the >146,000-year-old Harbin cranium",188,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Adenylosuccinate lyase (ADSL), an enzyme that is crucial for purine biosynthesis, carries an amino acid substitution that is present in almost all humans today but absent in Neandertals and Denisovans. This substitution reduces the stability of the enzyme, but what functional consequences it has are unknown. Here, we show that when introduced into mice, this substitution causes substrates of the enzyme to accumulate in amounts that correlate negatively with ADSL expression levels. In the brain, where the expression of the enzyme is low, the substitution results in particularly high substrate levels. When the behavior of the mice is analyzed, female mice expressing the modern human-like version of ADSL access water more efficiently for drinking than their wild-type littermates. In addition to the amino acid substitution, a haplotype in the ADSL gene occurs at a carrier frequency of >97% in present-day humans and exhibits evidence of positive selection. It is associated with less ADSL expression as well as with increased concentrations of succinyladenosine, one of the substrates of the enzyme, in cerebrospinal fluid. Thus, two genetic changes have reduced ADSL activity in human tissues since modern and archaic humans separated, affecting purine biosynthesis, particularly in the brain.","[""Journal Article""]","[""Ju XC"", ""Lee SY"", ""Ågren R"", ""Machado LC"", ""Xing J"", ""Azama C"", ""Roy MC"", ""Endo T"", ""Huttner W"", ""Siepel A"", ""Fukunaga I"", ""Zeberg H"", ""Pääbo S""]",10.1073/pnas.2508540122,Ju XC,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,32,Proc Natl Acad Sci U S A,eng,Pääbo S,"[""Adenylosuccinate Lyase"", ""Animals"", ""Humans"", ""Brain"", ""Mice"", ""Female"", ""Evolution, Molecular"", ""Amino Acid Substitution"", ""Biological Evolution"", ""Behavior, Animal""]",e2508540122,40758872,pmc-id: PMC12358879;,2025 Aug 12,2025,https://pubmed.ncbi.nlm.nih.gov/40758872/,"The activity and expression of adenylosuccinate lyase were reduced during modern human evolution, affecting brain and behavior",122,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"The enzyme AMPD1 is expressed in skeletal muscle and is involved in ATP production. All available Neandertal genomes carry a lysine-to-isoleucine substitution at position 287 in AMPD1. This variant, which occurs at an allele frequency of 0-8% outside Africa, was introduced to modern humans by gene flow from Neandertals. Here, we show that the catalytic activity of the purified Neandertal AMPD1 is ~25% lower than the ancestral enzyme, and when introduced in mice, it reduces AMPD activity in muscle extracts by ~80%. Among present-day Europeans, another AMPD1 variant encoding a stop codon occurs at an allele frequency of 9-14%. Individuals heterozygous for this variant are less likely to be top-performing athletes in various sports, but otherwise reduced AMPD1 activity is well tolerated in present-day humans. While being conserved among vertebrates, AMPD1 seems to have become less functionally important among Neandertals and modern humans.","[""Journal Article""]","[""Macak D"", ""Lee SY"", ""Nyman T"", ""Ampah-Korsah H"", ""Strandback E"", ""Pääbo S"", ""Zeberg H""]",10.1038/s41467-025-61605-4,Macak D,Nature communications,2041-1723,1,Nat Commun,eng,Zeberg H,"[""Animals"", ""Neanderthals"", ""Humans"", ""AMP Deaminase"", ""Muscle, Skeletal"", ""Mice"", ""Gene Frequency""]",6371,40640132,pmc-id: PMC12246493;,2025 Jul 10,2025,https://pubmed.ncbi.nlm.nih.gov/40640132/,Muscle AMP deaminase activity was lower in Neandertals than in modern humans,16,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Denisova Cave in southern Siberia is the only site known to have been occupied by Denisovans, Neanderthals and modern humans. The cave consists of three chambers (Main, East and South), with the archaeological assemblages and remains of hominins, fauna and flora recovered from Main and East Chambers being the most thoroughly investigated to date. Here we report the results of analyses of the Palaeolithic artefacts, faunal remains and hominin and mammalian mitochondrial (mt) DNA recovered from renewed excavations in South Chamber. We construct a calendar-year time scale for the stratified Pleistocene deposits from optical dating of the sediments. The timing of hominin occupation and major turnovers in the mtDNA of Denisovans and large mammals largely accords with the patterns detected in Main and East Chambers. Time gaps in those sequences are partly filled by the South Chamber data and the sediment DNA record of Denisovans after 80,000 years ago is more than doubled in size. We combine the sediment dating and DNA records for all three chambers to reveal the whole-of-cave history of this unique site and the climatic conditions experienced by hominins and fauna over the past 300,000 years, including potential changes in habitat suitability for Denisovans and Neanderthals.","[""Journal Article"", ""Historical Article""]","[""Jacobs Z"", ""Zavala EI"", ""Li B"", ""O'Gorman K"", ""Shunkov MV"", ""Kozlikin MB"", ""Derevianko AP"", ""Uliyanov VA"", ""Goldberg P"", ""Agadjanian AK"", ""Vasiliev SK"", ""Brink F"", ""Peyrégne S"", ""Slon V"", ""Pääbo S"", ""Kelso J"", ""Meyer M"", ""Roberts RG""]",10.1038/s41467-025-60140-6,Jacobs Z,Nature communications,2041-1723,1,Nat Commun,eng,Roberts RG,"[""Animals"", ""Caves"", ""Siberia"", ""Hominidae"", ""DNA, Mitochondrial"", ""Fossils"", ""Humans"", ""Neanderthals"", ""Geologic Sediments"", ""Archaeology"", ""DNA, Ancient"", ""Mammals"", ""History, Ancient""]",4738,40399313,pmc-id: PMC12095498;,2025 May 21,2025,https://pubmed.ncbi.nlm.nih.gov/40399313/,Pleistocene chronology and history of hominins and fauna at Denisova Cave,16,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"The aryl hydrocarbon receptor (AHR) is a transcription factor that has many functions in mammals. Its best known function is that it binds aromatic hydrocarbons and induces the expression of cytochrome P450 genes, which encode enzymes that metabolize aromatic hydrocarbons and other substrates. All present-day humans carry an amino acid substitution at position 381 in the AHR that occurred after the divergence of modern humans from Neandertals and Denisovans. Previous studies that have expressed the ancestral and modern versions of AHR from expression vectors have yielded conflicting results with regard to their activities. Here, we use genome editing to modify the endogenous AHR gene so that it encodes to the ancestral, Neandertal-like AHR protein in human cells. In the absence of exogenous ligands, the expression of AHR target genes is higher in cells expressing the ancestral AHR than in cells expressing the modern AHR, and similar to the expression in chimpanzee cells. Furthermore, the modern human AHR needs higher doses of three ligands than the ancestral AHR to induce the expression of target genes. Thus, the ability of AHR to induce the expression of many of its target genes is reduced in modern humans.","[""Journal Article""]","[""Helmbrecht N"", ""Lackner M"", ""Maricic T"", ""Pääbo S""]",10.1073/pnas.2402159121,Helmbrecht N,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,22,Proc Natl Acad Sci U S A,eng,Pääbo S,"[""Receptors, Aryl Hydrocarbon"", ""Humans"", ""Gene Editing"", ""Animals"", ""Basic Helix-Loop-Helix Proteins"", ""Evolution, Molecular"", ""Pan troglodytes"", ""Neanderthals"", ""Ligands""]",e2402159121,38739836,pmc-id: PMC11145187;,2024 May 28,2024,https://pubmed.ncbi.nlm.nih.gov/38739836/,The modern human aryl hydrocarbon receptor is more active when ancestralized by genome editing,121,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Metabolism has recently emerged as a major target of genes implicated in the evolutionary expansion of human neocortex. One such gene is the human-specific gene ARHGAP11B. During human neocortex development, ARHGAP11B increases the abundance of basal radial glia, key progenitors for neocortex expansion, by stimulating glutaminolysis (glutamine-to-glutamate-to-alpha-ketoglutarate) in mitochondria. Here we show that the ape-specific protein GLUD2 (glutamate dehydrogenase 2), which also operates in mitochondria and converts glutamate-to-αKG, enhances ARHGAP11B's ability to increase basal radial glia abundance. ARHGAP11B + GLUD2 double-transgenic bRG show increased production of aspartate, a metabolite essential for cell proliferation, from glutamate via alpha-ketoglutarate and the TCA cycle. Hence, during human evolution, a human-specific gene exploited the existence of another gene that emerged during ape evolution, to increase, via concerted changes in metabolism, progenitor abundance and neocortex size.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Xing L"", ""Gkini V"", ""Nieminen AI"", ""Zhou HC"", ""Aquilino M"", ""Naumann R"", ""Reppe K"", ""Tanaka K"", ""Carmeliet P"", ""Heikinheimo O"", ""Pääbo S"", ""Huttner WB"", ""Namba T""]",10.1038/s41467-024-47437-8,Xing L,Nature communications,2041-1723,1,Nat Commun,eng,Namba T,"[""Neocortex"", ""Humans"", ""Animals"", ""Glutamate Dehydrogenase"", ""GTPase-Activating Proteins"", ""Ketoglutaric Acids"", ""Neuroglia"", ""Glutamic Acid"", ""Mitochondria"", ""Mice"", ""Citric Acid Cycle"", ""Female""]",3468,38658571,pmc-id: PMC11043075;,2024 Apr 24,2024,https://pubmed.ncbi.nlm.nih.gov/38658571/,Functional synergy of a human-specific and an ape-specific metabolic regulator in human neocortex development,15,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Modern human ancestors diverged from the ancestors of Neandertals and Denisovans about 600,000 years ago. Until about 40,000 years ago, these three groups existed in parallel, occasionally met, and exchanged genes. A critical question is why modern humans, and not the other two groups, survived, became numerous, and developed complex cultures. Here, we discuss genetic differences among the groups and some of their functional consequences. As more present-day genome sequences become available from diverse groups, we predict that very few, if any, differences will distinguish all modern humans from all Neandertals and Denisovans. We propose that the genetic basis of what constitutes a modern human is best thought of as a combination of genetic features, where perhaps none of them is present in each and every present-day individual.","[""Journal Article"", ""Review""]","[""Zeberg H"", ""Jakobsson M"", ""Pääbo S""]",10.1016/j.cell.2023.12.029,Zeberg H,Cell,0092-8674,5,Cell,eng,Pääbo S,"[""Animals"", ""Humans"", ""Neanderthals"", ""Research"", ""Hominidae"", ""Human Genetics""]",1047-1058,38367615,,2024 Feb 29,2024,https://pubmed.ncbi.nlm.nih.gov/38367615/,"The genetic changes that shaped Neandertals, Denisovans, and modern humans",187,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Homology-directed repair (HDR), a method for repair of DNA double-stranded breaks can be leveraged for the precise introduction of mutations supplied by synthetic DNA donors, but remains limited by low efficiency and off-target effects. In this study, we report HDRobust, a high-precision method that, via the combined transient inhibition of nonhomologous end joining and microhomology-mediated end joining, resulted in the induction of point mutations by HDR in up to 93% (median 60%, s.e.m. 3) of chromosomes in populations of cells. We found that, using this method, insertions, deletions and rearrangements at the target site, as well as unintended changes at other genomic sites, were largely abolished. We validated this approach for 58 different target sites and showed that it allows efficient correction of pathogenic mutations in cells derived from patients suffering from anemia, sickle cell disease and thrombophilia.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Riesenberg S"", ""Kanis P"", ""Macak D"", ""Wollny D"", ""Düsterhöft D"", ""Kowalewski J"", ""Helmbrecht N"", ""Maricic T"", ""Pääbo S""]",10.1038/s41592-023-01949-1,Riesenberg S,Nature methods,1548-7091,9,Nat Methods,eng,Pääbo S,"[""Humans"", ""Gene Editing"", ""CRISPR-Cas Systems"", ""Recombinational DNA Repair"", ""DNA Breaks, Double-Stranded"", ""DNA End-Joining Repair"", ""DNA""]",1388-1399,37474806,pmc-id: PMC10482697;,2023 Sep,2023,https://pubmed.ncbi.nlm.nih.gov/37474806/,Efficient high-precision homology-directed repair-dependent genome editing by HDRobust,20,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Dupuytren's disease is characterized by fingers becoming permanently bent in a flexed position. Whereas people of African ancestry are rarely afflicted by Dupuytren's disease, up to ∼30% of men over 60 years suffer from this condition in northern Europe. Here, we meta-analyze 3 biobanks comprising 7,871 cases and 645,880 controls and find 61 genome-wide significant variants associated with Dupuytren's disease. We show that 3 of the 61 loci harbor alleles of Neandertal origin, including the second and third most strongly associated ones (P = 6.4 × 10-132 and P = 9.2 × 10-69, respectively). For the most strongly associated Neandertal variant, we identify EPDR1 as the causal gene. Dupuytren's disease is an example of how admixture with Neandertals has shaped regional differences in disease prevalence.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Ågren R"", ""Patil S"", ""Zhou X"", ""FinnGen."", ""Sahlholm K"", ""Pääbo S"", ""Zeberg H""]",10.1093/molbev/msad130,Ågren R,Molecular biology and evolution,0737-4038,6,Mol Biol Evol,eng,Zeberg H,"[""Animals"", ""Humans"", ""Male"", ""Alleles"", ""Dupuytren Contracture"", ""Neanderthals"", ""Risk Factors""]",,37315093,pmc-id: PMC10266526;,2023 Jun 1,2023,https://pubmed.ncbi.nlm.nih.gov/37315093/,Major Genetic Risk Factors for Dupuytren's Disease Are Inherited From Neandertals,40,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Artefacts made from stones, bones and teeth are fundamental to our understanding of human subsistence strategies, behaviour and culture in the Pleistocene. Although these resources are plentiful, it is impossible to associate artefacts to specific human individuals1 who can be morphologically or genetically characterized, unless they are found within burials, which are rare in this time period. Thus, our ability to discern the societal roles of Pleistocene individuals based on their biological sex or genetic ancestry is limited2-5. Here we report the development of a non-destructive method for the gradual release of DNA trapped in ancient bone and tooth artefacts. Application of the method to an Upper Palaeolithic deer tooth pendant from Denisova Cave, Russia, resulted in the recovery of ancient human and deer mitochondrial genomes, which allowed us to estimate the age of the pendant at approximately 19,000-25,000 years. Nuclear DNA analysis identifies the presumed maker or wearer of the pendant as a female individual with strong genetic affinities to a group of Ancient North Eurasian individuals who lived around the same time but were previously found only further east in Siberia. Our work redefines how cultural and genetic records can be linked in prehistoric archaeology.","[""Historical Article"", ""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Essel E"", ""Zavala EI"", ""Schulz-Kornas E"", ""Kozlikin MB"", ""Fewlass H"", ""Vernot B"", ""Shunkov MV"", ""Derevianko AP"", ""Douka K"", ""Barnes I"", ""Soulier MC"", ""Schmidt A"", ""Szymanski M"", ""Tsanova T"", ""Sirakov N"", ""Endarova E"", ""McPherron SP"", ""Hublin JJ"", ""Kelso J"", ""Pääbo S"", ""Hajdinjak M"", ""Soressi M"", ""Meyer M""]",10.1038/s41586-023-06035-2,Essel E,Nature,0028-0836,7964,Nature,eng,Meyer M,"[""Animals"", ""Female"", ""Humans"", ""Archaeology"", ""Bone and Bones"", ""Deer"", ""DNA, Ancient"", ""DNA, Mitochondrial"", ""History, Ancient"", ""Siberia"", ""Tooth"", ""Caves"", ""Russia""]",328-332,37138083,pmc-id: PMC10247382;,2023 Jun,2023,https://pubmed.ncbi.nlm.nih.gov/37138083/,Ancient human DNA recovered from a Palaeolithic pendant,618,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Herai et al. discuss the known fact that a low percentage of modern humans who lack any overt phenotypes carry the ancestral TKTL1 allele. Our paper demonstrates that the amino acid substitution in TKTL1 increases neural progenitor cells and neurogenesis in the developing brain. It is another question if, and to what extent, this has consequences for the adult brain.","[""Journal Article""]","[""Pinson A"", ""Maricic T"", ""Zeberg H"", ""Pääbo S"", ""Huttner WB""]",10.1126/science.adf2212,Pinson A,"Science (New York, N.Y.)",0036-8075,6636,Science,eng,Huttner WB,"[""Animals"", ""Humans"", ""Neanderthals"", ""Neocortex"", ""Neural Stem Cells"", ""Neurogenesis"", ""Transketolase""]",eadf2212,36893240,,2023 Mar 10,2023,https://pubmed.ncbi.nlm.nih.gov/36893240/,"Response to Comment on ""Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals""",379,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"The transcription factor forkhead box P2 (FOXP2) is involved in the development of language and speech in humans. Two amino acid substitutions (T303N, N325S) occurred in the human FOXP2 after the divergence from the chimpanzee lineage. It has previously been shown that when they are introduced into the FOXP2 protein of mice they alter striatal synaptic plasticity by increasing long-term depression in medium spiny neurons. Here we introduce each of these amino acid substitutions individually into mice and analyze their effects in the striatum. We find that long-term depression in medium spiny neurons is increased in mice carrying only the T303N substitution to the same extent as in mice carrying both amino acid substitutions. In contrast, the N325S substitution has no discernable effects.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Bornschein U"", ""Zeberg H"", ""Enard W"", ""Hevers W"", ""Pääbo S""]",10.1038/s41598-023-30663-3,Bornschein U,Scientific reports,2045-2322,1,Sci Rep,eng,Pääbo S,"[""Humans"", ""Animals"", ""Mice"", ""Amino Acid Substitution"", ""Blood Group Antigens"", ""Corpus Striatum"", ""Dissection"", ""Extremities"", ""Pan troglodytes"", ""Forkhead Transcription Factors"", ""Repressor Proteins""]",3747,36879029,pmc-id: PMC9988825;,2023 Mar 6,2023,https://pubmed.ncbi.nlm.nih.gov/36879029/,Functional dissection of two amino acid substitutions unique to the human FOXP2 protein,13,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"CRISPR nucleases can introduce double-stranded DNA breaks in genomes at positions specified by guide RNAs. When repaired by the cell, this may result in the introduction of insertions and deletions or nucleotide substitutions provided by exogenous DNA donors. However, cellular repair can also result in unintended on-target effects, primarily larger deletions and loss of heterozygosity due to gene conversion. Here we present a strategy that allows easy and reliable detection of unintended on-target effects as well as the generation of control cells that carry wild-type alleles but have demonstratively undergone genome editing at the target site. Our 'sequence-ascertained favorable editing' (SAFE) donor approach relies on the use of DNA donor mixtures containing the desired nucleotide substitutions or the wild-type alleles together with combinations of additional 'diagnostic' substitutions unlikely to have any effects. Sequencing of the target sites then results in that two different sequences are seen when both chromosomes are edited with 'SAFE' donors containing different sets of substitutions, while a single sequence indicates unintended effects such as deletions or gene conversion. We analyzed more than 850 human embryonic stem cell clones edited with 'SAFE' donors and detect all copy number changes and almost all clones with gene conversion.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Lackner M"", ""Helmbrecht N"", ""Pääbo S"", ""Riesenberg S""]",10.1093/nar/gkac1254,Lackner M,Nucleic acids research,0305-1048,5,Nucleic Acids Res,eng,Riesenberg S,"[""Humans"", ""Clustered Regularly Interspaced Short Palindromic Repeats"", ""CRISPR-Cas Systems"", ""DNA"", ""Gene Editing"", ""Nucleotides"", ""Embryonic Stem Cells"", ""DNA Mutational Analysis""]",e26,36620901,pmc-id: PMC10018342;,2023 Mar 21,2023,https://pubmed.ncbi.nlm.nih.gov/36620901/,Detection of unintended on-target effects in CRISPR genome editing by DNA donors carrying diagnostic substitutions,51,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"The testis produces gametes through spermatogenesis and evolves rapidly at both the morphological and molecular level in mammals1-6, probably owing to the evolutionary pressure on males to be reproductively successful7. However, the molecular evolution of individual spermatogenic cell types across mammals remains largely uncharacterized. Here we report evolutionary analyses of single-nucleus transcriptome data for testes from 11 species that cover the three main mammalian lineages (eutherians, marsupials and monotremes) and birds (the evolutionary outgroup), and include seven primates. We find that the rapid evolution of the testis was driven by accelerated fixation rates of gene expression changes, amino acid substitutions and new genes in late spermatogenic stages, probably facilitated by reduced pleiotropic constraints, haploid selection and transcriptionally permissive chromatin. We identify temporal expression changes of individual genes across species and conserved expression programs controlling ancestral spermatogenic processes. Genes predominantly expressed in spermatogonia (germ cells fuelling spermatogenesis) and Sertoli (somatic support) cells accumulated on X chromosomes during evolution, presumably owing to male-beneficial selective forces. Further work identified transcriptomal differences between X- and Y-bearing spermatids and uncovered that meiotic sex-chromosome inactivation (MSCI) also occurs in monotremes and hence is common to mammalian sex-chromosome systems. Thus, the mechanism of meiotic silencing of unsynapsed chromatin, which underlies MSCI, is an ancestral mammalian feature. Our study illuminates the molecular evolution of spermatogenesis and associated selective forces, and provides a resource for investigating the biology of the testis across mammals.","[""Comparative Study"", ""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Murat F"", ""Mbengue N"", ""Winge SB"", ""Trefzer T"", ""Leushkin E"", ""Sepp M"", ""Cardoso-Moreira M"", ""Schmidt J"", ""Schneider C"", ""Mößinger K"", ""Brüning T"", ""Lamanna F"", ""Belles MR"", ""Conrad C"", ""Kondova I"", ""Bontrop R"", ""Behr R"", ""Khaitovich P"", ""Pääbo S"", ""Marques-Bonet T"", ""Grützner F"", ""Almstrup K"", ""Schierup MH"", ""Kaessmann H""]",10.1038/s41586-022-05547-7,Murat F,Nature,0028-0836,7943,Nature,eng,Kaessmann H,"[""Animals"", ""Male"", ""Chromatin"", ""Evolution, Molecular"", ""Mammals"", ""Meiosis"", ""Spermatogenesis"", ""Testis"", ""Transcriptome"", ""Single-Cell Analysis"", ""Birds"", ""Primates"", ""Gene Expression Regulation"", ""Spermatogonia"", ""Sertoli Cells"", ""X Chromosome"", ""Y Chromosome"", ""Dosage Compensation, Genetic"", ""Gene Silencing""]",308-316,36544022,pmc-id: PMC9834047;,2023 Jan,2023,https://pubmed.ncbi.nlm.nih.gov/36544022/,The molecular evolution of spermatogenesis across mammals,613,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Genomic analyses of Neanderthals have previously provided insights into their population history and relationship to modern humans1-8, but the social organization of Neanderthal communities remains poorly understood. Here we present genetic data for 13 Neanderthals from two Middle Palaeolithic sites in the Altai Mountains of southern Siberia: 11 from Chagyrskaya Cave9,10 and 2 from Okladnikov Cave11-making this one of the largest genetic studies of a Neanderthal population to date. We used hybridization capture to obtain genome-wide nuclear data, as well as mitochondrial and Y-chromosome sequences. Some Chagyrskaya individuals were closely related, including a father-daughter pair and a pair of second-degree relatives, indicating that at least some of the individuals lived at the same time. Up to one-third of these individuals' genomes had long segments of homozygosity, suggesting that the Chagyrskaya Neanderthals were part of a small community. In addition, the Y-chromosome diversity is an order of magnitude lower than the mitochondrial diversity, a pattern that we found is best explained by female migration between communities. Thus, the genetic data presented here provide a detailed documentation of the social organization of an isolated Neanderthal community at the easternmost extent of their known range.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Skov L"", ""Peyrégne S"", ""Popli D"", ""Iasi LNM"", ""Devièse T"", ""Slon V"", ""Zavala EI"", ""Hajdinjak M"", ""Sümer AP"", ""Grote S"", ""Bossoms Mesa A"", ""López Herráez D"", ""Nickel B"", ""Nagel S"", ""Richter J"", ""Essel E"", ""Gansauge M"", ""Schmidt A"", ""Korlević P"", ""Comeskey D"", ""Derevianko AP"", ""Kharevich A"", ""Markin SV"", ""Talamo S"", ""Douka K"", ""Krajcarz MT"", ""Roberts RG"", ""Higham T"", ""Viola B"", ""Krivoshapkin AI"", ""Kolobova KA"", ""Kelso J"", ""Meyer M"", ""Pääbo S"", ""Peter BM""]",10.1038/s41586-022-05283-y,Skov L,Nature,0028-0836,7932,Nature,eng,Peter BM,"[""Animals"", ""Female"", ""Humans"", ""Caves"", ""Genome"", ""Hybridization, Genetic"", ""Neanderthals"", ""Siberia"", ""DNA, Mitochondrial"", ""Y Chromosome"", ""Male"", ""Family"", ""Homozygote""]",519-525,36261548,pmc-id: PMC9581778;,2022 Oct,2022,https://pubmed.ncbi.nlm.nih.gov/36261548/,Genetic insights into the social organization of Neanderthals,610,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Neanderthal brains were similar in size to those of modern humans. We sought to investigate potential differences in neurogenesis during neocortex development. Modern human transketolase-like 1 (TKTL1) differs from Neanderthal TKTL1 by a lysine-to-arginine amino acid substitution. Using overexpression in developing mouse and ferret neocortex, knockout in fetal human neocortical tissue, and genome-edited cerebral organoids, we found that the modern human variant, hTKTL1, but not the Neanderthal variant, increases the abundance of basal radial glia (bRG) but not that of intermediate progenitors (bIPs). bRG generate more neocortical neurons than bIPs. The hTKTL1 effect requires the pentose phosphate pathway and fatty acid synthesis. Inhibition of these metabolic pathways reduces bRG abundance in fetal human neocortical tissue. Our data suggest that neocortical neurogenesis in modern humans differs from that in Neanderthals.","[""Journal Article""]","[""Pinson A"", ""Xing L"", ""Namba T"", ""Kalebic N"", ""Peters J"", ""Oegema CE"", ""Traikov S"", ""Reppe K"", ""Riesenberg S"", ""Maricic T"", ""Derihaci R"", ""Wimberger P"", ""Pääbo S"", ""Huttner WB""]",10.1126/science.abl6422,Pinson A,"Science (New York, N.Y.)",0036-8075,6611,Science,eng,Huttner WB,"[""Animals"", ""Ependymoglial Cells"", ""Ferrets"", ""Humans"", ""Mice"", ""Neanderthals"", ""Neocortex"", ""Neurogenesis"", ""Transketolase""]",eabl6422,36074851,,2022 Sep 9,2022,https://pubmed.ncbi.nlm.nih.gov/36074851/,Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals,377,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Since the ancestors of modern humans separated from those of Neanderthals, around 100 amino acid substitutions spread to essentially all modern humans. The biological significance of these changes is largely unknown. Here, we examine all six such amino acid substitutions in three proteins known to have key roles in kinetochore function and chromosome segregation and to be highly expressed in the stem cells of the developing neocortex. When we introduce these modern human-specific substitutions in mice, three substitutions in two of these proteins, KIF18a and KNL1, cause metaphase prolongation and fewer chromosome segregation errors in apical progenitors of the developing neocortex. Conversely, the ancestral substitutions cause shorter metaphase length and more chromosome segregation errors in human brain organoids, similar to what we find in chimpanzee organoids. These results imply that the fidelity of chromosome segregation during neocortex development improved in modern humans after their divergence from Neanderthals.","[""Journal Article""]","[""Mora-Bermúdez F"", ""Kanis P"", ""Macak D"", ""Peters J"", ""Naumann R"", ""Xing L"", ""Sarov M"", ""Winkler S"", ""Oegema CE"", ""Haffner C"", ""Wimberger P"", ""Riesenberg S"", ""Maricic T"", ""Huttner WB"", ""Pääbo S""]",10.1126/sciadv.abn7702,Mora-Bermúdez F,Science advances,2375-2548,30,Sci Adv,eng,Pääbo S,"[""Animals"", ""Brain"", ""Chromosome Segregation"", ""Hominidae"", ""Humans"", ""Kinesins"", ""Metaphase"", ""Mice"", ""Neanderthals""]",eabn7702,35905187,pmc-id: PMC9337762;,2022 Jul 29,2022,https://pubmed.ncbi.nlm.nih.gov/35905187/,Longer metaphase and fewer chromosome segregation errors in modern human than Neanderthal brain development,8,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Proteins associated with the spindle apparatus, a cytoskeletal structure that ensures the proper segregation of chromosomes during cell division, experienced an unusual number of amino acid substitutions in modern humans after the split from the ancestors of Neandertals and Denisovans. Here, we analyze the history of these substitutions and show that some of the genes in which they occur may have been targets of positive selection. We also find that the two changes in the kinetochore scaffold 1 (KNL1) protein, previously believed to be specific to modern humans, were present in some Neandertals. We show that the KNL1 gene of these Neandertals shared a common ancestor with present-day Africans about 200,000 years ago due to gene flow from the ancestors (or relatives) of modern humans into Neandertals. Subsequently, some non-Africans inherited this modern human-like gene variant from Neandertals, but none inherited the ancestral gene variants. These results add to the growing evidence of early contacts between modern humans and archaic groups in Eurasia and illustrate the intricate relationships among these groups.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Peyrégne S"", ""Kelso J"", ""Peter BM"", ""Pääbo S""]",10.7554/eLife.75464,Peyrégne S,eLife,2050-084X,,Elife,eng,Pääbo S,"[""Animals"", ""Biological Evolution"", ""Black People"", ""Fossils"", ""Gene Flow"", ""Hominidae"", ""Humans"", ""Neanderthals""]",,35816093,pmc-id: PMC9273211;,2022 Jul 11,2022,https://pubmed.ncbi.nlm.nih.gov/35816093/,The evolutionary history of human spindle genes includes back-and-forth gene flow with Neandertals,11,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Genetic variation in genes encoding cytochrome P450 enzymes influences the metabolism of drugs and endogenous compounds. The locus containing the cytochrome genes CYP2C8 and CYP2C9 on chromosome 10 exhibits linkage disequilibrium between the CYP2C8*3 and CYP2C9*2 alleles, forming a haplotype of ~300 kilobases. This haplotype is associated with altered metabolism of several drugs, most notably reduced metabolism of warfarin and phenytoin, leading to toxicity at otherwise therapeutic doses. Here we show that this haplotype is inherited from Neandertals.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Haeggström S"", ""Ingelman-Sundberg M"", ""Pääbo S"", ""Zeberg H""]",10.1038/s41397-022-00284-6,Haeggström S,The pharmacogenomics journal,1470-269X,4,Pharmacogenomics J,eng,Zeberg H,"[""Animals"", ""Aryl Hydrocarbon Hydroxylases"", ""Cytochrome P-450 CYP2C8"", ""Cytochrome P-450 CYP2C9"", ""Gene Frequency"", ""Haplotypes"", ""Humans"", ""Neanderthals""]",247-249,35780191,pmc-id: PMC9363273;,2022 Jul,2022,https://pubmed.ncbi.nlm.nih.gov/35780191/,The clinically relevant CYP2C8*3 and CYP2C9*2 haplotype is inherited from Neandertals,22,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Skeletal muscle fiber type distribution has implications for human health, muscle function, and performance. This knowledge has been gathered using labor-intensive and costly methodology that limited these studies. Here, we present a method based on muscle tissue RNA sequencing data (totRNAseq) to estimate the distribution of skeletal muscle fiber types from frozen human samples, allowing for a larger number of individuals to be tested. By using single-nuclei RNA sequencing (snRNAseq) data as a reference, cluster expression signatures were produced by averaging gene expression of cluster gene markers and then applying these to totRNAseq data and inferring muscle fiber nuclei type via linear matrix decomposition. This estimate was then compared with fiber type distribution measured by ATPase staining or myosin heavy chain protein isoform distribution of 62 muscle samples in two independent cohorts (n = 39 and 22). The correlation between the sequencing-based method and the other two were rATPas = 0.44 [0.13-0.67], [95% CI], and rmyosin = 0.83 [0.61-0.93], with p = 5.70 × 10-3 and 2.00 × 10-6, respectively. The deconvolution inference of fiber type composition was accurate even for very low totRNAseq sequencing depths, i.e., down to an average of ~ 10,000 paired-end reads. This new method ( https://github.com/OlaHanssonLab/PredictFiberType ) consequently allows for measurement of fiber type distribution of a larger number of samples using totRNAseq in a cost and labor-efficient way. It is now feasible to study the association between fiber type distribution and e.g. health outcomes in large well-powered studies.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Oskolkov N"", ""Santel M"", ""Parikh HM"", ""Ekström O"", ""Camp GJ"", ""Miyamoto-Mikami E"", ""Ström K"", ""Mir BA"", ""Kryvokhyzha D"", ""Lehtovirta M"", ""Kobayashi H"", ""Kakigi R"", ""Naito H"", ""Eriksson KF"", ""Nystedt B"", ""Fuku N"", ""Treutlein B"", ""Pääbo S"", ""Hansson O""]",10.1186/s13395-022-00299-4,Oskolkov N,Skeletal muscle,2044-5040,1,Skelet Muscle,eng,Hansson O,"[""Base Sequence"", ""Humans"", ""Muscle Fibers, Skeletal"", ""RNA"", ""Sequence Analysis, RNA"", ""Exome Sequencing""]",16,35780170,pmc-id: PMC9250227;,2022 Jul 2,2022,https://pubmed.ncbi.nlm.nih.gov/35780170/,High-throughput muscle fiber typing from RNA sequencing data,12,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"The first step in CRISPR-Cas9-mediated genome editing is the cleavage of target DNA sequences that are complementary to so-called spacer sequences in CRISPR guide RNAs (gRNAs). However, some DNA sequences are refractory to CRISPR-Cas9 cleavage, which is at least in part due to gRNA misfolding. To overcome this problem, we have engineered gRNAs with highly stable hairpins in their constant parts and further enhanced their stability by chemical modifications. The 'Genome-editing Optimized Locked Design' (GOLD)-gRNA increases genome editing efficiency up to around 1000-fold (from 0.08 to 80.5%) with a mean increase across different other targets of 7.4-fold. We anticipate that this improved gRNA will allow efficient editing regardless of spacer sequence composition and will be especially useful if a desired genomic site is difficult to edit.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Riesenberg S"", ""Helmbrecht N"", ""Kanis P"", ""Maricic T"", ""Pääbo S""]",10.1038/s41467-022-28137-7,Riesenberg S,Nature communications,2041-1723,1,Nat Commun,eng,Pääbo S,"[""CRISPR-Cas Systems"", ""Cell Line"", ""Gene Editing"", ""Genome"", ""Humans"", ""Nucleic Acid Conformation"", ""Oligonucleotides"", ""RNA, Guide, CRISPR-Cas Systems""]",489,35078986,pmc-id: PMC8789806;,2022 Jan 25,2022,https://pubmed.ncbi.nlm.nih.gov/35078986/,Improved gRNA secondary structures allow editing of target sites resistant to CRISPR-Cas9 cleavage,13,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Glutathione reductase is a critical enzyme for preventing oxidative stress and maintaining a reduced intracellular environment. Almost all present-day humans carry an amino acid substitution (S232G) in this enzyme relative to apes and Neanderthals. We express the modern human and the ancestral enzymes and show that whereas the activity and stability are unaffected by the amino acid substitution, the ancestral enzyme produces more reactive oxygen species and increases cellular levels of transcripts encoding cytokines. We furthermore show that the ancestral enzyme has been reintroduced into the modern human gene pool by gene flow from Neanderthals and is associated with multiple traits in present-day people, including increased susceptibility for inflammatory-associated disorders and vascular disease.","[""Journal Article""]","[""Coppo L"", ""Mishra P"", ""Siefert N"", ""Holmgren A"", ""Pääbo S"", ""Zeberg H""]",10.1126/sciadv.abm1148,Coppo L,Science advances,2375-2548,1,Sci Adv,eng,Zeberg H,[],eabm1148,34985944,pmc-id: PMC8730399;,2022 Jan 7,2022,https://pubmed.ncbi.nlm.nih.gov/34985944/,A substitution in the glutathione reductase lowers electron leakage and inflammation in modern humans,8,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Ancient DNA recovered from Pleistocene sediments represents a rich resource for the study of past hominin and environmental diversity. However, little is known about how DNA is preserved in sediments and the extent to which it may be translocated between archaeological strata. Here, we investigate DNA preservation in 47 blocks of resin-impregnated archaeological sediment collected over the last four decades for micromorphological analyses at 13 prehistoric sites in Europe, Asia, Africa, and North America and show that such blocks can preserve DNA of hominins and other mammals. Extensive microsampling of sediment blocks from Denisova Cave in the Altai Mountains reveals that the taxonomic composition of mammalian DNA differs drastically at the millimeter-scale and that DNA is concentrated in small particles, especially in fragments of bone and feces (coprolites), suggesting that these are substantial sources of DNA in sediments. Three microsamples taken in close proximity in one of the blocks yielded Neanderthal DNA from at least two male individuals closely related to Denisova 5, a Neanderthal toe bone previously recovered from the same layer. Our work indicates that DNA can remain stably localized in sediments over time and provides a means of linking genetic information to the archaeological and ecological records on a microstratigraphic scale.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Massilani D"", ""Morley MW"", ""Mentzer SM"", ""Aldeias V"", ""Vernot B"", ""Miller C"", ""Stahlschmidt M"", ""Kozlikin MB"", ""Shunkov MV"", ""Derevianko AP"", ""Conard NJ"", ""Wurz S"", ""Henshilwood CS"", ""Vasquez J"", ""Essel E"", ""Nagel S"", ""Richter J"", ""Nickel B"", ""Roberts RG"", ""Pääbo S"", ""Slon V"", ""Goldberg P"", ""Meyer M""]",10.1073/pnas.2113666118,Massilani D,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,1,Proc Natl Acad Sci U S A,eng,Meyer M,"[""Animals"", ""Caves"", ""DNA, Ancient"", ""Fossils"", ""Hominidae"", ""Neanderthals""]",,34969841,pmc-id: PMC8740756;,2022 Jan 4,2022,https://pubmed.ncbi.nlm.nih.gov/34969841/,Microstratigraphic preservation of ancient faunal and hominin DNA in Pleistocene cave sediments,119,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Since the initial identification of the Denisovans a decade ago, only a handful of their physical remains have been discovered. Here we analysed ~3,800 non-diagnostic bone fragments using collagen peptide mass fingerprinting to locate new hominin remains from Denisova Cave (Siberia, Russia). We identified five new hominin bones, four of which contained sufficient DNA for mitochondrial analysis. Three carry mitochondrial DNA of the Denisovan type and one was found to carry mtDNA of the Neanderthal type. The former come from the same archaeological layer near the base of the cave's sequence and are the oldest securely dated evidence of Denisovans at 200 ka (thousand years ago) (205-192 ka at 68.2% or 217-187 ka at 95% probability). The stratigraphic context in which they were located contains a wealth of archaeological material in the form of lithics and faunal remains, allowing us to determine the material culture associated with these early hominins and explore their behavioural and environmental adaptations. The combination of bone collagen fingerprinting and genetic analyses has so far more-than-doubled the number of hominin bones at Denisova Cave and has expanded our understanding of Denisovan and Neanderthal interactions, as well as their archaeological signatures.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Brown S"", ""Massilani D"", ""Kozlikin MB"", ""Shunkov MV"", ""Derevianko AP"", ""Stoessel A"", ""Jope-Street B"", ""Meyer M"", ""Kelso J"", ""Pääbo S"", ""Higham T"", ""Douka K""]",10.1038/s41559-021-01581-2,Brown S,Nature ecology & evolution,2397-334X,1,Nat Ecol Evol,eng,Douka K,"[""Animals"", ""Archaeology"", ""Caves"", ""DNA, Mitochondrial"", ""Hominidae"", ""Neanderthals""]",28-35,34824388,pmc-id: PMC7612221;manuscript-id: EMS135559;,2022 Jan,2022,https://pubmed.ncbi.nlm.nih.gov/34824388/,The earliest Denisovans and their cultural adaptation,6,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Trujillo et al. (Research Articles, 12 February 2021, eaax2537) conclude that the reintroduction of an ancestral amino acid substitution in the protein NOVA1 drastically alters the development of brain organoids. We show that cell lines used by the authors carry heterozygous deletions of the target DNA sequence, providing another plausible explanation for the effects observed.","[""Journal Article"", ""Comment""]","[""Maricic T"", ""Helmbrecht N"", ""Riesenberg S"", ""Macak D"", ""Kanis P"", ""Lackner M"", ""Pugach-Matveeva AD"", ""Pääbo S""]",10.1126/science.abi6060,Maricic T,"Science (New York, N.Y.)",0036-8075,6565,Science,eng,Pääbo S,"[""Organoids""]",eabi6060,34648345,,2021 Oct 15,2021,https://pubmed.ncbi.nlm.nih.gov/34648345/,"Comment on ""Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment""",374,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Denisova Cave in southern Siberia is the type locality of the Denisovans, an archaic hominin group who were related to Neanderthals1-4. The dozen hominin remains recovered from the deposits also include Neanderthals5,6 and the child of a Neanderthal and a Denisovan7, which suggests that Denisova Cave was a contact zone between these archaic hominins. However, uncertainties persist about the order in which these groups appeared at the site, the timing and environmental context of hominin occupation, and the association of particular hominin groups with archaeological assemblages5,8-11. Here we report the analysis of DNA from 728 sediment samples that were collected in a grid-like manner from layers dating to the Pleistocene epoch. We retrieved ancient faunal and hominin mitochondrial (mt)DNA from 685 and 175 samples, respectively. The earliest evidence for hominin mtDNA is of Denisovans, and is associated with early Middle Palaeolithic stone tools that were deposited approximately 250,000 to 170,000 years ago; Neanderthal mtDNA first appears towards the end of this period. We detect a turnover in the mtDNA of Denisovans that coincides with changes in the composition of faunal mtDNA, and evidence that Denisovans and Neanderthals occupied the site repeatedly-possibly until, or after, the onset of the Initial Upper Palaeolithic at least 45,000 years ago, when modern human mtDNA is first recorded in the sediments.","[""Historical Article"", ""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Zavala EI"", ""Jacobs Z"", ""Vernot B"", ""Shunkov MV"", ""Kozlikin MB"", ""Derevianko AP"", ""Essel E"", ""de Fillipo C"", ""Nagel S"", ""Richter J"", ""Romagné F"", ""Schmidt A"", ""Li B"", ""O'Gorman K"", ""Slon V"", ""Kelso J"", ""Pääbo S"", ""Roberts RG"", ""Meyer M""]",10.1038/s41586-021-03675-0,Zavala EI,Nature,0028-0836,7867,Nature,eng,Meyer M,"[""Animals"", ""Archaeology"", ""Caves"", ""DNA, Ancient"", ""DNA, Mitochondrial"", ""Fossils"", ""Geologic Sediments"", ""History, Ancient"", ""Hominidae"", ""Neanderthals"", ""Siberia""]",399-403,34163072,pmc-id: PMC8277575;,2021 Jul,2021,https://pubmed.ncbi.nlm.nih.gov/34163072/,Pleistocene sediment DNA reveals hominin and faunal turnovers at Denisova Cave,595,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"We analyze the metabolomes of humans, chimpanzees, and macaques in muscle, kidney and three different regions of the brain. Although several compounds in amino acid metabolism occur at either higher or lower concentrations in humans than in the other primates, metabolites downstream of adenylosuccinate lyase, which catalyzes two reactions in purine synthesis, occur at lower concentrations in humans. This enzyme carries an amino acid substitution that is present in all humans today but absent in Neandertals. By introducing the modern human substitution into the genomes of mice, as well as the ancestral, Neandertal-like substitution into the genomes of human cells, we show that this amino acid substitution contributes to much or all of the reduction of de novo synthesis of purines in humans.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Stepanova V"", ""Moczulska KE"", ""Vacano GN"", ""Kurochkin I"", ""Ju X"", ""Riesenberg S"", ""Macak D"", ""Maricic T"", ""Dombrowski L"", ""Schörnig M"", ""Anastassiadis K"", ""Baker O"", ""Naumann R"", ""Khrameeva E"", ""Vanushkina A"", ""Stekolshchikova E"", ""Egorova A"", ""Tkachev A"", ""Mazzarino R"", ""Duval N"", ""Zubkov D"", ""Giavalisco P"", ""Wilkinson TG"", ""Patterson D"", ""Khaitovich P"", ""Pääbo S""]",10.7554/eLife.58741,Stepanova V,eLife,2050-084X,,Elife,eng,Pääbo S,"[""Animals"", ""Biosynthetic Pathways"", ""Female"", ""Gene Editing"", ""Humans"", ""Macaca"", ""Male"", ""Metabolome"", ""Mice"", ""Mice, Transgenic"", ""Mutation, Missense"", ""Neanderthals"", ""Pan troglodytes"", ""Purines""]",,33942714,pmc-id: PMC8133780;,2021 May 4,2021,https://pubmed.ncbi.nlm.nih.gov/33942714/,Reduced purine biosynthesis in humans after their divergence from Neandertals,10,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Modern humans appeared in Europe by at least 45,000 years ago1-5, but the extent of their interactions with Neanderthals, who disappeared by about 40,000 years ago6, and their relationship to the broader expansion of modern humans outside Africa are poorly understood. Here we present genome-wide data from three individuals dated to between 45,930 and 42,580 years ago from Bacho Kiro Cave, Bulgaria1,2. They are the earliest Late Pleistocene modern humans known to have been recovered in Europe so far, and were found in association with an Initial Upper Palaeolithic artefact assemblage. Unlike two previously studied individuals of similar ages from Romania7 and Siberia8 who did not contribute detectably to later populations, these individuals are more closely related to present-day and ancient populations in East Asia and the Americas than to later west Eurasian populations. This indicates that they belonged to a modern human migration into Europe that was not previously known from the genetic record, and provides evidence that there was at least some continuity between the earliest modern humans in Europe and later people in Eurasia. Moreover, we find that all three individuals had Neanderthal ancestors a few generations back in their family history, confirming that the first European modern humans mixed with Neanderthals and suggesting that such mixing could have been common.","[""Historical Article"", ""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Hajdinjak M"", ""Mafessoni F"", ""Skov L"", ""Vernot B"", ""Hübner A"", ""Fu Q"", ""Essel E"", ""Nagel S"", ""Nickel B"", ""Richter J"", ""Moldovan OT"", ""Constantin S"", ""Endarova E"", ""Zahariev N"", ""Spasov R"", ""Welker F"", ""Smith GM"", ""Sinet-Mathiot V"", ""Paskulin L"", ""Fewlass H"", ""Talamo S"", ""Rezek Z"", ""Sirakova S"", ""Sirakov N"", ""McPherron SP"", ""Tsanova T"", ""Hublin JJ"", ""Peter BM"", ""Meyer M"", ""Skoglund P"", ""Kelso J"", ""Pääbo S""]",10.1038/s41586-021-03335-3,Hajdinjak M,Nature,0028-0836,7853,Nature,eng,Pääbo S,"[""Alleles"", ""Americas"", ""Animals"", ""Archaeology"", ""Bulgaria"", ""Caves"", ""DNA, Ancient"", ""Asia, Eastern"", ""Female"", ""Genome, Human"", ""History, Ancient"", ""Humans"", ""Male"", ""Neanderthals"", ""Phylogeny""]",253-257,33828320,pmc-id: PMC8026394;manuscript-id: EMS115988;,2021 Apr,2021,https://pubmed.ncbi.nlm.nih.gov/33828320/,Initial Upper Palaeolithic humans in Europe had recent Neanderthal ancestry,592,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Efforts to contain the spread of SARS-CoV-2 have spurred the need for reliable, rapid, and cost-effective diagnostic methods which can be applied to large numbers of people. However, current standard protocols for the detection of viral nucleic acids while sensitive, require a high level of automation and sophisticated laboratory equipment to achieve throughputs that allow whole communities to be tested on a regular basis. Here we present Cap-iLAMP (capture and improved loop-mediated isothermal amplification) which combines a hybridization capture-based RNA extraction of gargle lavage samples with an improved colorimetric RT-LAMP assay and smartphone-based color scoring. Cap-iLAMP is compatible with point-of-care testing and enables the detection of SARS-CoV-2 positive samples in less than one hour. In contrast to direct addition of the sample to improved LAMP (iLAMP), Cap-iLAMP prevents false positives and allows single positive samples to be detected in pools of 25 negative samples, reducing the reagent cost per test to ~1 Euro per individual.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Bokelmann L"", ""Nickel O"", ""Maricic T"", ""Pääbo S"", ""Meyer M"", ""Borte S"", ""Riesenberg S""]",10.1038/s41467-021-21627-0,Bokelmann L,Nature communications,2041-1723,1,Nat Commun,eng,Riesenberg S,"[""COVID-19"", ""COVID-19 Testing"", ""Colorimetry"", ""Coronavirus Nucleocapsid Proteins"", ""Humans"", ""Molecular Diagnostic Techniques"", ""Nucleic Acid Amplification Techniques"", ""Nucleic Acid Hybridization"", ""Phosphoproteins"", ""Point-of-Care Testing"", ""RNA, Viral"", ""SARS-CoV-2"", ""Sensitivity and Specificity""]",1467,33674580,pmc-id: PMC7935920;,2021 Mar 5,2021,https://pubmed.ncbi.nlm.nih.gov/33674580/,Point-of-care bulk testing for SARS-CoV-2 by combining hybridization capture with improved colorimetric LAMP,12,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"It was recently shown that the major genetic risk factor associated with becoming severely ill with COVID-19 when infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is inherited from Neandertals. New, larger genetic association studies now allow additional genetic risk factors to be discovered. Using data from the Genetics of Mortality in Critical Care (GenOMICC) consortium, we show that a haplotype at a region on chromosome 12 associated with requiring intensive care when infected with the virus is inherited from Neandertals. This region encodes proteins that activate enzymes that are important during infections with RNA viruses. In contrast to the previously described Neandertal haplotype that increases the risk for severe COVID-19, this Neandertal haplotype is protective against severe disease. It also differs from the risk haplotype in that it has a more moderate effect and occurs at substantial frequencies in all regions of the world outside Africa. Among ancient human genomes in western Eurasia, the frequency of the protective Neandertal haplotype may have increased between 20,000 and 10,000 y ago and again during the past 1,000 y.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Zeberg H"", ""Pääbo S""]",10.1073/pnas.2026309118,Zeberg H,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,9,Proc Natl Acad Sci U S A,eng,Pääbo S,"[""Animals"", ""COVID-19"", ""Chromosomes, Human, Pair 12"", ""Evolution, Molecular"", ""Genetic Predisposition to Disease"", ""Haplotypes"", ""Humans"", ""Neanderthals"", ""Quantitative Trait Loci""]",,33593941,pmc-id: PMC7936282;,2021 Mar 2,2021,https://pubmed.ncbi.nlm.nih.gov/33593941/,A genomic region associated with protection against severe COVID-19 is inherited from Neandertals,118,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"SARS-CoV-2 causes substantial morbidity and mortality in elderly and immunocompromised individuals, particularly in retirement homes, where transmission from asymptomatic staff and visitors may introduce the infection. Here we present a cheap and fast screening method based on direct RT-qPCR to detect SARS-CoV-2 in single or pooled gargle lavages (""mouthwashes""). This method detects individuals with large viral loads (Ct≤29) and we use it to test all staff at a nursing home daily over a period of three weeks in order to reduce the risk that the infection penetrates the facility. This or similar approaches can be implemented to protect hospitals, nursing homes and other institutions in this and future viral epidemics.","[""Clinical Trial"", ""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Maricic T"", ""Nickel O"", ""Aximu-Petri A"", ""Essel E"", ""Gansauge M"", ""Kanis P"", ""Macak D"", ""Richter J"", ""Riesenberg S"", ""Bokelmann L"", ""Zeberg H"", ""Meyer M"", ""Borte S"", ""Pääbo S""]",10.1371/journal.pone.0244824,Maricic T,PloS one,1932-6203,12,PLoS One,eng,Pääbo S,"[""COVID-19"", ""COVID-19 Nucleic Acid Testing"", ""Humans"", ""Mass Screening"", ""Real-Time Polymerase Chain Reaction"", ""SARS-CoV-2""]",e0244824,33382830,pmc-id: PMC7774962;,2020,2020,https://pubmed.ncbi.nlm.nih.gov/33382830/,A direct RT-qPCR approach to test large numbers of individuals for SARS-CoV-2,15,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"A late Middle Pleistocene mandible from Baishiya Karst Cave (BKC) on the Tibetan Plateau has been inferred to be from a Denisovan, an Asian hominin related to Neanderthals, on the basis of an amino acid substitution in its collagen. Here we describe the stratigraphy, chronology, and mitochondrial DNA extracted from the sediments in BKC. We recover Denisovan mitochondrial DNA from sediments deposited ~100 thousand and ~60 thousand years ago (ka) and possibly as recently as ~45 ka. The long-term occupation of BKC by Denisovans suggests that they may have adapted to life at high altitudes and may have contributed such adaptations to modern humans on the Tibetan Plateau.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Zhang D"", ""Xia H"", ""Chen F"", ""Li B"", ""Slon V"", ""Cheng T"", ""Yang R"", ""Jacobs Z"", ""Dai Q"", ""Massilani D"", ""Shen X"", ""Wang J"", ""Feng X"", ""Cao P"", ""Yang MA"", ""Yao J"", ""Yang J"", ""Madsen DB"", ""Han Y"", ""Ping W"", ""Liu F"", ""Perreault C"", ""Chen X"", ""Meyer M"", ""Kelso J"", ""Pääbo S"", ""Fu Q""]",10.1126/science.abb6320,Zhang D,"Science (New York, N.Y.)",0036-8075,6516,Science,eng,Fu Q,"[""Animals"", ""Caves"", ""DNA, Ancient"", ""DNA, Mitochondrial"", ""Geologic Sediments"", ""Hominidae"", ""Humans"", ""Phylogeny"", ""Tibet""]",584-587,33122381,,2020 Oct 30,2020,https://pubmed.ncbi.nlm.nih.gov/33122381/,Denisovan DNA in Late Pleistocene sediments from Baishiya Karst Cave on the Tibetan Plateau,370,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"We present analyses of the genome of a ~34,000-year-old hominin skull cap discovered in the Salkhit Valley in northeastern Mongolia. We show that this individual was a female member of a modern human population that, following the split between East and West Eurasians, experienced substantial gene flow from West Eurasians. Both she and a 40,000-year-old individual from Tianyuan outside Beijing carried genomic segments of Denisovan ancestry. These segments derive from the same Denisovan admixture event(s) that contributed to present-day mainland Asians but are distinct from the Denisovan DNA segments in present-day Papuans and Aboriginal Australians.","[""Journal Article""]","[""Massilani D"", ""Skov L"", ""Hajdinjak M"", ""Gunchinsuren B"", ""Tseveendorj D"", ""Yi S"", ""Lee J"", ""Nagel S"", ""Nickel B"", ""Devièse T"", ""Higham T"", ""Meyer M"", ""Kelso J"", ""Peter BM"", ""Pääbo S""]",10.1126/science.abc1166,Massilani D,"Science (New York, N.Y.)",0036-8075,6516,Science,eng,Pääbo S,"[""Animals"", ""Asian People"", ""DNA, Ancient"", ""Evolution, Molecular"", ""Female"", ""Hominidae"", ""Humans"", ""Mongolia"", ""Population"", ""Skull""]",579-583,33122380,,2020 Oct 30,2020,https://pubmed.ncbi.nlm.nih.gov/33122380/,Denisovan ancestry and population history of early East Asians,370,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"A recent genetic association study1 identified a gene cluster on chromosome 3 as a risk locus for respiratory failure after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A separate study (COVID-19 Host Genetics Initiative)2 comprising 3,199 hospitalized patients with coronavirus disease 2019 (COVID-19) and control individuals showed that this cluster is the major genetic risk factor for severe symptoms after SARS-CoV-2 infection and hospitalization. Here we show that the risk is conferred by a genomic segment of around 50 kilobases in size that is inherited from Neanderthals and is carried by around 50% of people in south Asia and around 16% of people in Europe.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Zeberg H"", ""Pääbo S""]",10.1038/s41586-020-2818-3,Zeberg H,Nature,0028-0836,7835,Nature,eng,Pääbo S,"[""Animals"", ""Asia"", ""COVID-19"", ""Case-Control Studies"", ""Chromosomes, Human, Pair 3"", ""Europe"", ""Genetic Predisposition to Disease"", ""Genetic Variation"", ""Genome-Wide Association Study"", ""Haplotypes"", ""Hospitalization"", ""Humans"", ""Linkage Disequilibrium"", ""Multigene Family"", ""Neanderthals"", ""Phylogeny"", ""Severe Acute Respiratory Syndrome""]",610-612,32998156,,2020 Nov,2020,https://pubmed.ncbi.nlm.nih.gov/32998156/,The major genetic risk factor for severe COVID-19 is inherited from Neanderthals,587,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"The sodium channel Nav1.7 is crucial for impulse generation and conduction in peripheral pain pathways [1]. In Neanderthals, the Nav1.7 protein carried three amino acid substitutions (M932L, V991L, and D1908G) relative to modern humans. We expressed Nav1.7 proteins carrying all combinations of these substitutions and studied their electrophysiological effects. Whereas the single amino acid substitutions do not affect the function of the ion channel, the full Neanderthal variant carrying all three substitutions, as well as the combination of V991L with D1908G, shows reduced inactivation, suggesting that peripheral nerves were more sensitive to painful stimuli in Neanderthals than in modern humans. We show that, due to gene flow from Neanderthals, the three Neanderthal substitutions are found in ∼0.4% of present-day Britons, where they are associated with heightened pain sensitivity.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Zeberg H"", ""Dannemann M"", ""Sahlholm K"", ""Tsuo K"", ""Maricic T"", ""Wiebe V"", ""Hevers W"", ""Robinson HPC"", ""Kelso J"", ""Pääbo S""]",10.1016/j.cub.2020.06.045,Zeberg H,Current biology : CB,0960-9822,17,Curr Biol,eng,Pääbo S,"[""Adult"", ""Aged"", ""Amino Acid Substitution"", ""Animals"", ""Female"", ""Humans"", ""Male"", ""Middle Aged"", ""Mutation"", ""NAV1.7 Voltage-Gated Sodium Channel"", ""Neanderthals"", ""Pain"", ""Xenopus laevis""]",3465-3469.e4,32707058,,2020 Sep 7,2020,https://pubmed.ncbi.nlm.nih.gov/32707058/,A Neanderthal Sodium Channel Increases Pain Sensitivity in Present-Day Humans,30,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Induced pluripotent stem cells (iPSCs) from diverse humans offer the potential to study human functional variation in controlled culture environments. A portion of this variation originates from an ancient admixture between modern humans and Neandertals, which introduced alleles that left a phenotypic legacy on individual humans today. Here, we show that a large iPSC repository harbors extensive Neandertal DNA, including alleles that contribute to human phenotypes and diseases, encode hundreds of amino acid changes, and alter gene expression in specific tissues. We provide a database of the inferred introgressed Neandertal alleles for each individual iPSC line, together with the annotation of the predicted functional variants. We also show that transcriptomic data from organoids generated from iPSCs can be used to track Neandertal-derived RNA over developmental processes. Human iPSC resources provide an opportunity to experimentally explore Neandertal DNA function and its contribution to present-day phenotypes, and potentially study Neandertal traits.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Dannemann M"", ""He Z"", ""Heide C"", ""Vernot B"", ""Sidow L"", ""Kanton S"", ""Weigert A"", ""Treutlein B"", ""Pääbo S"", ""Kelso J"", ""Camp JG""]",10.1016/j.stemcr.2020.05.018,Dannemann M,Stem cell reports,2213-6711,1,Stem Cell Reports,eng,Camp JG,"[""Alleles"", ""Animals"", ""Brain"", ""Cell Line"", ""DNA"", ""Haplotypes"", ""Humans"", ""Neanderthals"", ""Phenotype"", ""Pluripotent Stem Cells"", ""RNA"", ""Stem Cells""]",214-225,32559457,pmc-id: PMC7363959;,2020 Jul 14,2020,https://pubmed.ncbi.nlm.nih.gov/32559457/,Human Stem Cell Resources Are an Inroad to Neandertal DNA Functions,15,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"We sequenced the genome of a Neandertal from Chagyrskaya Cave in the Altai Mountains, Russia, to 27-fold genomic coverage. We show that this Neandertal was a female and that she was more related to Neandertals in western Eurasia [Prüfer et al., Science 358, 655-658 (2017); Hajdinjak et al., Nature 555, 652-656 (2018)] than to Neandertals who lived earlier in Denisova Cave [Prüfer et al., Nature 505, 43-49 (2014)], which is located about 100 km away. About 12.9% of the Chagyrskaya genome is spanned by homozygous regions that are between 2.5 and 10 centiMorgans (cM) long. This is consistent with the fact that Siberian Neandertals lived in relatively isolated populations of less than 60 individuals. In contrast, a Neandertal from Europe, a Denisovan from the Altai Mountains, and ancient modern humans seem to have lived in populations of larger sizes. The availability of three Neandertal genomes of high quality allows a view of genetic features that were unique to Neandertals and that are likely to have been at high frequency among them. We find that genes highly expressed in the striatum in the basal ganglia of the brain carry more amino-acid-changing substitutions than genes expressed elsewhere in the brain, suggesting that the striatum may have evolved unique functions in Neandertals.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Mafessoni F"", ""Grote S"", ""de Filippo C"", ""Slon V"", ""Kolobova KA"", ""Viola B"", ""Markin SV"", ""Chintalapati M"", ""Peyrégne S"", ""Skov L"", ""Skoglund P"", ""Krivoshapkin AI"", ""Derevianko AP"", ""Meyer M"", ""Kelso J"", ""Peter B"", ""Prüfer K"", ""Pääbo S""]",10.1073/pnas.2004944117,Mafessoni F,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,26,Proc Natl Acad Sci U S A,eng,Pääbo S,"[""Animals"", ""Biological Evolution"", ""Female"", ""Fossils"", ""Gene Expression Regulation"", ""Genetic Variation"", ""Genome"", ""Humans"", ""Inbreeding"", ""Neanderthals"", ""Population Density"", ""Russia""]",15132-15136,32546518,pmc-id: PMC7334501;,2020 Jun 30,2020,https://pubmed.ncbi.nlm.nih.gov/32546518/,A high-coverage Neandertal genome from Chagyrskaya Cave,117,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"The hormone progesterone is important for preparing the uterine lining for egg implantation and for maintaining the early stages of pregnancy. The gene encoding the progesterone receptor (PGR) carries introgressed Neandertal haplotypes with two missense substitutions and a mobile Alu element. These Neandertal gene variants have reached nearly 20% frequency in non-Africans and have been associated with preterm birth. Here, we show that one of the missense substitutions appears fixed in Neandertals, while the other substitution as well as the Alu insertion were polymorphic among Neandertals. We show that two Neandertal haplotypes carrying the PGR gene entered the modern human population and that present-day carriers of the Neandertal haplotypes express higher levels of the receptor. In a cohort of present-day Britons, these carriers have more siblings, fewer miscarriages, and less bleeding during early pregnancy suggesting that the Neandertal progesterone receptor alleles promote fertility. This may explain their high frequency in modern human populations.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Zeberg H"", ""Kelso J"", ""Pääbo S""]",10.1093/molbev/msaa119,Zeberg H,Molecular biology and evolution,0737-4038,9,Mol Biol Evol,eng,Pääbo S,"[""Alleles"", ""Alu Elements"", ""Animals"", ""Female"", ""Fertility"", ""Genetic Introgression"", ""Haplotypes"", ""Humans"", ""Neanderthals"", ""Pregnancy"", ""Premature Birth"", ""Receptors, Progesterone""]",2655-2660,32437543,pmc-id: PMC7475037;,2020 Sep 1,2020,https://pubmed.ncbi.nlm.nih.gov/32437543/,The Neandertal Progesterone Receptor,37,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"The Middle to Upper Palaeolithic transition in Europe witnessed the replacement and partial absorption of local Neanderthal populations by Homo sapiens populations of African origin1. However, this process probably varied across regions and its details remain largely unknown. In particular, the duration of chronological overlap between the two groups is much debated, as are the implications of this overlap for the nature of the biological and cultural interactions between Neanderthals and H. sapiens. Here we report the discovery and direct dating of human remains found in association with Initial Upper Palaeolithic artefacts2, from excavations at Bacho Kiro Cave (Bulgaria). Morphological analysis of a tooth and mitochondrial DNA from several hominin bone fragments, identified through proteomic screening, assign these finds to H. sapiens and link the expansion of Initial Upper Palaeolithic technologies with the spread of H. sapiens into the mid-latitudes of Eurasia before 45 thousand years ago3. The excavations yielded a wealth of bone artefacts, including pendants manufactured from cave bear teeth that are reminiscent of those later produced by the last Neanderthals of western Europe4-6. These finds are consistent with models based on the arrival of multiple waves of H. sapiens into Europe coming into contact with declining Neanderthal populations7,8.","[""Historical Article"", ""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Hublin JJ"", ""Sirakov N"", ""Aldeias V"", ""Bailey S"", ""Bard E"", ""Delvigne V"", ""Endarova E"", ""Fagault Y"", ""Fewlass H"", ""Hajdinjak M"", ""Kromer B"", ""Krumov I"", ""Marreiros J"", ""Martisius NL"", ""Paskulin L"", ""Sinet-Mathiot V"", ""Meyer M"", ""Pääbo S"", ""Popov V"", ""Rezek Z"", ""Sirakova S"", ""Skinner MM"", ""Smith GM"", ""Spasov R"", ""Talamo S"", ""Tuna T"", ""Wacker L"", ""Welker F"", ""Wilcke A"", ""Zahariev N"", ""McPherron SP"", ""Tsanova T""]",10.1038/s41586-020-2259-z,Hublin JJ,Nature,0028-0836,7808,Nature,eng,Tsanova T,"[""Animals"", ""Asia"", ""Bone and Bones"", ""Bulgaria"", ""Caves"", ""DNA, Ancient"", ""DNA, Mitochondrial"", ""Europe"", ""Fossils"", ""History, Ancient"", ""Human Migration"", ""Humans"", ""Neanderthals"", ""Phylogeny"", ""Tool Use Behavior"", ""Tooth""]",299-302,32433609,,2020 May,2020,https://pubmed.ncbi.nlm.nih.gov/32433609/,"Initial Upper Palaeolithic Homo sapiens from Bacho Kiro Cave, Bulgaria",581,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Identification of gene expression traits unique to the human brain sheds light on the molecular mechanisms underlying human evolution. Here, we searched for uniquely human gene expression traits by analyzing 422 brain samples from humans, chimpanzees, bonobos, and macaques representing 33 anatomical regions, as well as 88,047 cell nuclei composing three of these regions. Among 33 regions, cerebral cortex areas, hypothalamus, and cerebellar gray and white matter evolved rapidly in humans. At the cellular level, astrocytes and oligodendrocyte progenitors displayed more differences in the human evolutionary lineage than the neurons. Comparison of the bulk tissue and single-nuclei sequencing revealed that conventional RNA sequencing did not detect up to two-thirds of cell-type-specific evolutionary differences.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Khrameeva E"", ""Kurochkin I"", ""Han D"", ""Guijarro P"", ""Kanton S"", ""Santel M"", ""Qian Z"", ""Rong S"", ""Mazin P"", ""Sabirov M"", ""Bulat M"", ""Efimova O"", ""Tkachev A"", ""Guo S"", ""Sherwood CC"", ""Camp JG"", ""Pääbo S"", ""Treutlein B"", ""Khaitovich P""]",10.1101/gr.256958.119,Khrameeva E,Genome research,1088-9051,5,Genome Res,eng,Khaitovich P,"[""Animals"", ""Brain"", ""Evolution, Molecular"", ""Humans"", ""Immunohistochemistry"", ""Macaca"", ""Neurons"", ""Pan paniscus"", ""Pan troglodytes"", ""RNA-Seq"", ""Single-Cell Analysis"", ""Transcriptome""]",776-789,32424074,pmc-id: PMC7263190;,2020 May,2020,https://pubmed.ncbi.nlm.nih.gov/32424074/,"Single-cell-resolution transcriptome map of human, chimpanzee, bonobo, and macaque brains",30,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"The human brain has undergone substantial change since humans diverged from chimpanzees and the other great apes1,2. However, the genetic and developmental programs that underlie this divergence are not fully understood. Here we have analysed stem cell-derived cerebral organoids using single-cell transcriptomics and accessible chromatin profiling to investigate gene-regulatory changes that are specific to humans. We first analysed cell composition and reconstructed differentiation trajectories over the entire course of human cerebral organoid development from pluripotency, through neuroectoderm and neuroepithelial stages, followed by divergence into neuronal fates within the dorsal and ventral forebrain, midbrain and hindbrain regions. Brain-region composition varied in organoids from different iPSC lines, but regional gene-expression patterns remained largely reproducible across individuals. We analysed chimpanzee and macaque cerebral organoids and found that human neuronal development occurs at a slower pace relative to the other two primates. Using pseudotemporal alignment of differentiation paths, we found that human-specific gene expression resolved to distinct cell states along progenitor-to-neuron lineages in the cortex. Chromatin accessibility was dynamic during cortex development, and we identified divergence in accessibility between human and chimpanzee that correlated with human-specific gene expression and genetic change. Finally, we mapped human-specific expression in adult prefrontal cortex using single-nucleus RNA sequencing analysis and identified developmental differences that persist into adulthood, as well as cell-state-specific changes that occur exclusively in the adult brain. Our data provide a temporal cell atlas of great ape forebrain development, and illuminate dynamic gene-regulatory features that are unique to humans.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Kanton S"", ""Boyle MJ"", ""He Z"", ""Santel M"", ""Weigert A"", ""Sanchís-Calleja F"", ""Guijarro P"", ""Sidow L"", ""Fleck JS"", ""Han D"", ""Qian Z"", ""Heide M"", ""Huttner WB"", ""Khaitovich P"", ""Pääbo S"", ""Treutlein B"", ""Camp JG""]",10.1038/s41586-019-1654-9,Kanton S,Nature,0028-0836,7778,Nature,eng,Camp JG,"[""Animals"", ""Biological Evolution"", ""Brain"", ""Genomics"", ""Humans"", ""Macaca"", ""Organoids"", ""Pan troglodytes"", ""Pluripotent Stem Cells"", ""Single-Cell Analysis"", ""Species Specificity""]",418-422,31619793,,2019 Oct,2019,https://pubmed.ncbi.nlm.nih.gov/31619793/,Organoid single-cell genomic atlas uncovers human-specific features of brain development,574,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"When double-strand breaks are introduced in a genome by CRISPR they are repaired either by non-homologous end joining (NHEJ), which often results in insertions or deletions (indels), or by homology-directed repair (HDR), which allows precise nucleotide substitutions to be introduced if a donor oligonucleotide is provided. Because NHEJ is more efficient than HDR, the frequency with which precise genome editing can be achieved is so low that simultaneous editing of more than one gene has hitherto not been possible. Here, we introduced a mutation in the human PRKDC gene that eliminates the kinase activity of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). This results in an increase in HDR irrespective of cell type and CRISPR enzyme used, sometimes allowing 87% of chromosomes in a population of cells to be precisely edited. It also allows for precise editing of up to four genes simultaneously (8 chromosomes) in the same cell. Transient inhibition of DNA-PKcs by the kinase inhibitor M3814 is similarly able to enhance precise genome editing.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Riesenberg S"", ""Chintalapati M"", ""Macak D"", ""Kanis P"", ""Maricic T"", ""Pääbo S""]",10.1093/nar/gkz669,Riesenberg S,Nucleic acids research,0305-1048,19,Nucleic Acids Res,eng,Pääbo S,"[""CRISPR-Cas Systems"", ""Chromosomes"", ""DNA Breaks, Double-Stranded"", ""DNA End-Joining Repair"", ""DNA-Activated Protein Kinase"", ""Gene Editing"", ""HEK293 Cells"", ""Humans"", ""INDEL Mutation"", ""Oligonucleotides"", ""Recombinational DNA Repair"", ""Sequence Deletion""]",e116,31392986,pmc-id: PMC6821318;,2019 Nov 4,2019,https://pubmed.ncbi.nlm.nih.gov/31392986/,Simultaneous precise editing of multiple genes in human cells,47,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"The Forbes' Quarry and Devil's Tower partial crania from Gibraltar are among the first Neanderthal remains ever found. Here, we show that small amounts of ancient DNA are preserved in the petrous bones of the 2 individuals despite unfavorable climatic conditions. However, the endogenous Neanderthal DNA is present among an overwhelming excess of recent human DNA. Using improved DNA library construction methods that enrich for DNA fragments carrying deaminated cytosine residues, we were able to sequence 70 and 0.4 megabase pairs (Mbp) nuclear DNA of the Forbes' Quarry and Devil's Tower specimens, respectively, as well as large parts of the mitochondrial genome of the Forbes' Quarry individual. We confirm that the Forbes' Quarry individual was a female and the Devil's Tower individual a male. We also show that the Forbes' Quarry individual is genetically more similar to the ∼120,000-y-old Neanderthals from Scladina Cave in Belgium (Scladina I-4A) and Hohlenstein-Stadel Cave in Germany, as well as to a ∼60,000- to 70,000-y-old Neanderthal from Russia (Mezmaiskaya 1), than to a ∼49,000-y-old Neanderthal from El Sidrón (El Sidrón 1253) in northern Spain and other younger Neanderthals from Europe and western Asia. This suggests that the Forbes' Quarry fossil predates the latter Neanderthals. The preservation of archaic human DNA in the warm coastal climate of Gibraltar, close to the shores of Africa, raises hopes for the future recovery of archaic human DNA from regions in which climatic conditions are less than optimal for DNA preservation.","[""Historical Article"", ""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Bokelmann L"", ""Hajdinjak M"", ""Peyrégne S"", ""Brace S"", ""Essel E"", ""de Filippo C"", ""Glocke I"", ""Grote S"", ""Mafessoni F"", ""Nagel S"", ""Kelso J"", ""Prüfer K"", ""Vernot B"", ""Barnes I"", ""Pääbo S"", ""Meyer M"", ""Stringer C""]",10.1073/pnas.1903984116,Bokelmann L,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,31,Proc Natl Acad Sci U S A,eng,Stringer C,"[""Animals"", ""DNA, Ancient"", ""Gibraltar"", ""History, Ancient"", ""Humans"", ""Neanderthals"", ""Oligonucleotide Array Sequence Analysis""]",15610-15615,31308224,pmc-id: PMC6681707;,2019 Jul 30,2019,https://pubmed.ncbi.nlm.nih.gov/31308224/,A genetic analysis of the Gibraltar Neanderthals,116,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Little is known about the population history of Neandertals over the hundreds of thousands of years of their existence. We retrieved nuclear genomic sequences from two Neandertals, one from Hohlenstein-Stadel Cave in Germany and the other from Scladina Cave in Belgium, who lived around 120,000 years ago. Despite the deeply divergent mitochondrial lineage present in the former individual, both Neandertals are genetically closer to later Neandertals from Europe than to a roughly contemporaneous individual from Siberia. That the Hohlenstein-Stadel and Scladina individuals lived around the time of their most recent common ancestor with later Neandertals suggests that all later Neandertals trace at least part of their ancestry back to these early European Neandertals.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Peyrégne S"", ""Slon V"", ""Mafessoni F"", ""de Filippo C"", ""Hajdinjak M"", ""Nagel S"", ""Nickel B"", ""Essel E"", ""Le Cabec A"", ""Wehrberger K"", ""Conard NJ"", ""Kind CJ"", ""Posth C"", ""Krause J"", ""Abrams G"", ""Bonjean D"", ""Di Modica K"", ""Toussaint M"", ""Kelso J"", ""Meyer M"", ""Pääbo S"", ""Prüfer K""]",10.1126/sciadv.aaw5873,Peyrégne S,Science advances,2375-2548,6,Sci Adv,eng,Prüfer K,"[""Animals"", ""Cell Lineage"", ""Cell Nucleus"", ""DNA"", ""Europe"", ""Evolution, Molecular"", ""Fossils"", ""Genome"", ""Germany"", ""Mitochondria"", ""Neanderthals""]",eaaw5873,31249872,pmc-id: PMC6594762;,2019 Jun,2019,https://pubmed.ncbi.nlm.nih.gov/31249872/,"Nuclear DNA from two early Neandertals reveals 80,000 years of genetic continuity in Europe",5,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.,"[""Published Erratum""]","[""Bozek K"", ""Khrameeva EE"", ""Reznick J"", ""Omerbašić D"", ""Bennett NC"", ""Lewin GR"", ""Azpurua J"", ""Gorbunova V"", ""Seluanov A"", ""Regnard P"", ""Wanert F"", ""Marchal J"", ""Pifferi F"", ""Aujard F"", ""Liu Z"", ""Shi P"", ""Pääbo S"", ""Schroeder F"", ""Willmitzer L"", ""Giavalisco P"", ""Khaitovich P""]",10.1038/s41598-019-43122-9,Bozek K,Scientific reports,2045-2322,1,Sci Rep,eng,Khaitovich P,[],6972,31043659,pmc-id: PMC6494842;,2019 May 1,2019,https://pubmed.ncbi.nlm.nih.gov/31043659/,Publisher Correction: Lipidome determinants of maximal lifespan in mammals,9,Gj7rM7G98R1iiN4a9,xN2RmkUBFZvNFdkT8
"Immune checkpoint inhibitors (ICIs) elicit durable responses in only a subset of patients with solid tumors, underscoring the need to define the cellular architectures that govern effective antitumor immunity. Here we identify a spatially organized multicellular immune unit comprising macrophages, cDC1s, CD4+ T-cells, and CD8+ T-cells that emerges in response to anti-CTLA-4 or dual checkpoint blockade. We term these structures tetrads. Using multiplexed imaging and spatial transcriptomics in mouse and human tumors, we show that tetrads assemble early during immune priming, depend on the ICOS-ICOSL pathway, and are enriched for ICOS+ Th1-like CD4+ T cells and ICOSLhigh cDC1s. CD8+ T-cells within tetrads exhibit an activated, non-terminally differentiated state, while tetrad-associated macrophages display an interferon-γ-responsive program that sustains CD8+ T-cell function and prevents dysfunction. Functionally, ICOSL+ cDC1s are required for tumor eradication in vivo. In patients with bladder cancer treated with neoadjuvant dual checkpoint blockade, tetrad, but not triad or dyad formation correlates with clinical response. These findings establish tetrads as a fundamental cellular unit coordinating antitumor immunity and responsiveness to ICIs.","[""Journal Article"", ""Preprint""]","[""Chaib M"", ""Aminu M"", ""Herbrich S"", ""Arabi M"", ""Xuan Y"", ""Basi A"", ""Casasent A"", ""Macaluso MD"", ""Hu KH"", ""Gubin M"", ""Chen X"", ""Mancuso JJ"", ""Basu S"", ""Jindal S"", ""Burks J"", ""Watowich S"", ""Wu J"", ""Allison JP"", ""Sharma P""]",10.64898/2025.12.24.696419,Chaib M,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Sharma P,[],,41509466,pmc-id: PMC12776307;,2025 Dec 29,2025,https://pubmed.ncbi.nlm.nih.gov/41509466/,Macrophage-Dendritic Cell-T-Cell Tetrads Orchestrate Antitumor Immunity and Response to Checkpoint Blockade,,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
,"[""Journal Article"", ""Expression of Concern""]","[""Chen PL"", ""Roh W"", ""Reuben A"", ""Cooper ZA"", ""Spencer CN"", ""Prieto PA"", ""Miller JP"", ""Bassett RL"", ""Gopalakrishnan V"", ""Wani K"", ""De Macedo MP"", ""Austin-Breneman JL"", ""Jiang H"", ""Chang Q"", ""Reddy SM"", ""Chen WS"", ""Tetzlaff MT"", ""Broaddus RJ"", ""Davies MA"", ""Gershenwald JE"", ""Haydu L"", ""Lazar AJ"", ""Patel SP"", ""Hwu P"", ""Hwu WJ"", ""Diab A"", ""Glitza IC"", ""Woodman SE"", ""Vence LM"", ""Wistuba II"", ""Amaria RN"", ""Kwong LN"", ""Prieto V"", ""Davis RE"", ""Ma W"", ""Overwijk WW"", ""Sharpe AH"", ""Hu J"", ""Futreal PA"", ""Blando J"", ""Sharma P"", ""Allison JP"", ""Chin L"", ""Wargo JA""]",10.1158/2159-8290.CD-25-1639,Chen PL,Cancer discovery,2159-8274,12,Cancer Discov,eng,Wargo JA,[],2574,41327972,,2025 Dec 2,2025,https://pubmed.ncbi.nlm.nih.gov/41327972/,Editor's Note: Analysis of Immune Signatures in Longitudinal Tumor Samples Yields Insight into Biomarkers of Response and Mechanisms of Resistance to Immune Checkpoint Blockade,15,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
,"[""Journal Article""]","[""Chaib M"", ""Allison JP""]",10.1038/s41577-025-01253-3,Chaib M,Nature reviews. Immunology,1474-1733,1,Nat Rev Immunol,eng,Allison JP,[],5,41298974,,2026 Jan,2026,https://pubmed.ncbi.nlm.nih.gov/41298974/,Local T(reg) cell loss reprogrammes systemic antitumour immunity without breaking tolerance,26,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Perineural invasion (PNI) is a well-established factor of poor prognosis in multiple cancer types1, yet its mechanism remains unclear. Here we provide clinical and mechanistic insights into the role of PNI and cancer-induced nerve injury (CINI) in resistance to anti-PD-1 therapy. Our study demonstrates that PNI and CINI of tumour-associated nerves are associated with poor response to anti-PD-1 therapy among patients with cutaneous squamous cell carcinoma, melanoma and gastric cancer. Electron microscopy and electrical conduction analyses reveal that cancer cells degrade the nerve fibre myelin sheets. The injured neurons respond by autonomously initiating IL-6- and type I interferon-mediated inflammation to promote nerve healing and regeneration. As the tumour grows, the CINI burden increases, and its associated inflammation becomes chronic and skews the general immune tone within the tumour microenvironment into a suppressive and exhaustive state. The CINI-driven anti-PD-1 resistance can be reversed by targeting multiple steps in the CINI signalling process: denervating the tumour, conditional knockout of the transcription factor mediating the injury signal within neurons (Atf3), knockout of interferon-α receptor signalling (Ifnar1-/-) or by combining anti-PD-1 and anti-IL-6-receptor blockade. Our findings demonstrate the direct immunoregulatory roles of CINI and its therapeutic potential.","[""Journal Article"", ""Research Support, N.I.H., Extramural""]","[""Baruch EN"", ""Gleber-Netto FO"", ""Nagarajan P"", ""Rao X"", ""Akhter S"", ""Eichwald T"", ""Xie T"", ""Balood M"", ""Adewale A"", ""Naara S"", ""Sathishkumar HN"", ""Islam S"", ""McCarthy W"", ""Mattson BJ"", ""Ferrarotto R"", ""Wong MK"", ""Davies MA"", ""Jindal S"", ""Basu S"", ""Roversi K"", ""Nikpoor AR"", ""Ahmadi M"", ""Ahmadi A"", ""Harwood C"", ""Leigh I"", ""Gong D"", ""Tallón de Lara P"", ""Tao DL"", ""Davidson TM"", ""Ajami NJ"", ""Futreal A"", ""Rai K"", ""Kochat V"", ""Castillo M"", ""Gunaratne P"", ""Goepfert RP"", ""Hernandez SD"", ""Khushalani NI"", ""Wang J"", ""Watowich SS"", ""Calin GA"", ""Migden MR"", ""Yuan M"", ""Liu N"", ""Ye Y"", ""Hwang WL"", ""Vermeer PD"", ""D'Silva NJ"", ""Bunimovich YL"", ""Yaniv D"", ""Burks JK"", ""Gomez J"", ""Dougherty PM"", ""Tsai KY"", ""Allison JP"", ""Sharma P"", ""Wargo JA"", ""Myers JN"", ""Talbot S"", ""Gross ND"", ""Amit M""]",10.1038/s41586-025-09370-8,Baruch EN,Nature,0028-0836,8084,Nature,eng,Amit M,"[""Animals"", ""Programmed Cell Death 1 Receptor"", ""Mice"", ""Humans"", ""Drug Resistance, Neoplasm"", ""Female"", ""Male"", ""Interleukin-6"", ""Melanoma"", ""Interferon Type I"", ""Tumor Microenvironment"", ""Receptor, Interferon alpha-beta"", ""Stomach Neoplasms"", ""Skin Neoplasms"", ""Peripheral Nerve Injuries"", ""Carcinoma, Squamous Cell"", ""Inflammation"", ""Signal Transduction"", ""Immune Checkpoint Inhibitors"", ""Neurons"", ""Neoplasms"", ""Neoplasm Invasiveness""]",462-473,40836096,pmc-id: PMC12406299;manuscript-id: NIHMS2102231;,2025 Oct,2025,https://pubmed.ncbi.nlm.nih.gov/40836096/,Cancer-induced nerve injury promotes resistance to anti-PD-1 therapy,646,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
,"[""Journal Article""]","[""Chaib M"", ""Allison JP""]",10.1038/s41577-025-01204-y,Chaib M,Nature reviews. Immunology,1474-1733,8,Nat Rev Immunol,eng,Allison JP,[],557,40596685,,2025 Aug,2025,https://pubmed.ncbi.nlm.nih.gov/40596685/,Tumour cells mimic erythroblasts to hijack iron from bone marrow macrophages,25,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
,"[""Journal Article""]","[""Ağaç Çobanoğlu D"", ""Allison JP""]",10.1038/s41577-025-01157-2,Ağaç Çobanoğlu D,Nature reviews. Immunology,1474-1733,4,Nat Rev Immunol,eng,Allison JP,[],233,40044812,,2025 Apr,2025,https://pubmed.ncbi.nlm.nih.gov/40044812/,Neutrophils are dispensable for Shigella control: macrophages take centre stage,25,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"The effects of T cell differentiation arising from immune checkpoint inhibition targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) on the immunological memory response remain unclear. Our investigation into the effects of anti-CTLA-4 and anti-PD-1 on memory T cell formation in mice reveals that memory T cells generated by anti-CTLA-4 exhibit greater expansion, cytokine production, and antitumor activity than those from anti-PD-1. Notably, anti-CTLA-4 preserves more T cell factor-1 (TCF-1)+ T cells during priming, while anti-PD-1 leads to more thymocyte selection-associated high mobility group box (TOX)+ T cells. Experiments using conditional Tcf7- or Tox-knockout mice highlight that TCF-1 is essential for the memory response generated by anti-CTLA-4, whereas TOX deletion alone in T cells has no effect on the response to anti-PD-1. Deepening our understanding of how checkpoint inhibition affects memory response is crucial for advancing our understanding of the enduring impacts of these immunotherapies on the immune system.","[""Journal Article""]","[""Mok S"", ""Liu H"", ""Ağaç Çobanoğlu D"", ""Anang NAS"", ""Mancuso JJ"", ""Wherry EJ"", ""Allison JP""]",10.1073/pnas.2418985122,Mok S,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,2,Proc Natl Acad Sci U S A,eng,Allison JP,"[""Animals"", ""Mice"", ""Immunologic Memory"", ""CTLA-4 Antigen"", ""Programmed Cell Death 1 Receptor"", ""Mice, Knockout"", ""Hepatocyte Nuclear Factor 1-alpha"", ""Immune Checkpoint Inhibitors"", ""Memory T Cells"", ""Mice, Inbred C57BL""]",e2418985122,39786926,pmc-id: PMC11745370;,2025 Jan 14,2025,https://pubmed.ncbi.nlm.nih.gov/39786926/,Anti-CTLA-4 generates greater memory response than anti-PD-1 via TCF-1,122,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"CD4+ T cells can either enhance or inhibit tumour immunity. Although regulatory T cells have long been known to impede antitumour responses1-5, other CD4+ T cells have recently been implicated in inhibiting this response6,7. Yet, the nature and function of the latter remain unclear. Here, using vaccines containing MHC class I (MHC-I) neoantigens (neoAgs) and different doses of tumour-derived MHC-II neoAgs, we discovered that whereas the inclusion of vaccines with low doses of MHC-II-restricted peptides (LDVax) promoted tumour rejection, vaccines containing high doses of the same MHC-II neoAgs (HDVax) inhibited rejection. Characterization of the inhibitory cells induced by HDVax identified them as type 1 regulatory T (Tr1) cells expressing IL-10, granzyme B, perforin, CCL5 and LILRB4. Tumour-specific Tr1 cells suppressed tumour rejection induced by anti-PD1, LDVax or adoptively transferred tumour-specific effector T cells. Mechanistically, HDVax-induced Tr1 cells selectively killed MHC-II tumour antigen-presenting type 1 conventional dendritic cells (cDC1s), leading to low numbers of cDC1s in tumours. We then documented modalities to overcome this inhibition, specifically via anti-LILRB4 blockade, using a CD8-directed IL-2 mutein, or targeted loss of cDC2/monocytes. Collectively, these data show that cytotoxic Tr1 cells, which maintain peripheral tolerance, also inhibit antitumour responses and thereby function to impede immune control of cancer.","[""Journal Article"", ""Research Support, N.I.H., Intramural""]","[""Sultan H"", ""Takeuchi Y"", ""Ward JP"", ""Sharma N"", ""Liu TT"", ""Sukhov V"", ""Firulyova M"", ""Song Y"", ""Ameh S"", ""Brioschi S"", ""Khantakova D"", ""Arthur CD"", ""White JM"", ""Kohlmiller H"", ""Salazar AM"", ""Burns R"", ""Costa HA"", ""Moynihan KD"", ""Yeung YA"", ""Djuretic I"", ""Schumacher TN"", ""Sheehan KCF"", ""Colonna M"", ""Allison JP"", ""Murphy KM"", ""Artyomov MN"", ""Schreiber RD""]",10.1038/s41586-024-07752-y,Sultan H,Nature,0028-0836,8023,Nature,eng,Schreiber RD,"[""Animals"", ""Female"", ""Humans"", ""Male"", ""Mice"", ""Antigens, Neoplasm"", ""Cancer Vaccines"", ""CD4-Positive T-Lymphocytes"", ""Cell Line, Tumor"", ""Chemokine CCL5"", ""Dendritic Cells"", ""Granzymes"", ""Histocompatibility Antigens Class I"", ""Histocompatibility Antigens Class II"", ""Immunotherapy"", ""Interleukin-10"", ""Mice, Inbred C57BL"", ""Neoplasms"", ""T-Lymphocytes, Regulatory"", ""Receptors, Immunologic"", ""Membrane Glycoproteins"", ""Cytotoxicity, Immunologic"", ""Immune Tolerance"", ""CD8-Positive T-Lymphocytes""]",182-191,39048822,pmc-id: PMC11291290;,2024 Aug,2024,https://pubmed.ncbi.nlm.nih.gov/39048822/,Neoantigen-specific cytotoxic Tr1 CD4 T cells suppress cancer immunotherapy,632,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Immune checkpoint therapies (ICT) improve overall survival of patients with cancer but may cause immune-related adverse events (irAEs) such as myocarditis. Cytotoxic T lymphocyte-associated antigen 4 immunoglobulin fusion protein (CTLA-4 Ig), an inhibitor of T cell costimulation through CD28, reverses irAEs in animal models. However, concerns exist about potentially compromising antitumor response of ICT. In mouse tumor models, we administered CTLA-4 Ig 1) concomitantly with ICT or 2) after ICT completion. Concomitant treatment reduced antitumor efficacy, while post-ICT administration improved efficacy without affecting frequency and function of CD8 T cells. The improved response was independent of the ICT used, whether CTLA-4 or PD-1 blockade. The frequency of Tregs was significantly decreased with CTLA-4 Ig. The resulting increased CD8/Treg ratio potentially underlies the enhanced efficacy of ICT followed by CTLA-4 Ig. This paradoxical mechanism shows that a CTLA-4 Ig regimen shown to reduce irAE severity does not compromise antitumor efficacy.","[""Journal Article""]","[""Mok S"", ""Ağaç Çobanoğlu D"", ""Liu H"", ""Mancuso JJ"", ""Allison JP""]",10.1073/pnas.2404661121,Mok S,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,27,Proc Natl Acad Sci U S A,eng,Allison JP,"[""Animals"", ""Mice"", ""Immunotherapy"", ""CTLA-4 Antigen"", ""Immune Checkpoint Inhibitors"", ""CD8-Positive T-Lymphocytes"", ""T-Lymphocytes, Regulatory"", ""Cell Line, Tumor"", ""Abatacept"", ""Female"", ""Humans"", ""Mice, Inbred C57BL"", ""Neoplasms"", ""Programmed Cell Death 1 Receptor""]",e2404661121,38923991,pmc-id: PMC11228532;,2024 Jul 2,2024,https://pubmed.ncbi.nlm.nih.gov/38923991/,Post-immunotherapy CTLA-4 Ig treatment improves antitumor efficacy,121,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"IL17 is required for the initiation and progression of pancreatic cancer, particularly in the context of inflammation, as previously shown by genetic and pharmacological approaches. However, the cellular compartment and downstream molecular mediators of IL17-mediated pancreatic tumorigenesis have not been fully identified. This study examined the cellular compartment required by generating transgenic animals with IL17 receptor A (IL17RA), which was genetically deleted from either the pancreatic epithelial compartment or the hematopoietic compartment via generation of IL17RA-deficient (IL17-RA-/-) bone marrow chimeras, in the context of embryonically activated or inducible Kras. Deletion of IL17RA from the pancreatic epithelial compartment, but not from hematopoietic compartment, resulted in delayed initiation and progression of premalignant lesions and increased infiltration of CD8+ cytotoxic T cells to the tumor microenvironment. Absence of IL17RA in the pancreatic compartment affected transcriptional profiles of epithelial cells, modulating stemness, and immunological pathways. B7-H4, a known inhibitor of T-cell activation encoded by the gene Vtcn1, was the checkpoint molecule most upregulated via IL17 early during pancreatic tumorigenesis, and its genetic deletion delayed the development of pancreatic premalignant lesions and reduced immunosuppression. Thus, our data reveal that pancreatic epithelial IL17RA promotes pancreatic tumorigenesis by reprogramming the immune pancreatic landscape, which is partially orchestrated by regulation of B7-H4. Our findings provide the foundation of the mechanisms triggered by IL17 to mediate pancreatic tumorigenesis and reveal the avenues for early pancreatic cancer immune interception. See related Spotlight by Lee and Pasca di Magliano, p. 1130.","[""Journal Article""]","[""Castro-Pando S"", ""Howell RM"", ""Li L"", ""Mascaro M"", ""Faraoni EY"", ""Le Roux O"", ""Romanin D"", ""Tahan V"", ""Riquelme E"", ""Zhang Y"", ""Kolls JK"", ""Allison JP"", ""Lozano G"", ""Moghaddam SJ"", ""McAllister F""]",10.1158/2326-6066.CIR-23-0527,Castro-Pando S,Cancer immunology research,2326-6066,9,Cancer Immunol Res,eng,McAllister F,"[""Animals"", ""Interleukin-17"", ""Pancreatic Neoplasms"", ""Receptors, Interleukin-17"", ""Mice"", ""Signal Transduction"", ""V-Set Domain-Containing T-Cell Activation Inhibitor 1"", ""Tumor Microenvironment"", ""Carcinogenesis"", ""Mice, Transgenic"", ""Humans"", ""Epithelial Cells"", ""Mice, Knockout"", ""Gene Expression Regulation, Neoplastic"", ""Mice, Inbred C57BL"", ""Cell Transformation, Neoplastic"", ""Pancreas""]",1170-1183,38842383,pmc-id: PMC11369627;,2024 Sep 3,2024,https://pubmed.ncbi.nlm.nih.gov/38842383/,Pancreatic Epithelial IL17/IL17RA Signaling Drives B7-H4 Expression to Promote Tumorigenesis,12,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Immune checkpoint therapies (ICT) can induce life-threatening immune-related adverse events, including myocarditis and myositis, which are rare but often concurrent. The molecular pathways and immune subsets underlying these toxicities remain poorly understood. To address this need, we performed single-cell RNA sequencing of heart and skeletal muscle biopsies obtained from living patients with cancers treated with ICTs and admitted to the hospital with myocarditis and/or myositis (overlapping myocarditis plus myositis, n = 10; myocarditis-only, n = 1) or ICT-exposed patients ruled out for toxicity utilized as controls (n = 9). All biopsies were obtained within 96 hours of clinical presentation. Analyses of 58,523 cells revealed CD8+ T cells with a cytotoxic phenotype expressing activation/exhaustion markers in both myocarditis and myositis. Furthermore, the analyses identified a population of myeloid cells expressing tissue-resident signatures and FcγRIIIa (CD16a), which is known to bind IgG and regulate complement activation. Immunohistochemistry of affected cardiac and skeletal muscle tissues revealed protein expression of pan-IgG and complement product C4d, which were associated with the presence of high-titer serum autoantibodies against muscle antigens in a subset of patients. We further identified a population of inflammatory IL1B+TNF+ myeloid cells specifically enriched in myocarditis and associated with greater toxicity severity and poorer clinical outcomes. These results provide insight into the myeloid subsets present in human immune-related myocarditis and myositis tissues and nominate new targets for investigation into rational treatments to overcome these high-mortality toxicities. See related Spotlight by Fankhauser et al., p. 954.","[""Journal Article""]","[""Siddiqui BA"", ""Palaskas NL"", ""Basu S"", ""Dai Y"", ""He Z"", ""Yadav SS"", ""Allison JP"", ""Sheth RA"", ""Tummala S"", ""Buja M"", ""Bhattacharjee MB"", ""Iliescu C"", ""Rawther-Karedath A"", ""Deswal A"", ""Wang L"", ""Sharma P"", ""Subudhi SK""]",10.1158/2326-6066.CIR-24-0011,Siddiqui BA,Cancer immunology research,2326-6066,8,Cancer Immunol Res,eng,Subudhi SK,"[""Humans"", ""Myocarditis"", ""Myositis"", ""Male"", ""Female"", ""Middle Aged"", ""Immune Checkpoint Inhibitors"", ""Aged"", ""Neoplasms"", ""CD8-Positive T-Lymphocytes"", ""Adult"", ""Receptors, IgG"", ""Muscle, Skeletal"", ""Single-Cell Analysis""]",964-987,38768394,pmc-id: PMC12302522;manuscript-id: NIHMS2096247;,2024 Aug 1,2024,https://pubmed.ncbi.nlm.nih.gov/38768394/,Molecular Pathways and Cellular Subsets Associated with Adverse Clinical Outcomes in Overlapping Immune-Related Myocarditis and Myositis,12,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"To determine the efficacy and safety of risk-adapted combinations of androgen signaling inhibitors and inform disease classifiers for metastatic castration-resistant prostate cancers. In a modular, randomized phase II trial, 192 men were treated with 8 weeks of abiraterone acetate, prednisone, and apalutamide (AAPA; module 1) and then allocated to modules 2 or 3 based on satisfactory (≥50% PSA decline from baseline and <5 circulating tumor cell/7.5 mL) versus unsatisfactory status. Men in the former were randomly assigned to continue AAPA alone (module 2A) or with ipilimumab (module 2B). Men in the latter group had carboplatin + cabazitaxel added to AAPA (module 3). Optional baseline biopsies were subjected to correlative studies. Median overall survival (from allocation) was 46.4 [95% confidence interval (CI), 39.2-68.2], 41.4 (95% CI, 33.3-49.9), and 18.7 (95% CI, 14.3-26.3) months in modules 2A (n = 64), 2B (n = 64), and 3 (n = 59), respectively. Toxicities were within expectations. Of 192 eligible patients, 154 (80.2%) underwent pretreatment metastatic biopsies. The aggressive-variant prostate cancer molecular profile (defects in ≥2 of p53, RB1, and PTEN) was associated with unsatisfactory status. Exploratory analyses suggested that secreted phosphoprotein 1-positive and insulin-like growth factor-binding protein 2-positive macrophages, druggable myeloid cell markers, and germline pathogenic mutations were enriched in the unsatisfactory group. Adding ipilimumab to AAPA did not improve outcomes in men with androgen-responsive metastatic castration-resistant prostate cancer. Despite the addition of carboplatin + cabazitaxel, men in the unsatisfactory group had shortened survivals. Adaptive designs can enrich for biologically and clinically relevant disease subgroups to contribute to the development of marker-informed, risk-adapted therapy strategies in men with prostate cancer.","[""Journal Article"", ""Randomized Controlled Trial"", ""Clinical Trial, Phase II""]","[""Aparicio AM"", ""Tidwell RSS"", ""Yadav SS"", ""Chen JS"", ""Zhang M"", ""Liu J"", ""Guo S"", ""Pilié PG"", ""Yu Y"", ""Song X"", ""Vundavilli H"", ""Jindal S"", ""Zhu K"", ""Viscuse PV"", ""Lebenthal JM"", ""Hahn AW"", ""Soundararajan R"", ""Corn PG"", ""Zurita-Saavedra A"", ""Subudhi SK"", ""Zhang J"", ""Wang W"", ""Huff C"", ""Troncoso P"", ""Allison JP"", ""Sharma P"", ""Logothetis CJ""]",10.1158/1078-0432.CCR-23-3740,Aparicio AM,Clinical cancer research : an official journal of the American Association for Cancer Research,1078-0432,13,Clin Cancer Res,eng,Logothetis CJ,"[""Humans"", ""Male"", ""Prostatic Neoplasms, Castration-Resistant"", ""Aged"", ""Antineoplastic Combined Chemotherapy Protocols"", ""Middle Aged"", ""Prednisone"", ""Abiraterone Acetate"", ""Thiohydantoins"", ""Aged, 80 and over"", ""Androgen Antagonists"", ""Carboplatin"", ""Ipilimumab"", ""Taxoids""]",2751-2763,38683200,pmc-id: PMC11216872;manuscript-id: NIHMS1990885;,2024 Jul 1,2024,https://pubmed.ncbi.nlm.nih.gov/38683200/,A Modular Trial of Androgen Signaling Inhibitor Combinations Testing a Risk-Adapted Strategy in Patients with Metastatic Castration-Resistant Prostate Cancer,30,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"We have previously demonstrated synergy between ICOS costimulation (IVAX; ICOSL-transduced B16-F10 cellular vaccine) and CTLA-4 blockade in antitumor therapy. In this study, we employed CyTOF and single-cell RNA sequencing and observed significant remodeling of the lymphoid and myeloid compartments in combination therapy. Compared with anti-CTLA-4 monotherapy, the combination therapy enriched Th1 CD4 T cells, effector CD8 T cells, and M1-like antitumor proinflammatory macrophages. These macrophages were critical to the therapeutic efficacy of anti-CTLA-4 combined with IVAX or anti-PD-1. Macrophage depletion with clodronate reduced the tumor-infiltrating effector CD4 and CD8 T cells, impairing their antitumor functions. Furthermore, the recruitment and polarization of M1-like macrophages required IFN-γ. Therefore, in this study, we show that there is a positive feedback loop between intratumoral effector T cells and tumor-associated macrophages (TAMs), in which the IFN-γ produced by the T cells polarizes the TAMs into M1-like phenotype, and the TAMs, in turn, reshape the tumor microenvironment to facilitate T cell infiltration, immune function, and tumor rejection.","[""Journal Article""]","[""Sharma N"", ""Fan X"", ""Atolagbe OT"", ""Ge Z"", ""Dao KN"", ""Sharma P"", ""Allison JP""]",10.1084/jem.20231263,Sharma N,The Journal of experimental medicine,0022-1007,4,J Exp Med,eng,Allison JP,"[""Humans"", ""CTLA-4 Antigen"", ""Tumor-Associated Macrophages"", ""Neoplasms"", ""CD8-Positive T-Lymphocytes"", ""Phenotype"", ""Tumor Microenvironment"", ""Inducible T-Cell Co-Stimulator Protein""]",,38517331,pmc-id: PMC10959121;,2024 Apr 1,2024,https://pubmed.ncbi.nlm.nih.gov/38517331/,ICOS costimulation in combination with CTLA-4 blockade remodels tumor-associated macrophages toward an antitumor phenotype,221,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"The 2022 yearly Think Tank Meeting in Siena, Tuscany (Italy), organized by the Italian Network for Tumor Biotherapy (NIBIT) Foundation, the Parker Institute for Cancer Immunotherapy and the World Immunotherapy Council, included a focus on the future of integrating and expanding the use of targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). The conference members exchanged their views on the lessons from targeting CTLA-4 and compared the effect to the impact of blocking Programmed cell death protein 1 (PD1) or its ligand (PDL1). The increasing experience with both therapeutic approaches and their combination suggests that targeting CTLA-4 may lead to more durable responses for a sizeable proportion of patients, though the specific mechanism is not entirely understood. Overcoming toxicity of blocking CTLA-4 is currently being addressed with different doses and dose regimens, especially when combined with PD1/PDL1 blocking antibodies. Novel therapeutics targeting CTLA-4 hold the promise to reduce toxicities and thus allow different combination strategies in the future. On the whole, the consent was that targeting CTLA-4 remains an important strategy to improve the efficacy of cancer immunotherapies.","[""Journal Article"", ""Review""]","[""Di Giacomo AM"", ""Lahn M"", ""Eggermont AM"", ""Fox B"", ""Ibrahim R"", ""Sharma P"", ""Allison JP"", ""Maio M""]",10.1016/j.ejca.2023.113501,Di Giacomo AM,"European journal of cancer (Oxford, England : 1990)",0959-8049,,Eur J Cancer,eng,Maio M,"[""Humans"", ""CTLA-4 Antigen"", ""T-Lymphocytes, Cytotoxic"", ""Neoplasms"", ""Italy"", ""Immunotherapy""]",113501,38169219,,2024 Feb,2024,https://pubmed.ncbi.nlm.nih.gov/38169219/,The future of targeting cytotoxic T-lymphocyte-associated protein-4: Is there a role?,198,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Lynch syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacologic intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers. To address this, we enrolled 21 patients with LS onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes 3 times weekly for 45 minutes versus usual care with a one-time exercise counseling session as control. We analyzed the effects of exercise on cardiorespiratory fitness, circulating, and colorectal-tissue biomarkers using metabolomics, gene expression by bulk mRNA sequencing, and spatial transcriptomics by NanoString GeoMx. We observed a significant increase in oxygen consumption (VO2peak) as a primary outcome of the exercise and a decrease in inflammatory markers (prostaglandin E) in colon and blood as the secondary outcomes in the exercise versus usual care group. Gene expression profiling and spatial transcriptomics on available colon biopsies revealed an increase in the colonic mucosa levels of natural killer and CD8+ T cells in the exercise group that were further confirmed by IHC studies. Together these data have important implications for cancer interception in LS, and document for the first-time biological effects of exercise in the immune system of a target organ in patients at-risk for cancer.","[""Clinical Trial"", ""Journal Article"", ""Research Support, Non-U.S. Gov't"", ""Research Support, N.I.H., Extramural""]","[""Deng N"", ""Reyes-Uribe L"", ""Fahrmann JF"", ""Thoman WS"", ""Munsell MF"", ""Dennison JB"", ""Murage E"", ""Wu R"", ""Hawk ET"", ""Thirumurthi S"", ""Lynch PM"", ""Dieli-Conwright CM"", ""Lazar AJ"", ""Jindal S"", ""Chu K"", ""Chelvanambi M"", ""Basen-Engquist K"", ""Li Y"", ""Wargo JA"", ""McAllister F"", ""Allison JP"", ""Sharma P"", ""Sinha KM"", ""Hanash S"", ""Gilchrist SC"", ""Vilar E""]",10.1158/1078-0432.CCR-23-0088,Deng N,Clinical cancer research : an official journal of the American Association for Cancer Research,1078-0432,21,Clin Cancer Res,eng,Vilar E,"[""Female"", ""Humans"", ""Colorectal Neoplasms, Hereditary Nonpolyposis"", ""Exercise"", ""Endometrial Neoplasms"", ""Gene Expression Profiling"", ""Intestinal Mucosa""]",4361-4372,37724990,pmc-id: PMC10618653;manuscript-id: NIHMS1930107;,2023 Nov 1,2023,https://pubmed.ncbi.nlm.nih.gov/37724990/,Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome,29,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
,"[""Journal Article""]","[""Sharma P"", ""Allison JP""]",10.1158/2326-6066.CIR-23-0672,Sharma P,Cancer immunology research,2326-6066,10,Cancer Immunol Res,eng,Allison JP,[],1298-1299,37702540,,2023 Oct 4,2023,https://pubmed.ncbi.nlm.nih.gov/37702540/,Cancer Immunology and Immunotherapy Showcased in the AACR Cancer Progress Report 2023,11,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"While the nervous system has reciprocal interactions with both cancer and the immune system, little is known about the potential role of tumor associated nerves (TANs) in modulating anti-tumoral immunity. Moreover, while peri-neural invasion is a well establish poor prognostic factor across cancer types, the mechanisms driving this clinical effect remain unknown. Here, we provide clinical and mechniastic association between TANs damage and resistance to anti-PD-1 therapy. Using electron microscopy, electrical conduction studies, and tumor samples of cutaneous squamous cell carcinoma (cSCC) patients, we showed that cancer cells can destroy myelin sheath and induce TANs degeneration. Multi-omics and spatial analyses of tumor samples from cSCC patients who underwent neoadjuvant anti-PD-1 therapy demonstrated that anti-PD-1 non-responders had higher rates of peri-neural invasion, TANs damage and degeneration compared to responders, both at baseline and following neoadjuvant treatment. Tumors from non-responders were also characterized by a sustained signaling of interferon type I (IFN-I) - known to both propagate nerve degeneration and to dampen anti-tumoral immunity. Peri-neural niches of non-responders were characterized by higher immune activity compared to responders, including immune-suppressive activity of M2 macrophages, and T regulatory cells. This tumor promoting inflammation expanded to the rest of the tumor microenvironment in non-responders. Anti-PD-1 efficacy was dampened by inducing nerve damage prior to treatment administration in a murine model. In contrast, anti-PD-1 efficacy was enhanced by denervation and by interleukin-6 blockade. These findings suggested a potential novel anti-PD-1 resistance drived by TANs damage and inflammation. This resistance mechanism is targetable and may have therapeutic implications in other neurotropic cancers with poor response to anti-PD-1 therapy such as pancreatic, prostate, and breast cancers.","[""Preprint""]","[""Baruch EN"", ""Nagarajan P"", ""Gleber-Netto FO"", ""Rao X"", ""Xie T"", ""Akhter S"", ""Adewale A"", ""Shajedul I"", ""Mattson BJ"", ""Ferrarotto R"", ""Wong MK"", ""Davies MA"", ""Jindal S"", ""Basu S"", ""Harwood C"", ""Leigh I"", ""Ajami N"", ""Futreal A"", ""Castillo M"", ""Gunaratne P"", ""Goepfert RP"", ""Khushalani N"", ""Wang J"", ""Watowich S"", ""Calin GA"", ""Migden MR"", ""Vermeer P"", ""D'Silva N"", ""Yaniv D"", ""Burks JK"", ""Gomez J"", ""Dougherty PM"", ""Tsai KY"", ""Allison JP"", ""Sharma P"", ""Wargo J"", ""Myers JN"", ""Gross ND"", ""Amit M""]",10.21203/rs.3.rs-3161761/v1,Baruch EN,Research square,2693-5015,,Res Sq,eng,Amit M,[],,37503252,pmc-id: PMC10371163;,2023 Jul 18,2023,https://pubmed.ncbi.nlm.nih.gov/37503252/,Inflammation induced by tumor-associated nerves promotes resistance to anti-PD-1 therapy in cancer patients and is targetable by interleukin-6 blockade,,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Immune checkpoint therapy (ICT) has dramatically altered clinical outcomes for cancer patients and conferred durable clinical benefits, including cure in a subset of patients. Varying response rates across tumor types and the need for predictive biomarkers to optimize patient selection to maximize efficacy and minimize toxicities prompted efforts to unravel immune and non-immune factors regulating the responses to ICT. This review highlights the biology of anti-tumor immunity underlying response and resistance to ICT, discusses efforts to address the current challenges with ICT, and outlines strategies to guide the development of subsequent clinical trials and combinatorial efforts with ICT.","[""Journal Article"", ""Review"", ""Research Support, Non-U.S. Gov't""]","[""Sharma P"", ""Goswami S"", ""Raychaudhuri D"", ""Siddiqui BA"", ""Singh P"", ""Nagarajan A"", ""Liu J"", ""Subudhi SK"", ""Poon C"", ""Gant KL"", ""Herbrich SM"", ""Anandhan S"", ""Islam S"", ""Amit M"", ""Anandappa G"", ""Allison JP""]",10.1016/j.cell.2023.03.006,Sharma P,Cell,0092-8674,8,Cell,eng,Allison JP,"[""Humans"", ""B7-H1 Antigen"", ""Immunotherapy"", ""Neoplasms"", ""Clinical Trials as Topic"", ""Immune Checkpoint Inhibitors""]",1652-1669,37059068,,2023 Apr 13,2023,https://pubmed.ncbi.nlm.nih.gov/37059068/,Immune checkpoint therapy-current perspectives and future directions,186,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Neoadjuvant ipilimumab + nivolumab (Ipi+Nivo) and nivolumab + chemotherapy (Nivo+CT) induce greater pathologic response rates than CT alone in patients with operable non-small cell lung cancer (NSCLC). The impact of adding ipilimumab to neoadjuvant Nivo+CT is unknown. Here we report the results and correlates of two arms of the phase 2 platform NEOSTAR trial testing neoadjuvant Nivo+CT and Ipi+Nivo+CT with major pathologic response (MPR) as the primary endpoint. MPR rates were 32.1% (7/22, 80% confidence interval (CI) 18.7-43.1%) in the Nivo+CT arm and 50% (11/22, 80% CI 34.6-61.1%) in the Ipi+Nivo+CT arm; the primary endpoint was met in both arms. In patients without known tumor EGFR/ALK alterations, MPR rates were 41.2% (7/17) and 62.5% (10/16) in the Nivo+CT and Ipi+Nivo+CT groups, respectively. No new safety signals were observed in either arm. Single-cell sequencing and multi-platform immune profiling (exploratory endpoints) underscored immune cell populations and phenotypes, including effector memory CD8+ T, B and myeloid cells and markers of tertiary lymphoid structures, that were preferentially increased in the Ipi+Nivo+CT cohort. Baseline fecal microbiota in patients with MPR were enriched with beneficial taxa, such as Akkermansia, and displayed reduced abundance of pro-inflammatory and pathogenic microbes. Neoadjuvant Ipi+Nivo+CT enhances pathologic responses and warrants further study in operable NSCLC. (ClinicalTrials.gov registration: NCT03158129 .).","[""Clinical Trial, Phase II"", ""Journal Article"", ""Research Support, Non-U.S. Gov't"", ""Research Support, N.I.H., Extramural"", ""Adaptive Clinical Trial""]","[""Cascone T"", ""Leung CH"", ""Weissferdt A"", ""Pataer A"", ""Carter BW"", ""Godoy MCB"", ""Feldman H"", ""William WN Jr"", ""Xi Y"", ""Basu S"", ""Sun JJ"", ""Yadav SS"", ""Rojas Alvarez FR"", ""Lee Y"", ""Mishra AK"", ""Chen L"", ""Pradhan M"", ""Guo H"", ""Sinjab A"", ""Zhou N"", ""Negrao MV"", ""Le X"", ""Gay CM"", ""Tsao AS"", ""Byers LA"", ""Altan M"", ""Glisson BS"", ""Fossella FV"", ""Elamin YY"", ""Blumenschein G Jr"", ""Zhang J"", ""Skoulidis F"", ""Wu J"", ""Mehran RJ"", ""Rice DC"", ""Walsh GL"", ""Hofstetter WL"", ""Rajaram R"", ""Antonoff MB"", ""Fujimoto J"", ""Solis LM"", ""Parra ER"", ""Haymaker C"", ""Wistuba II"", ""Swisher SG"", ""Vaporciyan AA"", ""Lin HY"", ""Wang J"", ""Gibbons DL"", ""Jack Lee J"", ""Ajami NJ"", ""Wargo JA"", ""Allison JP"", ""Sharma P"", ""Kadara H"", ""Heymach JV"", ""Sepesi B""]",10.1038/s41591-022-02189-0,Cascone T,Nature medicine,1078-8956,3,Nat Med,eng,Sepesi B,"[""Humans"", ""Nivolumab"", ""Ipilimumab"", ""Carcinoma, Non-Small-Cell Lung"", ""Neoadjuvant Therapy"", ""Melanoma"", ""Antineoplastic Combined Chemotherapy Protocols"", ""Lung Neoplasms""]",593-604,36928818,pmc-id: PMC10033402;,2023 Mar,2023,https://pubmed.ncbi.nlm.nih.gov/36928818/,Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial,29,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
,"[""Published Erratum""]","[""Amaria RN"", ""Postow M"", ""Burton EM"", ""Tetzlaff MT"", ""Ross MI"", ""Torres-Cabala C"", ""Glitza IC"", ""Duan F"", ""Milton DR"", ""Busam K"", ""Simpson L"", ""McQuade JL"", ""Wong MK"", ""Gershenwald JE"", ""Lee JE"", ""Goepfert RP"", ""Keung EZ"", ""Fisher SB"", ""Betof-Warner A"", ""Shoushtari AN"", ""Callahan M"", ""Coit D"", ""Bartlett EK"", ""Bello D"", ""Momtaz P"", ""Nicholas C"", ""Gu A"", ""Zhang X"", ""Korivi BR"", ""Patnana M"", ""Patel SP"", ""Diab A"", ""Lucci A"", ""Prieto VG"", ""Davies MA"", ""Allison JP"", ""Sharma P"", ""Wargo JA"", ""Ariyan C"", ""Tawbi HA""]",10.1038/s41586-023-05892-1,Amaria RN,Nature,0028-0836,7953,Nature,eng,Tawbi HA,[],E23,36894629,pmc-id: PMC10033416;,2023 Mar,2023,https://pubmed.ncbi.nlm.nih.gov/36894629/,Author Correction: Neoadjuvant relatlimab and nivolumab in resectable melanoma,615,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Immune-related adverse events, particularly severe toxicities such as myocarditis, are major challenges to the utility of immune checkpoint inhibitors (ICIs) in anticancer therapy1. The pathogenesis of ICI-associated myocarditis (ICI-MC) is poorly understood. Pdcd1-/-Ctla4+/- mice recapitulate clinicopathological features of ICI-MC, including myocardial T cell infiltration2. Here, using single-cell RNA and T cell receptor (TCR) sequencing of cardiac immune infiltrates from Pdcd1-/-Ctla4+/- mice, we identify clonal effector CD8+ T cells as the dominant cell population. Treatment with anti-CD8-depleting, but not anti-CD4-depleting, antibodies improved the survival of Pdcd1-/-Ctla4+/- mice. Adoptive transfer of immune cells from mice with myocarditis induced fatal myocarditis in recipients, which required CD8+ T cells. The cardiac-specific protein α-myosin, which is absent from the thymus3,4, was identified as the cognate antigen source for three major histocompatibility complex class I-restricted TCRs derived from mice with fulminant myocarditis. Peripheral blood T cells from three patients with ICI-MC were expanded by α-myosin peptides. Moreover, these α-myosin-expanded T cells shared TCR clonotypes with diseased heart and skeletal muscle, which indicates that α-myosin may be a clinically important autoantigen in ICI-MC. These studies underscore the crucial role for cytotoxic CD8+ T cells, identify a candidate autoantigen in ICI-MC and yield new insights into the pathogenesis of ICI toxicity.","[""Journal Article"", ""Research Support, Non-U.S. Gov't"", ""Research Support, N.I.H., Extramural""]","[""Axelrod ML"", ""Meijers WC"", ""Screever EM"", ""Qin J"", ""Carroll MG"", ""Sun X"", ""Tannous E"", ""Zhang Y"", ""Sugiura A"", ""Taylor BC"", ""Hanna A"", ""Zhang S"", ""Amancherla K"", ""Tai W"", ""Wright JJ"", ""Wei SC"", ""Opalenik SR"", ""Toren AL"", ""Rathmell JC"", ""Ferrell PB"", ""Phillips EJ"", ""Mallal S"", ""Johnson DB"", ""Allison JP"", ""Moslehi JJ"", ""Balko JM""]",10.1038/s41586-022-05432-3,Axelrod ML,Nature,0028-0836,7937,Nature,eng,Balko JM,"[""Animals"", ""Mice"", ""Autoantigens"", ""CD8-Positive T-Lymphocytes"", ""CTLA-4 Antigen"", ""Immunotherapy"", ""Myocarditis"", ""Ventricular Myosins"", ""Programmed Cell Death 1 Receptor""]",818-826,36385524,pmc-id: PMC9930174;manuscript-id: NIHMS1869777;,2022 Nov,2022,https://pubmed.ncbi.nlm.nih.gov/36385524/,T cells specific for α-myosin drive immunotherapy-related myocarditis,611,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Immune checkpoint blockade (ICB) has revolutionized cancer treatment, yet quality of life and continuation of therapy can be constrained by immune-related adverse events (irAEs). Limited understanding of irAE mechanisms hampers development of approaches to mitigate their damage. To address this, we examined whether mice gained sensitivity to anti-CTLA-4 (αCTLA-4)-mediated toxicity upon disruption of gut homeostatic immunity. We found αCTLA-4 drove increased inflammation and colonic tissue damage in mice with genetic predisposition to intestinal inflammation, acute gastrointestinal infection, transplantation with a dysbiotic fecal microbiome, or dextran sodium sulfate administration. We identified an immune signature of αCTLA-4-mediated irAEs, including colonic neutrophil accumulation and systemic interleukin-6 (IL-6) release. IL-6 blockade combined with antibiotic treatment reduced intestinal damage and improved αCTLA-4 therapeutic efficacy in inflammation-prone mice. Intestinal immune signatures were validated in biopsies from patients with ICB colitis. Our work provides new preclinical models of αCTLA-4 intestinal irAEs, mechanistic insights into irAE development, and potential approaches to enhance ICB efficacy while mitigating irAEs.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, U.S. Gov't, Non-P.H.S."", ""Research Support, Non-U.S. Gov't""]","[""Zhou Y"", ""Medik YB"", ""Patel B"", ""Zamler DB"", ""Chen S"", ""Chapman T"", ""Schneider S"", ""Park EM"", ""Babcock RL"", ""Chrisikos TT"", ""Kahn LM"", ""Dyevoich AM"", ""Pineda JE"", ""Wong MC"", ""Mishra AK"", ""Cass SH"", ""Cogdill AP"", ""Johnson DH"", ""Johnson SB"", ""Wani K"", ""Ledesma DA"", ""Hudgens CW"", ""Wang J"", ""Wadud Khan MA"", ""Peterson CB"", ""Joon AY"", ""Peng W"", ""Li HS"", ""Arora R"", ""Tang X"", ""Raso MG"", ""Zhang X"", ""Foo WC"", ""Tetzlaff MT"", ""Diehl GE"", ""Clise-Dwyer K"", ""Whitley EM"", ""Gubin MM"", ""Allison JP"", ""Hwu P"", ""Ajami NJ"", ""Diab A"", ""Wargo JA"", ""Watowich SS""]",10.1084/jem.20221333,Zhou Y,The Journal of experimental medicine,0022-1007,2,J Exp Med,eng,Watowich SS,"[""Mice"", ""Animals"", ""Interleukin-6"", ""Quality of Life"", ""Colitis"", ""Immunotherapy"", ""Inflammation""]",,36367776,pmc-id: PMC9664499;,2023 Feb 6,2023,https://pubmed.ncbi.nlm.nih.gov/36367776/,Intestinal toxicity to CTLA-4 blockade driven by IL-6 and myeloid infiltration,220,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
Spatiotemporal immune monitoring in clinical trials and reverse translation will help to determine optimal combination immune therapies to cure cancer.,"[""Editorial""]","[""Sharma P"", ""Allison JP""]",10.1126/scitranslmed.adf2947,Sharma P,Science translational medicine,1946-6234,670,Sci Transl Med,eng,Allison JP,"[""Humans"", ""Immunotherapy"", ""Neoplasms"", ""Combined Modality Therapy""]",eadf2947,36350993,,2022 Nov 9,2022,https://pubmed.ncbi.nlm.nih.gov/36350993/,Immune checkpoint therapy: Forging ahead,14,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Relatlimab and nivolumab combination immunotherapy improves progression-free survival over nivolumab monotherapy in patients with unresectable advanced melanoma1. We investigated this regimen in patients with resectable clinical stage III or oligometastatic stage IV melanoma (NCT02519322). Patients received two neoadjuvant doses (nivolumab 480 mg and relatlimab 160 mg intravenously every 4 weeks) followed by surgery, and then ten doses of adjuvant combination therapy. The primary end point was pathologic complete response (pCR) rate2. The combination resulted in 57% pCR rate and 70% overall pathologic response rate among 30 patients treated. The radiographic response rate using Response Evaluation Criteria in Solid Tumors 1.1 was 57%. No grade 3-4 immune-related adverse events were observed in the neoadjuvant setting. The 1- and 2-year recurrence-free survival rate was 100% and 92% for patients with any pathologic response, compared to 88% and 55% for patients who did not have a pathologic response (P = 0.005). Increased immune cell infiltration at baseline, and decrease in M2 macrophages during treatment, were associated with pathologic response. Our results indicate that neoadjuvant relatlimab and nivolumab induces a high pCR rate. Safety during neoadjuvant therapy is favourable compared to other combination immunotherapy regimens. These data, in combination with the results of the RELATIVITY-047 trial1, provide further confirmation of the efficacy and safety of this new immunotherapy regimen.","[""Clinical Trial"", ""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Amaria RN"", ""Postow M"", ""Burton EM"", ""Tetzlaff MT"", ""Ross MI"", ""Torres-Cabala C"", ""Glitza IC"", ""Duan F"", ""Milton DR"", ""Busam K"", ""Simpson L"", ""McQuade JL"", ""Wong MK"", ""Gershenwald JE"", ""Lee JE"", ""Goepfert RP"", ""Keung EZ"", ""Fisher SB"", ""Betof-Warner A"", ""Shoushtari AN"", ""Callahan M"", ""Coit D"", ""Bartlett EK"", ""Bello D"", ""Momtaz P"", ""Nicholas C"", ""Gu A"", ""Zhang X"", ""Korivi BR"", ""Patnana M"", ""Patel SP"", ""Diab A"", ""Lucci A"", ""Prieto VG"", ""Davies MA"", ""Allison JP"", ""Sharma P"", ""Wargo JA"", ""Ariyan C"", ""Tawbi HA""]",10.1038/s41586-022-05368-8,Amaria RN,Nature,0028-0836,7934,Nature,eng,Tawbi HA,"[""Humans"", ""Antibodies, Monoclonal"", ""Immune Checkpoint Inhibitors"", ""Melanoma"", ""Neoadjuvant Therapy"", ""Neoplasm Staging"", ""Nivolumab"", ""Macrophages"", ""Drug Therapy, Combination"", ""Survival Rate"", ""Antibodies, Monoclonal, Humanized""]",155-160,36289334,pmc-id: PMC9607737;,2022 Nov,2022,https://pubmed.ncbi.nlm.nih.gov/36289334/,Neoadjuvant relatlimab and nivolumab in resectable melanoma,611,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Immune checkpoint blockade (ICB) therapy frequently induces immune-related adverse events. To elucidate the underlying immunobiology, we performed a deep immune analysis of intestinal, colitis, and tumor tissue from ICB-treated patients with parallel studies in preclinical models. Expression of interleukin-6 (IL-6), neutrophil, and chemotactic markers was higher in colitis than in normal intestinal tissue; T helper 17 (Th17) cells were more prevalent in immune-related enterocolitis (irEC) than T helper 1 (Th1). Anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) induced stronger Th17 memory in colitis than anti-program death 1 (anti-PD-1). In murine models, IL-6 blockade associated with improved tumor control and a higher density of CD4+/CD8+ effector T cells, with reduced Th17, macrophages, and myeloid cells. In an experimental autoimmune encephalomyelitis (EAE) model with tumors, combined IL-6 blockade and ICB enhanced tumor rejection while simultaneously mitigating EAE symptoms versus ICB alone. IL-6 blockade with ICB could de-couple autoimmunity from antitumor immunity.","[""Journal Article"", ""Research Support, Non-U.S. Gov't"", ""Research Support, N.I.H., Extramural""]","[""Hailemichael Y"", ""Johnson DH"", ""Abdel-Wahab N"", ""Foo WC"", ""Bentebibel SE"", ""Daher M"", ""Haymaker C"", ""Wani K"", ""Saberian C"", ""Ogata D"", ""Kim ST"", ""Nurieva R"", ""Lazar AJ"", ""Abu-Sbeih H"", ""Fa'ak F"", ""Mathew A"", ""Wang Y"", ""Falohun A"", ""Trinh V"", ""Zobniw C"", ""Spillson C"", ""Burks JK"", ""Awiwi M"", ""Elsayes K"", ""Soto LS"", ""Melendez BD"", ""Davies MA"", ""Wargo J"", ""Curry J"", ""Yee C"", ""Lizee G"", ""Singh S"", ""Sharma P"", ""Allison JP"", ""Hwu P"", ""Ekmekcioglu S"", ""Diab A""]",10.1016/j.ccell.2022.04.004,Hailemichael Y,Cancer cell,1535-6108,5,Cancer Cell,eng,Diab A,"[""Animals"", ""Colitis"", ""Humans"", ""Immunologic Factors"", ""Immunotherapy"", ""Interleukin-6"", ""Mice"", ""Myeloid Cells"", ""Neoplasms""]",509-523.e6,35537412,pmc-id: PMC9221568;manuscript-id: NIHMS1811254;,2022 May 9,2022,https://pubmed.ncbi.nlm.nih.gov/35537412/,Interleukin-6 blockade abrogates immunotherapy toxicity and promotes tumor immunity,40,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"The accumulation of immune-suppressive myeloid cells is a critical determinant of resistance to anti-programmed death-1 (PD-1) therapy in advanced clear cell renal cell carcinoma (ccRCC). In preclinical models, the tyrosine kinase inhibitor sitravatinib enhanced responses to anti-PD-1 therapy by modulating immune-suppressive myeloid cells. We conducted a phase 1-2 trial to choose an optimal sitravatinib dose combined with a fixed dose of nivolumab in 42 immunotherapy-naïve patients with ccRCC refractory to prior antiangiogenic therapies. The combination demonstrated no unexpected toxicities and achieved an objective response rate of 35.7% and a median progression-free survival of 11.7 months, with 80.1% of patients alive after a median follow-up of 18.7 months. Baseline peripheral blood neutrophil-to-lymphocyte ratio correlated with response to sitravatinib and nivolumab. Patients with liver metastases showed durable responses comparable to patients without liver metastases. In addition, correlative studies demonstrated reduction of immune-suppressive myeloid cells in the periphery and tumor microenvironment following sitravatinib treatment. This study provides a rationally designed combinatorial strategy to improve outcomes of anti-PD-1 therapy in advanced ccRCC.","[""Clinical Trial, Phase I"", ""Clinical Trial, Phase II"", ""Journal Article"", ""Research Support, Non-U.S. Gov't"", ""Research Support, N.I.H., Extramural""]","[""Msaouel P"", ""Goswami S"", ""Thall PF"", ""Wang X"", ""Yuan Y"", ""Jonasch E"", ""Gao J"", ""Campbell MT"", ""Shah AY"", ""Corn PG"", ""Tam AL"", ""Ahrar K"", ""Rao P"", ""Sircar K"", ""Cohen L"", ""Basu S"", ""Duan F"", ""Jindal S"", ""Zhang Y"", ""Chen H"", ""Yadav SS"", ""Shazer R"", ""Der-Torossian H"", ""Allison JP"", ""Sharma P"", ""Tannir NM""]",10.1126/scitranslmed.abm6420,Msaouel P,Science translational medicine,1946-6234,641,Sci Transl Med,eng,Tannir NM,"[""Angiogenesis Inhibitors"", ""Anilides"", ""Carcinoma, Renal Cell"", ""Female"", ""Humans"", ""Kidney Neoplasms"", ""Liver Neoplasms"", ""Male"", ""Nivolumab"", ""Pyridines"", ""Tumor Microenvironment""]",eabm6420,35442707,pmc-id: PMC11924199;manuscript-id: NIHMS2056464;,2022 Apr 20,2022,https://pubmed.ncbi.nlm.nih.gov/35442707/,A phase 1-2 trial of sitravatinib and nivolumab in clear cell renal cell carcinoma following progression on antiangiogenic therapy,14,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
,"[""Published Erratum""]","[""Ferrarotto R"", ""Amit M"", ""Nagarajan P"", ""Rubin ML"", ""Yuan Y"", ""Bell D"", ""El-Naggar AK"", ""Johnson JM"", ""Morrison WH"", ""Rosenthal DI"", ""Glisson BS"", ""Johnson FM"", ""Lu C"", ""Mott FE"", ""Esmaeli B"", ""Diaz EM"", ""Gidley PW"", ""Goepfert RP"", ""Lewis CM"", ""Weber RS"", ""Wargo JA"", ""Basu S"", ""Duan F"", ""Yadav SS"", ""Sharma P"", ""Allison JP"", ""Myers JN"", ""Gross ND""]",10.1158/1078-0432.CCR-22-0468,Ferrarotto R,Clinical cancer research : an official journal of the American Association for Cancer Research,1078-0432,8,Clin Cancer Res,eng,Gross ND,[],1735,35419587,,2022 Apr 14,2022,https://pubmed.ncbi.nlm.nih.gov/35419587/,"Correction: Pilot Phase II Trial of Neoadjuvant Immunotherapy in Locoregionally Advanced, Resectable Cutaneous Squamous Cell Carcinoma of the Head and Neck",28,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Hepatocellular carcinoma has high recurrence rates after surgery; however, there are no approved standard-of-care neoadjuvant or adjuvant therapies. Immunotherapy has been shown to improve survival in advanced hepatocellular carcinoma; we therefore aimed to evaluate the safety and tolerability of perioperative immunotherapy in resectable hepatocellular carcinoma. In this single-centre, randomised, open-label, phase 2 trial, patients with resectable hepatocellular carcinoma were randomly assigned (1:1) to receive 240 mg of nivolumab intravenously every 2 weeks (for up to three doses before surgery at 6 weeks) followed in the adjuvant phase by 480 mg of nivolumab intravenously every 4 weeks for 2 years, or 240 mg of nivolumab intravenously every 2 weeks (for up to three doses before surgery) plus one dose of 1 mg/kg of ipilimumab intravenously concurrently with the first preoperative dose of nivolumab, followed in the adjuvant phase by 480 mg of nivolumab intravenously every 4 weeks for up to 2 years plus 1 mg/kg of ipilimumab intravenously every 6 weeks for up to four cycles. Patients were randomly assigned to the treatment groups by use of block randomisation with a random block size. The primary endpoint was the safety and tolerability of nivolumab with or without ipilimumab. Secondary endpoints were the proportion of patients with an overall response, time to progression, and progression-free survival. This trial is registered with ClinicalTrials.gov (NCT03222076) and is completed. Between Oct 30, 2017, and Dec 3, 2019, 30 patients were enrolled and 27 were randomly assigned: 13 to nivolumab and 14 to nivolumab plus ipilimumab. Grade 3-4 adverse events were higher with nivolumab plus ipilimumab (six [43%] of 14 patients) than with nivolumab alone (three [23%] of 13). The most common treatment-related adverse events of any grade were increased alanine aminotransferase (three [23%] of 13 patients on nivolumab vs seven [50%] of 14 patients on nivolumab plus ipilimumab) and increased aspartate aminotransferase (three [23%] vs seven [50%]). No patients in either group had their surgery delayed due to grade 3 or worse adverse events. Seven of 27 patients had surgical cancellations, but none was due to treatment-related adverse events. Estimated median progression-free survival was 9·4 months (95% CI 1·47-not estimable [NE]) with nivolumab and 19·53 months (2·33-NE) with nivolumab plus ipilimumab (hazard ratio [HR] 0·99, 95% CI 0·31-2·54); median time to progression was 9·4 months (95% CI 1·47-NE) in the nivolumab group and 19·53 months (2·33-NE) in the nivolumab plus ipilimumab group (HR 0·89, 95% CI 0·31-2·54). In an exploratory analysis, three (23%) of 13 patients had an overall response with nivolumab monotherapy, versus none with nivolumab plus ipilimumab. Three (33%) of nine patients had a major pathological response (ie, ≥70% necrosis in the resected tumour area) with nivolumab monotherapy compared with three (27%) of 11 with nivolumab plus ipilimumab. Perioperative nivolumab alone and nivolumab plus ipilimumab appears to be safe and feasible in patients with resectable hepatocellular carcinoma. Our findings support further studies of immunotherapy in the perioperative setting in hepatocellular carcinoma. Bristol Myers Squibb and the US National Institutes of Health.","[""Clinical Trial, Phase II"", ""Journal Article"", ""Randomized Controlled Trial"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Kaseb AO"", ""Hasanov E"", ""Cao HST"", ""Xiao L"", ""Vauthey JN"", ""Lee SS"", ""Yavuz BG"", ""Mohamed YI"", ""Qayyum A"", ""Jindal S"", ""Duan F"", ""Basu S"", ""Yadav SS"", ""Nicholas C"", ""Sun JJ"", ""Singh Raghav KP"", ""Rashid A"", ""Carter K"", ""Chun YS"", ""Tzeng CD"", ""Sakamuri D"", ""Xu L"", ""Sun R"", ""Cristini V"", ""Beretta L"", ""Yao JC"", ""Wolff RA"", ""Allison JP"", ""Sharma P""]",10.1016/S2468-1253(21)00427-1,Kaseb AO,The lancet. Gastroenterology & hepatology,2468-1253,3,Lancet Gastroenterol Hepatol,eng,Sharma P,"[""Aged"", ""Alanine Transaminase"", ""Antineoplastic Agents, Immunological"", ""Antineoplastic Combined Chemotherapy Protocols"", ""Aspartate Aminotransferases"", ""Carcinoma, Hepatocellular"", ""Female"", ""Humans"", ""Ipilimumab"", ""Liver Neoplasms"", ""Male"", ""Middle Aged"", ""Nivolumab"", ""Perioperative Care"", ""Progression-Free Survival""]",208-218,35065057,pmc-id: PMC8840977;manuscript-id: NIHMS1775116;,2022 Mar,2022,https://pubmed.ncbi.nlm.nih.gov/35065057/,"Perioperative nivolumab monotherapy versus nivolumab plus ipilimumab in resectable hepatocellular carcinoma: a randomised, open-label, phase 2 trial",7,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"An emerging strategy to enhance the efficacy of immune checkpoint blockade in relapsed/refractory cancers is increasing immunogenic cell death via combination with cytotoxic therapies. Understanding the effects of cytotoxic and immunotherapeutic agents on immune cell populations will enable improved mechanism-based design of combination therapies to maximum efficacy and minimum toxicity.See related article by Zeidner et al., p. 616.","[""Journal Article"", ""Comment""]","[""Wei SC"", ""Mancuso JJ"", ""Daver N"", ""Allison JP""]",10.1158/2643-3230.BCD-21-0130,Wei SC,Blood cancer discovery,2643-3230,6,Blood Cancer Discov,eng,Allison JP,[],551-554,35015675,pmc-id: PMC9894576;,2021 Nov,2021,https://pubmed.ncbi.nlm.nih.gov/35015675/,Checkpoint Blockade + Chemotherapy: the Right Combination for AML?,2,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Gut bacteria modulate the response to immune checkpoint blockade (ICB) treatment in cancer, but the effect of diet and supplements on this interaction is not well studied. We assessed fecal microbiota profiles, dietary habits, and commercially available probiotic supplement use in melanoma patients and performed parallel preclinical studies. Higher dietary fiber was associated with significantly improved progression-free survival in 128 patients on ICB, with the most pronounced benefit observed in patients with sufficient dietary fiber intake and no probiotic use. Findings were recapitulated in preclinical models, which demonstrated impaired treatment response to anti–programmed cell death 1 (anti–PD-1)–based therapy in mice receiving a low-fiber diet or probiotics, with a lower frequency of interferon-γ–positive cytotoxic T cells in the tumor microenvironment. Together, these data have clinical implications for patients receiving ICB for cancer.","[""Journal Article"", ""Observational Study"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Spencer CN"", ""McQuade JL"", ""Gopalakrishnan V"", ""McCulloch JA"", ""Vetizou M"", ""Cogdill AP"", ""Khan MAW"", ""Zhang X"", ""White MG"", ""Peterson CB"", ""Wong MC"", ""Morad G"", ""Rodgers T"", ""Badger JH"", ""Helmink BA"", ""Andrews MC"", ""Rodrigues RR"", ""Morgun A"", ""Kim YS"", ""Roszik J"", ""Hoffman KL"", ""Zheng J"", ""Zhou Y"", ""Medik YB"", ""Kahn LM"", ""Johnson S"", ""Hudgens CW"", ""Wani K"", ""Gaudreau PO"", ""Harris AL"", ""Jamal MA"", ""Baruch EN"", ""Perez-Guijarro E"", ""Day CP"", ""Merlino G"", ""Pazdrak B"", ""Lochmann BS"", ""Szczepaniak-Sloane RA"", ""Arora R"", ""Anderson J"", ""Zobniw CM"", ""Posada E"", ""Sirmans E"", ""Simon J"", ""Haydu LE"", ""Burton EM"", ""Wang L"", ""Dang M"", ""Clise-Dwyer K"", ""Schneider S"", ""Chapman T"", ""Anang NAS"", ""Duncan S"", ""Toker J"", ""Malke JC"", ""Glitza IC"", ""Amaria RN"", ""Tawbi HA"", ""Diab A"", ""Wong MK"", ""Patel SP"", ""Woodman SE"", ""Davies MA"", ""Ross MI"", ""Gershenwald JE"", ""Lee JE"", ""Hwu P"", ""Jensen V"", ""Samuels Y"", ""Straussman R"", ""Ajami NJ"", ""Nelson KC"", ""Nezi L"", ""Petrosino JF"", ""Futreal PA"", ""Lazar AJ"", ""Hu J"", ""Jenq RR"", ""Tetzlaff MT"", ""Yan Y"", ""Garrett WS"", ""Huttenhower C"", ""Sharma P"", ""Watowich SS"", ""Allison JP"", ""Cohen L"", ""Trinchieri G"", ""Daniel CR"", ""Wargo JA""]",10.1126/science.aaz7015,Spencer CN,"Science (New York, N.Y.)",0036-8075,6575,Science,eng,Wargo JA,"[""Animals"", ""Cohort Studies"", ""Dietary Fiber"", ""Fatty Acids, Volatile"", ""Fecal Microbiota Transplantation"", ""Feces"", ""Female"", ""Gastrointestinal Microbiome"", ""Humans"", ""Immune Checkpoint Inhibitors"", ""Immunotherapy"", ""Male"", ""Melanoma"", ""Melanoma, Experimental"", ""Mice"", ""Mice, Inbred C57BL"", ""Probiotics"", ""Progression-Free Survival"", ""T-Lymphocytes""]",1632-1640,34941392,pmc-id: PMC8970537;manuscript-id: NIHMS1785033;,2021 Dec 24,2021,https://pubmed.ncbi.nlm.nih.gov/34941392/,Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response,374,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Cryoablation in combination with immune checkpoint therapy was previously reported to improve anti-tumor immune responses in pre-clinical studies. Here we report a pilot study of anti-CTLA-4 (tremelimumab) with (n = 15) or without (n = 14) cryoablation in patients with metastatic renal cell carcinoma (NCT02626130), 18 patients with clear cell and 11 patients with non-clear cell histologies. The primary endpoint is safety, secondary endpoints include objective response rate, progression-free survival, and immune monitoring studies. Safety data indicate ≥ grade 3 treatment-related adverse events in 16 of 29 patients (55%) including 6 diarrhea/colitis, 3 hepatitis, 1 pneumonitis, and 1 glomerulonephritis. Toxicity leading to treatment discontinuation occurs in 5 patients in each arm. 3 patients with clear cell histology experience durable responses. One patient in the tremelimumab arm experiences an objective response, the median progression-free survival for all patients is 3.3 months (95% CI: 2.0, 5.3 months). Exploratory immune monitoring analysis of baseline and post-treatment tumor tissue samples shows that treatment increases immune cell infiltration and tertiary lymphoid structures in clear cell but not in non-clear cell. In clear cell, cryoablation plus tremelimumab leads to a significant increase in immune cell infiltration. These data highlight that treatment with tremelimumab plus cryotherapy is feasible and modulates the immune microenvironment in patients with metastatic clear cell histology.","[""Clinical Trial, Phase I"", ""Journal Article"", ""Randomized Controlled Trial"", ""Research Support, Non-U.S. Gov't""]","[""Campbell MT"", ""Matin SF"", ""Tam AL"", ""Sheth RA"", ""Ahrar K"", ""Tidwell RS"", ""Rao P"", ""Karam JA"", ""Wood CG"", ""Tannir NM"", ""Jonasch E"", ""Gao J"", ""Zurita AJ"", ""Shah AY"", ""Jindal S"", ""Duan F"", ""Basu S"", ""Chen H"", ""Espejo AB"", ""Allison JP"", ""Yadav SS"", ""Sharma P""]",10.1038/s41467-021-26415-4,Campbell MT,Nature communications,2041-1723,1,Nat Commun,eng,Sharma P,"[""Adult"", ""Aged"", ""Aged, 80 and over"", ""Antibodies, Monoclonal, Humanized"", ""Antineoplastic Agents, Immunological"", ""CTLA-4 Antigen"", ""Carcinoma, Renal Cell"", ""Combined Modality Therapy"", ""Cryosurgery"", ""Female"", ""Humans"", ""Kidney Neoplasms"", ""Male"", ""Middle Aged"", ""Neoplasm Metastasis"", ""Patient Safety"", ""Pilot Projects"", ""Survival Rate"", ""Treatment Outcome"", ""Young Adult""]",6375,34737281,pmc-id: PMC8569213;,2021 Nov 4,2021,https://pubmed.ncbi.nlm.nih.gov/34737281/,Pilot study of Tremelimumab with and without cryoablation in patients with metastatic renal cell carcinoma,12,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"In contrast to the curative effect of allogenic stem cell transplantation in acute myeloid leukemia via T cell activity, only modest responses are achieved with checkpoint-blockade therapy, which might be explained by T cell phenotypes and T cell receptor (TCR) repertoires. Here, we show by paired single-cell RNA analysis and TCR repertoire profiling of bone marrow cells in relapsed/refractory acute myeloid leukemia patients pre/post azacytidine+nivolumab treatment that the disease-related T cell subsets are highly heterogeneous, and their abundance changes following PD-1 blockade-based treatment. TCR repertoires expand and primarily emerge from CD8+ cells in patients responding to treatment or having a stable disease, while TCR repertoires contract in therapy-resistant patients. Trajectory analysis reveals a continuum of CD8+ T cell phenotypes, characterized by differential expression of granzyme B and a bone marrow-residing memory CD8+ T cell subset, in which a population with stem-like properties expressing granzyme K is enriched in responders. Chromosome 7/7q loss, on the other hand, is a cancer-intrinsic genomic marker of PD-1 blockade resistance in AML. In summary, our study reveals that adaptive T cell plasticity and genomic alterations determine responses to PD-1 blockade in acute myeloid leukemia.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Abbas HA"", ""Hao D"", ""Tomczak K"", ""Barrodia P"", ""Im JS"", ""Reville PK"", ""Alaniz Z"", ""Wang W"", ""Wang R"", ""Wang F"", ""Al-Atrash G"", ""Takahashi K"", ""Ning J"", ""Ding M"", ""Beird HC"", ""Mathews JT"", ""Little L"", ""Zhang J"", ""Basu S"", ""Konopleva M"", ""Marques-Piubelli ML"", ""Solis LM"", ""Parra ER"", ""Lu W"", ""Tamegnon A"", ""Garcia-Manero G"", ""Green MR"", ""Sharma P"", ""Allison JP"", ""Kornblau SM"", ""Rai K"", ""Wang L"", ""Daver N"", ""Futreal A""]",10.1038/s41467-021-26282-z,Abbas HA,Nature communications,2041-1723,1,Nat Commun,eng,Futreal A,"[""Aged"", ""Aged, 80 and over"", ""Azacitidine"", ""Bone Marrow"", ""CD8-Positive T-Lymphocytes"", ""Chromosome Deletion"", ""Chromosomes, Human, Pair 7"", ""Drug Resistance, Neoplasm"", ""Granzymes"", ""Humans"", ""Immune Checkpoint Inhibitors"", ""Leukemia, Myeloid, Acute"", ""Middle Aged"", ""Nivolumab"", ""Programmed Cell Death 1 Receptor"", ""Receptors, Antigen, T-Cell"", ""Single-Cell Analysis"", ""T-Lymphocyte Subsets"", ""T-Lymphocytes"", ""Transcriptome""]",6071,34663807,pmc-id: PMC8524723;,2021 Oct 18,2021,https://pubmed.ncbi.nlm.nih.gov/34663807/,Single cell T cell landscape and T cell receptor repertoire profiling of AML in context of PD-1 blockade therapy,12,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Immune checkpoint therapy (ICT) has low response rates in patients with metastatic castration-resistant prostate cancer (mCRPC), in part due to few T cells in the tumor microenvironment (TME). Anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) promotes intratumoral T cell infiltration but induces upregulation of PD-1 and programmed death ligand-1 (PD-L1) within the prostate TME. Combined anti-CTLA-4 plus anti-PD-1 can partly overcome this adaptive resistance and was recently shown to augment responses in patients with mCRPC with measurable disease. Although bone is the most common site of metastasis in prostate cancer, patients with bone-predominant disease are frequently excluded from trials because they lack measurable disease, which limits assessment of disease progression and tissue sampling. We therefore designed this study to investigate combined ICT in mCRPC to bone. Combined anti-CTLA-4 (tremelimumab) plus anti-PD-L1 (durvalumab) is safe and well tolerated in patients with chemotherapy-naïve mCRPC to bone. In this single-arm pilot study, men with chemotherapy-naïve mCRPC to bone received tremelimumab (75 mg intravenous) plus durvalumab (1500 mg intravenous) every 4 weeks (up to four doses), followed by durvalumab (1500 mg intravenous) maintenance every 4 weeks (up to nine doses). The primary endpoint was incidence of adverse events. Secondary endpoints included serum prostate-specific antigen (PSA), progression-free survival (PFS), radiographic PFS (rPFS), and maximal PSA decline. Twenty-six patients were treated between August 8, 2017 and March 28, 2019. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 11 patients (42%), with no grade 4 or 5 events. TRAEs leading to discontinuation occurred in three patients (12%). PSA decline ≥50% occurred in three patients (12%). Six patients (24%) achieved stable disease for >6 months. At a median follow-up of 43.6 months, median rPFS was 3.7 months (95% CI: 1.9 to 5.7), and median overall survival was 28.1 months (95% CI: 14.5 to 37.3). Post-treatment evaluation of the bone microenvironment revealed transcriptional upregulation in myeloid and neutrophil immune subset signatures and increased expression of inhibitory immune checkpoints. Tremelimumab plus durvalumab was safe and well tolerated in patients with chemotherapy-naïve mCRPC to bone, with potential activity in a small number of patients as measured by rPFS. Combination of CTLA-4 and PD-L1 blockade with therapies targeting the myeloid compartment or other inhibitory immune receptors may be necessary to overcome mechanisms of resistance within prostate bone microenvironment. NCT03204812.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Subudhi SK"", ""Siddiqui BA"", ""Aparicio AM"", ""Yadav SS"", ""Basu S"", ""Chen H"", ""Jindal S"", ""Tidwell RSS"", ""Varma A"", ""Logothetis CJ"", ""Allison JP"", ""Corn PG"", ""Sharma P""]",10.1136/jitc-2021-002919,Subudhi SK,Journal for immunotherapy of cancer,2051-1426,10,J Immunother Cancer,eng,Sharma P,"[""Aged"", ""Aged, 80 and over"", ""Antineoplastic Combined Chemotherapy Protocols"", ""CTLA-4 Antigen"", ""Humans"", ""Immune Checkpoint Inhibitors"", ""Male"", ""Middle Aged"", ""Neutrophils"", ""Pilot Projects"", ""Prostatic Neoplasms, Castration-Resistant"", ""Tumor Microenvironment""]",,34663638,pmc-id: PMC8524287;,2021 Oct,2021,https://pubmed.ncbi.nlm.nih.gov/34663638/,Combined CTLA-4 and PD-L1 blockade in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer is associated with increased myeloid and neutrophil immune subsets in the bone microenvironment,9,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Radiographic imaging is the standard approach for evaluating the disease involvement of lymph nodes in patients with operable NSCLC although the impact of neoadjuvant immune checkpoint inhibitors (ICIs) on lymph nodes has not yet been characterized. Herein, we present an ad hoc analysis of the NEOSTAR trial (NCT03158129) where we observed a phenomenon we refer to as ""nodal immune flare"" (NIF) in which patients treated with neoadjuvant ICIs demonstrate radiologically abnormal nodes post-therapy that upon pathological evaluation are devoid of cancer and demonstrate de novo non-caseating granulomas. Abnormal lymph nodes are analyzed by computed tomography and 18F-fluorodeoxyglucose positron emission tomography/computer tomography to evaluate the size and the maximum standard uptake value post- and pre-therapy in NEOSTAR and an independent neoadjuvant chemotherapy cohort. NIF occurs in 16% (7/44) of patients treated with ICIs but in 0% (0/28) of patients after neoadjuvant chemotherapy. NIF is associated with an inflamed nodal immune microenvironment and with fecal abundance of genera belonging to the family Coriobacteriaceae of phylum Actinobacteria, but not with tumor responses or treatment-related toxicity. Our findings suggest that this apparent radiological cancer progression in lymph nodes may occur due to an inflammatory response after neoadjuvant immunotherapy, and such cases should be evaluated by pathological examination to distinguish NIF from true nodal progression and to ensure appropriate clinical treatment planning.","[""Clinical Trial, Phase II"", ""Journal Article"", ""Randomized Controlled Trial"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Cascone T"", ""Weissferdt A"", ""Godoy MCB"", ""William WN Jr"", ""Leung CH"", ""Lin HY"", ""Basu S"", ""Yadav SS"", ""Pataer A"", ""Mitchell KG"", ""Khan MAW"", ""Shi Y"", ""Haymaker C"", ""Solis LM"", ""Parra ER"", ""Kadara H"", ""Wistuba II"", ""Sharma P"", ""Allison JP"", ""Ajami NJ"", ""Wargo JA"", ""Jenq RR"", ""Gibbons DL"", ""Lee JJ"", ""Swisher SG"", ""Vaporciyan AA"", ""Heymach JV"", ""Sepesi B""]",10.1038/s41467-021-25188-0,Cascone T,Nature communications,2041-1723,1,Nat Commun,eng,Sepesi B,"[""Aged"", ""Carcinoma, Non-Small-Cell Lung"", ""Disease Progression"", ""Female"", ""Humans"", ""Immune Checkpoint Inhibitors"", ""Lung Neoplasms"", ""Lymph Nodes"", ""Lymphatic Metastasis"", ""Male"", ""Middle Aged"", ""Multimodal Imaging"", ""Neoadjuvant Therapy""]",5045,34413300,pmc-id: PMC8376947;,2021 Aug 19,2021,https://pubmed.ncbi.nlm.nih.gov/34413300/,Nodal immune flare mimics nodal disease progression following neoadjuvant immune checkpoint inhibitors in non-small cell lung cancer,12,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Treatment with combined immune checkpoint blockade (CICB) targeting CTLA-4 and PD-1 is associated with clinical benefit across tumor types, but also a high rate of immune-related adverse events. Insights into biomarkers and mechanisms of response and toxicity to CICB are needed. To address this, we profiled the blood, tumor and gut microbiome of 77 patients with advanced melanoma treated with CICB, with a high rate of any ≥grade 3 immune-related adverse events (49%) with parallel studies in pre-clinical models. Tumor-associated immune and genomic biomarkers of response to CICB were similar to those identified for ICB monotherapy, and toxicity from CICB was associated with a more diverse peripheral T-cell repertoire. Profiling of gut microbiota demonstrated a significantly higher abundance of Bacteroides intestinalis in patients with toxicity, with upregulation of mucosal IL-1β in patient samples of colitis and in pre-clinical models. Together, these data offer potential new therapeutic angles for targeting toxicity to CICB.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Andrews MC"", ""Duong CPM"", ""Gopalakrishnan V"", ""Iebba V"", ""Chen WS"", ""Derosa L"", ""Khan MAW"", ""Cogdill AP"", ""White MG"", ""Wong MC"", ""Ferrere G"", ""Fluckiger A"", ""Roberti MP"", ""Opolon P"", ""Alou MT"", ""Yonekura S"", ""Roh W"", ""Spencer CN"", ""Curbelo IF"", ""Vence L"", ""Reuben A"", ""Johnson S"", ""Arora R"", ""Morad G"", ""Lastrapes M"", ""Baruch EN"", ""Little L"", ""Gumbs C"", ""Cooper ZA"", ""Prieto PA"", ""Wani K"", ""Lazar AJ"", ""Tetzlaff MT"", ""Hudgens CW"", ""Callahan MK"", ""Adamow M"", ""Postow MA"", ""Ariyan CE"", ""Gaudreau PO"", ""Nezi L"", ""Raoult D"", ""Mihalcioiu C"", ""Elkrief A"", ""Pezo RC"", ""Haydu LE"", ""Simon JM"", ""Tawbi HA"", ""McQuade J"", ""Hwu P"", ""Hwu WJ"", ""Amaria RN"", ""Burton EM"", ""Woodman SE"", ""Watowich S"", ""Diab A"", ""Patel SP"", ""Glitza IC"", ""Wong MK"", ""Zhao L"", ""Zhang J"", ""Ajami NJ"", ""Petrosino J"", ""Jenq RR"", ""Davies MA"", ""Gershenwald JE"", ""Futreal PA"", ""Sharma P"", ""Allison JP"", ""Routy B"", ""Zitvogel L"", ""Wargo JA""]",10.1038/s41591-021-01406-6,Andrews MC,Nature medicine,1078-8956,8,Nat Med,eng,Wargo JA,"[""Animals"", ""CTLA-4 Antigen"", ""Cell Line, Tumor"", ""Female"", ""Gastrointestinal Microbiome"", ""Humans"", ""Interleukin-1beta"", ""Melanoma"", ""Mice"", ""Mice, Inbred C57BL"", ""Programmed Cell Death 1 Receptor""]",1432-1441,34239137,pmc-id: PMC11107795;manuscript-id: NIHMS1990505;,2021 Aug,2021,https://pubmed.ncbi.nlm.nih.gov/34239137/,Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade,27,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"In locoregionally advanced, resectable cutaneous squamous cell carcinoma of the head and neck (CSCC-HN), surgery followed by radiotherapy is standard but can be cosmetically and functionally devastating, and many patients will have recurrence. Newly diagnosed or recurrent stage III-IVA CSCC-HN patients amenable to curative-intent surgery received two cycles of neoadjuvant PD-1 inhibition. The primary endpoint was ORR per RECIST 1.1. Secondary endpoints included pathologic response [pathologic complete response (pCR) or major pathologic response (MPR; ≤10% viable tumor)], safety, DSS, DFS, and OS. Exploratory endpoints included immune biomarkers of response. Of 20 patients enrolled, 7 had recurrent disease. While only 6 patients [30%; 95% confidence interval (CI), 11.9-54.3] had partial responses by RECIST, 14 patients (70%; 95% CI, 45.7-88.1) had a pCR (n = 11) or MPR (n = 3). No SAEs ocurred during or after the neoadjuvant treatment. At a median follow-up of 22.6 months (95% CI, 21.7-26.1), one patient progressed and died, one died without disease, and two developed recurrence. The 12-month DSS, DFS, and OS rates were 95% (95% CI, 85.9-100), 89.5% (95% CI, 76.7-100), and 95% (95% CI, 85.9-100), respectively. Gene expression studies revealed an inflamed tumor microenvironment in patients with pCR or MPR, and CyTOF analyses demonstrated a memory CD8+ T-cell cluster enriched in patients with pCR. Neoadjuvant immunotherapy in locoregionally advanced, resectable CSCC-HN is safe and induces a high pathologic response rate. Pathologic responses were associated with an inflamed tumor microenvironment.","[""Clinical Trial, Phase II"", ""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Ferrarotto R"", ""Amit M"", ""Nagarajan P"", ""Rubin ML"", ""Yuan Y"", ""Bell D"", ""El-Naggar AK"", ""Johnson JM"", ""Morrison WH"", ""Rosenthal DI"", ""Glisson BS"", ""Johnson FM"", ""Lu C"", ""Mott FE"", ""Esmaeli B"", ""Diaz EM Jr"", ""Gidley PW"", ""Goepfert RP"", ""Lewis CM"", ""Weber RS"", ""Wargo JA"", ""Basu S"", ""Duan F"", ""Yadav SS"", ""Sharma P"", ""Allison JP"", ""Myers JN"", ""Gross ND""]",10.1158/1078-0432.CCR-21-0585,Ferrarotto R,Clinical cancer research : an official journal of the American Association for Cancer Research,1078-0432,16,Clin Cancer Res,eng,Gross ND,"[""Aged"", ""Female"", ""Head and Neck Neoplasms"", ""Humans"", ""Immune Checkpoint Inhibitors"", ""Immunotherapy"", ""Male"", ""Middle Aged"", ""Neoadjuvant Therapy"", ""Neoplasm Staging"", ""Pilot Projects"", ""Skin Neoplasms"", ""Squamous Cell Carcinoma of Head and Neck""]",4557-4565,34187851,pmc-id: PMC8711237;manuscript-id: NIHMS1718764;,2021 Aug 15,2021,https://pubmed.ncbi.nlm.nih.gov/34187851/,"Pilot Phase II Trial of Neoadjuvant Immunotherapy in Locoregionally Advanced, Resectable Cutaneous Squamous Cell Carcinoma of the Head and Neck",27,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Sipuleucel-T is a US Food and Drug Administration-approved autologous cellular immunotherapy that improves survival in patients with metastatic castration-resistant prostate cancer (mCRPC). We examined whether administering ipilimumab after sipuleucel-T could modify immune and/or clinical responses to this treatment. A total of 50 patients with mCRPC were enrolled into a clinical trial (NCT01804465, ClinicalTrials.gov) where they received ipilimumab either immediately or delayed 3 weeks following completion of sipuleucel-T treatment. Blood was collected at various timepoints of the study. Luminex assay for anti-prostatic acid phosphatase (PAP) and anti-PA2024-specific serum immunoglobulin G (IgG) and ELISpot for interferon-γ (IFN-γ) production against PAP and PA2024 were used to assess antigen-specific B and T cell responses, respectively. Clinical response was defined as >30% reduction in serum prostate-specific antigen levels compared with pretreatment levels. The frequency and state of circulating immune cells were determined by mass cytometry by time-of-flight and statistical scaffold analysis. We found the combination to be well tolerated with no unexpected adverse events occurring. The timing of ipilimumab did not significantly alter the rates of antigen-specific B and T cell responses, the primary endpoint of the clinical trial. Clinical responses were observed in 6 of 50 patients, with 3 having responses lasting longer than 3 months. The timing of ipilimumab did not significantly associate with clinical response or toxicity. The combination treatment did induce CD4 and CD8 T cell activation that was most pronounced with the immediate schedule. Lower frequencies of CTLA-4 positive circulating T cells, even prior to treatment, were associated with better clinical outcomes. Interestingly, these differences in CTLA-4 expression were associated with prior localized radiation therapy (RT) to the prostate or prostatic fossa. Prior radiation treatment was also associated with improved radiographic progression-free survival. Combining CTLA-4 blockade with sipuleucel-T resulted in modest clinical activity. The timing of CTLA-4 blockade following sipuleucel-T did not alter antigen-specific responses. Clinical responses were associated with both lower baseline frequencies of CTLA-4 expressing T cells and a history of RT. Prior cancer therapy may therefore result in long-lasting immune changes that influence responsiveness to immunotherapy with sipuleucel-T and anti-CTLA-4.","[""Clinical Trial, Phase II"", ""Journal Article"", ""Multicenter Study"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Sinha M"", ""Zhang L"", ""Subudhi S"", ""Chen B"", ""Marquez J"", ""Liu EV"", ""Allaire K"", ""Cheung A"", ""Ng S"", ""Nguyen C"", ""Friedlander TW"", ""Aggarwal R"", ""Spitzer M"", ""Allison JP"", ""Small EJ"", ""Sharma P"", ""Fong L""]",10.1136/jitc-2020-002254,Sinha M,Journal for immunotherapy of cancer,2051-1426,5,J Immunother Cancer,eng,Fong L,"[""Aged"", ""Biomarkers, Tumor"", ""CTLA-4 Antigen"", ""Cancer Vaccines"", ""Cells, Cultured"", ""Humans"", ""Immune Checkpoint Inhibitors"", ""Ipilimumab"", ""Lymphocyte Activation"", ""Lymphocytes, Tumor-Infiltrating"", ""Male"", ""Middle Aged"", ""Prostatic Neoplasms, Castration-Resistant"", ""Th1 Cells"", ""Time Factors"", ""Tissue Extracts"", ""Treatment Outcome"", ""Tumor Microenvironment""]",,33986125,pmc-id: PMC8126308;,2021 May,2021,https://pubmed.ncbi.nlm.nih.gov/33986125/,Pre-existing immune status associated with response to combination of sipuleucel-T and ipilimumab in patients with metastatic castration-resistant prostate cancer,9,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Immune receptors expressed on TAMs are intriguing targets for tumor immunotherapy. In this study, we found inhibitory receptor LILRB4 on a variety of intratumoral immune cell types in murine tumor models and human cancers, most prominently on TAMs. LILRB4, known as gp49B in mice, is a LILRB family receptor. Human and murine LILRB4 have two extracellular domains but differ in the number of intracellular ITIMs (three versus two). We observed a high correlation in LILRB4 expression with other immune inhibitory receptors. After tumor challenge, LILRB4-/- mice and mice treated with anti-LILRB4 antibody showed reduced tumor burden and increased survival. LILRB4-/- genotype or LILRB4 blockade increased tumor immune infiltrates and the effector (Teff) to regulatory (Treg) T cell ratio and modulated phenotypes of TAMs toward less suppressive, CD4+ T cells to Th1 effector, and CD8+ T cells to less exhausted. These findings reveal that LILRB4 strongly suppresses tumor immunity in TME and that alleviating that suppression provides antitumor efficacy.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Sharma N"", ""Atolagbe OT"", ""Ge Z"", ""Allison JP""]",10.1084/jem.20201811,Sharma N,The Journal of experimental medicine,0022-1007,7,J Exp Med,eng,Allison JP,"[""Animals"", ""CD4-Positive T-Lymphocytes"", ""CD8-Positive T-Lymphocytes"", ""Cell Line, Tumor"", ""Cell Movement"", ""Humans"", ""Immunotherapy"", ""Membrane Glycoproteins"", ""Mice"", ""Mice, Inbred C57BL"", ""Neoplasms"", ""Receptors, Immunologic"", ""T-Lymphocytes, Regulatory""]",,33974041,pmc-id: PMC8117208;,2021 Jul 5,2021,https://pubmed.ncbi.nlm.nih.gov/33974041/,LILRB4 suppresses immunity in solid tumors and is a potential target for immunotherapy,218,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Leucine-rich repeat containing 15 (LRRC15) is expressed on stromal fibroblasts in the tumor microenvironment of multiple solid tumor types and may represent an interesting target for therapy, particularly in patients with sarcomas where LRRC15 is also expressed by malignant cells. ABBV-085 is a monomethyl auristatin-E antibody-drug conjugate that targets LRRC15 and showed antineoplastic efficacy in preclinical experiments. Herein, we report findings of ABBV-085 monotherapy or combination therapy in adult patients with sarcomas and other advanced solid tumors. This first-in-human phase I study (NCT02565758) assessed ABBV-085 safety, pharmacokinetics/pharmacodynamics, and preliminary antitumor activity. The study consisted of two parts: dose escalation and dose expansion. ABBV-085 was administered by intravenous infusion at 0.3 to 6.0 mg/kg every 14 days. In total, 85 patients were enrolled; 45 patients received the recommended expansion dose of 3.6 mg/kg ABBV-085 monotherapy, including 10 with osteosarcoma and 10 with undifferentiated pleomorphic sarcoma (UPS). Most common treatment-related adverse events were fatigue, nausea, and decreased appetite. The overall response rate for patients with osteosarcoma/UPS treated at 3.6 mg/kg was 20%, including four confirmed partial responses. No monotherapy responses were observed for other advanced cancers treated at 3.6 mg/kg. One patient treated with ABBV-085 plus gemcitabine achieved partial response. ABBV-085 appeared safe and tolerable at a dose of 3.6 mg/kg every 14 days, with preliminary antitumor activity noted in patients with osteosarcoma and UPS. Given the high unmet need in these orphan malignancies, further investigation into targeting LRRC15 in these sarcomas may be warranted.","[""Clinical Trial, Phase I"", ""Journal Article""]","[""Demetri GD"", ""Luke JJ"", ""Hollebecque A"", ""Powderly JD 2nd"", ""Spira AI"", ""Subbiah V"", ""Naumovski L"", ""Chen C"", ""Fang H"", ""Lai DW"", ""Yue H"", ""Polepally AR"", ""Purcell JW"", ""Robinson R"", ""Sharma P"", ""Allison JP"", ""Tolcher A"", ""Villalobos VM""]",10.1158/1078-0432.CCR-20-4513,Demetri GD,Clinical cancer research : an official journal of the American Association for Cancer Research,1078-0432,13,Clin Cancer Res,eng,Villalobos VM,"[""Adult"", ""Antineoplastic Agents"", ""Bone Neoplasms"", ""Humans"", ""Immunoconjugates"", ""Membrane Proteins"", ""Neoplasms"", ""Sarcoma"", ""Tumor Microenvironment""]",3556-3566,33820780,,2021 Jul 1,2021,https://pubmed.ncbi.nlm.nih.gov/33820780/,"First-in-Human Phase I Study of ABBV-085, an Antibody-Drug Conjugate Targeting LRRC15, in Sarcomas and Other Advanced Solid Tumors",27,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Immune checkpoint therapy (ICT) can provide durable clinical responses and improve overall survival. However, only subsets of patients with specific tumor types respond to ICT. Thus, significant challenges remain, including understanding pathways of resistance, optimizing patient selection, improving management of immune-related adverse events, and identifying rational therapeutic combinations. These challenges will need a focused approach encompassing both clinical and basic research, with the integration of reverse translational studies. This integrated approach will lead to identification of potential targets for subsequent clinical trials, which will guide decisions as we develop novel combination strategies to maximize efficacy and minimize toxicities for patients. SIGNIFICANCE: ICTs induce durable antitumor responses for subsets of patients with cancer. Recent evidence suggests that rational combinatorial strategies can improve response by overcoming primary and adaptive resistance mechanisms, although these may carry an increased risk of immune-mediated toxicities. This review surveys the current understanding of mechanisms of response and resistance to ICTs and active areas of investigation, and proposes a path forward to improving efficacy and minimizing toxicities through better patient selection and rational combinations.","[""Journal Article"", ""Review""]","[""Sharma P"", ""Siddiqui BA"", ""Anandhan S"", ""Yadav SS"", ""Subudhi SK"", ""Gao J"", ""Goswami S"", ""Allison JP""]",10.1158/2159-8290.CD-20-1680,Sharma P,Cancer discovery,2159-8274,4,Cancer Discov,eng,Allison JP,"[""Drug Discovery"", ""Forecasting"", ""Humans"", ""Immune Checkpoint Inhibitors"", ""Neoplasms""]",838-857,33811120,,2021 Apr,2021,https://pubmed.ncbi.nlm.nih.gov/33811120/,The Next Decade of Immune Checkpoint Therapy,11,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Ipilimumab improves clinical outcomes when combined with nivolumab in metastatic non-small cell lung cancer (NSCLC), but its efficacy and impact on the immune microenvironment in operable NSCLC remain unclear. We report the results of the phase 2 randomized NEOSTAR trial (NCT03158129) of neoadjuvant nivolumab or nivolumab + ipilimumab followed by surgery in 44 patients with operable NSCLC, using major pathologic response (MPR) as the primary endpoint. The MPR rate for each treatment arm was tested against historical controls of neoadjuvant chemotherapy. The nivolumab + ipilimumab arm met the prespecified primary endpoint threshold of 6 MPRs in 21 patients, achieving a 38% MPR rate (8/21). We observed a 22% MPR rate (5/23) in the nivolumab arm. In 37 patients resected on trial, nivolumab and nivolumab + ipilimumab produced MPR rates of 24% (5/21) and 50% (8/16), respectively. Compared with nivolumab, nivolumab + ipilimumab resulted in higher pathologic complete response rates (10% versus 38%), less viable tumor (median 50% versus 9%), and greater frequencies of effector, tissue-resident memory and effector memory T cells. Increased abundance of gut Ruminococcus and Akkermansia spp. was associated with MPR to dual therapy. Our data indicate that neoadjuvant nivolumab + ipilimumab-based therapy enhances pathologic responses, tumor immune infiltrates and immunologic memory, and merits further investigation in operable NSCLC.","[""Clinical Trial, Phase II"", ""Journal Article"", ""Randomized Controlled Trial"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Cascone T"", ""William WN Jr"", ""Weissferdt A"", ""Leung CH"", ""Lin HY"", ""Pataer A"", ""Godoy MCB"", ""Carter BW"", ""Federico L"", ""Reuben A"", ""Khan MAW"", ""Dejima H"", ""Francisco-Cruz A"", ""Parra ER"", ""Solis LM"", ""Fujimoto J"", ""Tran HT"", ""Kalhor N"", ""Fossella FV"", ""Mott FE"", ""Tsao AS"", ""Blumenschein G Jr"", ""Le X"", ""Zhang J"", ""Skoulidis F"", ""Kurie JM"", ""Altan M"", ""Lu C"", ""Glisson BS"", ""Byers LA"", ""Elamin YY"", ""Mehran RJ"", ""Rice DC"", ""Walsh GL"", ""Hofstetter WL"", ""Roth JA"", ""Antonoff MB"", ""Kadara H"", ""Haymaker C"", ""Bernatchez C"", ""Ajami NJ"", ""Jenq RR"", ""Sharma P"", ""Allison JP"", ""Futreal A"", ""Wargo JA"", ""Wistuba II"", ""Swisher SG"", ""Lee JJ"", ""Gibbons DL"", ""Vaporciyan AA"", ""Heymach JV"", ""Sepesi B""]",10.1038/s41591-020-01224-2,Cascone T,Nature medicine,1078-8956,3,Nat Med,eng,Sepesi B,"[""Adult"", ""Aged"", ""Antineoplastic Combined Chemotherapy Protocols"", ""Biomarkers, Tumor"", ""Carcinoma, Non-Small-Cell Lung"", ""Female"", ""Humans"", ""Ipilimumab"", ""Lung Neoplasms"", ""Male"", ""Middle Aged"", ""Neoadjuvant Therapy"", ""Nivolumab""]",504-514,33603241,pmc-id: PMC8818318;manuscript-id: NIHMS1761424;,2021 Mar,2021,https://pubmed.ncbi.nlm.nih.gov/33603241/,Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial,27,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Immune checkpoint inhibitors (ICI) targeting CTLA4 or PD-1/PD-L1 have transformed cancer therapy but are associated with immune-related adverse events, including myocarditis. Here, we report a robust preclinical mouse model of ICI-associated myocarditis in which monoallelic loss of Ctla4 in the context of complete genetic absence of Pdcd1 leads to premature death in approximately half of mice. Premature death results from myocardial infiltration by T cells and macrophages and severe ECG abnormalities, closely recapitulating the clinical and pathologic hallmarks of ICI-associated myocarditis observed in patients. Using this model, we show that Ctla4 and Pdcd1 functionally interact in a gene dosage-dependent manner, providing a mechanism by which myocarditis arises with increased frequency in the setting of combination ICI therapy. We demonstrate that intervention with CTLA4-Ig (abatacept) is sufficient to ameliorate disease progression and additionally provide a case series of patients in which abatacept mitigates the fulminant course of ICI myocarditis. SIGNIFICANCE: We provide a preclinical model of ICI-associated myocarditis which recapitulates this clinical syndrome. Using this model, we demonstrate that CTLA4 and PD-1 (ICI targets) functionally interact for myocarditis development and that intervention with CTLA4-Ig (abatacept) attenuates myocarditis, providing mechanistic rationale and preclinical support for therapeutic clinical studies.See related commentary by Young and Bluestone, p. 537.This article is highlighted in the In This Issue feature, p. 521.","[""Journal Article"", ""Research Support, N.I.H., Extramural""]","[""Wei SC"", ""Meijers WC"", ""Axelrod ML"", ""Anang NAS"", ""Screever EM"", ""Wescott EC"", ""Johnson DB"", ""Whitley E"", ""Lehmann L"", ""Courand PY"", ""Mancuso JJ"", ""Himmel LE"", ""Lebrun-Vignes B"", ""Wleklinski MJ"", ""Knollmann BC"", ""Srinivasan J"", ""Li Y"", ""Atolagbe OT"", ""Rao X"", ""Zhao Y"", ""Wang J"", ""Ehrlich LIR"", ""Sharma P"", ""Salem JE"", ""Balko JM"", ""Moslehi JJ"", ""Allison JP""]",10.1158/2159-8290.CD-20-0856,Wei SC,Cancer discovery,2159-8274,3,Cancer Discov,eng,Allison JP,"[""Animals"", ""Biomarkers, Tumor"", ""Cardiotoxicity"", ""Disease Management"", ""Disease Models, Animal"", ""Disease Susceptibility"", ""Electrocardiography"", ""Humans"", ""Immune Checkpoint Inhibitors"", ""Mice"", ""Molecular Targeted Therapy"", ""Myocarditis"", ""Neoplasms""]",614-625,33257470,pmc-id: PMC8041233;manuscript-id: NIHMS1650918;,2021 Mar,2021,https://pubmed.ncbi.nlm.nih.gov/33257470/,A Genetic Mouse Model Recapitulates Immune Checkpoint Inhibitor-Associated Myocarditis and Supports a Mechanism-Based Therapeutic Intervention,11,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Cancer immunotherapy has dramatically changed the approach to cancer treatment. The aim of targeting the immune system to recognize and destroy cancer cells has afforded many patients the prospect of achieving deep, long-term remission and potential cures. However, many challenges remain for achieving the goal of effective immunotherapy for all cancer patients. Checkpoint inhibitors have been able to achieve long-term responses in a minority of patients, yet improving response rates with combination therapies increases the possibility of toxicity. Chimeric antigen receptor T cells have demonstrated high response rates in hematological cancers, although most patients experience relapse. In addition, some cancers are notoriously immunologically ""cold"" and typically are not effective targets for immunotherapy. Overcoming these obstacles will require new strategies to improve upon the efficacy of current agents, identify biomarkers to select appropriate therapies, and discover new modalities to expand the accessibility of immunotherapy to additional tumor types and patient populations.","[""Journal Article"", ""Review""]","[""Cable J"", ""Greenbaum B"", ""Pe'er D"", ""Bollard CM"", ""Bruni S"", ""Griffin ME"", ""Allison JP"", ""Wu CJ"", ""Subudhi SK"", ""Mardis ER"", ""Brentjens R"", ""Sosman JA"", ""Cemerski S"", ""Zavitsanou AM"", ""Proia T"", ""Egeblad M"", ""Nolan G"", ""Goswami S"", ""Spranger S"", ""Mackall CL""]",10.1111/nyas.14526,Cable J,Annals of the New York Academy of Sciences,0077-8923,1,Ann N Y Acad Sci,eng,Mackall CL,"[""Biomarkers, Tumor"", ""Cancer Vaccines"", ""Combined Modality Therapy"", ""Humans"", ""Immune Checkpoint Inhibitors"", ""Immunotherapy"", ""Immunotherapy, Adoptive"", ""Neoplasm Recurrence, Local"", ""Neoplasms"", ""Tumor Microenvironment""]",30-47,33184911,,2021 Apr,2021,https://pubmed.ncbi.nlm.nih.gov/33184911/,Frontiers in cancer immunotherapy-a symposium report,1489,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Immune checkpoint therapy is being tested in the neoadjuvant setting for patients with localized urothelial carcinoma1,2, with one study reporting data in cisplatin-ineligible patients who received anti-PD-L1 monotherapy2. The study reported that patients with bulky tumors, a known high-risk feature defined as greater than clinical T2 disease, had fewer responses, with pathological complete response rate of 17%2. Here we report on the first pilot combination neoadjuvant trial ( NCT02812420 ) with anti-PD-L1 (durvalumab) plus anti-CTLA-4 (tremelimumab) in cisplatin-ineligible patients, with all tumors identified as having high-risk features (n = 28). High-risk features were defined by bulky tumors, variant histology, lymphovascular invasion, hydronephrosis and/or high-grade upper tract disease3-5. The primary endpoint was safety and we observed 6 of 28 patients (21%) with grade ≥3 immune-related adverse events, consisting of asymptomatic laboratory abnormalities (n = 4), hepatitis and colitis (n = 2). We also observed pathological complete response of 37.5% and downstaging to pT1 or less in 58% of patients who completed surgery (n = 24). In summary, we provide initial safety, efficacy and biomarker data with neoadjuvant combination anti-PD-L1 plus anti-CTLA-4, which warrants further development for patients with localized urothelial carcinoma, especially cisplatin-ineligible patients with high-risk features who do not currently have an established standard-of-care neoadjuvant treatment.","[""Clinical Trial"", ""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Gao J"", ""Navai N"", ""Alhalabi O"", ""Siefker-Radtke A"", ""Campbell MT"", ""Tidwell RS"", ""Guo CC"", ""Kamat AM"", ""Matin SF"", ""Araujo JC"", ""Shah AY"", ""Msaouel P"", ""Corn P"", ""Wang J"", ""Papadopoulos JN"", ""Yadav SS"", ""Blando JM"", ""Duan F"", ""Basu S"", ""Liu W"", ""Shen Y"", ""Zhang Y"", ""Macaluso MD"", ""Wang Y"", ""Chen J"", ""Zhang J"", ""Futreal A"", ""Dinney C"", ""Allison JP"", ""Goswami S"", ""Sharma P""]",10.1038/s41591-020-1086-y,Gao J,Nature medicine,1078-8956,12,Nat Med,eng,Sharma P,"[""Adult"", ""Aged"", ""Antibodies, Monoclonal"", ""Antibodies, Monoclonal, Humanized"", ""Antineoplastic Agents, Immunological"", ""Antineoplastic Combined Chemotherapy Protocols"", ""CTLA-4 Antigen"", ""Carcinoma"", ""Cisplatin"", ""Female"", ""Humans"", ""Male"", ""Middle Aged"", ""Neoplasm Staging"", ""Programmed Cell Death 1 Receptor"", ""Risk Factors"", ""Urothelium""]",1845-1851,33046869,pmc-id: PMC9768836;manuscript-id: NIHMS1850949;,2020 Dec,2020,https://pubmed.ncbi.nlm.nih.gov/33046869/,Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma,26,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Evaluation of potential immunity against the novel severe acute respiratory syndrome (SARS) coronavirus that emerged in 2019 (SARS-CoV-2) is essential for health, as well as social and economic recovery. Generation of antibody response to SARS-CoV-2 (seroconversion) may inform on acquired immunity from prior exposure, and antibodies against the SARS-CoV-2 spike protein receptor binding domain (S-RBD) are speculated to neutralize virus infection. Some serology assays rely solely on SARS-CoV-2 nucleocapsid protein (N-protein) as the antibody detection antigen; however, whether such immune responses correlate with S-RBD response and COVID-19 immunity remains unknown. Here, we generated a quantitative serological ELISA using recombinant S-RBD and N-protein for the detection of circulating antibodies in 138 serial serum samples from 30 reverse transcription PCR-confirmed, SARS-CoV-2-hospitalized patients, as well as 464 healthy and non-COVID-19 serum samples that were collected between June 2017 and June 2020. Quantitative detection of IgG antibodies against the 2 different viral proteins showed a moderate correlation. Antibodies against N-protein were detected at a rate of 3.6% in healthy and non-COVID-19 sera collected during the pandemic in 2020, whereas 1.9% of these sera were positive for S-RBD. Approximately 86% of individuals positive for S-RBD-binding antibodies exhibited neutralizing capacity, but only 74% of N-protein-positive individuals exhibited neutralizing capacity. Collectively, our studies show that detection of N-protein-binding antibodies does not always correlate with presence of S-RBD-neutralizing antibodies and caution against the extensive use of N-protein-based serology testing for determination of potential COVID-19 immunity.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""McAndrews KM"", ""Dowlatshahi DP"", ""Dai J"", ""Becker LM"", ""Hensel J"", ""Snowden LM"", ""Leveille JM"", ""Brunner MR"", ""Holden KW"", ""Hopkins NS"", ""Harris AM"", ""Kumpati J"", ""Whitt MA"", ""Lee JJ"", ""Ostrosky-Zeichner LL"", ""Papanna R"", ""LeBleu VS"", ""Allison JP"", ""Kalluri R""]",10.1172/jci.insight.142386,McAndrews KM,JCI insight,2379-3708,18,JCI Insight,eng,Kalluri R,"[""Adaptive Immunity"", ""Antibodies, Neutralizing"", ""Antibodies, Viral"", ""Betacoronavirus"", ""COVID-19"", ""COVID-19 Testing"", ""Clinical Laboratory Techniques"", ""Coronavirus Infections"", ""Female"", ""Humans"", ""Male"", ""Middle Aged"", ""Nucleocapsid"", ""Outcome Assessment, Health Care"", ""Pandemics"", ""Pneumonia, Viral"", ""Protein Binding"", ""SARS-CoV-2"", ""Sensitivity and Specificity"", ""Seroconversion"", ""Serologic Tests"", ""Spike Glycoprotein, Coronavirus""]",,32796155,pmc-id: PMC7526535;,2020 Sep 17,2020,https://pubmed.ncbi.nlm.nih.gov/32796155/,Heterogeneous antibodies against SARS-CoV-2 spike receptor binding domain and nucleocapsid with implications for COVID-19 immunity,5,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Immune checkpoint therapy (ICT) can produce durable antitumor responses in metastatic urothelial carcinoma (mUCC); however, the responses are not universal. Despite multiple approvals of ICT in mUCC, we lack predictive biomarkers to guide patient selection. The identification of biomarkers may require interrogation of both the tumor mutational status and the immune microenvironment. Through multi-platform immuno-genomic analyses of baseline tumor tissues, we identified the mutation of AT-rich interactive domain-containing protein 1A (ARID1A) in tumor cells and expression of immune cytokine CXCL13 in the baseline tumor tissues as two predictors of clinical responses in a discovery cohort (n = 31). Further, reverse translational studies revealed that CXCL13-/- tumor-bearing mice were resistant to ICT, whereas ARID1A knockdown enhanced sensitivity to ICT in a murine model of bladder cancer. Next, we tested the clinical relevance of ARID1A mutation and baseline CXCL13 expression in two independent confirmatory cohorts (CheckMate275 and IMvigor210). We found that ARID1A mutation and expression of CXCL13 in the baseline tumor tissues correlated with improved overall survival (OS) in both confirmatory cohorts (CheckMate275, CXCL13 data, n = 217; ARID1A data, n = 139, and IMvigor210, CXCL13 data, n = 348; ARID1A data, n = 275). We then interrogated CXCL13 expression plus ARID1A mutation as a combination biomarker in predicting response to ICT in CheckMate275 and IMvigor210. Combination of the two biomarkers in baseline tumor tissues suggested improved OS compared to either single biomarker. Cumulatively, this study revealed that the combination of CXCL13 plus ARID1A may improve prediction capability for patients receiving ICT.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Goswami S"", ""Chen Y"", ""Anandhan S"", ""Szabo PM"", ""Basu S"", ""Blando JM"", ""Liu W"", ""Zhang J"", ""Natarajan SM"", ""Xiong L"", ""Guan B"", ""Yadav SS"", ""Saci A"", ""Allison JP"", ""Galsky MD"", ""Sharma P""]",10.1126/scitranslmed.abc4220,Goswami S,Science translational medicine,1946-6234,548,Sci Transl Med,eng,Sharma P,"[""Animals"", ""Biomarkers"", ""Biomarkers, Tumor"", ""Chemokine CXCL13"", ""DNA-Binding Proteins"", ""Humans"", ""Mice"", ""Mutation"", ""Transcription Factors"", ""Tumor Microenvironment"", ""Urinary Bladder Neoplasms""]",,32554706,,2020 Jun 17,2020,https://pubmed.ncbi.nlm.nih.gov/32554706/,ARID1A mutation plus CXCL13 expression act as combinatorial biomarkers to predict responses to immune checkpoint therapy in mUCC,12,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Complex tumor microenvironmental (TME) features influence the outcome of cancer immunotherapy (IO). Here we perform immunogenomic analyses on 67 intratumor sub-regions of a PD-1 inhibitor-resistant melanoma tumor and 2 additional metastases arising over 8 years, to characterize TME interactions. We identify spatially distinct evolution of copy number alterations influencing local immune composition. Sub-regions with chromosome 7 gain display a relative lack of leukocyte infiltrate but evidence of neutrophil activation, recapitulated in The Cancer Genome Atlas (TCGA) samples, and associated with lack of response to IO across three clinical cohorts. Whether neutrophil activation represents cause or consequence of local tumor necrosis requires further study. Analyses of T-cell clonotypes reveal the presence of recurrent priming events manifesting in a dominant T-cell clonotype over many years. Our findings highlight the links between marked levels of genomic and immune heterogeneity within the physical space of a tumor, with implications for biomarker evaluation and immunotherapy response.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't"", ""Research Support, U.S. Gov't, Non-P.H.S.""]","[""Mitra A"", ""Andrews MC"", ""Roh W"", ""De Macedo MP"", ""Hudgens CW"", ""Carapeto F"", ""Singh S"", ""Reuben A"", ""Wang F"", ""Mao X"", ""Song X"", ""Wani K"", ""Tippen S"", ""Ng KS"", ""Schalck A"", ""Sakellariou-Thompson DA"", ""Chen E"", ""Reddy SM"", ""Spencer CN"", ""Wiesnoski D"", ""Little LD"", ""Gumbs C"", ""Cooper ZA"", ""Burton EM"", ""Hwu P"", ""Davies MA"", ""Zhang J"", ""Bernatchez C"", ""Navin N"", ""Sharma P"", ""Allison JP"", ""Wargo JA"", ""Yee C"", ""Tetzlaff MT"", ""Hwu WJ"", ""Lazar AJ"", ""Futreal PA""]",10.1038/s41467-020-15538-9,Mitra A,Nature communications,2041-1723,1,Nat Commun,eng,Futreal PA,"[""Biomarkers, Tumor"", ""DNA Copy Number Variations"", ""Genomics"", ""Humans"", ""Melanoma"", ""Mutation"", ""Neutrophil Activation"", ""Tumor Microenvironment""]",1839,32296058,pmc-id: PMC7160105;,2020 Apr 15,2020,https://pubmed.ncbi.nlm.nih.gov/32296058/,Spatially resolved analyses link genomic and immune diversity and reveal unfavorable neutrophil activation in melanoma,11,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Tumors with high mutational burden (TMB) tend to be responsive to immune checkpoint blockade (ICB) because there are neoantigens available for targeting by reinvigorated T cells, whereas those with low TMB demonstrate limited clinical responses. To determine whether antigen-specific T cell responses can be elicited after treatment with ICB in cancers that have a low TMB, we conducted a clinical trial with ipilimumab in 30 patients with metastatic castration-resistant prostate cancer. We identified two distinct cohorts by survival and progression times: ""favorable"" (n = 9) and ""unfavorable"" (n = 10). Patients in the favorable cohort had high intratumoral CD8 T cell density and IFN-γ response gene signature and/or antigen-specific T cell responses. Two patients with a relatively low TMB had T cell responses against unique neoantigens. Moreover, six of nine patients in the favorable group are still alive at the time of analysis, with survival ranging from 33 to 54 months after treatment. All 10 patients in the unfavorable cohort have succumbed to their disease and had survival ranging from 0.6 to 10.3 months. Collectively, our data indicate that immunological correlates associated with effector T cell responses are observed in patients with metastatic prostate cancer who benefit from ICB.","[""Clinical Trial"", ""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Subudhi SK"", ""Vence L"", ""Zhao H"", ""Blando J"", ""Yadav SS"", ""Xiong Q"", ""Reuben A"", ""Aparicio A"", ""Corn PG"", ""Chapin BF"", ""Pisters LL"", ""Troncoso P"", ""Tidwell RS"", ""Thall P"", ""Wu CJ"", ""Zhang J"", ""Logothetis CL"", ""Futreal A"", ""Allison JP"", ""Sharma P""]",10.1126/scitranslmed.aaz3577,Subudhi SK,Science translational medicine,1946-6234,537,Sci Transl Med,eng,Sharma P,"[""Antineoplastic Agents, Immunological"", ""Biomarkers, Tumor"", ""CD8-Positive T-Lymphocytes"", ""Cohort Studies"", ""Humans"", ""Ipilimumab"", ""Male"", ""Prostatic Neoplasms""]",,32238575,,2020 Apr 1,2020,https://pubmed.ncbi.nlm.nih.gov/32238575/,"Neoantigen responses, immune correlates, and favorable outcomes after ipilimumab treatment of patients with prostate cancer",12,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Immunotherapy targeting T cells is increasingly utilized to treat solid tumors including non-small cell lung cancer (NSCLC). This requires a better understanding of the T cells in the lungs of patients with NSCLC. Here, we report T cell repertoire analysis in a cohort of 236 early-stage NSCLC patients. T cell repertoire attributes are associated with clinicopathologic features, mutational and immune landscape. A considerable proportion of the most prevalent T cells in tumors are also prevalent in the uninvolved tumor-adjacent lungs and appear specific to shared background mutations or viral infections. Patients with higher T cell repertoire homology between the tumor and uninvolved tumor-adjacent lung, suggesting a less tumor-focused T cell response, exhibit inferior survival. These findings indicate that a concise understanding of antigens and T cells in NSCLC is needed to improve therapeutic efficacy and reduce toxicity with immunotherapy, particularly adoptive T cell therapy.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't"", ""Research Support, U.S. Gov't, Non-P.H.S.""]","[""Reuben A"", ""Zhang J"", ""Chiou SH"", ""Gittelman RM"", ""Li J"", ""Lee WC"", ""Fujimoto J"", ""Behrens C"", ""Liu X"", ""Wang F"", ""Quek K"", ""Wang C"", ""Kheradmand F"", ""Chen R"", ""Chow CW"", ""Lin H"", ""Bernatchez C"", ""Jalali A"", ""Hu X"", ""Wu CJ"", ""Eterovic AK"", ""Parra ER"", ""Yusko E"", ""Emerson R"", ""Benzeno S"", ""Vignali M"", ""Wu X"", ""Ye Y"", ""Little LD"", ""Gumbs C"", ""Mao X"", ""Song X"", ""Tippen S"", ""Thornton RL"", ""Cascone T"", ""Snyder A"", ""Wargo JA"", ""Herbst R"", ""Swisher S"", ""Kadara H"", ""Moran C"", ""Kalhor N"", ""Zhang J"", ""Scheet P"", ""Vaporciyan AA"", ""Sepesi B"", ""Gibbons DL"", ""Robins H"", ""Hwu P"", ""Heymach JV"", ""Sharma P"", ""Allison JP"", ""Baladandayuthapani V"", ""Lee JJ"", ""Davis MM"", ""Wistuba II"", ""Futreal PA"", ""Zhang J""]",10.1038/s41467-019-14273-0,Reuben A,Nature communications,2041-1723,1,Nat Commun,eng,Zhang J,"[""Adult"", ""Aged"", ""Carcinoma, Non-Small-Cell Lung"", ""Clone Cells"", ""ErbB Receptors"", ""Female"", ""Humans"", ""Lung"", ""Lung Neoplasms"", ""Lymphocyte Activation"", ""Lymphocyte Count"", ""Male"", ""Middle Aged"", ""Mutation"", ""Survival Analysis"", ""T-Lymphocytes""]",603,32001676,pmc-id: PMC6992630;,2020 Jan 30,2020,https://pubmed.ncbi.nlm.nih.gov/32001676/,Comprehensive T cell repertoire characterization of non-small cell lung cancer,11,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
,"[""Journal Article"", ""Review""]","[""Sharma P"", ""Allison JP""]",10.1038/s41577-020-0275-8,Sharma P,Nature reviews. Immunology,1474-1733,2,Nat Rev Immunol,eng,Allison JP,"[""Animals"", ""Antineoplastic Agents, Immunological"", ""Antineoplastic Combined Chemotherapy Protocols"", ""B7-H1 Antigen"", ""CD4-Positive T-Lymphocytes"", ""CD8-Positive T-Lymphocytes"", ""CTLA-4 Antigen"", ""Drug Resistance, Neoplasm"", ""Humans"", ""Mice"", ""Mice, Knockout"", ""Neoplasms"", ""Programmed Cell Death 1 Receptor""]",75-76,31925406,,2020 Feb,2020,https://pubmed.ncbi.nlm.nih.gov/31925406/,Dissecting the mechanisms of immune checkpoint therapy,20,yBj2TdeIomEieGdeq,XPhU2PuVb7lwS7iwZ
"Spinal cord injury (SCI) causes irreversible motor and sensory deficits, and no therapy currently restores the damaged neural circuitry. Previous work has shown that transplantation of induced pluripotent stem cell (iPSC)-derived neural stem/progenitor cells (NS/PCs) restored motor function in preclinical models of subacute SCI; however, the safety of this approach in humans remains unknown. Here we report results from a first-in-human, open-label study of iPSC-NS/PC transplantation in four patients with subacute cervical complete SCI. The primary safety end point was achieved, with no tumor formation or graft-related adverse events observed during 2-4 years of follow-up and stable graft sites on imaging. Exploratory efficacy was assessed as a secondary end point. Median improvement in the International Standards for Neurological Classification of Spinal Cord Injury motor score from baseline (2 weeks after injury) to week 52 was 13 points (range 10-40), with two patients improving in American Spinal Injury Association Impairment Scale (grade A → C and A → D). These gains were numerically greater than spontaneous recovery observed in a registry-based cohort. This study provides clinical evidence that transplantation of human iPSC-NS/PCs into the injured spinal cord is feasible and safe under short-term immunosuppression, with findings supporting further clinical evaluation. The trial is registered at UMIN000035074 , UMIN000050104 and jRCTa031190228 .","[""Journal Article""]","[""Sugai K"", ""Tsuji O"", ""Fujiyoshi K"", ""Ozaki M"", ""Abe T"", ""Kohzuki T"", ""Okawara H"", ""Sawada T"", ""Sumida M"", ""Yoshioka E"", ""Shofuda T"", ""Kawashima S"", ""Yamaguchi R"", ""Shinozaki M"", ""Takasu N"", ""Nagoshi N"", ""Okubo T"", ""Kohyama J"", ""Maeda T"", ""Yato Y"", ""Kanemura Y"", ""Yamanaka S"", ""Nakamura M"", ""Okano H""]",10.1038/s41591-026-04549-6,Sugai K,Nature medicine,1078-8956,,Nat Med,eng,Okano H,[],,42481854,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42481854/,An iPSC-derived neural progenitor cell therapy for subacute spinal cord injury: a phase 1 trial with long-term follow-up,,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Male germline development is characterized by a unique perinatal phase in which primordial germ cells (PGCs) differentiate into gonocytes (prospermatogonia) and subsequently give rise to spermatogonia. This chapter outlines the cellular, molecular, and epigenetic programs that orchestrate this transition, establishing the foundation of the lifelong spermatogenic lineage. Gonocytes undergo a transient G0/G1 arrest tightly regulated by retinoic acid (RA) metabolism, CDK inhibition, TGF family signaling, and the RNA-binding protein NANOS2, which integrates somatic cues to suppress meiosis and enforce male fate. Concurrently, gonocytes experience genome-wide de novo DNA methylation driven by NSD1-mediated H3K36me2 deposition and the DNMT3A/DNMT3L/DNMT3C machinery, accompanied by piRNA-directed transposon silencing and paternal imprint establishment. These processes collectively reshape the chromatin landscape and stabilize the male germline epigenome. The subsequent gonocyte-to-spermatogonia transition (GST) involves FGF, GDNF, and RA signaling, as well as dynamic histone demethylation, to generate spermatogonial stem cells (SSCs). Aberrant regulation of these pathways can arrest differentiation and predispose germ cells to transformation, as seen in testicular germ cell tumors (TGCTs), whose precursor cells retain gonocyte-like features. We further discuss the interplay between transposon control, imprinting, and chromatin architecture that underpins gonocyte identity. Emerging single-cell and small-input omics approaches are now redefining this transient developmental state, providing new insight into how epigenetic reprogramming and signaling convergence establish the male germline.","[""Journal Article"", ""Review""]","[""Li P"", ""Ohhata T"", ""Sakai S"", ""Niida H"", ""Yamanaka S""]",10.1007/978-981-92-1439-6_1,Li P,Advances in experimental medicine and biology,0065-2598,,Adv Exp Med Biol,eng,Yamanaka S,"[""Animals"", ""Male"", ""Humans"", ""Epigenesis, Genetic"", ""DNA Methylation"", ""Spermatogenesis"", ""Spermatogonia"", ""Cell Differentiation"", ""Signal Transduction"", ""Gene Expression Regulation, Developmental"", ""Germ Cells""]",3-16,42455434,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42455434/,Gonocytes in Transition: Establishing the Male Germline Identity,1517,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
,"[""Journal Article""]","[""Yamamoto S"", ""Yamanaka S"", ""Yokoo T"", ""Kimura T"", ""Egawa S""]",10.1016/j.eururo.2026.05.016,Yamamoto S,European urology,0302-2838,,Eur Urol,eng,Egawa S,[],,42350164,,2026 Jun 26,2026,https://pubmed.ncbi.nlm.nih.gov/42350164/,Re: Xenotransplantation of a Porcine Kidney for End-stage Kidney Disease,,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
,"[""Journal Article""]","[""Kobayashi N"", ""Tokuyama H"", ""Yamanaka S"", ""Kanamori T"", ""Sato N""]",10.1253/circj.CJ-26-0380,Kobayashi N,Circulation journal : official journal of the Japanese Circulation Society,1346-9843,8,Circ J,eng,Sato N,[],1113,42342341,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42342341/,Rupture of a Splenic Artery Aneurysm After Thrombolysis Mimicking a Pancreatic Cyst,90,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Thrombus formation after successful left atrial appendage occlusion (LAAO) has been well described; however, the clinical course after aborted LAAO remains poorly characterized. An 84-year-old man with atrial fibrillation and a history of cardioembolic events underwent an attempted LAAO procedure that was aborted because of unfavorable appendage anatomy. A small thrombus suspected on transthoracic echocardiography the day after the procedure progressively enlarged over 3 months and ultimately required surgical thrombus removal and left atrial appendage resection. Thrombus formation after an aborted LAAO attempt is not routinely observed, particularly under therapeutic anticoagulation. In this case, temporary interruption of anticoagulation, local endothelial disruption, blood stasis, and a possible prothrombotic milieu may have contributed. Progressive native left atrial appendage thrombus may occur after aborted LAAO despite anticoagulation therapy. Careful postprocedural imaging surveillance should be considered in high-risk patients.","[""Case Reports"", ""Journal Article""]","[""Kawahara R"", ""Tokuyama H"", ""Yamanaka S"", ""Yui Y"", ""Kobayashi N"", ""Ota H"", ""Miyauchi Y""]",10.1016/j.jaccas.2026.108798,Kawahara R,JACC. Case reports,2666-0849,,JACC Case Rep,eng,Miyauchi Y,[],108798,42283672,,2026 Jun 12,2026,https://pubmed.ncbi.nlm.nih.gov/42283672/,Progressive Giant Left Atrial Appendage Thrombus After Aborted Appendage Occlusion Despite Anticoagulation,,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Educational impact of point-of-care clinical decision support system (CDSS) on medical students remains insufficiently studied. Our aim was to evaluate the effect of a CDSS on team-based clinical quiz performance and confidence in using medical information resources. We conducted a nationwide, online, pre-post quasi-experimental pilot study on November 24, 2024. Eighteen teams of Japanese medical students (team size ranging from one to three members) completed ten multiple-choice questions based on two clinical cases. Teams first answered questions using any resources except UpToDate (Pre phase), then re-answered the same questions using UpToDate only (Post phase) under stricter time constraints. The primary outcome was team-based quiz score. Secondary outcomes were team-based confidence in using UpToDate and other resources. Paired t-tests and Wilcoxon signed-rank tests were performed. Sensitivity analyses addressed missing post-intervention confidence data. Seventeen teams (43 individuals) were included in the analysis. Mean quiz scores increased from 4.00 (SD 1.70) to 4.76 (SD 2.17) (paired t-test p = 0.01; Wilcoxon p = 0.026). Confidence in using UpToDate improved from 1.38 (SD 0.77) to 2.54 (SD 0.97) (paired t-test p = 0.0021), while confidence in other resources showed no significant change. Sensitivity analyses supported the confidence improvement under neutral and best-case assumptions but not under the extreme worst-case scenario. CDSS use may be associated with modest improvements in team-based quiz performance and confidence among medical students in this volunteer-based sample; generalizability to broader populations requires further investigation. Future studies should examine learning outcomes, clinical applicability, and curricular integration.","[""Journal Article""]","[""Isoda S"", ""Hashimoto T"", ""Nishizawa T"", ""Sekiya S"", ""Yamanaka S"", ""Misawa M"", ""Watari T"", ""Ueda E"", ""Suzuki T"", ""Tokuda Y""]",10.1002/jgf2.70142,Isoda S,Journal of general and family medicine,2189-6577,4,J Gen Fam Med,eng,Tokuda Y,[],e70142,42281563,pmc-id: PMC13250386;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42281563/,Effect of a Clinical Decision Support System on Team-Based Clinical Quiz Performance Among Japanese Medical Students: A Pre-Post Pilot Study,27,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Transposable elements (TEs), particularly retrotransposons that dominate mammalian genomes, are pervasive components of mammalian genomes whose activation is constrained by multilayered repression systems. In germ cells, this repression architecture is particularly elaborate, integrating chromatin-based silencing, DNA methylation, and small RNA-guided pathways to safeguard genome integrity during epigenetic reprogramming. These mechanisms are coordinated yet mechanistically specialized, targeting distinct phases of the transposon life cycle and different TE families across developmental stages. Yet the distinctive chromatin landscape of germ cells also creates windows of developmental permissiveness during which TE transcription can occur. Beyond the germline, TE expression can emerge in defined stages of early embryogenesis, extraembryonic development, neural differentiation, and aging, with consequences ranging from chromatin remodeling and regulatory co-option to inflammatory signaling and genome instability. Together, these observations raise a central question: how do different mammalian lineages balance epigenetic plasticity with genome defense? Here, we synthesize current understanding of the molecular logic of TE repression, emphasizing the germline, and integrate evidence across development and aging. We highlight shared principles-such as epigenetic permissiveness and RNA-guided targeting-while underscoring a key difference in regulatory outcome: somatic contexts may tolerate, co-opt, or pathologically amplify TE activity, whereas the germline converts transient activation into heritable, sequence-specific silencing.","[""Journal Article"", ""Review""]","[""Li P"", ""Yamanaka S""]",10.1080/17501911.2026.2685055,Li P,Epigenomics,1750-1911,7,Epigenomics,eng,Yamanaka S,"[""Animals"", ""DNA Transposable Elements"", ""Germ Cells"", ""Humans"", ""Epigenesis, Genetic"", ""Mammals"", ""Fertility"", ""DNA Methylation"", ""Gene Expression Regulation, Developmental"", ""Chromatin Assembly and Disassembly""]",843-860,42267589,pmc-id: PMC13390519;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42267589/,"Transposable element regulation in mammalian germ cells and other contexts: multilayered repression, fertility, and regulated activation",18,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Telomerase reverse transcriptase promoter (TERTp) mutations c.-124C > T (C228T) and c.-146C > T (C250T) are the most frequent single-nucleotide variants promoting telomerase activation in glioblastoma. Here, we describe a rare case of glioblastoma IDH-wildtype with dual TERTp mutations. Genomic analyses of multiregional tumor samples revealed co-occurring TERT C228T and C250T mutations across tumor regions, with variable copy number alterations of EGFR and CDKN2A. Notably, only the TERTp C228T mutation was retained in the corresponding patient-derived xenograft, accompanied by more extensive copy number alterations, implying a selective growth advantage for the TERT C228T-harboring subclone during tumor propagation in this case. These findings suggest that dual TERTp mutations may arise through subclonal evolutionary processes in glioblastoma and highlight telomere maintenance as a dynamic, heterogeneous process rather than invariably representing a fixed early oncogenic event.","[""Journal Article""]","[""Miyake Y"", ""Tateishi K"", ""Okagawa H"", ""Koyama A"", ""Hirata E"", ""Sasaoka K"", ""Saito S"", ""Fushimi S"", ""Natsumeda M"", ""Muraoka E"", ""Yamanaka S"", ""Fujii S"", ""Yamamoto T""]",10.1007/s10014-026-00540-8,Miyake Y,Brain tumor pathology,1433-7398,,Brain Tumor Pathol,eng,Yamamoto T,[],,42166078,,2026 May 21,2026,https://pubmed.ncbi.nlm.nih.gov/42166078/,"Dual TERT promoter mutations in glioblastoma, IDH-wildtype: a case report with preclinical investigations",,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) arises in various extranodal sites and has been linked to chronic inflammation, often triggered by infectious agents. Ocular adnexal (OA) MALT lymphoma has been associated with Chlamydophila psittaci (C. psittaci) in some regions. This study aimed to investigate the involvement of pathogenic microorganisms, including C. psittaci, in OA-MALT lymphoma. DNA was extracted from 17 formalin-fixed, paraffin-embedded OA-MALT lymphoma samples. Next-generation sequencing was performed, and reads were analyzed with bioinformatic pipelines to detect non-human DNA, focusing on complete or partial genomes of known pathogenic microorganisms, including C. psittaci strain 6BC and other bacteria implicated in lymphomagenesis. Most sequencing reads mapped to the human genome. No complete or partial genomes of C. psittaci 6BC or other non-human pathogenic microorganisms were detected above background levels, and no consistent enrichment of microbial sequences was observed. These findings suggest that, unlike in some Western cohorts, infectious agents such as C. psittaci are unlikely to play a major etiologic role in Japanese OA-MALT lymphoma. Our analysis suggests that infectious agents, including C. psittaci, may be not associated with OA-MALT lymphoma in Japan.","[""Journal Article""]","[""Yakushijin Y"", ""Horiba K"", ""Hashino M"", ""Yamanaka S"", ""Hasebe S"", ""Yamamoto S"", ""Fujii T"", ""Takenaka K"", ""Yasukawa M""]",10.1186/s13027-026-00765-4,Yakushijin Y,Infectious agents and cancer,1750-9378,1,Infect Agent Cancer,eng,Yasukawa M,[],,42083033,pmc-id: PMC13317347;,2026 May 4,2026,https://pubmed.ncbi.nlm.nih.gov/42083033/,Absence of chlamydial infection in ocular adnexal MALT lymphoma based on next-generation sequencing,21,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"eIF4G2 (DAP5/NAT1) is a non-canonical translation initiation factor, but its role in homeostasis is unclear. Using inducible Eif4g2 knockout mice and intestinal organoids, we show that eIF4G2 loss collapses Lgr5+ intestinal stem cell (ISC) and secretory maturation programs while preserving villus architecture. Transcriptomic and single-nucleus multiome analyses reveal a durable fetal-like/regenerative state with YAP-TEAD activation and regenerative absorptive cells. Ribosome profiling identifies selective translation-efficiency loss among chromatin regulators, especially the KAT3 coactivators CREBBP and EP300, resulting in reduced KAT3 abundance and global histone acetylation; chemical KAT3 inhibition phenocopies this state. CUT&Tag and assay for transposase-accessible chromatin sequencing (ATAC-seq) demonstrate that reduced eIF4G2-KAT3 output drives locus-selective enhancer remodeling, with loss of adult ISC/Wnt-Notch elements and activation of TEAD-enriched fetal loci, without inflammatory or integrated stress response programs driving the transition. Fetal intestinal spheroids remain viable despite similar biochemical defects, highlighting a stage-specific requirement for translational buffering in maintaining adult identity.","[""Journal Article""]","[""Kunitomi H"", ""Khaine AM"", ""Jamee R"", ""Arreola V"", ""Lancero M"", ""Raychaudhuri A"", ""Perli S"", ""Sato Y"", ""Iwasaki M"", ""Ruivo P"", ""Tomoda K"", ""Mito M"", ""Shichino Y"", ""Iwasaki S"", ""Yamanaka S""]",10.1016/j.stem.2026.04.006,Kunitomi H,Cell stem cell,1875-9777,6,Cell Stem Cell,eng,Yamanaka S,"[""Animals"", ""Cell Differentiation"", ""Intestines"", ""Mice"", ""Chromatin"", ""Eukaryotic Initiation Factor-4G"", ""Adult Stem Cells"", ""Protein Biosynthesis"", ""Mice, Knockout"", ""Histones"", ""E1A-Associated p300 Protein""]",1000-1015.e11,42066769,,2026 Jun 4,2026,https://pubmed.ncbi.nlm.nih.gov/42066769/,eIF4G2-mediated selective translation of chromatin regulators safeguards adult intestinal stem cell identity and differentiation,33,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Orthognathic surgery (OGS) is now widely performed, and postoperative nausea and vomiting (PONV) remains a common complication. Gastric decompression using a nasogastric tube (NT) is generally considered an effective prophylactic measure. In this retrospective observational study, we reviewed 667 OGS cases in 632 patients treated at our department between 2014 and 2024 to evaluate the role of NT placement in PONV by examining associations between clinical variables and PONV. Variables were extracted from electronic medical records, and descriptive statistics and annual trends were summarized. Univariable and multivariable logistic regression analyses were performed to examine associations with PONV. The mean age was 27.2 years, and 462 cases (69.3%) involved female patients. Single-jaw surgery was performed in 363 cases (54.4%) and double-jaw surgery in 304 cases (45.6%). Postoperative NT placement was used in 278 cases (41.7%), and PONV occurred in 53 cases (7.9%). The annual number of OGS cases increased from 48 in 2014 to 123 in 2024. Multivariable logistic regression analysis showed that age ≥ 30 years (odds ratio (OR), 0.43; 95% confidence interval (CI), 0.19-0.95; p = 0.04) and ondansetron administration (OR, 0.21; 95% CI, 0.04-0.97; p = 0.05) were associated with a lower risk of PONV, whereas postoperative NT placement was associated with a higher risk (OR, 4.03; 95% CI, 1.74-9.32; p = 0.001). These findings suggest that the number of OGS cases may be increasing, possibly reflecting growing societal awareness. In addition, postoperative NT placement may increase the risk of PONV, particularly in younger patients, while ondansetron may be effective in reducing PONV.","[""Journal Article"", ""Observational Study""]","[""Watanabe T"", ""Uozumi R"", ""Kawamura T"", ""Sasaki M"", ""Okada R"", ""Inoue S"", ""Kashiwagi M"", ""Fukuhara S"", ""Yamanaka S"", ""Mishima S"", ""Yamaguchi A"", ""Hirota M""]",10.1371/journal.pone.0346972,Watanabe T,PloS one,1932-6203,4,PLoS One,eng,Hirota M,"[""Humans"", ""Female"", ""Retrospective Studies"", ""Postoperative Nausea and Vomiting"", ""Adult"", ""Male"", ""Young Adult"", ""Orthognathic Surgical Procedures"", ""Middle Aged"", ""Adolescent"", ""Intubation, Gastrointestinal""]",e0346972,42008500,pmc-id: PMC13095023;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42008500/,Orthognathic surgery and postoperative nausea and vomiting: An 11-year retrospective observational study,21,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"To examine the Activities of Daily Living (ADL) level required to achieve catheter-free urination in cases where a urinary catheter was inserted due to urinary retention, urination difficulty, or urinary incontinence in an acute care hospital. This study included patients who were originally capable of self-urination but required rehabilitative therapy and intervention by the multidisciplinary urination care team for difficulty in removal of indwelled Foley catheter during hospitalization. The primary outcome was catheter-free independent urination. Patients who achieved urinary independence through self-catheterization for prolonged neurogenic bladder dysfunction were excluded. ADL scores before and after the intervention were evaluated using the Functional Independence Measure (FIM), which was consisted of motor FIM (mFIM), cognitive FIM, and total FIM, with and without deduction for urinary control score (-UC). Logistic regression analyses were performed to identify factors associated with independent urination, and Receiver Operating Characteristic (ROC) curve analysis was conducted to determine the appropriate cutoff. The study included 87 cases (72.8 ± 12.4 years old, male:female = 51:36). Catheter-free urination was achieved in 43 (49%) patients. There were no significant differences between the catheter-dependent and catheter-free groups in terms of gender, age, hospitalized departments, treatment methods, total duration of admission, duration of intervention, discharged destination, and comorbidities. At the end of the intervention, the FIM scores were all significantly higher in the catheter-free group than in the catheter-dependent group. To achieve catheter-free urination, mFIM-UC at the end of the intervention was the only statistically significant corelate (p < 0.001). In the ROC analysis, the AUC of mFIM-UC at the end of the intervention was 0.834, and the optimal cutoff value was 30 points (full score 84), with a sensitivity of 0.91 and specificity of 0.66. ADL as represented by mFIM is a major correlate of catheter-free urination.","[""Journal Article""]","[""Tanaka T"", ""Kanematsu A"", ""Nagai N"", ""Yoneda H"", ""Yamanaka S"", ""Kou Y"", ""Yanagi T"", ""Yamada Y"", ""Saito R"", ""Domen K"", ""Yamamoto S""]",10.1002/nau.70295,Tanaka T,Neurourology and urodynamics,0733-2467,6,Neurourol Urodyn,eng,Yamamoto S,"[""Humans"", ""Female"", ""Male"", ""Activities of Daily Living"", ""Urinary Catheterization"", ""Recovery of Function"", ""Aged"", ""Aged, 80 and over"", ""Middle Aged"", ""Urination"", ""Urinary Retention"", ""Hospitalization"", ""ROC Curve"", ""Treatment Outcome"", ""Urinary Catheters"", ""Urinary Incontinence"", ""Logistic Models""]",1196-1201,42003820,pmc-id: PMC13387999;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42003820/,Activities of Daily Living Level is Associated With Recovery of Catheter-Free Urination Among Patients Hospitalized in an Acute Care Hospital,45,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Retention forestry conserves biodiversity by retaining forest structures in logged areas. It has been demonstrated that dispersedly retained broad-leaved ectomycorrhizal (EcM) trees can mitigate the effect of logging on the diversity of EcM fungi in the surrounding Abies sachalinensis seedlings. However, it remains unclear how retained trees of different mycorrhizal types affect the diversity of EcM fungi in Abies seedlings. We investigated the neighborhood effect of different mycorrhizal types of retained trees on the diversity of EcM fungi symbiotic with surrounding Abies seedlings. At dispersed retention sites, the roots of Abies seedlings were collected near mature EcM trees (ET) or arbuscular mycorrhizal (AM) trees (AT), or in open areas where no retained trees existed within ten meters (NT). EcM fungi were identified based on ITS barcoding of the EcM roots. The diversity measures of EcM fungi under AT and NT were comparable and lower, respectively than those under ET. The community composition of the EcM fungi was similar between AT and NT, and both were significantly different from that of ET. These results indicate that AM trees do not have significant impact on EcM fungul community in the surrounding EcM seedlings.","[""Journal Article""]","[""Obase K"", ""Yamanaka S""]",10.47371/mycosci.2025.04.002,Obase K,Mycoscience,1340-3540,3,Mycoscience,eng,Yamanaka S,[],195-200,41969545,pmc-id: PMC13062905;,2025,2025,https://pubmed.ncbi.nlm.nih.gov/41969545/,Effects of different mycorrhizal types of dispersedly retained trees on the diversity of ectomycorrhizal fungi in neighboring Abies sachalinensis seedlings,66,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Foundational AI models have recently shown promise for predicting the impact of perturbations on cell states. However, current models typically consider only one cell state at a time, limiting their ability to learn how cellular responses unfold over time, particularly across long trajectories such as diseases of aging. Here, we develop a temporal AI model, MaxToki, trained on nearly 1 trillion gene tokens including cell state trajectories across the human lifespan to generate cell states across long timelapses of human aging. MaxToki generalized to unseen trajectories through in-context learning and predicted novel age-modulating targets that were experimentally verified to influence age-related gene programs and functional decline in vivo. MaxToki represents a promising strategy for temporal modeling to accelerate the discovery of interventions for programming therapeutic cellular trajectories.","[""Journal Article"", ""Preprint""]","[""Ortega JG"", ""Nadadur RD"", ""Kunitomi A"", ""Kothen-Hill S"", ""Wagner JUG"", ""Kurtoglu SD"", ""Kim B"", ""Reid MM"", ""Lu T"", ""Washizu K"", ""Zanders L"", ""Chen H"", ""Zhang Y"", ""Ancheta S"", ""Lichtarge S"", ""Johnson WA"", ""Thompson C"", ""Phan DM"", ""Combes AJ"", ""Yang AC"", ""Tadimeti N"", ""Dimmeler S"", ""Yamanaka S"", ""Alexanian M"", ""Theodoris CV""]",10.64898/2026.03.30.715396,Ortega JG,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Theodoris CV,[],,41959091,pmc-id: PMC13060336;,2026 Apr 1,2026,https://pubmed.ncbi.nlm.nih.gov/41959091/,Temporal AI model predicts drivers of cell state trajectories across human aging,,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Combined large cell neuroendocrine carcinoma (LCNEC) of the endometrium is rare and carries a poor prognosis. A 61-year-old woman with suspected endometrial serous carcinoma was referred to our hospital. Imaging studies staged the disease as stage IIIC1. We performed a total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and retroperitoneal lymph node dissection. Histopathological examination revealed a combination of LCNEC, endometrioid carcinoma, and multiple lymph node metastases. Postoperative computed tomography showed multiple pulmonary metastases not detected preoperatively. Given the advanced and recurrent nature of the disease, treatment with paclitaxel, carboplatin, and durvalumab was initiated. After the first cycle, the pulmonary metastases disappeared. Maintenance therapy with durvalumab and olaparib was continued because of proficient mismatch repair status. This case demonstrates that durvalumab may be a viable treatment option for endometrial LCNEC, as it is also approved for small cell lung cancer, which shares similarities with neuroendocrine carcinoma.","[""Case Reports"", ""Journal Article""]","[""Suzuki T"", ""Sonehara K"", ""Nabeshima H"", ""Shioya Y"", ""Yamanaka S"", ""Kondo S""]",10.1111/jog.70270,Suzuki T,The journal of obstetrics and gynaecology research,1341-8076,4,J Obstet Gynaecol Res,eng,Kondo S,"[""Humans"", ""Female"", ""Endometrial Neoplasms"", ""Middle Aged"", ""Carboplatin"", ""Carcinoma, Neuroendocrine"", ""Paclitaxel"", ""Phthalazines"", ""Antineoplastic Combined Chemotherapy Protocols"", ""Piperazines"", ""Antibodies, Monoclonal"", ""Carcinoma, Large Cell"", ""Maintenance Chemotherapy""]",e70270,41947481,,2026 Apr,2026,https://pubmed.ncbi.nlm.nih.gov/41947481/,"Combined Large Cell Neuroendocrine Carcinoma of the Endometrium Treated With Paclitaxel, Carboplatin, and Durvalumab, Followed by Maintenance Therapy With Durvalumab and Olaparib (DUO-E Regimen): A Case Report",52,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Deep vein thrombosis (DVT) is a common and serious complication in patients with cancer. We retrospectively analyzed patients newly diagnosed with solid cancers in a Japanese cohort. We retrospectively reviewed the medical records (2013-2020) of Japanese patients with solid cancers who were suspected of having DVT and were diagnosed and treated at Ehime University Hospital. Controls were patients with solid cancers in whom DVT was suspected on physical examination and/or laboratory testing but subsequently ruled out by definitive imaging. Candidate risk and prognostic variables were extracted from electronic medical records. This was a single-center cohort study. Among the initial 1399 patients, 224 with DVT and 560 without DVT (as controls) were included in the final analysis after excluding those with incomplete medical records, missing diagnostic tests, or unclear medical histories. The median overall survival (OS) period was 5.87 years for patients with DVT and 6.81 years for patients without DVT (p=0.0014). Anemia (Hb <11 g/dl) and thrombocytopenia (Plt <15 x 104 / μL) were found to be strong risk factors related to an increased incidence of DVT. Female cancer patients with DVT had a significantly worse outcome than those without DVT (p=0.028). Analysis of OS in patients with DVT associated with gynecological cancers following treatment with three different direct oral anticoagulants (DOACs; edoxaban, rivaroxaban, and apixaban) indicated that those treated with apixaban had a significantly worse outcome than those treated with the others (p=0.019) in this Japanese cohort. Japanese patients with solid cancers, particularly those with gynecologic cancers, tend to have poorer outcomes when DVT co-occurs with anemia and low platelet counts. In addition, the choice of DOAC for DVT treatment may be associated with differences in prognosis. These exploratory findings require more detailed, adjusted analyses and confirmation using other datasets or populations.","[""Journal Article""]","[""Masuda Y"", ""Yakushijin Y"", ""Yamanaka S"", ""Hasebe S"", ""Fujii T"", ""Yamanouchi J"", ""Takenaka K""]",10.2147/IJGM.S559679,Masuda Y,International journal of general medicine,1178-7074,,Int J Gen Med,eng,Takenaka K,[],559679,41938366,pmc-id: PMC13047771;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/41938366/,Factors Associated and Survival Outcomes Among Japanese Patients with Solid Cancer Who Developed Deep Vein Thrombosis (DVT),19,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"The DDB1- and CUL4-associated factor (DCAF) family functions as substrate receptors within Cullin4-really interesting new gene (RING) ubiquitin ligases (CRL4s), facilitating proteasomal degradation of targeted substrates. Although CRL4-based targeted protein degradation (TPD) has emerged as a promising strategy to modulate undruggable proteins, the complex formation, substrates, and functional properties of many DCAFs remain poorly defined. In this study, using proximity biotinylation-based interactome analysis in human HEK293T cells, we systematically annotated interactors and functional associations of individual DCAFs. Furthermore, we identified substrates of the model DCAFs COP1 and DCAF3 using proximity biotinylation coupled with multi-omics approaches. By combining biochemical and cell-based analyses, we establish CRL4 complex formation and DCAF autodegradation as experimentally tractable proxy indicators to evaluate DCAF degradation activity and propose a set of high-activity DCAFs. These datasets establish a resource for functional characterization of DCAFs and provide a framework for their prioritization in TPD.","[""Journal Article""]","[""Yamanaka S"", ""Nagaoka K"", ""Shoya Y"", ""Nishino K"", ""Mikura Y"", ""Tanaka K"", ""Konishi K"", ""Hasegawa Y"", ""Hijikata A"", ""Kosako H"", ""Sawasaki T""]",10.1016/j.molcel.2026.03.004,Yamanaka S,Molecular cell,1097-2765,7,Mol Cell,eng,Sawasaki T,"[""Humans"", ""HEK293 Cells"", ""Proteolysis"", ""DNA-Binding Proteins"", ""Cullin Proteins"", ""Ubiquitin-Protein Ligases"", ""Carrier Proteins"", ""Proteasome Endopeptidase Complex"", ""Ubiquitination"", ""Protein Binding"", ""Biotinylation"", ""Protein Interaction Mapping"", ""Protein Interaction Maps"", ""Peptide Termination Factors""]",1397-1416.e11,41932313,,2026 Apr 2,2026,https://pubmed.ncbi.nlm.nih.gov/41932313/,An interactome-based framework for DDB1- and CUL4-associated factor prioritization in targeted protein degradation,86,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Dr. Shinya Yamanaka is recognized for the generation of induced pluripotent stem cells (iPSCs) from fibroblasts by a combination of multiple transcription factors, and he won the Nobel Prize in Physiology or Medicine in 2012 jointly with Sir John B. Gurdon for this discovery. Twenty years after the discovery, the Cell Reports Medicine editorial team discusses with Dr. Yamanaka the scientific, technical, and translational milestones that have shaped the field of regenerative medicine. We also discuss the role of iPSCs in disease modeling and drug discovery, the interplay with genome editing, and ongoing issues that still prevent the widespread clinical application of iPSC-derived therapies. Finally, Dr. Yamanaka reflects on promising, yet underexplored, applications of iPSCs.","[""Journal Article"", ""Historical Article""]","[""Yamanaka S""]",10.1016/j.xcrm.2026.102719,Yamanaka S,Cell reports. Medicine,2666-3791,4,Cell Rep Med,eng,Yamanaka S,"[""Induced Pluripotent Stem Cells"", ""Humans"", ""History, 21st Century"", ""History, 20th Century"", ""Regenerative Medicine"", ""Animals"", ""Nobel Prize""]",102719,41895285,,2026 Apr 21,2026,https://pubmed.ncbi.nlm.nih.gov/41895285/,Shinya Yamanaka,7,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"This study introduces a divergent synthetic strategy in linkerology using preassembled linkers to generate structural diversity. The approach was validated by developing bromodomain-containing protein 4 (BRD4)-targeting proteolysis-targeting chimeras (PROTACs) based on an ""alkyne two-phase strategy,"" employing the BRD4 inhibitor TK-285 as the binding ligand. In the initial screening phase, alkyne-modified TK-285 derivatives were subjected to click chemistry to optimize linker length and the modification site, leading to the identification of TKP-5 as a potent degrader. TKP-5 exhibited stronger thymic stromal lymphopoietin─more suppressive activity than TK-285 and markedly suppressed IL-33 mRNA expression in a tape-stripping-induced skin injury model. In the subsequent optimization phase, late-stage diversification using 1,3-butadiyne-typed PROTAC intermediates revealed the critical contribution of the triazole moiety, supported by in silico analysis suggesting interaction with Trp81 of BRD4. The strategy is expected to be broadly applicable to modular functional molecules accessible via click chemistry.","[""Journal Article""]","[""Yamakoshi H"", ""Watanabe R"", ""Segawa R"", ""Ishihara R"", ""Tachibana R"", ""Kudo G"", ""Nagasawa S"", ""Yamanaka S"", ""Ito A"", ""Takeda H"", ""Sawasaki T"", ""Yoshino R"", ""Hirokawa T"", ""Doi T"", ""Hirasawa N"", ""Iwabuchi Y""]",10.1021/acs.jmedchem.5c03771,Yamakoshi H,Journal of medicinal chemistry,0022-2623,7,J Med Chem,eng,Iwabuchi Y,"[""Bromodomain Containing Proteins"", ""Proteolysis Targeting Chimera"", ""Cell Cycle Proteins"", ""Humans"", ""Transcription Factors"", ""Animals"", ""Alkynes"", ""Click Chemistry"", ""Structure-Activity Relationship"", ""Mice"", ""Triazoles"", ""Proteolysis""]",8388-8416,41852276,pmc-id: PMC13071873;,2026 Apr 9,2026,https://pubmed.ncbi.nlm.nih.gov/41852276/,Alkyne Two-Phase Strategy: Rapid Generation of TK-285-Derived PROTACs as BRD4 Degraders,69,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"High-grade glioma with pleomorphic and pseudopapillary features (HPAP) is a recently recognized glioma subtype defined by DNA methylation profiling. While it exhibits overlapping histological features with various CNS tumors, such as polymorphous low-grade neuroepithelial tumor of the young (PLNTY) and pleomorphic xanthoastrocytoma, its molecular pathogenesis and clinical behavior remain incompletely understood. We report a rare case of HPAP with BRAF p.V600E mutation and PLNTY-like histological features that showed rapid tumor progression during long-term follow-up. A 47-year-old woman harbored a lesion that remained asymptomatic and slow-growing for over 20 years, but later exhibited contrast enhancement and rapid expansion. Partial tumor resection was performed with hippocampal preservation based on intraoperative genetic testing and functional considerations. No regrowth of the residual hippocampal lesion was observed at 12 months postoperatively. Histologically, the tumor showed oligodendroglioma-like morphology, strong CD34 immunopositivity, consistent with PLNTY-like features, but indicated a high proliferative index. Molecular analysis revealed co-occurring BRAF p.V600E and TERT promoter (pTERT, c.-124C>T) mutations, with a lower variant allele frequency for the pTERT mutation. This disparity, confirmed by droplet digital PCR, suggests that the BRAF p.V600E mutation was an early, clonal event, whereas the pTERT mutation likely arose later in a subclonal population. DNA methylation profiling classified the tumor as HPAP with high confidence (NCI-Bethesda score: 0.969), and uniform manifold approximation and projection showed clustering within HPAP reference cases. This case represents a rare example of BRAF p.V600E-mutant HPAP with PLNTY-like features in which a subclonal pTERT mutation likely emerged during tumor evolution, contributing to rapid tumor progression. The combination of a prolonged indolent phase followed by rapid growth, along with the intratumoral genetic heterogeneity observed, provides novel insights into the biological diversity and evolutionary dynamics of HPAP.","[""Journal Article""]","[""Takayama Y"", ""Yaegashi M"", ""Satomi K"", ""Ishiyama T"", ""Shioda M"", ""Yazawa O"", ""Ye W"", ""Okagawa H"", ""Saito S"", ""Sasaoka K"", ""Okura M"", ""Koyama A"", ""Oshima A"", ""Sonoda M"", ""Natsumeda M"", ""Ichimura K"", ""Yamanaka S"", ""Fujii S"", ""Yamamoto T"", ""Tateishi K""]",10.1093/noajnl/vdag008,Takayama Y,Neuro-oncology advances,2632-2498,1,Neurooncol Adv,eng,Tateishi K,[],vdag008,41798681,pmc-id: PMC12962799;,2026 Jan-Dec,2026,https://pubmed.ncbi.nlm.nih.gov/41798681/,BRAF-mutant high-grade glioma with pleomorphic and pseudopapillary features (HPAP): A PLNTY mimic demonstrating tumor progression during longitudinal follow-up,8,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Twenty years have passed since the first demonstration of mouse induced pluripotent stem cells (iPSCs). What began as an unexpected observation in Kyoto quickly transformed stem cell biology and regenerative medicine worldwide. Over the past two decades, we have gained profound insights into the molecular mechanisms underlying cellular reprogramming and pluripotency. The technology has continued to evolve-becoming safer, more efficient, and more versatile. Today, iPSCs serve as a foundation for wide-ranging applications, from disease modeling and drug discovery to regenerative therapies and rejuvenation research. In this review, I reflect on the scientific journey of iPSCs, highlight key milestones in our understanding of reprogramming, and discuss the expanding clinical and societal impact of iPSCs.","[""Journal Article"", ""Review""]","[""Yamanaka S""]",10.1016/j.stem.2026.02.003,Yamanaka S,Cell stem cell,1875-9777,3,Cell Stem Cell,eng,Yamanaka S,"[""Induced Pluripotent Stem Cells"", ""Animals"", ""Humans"", ""Cellular Reprogramming"", ""Regenerative Medicine"", ""Stem Cell Research""]",372-381,41795426,,2026 Mar 5,2026,https://pubmed.ncbi.nlm.nih.gov/41795426/,Two decades of induced pluripotent stem cell research: From discovery to diverse applications,33,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
,"[""Journal Article""]","[""Yamamoto N"", ""Suzuki H"", ""Nakano M"", ""Yamanaka S"", ""Ito T"", ""Sato H"", ""Chiba T"", ""Nochioka K"", ""Takanami K"", ""Yasuda M"", ""Kunikata H"", ""Nakazawa T"", ""Yasuda S""]",10.1016/j.hrthm.2026.02.003,Yamamoto N,Heart rhythm,1547-5271,7,Heart Rhythm,eng,Yasuda S,[],e1257-e1259,41672211,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/41672211/,Linking the heart-eye-brain axis: Ocular and cerebral blood flow changes after catheter ablation in atrial fibrillation,23,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Diffuse large B-cell lymphoma (DLBCL) comprises biologically distinct subtypes, but whether cell-of-origin-related features remain stable over long disease courses is unclear. A woman was initially diagnosed with CD20-positive B-cell lymphoma in 1988 and treated with cyclophosphamide, vincristine and prednisolone (COP) chemotherapy. She experienced a first relapse in 1998 and received cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) chemotherapy. The second relapse occurred in 2008 and was managed with rituximab. At the third relapse in 2011, rituximab plus bendamustine (RB) was administered. During the fourth relapse in 2015, R-pirarubicin (THP)-COP chemotherapy was given. At the fifth relapse in 2017, at 80 years of age, RB therapy was administered again. A sixth relapse occurred in 2019, and the patient died within the same year. Histopathological evaluation throughout the disease course consistently demonstrated DLBCL. Notably, the immunophenotype showed sequential changes from a germinal centre B-cell-like pattern to an activated B-cell-like pattern and ultimately to a CD30-positive anaplastic B-cell variant. This unusually long clinical course highlights stepwise immunophenotypic evolution during repeated relapses, suggesting that surrogate subtype profiles may change over time. Repeat biopsies with comprehensive pathological (and, when available, molecular) re-evaluation are important to accurately characterize relapsed DLBCL and inform treatment selection. Diffuse large B-cell lymphoma (DLBCL) can undergo stepwise immunophenotypic and molecular evolution over decades, progressing from a germinal Center B-cell-like (GCB)-like phenotype to an activated B-cell -like/non-GCB pattern (MUM1+, CD30+) and ultimately to an aggressive anaplastic variant.The cell-of-origin profile and its associated molecular features are not necessarily static; thus, therapeutic strategies for relapsed DLBCL should be tailored to the current disease state rather than relying on the signature at initial diagnosis.Longitudinal re-evaluation through repeat biopsies is imperative to capture the evolving landscape of the malignancy, ensuring that treatment selection is guided by the most recent pathological and molecular findings.","[""Journal Article""]","[""Yamanaka S"", ""Hasebe S"", ""Fujii T"", ""Gondo T"", ""Kitazawa R"", ""Kitazawa S"", ""Yakushijin Y""]",10.12890/2026_006191,Yamanaka S,European journal of case reports in internal medicine,2284-2594,2,Eur J Case Rep Intern Med,eng,Yakushijin Y,[],006191,41668835,pmc-id: PMC12885577;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/41668835/,B-Cell Lymphoma Following an Indolent Course Over 30 Years with Immunophenotypic Changes at Each Recurrence,13,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Intraoperative hypotension is a common occurrence in patients undergoing anaesthesia, although there is no standardised definition of hypotension. International consensus statements provide some guidelines for the management of intraoperative hypotension, but general clinical practice is unknown. We aimed to survey anaesthesiologists' values and preferences regarding intraoperative blood pressure management, including whether they would support future research on this topic. We conducted an international, online survey of routine practice and opinion. The target population was anaesthesiologists who regularly anaesthetise adult patients. Results are reported descriptively and in accordance with the Consensus-Based Checklist for Reporting of Survey Studies (CROSS) checklist. A total of 1640 anaesthesiologists from 11 European countries participated in the survey. The majority of respondents were specialists (1322 of 1640, 80.6%, 95% CI 78.7-82.6). Almost all respondents worked in public hospitals (1613 of 1640, 98.4%). The overall response rate was 22.7%. Most respondents reported using absolute mean arterial pressure as their main unit of measurement to quantify hypotension (1098 of 1640, 67.0%, 95% CI 64.6-69.2). Respondents were most likely to initiate vasoactive treatment at a mean arterial pressure below 60 or 65 mmHg. Chronic arterial hypertension, traumatic brain injury and surgical procedures involving head-up positioning of the patient were the three most common scenarios where respondents would raise their threshold for treatment. Most respondents considered the establishment of safe intraoperative blood pressure thresholds a critical research question, and almost all respondents (1509 of 1640, 92.0%) indicated a willingness to randomise patients to specific blood pressure targets. For 72.9% (1196 of 1640), the lowest acceptable mean arterial pressure for randomisation was 60 mmHg. Respondents were also interested in the comparison of efficacy and safety of vasoactive agents, and the most sought-after comparison was phenylephrine versus noradrenaline (1252 of 1640, 76.3%). The willingness of respondents to administer these agents in peripheral venous access differed according to geography. In this international survey, mean arterial pressures of 60 or 65 mmHg were the most commonly reported blood pressure thresholds leading to initiation of treatment with vasoactive agents. Almost all respondents indicated patient groups for whom they would alter their treatment threshold, namely those suffering from chronic arterial hypertension, those undergoing surgery in a head-up position, and patients with traumatic brain injury. The majority of respondents supported future trials establishing optimal mean arterial pressure threshold and choice of vasoactive agent. We noticed a geographical variation in willingness to administer vasoactive agents in peripheral venous access. This survey of anaesthesiologists from European countries queried practitioner perceptions of blood pressure management in adults during anaesthesia with focus on hypotension. Queries and responses also concerned circumstances and blood pressure levels which clinicians report being willing to treat actively, and how they might do this practically.","[""Journal Article""]","[""Bækgaard ES"", ""Vester-Andersen M"", ""Crone V"", ""Møller MH"", ""Yamanaka S"", ""Palmarsdottir R"", ""Uusalo P"", ""Haidl F"", ""Rådestad M"", ""van der Sloot K"", ""Corona A"", ""Johnström A"", ""Nørskov AK"", ""Karlsen APH"", ""Faustad BI"", ""Sørensen CB"", ""Spies F"", ""Krogh HB"", ""El-Hallak H"", ""Mistry JM"", ""Mønnich JK"", ""Olesen KG"", ""Madsen KPD"", ""Voogd KL"", ""Reich LM"", ""Kolstrup LA"", ""Juhl-Olsen P"", ""Körner LK"", ""Sigurdsson MI"", ""Jensen-Holm MB"", ""Slavensky JA"", ""Toft MH"", ""Jørgensen ML"", ""Andersen M"", ""Jensen MSH"", ""Saei M"", ""Hedetoft M"", ""Hansen PM"", ""Hansen RT"", ""Lundsgaard RS"", ""Krarup SMI"", ""Wiberg S"", ""Laustrup T"", ""Brizzi G"", ""Kreutziger J"", ""Onyemuchara I"", ""Adeniji A"", ""Colville T"", ""Keitley JA"", ""Khan M"", ""Millar M"", ""Lennie I"", ""Kelly K"", ""Brooker V"", ""Roberts J"", ""Lipton G"", ""Keohone J"", ""Chebbout R"", ""Bond O"", ""Milligan W"", ""O'Brien C"", ""Wright E"", ""Linton F"", ""Towell C"", ""Shuttleworth J"", ""Norton J"", ""Butler D"", ""Frankland S"", ""Screech F"", ""Charig L"", ""Walsh S"", ""Davies R"", ""Jones E"", ""Dalmonte E"", ""Evans M"", ""Krag M""]",10.1111/aas.70197,Bækgaard ES,Acta anaesthesiologica Scandinavica,0001-5172,3,Acta Anaesthesiol Scand,eng,Krag M,"[""Humans"", ""Intraoperative Complications"", ""Hypotension"", ""Vasoconstrictor Agents"", ""Anesthesiologists"", ""Adult"", ""Female"", ""Surveys and Questionnaires"", ""Male"", ""Europe"", ""Middle Aged""]",e70197,41633958,pmc-id: PMC12895218;,2026 Mar,2026,https://pubmed.ncbi.nlm.nih.gov/41633958/,Intraoperative Hypotension and Vasoactive Treatment: An International Survey of Anaesthesiologists,70,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Congenital renal disorders, such as the Potter sequence, result from renal dysgenesis. To explore a prenatal therapeutic approach for fetuses with kidney insufficiency, we established an in utero transplantation protocol using donor fetal kidneys. Although numerous rodent studies have reported cellular injections into fetal recipients, no protocol to date has described whole-organ transplantation during gestation. Here, we present a step-by-step method for grafting donor fetal kidneys (embryonic day 14.0-16.5) into allogeneic rat fetuses at embryonic day 18.0-18.5, resulting in term neonates that retain the grafts postnatally. A 15-16 G needle preloaded with the donor kidney is inserted transuterinely, depositing the organ into the subcutaneous space of the fetus. Four days later, the term pups are delivered naturally and evaluated for graft development. This protocol enables organ-level transplantation and longitudinal assessment of graft maturation within the unique fetal environment, which differs markedly from adult settings in terms of growth factor availability and immune reactivity. To our knowledge, this is the first protocol to successfully achieve whole-organ transplantation directly into fetuses in utero. Therefore, the model provides a valuable platform for studying developmental organogenesis, fetal immunology, and regenerative strategies that leverage embryonic cues. Key features • Subcutaneous transplantation of fetal kidneys into recipient fetuses minimizes surgical invasiveness and significantly improves fetal survival. • Natural delivery enables pups to nurse from the dam, allowing extended postnatal observation. • Use of green fluorescent protein (GFP)-expressing donor tissue permits real-time visualization of graft location and growth. • The protocol is readily adaptable for xenotransplantation and studies of immunological tolerance during fetal development.","[""Journal Article""]","[""Morimoto K"", ""Yamanaka S"", ""Yokoo T""]",10.21769/BioProtoc.5565,Morimoto K,Bio-protocol,2331-8325,2,Bio Protoc,eng,Yokoo T,[],e5565,41613647,pmc-id: PMC12848318;,2026 Jan 20,2026,https://pubmed.ncbi.nlm.nih.gov/41613647/,Protocol for In Utero Fetal-to-Fetal Kidney Transplantation in Rats,16,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Lymphocytic vasculitis (LV), a histopathological subtype of primary angiitis of the CNS, is a rare inflammatory disorder that often presents as mass-like lesions mimicking malignant brain tumors. Owing to its rarity, the characteristics of LV remain poorly understood. The authors report the case of a young woman who presented with progressive headache. MRI revealed a solitary, ring-enhancing lesion with marked perifocal edema. Fluorodeoxyglucose positron emission tomography (FDG-PET) demonstrated relatively low uptake at the lesion margin, whereas fluciclovine-PET showed mild uptake. Given the high intracranial pressure and uncertain diagnosis, gross-total resection was performed. Histopathological analysis confirmed LV, characterized by perivascular lymphocytic infiltration, fibrin exudation, and the absence of neoplastic or demyelinating features. The patient did not receive additional immunosuppressive therapy and remained disease free for 12 months. To the best of the authors' knowledge, this is the first reported case of a solitary intracranial LV that was successfully managed with resection alone. This case suggests that resection may be a possible therapeutic option for select patients, particularly those with solitary lesions and negative autoimmune profiles. FDG-PET and fluciclovine-PET with MRI may provide supportive information for distinguishing LV from malignant neoplastic tumors. https://thejns.org/doi/10.3171/CASE25705.","[""Journal Article""]","[""Yazawa O"", ""Tateishi K"", ""Ikegaya N"", ""Kawai T"", ""Harada J"", ""Kato A"", ""Morihara K"", ""Yamanaka S"", ""Utsunomiya D"", ""Fujii S"", ""Tanaka F"", ""Yamamoto T""]",10.3171/CASE25705,Yazawa O,Journal of neurosurgery. Case lessons,2694-1902,3,J Neurosurg Case Lessons,eng,Yamamoto T,[],,41569678,pmc-id: PMC12814156;,2026 Jan 19,2026,https://pubmed.ncbi.nlm.nih.gov/41569678/,Complete remission of intracranial lymphocytic vasculitis following resection: illustrative case,11,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Optical tweezers have contributed to elucidating the folding mechanisms associated with biomolecules. By combining them with fluorescence imaging techniques, imaging can also be performed while measuring or applying forces that couple to biochemical reactions; however, they cannot capture structural information beyond the fluorophore spatial resolution. To overcome this limitation, here, we developed a hybrid high-speed atomic force microscopy (HS-AFM) and optical tweezers system. To resolve the challenge of incompatible instrumental configurations, we designed a customized optical tweezers system optimized for HS-AFM. Using this platform, we applied external forces to synthetic DNA secondary structures and directly visualized duplex dissociation and spontaneous reannealing upon force release, demonstrating reversible control of folding. We also captured reversible DNA overstretching and transient secondary structure formation in ssDNA. These findings were further analyzed using molecular dynamics simulations and viscoelastic modeling. This integrated approach provides a powerful platform for investigating folding dynamics and force-coupled mechanisms in biomolecules.","[""Journal Article""]","[""Umeda K"", ""Yamanaka S"", ""Imamura M"", ""Nagae F"", ""Fukuda S"", ""Watanabe H"", ""Uchihashi T"", ""Takada S"", ""Ando T""]",10.1021/acs.jpclett.5c03517,Umeda K,The journal of physical chemistry letters,1948-7185,4,J Phys Chem Lett,eng,Ando T,"[""Optical Tweezers"", ""Microscopy, Atomic Force"", ""Nucleic Acid Conformation"", ""DNA"", ""Molecular Dynamics Simulation"", ""DNA, Single-Stranded""]",1182-1191,41557950,,2026 Jan 29,2026,https://pubmed.ncbi.nlm.nih.gov/41557950/,Real-Time Sub-Molecular Visualization of DNA Folding Using a Hybrid High-Speed AFM and Optical Tweezers System,17,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"The AFIRE (Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease) trial demonstrated that rivaroxaban monotherapy was non-inferior in efficacy and superior in safety compared to rivaroxaban plus single antiplatelet therapy in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD). This study examined whether systolic blood pressure (SBP) affects clinical outcomes and modifies the impact of antithrombotic therapy. In this post hoc analysis, participants were stratified based on median SBP at baseline: >126 mmHg (High SBP group, n = 1042) and ≤126 mmHg (Low SBP group, n = 1093). The primary efficacy endpoint was a composite of cardiovascular events and all-cause death. The primary safety endpoint was major bleeding. The mean SBP was 139 mmHg and 114 mmHg in the High and Low SBP groups, respectively. In the propensity score-matched cohort (n = 1684), the Low SBP group had a significantly higher incidence of the primary efficacy endpoint (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.01-1.88; p = 0.039), while the primary safety endpoint was comparable between groups. In the Low SBP group, rivaroxaban monotherapy was associated with lower risks of both the primary efficacy (HR, 0.60; 95% CI, 0.41-0.86; p = 0.006) and safety endpoints (HR, 0.40; 95% CI, 0.22-0.74; p = 0.003) compared with combination therapy, whereas no significant differences were observed in the High SBP group. Lower SBP was associated with increased risk of cardiovascular events and all-cause death. Rivaroxaban monotherapy demonstrated more favorable efficacy and safety outcomes particularly patients with lower SBP.","[""Journal Article"", ""Randomized Controlled Trial"", ""Multicenter Study"", ""Research Support, Non-U.S. Gov't""]","[""Yamanaka S"", ""Noda T"", ""Nochioka K"", ""Higuma T"", ""Kaikita K"", ""Akao M"", ""Ako J"", ""Matoba T"", ""Nakamura M"", ""Miyauchi K"", ""Hagiwara N"", ""Kimura K"", ""Matsui K"", ""Ogawa H"", ""Yasuda S"", ""AFIRE Investigators""]",10.1038/s41440-025-02449-9,Yamanaka S,Hypertension research : official journal of the Japanese Society of Hypertension,0916-9636,4,Hypertens Res,eng,Yasuda S,"[""Humans"", ""Atrial Fibrillation"", ""Male"", ""Female"", ""Coronary Artery Disease"", ""Aged"", ""Blood Pressure"", ""Rivaroxaban"", ""Middle Aged"", ""Prognosis"", ""Fibrinolytic Agents"", ""Factor Xa Inhibitors"", ""Platelet Aggregation Inhibitors"", ""Treatment Outcome""]",1139-1149,41486379,pmc-id: PMC13050638;,2026 Apr,2026,https://pubmed.ncbi.nlm.nih.gov/41486379/,Prognostic impact of systolic blood pressure and antithrombotic strategy in patients with atrial fibrillation and stable coronary artery disease: a post-hoc analysis of the AFIRE trial,49,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Immunotherapy using immune checkpoint inhibitors is a standard treatment option for many types of malignancies but is not effective for differentiated thyroid cancer (DTC). Regulatory T-cells (Tregs), which are one of the main suppressive factors in the tumor microenvironment, are another important target for immunotherapy. This study investigated the characteristics of Tregs in DTC with the aim of further developing immunotherapy. Peripheral blood lymphocytes (PBLs) and tumor-infiltrating lymphocytes (TILs) were obtained from 12 patients with DTC and 12 patients with goiter (benign control group) who underwent primary surgery between February 2017 and September 2022. Flow cytometry analyses were performed for CD4, CD45RA, FOXP3, CC chemokine receptor 4 (CCR4; a candidate Treg-targeting molecule), and immune checkpoint molecules in order to characterize the features of Tregs. In the DTC patients, age ranged from 39 to 84 years, and the male:female ratio was 7:5. Pathological staging was pT1 or pT2 in 4 patients, pT3 in 8, pN0 in 5, and pN1 in 7, and extrathyroidal extension was observed in 5 patients. Effector Treg (eTreg) frequency in CD4+T-cells in TILs and PBLs was significantly higher in DTC than in goiter. Extrathyroidal extension was associated with a higher eTreg frequency in TILs. A positive correlation was found between eTreg frequency and the expression of immune checkpoint molecules (PD-1, TIM3, GITR, and OX40) on eTregs in TILs from DTC patients. These findings suggest that Tregs are activated in DTC and are important in the creation of an immunosuppressive microenvironment. In addition, the mean positive rate (±standard deviation) of CCR4 on eTregs was high in PBLs (95.8 % ± 3.8 %) and TILs (92.8 % ± 9.8 %) from DTC patients, suggesting that CCR4 is a potential target for eTreg-depletion immunotherapy for DTC. Tregs were increased and activated in DTC tumor tissue, indicating that they play an important role in creating an immunosuppressive microenvironment in DTC. The results suggest that eTreg-depletion immunotherapy using an anti-CCR4 antibody (mogamulizumab) might be effective for treating DTC.","[""Journal Article""]","[""Sano R"", ""Nakamura H"", ""Suzuki S"", ""Inukai D"", ""Okamoto H"", ""Yamanaka S"", ""Takahara T"", ""Satou A"", ""Fujimoto Y"", ""Tsuzuki T"", ""Ueda R"", ""Ogawa T""]",10.1016/j.anl.2025.12.004,Sano R,"Auris, nasus, larynx",0385-8146,1,Auris Nasus Larynx,eng,Ogawa T,"[""Humans"", ""Male"", ""Female"", ""T-Lymphocytes, Regulatory"", ""Thyroid Neoplasms"", ""Middle Aged"", ""Adult"", ""Aged"", ""Receptors, CCR4"", ""Aged, 80 and over"", ""Immunotherapy"", ""Lymphocytes, Tumor-Infiltrating"", ""Forkhead Transcription Factors"", ""Tumor Microenvironment"", ""Leukocyte Common Antigens""]",27-34,41380574,,2026 Feb,2026,https://pubmed.ncbi.nlm.nih.gov/41380574/,C-C chemokine receptor 4 is a candidate for regulatory T-cell-depletion immunotherapy in differentiated thyroid cancer,53,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for many hematological malignancies. The busulfan plus cyclophosphamide (Bu/Cy) combination is a standard myeloablative conditioning (MAC) regimen, but it is associated with significant regimen-related toxicity and non-relapse mortality (NRM). To mitigate these issues, a regimen combining high-dose busulfan with fludarabine (Bu/Flu) was developed, aiming to reduce toxicity while preserving efficacy. While a previous meta-analysis suggested Bu/Flu may reduce early mortality, it included non-randomized studies, and several large-scale trials have been published since. Therefore, an updated, robust comparison of these two widely used MAC regimens is clinically essential. The primary objective of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to comprehensively evaluate and compare the efficacy and safety profiles of Bu/Flu versus Bu/Cy as MAC regimens for adults undergoing allo-HSCT for hematological malignancies. This systematic review and meta-analysis was conducted following PRISMA guidelines, with a protocol registered on PROSPERO. We systematically searched PubMed, EMBASE, and CENTRAL databases for RCTs comparing Bu/Flu with Bu/Cy in adult patients with hematological malignancies receiving myeloablative busulfan doses. The primary outcome was NRM at 100 d and 1-yr. Secondary outcomes included all-cause mortality, relapse, and grade 3 to 5 adverse events. For statistical analysis, we calculated pooled risk ratios (RR) with 95% confidence intervals (CIs) using fixed- or random-effects models. The certainty of evidence was assessed using the Grades of Recommendations, Assessment, Development, and Evaluations methodology. Five RCTs met the inclusion criteria, encompassing a total of 975 patients. The meta-analysis demonstrated that the Bu/Flu regimen was associated with a significantly lower NRM at 1-yr compared to Bu/Cy (RR 0.49; 95% CI 0.31 to 0.79; I² = 0%; moderate certainty; 629 patients, 2 trials). Furthermore, Bu/Flu resulted in a significantly reduced incidence of grade 3 to 5 adverse events (RR 0.83, 95% CI 0.74 to 0.94; I² = 40%; high certainty; 385 patients, 2 trials). There were no statistically significant differences between the two regimens in terms of all-cause mortality at the end of the study (RR 0.99, 95% CI 0.83 to 1.19; I² = 48%; moderate certainty; 965 patients, 5 trials) or relapse rates (RR 1.11, 95% CI 0.86 to 1.44; I² = 20%; moderate certainty; 972 patients, 5 trials). Bu/Flu and Bu/Cy demonstrate comparable efficacy concerning long-term overall survival and relapse control in the setting of myeloablative allo-HSCT. However, the Bu/Flu regimen presents a superior safety profile, evidenced by a significant reduction in both NRM at 1-yr and severe adverse events. Bu/Flu should be considered a safer MAC alternative to Bu/Cy, particularly for patients at an increased risk of treatment-related toxicity.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Comparative Study""]","[""Shimada T"", ""Masaki T"", ""Koyamada R"", ""Ishikawa K"", ""Yamanaka S"", ""Sato K"", ""Ota E"", ""Yamashita T"", ""Mori S""]",10.1016/j.jtct.2025.11.040,Shimada T,Transplantation and cellular therapy,2666-6367,4,Transplant Cell Ther,eng,Mori S,"[""Humans"", ""Busulfan"", ""Hematopoietic Stem Cell Transplantation"", ""Vidarabine"", ""Cyclophosphamide"", ""Transplantation Conditioning"", ""Transplantation, Homologous"", ""Myeloablative Agonists"", ""Hematologic Neoplasms""]",505.e1-505.e11,41349636,,2026 Apr,2026,https://pubmed.ncbi.nlm.nih.gov/41349636/,Comparison of Myeloablative Busulfan/Cyclophosphamide and Busulfan/Fludarabine for Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis,32,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Ovarian clear cell carcinoma is characterized by HNF-1ß overexpression and is known to be resistant to chemotherapy. An inhibitor screening that specifically targets HNF-1ß led us to identify Actinonin as a candidate for cancer treatment. Actinonin, which is known to inhibit aminopeptidase M, has also been recognized for its antibacterial properties. We confirmed that GSK-3ß interference/inhibition, as a component of the HNF-1ß pathway, combined with Actinonin, has a highly potent antitumor effect compared to monotherapy. The same effect was observed in renal clear cell carcinoma lines expressing HNF-1ß. Actinonin promoted mitochondrial production by suppressing aerobic respiration, which decreased AMPK levels and increased ROS production. However, it also elevated GADD45α expression and induced mitophagy. GSK-3ß inhibition suppressed glycolysis and shifted energy production to OXPHOS, leading to increased ROS production. Furthermore, this combination produced excess ROS beyond metabolic capacity, which accumulated in lipid bilayers, leading to a further increase in CHOP gene expression and suppression of mitochondrial turnover. The GSK-3ß inhibitor and Actinonin combination demonstrated a powerful tumor-suppressive effect in vivo without severe side effects. Combining GSK-3ß inhibition with Actinonin can effectively eliminate cancer cells with HNF-1ß overexpression by inhibiting glycolysis and promoting mitochondrial turnover, highlighting new options for cancer therapy.","[""Journal Article""]","[""Kawahara N"", ""Kuniyasu H"", ""Mori S"", ""Kishi S"", ""Sugimoto S"", ""Maehana T"", ""Yamanaka S"", ""Kawaguchi R"", ""Kimura F""]",10.1038/s41419-025-08243-2,Kawahara N,Cell death & disease,2041-4889,1,Cell Death Dis,eng,Kimura F,"[""Reactive Oxygen Species"", ""Humans"", ""Glycolysis"", ""Cell Line, Tumor"", ""Mitochondria"", ""Female"", ""Animals"", ""Adenocarcinoma, Clear Cell"", ""Glycogen Synthase Kinase 3 beta"", ""Organelle Biogenesis"", ""Cell Death"", ""Mice"", ""Carcinoma, Renal Cell"", ""Mice, Nude"", ""Ovarian Neoplasms"", ""Kidney Neoplasms""]",879,41326368,pmc-id: PMC12669797;,2025 Dec 1,2025,https://pubmed.ncbi.nlm.nih.gov/41326368/,Inhibition of glycolysis and stimulation of mitochondrial biogenesis lead to increased ROS levels and cell death in HNF-1ß positive clear cell carcinoma,16,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Malignant peritoneal mesothelioma (MPM) as a secondary malignancy following radiotherapy is extremely rare. We report a case of MPM that developed as a secondary malignancy after initial concurrent chemoradiotherapy (CCRT) for cervical cancer.Case Presentation.A 52-year-old woman with no history of asbestos exposure underwent definitive CCRT for stage IIB cervical cancer, as classified by the International Federation of Gynecology and Obstetrics (FIGO) staging system. Over 10 years after initial treatment, she developed ascites. Diagnostic laparoscopy led to a pathological diagnosis of peritoneal mesothelioma. Given the absence of asbestos exposure and her medical history, the tumor was considered a radiation-induced secondary cancer. The patient received two lines of chemotherapy, but her performance status progressively declined, and she was transitioned to best supportive care. She died 1 year and 8 months after the MPM diagnosis. This case highlights the importance of long-term surveillance following radiotherapy for cervical cancer. Including this case, only four reports exist of MPM developing as a secondary malignancy following pelvic radiotherapy for cervical cancer. In all cases, patients presented with abdominal symptoms and ascites. The case findings underscore the need for clinicians to consider secondary malignancies such as MPM when ascites is detected during follow-up and to pursue a thorough diagnostic workup.","[""Case Reports"", ""Journal Article""]","[""Otsubo M"", ""Aichi M"", ""Kawashima Y"", ""Yamanaka S"", ""Imai Y"", ""Miyagi E"", ""Mizushima T""]",10.1016/j.gore.2025.101979,Otsubo M,Gynecologic oncology reports,2352-5789,,Gynecol Oncol Rep,eng,Mizushima T,[],101979,41293569,pmc-id: PMC12641188;,2025 Dec,2025,https://pubmed.ncbi.nlm.nih.gov/41293569/,Malignant peritoneal mesothelioma as a secondary cancer following radiotherapy for cervical cancer: a case report and literature review,62,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
[This corrects the article DOI: 10.1371/journal.pone.0016182.].,"[""Published Erratum""]","[""Ohta S"", ""Imaizumi Y"", ""Okada Y"", ""Akamatsu W"", ""Kuwahara R"", ""Ohyama M"", ""Amagai M"", ""Matsuzaki Y"", ""Yamanaka S"", ""Okano H"", ""Kawakami Y""]",10.1371/journal.pone.0337375,Ohta S,PloS one,1932-6203,11,PLoS One,eng,Kawakami Y,[],e0337375,41284624,pmc-id: PMC12643287;,2025,2025,https://pubmed.ncbi.nlm.nih.gov/41284624/,Correction: Generation of Human Melanocytes from Induced Pluripotent Stem Cells,20,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
,"[""Journal Article""]","[""Kawada A"", ""Ichikawa Y"", ""Goda M"", ""Yamanaka S""]",10.1111/ped.70275,Kawada A,Pediatrics international : official journal of the Japan Pediatric Society,1328-8067,1,Pediatr Int,eng,Yamanaka S,[],e70275,41254879,,2025 Jan-Dec,2025,https://pubmed.ncbi.nlm.nih.gov/41254879/,A true brachial artery aneurysm in a 1-year-old child: A case report,67,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"This study aimed to provide evidence regarding the treatment of patients with unresectable pancreatic cancer. We conducted a prospective single-arm phase II trial using the FOLFIRINOX regimen. After completing 4-8 cycles, patients underwent surgical resection when feasible. The primary endpoint was R0 resection rate. Fifteen patients were enrolled in this study. A median of six courses of FOLFIRINOX chemotherapy was administered, and a partial response or R0 resection was achieved in 26.7% and 33% of the patients, respectively. Severe adverse events due to chemotherapy and major surgical complications were observed in 33.3% and 6.7% of patients, respectively. The median overall survival of patients who underwent R0 resection or with R1 or unresectable disease was 47.8 months (95% confidence interval (CI), 22.5-73.1) or 14.5 months (95% CI, 11.8-17.2), respectively (P = 0.031). Well-selected patients with unresectable locally advanced pancreatic cancer treated with FOLFIRINOX achieved relatively high R0 resection rates and prolonged survival. Therefore, induction with FOLFIRINOX is feasible and well tolerated for locally advanced, initially unresectable pancreatic cancer and may be effective in facilitating R0 resection and prolonging survival.","[""Journal Article"", ""Clinical Trial, Phase II""]","[""Kobayashi N"", ""Yabushita Y"", ""Mori R"", ""Takahashi T"", ""Miyake K"", ""Sawada Y"", ""Homma Y"", ""Matsuyama R"", ""Okubo N"", ""Katsuta E"", ""Kubota K"", ""Yamanaka S"", ""Ichikawa Y"", ""Endo I""]",10.1038/s41598-025-23608-5,Kobayashi N,Scientific reports,2045-2322,1,Sci Rep,eng,Endo I,"[""Humans"", ""Pancreatic Neoplasms"", ""Male"", ""Antineoplastic Combined Chemotherapy Protocols"", ""Female"", ""Middle Aged"", ""Leucovorin"", ""Fluorouracil"", ""Oxaliplatin"", ""Irinotecan"", ""Aged"", ""Prospective Studies"", ""Adenocarcinoma"", ""Adult"", ""Treatment Outcome""]",39884,41233468,pmc-id: PMC12615679;,2025 Nov 13,2025,https://pubmed.ncbi.nlm.nih.gov/41233468/,Treatment of initially unresectable local advanced pancreatic adenocarcinoma with FOLFIRINOX: A prospective study YCOG1403 (C-FLAP study),15,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Rhabdomyosarcoma (RMS) is a rare malignant mesenchymal tumor, primarily affecting children. Occurrence in the uterine corpus of adults, particularly postmenopausal women, is extremely uncommon. A 60-year-old postmenopausal nulligravid woman presented with abnormal genital bleeding for three months. Pelvic examination revealed a friable mass extending from the uterine corpus. Biopsy confirmed embryonal RMS. She underwent modified radical hysterectomy with bilateral salpingo-oophorectomy for complete surgical resection. One cycle of adjuvant VAC chemotherapy (vincristine, actinomycin D, and cyclophosphamide) was administered but discontinued at her request. No residual disease was observed postoperatively, and she remains disease-free 12 months after surgery. Adult-onset uterine corpus embryonal RMS is rare, and standardized treatment protocols are lacking. Early diagnosis, complete surgical resection, and individualized therapy are essential. A literature review highlights clinical characteristics, treatment strategies, and prognostic considerations.","[""Journal Article"", ""Review""]","[""Omuro M"", ""Imai Y"", ""Ogawara Y"", ""Mizushima T"", ""Muraoka E"", ""Yamanaka S"", ""Fujii S"", ""Miyagi E""]",10.1016/j.gore.2025.101937,Omuro M,Gynecologic oncology reports,2352-5789,,Gynecol Oncol Rep,eng,Miyagi E,[],101937,41169952,pmc-id: PMC12570091;,2025 Oct,2025,https://pubmed.ncbi.nlm.nih.gov/41169952/,Embryonal rhabdomyosarcoma of the uterine corpus in a postmenopausal Woman: A case report and literature Review,61,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Silicon and its composites are key materials owing to their extensive use in the semiconductor industry. While the diamond-structured form dominates, other allotropes with superior properties at ambient conditions remain of interest. Toward this, Si46 clathrate type-I crystals containing alkali/alkaline-earth metals have been extensively studied, but the experimental observation of a guest-free Si46 structure has been challenging. Using advanced electron microscopy, we show experimental evidence of guest-free clathrate-I Si46 framework from Ba8-xSi46 under in situ heating. We reveal the stepwise Ba evacuation process, starting with loss of Ba1 from the smaller cages to form Ba6Si46, followed by removal of Ba2 in larger cages to reach Si46 that appears in the thin region of the nanocrystal with a thickness around 4-6 nm at 500 °C. Calculations give a quasi-direct bandgap of 1.89 eV and support the preferential evacuation of Ba1. The observation of this guest-free Si46 framework opens up possibilities for applications in high-speed transistors, optoelectronic devices or solar cell technologies.","[""Journal Article""]","[""Zhou Y"", ""Zhang Q"", ""Mayoral A"", ""Spackman PR"", ""Matsumoto T"", ""Li J"", ""Gale JD"", ""Anderson MW"", ""Fukuoka H"", ""Yamanaka S"", ""Terasaki O""]",10.1038/s41467-025-64277-2,Zhou Y,Nature communications,2041-1723,1,Nat Commun,eng,Terasaki O,[],9238,41107244,pmc-id: PMC12534387;,2025 Oct 17,2025,https://pubmed.ncbi.nlm.nih.gov/41107244/,Observation of a guest-free Si(46) clathrate-I framework from Ba(8-x)Si(46) upon in situ vacuum heating,16,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Anemia is a common comorbidity associated with adverse outcomes in patients with heart failure with preserved ejection fraction (HFpEF). However, the clinical relevance of new-onset anemia to sudden cardiac death (SCD) in patients with HFpEF remains unclear. This study investigated the association between new-onset anemia with ventricular arrhythmias (VAs) and SCD. Anemia was defined as a hemoglobin (Hb) level of <13 g/dL in men and <12 g/dL in women. Patients with Hb levels above these thresholds were categorized as without anemia. We analyzed data of 686 patients with symptomatic HFpEF (ejection fraction ≥ 50 %, New York Heart Association class II-IV) without anemia at baseline from a multicenter prospective observational CHART-2 study. The primary endpoint was a composite of ventricular tachycardia, ventricular fibrillation, and SCD. At the 1-year follow-up, 109 patients developed new-onset anemia (median Hb, 11.9 g/dL), whereas 577 remained without anemia (median Hb, 14.0 g/dL). Over a median follow-up of 9.2 years, patients with new-onset anemia had a significantly higher incidence of composite outcomes (12.8 % vs. 5.2 %, P = 0.008). After adjusting for potential confounders, new-onset anemia was associated with an elevated risk of the composite outcome (adjusted hazard ratio 2.20, 95 % confidence interval 1.10-4.42, P = 0.027). The association between new-onset anemia and lethal arrhythmias was independent of heart failure hospitalization or myocardial infarction occurring before the primary endpoint. New-onset anemia was significantly associated with an increased risk of VAs and SCD in patients with HFpEF, underscoring the importance of monitoring Hb levels for risk stratification.Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00418041.","[""Journal Article""]","[""Ito T"", ""Nochioka K"", ""Noda T"", ""Shiroto T"", ""Yamanaka S"", ""Yamamoto N"", ""Sato H"", ""Chiba T"", ""Nakano M"", ""Inoue T"", ""Susukita K"", ""Takahama H"", ""Takahashi J"", ""Miyata S"", ""Shimokawa H"", ""Yasuda S""]",10.1016/j.ijcha.2025.101812,Ito T,International journal of cardiology. Heart & vasculature,2352-9067,,Int J Cardiol Heart Vasc,eng,Yasuda S,[],101812,41069488,pmc-id: PMC12506443;,2025 Dec,2025,https://pubmed.ncbi.nlm.nih.gov/41069488/,New-onset anemia and its association with ventricular arrhythmias and sudden cardiac death in patients with heart failure with preserved ejection fraction,61,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
,"[""Journal Article""]","[""Yano S"", ""Takatsuki S"", ""Kotajima T"", ""Sasajima K"", ""Yamanaka S"", ""Himeno Y"", ""Yamashita S"", ""Yamaoka K"", ""Katsumata Y"", ""Nishiyama T"", ""Kimura T"", ""Ieda M""]",10.1016/j.hrthm.2025.09.040,Yano S,Heart rhythm,1547-5271,2,Heart Rhythm,eng,Ieda M,[],e276-e277,41067467,,2026 Feb,2026,https://pubmed.ncbi.nlm.nih.gov/41067467/,Incidence and clinical implications of microbubble formation during pulsed field ablation,23,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Immune-mediated colitis (IMC) is a common and potentially severe immune-related adverse event of immune checkpoint inhibitors (ICIs). Although corticosteroids and biologics are standard treatments, some cases remain refractory. Tofacitinib, a Janus kinase inhibitor, has shown promise in refractory IMC; however, evidence regarding its treatment effects remains limited. Here, we present a case of pembrolizumab-induced IMC and duodenitis refractory to corticosteroids, infliximab, and vedolizumab. The patient was successfully treated after receiving a 30-day course of tofacitinib, which resulted in rapid symptom resolution and mucosal healing. No recurrence of colitis was observed 3 months after treatment cessation. As ICIs are increasingly used, the incidence of refractory IMC and other immune-related toxicities is expected to rise. This case highlights the need for further studies to establish the optimal use of tofacitinib in refractory IMC and duodenitis.","[""Case Reports"", ""Journal Article""]","[""Misawa N"", ""Higurashi T"", ""Inoue K"", ""Suzuki H"", ""Tamura S"", ""Yoneda M"", ""Hori C"", ""Yamanaka S"", ""Nakajima A""]",10.1159/000547424,Misawa N,Case reports in gastroenterology,1662-0631,1,Case Rep Gastroenterol,eng,Nakajima A,[],621-629,41064542,pmc-id: PMC12503550;,2025 Jan-Dec,2025,https://pubmed.ncbi.nlm.nih.gov/41064542/,Successful Treatment of Refractory Immune-Mediated Colitis and Duodenitis with Tofacitinib,19,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"There are no previous reports of solitary renal metastases from urothelial carcinoma with trophoblastic differentiation, a rare bladder cancer subtype that is pathologically hCGβ positive. A 77-year-old male with urothelial carcinoma with trophoblastic differentiation underwent robot-assisted radical cystectomy following neoadjuvant chemotherapy. Pathological examination revealed urothelial carcinoma, classified as ypT2b and ypN0 with detection of focal hCGβ positivity. Postoperatively, serum hCGβ levels decreased from 1.6 to < 0.2 mIU/mL. At the 9-month follow-up, serum hCGβ was elevated to 20.1 mIU/mL with no recurrence on PET-CT. Gemcitabine-cisplatin chemotherapy was initiated; however, a solitary renal tumor was detected. Partial nephrectomy confirmed that the tumor was a renal metastasis of bladder cancer. Serum hCGβ levels decreased and remained < 0.2 mIU/mL, even 20 months after partial nephrectomy. We report a case of urothelial carcinoma with trophoblastic differentiation and elevated serum hCGβ levels, in which a solitary renal metastasis was successfully resected by robot-assisted partial nephrectomy.","[""Journal Article""]","[""Honda S"", ""Uemura K"", ""Ito H"", ""Muraoka E"", ""Tatenuma T"", ""Ito Y"", ""Muraoka K"", ""Hasumi H"", ""Kawano N"", ""Yamanaka S"", ""Makiyama K""]",10.1002/iju5.70072,Honda S,IJU case reports,2577-171X,5,IJU Case Rep,eng,Makiyama K,[],480-484,40909319,pmc-id: PMC12408180;,2025 Sep,2025,https://pubmed.ncbi.nlm.nih.gov/40909319/,A Case of Renal Metastasis of Urothelial Carcinoma With Trophoblastic Differentiation Successfully Treated With Robot-Assisted Partial Nephrectomy,8,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Heterobifunctional molecules, such as proteolysis-targeting and autophagy-targeting chimera, represent new drug concepts. They are composed of two protein binders that can induce proximity interactions between two proteins and protein catalysis. Currently, cereblon (CRBN)- and von Hippel-Lindau (VHL)-binders with thalidomide- and VH032-backbones are widely used as E3 ligase binders. Here, we developed a method to validate proteins that interact with heterobifunctional molecules in cells using AirID, a proximity biotinylation enzyme. Interactome of target proteins was validated for six heterobifunctional molecules. ThBD-AirID, a fusion of the thalidomide-binding domain (ThBD) of CRBN and AirID, effectively biotinylated the target proteins. AirID fused to full-length VHL also exhibited highly effective biotinylation. Heterobifunctional molecules with the same target binder but different E3 binders showed different proximity interactome profiles in cells. Analysis using ThBD-AirID revealed a nuclear interaction between androgen receptor and ARV-110. AirID-fused ThBD and VHL could be useful for validating the heterobifunctional molecular interactome in cells.","[""Journal Article""]","[""Yamada K"", ""Yamanaka S"", ""Yamakoshi H"", ""Kohyama A"", ""Iwabuchi Y"", ""Kosako H"", ""Sawasaki T""]",10.1038/s42003-025-08761-x,Yamada K,Communications biology,2399-3642,1,Commun Biol,eng,Sawasaki T,"[""Von Hippel-Lindau Tumor Suppressor Protein"", ""Humans"", ""Ubiquitin-Protein Ligases"", ""Adaptor Proteins, Signal Transducing"", ""Protein Binding"", ""HEK293 Cells"", ""Biotinylation"", ""Thalidomide""]",1323,40885760,pmc-id: PMC12398604;,2025 Aug 30,2025,https://pubmed.ncbi.nlm.nih.gov/40885760/,In-cell proximity target validation methods for heterobifunctional molecules with CRBN- or VHL-binder using AirID,8,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"unknown, but she remained symptom-free for 32 years. However, a CT scan performed for an unrelated condition revealed 2 liver tumors with calcifications located in S8(10 cm)and S6(3 cm). Given her medical history, liver metastasis from breast cancer was suspected. Core needle biopsies of the liver tumor and a left axillary lymph node detected on PET-CT, confirmed metastatic breast cancer that was estrogen receptor-positive, progesterone receptor-positive, and human epidermal growth factor receptor 2-negative. Upon diagnosis, chemotherapy with paclitaxel and bevacizumab was initiated. Follow-up CT scans at 6 and 15 months showed continued tumor regression in the liver and axilla. After 15 months of treatment, both tumors continued to shrink. Although late recurrence is common with breast cancer, recurrence more than 30 years post-surgery is rare. This case of late-stage metastatic breast cancer is presented alongside a literature review.","[""Journal Article"", ""Case Reports"", ""English Abstract""]","[""Aikawa A"", ""Oshi M"", ""Kawashima K"", ""Sasamoto M"", ""Fujiwara Y"", ""Adachi S"", ""Narui K"", ""Takase H"", ""Yamanaka S"", ""Fujii S"", ""Yamada A"", ""Endo I""]",,Aikawa A,Gan to kagaku ryoho. Cancer & chemotherapy,0385-0684,7,Gan To Kagaku Ryoho,jpn,Endo I,"[""Humans"", ""Breast Neoplasms"", ""Female"", ""Liver Neoplasms"", ""Lymphatic Metastasis"", ""Axilla"", ""Antineoplastic Combined Chemotherapy Protocols"", ""Time Factors"", ""Middle Aged""]",529-531,40840899,,2025 Jul,2025,https://pubmed.ncbi.nlm.nih.gov/40840899/,[A Case of Liver and Axillary Lymph Node Metastasis 32 Years after Breast Cancer Surgery],52,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"An aggregated retention system retains several groups of trees within cutblocks to maintain public functions such as biodiversity conservation. We examined ectomycorrhizal (EcM) fungal communities associated with regenerating Abies sachalinensis seedlings and their surrounding trees at different locations; inside and at the edge of the retained patches, and in clear-cut areas 10 and 50 m from the edge. The EcM fungi on the roots were grouped into operational taxonomic units (OTU) based on the similarity of their ribosomal DNA internal transcribed spacer sequences. Higher OTU richness was found inside (63 OTUs) and at the edge of the patches (59 OTUs) compared to clear-cut areas (33 or 25 OTUs). The ordination analysis inferred that location may influence the EcM fungal communities. However, further studies with more site replications are needed to clarify the effects of the patches on shaping EcM fungal communities.","[""Journal Article""]","[""Obase K"", ""Yamanaka S"", ""Ozaki K""]",10.47371/mycosci.2024.11.002,Obase K,Mycoscience,1340-3540,1,Mycoscience,eng,Ozaki K,[],116-119,40672138,pmc-id: PMC12260387;,2025,2025,https://pubmed.ncbi.nlm.nih.gov/40672138/,Root-associated ectomycorrhizal fungal communities in and around aggregated retention patches left in logged areas of Abies sachalinensis planted forests,66,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
,"[""Journal Article""]","[""Kinoshita Y"", ""Yamanaka S"", ""Iwai S"", ""Kume H"", ""Yokoo T"", ""Kobayashi E""]",10.1097/TP.0000000000005480,Kinoshita Y,Transplantation,0041-1337,10,Transplantation,eng,Kobayashi E,[],e621-e622,40624739,,2025 Oct 1,2025,https://pubmed.ncbi.nlm.nih.gov/40624739/,Surgical Integration of Metanephros-bladder Composite Tissue Transplants in Adult Pigs,109,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"To compare the transcriptomes induced by estrogens used in combined oral contraceptives (COCs): estetrol (E4), ethinylestradiol (EE), and estradiol (E2) in human primary endometriotic stromal cells. Endometriotic stromal cells were cultured in the presence of E4 (10-6 mol/L), E2 (10-8 mol/L) or EE (10-9 mol/L) for 24 hours. Transcriptomes induced by E4 were compared with those induced by E2 and EE. Endometriotic stromal cells were obtained from patients with ovarian endometriomas. Transcriptomes were examined using RNA sequencing analysis, and messenger RNA levels were measured using reverse transcription-quantitative polymerase chain reaction. Estetrol treatment resulted in 114 differentially expressed genes compared with the control (|log2fold change| >0.2). The number was higher than those differentially expressed between E4 and E2 (82 genes) and between E4 and EE (75 genes). Of the differentially expressed genes between E4 and the control, 79% (90 genes) changed in the same manner as in EE and E2. In contrast, 21% (24 genes) of the genes changed in an E4-preferential manner. The present study elucidated that although E4 induces the expression of specific unique genes in endometriotic stromal cells distinct from those regulated by other estrogens, the overall gene expression profile is largely analogous to that induced by other estrogens. When differences in progestin are not considered, it is suggested that the COC containing E4 exhibits effects on endometriosis comparable with those of other COCs.","[""Journal Article""]","[""Nakajima M"", ""Izumi G"", ""Koga K"", ""Silvana V"", ""Elsherbini M"", ""Okumura A"", ""Wada M"", ""Yamanaka S"", ""Hirota Y"", ""Osuga Y""]",10.1016/j.xfss.2025.06.002,Nakajima M,F&S science,2666-335X,4,F S Sci,eng,Osuga Y,"[""Humans"", ""Ethinyl Estradiol"", ""Female"", ""Stromal Cells"", ""Estradiol"", ""Transcriptome"", ""Estetrol"", ""Endometriosis"", ""Endometrium"", ""Cells, Cultured"", ""Adult""]",387-396,40578765,,2025 Nov,2025,https://pubmed.ncbi.nlm.nih.gov/40578765/,"Transcriptome landscapes induced by estetrol, estradiol, and ethinylestradiol in primary human endometriotic stromal cells",6,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Nephrogenesis occurs during the fetal period; because nephrogenesis does not occur after birth, preterm infants have low nephron numbers. However, whether a reduction in the number of pure nephrons alone affects renal function in conventional animal models remains unclear. Therefore, we aimed to examine whether differences in nephron number alone could lead to differences in future renal function by specifically ablating the nephrons. Mice transgenic for Cre recombinase in the nephron progenitor cells were crossed with the locus of X-over P1-diphtheria toxin receptor transgenic mice. Diphtheria toxin was administered on embryonic day 13.5 to suppress fetal nephrogenesis. Various renal function assessments were performed until the maximum age of 1 year. Some mice received a high-salt diet (HSD). The mouse model showed a glomerular loss of approximately half per cross-sectional area and no or mild renal damage at 1 year of age. Furthermore, HSD induced the early onset and exacerbation of renal impairment. The new mouse model used in this study showed HSD-induced early onset and exacerbation of renal damage, suggesting that appropriate salt management can prevent the onset and exacerbation of renal impairment in preterm infants known to have low nephron numbers. We established a new method for generating mice with low nephron numbers without affecting growth. The mouse model did not develop kidney disease but could develop mild kidney disease; however, kidney damage is exacerbated by a high-salt diet. Adequate salt management may prevent the future development of renal damage in infants with low nephron counts when born prematurely.","[""Journal Article""]","[""Inage Y"", ""Matsumoto K"", ""Haruhara K"", ""Hirano D"", ""Matsui K"", ""Kinoshita Y"", ""Morimoto K"", ""Koda N"", ""Yamamoto S"", ""Fujimoto T"", ""Fukunaga S"", ""Yamanaka S"", ""Oishi K"", ""Kobayashi E"", ""Yokoo T""]",10.1038/s41390-025-04123-9,Inage Y,Pediatric research,0031-3998,5,Pediatr Res,eng,Yokoo T,"[""Animals"", ""Nephrons"", ""Mice, Transgenic"", ""Mice"", ""Sodium Chloride, Dietary"", ""Kidney"", ""Female"", ""Disease Models, Animal"", ""Diphtheria Toxin"", ""Male""]",1941-1949,40425850,,2025 Nov,2025,https://pubmed.ncbi.nlm.nih.gov/40425850/,A novel mouse model for investigating the long-term impact of reduced nephron numbers on renal function and salt sensitivity,98,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Deep vein thrombosis (DVT) is a common complication in cancer patients associated with significant morbidity and mortality. D-dimer is a widely used screening tool for suspected DVT; however, its accuracy may be influenced by body mass index (BMI). We evaluated whether BMI modified the diagnostic utility of D-dimer levels in patients with cancer and DVT. We retrospectively analyzed 439 patients with newly diagnosed solid cancers suspected of having DVT between January 2013 and December 2020. DVT was confirmed or excluded by using computed tomography or echography. D-dimer was measured, and patients were classified by BMI as low- (< 18.5 kg/m2), normal- (18.5-24.9 kg/m2), or high-BMI (≥ 25.0 kg/m2). D-dimer levels, positive and negative predictive values (PPV and NPV), and overall survival (OS) were compared. Of 439 patients, 175 (39.9%) had DVT. BMI did not differ significantly between the DVT-positive and DVT-negative patients. In the normal and high BMI groups, D-dimer levels were significantly higher in patients with DVT than those without (p < 0.01), whereas patients with a low BMI did not show this difference (p = 0.12). Using a 1 µg/mL cut-off, PPV was 32% in low-, 52% in normal-, and 49% in high-BMI patients; NPV was 83%, 91%, and 97%, respectively. OS did not differ among the BMI groups, and no deaths were directly related to DVT. Diagnostic performance of D-dimer level may diminish in underweight patients with cancer. Clinicians should carefully interpret the D-dimer levels in low-BMI populations and consider additional diagnostic strategies.","[""Journal Article""]","[""Masuda Y"", ""Konishi T"", ""Yakushijin Y"", ""Yamanaka S"", ""Hasebe S"", ""Yamanouchi J"", ""Takenaka K""]",10.1007/s10147-025-02787-1,Masuda Y,International journal of clinical oncology,1341-9625,8,Int J Clin Oncol,eng,Takenaka K,"[""Humans"", ""Fibrin Fibrinogen Degradation Products"", ""Venous Thrombosis"", ""Male"", ""Female"", ""Retrospective Studies"", ""Neoplasms"", ""Body Mass Index"", ""Middle Aged"", ""Aged"", ""Adult"", ""Aged, 80 and over""]",1545-1552,40355784,,2025 Aug,2025,https://pubmed.ncbi.nlm.nih.gov/40355784/,Impact of body mass index on D-dimer diagnostic utility for deep vein thrombosis in patients with cancer: a single-center retrospective analysis,30,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"Wilson's disease is an autosomal recessive disorder of copper metabolism. A current unresolved issue is the worsening of neurological symptoms during the initial treatment phase, particularly with chelation therapy. This phenomenon, termed ""early neurological worsening,"" is attributed to the rapid mobilization and redistribution of copper during treatment initiation. We report the case of a 10-year-old boy, with neuro-hepatic Wilson's disease who developed treatment-refractory generalized dystonia, which improved with intrathecal baclofen therapy. The patient experienced walking discomfort 5 months before referral to our hospital, with rapid progression to dysphagia and a 3 kg weight loss. Initially, he presented with dystonia, including foot inversion. Wilson's disease was diagnosed based on physiological, clinical, and imaging findings, with confirmation of a homozygous mutation in the ATP7B gene. The patient was treated with trientine hydrochloride, followed by zinc monotherapy. Despite appropriate chelation therapy, dystonia progressed to severe axial torsion involving the trunk. His condition deteriorated to status dystonicus, with high-grade fever, elevated creatine phosphokinase levels, and dehydration, requiring midazolam sedation. These symptoms were attributed to ""early neurological worsening."" A trial of intrathecal baclofen injection provided symptom relief, leading to the implantation of a baclofen pump, which significantly reduced the status dystonicus. At discharge, the patient had a modified Rankin Scale score of 5. Three years later, although wheelchair-dependent, his oral intake and speech are progressively improving with training. This is the first reported case of status dystonicus in Wilson's disease successfully treated with intrathecal baclofen, highlighting its potential as a viable treatment option for Wilson's disease-associated debilitating dystonia.","[""Case Reports"", ""Journal Article""]","[""Yamanaka S"", ""Hanada T"", ""Higashi T"", ""Matsunaga M"", ""Yonee C"", ""Maruyama S"", ""Hanaya R""]",10.2176/jns-nmc.2024-0234,Yamanaka S,NMC case report journal,2188-4226,,NMC Case Rep J,eng,Hanaya R,[],91-95,40255925,pmc-id: PMC12009644;,2025,2025,https://pubmed.ncbi.nlm.nih.gov/40255925/,Intrathecal Baclofen Therapy Improves Refractory Status Dystonicus in Neuro-hepatic Wilson's Disease: A Case Report,12,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
"The clinical guidelines categorize heart failure (HF) based on left ventricular ejection fraction (LVEF). However, the current LVEF cutoffs, 40% and 50%, may not fully address the underlying characteristics and cardiovascular risk of HF, particularly for HF with higher LVEF. This study aimed to characterize HF with supranormal ejection fraction (HFsnEF) using different LVEF cutoffs (35%, 55%, and 70% for men, and 40%, 60%, and 75% for women). This study divided 442 patients from the CHART-Omics study into four groups: HF with reduced ejection fraction (HFrEF) (n = 55, 65.5 years), HF with mildly reduced ejection fraction (HFmrEF) (n = 125, 69.3 years), HF with normal ejection fraction (HFnEF) (n = 215, 69.0 years) and HFsnEF (n = 47, 67.1 years). When clinical backgrounds were adjusted and HFnEF served as the reference, HFsnEF carried an increased hazard ratio (HR) for the composite of cardiovascular death and HF hospitalization of 2.71 (95% confidence interval [CI] 1.10-6.66, p = 0.030), while HFrEF had a HR of 3.14 (95% CI 1.36-7.23, p = 0.007). HFsnEF was characterized by an increase in relative left ventricular wall thickness and a decrease in left ventricular dimensions, whereas increased left ventricular mass and dimensions characterized HFrEF. Quantitative analysis of 4670 plasma proteins showed essential differences between HFsnEF and HFrEF, for example, 'protein synthesis' versus 'cell morphology', 'cellular assembly and organization' and 'nucleic acid metabolism' for underlying pathophysiology, and 'energy production' versus 'connective tissue disorders' and 'cell-to-cell signalling and interaction' for prognostication. Heart failure with supranormal ejection fraction, an unnoticed but emerging entity in HF, carries a similarly increased cardiovascular risk as HFrEF but has unique structural and plasma proteomic characteristics.","[""Journal Article""]","[""Sakata Y"", ""Nochioka K"", ""Yasuda S"", ""Ishida K"", ""Shiroto T"", ""Takahashi J"", ""Kasahara S"", ""Abe R"", ""Yamanaka S"", ""Fujihashi T"", ""Hayashi H"", ""Kato S"", ""Horii K"", ""Teramoto K"", ""Tomita T"", ""Miyata S"", ""Sugimura K"", ""Waga I"", ""Nagasaki M"", ""Shimokawa H""]",10.1002/ejhf.3654,Sakata Y,European journal of heart failure,1388-9842,8,Eur J Heart Fail,eng,Shimokawa H,"[""Humans"", ""Heart Failure"", ""Stroke Volume"", ""Female"", ""Male"", ""Aged"", ""Proteomics"", ""Ventricular Function, Left"", ""Middle Aged"", ""Prognosis""]",1570-1583,40230291,pmc-id: PMC12482836;,2025 Aug,2025,https://pubmed.ncbi.nlm.nih.gov/40230291/,Clinical and plasma proteomic characterization of heart failure with supranormal left ventricular ejection fraction: An emerging entity of heart failure,27,3a2re71Ek4OjT7tM5,2s5WUk1iDLbp7ghNy
,"[""Published Erratum""]","[""Şahin U"", ""Muik A"", ""Vogler I"", ""Derhovanessian E"", ""Kranz LM"", ""Vormehr M"", ""Quandt J"", ""Bidmon N"", ""Ulges A"", ""Baum A"", ""Pascal KE"", ""Maurus D"", ""Brachtendorf S"", ""Lörks V"", ""Sikorski J"", ""Koch P"", ""Hilker R"", ""Becker D"", ""Eller AK"", ""Grützner J"", ""Tonigold M"", ""Boesler C"", ""Rosenbaum C"", ""Heesen L"", ""Kühnle MC"", ""Poran A"", ""Dong JZ"", ""Luxemburger U"", ""Kemmer-Brück A"", ""Langer D"", ""Bexon M"", ""Bolte S"", ""Palanche T"", ""Schultz A"", ""Baumann S"", ""Mahiny AJ"", ""Boros G"", ""Reinholz J"", ""Szabó GT"", ""Karikó K"", ""Shi PY"", ""Fontes-Garfias C"", ""Perez JL"", ""Cutler M"", ""Cooper D"", ""Kyratsous CA"", ""Dormitzer PR"", ""Jansen KU"", ""Türeci Ö""]",10.1038/s41586-025-09355-7,Şahin U,Nature,0028-0836,8074,Nature,eng,Türeci Ö,[],E27,40670800,,2025 Jul,2025,https://pubmed.ncbi.nlm.nih.gov/40670800/,Author Correction: BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans,643,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"The response to mRNA vaccines needs to be sufficient for immune cell activation and recruitment, but moderate enough to ensure efficacious antigen expression. The choice of the cap structure and use of N1-methylpseudouridine (m1Ψ) instead of uridine, which have been shown to reduce RNA sensing by the cellular innate immune system, has led to improved efficacy of mRNA vaccine platforms. Understanding how RNA modifications influence the cell intrinsic immune response may help in the development of more effective mRNA vaccines. In the current study, we compared mRNA vaccines in mice against influenza virus using three different mRNA formats: uridine-containing mRNA (D1-uRNA), m1Ψ-modified mRNA (D1-modRNA), and D1-modRNA with a cap1 structure (cC1-modRNA). D1-uRNA vaccine induced a significantly different gene expression profile to the modified mRNA vaccines, with an up-regulation of Stat1 and RnaseL, and increased systemic inflammation. This result correlated with significantly reduced antigen-specific antibody responses and reduced protection against influenza virus infection compared with D1-modRNA and cC1-modRNA. Incorporation of m1Ψ alone without cap1 improved antibodies, but both modifications were required for the optimum response. Therefore, the incorporation of m1Ψ and cap1 alters protective immunity from mRNA vaccines by altering the innate immune response to the vaccine material.","[""Journal Article""]","[""Wang Z"", ""Jacobus EJ"", ""Stirling DC"", ""Krumm S"", ""Flight KE"", ""Cunliffe RF"", ""Mottl J"", ""Singh C"", ""Mosscrop LG"", ""Santiago LA"", ""Vogel AB"", ""Kariko K"", ""Sahin U"", ""Erbar S"", ""Tregoning JS""]",10.1016/j.omtn.2023.102045,Wang Z,Molecular therapy. Nucleic acids,2162-2531,,Mol Ther Nucleic Acids,eng,Tregoning JS,[],102045,37876532,pmc-id: PMC10591005;,2023 Dec 12,2023,https://pubmed.ncbi.nlm.nih.gov/37876532/,Reducing cell intrinsic immunity to mRNA vaccine alters adaptive immune responses in mice,34,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"Argininosuccinic aciduria (ASA) is a metabolic disorder caused by a deficiency in argininosuccinate lyase (ASL), which cleaves argininosuccinic acid to arginine and fumarate in the urea cycle. ASL deficiency (ASLD) leads to hepatocyte dysfunction, hyperammonemia, encephalopathy, and respiratory alkalosis. Here we describe a novel therapeutic approach for treating ASA, based on nucleoside-modified messenger RNA (modRNA) formulated in lipid nanoparticles (LNP). To optimize ASL-encoding mRNA, we modified its cap, 5' and 3' untranslated regions, coding sequence, and the poly(A) tail. We tested multiple optimizations of the formulated mRNA in human cells and wild-type C57BL/6 mice. The ASL protein showed robust expression in vitro and in vivo and a favorable safety profile, with low cytokine and chemokine secretion even upon administration of increasing doses of ASL mRNA-LNP. In the ASLNeo/Neo mouse model of ASLD, intravenous administration of the lead therapeutic candidate LNP-ASL CDS2 drastically improved the survival of the mice. When administered twice a week lower doses partially protected and 3 mg/kg LNP-ASL CDS2 fully protected the mice. These results demonstrate the considerable potential of LNP-formulated, modified ASL-encoding mRNA as an effective alternative to AAV-based approaches for the treatment of ASA.","[""Journal Article""]","[""Daly O"", ""Mahiny AJ"", ""Majeski S"", ""McClintock K"", ""Reichert J"", ""Boros G"", ""Szabó GT"", ""Reinholz J"", ""Schreiner P"", ""Reid S"", ""Lam K"", ""Lepper M"", ""Adler M"", ""Meffen T"", ""Heyes J"", ""Karikó K"", ""Lutwyche P"", ""Vlatkovic I""]",10.3390/biomedicines11061735,Daly O,Biomedicines,2227-9059,6,Biomedicines,eng,Vlatkovic I,[],,37371829,pmc-id: PMC10296609;,2023 Jun 16,2023,https://pubmed.ncbi.nlm.nih.gov/37371829/,ASL mRNA-LNP Therapeutic for the Treatment of Argininosuccinic Aciduria Enables Survival Benefit in a Mouse Model,11,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"The COVID-19 pandemic has taught us many things, among the most important of which is that vaccines are one of the cornerstones of public health that help make modern longevity possible. While several different vaccines have been successful at stemming the morbidity and mortality associated with various infectious diseases, many pathogens/diseases remain recalcitrant to the development of effective vaccination. Recent advances in vaccine technology, immunology, structural biology, and other fields may yet yield insight that will address these diseases; they may also help improve societies' preparedness for future pandemics. On June 1-4, 2022, experts in vaccinology from academia, industry, and government convened for the Keystone symposium ""Progress in Vaccine Development for Infectious Diseases"" to discuss state-of-the-art technologies, recent advancements in understanding vaccine-mediated immunity, and new aspects of antigen design to aid vaccine effectiveness.","[""Journal Article"", ""Research Support, Non-U.S. Gov't"", ""Research Support, N.I.H., Extramural""]","[""Cable J"", ""Graham BS"", ""Koup RA"", ""Seder RA"", ""Karikó K"", ""Pardi N"", ""Barouch DH"", ""Sharma B"", ""Rauch S"", ""Nachbagauer R"", ""Forsell MNE"", ""Schotsaert M"", ""Ellebedy AH"", ""Loré K"", ""Irvine DJ"", ""Pilkington E"", ""Tahtinen S"", ""Thompson EA"", ""Feraoun Y"", ""King NP"", ""Saunders K"", ""Alter G"", ""Moin SM"", ""Sliepen K"", ""Karlsson Hedestam GB"", ""Wardemann H"", ""Pulendran B"", ""Doria-Rose NA"", ""He WT"", ""Juno JA"", ""Ataca S"", ""Wheatley AK"", ""McLellan JS"", ""Walker LM"", ""Lederhofer J"", ""Lindesmith LC"", ""Wille H"", ""Hotez PJ"", ""Bekker LG""]",10.1111/nyas.14975,Cable J,Annals of the New York Academy of Sciences,0077-8923,1,Ann N Y Acad Sci,eng,Bekker LG,"[""Humans"", ""Pandemics"", ""COVID-19"", ""Vaccines"", ""Communicable Diseases"", ""Vaccination"", ""Vaccine Development""]",65-86,37020354,,2023 Jun,2023,https://pubmed.ncbi.nlm.nih.gov/37020354/,Progress in vaccine development for infectious diseases-a Keystone Symposia report,1524,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"As mRNA vaccines have proved to be very successful in battling the coronavirus disease 2019 (COVID-19) pandemic, this new modality has attracted widespread interest for the development of potent vaccines against other infectious diseases and cancer. Cervical cancer caused by persistent human papillomavirus (HPV) infection is a major cause of cancer-related deaths in women, and the development of safe and effective therapeutic strategies is urgently needed. In the present study, we compared the performance of three different mRNA vaccine modalities to target tumors associated with HPV-16 infection in mice. We generated lipid nanoparticle (LNP)-encapsulated self-amplifying mRNA as well as unmodified and nucleoside-modified non-replicating mRNA vaccines encoding a chimeric protein derived from the fusion of the HPV-16 E7 oncoprotein and the herpes simplex virus type 1 glycoprotein D (gDE7). We demonstrated that single low-dose immunizations with any of the three gDE7 mRNA vaccines induced activation of E7-specific CD8+ T cells, generated memory T cell responses capable of preventing tumor relapses, and eradicated subcutaneous tumors at different growth stages. In addition, the gDE7 mRNA-LNP vaccines induced potent tumor protection in two different orthotopic mouse tumor models after administration of a single vaccine dose. Last, comparative studies demonstrated that all three gDE7 mRNA-LNP vaccines proved to be superior to gDE7 DNA and gDE7 recombinant protein vaccines. Collectively, we demonstrated the immunogenicity and therapeutic efficacy of three different mRNA vaccines in extensive comparative experiments. Our data support further evaluation of these mRNA vaccines in clinical trials.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Ramos da Silva J"", ""Bitencourt Rodrigues K"", ""Formoso Pelegrin G"", ""Silva Sales N"", ""Muramatsu H"", ""de Oliveira Silva M"", ""Porchia BFMM"", ""Moreno ACR"", ""Aps LRMM"", ""Venceslau-Carvalho AA"", ""Tombácz I"", ""Fotoran WL"", ""Karikó K"", ""Lin PJC"", ""Tam YK"", ""de Oliveira Diniz M"", ""Pardi N"", ""de Souza Ferreira LC""]",10.1126/scitranslmed.abn3464,Ramos da Silva J,Science translational medicine,1946-6234,686,Sci Transl Med,eng,de Souza Ferreira LC,"[""Animals"", ""Female"", ""Mice"", ""Cancer Vaccines"", ""CD8-Positive T-Lymphocytes"", ""Disease Models, Animal"", ""Immunization"", ""Mice, Inbred C57BL"", ""Neoplasms"", ""Papillomavirus E7 Proteins"", ""Papillomavirus Infections"", ""Papillomavirus Vaccines"", ""Recombinant Proteins"", ""RNA, Messenger"", ""Vaccines, DNA""]",eabn3464,36867683,,2023 Mar 8,2023,https://pubmed.ncbi.nlm.nih.gov/36867683/,Single immunizations of self-amplifying or non-replicating mRNA-LNP vaccines control HPV-associated tumors in mice,15,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"Pediatric brain tumors are the leading cause of cancer death in children with an urgent need for innovative therapies. Glypican 2 (GPC2) is a cell surface oncoprotein expressed in neuroblastoma for which targeted immunotherapies have been developed. This work aimed to characterize GPC2 expression in pediatric brain tumors and develop an mRNA CAR T cell approach against this target. We investigated GPC2 expression across a cohort of primary pediatric brain tumor samples and cell lines using RNA sequencing, immunohistochemistry, and flow cytometry. To target GPC2 in the brain with adoptive cellular therapies and mitigate potential inflammatory neurotoxicity, we used optimized mRNA to create transient chimeric antigen receptor (CAR) T cells. We developed four mRNA CAR T cell constructs using the highly GPC2-specific fully human D3 single chain variable fragment for preclinical testing. We identified high GPC2 expression across multiple pediatric brain tumor types including medulloblastomas, embryonal tumors with multilayered rosettes, other central nervous system embryonal tumors, as well as definable subsets of highly malignant gliomas. We next validated and prioritized CAR configurations using in vitro cytotoxicity assays with GPC2-expressing neuroblastoma cells, where the light-to-heavy single chain variable fragment configurations proved to be superior. We expanded the testing of the two most potent GPC2-directed CAR constructs to GPC2-expressing medulloblastoma and high-grade glioma cell lines, showing significant GPC2-specific cell death in multiple models. Finally, biweekly locoregional delivery of 2-4 million GPC2-directed mRNA CAR T cells induced significant tumor regression in an orthotopic medulloblastoma model and significantly prolonged survival in an aggressive orthotopic thalamic diffuse midline glioma xenograft model. No GPC2-directed CAR T cell related neurologic or systemic toxicity was observed. Taken together, these data show that GPC2 is a highly differentially expressed cell surface protein on multiple malignant pediatric brain tumors that can be targeted safely with local delivery of mRNA CAR T cells, laying the framework for the clinical translation of GPC2-directed immunotherapies for pediatric brain tumors.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Foster JB"", ""Griffin C"", ""Rokita JL"", ""Stern A"", ""Brimley C"", ""Rathi K"", ""Lane MV"", ""Buongervino SN"", ""Smith T"", ""Madsen PJ"", ""Martinez D"", ""Delaidelli A"", ""Sorensen PH"", ""Wechsler-Reya RJ"", ""Karikó K"", ""Storm PB"", ""Barrett DM"", ""Resnick AC"", ""Maris JM"", ""Bosse KR""]",10.1136/jitc-2021-004450,Foster JB,Journal for immunotherapy of cancer,2051-1426,9,J Immunother Cancer,eng,Bosse KR,"[""Brain Neoplasms"", ""Cell Line, Tumor"", ""Cerebellar Neoplasms"", ""Child"", ""Glioma"", ""Glypicans"", ""Humans"", ""Medulloblastoma"", ""Neuroblastoma"", ""Oncogene Proteins"", ""RNA, Messenger"", ""Receptors, Chimeric Antigen"", ""Single-Chain Antibodies"", ""Xenograft Model Antitumor Assays""]",,36167467,pmc-id: PMC9516314;,2022 Sep,2022,https://pubmed.ncbi.nlm.nih.gov/36167467/,Development of GPC2-directed chimeric antigen receptors using mRNA for pediatric brain tumors,10,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
,"[""Published Erratum""]","[""Alameh MG"", ""Tombácz I"", ""Bettini E"", ""Lederer K"", ""Sittplangkoon C"", ""Wilmore JR"", ""Gaudette BT"", ""Soliman OY"", ""Pine M"", ""Hicks P"", ""Manzoni TB"", ""Knox JJ"", ""Johnson JL"", ""Laczkó D"", ""Muramatsu H"", ""Davis B"", ""Meng W"", ""Rosenfeld AM"", ""Strohmeier S"", ""Lin PJC"", ""Mui BL"", ""Tam YK"", ""Karikó K"", ""Jacquet A"", ""Krammer F"", ""Bates P"", ""Cancro MP"", ""Weissman D"", ""Luning Prak ET"", ""Allman D"", ""Locci M"", ""Pardi N""]",10.1016/j.immuni.2022.05.007,Alameh MG,Immunity,1074-7613,6,Immunity,eng,Pardi N,[],1136-1138,35704995,pmc-id: PMC9195404;,2022 Jun 14,2022,https://pubmed.ncbi.nlm.nih.gov/35704995/,Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses,55,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"RNA can be extensively modified post-transcriptionally with >170 covalent modifications, expanding its functional and structural repertoire. Pseudouridine (Ψ), the most abundant modified nucleoside in rRNA and tRNA, has recently been found within mRNA molecules. It remains unclear whether pseudouridylation of mRNA can be snoRNA-guided, bearing important implications for understanding the physiological target spectrum of snoRNAs and for their potential therapeutic exploitation in genetic diseases. Here, using a massively parallel reporter based strategy we simultaneously interrogate Ψ levels across hundreds of synthetic constructs with predesigned complementarity against endogenous snoRNAs. Our results demonstrate that snoRNA-mediated pseudouridylation can occur on mRNA targets. However, this is typically achieved at relatively low efficiencies, and is constrained by mRNA localization, snoRNA expression levels and the length of the snoRNA:mRNA complementarity stretches. We exploited these insights for the design of snoRNAs targeting pseudouridylation at premature termination codons, which was previously shown to suppress translational termination. However, in this and follow-up experiments in human cells we observe no evidence for significant levels of readthrough of pseudouridylated stop codons. Our study enhances our understanding of the scope, 'design rules', constraints and consequences of snoRNA-mediated pseudouridylation.","[""Journal Article""]","[""Nir R"", ""Hoernes TP"", ""Muramatsu H"", ""Faserl K"", ""Karikó K"", ""Erlacher MD"", ""Sas-Chen A"", ""Schwartz S""]",10.1093/nar/gkac347,Nir R,Nucleic acids research,0305-1048,9,Nucleic Acids Res,eng,Schwartz S,"[""Humans"", ""Protein Biosynthesis"", ""Pseudouridine"", ""RNA Processing, Post-Transcriptional"", ""RNA, Messenger"", ""RNA, Ribosomal"", ""RNA, Small Nucleolar""]",4900-4916,35536311,pmc-id: PMC9122591;,2022 May 20,2022,https://pubmed.ncbi.nlm.nih.gov/35536311/,A systematic dissection of determinants and consequences of snoRNA-guided pseudouridylation of human mRNA,50,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"Messenger RNA was discovered in 1961 and it took 60 years until the first mRNA became FDA-approved product in the form of COVID-19 mRNA vaccine. During those years a lot of progress has been made by hundreds of scientists. It was 1978 when the first-time isolated mRNA delivered into mammalian cells produced the encoded protein. In vitro transcription introduced in 1984 made it possible to generate any desired mRNA from the encoding plasmid using phage RNA polymerases. In the early 90s mRNA was used for therapy as well as vaccine against infectious diseases and cancer. Inflammatory nature of the mRNAs limited their in vivo use. Replacing uridine with pseudouridine made the mRNA non-immunogenic, more stable and highly translatable. Delivery of the lipid nanoparticle-formulated nucleoside-modified mRNA encoding viral antigens became a platform for effective vaccine. Labile nature of the mRNA is ideal for transient production of the viral antigen, to generate effective antibody and cellular immune response. The mRNA platform is revolutionizing the delivery of effective and safe vaccines, therapeutics and gene therapies.","[""Journal Article""]","[""Karikó K""]",10.2302/kjm.71-001-ABST,Karikó K,The Keio journal of medicine,0022-9717,1,Keio J Med,eng,Karikó K,"[""Animals"", ""COVID-19"", ""COVID-19 Vaccines"", ""Humans"", ""Liposomes"", ""Mammals"", ""Nanoparticles"", ""RNA, Messenger"", ""Vaccines, Synthetic"", ""mRNA Vaccines""]",31,35342149,,2022,2022,https://pubmed.ncbi.nlm.nih.gov/35342149/,Developing mRNA for Therapy,71,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"The presence of the cap structure on the 5'-end of in vitro-transcribed (IVT) mRNA determines its translation and stability, underpinning its use in therapeutics. Both enzymatic and co-transcriptional capping may lead to incomplete positioning of the cap on newly synthesized RNA molecules. IVT mRNAs are rapidly emerging as novel biologics, including recent vaccines against COVID-19 and vaccine candidates against other infectious diseases, as well as for cancer immunotherapies and protein replacement therapies. Quality control methods necessary for the preclinical and clinical stages of development of these therapeutics are under ongoing development. Here, we described a method to assess the presence of the cap structure of IVT mRNAs. We designed a set of ribozyme assays to specifically cleave IVT mRNAs at a unique position and release 5'-end capped or uncapped cleavage products up to 30 nt long. We purified these products using silica-based columns and visualized/quantified them using denaturing polyacrylamide gel electrophoresis (PAGE) or liquid chromatography and mass spectrometry (LC-MS). Using this technology, we determined the capping efficiencies of IVT mRNAs with different features, which include: Different cap structures, diverse 5' untranslated regions, different nucleoside modifications, and diverse lengths. Taken together, the ribozyme cleavage assays we developed are fast and reliable for the analysis of capping efficiency for research and development purposes, as well as a general quality control for mRNA-based therapeutics.","[""Journal Article""]","[""Vlatkovic I"", ""Ludwig J"", ""Boros G"", ""Szabó GT"", ""Reichert J"", ""Buff M"", ""Baiersdörfer M"", ""Reinholz J"", ""Mahiny AJ"", ""Şahin U"", ""Karikó K""]",10.3390/pharmaceutics14020328,Vlatkovic I,Pharmaceutics,1999-4923,2,Pharmaceutics,eng,Karikó K,[],,35214060,pmc-id: PMC8879150;,2022 Jan 29,2022,https://pubmed.ncbi.nlm.nih.gov/35214060/,Ribozyme Assays to Quantify the Capping Efficiency of In Vitro-Transcribed mRNA,14,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"Lipid nanoparticle (LNP)-formulated nucleoside-modified mRNA vaccines have proven to be very successful in the fight against the coronavirus disease 2019 (COVID-19) pandemic. They are effective, safe, and can be produced in large quantities. However, the long-term storage of mRNA-LNP vaccines without freezing is still a challenge. Here, we demonstrate that nucleoside-modified mRNA-LNPs can be lyophilized, and the physicochemical properties of the lyophilized material do not significantly change for 12 weeks after storage at room temperature and for at least 24 weeks after storage at 4°C. Importantly, we show in comparative mouse studies that lyophilized firefly luciferase-encoding mRNA-LNPs maintain their high expression, and no decrease in the immunogenicity of a lyophilized influenza virus hemagglutinin-encoding mRNA-LNP vaccine was observed after 12 weeks of storage at room temperature or for at least 24 weeks after storage at 4°C. Our studies offer a potential solution to overcome the long-term storage-related limitations of nucleoside-modified mRNA-LNP vaccines.","[""Journal Article"", ""Research Support, Non-U.S. Gov't"", ""Research Support, N.I.H., Extramural""]","[""Muramatsu H"", ""Lam K"", ""Bajusz C"", ""Laczkó D"", ""Karikó K"", ""Schreiner P"", ""Martin A"", ""Lutwyche P"", ""Heyes J"", ""Pardi N""]",10.1016/j.ymthe.2022.02.001,Muramatsu H,Molecular therapy : the journal of the American Society of Gene Therapy,1525-0016,5,Mol Ther,eng,Pardi N,"[""Animals"", ""COVID-19"", ""Freeze Drying"", ""Influenza Vaccines"", ""Liposomes"", ""Mice"", ""Nanoparticles"", ""Nucleosides"", ""RNA, Messenger"", ""Vaccines, Synthetic"", ""mRNA Vaccines""]",1941-1951,35131437,pmc-id: PMC8815268;,2022 May 4,2022,https://pubmed.ncbi.nlm.nih.gov/35131437/,"Lyophilization provides long-term stability for a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine",30,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"Adjuvants are critical for improving the quality and magnitude of adaptive immune responses to vaccination. Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines have shown great efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the mechanism of action of this vaccine platform is not well-characterized. Using influenza virus and SARS-CoV-2 mRNA and protein subunit vaccines, we demonstrated that our LNP formulation has intrinsic adjuvant activity that promotes induction of strong T follicular helper cell, germinal center B cell, long-lived plasma cell, and memory B cell responses that are associated with durable and protective antibodies in mice. Comparative experiments demonstrated that this LNP formulation outperformed a widely used MF59-like adjuvant, AddaVax. The adjuvant activity of the LNP relies on the ionizable lipid component and on IL-6 cytokine induction but not on MyD88- or MAVS-dependent sensing of LNPs. Our study identified LNPs as a versatile adjuvant that enhances the efficacy of traditional and next-generation vaccine platforms.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Alameh MG"", ""Tombácz I"", ""Bettini E"", ""Lederer K"", ""Sittplangkoon C"", ""Wilmore JR"", ""Gaudette BT"", ""Soliman OY"", ""Pine M"", ""Hicks P"", ""Manzoni TB"", ""Knox JJ"", ""Johnson JL"", ""Laczkó D"", ""Muramatsu H"", ""Davis B"", ""Meng W"", ""Rosenfeld AM"", ""Strohmeier S"", ""Lin PJC"", ""Mui BL"", ""Tam YK"", ""Karikó K"", ""Jacquet A"", ""Krammer F"", ""Bates P"", ""Cancro MP"", ""Weissman D"", ""Luning Prak ET"", ""Allman D"", ""Locci M"", ""Pardi N""]",10.1016/j.immuni.2021.11.001,Alameh MG,Immunity,1074-7613,12,Immunity,eng,Pardi N,"[""Adaptor Proteins, Signal Transducing"", ""Adjuvants, Immunologic"", ""Animals"", ""B-Lymphocytes"", ""COVID-19"", ""COVID-19 Vaccines"", ""Germinal Center"", ""HEK293 Cells"", ""Humans"", ""Immunity, Humoral"", ""Interleukin-6"", ""Liposomes"", ""Mice"", ""Mice, Inbred BALB C"", ""Nanoparticles"", ""Protein Subunits"", ""SARS-CoV-2"", ""T-Lymphocytes, Helper-Inducer"", ""mRNA Vaccines""]",2877-2892.e7,34852217,pmc-id: PMC8566475;,2021 Dec 14,2021,https://pubmed.ncbi.nlm.nih.gov/34852217/,Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses,54,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
,"[""Journal Article""]","[""Karikó K""]",10.1038/s41577-021-00608-w,Karikó K,Nature reviews. Immunology,1474-1733,10,Nat Rev Immunol,eng,Karikó K,[],619,34580453,,2021 Oct,2021,https://pubmed.ncbi.nlm.nih.gov/34580453/,Modified uridines are the key to a successful message,21,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"Local immunotherapy ideally stimulates immune responses against tumors while avoiding toxicities associated with systemic administration. Current strategies for tumor-targeted, gene-based delivery, however, are limited by adverse effects such as off-targeting or antivector immunity. We investigated the intratumoral administration of saline-formulated messenger (m)RNA encoding four cytokines that were identified as mediators of tumor regression across different tumor models: interleukin-12 (IL-12) single chain, interferon-α (IFN-α), granulocyte-macrophage colony-stimulating factor, and IL-15 sushi. Effective antitumor activity of these cytokines relied on multiple immune cell populations and was accompanied by intratumoral IFN-γ induction, systemic antigen-specific T cell expansion, increased granzyme B+ T cell infiltration, and formation of immune memory. Antitumor activity extended beyond the treated lesions and inhibited growth of distant tumors and disseminated tumors. Combining the mRNAs with immunomodulatory antibodies enhanced antitumor responses in both injected and uninjected tumors, thus improving survival and tumor regression. Consequently, clinical testing of this cytokine-encoding mRNA mixture is now underway.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Hotz C"", ""Wagenaar TR"", ""Gieseke F"", ""Bangari DS"", ""Callahan M"", ""Cao H"", ""Diekmann J"", ""Diken M"", ""Grunwitz C"", ""Hebert A"", ""Hsu K"", ""Bernardo M"", ""Karikó K"", ""Kreiter S"", ""Kuhn AN"", ""Levit M"", ""Malkova N"", ""Masciari S"", ""Pollard J"", ""Qu H"", ""Ryan S"", ""Selmi A"", ""Schlereth J"", ""Singh K"", ""Sun F"", ""Tillmann B"", ""Tolstykh T"", ""Weber W"", ""Wicke L"", ""Witzel S"", ""Yu Q"", ""Zhang YA"", ""Zheng G"", ""Lager J"", ""Nabel GJ"", ""Sahin U"", ""Wiederschain D""]",10.1126/scitranslmed.abc7804,Hotz C,Science translational medicine,1946-6234,610,Sci Transl Med,eng,Wiederschain D,"[""Cytokines"", ""Humans"", ""Neoplasms"", ""RNA, Messenger""]",eabc7804,34516826,,2021 Sep 8,2021,https://pubmed.ncbi.nlm.nih.gov/34516826/,Local delivery of mRNA-encoded cytokines promotes antitumor immunity and tumor eradication across multiple preclinical tumor models,13,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
,"[""Journal Article""]","[""Karikó K"", ""Whitehead K"", ""van der Meel R""]",10.1016/j.cels.2021.07.005,Karikó K,Cell systems,2405-4712,8,Cell Syst,eng,van der Meel R,"[""Vaccines, Synthetic"", ""mRNA Vaccines""]",757-758,34411542,pmc-id: PMC8372463;,2021 Aug 18,2021,https://pubmed.ncbi.nlm.nih.gov/34411542/,What does the success of mRNA vaccines tell us about the future of biological therapeutics?,12,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"Lack or dysfunction of the lymphatics leads to secondary lymphedema formation that seriously reduces the function of the affected organs and results in degradation of quality of life. Currently, there is no definitive treatment option for lymphedema. Here, we utilized nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNPs) encoding murine Vascular Endothelial Growth Factor C (VEGFC) to stimulate lymphatic growth and function and reduce experimental lymphedema in mouse models. We demonstrated that administration of a single low-dose of VEGFC mRNA-LNPs induced durable, organ-specific lymphatic growth and formation of a functional lymphatic network. Importantly, VEGFC mRNA-LNP treatment reversed experimental lymphedema by restoring lymphatic function without inducing any obvious adverse events. Collectively, we present a novel application of the nucleoside-modified mRNA-LNP platform, describe a model for identifying the organ-specific physiological and pathophysiological roles of the lymphatics, and propose an efficient and safe treatment option that may serve as a novel therapeutic tool to reduce lymphedema.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Szőke D"", ""Kovács G"", ""Kemecsei É"", ""Bálint L"", ""Szoták-Ajtay K"", ""Aradi P"", ""Styevkóné Dinnyés A"", ""Mui BL"", ""Tam YK"", ""Madden TD"", ""Karikó K"", ""Kataru RP"", ""Hope MJ"", ""Weissman D"", ""Mehrara BJ"", ""Pardi N"", ""Jakus Z""]",10.1038/s41467-021-23546-6,Szőke D,Nature communications,2041-1723,1,Nat Commun,eng,Jakus Z,"[""Animals"", ""Blood Vessels"", ""Cell Proliferation"", ""Diphtheria Toxin"", ""Disease Models, Animal"", ""HEK293 Cells"", ""Humans"", ""Immunity"", ""Injections, Intradermal"", ""Lipids"", ""Lymphangiogenesis"", ""Lymphatic Vessels"", ""Lymphedema"", ""Mice, Inbred C57BL"", ""Nanoparticles"", ""Nucleosides"", ""Organ Specificity"", ""Poly C"", ""RNA, Messenger"", ""Tamoxifen"", ""Vascular Endothelial Growth Factor C"", ""Mice""]",3460,34103491,pmc-id: PMC8187400;,2021 Jun 8,2021,https://pubmed.ncbi.nlm.nih.gov/34103491/,Nucleoside-modified VEGFC mRNA induces organ-specific lymphatic growth and reverses experimental lymphedema,12,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"BNT162b2, a nucleoside-modified mRNA formulated in lipid nanoparticles that encodes the SARS-CoV-2 spike glycoprotein (S) stabilized in its prefusion conformation, has demonstrated 95% efficacy in preventing COVID-191. Here we extend a previous phase-I/II trial report2 by presenting data on the immune response induced by BNT162b2 prime-boost vaccination from an additional phase-I/II trial in healthy adults (18-55 years old). BNT162b2 elicited strong antibody responses: at one week after the boost, SARS-CoV-2 serum geometric mean 50% neutralizing titres were up to 3.3-fold above those observed in samples from individuals who had recovered from COVID-19. Sera elicited by BNT162b2 neutralized 22 pseudoviruses bearing the S of different SARS-CoV-2 variants. Most participants had a strong response of IFNγ+ or IL-2+ CD8+ and CD4+ T helper type 1 cells, which was detectable throughout the full observation period of nine weeks following the boost. Using peptide-MHC multimer technology, we identified several BNT162b2-induced epitopes that were presented by frequent MHC alleles and conserved in mutant strains. One week after the boost, epitope-specific CD8+ T cells of the early-differentiated effector-memory phenotype comprised 0.02-2.92% of total circulating CD8+ T cells and were detectable (0.01-0.28%) eight weeks later. In summary, BNT162b2 elicits an adaptive humoral and poly-specific cellular immune response against epitopes that are conserved in a broad range of variants, at well-tolerated doses.","[""Clinical Trial, Phase I"", ""Clinical Trial, Phase II"", ""Journal Article""]","[""Sahin U"", ""Muik A"", ""Vogler I"", ""Derhovanessian E"", ""Kranz LM"", ""Vormehr M"", ""Quandt J"", ""Bidmon N"", ""Ulges A"", ""Baum A"", ""Pascal KE"", ""Maurus D"", ""Brachtendorf S"", ""Lörks V"", ""Sikorski J"", ""Koch P"", ""Hilker R"", ""Becker D"", ""Eller AK"", ""Grützner J"", ""Tonigold M"", ""Boesler C"", ""Rosenbaum C"", ""Heesen L"", ""Kühnle MC"", ""Poran A"", ""Dong JZ"", ""Luxemburger U"", ""Kemmer-Brück A"", ""Langer D"", ""Bexon M"", ""Bolte S"", ""Palanche T"", ""Schultz A"", ""Baumann S"", ""Mahiny AJ"", ""Boros G"", ""Reinholz J"", ""Szabó GT"", ""Karikó K"", ""Shi PY"", ""Fontes-Garfias C"", ""Perez JL"", ""Cutler M"", ""Cooper D"", ""Kyratsous CA"", ""Dormitzer PR"", ""Jansen KU"", ""Türeci Ö""]",10.1038/s41586-021-03653-6,Sahin U,Nature,0028-0836,7868,Nature,eng,Türeci Ö,"[""Adolescent"", ""Adult"", ""Antibodies, Neutralizing"", ""Antibodies, Viral"", ""BNT162 Vaccine"", ""CD8-Positive T-Lymphocytes"", ""COVID-19"", ""COVID-19 Vaccines"", ""Epitopes, T-Lymphocyte"", ""Female"", ""Humans"", ""Immunoglobulin G"", ""Immunologic Memory"", ""Interferon-gamma"", ""Interleukin-2"", ""Male"", ""Middle Aged"", ""SARS-CoV-2"", ""Spike Glycoprotein, Coronavirus"", ""T-Lymphocytes"", ""Th1 Cells"", ""Young Adult""]",572-577,34044428,,2021 Jul,2021,https://pubmed.ncbi.nlm.nih.gov/34044428/,BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans,595,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
,"[""Published Erratum""]","[""Sahin U"", ""Muik A"", ""Derhovanessian E"", ""Vogler I"", ""Kranz LM"", ""Vormehr M"", ""Baum A"", ""Pascal K"", ""Quandt J"", ""Maurus D"", ""Brachtendorf S"", ""Lörks V"", ""Sikorski J"", ""Hilker R"", ""Becker D"", ""Eller AK"", ""Grützner J"", ""Boesler C"", ""Rosenbaum C"", ""Kühnle MC"", ""Luxemburger U"", ""Kemmer-Brück A"", ""Langer D"", ""Bexon M"", ""Bolte S"", ""Karikó K"", ""Palanche T"", ""Fischer B"", ""Schultz A"", ""Shi PY"", ""Fontes-Garfias C"", ""Perez JL"", ""Swanson KA"", ""Loschko J"", ""Scully IL"", ""Cutler M"", ""Kalina W"", ""Kyratsous CA"", ""Cooper D"", ""Dormitzer PR"", ""Jansen KU"", ""Türeci Ö""]",10.1038/s41586-020-03102-w,Sahin U,Nature,0028-0836,7844,Nature,eng,Türeci Ö,[],E17,33469214,,2021 Feb,2021,https://pubmed.ncbi.nlm.nih.gov/33469214/,Publisher Correction: COVID-19 vaccine BNT162b1 elicits human antibody and T(H)1 T cell responses,590,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"The ability to control autoreactive T cells without inducing systemic immune suppression is the major goal for treatment of autoimmune diseases. The key challenge is the safe and efficient delivery of pharmaceutically well-defined antigens in a noninflammatory context. Here, we show that systemic delivery of nanoparticle-formulated 1 methylpseudouridine-modified messenger RNA (m1Ψ mRNA) coding for disease-related autoantigens results in antigen presentation on splenic CD11c+ antigen-presenting cells in the absence of costimulatory signals. In several mouse models of multiple sclerosis, the disease is suppressed by treatment with such m1Ψ mRNA. The treatment effect is associated with a reduction of effector T cells and the development of regulatory T cell (Treg cell) populations. Notably, these Treg cells execute strong bystander immunosuppression and thus improve disease induced by cognate and noncognate autoantigens.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Krienke C"", ""Kolb L"", ""Diken E"", ""Streuber M"", ""Kirchhoff S"", ""Bukur T"", ""Akilli-Öztürk Ö"", ""Kranz LM"", ""Berger H"", ""Petschenka J"", ""Diken M"", ""Kreiter S"", ""Yogev N"", ""Waisman A"", ""Karikó K"", ""Türeci Ö"", ""Sahin U""]",10.1126/science.aay3638,Krienke C,"Science (New York, N.Y.)",0036-8075,6525,Science,eng,Sahin U,"[""Animals"", ""Antigen-Presenting Cells"", ""Autoantigens"", ""Bystander Effect"", ""Encephalomyelitis, Autoimmune, Experimental"", ""Immunosuppression Therapy"", ""Inflammation"", ""Mice"", ""Mice, Inbred C57BL"", ""Multiple Sclerosis"", ""Pseudouridine"", ""RNA, Messenger"", ""T-Lymphocytes, Regulatory"", ""Vaccines, Synthetic"", ""mRNA Vaccines""]",145-153,33414215,,2021 Jan 8,2021,https://pubmed.ncbi.nlm.nih.gov/33414215/,A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis,371,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"An effective vaccine is needed to halt the spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. Recently, we reported safety, tolerability and antibody response data from an ongoing placebo-controlled, observer-blinded phase I/II coronavirus disease 2019 (COVID-19) vaccine trial with BNT162b1, a lipid nanoparticle-formulated nucleoside-modified mRNA that encodes the receptor binding domain (RBD) of the SARS-CoV-2 spike protein1. Here we present antibody and T cell responses after vaccination with BNT162b1 from a second, non-randomized open-label phase I/II trial in healthy adults, 18-55 years of age. Two doses of 1-50 μg of BNT162b1 elicited robust CD4+ and CD8+ T cell responses and strong antibody responses, with RBD-binding IgG concentrations clearly above those seen in serum from a cohort of individuals who had recovered from COVID-19. Geometric mean titres of SARS-CoV-2 serum-neutralizing antibodies on day 43 were 0.7-fold (1-μg dose) to 3.5-fold (50-μg dose) those of the recovered individuals. Immune sera broadly neutralized pseudoviruses with diverse SARS-CoV-2 spike variants. Most participants had T helper type 1 (TH1)-skewed T cell immune responses with RBD-specific CD8+ and CD4+ T cell expansion. Interferon-γ was produced by a large fraction of RBD-specific CD8+ and CD4+ T cells. The robust RBD-specific antibody, T cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest that it has the potential to protect against COVID-19 through multiple beneficial mechanisms.","[""Clinical Trial, Phase I"", ""Clinical Trial, Phase II"", ""Journal Article""]","[""Sahin U"", ""Muik A"", ""Derhovanessian E"", ""Vogler I"", ""Kranz LM"", ""Vormehr M"", ""Baum A"", ""Pascal K"", ""Quandt J"", ""Maurus D"", ""Brachtendorf S"", ""Lörks V"", ""Sikorski J"", ""Hilker R"", ""Becker D"", ""Eller AK"", ""Grützner J"", ""Boesler C"", ""Rosenbaum C"", ""Kühnle MC"", ""Luxemburger U"", ""Kemmer-Brück A"", ""Langer D"", ""Bexon M"", ""Bolte S"", ""Karikó K"", ""Palanche T"", ""Fischer B"", ""Schultz A"", ""Shi PY"", ""Fontes-Garfias C"", ""Perez JL"", ""Swanson KA"", ""Loschko J"", ""Scully IL"", ""Cutler M"", ""Kalina W"", ""Kyratsous CA"", ""Cooper D"", ""Dormitzer PR"", ""Jansen KU"", ""Türeci Ö""]",10.1038/s41586-020-2814-7,Sahin U,Nature,0028-0836,7830,Nature,eng,Türeci Ö,"[""Adult"", ""Antibodies, Neutralizing"", ""Antibodies, Viral"", ""CD8-Positive T-Lymphocytes"", ""COVID-19"", ""COVID-19 Vaccines"", ""Coronavirus Infections"", ""Cytokines"", ""Female"", ""Germany"", ""Humans"", ""Immunoglobulin G"", ""Male"", ""Middle Aged"", ""Pandemics"", ""Pneumonia, Viral"", ""Th1 Cells"", ""Viral Vaccines"", ""Young Adult""]",594-599,32998157,,2020 Oct,2020,https://pubmed.ncbi.nlm.nih.gov/32998157/,COVID-19 vaccine BNT162b1 elicits human antibody and T(H)1 T cell responses,586,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"SARS-CoV-2 infection has emerged as a serious global pandemic. Because of the high transmissibility of the virus and the high rate of morbidity and mortality associated with COVID-19, developing effective and safe vaccines is a top research priority. Here, we provide a detailed evaluation of the immunogenicity of lipid nanoparticle-encapsulated, nucleoside-modified mRNA (mRNA-LNP) vaccines encoding the full-length SARS-CoV-2 spike protein or the spike receptor binding domain in mice. We demonstrate that a single dose of these vaccines induces strong type 1 CD4+ and CD8+ T cell responses, as well as long-lived plasma and memory B cell responses. Additionally, we detect robust and sustained neutralizing antibody responses and the antibodies elicited by nucleoside-modified mRNA vaccines do not show antibody-dependent enhancement of infection in vitro. Our findings suggest that the nucleoside-modified mRNA-LNP vaccine platform can induce robust immune responses and is a promising candidate to combat COVID-19.","[""Journal Article"", ""Research Support, N.I.H., Extramural""]","[""Laczkó D"", ""Hogan MJ"", ""Toulmin SA"", ""Hicks P"", ""Lederer K"", ""Gaudette BT"", ""Castaño D"", ""Amanat F"", ""Muramatsu H"", ""Oguin TH 3rd"", ""Ojha A"", ""Zhang L"", ""Mu Z"", ""Parks R"", ""Manzoni TB"", ""Roper B"", ""Strohmeier S"", ""Tombácz I"", ""Arwood L"", ""Nachbagauer R"", ""Karikó K"", ""Greenhouse J"", ""Pessaint L"", ""Porto M"", ""Putman-Taylor T"", ""Strasbaugh A"", ""Campbell TA"", ""Lin PJC"", ""Tam YK"", ""Sempowski GD"", ""Farzan M"", ""Choe H"", ""Saunders KO"", ""Haynes BF"", ""Andersen H"", ""Eisenlohr LC"", ""Weissman D"", ""Krammer F"", ""Bates P"", ""Allman D"", ""Locci M"", ""Pardi N""]",10.1016/j.immuni.2020.07.019,Laczkó D,Immunity,1074-7613,4,Immunity,eng,Pardi N,"[""Animals"", ""Antibodies, Neutralizing"", ""Antibodies, Viral"", ""B-Lymphocytes"", ""Betacoronavirus"", ""CD4-Positive T-Lymphocytes"", ""CD8-Positive T-Lymphocytes"", ""COVID-19"", ""COVID-19 Vaccines"", ""Coronavirus Infections"", ""Disease Models, Animal"", ""Furin"", ""Humans"", ""Immunity, Humoral"", ""Immunization"", ""Immunogenicity, Vaccine"", ""Immunologic Memory"", ""Lymphocyte Activation"", ""Mice"", ""Mice, Inbred BALB C"", ""Nanoparticles"", ""Pandemics"", ""Pneumonia, Viral"", ""RNA, Messenger"", ""RNA, Viral"", ""SARS-CoV-2"", ""Spike Glycoprotein, Coronavirus"", ""Vaccines, Synthetic"", ""Viral Vaccines""]",724-732.e7,32783919,pmc-id: PMC7392193;manuscript-id: NIHMS1617591;,2020 Oct 13,2020,https://pubmed.ncbi.nlm.nih.gov/32783919/,A Single Immunization with Nucleoside-Modified mRNA Vaccines Elicits Strong Cellular and Humoral Immune Responses against SARS-CoV-2 in Mice,53,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"Despite the enormous effort in the development of effective vaccines against HIV-1, no vaccine candidate has elicited broadly neutralizing antibodies in humans. Thus, generation of more effective anti-HIV vaccines is critically needed. Here we characterize the immune responses induced by nucleoside-modified and purified mRNA-lipid nanoparticle (mRNA-LNP) vaccines encoding the clade C transmitted/founder HIV-1 envelope (Env) 1086C. Intradermal vaccination with nucleoside-modified 1086C Env mRNA-LNPs elicited high levels of gp120-specific antibodies in rabbits and rhesus macaques. Antibodies generated in rabbits neutralized a tier 1 virus, but no tier 2 neutralization activity could be measured. Importantly, three of six non-human primates developed antibodies that neutralized the autologous tier 2 strain. Despite stable anti-gp120 immunoglobulin G (IgG) levels, tier 2 neutralization titers started to drop 4 weeks after booster immunizations. Serum from both immunized rabbits and non-human primates demonstrated antibody-dependent cellular cytotoxicity activity. Collectively, these results are supportive of continued development of nucleoside-modified and purified mRNA-LNP vaccines for HIV. Optimization of Env immunogens and vaccination protocols are needed to increase antibody neutralization breadth and durability.","[""Journal Article""]","[""Pardi N"", ""LaBranche CC"", ""Ferrari G"", ""Cain DW"", ""Tombácz I"", ""Parks RJ"", ""Muramatsu H"", ""Mui BL"", ""Tam YK"", ""Karikó K"", ""Polacino P"", ""Barbosa CJ"", ""Madden TD"", ""Hope MJ"", ""Haynes BF"", ""Montefiori DC"", ""Hu SL"", ""Weissman D""]",10.1016/j.omtn.2019.03.003,Pardi N,Molecular therapy. Nucleic acids,2162-2531,,Mol Ther Nucleic Acids,eng,Weissman D,[],36-47,30974332,pmc-id: PMC6454128;,2019 Apr 15,2019,https://pubmed.ncbi.nlm.nih.gov/30974332/,Characterization of HIV-1 Nucleoside-Modified mRNA Vaccines in Rabbits and Rhesus Macaques,15,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"The increasing importance of in vitro-transcribed (IVT) mRNA for synthesizing the encoded therapeutic protein in vivo demands the manufacturing of pure mRNA products. The major contaminant in the IVT mRNA is double-stranded RNA (dsRNA), a transcriptional by-product that can be removed only by burdensome procedure requiring special instrumentation and generating hazardous waste. Here we present an alternative simple, fast, and cost-effective method involving only standard laboratory techniques. The purification of IVT mRNA is based on the selective binding of dsRNA to cellulose in an ethanol-containing buffer. We demonstrate that at least 90% of the dsRNA contaminants can be removed with a good, >65% recovery rate, regardless of the length, coding sequence, and nucleoside composition of the IVT mRNA. The procedure is scalable; purification of microgram or milligram amounts of IVT mRNA is achievable. Evaluating the impact of the mRNA purification in vivo in mice, increased translation could be measured for the administered transcripts, including the 1-methylpseudouridine-containing IVT mRNA, which no longer induced interferon (IFN)-α. The cellulose-based removal of dsRNA contaminants is an effective, reliable, and safe method to obtain highly pure IVT mRNA suitable for in vivo applications.","[""Journal Article""]","[""Baiersdörfer M"", ""Boros G"", ""Muramatsu H"", ""Mahiny A"", ""Vlatkovic I"", ""Sahin U"", ""Karikó K""]",10.1016/j.omtn.2019.02.018,Baiersdörfer M,Molecular therapy. Nucleic acids,2162-2531,,Mol Ther Nucleic Acids,eng,Karikó K,[],26-35,30933724,pmc-id: PMC6444222;,2019 Apr 15,2019,https://pubmed.ncbi.nlm.nih.gov/30933724/,A Facile Method for the Removal of dsRNA Contaminant from In Vitro-Transcribed mRNA,15,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
,"[""Editorial""]","[""Karikó K""]",10.1016/j.ymthe.2019.03.009,Karikó K,Molecular therapy : the journal of the American Society of Gene Therapy,1525-0016,4,Mol Ther,eng,Karikó K,"[""Cancer Vaccines"", ""Drug Delivery Systems"", ""Genetic Therapy"", ""Humans"", ""In Vitro Techniques"", ""RNA, Messenger"", ""Transcription, Genetic""]",691-692,30905578,pmc-id: PMC6453554;,2019 Apr 10,2019,https://pubmed.ncbi.nlm.nih.gov/30905578/,In vitro-Transcribed mRNA Therapeutics: Out of the Shadows and Into the Spotlight,27,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"Adoptive T cell therapy is a form of cellular therapy that utilizes human immune cells, often empowered by the expression of recombinant proteins, to attack selected targets present on tumor or infected cells. T cell-based immunotherapy has been progressing over the past several decades, and reached a milestone with the recent US Food and Drug Administration (FDA) approval of chimeric antigen receptor T cell therapy for relapsed and refractory leukemia and lymphoma. Although most studies have used viral vectors, a growing number of researchers have come to appreciate in vitro-transcribed (IVT) mRNA for the development, testing, and application of T cell-based immunotherapeutics. IVT mRNA offers inherent safety features, highly efficient recombinant protein translation, and the ability to control pharmacokinetic properties of the therapy. In this review, we discuss the history of IVT mRNA in adoptive T cell therapy, from tumor-infiltrating lymphocytes and T cell receptor-based therapies to chimeric antigen receptor therapy and gene-editing techniques, as well as prior and ongoing clinical trials.","[""Journal Article"", ""Review""]","[""Foster JB"", ""Barrett DM"", ""Karikó K""]",10.1016/j.ymthe.2019.01.018,Foster JB,Molecular therapy : the journal of the American Society of Gene Therapy,1525-0016,4,Mol Ther,eng,Karikó K,"[""Animals"", ""Cell- and Tissue-Based Therapy"", ""Gene Editing"", ""Genetic Vectors"", ""Humans"", ""Immunotherapy, Adoptive"", ""In Vitro Techniques"", ""Lymphocytes, Tumor-Infiltrating"", ""Mice"", ""Neoplasms"", ""RNA, Messenger"", ""Receptors, Antigen, T-Cell"", ""Receptors, Chimeric Antigen"", ""T-Lymphocytes"", ""Transcription, Genetic""]",747-756,30819612,pmc-id: PMC6453504;,2019 Apr 10,2019,https://pubmed.ncbi.nlm.nih.gov/30819612/,The Emerging Role of In Vitro-Transcribed mRNA in Adoptive T Cell Immunotherapy,27,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"Currently available influenza virus vaccines have inadequate effectiveness and are reformulated annually due to viral antigenic drift. Thus, development of a vaccine that confers long-term protective immunity against antigenically distant influenza virus strains is urgently needed. The highly conserved influenza virus hemagglutinin (HA) stalk represents one of the potential targets of broadly protective/universal influenza virus vaccines. Here, we evaluate a potent broadly protective influenza virus vaccine candidate that uses nucleoside-modified and purified mRNA encoding full-length influenza virus HA formulated in lipid nanoparticles (LNPs). We demonstrate that immunization with HA mRNA-LNPs induces antibody responses against the HA stalk domain of influenza virus in mice, rabbits, and ferrets. The HA stalk-specific antibody response is associated with protection from homologous, heterologous, and heterosubtypic influenza virus infection in mice.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Pardi N"", ""Parkhouse K"", ""Kirkpatrick E"", ""McMahon M"", ""Zost SJ"", ""Mui BL"", ""Tam YK"", ""Karikó K"", ""Barbosa CJ"", ""Madden TD"", ""Hope MJ"", ""Krammer F"", ""Hensley SE"", ""Weissman D""]",10.1038/s41467-018-05482-0,Pardi N,Nature communications,2041-1723,1,Nat Commun,eng,Weissman D,"[""Animals"", ""Antibodies, Viral"", ""Cells, Cultured"", ""Dogs"", ""Enzyme-Linked Immunosorbent Assay"", ""Female"", ""Ferrets"", ""Flow Cytometry"", ""Hemagglutinins"", ""Influenza A Virus, H5N1 Subtype"", ""Madin Darby Canine Kidney Cells"", ""Mice"", ""Mice, Inbred BALB C"", ""Orthomyxoviridae"", ""Phylogeny"", ""RNA, Messenger"", ""Rabbits""]",3361,30135514,pmc-id: PMC6105651;,2018 Aug 22,2018,https://pubmed.ncbi.nlm.nih.gov/30135514/,Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies,9,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"T cells made with messenger RNA (mRNA) encoding chimeric antigen receptor (CAR) offer a safe alternative to those transduced with viral CARs by mitigating the side effects of constitutively active T cells. Previous studies have shown that mRNA CAR T cells are transiently effective but lack persistence and potency across tumor types. It was hypothesized that the efficacy of mRNA CARs could be improved by utilizing recent advancements in RNA technology, such as incorporating a modified nucleoside, 1-methylpseudouridine, into the mRNA and applying a novel purification method using RNase III to eliminate dsRNA contaminants. T cells electroporated with nucleoside-modified and purified mRNA encoding CD19 CAR showed an initial twofold increase in CAR surface expression, as well as a twofold improvement in cytotoxic killing of leukemia cells that persisted up to 5 days. T cells generated with nucleoside-modified and purified CAR mRNA also showed reduced expression of checkpoint regulators and a differential pattern of genetic activation compared to those made with conventional mRNA. In vivo studies using a leukemia mouse model revealed that the most robust 100-fold suppression of leukemic burden was achieved using T cells electroporated with purified mRNAs, regardless of their nucleoside modification. The results provide a novel approach to generate mRNA for clinical trials, and poise mRNA CAR T cells for increased efficacy during testing as new CAR targets emerge.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Foster JB"", ""Choudhari N"", ""Perazzelli J"", ""Storm J"", ""Hofmann TJ"", ""Jain P"", ""Storm PB"", ""Pardi N"", ""Weissman D"", ""Waanders AJ"", ""Grupp SA"", ""Karikó K"", ""Resnick AC"", ""Barrett DM""]",10.1089/hum.2018.145,Foster JB,Human gene therapy,1043-0342,2,Hum Gene Ther,eng,Barrett DM,"[""Adoptive Transfer"", ""Animals"", ""Antigens, CD19"", ""Cell Line, Tumor"", ""Electroporation"", ""Humans"", ""Leukemia"", ""Mice"", ""Mice, Inbred NOD"", ""Mice, Knockout"", ""Mice, SCID"", ""RNA, Messenger"", ""Receptors, Chimeric Antigen"", ""T-Lymphocytes"", ""Xenograft Model Antitumor Assays""]",168-178,30024272,pmc-id: PMC6383579;,2019 Feb,2019,https://pubmed.ncbi.nlm.nih.gov/30024272/,Purification of mRNA Encoding Chimeric Antigen Receptor Is Critical for Generation of a Robust T-Cell Response,30,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"T follicular helper (Tfh) cells are required to develop germinal center (GC) responses and drive immunoglobulin class switch, affinity maturation, and long-term B cell memory. In this study, we characterize a recently developed vaccine platform, nucleoside-modified, purified mRNA encapsulated in lipid nanoparticles (mRNA-LNPs), that induces high levels of Tfh and GC B cells. Intradermal vaccination with nucleoside-modified mRNA-LNPs encoding various viral surface antigens elicited polyfunctional, antigen-specific, CD4+ T cell responses and potent neutralizing antibody responses in mice and nonhuman primates. Importantly, the strong antigen-specific Tfh cell response and high numbers of GC B cells and plasma cells were associated with long-lived and high-affinity neutralizing antibodies and durable protection. Comparative studies demonstrated that nucleoside-modified mRNA-LNP vaccines outperformed adjuvanted protein and inactivated virus vaccines and pathogen infection. The incorporation of noninflammatory, modified nucleosides in the mRNA is required for the production of large amounts of antigen and for robust immune responses.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't"", ""Research Support, U.S. Gov't, Non-P.H.S.""]","[""Pardi N"", ""Hogan MJ"", ""Naradikian MS"", ""Parkhouse K"", ""Cain DW"", ""Jones L"", ""Moody MA"", ""Verkerke HP"", ""Myles A"", ""Willis E"", ""LaBranche CC"", ""Montefiori DC"", ""Lobby JL"", ""Saunders KO"", ""Liao HX"", ""Korber BT"", ""Sutherland LL"", ""Scearce RM"", ""Hraber PT"", ""Tombácz I"", ""Muramatsu H"", ""Ni H"", ""Balikov DA"", ""Li C"", ""Mui BL"", ""Tam YK"", ""Krammer F"", ""Karikó K"", ""Polacino P"", ""Eisenlohr LC"", ""Madden TD"", ""Hope MJ"", ""Lewis MG"", ""Lee KK"", ""Hu SL"", ""Hensley SE"", ""Cancro MP"", ""Haynes BF"", ""Weissman D""]",10.1084/jem.20171450,Pardi N,The Journal of experimental medicine,0022-1007,6,J Exp Med,eng,Weissman D,"[""Adjuvants, Immunologic"", ""Animals"", ""Antibodies, Neutralizing"", ""Antibody Formation"", ""Antigens"", ""B-Lymphocytes"", ""Germinal Center"", ""Lipids"", ""Macaca mulatta"", ""Nanoparticles"", ""Nucleosides"", ""Protein Subunits"", ""RNA, Messenger"", ""T-Lymphocytes, Helper-Inducer"", ""Time Factors"", ""Vaccination"", ""Vaccines, Subunit""]",1571-1588,29739835,pmc-id: PMC5987916;,2018 Jun 4,2018,https://pubmed.ncbi.nlm.nih.gov/29739835/,Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses,215,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"The asthmatic airways are highly susceptible to inflammatory injury by air pollutants such as ozone (O3 ), characterized by enhanced activation of eosinophilic granulocytes and a failure of immune protective mechanisms. Eosinophil activation during asthma exacerbation contributes to the proinflammatory oxidative stress by high levels of nitric oxide (NO) production and extracellular DNA release. Surfactant protein-D (SP-D), an epithelial cell product of the airways, is a critical immune regulatory molecule with a multimeric structure susceptible to oxidative modifications. Using recombinant proteins and confocal imaging, we demonstrate here that SP-D directly bound to the membrane and inhibited extracellular DNA trap formation by human and murine eosinophils in a concentration and carbohydrate-dependent manner. Combined allergic airway sensitization and O3 exposure heightened eosinophilia and nos2 mRNA (iNOS) activation in the lung tissue and S-nitrosylation related de-oligomerisation of SP-D in the airways. In vitro reproduction of the iNOS action led to similar effects on SP-D. Importantly, S-nitrosylation abolished the ability of SP-D to block extracellular DNA trap formation. Thus, the homeostatic negative regulatory feedback between SP-D and eosinophils is destroyed by the NO-rich oxidative lung tissue environment in asthma exacerbations.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Yousefi S"", ""Sharma SK"", ""Stojkov D"", ""Germic N"", ""Aeschlimann S"", ""Ge MQ"", ""Flayer CH"", ""Larson ED"", ""Redai IG"", ""Zhang S"", ""Koziol-White CJ"", ""Karikó K"", ""Simon HU"", ""Haczku A""]",10.1002/JLB.3AB1117-455R,Yousefi S,Journal of leukocyte biology,0741-5400,1,J Leukoc Biol,eng,Haczku A,"[""Animals"", ""Asthma"", ""Cells, Cultured"", ""Eosinophils"", ""Extracellular Traps"", ""Humans"", ""Hypersensitivity"", ""Mice"", ""Oxidants, Photochemical"", ""Oxidative Stress"", ""Ozone"", ""Pulmonary Surfactant-Associated Protein D""]",205-214,29733456,pmc-id: PMC6450398;manuscript-id: NIHMS977812;,2018 Jul,2018,https://pubmed.ncbi.nlm.nih.gov/29733456/,Oxidative damage of SP-D abolishes control of eosinophil extracellular DNA trap formation,104,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
This corrects the article DOI: 10.1038/nm.4356.,"[""Journal Article"", ""Published Erratum""]","[""Stadler CR"", ""Bähr-Mahmud H"", ""Celik L"", ""Hebich B"", ""Roth AS"", ""Roth RP"", ""Karikó K"", ""Türeci Ö"", ""Sahin U""]",10.1038/nm1017-1241d,Stadler CR,Nature medicine,1078-8956,10,Nat Med,eng,Sahin U,[],1241,28985209,,2017 Oct 6,2017,https://pubmed.ncbi.nlm.nih.gov/28985209/,Erratum: Elimination of large tumors in mice by mRNA-encoded bispecific antibodies,23,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"The potential of bispecific T cell-engaging antibodies is hindered by manufacturing challenges and short serum half-life. We circumvented these limitations by treating mice with in vitro-transcribed pharmacologically optimized, nucleoside-modified mRNA encoding the antibody. We achieved sustained endogenous synthesis of the antibody, which eliminated advanced tumors as effectively as the corresponding purified bispecific antibody. Because manufacturing of pharmaceutical mRNA is fast, this approach could accelerate the clinical development of novel bispecific antibodies.","[""Journal Article""]","[""Stadler CR"", ""Bähr-Mahmud H"", ""Celik L"", ""Hebich B"", ""Roth AS"", ""Roth RP"", ""Karikó K"", ""Türeci Ö"", ""Sahin U""]",10.1038/nm.4356,Stadler CR,Nature medicine,1078-8956,7,Nat Med,eng,Sahin U,"[""Animals"", ""Antibodies, Bispecific"", ""Cell Line, Tumor"", ""Cytokines"", ""Enzyme-Linked Immunosorbent Assay"", ""Female"", ""Humans"", ""Immunoblotting"", ""Immunohistochemistry"", ""In Vitro Techniques"", ""Luminescent Measurements"", ""Male"", ""Mice"", ""Mice, Inbred BALB C"", ""Mice, Inbred NOD"", ""Neoplasms"", ""RNA, Messenger"", ""T-Lymphocytes"", ""Tumor Burden"", ""Xenograft Model Antitumor Assays""]",815-817,28604701,,2017 Jul,2017,https://pubmed.ncbi.nlm.nih.gov/28604701/,Elimination of large tumors in mice by mRNA-encoded bispecific antibodies,23,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"Monoclonal antibodies are one of the fastest growing classes of pharmaceutical products, however, their potential is limited by the high cost of development and manufacturing. Here we present a safe and cost-effective platform for in vivo expression of therapeutic antibodies using nucleoside-modified mRNA. To demonstrate feasibility and protective efficacy, nucleoside-modified mRNAs encoding the light and heavy chains of the broadly neutralizing anti-HIV-1 antibody VRC01 are generated and encapsulated into lipid nanoparticles. Systemic administration of 1.4 mg kg-1 of mRNA into mice results in ∼170 μg ml-1 VRC01 antibody concentrations in the plasma 24 h post injection. Weekly injections of 1 mg kg-1 of mRNA into immunodeficient mice maintain trough VRC01 levels above 40 μg ml-1. Most importantly, the translated antibody from a single injection of VRC01 mRNA protects humanized mice from intravenous HIV-1 challenge, demonstrating that nucleoside-modified mRNA represents a viable delivery platform for passive immunotherapy against HIV-1 with expansion to a variety of diseases.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Pardi N"", ""Secreto AJ"", ""Shan X"", ""Debonera F"", ""Glover J"", ""Yi Y"", ""Muramatsu H"", ""Ni H"", ""Mui BL"", ""Tam YK"", ""Shaheen F"", ""Collman RG"", ""Karikó K"", ""Danet-Desnoyers GA"", ""Madden TD"", ""Hope MJ"", ""Weissman D""]",10.1038/ncomms14630,Pardi N,Nature communications,2041-1723,,Nat Commun,eng,Weissman D,"[""Animals"", ""Antibodies, Monoclonal"", ""Antibodies, Neutralizing"", ""Broadly Neutralizing Antibodies"", ""Drug Administration Schedule"", ""Female"", ""HIV Antibodies"", ""HIV Infections"", ""HIV-1"", ""Humans"", ""Immunization, Passive"", ""Lipids"", ""Mice"", ""Mice, Inbred BALB C"", ""Mice, Inbred C57BL"", ""Mice, Inbred NOD"", ""Mice, SCID"", ""Mice, Transgenic"", ""Nanoparticles"", ""Nucleosides"", ""RNA, Messenger""]",14630,28251988,pmc-id: PMC5337964;,2017 Mar 2,2017,https://pubmed.ncbi.nlm.nih.gov/28251988/,Administration of nucleoside-modified mRNA encoding broadly neutralizing antibody protects humanized mice from HIV-1 challenge,8,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"Zika virus (ZIKV) has recently emerged as a pandemic associated with severe neuropathology in newborns and adults. There are no ZIKV-specific treatments or preventatives. Therefore, the development of a safe and effective vaccine is a high priority. Messenger RNA (mRNA) has emerged as a versatile and highly effective platform to deliver vaccine antigens and therapeutic proteins. Here we demonstrate that a single low-dose intradermal immunization with lipid-nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) encoding the pre-membrane and envelope glycoproteins of a strain from the ZIKV outbreak in 2013 elicited potent and durable neutralizing antibody responses in mice and non-human primates. Immunization with 30 μg of nucleoside-modified ZIKV mRNA-LNP protected mice against ZIKV challenges at 2 weeks or 5 months after vaccination, and a single dose of 50 μg was sufficient to protect non-human primates against a challenge at 5 weeks after vaccination. These data demonstrate that nucleoside-modified mRNA-LNP elicits rapid and durable protective immunity and therefore represents a new and promising vaccine candidate for the global fight against ZIKV.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, N.I.H., Intramural"", ""Research Support, Non-U.S. Gov't""]","[""Pardi N"", ""Hogan MJ"", ""Pelc RS"", ""Muramatsu H"", ""Andersen H"", ""DeMaso CR"", ""Dowd KA"", ""Sutherland LL"", ""Scearce RM"", ""Parks R"", ""Wagner W"", ""Granados A"", ""Greenhouse J"", ""Walker M"", ""Willis E"", ""Yu JS"", ""McGee CE"", ""Sempowski GD"", ""Mui BL"", ""Tam YK"", ""Huang YJ"", ""Vanlandingham D"", ""Holmes VM"", ""Balachandran H"", ""Sahu S"", ""Lifton M"", ""Higgs S"", ""Hensley SE"", ""Madden TD"", ""Hope MJ"", ""Karikó K"", ""Santra S"", ""Graham BS"", ""Lewis MG"", ""Pierson TC"", ""Haynes BF"", ""Weissman D""]",10.1038/nature21428,Pardi N,Nature,0028-0836,7644,Nature,eng,Weissman D,"[""Animals"", ""Antibodies, Neutralizing"", ""Antibodies, Viral"", ""Antigens, Viral"", ""Female"", ""Glycoproteins"", ""Injections, Intradermal"", ""Macaca mulatta"", ""Mice"", ""Mice, Inbred BALB C"", ""Mice, Inbred C57BL"", ""Nanoparticles"", ""RNA Stability"", ""RNA, Messenger"", ""RNA, Viral"", ""Time Factors"", ""Vaccination"", ""Viral Envelope Proteins"", ""Viral Vaccines"", ""Zika Virus"", ""Zika Virus Infection""]",248-251,28151488,pmc-id: PMC5344708;manuscript-id: NIHMS847615;,2017 Mar 9,2017,https://pubmed.ncbi.nlm.nih.gov/28151488/,Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination,543,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"In vitro-transcribed (IVT) mRNA encoding therapeutic protein has the potential to treat a variety of diseases by serving as template for translation in the patient. To optimize conditions for such therapy, reporter protein-encoding mRNAs are usually used. One preferred reporter is erythropoietin (EPO), which stimulates erythropoiesis and leads to an increase in hematocrit. Measurement of hematocrit is a fast and reliable method to determine the potency of the in vitro-transcribed EPO mRNA. However, frequent blood draw from mice can increase hematocrit due to blood loss. Therefore, instead of using conventional hematocrit capillary tubes, we adapted glass microcapillaries for hematocrit measurement. Daily monitoring of mice can be accomplished by drawing less than 20 μL of blood, thus avoiding blood loss-related hematocrit increase. Due to the small volume of the withdrawn blood the hematocrit remains the same for mice injected with control mRNA, whereas significant hematocrit increase is measured between day 4 and 20 postinjection for those injected with pseudouridine-modified EPO mRNA. Following hematocrit measurement the microcapillaries are snapped easily to recover plasma for further analyses, including EPO measurement by ELISA.","[""Journal Article""]","[""Mahiny AJ"", ""Karikó K""]",10.1007/978-1-4939-3625-0_20,Mahiny AJ,"Methods in molecular biology (Clifton, N.J.)",1064-3745,,Methods Mol Biol,eng,Karikó K,"[""Animals"", ""Erythrocytes"", ""Erythropoietin"", ""Hematocrit"", ""Humans"", ""In Vitro Techniques"", ""Mice"", ""Mice, Inbred BALB C"", ""RNA, Messenger""]",297-306,27236808,,2016,2016,https://pubmed.ncbi.nlm.nih.gov/27236808/,Measuring Hematocrit in Mice Injected with In Vitro-Transcribed Erythropoietin mRNA,1428,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"In vitro-synthesized mRNA containing nucleoside modifications has great therapeutical potential to transiently express proteins with physiological importance. One such protein is photolyase which rapidly removes UV-induced DNA damages, but this enzyme is absent in humans. Here, we apply a novel mRNA-based platform to achieve functional nonhuman photolyase production in cultured human keratinocytes. Transfection of nucleoside-modified mRNA encoding photolyase leads to accelerated repair of DNA photolesions in human keratinocytes.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Boros G"", ""Karikó K"", ""Muramatsu H"", ""Miko E"", ""Emri E"", ""Hegedűs C"", ""Emri G"", ""Remenyik É""]",10.1007/978-1-4939-3625-0_14,Boros G,"Methods in molecular biology (Clifton, N.J.)",1064-3745,,Methods Mol Biol,eng,Remenyik É,"[""Cell Line"", ""DNA"", ""DNA Damage"", ""DNA Repair"", ""Deoxyribodipyrimidine Photo-Lyase"", ""Humans"", ""Keratinocytes"", ""Nucleosides"", ""RNA, Messenger"", ""Transfection""]",219-28,27236802,,2016,2016,https://pubmed.ncbi.nlm.nih.gov/27236802/,Transfection of Human Keratinocytes with Nucleoside-Modified mRNA Encoding CPD-Photolyase to Repair DNA Damage,1428,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
,"[""Journal Article"", ""Comment""]","[""Weissman D"", ""Karikó K""]",10.1038/mt.2015.138,Weissman D,Molecular therapy : the journal of the American Society of Gene Therapy,1525-0016,9,Mol Ther,eng,Karikó K,"[""Animals"", ""Gene Expression"", ""Genetic Therapy"", ""Humans"", ""RNA, Messenger""]",1416-7,26321183,pmc-id: PMC4817894;,2015 Sep,2015,https://pubmed.ncbi.nlm.nih.gov/26321183/,mRNA: Fulfilling the Promise of Gene Therapy,23,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"In recent years, in vitro transcribed messenger RNA (mRNA) has emerged as a potential therapeutic platform. To fulfill its promise, effective delivery of mRNA to specific cell types and tissues needs to be achieved. Lipid nanoparticles (LNPs) are efficient carriers for short-interfering RNAs and have entered clinical trials. However, little is known about the potential of LNPs to deliver mRNA. Here, we generated mRNA-LNPs by incorporating HPLC purified, 1-methylpseudouridine-containing mRNA comprising codon-optimized firefly luciferase into stable LNPs. Mice were injected with 0.005-0.250mg/kg doses of mRNA-LNPs by 6 different routes and high levels of protein translation could be measured using in vivo imaging. Subcutaneous, intramuscular and intradermal injection of the LNP-encapsulated mRNA translated locally at the site of injection for up to 10days. For several days, high levels of protein production could be achieved in the lung from the intratracheal administration of mRNA. Intravenous and intraperitoneal and to a lesser extent intramuscular and intratracheal deliveries led to trafficking of mRNA-LNPs systemically resulting in active translation of the mRNA in the liver for 1-4 days. Our results demonstrate that LNPs are appropriate carriers for mRNA in vivo and have the potential to become valuable tools for delivering mRNA encoding therapeutic proteins.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Pardi N"", ""Tuyishime S"", ""Muramatsu H"", ""Kariko K"", ""Mui BL"", ""Tam YK"", ""Madden TD"", ""Hope MJ"", ""Weissman D""]",10.1016/j.jconrel.2015.08.007,Pardi N,Journal of controlled release : official journal of the Controlled Release Society,0168-3659,,J Control Release,eng,Weissman D,"[""Animals"", ""Cells, Cultured"", ""Dendritic Cells"", ""Female"", ""HEK293 Cells"", ""Humans"", ""Kinetics"", ""Luciferases, Firefly"", ""Lung"", ""Mice, Inbred BALB C"", ""Nanoparticles"", ""Phosphatidylethanolamines"", ""Pseudouridine"", ""RNA, Messenger"", ""Transfection""]",345-51,26264835,pmc-id: PMC4624045;manuscript-id: NIHMS723881;,2015 Nov 10,2015,https://pubmed.ncbi.nlm.nih.gov/26264835/,Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes,217,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"Major biological effects of UVB are attributed to cyclobutane pyrimidine dimers (CPDs), the most common photolesions formed on DNA. To investigate the contribution of CPDs to UVB-induced changes of gene expression, a model system was established by transfecting keratinocytes with pseudouridine-modified mRNA (Ψ-mRNA) encoding CPD-photolyase. Microarray analyses of this model system demonstrated that more than 50% of the gene expression altered by UVB was mediated by CPD photolesions. Functional classification of the gene targets revealed strong effects of CPDs on the regulation of the cell cycle and transcriptional machineries. To confirm the microarray data, cell cycle-regulatory genes, CCNE1 and CDKN2B that were induced exclusively by CPDs were selected for further investigation. Following UVB irradiation, expression of these genes increased significantly at both mRNA and protein levels, but not in cells transfected with CPD-photolyase Ψ-mRNA and exposed to photoreactivating light. Treatment of cells with inhibitors of c-Jun N-terminal kinase (JNK) blocked the UVB-dependent upregulation of both genes suggesting a role for JNK in relaying the signal of UVB-induced CPDs into transcriptional responses. Thus, photolyase mRNA-based experimental platform demonstrates CPD-dependent and -independent events of UVB-induced cellular responses, and, as such, has the potential to identify novel molecular targets for treatment of UVB-mediated skin diseases.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Boros G"", ""Miko E"", ""Muramatsu H"", ""Weissman D"", ""Emri E"", ""van der Horst GT"", ""Szegedi A"", ""Horkay I"", ""Emri G"", ""Karikó K"", ""Remenyik É""]",10.1371/journal.pone.0131141,Boros G,PloS one,1932-6203,6,PLoS One,eng,Remenyik É,"[""Animals"", ""Cell Line"", ""Cyclin E"", ""Cyclin-Dependent Kinase Inhibitor p15"", ""DNA Repair"", ""Deoxyribodipyrimidine Photo-Lyase"", ""Gene Expression Regulation"", ""Humans"", ""JNK Mitogen-Activated Protein Kinases"", ""Keratinocytes"", ""MAP Kinase Signaling System"", ""Oligonucleotide Array Sequence Analysis"", ""Oncogene Proteins"", ""Potoroidae"", ""Pyrimidine Dimers"", ""RNA, Messenger"", ""Real-Time Polymerase Chain Reaction"", ""Reproducibility of Results"", ""Stress, Physiological"", ""Transcription, Genetic"", ""Transfection"", ""Ultraviolet Rays""]",e0131141,26121660,pmc-id: PMC4488231;,2015,2015,https://pubmed.ncbi.nlm.nih.gov/26121660/,Identification of Cyclobutane Pyrimidine Dimer-Responsive Genes Using UVB-Irradiated Human Keratinocytes Transfected with In Vitro-Synthesized Photolyase mRNA,10,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"In vitro transcribed (IVT) mRNA has recently come into focus as a potential new drug class to deliver genetic information. Such synthetic mRNA can be engineered to transiently express proteins by structurally resembling natural mRNA. Advances in addressing the inherent challenges of this drug class, particularly related to controlling the translational efficacy and immunogenicity of the IVTmRNA, provide the basis for a broad range of potential applications. mRNA-based cancer immunotherapies and infectious disease vaccines have entered clinical development. Meanwhile, emerging novel approaches include in vivo delivery of IVT mRNA to replace or supplement proteins, IVT mRNA-based generation of pluripotent stem cells and genome engineering using IVT mRNA-encoded designer nucleases. This Review provides a comprehensive overview of the current state of mRNA-based drug technologies and their applications, and discusses the key challenges and opportunities in developing these into a new class of drugs.","[""Journal Article"", ""Review""]","[""Sahin U"", ""Karikó K"", ""Türeci Ö""]",10.1038/nrd4278,Sahin U,Nature reviews. Drug discovery,1474-1776,10,Nat Rev Drug Discov,eng,Türeci Ö,"[""Animals"", ""Drug Delivery Systems"", ""Drug Design"", ""Humans"", ""Immunotherapy"", ""Pluripotent Stem Cells"", ""Proteins"", ""RNA, Messenger""]",759-80,25233993,,2014 Oct,2014,https://pubmed.ncbi.nlm.nih.gov/25233993/,mRNA-based therapeutics--developing a new class of drugs,13,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"UVB irradiation induces harmful photochemical reactions, including formation of Cyclobutane Pyrimidine Dimers (CPDs) in DNA. Accumulation of unrepaired CPD lesions causes inflammation, premature ageing and skin cancer. Photolyases are DNA repair enzymes that can rapidly restore DNA integrity in a light-dependent process called photoreactivation, but these enzymes are absent in humans. Here, we present a novel mRNA-based gene therapy method that directs synthesis of a marsupial, Potorous tridactylus, CPD-photolyase in cultured human keratinocytes. Pseudouridine was incorporated during in vitro transcription to make the mRNA non-immunogenic and highly translatable. Keratinocytes transfected with lipofectamine-complexed mRNA expressed photolyase in the nuclei for at least 2days. Exposing photolyase mRNA-transfected cells to UVB irradiation resulted in significantly less CPD in those cells that were also treated with photoreactivating light, which is required for photolyase activity. The functional photolyase also diminished other UVB-mediated effects, including induction of IL-6 and inhibition of cell proliferation. These results demonstrate that pseudouridine-containing photolyase mRNA is a powerful tool to repair UVB-induced DNA lesions. The pseudouridine-modified mRNA approach has a strong potential to discern cellular effects of CPD in UV-related cell biological studies. The mRNA-based transient expression of proteins offers a number of opportunities for future application in medicine.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Boros G"", ""Miko E"", ""Muramatsu H"", ""Weissman D"", ""Emri E"", ""Rózsa D"", ""Nagy G"", ""Juhász A"", ""Juhász I"", ""van der Horst G"", ""Horkay I"", ""Remenyik É"", ""Karikó K"", ""Emri G""]",10.1016/j.jphotobiol.2013.09.010,Boros G,"Journal of photochemistry and photobiology. B, Biology",1011-1344,,J Photochem Photobiol B,eng,Emri G,"[""Animals"", ""Cell Line"", ""Cell Proliferation"", ""DNA Repair"", ""Deoxyribodipyrimidine Photo-Lyase"", ""Humans"", ""Interleukin-6"", ""Keratinocytes"", ""Light"", ""Lipids"", ""Potoroidae"", ""Pseudouridine"", ""Pyrimidine Dimers"", ""RNA, Messenger"", ""Transfection"", ""Ultraviolet Rays""]",93-9,24211294,pmc-id: PMC3888937;manuscript-id: NIHMS538757;,2013 Dec 5,2013,https://pubmed.ncbi.nlm.nih.gov/24211294/,Transfection of pseudouridine-modified mRNA encoding CPD-photolyase leads to repair of DNA damage in human keratinocytes: a new approach with future therapeutic potential,129,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"In vitro transcription of DNA with phage RNA polymerases is currently the most efficient method to produce long sequence-specific RNA. While the reaction can yield large quantities of RNA, it contains impurities due to various unwanted activities of the polymerases. Here, we described an easily performed HPLC purification that removes multiple contaminants from in vitro transcribed RNA and is scalable. The purified RNA is translated at much greater levels, especially in primary cells and in vivo. HPLC purification of RNA containing modified nucleosides that suppress RNA-mediated activation of innate immune sensors leads to a non-immunogenic RNA with superior translational capacity.","[""Journal Article"", ""Research Support, N.I.H., Extramural""]","[""Weissman D"", ""Pardi N"", ""Muramatsu H"", ""Karikó K""]",10.1007/978-1-62703-260-5_3,Weissman D,"Methods in molecular biology (Clifton, N.J.)",1064-3745,,Methods Mol Biol,eng,Karikó K,"[""Chromatography, High Pressure Liquid"", ""DNA"", ""DNA-Directed RNA Polymerases"", ""Nucleosides"", ""RNA"", ""Transcription, Genetic""]",43-54,23296926,,2013,2013,https://pubmed.ncbi.nlm.nih.gov/23296926/,HPLC purification of in vitro transcribed long RNA,969,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"The in vitro synthesis of long RNA can be accomplished using phage RNA polymerase and template DNA. However, the in vitro synthesized RNA, unlike those transcribed in vivo in cells, lacks nucleoside modifications. Introducing modified nucleosides into in vitro transcripts is important because they reduce the potential of RNA to activate RNA sensors and translation of such nucleoside-modified RNA is increased in cell lines, primary cells, and after in vivo delivery. Here, we describe the in vitro synthesis of nucleoside-modified RNA with enhanced translational capacity and reduced ability to activate immune sensors.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Review""]","[""Pardi N"", ""Muramatsu H"", ""Weissman D"", ""Karikó K""]",10.1007/978-1-62703-260-5_2,Pardi N,"Methods in molecular biology (Clifton, N.J.)",1064-3745,,Methods Mol Biol,eng,Karikó K,"[""Animals"", ""Bacteriophages"", ""Cell Line"", ""DNA-Directed RNA Polymerases"", ""Genetic Engineering"", ""Humans"", ""Nucleosides"", ""RNA"", ""Transfection"", ""Viral Proteins""]",29-42,23296925,,2013,2013,https://pubmed.ncbi.nlm.nih.gov/23296925/,In vitro transcription of long RNA containing modified nucleosides,969,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"Advances in the optimization of in vitro-transcribed mRNA are bringing mRNA-mediated therapy closer to reality. In cultured cells, we recently achieved high levels of translation with high-performance liquid chromatography (HPLC)-purified, in vitro-transcribed mRNAs containing the modified nucleoside pseudouridine. Importantly, pseudouridine rendered the mRNA non-immunogenic. Here, using erythropoietin (EPO)-encoding mRNA complexed with TransIT-mRNA, we evaluated this new generation of mRNA in vivo. A single injection of 100 ng (0.005 mg/kg) mRNA elevated serum EPO levels in mice significantly by 6 hours and levels were maintained for 4 days. In comparison, mRNA containing uridine produced 10-100-fold lower levels of EPO lasting only 1 day. EPO translated from pseudouridine-mRNA was functional and caused a significant increase of both reticulocyte counts and hematocrits. As little as 10 ng mRNA doubled reticulocyte numbers. Weekly injection of 100 ng of EPO mRNA was sufficient to increase the hematocrit from 43 to 57%, which was maintained with continued treatment. Even when a large amount of pseudouridine-mRNA was injected, no inflammatory cytokines were detectable in plasma. Using macaques, we could also detect significantly-increased serum EPO levels following intraperitoneal injection of rhesus EPO mRNA. These results demonstrate that HPLC-purified, pseudouridine-containing mRNAs encoding therapeutic proteins have great potential for clinical applications.","[""Journal Article"", ""Research Support, N.I.H., Extramural""]","[""Karikó K"", ""Muramatsu H"", ""Keller JM"", ""Weissman D""]",10.1038/mt.2012.7,Karikó K,Molecular therapy : the journal of the American Society of Gene Therapy,1525-0016,5,Mol Ther,eng,Weissman D,"[""Animals"", ""Cell Count"", ""Cell Proliferation"", ""Chromatography, High Pressure Liquid"", ""Drug Delivery Systems"", ""Erythropoiesis"", ""Erythropoietin"", ""Female"", ""Genetic Vectors"", ""Hematocrit"", ""Humans"", ""Injections, Intraperitoneal"", ""Macaca mulatta"", ""Mice"", ""Mice, Inbred BALB C"", ""Pseudouridine"", ""RNA, Messenger"", ""Reticulocytes""]",948-53,22334017,pmc-id: PMC3345990;,2012 May,2012,https://pubmed.ncbi.nlm.nih.gov/22334017/,Increased erythropoiesis in mice injected with submicrogram quantities of pseudouridine-containing mRNA encoding erythropoietin,20,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"Nucleofection permits efficient transfection even with difficult cell types such as primary and non-dividing cells, and is used to deliver various nucleic acids, including DNA, mRNA, and small interfering RNA. Unlike DNA and small interfering RNA, mRNA is subject to rapid degradation, which necessitates instant early translation following mRNA delivery. We examined the factors that are important in translation following nucleofection and observed rapid phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) following nucleofection, which occurred in the absence of the delivered nucleic acid. We studied the involvement of three ubiquitous kinases capable of phosphorylating eIF2α in mammalian cells and identified that nucleofection-mediated phosphorylation of eIF2α was dependent on general control non-derepressible 2 (GCN2) and RNA-dependent protein kinase (PKR)-like endoplasmic reticulum kinase (PERK) but not PKR. A reduction in translation due to eIF2α phosphorylation was observed post nucleofection, demonstrating functional significance. Understanding the impact of nucleofection on translational machinery has important implications for therapeutics currently under development based on the delivery of mRNA, DNA, and small interfering RNA. Strategies to circumvent eIF2α phosphorylation and other downstream effects of activating GCN2 and PERK will facilitate further advancement of nucleic acid-based therapies.","[""Journal Article"", ""Research Support, N.I.H., Extramural""]","[""Anderson BR"", ""Karikó K"", ""Weissman D""]",10.1038/gt.2012.5,Anderson BR,Gene therapy,0969-7128,2,Gene Ther,eng,Weissman D,"[""Animals"", ""Cell Line"", ""Eukaryotic Initiation Factor-2"", ""Humans"", ""Mice"", ""Phosphorylation"", ""Protein Serine-Threonine Kinases"", ""Transfection"", ""eIF-2 Kinase""]",136-42,22301437,pmc-id: PMC3345295;manuscript-id: NIHMS332400;,2013 Feb,2013,https://pubmed.ncbi.nlm.nih.gov/22301437/,Nucleofection induces transient eIF2α phosphorylation by GCN2 and PERK,20,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"Intracerebral hemorrhage (ICH) is a devastating stroke subtype in which perihematomal inflammation contributes to neuronal injury and functional disability. Histologically, the region becomes infiltrated with neutrophils and activated microglia followed by neuronal loss, but little is known about the immune signals that coordinate these events. This study aimed to determine the role of Toll-like receptor 4 (TLR4) in the innate immune response after ICH and its impact on neurobehavioral outcome. Transgenic mice incapable of TLR4 signaling and wild-type controls were subjected to striatal blood injection to model ICH. The perihematomal inflammatory response was then quantified by immunohistochemistry, whole brain flow cytometry, and polymerase chain reaction. The critical location of TLR4 signaling was determined by blood transfer experiments between genotypes. Functional outcomes were quantified in all cohorts using the cylinder and open field tests. TLR4-deficient mice had markedly decreased perihematomal inflammation, associated with reduced recruitment of neutrophils and monocytes, fewer microglia, and improved functional outcome by day 3 after ICH. Moreover, blood transfer experiments revealed that TLR4 on leukocytes or platelets within the hemorrhage contributes to perihematomal leukocyte infiltration and the neurological deficit. Together, these data identify a critical role for TLR4 signaling in perihematomal inflammation and injury and indicate this pathway may be a target for therapeutic intervention.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Sansing LH"", ""Harris TH"", ""Welsh FA"", ""Kasner SE"", ""Hunter CA"", ""Kariko K""]",10.1002/ana.22528,Sansing LH,Annals of neurology,0364-5134,4,Ann Neurol,eng,Kariko K,"[""Animals"", ""Brain Injuries"", ""Cerebral Hemorrhage"", ""Inflammation"", ""Male"", ""Mice"", ""Mice, Inbred C3H"", ""Mice, Knockout"", ""Severity of Illness Index"", ""Signal Transduction"", ""Toll-Like Receptor 4""]",646-56,22028224,pmc-id: PMC3671585;manuscript-id: NIHMS469371;,2011 Oct,2011,https://pubmed.ncbi.nlm.nih.gov/22028224/,Toll-like receptor 4 contributes to poor outcome after intracerebral hemorrhage,70,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"In vitro-transcribed mRNA has great therapeutic potential to transiently express the encoded protein without the adverse effects of viral and DNA-based constructs. Mammalian cells, however, contain RNA sensors of the innate immune system that must be considered in the generation of therapeutic RNA. Incorporation of modified nucleosides both reduces innate immune activation and increases translation of mRNA, but residual induction of type I interferons (IFNs) and proinflammatory cytokines remains. We identify that contaminants, including double-stranded RNA, in nucleoside-modified in vitro-transcribed RNA are responsible for innate immune activation and their removal by high performance liquid chromatography (HPLC) results in mRNA that does not induce IFNs and inflammatory cytokines and is translated at 10- to 1000-fold greater levels in primary cells. Although unmodified mRNAs were translated significantly better following purification, they still induced high levels of cytokine secretion. HPLC purified nucleoside-modified mRNA is a powerful vector for applications ranging from ex vivo stem cell generation to in vivo gene therapy.","[""Journal Article"", ""Research Support, N.I.H., Extramural""]","[""Karikó K"", ""Muramatsu H"", ""Ludwig J"", ""Weissman D""]",10.1093/nar/gkr695,Karikó K,Nucleic acids research,0305-1048,21,Nucleic Acids Res,eng,Weissman D,"[""Animals"", ""Cells, Cultured"", ""Chromatography, High Pressure Liquid"", ""Cytidine"", ""Genetic Therapy"", ""HEK293 Cells"", ""Humans"", ""Mice"", ""Protein Biosynthesis"", ""Pseudouridine"", ""RNA, Double-Stranded"", ""RNA, Messenger"", ""Transcription, Genetic"", ""Transfection""]",e142,21890902,pmc-id: PMC3241667;,2011 Nov,2011,https://pubmed.ncbi.nlm.nih.gov/21890902/,"Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA",39,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"Investigation of the pathophysiology of injury after intracerebral hemorrhage (ICH) requires a reproducible animal model. While ICH accounts for 10-15% of all strokes, there remains no specific effective therapy. The autologous blood injection model in mice involves the stereotaxic injection of arterial blood into the basal ganglia mimicking a spontaneous hypertensive hemorrhage in man. The response to hemorrhage can then be studied in vivo and the neurobehavioral deficits quantified, allowing for description of the ensuing pathology and the testing of potential therapeutic agents. The procedure described in this protocol uses the double injection technique to minimize risk of blood reflux up the needle track, no anticoagulants in the pumping system, and eliminates all dead space and expandable tubing in the system.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't"", ""Video-Audio Media""]","[""Sansing LH"", ""Kasner SE"", ""McCullough L"", ""Agarwal P"", ""Welsh FA"", ""Kariko K""]",10.3791/2618,Sansing LH,Journal of visualized experiments : JoVE,1940-087X,54,J Vis Exp,eng,Kariko K,"[""Animals"", ""Basal Ganglia"", ""Blood"", ""Cerebral Hemorrhage"", ""Disease Models, Animal"", ""Mice"", ""Wounds and Injuries""]",,21876533,pmc-id: PMC3217617;,2011 Aug 24,2011,https://pubmed.ncbi.nlm.nih.gov/21876533/,Autologous blood injection to model spontaneous intracerebral hemorrhage in mice,,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"The interferon-induced enzymes 2'-5'-oligoadenylate synthetase (OAS) and RNase L are key components of innate immunity involved in sensory and effector functions following viral infections. Upon binding target RNA, OAS is activated to produce 2'-5'-linked oligoadenylates (2-5A) that activate RNase L, which then cleaves single-stranded self and non-self RNA. Modified nucleosides that are present in cellular transcripts have been shown to suppress activation of several RNA sensors. Here, we demonstrate that in vitro transcribed, unmodified RNA activates OAS, induces RNase L-mediated ribosomal RNA (rRNA) cleavage and is rapidly cleaved by RNase L. In contrast, RNA containing modified nucleosides activates OAS less efficiently and induces limited rRNA cleavage. Nucleoside modifications also make RNA resistant to cleavage by RNase L. Examining translation in RNase L(-/-) cells and mice confirmed that RNase L activity reduces translation of unmodified mRNA, which is not observed with modified mRNA. Additionally, mRNA containing the nucleoside modification pseudouridine is translated longer and has an extended half-life. The observation that modified nucleosides in RNA reduce 2-5A pathway activation joins OAS and RNase L to the list of RNA sensors and effectors whose functions are limited when RNA is modified, confirming the role of nucleoside modifications in suppressing immune recognition of RNA.","[""Journal Article"", ""Research Support, N.I.H., Extramural""]","[""Anderson BR"", ""Muramatsu H"", ""Jha BK"", ""Silverman RH"", ""Weissman D"", ""Karikó K""]",10.1093/nar/gkr586,Anderson BR,Nucleic acids research,0305-1048,21,Nucleic Acids Res,eng,Karikó K,"[""2',5'-Oligoadenylate Synthetase"", ""Animals"", ""Cells, Cultured"", ""Endoribonucleases"", ""Half-Life"", ""Humans"", ""Mice"", ""Nucleosides"", ""Protein Biosynthesis"", ""Pseudouridine"", ""RNA"", ""RNA, Ribosomal"", ""Uridine""]",9329-38,21813458,pmc-id: PMC3241635;,2011 Nov,2011,https://pubmed.ncbi.nlm.nih.gov/21813458/,Nucleoside modifications in RNA limit activation of 2'-5'-oligoadenylate synthetase and increase resistance to cleavage by RNase L,39,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"Inflammation contributes to secondary injury and neuronal loss after intracerebral hemorrhage, but the role of individual immune populations in these processes is unclear. In a mouse model, the injection of autologous blood into the striatum was associated with an intense inflammatory cell infiltrate composed of neutrophils, monocytes, and dendritic cells. Selective depletion of neutrophils resulted in decreased infiltration of monocytes and improved functional outcomes at day 3 post-hemorrhage. These findings indicate that neutrophil infiltration into the site of hemorrhage contributes to brain injury either by direct cellular damage or the recruitment of monocytes.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Sansing LH"", ""Harris TH"", ""Kasner SE"", ""Hunter CA"", ""Kariko K""]",10.1007/978-3-7091-0693-8_29,Sansing LH,Acta neurochirurgica. Supplement,0065-1419,,Acta Neurochir Suppl,eng,Kariko K,"[""Analysis of Variance"", ""Animals"", ""Antibodies, Monoclonal"", ""Antigens, Ly"", ""CD11b Antigen"", ""CD11c Antigen"", ""Cerebral Hemorrhage"", ""Dendritic Cells"", ""Disease Models, Animal"", ""Functional Laterality"", ""Inflammation"", ""Lymphocyte Count"", ""Male"", ""Mice"", ""Mice, Inbred C3H"", ""Monocytes"", ""Neutrophil Infiltration"", ""Neutrophils""]",173-8,21725751,pmc-id: PMC3702167;manuscript-id: NIHMS470688;,2011,2011,https://pubmed.ncbi.nlm.nih.gov/21725751/,Neutrophil depletion diminishes monocyte infiltration and improves functional outcome after experimental intracerebral hemorrhage,111,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"Geographic atrophy (GA), an untreatable advanced form of age-related macular degeneration, results from retinal pigmented epithelium (RPE) cell degeneration. Here we show that the microRNA (miRNA)-processing enzyme DICER1 is reduced in the RPE of humans with GA, and that conditional ablation of Dicer1, but not seven other miRNA-processing enzymes, induces RPE degeneration in mice. DICER1 knockdown induces accumulation of Alu RNA in human RPE cells and Alu-like B1 and B2 RNAs in mouse RPE. Alu RNA is increased in the RPE of humans with GA, and this pathogenic RNA induces human RPE cytotoxicity and RPE degeneration in mice. Antisense oligonucleotides targeting Alu/B1/B2 RNAs prevent DICER1 depletion-induced RPE degeneration despite global miRNA downregulation. DICER1 degrades Alu RNA, and this digested Alu RNA cannot induce RPE degeneration in mice. These findings reveal a miRNA-independent cell survival function for DICER1 involving retrotransposon transcript degradation, show that Alu RNA can directly cause human pathology, and identify new targets for a major cause of blindness.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Kaneko H"", ""Dridi S"", ""Tarallo V"", ""Gelfand BD"", ""Fowler BJ"", ""Cho WG"", ""Kleinman ME"", ""Ponicsan SL"", ""Hauswirth WW"", ""Chiodo VA"", ""Karikó K"", ""Yoo JW"", ""Lee DK"", ""Hadziahmetovic M"", ""Song Y"", ""Misra S"", ""Chaudhuri G"", ""Buaas FW"", ""Braun RE"", ""Hinton DR"", ""Zhang Q"", ""Grossniklaus HE"", ""Provis JM"", ""Madigan MC"", ""Milam AH"", ""Justice NL"", ""Albuquerque RJ"", ""Blandford AD"", ""Bogdanovich S"", ""Hirano Y"", ""Witta J"", ""Fuchs E"", ""Littman DR"", ""Ambati BK"", ""Rudin CM"", ""Chong MM"", ""Provost P"", ""Kugel JF"", ""Goodrich JA"", ""Dunaief JL"", ""Baffi JZ"", ""Ambati J""]",10.1038/nature09830,Kaneko H,Nature,0028-0836,7338,Nature,eng,Ambati J,"[""Alu Elements"", ""Animals"", ""Cell Death"", ""Cell Survival"", ""Cells, Cultured"", ""DEAD-box RNA Helicases"", ""Gene Knockdown Techniques"", ""Humans"", ""Macular Degeneration"", ""Mice"", ""MicroRNAs"", ""Molecular Sequence Data"", ""Oligonucleotides, Antisense"", ""Phenotype"", ""RNA"", ""Retinal Pigment Epithelium"", ""Ribonuclease III""]",325-30,21297615,pmc-id: PMC3077055;manuscript-id: NIHMS265989;,2011 Mar 17,2011,https://pubmed.ncbi.nlm.nih.gov/21297615/,DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration,471,93XkJrUvfYyutHSZS,ehrTjgKQjCkT4usrc
"Single-atom (SA) engineering offers atomic-level control over interfacial reactivity, yet the lack of printable SA-based inks hinders its practical translation into electrochemical sensing. Here, a fully water-based inkjet-printable ink is introduced based on nitrogen-doped graphene acid (NGA) hosting atomically dispersed Cu centers (NGA-Cu-ink). The ink enables digitally controlled, spatially defined deposition and fabrication of low-cost ($0.04 per sensor), fully inkjet-printed sustainable electrodes on paper. A comparison of NGA functionalized with different SA dopants (Cu, Mn, Fe, Ce) identifies a strong dopant-dependent electrochemical response, with Cu uniquely enhancing the analyte signal while other dopants suppress it, demonstrating that SA identity is a decisive design parameter in printed sensing interfaces profiling sensitivity and selectivity. The functional role of the NGA support is to provide dense anchoring sites (nitrogen and carboxylate groups) that stabilize atomically dispersed metal centers and create adsorption- and electron-transfer-active microenvironments. The NGA-Cu-ink yields enhanced dopamine oxidation, enabling quantitative detection on fully printed devices (limit of detection 9.7 µM; linear range 50-400 µM) and printed-on-electrode platforms (10.6 µM), while maintaining <10% signal variation over 11 weeks. The approach establishes a general route to single-atom graphene-based inks for scalable, reproducible, and low-material-consumption manufacturing of advanced electrochemical sensors.","[""Journal Article""]","[""Nalepa MA"", ""Panáček D"", ""Hrubý V"", ""Jendrišák M"", ""Langer R"", ""Langer M"", ""Jakubec P"", ""Dědek I"", ""Kupka V"", ""Mazur M"", ""Zbořil R"", ""Otyepka M""]",10.1002/advs.76796,Nalepa MA,"Advanced science (Weinheim, Baden-Wurttemberg, Germany)",2198-3844,,Adv Sci (Weinh),eng,Otyepka M,[],e76796,42504988,pmc-id: PMC13403738;,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42504988/,Single-Atom-Enhanced Fully Inkjet-Printed Electrochemical Sensor for Dopamine Detection,,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Sandwich composite panels offer a promising pathway for developing lightweight yet mechanically robust portable outdoor tabletops, but their industrialization outside traditional aerospace and transportation sectors remains challenging. This study investigates how sandwich composites can be adapted for mass‑market outdoor tabletops by linking market‑driven requirements to engineering design decisions. Five representative panel configurations were developed, varying in core materials, face‑sheet systems, surface finishing, edge‑sealing strategies, and fastening solutions. A structured evaluation matrix was established to assess both material‑level and product‑level performance, aligned with customer‑relevant requirements, applicable standards, and company‑defined acceptance criteria. Results show that industrial feasibility is governed not by any single metric but by the coupled interactions among material selection, surface durability, moisture‑resistant edge sealing, fastening reliability, and manufacturability-cost trade‑offs. Blind rivets emerged as a practical fastening solution, while surface durability and thermal stability were strongly influenced by the combined behavior of finishing chemistry and substrate. The findings establish practical architecture-performance relationships and outline viable industrialization pathways for mass‑market portable outdoor tabletops based on sandwich composite panels.","[""Journal Article""]","[""Yu W"", ""Langer R""]",10.1371/journal.pone.0353571,Yu W,PloS one,1932-6203,7,PLoS One,eng,Langer R,[],e0353571,42424369,pmc-id: PMC13349161;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42424369/,Industrialization of sandwich composite panels for portable outdoor tabletops,21,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Invasive Paget's disease of the breast is a rare entity with therapeutic challenges. Herein, we report three patients with Paget's disease of the breast with dermal invasion, of which two cases had coexistent invasive breast carcinoma, while the third had an extensive in situ component. Case 1 was a 49-year-old lady presenting with nipple ulceration and discharge along with concomitant multicentric right breast lesions detected on mammography. Breast conservation surgery was performed which revealed extensive high-grade ductal carcinoma in situ on histopathology, associated with invasive Paget's disease. The patient completed adjuvant radiotherapy and shows no evidence of disease at present, four months following the completion of therapy. Case 2 was a middle-aged woman of 45 years, who was detected with multiple hypoechoic space-occupying lesions in the right breast on ultrasonography. Modified radical mastectomy was performed which showed a tumor-infiltrating lymphocyte-rich breast carcinoma along with invasive Paget's disease. Following surgery, she is currently on adjuvant chemotherapy with no evidence of disease. Case 3 was a 47-year-old lady presenting with a lump in the right breast with nipple ulceration. Microscopic examination of the modified radical mastectomy specimen showed a high-grade invasive breast carcinoma along with invasive mammary Paget's disease. Follow-up imaging showed generalized lymphadenopathy. The patient was advised adjuvant chemotherapy; however, she was lost to follow-up after receiving the first cycle of treatment. We present three cases of invasive Paget's disease of the breast highlighting the importance of recognition of this rare entity with distinct therapeutic implications.","[""Case Reports"", ""Journal Article""]","[""Sharma A"", ""Langer R"", ""Chadha P"", ""Gupta G"", ""Singh S""]",10.7759/cureus.110432,Sharma A,Cureus,2168-8184,6,Cureus,eng,Singh S,[],e110432,42422618,pmc-id: PMC13343245;,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42422618/,Invasive Paget's Disease of the Breast: A Staging Pitfall Mimicking pT4 Disease,18,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Artificial intelligence has transformed digital pathology by enabling biomarker prediction from high-resolution whole-slide images. However, current methods are computationally inefficient, processing thousands of redundant tiles per slide and requiring complex aggregation models. We introduce EAGLE (Efficient Approach for Guided Local Examination), a deep learning framework that emulates pathologists by selectively analyzing informative regions. EAGLE combines task-agnostic tile selection with detailed feature extraction and is benchmarked against leading slide- and tile-level foundation models across 43 tasks from nine cancer types spanning morphology, biomarker prediction, treatment response and prognosis. EAGLE outperforms patch aggregation methods by up to 23% and achieves the highest overall classification performance. It processes one slide in 2.27 s, reducing computational time by more than 99% compared with existing models. This efficiency supports rapid and auditable workflows by enabling review of the exact tiles used for each prediction and reducing dependence on high-performance computing. By reliably identifying informative regions and minimizing artifacts, EAGLE provides robust and auditable outputs, supported by systematic negative controls and attention concentration analyses. Its unified embedding enables rapid slide search, integration into multi-omics pipelines and emerging clinical foundation models.","[""Journal Article"", ""Research Support, Non-U.S. Gov't"", ""Research Support, N.I.H., Extramural""]","[""Neidlinger P"", ""Lenz T"", ""Foersch S"", ""Loeffler CML"", ""Clusmann J"", ""Gustav M"", ""Shaktah LA"", ""Langer R"", ""Dislich B"", ""Boardman LA"", ""French AJ"", ""Goode EL"", ""Gsur A"", ""Brezina S"", ""Gunter MJ"", ""Steinfelder R"", ""Behrens HM"", ""Röcken C"", ""Harrison T"", ""Peters U"", ""Phipps AI"", ""Curigliano G"", ""Fusco N"", ""Marra A"", ""Hoffmeister M"", ""Brenner H"", ""Kather JN""]",10.1038/s41467-026-74918-9,Neidlinger P,Nature communications,2041-1723,1,Nat Commun,eng,Kather JN,"[""Deep Learning"", ""Humans"", ""Image Processing, Computer-Assisted"", ""Neoplasms""]",,42386722,pmc-id: PMC13324285;,2026 Jul 1,2026,https://pubmed.ncbi.nlm.nih.gov/42386722/,A deep learning framework for efficient pathology image analysis,17,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Hydrogels that adhere to biological tissues and resist fibrosis are required to provide both optimal functionality and appropriate stiffness on diverse soft tissues to achieve therapeutic efficacy and biocompatibility. However, their performance is often limited by an intrinsic trade-off between functionality and stiffness. Through the incorporation of polymer brush coatings, we develop a modular hydrogel system to enable independent control of functionality and stiffness. By tailoring coating chemistry, coating thickness, and hydrogel network topology, we obtain consistent bioadhesion (~100 joules per square meter) and fibrosis suppression across the full stiffness range of soft tissues (1 kilopascal to 1 megapascal). Using this approach, we design a hydrogel that can maintain stable adhesion in vivo on a beating mouse heart and a hydrogel with no fibrotic capsule in immunocompetent mice over 40 days. This modular system offers a customizable approach for designing functional implants with tailored mechanical properties.","[""Journal Article""]","[""Yang J"", ""Zhao Y"", ""Jeang WJ"", ""Pabel S"", ""Wong BM"", ""Manan R"", ""Nahrendorf M"", ""Langer R"", ""Anderson DG""]",10.1126/sciadv.aee3894,Yang J,Science advances,2375-2548,26,Sci Adv,eng,Anderson DG,"[""Animals"", ""Mice"", ""Hydrogels"", ""Fibrosis"", ""Biocompatible Materials"", ""Polymers""]",eaee3894,42341113,pmc-id: PMC13292947;,2026 Jun 26,2026,https://pubmed.ncbi.nlm.nih.gov/42341113/,"A modular hydrogel system with independent control of bioadhesion, fibrosis, and stiffness",12,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Short-term preoperative endocrine therapy (ET) is increasingly used in oestrogen receptor (ER)-positive, HER2-negative breast cancer as a functional test of endocrine sensitivity. We aimed to characterise histomorphological and immunophenotypic changes following preoperative ET and to identify predictors of endocrine response, defined as post-treatment Ki67 ≤ 10%. In this retrospective single-centre study, 180 patients treated with short-course preoperative ET (median duration 29 days) were compared with 151 patients undergoing primary surgery without ET. Paired biopsy and resection specimens were assessed for histological features, stromal proportion, stromal tumour-infiltrating lymphocytes (strTILs) and expression of ER, progesterone receptor (PR), HER2 and Ki67. Genomic risk was determined using the MammaPrint assay. Preoperative ET was associated with a significant reduction in tumour proliferation, with 73.9% of cases showing post-treatment Ki67 ≤ 10% compared with none in controls (P < 0.001). Histological grade decreased in 36.7% of ET-treated tumours versus 7.9% of controls (P < 0.001), predominantly reflecting reduced mitotic activity. ER expression remained stable, whereas PR expression decreased more frequently following ET (P < 0.001) and was independently associated with Ki67-defined response. HER2-low status was more frequently observed after ET (P < 0.001), but HER2 expression and microenvironmental parameters, including strTILs, were not associated with response. High genomic risk was independently associated with a lower likelihood of achieving post-treatment Ki67 ≤ 10% (P < 0.001). Short-course preoperative ET induces rapid and reproducible morphological and immunophenotypic changes in ER-positive, HER2-negative breast cancer. Ki67-defined response is associated with genomic risk and PR expression, whereas microenvironmental features appear to have limited predictive value.","[""Journal Article""]","[""Grosse C"", ""Grosse A"", ""Noack P"", ""Preuss CI"", ""Schwarz HK"", ""Schneeweiss B"", ""Gitter T"", ""Schrenk P"", ""Langer R""]",10.1111/his.70203,Grosse C,Histopathology,0309-0167,,Histopathology,eng,Langer R,[],,42315983,,2026 Jun 18,2026,https://pubmed.ncbi.nlm.nih.gov/42315983/,"Effects of short-course preoperative endocrine therapy on tumour morphology and immunohistochemical profile in oestrogen receptor-positive, HER2-negative breast cancer",,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Ribonucleic acid (RNA)-based therapeutics have emerged as promising methods of disease treatment due to their ability to target the human genome and influence protein production, their versatility, and their relative lack of toxicity compared to other gene therapies. However, the RNA therapeutic design space is extremely large, encompassing multiple variables, including codon identities, secondary structure, and design of specific regions. RNA therapeutic optimization is difficult due to the impracticality of exploring such a vast design space experimentally. To address this limitation, deep learning methods have been employed to optimize RNA therapeutic development. In this review, we examine the application of deep learning models across three key aspects of RNA therapeutic development (RNA structure prediction, CRISPR activity, and RNA delivery), highlighting major contributions in these fields and analyzing how deep learning model architectures could affect model performance. We then discuss challenges associated with using deep learning for RNA therapeutics, such as computational and data limitations. Finally, we offer perspectives on areas for future exploration, such as emerging model architectures and methods of integration with more advanced high-throughput screening techniques. Ultimately, this review provides an overview of how deep learning is used in RNA therapeutic development and how it can evolve in the future.","[""Journal Article"", ""Review""]","[""Subramanian DA"", ""Yao SL"", ""Chan A"", ""Witten J"", ""Reker D"", ""Anderson DG"", ""Langer R"", ""Traverso G""]",10.1021/acsnano.6c02090,Subramanian DA,ACS nano,1936-0851,24,ACS Nano,eng,Traverso G,"[""Deep Learning"", ""Humans"", ""RNA"", ""Nucleic Acid Conformation"", ""Genetic Therapy""]",17163-17177,42269714,,2026 Jun 23,2026,https://pubmed.ncbi.nlm.nih.gov/42269714/,The Use of Deep Learning in RNA Therapeutic Development,20,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Enteric pathogens are a major contributor to the global disease burden, necessitating vaccines capable of inducing robust gastrointestinal mucosal immunity. Achieving this response is especially challenging with inactivated or subunit vaccines, which lack the ability of live-attenuated formulations to mimic the natural infection process needed to induce strong intestinal mucosal immunity. Specifically, the inactivated polio vaccine (IPV), administered parenterally, elicits strong systemic immunity but fails to induce the mucosal IgA responses required to fully block poliovirus transmission, a critical step toward complete eradication. To address this limitation, we developed a clinically translatable and scalable nanoparticle-based intestinal mucosal adjuvant by encapsulating Am80, a small hydrophobic molecule known to promote intestinal mucosal immunity, within nanoparticles (NPs) designed for lymph node delivery, without requiring antigen modification, encapsulation, or adsorption. Encapsulation in NPs eliminated the need for the use of organic solvents, reduced toxicity, and prevented degradation, while lipid nanoparticles (Am80-LNPs) were engineered for sustained release over 3 to 5 days with high encapsulation efficiency (78 ± 9%). Cy5-labeled Am80-LNPs localized to draining lymph nodes within 6 hours and were retained for up to 72 hours. Coadministration of Am80-LNPs with the licensed IPV-2 in a Wistar rat model significantly boosted IPV-2-specific fecal IgA by 20-fold compared to IPV-2 alone and threefold over free Am80. These findings demonstrate that Am80-LNPs significantly enhance IPV-2-specific mucosal immunity in vivo and suggest their potential as a potent mucosal adjuvant against other enteric pathogens.","[""Journal Article""]","[""Eshaghi B"", ""Wang EY"", ""Mursalova S"", ""Forster TA"", ""Lasrado N"", ""Tian J"", ""Artzi D"", ""Lin SQ"", ""Wu Z"", ""Yang X"", ""Chung W"", ""Sadeghi I"", ""Garcia J"", ""Chen Z"", ""Sheridan O"", ""Das R"", ""Lau A"", ""Gurram A"", ""Mainou BA"", ""Jones KAV"", ""Liu Y"", ""Barouch DH"", ""von Andrian U"", ""Langer R"", ""Jaklenec A""]",10.1126/sciadv.aea5433,Eshaghi B,Science advances,2375-2548,23,Sci Adv,eng,Jaklenec A,"[""Animals"", ""Female"", ""Rats"", ""Adjuvants, Immunologic"", ""Immunity, Mucosal"", ""Immunization"", ""Immunoglobulin A"", ""Intestinal Mucosa"", ""Lipids"", ""Lymph Nodes"", ""Nanoparticles"", ""Nanovaccines"", ""Poliomyelitis"", ""Poliovirus Vaccine, Inactivated"", ""Liposomes"", ""Humans""]",eaea5433,42234750,pmc-id: PMC13232564;,2026 Jun 5,2026,https://pubmed.ncbi.nlm.nih.gov/42234750/,Am80-lipid nanoparticles serve as an enteric mucosal adjuvant following parenteral immunization with inactivated polio vaccine,12,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
,"[""Published Erratum""]","[""Gu W"", ""Luozhong S"", ""Cai S"", ""Londhe K"", ""Elkasri N"", ""Hawkins R"", ""Yuan Z"", ""Su-Greene K"", ""Yin Y"", ""Cruz M"", ""Chang YW"", ""McMullen P"", ""Wu C"", ""Seo C"", ""Guru A"", ""Gao W"", ""Sarmiento T"", ""Schaffer C"", ""Nishimura N"", ""Cerione R"", ""Yu Q"", ""Warden M"", ""Langer R"", ""Jiang S""]",10.1038/s41551-026-01721-8,Gu W,Nature biomedical engineering,2157-846X,6,Nat Biomed Eng,eng,Jiang S,[],1263,42204291,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42204291/,Author Correction: Extracellular vesicles incorporating retrovirus-like capsids for the enhanced packaging and systemic delivery of mRNA into neurons,10,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Here, we develop a next-generation wireless, battery-free oxygen generating O2-Macrodevice and wearable power transfer platform that can enable long-term immune protection and subcutaneous function of therapeutic cells. We demonstrate this device supports xenogeneic islet transplantation in C57BL/6J mice evidenced by 90-day diabetes reversal and glucose responsiveness in vivo. We also show partial glycemic control via high-density (>8,000 islets/cm2) human stem-cell derived islets (SC-islets) without immune-suppression in subcutaneous sites for 90 days. Additionally, we confirmed the device supports allogenic islet cell survival and 90-day diabetic reversal in rats. Finally, we demonstrate 1-month islet survival in a nonhuman primate without the need for immune suppression in the subcutaneous space. Collectively, these results indicate the device supports cell survival and function across multiple transplant models in three species without the need for any immunosuppression or external user intervention. These results represent an important set of advances towards immunosuppression free, minimally invasive islet transplantation.","[""Journal Article""]","[""Krishnan SR"", ""Bochenek MA"", ""Pan J"", ""Pendyala S"", ""Chan SN"", ""Liu C"", ""Prokop E"", ""Hogrebe N"", ""Rios PD"", ""Lopez D"", ""Potdar S"", ""Gumustop D"", ""Her BS"", ""O'Keeffe L"", ""Millman JR"", ""Oberholzer J"", ""Langer R"", ""Anderson DG""]",10.1016/j.device.2026.101084,Krishnan SR,Device,2666-9994,5,Device,eng,Anderson DG,[],,42182975,pmc-id: PMC13196877;manuscript-id: NIHMS2161415;embargo-date: 2027/05/15;,2026 May 15,2026,https://pubmed.ncbi.nlm.nih.gov/42182975/,Wireless battery-free oxygenation devices enable extended immunosuppression-free islet transplantation in minimally invasive sites,4,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Expansion revealing (ExR) elucidates cellular organization by separating proteins within dense nanostructures by 20x linear expansion, but requires fixation procedures incompatible with human pathology specimens. Here, we report ExR of pathology (ExRPath), which attains ~20 nm resolution and decrowding of such tissues, through iterative 20x expansion, adapted to human brain pathology specimens. We also report a single-shot 15x expansion protocol for such tissues (15ExMPath), achieved through one-shot 15x expansion. Applying ExRPath and 15ExMPath to COVID-19-decedent brain tissue reveals periodic amyloid nanoclusters that co-localize with SARS-CoV-2 in a rare minority of patient specimens, pointing to a potential neuroinflammatory phenotype associated with COVID-19, and highlighting the power of high-throughput nanoimaging, empowered by expansion microscopy, for discovering potential novel disease mechanisms.","[""Journal Article"", ""Preprint""]","[""Stanton AE"", ""Kang J"", ""Blanchard JW"", ""Boix CA"", ""Schroeder ME"", ""Lee Y"", ""Su H"", ""Wang S"", ""Yu E"", ""Emenari A"", ""Peng Z"", ""Agbas E"", ""Cerit O"", ""Park D"", ""Zhang R"", ""Bennett DA"", ""Yin P"", ""Kellis M"", ""Langer R"", ""Boyden E"", ""Tsai LH""]",10.64898/2026.05.14.725177,Stanton AE,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Tsai LH,[],,42182160,pmc-id: PMC13192606;,2026 May 15,2026,https://pubmed.ncbi.nlm.nih.gov/42182160/,Expansion Revealing of Pathology Resolves Nanostructures Associated with Inflammatory Phenotypes in COVID-19 Decedent Human Brain Tissue,,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Although immunotherapy has benefited a subset of persons with cancer, its broader efficacy remains limited, primarily because of an immunosuppressive tumor microenvironment characterized by insufficient numbers of functional tumor-specific T cells, antigen-presenting cells (APCs) and tumor-infiltrating lymphocytes. Here we engineer immune cells in the tumor microenvironment using lipid nanoparticles (LNPs) to deliver immune-remodeling mRNAs (IR-mRNAs) encoding NF-κB-inducing kinase or interferon regulatory factor 8. These IR-mRNAs activate APCs in tumors, significantly increasing activated type 1 conventional dendritic cells, immunostimulatory cytokines and priming antitumor CD8+ T cells. IR-mRNAs encapsulated in LNPs elicited durable antitumor responses in multiple syngeneic mouse tumor models through both intratumoral and intravenous delivery. Coadministration of IR-mRNA and ovalbumin mRNA elicited a ~10-fold increase in antigen-specific CD8+ T cell responses, sustained long-term memory and effectively prevented tumor growth in vaccinated mice. Additionally, coadministration of IR-mRNA and hemagglutinin mRNA enhanced the humoral response ~5-fold and the cellular response ~15-fold, underscoring their potential as adjuvants for boosting adaptive immunity.","[""Journal Article""]","[""Gupta A"", ""Das R"", ""Reed K"", ""Jeon T"", ""Nguyen QTC"", ""Rudra A"", ""Ge X"", ""Trongjit S"", ""Vanrobaeys YS"", ""Langer R"", ""Weissleder R"", ""Garris C"", ""Anderson DG""]",10.1038/s41587-026-03115-2,Gupta A,Nature biotechnology,1087-0156,,Nat Biotechnol,eng,Anderson DG,[],,42129506,pmc-id: PMC13242704;manuscript-id: NIHMS2181530;,2026 May 13,2026,https://pubmed.ncbi.nlm.nih.gov/42129506/,Immune-remodeling mRNAs expressing IRF8 or NIK generate durable antitumor immunity in multiple cancer models,,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Real-time monitoring of cerebrospinal fluid (CSF) is critical in intensive care units for the timely management of complications such as infection and mechanical malfunction in patients with external ventricular drainage systems. Current practice relies on intermittent CSF sampling for laboratory-based biomarker analysis and manual inspection, resulting in delayed reporting and intervention. To address these limitations, we developed NeuroSense, a multiplexed sensing platform that integrates with standard external ventricular drainage systems to enable near real-time monitoring of key CSF (bio)markers, including glucose, lactate, pH, and flow rate, that are essential for detecting infection and drain dysfunction. NeuroSense incorporates glucose and lactate aptamer-based electrochemical biosensors, a polydopamine pH sensor, and an impedance-based flow sensor. Validation in simulated conditions demonstrated sensor specificity, stability in human CSF for several days, and ethylene-oxide sterilization compatibility. Evaluation in patients hospitalized in intensive care unit demonstrated strong correlation with clinical reference standards. By providing near real-time bedside assessment, NeuroSense has the potential to improve temporal resolution for detection of biomarker trends and drain malfunction indicators.","[""Journal Article""]","[""Keyvani F"", ""Muller LM"", ""Fudge N"", ""MacLean B"", ""Saini A"", ""Khatri J"", ""Kriesen T"", ""Wittstock M"", ""Gessler FA"", ""Langer R"", ""Bernstock JD"", ""Srinivasan S"", ""Poudineh M""]",10.1126/scitranslmed.aeb1381,Keyvani F,Science translational medicine,1946-6234,849,Sci Transl Med,eng,Poudineh M,"[""Humans"", ""Biomarkers"", ""Critical Care"", ""Biosensing Techniques"", ""Hydrogen-Ion Concentration"", ""Monitoring, Physiologic"", ""Lactic Acid"", ""Time Factors""]",eaeb1381,42127221,,2026 May 13,2026,https://pubmed.ncbi.nlm.nih.gov/42127221/,A platform for near real-time and multiplexed monitoring of cerebrospinal fluid biomarkers and flow in neurocritical care,18,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Microneedle (MN) devices provide a platform for development of products that can facilitate intra-and trans-dermal delivery and sampling of active pharmaceutical ingredient (APIs) and biomarkers that would otherwise be restricted by the skin barrier. Despite significant progress in the development of laboratory-based prototypes, no Microneedle Array Patch (MAP) drug delivery products have been approved for commercial use by the relevant national regulatory authorities. This discrepancy reflects the technical, commercial, and regulatory challenges to their clinical translation. This review presents some of the pertinent challenges facing MN development, discusses potential approaches to them, and provides a future outlook. MN design is discussed, including their intrinsically conflicting requirement of being slender enough for skin penetration and voluminous enough to accommodate clinically relevant doses of APIs. The anatomy and constitutive behavior of skin tissue, and the related insertion mechanics of MNs with distinct morphologies are also considered, enabling understanding of how MNs achieve the mechanical strength to withstand handling and use. The fabrication methods for these materials are compared, including their amenability to large-scale manufacturing based on factors such as high throughput, cost efficiency, and process capability. Biocompatibility and dissolution behaviors in the dermal compartment are also considered. MN applicator designs are summarized, with a focus on their different mechanisms of application and impact energies. Key elements of the regulatory science of MAPs are also discussed. This review highlights challenges in the development of MN-based drug delivery systems compatible with applicators for on-demand, self-applied patient-specific intra- and trans-dermal therapy.","[""Journal Article"", ""Review"", ""Research Support, Non-U.S. Gov't""]","[""Zhou J"", ""Wu L"", ""Wyttenbach M"", ""Lennon R"", ""Liu Y"", ""Christian M"", ""Scherr S"", ""Charara M"", ""Kommalapati R"", ""Blum J"", ""Chatzilakou E"", ""Schlueter A"", ""Theobald F"", ""Valenti L"", ""Kosuda K"", ""Jacobson GB"", ""Kwon M"", ""Ding S"", ""Quinn C"", ""Rosen C"", ""Springall IC"", ""Tran KTM"", ""Tian J"", ""Yetisen AK"", ""Jaklenec A"", ""Shalabi N"", ""Li J"", ""Kang Z"", ""Farra R"", ""Kendall M"", ""Park JH"", ""DeSimone J"", ""Donnelly RF"", ""Wang J"", ""Mistilis JJ"", ""Prausnitz MR"", ""Birchall JC"", ""Coulman SA"", ""Hart AJ"", ""Portela CM"", ""Langer R"", ""Francese G"", ""Traverso G""]",10.1016/j.jconrel.2026.114980,Zhou J,Journal of controlled release : official journal of the Controlled Release Society,0168-3659,,J Control Release,eng,Traverso G,"[""Animals"", ""Humans"", ""Administration, Cutaneous"", ""Biomarkers"", ""Equipment Design"", ""Microneedle Drug Delivery"", ""Needles"", ""Skin"", ""Skin Absorption""]",114980,42092613,,2026 Jul 10,2026,https://pubmed.ncbi.nlm.nih.gov/42092613/,Microneedle array platforms for drug delivery and biomarker sensing: From skin mechanics guided design to scalable manufacture for clinical utility,395,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Type 1 Diabetes (T1D) is a devastating disease in which the immune system attacks insulin- producing beta cells in the pancreas, disrupting the normal blood glucose regulation mechanism and resulting in the significant burden of ongoing blood glucose monitoring and management and longer-term damage to organs and tissues. An emerging therapy for T1D includes transplanting insulin-producing stem cell (SC)-derived aggregates into patients, restoring normal regulation of blood glucose and eliminating the need for insulin injections. To enable stable storage, distribution, and clinical administration of this therapeutic, reliable cryopreservation methods are required. However, current cryopreservation protocols result in low cell viability post thaw and have challenges in scalability. This review provides background on stem cell therapy for T1D and the production and storage pipeline of these SC-derived aggregates, with a focus on the challenges of cryopreservation. We review the fundamental physics involved in cryopreservation, including cryoprotective agents (CPAs), CPA loading and unloading, the importance of cooling and rewarming rate selection, and why the cell aggregate microstructure of islets presents a particularly difficult challenge for cryopreservation. Finally, we highlight important developments in SC-derived aggregate cryopreservation and the state of the art.","[""Journal Article"", ""Review"", ""Research Support, Non-U.S. Gov't""]","[""Barsukova AD"", ""Weng L"", ""Szymanska-Vandendriessche K"", ""Scott M"", ""Langer R"", ""Traverso G""]",10.1016/j.jconrel.2026.114914,Barsukova AD,Journal of controlled release : official journal of the Controlled Release Society,0168-3659,,J Control Release,eng,Traverso G,"[""Humans"", ""Cryopreservation"", ""Diabetes Mellitus, Type 1"", ""Animals"", ""Cryoprotective Agents"", ""Stem Cells"", ""Stem Cell Transplantation"", ""Insulin-Secreting Cells""]",114914,41967811,,2026 Jul 10,2026,https://pubmed.ncbi.nlm.nih.gov/41967811/,Cryopreservation of stem cell-derived aggregates for type 1 diabetes cell therapy: Considerations and challenges,395,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Correction for 'Cell docking inside microwells within reversibly sealed microfluidic channels for fabricating multiphenotype cell arrays' by Ali Khademhosseini et al., Lab Chip, 2005, 5, 1380-1386, https://doi.org/10.1039/B508096G.","[""Published Erratum""]","[""Khademhosseini A"", ""Yeh J"", ""Eng G"", ""Karp J"", ""Kaji H"", ""Borenstein J"", ""Farokhzad OC"", ""Langer R""]",10.1039/d6lc90032a,Khademhosseini A,Lab on a chip,1473-0189,8,Lab Chip,eng,Langer R,[],2622,41947634,,2026 Apr 22,2026,https://pubmed.ncbi.nlm.nih.gov/41947634/,Correction: Cell docking inside microwells within reversibly sealed microfluidic channels for fabricating multiphenotype cell arrays,26,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Advances at the intersection of biotechnology, artificial intelligence, electronics and materials science are reshaping how drugs can be delivered inside the body. Intelligent and miniaturized drug delivery devices (IMDDDs) leverage these technologies to achieve precise pharmacokinetics, targeted distribution and programmable release while minimizing toxicity and improving patient adherence. Unlike conventional approaches, IMDDDs can incorporate real-time sensing and adaptive control, enabling drug administration that is more precise and more responsive to dynamic physiological conditions. In this Review, we outline key categories and design principles, highlight artificial intelligence technologies for augmenting performance, discuss potential clinical applications across cancer, diabetes, cardiovascular disease, vaccination and beyond, and examine translation challenges and opportunities. By uniting engineering innovation with medical need, IMDDDs exemplify the next generation of drug delivery technologies.","[""Journal Article"", ""Review"", ""Research Support, Non-U.S. Gov't""]","[""Wei X"", ""Buse JB"", ""Chen H"", ""Desai TA"", ""Stevens MM"", ""Traverso G"", ""Langer R"", ""Gu Z""]",10.1038/s41586-026-10221-3,Wei X,Nature,0028-0836,8107,Nature,eng,Gu Z,"[""Humans"", ""Drug Delivery Systems"", ""Miniaturization"", ""Artificial Intelligence"", ""Animals"", ""Neoplasms"", ""Cardiovascular Diseases""]",897-908,41882132,,2026 Mar,2026,https://pubmed.ncbi.nlm.nih.gov/41882132/,Towards intelligent and miniaturized drug delivery devices,651,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Group 14 monoelemental two-dimensional (2D) materials beyond graphene, such as silicene and germanene, have gained significant attention in the scientific community. Covalent functionalization of germanene with hydrogen and methyl leads to germanane (hydrogen/methyl-terminated germanene; HGe/MGe). While the optical and electronic properties of HGe and MGe were explored previously, there is no report on their zinc ion storage electrochemistry. Though the layered HGe/MGe sheets have tunable interlayer spacing, which cushions the volume expansion during ion storage, their inferior electrical conductivity limits the charge transfer kinetics. Herein, we demonstrate a single-step, facile approach for in situ decoration of 2D HGe/MGe sheets over laser-induced graphene (LIG) using a pulsed laser and examine their morphological, chemical, and electrochemical (EC) characteristics. The HGe/MGe-decorated LIG is tested as a cathode for a zinc ion hybrid capacitor (ZHC) in an aqueous electrolyte and polyacrylamide organohydrogel to unveil the selective sites for zinc ion electrochemistry by experimental and theoretical aspects. This ZHC design enables a notable Zn2+ storage capacity (104 F g-1 @ 0.25 A g-1 in aqueous electrolyte) for HGe-decorated LIG, whereas MGe-decorated LIG records impressive cyclic stability (capacity retention 83% after 12000 cycles). Density functional theory calculations elucidate favorable adsorption of Zn at MGe and HGe networks. These findings summarize the applicability of 2D functionalized germanane, which has the potential to expand by numerous alkyl chains and terminal groups for targeted energy storage applications.","[""Journal Article""]","[""Deshmukh S"", ""Sonigara KK"", ""Langer R"", ""Otyepka M"", ""Pumera M""]",10.1021/acsnano.5c13803,Deshmukh S,ACS nano,1936-0851,10,ACS Nano,eng,Pumera M,[],8275-8288,41757735,pmc-id: PMC13001108;,2026 Mar 17,2026,https://pubmed.ncbi.nlm.nih.gov/41757735/,Laser-Processed 2D Germanane on Graphene for Organohydrogel-Based Zinc-Ion Hybrid Capacitors,20,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Chronic pelvic pain (CPP) affects ∼15% of women and gender-diverse people, yet it is often dismissed by health care providers, partly due to a lack of related medical education. This brief communication describes the findings of a needs assessment survey for health care trainees. The findings suggest that current health care trainees felt inadequately prepared to manage CPP. Resources tailored to the diagnostic workup and treatment of CPP are needed in medical education.","[""Journal Article""]","[""Orr NL"", ""Yang L"", ""Howard AF"", ""Langer R"", ""Bruce B"", ""Lisonek M"", ""Phulka N"", ""Hayward A"", ""Currie L"", ""Qayumi K"", ""Carlyle M"", ""Daudt H"", ""Yong PJ""]",10.1016/j.jogc.2026.103225,Orr NL,Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC,1701-2163,3,J Obstet Gynaecol Can,eng,Yong PJ,"[""Humans"", ""Pelvic Pain"", ""Needs Assessment"", ""Chronic Pain"", ""Female"", ""British Columbia"", ""Health Personnel"", ""Education, Medical"", ""Clinical Competence""]",103225,41621802,,2026 Mar,2026,https://pubmed.ncbi.nlm.nih.gov/41621802/,Chronic Pelvic Pain in Medical Education: A Needs Assessment of British Columbian Health Care Providers in Training,48,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Lipid nanoparticles (LNPs) are the leading nonviral nucleic acid delivery technology, but LNP structure-function data remains fragmented and nonstandardized. Unlike protein engineering which is anchored by the centralized Protein Data Bank, the LNP field lacks a unified repository for systematic analysis. To address this, we develop Lipid Nanoparticle Database (LNPDB) ( https://lnpdb.molcube.com ), an integrated database and web tool that consolidates structural and functional data for 19,528 LNPs. LNPDB standardizes LNP featurization by encoding lipid composition, experimental methods, and functional results, and generates CHARMM force field files for constituent lipids to enable molecular dynamics simulations. LNPDB also supports future data contributions for continued growth. We examine the utility of LNPDB through two applications: advancing our deep learning model for predicting LNP delivery performance, and simulating bilayer dynamics to identify structural features - bilayer stability and critical packing parameter - that correlate with LNP delivery performance. Altogether, LNPDB provides the digital framework for LNP modeling and data-driven rational design.","[""Journal Article""]","[""Collins E"", ""Ji J"", ""Kim SG"", ""Witten J"", ""Kim S"", ""Zhu R"", ""Park P"", ""Jung M"", ""Park A"", ""Manan RS"", ""Rudra A"", ""Keum G"", ""Bang EK"", ""Jin JO"", ""Jeang WJ"", ""Langer R"", ""Anderson DG"", ""Im W""]",10.1038/s41467-026-68818-1,Collins E,Nature communications,2041-1723,1,Nat Commun,eng,Im W,"[""Nanoparticles"", ""Lipids"", ""Nucleic Acids"", ""Molecular Dynamics Simulation"", ""Structure-Activity Relationship"", ""Lipid Bilayers"", ""Liposomes""]",,41605942,pmc-id: PMC12992592;,2026 Jan 28,2026,https://pubmed.ncbi.nlm.nih.gov/41605942/,Lipid Nanoparticle Database towards structure-function modeling and data-driven design for nucleic acid delivery,17,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Immunoisolation devices containing therapeutic protein-secreting cells offer potential for long-term therapy without immune suppression. However, scar tissue formation driven by the foreign body response (FBR) hinders nutritional exchange and ultimately leads to graft failure. We previously showed that inhibiting the colony-stimulating factor-1 receptor (CSF1R) pathway in monocytes and macrophages can block the FBR to implanted materials. Here, we demonstrate that coencapsulation of slow-releasing CSF1R inhibitor (GW2580) crystals with human stem cell-derived β cells (SC-β) in alginate spheres enables stable glycemic control for 1 year in immune-competent diabetic C57BL/6 mice. In nonhuman primates (NHPs), GW2580 crystals similarly protected viable, glucose-responsive allogeneic β cells for 1 month without systemic immune suppression. In contrast, the same xenogeneic human SC-β cell formulation that functioned long-term in mice elicited extensive sphere overgrowth and graft failure in NHPs. Serum cytokine profiling and transcriptomic analysis of omental biopsies at day 30 revealed pronounced adaptive immune activation in xenogeneic recipients, including enrichment of CD4+ T cells, CD19+ B cells, and antigen-presenting cell programs marked by elevated MHC class II expression. Chemokines CCL17, CCL22, and CXCL13 were among the most highly up-regulated transcripts, mirroring responses observed previously with profibrotic alginate formulations without cells. These findings underscore the issues associated with xenogeneic cell sources in higher-order species yet indicate that targeting innate immune pathways with localized CSF1R inhibition may be sufficient to enable function of encapsulated allogeneic cell therapies.","[""Journal Article""]","[""Bochenek MA"", ""Farah S"", ""Doloff JC"", ""Han HJ"", ""Sadraei A"", ""Jeang WJ"", ""Shaheen-Mualim M"", ""Kutner N"", ""Odeh E"", ""Facklam A"", ""DiNardo A"", ""Engquist EN"", ""Rios P"", ""Isa D"", ""Ghani S"", ""Joshi I"", ""Xing Y"", ""Wang Y"", ""Pop R"", ""Greiner DL"", ""Oberholzer J"", ""Langer R"", ""Anderson DG""]",10.1126/scitranslmed.adt1055,Bochenek MA,Science translational medicine,1946-6234,834,Sci Transl Med,eng,Anderson DG,"[""Animals"", ""Humans"", ""Mice, Inbred C57BL"", ""Transplantation, Homologous"", ""Transplantation, Heterologous"", ""Receptor, Macrophage Colony-Stimulating Factor"", ""Alginates"", ""Insulin-Secreting Cells"", ""Cytokines"", ""Mice"", ""Receptors, Granulocyte-Macrophage Colony-Stimulating Factor"", ""Hexuronic Acids"", ""Glucuronic Acid""]",eadt1055,41604464,,2026 Jan 28,2026,https://pubmed.ncbi.nlm.nih.gov/41604464/,Crystallized colony-stimulating factor-1 receptor inhibitor protects immunoisolated allo but not xeno transplants in primates,18,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Decentralized on-patient medical record (OPMR) storage would enable medical staff to access patients' medical information on demand, especially in low-resource settings lacking centralized recordkeeping infrastructure. We incorporated near-infrared (NIR) microparticles into microneedle patches (MNPs) to invisibly encode medical information in the skin for OPMR using a specialized reader. NIR particles were co-encapsulated with inactivated polio vaccine in the same microneedles without loss of antigenicity. However, measles and rubella vaccines combined with NIR particles lost almost all potency. We therefore developed hybrid MNPs that spatially separated NIR particles in patterned microneedles in the central part of the patch and vaccines in separate microneedles around the periphery. This approach preserved vaccine potency. Ex vivo testing in pig skin demonstrated effective microneedle penetration and reliable OPMR signal readability. In vivo studies in rats and guinea pigs demonstrated OPMR signal retention for up to 21 months. Immunogenicity studies in cotton rats confirmed that neutralizing antibody titers were similar after measles vaccination by hybrid MNPs (containing NIR particles), conventional MNPs (without NIR particles) and subcutaneous injection. These findings suggest that hybrid MNPs enable co-administration of vaccines and NIR particles for OPMR or co-delivery of other materials requiring sequestration.","[""Journal Article"", ""Research Support, Non-U.S. Gov't"", ""Research Support, N.I.H., Extramural"", ""Research Support, U.S. Gov't, P.H.S.""]","[""Sadeqi A"", ""Lee JW"", ""Gomaa Y"", ""Nguyen TC"", ""Azizoglu E"", ""Hasin T"", ""Ryu YJ"", ""Dixon JB"", ""Kanelli M"", ""Han J"", ""Langer R"", ""Jaklenec A"", ""Prausnitz MR""]",10.1016/j.jconrel.2026.114635,Sadeqi A,Journal of controlled release : official journal of the Controlled Release Society,0168-3659,,J Control Release,eng,Prausnitz MR,"[""Animals"", ""Microneedle Drug Delivery"", ""Measles Vaccine"", ""Guinea Pigs"", ""Rubella Vaccine"", ""Female"", ""Antibodies, Neutralizing"", ""Needles"", ""Humans"", ""Rats"", ""Antibodies, Viral"", ""Administration, Cutaneous""]",114635,41544667,,2026 Mar 10,2026,https://pubmed.ncbi.nlm.nih.gov/41544667/,Hybrid microneedle patch for administration of measles and rubella vaccine with an on-patient medical record,391,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Endoscopic submucosal dissection (ESD) has revolutionized the management of early upper gastrointestinal (GI) carcinomas. While technically demanding, it offers, in experienced hands, definitive local therapy for early GI neoplasia by allowing complete En bloc resection of mucosal and superficially invasive neoplasms, thus enabling precise histopathological risk stratification and organ preservation. Appropriate patient selection relies on meticulous endoscopic assessment using high-definition and image-enhanced endoscopy to define lesion boundaries and predict invasion depth. The principal indications include high-grade intraepithelial neoplasia and early carcinomas without endoscopic evidence of deep submucosal invasion or lymph node metastasis risk factors. Pathological analysis of the resection specimens includes histological typing and grading per WHO classification and precise assessment of invasion depth-in case of submucosal invasion measurement in micrometers-and evaluation of margin status and lymphovascular invasion. The presence of risk factors such as deep invasion in the submucosa, poor differentiation, or lymphovascular invasion may require additional surgery, guided by validated risk scores such as the eCura system. This narrative review summarizes current clinical and pathological practices for ESD in upper GI lesions. This includes the discussion of technical and biological challenges and the need of accurate assessment of risk factors for systemic metastatic spread and local recurrence as a limitation for this sophisticated but highly effective therapeutic method.","[""Journal Article"", ""Review""]","[""Ziachehabi A"", ""Worm M"", ""Liu DHW"", ""Pimingstorfer P"", ""Langer R""]",10.3390/jcm14248817,Ziachehabi A,Journal of clinical medicine,2077-0383,24,J Clin Med,eng,Langer R,[],,41464719,pmc-id: PMC12733988;,2025 Dec 12,2025,https://pubmed.ncbi.nlm.nih.gov/41464719/,Endoscopic Submucosal Dissection (ESD) of Upper Gastrointestinal Carcinomas: An Integrated Clinical and Pathological Perspective,14,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Predictive biomarker testing is nowadays an integral part of modern diagnostics and treatment planning for esophageal and gastric cancer. It currently consists mainly of immunohistochemically determined markers, namely the PD-L1 status (stated by the Tumor Proportion Score [TPS], Combined Positivity Score [CPS] and Tumor Area Proportion [TAP] Score) in esophageal squamous cell carcinomas, as well as the HER2 status (supplemented by in situ hybridization in case of equivocal results), the mismatch repair status (optionally supplemented by molecular pathological determination of microsatellite status), and, since mid-2024, the expression of claudin 18.2 in gastroesophageal adenocarcinomas. An expansion of the panel by FGFR2b is expected in the near future. In addition to the quality guideline-compliant technical performance of the tests, the biological heterogeneity of many of these biomarkers is also a diagnostic and clinical challenge. The current article provides an overview of current biomarker testing in the context of current treatment options for cancer of the upper gastrointestinal tract.","[""Journal Article"", ""Review"", ""English Abstract""]","[""Liu DHW"", ""Piringer G"", ""Köfler S"", ""Langer R""]",10.1007/s00292-025-01506-x,Liu DHW,"Pathologie (Heidelberg, Germany)",2731-7188,3,Pathologie (Heidelb),ger,Langer R,"[""Humans"", ""Biomarkers, Tumor"", ""Esophageal Neoplasms"", ""Stomach Neoplasms"", ""Adenocarcinoma"", ""B7-H1 Antigen"", ""Erb-b2 Receptor Tyrosine Kinases"", ""DNA Mismatch Repair"", ""Carcinoma, Squamous Cell"", ""Gastrointestinal Neoplasms"", ""Immunohistochemistry""]",220-230,41369745,pmc-id: PMC13109289;,2026 May,2026,https://pubmed.ncbi.nlm.nih.gov/41369745/,[Biomarker testing for carcinomas of the upper gastrointestinal tract],47,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Action potentials, the primary information units of the nervous system, are usually generated at the axon initial segment. Changes in the length and position of the axon initial segment are associated with alterations in neuronal excitability, but there is only limited information about the baseline structural variability of this compartment. This work provides a comprehensive analysis of the diversity of proximal cell geometries across all anatomical axes of the murine hippocampus, encompassing dorsal-ventral, superficial-deep, and proximal-distal regions. We analyzed the morphology of 3,681 hippocampal pyramidal neurons in 12 animals of both sexes, focusing on axon initial segment length, position, and association with proximal cellular features such as the soma and apical dendrite. Notably, neurons with axon-carrying dendrites were significantly more common in ventral compared to dorsal hippocampal areas, which we also found in two of three human samples. We employed NEURON simulations to assess the functional implications of this variability. Here, variation in proximal geometry contributed only minimally to neuronal homeostasis, but instead increased heterogeneity of response patterns across neurons.","[""Journal Article""]","[""Stevens NA"", ""Achilles M"", ""Monath J"", ""Langer R"", ""Engelhardt M"", ""Both M"", ""Thome C""]",10.1093/cercor/bhaf297,Stevens NA,"Cerebral cortex (New York, N.Y. : 1991)",1047-3211,12,Cereb Cortex,eng,Thome C,"[""Animals"", ""Male"", ""Hippocampus"", ""Axon Initial Segment"", ""Female"", ""Pyramidal Cells"", ""Mice"", ""Mice, Inbred C57BL"", ""Action Potentials"", ""Axons"", ""Dendrites"", ""Humans""]",,41364662,pmc-id: PMC12687872;,2025 Nov 27,2025,https://pubmed.ncbi.nlm.nih.gov/41364662/,Diversity of axon initial segment geometry in the mouse hippocampus and its predicted influence on neuronal excitability,35,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Stress granules (SGs) represent membrane-free cytoplasmic structures rapidly aggregating during cellular stress responses arguably useful as markers of molecular inflammation. To provide an automated, reproducible, and unbiased analytic workflow, we used the open-source software CellProfiler to quantify SGs in distinct cell types in inflammatory bowel disease. The EpiCellProfiler (ECP) and PropiCellProfiler (PCP) pipelines enable segmentation within intestinal epithelial cells and lamina propria cells, respectively. The SG marker Ras GTPase-activating protein-binding protein 1 (G3BP1) was quantified for fluorescence intensity, granule size, and morphology on tissue sections of patients with ulcerative colitis (UC) and Crohn's disease (CD) in deep remission. Both pipelines detected elevated G3BP1 fluorescence intensities in inactive UC and CD. Additionally, SGs spot counts and spot sizes were increased in CD and UC compared with controls. The distribution of G3BP1 was homogenous in intestinal epithelial cells, without SG typical aggregations. In UC, PCP analysis revealed nuclear morphology alterations in terms of size, regularity, and compactness. Herein, we provide a powerful, reproducible, versatile and open-source software tool to quantify remnant molecular inflammation in patients with CD and UC, enabling research to openly share, reproduce and compare results within the field of quantitative image analysis. Our pipeline separates and distinguishes between epithelial and lamina propria events and provides insights into the spatial distribution and dynamics of SGs, revealing their homogeneous distribution and persistent accumulation in patients with CD and UC, notably in such without clinical, endoscopic, biochemical and histological disease activity. The sensitivity of the pipelines allows detection of subtle morphologic alterations that warrant further investigation, as does the usage of G3BP1 as an inflammatory bowel disease stress marker.","[""Journal Article""]","[""Hödlmayr H"", ""Watschinger C"", ""Wallner GK"", ""Knipp S"", ""Rohwedder A"", ""Prommer R"", ""Langer R"", ""Moschen AR""]",10.1016/j.jcmgh.2025.101680,Hödlmayr H,Cellular and molecular gastroenterology and hepatology,2352-345X,6,Cell Mol Gastroenterol Hepatol,eng,Moschen AR,"[""Humans"", ""Intestinal Mucosa"", ""RNA Recognition Motif Proteins"", ""Colitis, Ulcerative"", ""Biomarkers"", ""RNA Helicases"", ""Colon"", ""Software"", ""Stress Granules"", ""Crohn Disease"", ""DNA Helicases"", ""Male"", ""Epithelial Cells"", ""Female"", ""Stress, Physiological"", ""Adult"", ""Poly-ADP-Ribose Binding Proteins""]",101680,41354404,pmc-id: PMC13094656;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/41354404/,Design of CellProfiler-Based Pipelines Enabling the Attribution of Molecular Stress Markers to Specific Tissue and Subcellular Compartments of the Colonic Mucosa,20,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Malnutrition can severely compromise immune function, rendering populations more vulnerable to both communicable and non-communicable diseases. Here, we discuss food fortification and micronutrient supplementation programs that have been instrumental in mitigating malnutrition across Africa and in controlling disease spread, marking considerable advances in public health throughout the continent.","[""Journal Article""]","[""Yang X"", ""Zhang L"", ""MacDonald S"", ""Langer R"", ""Jaklenec A""]",10.1038/s43856-025-01276-w,Yang X,Communications medicine,2730-664X,1,Commun Med (Lond),eng,Jaklenec A,[],17,41353470,pmc-id: PMC12789419;,2025 Dec 6,2025,https://pubmed.ncbi.nlm.nih.gov/41353470/,The critical role of food fortification in combatting malnutrition and disease susceptibility in Africa,6,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Research on the tumour microenvironment in brain metastases (BM) has predominantly focused on the immune response, while the presence, morphological patterns, and potential clinical relevance of intratumoural stroma remain less intensively investigated. We retrospectively analysed 604 BM (529 carcinomas, 75 melanomas) from 556 patients. Intratumoural stroma was histomorphologically classified into absent/unclear (Group 0), present without desmoplasia (Group 1) or with desmoplasia (Group 2). Associations with histological features, clinical parameters, and survival were evaluated. Intratumoural stroma was absent in 63.2% of tumours (n = 382), was present without desmoplasia in 14.9% (n = 90), and was desmoplastic in 21.9% (n = 132). Desmoplasia was most frequent in metastases from breast carcinomas and pulmonary squamous cell carcinomas. No significant associations were found between stroma groups and age, sex, brain location, PD-L1 expression, oncogenic mutations in lung carcinoma, or breast-cancer molecular subtype. Independent predictors of poorer survival were increasing age (HR = 1.029, 95% CI: 1.018-1.039, p < 0.001), male sex (HR = 1.492, 95% CI: 1.204-1.849, p < 0.001), and infratentorial location (HR = 1.402, 95% CI: 1.125-1.748, p = 0.003). Stroma groups showed no independent prognostic value in the overall cohort. However, subgroup analysis of non-small cell lung cancer revealed a U-shaped relationship, with Group 1 stroma linked to better survival (p = 0.020). In summary, intratumoural stroma in BM is a carcinoma-specific phenomenon, absent in melanoma. Patient outcomes, however, were primarily determined by demographic and anatomical factors rather than stromal morphology in the overall cohort but may have clinical relevance in particular tumour subgroups.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Bandke D"", ""Weis S"", ""Gruber A"", ""Noack P"", ""Kalev O"", ""Ornig K"", ""Langer R""]",10.1002/2056-4538.70061,Bandke D,The journal of pathology. Clinical research,2056-4538,1,J Pathol Clin Res,eng,Langer R,"[""Humans"", ""Female"", ""Male"", ""Brain Neoplasms"", ""Middle Aged"", ""Melanoma"", ""Retrospective Studies"", ""Aged"", ""Stromal Cells"", ""Tumor Microenvironment"", ""Adult"", ""Aged, 80 and over"", ""Skin Neoplasms"", ""Lung Neoplasms"", ""Carcinoma""]",e70061,41317317,pmc-id: PMC12664527;,2026 Jan,2026,https://pubmed.ncbi.nlm.nih.gov/41317317/,Characterisation and impact of intratumoural stroma in melanoma and carcinoma brain metastases,12,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Rare diseases of the gastrointestinal (GI) tract present a significant diagnostic challenge. This paper focusses on two particular groups of conditions: drug-induced injuries and parasitic infections. With aging populations and increased use of complex pharmacologic regimens-including immunosuppressants and biologics-drug-related GI pathology is nowadays more frequently encountered. However, the histologic changes are often non-specific and overlap with more common conditions such as inflammatory bowel disease (IBD), ischemia, autoimmune diseases, or infections. Key patterns include lymphocytic or neutrophilic inflammation, crypt apoptosis, crypt abscesses, and architectural distortion. Certain agents, such as mycophenolate, olmesartan, immune checkpoint inhibitors, or ion exchange resins (e.g. sodium polystyrene sulfonate/kayexalate, sevelamer), have distinct but subtle histopathologic signatures. Parasitic infections, although less frequent in high-income countries, remain relevant due to global travel and migration. Organisms such as Schistosoma, Strongyloides, or Giardia can mimic IBD, neoplasia, or cause unexpected eosinophilic or granulomatous inflammation. Parasite ova may require special stains and careful morphologic assessment to be identified. Importantly, some helminths have been associated with chronic complications including cancer or fibrosis, thus underscoring the need for accurate recognition. For the practicing pathologist, these rare but impactful conditions demand a high index of suspicion, especially in cases with atypical histology or poor clinical correlation. Using some illustrative cases, this paper highlights diagnostic strategies and key morphologic features to improve recognition and avoid misdiagnosis of these underappreciated entities.","[""Journal Article"", ""Review""]","[""Angerer L"", ""Zauner T"", ""Langer R""]",10.1007/s00292-025-01501-2,Angerer L,"Pathologie (Heidelberg, Germany)",2731-7188,Suppl 1,Pathologie (Heidelb),eng,Langer R,"[""Humans"", ""Gastrointestinal Diseases"", ""Rare Diseases"", ""Animals"", ""Diagnosis, Differential"", ""Parasitic Diseases""]",51-58,41284018,pmc-id: PMC12816097;,2026 Jan,2026,https://pubmed.ncbi.nlm.nih.gov/41284018/,Rare non-neoplastic gastrointestinal diseases-drugs and bugs,47,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"In 2019, in this journal, I discussed approaches for controlling the movement of molecules, in particular macromolecules, with an emphasis on how this enabled advances in the field of drug delivery - a field that has impacted billions of people worldwide. Since 2019, there have been advances in our work and this field including a striking demonstration in which drug delivery nanoparticles were crucial to the success of mRNA therapies and the Covid-19 vaccine. In this paper, I provide updates in such areas as i) developing new methods for oral drug delivery systems, ii) delivery of molecules to specific sites of the body, iii) new types of delivery systems, and iv) examples of machine learning/artificial intelligence in these areas. I also discuss advances in mRNA technology as it relates to drug delivery and the development of nanoparticles to protect and deliver vaccines, which saved and improved the lives of hundreds of millions of people throughout the world.","[""Journal Article"", ""Review"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Langer R""]",10.1017/S0033583525100073,Langer R,Quarterly reviews of biophysics,0033-5835,,Q Rev Biophys,eng,Langer R,"[""Humans"", ""Drug Delivery Systems"", ""Macromolecular Substances"", ""Nanoparticles"", ""COVID-19 Vaccines"", ""COVID-19"", ""Animals"", ""SARS-CoV-2"", ""Machine Learning""]",e19,41249147,,2025 Nov 18,2025,https://pubmed.ncbi.nlm.nih.gov/41249147/,Delivery of macromolecular drugs: An update,58,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Membranes that prevent cellular infiltration are essential components of immune-isolation devices. Stringent pore size control is critical to robustly exclude immune cells while preserving the efficient transport of nutrients and therapeutic molecules. Conventional membrane fabrication methods, however, struggle to balance these two properties. For instance, phase separation and fiber spinning generate highly tortuous pores that restrict diffusion, while random pore overlaps due to ion track etching result in oversized defects that compromise immune isolation. Here, we leverage scalable laser-writing tools to achieve spatially controlled open-through and dense pores with uniformly distributed submicrometer sizes for rapid transport and robust immune cell exclusion. Given the optical limits of laser aligners when fabricating submicrometer features, we tuned substrate reflectivity and exposure parameters to overcome these resolution limits. Self-standing and flexible membranes were achieved via thickness-tunable grid layers supporting membrane mechanical integrity. We report pore sizes as small as ca. 600 nm (below the resolution limits of the laser exposure systems) and over 20% open area at the exposure times of ∼3 min/cm2. Compared with conventional methods, this approach minimizes pore tortuosity, narrows the pore distribution, and improves the open pore density. Enhanced pore control is highlighted by macrophage infiltration studies, which indicate that these membranes reliably exclude macrophages at nominal pore sizes greater than those previously achievable. This approach thus provides a scalable pathway toward next-generation immunoisolation membranes for enhanced implantable therapeutic devices.","[""Journal Article""]","[""Montazerian H"", ""Jeang WJ"", ""Zhao Y"", ""Manan RS"", ""Bochenek MA"", ""Krishnan SR"", ""Langer R"", ""Anderson DG""]",10.1021/acsnano.5c09814,Montazerian H,ACS nano,1936-0851,49,ACS Nano,eng,Anderson DG,"[""Lasers"", ""Nanopores"", ""Porosity"", ""Particle Size"", ""Animals"", ""Mice"", ""Membranes, Artificial"", ""Surface Properties"", ""Macrophages"", ""Humans""]",41528-41539,41231227,,2025 Dec 16,2025,https://pubmed.ncbi.nlm.nih.gov/41231227/,Wafer-Scale Laser-Writing of Nanoporous Membranes with Monodisperse Pores for Robust Immunoisolation,19,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"The next generation of mRNA vaccines must address several limitations, including enhancing vaccine potency and reducing toxicity. Here we develop a class of degradable, cyclic amino ionizable lipids via sequential combinatorial chemistry and rational design. Lipid nanoparticles (LNPs) formulated with the top-performing ionizable lipid, AMG1541, elicited similar protective neutralization antibody titres against an H3 influenza antigen when compared with the FDA-approved ionizable lipid SM-102 at a 100-fold lower dose, with enhanced clearance in vivo. AMG1541 mRNA LNPs substantially reduced expression in the liver following intramuscular injection, mitigating the associated toxicity. We also observed improved mRNA delivery to antigen-presenting cells at the injection site and the draining lymph node, leading to stronger germinal centre reactions. Structure-activity relationship studies suggest that cyclic headgroups and β-amino alcohols facilitate interactions with the mRNA backbone and enhance endosomal escape. The formulations developed here significantly enhance the potency of mRNA vaccines, and our structural insights may guide the development of next-generation vaccine delivery systems.","[""Journal Article""]","[""Rudra A"", ""Gupta A"", ""Reed K"", ""Deik A"", ""Min J"", ""Mansour HMA"", ""Nguyen QTC"", ""Danko A"", ""Hu Y"", ""Berger A"", ""Prado M"", ""Beck A"", ""Clish CB"", ""Klauda JB"", ""Langer R"", ""Anderson DG""]",10.1038/s41565-025-02044-6,Rudra A,Nature nanotechnology,1748-3387,12,Nat Nanotechnol,eng,Anderson DG,"[""Influenza Vaccines"", ""Lipids"", ""Animals"", ""RNA, Messenger"", ""Nanoparticles"", ""Mice"", ""Amino Alcohols"", ""mRNA Vaccines"", ""Female"", ""Humans"", ""Mice, Inbred BALB C"", ""Liposomes""]",1831-1842,41203968,pmc-id: PMC13387048;manuscript-id: NIHMS2181491;,2025 Dec,2025,https://pubmed.ncbi.nlm.nih.gov/41203968/,Degradable cyclic amino alcohol ionizable lipids as vectors for potent influenza mRNA vaccines,20,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Selective multiboration including di- and triboration and hydroboration of alkynes and alkenes face significant challenges in organic synthesis, including achieving high regioselectivity, functional group tolerance, and catalyst stability while requiring mild conditions to maintain reactivity. These transformations have been predominantly explored by using homogeneous catalysts. In this study, we report the scalable synthesis of heterogeneous platinum single-atom catalyst (Pt-SAC) supported on ultrathin nanosheets of graphitic carbon nitride via a rapid microwave-assisted method. The Pt-SAC enables 1,2-diboration of sterically hindered alkenes and 1,2,2-triboration of alkynes with B2pin2 under mild conditions. For the diboration of styrene, the catalyst achieves 99% yield with 95% selectivity, a turnover number (TON) of 3711, and a turnover frequency (TOF) of 247 h-1. The catalyst also promotes the regioselective hydroboration of alkenes and alkynes, yielding anti-Markovnikov alkylboranes and vinylboranes, respectively. Computational calculations reveal that the enhanced reactivity on the Pt-SAC catalyst arises from adsorption-induced weakening of key bonds (C=C and B-H), thereby significantly lowering the activation energy barriers. The Pt-SAC exhibits stability and recyclability, maintaining performance over at least eight consecutive runs without detectable Pt leaching. This study highlights the potential of Pt-SAC as a robust and versatile platform for organoboron transformations under mild conditions, with relevance to applications in pharmaceutical, agrochemical, and polymer synthesis.","[""Journal Article""]","[""Huninik P"", ""Sharma P"", ""Saptal VB"", ""Slaby M"", ""Langer R"", ""Kumar P"", ""Shayesteh Zeraati A"", ""Wang X"", ""Petr M"", ""Otyepka M"", ""Gawande MB"", ""Zbořil R"", ""Kment S"", ""Walkowiak J""]",10.1021/acscatal.5c03767,Huninik P,ACS catalysis,2155-5435,20,ACS Catal,eng,Walkowiak J,[],17347-17360,41127639,pmc-id: PMC12538553;,2025 Oct 17,2025,https://pubmed.ncbi.nlm.nih.gov/41127639/,Regioselective Multiboration and Hydroboration of Alkenes and Alkynes Enabled by a Platinum Single-Atom Catalyst,15,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Oral delivery of macromolecules is hindered by enzymatic degradation, poor epithelial permeability, and rapid gastric transit, leading to low bioavailability. Existing permeation enhancers (PEs), such as salcaprozate sodium and sodium caprate, improve absorption but do not fully address proteolytic degradation and require high doses due in part to short gastrointestinal residence times. We developed the Peroral Mucosal Epithelium Absorption Enhancer (PERMEATE) system, an orally administered polymer film designed to adhere to the small intestinal mucosa, maximizing contact between therapeutics, PEs, and the absorptive tissue. Utilizing Synthetic Tissue-Lining (SYNT™) technology, PERMEATE triggers endogenous catalase-dependent dopamine polymerization to form an in situ polydopamine coating, creating a temporary depot that enhances co-localization and prolongs exposure to the absorptive mucosa. We assessed PERMEATE's potential to enhance the oral bioavailability of semaglutide (SEMA). High-throughput screening using the GI tissue robotic interface system (GI-ORIS) identified glycocholic acid (GCA) and ammonium carbonate (NHCO) as effective PEs when combined with SYNT. Ex vivo studies (n = 8-24) and in vivo tests in Sprague-Dawley rats (n = 5-11/group) demonstrated a 200-fold increase in bioavailability compared to SEMA alone (P = 0.0001) and a 6-fold increase relative to SEMA+PE without SYNT (P = 0.0011). In Yorkshire pigs (n = 3-4), PERMEATE achieved a 2.4 % absolute bioavailability, a 6-fold improvement over SEMA+PE controls (P = 0.0316). These results suggest PERMEATE as a promising platform for improving oral macromolecule delivery through enhanced mucosal adhesion and prolonged therapeutic contact, supporting further development for clinical application.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Kanelli M"", ""Yu AC"", ""Susilo D"", ""Petropulos O"", ""Kadasia K"", ""Sandoval L"", ""Hudson MA"", ""Sim D"", ""Dial C"", ""Mena MB"", ""Liang J"", ""Rivera-Delgado E"", ""Sepich L"", ""Hollfelder K"", ""Wright J"", ""von Erlach T"", ""Hayward A"", ""Gaspie KA"", ""Barron SM"", ""Pombo M"", ""Basani RR"", ""Lanchantin M"", ""Lopes A"", ""Pizzo S"", ""Sethuraman V"", ""Dhanda RK"", ""Langer R"", ""Traverso G""]",10.1016/j.jconrel.2025.114338,Kanelli M,Journal of controlled release : official journal of the Controlled Release Society,0168-3659,Pt 2,J Control Release,eng,Traverso G,"[""Animals"", ""Biological Availability"", ""Rats, Sprague-Dawley"", ""Male"", ""Swine"", ""Intestinal Mucosa"", ""Administration, Oral"", ""Rats"", ""Polymers"", ""Drug Delivery Systems"", ""Intestinal Absorption"", ""Indoles""]",114338,41109558,pmc-id: PMC13078412;manuscript-id: NIHMS2153351;,2025 Dec 10,2025,https://pubmed.ncbi.nlm.nih.gov/41109558/,Enhanced macromolecule bioavailability in rats and pigs using an in situ forming synthetic epithelial lining,388,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Patient-specific, human-based cellular models integrating a biomimetic blood-brain barrier, immune, and myelinated neuron components are critically needed to enable accelerated, translationally relevant discovery of neurological disease mechanisms and interventions. To construct a human cell-based model that includes these features and all six major brain cell types needed to mimic disease and dissect pathological mechanisms, we have constructed, characterized, and utilized a multicellular integrated brain (miBrain) immuno-glial-neurovascular model by engineering a brain-inspired 3D hydrogel and identifying conditions to coculture these six brain cell types, all differentiated from patient induced pluripotent stem cells. miBrains recapitulate in vivo-like hallmarks inclusive of neuronal activity, functional connectivity, barrier function, myelin-producing oligodendrocyte engagement with neurons, multicellular interactions, and transcriptomic profiles. We implemented the model to study Alzheimer's Disease pathologies associated with APOE4 genetic risk. APOE4 miBrains differentially exhibit amyloid aggregation, tau phosphorylation, and astrocytic glial fibrillary acidic protein. Unlike the coemergent fate specification of glia and neurons in other organoid approaches, miBrains integrate independently differentiated cell types, a feature we harnessed to identify that APOE4 in astrocytes promotes neuronal tau pathogenesis and dysregulation through crosstalk with microglia.","[""Journal Article""]","[""Stanton AE"", ""Bubnys A"", ""Agbas E"", ""James B"", ""Park DS"", ""Jiang A"", ""Pinals RL"", ""Liu L"", ""Truong N"", ""Loon A"", ""Staab C"", ""Cerit O"", ""Wen HL"", ""Mankus D"", ""Bisher ME"", ""Lytton-Jean AKR"", ""Kellis M"", ""Blanchard JW"", ""Langer R"", ""Tsai LH""]",10.1073/pnas.2511596122,Stanton AE,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,42,Proc Natl Acad Sci U S A,eng,Tsai LH,"[""Humans"", ""Neuroglia"", ""Induced Pluripotent Stem Cells"", ""Neurons"", ""Coculture Techniques"", ""Brain"", ""Blood-Brain Barrier"", ""Alzheimer Disease"", ""Cell Differentiation"", ""Astrocytes"", ""Models, Biological"", ""Oligodendroglia""]",e2511596122,41105712,pmc-id: PMC12557797;,2025 Oct 21,2025,https://pubmed.ncbi.nlm.nih.gov/41105712/,Engineered 3D immuno-glial-neurovascular human miBrain model,122,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Heterotopia refers to the presence of normal cells or tissue located in anatomically unusual sites of the body. In the gastrointestinal tract, most heterotopic lesions do not cause any symptoms, but rarely, they can be mistaken for neoplasms during endoscopic examinations. A 45-year-old man presented with lower abdominal pain and blood in the stool. Macroscopically, a polypoid lesion was found and resected by endoscopic submucosal dissection. Histologically, ectopic gastric mucosa, salivary gland-like structures compatible with bronchial glands, and respiratory epithelium were found. This combination of a gastric and respiratory ectopia has so far been rarely documented in the literature.","[""Journal Article"", ""Case Reports"", ""English Abstract""]","[""Siegl N"", ""Langer R"", ""Ziachehabi A"", ""Noack P""]",10.1007/s00292-025-01473-3,Siegl N,"Pathologie (Heidelberg, Germany)",2731-7188,1,Pathologie (Heidelb),ger,Noack P,"[""Humans"", ""Male"", ""Choristoma"", ""Middle Aged"", ""Gastric Mucosa"", ""Rectal Diseases"", ""Diagnosis, Differential"", ""Respiratory Mucosa"", ""Salivary Glands"", ""Rectal Neoplasms"", ""Rectum""]",60-62,41065810,pmc-id: PMC12852206;,2026 Feb,2026,https://pubmed.ncbi.nlm.nih.gov/41065810/,[Combined gastric and respiratory heterotopia in the rectum suggesting malignancy],47,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Blood-brain barrier (BBB) dysfunction is an early feature of Alzheimer's disease (AD), yet the endothelial gene-regulatory programs involved remain incompletely understood. We integrate postmortem human single-nucleus transcriptomics with iPSC-based BBB models to define a conserved, inflammation-driven pathway that compromises barrier integrity. We identify an NF-κB-associated endothelial gene module endoM2 that is elevated in AD, inversely correlated with cognition, and enriched for inflammation and endothelial-to-mesenchymal transition signatures. Cytokine stimulation of iPSC-derived brain endothelial cells induces morphological remodeling, lipid accumulation, junctional disruption, and transcriptomic shifts that mirror endoM2. A targeted drug screen identifies the NF-κB inhibitor BAY11-7082 as protective against cytokine-induced changes. In our perfusable iPSC-derived BBB-Chip that recapitulates human BBB signatures, single-cell profiling reveals inflammatory endothelial state-specific programs reflecting those in AD brains and demonstrates that BAY11-7082 suppresses cytokine-triggered dysfunction and reverses inflammation-associated gene activation. Together, these findings position cerebrovascular inflammation as a therapeutic target to preserve BBB integrity in AD.","[""Journal Article"", ""Preprint""]","[""Pinals RL"", ""Islam MR"", ""King O"", ""Choi A"", ""Kang E"", ""Nakano M"", ""Tuyéras A"", ""Naomi MT"", ""Ngo A"", ""Jiang A"", ""Truong N"", ""Agbas E"", ""Lozano Cruz CF"", ""Staab C"", ""Ko T"", ""Bennett DA"", ""Stanton AE"", ""Langer R"", ""Tsai LH""]",10.1101/2025.09.26.678918,Pinals RL,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Tsai LH,[],,41040406,pmc-id: PMC12485894;,2025 Sep 27,2025,https://pubmed.ncbi.nlm.nih.gov/41040406/,Inflammatory reprogramming of human brain endothelial cells compromises blood-brain barrier integrity in Alzheimer's disease,,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Numerous pathology foundation models have been developed to extract clinically relevant information. There is currently limited literature independently evaluating these foundation models on external cohorts and clinically relevant tasks to uncover adjustments for future improvements. Here we benchmark 19 histopathology foundation models on 13 patient cohorts with 6,818 patients and 9,528 slides from lung, colorectal, gastric and breast cancers. The models were evaluated on weakly supervised tasks related to biomarkers, morphological properties and prognostic outcomes. We show that a vision-language foundation model, CONCH, yielded the highest overall performance when compared with vision-only foundation models, with Virchow2 as close second, although its superior performance was less pronounced in low-data scenarios and low-prevalence tasks. The experiments reveal that foundation models trained on distinct cohorts learn complementary features to predict the same label, and can be fused to outperform the current state of the art. An ensemble combining CONCH and Virchow2 predictions outperformed individual models in 55% of tasks, leveraging their complementary strengths in classification scenarios. Moreover, our findings suggest that data diversity outweighs data volume for foundation models.","[""Journal Article""]","[""Neidlinger P"", ""El Nahhas OSM"", ""Muti HS"", ""Lenz T"", ""Hoffmeister M"", ""Brenner H"", ""van Treeck M"", ""Langer R"", ""Dislich B"", ""Behrens HM"", ""Röcken C"", ""Foersch S"", ""Truhn D"", ""Marra A"", ""Saldanha OL"", ""Kather JN""]",10.1038/s41551-025-01516-3,Neidlinger P,Nature biomedical engineering,2157-846X,6,Nat Biomed Eng,eng,Kather JN,"[""Humans"", ""Benchmarking"", ""Neoplasms"", ""Computational Biology"", ""Algorithms"", ""Female"", ""Prognosis""]",1113-1123,41034516,pmc-id: PMC13279263;,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/41034516/,Benchmarking foundation models as feature extractors for weakly supervised computational pathology,10,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
,"[""Journal Article""]","[""Collins E"", ""Langer R"", ""Anderson DG""]",10.1038/s43588-025-00885-8,Collins E,Nature computational science,2662-8457,11,Nat Comput Sci,eng,Anderson DG,[],976-979,41034460,,2025 Nov,2025,https://pubmed.ncbi.nlm.nih.gov/41034460/,Self-driving labs for biotechnology,5,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Development and delivery of treatments for neurological diseases are limited by the tight and selective human blood-brain barrier (BBB). Although animal models have been important research and preclinical tools, the rodent BBB exhibits species differences and fails to capture the complexity of human genetics. Microphysiological systems incorporating human-derived cells hold great potential for modeling disease and therapeutic development, with advantages in screening throughput, real-time monitoring, and tunable genetic backgrounds when combined with induced pluripotent stem cell (iPSC) technology. Existing 3D BBB-on-chip systems have incorporated iPSC-derived endothelial cells but not the other major brain cell types from iPSCs, each of which contributes to brain physiology and disease. Here we developed a 3D Brain-Chip system incorporating endothelial cells, pericytes, astrocytes, neurons, microglia, and oligodendroglia from iPSCs. To enable this multicellular 3D co-culture in-chip, we designed a GelChip microfluidic platform using a 3D printing-based approach and dextran-based engineered hydrogel. Leveraging this platform, we co-cultured and characterized iPSC-derived brain-on-chips and modeled the brain microvasculature of APOE4 , the strongest known genetic risk factor for sporadic Alzheimer's disease. These 3D brain-on-chips provide a versatile system to assess BBB vascular morphology and function, investigate downstream neurological effects in disease, and screen therapeutics to optimize delivery to the brain. The blood-brain barrier (BBB) is both a contributing factor to neurological disease and a major obstacle to its treatment, yet human-relevant models remain limited. Most existing brain-on-chip systems incorporate only subsets of BBB cell types and cannot capture the full cellular complexity of the human neurovascular unit. Here, we establish a vascular-perfusable 3D Brain-Chip using human induced pluripotent stem cell-derived brain cells including endothelial cells, pericytes, astrocytes, neurons, microglia, and oligodendroglia. This system enables systematic analysis of human genetic risk factors, such as APOE4 in Alzheimer's disease, and provides a powerful platform to investigate BBB function and dysfunction and accelerate the development of more effective neurological therapies.","[""Journal Article"", ""Preprint""]","[""Stanton AE"", ""Pinals RL"", ""Choi A"", ""Truong N"", ""Kang E"", ""Jiang A"", ""Lozano Cruz CF"", ""Hawkins S"", ""Sarcar R"", ""Volkova A"", ""King O"", ""Agbas E"", ""Nakano M"", ""Chiu CC"", ""Bubnys A"", ""Wright S"", ""Staab C"", ""Bikdash R"", ""Forden E"", ""Langer R"", ""Tsai LH""]",10.1101/2025.09.18.676925,Stanton AE,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Tsai LH,[],,41000798,pmc-id: PMC12458943;,2025 Sep 25,2025,https://pubmed.ncbi.nlm.nih.gov/41000798/,Vascular-Perfusable Human 3D Brain-on-Chip,,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Prime editors make programmed genome modifications by writing new sequences into extensions of nicked DNA 3' ends1. These edited 3' new strands must displace competing 5' strands to install edits, yet a bias towards retaining the competing 5' strands hinders efficiency and can cause indel errors2. Here we discover that nicked end degradation, consistent with competing 5' strand destabilization, can be promoted by Cas9-nickase mutations that relax nick positioning. We exploit this mechanism to engineer efficient prime editors with strikingly low indel errors. Combining this error-suppressing strategy with the latest efficiency-boosting architecture, we design a next-generation prime editor (vPE). Compared with previous editors, vPE features comparable efficiency yet up to 60-fold lower indel errors, enabling edit:indel ratios as high as 543:1.","[""Journal Article"", ""Research Support, U.S. Gov't, Non-P.H.S."", ""Research Support, N.I.H., Extramural""]","[""Chauhan VP"", ""Sharp PA"", ""Langer R""]",10.1038/s41586-025-09537-3,Chauhan VP,Nature,0028-0836,8087,Nature,eng,Langer R,"[""Gene Editing"", ""INDEL Mutation"", ""CRISPR-Associated Protein 9"", ""CRISPR-Cas Systems"", ""Deoxyribonuclease I"", ""Humans"", ""Genome"", ""DNA"", ""Genomics""]",1254-1260,40963020,pmc-id: PMC12571883;,2025 Oct,2025,https://pubmed.ncbi.nlm.nih.gov/40963020/,Engineered prime editors with minimal genomic errors,646,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Tuberculosis (TB) is the leading cause of death from infectious disease worldwide, and Bacillus Calmette-Guérin (BCG) remains the only clinically approved vaccine. An enduring challenge in TB vaccine development is systematic antigen selection from a large repertoire of potential candidates. We performed an efficacy screen in mice of antigens that are targets of CD4 T cells in humans. We found striking heterogeneity in protective efficacy, and most of the top protective antigens are not currently in clinical development. We observed immunologic cross-reactivity among phylogenetically clustered antigens, reflecting common CD4 epitopes. We developed a trivalent mRNA vaccine consisting of PPE20 (Rv1387), EsxG (Rv0287), and PE18 (Rv1788), which augmented and exceeded BCG protection in multiple mouse models. Finally, we observed cellular immune responses to these antigens in 84% of humans exposed to M. tuberculosis. These data advance our understanding of TB vaccine immunology and define a vaccine concept for clinical development.","[""Journal Article""]","[""Vidal SJ"", ""Lasrado N"", ""Tostanoski LH"", ""Chaudhari J"", ""Mbiwan ER"", ""Neka GD"", ""Strutton EA"", ""Espinosa Perez AA"", ""Sellers D"", ""Barrett J"", ""Lifton M"", ""Wakabayashi S"", ""Eshaghi B"", ""Borducchi EN"", ""Aid M"", ""Li W"", ""Scriba TJ"", ""Jaklenec A"", ""Langer R"", ""Barouch DH""]",10.1016/j.cell.2025.08.027,Vidal SJ,Cell,0092-8674,24,Cell,eng,Barouch DH,"[""Tuberculosis Vaccines"", ""Animals"", ""Humans"", ""Antigens, Bacterial"", ""Mice"", ""Mycobacterium tuberculosis"", ""Tuberculosis"", ""CD4-Positive T-Lymphocytes"", ""Female"", ""Mice, Inbred C57BL"", ""Cross Reactions"", ""BCG Vaccine"", ""Vaccine Development""]",6791-6803.e13,40957415,pmc-id: PMC12445596;manuscript-id: NIHMS2110632;,2025 Nov 26,2025,https://pubmed.ncbi.nlm.nih.gov/40957415/,Mining the CD4 antigen repertoire for next-generation tuberculosis vaccines,188,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
,"[""Published Erratum""]","[""Potineni A"", ""Lynn DM"", ""Langer R"", ""Amiji MM""]",10.1016/j.jconrel.2025.114170,Potineni A,Journal of controlled release : official journal of the Controlled Release Society,0168-3659,,J Control Release,eng,Amiji MM,[],114170,40886460,,2025 Nov 10,2025,https://pubmed.ncbi.nlm.nih.gov/40886460/,"Corrigendum to ""Poly(ethylene oxide)-modified poly(β-amino Ester) nanoparticles as a pH-sensitive biodegradable system for paclitaxel delivery"" [Journal of Controlled Release, 86 (2003) 223-234]",387,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Sulfur-containing polymers offer unique opportunities for advanced materials due to their inherent degradability, high refractive indices, and potential for chemical recyclability. Yet, synthetic strategies for their precise construction remain underdeveloped and monomer selection rules to achieve this are elusive. Herein, we achieve the first comprehensive evaluation of sulfurated ring-opening copolymerisations (ROCOP) performed under unified conditions using a single heterobimetallic Cr(III)/Rb(I) catalyst platform. Although such catalysts are largely unexplored in sulfur-based ROCOP, our study demonstrates their remarkable synergistic performance in controlling both activity and selectivity across diverse heteroallene/epoxide systems. We identify carbonyl sulfide (COS) as the most promising monomer, enabling perfectly alternating copolymers under mild conditions on kinetic grounds. As a close second, PhNCS emerges as a viable, easier to handle, alternative that offers selective access to sulfur-containing copolymers. In contrast, thioanhydrides and CS2 show progressively lower selectivity, with increasing O/S scrambling and small molecule byproduct formation. This study provides the first predictive framework linking sulfur monomer identity to selectivity and reactivity under unified conditions, enabling rational design of degradable sulfur-rich polymers.","[""Journal Article""]","[""Manjunatha BR"", ""Sengoden M"", ""Stühler MR"", ""Langer R"", ""Darensbourg DJ"", ""Plajer AJ""]",10.1002/anie.202508985,Manjunatha BR,Angewandte Chemie (International ed. in English),1433-7851,42,Angew Chem Int Ed Engl,eng,Plajer AJ,[],e202508985,40856212,pmc-id: PMC12518690;,2025 Oct 13,2025,https://pubmed.ncbi.nlm.nih.gov/40856212/,Monomer-Dependent Selectivity in Sulfur-Containing Ring-Opening Copolymerisation: Bimetallic Catalysis for Predictive Design of Degradable Polymers,64,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"This study aimed to evaluate the prognostic impact of adjuvant and neoadjuvant chemotherapy (ACT, NACT) in high-grade triple-negative metaplastic breast cancer (TNMBC) and to compare survival outcomes with those of triple-negative breast cancer of no special type (TNBC NST). A total of 73 patients with high-grade TNMBC and 369 patients with TNBC NST were included in the study. In the non-NACT and ACT subgroups, TNMBC patients exhibited significantly worse overall survival (OS), distant disease-free survival (DDFS), breast cancer-specific survival (BCSS), and disease-free survival (DFS) than TNBC NST patients (non-NACT: p < 0.001 for all endpoints; ACT: OS, p < 0.001; DDFS, p < 0.001; BCSS, p = 0.004; DFS, p < 0.001). In the NACT subgroup, TNMBC and TNBC NST patients had similar survival outcomes. Within the TNMBC cohort, patients treated with NACT without achieving a pathological complete response (pCR) demonstrated improved OS (p = 0.045) and a trend toward improved BCSS (p = 0.056) compared to TNMBC patients who did not receive CT. No significant survival difference was observed between TNMBC patients treated with ACT and those without CT, nor between NACT-treated TNMBC patients without a pCR and those treated with ACT. We conclude that survival outcomes of TNMBC vs. TNBC NST patients may be influenced by systemic treatment. NACT-treated TNMBC patients without a pCR demonstrated superior OS compared to TNMBC patients receiving no CT, while no survival difference was observed among TNMBC patients based on treatment sequencing (ACT vs. NACT).","[""Journal Article""]","[""Grosse C"", ""Grosse A"", ""Schwarz HK"", ""Frauchiger-Heuer H"", ""Rordorf T"", ""Ring A"", ""Langer R"", ""Varga Z""]",10.1007/s00428-025-04224-0,Grosse C,Virchows Archiv : an international journal of pathology,0945-6317,,Virchows Arch,eng,Varga Z,[],,40841714,,2025 Aug 22,2025,https://pubmed.ncbi.nlm.nih.gov/40841714/,Survival outcomes after systemic treatment of high-grade triple-negative metaplastic breast cancer versus triple-negative breast cancer of no special type,,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Rotator cuff injuries are a common cause of shoulder pain, primarily affecting individuals older than 40 years, with the incidence increasing progressively with age. Advancements in surgical techniques have led to the development of arthroscopic techniques. This evolution has transitioned through various arthroscopic suture anchor rotator cuff repair configurations, including single-row, double-row, and transosseous-equivalent constructs. Although these innovations have replicated the biomechanics of the original transosseous technique conducted using an open approach, they often require multiple anchors, significantly increasing surgical costs. Additionally, anchor-related complications persist. To enhance the feasibility and affordability of implant-free transosseous repair, a reusable instrumentation system, was developed by Drillbone (Brno, Czechia). This innovative device facilitates robust and reproducible transosseous rotator cuff repairs while substantially reducing procedural costs. We present a surgical technique using bone tunneling device, showing its application in arthroscopic rotator cuff repair.","[""Journal Article""]","[""Hudeček F"", ""Apostolopoulos V"", ""Kužma J"", ""Liskay J"", ""Langer R"", ""Tomáš T""]",10.1016/j.eats.2025.103566,Hudeček F,Arthroscopy techniques,2212-6287,7,Arthrosc Tech,eng,Tomáš T,[],103566,40822231,pmc-id: PMC12350226;,2025 Jul,2025,https://pubmed.ncbi.nlm.nih.gov/40822231/,Arthroscopic Transosseous Rotator Cuff Repair Using Bone Tunneling Device,14,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"ANCA-vasculitis (AAV) is a small-vessel vasculitis characterized by the presence of autoantibodies against proteinase-3 (PR3) or myeloperoxidase (MPO). The dynamics of the T-cell response within tissues is studied best in animal models. It was the aim to analyze the lesional T-cell dynamics in the experimental autoimmune vasculitis model. Female Wistar Kyoto-rats were immunized with human MPO emulsified in complete Freund's adjuvant. Control animals received complete Freund's adjuvant without MPO. Selected groups received anti-IL17A treatment. Lesional T-cells from kidneys were assessed by flow cytometry (FACS), realtime polymerase chain reaction (PCR) and EliSpot. All animals immunized with MPO developed signs of vasculitis. At week six, lung damage expressed as petechial bleeding score and renal damage quantified by albuminuria were highest. As analyzed by FACS, the fraction of renal Th17 cells peaked at week six in MPO rats equaling the proportion of Th1 cells. MPO-specific renal Th1 and Th17 cells were detectable by EliSpot at weeks four and six post-immunization in MPO-immunized rats being absent in control rats. Neutralization of IL-17A did not affect the development of humoral and cellular anti-MPO immunity. Likewise, pulmonary and renal vasculitis were not ameliorated. In summary, the dynamics of the lesional T-cell response in the EAV model shows a major participation of MPO-specific Th17 and Th1 cells in renal vasculitis. Simple cytokine neutralization was not efficacious in this disease model so that combined neutralization approaches should be studied further.","[""Journal Article""]","[""Zeng Y"", ""Boschmann E"", ""Kotte J"", ""Sun M"", ""Hess L"", ""Dolff S"", ""Hinkeldein T"", ""Hagedorn J"", ""Langer R"", ""van Paassen P"", ""Damoiseaux J"", ""Cohen Tervaert JW"", ""Witzke O"", ""Kribben A"", ""Wilde B""]",10.1016/j.jtauto.2025.100305,Zeng Y,Journal of translational autoimmunity,2589-9090,,J Transl Autoimmun,eng,Wilde B,[],100305,40821760,pmc-id: PMC12356024;,2025 Dec,2025,https://pubmed.ncbi.nlm.nih.gov/40821760/,T-cell immunity in the experimental autoimmune vasculitis rat model,11,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Gastrointestinal (GI) dysmotility and associated conditions affect over 20% of population, yet pharmacological, behavioural, and surgical interventions offer limited therapeutic efficacy. Targeted electrical stimulation addressing underlying neuromuscular pathology stands to transform our ability to treat dysmotility. Here, we developed a closed-loop GI neuroprosthesis which activates or relaxes GI tract musculature through electrochemical stimulation in response to sensed food stimuli. We additionally describe a tool supporting minimally invasive endoscopically guided implantation that can penetrate the mucosa, accurately localize the submucosa, and safely deploy this device to directly interface with the enteric nervous system. The neuroprosthesis enables generation of coordinated peristaltic waves, significantly increasing the motility rate in a swine model of oesophageal and stomach dysmotility (p < 0.05, student's t-test). Further, by directly modulating the myenteric plexus and thus mimicking meal ingestion, we induce peristalsis in a fasted state and achieve a metabolic response commensurate with a fed or satiated state. This neuroprosthesis and implantation platform expand opportunities in fundamental studies and treatments of metabolic and neuromuscular pathologies affecting the GI tract.","[""Journal Article""]","[""Srinivasan S"", ""Antonini MJ"", ""Alshareef A"", ""Sahasrabudhe A"", ""Jenkins J"", ""Ishida K"", ""Kuosmanen J"", ""Hayward A"", ""Min S"", ""Langer R"", ""Anikeeva P"", ""Traverso G""]",10.1038/s41467-025-62413-6,Srinivasan S,Nature communications,2041-1723,1,Nat Commun,eng,Traverso G,"[""Animals"", ""Swine"", ""Gastrointestinal Motility"", ""Peristalsis"", ""Electric Stimulation"", ""Gastrointestinal Tract"", ""Neural Prostheses"", ""Enteric Nervous System"", ""Myenteric Plexus"", ""Electric Stimulation Therapy"", ""Esophagus"", ""Female""]",7374,40783382,pmc-id: PMC12335536;,2025 Aug 10,2025,https://pubmed.ncbi.nlm.nih.gov/40783382/,Gastrointestinal neuroprosthesis for motility and metabolic neuromodulation,16,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Breast lymphomas, though rare, present a unique spectrum of clinical and pathological characteristics. This multicenter retrospective study evaluates 92 cases from four international institutions over a ten-year period to provide a comprehensive analysis of primary breast lymphomas (PBLs), secondary breast lymphomas (SBLs), and related subtypes, including breast implant-associated lymphomas (BIA-ALCL) and intra-mammary lymph node lymphomas. Primary breast lymphomas accounted for 46.7% of cases, with a predominance of diffuse large B-cell lymphoma (DLBCL). Secondary breast involvement, observed in 43.5% of cases, displayed a more diverse histological distribution, with follicular lymphoma being the most common subtype. Breast implant-associated lymphomas (BIA-ALCL) constituted 6.5% of cases, exclusively involving anaplastic large cell T-cell lymphoma, ALK-negative. The study highlights significant differences in patient demographics, clinical presentation, and survival outcomes. PBLs primarily affected older patients (mean age: 68.4 years) and were associated with longer lymphoma-specific survival compared to SBLs (76.12 vs. 59.45 months; p = 0.001). Notably, survival differences were evident within histological subtypes, emphasizing the impact of disease origin on prognosis. BIA-ALCL cases were distinct in clinical features and histology, with a younger mean age (47.5 years) and frequent association with unilateral effusion. This analysis underscores the necessity for precise diagnostic and therapeutic strategies tailored to the unique biology of breast lymphomas. Future research should aim to elucidate molecular mechanisms and optimize management protocols to improve patient outcomes.","[""Journal Article"", ""Multicenter Study""]","[""Maccio U"", ""Rets A"", ""Grosse C"", ""Ferguson NA"", ""Langer R"", ""Bühler MM"", ""Gallo A"", ""Witzel I"", ""Beham-Schmid C"", ""Wieler J"", ""Orsaria M"", ""Varga Z""]",10.1038/s41598-025-13214-w,Maccio U,Scientific reports,2045-2322,1,Sci Rep,eng,Varga Z,"[""Humans"", ""Female"", ""Aged"", ""Middle Aged"", ""Breast Neoplasms"", ""Retrospective Studies"", ""Adult"", ""Aged, 80 and over"", ""Lymphoma"", ""Lymphoma, Large-Cell, Anaplastic"", ""Breast Implants"", ""Prognosis""]",29032,40781261,pmc-id: PMC12334564;,2025 Aug 8,2025,https://pubmed.ncbi.nlm.nih.gov/40781261/,Clinical and pathological features of lymphomas in the breast: a comprehensive multicentric study,15,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Rapidly administered emergency drug therapy represents life-saving treatment for a range of acute conditions including hypoglycaemia, anaphylaxis and cardiac arrest. Devices that automate emergency delivery, such as pumps and automated injectors, are limited by the low stability of liquid formulations. In contrast, dry particulate formulations of these drugs are stable but are incompatible with drug pumps and require reconstitution before administration. Here we develop a miniaturized (<3 cm3), lightweight (<2 g), minimally invasive, fully wireless emergency rescue device for the storage and active burst-release of indefinitely stable particulate forms of peptide and hormone drugs into subcutaneous sites for direct reconstitution in interstitial biofluids and rapid (<5 min) therapeutic effect. Importantly, the device delivers drug across fibrotic tissue, which commonly accumulates following in vivo implantation, thereby accelerating systemic delivery. Fully wireless delivery of dry particulate glucagon in vivo is demonstrated, providing emergency hypoglycaemic rescue in diabetic mice. In addition, triggered delivery of epinephrine is demonstrated in vivo. This work provides a platform for the long-term in vivo closed-loop delivery of emergency rescue drugs.","[""Journal Article""]","[""Krishnan SR"", ""O'Keeffe L"", ""Rudra A"", ""Gumustop D"", ""Khatib N"", ""Liu C"", ""Yang J"", ""Wang A"", ""Bochenek MA"", ""Lu YC"", ""Bose S"", ""Reed K"", ""Langer R"", ""Anderson DG""]",10.1038/s41551-025-01436-2,Krishnan SR,Nature biomedical engineering,2157-846X,1,Nat Biomed Eng,eng,Anderson DG,"[""Animals"", ""Mice"", ""Drug Delivery Systems"", ""Wireless Technology"", ""Epinephrine"", ""Glucagon"", ""Male"", ""Mice, Inbred C57BL"", ""Diabetes Mellitus, Experimental""]",144-160,40634646,pmc-id: PMC13120775;manuscript-id: NIHMS2156373;,2026 Jan,2026,https://pubmed.ncbi.nlm.nih.gov/40634646/,Emergency delivery of particulate drugs by active ejection using in vivo wireless devices,10,MentO54PEbYHJaHuv,dy1RmDkr6StK7xc1X
"Nucleoside-modified messenger RNA lipid nanoparticle (mRNA-LNP) vaccines have had a tremendous impact on vaccine development against infectious pathogens, particularly since the onset of the COVID-19 pandemic. The platform is an effective stimulator of humoral and cellular immune responses due to unique features of the mRNA and LNP components. We sought to optimize the performance of the mRNA-LNP platform against a specific viral target, developing a vaccine against Hepatitis C virus (HCV) that would improve HCV-like particle secretion and enhance the humoral immune response. We designed an mRNA-LNP vaccine targeting HCV and improved its efficacy by including the nonstructural HCV viroporin p7, and measured cellular and humoral immune responses in immunized mice. Both constructs induced antigen-specific functional CD4+ and CD8+ T cell responses, as well as T follicular helper cell responses associated with humoral immunity, consistent with other applications of the mRNA-LNP platform. Mice immunized with the optimized construct showed superior binding and neutralizing antibody responses compared to the non-optimized one. Notably, the optimized construct elicited stronger humoral responses against heterologous viral strains. Our findings underscore the potential of mRNA-LNP vaccines for HCV, yet translating these findings into humans requires further investigation. These results demonstrate the value of optimizing the mRNA-LNP platform through inclusion of elements with utility beyond presenting epitopes of the pathogen being targeted. This study pushes HCV vaccine development forward and extends the utility of the mRNA-LNP platform against infectious diseases.","[""Journal Article""]","[""Reagan EK"", ""Wright DA"", ""Clark KE"", ""Mercado-Lopez X"", ""Atochina-Vasserman EN"", ""Ni H"", ""Mui BL"", ""Hu F"", ""Bailey JR"", ""Bar KJ"", ""Weissman D""]",10.1016/j.vaccine.2026.128938,Reagan EK,Vaccine,0264-410X,,Vaccine,eng,Weissman D,[],128938,42486050,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42486050/,mRNA-LNP hepatitis C vaccine encoding p7 elicits improved humoral immunogenicity,88,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Oral squamous cell carcinoma (OSCC) represents 90% of all head and neck cancers. Despite decades of research, the 5-year survival rate is 50%. Strikingly, the overall incidence rate is projected to increase by 30% in the next 10 years, which may result in a sharp increase in mortality. Two fundamental aspects of OSCC are that it progresses via the inactivation and mutation of tumor suppressor genes (TSGs) and has a ""cold"" tumor microenvironment (TME). A major barrier in the treatment of OSCC is the lack of novel therapies clinicians have at their disposal that are designed to disrupt tumor progression by reshaping the cold tumors into inflammatory ""hot"" tumors. To overcome these obstacles, we employed a lipid nanoparticle (LNP) that co-encapsulates p53 mRNA and the small molecule ciclopirox (CPX). We demonstrate that both drugs have innate chemotherapeutic properties by facilitating caspase activation. Moreover, these therapies can create a less immunosuppressive TME in part by repolarizing tumor-associated macrophages (TAMs) to M1-like phenotypes. When formulated together, our platform provides an all-in-one approach for OSCC, effective in both p53-therapy-susceptible and p53-therapy-resistant models. Additionally, this work offers a template for a delivery platform capable of tackling multiple mechanisms of OSCC progression and survival.","[""Journal Article""]","[""Padilla MS"", ""Li JJ"", ""Zhang Q"", ""Patwari K"", ""Shi S"", ""Yamagata HM"", ""Joseph RA"", ""Hymms BN"", ""Teerdhala SV"", ""Fitzgerald E"", ""Chalom OZ"", ""Gupta K"", ""Alameh MG"", ""Weissman D"", ""Le AD"", ""Mitchell MJ""]",10.1002/adma.73721,Padilla MS,"Advanced materials (Deerfield Beach, Fla.)",0935-9648,,Adv Mater,eng,Mitchell MJ,[],e73721,42446053,,2026 Jul 14,2026,https://pubmed.ncbi.nlm.nih.gov/42446053/,Lipid Nanoparticle Co-Delivery of mRNA and a Small Molecule Drug for Oral Cancer Chemoimmunotherapy,,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"mRNA-based cancer vaccines offer a modular and safe platform to elicit antitumor immunity, yet their efficacy is often limited by inefficient mRNA delivery and inadequate dendritic cell (DC) activation, both of which are essential for initiating robust cytotoxic T cell responses. Inadequate innate immune activation coupled with poor antigen presentation further diminishes their effectiveness, particularly in immunologically ""cold"" tumors. While stimulator of interferon genes (STING) agonists can enhance DC maturation and cross-presentation, their therapeutic utility is constrained by poor intracellular delivery and limited colocalization with tumor antigens. In this study, we developed a lipid nanoparticle (LNP) platform via high-throughput screening of ionizable lipids for potent mRNA delivery to DCs both in vitro and in vivo. To amplify immune activation, we coencapsulated the STING agonists c-di-AMP (AMP) and manganese (Mn2+) together with tumor antigen-encoding mRNA into the lead LNP formulation. This codelivery strategy synergistically activated type I interferon signaling, upregulated costimulatory molecules, enhanced antigen presentation, and elicited potent tumor-specific T cell responses and superior antitumor efficacy. Our results demonstrate that integrating innate immune stimulation with mRNA-LNP delivery provides a promising strategy to overcome current limitations in mRNA vaccine efficacy and to improve cancer immunotherapy outcomes.","[""Journal Article""]","[""Zeng Y"", ""Xu J"", ""Wang J"", ""Xue L"", ""Liu J"", ""Geisler HC"", ""Ma X"", ""Melamed JR"", ""Shi Q"", ""Padilla MS"", ""Luo Z"", ""Zhu J"", ""Thatte AS"", ""Figueroa-Espada CG"", ""Ang MJY"", ""Murray AM"", ""Yamagata HM"", ""Kim D"", ""Metzloff AE"", ""Weissman D"", ""Mitchell MJ""]",10.1073/pnas.2525718123,Zeng Y,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,28,Proc Natl Acad Sci U S A,eng,Mitchell MJ,"[""Cancer Vaccines"", ""Animals"", ""Membrane Proteins"", ""Mice"", ""Dendritic Cells"", ""Nanoparticles"", ""RNA, Messenger"", ""STING Protein"", ""Lipids"", ""cGAS-STING Signaling Pathway"", ""Nanovaccines"", ""Female"", ""Mice, Inbred C57BL"", ""Humans"", ""Antigens, Neoplasm"", ""Cell Line, Tumor"", ""Antigen Presentation"", ""Interferon Type I"", ""Liposomes""]",e2525718123,42418483,pmc-id: PMC13367780;embargo-date: 2027/01/08;,2026 Jul 14,2026,https://pubmed.ncbi.nlm.nih.gov/42418483/,mRNA lipid nanoparticle cancer vaccine platform delivering multiple STING activators for enhanced antitumor activity,123,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Efficient priming of B cell precursors is a rate-limiting step in the induction of V2 apex broadly neutralizing antibodies (bNAbs)1,2. Here, we describe a novel germline-targeted HIV-1 Env (CAP256.OPT4) that increases the efficiency of V2 apex bNAb precursor priming by 30-400 fold compared with wild-type HIV-1 Envs and induces - in >90% of macaques - neutralization breadth that includes N130-containing viruses. Using three different delivery platforms - persistently replicating simian human immunodeficiency viruses (SHIVs), protein nanoparticles, and mRNA - we show bNAb priming as early as 4 weeks post-infection or immunization, and neutralization breadth in plasma by 12 weeks. In 14 SHIV-infected macaques, neutralization breadth reached as high as 90% on a 21-virus panel with potency as great as 1:20,000 (50% inhibitory dilution, ID50). Monoclonal bNAbs isolated from these animals were similarly broad and potent, with cryo-EM structures representing three distinct lineages revealing canonical needle-like HCDR3 binding. Env-Ab coevolution and structural analyses identified five key residues and loop features under positive selection and temporally associated with neutralization breadth. Importantly, prime-boost immunogens designed to capture these features induced broad and potent neutralization of globally diverse viruses including those containing N130 glycan. Further, rhesus bNAbs were not restricted to IGHD3-15*01 heavy chain alleles. These results expand the utility of the rhesus model for HIV-1 vaccine design and provide a molecular blueprint for inducing V2 apex bNAbs in rhesus and humans.","[""Journal Article""]","[""Marchitto L"", ""Wagh K"", ""Roark RS"", ""Coleon S"", ""Li H"", ""Skelly AN"", ""Hogarty MP"", ""Habib R"", ""Ding W"", ""Ayyanathan K"", ""Liu W"", ""Sheng Z"", ""Guo Y"", ""Bal J"", ""Smith LM"", ""Sutherland LL"", ""Park Y"", ""Connell AJ"", ""Bibollet-Ruche F"", ""Lewis E"", ""Plante SJ"", ""Akeley MJ"", ""Lora J"", ""Zhao C"", ""Carey JW"", ""Martella CL"", ""Li Y"", ""Campion MS"", ""Lituchy MG"", ""Osbaldeston RA"", ""Gordon CG"", ""Albertus A"", ""Su J"", ""Noguchi C"", ""Tam YK"", ""Barbosa C"", ""Liang B"", ""Amereh K"", ""Li X"", ""Walsh AA"", ""Irvine DJ"", ""Andrabi R"", ""Edwards RJ"", ""Kreider EF"", ""Weissman D"", ""Shapiro L"", ""Kwong PD"", ""Korber BT"", ""Haynes BF"", ""Saunders KO"", ""Hahn BH"", ""Shaw GM""]",10.1038/s41586-026-10838-4,Marchitto L,Nature,0028-0836,,Nature,eng,Shaw GM,[],,42380659,,2026 Jun 30,2026,https://pubmed.ncbi.nlm.nih.gov/42380659/,Enhanced B cell priming induces broadly neutralizing HIV-1 apex antibodies,,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Human norovirus is the leading cause of viral gastroenteritis, yet effective vaccines and therapeutics remain elusive. Using murine norovirus as a model, we found that mucosal immunoglobulin A (IgA) is both necessary and sufficient for protection against infection, whereas CD8+ T cells are dispensable. Robust intestinal IgA production requires at least 4 weeks of enteric infection, consistent with kinetics of human norovirus RNA clearance. Systemic vaccination elicits high titers of neutralizing serum IgG but fails to prevent enteric norovirus infection, phenocopying a recent human norovirus vaccine failure. In contrast, prophylactic delivery of dimeric anti-norovirus IgA via mRNA lipid nanoparticles confers sterilizing immunity. Together, these findings define a critical role for mucosal IgA in norovirus protection and identify IgA-based treatments as a therapeutic approach for human norovirus.","[""Journal Article""]","[""Ökten AB"", ""Filler RB"", ""Kung JL"", ""Fang Z"", ""McWilliams BC"", ""Muscat-Rivera JE"", ""Kegel MS"", ""Olivi Gomes IM"", ""Mankowski MC"", ""Skelly AN"", ""Melamed JR"", ""Nice TJ"", ""Lee S"", ""Baldridge MT"", ""Smith TJ"", ""Wobus CE"", ""Eisenbarth SC"", ""Williams A"", ""Serebryannyy LA"", ""Douek DC"", ""Weissman D"", ""Chen S"", ""Kreider EF"", ""Craft JE"", ""Wilen CB""]",10.1126/scitranslmed.aeb4878,Ökten AB,Science translational medicine,1946-6234,855,Sci Transl Med,eng,Wilen CB,"[""Animals"", ""Norovirus"", ""Caliciviridae Infections"", ""Immunoglobulin A"", ""Mice"", ""Humans"", ""CD8-Positive T-Lymphocytes"", ""Mice, Inbred C57BL"", ""Antibodies, Viral"", ""Immunoglobulin G""]",eaeb4878,42341085,,2026 Jun 24,2026,https://pubmed.ncbi.nlm.nih.gov/42341085/,IgA is necessary and sufficient to prevent norovirus infection in mice,18,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Antibody conjugation is essential for targeted lipid nanoparticle (LNP) delivery, but here we show that click-chemistry produces artifacts that confound accurate measurement of covalent antibody-LNP bonding. We demonstrate that hydrophobic interactions between the most common click alkyne linker, dibenzocyclooctyne (DBCO), and the inherently hydrophobic LNP surface drive extensive nonspecific antibody physisorption, even in the absence of LNP azide groups. This physisorption yields artificially high apparent conjugation efficiencies measured by chromatographic methods. In contrast, less hydrophobic liposomes exhibit azide-dependent conjugation, highlighting a consequence of nanoparticle surface chemistry. Plasma incubation rapidly displaces physisorbed antibodies from LNPs, confirming their weak, noncovalent association, whereas covalently bound antibodies remain attached and enable effective in vivo targeting. Substituting DBCO with the less hydrophobic bicyclononyne (BCN) also reduces nonspecific associations. Our findings reveal hydrophobicity as a hidden variable in antibody-LNP conjugation and establish new standards for quantitative and reproducible measurement of targeted LNPs.","[""Journal Article""]","[""Brysgel TV"", ""Hood ED"", ""Milosavljevic A"", ""Marzolini N"", ""Zamora ME"", ""Wu J"", ""Shuvaev VV"", ""Shuvaeva T"", ""Kegel M"", ""Muscat-Rivera J"", ""Weissman D"", ""Melamed JR"", ""Myerson JW"", ""Brenner JS"", ""Muzykantov VR"", ""Nong J""]",10.1021/acsnanoscienceau.5c00170,Brysgel TV,ACS nanoscience Au,2694-2496,3,ACS Nanosci Au,eng,Nong J,[],348-356,42327930,pmc-id: PMC13281171;,2026 Jun 17,2026,https://pubmed.ncbi.nlm.nih.gov/42327930/,Decoupling Physisorption from Chemisorption in Clickable Lipid Nanoparticles,6,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Persistent infection with high-risk human papillomavirus (HPV) drives the development of cervical and other anogenital cancers, with limited therapeutic options for early-stage disease and precancerous lesions. There is a critical unmet need for effective therapeutic vaccines capable of inducing durable immune responses to eliminate early tumor cells and prevent disease progression. In this study, we developed lipid nanoparticle (LNP)-formulated mRNA vaccines encoding HPV16 E6 and E7 oncoproteins and evaluated their efficacy in a murine model using a low tumor inoculum (5,000-10,000 TC-1 cells) to represent a low tumor burden, early-intervention setting. E7 mRNA/LNP induced stronger antigen-specific T cell responses than E6 when administered intramuscularly at a low dose (1 µg). In therapeutic settings, initiated 3 d after tumor implantation, either as a single 10 µg dose or a two-dose regimen (10 µg followed by 5 µg, 6 d apart), E7 vaccination elicited robust T cell responses, significant tumor regression, and undetectable HPV16 E6/E7 DNA, outperforming E6 across regimens. In the preventive setting, administration of two 5 µg doses of HPV16 E7 prevented tumor establishment following TC-1 cell inoculation. Importantly, E7 vaccination induced durable immune memory, as demonstrated by sustained tumor protection and undetectable HPV E6/E7 DNA upon rechallenge at 5 months. These findings highlight the potential of HPV16 E7 mRNA/LNP as a therapeutic vaccine targeting low tumor burden HPV-associated disease and support further clinical development. A multivalent mRNA vaccine targeting multiple high-risk HPV genotypes is currently under development.","[""Journal Article""]","[""Saithong S"", ""Prompetchara E"", ""Ketloy C"", ""Khawsang C"", ""Tharakhet K"", ""Kaewpang P"", ""Yostrerat N"", ""Wangsoontorn P"", ""Charsangbong K"", ""Lam K"", ""Heyes J"", ""Weissman D"", ""Ruxrungtham K""]",10.1080/21645515.2026.2686510,Saithong S,Human vaccines & immunotherapeutics,2164-5515,1,Hum Vaccin Immunother,eng,Ruxrungtham K,"[""Animals"", ""Oncogene Proteins, Viral"", ""Papillomavirus E7 Proteins"", ""Repressor Proteins"", ""Female"", ""Papillomavirus Vaccines"", ""Disease Models, Animal"", ""Papillomavirus Infections"", ""Mice"", ""Vaccines, Synthetic"", ""Nanoparticles"", ""RNA, Messenger"", ""T-Lymphocytes"", ""Nanovaccines"", ""mRNA Vaccines"", ""Mice, Inbred C57BL"", ""Humans"", ""Cancer Vaccines"", ""Liposomes""]",2686510,42301768,pmc-id: PMC13274139;,2026 Dec,2026,https://pubmed.ncbi.nlm.nih.gov/42301768/,Preventive and therapeutic efficacy of mRNA/LNP vaccines encoding HPV16 E6 and E7 in an early-intervention HPV tumor mouse models,22,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Solid tumors remain difficult to treat via conventional and novel therapeutic strategies. Immunotherapies such as chimeric antigen receptor T (CAR-T) cell therapy have been remarkably effective in treating hematological cancers, but their efficacy is limited in solid tumors. Recently, CAR macrophages (CAR-Ms) have emerged as a promising solid tumor immunotherapy, primarily for their intrinsic tumor infiltration and effector functions. However, CAR-Ms are engineered using viral transduction, which is associated with aberrant immunogenicity and toxicity. To overcome these challenges, we developed a bioinspired oxidized lipid nanoparticle (LNP) platform for mRNA-based engineering of human CAR-Ms. A library of 24 ionizable lipids was synthesized, formulated into LNPs, and screened for delivery to human macrophages. The top LNP was subsequently optimized using an orthogonal design of experiments and the physicochemical properties, such as size and mRNA encapsulation, were tuned via optimization of microfluidic mixing parameters, yielding an LNP formulation that significantly outperformed a gold standard C12-200 LNP. Utilizing small molecule and antibody inhibitors, we demonstrate that uptake of optimized LNPs into macrophages is driven by apolipoprotein E independent macropinocytosis, which is further supported by potent extrahepatic spleen tropism upon intravenous administration to mice. Lastly, we demonstrate the translatability of this LNP platform and utilize it to engineer functional primary human HER2-CAR-Ms ex vivo with potent antigen-specific tumor cell killing, validated in an ex vivo co-culture with ovarian cancer cells. This bioinspired oxidized LNP platform demonstrates potential for engineering a range of human CAR-M immunotherapies to treat various types of solid tumors.","[""Journal Article""]","[""Mukalel AJ"", ""Tylek T"", ""Geisler HC"", ""O'Brien E"", ""Frazee C"", ""Li J"", ""Thatte AS"", ""Safford HC"", ""Figueroa-Espada CG"", ""Alameh MG"", ""Hamilton AG"", ""Mai D"", ""Sheppard NC"", ""June CH"", ""Weissman D"", ""Spiller KL"", ""Mitchell MJ""]",10.1002/btm2.70138,Mukalel AJ,Bioengineering & translational medicine,2380-6761,3,Bioeng Transl Med,eng,Mitchell MJ,[],e70138,42272981,pmc-id: PMC13247429;,2026 May,2026,https://pubmed.ncbi.nlm.nih.gov/42272981/,Bioinspired oxidized mRNA lipid nanoparticles for ex vivo engineering of chimeric antigen receptor macrophages targeting solid tumors,11,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Immune tolerance in allergic diseases is associated with attenuation of TH2 responses by shifting of antigen-specific immunity toward TH1 and regulatory T-cell pathways, but current strategies incompletely induce durable regulatory immunity. We determined whether combining an allergen-encoded messenger RNA (mRNA) lipid nanoparticle (LNP) vaccine with inhibition of the mechanistic target of rapamycin (mTOR) enhances regulatory T-cell responses. Mice were immunized with an allergen-encoded mRNA-LNP vaccine alone or in combination with an mTOR inhibitor, followed by induction of a preclinical model of allergic asthma. Antigen-specific T-cell responses, eosinophil activation, airway hyperresponsiveness, mucus production, and markers of cytotoxicity were assessed. Immunization with allergen-encoded mRNA-LNP elicited TH1-associated and cytotoxic CD8+ T responses that counterbalanced TH2 immunity. Coadministration with an mTOR inhibitor shifted this profile by promoting generation of functional regulatory T cells and attenuating IFN-γ production and CD8+ T-cell responses. This combinatorial strategy preserved the antiallergic effects of mRNA-LNP immunization, reduced eosinophil activation markers, and limited vaccine-associated cytotoxicity. The ability of an mTOR inhibitor to profoundly modify mRNA-LNP therapy by inducing regulatory T cells presents a potential strategy to enhance regulatory immunity in the treatment of allergy and other inflammatory diseases.","[""Journal Article""]","[""Rochman Y"", ""Melamed JR"", ""Klingler AM"", ""Kotliar M"", ""Rochman M"", ""Caldwell JM"", ""Felton JM"", ""Osswald GA"", ""Muscat-Rivera J"", ""Kegel M"", ""Barski A"", ""Lewkowich IP"", ""Weissman D"", ""Rothenberg ME""]",10.1016/j.jaci.2026.05.023,Rochman Y,The Journal of allergy and clinical immunology,0091-6749,,J Allergy Clin Immunol,eng,Rothenberg ME,[],,42263787,,2026 Jun 9,2026,https://pubmed.ncbi.nlm.nih.gov/42263787/,Antigen-specific messenger RNA lipid nanoparticle therapy with mTOR inhibition promotes regulatory T cells and limits allergy,,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"The unyielding antigenic drift of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as the threat of future zoonotic sarbecovirus spillovers, has prompted the search for broadly neutralizing antibodies (bNAbs) to inform rational therapeutic and vaccine design. Here, we isolated and characterized 20 receptor binding domain (RBD)-directed bNAb lineages from a serially sampled SARS-CoV-2 patient who was infected and vaccinated during the early months of the pandemic. Thirteen of these targeted the highly conserved, cryptic class 1/4 or class 4 RBD epitopes and had long (18 to 26 amino acid) heavy chain complementarity determining region 3 loops that utilized the IGHD3-22 gene segment. Five bNAbs potently neutralized all 18 viruses in a panel containing SARS-CoV-2 variants up to the recently emerged XBB.1.5 and JN.1 strains as well as diverse sarbecoviruses from other clades. Structural analyses of the Ab401 and Ab568 bNAbs complexed with RBD and Spike trimer, respectively, revealed recognition features in common with other class 1/4 bNAbs. Prophylactic administration of Ab401 as a recombinant protein afforded robust protection against infectious challenge with either SARS-CoV-2_WA1 or a related bat sarbecovirus with zoonotic potential. A similar level of protection was achieved when the heavy and light chains of Ab401 were delivered as lipid nanoparticle-encapsulated mRNAs. These data expand the arsenal of SARS-CoV-2 bNAbs for clinical development and identify mRNA-based antibody delivery as a promising platform for both pandemic preparedness and protection of immunocompromised patients against emerging sarbecovirus variants.","[""Journal Article""]","[""Skelly AN"", ""Fan C"", ""Keeffe JR"", ""Ökten AB"", ""Gavor E"", ""Newby ML"", ""Allen JD"", ""Kreider EF"", ""Ding W"", ""Osbaldeston RA"", ""Park Y"", ""Connell AJ"", ""Lituchy MG"", ""Bibollet-Ruche F"", ""Radford KM"", ""P West A Jr"", ""Peña-Hernández MA"", ""Cruickshank K"", ""Liu W"", ""Li Y"", ""Albertus A"", ""McWilliams B"", ""Russell RM"", ""Konrath KM"", ""Torres JL"", ""Yuan M"", ""Gao H"", ""Montefiori DC"", ""Saag MS"", ""Goepfert PA"", ""Kulp DW"", ""Ward AB"", ""Wilson IA"", ""Shaw GM"", ""Andrabi R"", ""Crispin M"", ""Weissman D"", ""Wilen CB"", ""Bjorkman PJ"", ""Hahn BH""]",10.1073/pnas.2536870123,Skelly AN,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,24,Proc Natl Acad Sci U S A,eng,Hahn BH,"[""Animals"", ""SARS-CoV-2"", ""COVID-19"", ""Mice"", ""Antibodies, Viral"", ""Antibodies, Neutralizing"", ""Humans"", ""Epitopes"", ""Spike Glycoprotein, Coronavirus"", ""RNA, Messenger"", ""Disease Models, Animal""]",e2536870123,42258728,pmc-id: PMC13268366;manuscript-id: NIHMS2182547;,2026 Jun 16,2026,https://pubmed.ncbi.nlm.nih.gov/42258728/,mRNA delivery of a class 1/4 SARS-CoV-2 neutralizing antibody protects against diverse sarbecoviruses in a lethal mouse challenge model,123,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"mRNA-based gene editing therapeutics offer the potential to permanently cure diseases but are hindered by suboptimal delivery platforms. Here, we devise a robust combinatorial chemistry for the plug-and-play assembly of structurally diverse biodegradable ionizable lipids from amines/thiols and dialkyl maleates. After screening 500 ionizable lipids, we obtained structure-activity relationships essential for effective in vitro mRNA delivery with the help of machine learning. Furthermore, we identified a lead ionizable lipid candidate that produced potent lipid nanoparticles for the delivery of various gene editing tools in wild-type and genetically modified mice compared to literature and industry benchmark lipid nanoparticles. Mechanistically, our lipid nanoparticles show favorable physicochemical properties, which could synergistically contribute to the superior delivery performance. This study highlights the utility of this synthetic method as well as the generality of this platform for potent in vivo gene editing.","[""Journal Article""]","[""Han X"", ""Xu Y"", ""Ricciardi AS"", ""Xu J"", ""Xiang Y"", ""Palanki R"", ""Chowdhary V"", ""Xue L"", ""Gong N"", ""Alameh MG"", ""Peranteau WH"", ""Wilson JM"", ""Reker D"", ""Weissman D"", ""Mitchell MJ""]",10.1073/pnas.2528144123,Han X,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,22,Proc Natl Acad Sci U S A,eng,Mitchell MJ,"[""Animals"", ""Lipids"", ""RNA, Messenger"", ""Gene Editing"", ""Mice"", ""Nanoparticles"", ""Gene Transfer Techniques"", ""Humans"", ""Structure-Activity Relationship"", ""Liposomes""]",e2528144123,42190011,pmc-id: PMC13229237;embargo-date: 2026/11/26;,2026 Jun 2,2026,https://pubmed.ncbi.nlm.nih.gov/42190011/,Plug-and-play assembly of biodegradable ionizable lipids for potent mRNA delivery and gene editing in vivo,123,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Selective in vivo reprogramming of cytotoxic effector CD8 T (Teff) cells holds tremendous promise as a therapeutic tool but has not yet been accomplished. Here, we demonstrate that fractalkine-conjugated mRNA lipid nanoparticles (mRNA-LNPs) can specifically target and deliver mRNA to CX3CR1+ Teff cells in vitro and in vivo. In mice, fractalkine-conjugated mRNA-LNPs targeted up to 95% of blood and splenic Teff cells. In addition, delivery of IL-2-encoding mRNA and human CD62L-encoding mRNA to mouse Teff cells enabled robust exogenous IL-2 secretion and CD62L expression. In rhesus macaques, fractalkine-conjugated mRNA-LNPs targeted up to ~100% of peripheral blood Teff cells, and delivery of human CD62L-encoding mRNA enabled cell-surface human CD62L expression on peripheral blood Teff cells and detection of human CD62L+ Teff cells in lymphoid tissue. Collectively, these data demonstrate the potential of natural receptor ligand-based targeting of mRNA-LNPs for rapid, efficient, and transient in vivo modification of Teff cells.","[""Journal Article""]","[""Corrigan AR"", ""Ngiow SF"", ""Statzu M"", ""Albertus A"", ""Pampena MB"", ""Nordin JML"", ""Carro SD"", ""Harper J"", ""Stammen RL"", ""Wood J"", ""Ni H"", ""Su J"", ""Hajialyani M"", ""Shuvaev VV"", ""Alcalde V"", ""Ali MA"", ""Hamilton JT"", ""Ramalingam R"", ""Wu VH"", ""Paiardini M"", ""Weissman D"", ""Wherry EJ"", ""Kreider EF"", ""Betts MR""]",10.1126/sciimmunol.aec3436,Corrigan AR,Science immunology,2470-9468,119,Sci Immunol,eng,Betts MR,"[""Animals"", ""RNA, Messenger"", ""Humans"", ""Mice"", ""Chemokine CX3CL1"", ""Macaca mulatta"", ""Nanoparticles"", ""L-Selectin"", ""T-Lymphocytes, Cytotoxic"", ""Mice, Inbred C57BL"", ""CD8-Positive T-Lymphocytes"", ""Liposomes""]",eaec3436,42102231,,2026 May 8,2026,https://pubmed.ncbi.nlm.nih.gov/42102231/,In vivo reprogramming of cytotoxic effector CD8 T cells via fractalkine-conjugated mRNA-LNPs,11,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"A major obstacle confronting HIV-1 vaccine and cure research is the lack of an outbred animal model for rapid and consistent induction of broadly neutralizing antibodies (bNAbs). We designed an epitope-focused simian-human immunodeficiency virus (SHIV.5MUT) that elicited broad and potent V3-glycan-targeted antibodies within a year of infection in 14 of 22 macaques compared with 0 of 14 control animals. SHIV.5MUT elicited bNAbs by a two-step mechanism, inducing an initial wave of V1-directed antibodies that selected for envelope (Env) glycoprotein variants with shortened, hypoglycosylated V1 loops, which in turn primed V3-glycan bNAb precursors. Rhesus bNAbs were immunogenetically and structurally diverse, closely resembling human V3-glycan bNAbs. Env-bNAb coevolution revealed a diverse repertoire of bNAb precursors and the Env variants that matured them, yielding a molecular blueprint for vaccine design.","[""Journal Article""]","[""Skelly AN"", ""Gristick HB"", ""Li H"", ""Gavor E"", ""Connell AJ"", ""Kreider EF"", ""Marchitto L"", ""Hogarty MP"", ""Newby ML"", ""Allen JD"", ""Liu W"", ""West AP Jr"", ""Ayyanathan K"", ""Campion MS"", ""Winters K"", ""Gordon CG"", ""Osbaldeston RA"", ""Akeley MJ"", ""Lewis E"", ""Li Y"", ""Singh A"", ""Cruickshank K"", ""Park Y"", ""Zhao C"", ""Li X"", ""Amereh K"", ""Van Itallie E"", ""Carey JW"", ""Albertus A"", ""DeLaitsch AT"", ""Keeffe JR"", ""Lituchy MG"", ""Walsh AA"", ""Morris DJ"", ""Habib R"", ""Bibollet-Ruche F"", ""Mishra N"", ""Avillion G"", ""Koranda NS"", ""Plante SJ"", ""Martella CL"", ""Lora J"", ""Wang EJD"", ""Lewis MG"", ""Martin MA"", ""Nussenzweig MC"", ""Seaman MS"", ""Irvine DJ"", ""Wiehe KJ"", ""Haynes BF"", ""Wagh K"", ""Korber B"", ""Andrabi R"", ""Crispin M"", ""Weissman D"", ""Bjorkman PJ"", ""Hahn BH"", ""Shaw GM""]",10.1126/science.aec6396,Skelly AN,"Science (New York, N.Y.)",0036-8075,6804,Science,eng,Shaw GM,"[""Animals"", ""Humans"", ""AIDS Vaccines"", ""Broadly Neutralizing Antibodies"", ""env Gene Products, Human Immunodeficiency Virus"", ""Epitopes"", ""HIV Antibodies"", ""HIV Infections"", ""HIV-1"", ""Macaca mulatta"", ""Simian Immunodeficiency Virus"", ""Vaccine Development""]",eaec6396,42096521,pmc-id: PMC13308464;manuscript-id: NIHMS2174568;,2026 Jun 18,2026,https://pubmed.ncbi.nlm.nih.gov/42096521/,Induction of broadly neutralizing HIV antibodies by a two-step mechanism informs vaccine design,392,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"While current influenza vaccines often lack broad protection against antigenically drifted strains, some modified hemagglutinin (HA) protein antigens have shown promise in eliciting broadly neutralizing antibodies against conserved epitopes. During infection, the mildly acidic environment of the late endosome triggers irreversible HA conformational changes resulting in a post-fusion structure with altered antigenicity. While enhancing the stability of other structural class I viral fusion protein antigens has been instrumental in improving the effectiveness of COVID-19 and RSV vaccines, the role of HA stability in influenza vaccine immunogenicity is relatively unclear. Here, we used the nucleoside-modified mRNA-LNP platform to test engineered HA antigens with specific acid-stabilizing mutations (E47K, K58I, R106K, and K153E) in the HA stalk. All mutations increased HA acid stability, but E47K and R106K did not increase immunogenicity. K153E and K58I, but not E47K and R106K, enhanced the cell-surface expression of the HA protein in vitro. In mice, K153E- and K58I-containing mRNA-LNP vaccines elicited increased neutralizing antibody titers against homologous virus. K153E conferred greater protection than wild-type vaccine against lethal heterologous A/PR/8/34 challenge at low doses (0.5-1.0 µg), despite the absence of neutralizing antibodies against the challenge strain. K153E also elicited greater expansion of antigen-specific antibody-secreting cells (ASCs) in the bone marrow, as well as cross-reactive T follicular helper (Tfh) cells in the spleen. For the vaccines studied, increased HA expression was a stronger correlate of mRNA-LNP enhancement than increased HA stability.","[""Journal Article""]","[""Ojha CR"", ""Rovito SW"", ""Banoth B"", ""Kim H"", ""Jones JC"", ""Alameh MG"", ""Chen PL"", ""Webby RJ"", ""Weissman D"", ""Russell CJ""]",10.3390/v18040467,Ojha CR,Viruses,1999-4915,4,Viruses,eng,Russell CJ,"[""Animals"", ""Hemagglutinin Glycoproteins, Influenza Virus"", ""Influenza Vaccines"", ""Antibodies, Viral"", ""Mice"", ""Antibodies, Neutralizing"", ""Influenza A Virus, H1N1 Subtype"", ""Immunogenicity, Vaccine"", ""Orthomyxoviridae Infections"", ""Mutation"", ""Female"", ""Mice, Inbred BALB C"", ""Nanovaccines"", ""RNA, Messenger"", ""Immunity, Heterologous"", ""Vaccines, Synthetic""]",,42043256,pmc-id: PMC13119996;,2026 Apr 15,2026,https://pubmed.ncbi.nlm.nih.gov/42043256/,Effect of Acid-Stabilizing Hemagglutinin Mutations on Immunogenicity and Heterologous Protection by H1N1 Influenza Virus mRNA-LNP Vaccines,18,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Placental dysfunction leads to pregnancy-related disorders that affect up to 15% of pregnancies. Several of these, such as preeclampsia, are symptomatically managed but have no curative treatments other than preterm delivery. Placental dysfunction arises from improper placental development, leading to restricted blood vessel formation and a hypoxic placental microenvironment. The development of placental therapeutics is challenging due to the complex physiology that enables the placenta to control uptake and transport. Here, we use a simple culture system that combines hypoxia and trophoblast syncytialization to model the functional syncytiotrophoblast layer of the placenta under hypoxic stress. Using this model, we evaluate the impact of hypoxia on lipid nanoparticle (LNP)-mediated mRNA delivery. Our data show that hypoxia hinders syncytiotrophoblast formation in vitro. Despite this, LNP delivery to syncytiotrophoblasts increases protein translation and secretion, particularly under hypoxic conditions. Further, we show delivery of a therapeutic mRNA, placental growth factor (PlGF), to syncytiotrophoblasts in hypoxia, which restored diminished PlGF levels back to normoxic controls. These findings provide an LNP platform for efficient mRNA delivery to hypoxic trophoblasts and demonstrate the importance of considering hypoxia towards the development of drug delivery platforms for placental therapeutics.","[""Journal Article""]","[""Young RE"", ""Vijayakumar T"", ""Reilley LJ"", ""Darji K"", ""Patel D"", ""Hofbauer S"", ""Alameh MG"", ""Weissman D"", ""Riley R""]",10.1002/btm2.70114,Young RE,Bioengineering & translational medicine,2380-6761,2,Bioeng Transl Med,eng,Riley R,[],e70114,42016867,pmc-id: PMC13093655;,2026 Mar,2026,https://pubmed.ncbi.nlm.nih.gov/42016867/,Investigating the impact of hypoxia and syncytialization on lipid nanoparticle-mediated mRNA delivery to placental cells,11,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Autologous chimeric antigen receptor (CAR) T-cell therapies have demonstrated remarkable efficacy in hematologic malignancies but remain limited by complex manufacturing processes. Allogeneic, off-the-shelf CAR T cells derived from healthy donors represent a promising alternative; however, safe implementation requires elimination of endogenous T-cell receptor (TCR) expression and flexible CAR expression strategies. This study aimed to develop an optimized manufacturing workflow for allogeneic CAR T cells by combining CRISPR/Cas9-mediated TCR knockout with mRNA-based CAR expression, and to evaluate cryopreservation strategies enabling on-demand CAR T-cell generation. Healthy donor T cells were edited at the TRAC locus using CRISPR/Cas9 to generate TCR-deficient T cells. These cells were cryopreserved and subsequently transfected with mRNA encoding CD117, BCMA, or CD19 CARs. CAR expression, cell viability, immunophenotype, cytokine secretion, and antigen-specific cytotoxicity were assessed under different cryopreservation-transfection conditions. TCR knockout T cells exhibited efficient TCR disruption with reduced alloreactive proliferation. CD117 mRNA CAR T cells derived from TCR-deficient T cells demonstrated CAR expression kinetics, immunophenotypic profiles, and antigen-specific cytotoxicity comparable to wild-type CAR T cells. Evaluation of two cryopreservation strategies revealed that cryopreservation prior to mRNA electroporation preserved cell viability, phenotype, and cytotoxic function, whereas cryopreservation after mRNA transfection was associated with reduced functional activity. The optimized protocol was successfully extended to CD19- and BCMA-targeting CAR mRNAs. Collectively, these findings establish a modular platform for producing allogeneic CAR T cells using mRNA technology, offering a practical approach for rapid, on-demand CAR T-cell therapy.","[""Journal Article""]","[""Buakaew T"", ""Thaiwong R"", ""Inthanachai T"", ""Palaga T"", ""Weissman D"", ""Suppipat K"", ""Ausavarungnirun C"", ""Tawinwung S""]",10.1016/j.biopha.2026.119300,Buakaew T,Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie,0753-3322,,Biomed Pharmacother,eng,Tawinwung S,"[""Humans"", ""RNA, Messenger"", ""CRISPR-Cas Systems"", ""T-Lymphocytes"", ""Cryopreservation"", ""Receptors, Chimeric Antigen"", ""Immunotherapy, Adoptive"", ""Receptors, Antigen, T-Cell"", ""Cell Survival"", ""Gene Knockout Techniques"", ""Transfection""]",119300,41916134,,2026 May,2026,https://pubmed.ncbi.nlm.nih.gov/41916134/,Combining CRISPR/Cas9-mediated TRAC knockout with mRNA-based CAR expression enables flexible generation of allogeneic CAR T cells,198,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"There have been rapid advances in nucleoside-modified messenger RNA-based vaccines, particularly during the SARS-CoV-2 pandemic, demonstrating a rapid and cost-effective approach for addressing infectious diseases. A major challenge remains in developing a delivery system that protects mRNA from degradation and facilitates its passage through tissue and cellular barriers. Current four-component lipid nanoparticles enable efficient endosomal escape and are a pivotal technology for the delivery of mRNA vaccines. However, challenges such as stability, availability, durability, and adverse effects persist. We have developed a self-assembling one-component ionizable amphiphilic Janus dendrimers (IAJD) delivery system with naturally occurring amino heads, capable of efficiently delivering mRNA to the spleen and lymph nodes. This single-component system simplifies synthesis, reduces development complexity, and enables rapid global distribution of mRNA vaccines during pandemics. As a proof of concept, one-component IAJD97, formulated with mRNA encoding norovirus mRNA capsid protein, demonstrates the potential of IAJDs as efficient delivery platform for mRNA vaccines, advancing their effectiveness and expanding applications to improve public health outcomes.","[""Journal Article""]","[""Ona NA"", ""Zhang D"", ""Lindesmith LC"", ""Park WJ"", ""Meshanni JA"", ""Berkihiser S"", ""Vasserman JA"", ""Toshtzar S"", ""Moore NC"", ""Williams B"", ""Nakagawa B"", ""Baboo I"", ""Pan L"", ""Cheng W"", ""Mercado-López X"", ""Bonilla-Acosta W"", ""Brewer-Jensen PD"", ""Zweigart MR"", ""Reyes YI"", ""Mallory ML"", ""May SR"", ""Zhou Y"", ""Percec V"", ""Baric RS"", ""Li Y"", ""Weissman D"", ""Atochina-Vasserman EN""]",10.1126/sciadv.adv1554,Ona NA,Science advances,2375-2548,13,Sci Adv,eng,Atochina-Vasserman EN,"[""Dendrimers"", ""Animals"", ""RNA, Messenger"", ""Humans"", ""SARS-CoV-2"", ""COVID-19 Vaccines"", ""COVID-19"", ""Vaccine Development"", ""mRNA Vaccines"", ""Nanoparticles"", ""Mice""]",eadv1554,41894505,pmc-id: PMC13025126;,2026 Mar 27,2026,https://pubmed.ncbi.nlm.nih.gov/41894505/,One-component ionizable amphiphilic Janus dendrimers as a delivery platform for efficient mRNA vaccine development,12,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Lipid nanoparticles (LNPs) have been immensely successful in facilitating the delivery of nucleic acids to tissues of interest and continue to be optimized for mRNA delivery. These vehicles are particularly advantageous for vaccination due to their ease of production, highly tunable composition, and ability to induce robust immune responses without an adjuvant, as exemplified most recently by the clinical success of the Pfizer/BioNTech and Moderna COVID-19 vaccines. However, LNPs are known to exhibit off-target liver tropism. To address this limitation, we developed a library of aromatic bioreducible ionizable lipids that potently transfect secondary lymphoid tissues with liver detargeting capabilities compared with an industry standard ionizable lipid used in the COVID-19 vaccine. The library consists of three modular components: amine core structure, lipid tail length, and regiochemistry. These aromatic ionizable lipids employ benzene rings both as a scaffold for regiochemical differences and as a moiety to improve transfection. Bioreducible disulfide bonds in the lipids additionally serve to increase their biodegradability. When these aromatic ionizable lipids are formulated as LNPs, top-performing aromatic LNPs (aroLNPs) accumulate in and transfect lymph nodes while minimizing off-target liver tropism. Top-performing aroLNPs also induce strong antigen-specific immune responses, increased effector memory T cell generation, and decreased terminal effector T cell generation in mice when utilized in a preclinical SARS-CoV-2 vaccine study. Additionally, aroLNPs are strongly retained in the injection site and induce low levels of systemic inflammatory cytokines. Together, these results establish aroLNPs as a promising platform for vaccine delivery and potentially other immune-focused therapeutic applications.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Yamagata HM"", ""Padilla MS"", ""Hamilton AG"", ""Swingle KL"", ""Thatte AS"", ""Ricciardi AS"", ""Agrawal A"", ""Fitzgerald E"", ""Poirier AJ"", ""Geisler HC"", ""Joseph RA"", ""Chalom OZ"", ""Du S"", ""Li JJ"", ""Kim D"", ""Whitaker RC"", ""Figueroa-Espada CG"", ""Han EL"", ""Murray AM"", ""Alameh MG"", ""Weissman D"", ""Mitchell MJ""]",10.1021/jacs.6c00080,Yamagata HM,Journal of the American Chemical Society,0002-7863,13,J Am Chem Soc,eng,Mitchell MJ,"[""Animals"", ""Nanoparticles"", ""Lipids"", ""Mice"", ""Liver"", ""Lymph Nodes"", ""RNA, Messenger"", ""COVID-19 Vaccines"", ""Humans"", ""SARS-CoV-2"", ""COVID-19"", ""Mice, Inbred C57BL"", ""Liposomes""]",14137-14150,41873855,,2026 Apr 8,2026,https://pubmed.ncbi.nlm.nih.gov/41873855/,Liver-Detargeted Aromatic Bioreducible mRNA Lipid Nanoparticles Confer Lymph Node Tropism and Robust Antigen-Specific Immunity,148,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"We use simple mathematical models to explore the factors that influence the evolutionary emergence of mpox to a pathogen capable of sustained human to human transmission that poses a global threat. Smallpox eradication followed by the discontinuation of immunization with vaccinia has led to a decline in the level of population immunity against related poxviruses such as mpox. This decline in immunity results in an increase in both the number of spillovers and the extent of human to human transmission. We find that increases in transmissibility of mpox between humans have a much greater effect on the probability of evolutionary emergence compared with increases in the number of zoonotic spillovers. We suggest that while mpox only needs to have a reproductive number slightly greater than one to become endemic, subsequent adaptation is likely to further increase its transmissibility in the human population. As a consequence a much higher level of vaccination (or other intervention) is needed to control the pathogen after its evolutionary emergence compared with what is needed to prevent it from emerging in the first place.","[""Journal Article"", ""Preprint""]","[""Hirst C"", ""Deichmann J"", ""Saha A"", ""Longini I"", ""Handel A"", ""Lipsitch M"", ""Weissman D"", ""Antia R""]",10.64898/2026.03.03.709287,Hirst C,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Antia R,[],,41867765,pmc-id: PMC13001426;,2026 Mar 4,2026,https://pubmed.ncbi.nlm.nih.gov/41867765/,Preventing Disease Emergence Following Eradication: Application to Mpox,,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Regulating T cell phenotypes between activation and exhaustion remains a significant challenge for messenger RNA-based cancer immunotherapy. A potential approach to improve anti-cancer T cell activity is to co-deliver interleukin-12 (IL-12), to stimulate effector T cells, and indoleamine 2,3-dioxygenase (IDO) inhibitor, to suppress T cell exhaustion. Here we design prodrug ionizable lipid nanoparticles (pLNPs), via a library of prodrug ionizable lipids (pILs), incorporating an intracellularly cleavable IDO inhibitor within the pIL structure and encapsulating IL-12 messenger RNA. The lead pIL shows enhanced mRNA transfection over a clinically utilized ionizable lipid, as well as strong immunomodulatory effects via release of the IDO inhibitor. In a subcutaneous colon cancer mouse model, pLNP drives complete regression of primary tumours by eliciting effector T cell infiltration while reducing exhaustion, induces a memory T cell response and stimulates a systemic immune response that allows for regression of distal tumours in this study. These results highlight the promise of pLNPs for small-molecule drug and mRNA combination cancer immunotherapy.","[""Journal Article""]","[""Shi Q"", ""Gong N"", ""Wang J"", ""Palanki R"", ""Zheng Q"", ""Alameh MG"", ""Dwivedi G"", ""Davis B"", ""Melamed J"", ""Luo Z"", ""Xu J"", ""Figueroa-Espada CG"", ""Xue L"", ""Zeng Y"", ""Han X"", ""Kim D"", ""Chen Q"", ""Yamagata H"", ""Geisler HC"", ""El-Mayta R"", ""Yoon IC"", ""Weissman D"", ""Mitchell MJ""]",10.1038/s41565-025-02102-z,Shi Q,Nature nanotechnology,1748-3387,3,Nat Nanotechnol,eng,Mitchell MJ,"[""Prodrugs"", ""Animals"", ""Nanoparticles"", ""Immunotherapy"", ""Mice"", ""RNA, Messenger"", ""Lipids"", ""Interleukin-12"", ""Cell Line, Tumor"", ""Humans"", ""Indoleamine-Pyrrole 2,3,-Dioxygenase"", ""Mice, Inbred C57BL"", ""Colonic Neoplasms"", ""T-Lymphocytes"", ""Female"", ""Liposomes""]",430-442,41851499,,2026 Mar,2026,https://pubmed.ncbi.nlm.nih.gov/41851499/,Prodrug-tethered lipid nanoparticles for synergistic messenger RNA cancer immunotherapy,21,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Highly pathogenic avian influenza (HPAI) clade 2.3.4.4b H5N1 virus has recently emerged in dairy cattle in the United States. The virus replicates primarily in the mammary gland of infected cattle, leading to dramatic reductions in milk production. It is thought that the virus transmits from animal to animal through viral shedding in milk, and therefore, vaccines that decrease the amount of virus in milk can potentially limit the current outbreak and reduce the risk of H5N1 spillover into humans. Here, we assess the immunogenicity and efficacy of a clade 2.3.4.4b H5 mRNA-LNP vaccine in lactating dairy cows. We found that the H5 mRNA-LNP vaccine elicited robust antibody responses in sera and milk and significantly reduced viral replication and disease caused by clade 2.3.4.4b H5N1 intramammary infection.","[""Journal Article"", ""Preprint""]","[""Santos JJS"", ""Souza CK"", ""Zanella GC"", ""Goulart DB"", ""Arruda B"", ""Boggiatto P"", ""Palmer MV"", ""Snyder CA"", ""Kristula MA"", ""Dickens C"", ""Webb TL"", ""Atkinson RK"", ""Dadonaite B"", ""Dwivedi G"", ""Alameh MG"", ""Bloom JD"", ""Weissman D"", ""Althouse GC"", ""Baker AL"", ""Hensley SE""]",10.64898/2026.03.03.709308,Santos JJS,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Hensley SE,[],,41846968,pmc-id: PMC12991112;,2026 Mar 4,2026,https://pubmed.ncbi.nlm.nih.gov/41846968/,Evaluation of an H5 influenza virus mRNA-lipid nanoparticle (LNP) vaccine in lactating dairy cows,,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Modulating metabolism in immune cells is an effective approach to induce desired immune responses. Here we develop a lipid nanoparticle (LNP) capable of metabolic reprogramming of dendritic cells for mRNA vaccine applications. Using imidoester-based conjugation chemistry, we design a crosslinked ionizable lipid, C12-2aN, which possesses intrinsic metabolic modulatory properties. This multifunctional ionizable lipid not only promotes effective mRNA expression by facilitating endosomal escape but also stimulates glycolysis through mTORC2 pathway activation. As both an mRNA carrier and a metabolic modulator, C12-2aN LNPs lead to potent vaccine efficacy in both SARS-CoV-2 and OVA cancer vaccine models, resulting in stronger neutralization of pseudovirus infection and improved survival rates, respectively, compared with control LNPs without the crosslinker. Moreover, C12-2aN LNPs outperformed FDA-approved LNPs in terms of reduced off-target delivery and lower immunogenicity. Overall, the integration of mRNA delivery and metabolic reprogramming induced by the ionizable lipid component presents significant potential for next-generation mRNA LNP vaccines.","[""Journal Article""]","[""Kim D"", ""Gong N"", ""Alameh MG"", ""Han EL"", ""Wang H"", ""Wang J"", ""Feng E"", ""Yoon IC"", ""Murray AM"", ""Shi Q"", ""Moon SJ"", ""Mrksich K"", ""Weissman D"", ""Mitchell MJ""]",10.1038/s41563-026-02512-x,Kim D,Nature materials,1476-1122,,Nat Mater,eng,Mitchell MJ,[],,41844984,,2026 Mar 17,2026,https://pubmed.ncbi.nlm.nih.gov/41844984/,Crosslinked ionizable lipids reprogram dendritic cell metabolism for potent mRNA vaccination,,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"A rickettsial pathogen, Ehrlichia chaffeensis, causes an emerging tick-borne disease called human monocytic ehrlichiosis (HME). E. chaffeensis in ticks expresses a porin OMP-1B, the immunodominant major outer membrane protein, which is required for nutrient uptake across the outer membrane of bacteria. We developed an OMP-1B-encoding mRNA-lipid nanoparticle (hereafter OMP-1B mRNA-LNP) vaccine. Immunization of naïve mice with OMP-1B mRNA-LNP showed significant protection against E. chaffeensis infection following a challenge with E. chaffeensis-infected tick cells. Following vaccination, increased OMP-1B-specific serum IgG, IgG1, and IgG2a titres, as well as E. chaffeensis infection-neutralizing antibodies were detected. An ELISpot assay revealed significant increase in OMP-1B-specific IFN-γ-secreting cells in the blood and spleen samples from mice vaccinated with OMP-1B mRNA-LNP. Flow cytometry analysis of spleen samples showed that OMP-1B antigen-specific IFN-γ-producing CD4+ and CD8+ T cells as well as granzyme B-producing cytotoxic CD8+ T cells were significantly increased in the vaccinated mice. Our results demonstrate that an mRNA vaccine targeting OMP-1B conferred protection against E. chaffeensis infection, with significant humoral immune responses including infection-neutralizing antibodies, balanced Th1/Th2 response, and antigen-specific T helper and cytotoxic T cell activation. These data suggest that the mRNA-LNP approach is a viable strategy for developing efficient anti-rickettsial vaccines.","[""Journal Article""]","[""Lin M"", ""Denton S"", ""Duan N"", ""Iqbal N"", ""Boyaka PN"", ""Dwivedi G"", ""Alameh MG"", ""Weissman D"", ""Rikihisa Y""]",10.1080/22221751.2026.2645860,Lin M,Emerging microbes & infections,2222-1751,1,Emerg Microbes Infect,eng,Rikihisa Y,"[""Animals"", ""Mice"", ""Antibodies, Bacterial"", ""Female"", ""Bacterial Outer Membrane Proteins"", ""Immunoglobulin G"", ""RNA, Messenger"", ""Porins"", ""Bacterial Vaccines"", ""Nanoparticles"", ""CD4-Positive T-Lymphocytes"", ""CD8-Positive T-Lymphocytes"", ""Interferon-gamma"", ""Antibodies, Neutralizing"", ""Humans"", ""Ticks"", ""Vaccination"", ""Liposomes""]",2645860,41823664,pmc-id: PMC13159599;,2026 Dec,2026,https://pubmed.ncbi.nlm.nih.gov/41823664/,Efficacy and immunological correlates of an mRNA-LNP vaccine for protection against an emerging rickettsial pathogen,15,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Fibroblast activation protein (FAP), which is highly expressed on cancer-associated fibroblasts (CAF), is a promising therapeutic target to achieve normalization of the tumor microenvironment. We previously established an ex vivo retroviral-transduced FAP-specific chimeric antigen receptor (FAP-CAR) T-cell approach to deplete FAP+ CAFs that resulted in delayed tumor growth associated with disruption of desmoplastic matrix and enhanced immune cell infiltration and reversed immune exclusion and immunosuppression. In this study, we describe an in vivo strategy for generating FAP-CAR T cells using anti-CD5-conjugated targeted lipid nanoparticles (tLNP) encapsulating FAP-CAR mRNA and assessed the efficacy of this approach compared with adoptive transfer of retrovirus-transduced CAR T cells in a preclinical model of pancreatic ductal adenocarcinoma. With transient CAR expression in >45% of splenic, >69% of circulating, and >35% of tumor-infiltrating T cells, the abundance of peripheral and intratumoral FAP-CAR+ T cells detected following a single intravenous dose of FAP-CAR mRNA tLNPs was greater than that detected following administration of 1 × 107ex vivo retrovirally transduced FAP-CAR T cells. Furthermore, in vivo mRNA CAR T-cell engineering resulted in as good or greater inhibition of tumor growth as compared with adoptive transfer of ex vivo retroviral-engineered T cells. Given that in vivo generation of CAR T cells resulted in transient CAR expression and circumvented the need for autologous T-cell isolation, viral vectors, and lymphodepletion, this platform represents a potentially safer, more accessible, and cost-effective method for targeting stromal cells to normalize the tumor microenvironment in desmoplastic tumors and has potential implications for tumor antigen-targeted CAR T cells.","[""Journal Article""]","[""Bajbouj K"", ""Xiao Z"", ""Todd L"", ""Huang L"", ""Papp TE"", ""Halilovic F"", ""Ramani J"", ""Bao Y"", ""Butcher M"", ""Bot A"", ""Aghajanian H"", ""June CH"", ""Weissman D"", ""Parhiz H"", ""Albelda SM"", ""Puré E""]",10.1158/2326-6066.CIR-25-0663,Bajbouj K,Cancer immunology research,2326-6066,4,Cancer Immunol Res,eng,Puré E,"[""Animals"", ""Fibroblast Activation Protein Alpha"", ""Nanoparticles"", ""Humans"", ""Pancreatic Neoplasms"", ""Endopeptidases"", ""RNA, Messenger"", ""T-Lymphocytes"", ""Receptors, Chimeric Antigen"", ""Mice"", ""Immunotherapy, Adoptive"", ""Gelatinases"", ""Membrane Proteins"", ""Serine Endopeptidases"", ""Cell Line, Tumor"", ""Lipids"", ""Tumor Microenvironment"", ""Female"", ""Xenograft Model Antitumor Assays"", ""Liposomes""]",559-570,41686204,,2026 Apr 2,2026,https://pubmed.ncbi.nlm.nih.gov/41686204/,Targeted Lipid Nanoparticle Delivery of FAP-CAR mRNA Enables Potent In Vivo T-cell Engineering against Pancreatic Tumors,14,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"A vaccine based on an mRNA platform was first licensed for human use during the COVID-19 pandemic. However, data on the immunogenicity of SARS-CoV-2 mRNA vaccines in neonates is insufficient and the vaccines were only authorized for those over six months of age. Here, we compared the antibody responses induced by both recombinant receptor binding domain (rRBD) of SARS-CoV-2 spike protein (RBD) and mRNA encoded RBD (RBD-mRNA-LNP) forms in neonatal mice. When administered twice three weeks apart, both forms induced detectable anti-RBD antibodies. However, levels of IgG antibodies against RBD were significantly higher with more potent inhibition of RBD binding to ACE2 in neonatal mice immunized with RBD-mRNA-LNP vaccine compared to those immunized with rRBD vaccine adjuvanted with AddaVax™, a squalene-based adjuvant. Thus, the mRNA vaccine platform elicits higher levels of antibodies with improved functional capability in neonatal mice compared to the recombinant protein platform.","[""Journal Article""]","[""Lotspeich-Cole L"", ""Jha MK"", ""Parvathaneni S"", ""Lee RC"", ""Weissman D"", ""Major M"", ""Akkoyunlu M""]",10.1016/j.vaccine.2026.128271,Lotspeich-Cole L,Vaccine,0264-410X,,Vaccine,eng,Akkoyunlu M,"[""Animals"", ""COVID-19 Vaccines"", ""Mice"", ""Antibodies, Viral"", ""Spike Glycoprotein, Coronavirus"", ""Animals, Newborn"", ""COVID-19"", ""Vaccines, Synthetic"", ""SARS-CoV-2"", ""Immunoglobulin G"", ""Female"", ""mRNA Vaccines"", ""Adjuvants, Immunologic"", ""RNA, Messenger"", ""Angiotensin-Converting Enzyme 2"", ""Mice, Inbred BALB C""]",128271,41610463,,2026 Mar 7,2026,https://pubmed.ncbi.nlm.nih.gov/41610463/,Neonatal mice immune response to COVID-19 mRNA vaccine,75,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Interest continues to grow in the use of mRNA vaccines and therapeutics. While effective for immunization against infectious diseases, lipid nanoparticle (LNP) formulations used for other mRNA delivery applications suffer from off-target accumulation, poor immune transfection, and reactogenicity, limiting their application to immunoengineering. Development of new mRNA LNPs is severely bottlenecked by the LNP discovery process, which is historically low-throughput due to reliance on low-plex measurements. Here, we develop a high-throughput in vivo mRNA LNP screening platform based on barcoded mRNA (b-mRNA). Using this b-mRNA screening platform to simultaneously evaluate 122 LNPs, we identify novel LNP formulations capable of potent hepatic and extrahepatic transfection. We evaluate a lead LNP candidate for in situ immune modulation in a syngeneic mouse model of melanoma and demonstrate a significant reduction in tumor burden and extended survival compared to mice treated with a gold standard mRNA LNP formulation. We employ novel biochemical characterization techniques to analyze nanoparticle protein corona formation with single-particle resolution and gain insight into the influence of protein adsorption on hepatic and splenic transfection. Together, our results demonstrate the value of advanced LNP screening and characterization techniques for the development of next-generation mRNA LNPs for immunoengineering.","[""Journal Article""]","[""Hamilton AG"", ""Thatte AS"", ""Xu J"", ""Luo Z"", ""Safford HC"", ""Swingle KL"", ""Muscat-Rivera J"", ""Kegel M"", ""Han X"", ""Joseph RA"", ""Murray AM"", ""Geisler HC"", ""Whitaker RC"", ""Xue L"", ""Spektor R"", ""Melamed JR"", ""Weissman D"", ""Mitchell MJ""]",10.1002/adma.202514370,Hamilton AG,"Advanced materials (Deerfield Beach, Fla.)",0935-9648,13,Adv Mater,eng,Mitchell MJ,"[""Animals"", ""Nanoparticles"", ""RNA, Messenger"", ""Lipids"", ""Mice"", ""High-Throughput Screening Assays"", ""Cell Line, Tumor"", ""Transfection"", ""Liver"", ""Female"", ""Liposomes""]",e14370,41603124,pmc-id: PMC12957869;,2026 Mar,2026,https://pubmed.ncbi.nlm.nih.gov/41603124/,High-Throughput In Vivo Screening Using Barcoded mRNA Identifies Lipid Nanoparticles With Extrahepatic Tropism for In Situ Immunoengineering,38,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Dengue virus (DENV) infection represents a significant public health concern in tropical and subtropical areas, with increasing cases in parts of Europe. Currently, licensed vaccines, Dengvaxia® and Qdenga®, rely on live-attenuated platforms but show limited efficacy due to imbalanced immune responses and risks associated with antibody-dependent enhancement (ADE). In this study, we developed and evaluated nucleoside-modified mRNA vaccine encoding the dengue virus serotype 1 (DENV1) pre-membrane and envelope (prME) proteins. To reduce the potential for ADE, we incorporated the F108A mutation in the fusion loop, substituted the pr region with that from Japanese encephalitis virus (JEV), and incorporated a consensus envelope domain III (cEDIII) sequence to broaden neutralizing antibody responses. Immunogenicity was assessed in BALB/C mice immunized twice at three-week intervals with 1, 2.5, or 10 μg doses. The WT prME construct induced the highest DENV1 neutralizing antibody (NtAb) titers in a dose-dependent manner and robust T cell responses, particularly with the 2.5 μg dose. While the F108A and cEDIII modifications modulated antigen expression and broadened cross-reactivity, they also slightly reduced DENV-1-specific neutralizing titers. Among constructs, F108A+cEDIII demonstrated reduced ADE activity with improved cross-neutralization, especially against DENV3. However, the prJEV chimera exhibited low immunogenicity, likely due to prM-E domain incompatibility. Overall, the WT prME construct showed the most favorable balance of immunogenicity and safety, supporting its advancement as a prototype for future tetravalent dengue mRNA vaccine development.","[""Journal Article""]","[""Khawsang C"", ""Prompetchara E"", ""Saithong S"", ""Tharakhet K"", ""Kaewpang P"", ""Yostrerat N"", ""Wangsoontorn P"", ""Pitakpolrat P"", ""Buranapraditkun S"", ""Puttikhunt C"", ""Lam K"", ""Heyes J"", ""Ketloy C"", ""Weissman D"", ""Ruxrungtham K""]",10.1016/j.biopha.2026.119037,Khawsang C,Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie,0753-3322,,Biomed Pharmacother,eng,Ruxrungtham K,"[""Animals"", ""Antibodies, Neutralizing"", ""Dengue Virus"", ""T-Lymphocytes"", ""Mice, Inbred BALB C"", ""Dengue Vaccines"", ""Mice"", ""Antibodies, Viral"", ""Dengue"", ""Female"", ""RNA, Messenger"", ""mRNA Vaccines"", ""Viral Envelope Proteins""]",119037,41579705,,2026 Feb,2026,https://pubmed.ncbi.nlm.nih.gov/41579705/,Preclinical evaluation of DENV1 mRNA vaccines in mice: Toward improved neutralizing antibody and T cell responses,195,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"DNA-lipid nanoparticles (DNA-LNPs) loaded with inhibitors of the cGAS-STING pathway enable safe and effective delivery of DNA in vivo. Herein, we report the first instances of extrahepatic DNA-LNP targeting. DNA-LNPs conjugated to antibodies against PECAM-1 or VCAM-1 target the endothelium of the lungs and brain/spleen, respectively. These LNPs drive robust transgene expression in their target organs, with greater magnitude and duration than untargeted LNPs. Lung specificity of PECAM-targeted transgene expression increases over two weeks, resulting in markedly higher lung-to-liver expression ratios than our previous PECAM-targeted mRNA-LNPs. Off-target liver DNA expression declines to undetectable levels but persists in the lungs, while mRNA expression uniformly decreases due to its short half-life. We further improve this expression specificity by replacing full-length antibodies with Fab fragments. Single-cell analysis reveals a key mechanism underlying the improvements in organ-specificity: target organ expression is dominated by long-lived endothelial cells, while off-target liver delivery and expression are in non-endothelial cells with shorter half-lives. Collectively, these studies demonstrate that targeted DNA-LNPs achieve high levels of organ- and cell-type-specific transgene expression and thus provide a therapeutic platform for dozens of endothelial-centric diseases.","[""Journal Article""]","[""Marzolini N"", ""Brysgel TV"", ""Rahman RJ"", ""Essien EO"", ""Nwe SY"", ""Wu J"", ""Majumder A"", ""Patel MN"", ""Tiwari S"", ""Espy CL"", ""Dong F"", ""Santos-De León SA"", ""Shah A"", ""Shuvaev VV"", ""Hood ED"", ""Chase LS"", ""Weissman D"", ""Katzen JB"", ""Frank DB"", ""Bennett ML"", ""Marcos-Contreras OA"", ""Myerson JW"", ""Muzykantov VR"", ""Reyes-Esteves S"", ""Brenner JS""]",10.1002/advs.202515480,Marzolini N,"Advanced science (Weinheim, Baden-Wurttemberg, Germany)",2198-3844,14,Adv Sci (Weinh),eng,Brenner JS,"[""Animals"", ""Endothelial Cells"", ""DNA"", ""Nanoparticles"", ""Mice"", ""Lipids"", ""Vascular Cell Adhesion Molecule-1"", ""Lung"", ""Platelet Endothelial Cell Adhesion Molecule-1"", ""Liver"", ""Liposomes""]",e15480,41556437,pmc-id: PMC12970279;,2026 Mar,2026,https://pubmed.ncbi.nlm.nih.gov/41556437/,"Targeting DNA-LNPs to Endothelial Cells Improves Expression Magnitude, Duration, and Specificity",13,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Influenza virus infection poses a significant health risk to newborns, with this population experiencing higher hospitalization and mortality rates compared to older children. The heightened vulnerability of this age group results from a combination of an altered immune system and lack of a licensed vaccine for children under six months of age. mRNA-LNP vaccines have shown remarkable efficacy, including the capacity to induce antibodies in poorly responding populations. This makes them a promising candidate for addressing the unique immunological environment of newborns. Here, we leveraged the close immunological and physiological similarity of NHP to evaluate the efficacy of an influenza hemagglutinin mRNA-LNP vaccine in newborns. Our findings show the HA mRNA-LNP vaccine elicits robust, multi-functional antibody responses in newborn NHP that result in significantly reduced viral load and disease severity following challenge. These results highlight the potential of mRNA-based vaccines as a transformative approach to protect the vulnerable newborn population against influenza. Continued development and optimization of this platform could address the critical gap in influenza virus and other pathogen vaccine coverage for infants under six months of age.","[""Journal Article""]","[""Page CL"", ""Holbrook BC"", ""Crofts KF"", ""Alameh MG"", ""Davis B"", ""Caudell D"", ""Weissman D"", ""Alexander-Miller MA""]",10.1038/s41541-025-01317-4,Page CL,NPJ vaccines,2059-0105,1,NPJ Vaccines,eng,Alexander-Miller MA,[],2,41453893,pmc-id: PMC12764487;,2025 Dec 26,2025,https://pubmed.ncbi.nlm.nih.gov/41453893/,An influenza HA mRNA-LNP vaccine induces potent responses in newborn nonhuman primates that enhance protection from challenge,11,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Leptospirosis is a neglected tropical disease with significant global health and economic impacts, particularly in resource-limited regions. This study reports the development of the first mRNA-based vaccines for leptospirosis, targeting the C-terminal region of LigA (LigAc) and the N-terminal region of LigB (LigBn) of Leptospira interrogans serovar Pomona. Transfection of lipid nanoparticle (LNP)-encapsulated mRNA constructs into HEK293T cells confirmed antigen expression and secretion, with proteins exhibiting higher-than-expected molecular weights due to glycosylation. In Jcl:ICR mice, LigAc- and LigBn-mRNA-LNPs elicited rapid and robust antibody responses, with significantly higher IgG titers than recombinant proteins formulated with AddaVax adjuvant. Immune sera from Lig-mRNA-LNP-vaccinated mice promoted complement-mediated killing of pathogenic leptospires in vitro. Moreover, the mRNA-LNP vaccines generated antigen-stimulated IFN-γ-ELISpot responses consistent with Th1-associated cellular activation, similar to recombinant proteins. Protective efficacy was then evaluated in golden Syrian hamsters immunized either intramuscularly or intradermally. Lig-mRNA-LNPs conferred partial protection, with a maximum survival rate of 25 % in LigBn-mRNA-LNPs vaccinated hamsters. The protective rates of Lig-mRNA-LNPs were equivalent to those of recombinant Lig protein formulations. The surviving hamsters showed reduced renal leptospiral colonization and histopathological changes, comparable to those observed in the uniformly surviving killed-leptospires group. These findings establish proof-of-concept for an mRNA vaccine platform against leptospirosis and highlight its potential application pending further optimization.","[""Journal Article""]","[""Techawiwattanaboon T"", ""Leekitcharoenphon R"", ""Alameh MG"", ""Boonkea S"", ""Sangkanjanavanich N"", ""Nakornpakdee Y"", ""Ajimathorn Y"", ""Prompetchara E"", ""Ketloy C"", ""Buranapraditkun S"", ""Palaga T"", ""Kanthawong S"", ""Heyes J"", ""Weissman D"", ""Ruxrungtham K"", ""Patarakul K""]",10.1016/j.vaccine.2025.128099,Techawiwattanaboon T,Vaccine,0264-410X,,Vaccine,eng,Patarakul K,"[""Animals"", ""Leptospirosis"", ""Mice"", ""Disease Models, Animal"", ""Antibodies, Bacterial"", ""Cricetinae"", ""Bacterial Vaccines"", ""Antigens, Bacterial"", ""Humans"", ""Vaccines, Synthetic"", ""Immunoglobulin G"", ""HEK293 Cells"", ""Female"", ""Bacterial Proteins"", ""Leptospira"", ""Mesocricetus"", ""Leptospira interrogans"", ""mRNA Vaccines"", ""Nanoparticles"", ""Leptospira interrogans serovar pomona"", ""RNA, Messenger""]",128099,41453244,,2026 Feb 15,2026,https://pubmed.ncbi.nlm.nih.gov/41453244/,mRNA vaccines targeting Leptospira immunoglobulin-like proteins confer partial protection in a hamster model of leptospirosis,73,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Cryo-EM has revolutionized structural biology, especially for flexible and heterogeneous samples, although access to high end microscopes that enable these studies remains a bottleneck. While 300 keV microscopes have been the go-to for high-resolution structural determination, they are expensive and restricted to institutional and national facilities needing specialized expertise, with access falling far short of the demand. Here, we present the user-managed operation of a cheaper 100 keV electron microscope within a structural biology laboratory enabling close integration with protein production, biochemical and biophysical studies. We provide details and considerations for the installation of the microscope, its day-to-day maintenance, and operations. Using virus surface glycoproteins as case studies, we illustrate the workflow from grid screening, data collection, and data processing, and provide examples of data quality. This user-administered setup provides a training platform for researchers at all levels, with beginners in cryo-EM achieving proficiency to independently operate the microscope within a month of regular use and training. We have demonstrated routine high-quality low-resolution reconstructions using a Ceta CMOS camera and high-resolution reconstructions enabling building of atomic models using a Falcon C direct detector. While there are several examples of facilities that manage cryo-EM and individual laboratories leveraging cryo-EM, we provide here the first demonstration of a modern group independently doing both successfully, something that has been talked about frequently but rarely seen.","[""Journal Article"", ""Preprint""]","[""Pathirage R"", ""Dutta M"", ""Parsons RJ"", ""Lella M"", ""Atwood E"", ""Zhang QE"", ""May A"", ""Johnson A"", ""Huang X"", ""Flemming J"", ""Kumar U"", ""Marayati BF"", ""Spurrier MA"", ""Liu C"", ""Zhuo J"", ""Song K"", ""Adhikari RD"", ""Sammour S"", ""Ilevbare V"", ""Abram C"", ""Diaz M"", ""Guzman A"", ""Rai J"", ""Skelly AN"", ""Hogarty MP"", ""Anasti K"", ""Purro M"", ""Lindsay M"", ""Alam M"", ""Weissman D"", ""Herschchorn A"", ""Hahn BH"", ""Shaw GM"", ""Sharma A"", ""Heaton NS"", ""Edwards RJ"", ""Henderson R"", ""Denny T"", ""Saunders KO"", ""Siliciano J"", ""Siliciano R"", ""Haynes BF"", ""Janowska K"", ""Acharya P""]",10.64898/2025.12.08.693081,Pathirage R,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Acharya P,[],,41427412,pmc-id: PMC12713605;,2025 Dec 10,2025,https://pubmed.ncbi.nlm.nih.gov/41427412/,An integrated workflow for structural virology with a 100 keV electron microscope,,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"The use of macrophage cell therapies is limited by their tendency to change phenotype in response to external cues in situ. Here we demonstrate that an optimized lipid nanoparticle (LNP) formulation effectively delivers IL4 mRNA to human and murine primary macrophages, resulting in rapid transfection, IL-4 secretion, and reparative phenotype modulation. In a model of murine volumetric muscle loss, adoptively transferred macrophages pre-treated with IL4-LNPs maintained a reparative phenotype for at least one week, despite the inflammatory injury microenvironment. IL4-LNP-treated macrophages also promoted a reparative phenotype in endogenous macrophages and supported muscle repair outcomes, including increased vascularization, fiber size distribution, and remodeling of the scaffold. T cell subtype in the muscle or the draining lymph node was not affected. The novel strategy established here may facilitate the control and use of macrophage cell therapies for other applications in regenerative medicine.","[""Journal Article""]","[""O'Brien EM"", ""Tylek T"", ""Geisler HC"", ""Mukalel AJ"", ""Whitaker RC"", ""Sung S"", ""Binder-Markey BI"", ""Weissman D"", ""Mitchell MJ"", ""Spiller KL""]",10.1016/j.biomaterials.2025.123869,O'Brien EM,Biomaterials,0142-9612,,Biomaterials,eng,Spiller KL,"[""Macrophages"", ""Animals"", ""Interleukin-4"", ""Nanoparticles"", ""Humans"", ""RNA, Messenger"", ""Inflammation"", ""Mice"", ""Lipids"", ""Phenotype"", ""Mice, Inbred C57BL"", ""Cell- and Tissue-Based Therapy"", ""Liposomes""]",123869,41317703,pmc-id: PMC13112448;manuscript-id: NIHMS2163147;,2026 May,2026,https://pubmed.ncbi.nlm.nih.gov/41317703/,Macrophage cell therapy enabled by interleukin-4 mRNA-loaded lipid nanoparticles to sustain a pro-reparative phenotype in inflammatory injuries,328,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"The modularity of mRNA-lipid nanoparticle (mRNA-LNP) platforms has enabled their rapid adaptation from infectious disease vaccines to emerging applications in immune-mediated disorders. However, extending mRNA-LNPs to autoimmune and inflammatory diseases requires precise control over immune cell targeting and immunogenicity. Here, we systematically investigate how incorporating anionic lipids into LNPs modulates both immune cell tropism and innate immune activation. Using a library of 40 distinct LNP formulations, we demonstrate that anionic lipids enhance mRNA delivery to splenic dendritic cells, reduce early cellular markers of adjuvant activity and tune cytokine responses in a lipid-dependent manner. We identify formulations that retain pro-inflammatory adjuvant activity and others that promote tolerogenic responses. A lead formulation containing the anionic lipid DOPG selectively dampens innate activation and induces IL-10 production. When encoding the myelin antigen MOG35-55, this LNP suppresses disease in a mouse model of multiple sclerosis, reducing neuroinflammation, T cell infiltration, and maintaining myelin morphology. These findings establish a framework for designing immune-targeted mRNA-LNPs with tunable immunogenicity and promote the development of antigen-specific tolerizing immunotherapies for autoimmune disease.","[""Journal Article"", ""Preprint""]","[""Melamed JR"", ""Muscat-Rivera J"", ""Kegel M"", ""Chaboub LS"", ""Perez-Tremble R"", ""Bhalla NS"", ""Ni H"", ""Sun H"", ""Weissman D""]",10.1101/2025.10.17.683125,Melamed JR,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Weissman D,[],,41280059,pmc-id: PMC12632872;,2025 Oct 17,2025,https://pubmed.ncbi.nlm.nih.gov/41280059/,Anionic lipids modulate mRNA-lipid nanoparticle immunogenicity and confer protection in a mouse model of multiple sclerosis,,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"A major obstacle confronting HIV-1 vaccine and cure research is the lack of an outbred animal model for rapid and consistent induction of broadly neutralizing antibodies (bNAbs). We designed an epitope-focused simian-human immunodeficiency virus (SHIV.5MUT) that elicited broad and potent V3-glycan-targeted antibodies within a year of infection in 14 of 22 macaques compared with 0 of 14 control animals. SHIV.5MUT elicited bNAbs by a novel two-step mechanism, inducing an initial wave of V1-directed antibodies that selected for Envs with shortened, hypoglycosylated V1 loops, which in turn primed V3-glycan bNAb precursors. Rhesus bNAbs were immunogenetically and structurally diverse, closely resembling human V3-glycan bNAbs. Env-bNAb coevolution revealed a diverse repertoire of bNAb precursors and the Env variants that matured them, yielding a molecular blueprint for vaccine design.","[""Journal Article"", ""Preprint""]","[""Skelly AN"", ""Gristick HB"", ""Li H"", ""Gavor E"", ""Connell AJ"", ""Kreider EF"", ""Marchitto L"", ""Hogarty MP"", ""Newby ML"", ""Allen JD"", ""Liu W"", ""West AP Jr"", ""Ayyanathan K"", ""Campion MS"", ""Winters K"", ""Gordon CG"", ""Osbaldeston RA"", ""Akeley MJ"", ""Li Y"", ""Singh A"", ""Cruickshank K"", ""Park Y"", ""Zhao C"", ""Li X"", ""Amereh K"", ""Itallie EV"", ""Carey JW"", ""Albertus A"", ""DeLaitsch AT"", ""Keeffe JR"", ""Lituchy MG"", ""Walsh AA"", ""Morris DJ"", ""Habib R"", ""Bibollet-Ruche F"", ""Mishra N"", ""Avillion G"", ""Koranda NS"", ""Plante SJ"", ""Martella CL"", ""Lora J"", ""Wang EJD"", ""Lewis MG"", ""Martin MA"", ""Nussenzweig MC"", ""Seaman MS"", ""Irvine DJ"", ""Wiehe KJ"", ""Haynes BF"", ""Wagh K"", ""Korber BT"", ""Andrabi R"", ""Crispin M"", ""Weissman D"", ""Bjorkman PJ"", ""Hahn BH"", ""Shaw GM""]",10.1101/2025.10.06.680687,Skelly AN,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Shaw GM,[],,41278942,pmc-id: PMC12632488;,2025 Oct 6,2025,https://pubmed.ncbi.nlm.nih.gov/41278942/,Consistent Induction of Broadly Neutralizing HIV Antibodies by a Novel Two-Step Mechanism Informs Immunogen Design,,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Selective in vivo reprogramming of cytotoxic effector CD8 + T (T eff ) cells holds tremendous promise as a therapeutic tool but has not yet been accomplished. Here, we demonstrate that fractalkine-conjugated mRNA lipid nanoparticles (mRNA-LNP) can specifically target and deliver mRNA to CX3CR1 + T eff cells in vitro and in vivo. In mice, fractalkine-conjugated LNP target up to 90% of blood and splenic T eff cells, and delivery of IL-2-encoding mRNA to T eff cells enables robust exogenous IL-2 secretion. In rhesus macaques, fractalkine-conjugated mRNA-LNP target up to ∼100% of peripheral blood T eff cells and delivery of CD62L-mRNA enables transient CD62L expression. Collectively, these data demonstrate the potential of natural receptor ligand-based targeting of mRNA-LNP for effective and efficient transient in vivo modification of T eff cells.","[""Journal Article"", ""Preprint""]","[""Corrigan AR"", ""Ngiow SF"", ""Statzu M"", ""Pampena MB"", ""Nordin JML"", ""Albertus A"", ""Carro SD"", ""Harper J"", ""Stammen RL"", ""Wood J"", ""Hamilton JT"", ""Ni H"", ""Su J"", ""Ramalingam R"", ""Wu VH"", ""Paiardini M"", ""Weissman D"", ""Wherry EJ"", ""Kreider EF"", ""Betts MR""]",10.1101/2025.10.29.685358,Corrigan AR,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Betts MR,[],,41278637,pmc-id: PMC12636507;,2025 Oct 30,2025,https://pubmed.ncbi.nlm.nih.gov/41278637/,In vivo reprogramming of cytotoxic effector CD8 (+) T cells via fractalkine-conjugated mRNA-LNP,,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Oral squamous cell carcinoma (OSCC) represents 90% of all head and neck cancers. Despite decades of research, the 5-year survival rate is 50%, and strikingly, the overall incidence rate is projected to increase by 30% in the next ten years, which will result in a sharp increase in mortality. Two fundamental aspects of OSCC are that it progresses via the inactivation and mutation of tumor suppressor (TS) genes and has a ""cold"" tumor immune microenvironment (TIME). A major barrier in the treatment of OSCC is the lack of novel therapies clinicians have at their disposal that are designed to disrupt tumor progression by reshaping the cold tumors into inflammatory ""hot"" tumors. To overcome these obstacles, we employed a lipid nanoparticle (LNP) that co-encapsulates p53 mRNA and the small molecule ciclopirox (CPX). We demonstrate that both drugs have innate chemotherapeutic properties by facilitating caspase activation. Moreover, these therapies can create a less immunosuppressive TIME in part by repolarizing tumor-associated macrophages (TAMs) to M1-like phenotypes. When formulated together, our platform provides an all-in-one approach for OSCC, effective in both p53-therapy-susceptible and p53-therapy-resistant models. Additionally, this work provides a template for a delivery platform capable of tackling multiple mechanisms of OSCC progression and survival.","[""Journal Article"", ""Preprint""]","[""Padilla MS"", ""Li JJ"", ""Zhang Q"", ""Patwari K"", ""Shi S"", ""Yamagata HM"", ""Joseph RA"", ""Hymms BN"", ""Teerdhala SV"", ""Alameh MG"", ""Weissman D"", ""Le AD"", ""Mitchell MJ""]",10.1101/2025.09.26.678832,Padilla MS,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Mitchell MJ,[],,41256582,pmc-id: PMC12621659;,2025 Oct 6,2025,https://pubmed.ncbi.nlm.nih.gov/41256582/,Lipid nanoparticle co-delivery of mRNA and a small molecule drug for oral cancer chemoimmunotherapy,,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Tyrosine kinase (TK) inhibitors improve clinical outcomes in non-small cell lung cancer (NSCLC) with targetable mutations. However, such NSCLC cases account for only about 50% in the western populations. Inhibition of the splicing factor SRSF3 has been reported to be tumor-suppressive in other cancer cell types. This study for the first time explores the tumor-suppressive activity of siRNA knockdown of SRSF3 in NSCLC cells. The cell lines used were A549 (no TK mutation; TP53 wild type), NCI-H1975 (EGFR L858R/T790M; TP53 R273H mutant), NCI-H322 (no TK mutation; TP53 R248L mutant), and NCI-H596 (no TK mutation; TP53 G245C mutant). In all these cell lines, SRSF3 knockdown increased cellular senescence, as indicated by increased senescence-associated β-galactosidase activity and reduced cell proliferation. In A549 cells, increased apoptotic cleavage of caspase-3 and poly(ADP-ribose) polymerase was also observed. A tumor-suppressive p53 isoform, p53β, was shown to be upregulated by SRSF3 knockdown. However, overexpression of p53β did not induce cellular senescence or apoptosis, suggesting that this p53 isoform is not a primary effector of SRSF3 knockdown in NSCLC cells. Gene expression analyses suggested that the SRSF3 knockdown-induced senescence in NSCLC cells may be mediated by the downregulation of TOP2A, UBE2C, or ASPM, which are known oncogenic factors associated with poor patient prognosis. We also generated SRSF3 siRNA-encapsulating lipid nanoparticles as a future therapeutic tool. This study proposes a therapeutic strategy for NSCLC that is independent of the mutation status of TP53 and TK-encoding genes.","[""Journal Article"", ""Research Support, N.I.H., Intramural""]","[""Nakamichi S"", ""von Muhlinen N"", ""Yamada L"", ""Melamed JR"", ""Papp TE"", ""Parhiz H"", ""Weissman D"", ""Horikawa I"", ""Harris CC""]",10.1093/carcin/bgaf082,Nakamichi S,Carcinogenesis,0143-3334,4,Carcinogenesis,eng,Harris CC,"[""Humans"", ""Carcinoma, Non-Small-Cell Lung"", ""Serine-Arginine Splicing Factors"", ""Cellular Senescence"", ""Lung Neoplasms"", ""Cell Proliferation"", ""Apoptosis"", ""Tumor Suppressor Protein p53"", ""Cell Line, Tumor"", ""Gene Expression Regulation, Neoplastic"", ""RNA, Small Interfering"", ""A549 Cells"", ""Gene Knockdown Techniques"", ""Mutation""]",,41225668,pmc-id: PMC12629605;manuscript-id: NIHMS2122621;,2025 Nov 21,2025,https://pubmed.ncbi.nlm.nih.gov/41225668/,SRSF3 knockdown-induced cellular senescence as a possible therapeutic strategy for non-small cell lung cancer,46,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Hypertrophic cardiomyopathy (HCM) is a prevalent inherited cardiac disorder marked by left ventricular hypertrophy and hypercontractility. This excessive mechanical workload creates an energetic mismatch in which consumption exceeds production, leading to myocardial energy depletion. Although CK (creatine kinase) plays a key role in cardiac energy homeostasis, its involvement in HCM remains unclear. This study investigates how hypercontractility-driven mitochondrial stress and the resulting increase in mitochondrial H2O2 disrupt CK function in HCM. CK function was analyzed using myocardial left ventricular tissue from 92 patients with HCM (with and without pathogenic sarcomere variants) and 30 non-failing human controls. Myofilament and mitochondrial CK isoforms were measured using mRNA analysis, protein immunoblotting, enzyme activity assays, mass spectrometry, and redox-sensitive proteomics. To explore links between hypercontractility, mitochondrial reactive oxygen species, and CK dysfunction, we used isolated cardiomyocytes from wild-type, mitochondrial-targeted catalase-overexpressing, CK knockout (myofilament and mitochondrial CK deletion), HCM-associated Mybpc3 knock-in, and mito-roGFP2-Orp1 mouse models. We also tested the effects of the Ca2+ sensitizer EMD-57033, the CK inhibitor 1-fluoro-2,4-dinitrobenzene (DNFB), and the myosin inhibitor MYK-581, a mavacamten derivative. Our analysis revealed significant reductions in myofilament and mitochondrial CK protein levels, as well as CK activity, in myocardium of patients with HCM, primarily because of oxidative modifications of CK. In isolated mouse cardiomyocytes from wild-type and CK knockouts, hypercontractility induced by EMD-57033 elevated mitochondrial H2O2, causing cellular arrhythmias and CK inactivation. Hypercontractility-induced oxidative stress, arrhythmias, and CK dysfunction were also observed in Mybpc3 knock-in cardiomyocytes. Mitochondrial-targeted catalase-overexpressing mice with enhanced H2O2 scavenging were protected against H2O2-induced (EMD-57033-mediated) arrhythmias and CK dysfunction. MYK-581 treatment in Mybpc3 knock-in cardiomyocytes reduced hypercontractility, lowered H2O2 production and arrhythmias, and preserved CK function. CK inhibition using DNFB in wild-type cardiomyocytes elevated mitochondrial H2O2 levels and triggered cellular arrhythmias. This mitochondrial oxidation was independently confirmed in mito-roGFP2-Orp1 cardiomyocytes exposed to DNFB. Mitochondrial-targeted catalase-overexpressing mice were protected from DNFB-induced oxidative stress and arrhythmogenic events. This study reveals a mechanistic link between hypercontractility, mitochondrial reactive oxygen species, and CK dysfunction in HCM, perpetuating a cycle of energetic dysfunction. Targeting hypercontractility and oxidative stress through myosin inhibition offers a strategy to restore energy balance and reduce arrhythmic risk in HCM.","[""Journal Article""]","[""Xu A"", ""Weissman D"", ""Ermer KJ"", ""Bertero E"", ""Federspiel JM"", ""Stadler F"", ""Grünler E"", ""Tangos M"", ""Zervou S"", ""Waddingham MT"", ""Pearson JT"", ""Reil JC"", ""Scholtz S"", ""Dudek J"", ""Kohlhaas M"", ""Nickel AG"", ""Carrier L"", ""Eschenhagen T"", ""Michels M"", ""Dos Remedios C"", ""Lal S"", ""Prates Roma L"", ""Hamdani N"", ""Kuster DWD"", ""Falcão-Pires I"", ""Johnson CN"", ""Lygate CA"", ""van der Velden J"", ""Maack C"", ""Sequeira V""]",10.1161/CIRCULATIONAHA.125.074120,Xu A,Circulation,0009-7322,24,Circulation,eng,Sequeira V,"[""Animals"", ""Oxidative Stress"", ""Humans"", ""Cardiomyopathy, Hypertrophic"", ""Male"", ""Myocytes, Cardiac"", ""Mice"", ""Female"", ""Middle Aged"", ""Creatine Kinase"", ""Mitochondria, Heart"", ""Myocardial Contraction"", ""Adult"", ""Mice, Knockout"", ""Mice, Inbred C57BL"", ""Hydrogen Peroxide"", ""Carrier Proteins"", ""Myosin Binding Protein C""]",1705-1727,41111389,pmc-id: PMC13227915;manuscript-id: NIHMS2115955;embargo-date: 2026/10/20;,2025 Dec 16,2025,https://pubmed.ncbi.nlm.nih.gov/41111389/,Hypercontractility and Oxidative Stress Drive Creatine Kinase Dysfunction in Hypertrophic Cardiomyopathy,152,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Chimeric antigen receptor (CAR)-T cell therapy has transformed the outcomes of patients with haematological malignancies, yet its use is limited by labour-intensive manufacturing, constrained production capacity and variable clinical performance. In vivo CAR-T cell engineering, in which CAR-T cells are generated directly inside the patient's body, seeks to overcome these challenges by eliminating the need for ex vivo cell processing and complex logistics, as well as improve clinical performance. Recent advances in virology, RNA medicines and nanotechnology have catalysed a radical overhaul of this approach, which uses targeted delivery systems such as lentiviral vectors and lipid nanoparticles to introduce CAR-encoding genetic material into endogenous T cells. Early clinical studies have shown efficient transduction, sustained CAR expression and initial signs of antitumour activity, establishing proof of concept. This Review explores the underlying technologies - including RNA delivered by lipid nanoparticles and engineered viral vectors - and discusses how they are being adapted to develop more broadly applicable, scalable, safe and effective CAR-T cell therapies. By removing the need for ex vivo manipulation and chemotherapeutic conditioning, this strategy could enable the wider application of CAR-T cell therapies not just to blood cancers but to autoimmune diseases for which ex vivo CAR-T cell therapies have shown strong promise, such as systemic lupus erythematosus.","[""Journal Article"", ""Review""]","[""Bot A"", ""Scharenberg A"", ""Friedman K"", ""Guey L"", ""Hofmeister R"", ""Andorko JI"", ""Klichinsky M"", ""Neumann F"", ""Shah JV"", ""Swayer AJ"", ""Trudeau K"", ""Weissman D"", ""Stephan MT"", ""Buchholz CJ"", ""June CH""]",10.1038/s41573-025-01291-5,Bot A,Nature reviews. Drug discovery,1474-1776,2,Nat Rev Drug Discov,eng,June CH,"[""Humans"", ""Receptors, Chimeric Antigen"", ""Animals"", ""Immunotherapy, Adoptive"", ""T-Lymphocytes"", ""Nanoparticles"", ""Genetic Vectors"", ""Hematologic Neoplasms""]",116-137,41028170,,2026 Feb,2026,https://pubmed.ncbi.nlm.nih.gov/41028170/,In vivo chimeric antigen receptor (CAR)-T cell therapy,25,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Allergic diseases have reached epidemic proportions globally, calling attention to the need for better treatment and preventive approaches. Herein, we developed allergen-encoding messenger RNA (mRNA)-lipid nanoparticle (LNP) strategies for both therapy and prevention of allergic responses. Immunization with allergen-encoded mRNA-LNPs modulated T cell differentiation, inhibiting the generation of T helper type 2 and type 17 cells upon allergen exposure in experimental asthma models induced by ovalbumin, and naturally occurring house dust mite (HDM) and the major HDM allergen Der p1. Allergen-specific mRNA-LNP treatment attenuated clinicopathology in both preventive and established allergy models, including reduction in eosinophilia, mucus production, and airway hypersensitivity, while enhancing production of allergen-specific IgG antibodies and maintaining low IgE levels. Additionally, allergen-specific mRNA-LNP vaccines in mice elicited a CD8+CD38+KLRG- T cell response as seen following SARS-CoV-2 mRNA vaccination in humans, underscoring a conserved immune mechanism across species, regardless of the mRNA-encoded protein. Notably, mRNA-LNP vaccination in combination with an mTOR inhibitor reduced the CD8+ T cell response without affecting the vaccine-induced anti-allergic effect in the preventive model of asthma. This technology renders allergen-specific mRNA-LNP therapy a promising approach for prevention and treatment of allergic diseases.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Rochman Y"", ""Kotliar M"", ""Klingler AM"", ""Rochman M"", ""Alameh MG"", ""Melamed JR"", ""Osswald GA"", ""Caldwell JM"", ""Felton JM"", ""Mack LE"", ""Hargis J"", ""Lewkowich IP"", ""Barski A"", ""Weissman D"", ""Rothenberg ME""]",10.1172/JCI194080,Rochman Y,The Journal of clinical investigation,0021-9738,21,J Clin Invest,eng,Rothenberg ME,"[""Animals"", ""Mice"", ""Nanoparticles"", ""Asthma"", ""RNA, Messenger"", ""Allergens"", ""Antigens, Dermatophagoides"", ""Disease Models, Animal"", ""Female"", ""Humans"", ""Lipids"", ""Arthropod Proteins"", ""Mice, Inbred BALB C"", ""Pyroglyphidae"", ""SARS-CoV-2"", ""Ovalbumin"", ""COVID-19 Vaccines"", ""Hypersensitivity"", ""Liposomes""]",,40985871,pmc-id: PMC12578384;,2025 Nov 3,2025,https://pubmed.ncbi.nlm.nih.gov/40985871/,Allergen-specific mRNA-lipid nanoparticle therapy for prevention and treatment of experimental allergy in mice,135,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Autoimmune diseases are chronic conditions where the immune system mistakenly attacks healthy tissues, leading to potentially debilitating symptoms that require lifelong management. There are no cures for autoimmune diseases, and new treatments are urgently needed to improve patient outcomes. This review delves into the compelling advancements and ongoing challenges in harnessing mRNA-lipid nanoparticles (LNPs) as innovative therapies for autoimmune diseases. mRNA-LNPs enable a range of therapeutic approaches to combat autoimmune diseases, including targeted immune cell modulation, tissue regeneration, antigen-specific tolerizing immunotherapy, and in vivo chimeric antigen T cell therapies. To successfully advance this promising class of therapies to the clinic, key challenges must be addressed, such as mitigating unwanted inflammation caused by LNPs, overcoming biological barriers to delivery, and ensuring the long-term safety of mRNA-LNPs specifically in autoimmune contexts. Through their modular design, flexible application, and potential for cost-effective production, mRNA-LNP therapies offer exciting clinical potential to transform the management of autoimmune diseases.","[""Journal Article"", ""Review""]","[""Razavi R"", ""Kegel M"", ""Muscat-Rivera J"", ""Weissman D"", ""Melamed JR""]",10.1016/j.omtm.2025.101566,Razavi R,Molecular therapy. Methods & clinical development,2329-0501,3,Mol Ther Methods Clin Dev,eng,Melamed JR,[],101566,40969676,pmc-id: PMC12441705;,2025 Sep 11,2025,https://pubmed.ncbi.nlm.nih.gov/40969676/,Harnessing mRNA-lipid nanoparticles as innovative therapies for autoimmune diseases,33,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"T cells play an important role in initiating antibody responses by instructive signals of cell-cell contacts and secretion of soluble cytokines as mediators. We investigated the role of the modified soluble E2 (sE2F442NYT) antigen from hepatitis C virus (HCV) on healthy human peripheral blood mononuclear cell (PBMC)-derived immune cells or immunized mouse cells to understand the mechanisms of immune regulation by the candidate vaccine antigen. HCV E2 and E2F442NYT displayed a role in inducing type 17 T-helper cell (Th17) phenotype, as indicated by interleukin-17 (IL-17) expression and signal transducer and activator of transcription 3 (Stat3) phosphorylation. The spleen cells from sE2-mRNA-lipid nanoparticles (LNPs) or sE2F442NYT-mRNA-LNP-immunized mice exhibited similar IL-17A mRNA levels, and Th17 (CXCR3-CCR6+) cells in CD4+CD44+ spleen cells, supporting both sE2 and modified sE2F442NYT-induced Th17 polarization. Immunohistochemical and multiplex immunofluorescence imaging studies revealed abundant CD4+CXCR5+T cells co-localized with BCL6 in sE2F442NYT-mRNA-LNP immunized mouse spleen cells than unmodified sE2-mRNA-LNP immunized animals, suggesting sE2F442NYT induces stronger follicular helper T cell generation. We previously demonstrated increased total IgG production and isotype switching from IgG1 to IgG2a and IgG2b in sE2442NYT immunized mice. The stronger B and T cell responses observed from modified sE2F442NYT support the overall in vivo outcome of the study toward a higher B helper T cell generation from sE2F442NYT-mRNA-LNP immunization as compared to unmodified sE2-mRNA-LNP.IMPORTANCEThe study will help rationalize HCV vaccine antigen selection for an effective immune response. Extension by additional strategies may be useful to direct stronger B helper T cell generation for prolonged vaccine-associated protection.","[""Journal Article"", ""Research Support, N.I.H., Extramural""]","[""Haga Y"", ""Babu E P"", ""Swiderska-Syn M"", ""Reagan EK"", ""Weissman D"", ""Ray R""]",10.1128/jvi.01355-25,Haga Y,Journal of virology,0022-538X,10,J Virol,eng,Ray R,"[""Animals"", ""Humans"", ""Mice"", ""Hepacivirus"", ""Th17 Cells"", ""Receptors, CXCR5"", ""Viral Hepatitis Vaccines"", ""RNA, Messenger"", ""Nanoparticles"", ""Female"", ""Interleukin-17"", ""Hepatitis C"", ""Leukocytes, Mononuclear"", ""T-Lymphocytes, Helper-Inducer"", ""Liposomes"", ""Viral Envelope Proteins""]",e0135525,40910688,pmc-id: PMC12548457;,2025 Oct 23,2025,https://pubmed.ncbi.nlm.nih.gov/40910688/,Hepatitis C virus modified (S)E2(F442NYT)-mRNA-LNP candidate vaccine promotes helper CXCR5(+)T cells,99,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Strengthening mRNA vaccine development in LMICs is essential for enhancing global pandemic preparedness. This study evaluated the safety and immunogenicity of Comvigen, a bivalent SARS-CoV-2 vaccine, in comparison to the Comirnaty bivalent vaccine (Comirnaty). This phase II, randomised, open-label, non-inferiority trial was conducted in Thailand across four centres. Participants (n = 450) were randomly assigned (2:1) to receive either Comvigen (50 μg) or Comirnaty (30 μg), using block randomisation (size = 9). Eligible participants had completed at least 2 doses of any approved COVID-19 vaccine, with the last mRNA-vaccine dose given over 3 months before enrolment. The non-inferiority margin of a geometric mean ratio (GMR) of 0.67. The primary immunogenicity endpoint was pseudovirus neutralisation titres (psVNT-50) against SARS-CoV-2 wild-type and Omicron BA.4/BA.5 at Day 29. Safety outcomes included local and systemic adverse reactions up to six months post-vaccination. Immunogenicity analyses were conducted on the Per-Protocol (PP) population and the modified Intent-to-Treat (mITT) population; safety analyses included all participants. Laboratory personnel were blinded to vaccine assignment (ClinicalTrials.gov: NCT05930730). Between October and November 2023, 450 participants were enrolled (median age of 36 years, IQR 30-45). At day 29, the geometric mean titre (GMT) of psVNT-50 against wild-type virus increased from 475.9 to 2062.9 for Comvigen and from 458.8 to 1905.1 for Comirnaty (GMR 1.1, 95% CI: 1.0-1.2), meeting non-inferiority criteria. Against Omicron BA.4/BA.5, GMTs were 3909.8 for Comvigen and 3288.6 for Comirnaty (GMR 1.2, 95% 1.0-1.4). Local and systemic reactions were more frequent with Comvigen (91% vs. 78%, p = 0.0002, 79% vs. 70%, p = 0.028) but were mild or moderate and transient with no difference in fever (6% vs. 5%, p = 0.84). Comvigen demonstrated non-inferiority immunogenicity to Comirnaty and had a comparable safety profile, supporting mRNA vaccine development for global access and pandemic preparedness. Covid-19 Pandemic Emergency Fund granted by Thailand's National Economic and Social Development Council provided major funding. Supplementary funding was provided by National Vaccine Institute (NVI), Thailand; Center of Excellence in Vaccine Research and Development (Chula VRC), Faculty of Medicine, Chulalongkorn University; Chulalongkorn University Second Century Fund (C2F); BioNet-Asia and Public Donation through Covid-19 vaccine development fund of the Faculty of Medicine, Chulalongkorn University and the Thai Red Cross Society, Thailand.","[""Journal Article""]","[""Jantarabenjakul W"", ""Nantanee R"", ""Puthanakit T"", ""Gatechompol S"", ""Avihingsanon A"", ""Punrin S"", ""Tantawichien T"", ""Nitayaphan S"", ""Thitithanyanont A"", ""Buranapraditkun S"", ""Jongkaewwattana A"", ""Ketloy C"", ""Prompetchara E"", ""Lawpoolsri S"", ""Wijagkanalan W"", ""Alameh MG"", ""Hong L"", ""Samija M"", ""Weissman D"", ""Ruxrungtham K"", ""ChulaVac006 Study Team""]",10.1016/j.lansea.2025.100650,Jantarabenjakul W,The Lancet regional health. Southeast Asia,2772-3682,,Lancet Reg Health Southeast Asia,eng,Ruxrungtham K,[],100650,40895389,pmc-id: PMC12390948;,2025 Sep,2025,https://pubmed.ncbi.nlm.nih.gov/40895389/,"Immunogenicity and safety of 'Comvigen', a bivalent SARS-CoV-2 vaccine, in comparison to Comirnaty bivalent vaccine in Thailand: a phase 2, non-inferiority randomised trial",40,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Severe fever with thrombocytopenia syndrome virus (SFTSV) is a highly pathogenic bunyavirus with a high case-fatality ratio for which there is no approved vaccine. Studies have assessed different vaccine technologies. However, few studies have yet assessed the immunogenicity of heterologous prime-boost regimens. Here, we compare a lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA-based vaccine encoding the SFTSV glycoproteins, Gn and Gc, to our recently described recombinant VSV SFTSV (rVSV-SFTSV) vaccine in single dose, homologous, and heterologous prime-boost regimens in mice. We show that all regimens protect from pathogenic SFTSV challenge and elicit strong long-lasting antibody responses. Furthermore, strong cellular immunity is elicited by mRNA-LNP immunizations and by heterologous immunization with an rVSV-SFTSV prime and mRNA-LNP boost. Cellular responses robustly polarized towards a type 1 response, characterized by high levels of IFNγ, TNFα, and IL-2. Immunization with mRNA led to a mixed type 1/type 2 immune response, as determined by antibody isotypes IgG1 and IgG2c. We found that homologous immunization leads to stronger antibody responses while heterologous immunization drives a slightly stronger cellular response. Taken together, the vaccine platforms described here represent strong vaccine candidates for further development.","[""Journal Article""]","[""Manzoni TB"", ""Westover JB"", ""Lundgreen KA"", ""Hicks PD"", ""Petch RJ"", ""Ort JT"", ""Weissman D"", ""Fan SHY"", ""Hensley SE"", ""Pardi N"", ""Gowen BB"", ""Bates P""]",10.3390/v17081095,Manzoni TB,Viruses,1999-4915,8,Viruses,eng,Bates P,"[""Animals"", ""Mice"", ""Viral Vaccines"", ""Antibodies, Viral"", ""RNA, Messenger"", ""Phlebovirus"", ""Vaccination"", ""Female"", ""Glycoproteins"", ""Vaccines, Synthetic"", ""Severe Fever with Thrombocytopenia Syndrome"", ""Immunity, Cellular"", ""Mice, Inbred BALB C"", ""Antibodies, Neutralizing"", ""Immunoglobulin G"", ""mRNA Vaccines"", ""Nanoparticles""]",,40872809,pmc-id: PMC12390526;,2025 Aug 8,2025,https://pubmed.ncbi.nlm.nih.gov/40872809/,Homologous and Heterologous Vaccination Regimens with mRNA and rVSV Platforms Induce Potent Immune Responses Against SFTSV Glycoprotein,17,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Plasmodium vivax poses significant challenges to malaria control due to its relapsing nature. This study explores the immunogenicity and efficacy of nucleoside-modified mRNA-lipid nanoparticle (LNP) vaccines targeting the P. vivax circumsporozoite protein (PvCSP). Two mRNA constructs encoding PvCSP were designed and tested in mice. Despite lower protein expression, the vaccine encoding the wild-type signal peptide (SP) and glycosylphosphatidylinositol (GPI) anchor of PvCSP induced significantly higher antibody titers against the PvCSP and its repeat region compared with the mRNA construct with SP but without GPI. The immunogenicity of PvCSP mRNA-LNP vaccines was evaluated using various administration routes and immunization schedules. Both intradermal and intramuscular delivery generated dose-dependent antibody responses, but the former demonstrated superior responses at a lower dose. Conversely, intravenous administration resulted in very poor responses. Notably, administering a delayed third dose intramuscularly 5 months after the second dose resulted in significantly higher levels of anti-repeat region antibodies and enhanced T cell responses in both the spleen and liver. This delayed regimen provided strong protection against sporozoite challenge, with the magnitude and avidity of anti-repeat region antibodies linked to this protection. These findings highlight the potential of the nucleoside-modified mRNA-LNP vaccine platform in combating P. vivax pre-erythrocytic stage infection.","[""Journal Article""]","[""Limsalakpetch A"", ""Kum-Arb U"", ""Yongvanitchit K"", ""Im-Erbsin R"", ""Ubalee R"", ""Waters N"", ""Vesely BA"", ""Muramatsu H"", ""Weissman D"", ""Tam YK"", ""Yoshida S"", ""Adams J"", ""Yadava A"", ""Pardi N"", ""Pichyangkul S""]",10.1016/j.omtn.2025.102645,Limsalakpetch A,Molecular therapy. Nucleic acids,2162-2531,3,Mol Ther Nucleic Acids,eng,Pichyangkul S,[],102645,40832631,pmc-id: PMC12359152;,2025 Sep 9,2025,https://pubmed.ncbi.nlm.nih.gov/40832631/,mRNA-LNP vaccine encoding the Plasmodium vivax circumsporozoite protein is highly immunogenic and confers protection in mice,36,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
,"[""Published Erratum""]","[""Gong N"", ""Kim D"", ""Alameh MG"", ""El-Mayta R"", ""Han EL"", ""Dwivedi G"", ""Palanki R"", ""Shi Q"", ""Han X"", ""Xue L"", ""Xu J"", ""Meng Z"", ""Luo T"", ""Figueroa-Espada CG"", ""Weissman D"", ""Li J"", ""Mitchell MJ""]",10.1038/s41551-025-01486-6,Gong N,Nature biomedical engineering,2157-846X,12,Nat Biomed Eng,eng,Mitchell MJ,[],2215,40745065,,2025 Dec,2025,https://pubmed.ncbi.nlm.nih.gov/40745065/,Author Correction: Mannich reaction-based combinatorial libraries identify antioxidant ionizable lipids for mRNA delivery with reduced immunogenicity,9,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
,"[""Editorial""]","[""Weissman D"", ""Maack C""]",10.1016/j.jacbts.2025.101333,Weissman D,JACC. Basic to translational science,2452-302X,7,JACC Basic Transl Sci,eng,Maack C,[],101333,40738519,pmc-id: PMC12434228;,2025 Jul,2025,https://pubmed.ncbi.nlm.nih.gov/40738519/,ATP-Citrate Lyase in Heart Failure: A Redox Node in NAD(+)/NADH Homeostasis,10,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"The immunogenicity of lipid nanoparticles (LNPs) used for the delivery of nucleoside-modified messenger RNA limits the levels and durability of expression of the encoded protein. Here, by leveraging the Mannich reaction for ionizable lipid synthesis, and via the in vitro and in vivo screening of six combinatorial libraries of synthesized lipids, we report the identification of an antioxidant ionizable lipid, C-a16, exhibiting reduced immunogenicity. When incorporated into LNPs for mRNA delivery, C-a16 mitigated the generation of intracellular reactive oxygen species, thereby extending the duration of protein expression. In mice, and compared with commercial LNPs, LNPs incorporating C-a16 and co-delivering Cas9 mRNA and guide RNA for the editing of the transthyretin gene led to 2.8-fold higher editing efficiency; LNPs with C-a16 delivering fibroblast growth factor 21 mRNA increased the expression of the protein 3.6-fold; and when delivering mRNA encoding a tumour neoantigen or the spike protein of SARS-CoV-2, LNPs with C-a16 induced stronger antigen-specific immune responses. Our findings support the further testing of C-a16 as a promising ionizable lipid for mRNA delivery in therapeutic applications.","[""Journal Article""]","[""Gong N"", ""Kim D"", ""Alameh MG"", ""El-Mayta R"", ""Han EL"", ""Dwivedi G"", ""Palanki R"", ""Shi Q"", ""Han X"", ""Xue L"", ""Xu J"", ""Meng Z"", ""Luo T"", ""Figueroa-Espada CG"", ""Weissman D"", ""Li J"", ""Mitchell MJ""]",10.1038/s41551-025-01422-8,Gong N,Nature biomedical engineering,2157-846X,12,Nat Biomed Eng,eng,Mitchell MJ,"[""Animals"", ""Lipids"", ""Mice"", ""RNA, Messenger"", ""Humans"", ""Nanoparticles"", ""Antioxidants"", ""SARS-CoV-2"", ""Spike Glycoprotein, Coronavirus"", ""COVID-19"", ""Female"", ""Reactive Oxygen Species"", ""Gene Transfer Techniques"", ""Combinatorial Chemistry Techniques"", ""Gene Editing"", ""Liposomes""]",2181-2195,40681859,,2025 Dec,2025,https://pubmed.ncbi.nlm.nih.gov/40681859/,Mannich reaction-based combinatorial libraries identify antioxidant ionizable lipids for mRNA delivery with reduced immunogenicity,9,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"DNA-lipid nanoparticles (DNA-LNPs) loaded with inhibitors of the cGAS-STING pathway enable safe and effective delivery of DNA in vivo . Herein, we report the first instances of extrahepatic DNA-LNP targeting. DNA-LNPs conjugated to antibodies against PECAM-1 or VCAM-1 target the endothelium of the lungs and brain/spleen, respectively. These LNPs drive robust transgene expression in their target organs, with greater magnitude and duration than untargeted LNPs. Lung specificity of PECAM-targeted transgene expression increases over two weeks, resulting in markedly higher lung-to-liver expression ratios than our previous PECAM-targeted mRNA-LNPs. Off-target liver DNA expression declines to undetectable levels but persists in the lungs, while mRNA expression uniformly decreases due to its short half-life. We further improve this expression specificity by replacing full-length antibodies with Fab fragments. Single-cell analysis reveals a key mechanism underlying the improvements in organ-specificity: target organ expression is dominated by long-lived endothelial cells, while off-target liver delivery and expression are in non-endothelial cells with shorter half-lives. Collectively, these studies demonstrate that targeted DNA-LNPs achieve high levels of organ- and cell-type-specific transgene expression and thus provide a therapeutic platform for dozens of endothelial-centric diseases.","[""Journal Article"", ""Preprint""]","[""Marzolini N"", ""Brysgel TV"", ""Rahman RJ"", ""Essien EO"", ""Nwe SY"", ""Wu J"", ""Majumder A"", ""Patel MN"", ""Tiwari S"", ""Espy CL"", ""Dong F"", ""Shah A"", ""Shuvaev VV"", ""Hood ED"", ""Chase LS"", ""Weissman D"", ""Katzen JB"", ""Frank DB"", ""Bennett ML"", ""Marcos-Contreras OA"", ""Myerson JW"", ""Muzykantov VR"", ""Reyes-Esteves S"", ""Brenner JS""]",10.1101/2025.07.09.663747,Marzolini N,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Brenner JS,[],,40672218,pmc-id: PMC12265523;,2025 Oct 23,2025,https://pubmed.ncbi.nlm.nih.gov/40672218/,"Targeting DNA-LNPs to Endothelial Cells Improves Expression Magnitude, Duration, and Specificity",,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Dermal resident memory CD4+ T cells (dTrm) provide protection against vector-borne infections. However, the factors that promote their development remain unclear. We tested if an mRNA vaccine, encoding a protective leishmanial antigen, induced dTrm cells. The mRNA vaccine induced robust systemic T-cell responses, but few Trm cells were found in the skin. Since IL-12 promotes Th1 responses, we tested whether IL-12 mRNA combined with the mRNA vaccine could enhance dTrm cell development. This combination significantly expanded Leishmania-specific Th1 cells expressing skin-homing molecules and memory T cell markers in the draining lymph node. Additionally, higher numbers of dTrm cells were maintained in the skin, and mice exhibited functional immunity indicated by a delayed hypersensitivity response and protection upon challenge with Leishmania. These findings highlight IL-12 as a key driver of CD4+ dTrm development, enabling their global seeding across the skin, and underscore the potential of IL-12-enhanced mRNA vaccines to generate durable immunity against cutaneous leishmaniasis and other skin-targeted infections.","[""Journal Article""]","[""Zabala-Peñafiel A"", ""Gonzalez-Lombana C"", ""Alameh MG"", ""Sacramento LA"", ""Mou Z"", ""Phan AT"", ""Aunins EA"", ""Tam YK"", ""Uzonna JE"", ""Weissman D"", ""Hunter CA"", ""Scott P""]",10.1038/s41541-025-01213-x,Zabala-Peñafiel A,NPJ vaccines,2059-0105,1,NPJ Vaccines,eng,Scott P,[],154,40670370,pmc-id: PMC12267433;,2025 Jul 16,2025,https://pubmed.ncbi.nlm.nih.gov/40670370/,IL-12 mRNA-LNP promotes dermal resident memory CD4(+) T cell development,10,BaQcQa62qrhFCBhYV,vZLiaTlv24nA5laiM
"Severe proteinopathies-such as retinitis pigmentosa, a form of inherited blindness-are driven by genetic mutations that overwhelm the quality control of the post-endoplasmic reticulum (post-ER) secretory pathway, causing toxic protein accumulation. Here, we identify a therapeutic node defined by a hetero-oligomeric cargo receptor complex consisting of TMED7, 2, 9, and 10. This ""entrapment complex"" anchors structurally and functionally diverse mutant clients within the early secretory pathway via TMED7 binding to the integral Golgi protein GRASP55. Disruption of the entrapment complex results in the clearance of accumulated protein cargoes. In vivo ablation of the entrapment node via inducible genetic deletion or via the small molecule BRD7635 reverses histopathological hallmarks and rescues functional deficits in clinically distinct proteinopathies of the kidney and the eye, including mitigating vision loss in a mouse model of retinitis pigmentosa.","[""Journal Article"", ""Preprint""]","[""Khursigara MR"", ""Goss AC"", ""Kost-Alimova M"", ""Keller K"", ""De Mata CD"", ""Muraleedharan R"", ""Collantes ER"", ""Brown M"", ""Grinkevich E"", ""Arines FM"", ""Lin J"", ""Byrne P"", ""Valenti SB"", ""Morici E"", ""Roignot J"", ""Zavras J"", ""Silverman BR"", ""Ignacio JC"", ""Myung Y"", ""Kwon S"", ""Nelson A"", ""Yoo H"", ""Melanson M"", ""Racette M"", ""Padovano V"", ""Alper SL"", ""Carey D"", ""Udeshi ND"", ""Carr SA"", ""Dvela-Levitt M"", ""Narimatsu T"", ""Sakuno G"", ""Correa VSMC"", ""Efstathiou NE"", ""Ntentakis DP"", ""Cao T"", ""Dong Z"", ""Nguyen KT"", ""Menezes CR"", ""Kurumbail R"", ""Kazmirski S"", ""Xiao L"", ""Wu H"", ""Liu D"", ""Iqbal S"", ""Lander ES"", ""Vavvas DG"", ""Palczewski K"", ""Pablo JLB"", ""Greka A""]",10.64898/2026.07.10.737576,Khursigara MR,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Greka A,[],,42523240,pmc-id: PMC13404660;,2026 Jul 13,2026,https://pubmed.ncbi.nlm.nih.gov/42523240/,A cargo receptor entrapment complex is a therapeutic node for genetically and clinically distinct proteinopathies,,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Ancient DNA has transformed our understanding of population history1, but its potential to reveal as much about human evolutionary biology has not been realized because of limited sample sizes and the difficulty of distinguishing sustained rises in allele frequency increasing fitness-directional selection-from shifts due to migrations, population structure, or non-adaptive purifying or stabilizing selection2-7. Here we present a method for detecting directional selection in ancient DNA time-series data that tests for consistent trends in allele frequency change over time, and apply it to 15,836 West Eurasians (10,016 with new data). Previous work has shown that classic hard sweeps driving advantageous mutations to fixation have been rare over the broad span of human evolution8,9. By contrast, in the past ten millennia, we find that many hundreds of alleles have been affected by strong directional selection. We also document one-standard-deviation changes on the scale of modern variation in combinations of alleles that today predict complex traits. This includes decreases in predicted body fat and schizophrenia, and increases in measures of cognitive performance. These effects were measured in industrialized societies, and it remains unclear how these relate to phenotypes that were adaptive in the past. We estimate selection coefficients at 9.7 million variants, enabling study of how Darwinian forces couple to allelic effects and shape the genetic architecture of complex traits.","[""Journal Article""]","[""Akbari A"", ""Perry A"", ""Barton AR"", ""Kariminejad M"", ""Gazal S"", ""Li Z"", ""Zeng Y"", ""Mittnik A"", ""Patterson N"", ""Mah M"", ""Zhou X"", ""Price AL"", ""Lander ES"", ""Pinhasi R"", ""Rohland N"", ""Mallick S"", ""Reich D""]",10.1038/s41586-026-10358-1,Akbari A,Nature,0028-0836,8118,Nature,eng,Reich D,"[""Humans"", ""Alleles"", ""Asia"", ""DNA, Ancient"", ""Europe"", ""Evolution, Molecular"", ""Gene Frequency"", ""History, Ancient"", ""Phenotype"", ""Selection, Genetic""]",419-428,41986721,pmc-id: PMC13189228;manuscript-id: NIHMS2168269;,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/41986721/,Ancient DNA reveals pervasive directional selection across West Eurasia,654,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Identifying the causal variants and mechanisms that drive complex traits and diseases remains a core problem in human genetics1-5. Most of these variants individually have weak effects6 and lie in non-coding gene-regulatory elements7-10, for which we lack a complete understanding of how single-nucleotide alterations modulate transcriptional processes to affect human phenotypes5,11-15. To address this problem, we measured the activity of 221,412 fine-mapped trait-associated variants using a massively parallel reporter assay16-20 in 5 diverse cell types. We show that this assay effectively discriminates between likely causal variants and controls, and identified 13,121 regulatory variants with high precision. Although the effects of these variants largely agree with orthogonal measures of function, only 69% of them can plausibly be explained by the disruption of a known transcription factor binding motif. We investigated the mechanisms of 136 variants using saturation mutagenesis and assigned affected transcription factors for 91% of variants without a clear canonical mechanism. Finally, we detected regulatory epistasis at 11% of tested regulatory variants in close proximity and identified multiple functional variants on the same haplotype at a small, but important, subset of trait-associated loci. Overall, our study provides a systematic functional characterization of likely causal common variants that underlie complex and molecular human traits, enabling new insights into the regulatory grammar underlying disease risk.","[""Journal Article""]","[""Siraj L"", ""Castro RI"", ""Dewey HB"", ""Kales S"", ""Butts JC"", ""Nguyen TTL"", ""Kanai M"", ""Berenzy D"", ""Mouri K"", ""Wang QS"", ""Fiziev PP"", ""Tsuo K"", ""McCaw ZR"", ""Gosai SJ"", ""Aguet F"", ""Cui R"", ""Kassam I"", ""McRae J"", ""Vockley CM"", ""Lareau CA"", ""Abramov S"", ""Boystov A"", ""Vierstra J"", ""Okada Y"", ""Gusev A"", ""Jones TR"", ""Lander ES"", ""Sabeti PC"", ""Finucane HK"", ""Reilly SK"", ""Ulirsch JC"", ""Tewhey R""]",10.1038/s41586-026-10121-6,Siraj L,Nature,0028-0836,,Nature,eng,Tewhey R,[],,41741648,,2026 Feb 25,2026,https://pubmed.ncbi.nlm.nih.gov/41741648/,Functional dissection of complex trait variants at single-nucleotide resolution,,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Large-scale scientific datasets today contain tens of thousands of random variables across millions of samples (for example, the RNA expression levels of 20,000 protein-coding genes across 30 million single cells). Being able to quantify dependencies between these variables would help us discover novel relationships between variables of interest. Simple measures of dependence, such as Pearson correlation, are fast to compute, but limited in that they are designed to detect linear relationships between variables. Complex measures are known with the ability to detect any kind of dependence, but they do not readily scale to many modern datasets of interest. We introduce the InterDependence Score (IDS), a scalable measure of dependence that captures linear and various nonlinear dependencies between random variables. Our IDS algorithm is motivated by a dependence measure defined in infinite-dimensional Hilbert spaces, capable of capturing any type of dependence, and a fast (linear time) algorithm that neural networks natively implement to compute dependencies between random variables. We apply IDS to identify 1) relevant variables for predictive modeling tasks, 2) sets of words forming topics from millions of documents, and 3) sets of genes related to ""gene-expression programs"" in tens of millions of cells. We provide an efficient implementation that computes IDS between billions of pairs of variables across millions of samples in several hours on a single GPU. Given its speed and effectiveness in identifying nonlinear dependencies, we envision IDS will be a valuable tool for uncovering insights from scientific data.","[""Journal Article""]","[""Radhakrishnan A"", ""Jain Y"", ""Uhler C"", ""Lander ES""]",10.1073/pnas.2509860122,Radhakrishnan A,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,34,Proc Natl Acad Sci U S A,eng,Lander ES,"[""Algorithms"", ""Humans"", ""Computational Biology""]",e2509860122,40833404,pmc-id: PMC12403096;,2025 Aug 26,2025,https://pubmed.ncbi.nlm.nih.gov/40833404/,Efficiently quantifying dependence in massive scientific datasets using InterDependence Scores,122,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Regulatory DNA provides a platform for transcription factor binding to encode cell-type-specific patterns of gene expression. However, the effects and programmability of regulatory DNA sequences remain difficult to map or predict. Here, we develop variant effects from flow-sorting experiments with CRISPR targeting screens (Variant-EFFECTS) to introduce hundreds of designed edits to endogenous regulatory DNA and quantify their effects on gene expression. We systematically dissect and reprogram 3 regulatory elements for 2 genes in 2 cell types. These data reveal endogenous binding sites with effects specific to genomic context, transcription factor motifs with cell-type-specific activities, and limitations of computational models for predicting the effect sizes of variants. We identify small edits that can tune gene expression over a large dynamic range, suggesting new possibilities for prime-editing-based therapeutics targeting regulatory DNA. Variant-EFFECTS provides a generalizable tool to dissect regulatory DNA and to identify genome editing reagents that tune gene expression in an endogenous context.","[""Journal Article""]","[""Martyn GE"", ""Montgomery MT"", ""Jones H"", ""Guo K"", ""Doughty BR"", ""Linder J"", ""Bisht D"", ""Xia F"", ""Cai XS"", ""Chen Z"", ""Cochran K"", ""Lawrence KA"", ""Munson G"", ""Pampari A"", ""Fulco CP"", ""Sahni N"", ""Kelley DR"", ""Lander ES"", ""Kundaje A"", ""Engreitz JM""]",10.1016/j.cell.2025.03.034,Martyn GE,Cell,0092-8674,12,Cell,eng,Engreitz JM,"[""Humans"", ""Gene Editing"", ""CRISPR-Cas Systems"", ""DNA"", ""Transcription Factors"", ""Regulatory Sequences, Nucleic Acid"", ""Gene Expression Regulation"", ""Binding Sites"", ""Animals"", ""Mice"", ""HEK293 Cells"", ""Clustered Regularly Interspaced Short Palindromic Repeats""]",3349-3366.e23,40245860,pmc-id: PMC12167154;manuscript-id: NIHMS2068679;,2025 Jun 12,2025,https://pubmed.ncbi.nlm.nih.gov/40245860/,Rewriting regulatory DNA to dissect and reprogram gene expression,188,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Most phenotype-associated genetic variants map to noncoding regulatory regions of the human genome, but their mechanisms remain elusive in most cases. We developed a highly efficient strategy, Perturb-multiome, to simultaneously profile chromatin accessibility and gene expression in single cells with CRISPR-mediated perturbation of master transcription factors (TFs). We examined the connection between TFs, accessible regions, and gene expression across the genome throughout hematopoietic differentiation. We discovered that variants within TF-sensitive accessible chromatin regions in erythroid differentiation, although representing <0.3% of the genome, show a ~100-fold enrichment for blood cell phenotype heritability, which is substantially higher than that for other accessible chromatin regions. Our approach facilitates large-scale mechanistic understanding of phenotype-associated genetic variants by connecting key cis-regulatory elements and their target genes within gene regulatory networks.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Martin-Rufino JD"", ""Caulier A"", ""Lee S"", ""Castano N"", ""King E"", ""Joubran S"", ""Jones M"", ""Goldman SR"", ""Arora UP"", ""Wahlster L"", ""Lander ES"", ""Sankaran VG""]",10.1126/science.ads7951,Martin-Rufino JD,"Science (New York, N.Y.)",0036-8075,6742,Science,eng,Sankaran VG,"[""Humans"", ""Transcription Factors"", ""Gene Regulatory Networks"", ""Chromatin"", ""Phenotype"", ""Single-Cell Analysis"", ""CRISPR-Cas Systems"", ""Genome, Human"", ""Genetic Variation"", ""Blood Cells"", ""Cell Differentiation"", ""Erythropoiesis"", ""Erythroid Cells""]",52-59,40179192,pmc-id: PMC12168499;manuscript-id: NIHMS2076308;,2025 Apr 4,2025,https://pubmed.ncbi.nlm.nih.gov/40179192/,Transcription factor networks disproportionately enrich for heritability of blood cell phenotypes,388,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"The time required to conduct clinical trials limits the rate at which we can evaluate and deliver new treatment options to patients with cancer. New approaches to increase trial efficiency while maintaining rigor would benefit patients, especially in oncology, in which adjuvant trials hold promise for intercepting metastatic disease, but typically require large numbers of patients and many years to complete. We envision a standing platform - an infrastructure to support ongoing identification and trial enrolment of patients with cancer with early molecular evidence of disease (MED) after curative-intent therapy for early-stage cancer, based on the presence of circulating tumour DNA. MED strongly predicts subsequent recurrence, with the vast majority of patients showing radiographic evidence of disease within 18 months. Such a platform would allow efficient testing of many treatments, from small exploratory studies to larger pivotal trials. Trials enrolling patients with MED but without radiographic evidence of disease have the potential to advance drug evaluation because they can be smaller (given high probability of recurrence) and faster (given short time to recurrence) than conventional adjuvant trials. Circulating tumour DNA may also provide a valuable early biomarker of treatment effect, which would allow small signal-finding trials. In this Perspective, we discuss how such a platform could be established.","[""Journal Article"", ""Review""]","[""Medford AJ"", ""Carmeli AB"", ""Ritchie A"", ""Wagle N"", ""Garraway L"", ""Lander ES"", ""Parikh A""]",10.1038/s41568-024-00742-2,Medford AJ,Nature reviews. Cancer,1474-175X,11,Nat Rev Cancer,eng,Parikh A,"[""Humans"", ""Circulating Tumor DNA"", ""Neoplasms"", ""Neoplasm Recurrence, Local"", ""Biomarkers, Tumor"", ""Drug Development"", ""Antineoplastic Agents"", ""Clinical Trials as Topic""]",810-821,39349822,,2024 Nov,2024,https://pubmed.ncbi.nlm.nih.gov/39349822/,A standing platform for cancer drug development using ctDNA-based evidence of recurrence,24,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"We present a method for detecting evidence of natural selection in ancient DNA time-series data that leverages an opportunity not utilized in previous scans: testing for a consistent trend in allele frequency change over time. By applying this to 8433 West Eurasians who lived over the past 14000 years and 6510 contemporary people, we find an order of magnitude more genome-wide significant signals than previous studies: 347 independent loci with >99% probability of selection. Previous work showed that classic hard sweeps driving advantageous mutations to fixation have been rare over the broad span of human evolution, but in the last ten millennia, many hundreds of alleles have been affected by strong directional selection. Discoveries include an increase from ~0% to ~20% in 4000 years for the major risk factor for celiac disease at HLA-DQB1; a rise from ~0% to ~8% in 6000 years of blood type B; and fluctuating selection at the TYK2 tuberculosis risk allele rising from ~2% to ~9% from ~5500 to ~3000 years ago before dropping to ~3%. We identify instances of coordinated selection on alleles affecting the same trait, with the polygenic score today predictive of body fat percentage decreasing by around a standard deviation over ten millennia, consistent with the ""Thrifty Gene"" hypothesis that a genetic predisposition to store energy during food scarcity became disadvantageous after farming. We also identify selection for combinations of alleles that are today associated with lighter skin color, lower risk for schizophrenia and bipolar disease, slower health decline, and increased measures related to cognitive performance (scores on intelligence tests, household income, and years of schooling). These traits are measured in modern industrialized societies, so what phenotypes were adaptive in the past is unclear. We estimate selection coefficients at 9.9 million variants, enabling study of how Darwinian forces couple to allelic effects and shape the genetic architecture of complex traits.","[""Journal Article"", ""Preprint""]","[""Akbari A"", ""Barton AR"", ""Gazal S"", ""Li Z"", ""Kariminejad M"", ""Perry A"", ""Zeng Y"", ""Mittnik A"", ""Patterson N"", ""Mah M"", ""Zhou X"", ""Price AL"", ""Lander ES"", ""Pinhasi R"", ""Rohland N"", ""Mallick S"", ""Reich D""]",10.1101/2024.09.14.613021,Akbari A,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Reich D,[],,39314480,pmc-id: PMC11419161;,2024 Sep 15,2024,https://pubmed.ncbi.nlm.nih.gov/39314480/,Pervasive findings of directional selection realize the promise of ancient DNA to elucidate human adaptation,,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Most phenotype-associated genetic variants map to non-coding regulatory regions of the human genome. Moreover, variants associated with blood cell phenotypes are enriched in regulatory regions active during hematopoiesis. To systematically explore the nature of these regions, we developed a highly efficient strategy, Perturb-multiome, that makes it possible to simultaneously profile both chromatin accessibility and gene expression in single cells with CRISPR-mediated perturbation of a range of master transcription factors (TFs). This approach allowed us to examine the connection between TFs, accessible regions, and gene expression across the genome throughout hematopoietic differentiation. We discovered that variants within the TF-sensitive accessible chromatin regions, while representing less than 0.3% of the genome, show a ~100-fold enrichment in heritability across certain blood cell phenotypes; this enrichment is strikingly higher than for other accessible chromatin regions. Our approach facilitates large-scale mechanistic understanding of phenotype-associated genetic variants by connecting key cis-regulatory elements and their target genes within gene regulatory networks.","[""Journal Article"", ""Preprint""]","[""Martin-Rufino JD"", ""Caulier A"", ""Lee S"", ""Castano N"", ""King E"", ""Joubran S"", ""Jones M"", ""Goldman SR"", ""Arora UP"", ""Wahlster L"", ""Lander ES"", ""Sankaran VG""]",10.1101/2024.09.09.611392,Martin-Rufino JD,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Sankaran VG,[],,39314298,pmc-id: PMC11419094;,2024 Sep 9,2024,https://pubmed.ncbi.nlm.nih.gov/39314298/,Transcription factor networks disproportionately enrich for heritability of blood cell phenotypes,,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Enhancers are key drivers of gene regulation thought to act via 3D physical interactions with the promoters of their target genes. However, genome-wide depletions of architectural proteins such as cohesin result in only limited changes in gene expression, despite a loss of contact domains and loops. Consequently, the role of cohesin and 3D contacts in enhancer function remains debated. Here, we developed CRISPRi of regulatory elements upon degron operation (CRUDO), a novel approach to measure how changes in contact frequency impact enhancer effects on target genes by perturbing enhancers with CRISPRi and measuring gene expression in the presence or absence of cohesin. We systematically perturbed all 1,039 candidate enhancers near five cohesin-dependent genes and identified 34 enhancer-gene regulatory interactions. Of 26 regulatory interactions with sufficient statistical power to evaluate cohesin dependence, 18 show cohesin-dependent effects. A decrease in enhancer-promoter contact frequency upon removal of cohesin is frequently accompanied by a decrease in the regulatory effect of the enhancer on gene expression, consistent with a contact-based model for enhancer function. However, changes in contact frequency and regulatory effects on gene expression vary as a function of distance, with distal enhancers (e.g., >50Kb) experiencing much larger changes than proximal ones (e.g., <50Kb). Because most enhancers are located close to their target genes, these observations can explain how only a small subset of genes - those with strong distal enhancers - are sensitive to cohesin. Together, our results illuminate how 3D contacts, influenced by both cohesin and genomic distance, tune enhancer effects on gene expression.","[""Journal Article"", ""Preprint""]","[""Guckelberger P"", ""Doughty BR"", ""Munson G"", ""Rao SSP"", ""Tan Y"", ""Cai XS"", ""Fulco CP"", ""Nasser J"", ""Mualim KS"", ""Bergman DT"", ""Ray J"", ""Jagoda E"", ""Munger CJ"", ""Gschwind AR"", ""Sheth MU"", ""Tan AS"", ""Pulido SG"", ""Mitra N"", ""Weisz D"", ""Shamim MS"", ""Durand NC"", ""Mahajan R"", ""Khan R"", ""Steinmetz LM"", ""Kanemaki MT"", ""Lander ES"", ""Meissner A"", ""Aiden EL"", ""Engreitz JM""]",10.1101/2024.07.12.603288,Guckelberger P,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Engreitz JM,[],,39026740,pmc-id: PMC11257546;,2024 Jul 22,2024,https://pubmed.ncbi.nlm.nih.gov/39026740/,Cohesin-mediated 3D contacts tune enhancer-promoter regulation,,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Analyses of ancient DNA typically involve sequencing the surviving short oligonucleotides and aligning to genome assemblies from related, modern species. Here, we report that skin from a female woolly mammoth (†Mammuthus primigenius) that died 52,000 years ago retained its ancient genome architecture. We use PaleoHi-C to map chromatin contacts and assemble its genome, yielding 28 chromosome-length scaffolds. Chromosome territories, compartments, loops, Barr bodies, and inactive X chromosome (Xi) superdomains persist. The active and inactive genome compartments in mammoth skin more closely resemble Asian elephant skin than other elephant tissues. Our analyses uncover new biology. Differences in compartmentalization reveal genes whose transcription was potentially altered in mammoths vs. elephants. Mammoth Xi has a tetradic architecture, not bipartite like human and mouse. We hypothesize that, shortly after this mammoth's death, the sample spontaneously freeze-dried in the Siberian cold, leading to a glass transition that preserved subfossils of ancient chromosomes at nanometer scale.","[""Journal Article""]","[""Sandoval-Velasco M"", ""Dudchenko O"", ""Rodríguez JA"", ""Pérez Estrada C"", ""Dehasque M"", ""Fontsere C"", ""Mak SST"", ""Khan R"", ""Contessoto VG"", ""Oliveira Junior AB"", ""Kalluchi A"", ""Zubillaga Herrera BJ"", ""Jeong J"", ""Roy RP"", ""Christopher I"", ""Weisz D"", ""Omer AD"", ""Batra SS"", ""Shamim MS"", ""Durand NC"", ""O'Connell B"", ""Roca AL"", ""Plikus MV"", ""Kusliy MA"", ""Romanenko SA"", ""Lemskaya NA"", ""Serdyukova NA"", ""Modina SA"", ""Perelman PL"", ""Kizilova EA"", ""Baiborodin SI"", ""Rubtsov NB"", ""Machol G"", ""Rath K"", ""Mahajan R"", ""Kaur P"", ""Gnirke A"", ""Garcia-Treviño I"", ""Coke R"", ""Flanagan JP"", ""Pletch K"", ""Ruiz-Herrera A"", ""Plotnikov V"", ""Pavlov IS"", ""Pavlova NI"", ""Protopopov AV"", ""Di Pierro M"", ""Graphodatsky AS"", ""Lander ES"", ""Rowley MJ"", ""Wolynes PG"", ""Onuchic JN"", ""Dalén L"", ""Marti-Renom MA"", ""Gilbert MTP"", ""Aiden EL""]",10.1016/j.cell.2024.06.002,Sandoval-Velasco M,Cell,0092-8674,14,Cell,eng,Aiden EL,"[""Animals"", ""Mammoths"", ""Genome"", ""Female"", ""Skin"", ""Elephants"", ""Chromatin"", ""Fossils"", ""DNA, Ancient"", ""Mice"", ""Humans"", ""X Chromosome""]",3541-3562.e51,38996487,pmc-id: PMC12128189;manuscript-id: NIHMS2080664;,2024 Jul 11,2024,https://pubmed.ncbi.nlm.nih.gov/38996487/,"Three-dimensional genome architecture persists in a 52,000-year-old woolly mammoth skin sample",187,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Identifying the causal variants and mechanisms that drive complex traits and diseases remains a core problem in human genetics. The majority of these variants have individually weak effects and lie in non-coding gene-regulatory elements where we lack a complete understanding of how single nucleotide alterations modulate transcriptional processes to affect human phenotypes. To address this, we measured the activity of 221,412 trait-associated variants that had been statistically fine-mapped using a Massively Parallel Reporter Assay (MPRA) in 5 diverse cell-types. We show that MPRA is able to discriminate between likely causal variants and controls, identifying 12,025 regulatory variants with high precision. Although the effects of these variants largely agree with orthogonal measures of function, only 69% can plausibly be explained by the disruption of a known transcription factor (TF) binding motif. We dissect the mechanisms of 136 variants using saturation mutagenesis and assign impacted TFs for 91% of variants without a clear canonical mechanism. Finally, we provide evidence that epistasis is prevalent for variants in close proximity and identify multiple functional variants on the same haplotype at a small, but important, subset of trait-associated loci. Overall, our study provides a systematic functional characterization of likely causal common variants underlying complex and molecular human traits, enabling new insights into the regulatory grammar underlying disease risk.","[""Journal Article"", ""Preprint""]","[""Siraj L"", ""Castro RI"", ""Dewey H"", ""Kales S"", ""Nguyen TTL"", ""Kanai M"", ""Berenzy D"", ""Mouri K"", ""Wang QS"", ""McCaw ZR"", ""Gosai SJ"", ""Aguet F"", ""Cui R"", ""Vockley CM"", ""Lareau CA"", ""Okada Y"", ""Gusev A"", ""Jones TR"", ""Lander ES"", ""Sabeti PC"", ""Finucane HK"", ""Reilly SK"", ""Ulirsch JC"", ""Tewhey R""]",10.1101/2024.05.05.592437,Siraj L,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Tewhey R,[],,38766054,pmc-id: PMC11100724;,2024 May 6,2024,https://pubmed.ncbi.nlm.nih.gov/38766054/,Functional dissection of complex and molecular trait variants at single nucleotide resolution,,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Linking variants from genome-wide association studies (GWAS) to underlying mechanisms of disease remains a challenge1-3. For some diseases, a successful strategy has been to look for cases in which multiple GWAS loci contain genes that act in the same biological pathway1-6. However, our knowledge of which genes act in which pathways is incomplete, particularly for cell-type-specific pathways or understudied genes. Here we introduce a method to connect GWAS variants to functions. This method links variants to genes using epigenomics data, links genes to pathways de novo using Perturb-seq and integrates these data to identify convergence of GWAS loci onto pathways. We apply this approach to study the role of endothelial cells in genetic risk for coronary artery disease (CAD), and discover 43 CAD GWAS signals that converge on the cerebral cavernous malformation (CCM) signalling pathway. Two regulators of this pathway, CCM2 and TLNRD1, are each linked to a CAD risk variant, regulate other CAD risk genes and affect atheroprotective processes in endothelial cells. These results suggest a model whereby CAD risk is driven in part by the convergence of causal genes onto a particular transcriptional pathway in endothelial cells. They highlight shared genes between common and rare vascular diseases (CAD and CCM), and identify TLNRD1 as a new, previously uncharacterized member of the CCM signalling pathway. This approach will be widely useful for linking variants to functions for other common polygenic diseases.","[""Journal Article"", ""Research Support, N.I.H., Extramural""]","[""Schnitzler GR"", ""Kang H"", ""Fang S"", ""Angom RS"", ""Lee-Kim VS"", ""Ma XR"", ""Zhou R"", ""Zeng T"", ""Guo K"", ""Taylor MS"", ""Vellarikkal SK"", ""Barry AE"", ""Sias-Garcia O"", ""Bloemendal A"", ""Munson G"", ""Guckelberger P"", ""Nguyen TH"", ""Bergman DT"", ""Hinshaw S"", ""Cheng N"", ""Cleary B"", ""Aragam K"", ""Lander ES"", ""Finucane HK"", ""Mukhopadhyay D"", ""Gupta RM"", ""Engreitz JM""]",10.1038/s41586-024-07022-x,Schnitzler GR,Nature,0028-0836,8000,Nature,eng,Engreitz JM,"[""Humans"", ""Coronary Artery Disease"", ""Endothelial Cells"", ""Genetic Predisposition to Disease"", ""Genome-Wide Association Study"", ""Hemangioma, Cavernous, Central Nervous System"", ""Polymorphism, Single Nucleotide"", ""Epigenomics"", ""Signal Transduction"", ""Multifactorial Inheritance"", ""Carrier Proteins"", ""Molecular Chaperones""]",799-807,38326615,pmc-id: PMC10921916;manuscript-id: NIHMS1968238;,2024 Feb,2024,https://pubmed.ncbi.nlm.nih.gov/38326615/,Convergence of coronary artery disease genes onto endothelial cell programs,626,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Infection with Lassa virus (LASV) can cause Lassa fever, a haemorrhagic illness with an estimated fatality rate of 29.7%, but causes no or mild symptoms in many individuals. Here, to investigate whether human genetic variation underlies the heterogeneity of LASV infection, we carried out genome-wide association studies (GWAS) as well as seroprevalence surveys, human leukocyte antigen typing and high-throughput variant functional characterization assays. We analysed Lassa fever susceptibility and fatal outcomes in 533 cases of Lassa fever and 1,986 population controls recruited over a 7 year period in Nigeria and Sierra Leone. We detected genome-wide significant variant associations with Lassa fever fatal outcomes near GRM7 and LIF in the Nigerian cohort. We also show that a haplotype bearing signatures of positive selection and overlapping LARGE1, a required LASV entry factor, is associated with decreased risk of Lassa fever in the Nigerian cohort but not in the Sierra Leone cohort. Overall, we identified variants and genes that may impact the risk of severe Lassa fever, demonstrating how GWAS can provide insight into viral pathogenesis.","[""Journal Article""]","[""Kotliar D"", ""Raju S"", ""Tabrizi S"", ""Odia I"", ""Goba A"", ""Momoh M"", ""Sandi JD"", ""Nair P"", ""Phelan E"", ""Tariyal R"", ""Eromon PE"", ""Mehta S"", ""Robles-Sikisaka R"", ""Siddle KJ"", ""Stremlau M"", ""Jalloh S"", ""Gire SK"", ""Winnicki S"", ""Chak B"", ""Schaffner SF"", ""Pauthner M"", ""Karlsson EK"", ""Chapin SR"", ""Kennedy SG"", ""Branco LM"", ""Kanneh L"", ""Vitti JJ"", ""Broodie N"", ""Gladden-Young A"", ""Omoniwa O"", ""Jiang PP"", ""Yozwiak N"", ""Heuklom S"", ""Moses LM"", ""Akpede GO"", ""Asogun DA"", ""Rubins K"", ""Kales S"", ""Happi AN"", ""Iruolagbe CO"", ""Dic-Ijiewere M"", ""Iraoyah K"", ""Osazuwa OO"", ""Okonkwo AK"", ""Kunz S"", ""McCormick JB"", ""Khan SH"", ""Honko AN"", ""Lander ES"", ""Oldstone MBA"", ""Hensley L"", ""Folarin OA"", ""Okogbenin SA"", ""Günther S"", ""Ollila HM"", ""Tewhey R"", ""Okokhere PO"", ""Schieffelin JS"", ""Andersen KG"", ""Reilly SK"", ""Grant DS"", ""Garry RF"", ""Barnes KG"", ""Happi CT"", ""Sabeti PC""]",10.1038/s41564-023-01589-3,Kotliar D,Nature microbiology,2058-5276,3,Nat Microbiol,eng,Sabeti PC,"[""Humans"", ""Lassa Fever"", ""Genome-Wide Association Study"", ""Seroepidemiologic Studies"", ""Lassa virus"", ""Fever"", ""Human Genetics""]",751-762,38326571,pmc-id: PMC10914620;,2024 Mar,2024,https://pubmed.ncbi.nlm.nih.gov/38326571/,Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever,9,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Regulatory DNA sequences within enhancers and promoters bind transcription factors to encode cell type-specific patterns of gene expression. However, the regulatory effects and programmability of such DNA sequences remain difficult to map or predict because we have lacked scalable methods to precisely edit regulatory DNA and quantify the effects in an endogenous genomic context. Here we present an approach to measure the quantitative effects of hundreds of designed DNA sequence variants on gene expression, by combining pooled CRISPR prime editing with RNA fluorescence in situ hybridization and cell sorting (Variant-FlowFISH). We apply this method to mutagenize and rewrite regulatory DNA sequences in an enhancer and the promoter of PPIF in two immune cell lines. Of 672 variant-cell type pairs, we identify 497 that affect PPIF expression. These variants appear to act through a variety of mechanisms including disruption or optimization of existing transcription factor binding sites, as well as creation of de novo sites. Disrupting a single endogenous transcription factor binding site often led to large changes in expression (up to -40% in the enhancer, and -50% in the promoter). The same variant often had different effects across cell types and states, demonstrating a highly tunable regulatory landscape. We use these data to benchmark performance of sequence-based predictive models of gene regulation, and find that certain types of variants are not accurately predicted by existing models. Finally, we computationally design 185 small sequence variants (≤10 bp) and optimize them for specific effects on expression in silico. 84% of these rationally designed edits showed the intended direction of effect, and some had dramatic effects on expression (-100% to +202%). Variant-FlowFISH thus provides a powerful tool to map the effects of variants and transcription factor binding sites on gene expression, test and improve computational models of gene regulation, and reprogram regulatory DNA.","[""Journal Article"", ""Preprint""]","[""Martyn GE"", ""Montgomery MT"", ""Jones H"", ""Guo K"", ""Doughty BR"", ""Linder J"", ""Chen Z"", ""Cochran K"", ""Lawrence KA"", ""Munson G"", ""Pampari A"", ""Fulco CP"", ""Kelley DR"", ""Lander ES"", ""Kundaje A"", ""Engreitz JM""]",10.1101/2023.12.20.572268,Martyn GE,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Engreitz JM,[],,38187584,pmc-id: PMC10769263;,2023 Dec 21,2023,https://pubmed.ncbi.nlm.nih.gov/38187584/,Rewriting regulatory DNA to dissect and reprogram gene expression,,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Linkage disequilibrium (LD) is the correlation among nearby genetic variants. In genetic association studies, LD is often modeled using large correlation matrices, but this approach is inefficient, especially in ancestrally diverse studies. In the present study, we introduce LD graphical models (LDGMs), which are an extremely sparse and efficient representation of LD. LDGMs are derived from genome-wide genealogies; statistical relationships among alleles in the LDGM correspond to genealogical relationships among haplotypes. We published LDGMs and ancestry-specific LDGM precision matrices for 18 million common variants (minor allele frequency >1%) in five ancestry groups, validated their accuracy and demonstrated order-of-magnitude improvements in runtime for commonly used LD matrix computations. We implemented an extremely fast multiancestry polygenic prediction method, BLUPx-ldgm, which performs better than a similar method based on the reference LD correlation matrix. LDGMs will enable sophisticated methods that scale to ancestrally diverse genetic association data across millions of variants and individuals.","[""Journal Article""]","[""Salehi Nowbandegani P"", ""Wohns AW"", ""Ballard JL"", ""Lander ES"", ""Bloemendal A"", ""Neale BM"", ""O'Connor LJ""]",10.1038/s41588-023-01487-8,Salehi Nowbandegani P,Nature genetics,1061-4036,9,Nat Genet,eng,O'Connor LJ,"[""Humans"", ""Linkage Disequilibrium"", ""Alleles"", ""Gene Frequency"", ""Genetic Association Studies"", ""Haplotypes""]",1494-1502,37640881,,2023 Sep,2023,https://pubmed.ncbi.nlm.nih.gov/37640881/,Extremely sparse models of linkage disequilibrium in ancestrally diverse association studies,55,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Genome-wide association studies (GWASs) are a valuable tool for understanding the biology of complex human traits and diseases, but associated variants rarely point directly to causal genes. In the present study, we introduce a new method, polygenic priority score (PoPS), that learns trait-relevant gene features, such as cell-type-specific expression, to prioritize genes at GWAS loci. Using a large evaluation set of genes with fine-mapped coding variants, we show that PoPS and the closest gene individually outperform other gene prioritization methods, but observe the best overall performance by combining PoPS with orthogonal methods. Using this combined approach, we prioritize 10,642 unique gene-trait pairs across 113 complex traits and diseases with high precision, finding not only well-established gene-trait relationships but nominating new genes at unresolved loci, such as LGR4 for estimated glomerular filtration rate and CCR7 for deep vein thrombosis. Overall, we demonstrate that PoPS provides a powerful addition to the gene prioritization toolbox.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Weeks EM"", ""Ulirsch JC"", ""Cheng NY"", ""Trippe BL"", ""Fine RS"", ""Miao J"", ""Patwardhan TA"", ""Kanai M"", ""Nasser J"", ""Fulco CP"", ""Tashman KC"", ""Aguet F"", ""Li T"", ""Ordovas-Montanes J"", ""Smillie CS"", ""Biton M"", ""Shalek AK"", ""Ananthakrishnan AN"", ""Xavier RJ"", ""Regev A"", ""Gupta RM"", ""Lage K"", ""Ardlie KG"", ""Hirschhorn JN"", ""Lander ES"", ""Engreitz JM"", ""Finucane HK""]",10.1038/s41588-023-01443-6,Weeks EM,Nature genetics,1061-4036,8,Nat Genet,eng,Finucane HK,"[""Humans"", ""Multifactorial Inheritance"", ""Quantitative Trait Loci"", ""Genome-Wide Association Study"", ""Genetic Predisposition to Disease"", ""Phenotype"", ""Polymorphism, Single Nucleotide""]",1267-1276,37443254,pmc-id: PMC10836580;manuscript-id: NIHMS1956161;,2023 Aug,2023,https://pubmed.ncbi.nlm.nih.gov/37443254/,Leveraging polygenic enrichments of gene features to predict genes underlying complex traits and diseases,55,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Systematic evaluation of the impact of genetic variants is critical for the study and treatment of human physiology and disease. While specific mutations can be introduced by genome engineering, we still lack scalable approaches that are applicable to the important setting of primary cells, such as blood and immune cells. Here, we describe the development of massively parallel base-editing screens in human hematopoietic stem and progenitor cells. Such approaches enable functional screens for variant effects across any hematopoietic differentiation state. Moreover, they allow for rich phenotyping through single-cell RNA sequencing readouts and separately for characterization of editing outcomes through pooled single-cell genotyping. We efficiently design improved leukemia immunotherapy approaches, comprehensively identify non-coding variants modulating fetal hemoglobin expression, define mechanisms regulating hematopoietic differentiation, and probe the pathogenicity of uncharacterized disease-associated variants. These strategies will advance effective and high-throughput variant-to-function mapping in human hematopoiesis to identify the causes of diverse diseases.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Martin-Rufino JD"", ""Castano N"", ""Pang M"", ""Grody EI"", ""Joubran S"", ""Caulier A"", ""Wahlster L"", ""Li T"", ""Qiu X"", ""Riera-Escandell AM"", ""Newby GA"", ""Al'Khafaji A"", ""Chaudhary S"", ""Black S"", ""Weng C"", ""Munson G"", ""Liu DR"", ""Wlodarski MW"", ""Sims K"", ""Oakley JH"", ""Fasano RM"", ""Xavier RJ"", ""Lander ES"", ""Klein DE"", ""Sankaran VG""]",10.1016/j.cell.2023.03.035,Martin-Rufino JD,Cell,0092-8674,11,Cell,eng,Sankaran VG,"[""Humans"", ""Cell Differentiation"", ""CRISPR-Cas Systems"", ""Gene Editing"", ""Genome"", ""Hematopoiesis"", ""Hematopoietic Stem Cells"", ""Genetic Engineering"", ""Single-Cell Analysis""]",2456-2474.e24,37137305,pmc-id: PMC10225359;manuscript-id: NIHMS1892260;,2023 May 25,2023,https://pubmed.ncbi.nlm.nih.gov/37137305/,Massively parallel base editing to map variant effects in human hematopoiesis,186,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"A key goal of precision medicine is to disaggregate common, complex diseases into discrete molecular subtypes. Rare coding variants in the low-density lipoprotein receptor gene (LDLR) are identified in 1% to 2% of coronary artery disease (CAD) patients, defining a molecular subtype with risk driven by hypercholesterolemia. To search for additional subtypes, we compared the frequency of rare, predicted loss-of-function and damaging missense variants aggregated within a given gene in 41 081 CAD cases versus 217 115 controls. Rare variants in LDLR were most strongly associated with CAD, present in 1% of cases and associated with 4.4-fold increased CAD risk. A second subtype was characterized by variants in endothelial nitric oxide synthase gene (NOS3), a key enzyme regulating vascular tone, endothelial function, and platelet aggregation. A rare predicted loss-of-function or damaging missense variants in NOS3 was present in 0.6% of cases and associated with 2.42-fold increased risk of CAD (95% CI, 1.80-3.26; P=5.50×10-9). These variants were associated with higher systolic blood pressure (+3.25 mm Hg; [95% CI, 1.86-4.65]; P=5.00×10-6) and increased risk of hypertension (adjusted odds ratio 1.31; [95% CI, 1.14-1.51]; P=2.00×10-4) but not circulating cholesterol concentrations, suggesting that, beyond lipid pathways, nitric oxide synthesis is a key nonlipid driver of CAD risk. Beyond LDLR, we identified an additional nonlipid molecular subtype of CAD characterized by rare variants in the NOS3 gene.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Khera AV"", ""Wang M"", ""Chaffin M"", ""Emdin CA"", ""Samani NJ"", ""Schunkert H"", ""Watkins H"", ""McPherson R"", ""Erdmann J"", ""Elosua R"", ""Boerwinkle E"", ""Ardissino D"", ""Butterworth AS"", ""Di Angelantonio E"", ""Naheed A"", ""Danesh J"", ""Chowdhury R"", ""Krumholz HM"", ""Sheu WH"", ""Rich SS"", ""Rotter JI"", ""Chen YI"", ""Gabriel S"", ""Lander ES"", ""Saleheen D"", ""Kathiresan S""]",10.1161/CIRCGEN.121.003598,Khera AV,Circulation. Genomic and precision medicine,2574-8300,6,Circ Genom Precis Med,eng,Kathiresan S,"[""Humans"", ""Coronary Artery Disease"", ""Polymorphism, Genetic"", ""Nitric Oxide"", ""Cholesterol"", ""Hypercholesterolemia""]",e003598,36215124,pmc-id: PMC9771961;manuscript-id: NIHMS1837855;,2022 Dec,2022,https://pubmed.ncbi.nlm.nih.gov/36215124/,Gene Sequencing Identifies Perturbation in Nitric Oxide Signaling as a Nonlipid Molecular Subtype of Coronary Artery Disease,15,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Molecular profiling studies have enabled discoveries for metastatic prostate cancer (MPC) but have predominantly occurred in academic medical institutions and involved non-representative patient populations. We established the Metastatic Prostate Cancer Project (MPCproject, mpcproject.org), a patient-partnered initiative to involve patients with MPC living anywhere in the US and Canada in molecular research. Here, we present results from our partnership with the first 706 MPCproject participants. While 41% of patient partners live in rural, physician-shortage, or medically underserved areas, the MPCproject has not yet achieved racial diversity, a disparity that demands new initiatives detailed herein. Among molecular data from 333 patient partners (572 samples), exome sequencing of 63 tumor and 19 cell-free DNA (cfDNA) samples recapitulated known findings in MPC, while inexpensive ultra-low-coverage sequencing of 318 cfDNA samples revealed clinically relevant AR amplifications. This study illustrates the power of a growing, longitudinal partnership with patients to generate a more representative understanding of MPC.","[""Journal Article""]","[""Crowdis J"", ""Balch S"", ""Sterlin L"", ""Thomas BS"", ""Camp SY"", ""Dunphy M"", ""Anastasio E"", ""Shah S"", ""Damon AL"", ""Ramos R"", ""Sosa DM"", ""Small IK"", ""Tomson BN"", ""Nguyen CM"", ""McGillicuddy M"", ""Chastain PS"", ""He MX"", ""Cheung ATM"", ""Wankowicz S"", ""Tewari AK"", ""Kim D"", ""AlDubayan SH"", ""Dowdye A"", ""Zola B"", ""Nowak J"", ""Manarite J"", ""Gunn IH"", ""Olson B"", ""Lander ES"", ""Painter CA"", ""Wagle N"", ""Van Allen EM""]",10.1016/j.xgen.2022.100169,Crowdis J,Cell genomics,2666-979X,9,Cell Genom,eng,Van Allen EM,[],,36177448,pmc-id: PMC9518748;manuscript-id: NIHMS1836575;,2022 Sep 14,2022,https://pubmed.ncbi.nlm.nih.gov/36177448/,A patient-driven clinicogenomic partnership for metastatic prostate cancer,2,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"For Alzheimer's disease-a leading cause of dementia and global morbidity-improved identification of presymptomatic high-risk individuals and identification of new circulating biomarkers are key public health needs. Here, we tested the hypothesis that a polygenic predictor of risk for Alzheimer's disease would identify a subset of the population with increased risk of clinically diagnosed dementia, subclinical neurocognitive dysfunction, and a differing circulating proteomic profile. Using summary association statistics from a recent genome-wide association study, we first developed a polygenic predictor of Alzheimer's disease comprised of 7.1 million common DNA variants. We noted a 7.3-fold (95% CI 4.8 to 11.0; p < 0.001) gradient in risk across deciles of the score among 288,289 middle-aged participants of the UK Biobank study. In cross-sectional analyses stratified by age, minimal differences in risk of Alzheimer's disease and performance on a digit recall test were present according to polygenic score decile at age 50 years, but significant gradients emerged by age 65. Similarly, among 30,541 participants of the Mass General Brigham Biobank, we again noted no significant differences in Alzheimer's disease diagnosis at younger ages across deciles of the score, but for those over 65 years we noted an odds ratio of 2.0 (95% CI 1.3 to 3.2; p = 0.002) in the top versus bottom decile of the polygenic score. To understand the proteomic signature of inherited risk, we performed aptamer-based profiling in 636 blood donors (mean age 43 years) with very high or low polygenic scores. In addition to the well-known apolipoprotein E biomarker, this analysis identified 27 additional proteins, several of which have known roles related to disease pathogenesis. Differences in protein concentrations were consistent even among the youngest subset of blood donors (mean age 33 years). Of these 28 proteins, 7 of the 8 proteins with concentrations available were similarly associated with the polygenic score in participants of the Multi-Ethnic Study of Atherosclerosis. These data highlight the potential for a DNA-based score to identify high-risk individuals during the prolonged presymptomatic phase of Alzheimer's disease and to enable biomarker discovery based on profiling of young individuals in the extremes of the score distribution.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Paranjpe MD"", ""Chaffin M"", ""Zahid S"", ""Ritchie S"", ""Rotter JI"", ""Rich SS"", ""Gerszten R"", ""Guo X"", ""Heckbert S"", ""Tracy R"", ""Danesh J"", ""Lander ES"", ""Inouye M"", ""Kathiresan S"", ""Butterworth AS"", ""Khera AV""]",10.1371/journal.pgen.1010294,Paranjpe MD,PLoS genetics,1553-7390,9,PLoS Genet,eng,Khera AV,"[""Adult"", ""Aged"", ""Alzheimer Disease"", ""Biomarkers"", ""Cross-Sectional Studies"", ""Genome-Wide Association Study"", ""Humans"", ""Middle Aged"", ""Proteomics""]",e1010294,36048760,pmc-id: PMC9436054;,2022 Sep,2022,https://pubmed.ncbi.nlm.nih.gov/36048760/,Neurocognitive trajectory and proteomic signature of inherited risk for Alzheimer's disease,18,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Regulatory relationships between transcription factors (TFs) and their target genes lie at the heart of cellular identity and function; however, uncovering these relationships is often labor-intensive and requires perturbations. Here, we propose a principled framework to systematically infer gene regulation for all TFs simultaneously in cells at steady state by leveraging the intrinsic variation in the transcriptional abundance across single cells. Through modeling and simulations, we characterize how transcriptional bursts of a TF gene are propagated to its target genes, including the expected ranges of time delay and magnitude of maximum covariation. We distinguish these temporal trends from the time-invariant covariation arising from cell states, and we delineate the experimental and technical requirements for leveraging these small but meaningful cofluctuations in the presence of measurement noise. While current technology does not yet allow adequate power for definitively detecting regulatory relationships for all TFs simultaneously in cells at steady state, we investigate a small-scale dataset to inform future experimental design. This study supports the potential value of mapping regulatory connections through stochastic variation, and it motivates further technological development to achieve its full potential.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Gupta A"", ""Martin-Rufino JD"", ""Jones TR"", ""Subramanian V"", ""Qiu X"", ""Grody EI"", ""Bloemendal A"", ""Weng C"", ""Niu SY"", ""Min KH"", ""Mehta A"", ""Zhang K"", ""Siraj L"", ""Al' Khafaji A"", ""Sankaran VG"", ""Raychaudhuri S"", ""Cleary B"", ""Grossman S"", ""Lander ES""]",10.1073/pnas.2207392119,Gupta A,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,34,Proc Natl Acad Sci U S A,eng,Lander ES,"[""Computer Simulation"", ""Gene Expression Regulation"", ""Gene Regulatory Networks"", ""Models, Biological"", ""Transcription Factors""]",e2207392119,35969771,pmc-id: PMC9407670;,2022 Aug 23,2022,https://pubmed.ncbi.nlm.nih.gov/35969771/,Inferring gene regulation from stochastic transcriptional variation across single cells at steady state,119,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Gene regulation in the human genome is controlled by distal enhancers that activate specific nearby promoters1. A proposed model for this specificity is that promoters have sequence-encoded preferences for certain enhancers, for example, mediated by interacting sets of transcription factors or cofactors2. This 'biochemical compatibility' model has been supported by observations at individual human promoters and by genome-wide measurements in Drosophila3-9. However, the degree to which human enhancers and promoters are intrinsically compatible has not yet been systematically measured, and how their activities combine to control RNA expression remains unclear. Here we design a high-throughput reporter assay called enhancer × promoter self-transcribing active regulatory region sequencing (ExP STARR-seq) and applied it to examine the combinatorial compatibilities of 1,000 enhancer and 1,000 promoter sequences in human K562 cells. We identify simple rules for enhancer-promoter compatibility, whereby most enhancers activate all promoters by similar amounts, and intrinsic enhancer and promoter activities multiplicatively combine to determine RNA output (R2 = 0.82). In addition, two classes of enhancers and promoters show subtle preferential effects. Promoters of housekeeping genes contain built-in activating motifs for factors such as GABPA and YY1, which decrease the responsiveness of promoters to distal enhancers. Promoters of variably expressed genes lack these motifs and show stronger responsiveness to enhancers. Together, this systematic assessment of enhancer-promoter compatibility suggests a multiplicative model tuned by enhancer and promoter class to control gene transcription in the human genome.","[""Journal Article""]","[""Bergman DT"", ""Jones TR"", ""Liu V"", ""Ray J"", ""Jagoda E"", ""Siraj L"", ""Kang HY"", ""Nasser J"", ""Kane M"", ""Rios A"", ""Nguyen TH"", ""Grossman SR"", ""Fulco CP"", ""Lander ES"", ""Engreitz JM""]",10.1038/s41586-022-04877-w,Bergman DT,Nature,0028-0836,7917,Nature,eng,Engreitz JM,"[""Enhancer Elements, Genetic"", ""Humans"", ""Promoter Regions, Genetic"", ""RNA"", ""Transcription Factors""]",176-184,35594906,pmc-id: PMC9262863;manuscript-id: NIHMS1816171;,2022 Jul,2022,https://pubmed.ncbi.nlm.nih.gov/35594906/,Compatibility rules of human enhancer and promoter sequences,607,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Single-cell (sc)RNA-seq, together with RNA velocity and metabolic labeling, reveals cellular states and transitions at unprecedented resolution. Fully exploiting these data, however, requires kinetic models capable of unveiling governing regulatory functions. Here, we introduce an analytical framework dynamo (https://github.com/aristoteleo/dynamo-release), which infers absolute RNA velocity, reconstructs continuous vector fields that predict cell fates, employs differential geometry to extract underlying regulations, and ultimately predicts optimal reprogramming paths and perturbation outcomes. We highlight dynamo's power to overcome fundamental limitations of conventional splicing-based RNA velocity analyses to enable accurate velocity estimations on a metabolically labeled human hematopoiesis scRNA-seq dataset. Furthermore, differential geometry analyses reveal mechanisms driving early megakaryocyte appearance and elucidate asymmetrical regulation within the PU.1-GATA1 circuit. Leveraging the least-action-path method, dynamo accurately predicts drivers of numerous hematopoietic transitions. Finally, in silico perturbations predict cell-fate diversions induced by gene perturbations. Dynamo, thus, represents an important step in advancing quantitative and predictive theories of cell-state transitions.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't"", ""Research Support, U.S. Gov't, Non-P.H.S.""]","[""Qiu X"", ""Zhang Y"", ""Martin-Rufino JD"", ""Weng C"", ""Hosseinzadeh S"", ""Yang D"", ""Pogson AN"", ""Hein MY"", ""Hoi Joseph Min K"", ""Wang L"", ""Grody EI"", ""Shurtleff MJ"", ""Yuan R"", ""Xu S"", ""Ma Y"", ""Replogle JM"", ""Lander ES"", ""Darmanis S"", ""Bahar I"", ""Sankaran VG"", ""Xing J"", ""Weissman JS""]",10.1016/j.cell.2021.12.045,Qiu X,Cell,0092-8674,4,Cell,eng,Weissman JS,"[""Algorithms"", ""Female"", ""Gene Expression Regulation"", ""HL-60 Cells"", ""Hematopoiesis"", ""Hematopoietic Stem Cells"", ""Humans"", ""Kinetics"", ""Models, Biological"", ""RNA, Messenger"", ""Single-Cell Analysis"", ""Staining and Labeling"", ""Transcriptome""]",690-711.e45,35108499,pmc-id: PMC9332140;manuscript-id: NIHMS1802444;,2022 Feb 17,2022,https://pubmed.ncbi.nlm.nih.gov/35108499/,Mapping transcriptomic vector fields of single cells,185,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Transmission of coronavirus disease 2019 (COVID-19) from people without symptoms confounds societal mitigation strategies. From April to June 2020, we tested nasopharyngeal swabs by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) from 15 514 staff and 16 966 residents of nursing homes and assisted living facilities in Massachusetts. Cycle threshold (Ct) distributions were very similar between populations with (n = 739) and without (n = 2179) symptoms at the time of sampling (mean Ct, 25.7 vs 26.4; ranges 12-38). However, as local cases waned, those without symptoms shifted towards higher Ct. With such similar viral load distributions, existing testing modalities should perform comparably regardless of symptoms, contingent upon time since infection.","[""Journal Article""]","[""Lennon NJ"", ""Bhattacharyya RP"", ""Mina MJ"", ""Rehm HL"", ""Hung DT"", ""Smole S"", ""Woolley A"", ""Lander ES"", ""Gabriel SB""]",10.1093/infdis/jiab367,Lennon NJ,The Journal of infectious diseases,0022-1899,10,J Infect Dis,eng,Gabriel SB,"[""COVID-19"", ""Cross-Sectional Studies"", ""Humans"", ""Reverse Transcriptase Polymerase Chain Reaction"", ""SARS-CoV-2"", ""Viral Load""]",1658-1663,34255846,pmc-id: PMC8420626;,2021 Nov 22,2021,https://pubmed.ncbi.nlm.nih.gov/34255846/,Cross-Sectional Assessment of SARS-CoV-2 Viral Load by Symptom Status in Massachusetts Congregate Living Facilities,224,ENDC5psocNV258waT,fBiR6Lki005vebWjt
,"[""Journal Article""]","[""Collins FS"", ""Schwetz TA"", ""Tabak LA"", ""Lander ES""]",10.1126/science.abj8547,Collins FS,"Science (New York, N.Y.)",0036-8075,6551,Science,eng,Lander ES,[],165-167,34244402,,2021 Jul 9,2021,https://pubmed.ncbi.nlm.nih.gov/34244402/,ARPA-H: Accelerating biomedical breakthroughs,373,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Recent methods for spatial imaging of tissue samples can identify up to ~100 individual proteins1-3 or RNAs4-10 at single-cell resolution. However, the number of proteins or genes that can be studied in these approaches is limited by long imaging times. Here we introduce Composite In Situ Imaging (CISI), a method that leverages structure in gene expression across both cells and tissues to limit the number of imaging cycles needed to obtain spatially resolved gene expression maps. CISI defines gene modules that can be detected using composite measurements from imaging probes for subsets of genes. The data are then decompressed to recover expression values for individual genes. CISI further reduces imaging time by not relying on spot-level resolution, enabling lower magnification acquisition, and is overall about 500-fold more efficient than current methods. Applying CISI to 12 mouse brain sections, we accurately recovered the spatial abundance of 37 individual genes from 11 composite measurements covering 180 mm2 and 476,276 cells.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Cleary B"", ""Simonton B"", ""Bezney J"", ""Murray E"", ""Alam S"", ""Sinha A"", ""Habibi E"", ""Marshall J"", ""Lander ES"", ""Chen F"", ""Regev A""]",10.1038/s41587-021-00883-x,Cleary B,Nature biotechnology,1087-0156,8,Nat Biotechnol,eng,Regev A,"[""Animals"", ""Brain"", ""Brain Chemistry"", ""Gene Expression Profiling"", ""Mice"", ""Mice, Inbred C57BL"", ""Molecular Imaging"", ""Signal Processing, Computer-Assisted"", ""Transcriptome""]",936-942,33859401,pmc-id: PMC8355028;manuscript-id: NIHMS1689292;,2021 Aug,2021,https://pubmed.ncbi.nlm.nih.gov/33859401/,Compressed sensing for highly efficient imaging transcriptomics,39,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Genome-wide association studies (GWAS) have identified thousands of noncoding loci that are associated with human diseases and complex traits, each of which could reveal insights into the mechanisms of disease1. Many of the underlying causal variants may affect enhancers2,3, but we lack accurate maps of enhancers and their target genes to interpret such variants. We recently developed the activity-by-contact (ABC) model to predict which enhancers regulate which genes and validated the model using CRISPR perturbations in several cell types4. Here we apply this ABC model to create enhancer-gene maps in 131 human cell types and tissues, and use these maps to interpret the functions of GWAS variants. Across 72 diseases and complex traits, ABC links 5,036 GWAS signals to 2,249 unique genes, including a class of 577 genes that appear to influence multiple phenotypes through variants in enhancers that act in different cell types. In inflammatory bowel disease (IBD), causal variants are enriched in predicted enhancers by more than 20-fold in particular cell types such as dendritic cells, and ABC achieves higher precision than other regulatory methods at connecting noncoding variants to target genes. These variant-to-function maps reveal an enhancer that contains an IBD risk variant and that regulates the expression of PPIF to alter the membrane potential of mitochondria in macrophages. Our study reveals principles of genome regulation, identifies genes that affect IBD and provides a resource and generalizable strategy to connect risk variants of common diseases to their molecular and cellular functions.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't"", ""Research Support, U.S. Gov't, Non-P.H.S.""]","[""Nasser J"", ""Bergman DT"", ""Fulco CP"", ""Guckelberger P"", ""Doughty BR"", ""Patwardhan TA"", ""Jones TR"", ""Nguyen TH"", ""Ulirsch JC"", ""Lekschas F"", ""Mualim K"", ""Natri HM"", ""Weeks EM"", ""Munson G"", ""Kane M"", ""Kang HY"", ""Cui A"", ""Ray JP"", ""Eisenhaure TM"", ""Collins RL"", ""Dey K"", ""Pfister H"", ""Price AL"", ""Epstein CB"", ""Kundaje A"", ""Xavier RJ"", ""Daly MJ"", ""Huang H"", ""Finucane HK"", ""Hacohen N"", ""Lander ES"", ""Engreitz JM""]",10.1038/s41586-021-03446-x,Nasser J,Nature,0028-0836,7858,Nature,eng,Engreitz JM,"[""Cell Line"", ""Chromosomes, Human, Pair 10"", ""Cyclophilins"", ""Dendritic Cells"", ""Enhancer Elements, Genetic"", ""Female"", ""Genetic Predisposition to Disease"", ""Genetic Variation"", ""Genome, Human"", ""Genome-Wide Association Study"", ""Humans"", ""Inflammatory Bowel Diseases"", ""Macrophages"", ""Male"", ""Mitochondria"", ""Organ Specificity"", ""Phenotype"", ""Peptidyl-Prolyl Isomerase D""]",238-243,33828297,pmc-id: PMC9153265;manuscript-id: NIHMS1785562;,2021 May,2021,https://pubmed.ncbi.nlm.nih.gov/33828297/,Genome-wide enhancer maps link risk variants to disease genes,593,ENDC5psocNV258waT,fBiR6Lki005vebWjt
,"[""Published Erratum""]","[""Bick AG"", ""Weinstock JS"", ""Nandakumar SK"", ""Fulco CP"", ""Bao EL"", ""Zekavat SM"", ""Szeto MD"", ""Liao X"", ""Leventhal MJ"", ""Nasser J"", ""Chang K"", ""Laurie C"", ""Burugula BB"", ""Gibson CJ"", ""Niroula A"", ""Lin AE"", ""Taub MA"", ""Aguet F"", ""Ardlie K"", ""Mitchell BD"", ""Barnes KC"", ""Moscati A"", ""Fornage M"", ""Redline S"", ""Psaty BM"", ""Silverman EK"", ""Weiss ST"", ""Palmer ND"", ""Vasan RS"", ""Burchard EG"", ""Kardia SLR"", ""He J"", ""Kaplan RC"", ""Smith NL"", ""Arnett DK"", ""Schwartz DA"", ""Correa A"", ""de Andrade M"", ""Guo X"", ""Konkle BA"", ""Custer B"", ""Peralta JM"", ""Gui H"", ""Meyers DA"", ""McGarvey ST"", ""Chen IY"", ""Shoemaker MB"", ""Peyser PA"", ""Broome JG"", ""Gogarten SM"", ""Wang FF"", ""Wong Q"", ""Montasser ME"", ""Daya M"", ""Kenny EE"", ""North KE"", ""Launer LJ"", ""Cade BE"", ""Bis JC"", ""Cho MH"", ""Lasky-Su J"", ""Bowden DW"", ""Cupples LA"", ""Mak ACY"", ""Becker LC"", ""Smith JA"", ""Kelly TN"", ""Aslibekyan S"", ""Heckbert SR"", ""Tiwari HK"", ""Yang IV"", ""Heit JA"", ""Lubitz SA"", ""Johnsen JM"", ""Curran JE"", ""Wenzel SE"", ""Weeks DE"", ""Rao DC"", ""Darbar D"", ""Moon JY"", ""Tracy RP"", ""Buth EJ"", ""Rafaels N"", ""Loos RJF"", ""Durda P"", ""Liu Y"", ""Hou L"", ""Lee J"", ""Kachroo P"", ""Freedman BI"", ""Levy D"", ""Bielak LF"", ""Hixson JE"", ""Floyd JS"", ""Whitsel EA"", ""Ellinor PT"", ""Irvin MR"", ""Fingerlin TE"", ""Raffield LM"", ""Armasu SM"", ""Wheeler MM"", ""Sabino EC"", ""Blangero J"", ""Williams LK"", ""Levy BD"", ""Sheu WH"", ""Roden DM"", ""Boerwinkle E"", ""Manson JE"", ""Mathias RA"", ""Desai P"", ""Taylor KD"", ""Johnson AD"", ""NHLBI Trans-Omics for Precision Medicine Consortium"", ""Auer PL"", ""Kooperberg C"", ""Laurie CC"", ""Blackwell TW"", ""Smith AV"", ""Zhao H"", ""Lange E"", ""Lange L"", ""Rich SS"", ""Rotter JI"", ""Wilson JG"", ""Scheet P"", ""Kitzman JO"", ""Lander ES"", ""Engreitz JM"", ""Ebert BL"", ""Reiner AP"", ""Jaiswal S"", ""Abecasis G"", ""Sankaran VG"", ""Kathiresan S"", ""Natarajan P""]",10.1038/s41586-021-03280-1,Bick AG,Nature,0028-0836,7851,Nature,eng,Natarajan P,[],E27,33707633,,2021 Mar,2021,https://pubmed.ncbi.nlm.nih.gov/33707633/,"Author Correction: Inherited causes of clonal haematopoiesis in 97,691 whole genomes",591,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Skeletal and glycemic traits have shared etiology, but the underlying genetic factors remain largely unknown. To identify genetic loci that may have pleiotropic effects, we studied Genome-wide association studies (GWASs) for bone mineral density and glycemic traits and identified a bivariate risk locus at 3q21. Using sequence and epigenetic modeling, we prioritized an adenylate cyclase 5 (ADCY5) intronic causal variant, rs56371916. This SNP changes the binding affinity of SREBP1 and leads to differential ADCY5 gene expression, altering the chromatin landscape from poised to repressed. These alterations result in bone- and type 2 diabetes-relevant cell-autonomous changes in lipid metabolism in osteoblasts and adipocytes. We validated our findings by directly manipulating the regulator SREBP1, the target gene ADCY5, and the variant rs56371916, which together imply a novel link between fatty acid oxidation and osteoblast differentiation. Our work, by systematic functional dissection of pleiotropic GWAS loci, represents a framework to uncover biological mechanisms affecting pleiotropic traits.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Sinnott-Armstrong N"", ""Sousa IS"", ""Laber S"", ""Rendina-Ruedy E"", ""Nitter Dankel SE"", ""Ferreira T"", ""Mellgren G"", ""Karasik D"", ""Rivas M"", ""Pritchard J"", ""Guntur AR"", ""Cox RD"", ""Lindgren CM"", ""Hauner H"", ""Sallari R"", ""Rosen CJ"", ""Hsu YH"", ""Lander ES"", ""Kiel DP"", ""Claussnitzer M""]",10.1016/j.cmet.2021.01.001,Sinnott-Armstrong N,Cell metabolism,1550-4131,3,Cell Metab,eng,Claussnitzer M,"[""Adenylyl Cyclases"", ""Adipocytes"", ""Adult"", ""Bone Density"", ""Cell Differentiation"", ""Cells, Cultured"", ""Diabetes Mellitus, Type 2"", ""Female"", ""Genetic Loci"", ""Genome-Wide Association Study"", ""Haplotypes"", ""Humans"", ""Lipid Peroxidation"", ""Male"", ""Middle Aged"", ""Osteoblasts"", ""Polymorphism, Single Nucleotide"", ""Risk Factors"", ""Stem Cells"", ""Sterol Regulatory Element Binding Protein 1""]",615-628.e13,33513366,pmc-id: PMC7928941;,2021 Mar 2,2021,https://pubmed.ncbi.nlm.nih.gov/33513366/,A regulatory variant at 3q21.1 confers an increased pleiotropic risk for hyperglycemia and altered bone mineral density,33,ENDC5psocNV258waT,fBiR6Lki005vebWjt
,"[""Historical Article"", ""Journal Article""]","[""Collins FS"", ""Doudna JA"", ""Lander ES"", ""Rotimi CN""]",10.1056/NEJMp2030694,Collins FS,The New England journal of medicine,0028-4793,1,N Engl J Med,eng,Rotimi CN,"[""Clustered Regularly Interspaced Short Palindromic Repeats"", ""Genetic Diseases, Inborn"", ""Genetics, Medical"", ""Genomics"", ""History, 20th Century"", ""History, 21st Century"", ""Human Genome Project"", ""Humans"", ""Molecular Biology"", ""National Academies of Science, Engineering, and Medicine, U.S., Health and Medicine Division"", ""United States""]",1-4,33393745,,2021 Jan 7,2021,https://pubmed.ncbi.nlm.nih.gov/33393745/,Human Molecular Genetics and Genomics - Important Advances and Exciting Possibilities,384,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Mode of delivery strongly influences the early infant gut microbiome. Children born by cesarean section (C-section) lack Bacteroides species until 6-18 months of age. One hypothesis is that these differences stem from lack of exposure to the maternal vaginal microbiome. Here, we re-evaluate this hypothesis by comparing the microbial profiles of 75 infants born vaginally or by planned versus emergent C-section. Multiple children born by C-section have a high abundance of Bacteroides in their first few days of life, but at 2 weeks, both C-section groups lack Bacteroides (primarily according to 16S sequencing), despite their difference in exposure to the birth canal. Finally, a comparison of microbial strain profiles between infants and maternal vaginal or rectal samples finds evidence for mother-to-child transmission of rectal rather than vaginal strains. These results suggest differences in colonization stability as an important factor in infant gut microbiome composition rather than birth canal exposure.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Mitchell CM"", ""Mazzoni C"", ""Hogstrom L"", ""Bryant A"", ""Bergerat A"", ""Cher A"", ""Pochan S"", ""Herman P"", ""Carrigan M"", ""Sharp K"", ""Huttenhower C"", ""Lander ES"", ""Vlamakis H"", ""Xavier RJ"", ""Yassour M""]",10.1016/j.xcrm.2020.100156,Mitchell CM,Cell reports. Medicine,2666-3791,9,Cell Rep Med,eng,Yassour M,"[""Bacteroides"", ""Cesarean Section"", ""Delivery, Obstetric"", ""Female"", ""Gastrointestinal Microbiome"", ""Humans"", ""Infant"", ""Infectious Disease Transmission, Vertical"", ""Microbiota"", ""Pregnancy""]",100156,33377127,pmc-id: PMC7762768;,2020 Dec 22,2020,https://pubmed.ncbi.nlm.nih.gov/33377127/,Delivery Mode Affects Stability of Early Infant Gut Microbiota,1,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Single-cell quantification of RNAs is important for understanding cellular heterogeneity and gene regulation, yet current approaches suffer from low sensitivity for individual transcripts, limiting their utility for many applications. Here we present Hybridization of Probes to RNA for sequencing (HyPR-seq), a method to sensitively quantify the expression of hundreds of chosen genes in single cells. HyPR-seq involves hybridizing DNA probes to RNA, distributing cells into nanoliter droplets, amplifying the probes with PCR, and sequencing the amplicons to quantify the expression of chosen genes. HyPR-seq achieves high sensitivity for individual transcripts, detects nonpolyadenylated and low-abundance transcripts, and can profile more than 100,000 single cells. We demonstrate how HyPR-seq can profile the effects of CRISPR perturbations in pooled screens, detect time-resolved changes in gene expression via measurements of gene introns, and detect rare transcripts and quantify cell-type frequencies in tissue using low-abundance marker genes. By directing sequencing power to genes of interest and sensitively quantifying individual transcripts, HyPR-seq reduces costs by up to 100-fold compared to whole-transcriptome single-cell RNA-sequencing, making HyPR-seq a powerful method for targeted RNA profiling in single cells.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't"", ""Research Support, U.S. Gov't, Non-P.H.S.""]","[""Marshall JL"", ""Doughty BR"", ""Subramanian V"", ""Guckelberger P"", ""Wang Q"", ""Chen LM"", ""Rodriques SG"", ""Zhang K"", ""Fulco CP"", ""Nasser J"", ""Grinkevich EJ"", ""Noel T"", ""Mangiameli S"", ""Bergman DT"", ""Greka A"", ""Lander ES"", ""Chen F"", ""Engreitz JM""]",10.1073/pnas.2010738117,Marshall JL,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,52,Proc Natl Acad Sci U S A,eng,Engreitz JM,"[""Animals"", ""CRISPR-Cas Systems"", ""DNA Probes"", ""Gene Expression"", ""High-Throughput Nucleotide Sequencing"", ""Humans"", ""Introns"", ""K562 Cells"", ""Kidney"", ""Mice"", ""Nucleic Acid Hybridization"", ""Polyadenylation"", ""RNA"", ""RNA, Messenger"", ""Single-Cell Analysis"", ""THP-1 Cells"", ""Time Factors""]",33404-33413,33376219,pmc-id: PMC7776864;,2020 Dec 29,2020,https://pubmed.ncbi.nlm.nih.gov/33376219/,HyPR-seq: Single-cell quantification of chosen RNAs via hybridization and sequencing of DNA probes,117,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Characterizing the interactions that SARS-CoV-2 viral RNAs make with host cell proteins during infection can improve our understanding of viral RNA functions and the host innate immune response. Using RNA antisense purification and mass spectrometry, we identified up to 104 human proteins that directly and specifically bind to SARS-CoV-2 RNAs in infected human cells. We integrated the SARS-CoV-2 RNA interactome with changes in proteome abundance induced by viral infection and linked interactome proteins to cellular pathways relevant to SARS-CoV-2 infections. We demonstrated by genetic perturbation that cellular nucleic acid-binding protein (CNBP) and La-related protein 1 (LARP1), two of the most strongly enriched viral RNA binders, restrict SARS-CoV-2 replication in infected cells and provide a global map of their direct RNA contact sites. Pharmacological inhibition of three other RNA interactome members, PPIA, ATP1A1, and the ARP2/3 complex, reduced viral replication in two human cell lines. The identification of host dependency factors and defence strategies as presented in this work will improve the design of targeted therapeutics against SARS-CoV-2.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Schmidt N"", ""Lareau CA"", ""Keshishian H"", ""Ganskih S"", ""Schneider C"", ""Hennig T"", ""Melanson R"", ""Werner S"", ""Wei Y"", ""Zimmer M"", ""Ade J"", ""Kirschner L"", ""Zielinski S"", ""Dölken L"", ""Lander ES"", ""Caliskan N"", ""Fischer U"", ""Vogel J"", ""Carr SA"", ""Bodem J"", ""Munschauer M""]",10.1038/s41564-020-00846-z,Schmidt N,Nature microbiology,2058-5276,3,Nat Microbiol,eng,Munschauer M,"[""Autoantigens"", ""COVID-19"", ""Cell Line"", ""Host-Pathogen Interactions"", ""Humans"", ""Protein Interaction Maps"", ""Proteome"", ""RNA, Viral"", ""RNA-Binding Proteins"", ""Ribonucleoproteins"", ""SARS-CoV-2"", ""Virus Replication"", ""SS-B Antigen""]",339-353,33349665,pmc-id: PMC7906908;,2021 Mar,2021,https://pubmed.ncbi.nlm.nih.gov/33349665/,The SARS-CoV-2 RNA-protein interactome in infected human cells,6,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Age is the dominant risk factor for most chronic human diseases, but the mechanisms through which ageing confers this risk are largely unknown1. The age-related acquisition of somatic mutations that lead to clonal expansion in regenerating haematopoietic stem cell populations has recently been associated with both haematological cancer2-4 and coronary heart disease5-this phenomenon is termed clonal haematopoiesis of indeterminate potential (CHIP)6. Simultaneous analyses of germline and somatic whole-genome sequences provide the opportunity to identify root causes of CHIP. Here we analyse high-coverage whole-genome sequences from 97,691 participants of diverse ancestries in the National Heart, Lung, and Blood Institute Trans-omics for Precision Medicine (TOPMed) programme, and identify 4,229 individuals with CHIP. We identify associations with blood cell, lipid and inflammatory traits that are specific to different CHIP driver genes. Association of a genome-wide set of germline genetic variants enabled the identification of three genetic loci associated with CHIP status, including one locus at TET2 that was specific to individuals of African ancestry. In silico-informed in vitro evaluation of the TET2 germline locus enabled the identification of a causal variant that disrupts a TET2 distal enhancer, resulting in increased self-renewal of haematopoietic stem cells. Overall, we observe that germline genetic variation shapes haematopoietic stem cell function, leading to CHIP through mechanisms that are specific to clonal haematopoiesis as well as shared mechanisms that lead to somatic mutations across tissues.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Bick AG"", ""Weinstock JS"", ""Nandakumar SK"", ""Fulco CP"", ""Bao EL"", ""Zekavat SM"", ""Szeto MD"", ""Liao X"", ""Leventhal MJ"", ""Nasser J"", ""Chang K"", ""Laurie C"", ""Burugula BB"", ""Gibson CJ"", ""Lin AE"", ""Taub MA"", ""Aguet F"", ""Ardlie K"", ""Mitchell BD"", ""Barnes KC"", ""Moscati A"", ""Fornage M"", ""Redline S"", ""Psaty BM"", ""Silverman EK"", ""Weiss ST"", ""Palmer ND"", ""Vasan RS"", ""Burchard EG"", ""Kardia SLR"", ""He J"", ""Kaplan RC"", ""Smith NL"", ""Arnett DK"", ""Schwartz DA"", ""Correa A"", ""de Andrade M"", ""Guo X"", ""Konkle BA"", ""Custer B"", ""Peralta JM"", ""Gui H"", ""Meyers DA"", ""McGarvey ST"", ""Chen IY"", ""Shoemaker MB"", ""Peyser PA"", ""Broome JG"", ""Gogarten SM"", ""Wang FF"", ""Wong Q"", ""Montasser ME"", ""Daya M"", ""Kenny EE"", ""North KE"", ""Launer LJ"", ""Cade BE"", ""Bis JC"", ""Cho MH"", ""Lasky-Su J"", ""Bowden DW"", ""Cupples LA"", ""Mak ACY"", ""Becker LC"", ""Smith JA"", ""Kelly TN"", ""Aslibekyan S"", ""Heckbert SR"", ""Tiwari HK"", ""Yang IV"", ""Heit JA"", ""Lubitz SA"", ""Johnsen JM"", ""Curran JE"", ""Wenzel SE"", ""Weeks DE"", ""Rao DC"", ""Darbar D"", ""Moon JY"", ""Tracy RP"", ""Buth EJ"", ""Rafaels N"", ""Loos RJF"", ""Durda P"", ""Liu Y"", ""Hou L"", ""Lee J"", ""Kachroo P"", ""Freedman BI"", ""Levy D"", ""Bielak LF"", ""Hixson JE"", ""Floyd JS"", ""Whitsel EA"", ""Ellinor PT"", ""Irvin MR"", ""Fingerlin TE"", ""Raffield LM"", ""Armasu SM"", ""Wheeler MM"", ""Sabino EC"", ""Blangero J"", ""Williams LK"", ""Levy BD"", ""Sheu WH"", ""Roden DM"", ""Boerwinkle E"", ""Manson JE"", ""Mathias RA"", ""Desai P"", ""Taylor KD"", ""Johnson AD"", ""NHLBI Trans-Omics for Precision Medicine Consortium"", ""Auer PL"", ""Kooperberg C"", ""Laurie CC"", ""Blackwell TW"", ""Smith AV"", ""Zhao H"", ""Lange E"", ""Lange L"", ""Rich SS"", ""Rotter JI"", ""Wilson JG"", ""Scheet P"", ""Kitzman JO"", ""Lander ES"", ""Engreitz JM"", ""Ebert BL"", ""Reiner AP"", ""Jaiswal S"", ""Abecasis G"", ""Sankaran VG"", ""Kathiresan S"", ""Natarajan P""]",10.1038/s41586-020-2819-2,Bick AG,Nature,0028-0836,7831,Nature,eng,Natarajan P,"[""Adult"", ""Africa"", ""Aged"", ""Aged, 80 and over"", ""Black People"", ""Cell Self Renewal"", ""Clonal Hematopoiesis"", ""DNA-Binding Proteins"", ""Dioxygenases"", ""Female"", ""Genetic Predisposition to Disease"", ""Genome, Human"", ""Germ-Line Mutation"", ""Hematopoietic Stem Cells"", ""Humans"", ""Intracellular Signaling Peptides and Proteins"", ""Male"", ""Middle Aged"", ""National Heart, Lung, and Blood Institute (U.S.)"", ""Phenotype"", ""Precision Medicine"", ""Proto-Oncogene Proteins"", ""Tripartite Motif Proteins"", ""United States"", ""Whole Genome Sequencing"", ""alpha Karyopherins"", ""Black or African American""]",763-768,33057201,pmc-id: PMC7944936;manuscript-id: NIHMS1609346;,2020 Oct,2020,https://pubmed.ncbi.nlm.nih.gov/33057201/,"Inherited causes of clonal haematopoiesis in 97,691 whole genomes",586,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Genetic variation can predispose to disease both through (i) monogenic risk variants that disrupt a physiologic pathway with large effect on disease and (ii) polygenic risk that involves many variants of small effect in different pathways. Few studies have explored the interplay between monogenic and polygenic risk. Here, we study 80,928 individuals to examine whether polygenic background can modify penetrance of disease in tier 1 genomic conditions - familial hypercholesterolemia, hereditary breast and ovarian cancer, and Lynch syndrome. Among carriers of a monogenic risk variant, we estimate substantial gradients in disease risk based on polygenic background - the probability of disease by age 75 years ranged from 17% to 78% for coronary artery disease, 13% to 76% for breast cancer, and 11% to 80% for colon cancer. We propose that accounting for polygenic background is likely to increase accuracy of risk estimation for individuals who inherit a monogenic risk variant.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Fahed AC"", ""Wang M"", ""Homburger JR"", ""Patel AP"", ""Bick AG"", ""Neben CL"", ""Lai C"", ""Brockman D"", ""Philippakis A"", ""Ellinor PT"", ""Cassa CA"", ""Lebo M"", ""Ng K"", ""Lander ES"", ""Zhou AY"", ""Kathiresan S"", ""Khera AV""]",10.1038/s41467-020-17374-3,Fahed AC,Nature communications,2041-1723,1,Nat Commun,eng,Khera AV,"[""Aged"", ""Breast Neoplasms"", ""Case-Control Studies"", ""Colorectal Neoplasms"", ""Coronary Artery Disease"", ""Female"", ""Genetic Predisposition to Disease"", ""Genome, Human"", ""Humans"", ""Male"", ""Middle Aged"", ""Multifactorial Inheritance"", ""Odds Ratio"", ""Penetrance"", ""Risk Factors""]",3635,32820175,pmc-id: PMC7441381;,2020 Aug 20,2020,https://pubmed.ncbi.nlm.nih.gov/32820175/,Polygenic background modifies penetrance of monogenic variants for tier 1 genomic conditions,11,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"A key goal of whole-genome sequencing for studies of human genetics is to interrogate all forms of variation, including single-nucleotide variants, small insertion or deletion (indel) variants and structural variants. However, tools and resources for the study of structural variants have lagged behind those for smaller variants. Here we used a scalable pipeline1 to map and characterize structural variants in 17,795 deeply sequenced human genomes. We publicly release site-frequency data to create the largest, to our knowledge, whole-genome-sequencing-based structural variant resource so far. On average, individuals carry 2.9 rare structural variants that alter coding regions; these variants affect the dosage or structure of 4.2 genes and account for 4.0-11.2% of rare high-impact coding alleles. Using a computational model, we estimate that structural variants account for 17.2% of rare alleles genome-wide, with predicted deleterious effects that are equivalent to loss-of-function coding alleles; approximately 90% of such structural variants are noncoding deletions (mean 19.1 per genome). We report 158,991 ultra-rare structural variants and show that 2% of individuals carry ultra-rare megabase-scale structural variants, nearly half of which are balanced or complex rearrangements. Finally, we infer the dosage sensitivity of genes and noncoding elements, and reveal trends that relate to element class and conservation. This work will help to guide the analysis and interpretation of structural variants in the era of whole-genome sequencing.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Abel HJ"", ""Larson DE"", ""Regier AA"", ""Chiang C"", ""Das I"", ""Kanchi KL"", ""Layer RM"", ""Neale BM"", ""Salerno WJ"", ""Reeves C"", ""Buyske S"", ""NHGRI Centers for Common Disease Genomics"", ""Matise TC"", ""Muzny DM"", ""Zody MC"", ""Lander ES"", ""Dutcher SK"", ""Stitziel NO"", ""Hall IM""]",10.1038/s41586-020-2371-0,Abel HJ,Nature,0028-0836,7814,Nature,eng,Hall IM,"[""Alleles"", ""Case-Control Studies"", ""Epigenesis, Genetic"", ""Female"", ""Gene Dosage"", ""Genetic Variation"", ""Genetics, Population"", ""Genome, Human"", ""High-Throughput Nucleotide Sequencing"", ""Humans"", ""Male"", ""Molecular Sequence Annotation"", ""Quantitative Trait Loci"", ""Racial Groups"", ""Software"", ""Whole Genome Sequencing""]",83-89,32460305,pmc-id: PMC7547914;manuscript-id: NIHMS1595842;,2020 Jul,2020,https://pubmed.ncbi.nlm.nih.gov/32460305/,"Mapping and characterization of structural variation in 17,795 human genomes",583,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Prion disease is a rare, fatal, and exceptionally rapid neurodegenerative disease. Although incurable, prion disease follows a clear pathogenic mechanism, in which a single gene gives rise to a single prion protein (PrP) capable of converting into the sole causal disease agent, the misfolded prion. As efforts progress to leverage this mechanistic knowledge toward rational therapies, a principal challenge will be the design of clinical trials. Previous trials in prion disease have been done in symptomatic patients who are often profoundly debilitated at enrolment. About 15% of prion disease cases are genetic, creating an opportunity for early therapeutic intervention to delay or prevent disease. Highly variable age of onset and absence of established prodromal biomarkers might render infeasible existing models for testing drugs before disease onset. Advancement of near-term targeted therapeutics could crucially depend on thoughtful design of rigorous presymptomatic trials.","[""Journal Article"", ""Review""]","[""Vallabh SM"", ""Minikel EV"", ""Schreiber SL"", ""Lander ES""]",10.1016/S1474-4422(19)30403-X,Vallabh SM,The Lancet. Neurology,1474-4422,4,Lancet Neurol,eng,Lander ES,"[""Animals"", ""Biomarkers"", ""Humans"", ""Neurodegenerative Diseases"", ""Prion Diseases"", ""Prion Proteins"", ""Prions""]",361-368,32199098,,2020 Apr,2020,https://pubmed.ncbi.nlm.nih.gov/32199098/,Towards a treatment for genetic prion disease: trials and biomarkers,19,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Genome-wide association studies have associated thousands of genetic variants with complex traits and diseases, but pinpointing the causal variant(s) among those in tight linkage disequilibrium with each associated variant remains a major challenge. Here, we use seven experimental assays to characterize all common variants at the multiple disease-associated TNFAIP3 locus in five disease-relevant immune cell lines, based on a set of features related to regulatory potential. Trait/disease-associated variants are enriched among SNPs prioritized based on either: (1) residing within CRISPRi-sensitive regulatory regions, or (2) localizing in a chromatin accessible region while displaying allele-specific reporter activity. Of the 15 trait/disease-associated haplotypes at TNFAIP3, 9 have at least one variant meeting one or both of these criteria, 5 of which are further supported by genetic fine-mapping. Our work provides a comprehensive strategy to characterize genetic variation at important disease-associated loci, and aids in the effort to identify trait causal genetic variants.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Ray JP"", ""de Boer CG"", ""Fulco CP"", ""Lareau CA"", ""Kanai M"", ""Ulirsch JC"", ""Tewhey R"", ""Ludwig LS"", ""Reilly SK"", ""Bergman DT"", ""Engreitz JM"", ""Issner R"", ""Finucane HK"", ""Lander ES"", ""Regev A"", ""Hacohen N""]",10.1038/s41467-020-15022-4,Ray JP,Nature communications,2041-1723,1,Nat Commun,eng,Hacohen N,"[""Autoimmune Diseases"", ""Cell Line, Tumor"", ""Genetic Loci"", ""Genetic Predisposition to Disease"", ""Genetic Variation"", ""Genome-Wide Association Study"", ""Haplotypes"", ""Humans"", ""Linkage Disequilibrium"", ""Multifactorial Inheritance"", ""Proof of Concept Study"", ""Tumor Necrosis Factor alpha-Induced Protein 3""]",1237,32144282,pmc-id: PMC7060350;,2020 Mar 6,2020,https://pubmed.ncbi.nlm.nih.gov/32144282/,Prioritizing disease and trait causal variants at the TNFAIP3 locus using functional and genomic features,11,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Despite rare cancers accounting for 25% of adult tumors1, they are difficult to study due to the low disease incidence and geographically dispersed patient populations, which has resulted in significant unmet clinical needs for patients with rare cancers. We assessed whether a patient-partnered research approach using online engagement can overcome these challenges, focusing on angiosarcoma, a sarcoma with an annual incidence of 300 cases in the United States. Here we describe the development of the Angiosarcoma Project (ASCproject), an initiative enabling US and Canadian patients to remotely share their clinical information and biospecimens for research. The project generates and publicly releases clinically annotated genomic data on tumor and germline specimens on an ongoing basis. Over 18 months, 338 patients registered for the ASCproject, which comprises a large proportion of all patients with angiosarcoma. Whole-exome sequencing (WES) of 47 tumors revealed recurrently mutated genes that included KDR, TP53, and PIK3CA. PIK3CA-activating mutations were observed predominantly in primary breast angiosarcoma, which suggested a therapeutic rationale. Angiosarcoma of the head, neck, face and scalp (HNFS) was associated with a high tumor mutation burden (TMB) and a dominant ultraviolet damage mutational signature, which suggested that for the subset of patients with angiosarcoma of HNFS, ultraviolet damage may be a causative factor and that immune checkpoint inhibition may be beneficial. Medical record review revealed that two patients with HNFS angiosarcoma had received off-label therapeutic use of antibody to the programmed death-1 protein (anti-PD-1) and had experienced exceptional responses, which highlights immune checkpoint inhibition as a therapeutic avenue for HNFS angiosarcoma. This patient-partnered approach has catalyzed an opportunity to discover the etiology and potential therapies for patients with angiosarcoma. Collectively, this proof-of-concept study demonstrates that empowering patients to directly participate in research can overcome barriers in rare diseases and can enable discoveries.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Painter CA"", ""Jain E"", ""Tomson BN"", ""Dunphy M"", ""Stoddard RE"", ""Thomas BS"", ""Damon AL"", ""Shah S"", ""Kim D"", ""Gómez Tejeda Zañudo J"", ""Hornick JL"", ""Chen YL"", ""Merriam P"", ""Raut CP"", ""Demetri GD"", ""Van Tine BA"", ""Lander ES"", ""Golub TR"", ""Wagle N""]",10.1038/s41591-019-0749-z,Painter CA,Nature medicine,1078-8956,2,Nat Med,eng,Wagle N,"[""Adult"", ""Aged"", ""Aged, 80 and over"", ""Breast Neoplasms"", ""Canada"", ""Class I Phosphatidylinositol 3-Kinases"", ""DNA Mutational Analysis"", ""Exome"", ""Female"", ""Genome, Human"", ""Genomics"", ""Hemangiosarcoma"", ""Humans"", ""Middle Aged"", ""Mutation"", ""Patient Participation"", ""Program Development"", ""Rare Diseases"", ""Tumor Suppressor Protein p53"", ""United States"", ""Vascular Endothelial Growth Factor Receptor-2"", ""Exome Sequencing"", ""Young Adult""]",181-187,32042194,,2020 Feb,2020,https://pubmed.ncbi.nlm.nih.gov/32042194/,The Angiosarcoma Project: enabling genomic and clinical discoveries in a rare cancer through patient-partnered research,26,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Cancer genomes contain large numbers of somatic mutations but few of these mutations drive tumor development. Current approaches either identify driver genes on the basis of mutational recurrence or approximate the functional consequences of nonsynonymous mutations by using bioinformatic scores. Passenger mutations are enriched in characteristic nucleotide contexts, whereas driver mutations occur in functional positions, which are not necessarily surrounded by a particular nucleotide context. We observed that mutations in contexts that deviate from the characteristic contexts around passenger mutations provide a signal in favor of driver genes. We therefore developed a method that combines this feature with the signals traditionally used for driver-gene identification. We applied our method to whole-exome sequencing data from 11,873 tumor-normal pairs and identified 460 driver genes that clustered into 21 cancer-related pathways. Our study provides a resource of driver genes across 28 tumor types with additional driver genes identified according to mutations in unusual nucleotide contexts.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Dietlein F"", ""Weghorn D"", ""Taylor-Weiner A"", ""Richters A"", ""Reardon B"", ""Liu D"", ""Lander ES"", ""Van Allen EM"", ""Sunyaev SR""]",10.1038/s41588-019-0572-y,Dietlein F,Nature genetics,1061-4036,2,Nat Genet,eng,Sunyaev SR,"[""Cluster Analysis"", ""Computational Biology"", ""Humans"", ""Mutation"", ""Neoplasms"", ""Nucleotides"", ""Proteins"", ""Exome Sequencing""]",208-218,32015527,pmc-id: PMC7031046;manuscript-id: NIHMS1546846;,2020 Feb,2020,https://pubmed.ncbi.nlm.nih.gov/32015527/,Identification of cancer driver genes based on nucleotide context,52,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Increased production of fetal hemoglobin (HbF) can ameliorate the severity of sickle cell disease and β-thalassemia1. BCL11A represses the genes encoding HbF and regulates human hemoglobin switching through variation in its expression during development2-7. However, the mechanisms underlying the developmental expression of BCL11A remain mysterious. Here we show that BCL11A is regulated at the level of messenger RNA (mRNA) translation during human hematopoietic development. Despite decreased BCL11A protein synthesis earlier in development, BCL11A mRNA continues to be associated with ribosomes. Through unbiased genomic and proteomic analyses, we demonstrate that the RNA-binding protein LIN28B, which is developmentally expressed in a pattern reciprocal to that of BCL11A, directly interacts with ribosomes and BCL11A mRNA. Furthermore, we show that BCL11A mRNA translation is suppressed by LIN28B through direct interactions, independently of its role in regulating let-7 microRNAs, and that BCL11A is the major target of LIN28B-mediated HbF induction. Our results reveal a previously unappreciated mechanism underlying human hemoglobin switching that illuminates new therapeutic opportunities.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Basak A"", ""Munschauer M"", ""Lareau CA"", ""Montbleau KE"", ""Ulirsch JC"", ""Hartigan CR"", ""Schenone M"", ""Lian J"", ""Wang Y"", ""Huang Y"", ""Wu X"", ""Gehrke L"", ""Rice CM"", ""An X"", ""Christou HA"", ""Mohandas N"", ""Carr SA"", ""Chen JJ"", ""Orkin SH"", ""Lander ES"", ""Sankaran VG""]",10.1038/s41588-019-0568-7,Basak A,Nature genetics,1061-4036,2,Nat Genet,eng,Sankaran VG,"[""Adult"", ""Animals"", ""Binding Sites"", ""Cells, Cultured"", ""Erythroid Cells"", ""Erythropoiesis"", ""Gene Expression Regulation"", ""Hemoglobins"", ""Humans"", ""Infant, Newborn"", ""MicroRNAs"", ""Protein Biosynthesis"", ""RNA, Messenger"", ""RNA, Ribosomal, 18S"", ""RNA-Binding Proteins"", ""Repressor Proteins"", ""Ribosomes""]",138-145,31959994,pmc-id: PMC7031047;manuscript-id: NIHMS1546343;,2020 Feb,2020,https://pubmed.ncbi.nlm.nih.gov/31959994/,Control of human hemoglobin switching by LIN28B-mediated regulation of BCL11A translation,52,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Enhancer elements in the human genome control how genes are expressed in specific cell types and harbor thousands of genetic variants that influence risk for common diseases1-4. Yet, we still do not know how enhancers regulate specific genes, and we lack general rules to predict enhancer-gene connections across cell types5,6. We developed an experimental approach, CRISPRi-FlowFISH, to perturb enhancers in the genome, and we applied it to test >3,500 potential enhancer-gene connections for 30 genes. We found that a simple activity-by-contact model substantially outperformed previous methods at predicting the complex connections in our CRISPR dataset. This activity-by-contact model allows us to construct genome-wide maps of enhancer-gene connections in a given cell type, on the basis of chromatin state measurements. Together, CRISPRi-FlowFISH and the activity-by-contact model provide a systematic approach to map and predict which enhancers regulate which genes, and will help to interpret the functions of the thousands of disease risk variants in the noncoding genome.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't"", ""Research Support, U.S. Gov't, Non-P.H.S.""]","[""Fulco CP"", ""Nasser J"", ""Jones TR"", ""Munson G"", ""Bergman DT"", ""Subramanian V"", ""Grossman SR"", ""Anyoha R"", ""Doughty BR"", ""Patwardhan TA"", ""Nguyen TH"", ""Kane M"", ""Perez EM"", ""Durand NC"", ""Lareau CA"", ""Stamenova EK"", ""Aiden EL"", ""Lander ES"", ""Engreitz JM""]",10.1038/s41588-019-0538-0,Fulco CP,Nature genetics,1061-4036,12,Nat Genet,eng,Engreitz JM,"[""Animals"", ""Clustered Regularly Interspaced Short Palindromic Repeats"", ""Enhancer Elements, Genetic"", ""GATA1 Transcription Factor"", ""Gene Expression Regulation"", ""Histone Deacetylase 6"", ""Humans"", ""In Situ Hybridization, Fluorescence"", ""K562 Cells"", ""Mice"", ""Models, Genetic"", ""Promoter Regions, Genetic"", ""RNA, Guide, CRISPR-Cas Systems""]",1664-1669,31784727,pmc-id: PMC6886585;manuscript-id: NIHMS1541544;,2019 Dec,2019,https://pubmed.ncbi.nlm.nih.gov/31784727/,Activity-by-contact model of enhancer-promoter regulation from thousands of CRISPR perturbations,51,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Sudden cardiac death occurs in ∼220,000 U.S. adults annually, the majority of whom have no prior symptoms or cardiovascular diagnosis. Rare pathogenic DNA variants in any of 49 genes can pre-dispose to 4 important causes of sudden cardiac death: cardiomyopathy, coronary artery disease, inherited arrhythmia syndrome, and aortopathy or aortic dissection. This study assessed the prevalence of rare pathogenic variants in sudden cardiac death cases versus controls, and the prevalence and clinical importance of such mutations in an asymptomatic adult population. The authors performed whole-exome sequencing in a case-control cohort of 600 adult-onset sudden cardiac death cases and 600 matched controls from 106,098 participants of 6 prospective cohort studies. Observed DNA sequence variants in any of 49 genes with known association to cardiovascular disease were classified as pathogenic or likely pathogenic by a clinical laboratory geneticist blinded to case status. In an independent population of 4,525 asymptomatic adult participants of a prospective cohort study, the authors performed whole-genome sequencing and determined the prevalence of pathogenic or likely pathogenic variants and prospective association with cardiovascular death. Among the 1,200 sudden cardiac death cases and controls, the authors identified 5,178 genetic variants and classified 14 as pathogenic or likely pathogenic. These 14 variants were present in 15 individuals, all of whom had experienced sudden cardiac death-corresponding to a pathogenic variant prevalence of 2.5% in cases and 0% in controls (p < 0.0001). Among the 4,525 participants of the prospective cohort study, 41 (0.9%) carried a pathogenic or likely pathogenic variant and these individuals had 3.24-fold higher risk of cardiovascular death over a median follow-up of 14.3 years (p = 0.02). Gene sequencing identifies a pathogenic or likely pathogenic variant in a small but potentially important subset of adults experiencing sudden cardiac death; these variants are present in ∼1% of asymptomatic adults.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Khera AV"", ""Mason-Suares H"", ""Brockman D"", ""Wang M"", ""VanDenburgh MJ"", ""Senol-Cosar O"", ""Patterson C"", ""Newton-Cheh C"", ""Zekavat SM"", ""Pester J"", ""Chasman DI"", ""Kabrhel C"", ""Jensen MK"", ""Manson JE"", ""Gaziano JM"", ""Taylor KD"", ""Sotoodehnia N"", ""Post WS"", ""Rich SS"", ""Rotter JI"", ""Lander ES"", ""Rehm HL"", ""Ng K"", ""Philippakis A"", ""Lebo M"", ""Albert CM"", ""Kathiresan S""]",10.1016/j.jacc.2019.08.1060,Khera AV,Journal of the American College of Cardiology,0735-1097,21,J Am Coll Cardiol,eng,Kathiresan S,"[""Aged"", ""Aged, 80 and over"", ""Case-Control Studies"", ""Death, Sudden, Cardiac"", ""Female"", ""Genetic Predisposition to Disease"", ""Humans"", ""Male"", ""Middle Aged"", ""Exome Sequencing""]",2623-2634,31727422,pmc-id: PMC7067308;manuscript-id: NIHMS1546999;,2019 Nov 26,2019,https://pubmed.ncbi.nlm.nih.gov/31727422/,Rare Genetic Variants Associated With Sudden Cardiac Death in Adults,74,ENDC5psocNV258waT,fBiR6Lki005vebWjt
A correction to this paper has been published and can be accessed via a link at the top of the paper.,"[""Published Erratum""]","[""Bis JC"", ""Jian X"", ""Kunkle BW"", ""Chen Y"", ""Hamilton-Nelson KL"", ""Bush WS"", ""Salerno WJ"", ""Lancour D"", ""Ma Y"", ""Renton AE"", ""Marcora E"", ""Farrell JJ"", ""Zhao Y"", ""Qu L"", ""Ahmad S"", ""Amin N"", ""Amouyel P"", ""Beecham GW"", ""Below JE"", ""Campion D"", ""Cantwell L"", ""Charbonnier C"", ""Chung J"", ""Crane PK"", ""Cruchaga C"", ""Cupples LA"", ""Dartigues JF"", ""Debette S"", ""Deleuze JF"", ""Fulton L"", ""Gabriel SB"", ""Genin E"", ""Gibbs RA"", ""Goate A"", ""Grenier-Boley B"", ""Gupta N"", ""Haines JL"", ""Havulinna AS"", ""Helisalmi S"", ""Hiltunen M"", ""Howrigan DP"", ""Ikram MA"", ""Kaprio J"", ""Konrad J"", ""Kuzma A"", ""Lander ES"", ""Lathrop M"", ""Lehtimäki T"", ""Lin H"", ""Mattila K"", ""Mayeux R"", ""Muzny DM"", ""Nasser W"", ""Neale B"", ""Nho K"", ""Nicolas G"", ""Patel D"", ""Pericak-Vance MA"", ""Perola M"", ""Psaty BM"", ""Quenez O"", ""Rajabli F"", ""Redon R"", ""Reitz C"", ""Remes AM"", ""Salomaa V"", ""Sarnowski C"", ""Schmidt H"", ""Schmidt M"", ""Schmidt R"", ""Soininen H"", ""Thornton TA"", ""Tosto G"", ""Tzourio C"", ""van der Lee SJ"", ""van Duijn CM"", ""Valladares O"", ""Vardarajan B"", ""Wang LS"", ""Wang W"", ""Wijsman E"", ""Wilson RK"", ""Witten D"", ""Worley KC"", ""Zhang X"", ""Alzheimer’s Disease Sequencing Project"", ""Bellenguez C"", ""Lambert JC"", ""Kurki MI"", ""Palotie A"", ""Daly M"", ""Boerwinkle E"", ""Lunetta KL"", ""Destefano AL"", ""Dupuis J"", ""Martin ER"", ""Schellenberg GD"", ""Seshadri S"", ""Naj AC"", ""Fornage M"", ""Farrer LA""]",10.1038/s41380-019-0529-7,Bis JC,Molecular psychiatry,1359-4184,8,Mol Psychiatry,eng,Farrer LA,[],1901-1903,31636380,pmc-id: PMC7387240;,2020 Aug,2020,https://pubmed.ncbi.nlm.nih.gov/31636380/,Correction: Whole exome sequencing study identifies novel rare and common Alzheimer's-Associated variants involved in immune response and transcriptional regulation,25,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Human genetic variants in SLC16A11 are associated with increased risk of type 2 diabetes (T2D). We previously identified two distinct mechanisms through which co-inherited T2D-risk coding and non-coding variants disrupt SLC16A11 expression and activity, thus implicating reduced SLC16A11 function as the disease-relevant direction of effect. In a recent publication, Zhao et al. (2019a) argue that human SLC16A11 coding variants confer gain of function, basing their conclusions on phenotypic changes observed following overexpression of mutant murine Slc16a11. However, data necessary to demonstrate gain-of-function activity are not reported. Furthermore, several fundamental flaws in their experimental system-including inaccurate modeling of the human variant haplotype and expression conditions that are not physiologically relevant-prevent conclusions about T2D-risk variant effects on human physiology. This Matters Arising paper is in response to Zhao et al. (2019a), published in Cell Reports. See also the response by Zhao et al. (2019b) in this issue of Cell Reports.","[""Journal Article"", ""Comment""]","[""Hoch E"", ""Florez JC"", ""Lander ES"", ""Jacobs SBR""]",10.1016/j.celrep.2019.09.021,Hoch E,Cell reports,2211-1247,3,Cell Rep,eng,Jacobs SBR,"[""Animals"", ""Diabetes Mellitus, Type 2"", ""Gain of Function Mutation"", ""Haplotypes"", ""Humans"", ""Mice"", ""Monocarboxylic Acid Transporters""]",778-780,31618643,,2019 Oct 15,2019,https://pubmed.ncbi.nlm.nih.gov/31618643/,Gain-of-Function Claims for Type-2-Diabetes-Associated Coding Variants in SLC16A11 Are Not Supported by the Experimental Data,29,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Intracellular accumulation of misfolded proteins causes toxic proteinopathies, diseases without targeted therapies. Mucin 1 kidney disease (MKD) results from a frameshift mutation in the MUC1 gene (MUC1-fs). Here, we show that MKD is a toxic proteinopathy. Intracellular MUC1-fs accumulation activated the ATF6 unfolded protein response (UPR) branch. We identified BRD4780, a small molecule that clears MUC1-fs from patient cells, from kidneys of knockin mice and from patient kidney organoids. MUC1-fs is trapped in TMED9 cargo receptor-containing vesicles of the early secretory pathway. BRD4780 binds TMED9, releases MUC1-fs, and re-routes it for lysosomal degradation, an effect phenocopied by TMED9 deletion. Our findings reveal BRD4780 as a promising lead for the treatment of MKD and other toxic proteinopathies. Generally, we elucidate a novel mechanism for the entrapment of misfolded proteins by cargo receptors and a strategy for their release and anterograde trafficking to the lysosome.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Dvela-Levitt M"", ""Kost-Alimova M"", ""Emani M"", ""Kohnert E"", ""Thompson R"", ""Sidhom EH"", ""Rivadeneira A"", ""Sahakian N"", ""Roignot J"", ""Papagregoriou G"", ""Montesinos MS"", ""Clark AR"", ""McKinney D"", ""Gutierrez J"", ""Roth M"", ""Ronco L"", ""Elonga E"", ""Carter TA"", ""Gnirke A"", ""Melanson M"", ""Hartland K"", ""Wieder N"", ""Hsu JC"", ""Deltas C"", ""Hughey R"", ""Bleyer AJ"", ""Kmoch S"", ""Živná M"", ""Barešova V"", ""Kota S"", ""Schlondorff J"", ""Heiman M"", ""Alper SL"", ""Wagner F"", ""Weins A"", ""Golub TR"", ""Lander ES"", ""Greka A""]",10.1016/j.cell.2019.07.002,Dvela-Levitt M,Cell,0092-8674,3,Cell,eng,Greka A,"[""Activating Transcription Factor 6"", ""Animals"", ""Benzamides"", ""Bridged Bicyclo Compounds"", ""Epithelial Cells"", ""Female"", ""Frameshift Mutation"", ""Heptanes"", ""Humans"", ""Imidazoline Receptors"", ""Induced Pluripotent Stem Cells"", ""Kidney"", ""Kidney Diseases"", ""Lysosomes"", ""Male"", ""Mice"", ""Mice, Transgenic"", ""Mucin-1"", ""RNA Interference"", ""RNA, Small Interfering"", ""Unfolded Protein Response"", ""Vesicular Transport Proteins""]",521-535.e23,31348885,,2019 Jul 25,2019,https://pubmed.ncbi.nlm.nih.gov/31348885/,Small Molecule Targets TMED9 and Promotes Lysosomal Degradation to Reverse Proteinopathy,178,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"New antibiotics are needed to combat rising levels of resistance, with new Mycobacterium tuberculosis (Mtb) drugs having the highest priority. However, conventional whole-cell and biochemical antibiotic screens have failed. Here we develop a strategy termed PROSPECT (primary screening of strains to prioritize expanded chemistry and targets), in which we screen compounds against pools of strains depleted of essential bacterial targets. We engineered strains that target 474 essential Mtb genes and screened pools of 100-150 strains against activity-enriched and unbiased compound libraries, probing more than 8.5 million chemical-genetic interactions. Primary screens identified over tenfold more hits than screening wild-type Mtb alone, with chemical-genetic interactions providing immediate, direct target insights. We identified over 40 compounds that target DNA gyrase, the cell wall, tryptophan, folate biosynthesis and RNA polymerase, as well as inhibitors that target EfpA. Chemical optimization yielded EfpA inhibitors with potent wild-type activity, thus demonstrating the ability of PROSPECT to yield inhibitors against targets that would have eluded conventional drug discovery.","[""Journal Article""]","[""Johnson EO"", ""LaVerriere E"", ""Office E"", ""Stanley M"", ""Meyer E"", ""Kawate T"", ""Gomez JE"", ""Audette RE"", ""Bandyopadhyay N"", ""Betancourt N"", ""Delano K"", ""Da Silva I"", ""Davis J"", ""Gallo C"", ""Gardner M"", ""Golas AJ"", ""Guinn KM"", ""Kennedy S"", ""Korn R"", ""McConnell JA"", ""Moss CE"", ""Murphy KC"", ""Nietupski RM"", ""Papavinasasundaram KG"", ""Pinkham JT"", ""Pino PA"", ""Proulx MK"", ""Ruecker N"", ""Song N"", ""Thompson M"", ""Trujillo C"", ""Wakabayashi S"", ""Wallach JB"", ""Watson C"", ""Ioerger TR"", ""Lander ES"", ""Hubbard BK"", ""Serrano-Wu MH"", ""Ehrt S"", ""Fitzgerald M"", ""Rubin EJ"", ""Sassetti CM"", ""Schnappinger D"", ""Hung DT""]",10.1038/s41586-019-1315-z,Johnson EO,Nature,0028-0836,7763,Nature,eng,Hung DT,"[""Antitubercular Agents"", ""DNA Gyrase"", ""Drug Discovery"", ""Drug Resistance, Microbial"", ""Folic Acid"", ""Gene Deletion"", ""Microbial Sensitivity Tests"", ""Molecular Targeted Therapy"", ""Mycobacterium tuberculosis"", ""Mycolic Acids"", ""Reproducibility of Results"", ""Small Molecule Libraries"", ""Substrate Specificity"", ""Topoisomerase II Inhibitors"", ""Tryptophan"", ""Tuberculosis""]",72-78,31217586,,2019 Jul,2019,https://pubmed.ncbi.nlm.nih.gov/31217586/,Large-scale chemical-genetics yields new M. tuberculosis inhibitor classes,571,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Genomics offered the promise of transforming antibiotic discovery by revealing many new essential genes as good targets, but the results fell short of the promise. While numerous factors contributed to the disappointing yield, one factor was that essential genes for a bacterial species were often defined based on a single or limited number of strains grown under a single or limited number of in vitro laboratory conditions. In fact, the essentiality of a gene can depend on both the genetic background and growth condition. We thus developed a strategy for more rigorously defining the core essential genome of a bacterial species by studying many pathogen strains and growth conditions. We assessed how many strains must be examined to converge on a set of core essential genes for a species. We used transposon insertion sequencing (Tn-Seq) to define essential genes in nine strains of Pseudomonas aeruginosa on five different media and developed a statistical model, FiTnEss, to classify genes as essential versus nonessential across all strain-medium combinations. We defined a set of 321 core essential genes, representing 6.6% of the genome. We determined that analysis of four strains was typically sufficient in P. aeruginosa to converge on a set of core essential genes likely to be essential across the species across a wide range of conditions relevant to in vivo infection, and thus to represent attractive targets for novel drug discovery.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Poulsen BE"", ""Yang R"", ""Clatworthy AE"", ""White T"", ""Osmulski SJ"", ""Li L"", ""Penaranda C"", ""Lander ES"", ""Shoresh N"", ""Hung DT""]",10.1073/pnas.1900570116,Poulsen BE,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,20,Proc Natl Acad Sci U S A,eng,Hung DT,"[""DNA Transposable Elements"", ""Genes, Essential"", ""Genome, Bacterial"", ""Models, Statistical"", ""Pseudomonas aeruginosa""]",10072-10080,31036669,pmc-id: PMC6525520;,2019 May 14,2019,https://pubmed.ncbi.nlm.nih.gov/31036669/,Defining the core essential genome of Pseudomonas aeruginosa,116,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Severe obesity is a rapidly growing global health threat. Although often attributed to unhealthy lifestyle choices or environmental factors, obesity is known to be heritable and highly polygenic; the majority of inherited susceptibility is related to the cumulative effect of many common DNA variants. Here we derive and validate a new polygenic predictor comprised of 2.1 million common variants to quantify this susceptibility and test this predictor in more than 300,000 individuals ranging from middle age to birth. Among middle-aged adults, we observe a 13-kg gradient in weight and a 25-fold gradient in risk of severe obesity across polygenic score deciles. In a longitudinal birth cohort, we note minimal differences in birthweight across score deciles, but a significant gradient emerged in early childhood and reached 12 kg by 18 years of age. This new approach to quantify inherited susceptibility to obesity affords new opportunities for clinical prevention and mechanistic assessment.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, N.I.H., Intramural"", ""Research Support, Non-U.S. Gov't""]","[""Khera AV"", ""Chaffin M"", ""Wade KH"", ""Zahid S"", ""Brancale J"", ""Xia R"", ""Distefano M"", ""Senol-Cosar O"", ""Haas ME"", ""Bick A"", ""Aragam KG"", ""Lander ES"", ""Smith GD"", ""Mason-Suares H"", ""Fornage M"", ""Lebo M"", ""Timpson NJ"", ""Kaplan LM"", ""Kathiresan S""]",10.1016/j.cell.2019.03.028,Khera AV,Cell,0092-8674,3,Cell,eng,Kathiresan S,"[""Adolescent"", ""Body Mass Index"", ""Body Weight"", ""Child"", ""Databases, Factual"", ""Female"", ""Genome-Wide Association Study"", ""Humans"", ""Infant, Newborn"", ""Longitudinal Studies"", ""Male"", ""Middle Aged"", ""Multifactorial Inheritance"", ""Obesity"", ""Risk Factors"", ""Severity of Illness Index""]",587-596.e9,31002795,pmc-id: PMC6661115;manuscript-id: NIHMS1535553;,2019 Apr 18,2019,https://pubmed.ncbi.nlm.nih.gov/31002795/,Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood,177,ENDC5psocNV258waT,fBiR6Lki005vebWjt
"Genome-wide association studies (GWAS) have identified >1,200 signals associated with type 2 diabetes (T2D), yet identifying functional variants remains challenging because the majority of them lie in noncoding regions of the genome and are in areas of high linkage disequilibrium (LD). While chromatin accessibility QTL (caQTL) and expression QTL (eQTL) analyses are useful for nominating regulatory mechanisms underlying GWAS signals, limitations still exist in pinpointing functional variants within regions of high LD. A complementary approach that has been less frequently applied is to focus on the allele-specific effect on chromatin accessibility at heterozygous single-nucleotide polymorphisms (SNPs), hereafter referred to as ""allelic imbalance"". We analyzed the allelic imbalance of reads generated from an assay for transposase-accessible chromatin with sequencing (ATAC-seq) across genotyped samples from 490 donors in T2D-relevant tissues: skeletal muscle, liver, pancreatic islets, adipose tissue, and relevant cell types. We identified 119,949 allelically imbalanced SNPs (FDR<0.05) across the genome. The allelic imbalance was often most prominent in one tissue and showed an enrichment overlapping with tissue-specific transcription factor (TF) binding footprints. Focusing on the 8,581 SNPs in previously published 99% credible sets from 338 T2D GWAS signals, we identified 256 imbalanced SNPs across 123 (36.4% of) signals, each showing allelic imbalance in at least one tissue or cell type. Of these, 71 signals contained only a single imbalanced SNP, representing excellent candidate causative variants. As a proof-of-concept, we showed that 23 of the 256 imbalanced SNPs were supported by allelic assays from previous studies. Further, we experimentally validated two imbalanced SNPs as likely functional variants: rs34584161 among a seven-SNP T2D credible set at the RNF6 signal in islets and rs849134 among a 13-SNP credible set at the JAZF1 signal in liver. This study demonstrates the power of integrating ATAC-seq allelic imbalance (ASAI) with GWAS statistical fine-mapping to identify candidate functional regulatory variants from among tightly linked GWAS variants in disease-relevant tissues. While applied here in T2D, this approach represents a widely applicable high-throughput framework for refining the genetic architecture of complex traits.","[""Journal Article"", ""Preprint""]","[""Narisu N"", ""Li HX"", ""Rathbun CJM"", ""Varshney A"", ""Swift AJ"", ""Yan T"", ""Sinha N"", ""Currin KW"", ""Xue D"", ""Robertson CC"", ""Taylor DL"", ""Taylor HJ"", ""Beck A"", ""Lee BN"", ""Wang L"", ""Broadaway KA"", ""Wilson EP"", ""Stringham H"", ""Saramies J"", ""Lakka TA"", ""Spracklen CN"", ""Scott LJ"", ""Stitzel ML"", ""Tuomilehto J"", ""Laakso M"", ""Koistinen HA"", ""Boehnke M"", ""Arda HE"", ""Chen S"", ""Biesecker LG"", ""Bonnycastle LL"", ""Erdos MR"", ""Mohlke KL"", ""Parker SCJ"", ""Collins FS""]",10.64898/2026.07.14.26358094,Narisu N,medRxiv : the preprint server for health sciences,,,medRxiv,eng,Collins FS,[],,42523508,pmc-id: PMC13405542;,2026 Jul 15,2026,https://pubmed.ncbi.nlm.nih.gov/42523508/,Multi-tissue analyses of allele-specific chromatin accessibility nominate likely functional variants for type 2 diabetes,,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"The hypothalamus, composed of multiple nuclei, is essential for maintaining the body's homeostasis. Within the mediobasal hypothalamus, the arcuate nucleus (ARC) contains key neuronal populations, including appetite-suppressing pro-opiomelanocortin (POMC) neurons that regulate energy and glucose balance. Here, we present a chemically defined, scalable method for differentiating human pluripotent stem cells (hPSCs) into hypothalamic neurons enriched for POMC cells, compatible with robotic cell culture platforms for high-throughput use. Neuronal identity was validated by MERFISH single-cell transcriptomics, RNA-Seq, ATAC-Seq, and comparison to human hypothalamus. The method is robust across multiple hPSC lines, showing consistent induction of ventral diencephalon and hypothalamic markers. Derived neurons display metabolic disease-relevant features, including body mass index (BMI)-associated gene enrichment, and ATAC-Seq identifies potential candidate regulatory regions linked to hypothalamic development and metabolic traits. Functional assays reveal neuronal responses to insulin and the GLP-1 receptor agonist Exendin-4, and transcriptional responses to altered glucose conditions. This platform delivers a physiologically relevant model of human hypothalamic neurons that enables deeper mechanistic and therapeutic studies of metabolic disease.","[""Journal Article""]","[""Jovanovic VM"", ""Narisu N"", ""Bonnycastle LL"", ""Castellano D"", ""Ryu S"", ""Tharakan R"", ""Mesch KT"", ""Chen Q"", ""Betül Erol FM"", ""Glover HJ"", ""Yan T"", ""Sinha N"", ""Sen C"", ""Yang S"", ""Blivis D"", ""Bennett DF"", ""Rosales-Soto G"", ""Inman J"", ""Ormanoglu P"", ""LeClair CA"", ""Shaw ND"", ""Xia M"", ""Schneider M"", ""Hernandez-Ochoa EO"", ""Erdos MR"", ""Simeonov A"", ""Chen S"", ""Collins FS"", ""Doege CA"", ""Tristan CA""]",10.1016/j.stemcr.2026.102958,Jovanovic VM,Stem cell reports,2213-6711,7,Stem Cell Reports,eng,Tristan CA,"[""Humans"", ""Neurons"", ""Pluripotent Stem Cells"", ""Cell Differentiation"", ""Hypothalamus"", ""Metabolic Diseases"", ""Pro-Opiomelanocortin"", ""Models, Biological"", ""Insulin"", ""Glucose""]",102958,42276059,pmc-id: PMC13385436;,2026 Jul 14,2026,https://pubmed.ncbi.nlm.nih.gov/42276059/,Scalable hypothalamic neuron differentiation from human pluripotent stem cells suitable for modeling metabolic disorders,21,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Induced pluripotent stem cells (iPSCs) enabled the generation of diverse cell types; however, certain fundamental biological properties, such as the genetic and epigenetic determinants of proliferation, remain poorly characterized. We quantified proliferation across 602 unique donors with a time-lapse imaging-based growth area under the curve (gAUC) phenotype and correlated gAUC with cell line gene expression and genotype. We identified 3,091 differentially expressed genes and found that rare deleterious variants in WDR54, TMEM250, and C2orf81 were associated with reduced iPSC growth. Notably, WDR54 was differentially expressed with respect to gAUC. Although no common variants were associated, common genetic variation explained 71%-75% of the variance. These results indicate a complex genetic architecture of iPSC growth rates, where rare, large-effect variants in important growth regulators are layered onto a highly polygenic background. These findings can impact the design of pooled iPSC-based studies and disease models, which may be confounded by intrinsic growth differences.","[""Journal Article""]","[""Lee BN"", ""Taylor HJ"", ""Cipriani F"", ""Narisu N"", ""Robertson CC"", ""Swift AJ"", ""Sinha N"", ""Yan T"", ""Bonnycastle LL"", ""Dale N"", ""Butt A"", ""Parsaud H"", ""Semrau S"", ""NYSCF Global Stem Cell Array Team"", ""GENESiPS Consortium"", ""iPSCORE Consortium"", ""Knowles JW"", ""Carcamo-Orive I"", ""D'Antonio-Chronowska A"", ""Frazer KA"", ""Biesecker LG"", ""Noggle S"", ""Erdos MR"", ""Paull D"", ""Collins FS"", ""Taylor DL""]",10.1016/j.stemcr.2026.102928,Lee BN,Stem cell reports,2213-6711,6,Stem Cell Reports,eng,Taylor DL,"[""Induced Pluripotent Stem Cells"", ""Humans"", ""Cell Proliferation"", ""Phenotype"", ""Polymorphism, Single Nucleotide""]",102928,42167220,pmc-id: PMC13261958;,2026 Jun 9,2026,https://pubmed.ncbi.nlm.nih.gov/42167220/,Genetics of growth rate in induced pluripotent stem cells,21,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Fibro-adipogenic progenitors (FAPs) in skeletal muscle have been implicated in type 2 diabetes (T2D) risk, yet their heterogeneity and context-dependent regulation remain poorly understood. Here, we establish induced pluripotent stem cell (iPSC)-derived FAPs as a faithful model of primary FAPs by leveraging a unique resource: iPSC lines and skeletal muscle biopsies obtained from the same 30 individuals. Donor-matched comparisons reveal that iPSC-FAPs recapitulate the transcriptome, epigenome, and subtype composition of muscle tissue FAPs. Using single-nucleus multiomics, we show that high-insulin exposure drives iPSC-FAPs toward an adipogenic fate - and that this adipogenic subtype is enriched for T2D GWAS signals, an enrichment undetectable under baseline conditions. We map the T2D-associated rs3814707 non-coding signal to LTBP3, a gene that influences FAP adipogenic differentiation. These findings reveal how disease-relevant regulatory mechanisms can be masked in unstimulated cells and establish iPSC-FAPs as a powerful platform for dissecting the state-dependent biology of complex metabolic disease.","[""Journal Article"", ""Preprint""]","[""Ventresca C"", ""Varshney A"", ""Orchard P"", ""Vu HTH"", ""Tsan YC"", ""Monteiro da Rocha A"", ""Erdos MR"", ""Kinnunen L"", ""Lakka TA"", ""Saramies J"", ""Laakso M"", ""Tuomilehto J"", ""Mohlke KL"", ""Boehnke M"", ""Scott LJ"", ""Koistinen HA"", ""Collins FS"", ""Herron T"", ""Bielas S"", ""Parker SCJ""]",10.64898/2026.02.04.702388,Ventresca C,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Parker SCJ,[],,41676558,pmc-id: PMC12889671;,2026 Feb 6,2026,https://pubmed.ncbi.nlm.nih.gov/41676558/,Donor-matched iPSC model reveals context-dependent T2D genetic signals in fibro-adipogenic progenitors,,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Cell type-specific chromatin accessibility QTL (caQTL) mapping is a promising approach to understand genetic control of chromatin landscapes and identify regulatory mechanisms underlying GWAS associations. However, current caQTL studies lack resolution and do not distinguish nucleosome-free regions (NFR) from positioned nucleosomes. Here, we leverage statistical modeling of fragment position and length to decompose ATAC-seq profiles into NFRs and phased nucleosomes. With single nucleus (sn)ATAC-seq from 281 human muscle biopsies, we map cell type-specific genetic effects on NFRs (76,027 nfrQTLs) and nucleosome occupancy (24,623 nucQTLs) across skeletal muscle cell types. Colocalization and causal inference between nucQTLs and nearby nfrQTLs and show that nfrQTLs are substantially more likely to causally influence nucQTLs and phase adjacent nucleosomes, indicating a causal relationship in shaping chromatin profiles. Hundreds of nfrQTLs colocalize with GWAS signals for muscle-related traits, including grip strength, atrial fibrillation, and fasting insulin, and the majority of colocalizing signals mapped to credible sets overlapping the corresponding nfrPeak. This approach adds mechanistic insights for how variants underlying caQTLs and GWAS signals exert their cis regulatory effects by initially modifying NFR accessibility and subsequently shaping broader chromatin landscapes, nucleosome positioning, gene expression, and ultimately higher-level traits and disease.","[""Journal Article"", ""Preprint""]","[""Wang X"", ""Robertson CC"", ""Varshney A"", ""Manickam N"", ""Orchard P"", ""Laakso M"", ""Tuomilehto J"", ""Lakka TA"", ""Mohlke KL"", ""Boehnke M"", ""Scott LJ"", ""Koistinen HA"", ""Collins FS"", ""Parker SCJ""]",10.1101/2025.09.09.674883,Wang X,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Parker SCJ,[],,41279487,pmc-id: PMC12636358;,2025 Oct 28,2025,https://pubmed.ncbi.nlm.nih.gov/41279487/,Genetic integration with cell-specific nucleosome positioning resolves causal relationships underlying chromatin accessibility profiles,,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"To investigate the interplay between physical activity and cardiometabolic traits in human skeletal muscle, we characterized gene expression and chromatin accessibility across skeletal muscle cell types in 263 Finnish individuals from the FUSION Tissue Biopsy Study. We analyzed skeletal muscle single-nucleus RNA-seq data (168,309 nuclei, 23,849 genes), ATAC-seq data (242,069 nuclei, 927,588 peaks), and bulk RNA-seq data (22,309 genes). Lower insulin resistance (HOMA-IR) and higher total physical activity were both associated with higher proportions of Type 1 nuclei and lower proportions of Type 2x nuclei. We identified cell-type-level and tissue-level gene expression-trait and gene set-trait associations for cardiometabolic and physical activity traits, and a smaller proportion of cell-type-level chromatin accessibility-trait associations. Traits typically associated with better health-lower trait values of cardiometabolic traits (BMI, HOMA-IR, normal glucose tolerance vs. type 2 diabetes, 2-hour plasma glucose) and higher physical activity levels (total and vigorous)-were associated with higher expression of energy metabolism genes and lower expression of signaling pathway genes across muscle fiber types, total pseudobulk, and to some extent in bulk tissue. For HOMA-IR and physical activity, these directions of association remained when adjusting for both traits in the same model, indicating apparently independent associations in the same pathways.","[""Journal Article"", ""Preprint""]","[""Ciotlos DL"", ""Hanks SC"", ""Varshney A"", ""Erdos MR"", ""Manickam N"", ""Stringham HM"", ""Orchard P"", ""Hill-Burns EM"", ""Narisu N"", ""Bonnycastle LL"", ""Sweeney MD"", ""Saramies J"", ""Laakso M"", ""Tuomilehto J"", ""Lakka TA"", ""Mohlke KL"", ""Boehnke M"", ""Collins FS"", ""Koistinen HA"", ""Parker SCJ"", ""Scott LJ""]",10.1101/2025.10.27.683567,Ciotlos DL,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Scott LJ,[],,41279274,pmc-id: PMC12636436;,2025 Nov 28,2025,https://pubmed.ncbi.nlm.nih.gov/41279274/,Inverse directions of association of higher physical activity and higher insulin resistance with human skeletal muscle cell type abundance and fiber-type-level gene expression,,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
,"[""Journal Article""]","[""Fleurence RL"", ""Collins FS""]",10.1001/jama.2025.17074,Fleurence RL,JAMA,0098-7484,22,JAMA,eng,Collins FS,[],2038-2039,41165680,,2025 Dec 9,2025,https://pubmed.ncbi.nlm.nih.gov/41165680/,Screening for Hepatitis C in Emergency Departments,334,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Identifying genetic variants that regulate gene expression can help uncover mechanisms underlying complex traits. We performed a meta-analysis of skeletal muscle expression quantitative trait locus (eQTL) using data from 1,002 individuals from two studies. A stepwise analysis identified 18,818 conditionally distinct signals for 12,283 genes, and 35% of these genes contained two or more signals. Colocalization of these eQTL signals with 26 muscular and cardiometabolic trait genome-wide association studies (GWASs) identified 2,252 GWAS-eQTL colocalizations that nominated 1,342 candidate genes. Notably, 22% of the GWAS-eQTL colocalizations involved non-primary eQTL signals. Additionally, 37% of the colocalized GWAS-eQTL signals corresponded to the closest protein-coding gene, while 44% were located >50 kb from the transcription start site of the nominated gene. To assess tissue specificity for a heterogeneous trait, we compared colocalizations with type 2 diabetes (T2D) signals across muscle, adipose, liver, and islet eQTLs; we identified 551 candidate genes for 309 T2D signals representing 36% of T2D signals tested and over 100 more than were detected with any one tissue alone. We then functionally validated the allelic regulatory effect of an eQTL variant for INHBB linked to T2D in both muscle and adipose tissue. Together, these results further demonstrate the value of skeletal muscle eQTLs in elucidating mechanisms underlying complex traits.","[""Journal Article"", ""Meta-Analysis"", ""Research Support, N.I.H., Intramural"", ""Research Support, N.I.H., Extramural""]","[""Wilson EP"", ""Broadaway KA"", ""Parsons VA"", ""Vadlamudi S"", ""Narisu N"", ""Brotman SM"", ""Currin KW"", ""Stringham HM"", ""Erdos MR"", ""Welch R"", ""Holtzman JK"", ""Lakka TA"", ""Laakso M"", ""Tuomilehto J"", ""Boehnke M"", ""Koistinen HA"", ""Collins FS"", ""Parker SCJ"", ""Scott LJ"", ""Mohlke KL""]",10.1016/j.ajhg.2025.09.003,Wilson EP,American journal of human genetics,0002-9297,11,Am J Hum Genet,eng,Mohlke KL,"[""Quantitative Trait Loci"", ""Humans"", ""Muscle, Skeletal"", ""Genome-Wide Association Study"", ""Diabetes Mellitus, Type 2"", ""Polymorphism, Single Nucleotide"", ""Genetic Predisposition to Disease""]",2693-2707,40992379,pmc-id: PMC12614742;manuscript-id: NIHMS2112495;,2025 Nov 6,2025,https://pubmed.ncbi.nlm.nih.gov/40992379/,Skeletal muscle eQTL meta-analysis implicates genes in the genetic architecture of muscular and cardiometabolic traits,112,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Understanding the spatial distribution of gene expression in the pancreas is essential for establishing the molecular basis of pancreatic function in healthy and disease contexts. Recent platforms offer a robust method for quantifying gene expression within a spatial context. Here, we report spatial transcriptomic profiling from pancreas samples obtained from three donors with type 2 diabetes (T2D) and three donors with normal glucose tolerance (NGT). Our analysis identified a major technical challenge: substantial transcript bleed of highly abundant genes (e.g., INS and GCG) into adjacent tissue regions. We demonstrate that this bleed can be computationally corrected using probabilistic models. Our analysis highlights the importance of incorporating bleed-correction techniques in the preprocessing of spatial transcriptomic profiling data. In summary, this study provides a dataset, methods, and resources to investigate the spatial regulation of gene expression in normal and T2D-affected human pancreas.","[""Journal Article"", ""Dataset""]","[""Howell N"", ""Weiss Z"", ""Bonnycastle LL"", ""Grenko CM"", ""Randazzo D"", ""Dampier CH"", ""Sinha N"", ""Narisu N"", ""Swift AJ"", ""Erdos MR"", ""Biesecker LG"", ""Collins FS"", ""Robertson CC"", ""Taylor DL""]",10.1038/s41597-025-05450-6,Howell N,Scientific data,2052-4463,1,Sci Data,eng,Taylor DL,"[""Humans"", ""Diabetes Mellitus, Type 2"", ""Pancreas"", ""Transcriptome"", ""Gene Expression Profiling""]",1526,40890166,pmc-id: PMC12402493;,2025 Sep 1,2025,https://pubmed.ncbi.nlm.nih.gov/40890166/,A spatial transcriptomics dataset of pancreas sections in normal glucose tolerance and type 2 diabetic donors,12,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Genome-wide association studies (GWASs) have identified over 100 signals associated with type 1 diabetes (T1D). However, it has been challenging to translate any given T1D GWAS signal into mechanistic insights, such as causal variants, their target genes, and the specific cell types involved. Here, we present a comprehensive multi-omic integrative analysis of single-cell/nucleus resolution profiles of gene expression and chromatin accessibility in human pancreatic islets under baseline and T1D-stimulating conditions. We nominate effector cell types for all T1D GWAS signals and the regulatory elements and genes for three independent T1D signals acting through β cells at the DLK1/MEG3, RASGRP1, and TOX loci. Subsequently, we validated the functional impact of these genes and regulatory regions using isogenic human embryonic stem cells (hESCs). We found that loss of RASGRP1 or DLK1, as well as disruption of their corresponding regulatory regions, led to increased β cell apoptosis. Furthermore, β cells derived from isogenic hESCs carrying the T1D risk allele of rs3783355 associated with DLK1 showed elevated β cell death. Through additional RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) analyses, we identified five genes upregulated in both RASGRP1-/- and DLK1-/- β-like cells, four of which are near T1D GWAS signals. This integrative approach combining single-cell multi-omics, GWASs, and isogenic human pluripotent stem cell (hPSC)-derived β-like cells illuminates cell type context, genes, single nucleotide polymorphisms (SNPs), and regulatory elements underlying T1D-associated signals, providing insights into the biological functions and molecular mechanisms involved.","[""Journal Article""]","[""D'Oliveira Albanus R"", ""Zhang X"", ""Zhao Z"", ""Taylor HJ"", ""Tang X"", ""Han Y"", ""Orchard P"", ""Varshney A"", ""Zhang T"", ""Manickam N"", ""Erdos MR"", ""Narisu N"", ""Taylor L"", ""Saavedra X"", ""Liu X"", ""Zhong A"", ""Li B"", ""Zhou T"", ""Naji A"", ""Liu C"", ""Collins FS"", ""Parker SCJ"", ""Chen S""]",10.1016/j.celrep.2025.116065,D'Oliveira Albanus R,Cell reports,2211-1247,8,Cell Rep,eng,Chen S,"[""Humans"", ""Diabetes Mellitus, Type 1"", ""Single-Cell Analysis"", ""Genome-Wide Association Study"", ""Islets of Langerhans"", ""Insulin-Secreting Cells"", ""Polymorphism, Single Nucleotide"", ""Human Embryonic Stem Cells"", ""Apoptosis"", ""Multiomics"", ""Calcium-Binding Proteins"", ""Membrane Proteins""]",116065,40737125,pmc-id: PMC12477748;manuscript-id: NIHMS2107267;,2025 Aug 26,2025,https://pubmed.ncbi.nlm.nih.gov/40737125/,Integrative single-cell multi-omics profiling of human pancreatic islets identifies T1D-associated genes and regulatory signals,44,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Polygenic scores (PGSs) for body mass index (BMI) may guide early prevention and targeted treatment of obesity. Using genetic data from up to 5.1 million people (4.6% African ancestry, 14.4% American ancestry, 8.4% East Asian ancestry, 71.1% European ancestry and 1.5% South Asian ancestry) from the GIANT consortium and 23andMe, Inc., we developed ancestry-specific and multi-ancestry PGSs. The multi-ancestry score explained 17.6% of BMI variation among UK Biobank participants of European ancestry. For other populations, this ranged from 16% in East Asian-Americans to 2.2% in rural Ugandans. In the ALSPAC study, children with higher PGSs showed accelerated BMI gain from age 2.5 years to adolescence, with earlier adiposity rebound. Adding the PGS to predictors available at birth nearly doubled explained variance for BMI from age 5 onward (for example, from 11% to 21% at age 8). Up to age 5, adding the PGS to early-life BMI improved prediction of BMI at age 18 (for example, from 22% to 35% at age 5). Higher PGSs were associated with greater adult weight gain. In intensive lifestyle intervention trials, individuals with higher PGSs lost modestly more weight in the first year (0.55 kg per s.d.) but were more likely to regain it. Overall, these data show that PGSs have the potential to improve obesity prediction, particularly when implemented early in life.","[""Journal Article""]","[""Smit RAJ"", ""Wade KH"", ""Hui Q"", ""Arias JD"", ""Yin X"", ""Christiansen MR"", ""Yengo L"", ""Preuss MH"", ""Nakabuye M"", ""Rocheleau G"", ""Graham SE"", ""Buchanan VL"", ""Chittoor G"", ""Graff M"", ""Guindo-Martínez M"", ""Lu Y"", ""Marouli E"", ""Sakaue S"", ""Spracklen CN"", ""Vedantam S"", ""Wilson EP"", ""Chen SH"", ""Ferreira T"", ""Ji Y"", ""Karaderi T"", ""Lüll K"", ""Machado M"", ""Malden DE"", ""Medina-Gomez C"", ""Moore A"", ""Rüeger S"", ""Akiyama M"", ""Allison MA"", ""Alvarez M"", ""Andersen MK"", ""Appadurai V"", ""Arbeeva L"", ""Bartell E"", ""Bhaskar S"", ""Bielak LF"", ""Bis JC"", ""Bollepalli S"", ""Bork-Jensen J"", ""Bradfield JP"", ""Bradford Y"", ""Brandl C"", ""Braund PS"", ""Brody JA"", ""Broeckel U"", ""Burgdorf KS"", ""Cade BE"", ""Cai Q"", ""Camarda S"", ""Campbell A"", ""Cañadas-Garre M"", ""Chai JF"", ""Chesi A"", ""Choi SH"", ""Christofidou P"", ""Couture C"", ""Cuellar-Partida G"", ""Danning R"", ""Degenhardt F"", ""Delgado GE"", ""Delitala A"", ""Demirkan A"", ""Deng X"", ""Dietl A"", ""Dimitriou M"", ""Dimitrov L"", ""Dorajoo R"", ""Eichelmann F"", ""Eliasen AU"", ""Engmann JE"", ""Erdos MR"", ""Fairhurst-Hunter Z"", ""Farmaki AE"", ""Faul JD"", ""Fernandez-Lopez JC"", ""Forer L"", ""Frank M"", ""Freitag-Wolf S"", ""Fritsche LG"", ""Fuchsberger C"", ""Galesloot TE"", ""Gao Y"", ""Geller F"", ""Giannakopoulou O"", ""Giulianini F"", ""Gjesing AP"", ""Goel A"", ""Gordon SD"", ""Gorski M"", ""Grove J"", ""Guo X"", ""Gustafsson S"", ""Haessler J"", ""Hansen TF"", ""Havulinna AS"", ""Haworth SJ"", ""Heard-Costa N"", ""Hemerich D"", ""Highland HM"", ""Hindy G"", ""Ho YL"", ""Hofer E"", ""Holliday E"", ""Horn K"", ""Hornsby WE"", ""Hottenga JJ"", ""Huang H"", ""Huang J"", ""Huerta-Chagoya A"", ""Huo S"", ""Hwang MY"", ""Hwu CM"", ""Iha H"", ""Ikeda DD"", ""Isono M"", ""Jackson AU"", ""Jansen IE"", ""Jiang Y"", ""Johansson I"", ""Jonsson A"", ""Jørgensen T"", ""Kalafati IP"", ""Kanai M"", ""Kanoni S"", ""Kårhus LL"", ""Kasturiratne A"", ""Katsuya T"", ""Kawaguchi T"", ""Kember RL"", ""Kentistou KA"", ""Kim D"", ""Kim HN"", ""Kim YJ"", ""Kleber ME"", ""Knol MJ"", ""Kurbasic A"", ""Lauzon M"", ""Le P"", ""Lea R"", ""Lee JY"", ""Lee WJ"", ""Leonard HL"", ""Li H"", ""Li SA"", ""Li X"", ""Li X"", ""Liang J"", ""Lin H"", ""Lin K"", ""Liu J"", ""Liu X"", ""Lo KS"", ""Long J"", ""Lores-Motta L"", ""Luan J"", ""Lyssenko V"", ""Lyytikäinen LP"", ""Mahajan A"", ""Malik MZ"", ""Mamakou V"", ""Mangino M"", ""Manichaikul A"", ""Marten J"", ""Mattheisen M"", ""McDaid AF"", ""Mei Q"", ""Meiselbach H"", ""Melendez TL"", ""Milaneschi Y"", ""Miller JE"", ""Millwood IY"", ""Mishra PP"", ""Mitchell RE"", ""Møllehave LT"", ""Mononen N"", ""Mucha S"", ""Munz M"", ""Mykkänen J"", ""Nakatochi M"", ""Nardone GG"", ""Nelson CP"", ""Nethander M"", ""Nho CW"", ""Nielsen AA"", ""Nolte IM"", ""Nongmaithem SS"", ""Noordam R"", ""Ntalla I"", ""Nutile T"", ""Pandit A"", ""Pauper M"", ""Petersen ERB"", ""Petersen LV"", ""Piluso F"", ""Polašek O"", ""Poveda A"", ""Pyarajan S"", ""Raffield LM"", ""Rakugi H"", ""Ramirez J"", ""Rasheed A"", ""Raven D"", ""Rayner NW"", ""Riveros C"", ""Rohde R"", ""Ruggiero D"", ""Ruotsalainen SE"", ""Ryan KA"", ""Sabater-Lleal M"", ""Santin A"", ""Saxena R"", ""Scholz M"", ""Shen B"", ""Shi J"", ""Shin JH"", ""Sidore C"", ""Sidorenko J"", ""Sim X"", ""Slieker RC"", ""Smith AV"", ""Smith JA"", ""Smyth LJ"", ""Southam L"", ""Steinthorsdottir V"", ""Sun L"", ""Takeuchi F"", ""Taylor KD"", ""Tayo BO"", ""Tcheandjieu C"", ""Terzikhan N"", ""Tesolin P"", ""Teumer A"", ""Theusch E"", ""Thompson DJ"", ""Thorleifsson G"", ""Timmers PRHJ"", ""Trompet S"", ""Turman C"", ""Vaccargiu S"", ""van der Laan SW"", ""van der Most PJ"", ""van Klinken JB"", ""van Setten J"", ""Verma SS"", ""Verweij N"", ""Veturi Y"", ""Wang CA"", ""Wang C"", ""Wang JS"", ""Wang L"", ""Wang YX"", ""Wang Z"", ""Warren HR"", ""Bin Wei W"", ""Wen W"", ""Wheeler WA"", ""Wickremasinghe AR"", ""Wielscher M"", ""Winsvold BS"", ""Wong A"", ""Wuttke M"", ""Xia R"", ""Yamamoto K"", ""Yang J"", ""Yao J"", ""Young H"", ""Yousri NA"", ""Yu L"", ""Zeng L"", ""Zhang W"", ""Zhang X"", ""Zhao JH"", ""Zhao W"", ""Zhou W"", ""Zimmermann ME"", ""Zoledziewska M"", ""'t Hart LM"", ""Adair LS"", ""Adams HHH"", ""Aguilar-Salinas CA"", ""Al-Mulla F"", ""Arnett DK"", ""Asselbergs FW"", ""Åsvold BO"", ""Attia J"", ""Banas B"", ""Bandinelli S"", ""Beilin LJ"", ""Bennett DA"", ""Bergler T"", ""Bharadwaj D"", ""Biino G"", ""Boerwinkle E"", ""Böger CA"", ""Borja JB"", ""Bouchard C"", ""Bowden DW"", ""Brandslund I"", ""Brumpton B"", ""Buring JE"", ""Caulfield MJ"", ""Chambers JC"", ""Chandak GR"", ""Chanock SJ"", ""Chaturvedi N"", ""Ida Chen YD"", ""Chen Z"", ""Cheng CY"", ""Cho YS"", ""Christensen K"", ""Christophersen IE"", ""Ciullo M"", ""Cole JW"", ""Collins FS"", ""Concas MP"", ""Cooper RS"", ""Cruz M"", ""Cucca F"", ""Cutler MJ"", ""Damrauer SM"", ""Dantoft TM"", ""de Borst GJ"", ""de Geus EJC"", ""de Groot LCPGM"", ""De Jager PL"", ""de Kleijn DPV"", ""de Silva HJ"", ""Dedoussis GV"", ""den Hollander AI"", ""Du S"", ""Easton DF"", ""Eckardt KU"", ""Elders PJM"", ""Eliassen AH"", ""Ellinor PT"", ""Elmståhl S"", ""Erdmann J"", ""Evans MK"", ""Fatkin D"", ""Feenstra B"", ""Feitosa MF"", ""Ferrucci L"", ""Florez JC"", ""Ford I"", ""Fornage M"", ""Franke A"", ""Franks PW"", ""Freedman BI"", ""Gieger C"", ""Girotto G"", ""Golightly YM"", ""Gonzalez-Villalpando C"", ""Gordon-Larsen P"", ""Grallert H"", ""Grant SFA"", ""Grarup N"", ""Griffiths L"", ""Gudnason V"", ""Haiman C"", ""Hakonarson H"", ""Hansen T"", ""Hartman CA"", ""Hattersley AT"", ""Hayward C"", ""Heid IM"", ""Heng CK"", ""Hengstenberg C"", ""Herzig KH"", ""Hewitt AW"", ""Hishigaki H"", ""Hougaard DM"", ""Hoyng CB"", ""Huang PL"", ""Huang W"", ""Huang WY"", ""Huffman JE"", ""Hunt SC"", ""Hutri N"", ""Hveem K"", ""Hyppönen E"", ""Iacono WG"", ""Ichihara S"", ""Ikram MA"", ""Isasi CR"", ""Jarvelin MR"", ""Jin ZB"", ""Jöckel KH"", ""Jonas JB"", ""Joshi PK"", ""Jousilahti P"", ""Jukema JW"", ""Kähönen M"", ""Kamatani Y"", ""Kang KD"", ""Kaprio J"", ""Kardia SLR"", ""Karpe F"", ""Kato N"", ""Kavousi M"", ""Kee F"", ""Kessler T"", ""Khera AV"", ""Khor CC"", ""Kiemeney LALM"", ""Kim BJ"", ""Kim EK"", ""Kim HL"", ""Kirchhof P"", ""Kivimaki M"", ""Koh WP"", ""Koistinen HA"", ""Kokkinos A"", ""Kooner JS"", ""Kooperberg C"", ""Kovacs P"", ""Kraaijeveld A"", ""Kraft P"", ""Krauss RM"", ""Kumari M"", ""Kutalik Z"", ""Laakso M"", ""Lange LA"", ""Langenberg C"", ""Launer LJ"", ""Lee H"", ""Lee NR"", ""Lehtimäki T"", ""Lemaitre RN"", ""Li H"", ""Li L"", ""Lieb W"", ""Lin X"", ""Lind L"", ""Linneberg A"", ""Liu CT"", ""Liu J"", ""Loeffler M"", ""London B"", ""Lu F"", ""Lubitz SA"", ""Mackey DA"", ""Magnusson PKE"", ""Manson JE"", ""Marcus GM"", ""Marques Vidal P"", ""Martin NG"", ""März W"", ""Matsuda F"", ""McCarthy MI"", ""McGarrah RW"", ""McGue M"", ""McKnight AJ"", ""Medland SE"", ""Mellström D"", ""Metspalu A"", ""Mitchell BD"", ""Mitchell P"", ""Mook-Kanamori DO"", ""Mori TA"", ""Morris AD"", ""Mucci LA"", ""Munroe PB"", ""Nalls MA"", ""Nazarian S"", ""Nelson AE"", ""Neville MJ"", ""Newton-Cheh C"", ""Nielsen CS"", ""Niinikoski H"", ""Nikus K"", ""Nöthen MM"", ""Ogunniyi A"", ""Ohlsson C"", ""Oldehinkel AJ"", ""Orozco L"", ""Pahkala K"", ""Pajukanta P"", ""Palmer CNA"", ""Parra EJ"", ""Pattaro C"", ""Pedersen O"", ""Pennell CE"", ""Penninx BWJH"", ""Perusse L"", ""Peters A"", ""Peyser PA"", ""Porteous DJ"", ""Posthuma D"", ""Power C"", ""Pramstaller PP"", ""Province MA"", ""Psaty BM"", ""Qi Q"", ""Qu J"", ""Rader DJ"", ""Raitakari OT"", ""Rallidis LS"", ""Rao DC"", ""Redline S"", ""Reilly DF"", ""Reiner AP"", ""Rhee SY"", ""Ridker PM"", ""Rienstra M"", ""Ripatti S"", ""Ritchie MD"", ""Rivadeneira F"", ""Roden DM"", ""Rosendaal FR"", ""Rotter JI"", ""Rudan I"", ""Rutters F"", ""Ryu S"", ""Sabanayagam C"", ""Salako B"", ""Saleheen D"", ""Salomaa V"", ""Samani NJ"", ""Sanghera DK"", ""Sattar N"", ""Schmidt B"", ""Schmidt H"", ""Schmidt R"", ""Schulze MB"", ""Schunkert H"", ""Scott LJ"", ""Scott RJ"", ""Sever P"", ""Sheu WHH"", ""Shoemaker MB"", ""Shu XO"", ""Simonsick EM"", ""Sims M"", ""Singleton AB"", ""Sinner MF"", ""Smith JG"", ""Snieder H"", ""Spector TD"", ""Spedicati B"", ""Stampfer MJ"", ""Stark KJ"", ""Strachan DP"", ""Tabara Y"", ""Tai ES"", ""Tang H"", ""Tardif JC"", ""Thanaraj TA"", ""Tönjes A"", ""Tuomi T"", ""Tuomilehto J"", ""Tusié-Luna MT"", ""van Dam RM"", ""van der Harst P"", ""Van der Velde N"", ""van Duijn CM"", ""van Schoor NM"", ""Vitart V"", ""Vohl MC"", ""Völker U"", ""Vollenweider P"", ""Völzke H"", ""Vrieze S"", ""Wacher-Rodarte NH"", ""Walker M"", ""Wander GS"", ""Wareham NJ"", ""Watanabe RM"", ""Watkins H"", ""Weir DR"", ""Werge TM"", ""Widen E"", ""Willemsen G"", ""Willett WC"", ""Wilson JF"", ""Wilson PWF"", ""Wong TY"", ""Woo JT"", ""Wright AF"", ""Xu H"", ""Yajnik CS"", ""Yang J"", ""Yokota M"", ""Yuan JM"", ""Zeggini E"", ""Zemel BS"", ""Zheng W"", ""Zhu X"", ""Zillikens MC"", ""Zonderman AB"", ""Zwart JA"", ""23andMe Research Team"", ""DiscovEHR (DiscovEHR and MyCode Community Health Initiative)"", ""eMERGE (Electronic Medical Records and Genomics Network)"", ""GPC-UGR"", ""PRACTICAL Consortium"", ""Understanding Society Scientific Group"", ""VA Million Veteran Program"", ""Abecasis GR"", ""Assimes TL"", ""Auton A"", ""Boehnke M"", ""Chasman DI"", ""Esko T"", ""Stefansson K"", ""Lettre G"", ""Lindgren CM"", ""Ng MCY"", ""O'Donnell CJ"", ""Thorsteinsdottir U"", ""Visscher PM"", ""Walters RG"", ""Winkler TW"", ""Wood AR"", ""Deloukas P"", ""Frayling TM"", ""Justice AE"", ""Kilpeläinen TO"", ""Locke AE"", ""Mohlke KL"", ""North KE"", ""Okada Y"", ""Willer CJ"", ""Young KL"", ""Fatumo S"", ""McCaffery JM"", ""Timpson NJ"", ""Hirschhorn JN"", ""Sun YV"", ""Berndt SI"", ""Loos RJF""]",10.1038/s41591-025-03827-z,Smit RAJ,Nature medicine,1078-8956,9,Nat Med,eng,Loos RJF,"[""Adolescent"", ""Adult"", ""Child"", ""Child, Preschool"", ""Female"", ""Humans"", ""Male"", ""Middle Aged"", ""Young Adult"", ""Adiposity"", ""Body Mass Index"", ""Genetic Predisposition to Disease"", ""Multifactorial Inheritance"", ""Obesity"", ""White People"", ""Racial Groups""]",3151-3168,40691366,pmc-id: PMC12443623;manuscript-id: NIHMS2107046;,2025 Sep,2025,https://pubmed.ncbi.nlm.nih.gov/40691366/,Polygenic prediction of body mass index and obesity through the life course and across ancestries,31,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"To explore the phenotypic spectrum and genetic etiologies of Moebius Syndrome (MBS), a rare neurological disorder defined by congenital, nonprogressive facial weakness and limitations in ocular abduction. We applied strict diagnostic criteria and conducted clinical phenotyping of 149 individuals with MBS. Subsequently, we performed exome and/or genome sequencing on 67 of these individuals and 117 unaffected family members. All 149 individuals had sporadic MBS, with no recurrence within or across generations. Common co-occurring phenotypes included tongue hypoplasia (81.9%), micrognathia (66.4%), congenital talipes equinovarus (42.3%), major limb anomalies (31.5%), intellectual disability (30.9%), sleep difficulties (22.8%), and Poland anomaly (14.1%). Filtering for rare de novo or autosomal recessive single-nucleotide, insertion/deletion, and structural variants in the sequenced cohort yielded 173 single-nucleotide variant/indels in 113 genes. Although we prioritized 7 candidate genes with de novo variants and 5 with biallelic variants, no compelling recurrently mutated genes were identified. Similarly, we found no convincing variants in 2 putative genes previously implicated in MBS: PLXND1 (HGNC:9107) and REV3L (HGNC:9968). We did not identify a strong or unifying germline genetic etiology for MBS. Future studies may explore alternative causes, including environmental exposures, somatic variants, and/or complex inheritance patterns affecting brainstem and organ embryogenesis.","[""Journal Article""]","[""Webb BD"", ""Jurgens JA"", ""Narisu N"", ""Zhang Z"", ""Barry BJ"", ""Van Ryzin C"", ""Bonnycastle LL"", ""Chan WM"", ""Yan T"", ""Di Gioia SA"", ""Swift AJ"", ""MacKinnon SE"", ""Oystreck DT"", ""Rucker JC"", ""Frempong T"", ""Whitman MC"", ""FitzGibbon EJ"", ""Lee JS"", ""Hao K"", ""Andrews C"", ""Erazo M"", ""Facio FM"", ""Shaaban S"", ""Naidich TP"", ""Chines PS"", ""Lehky TJ"", ""Toro C"", ""Gropman AL"", ""Butman JA"", ""Zalewski CK"", ""Brewer CC"", ""Thurm A"", ""Snow J"", ""Paul SM"", ""Brooks BP"", ""Pierpaoli C"", ""Robson CD"", ""Hunter DG"", ""Collins FS"", ""Jabs EW"", ""Engle EC"", ""Manoli I""]",10.1016/j.gimo.2025.103437,Webb BD,Genetics in medicine open,2949-7744,,Genet Med Open,eng,Manoli I,[],103437,40662098,pmc-id: PMC12256340;,2025,2025,https://pubmed.ncbi.nlm.nih.gov/40662098/,Systematic phenotype and genotype characterization of Moebius syndrome,3,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Human induced pluripotent stem cells (iPSCs) have transformed biomedical research by enabling the generation of diverse cell types from accessible somatic tissues. However, certain fundamental biological properties, such as the genetic and epigenetic determinants of iPSC proliferation, remain poorly characterized. We measured the growth of iPSC lines derived from 602 unique donors using high-throughput time-lapse imaging, quantified proliferation through a growth Area-Under-the-Curve (gAUC) phenotype, and correlated gAUC with the gene expression and genotype of the cell lines. We identified 3,091 genes associated with gAUC, many of which are well established regulators of cell proliferation. We also found that rare deleterious variants in WDR54 were associated with reduced iPSC growth and that WDR54 was differentially expressed with respect to gAUC. Although no common variants showed a genome-wide association with gAUC, iPSC lines from monozygotic twins were highly correlated, and common genetic variation explained approximately 71-75% of the variance in iPSC growth rates. These results indicate a complex genetic architecture of iPSC growth rates, where rare, large-effect variants in important growth regulators, including WDR54, are layered onto a highly polygenic background. These findings have important implications for the design of pooled iPSC-based studies and disease models, which may be confounded by intrinsic growth differences.","[""Journal Article"", ""Preprint""]","[""Lee BN"", ""Taylor HJ"", ""Cipriani F"", ""Narisu N"", ""Robertson CC"", ""Swift AJ"", ""Sinha N"", ""Yan T"", ""Bonnycastle LL"", ""Dale N"", ""Butt A"", ""Parsaud H"", ""Semrau S"", ""NYSCF Global Stem Cell Array Team"", ""GENESiPS Consortium"", ""iPSCORE Consortium"", ""Knowles JW"", ""Carcamo-Orive I"", ""D'Antonio-Chronowska A"", ""Frazer KA"", ""Biesecker LG"", ""Noggle S"", ""Erdos MR"", ""Paull D"", ""Collins FS"", ""Taylor DL""]",10.1101/2025.07.02.662844,Lee BN,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Taylor DL,[],,40631191,pmc-id: PMC12236597;,2025 Jul 3,2025,https://pubmed.ncbi.nlm.nih.gov/40631191/,Genetics of growth rate in induced pluripotent stem cells,,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"ObjectiveCongenital facial weakness (CFW) disorders are a heterogeneous group of rare conditions, that present at birth, with reduced facial movement, and mask-like facies. This study utilized a multimodality approach to examine the craniofacial and intraoral phenotypes among CFW disorders: Moebius syndrome (MBS), Hereditary Congenital Facial Palsy (HCFP), β-tubulin isotype 3 syndrome (CFEOM3A-TUBB3), Carey-Fineman-Ziter syndrome (CFZS), and a group of rarer disorders (Other).DesignProspective cohort study.Setting: Dental clinic.Participants: Sixty individuals (sex ratio 1:1, mean age 26.2 ± 17.5 years) with a diagnosis of CFW.Interventions: Deep clinical craniofacial and dental phenotyping, three-dimensional facial surface and cone-beam computed tomography scans, and cephalometric and geometric morphometric analyses.ResultsCFEOM3A-TUBB3, MBS, and CFZS groups had the highest prevalence of craniofacial anomalies; HCFP individuals were least affected. CFEOM3A-TUBB3 had a higher prevalence of short lower face (75%), poor oral hygiene (100%)/decay (75%), and Class II malocclusion (87.5%). Moebius syndrome was associated with lagophthalmos (90.9%), tongue fissures (72.4%), tight/small oral orifice (51.7%), and tongue fasciculations (50%). Carey-Fineman-Ziter syndrome had oblong facial shape (100%), downward lip commissures (100%), and abnormal hearing (60%). Moderate-severe decay/gingivitis correlated with restricted oral orifice, common among patients with facial animation/sling surgery. Morphologically, the CFW cohort had a relatively small craniofacial centroid size, anthropometric measurements, and distinct craniofacial shapes for each subtype.ConclusionsCongenital facial weakness can result in abnormal craniofacial development in addition to the loss of facial movement. Multimodality phenotypic characterization of CFW disorders elucidated key clinical findings and distinct craniofacial shape segregation among the different groups.","[""Journal Article""]","[""Almpani K"", ""Devine KR"", ""Liberton DK"", ""Mishra R"", ""Bassim C"", ""Van Ryzin C"", ""Facio FM"", ""Webb BD"", ""Barry BJ"", ""Engle EC"", ""Wang Jabs E"", ""Collins FS"", ""Manoli I"", ""Lee JS"", ""Moebius Syndrome Research Consortium""]",10.1177/10556656251344128,Almpani K,The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association,1055-6656,6,Cleft Palate Craniofac J,eng,Lee JS,"[""Humans"", ""Phenotype"", ""Male"", ""Female"", ""Facial Paralysis"", ""Adult"", ""Craniofacial Abnormalities"", ""Cephalometry"", ""Cone-Beam Computed Tomography"", ""Imaging, Three-Dimensional"", ""Cohort Studies"", ""Child"", ""Adolescent"", ""Mobius Syndrome""]",1455-1468,40611650,pmc-id: PMC12826332;manuscript-id: NIHMS2131101;,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/40611650/,Multimodality Craniofacial Phenotyping of Congenital Facial Weakness Disorders,63,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Characterization of DNA binding sites for specific proteins is of fundamental importance in molecular biology. It is commonly addressed experimentally by chromatin immunoprecipitation and sequencing (ChIP-seq) of bulk samples (103-107 cells). We have developed an alternative method that uses a Chromatin Antibody-mediated Methylating Protein (ChAMP) composed of a GpC methyltransferase fused to protein G. By tethering ChAMP to a primary antibody directed against the DNA-binding protein of interest, and selectively switching on its enzymatic activity in situ, we generated distinct and identifiable methylation patterns adjacent to the protein binding sites. This method is compatible with methods of single-cell methylation-detection and single molecule methylation identification. Indeed, as every binding event generates multiple nearby methylations, we were able to confidently detect protein binding in long single molecules.","[""Journal Article""]","[""Thatavarty A"", ""Sagy N"", ""Erdos MR"", ""Lee I"", ""Simpson JT"", ""Timp W"", ""Collins FS"", ""Bar DZ""]",10.1186/s13072-025-00602-9,Thatavarty A,Epigenetics & chromatin,1756-8935,1,Epigenetics Chromatin,eng,Bar DZ,"[""DNA Methylation"", ""Humans"", ""Protein Binding"", ""DNA-Binding Proteins"", ""DNA"", ""Antibodies"", ""Binding Sites""]",39,40598583,pmc-id: PMC12210839;,2025 Jul 1,2025,https://pubmed.ncbi.nlm.nih.gov/40598583/,Detecting Protein-DNA binding in single molecules using antibody guided methylation,18,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"RNA modifications are critical regulators of gene expression and cellular processes; however, the epitranscriptome is less well studied than the epigenome. Here, we studied transcriptome-wide changes in RNA modifications and expression levels in two human pancreatic beta-cell lines, EndoC-BH1 and EndoC-BH3, after one hour of glucose stimulation. Using direct RNA nanopore sequencing (dRNA-seq), we measured N6-methyladenosine (m6A), 5-methylcytosine (m5C), inosine, and pseudouridine concurrently across the transcriptome. We developed a differential RNA modification method and identified 1,697 differentially modified sites (DMSs) across all modifications. These DMSs were largely independent of changes in gene expression levels and enriched in transcripts for type 2 diabetes (T2D) genes. Our study demonstrates how dRNA-seq can be used to detect and quantify RNA modification changes in response to cellular stimuli at the single-nucleotide level and provides new insights into RNA-mediated mechanisms that may contribute to normal beta-cell response and potential dysfunction in T2D.","[""Journal Article"", ""Preprint""]","[""Mulroney L"", ""Taylor HJ"", ""Lee A"", ""Swift AJ"", ""Zdravkov M"", ""Bonnycastle LL"", ""Brooks SY"", ""Lee BN"", ""Fitzgerald T"", ""Narisu N"", ""Biesecker LG"", ""Erdos MR"", ""Nicassio F"", ""Birney E"", ""Collins FS"", ""Taylor DL""]",10.1101/2025.06.12.659352,Mulroney L,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Taylor DL,[],,40568065,pmc-id: PMC12190750;,2025 Jun 12,2025,https://pubmed.ncbi.nlm.nih.gov/40568065/,Direct RNA nanopore sequencing reveals rapid RNA modification changes following glucose stimulation of human pancreatic beta-cell lines,,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Traditional chemical screens have focused on a single assay per screen, making them labor intensive and costly. Here, we combined a chemical screen with single-cell RNA sequencing (scRNA-seq) to perform Chemical Perturb-seq (ChemPerturb-seq), enabling a systematic analysis of the molecular changes of human beta cells upon individual small molecule treatments. Using this platform, we performed an in vivo barcoded screen and discovered a small molecule cocktail, including beta-lipotropin 61-91, insulin growth factor-1, and prostaglandin E2, with which preconditioning human beta cells and primary islets significantly enhanced function and survival when transplanted subcutaneously to female, but not to male, mice. We identified two additional molecules, serotonin and histamine, that promote islet function when transplanted subcutaneously to male mice using ChemPerturb-seq. Such small molecule cocktails could be applied to improve the current FDA-approved islet transplantation procedure. Finally, we developed an artificial intelligence (AI)-powered website, ChemPerturbDB, which provides user-friendly open access analysis of the extensive ChemPerturb-seq dataset.","[""Journal Article""]","[""Vandana JJ"", ""Zhu J"", ""Giani AM"", ""Zhang T"", ""Lacko LA"", ""Leng D"", ""Taylor DL"", ""Lee BN"", ""Han Z"", ""Jiao T"", ""Huang Y"", ""Zhao M"", ""Liu X"", ""Chong ACN"", ""Xue D"", ""Meng Z"", ""Xiang JZ"", ""Pan C"", ""Wang W"", ""Naji A"", ""Evans T"", ""Liu J"", ""Collins FS"", ""Liu C"", ""Chen S""]",10.1016/j.stem.2025.06.002,Vandana JJ,Cell stem cell,1934-5909,8,Cell Stem Cell,eng,Chen S,"[""Humans"", ""Animals"", ""Insulin-Secreting Cells"", ""Mice"", ""Female"", ""Male"", ""Islets of Langerhans Transplantation"", ""Cell Survival"", ""Small Molecule Libraries"", ""Single-Cell Analysis"", ""Sequence Analysis, RNA""]",1299-1307.e8,40562034,pmc-id: PMC12335368;manuscript-id: NIHMS2088613;,2025 Aug 7,2025,https://pubmed.ncbi.nlm.nih.gov/40562034/,ChemPerturb-seq screen identifies a small molecule cocktail enhancing human beta cell survival after subcutaneous transplantation,32,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"The identification of sex-differential gene regulatory elements is essential for understanding sex-differential patterns of health and disease. We leveraged bulk and single-nucleus RNA sequencing (RNA-seq) and single-nucleus ATAC-seq data from 281 skeletal muscle biopsies to characterize sex differences in gene expression and regulation at the cell-type and whole-tissue levels. We found highly concordant sex-biased expression of over 2,100 genes across the three muscle fiber types and bulk tissue. Gene pathways related to mitochondrial activity and energy metabolism were enriched for male-biased expression, whereas those related to signal transduction and cell differentiation were enriched for female-biased expression. We found widespread sex-biased chromatin accessibility enriched in proximal and distal gene regulatory states; in gene promoters, sex-biased chromatin accessibility was positively associated with sex-biased expression. Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) also showed extensive sex-biased expression in the fiber-type and bulk data, respectively. Together, these results highlight nuclear and cytoplasmic mechanisms for sex-differential gene regulation in skeletal muscle.","[""Journal Article""]","[""Hanks SC"", ""Mauger AS"", ""Varshney A"", ""Ciotlos DL"", ""Manickam N"", ""Narisu N"", ""Shumway AJ"", ""Orchard P"", ""Erdos MR"", ""Sweeney MD"", ""Okamoto J"", ""Jackson AU"", ""Stringham HM"", ""Bonnycastle LL"", ""Zhou X"", ""Lakka TA"", ""Mohlke KL"", ""Tuomilehto J"", ""Laakso M"", ""Boehnke M"", ""Sethupathy P"", ""Collins FS"", ""Koistinen HA"", ""Parker SCJ"", ""Scott LJ""]",10.1016/j.xgen.2025.100915,Hanks SC,Cell genomics,2666-979X,8,Cell Genom,eng,Scott LJ,"[""Humans"", ""Male"", ""Female"", ""Muscle, Skeletal"", ""RNA, Long Noncoding"", ""Gene Expression Regulation"", ""MicroRNAs"", ""Sex Characteristics"", ""Chromatin"", ""Sex Factors""]",100915,40480217,pmc-id: PMC12366654;,2025 Aug 13,2025,https://pubmed.ncbi.nlm.nih.gov/40480217/,Extensive differential gene expression and regulation by sex in human skeletal muscle,5,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
,"[""Review""]","[""Adam MP"", ""Bick S"", ""Mirzaa GM"", ""Pagon RA"", ""Wallace SE"", ""Amemiya A"", ""Gordon LB"", ""Brown WT"", ""Collins FS""]",,Gordon LB,,,,,eng,Collins FS,[],,20301300,,1993,1993,https://pubmed.ncbi.nlm.nih.gov/20301300/,Hutchinson-Gilford Progeria Syndrome,,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Complete characterization of the genetic effects on gene expression is needed to elucidate tissue biology and the etiology of complex traits. In the present study, we analyzed 2,344 subcutaneous adipose tissue samples and identified 34,774 conditionally distinct expression quantitative trait locus (eQTL) signals at 18,476 genes. Over half of eQTL genes exhibited at least two eQTL signals. Compared with primary eQTL signals, nonprimary eQTL signals had lower effect sizes, lower minor allele frequencies and less promoter enrichment; they corresponded to genes with higher heritability and higher tolerance for loss of function. Colocalization of eQTLs with genome-wide association study (GWAS) signals for 28 cardiometabolic traits identified 1,835 genes. Inclusion of nonprimary eQTL signals increased discovery of colocalized GWAS-eQTL signals by 46%. Furthermore, 21 genes with ≥2 colocalized GWAS-eQTL signals showed a mediating gene dosage effect on the GWAS trait. Thus, expanded eQTL identification reveals more mechanisms underlying complex traits and improves understanding of the complexity of gene expression regulation.","[""Journal Article"", ""Meta-Analysis"", ""Research Support, N.I.H., Extramural""]","[""Brotman SM"", ""El-Sayed Moustafa JS"", ""Guan L"", ""Broadaway KA"", ""Wang D"", ""Jackson AU"", ""Welch R"", ""Currin KW"", ""Tomlinson M"", ""Vadlamudi S"", ""Stringham HM"", ""Roberts AL"", ""Lakka TA"", ""Oravilahti A"", ""Fernandes Silva L"", ""Narisu N"", ""Erdos MR"", ""Yan T"", ""Bonnycastle LL"", ""Raulerson CK"", ""Raza Y"", ""Yan X"", ""Parker SCJ"", ""Kuusisto J"", ""Pajukanta P"", ""Tuomilehto J"", ""Collins FS"", ""Boehnke M"", ""Love MI"", ""Koistinen HA"", ""Laakso M"", ""Mohlke KL"", ""Small KS"", ""Scott LJ""]",10.1038/s41588-024-01982-6,Brotman SM,Nature genetics,1061-4036,1,Nat Genet,eng,Scott LJ,"[""Quantitative Trait Loci"", ""Humans"", ""Genome-Wide Association Study"", ""Gene Expression Regulation"", ""Polymorphism, Single Nucleotide"", ""Alleles"", ""Adipose Tissue"", ""Genetic Heterogeneity"", ""Gene Frequency"", ""Male"", ""Cardiovascular Diseases""]",180-192,39747594,pmc-id: PMC12257492;manuscript-id: NIHMS2095871;,2025 Jan,2025,https://pubmed.ncbi.nlm.nih.gov/39747594/,Adipose tissue eQTL meta-analysis highlights the contribution of allelic heterogeneity to gene expression regulation and cardiometabolic traits,57,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Hutchison-Gilford progeria syndrome (HGPS) is a rare genetic disease caused by a mutation in LMNA, the gene encoding A-type lamins, leading to premature aging with severely reduced life span. HGPS is characterized by growth deficiency, subcutaneous fat and muscle issues, wrinkled skin, alopecia, and atherosclerosis. Patients also develop a bone phenotype with reduced bone mineral density, osteolysis and striking demineralization of long bones. To further clarify the tissue modifications in HGPS, we characterized bone mineralization in the LmnaG609G/G609G progeria mouse model. Femurs from 8-week-old mice and humeri from 15-week-old mice were analyzed using quantitative backscattered electron imaging to assess bone mineralization density distribution, osteocyte lacunae sections and structural bone histomorphometry. Tissue sections were stained with Giemsa and Goldner trichrome for histologic evaluation. Bone tissue from Lmna+/+ and LmnaG609G/G609G mice had similar mineral content at 3 different bone sites with specific tissue ages. The osteocyte lacunae features were not statistically different, but more empty lacunae were found in LmnaG609G/G609G at both animal ages. Bone histomorphometry and histology demonstrated decreased bone volume per tissue volume in primary (8W: -23%, p=0.001; 15W: -38%, p=0.002) and secondary spongiosa (8W: -36%, p=0.001; 15W: -49 %, ns), as well as growth plate dysplasia with thinner unmineralized resting and proliferative zones in the LmnaG609G/G609G mice versus controls (8W: -18%, p=0.006; 15W: -25%, p=0.001). Overall, the LmnaG609G/G609G mouse develops chondrodysplasia with reduced trabecular bone volume. Mineral content findings at several tissue sites and ages suggest that bone dysplasia results from impaired bone formation with normal bone turnover.","[""Journal Article"", ""Research Support, Non-U.S. Gov't"", ""Research Support, N.I.H., Intramural""]","[""Blouin S"", ""Hartmann MA"", ""Fratzl-Zelman N"", ""Messmer P"", ""Whisenant D"", ""Erdos MR"", ""Collins FS"", ""Eriksson M"", ""Strandgren C"", ""Cabral WA"", ""Dechat T""]",10.14336/AD.2024.1094,Blouin S,Aging and disease,2152-5250,5,Aging Dis,eng,Dechat T,"[""Animals"", ""Progeria"", ""Disease Models, Animal"", ""Mice"", ""Lamin Type A"", ""Growth Plate"", ""Calcification, Physiologic"", ""Bone Matrix"", ""Bone Density"", ""Male""]",3204-3218,39571160,pmc-id: PMC12339082;,2024 Nov 4,2024,https://pubmed.ncbi.nlm.nih.gov/39571160/,Normal Bone Matrix Mineralization but Altered Growth Plate Morphology in the Lmna(G609G/G609G) Mouse Model of Progeria,16,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic condition characterized by premature aging, impacting multiple organ systems, including cardiovascular, musculoskeletal, and integumentary. Significant abnormalities in a transgenic mouse model (homozygous G608G mutation), specifically targeting the development of skull and facial bone indices through high-resolution CT scanning and cephalometric analysis. Key measurements include bone thickness, skull volume, and cranial suture integrity. Bone volume increased significantly in HGPS mice by 8 months of age compared to wildtype mice. Cortical thickness showed a trend toward increased values in HGPS mice. Cranial metrics revealed distinct differences. HGPS mice exhibited smaller internasal width, interzygomatic distance, and palatine length compared to WT mice over time.","[""Journal Article""]","[""Beeram I"", ""Cubria MB"", ""Kamalapathy P"", ""Yeritsyan D"", ""Dubose AJ"", ""Razavi AH"", ""Nafisi N"", ""Erdos MR"", ""Snyder BD"", ""Cabral WA"", ""Collins FS"", ""Nazarian A""]",10.3389/fphys.2024.1481985,Beeram I,Frontiers in physiology,1664-042X,,Front Physiol,eng,Nazarian A,[],1481985,39568542,pmc-id: PMC11576425;,2024,2024,https://pubmed.ncbi.nlm.nih.gov/39568542/,Characterization of the craniofacial abnormalities of the homozygous G608G progeria mouse model,15,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Hepatitis C virus (HCV) is predominantly transmitted through parenteral exposures to infectious blood or body fluids. In 2019, approximately 58 million people worldwide were infected with HCV, and 290,000 deaths occurred due to hepatitis C-related conditions, despite hepatitis C being curable. There are substantial barriers to elimination, including the lack of widespread point-of-care diagnostics, cost of treatment, stigma associated with hepatitis C, and challenges in reaching marginalized populations, such as people who inject drugs. The World Health Organization (WHO) has set goals to eliminate hepatitis C by 2030. Several countries, including Australia, Egypt, Georgia, and Rwanda, have made remarkable progress toward hepatitis C elimination. In the United States, the Biden-Harris administration recently issued a plan for the national elimination of hepatitis C. Global progress has been uneven, however, and will need to accelerate considerably to reach the WHO's 2030 goals. Nevertheless, the global elimination of hepatitis C is within reach and should remain a high public health priority.","[""Journal Article"", ""Review"", ""Research Support, Non-U.S. Gov't""]","[""Fleurence RL"", ""Alter HJ"", ""Collins FS"", ""Ward JW""]",10.1146/annurev-med-050223-111239,Fleurence RL,Annual review of medicine,0066-4219,1,Annu Rev Med,eng,Ward JW,"[""Humans"", ""Global Health"", ""Hepatitis C"", ""Disease Eradication"", ""World Health Organization"", ""Hepacivirus"", ""Antiviral Agents""]",29-41,39485830,,2025 Jan,2025,https://pubmed.ncbi.nlm.nih.gov/39485830/,Global Elimination of Hepatitis C Virus,76,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disorder in children caused by a point mutation in the lamin A gene, resulting in a toxic form of lamin A called progerin. Accelerated atherosclerosis leading to heart attack and stroke are the major causes of death in these patients. Endothelial cell (EC) dysfunction contributes to the pathogenesis of HGPS related cardiovascular diseases (CVD). Endothelial cell-cell communications are important in the development of the vasculature, and their disruptions contribute to cardiovascular pathology. However, it is unclear how progerin interferes with such communications that lead to vascular dysfunction. An antibody array screening of healthy and HGPS patient EC secretomes identified Angiopoietin-2 (Ang2) as a down-regulated signaling molecule in HGPS ECs. A similar down-regulation of Ang2 mRNA and protein was detected in the aortas from an HGPS mouse model. Addition of Ang2 to HGPS ECs rescues vasculogenesis, normalizes endothelial cell migration and gene expression, and restores nitric oxide bioavailability through eNOS activation. Furthermore, Ang2 addition reverses unfavorable paracrine effects of HGPS ECs on vascular smooth muscle cells. Lastly, by utilizing adenine base editor (ABE)-corrected HGPS ECs and progerin-expressing HUVECs, we demonstrated a negative correlation between progerin and Ang2 expression. Lastly, our results indicated that Ang2 exerts its beneficial effect in ECs through Tie2 receptor binding, activating an Akt-mediated pathway. Together, these results provide molecular insights into EC dysfunction in HGPS and suggest that Ang2 treatment has potential therapeutic effects in HGPS-related CVD.","[""Journal Article""]","[""Vakili S"", ""Izydore EK"", ""Losert L"", ""Cabral WA"", ""Tavarez UL"", ""Shores K"", ""Xue H"", ""Erdos MR"", ""Truskey GA"", ""Collins FS"", ""Cao K""]",10.1111/acel.14375,Vakili S,Aging cell,1474-9718,2,Aging Cell,eng,Cao K,"[""Angiopoietin-2"", ""Animals"", ""Humans"", ""Progeria"", ""Mice"", ""Endothelial Cells"", ""Cell Movement"", ""Signal Transduction"", ""Disease Models, Animal""]",e14375,39422121,pmc-id: PMC11822663;,2025 Feb,2025,https://pubmed.ncbi.nlm.nih.gov/39422121/,Angiopoietin-2 reverses endothelial cell dysfunction in progeria vasculature,24,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Genome-wide association studies for glycemic traits have identified hundreds of loci associated with these biomarkers of glucose homeostasis. Despite this success, the challenge remains to link variant associations to genes, and underlying biological pathways. To identify coding variant associations which may pinpoint effector genes at both novel and previously established genome-wide association loci, we performed meta-analyses of exome-array studies for four glycemic traits: glycated hemoglobin (HbA1c, up to 144,060 participants), fasting glucose (FG, up to 129,665 participants), fasting insulin (FI, up to 104,140) and 2hr glucose post-oral glucose challenge (2hGlu, up to 57,878). In addition, we performed network and pathway analyses. Single-variant and gene-based association analyses identified coding variant associations at more than 60 genes, which when combined with other datasets may be useful to nominate effector genes. Network and pathway analyses identified pathways related to insulin secretion, zinc transport and fatty acid metabolism. HbA1c associations were strongly enriched in pathways related to blood cell biology. Our results provided novel glycemic trait associations and highlighted pathways implicated in glycemic regulation. Exome-array summary statistic results are being made available to the scientific community to enable further discoveries.","[""Journal Article""]","[""Willems SM"", ""Ng NHJ"", ""Fernandez J"", ""Fine RS"", ""Wheeler E"", ""Wessel J"", ""Kitajima H"", ""Marenne G"", ""Sim X"", ""Yaghootkar H"", ""Wang S"", ""Chen S"", ""Chen Y"", ""Chen YI"", ""Grarup N"", ""Li-Gao R"", ""Varga TV"", ""Asimit JL"", ""Feng S"", ""Strawbridge RJ"", ""Kleinbrink EL"", ""Ahluwalia TS"", ""An P"", ""Appel EV"", ""Arking DE"", ""Auvinen J"", ""Bielak LF"", ""Bihlmeyer NA"", ""Bork-Jensen J"", ""Brody JA"", ""Campbell A"", ""Chu AY"", ""Davies G"", ""Demirkan A"", ""Floyd JS"", ""Giulianini F"", ""Guo X"", ""Gustafsson S"", ""Jackson AU"", ""Jakobsdottir J"", ""Järvelin MR"", ""Jensen RA"", ""Kanoni S"", ""Keinanen-Kiukaanniemi S"", ""Li M"", ""Lu Y"", ""Luan J"", ""Manning AK"", ""Marten J"", ""Meidtner K"", ""Mook-Kanamori DO"", ""Muka T"", ""Pistis G"", ""Prins B"", ""Rice KM"", ""Sanna S"", ""Smith AV"", ""Smith JA"", ""Southam L"", ""Stringham HM"", ""Tragante V"", ""van der Laan SW"", ""Warren HR"", ""Yao J"", ""Yiorkas AM"", ""Zhang W"", ""Zhao W"", ""Graff M"", ""Highland HM"", ""Justice AE"", ""Marouli E"", ""Medina-Gomez C"", ""Afaq S"", ""Alhejily WA"", ""Amin N"", ""Asselbergs FW"", ""Bonnycastle LL"", ""Bots ML"", ""Brandslund I"", ""Chen J"", ""Danesh J"", ""de Mutsert R"", ""Dehghan A"", ""Ebeling T"", ""Elliott P"", ""EPIC-Interact Consortium"", ""Farmaki AE"", ""Faul JD"", ""Franks PW"", ""Franks S"", ""Fritsche A"", ""Gjesing AP"", ""Goodarzi MO"", ""Gudnason V"", ""Hallmans G"", ""Harris TB"", ""Herzig KH"", ""Hivert MF"", ""Jørgensen T"", ""Jørgensen ME"", ""Jousilahti P"", ""Kajantie E"", ""Karaleftheri M"", ""Kardia SLR"", ""Kinnunen L"", ""Koistinen HA"", ""Komulainen P"", ""Kovacs P"", ""Kuusisto J"", ""Laakso M"", ""Lange LA"", ""Launer LJ"", ""Leong A"", ""Lindström J"", ""Manning Fox JE"", ""Männistö S"", ""Maruthur NM"", ""Moilanen L"", ""Mulas A"", ""Nalls MA"", ""Neville M"", ""Pankow JS"", ""Pattie A"", ""Petersen ERB"", ""Puolijoki H"", ""Rasheed A"", ""Redmond P"", ""Renström F"", ""Roden M"", ""Saleheen D"", ""Saltevo J"", ""Savonen K"", ""Sebert S"", ""Skaaby T"", ""Small KS"", ""Stančáková A"", ""Stokholm J"", ""Strauch K"", ""Tai ES"", ""Taylor KD"", ""Thuesen BH"", ""Tönjes A"", ""Tsafantakis E"", ""Tuomi T"", ""Tuomilehto J"", ""Understanding Society Scientific Group"", ""Uusitupa M"", ""Vääräsmäki M"", ""Vaartjes I"", ""Zoledziewska M"", ""Abecasis G"", ""Balkau B"", ""Bisgaard H"", ""Blakemore AI"", ""Blüher M"", ""Boeing H"", ""Boerwinkle E"", ""Bønnelykke K"", ""Bottinger EP"", ""Caulfield MJ"", ""Chambers JC"", ""Chasman DI"", ""Cheng CY"", ""Collins FS"", ""Coresh J"", ""Cucca F"", ""de Borst GJ"", ""Deary IJ"", ""Dedoussis G"", ""Deloukas P"", ""den Ruijter HM"", ""Dupuis J"", ""Evans MK"", ""Ferrannini E"", ""Franco OH"", ""Grallert H"", ""Hansen T"", ""Hattersley AT"", ""Hayward C"", ""Hirschhorn JN"", ""Ikram A"", ""Ingelsson E"", ""Karpe F"", ""Kaw KT"", ""Kiess W"", ""Kooner JS"", ""Körner A"", ""Lakka T"", ""Langenberg C"", ""Lind L"", ""Lindgren CM"", ""Linneberg A"", ""Lipovich L"", ""Liu CT"", ""Liu J"", ""Liu Y"", ""Loos RJF"", ""MacDonald PE"", ""Mohlke KL"", ""Morris AD"", ""Munroe PB"", ""Murray A"", ""Padmanabhan S"", ""Palmer CNA"", ""Pasterkamp G"", ""Pedersen O"", ""Peyser PA"", ""Polasek O"", ""Porteous D"", ""Province MA"", ""Psaty BM"", ""Rauramaa R"", ""Ridker PM"", ""Rolandsson O"", ""Rorsman P"", ""Rosendaal FR"", ""Rudan I"", ""Salomaa V"", ""Schulze MB"", ""Sladek R"", ""Smith BH"", ""Spector TD"", ""Starr JM"", ""Stumvoll M"", ""van Duijn CM"", ""Walker M"", ""Wareham NJ"", ""Weir DR"", ""Wilson JG"", ""Wong TY"", ""Zeggini E"", ""Zonderman AB"", ""Rotter JI"", ""Morris AP"", ""Boehnke M"", ""Florez JC"", ""McCarthy MI"", ""Meigs JB"", ""Mahajan A"", ""Scott RA"", ""Gloyn AL"", ""Barroso I""]",10.12688/wellcomeopenres.18754.1,Willems SM,Wellcome open research,2398-502X,,Wellcome Open Res,eng,Barroso I,[],483,39280063,pmc-id: PMC11399760;,2023,2023,https://pubmed.ncbi.nlm.nih.gov/39280063/,Large-scale exome array summary statistics resources for glycemic traits to aid effector gene prioritization,8,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Combining information from multiple GWASs for a disease and its risk factors has proven a powerful approach for development of polygenic risk scores (PRSs). This may be particularly useful for type 2 diabetes (T2D), a highly polygenic and heterogeneous disease where the additional predictive value of a PRS is unclear. Here, we use a meta-scoring approach to develop a metaPRS for T2D that incorporated genome-wide associations from both European and non-European genetic ancestries and T2D risk factors. We evaluated the performance of this metaPRS and benchmarked it against existing genome-wide PRS in 620,059 participants and 50,572 T2D cases amongst six diverse genetic ancestries from UK Biobank, INTERVAL, the All of Us Research Program, and the Singapore Multi-Ethnic Cohort. We show that our metaPRS was the most powerful PRS for predicting T2D in European population-based cohorts and had comparable performance to the top ancestry-specific PRS, highlighting its transferability. In UK Biobank, we show the metaPRS had stronger predictive power for 10-year risk than all individual risk factors apart from BMI and biomarkers of dysglycemia. The metaPRS modestly improved T2D risk stratification of QDiabetes risk scores for 10-year risk prediction, particularly when prioritising individuals for blood tests of dysglycemia. Overall, we present a highly predictive and transferrable PRS for T2D and demonstrate that the potential for PRS to incrementally improve T2D risk prediction when incorporated into UK guideline-recommended screening and risk prediction with a clinical risk score.","[""Journal Article"", ""Preprint""]","[""Ritchie SC"", ""Taylor HJ"", ""Liang Y"", ""Manikpurage HD"", ""Pennells L"", ""Foguet C"", ""Abraham G"", ""Gibson JT"", ""Jiang X"", ""Liu Y"", ""Xu Y"", ""Kim LG"", ""Mahajan A"", ""McCarthy MI"", ""Kaptoge S"", ""Lambert SA"", ""Wood A"", ""Sim X"", ""Collins FS"", ""Denny JC"", ""Danesh J"", ""Butterworth AS"", ""Di Angelantonio E"", ""Inouye M""]",10.1101/2024.08.22.24312440,Ritchie SC,medRxiv : the preprint server for health sciences,,,medRxiv,eng,Inouye M,[],,39228710,pmc-id: PMC11370520;,2024 Sep 23,2024,https://pubmed.ncbi.nlm.nih.gov/39228710/,Integrated clinical risk prediction of type 2 diabetes with a multifactorial polygenic risk score,,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disease caused primarily by a C1824T mutation in LMNA. This mutation activates a cryptic splice donor site, producing a lamin variant called progerin. Interestingly, progerin has also been detected in cells and tissues of non-HGPS patients. Here, we investigated progerin expression using publicly available RNA-seq data from non-HGPS patients in the GTEx project. We found that progerin expression is present across all tissue types in non-HGPS patients and correlated with telomere shortening in the skin. Transcriptome-wide correlation analyses suggest that the level of progerin expression is correlated with switches in gene isoform expression patterns. Differential expression analyses show that progerin expression is correlated with significant changes in genes involved in splicing regulation and mitochondrial function. Interestingly, 5' splice sites whose use is correlated with progerin expression have significantly altered frequencies of consensus trinucleotides within the core 5' splice site. Furthermore, introns whose alternative splicing correlates with progerin have reduced GC content. Our study suggests that progerin expression in non-HGPS patients is part of a global shift in splicing patterns.","[""Journal Article""]","[""Yu R"", ""Xue H"", ""Lin W"", ""Collins FS"", ""Mount SM"", ""Cao K""]",10.1093/nargab/lqae115,Yu R,NAR genomics and bioinformatics,2631-9268,3,NAR Genom Bioinform,eng,Cao K,[],lqae115,39211333,pmc-id: PMC11358823;,2024 Sep,2024,https://pubmed.ncbi.nlm.nih.gov/39211333/,Progerin mRNA expression in non-HGPS patients is correlated with widespread shifts in transcript isoforms,6,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"The hypothalamus, composed of several nuclei, is essential for maintaining our body's homeostasis. The arcuate nucleus (ARC), located in the mediobasal hypothalamus, contains neuronal populations with eminent roles in energy and glucose homeostasis as well as reproduction. These neuronal populations are of great interest for translational research. To fulfill this promise, we used a robotic cell culture platform to provide a scalable and chemically defined approach for differentiating human pluripotent stem cells (hPSCs) into pro-opiomelanocortin (POMC), somatostatin (SST), tyrosine hydroxylase (TH) and gonadotropin-releasing hormone (GnRH) neuronal subpopulations with an ARC-like signature. This robust approach is reproducible across several distinct hPSC lines and exhibits a stepwise induction of key ventral diencephalon and ARC markers in transcriptomic profiling experiments. This is further corroborated by direct comparison to human fetal hypothalamus, and the enriched expression of genes implicated in obesity and type 2 diabetes (T2D). Genome-wide chromatin accessibility profiling by ATAC-seq identified accessible regulatory regions that can be utilized to predict candidate enhancers related to metabolic disorders and hypothalamic development. In depth molecular, cellular, and functional experiments unveiled the responsiveness of the hPSC-derived hypothalamic neurons to hormonal stimuli, such as insulin, neuropeptides including kisspeptin, and incretin mimetic drugs such as Exendin-4, highlighting their potential utility as physiologically relevant cellular models for disease studies. In addition, differential glucose and insulin treatments uncovered adaptability within the generated ARC neurons in the dynamic regulation of POMC and insulin receptors. In summary, the establishment of this model represents a novel, chemically defined, and scalable platform for manufacturing large numbers of hypothalamic arcuate neurons and serves as a valuable resource for modeling metabolic and reproductive disorders.","[""Journal Article"", ""Preprint""]","[""Jovanovic VM"", ""Narisu N"", ""Bonnycastle LL"", ""Tharakan R"", ""Mesch KT"", ""Glover HJ"", ""Yan T"", ""Sinha N"", ""Sen C"", ""Castellano D"", ""Yang S"", ""Blivis D"", ""Ryu S"", ""Bennett DF"", ""Rosales-Soto G"", ""Inman J"", ""Ormanoglu P"", ""LeClair CA"", ""Xia M"", ""Schneider M"", ""Hernandez-Ochoa EO"", ""Erdos MR"", ""Simeonov A"", ""Chen S"", ""Collins FS"", ""Doege CA"", ""Tristan CA""]",10.1101/2024.06.27.601062,Jovanovic VM,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Tristan CA,[],,39005353,pmc-id: PMC11244856;,2024 Sep 20,2024,https://pubmed.ncbi.nlm.nih.gov/39005353/,Scalable Hypothalamic Arcuate Neuron Differentiation from Human Pluripotent Stem Cells Suitable for Modeling Metabolic and Reproductive Disorders,,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Disruption of pancreatic islet function and glucose homeostasis can lead to the development of sustained hyperglycaemia, beta cell glucotoxicity and subsequently type 2 diabetes. In this study, we explored the effects of in vitro hyperglycaemic conditions on human pancreatic islet gene expression across 24 h in six pancreatic cell types: alpha; beta; gamma; delta; ductal; and acinar. We hypothesised that genes associated with hyperglycaemic conditions may be relevant to the onset and progression of diabetes. We exposed human pancreatic islets from two donors to low (2.8 mmol/l) and high (15.0 mmol/l) glucose concentrations over 24 h in vitro. To assess the transcriptome, we performed single-cell RNA-seq (scRNA-seq) at seven time points. We modelled time as both a discrete and continuous variable to determine momentary and longitudinal changes in transcription associated with islet time in culture or glucose exposure. Additionally, we integrated genomic features and genetic summary statistics to nominate candidate effector genes. For three of these genes, we functionally characterised the effect on insulin production and secretion using CRISPR interference to knock down gene expression in EndoC-βH1 cells, followed by a glucose-stimulated insulin secretion assay. In the discrete time models, we identified 1344 genes associated with time and 668 genes associated with glucose exposure across all cell types and time points. In the continuous time models, we identified 1311 genes associated with time, 345 genes associated with glucose exposure and 418 genes associated with interaction effects between time and glucose across all cell types. By integrating these expression profiles with summary statistics from genetic association studies, we identified 2449 candidate effector genes for type 2 diabetes, HbA1c, random blood glucose and fasting blood glucose. Of these candidate effector genes, we showed that three (ERO1B, HNRNPA2B1 and RHOBTB3) exhibited an effect on glucose-stimulated insulin production and secretion in EndoC-βH1 cells. The findings of our study provide an in-depth characterisation of the 24 h transcriptomic response of human pancreatic islets to glucose exposure at a single-cell resolution. By integrating differentially expressed genes with genetic signals for type 2 diabetes and glucose-related traits, we provide insights into the molecular mechanisms underlying glucose homeostasis. Finally, we provide functional evidence to support the role of three candidate effector genes in insulin secretion and production. The scRNA-seq data from the 24 h glucose exposure experiment performed in this study are available in the database of Genotypes and Phenotypes (dbGap; https://www.ncbi.nlm.nih.gov/gap/ ) with accession no. phs001188.v3.p1. Study metadata and summary statistics for the differential expression, gene set enrichment and candidate effector gene prediction analyses are available in the Zenodo data repository ( https://zenodo.org/ ) under accession number 11123248. The code used in this study is publicly available at https://github.com/CollinsLabBioComp/publication-islet_glucose_timecourse .","[""Journal Article""]","[""Grenko CM"", ""Taylor HJ"", ""Bonnycastle LL"", ""Xue D"", ""Lee BN"", ""Weiss Z"", ""Yan T"", ""Swift AJ"", ""Mansell EC"", ""Lee A"", ""Robertson CC"", ""Narisu N"", ""Erdos MR"", ""Chen S"", ""Collins FS"", ""Taylor DL""]",10.1007/s00125-024-06214-4,Grenko CM,Diabetologia,0012-186X,10,Diabetologia,eng,Taylor DL,"[""Humans"", ""Islets of Langerhans"", ""Glucose"", ""Single-Cell Analysis"", ""Gene Expression Profiling"", ""Transcriptome"", ""Diabetes Mellitus, Type 2"", ""Insulin"", ""Insulin-Secreting Cells"", ""Hyperglycemia""]",2246-2259,38967666,pmc-id: PMC11447040;,2024 Oct,2024,https://pubmed.ncbi.nlm.nih.gov/38967666/,Single-cell transcriptomic profiling of human pancreatic islets reveals genes responsive to glucose exposure over 24 h,67,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Congenital facial weakness (CFW) encompasses a heterogenous set of rare disorders presenting with decreased facial movement from birth, secondary to impaired function of the facial musculature. The aim of the present study is to provide an analysis of subject-reported oral health-related quality of life (OHRQoL) in congenital facial weakness (CFW) disorders. Forty-four subjects with CFW and age- and sex- matched controls were enrolled in an Institutional Review Board (IRB)-approved study. Demographic data, medical and surgical history, comprehensive oral examination, and the Oral Health Impact Profile (OHIP-14) were obtained. Compared to unaffected controls, subjects with CFW had higher OHIP-14 scores overall (mean ± SD: 13.11 ± 8.11 vs. 4.46 ± 4.98, p < 0.0001) and within five of seven oral health domains, indicating decreased OHRQoL. Although subjects with Moebius syndrome (MBS) were noted to have higher OHIP-14 scores than those with Hereditary Congenital Facial Paresis (HCFP), there was no significant correlation in OHIP-14 score to age, sex, or specific diagnosis. An increase in OHIP-14 scores in subjects was detected in those who had undergone reanimation surgery. In conclusion, subjects with CFW had poorer OHRQoL compared to controls, and subjects with MBS had poorer OHRQoL than subjects with HCFP. This study provides better understanding of oral health care needs and quality of life in a CFW cohort and suggests that guidelines for dental treatment are required.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, N.I.H., Intramural""]","[""Liberton DK"", ""Almpani K"", ""Mishra R"", ""Bassim C"", ""Van Ryzin C"", ""On Behalf Of The Moebius Syndrome Research Consortium"", ""Webb BD"", ""Jabs EW"", ""Engle EC"", ""Collins FS"", ""Manoli I"", ""Lee JS""]",10.3390/ijerph21050615,Liberton DK,International journal of environmental research and public health,1661-7827,5,Int J Environ Res Public Health,eng,Lee JS,"[""Humans"", ""Quality of Life"", ""Male"", ""Female"", ""Oral Health"", ""Adult"", ""Young Adult"", ""Adolescent"", ""Child"", ""Middle Aged"", ""Facial Paralysis"", ""Case-Control Studies"", ""Rare Diseases""]",,38791829,pmc-id: PMC11121611;,2024 May 13,2024,https://pubmed.ncbi.nlm.nih.gov/38791829/,Oral Health-Related Quality of Life in Rare Disorders of Congenital Facial Weakness,21,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
,"[""Journal Article""]","[""Chen WG"", ""Edwards E"", ""Iyengar S"", ""Finkelstein R"", ""Rutter DF"", ""Fleming R"", ""Collins FS""]",10.1016/S0140-6736(24)00477-X,Chen WG,"Lancet (London, England)",0140-6736,10433,Lancet,eng,Collins FS,"[""Humans"", ""Music"", ""Heart Rate"", ""Fetal Movement"", ""Medicine""]",1213-1215,38513679,,2024 Mar 30,2024,https://pubmed.ncbi.nlm.nih.gov/38513679/,Music and medicine: quickening the tempo of progress,403,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Suzuki K"", ""Hatzikotoulas K"", ""Southam L"", ""Taylor HJ"", ""Yin X"", ""Lorenz KM"", ""Mandla R"", ""Huerta-Chagoya A"", ""Melloni GEM"", ""Kanoni S"", ""Rayner NW"", ""Bocher O"", ""Arruda AL"", ""Sonehara K"", ""Namba S"", ""Lee SSK"", ""Preuss MH"", ""Petty LE"", ""Schroeder P"", ""Vanderwerff B"", ""Kals M"", ""Bragg F"", ""Lin K"", ""Guo X"", ""Zhang W"", ""Yao J"", ""Kim YJ"", ""Graff M"", ""Takeuchi F"", ""Nano J"", ""Lamri A"", ""Nakatochi M"", ""Moon S"", ""Scott RA"", ""Cook JP"", ""Lee JJ"", ""Pan I"", ""Taliun D"", ""Parra EJ"", ""Chai JF"", ""Bielak LF"", ""Tabara Y"", ""Hai Y"", ""Thorleifsson G"", ""Grarup N"", ""Sofer T"", ""Wuttke M"", ""Sarnowski C"", ""Gieger C"", ""Nousome D"", ""Trompet S"", ""Kwak SH"", ""Long J"", ""Sun M"", ""Tong L"", ""Chen WM"", ""Nongmaithem SS"", ""Noordam R"", ""Lim VJY"", ""Tam CHT"", ""Joo YY"", ""Chen CH"", ""Raffield LM"", ""Prins BP"", ""Nicolas A"", ""Yanek LR"", ""Chen G"", ""Brody JA"", ""Kabagambe E"", ""An P"", ""Xiang AH"", ""Choi HS"", ""Cade BE"", ""Tan J"", ""Broadaway KA"", ""Williamson A"", ""Kamali Z"", ""Cui J"", ""Thangam M"", ""Adair LS"", ""Adeyemo A"", ""Aguilar-Salinas CA"", ""Ahluwalia TS"", ""Anand SS"", ""Bertoni A"", ""Bork-Jensen J"", ""Brandslund I"", ""Buchanan TA"", ""Burant CF"", ""Butterworth AS"", ""Canouil M"", ""Chan JCN"", ""Chang LC"", ""Chee ML"", ""Chen J"", ""Chen SH"", ""Chen YT"", ""Chen Z"", ""Chuang LM"", ""Cushman M"", ""Danesh J"", ""Das SK"", ""de Silva HJ"", ""Dedoussis G"", ""Dimitrov L"", ""Doumatey AP"", ""Du S"", ""Duan Q"", ""Eckardt KU"", ""Emery LS"", ""Evans DS"", ""Evans MK"", ""Fischer K"", ""Floyd JS"", ""Ford I"", ""Franco OH"", ""Frayling TM"", ""Freedman BI"", ""Genter P"", ""Gerstein HC"", ""Giedraitis V"", ""González-Villalpando C"", ""González-Villalpando ME"", ""Gordon-Larsen P"", ""Gross M"", ""Guare LA"", ""Hackinger S"", ""Hakaste L"", ""Han S"", ""Hattersley AT"", ""Herder C"", ""Horikoshi M"", ""Howard AG"", ""Hsueh W"", ""Huang M"", ""Huang W"", ""Hung YJ"", ""Hwang MY"", ""Hwu CM"", ""Ichihara S"", ""Ikram MA"", ""Ingelsson M"", ""Islam MT"", ""Isono M"", ""Jang HM"", ""Jasmine F"", ""Jiang G"", ""Jonas JB"", ""Jørgensen T"", ""Kamanu FK"", ""Kandeel FR"", ""Kasturiratne A"", ""Katsuya T"", ""Kaur V"", ""Kawaguchi T"", ""Keaton JM"", ""Kho AN"", ""Khor CC"", ""Kibriya MG"", ""Kim DH"", ""Kronenberg F"", ""Kuusisto J"", ""Läll K"", ""Lange LA"", ""Lee KM"", ""Lee MS"", ""Lee NR"", ""Leong A"", ""Li L"", ""Li Y"", ""Li-Gao R"", ""Ligthart S"", ""Lindgren CM"", ""Linneberg A"", ""Liu CT"", ""Liu J"", ""Locke AE"", ""Louie T"", ""Luan J"", ""Luk AO"", ""Luo X"", ""Lv J"", ""Lynch JA"", ""Lyssenko V"", ""Maeda S"", ""Mamakou V"", ""Mansuri SR"", ""Matsuda K"", ""Meitinger T"", ""Melander O"", ""Metspalu A"", ""Mo H"", ""Morris AD"", ""Moura FA"", ""Nadler JL"", ""Nalls MA"", ""Nayak U"", ""Ntalla I"", ""Okada Y"", ""Orozco L"", ""Patel SR"", ""Patil S"", ""Pei P"", ""Pereira MA"", ""Peters A"", ""Pirie FJ"", ""Polikowsky HG"", ""Porneala B"", ""Prasad G"", ""Rasmussen-Torvik LJ"", ""Reiner AP"", ""Roden M"", ""Rohde R"", ""Roll K"", ""Sabanayagam C"", ""Sandow K"", ""Sankareswaran A"", ""Sattar N"", ""Schönherr S"", ""Shahriar M"", ""Shen B"", ""Shi J"", ""Shin DM"", ""Shojima N"", ""Smith JA"", ""So WY"", ""Stančáková A"", ""Steinthorsdottir V"", ""Stilp AM"", ""Strauch K"", ""Taylor KD"", ""Thorand B"", ""Thorsteinsdottir U"", ""Tomlinson B"", ""Tran TC"", ""Tsai FJ"", ""Tuomilehto J"", ""Tusie-Luna T"", ""Udler MS"", ""Valladares-Salgado A"", ""van Dam RM"", ""van Klinken JB"", ""Varma R"", ""Wacher-Rodarte N"", ""Wheeler E"", ""Wickremasinghe AR"", ""van Dijk KW"", ""Witte DR"", ""Yajnik CS"", ""Yamamoto K"", ""Yamamoto K"", ""Yoon K"", ""Yu C"", ""Yuan JM"", ""Yusuf S"", ""Zawistowski M"", ""Zhang L"", ""Zheng W"", ""VA Million Veteran Program"", ""Raffel LJ"", ""Igase M"", ""Ipp E"", ""Redline S"", ""Cho YS"", ""Lind L"", ""Province MA"", ""Fornage M"", ""Hanis CL"", ""Ingelsson E"", ""Zonderman AB"", ""Psaty BM"", ""Wang YX"", ""Rotimi CN"", ""Becker DM"", ""Matsuda F"", ""Liu Y"", ""Yokota M"", ""Kardia SLR"", ""Peyser PA"", ""Pankow JS"", ""Engert JC"", ""Bonnefond A"", ""Froguel P"", ""Wilson JG"", ""Sheu WHH"", ""Wu JY"", ""Hayes MG"", ""Ma RCW"", ""Wong TY"", ""Mook-Kanamori DO"", ""Tuomi T"", ""Chandak GR"", ""Collins FS"", ""Bharadwaj D"", ""Paré G"", ""Sale MM"", ""Ahsan H"", ""Motala AA"", ""Shu XO"", ""Park KS"", ""Jukema JW"", ""Cruz M"", ""Chen YI"", ""Rich SS"", ""McKean-Cowdin R"", ""Grallert H"", ""Cheng CY"", ""Ghanbari M"", ""Tai ES"", ""Dupuis J"", ""Kato N"", ""Laakso M"", ""Köttgen A"", ""Koh WP"", ""Bowden DW"", ""Palmer CNA"", ""Kooner JS"", ""Kooperberg C"", ""Liu S"", ""North KE"", ""Saleheen D"", ""Hansen T"", ""Pedersen O"", ""Wareham NJ"", ""Lee J"", ""Kim BJ"", ""Millwood IY"", ""Walters RG"", ""Stefansson K"", ""Ahlqvist E"", ""Goodarzi MO"", ""Mohlke KL"", ""Langenberg C"", ""Haiman CA"", ""Loos RJF"", ""Florez JC"", ""Rader DJ"", ""Ritchie MD"", ""Zöllner S"", ""Mägi R"", ""Marston NA"", ""Ruff CT"", ""van Heel DA"", ""Finer S"", ""Denny JC"", ""Yamauchi T"", ""Kadowaki T"", ""Chambers JC"", ""Ng MCY"", ""Sim X"", ""Below JE"", ""Tsao PS"", ""Chang KM"", ""McCarthy MI"", ""Meigs JB"", ""Mahajan A"", ""Spracklen CN"", ""Mercader JM"", ""Boehnke M"", ""Rotter JI"", ""Vujkovic M"", ""Voight BF"", ""Morris AP"", ""Zeggini E""]",10.1038/s41586-024-07019-6,Suzuki K,Nature,0028-0836,8003,Nature,eng,Zeggini E,"[""Humans"", ""Adipocytes"", ""Chromatin"", ""Coronary Artery Disease"", ""Diabetes Mellitus, Type 2"", ""Diabetic Nephropathies"", ""Disease Progression"", ""Endothelial Cells"", ""Enteroendocrine Cells"", ""Epigenomics"", ""Genetic Predisposition to Disease"", ""Genome-Wide Association Study"", ""Islets of Langerhans"", ""Multifactorial Inheritance"", ""Peripheral Arterial Disease"", ""Single-Cell Analysis""]",347-357,38374256,pmc-id: PMC10937372;,2024 Mar,2024,https://pubmed.ncbi.nlm.nih.gov/38374256/,Genetic drivers of heterogeneity in type 2 diabetes pathophysiology,627,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"We developed an efficient CRISPR prime editing protocol and generated isogenic-induced pluripotent stem cell (iPSC) lines carrying heterozygous or homozygous alleles for putatively causal single nucleotide variants at six type 2 diabetes loci (ABCC8, MTNR1B, TCF7L2, HNF4A, CAMK1D, and GCK). Our two-step sequence-based approach to first identify transfected cell pools with the highest fraction of edited cells significantly reduced the downstream efforts to isolate single clones of edited cells. We found that prime editing can make targeted genetic changes in iPSC and optimization of system components and guide RNA designs that were critical to achieve acceptable efficiency. Systems utilizing PEmax, epegRNA modifications, and MLH1dn provided significant benefit, producing editing efficiencies of 36-73%. Editing success and pegRNA design optimization required for each variant differed depending on the sequence at the target site. With attention to design, prime editing is a promising approach to generate isogenic iPSC lines, enabling the study of specific genetic changes in a common genetic background.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, N.I.H., Intramural""]","[""Bonnycastle LL"", ""Swift AJ"", ""Mansell EC"", ""Lee A"", ""Winnicki E"", ""Li ES"", ""Robertson CC"", ""Parsons VA"", ""Huynh T"", ""Krilow C"", ""Mohlke KL"", ""Erdos MR"", ""Narisu N"", ""Collins FS""]",10.1089/crispr.2023.0066,Bonnycastle LL,The CRISPR journal,2573-1599,1,CRISPR J,eng,Collins FS,"[""Humans"", ""Clustered Regularly Interspaced Short Palindromic Repeats"", ""Diabetes Mellitus, Type 2"", ""Induced Pluripotent Stem Cells"", ""CRISPR-Cas Systems"", ""Gene Editing"", ""RNA, Guide, CRISPR-Cas Systems""]",53-67,38353623,pmc-id: PMC10880268;,2024 Feb,2024,https://pubmed.ncbi.nlm.nih.gov/38353623/,Generation of Human Isogenic Induced Pluripotent Stem Cell Lines with CRISPR Prime Editing,7,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Skeletal muscle, the largest human organ by weight, is relevant in several polygenic metabolic traits and diseases including type 2 diabetes (T2D). Identifying genetic mechanisms underlying these traits requires pinpointing cell types, regulatory elements, target genes, and causal variants. Here, we use genetic multiplexing to generate population-scale single nucleus (sn) chromatin accessibility (snATAC-seq) and transcriptome (snRNA-seq) maps across 287 frozen human skeletal muscle biopsies representing nearly half a million nuclei. We identify 13 cell types and integrate genetic variation to discover >7,000 expression quantitative trait loci (eQTL) and >100,000 chromatin accessibility QTLs (caQTL) across cell types. Learning patterns of e/caQTL sharing across cell types increased precision of effect estimates. We identify high-resolution cell-states and context-specific e/caQTL with significant genotype by context interaction. We identify nearly 2,000 eGenes colocalized with caQTL and construct causal directional maps for chromatin accessibility and gene expression. Almost 3,500 genome-wide association study (GWAS) signals across 38 relevant traits colocalize with sn-e/caQTL, most in a cell-specific manner. These signals typically colocalize with caQTL and not eQTL, highlighting the importance of population-scale chromatin profiling for GWAS functional studies. Finally, our GWAS-caQTL colocalization data reveal distinct cell-specific regulatory paradigms. Our results illuminate the genetic regulatory architecture of human skeletal muscle at high resolution epigenomic, transcriptomic, and cell-state scales and serve as a template for population-scale multi-omic mapping in complex tissues and traits.","[""Journal Article"", ""Preprint""]","[""Varshney A"", ""Manickam N"", ""Orchard P"", ""Tovar A"", ""Ventresca C"", ""Zhang Z"", ""Feng F"", ""Mears J"", ""Erdos MR"", ""Narisu N"", ""Nishino K"", ""Rai V"", ""Stringham HM"", ""Jackson AU"", ""Tamsen T"", ""Gao C"", ""Yang M"", ""Koues OI"", ""Welch JD"", ""Burant CF"", ""Williams LK"", ""Jenkinson C"", ""DeFronzo RA"", ""Norton L"", ""Saramies J"", ""Lakka TA"", ""Laakso M"", ""Tuomilehto J"", ""Mohlke KL"", ""Kitzman JO"", ""Koistinen HA"", ""Liu J"", ""Boehnke M"", ""Collins FS"", ""Scott LJ"", ""Parker SCJ""]",10.1101/2023.12.15.571696,Varshney A,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Parker SCJ,[],,38168419,pmc-id: PMC10760134;,2024 Dec 17,2024,https://pubmed.ncbi.nlm.nih.gov/38168419/,Population-scale skeletal muscle single-nucleus multi-omic profiling reveals extensive context specific genetic regulation,,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Complete characterization of the genetic effects on gene expression is needed to elucidate tissue biology and the etiology of complex traits. Here, we analyzed 2,344 subcutaneous adipose tissue samples and identified 34K conditionally distinct expression quantitative trait locus (eQTL) signals in 18K genes. Over half of eQTL genes exhibited at least two eQTL signals. Compared to primary signals, non-primary signals had lower effect sizes, lower minor allele frequencies, and less promoter enrichment; they corresponded to genes with higher heritability and higher tolerance for loss of function. Colocalization of eQTL with conditionally distinct genome-wide association study signals for 28 cardiometabolic traits identified 3,605 eQTL signals for 1,861 genes. Inclusion of non-primary eQTL signals increased colocalized signals by 46%. Among 30 genes with ≥2 pairs of colocalized signals, 21 showed a mediating gene dosage effect on the trait. Thus, expanded eQTL identification reveals more mechanisms underlying complex traits and improves understanding of the complexity of gene expression regulation.","[""Preprint"", ""Journal Article""]","[""Brotman SM"", ""El-Sayed Moustafa JS"", ""Guan L"", ""Broadaway KA"", ""Wang D"", ""Jackson AU"", ""Welch R"", ""Currin KW"", ""Tomlinson M"", ""Vadlamudi S"", ""Stringham HM"", ""Roberts AL"", ""Lakka TA"", ""Oravilahti A"", ""Silva LF"", ""Narisu N"", ""Erdos MR"", ""Yan T"", ""Bonnycastle LL"", ""Raulerson CK"", ""Raza Y"", ""Yan X"", ""Parker SCJ"", ""Kuusisto J"", ""Pajukanta P"", ""Tuomilehto J"", ""Collins FS"", ""Boehnke M"", ""Love MI"", ""Koistinen HA"", ""Laakso M"", ""Mohlke KL"", ""Small KS"", ""Scott LJ""]",10.1101/2023.10.26.563798,Brotman SM,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Scott LJ,[],,37961277,pmc-id: PMC10634839;,2023 Oct 27,2023,https://pubmed.ncbi.nlm.nih.gov/37961277/,Adipose tissue eQTL meta-analysis reveals the contribution of allelic heterogeneity to gene expression regulation and cardiometabolic traits,,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Genetic studies have identified numerous loci associated with type 2 diabetes (T2D), but the functional roles of many loci remain unexplored. Here, we engineered isogenic knockout human embryonic stem cell lines for 20 genes associated with T2D risk. We examined the impacts of each knockout on β cell differentiation, functions, and survival. We generated gene expression and chromatin accessibility profiles on β cells derived from each knockout line. Analyses of T2D-association signals overlapping HNF4A-dependent ATAC peaks identified a likely causal variant at the FAIM2 T2D-association signal. Additionally, the integrative association analyses identified four genes (CP, RNASE1, PCSK1N, and GSTA2) associated with insulin production, and two genes (TAGLN3 and DHRS2) associated with β cell sensitivity to lipotoxicity. Finally, we leveraged deep ATAC-seq read coverage to assess allele-specific imbalance at variants heterozygous in the parental line and identified a single likely functional variant at each of 23 T2D-association signals.","[""Journal Article"", ""Research Support, N.I.H., Intramural"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Xue D"", ""Narisu N"", ""Taylor DL"", ""Zhang M"", ""Grenko C"", ""Taylor HJ"", ""Yan T"", ""Tang X"", ""Sinha N"", ""Zhu J"", ""Vandana JJ"", ""Nok Chong AC"", ""Lee A"", ""Mansell EC"", ""Swift AJ"", ""Erdos MR"", ""Zhong A"", ""Bonnycastle LL"", ""Zhou T"", ""Chen S"", ""Collins FS""]",10.1016/j.cmet.2023.09.013,Xue D,Cell metabolism,1550-4131,11,Cell Metab,eng,Collins FS,"[""Humans"", ""Diabetes Mellitus, Type 2"", ""Human Embryonic Stem Cells"", ""Genetic Predisposition to Disease"", ""Genome-Wide Association Study"", ""Insulin-Secreting Cells"", ""Polymorphism, Single Nucleotide"", ""Carbonyl Reductase (NADPH)""]",1897-1914.e11,37858332,pmc-id: PMC10841752;manuscript-id: NIHMS1936895;,2023 Nov 7,2023,https://pubmed.ncbi.nlm.nih.gov/37858332/,Functional interrogation of twenty type 2 diabetes-associated genes using isogenic human embryonic stem cell-derived β-like cells,35,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
,"[""Letter"", ""Comment""]","[""Fleurence RL"", ""Collins FS""]",10.1001/jama.2023.11763,Fleurence RL,JAMA,0098-7484,9,JAMA,eng,Collins FS,"[""Humans"", ""Disease Eradication"", ""Hepacivirus"", ""Hepatitis C"", ""United States""]",878,37668623,,2023 Sep 5,2023,https://pubmed.ncbi.nlm.nih.gov/37668623/,US Hepatitis C Elimination Plan-Reply,330,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Genetic association studies have identified hundreds of independent signals associated with type 2 diabetes (T2D) and related traits. Despite these successes, the identification of specific causal variants underlying a genetic association signal remains challenging. In this study, we describe a deep learning (DL) method to analyze the impact of sequence variants on enhancers. Focusing on pancreatic islets, a T2D relevant tissue, we show that our model learns islet-specific transcription factor (TF) regulatory patterns and can be used to prioritize candidate causal variants. At 101 genetic signals associated with T2D and related glycemic traits where multiple variants occur in linkage disequilibrium, our method nominates a single causal variant for each association signal, including three variants previously shown to alter reporter activity in islet-relevant cell types. For another signal associated with blood glucose levels, we biochemically test all candidate causal variants from statistical fine-mapping using a pancreatic islet beta cell line and show biochemical evidence of allelic effects on TF binding for the model-prioritized variant. To aid in future research, we publicly distribute our model and islet enhancer perturbation scores across ~67 million genetic variants. We anticipate that DL methods like the one presented in this study will enhance the prioritization of candidate causal variants for functional studies.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, N.I.H., Intramural"", ""Research Support, U.S. Gov't, Non-P.H.S.""]","[""Hudaiberdiev S"", ""Taylor DL"", ""Song W"", ""Narisu N"", ""Bhuiyan RM"", ""Taylor HJ"", ""Tang X"", ""Yan T"", ""Swift AJ"", ""Bonnycastle LL"", ""Consortium D"", ""Chen S"", ""Stitzel ML"", ""Erdos MR"", ""Ovcharenko I"", ""Collins FS""]",10.1073/pnas.2206612120,Hudaiberdiev S,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,35,Proc Natl Acad Sci U S A,eng,Collins FS,"[""Diabetes Mellitus, Type 2"", ""Deep Learning"", ""Enhancer Elements, Genetic"", ""Islets of Langerhans"", ""Genetic Variation"", ""Humans"", ""Computer Simulation""]",e2206612120,37603758,pmc-id: PMC10469333;,2023 Aug 29,2023,https://pubmed.ncbi.nlm.nih.gov/37603758/,Modeling islet enhancers using deep learning identifies candidate causal variants at loci associated with T2D and glycemic traits,120,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Hereditary congenital facial paresis type 1 (HCFP1) is an autosomal dominant disorder of absent or limited facial movement that maps to chromosome 3q21-q22 and is hypothesized to result from facial branchial motor neuron (FBMN) maldevelopment. In the present study, we report that HCFP1 results from heterozygous duplications within a neuron-specific GATA2 regulatory region that includes two enhancers and one silencer, and from noncoding single-nucleotide variants (SNVs) within the silencer. Some SNVs impair binding of NR2F1 to the silencer in vitro and in vivo and attenuate in vivo enhancer reporter expression in FBMNs. Gata2 and its effector Gata3 are essential for inner-ear efferent neuron (IEE) but not FBMN development. A humanized HCFP1 mouse model extends Gata2 expression, favors the formation of IEEs over FBMNs and is rescued by conditional loss of Gata3. These findings highlight the importance of temporal gene regulation in development and of noncoding variation in rare mendelian disease.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, N.I.H., Intramural"", ""Research Support, Non-U.S. Gov't"", ""Research Support, U.S. Gov't, Non-P.H.S.""]","[""Tenney AP"", ""Di Gioia SA"", ""Webb BD"", ""Chan WM"", ""de Boer E"", ""Garnai SJ"", ""Barry BJ"", ""Ray T"", ""Kosicki M"", ""Robson CD"", ""Zhang Z"", ""Collins TE"", ""Gelber A"", ""Pratt BM"", ""Fujiwara Y"", ""Varshney A"", ""Lek M"", ""Warburton PE"", ""Van Ryzin C"", ""Lehky TJ"", ""Zalewski C"", ""King KA"", ""Brewer CC"", ""Thurm A"", ""Snow J"", ""Facio FM"", ""Narisu N"", ""Bonnycastle LL"", ""Swift A"", ""Chines PS"", ""Bell JL"", ""Mohan S"", ""Whitman MC"", ""Staffieri SE"", ""Elder JE"", ""Demer JL"", ""Torres A"", ""Rachid E"", ""Al-Haddad C"", ""Boustany RM"", ""Mackey DA"", ""Brady AF"", ""Fenollar-Cortés M"", ""Fradin M"", ""Kleefstra T"", ""Padberg GW"", ""Raskin S"", ""Sato MT"", ""Orkin SH"", ""Parker SCJ"", ""Hadlock TA"", ""Vissers LELM"", ""van Bokhoven H"", ""Jabs EW"", ""Collins FS"", ""Pennacchio LA"", ""Manoli I"", ""Engle EC""]",10.1038/s41588-023-01424-9,Tenney AP,Nature genetics,1061-4036,7,Nat Genet,eng,Engle EC,"[""Animals"", ""Mice"", ""Facial Paralysis"", ""GATA2 Transcription Factor"", ""Motor Neurons"", ""Neurogenesis"", ""Neurons, Efferent""]",1149-1163,37386251,pmc-id: PMC10335940;,2023 Jul,2023,https://pubmed.ncbi.nlm.nih.gov/37386251/,Noncoding variants alter GATA2 expression in rhombomere 4 motor neurons and cause dominant hereditary congenital facial paresis,55,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder affecting tissues of mesenchymal origin. Most individuals with HGPS harbor a de novo c.1824C > T (p.G608G) mutation in the gene encoding lamin A (LMNA), which activates a cryptic splice donor site resulting in production of the toxic ""progerin"" protein. Clinical manifestations include growth deficiency, lipodystrophy, sclerotic dermis, cardiovascular defects, and bone dysplasia. Here we utilized the LmnaG609G knock-in (KI) mouse model of HGPS to further define mechanisms of bone loss associated with normal and premature aging disorders. Newborn skeletal staining of KI mice revealed altered rib cage shape and spinal curvature, and delayed calvarial mineralization with increased craniofacial and mandibular cartilage content. MicroCT analysis and mechanical testing of adult femurs indicated increased fragility associated with reduced bone mass, recapitulating the progressive bone deterioration that occurs in HGPS patients. We investigated mechanisms of bone loss in KI mice at the cellular level in bone cell populations. Formation of wild-type and KI osteoclasts from marrow-derived precursors was inhibited by KI osteoblast-conditioned media in vitro, suggesting a secreted factor(s) responsible for decreased osteoclasts on KI trabecular surfaces in vivo. Cultured KI osteoblasts exhibited abnormal differentiation characterized by reduced deposition and mineralization of extracellular matrix with increased lipid accumulation compared to wild-type, providing a mechanism for altered bone formation. Furthermore, quantitative analyses of KI transcripts confirmed upregulation of adipogenic genes both in vitro and in vivo. Thus, osteoblast phenotypic plasticity, inflammation and altered cellular cross-talk contribute to abnormal bone formation in HGPS mice.","[""Journal Article"", ""Research Support, Non-U.S. Gov't"", ""Research Support, N.I.H., Extramural"", ""Research Support, N.I.H., Intramural""]","[""Cabral WA"", ""Stephan C"", ""Terajima M"", ""Thaivalappil AA"", ""Blanchard O"", ""Tavarez UL"", ""Narisu N"", ""Yan T"", ""Wincovitch SM"", ""Taga Y"", ""Yamauchi M"", ""Kozloff KM"", ""Erdos MR"", ""Collins FS""]",10.1111/acel.13903,Cabral WA,Aging cell,1474-9718,9,Aging Cell,eng,Collins FS,"[""Mice"", ""Animals"", ""Progeria"", ""Aging, Premature"", ""Mutation"", ""Lamin Type A"", ""Cell Differentiation"", ""Bone Diseases, Developmental""]",e13903,37365004,pmc-id: PMC10497813;,2023 Sep,2023,https://pubmed.ncbi.nlm.nih.gov/37365004/,Bone dysplasia in Hutchinson-Gilford progeria syndrome is associated with dysregulated differentiation and function of bone cell populations,22,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Disruption of pancreatic islet function and glucose homeostasis can lead to the development of sustained hyperglycemia, beta cell glucotoxicity, and ultimately type 2 diabetes (T2D). In this study, we sought to explore the effects of hyperglycemia on human pancreatic islet (HPI) gene expression by exposing HPIs from two donors to low (2.8mM) and high (15.0mM) glucose concentrations over 24 hours, assaying the transcriptome at seven time points using single-cell RNA sequencing (scRNA-seq). We modeled time as both a discrete and continuous variable to determine momentary and longitudinal changes in transcription associated with islet time in culture or glucose exposure. Across all cell types, we identified 1,528 genes associated with time, 1,185 genes associated with glucose exposure, and 845 genes associated with interaction effects between time and glucose. We clustered differentially expressed genes across cell types and found 347 modules of genes with similar expression patterns across time and glucose conditions, including two beta cell modules enriched in genes associated with T2D. Finally, by integrating genomic features from this study and genetic summary statistics for T2D and related traits, we nominate 363 candidate effector genes that may underlie genetic associations for T2D and related traits.","[""Preprint"", ""Journal Article""]","[""Grenko CM"", ""Bonnycastle LL"", ""Taylor HJ"", ""Yan T"", ""Swift AJ"", ""Robertson CC"", ""Narisu N"", ""Erdos MR"", ""Collins FS"", ""Taylor DL""]",10.1101/2023.06.06.543931,Grenko CM,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Taylor DL,[],,37333221,pmc-id: PMC10274787;,2023 Jul 17,2023,https://pubmed.ncbi.nlm.nih.gov/37333221/,Single-cell transcriptomic profiling of human pancreatic islets reveals genes responsive to glucose exposure over 24 hours,,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Williamson A"", ""Norris DM"", ""Yin X"", ""Broadaway KA"", ""Moxley AH"", ""Vadlamudi S"", ""Wilson EP"", ""Jackson AU"", ""Ahuja V"", ""Andersen MK"", ""Arzumanyan Z"", ""Bonnycastle LL"", ""Bornstein SR"", ""Bretschneider MP"", ""Buchanan TA"", ""Chang YC"", ""Chuang LM"", ""Chung RH"", ""Clausen TD"", ""Damm P"", ""Delgado GE"", ""de Mello VD"", ""Dupuis J"", ""Dwivedi OP"", ""Erdos MR"", ""Fernandes Silva L"", ""Frayling TM"", ""Gieger C"", ""Goodarzi MO"", ""Guo X"", ""Gustafsson S"", ""Hakaste L"", ""Hammar U"", ""Hatem G"", ""Herrmann S"", ""Højlund K"", ""Horn K"", ""Hsueh WA"", ""Hung YJ"", ""Hwu CM"", ""Jonsson A"", ""Kårhus LL"", ""Kleber ME"", ""Kovacs P"", ""Lakka TA"", ""Lauzon M"", ""Lee IT"", ""Lindgren CM"", ""Lindström J"", ""Linneberg A"", ""Liu CT"", ""Luan J"", ""Aly DM"", ""Mathiesen E"", ""Moissl AP"", ""Morris AP"", ""Narisu N"", ""Perakakis N"", ""Peters A"", ""Prasad RB"", ""Rodionov RN"", ""Roll K"", ""Rundsten CF"", ""Sarnowski C"", ""Savonen K"", ""Scholz M"", ""Sharma S"", ""Stinson SE"", ""Suleman S"", ""Tan J"", ""Taylor KD"", ""Uusitupa M"", ""Vistisen D"", ""Witte DR"", ""Walther R"", ""Wu P"", ""Xiang AH"", ""Zethelius B"", ""Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC)"", ""Ahlqvist E"", ""Bergman RN"", ""Chen YI"", ""Collins FS"", ""Fall T"", ""Florez JC"", ""Fritsche A"", ""Grallert H"", ""Groop L"", ""Hansen T"", ""Koistinen HA"", ""Komulainen P"", ""Laakso M"", ""Lind L"", ""Loeffler M"", ""März W"", ""Meigs JB"", ""Raffel LJ"", ""Rauramaa R"", ""Rotter JI"", ""Schwarz PEH"", ""Stumvoll M"", ""Sundström J"", ""Tönjes A"", ""Tuomi T"", ""Tuomilehto J"", ""Wagner R"", ""Barroso I"", ""Walker M"", ""Grarup N"", ""Boehnke M"", ""Wareham NJ"", ""Mohlke KL"", ""Wheeler E"", ""O'Rahilly S"", ""Fazakerley DJ"", ""Langenberg C""]",10.1038/s41588-023-01408-9,Williamson A,Nature genetics,1061-4036,6,Nat Genet,eng,Langenberg C,"[""Humans"", ""Insulin"", ""Genome-Wide Association Study"", ""Insulin Resistance"", ""Diabetes Mellitus, Type 2"", ""Glucose"", ""Blood Glucose""]",973-983,37291194,pmc-id: PMC7614755;manuscript-id: EMS178611;,2023 Jun,2023,https://pubmed.ncbi.nlm.nih.gov/37291194/,Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake,55,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Genetic studies have identified numerous loci associated with type 2 diabetes (T2D), but the functional role of many loci has remained unexplored. In this study, we engineered isogenic knockout human embryonic stem cell (hESC) lines for 20 genes associated with T2D risk. We systematically examined β-cell differentiation, insulin production and secretion, and survival. We performed RNA-seq and ATAC-seq on hESC-β cells from each knockout line. Analyses of T2D GWAS signals overlapping with HNF4A-dependent ATAC peaks identified a specific SNP as a likely causal variant. In addition, we performed integrative association analyses and identified four genes ( CP, RNASE1, PCSK1N and GSTA2 ) associated with insulin production, and two genes ( TAGLN3 and DHRS2 ) associated with sensitivity to lipotoxicity. Finally, we leveraged deep ATAC-seq read coverage to assess allele-specific imbalance at variants heterozygous in the parental hESC line, to identify a single likely functional variant at each of 23 T2D GWAS signals.","[""Preprint"", ""Journal Article""]","[""Xue D"", ""Narisu N"", ""Taylor DL"", ""Zhang M"", ""Grenko C"", ""Taylor HJ"", ""Yan T"", ""Tang X"", ""Sinha N"", ""Zhu J"", ""Vandana JJ"", ""Chong ACN"", ""Lee A"", ""Mansell EC"", ""Swift AJ"", ""Erdos MR"", ""Zhou T"", ""Bonnycastle LL"", ""Zhong A"", ""Chen S"", ""Collins FS""]",10.1101/2023.05.07.539774,Xue D,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Collins FS,[],,37214922,pmc-id: PMC10197532;,2023 May 8,2023,https://pubmed.ncbi.nlm.nih.gov/37214922/,Functional interrogation of twenty type 2 diabetes-associated genes using isogenic hESC-derived β-like cells,,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes. To characterise the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study (GWAS) data from 2,535,601 individuals (39.7% non-European ancestry), including 428,452 T2D cases. We identify 1,289 independent association signals at genome-wide significance (P<5×10-8) that map to 611 loci, of which 145 loci are previously unreported. We define eight non-overlapping clusters of T2D signals characterised by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial, and enteroendocrine cells. We build cluster-specific partitioned genetic risk scores (GRS) in an additional 137,559 individuals of diverse ancestry, including 10,159 T2D cases, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned GRS are more strongly associated with coronary artery disease and end-stage diabetic nephropathy than an overall T2D GRS across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings demonstrate the value of integrating multi-ancestry GWAS with single-cell epigenomics to disentangle the aetiological heterogeneity driving the development and progression of T2D, which may offer a route to optimise global access to genetically-informed diabetes care.","[""Preprint"", ""Journal Article""]","[""Suzuki K"", ""Hatzikotoulas K"", ""Southam L"", ""Taylor HJ"", ""Yin X"", ""Lorenz KM"", ""Mandla R"", ""Huerta-Chagoya A"", ""Rayner NW"", ""Bocher O"", ""Arruda ALSV"", ""Sonehara K"", ""Namba S"", ""Lee SSK"", ""Preuss MH"", ""Petty LE"", ""Schroeder P"", ""Vanderwerff B"", ""Kals M"", ""Bragg F"", ""Lin K"", ""Guo X"", ""Zhang W"", ""Yao J"", ""Kim YJ"", ""Graff M"", ""Takeuchi F"", ""Nano J"", ""Lamri A"", ""Nakatochi M"", ""Moon S"", ""Scott RA"", ""Cook JP"", ""Lee JJ"", ""Pan I"", ""Taliun D"", ""Parra EJ"", ""Chai JF"", ""Bielak LF"", ""Tabara Y"", ""Hai Y"", ""Thorleifsson G"", ""Grarup N"", ""Sofer T"", ""Wuttke M"", ""Sarnowski C"", ""Gieger C"", ""Nousome D"", ""Trompet S"", ""Kwak SH"", ""Long J"", ""Sun M"", ""Tong L"", ""Chen WM"", ""Nongmaithem SS"", ""Noordam R"", ""Lim VJY"", ""Tam CHT"", ""Joo YY"", ""Chen CH"", ""Raffield LM"", ""Prins BP"", ""Nicolas A"", ""Yanek LR"", ""Chen G"", ""Brody JA"", ""Kabagambe E"", ""An P"", ""Xiang AH"", ""Choi HS"", ""Cade BE"", ""Tan J"", ""Broadaway KA"", ""Williamson A"", ""Kamali Z"", ""Cui J"", ""Adair LS"", ""Adeyemo A"", ""Aguilar-Salinas CA"", ""Ahluwalia TS"", ""Anand SS"", ""Bertoni A"", ""Bork-Jensen J"", ""Brandslund I"", ""Buchanan TA"", ""Burant CF"", ""Butterworth AS"", ""Canouil M"", ""Chan JCN"", ""Chang LC"", ""Chee ML"", ""Chen J"", ""Chen SH"", ""Chen YT"", ""Chen Z"", ""Chuang LM"", ""Cushman M"", ""Danesh J"", ""Das SK"", ""de Silva HJ"", ""Dedoussis G"", ""Dimitrov L"", ""Doumatey AP"", ""Du S"", ""Duan Q"", ""Eckardt KU"", ""Emery LS"", ""Evans DS"", ""Evans MK"", ""Fischer K"", ""Floyd JS"", ""Ford I"", ""Franco OH"", ""Frayling TM"", ""Freedman BI"", ""Genter P"", ""Gerstein HC"", ""Giedraitis V"", ""González-Villalpando C"", ""González-Villalpando ME"", ""Gordon-Larsen P"", ""Gross M"", ""Guare LA"", ""Hackinger S"", ""Han S"", ""Hattersley AT"", ""Herder C"", ""Horikoshi M"", ""Howard AG"", ""Hsueh W"", ""Huang M"", ""Huang W"", ""Hung YJ"", ""Hwang MY"", ""Hwu CM"", ""Ichihara S"", ""Ikram MA"", ""Ingelsson M"", ""Islam MT"", ""Isono M"", ""Jang HM"", ""Jasmine F"", ""Jiang G"", ""Jonas JB"", ""Jørgensen T"", ""Kandeel FR"", ""Kasturiratne A"", ""Katsuya T"", ""Kaur V"", ""Kawaguchi T"", ""Keaton JM"", ""Kho AN"", ""Khor CC"", ""Kibriya MG"", ""Kim DH"", ""Kronenberg F"", ""Kuusisto J"", ""Läll K"", ""Lange LA"", ""Lee KM"", ""Lee MS"", ""Lee NR"", ""Leong A"", ""Li L"", ""Li Y"", ""Li-Gao R"", ""Lithgart S"", ""Lindgren CM"", ""Linneberg A"", ""Liu CT"", ""Liu J"", ""Locke AE"", ""Louie T"", ""Luan J"", ""Luk AO"", ""Luo X"", ""Lv J"", ""Lynch JA"", ""Lyssenko V"", ""Maeda S"", ""Mamakou V"", ""Mansuri SR"", ""Matsuda K"", ""Meitinger T"", ""Metspalu A"", ""Mo H"", ""Morris AD"", ""Nadler JL"", ""Nalls MA"", ""Nayak U"", ""Ntalla I"", ""Okada Y"", ""Orozco L"", ""Patel SR"", ""Patil S"", ""Pei P"", ""Pereira MA"", ""Peters A"", ""Pirie FJ"", ""Polikowsky HG"", ""Porneala B"", ""Prasad G"", ""Rasmussen-Torvik LJ"", ""Reiner AP"", ""Roden M"", ""Rohde R"", ""Roll K"", ""Sabanayagam C"", ""Sandow K"", ""Sankareswaran A"", ""Sattar N"", ""Schönherr S"", ""Shahriar M"", ""Shen B"", ""Shi J"", ""Shin DM"", ""Shojima N"", ""Smith JA"", ""So WY"", ""Stančáková A"", ""Steinthorsdottir V"", ""Stilp AM"", ""Strauch K"", ""Taylor KD"", ""Thorand B"", ""Thorsteinsdottir U"", ""Tomlinson B"", ""Tran TC"", ""Tsai FJ"", ""Tuomilehto J"", ""Tusie-Luna T"", ""Udler MS"", ""Valladares-Salgado A"", ""van Dam RM"", ""van Klinken JB"", ""Varma R"", ""Wacher-Rodarte N"", ""Wheeler E"", ""Wickremasinghe AR"", ""van Dijk KW"", ""Witte DR"", ""Yajnik CS"", ""Yamamoto K"", ""Yamamoto K"", ""Yoon K"", ""Yu C"", ""Yuan JM"", ""Yusuf S"", ""Zawistowski M"", ""Zhang L"", ""Zheng W"", ""VA Million Veteran Program"", ""AMED GRIFIN Diabetes Initiative Japan"", ""Biobank Japan Project"", ""Penn Medicine BioBank"", ""Regeneron Genetics Center"", ""eMERGE Consortium"", ""International Consortium for Blood Pressure (ICBP)"", ""Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC)"", ""Raffel LJ"", ""Igase M"", ""Ipp E"", ""Redline S"", ""Cho YS"", ""Lind L"", ""Province MA"", ""Fornage M"", ""Hanis CL"", ""Ingelsson E"", ""Zonderman AB"", ""Psaty BM"", ""Wang YX"", ""Rotimi CN"", ""Becker DM"", ""Matsuda F"", ""Liu Y"", ""Yokota M"", ""Kardia SLR"", ""Peyser PA"", ""Pankow JS"", ""Engert JC"", ""Bonnefond A"", ""Froguel P"", ""Wilson JG"", ""Sheu WHH"", ""Wu JY"", ""Hayes MG"", ""Ma RCW"", ""Wong TY"", ""Mook-Kanamori DO"", ""Tuomi T"", ""Chandak GR"", ""Collins FS"", ""Bharadwaj D"", ""Paré G"", ""Sale MM"", ""Ahsan H"", ""Motala AA"", ""Shu XO"", ""Park KS"", ""Jukema JW"", ""Cruz M"", ""Chen YI"", ""Rich SS"", ""McKean-Cowdin R"", ""Grallert H"", ""Cheng CY"", ""Ghanbari M"", ""Tai ES"", ""Dupuis J"", ""Kato N"", ""Laakso M"", ""Köttgen A"", ""Koh WP"", ""Bowden DW"", ""Palmer CNA"", ""Kooner JS"", ""Kooperberg C"", ""Liu S"", ""North KE"", ""Saleheen D"", ""Hansen T"", ""Pedersen O"", ""Wareham NJ"", ""Lee J"", ""Kim BJ"", ""Millwood IY"", ""Walters RG"", ""Stefansson K"", ""Goodarzi MO"", ""Mohlke KL"", ""Langenberg C"", ""Haiman CA"", ""Loos RJF"", ""Florez JC"", ""Rader DJ"", ""Ritchie MD"", ""Zöllner S"", ""Mägi R"", ""Denny JC"", ""Yamauchi T"", ""Kadowaki T"", ""Chambers JC"", ""Ng MCY"", ""Sim X"", ""Below JE"", ""Tsao PS"", ""Chang KM"", ""McCarthy MI"", ""Meigs JB"", ""Mahajan A"", ""Spracklen CN"", ""Mercader JM"", ""Boehnke M"", ""Rotter JI"", ""Vujkovic M"", ""Voight BF"", ""Morris AP"", ""Zeggini E""]",10.1101/2023.03.31.23287839,Suzuki K,medRxiv : the preprint server for health sciences,,,medRxiv,eng,Zeggini E,[],,37034649,pmc-id: PMC10081410;,2023 Mar 31,2023,https://pubmed.ncbi.nlm.nih.gov/37034649/,Multi-ancestry genome-wide study in >2.5 million individuals reveals heterogeneity in mechanistic pathways of type 2 diabetes and complications,,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
,"[""Journal Article""]","[""Fleurence RL"", ""Collins FS""]",10.1001/jama.2023.3692,Fleurence RL,JAMA,0098-7484,15,JAMA,eng,Collins FS,"[""Humans"", ""Antiviral Agents"", ""Hepacivirus"", ""Hepatitis C"", ""Hepatitis C, Chronic"", ""United States"", ""Disease Eradication""]",1251-1252,36892976,,2023 Apr 18,2023,https://pubmed.ncbi.nlm.nih.gov/36892976/,A National Hepatitis C Elimination Program in the United States: A Historic Opportunity,329,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Genetic studies have identified ≥240 loci associated with the risk of type 2 diabetes (T2D), yet most of these loci lie in non-coding regions, masking the underlying molecular mechanisms. Recent studies investigating mRNA expression in human pancreatic islets have yielded important insights into the molecular drivers of normal islet function and T2D pathophysiology. However, similar studies investigating microRNA (miRNA) expression remain limited. Here, we present data from 63 individuals, the largest sequencing-based analysis of miRNA expression in human islets to date. We characterized the genetic regulation of miRNA expression by decomposing the expression of highly heritable miRNAs into cis- and trans-acting genetic components and mapping cis-acting loci associated with miRNA expression [miRNA-expression quantitative trait loci (eQTLs)]. We found i) 84 heritable miRNAs, primarily regulated by trans-acting genetic effects, and ii) 5 miRNA-eQTLs. We also used several different strategies to identify T2D-associated miRNAs. First, we colocalized miRNA-eQTLs with genetic loci associated with T2D and multiple glycemic traits, identifying one miRNA, miR-1908, that shares genetic signals for blood glucose and glycated hemoglobin (HbA1c). Next, we intersected miRNA seed regions and predicted target sites with credible set SNPs associated with T2D and glycemic traits and found 32 miRNAs that may have altered binding and function due to disrupted seed regions. Finally, we performed differential expression analysis and identified 14 miRNAs associated with T2D status-including miR-187-3p, miR-21-5p, miR-668, and miR-199b-5p-and 4 miRNAs associated with a polygenic score for HbA1c levels-miR-216a, miR-25, miR-30a-3p, and miR-30a-5p.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Taylor HJ"", ""Hung YH"", ""Narisu N"", ""Erdos MR"", ""Kanke M"", ""Yan T"", ""Grenko CM"", ""Swift AJ"", ""Bonnycastle LL"", ""Sethupathy P"", ""Collins FS"", ""Taylor DL""]",10.1073/pnas.2206797120,Taylor HJ,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,7,Proc Natl Acad Sci U S A,eng,Taylor DL,"[""Humans"", ""MicroRNAs"", ""Diabetes Mellitus, Type 2"", ""Glycated Hemoglobin"", ""Islets of Langerhans"", ""Quantitative Trait Loci""]",e2206797120,36757889,pmc-id: PMC9963967;,2023 Feb 14,2023,https://pubmed.ncbi.nlm.nih.gov/36757889/,Human pancreatic islet microRNAs implicated in diabetes and related traits by large-scale genetic analysis,120,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Music-based interventions (MBIs) show promise for managing symptoms of various brain disorders. To fully realize the potential of MBIs and dispel the outdated misconception that MBIs are rooted in soft science, the NIH is promoting rigorously designed, well-powered MBI clinical trials. The pressing need of guidelines for scientifically rigorous studies with enhanced data collection brought together the Renée Fleming Foundation, the Foundation for the NIH, the Trans-NIH Music and Health Working Group, and an interdisciplinary scientific expert panel to create the NIH MBI Toolkit for research on music and health across the lifespan. The Toolkit defines the building blocks of MBIs, including a consolidated set of common data elements for MBI protocols, and core datasets of outcome measures and biomarkers for brain disorders of aging that researchers may select for their studies. Utilization of the guiding principles in this Toolkit will be strongly recommended for NIH-funded studies of MBIs.","[""Journal Article""]","[""Edwards E"", ""St Hillaire-Clarke C"", ""Frankowski DW"", ""Finkelstein R"", ""Cheever T"", ""Chen WG"", ""Onken L"", ""Poremba A"", ""Riddle R"", ""Schloesser D"", ""Burgdorf CE"", ""Wells N"", ""Fleming R"", ""Collins FS""]",10.1212/WNL.0000000000206797,Edwards E,Neurology,0028-3878,18,Neurology,eng,Collins FS,"[""Humans"", ""Music"", ""Mindfulness"", ""Brain Diseases"", ""Data Collection"", ""Aging""]",868-878,36639235,pmc-id: PMC10159759;,2023 May 2,2023,https://pubmed.ncbi.nlm.nih.gov/36639235/,NIH Music-Based Intervention Toolkit: Music-Based Interventions for Brain Disorders of Aging,100,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Yengo L"", ""Vedantam S"", ""Marouli E"", ""Sidorenko J"", ""Bartell E"", ""Sakaue S"", ""Graff M"", ""Eliasen AU"", ""Jiang Y"", ""Raghavan S"", ""Miao J"", ""Arias JD"", ""Graham SE"", ""Mukamel RE"", ""Spracklen CN"", ""Yin X"", ""Chen SH"", ""Ferreira T"", ""Highland HH"", ""Ji Y"", ""Karaderi T"", ""Lin K"", ""Lüll K"", ""Malden DE"", ""Medina-Gomez C"", ""Machado M"", ""Moore A"", ""Rüeger S"", ""Sim X"", ""Vrieze S"", ""Ahluwalia TS"", ""Akiyama M"", ""Allison MA"", ""Alvarez M"", ""Andersen MK"", ""Ani A"", ""Appadurai V"", ""Arbeeva L"", ""Bhaskar S"", ""Bielak LF"", ""Bollepalli S"", ""Bonnycastle LL"", ""Bork-Jensen J"", ""Bradfield JP"", ""Bradford Y"", ""Braund PS"", ""Brody JA"", ""Burgdorf KS"", ""Cade BE"", ""Cai H"", ""Cai Q"", ""Campbell A"", ""Cañadas-Garre M"", ""Catamo E"", ""Chai JF"", ""Chai X"", ""Chang LC"", ""Chang YC"", ""Chen CH"", ""Chesi A"", ""Choi SH"", ""Chung RH"", ""Cocca M"", ""Concas MP"", ""Couture C"", ""Cuellar-Partida G"", ""Danning R"", ""Daw EW"", ""Degenhard F"", ""Delgado GE"", ""Delitala A"", ""Demirkan A"", ""Deng X"", ""Devineni P"", ""Dietl A"", ""Dimitriou M"", ""Dimitrov L"", ""Dorajoo R"", ""Ekici AB"", ""Engmann JE"", ""Fairhurst-Hunter Z"", ""Farmaki AE"", ""Faul JD"", ""Fernandez-Lopez JC"", ""Forer L"", ""Francescatto M"", ""Freitag-Wolf S"", ""Fuchsberger C"", ""Galesloot TE"", ""Gao Y"", ""Gao Z"", ""Geller F"", ""Giannakopoulou O"", ""Giulianini F"", ""Gjesing AP"", ""Goel A"", ""Gordon SD"", ""Gorski M"", ""Grove J"", ""Guo X"", ""Gustafsson S"", ""Haessler J"", ""Hansen TF"", ""Havulinna AS"", ""Haworth SJ"", ""He J"", ""Heard-Costa N"", ""Hebbar P"", ""Hindy G"", ""Ho YA"", ""Hofer E"", ""Holliday E"", ""Horn K"", ""Hornsby WE"", ""Hottenga JJ"", ""Huang H"", ""Huang J"", ""Huerta-Chagoya A"", ""Huffman JE"", ""Hung YJ"", ""Huo S"", ""Hwang MY"", ""Iha H"", ""Ikeda DD"", ""Isono M"", ""Jackson AU"", ""Jäger S"", ""Jansen IE"", ""Johansson I"", ""Jonas JB"", ""Jonsson A"", ""Jørgensen T"", ""Kalafati IP"", ""Kanai M"", ""Kanoni S"", ""Kårhus LL"", ""Kasturiratne A"", ""Katsuya T"", ""Kawaguchi T"", ""Kember RL"", ""Kentistou KA"", ""Kim HN"", ""Kim YJ"", ""Kleber ME"", ""Knol MJ"", ""Kurbasic A"", ""Lauzon M"", ""Le P"", ""Lea R"", ""Lee JY"", ""Leonard HL"", ""Li SA"", ""Li X"", ""Li X"", ""Liang J"", ""Lin H"", ""Lin SY"", ""Liu J"", ""Liu X"", ""Lo KS"", ""Long J"", ""Lores-Motta L"", ""Luan J"", ""Lyssenko V"", ""Lyytikäinen LP"", ""Mahajan A"", ""Mamakou V"", ""Mangino M"", ""Manichaikul A"", ""Marten J"", ""Mattheisen M"", ""Mavarani L"", ""McDaid AF"", ""Meidtner K"", ""Melendez TL"", ""Mercader JM"", ""Milaneschi Y"", ""Miller JE"", ""Millwood IY"", ""Mishra PP"", ""Mitchell RE"", ""Møllehave LT"", ""Morgan A"", ""Mucha S"", ""Munz M"", ""Nakatochi M"", ""Nelson CP"", ""Nethander M"", ""Nho CW"", ""Nielsen AA"", ""Nolte IM"", ""Nongmaithem SS"", ""Noordam R"", ""Ntalla I"", ""Nutile T"", ""Pandit A"", ""Christofidou P"", ""Pärna K"", ""Pauper M"", ""Petersen ERB"", ""Petersen LV"", ""Pitkänen N"", ""Polašek O"", ""Poveda A"", ""Preuss MH"", ""Pyarajan S"", ""Raffield LM"", ""Rakugi H"", ""Ramirez J"", ""Rasheed A"", ""Raven D"", ""Rayner NW"", ""Riveros C"", ""Rohde R"", ""Ruggiero D"", ""Ruotsalainen SE"", ""Ryan KA"", ""Sabater-Lleal M"", ""Saxena R"", ""Scholz M"", ""Sendamarai A"", ""Shen B"", ""Shi J"", ""Shin JH"", ""Sidore C"", ""Sitlani CM"", ""Slieker RC"", ""Smit RAJ"", ""Smith AV"", ""Smith JA"", ""Smyth LJ"", ""Southam L"", ""Steinthorsdottir V"", ""Sun L"", ""Takeuchi F"", ""Tallapragada DSP"", ""Taylor KD"", ""Tayo BO"", ""Tcheandjieu C"", ""Terzikhan N"", ""Tesolin P"", ""Teumer A"", ""Theusch E"", ""Thompson DJ"", ""Thorleifsson G"", ""Timmers PRHJ"", ""Trompet S"", ""Turman C"", ""Vaccargiu S"", ""van der Laan SW"", ""van der Most PJ"", ""van Klinken JB"", ""van Setten J"", ""Verma SS"", ""Verweij N"", ""Veturi Y"", ""Wang CA"", ""Wang C"", ""Wang L"", ""Wang Z"", ""Warren HR"", ""Bin Wei W"", ""Wickremasinghe AR"", ""Wielscher M"", ""Wiggins KL"", ""Winsvold BS"", ""Wong A"", ""Wu Y"", ""Wuttke M"", ""Xia R"", ""Xie T"", ""Yamamoto K"", ""Yang J"", ""Yao J"", ""Young H"", ""Yousri NA"", ""Yu L"", ""Zeng L"", ""Zhang W"", ""Zhang X"", ""Zhao JH"", ""Zhao W"", ""Zhou W"", ""Zimmermann ME"", ""Zoledziewska M"", ""Adair LS"", ""Adams HHH"", ""Aguilar-Salinas CA"", ""Al-Mulla F"", ""Arnett DK"", ""Asselbergs FW"", ""Åsvold BO"", ""Attia J"", ""Banas B"", ""Bandinelli S"", ""Bennett DA"", ""Bergler T"", ""Bharadwaj D"", ""Biino G"", ""Bisgaard H"", ""Boerwinkle E"", ""Böger CA"", ""Bønnelykke K"", ""Boomsma DI"", ""Børglum AD"", ""Borja JB"", ""Bouchard C"", ""Bowden DW"", ""Brandslund I"", ""Brumpton B"", ""Buring JE"", ""Caulfield MJ"", ""Chambers JC"", ""Chandak GR"", ""Chanock SJ"", ""Chaturvedi N"", ""Chen YI"", ""Chen Z"", ""Cheng CY"", ""Christophersen IE"", ""Ciullo M"", ""Cole JW"", ""Collins FS"", ""Cooper RS"", ""Cruz M"", ""Cucca F"", ""Cupples LA"", ""Cutler MJ"", ""Damrauer SM"", ""Dantoft TM"", ""de Borst GJ"", ""de Groot LCPGM"", ""De Jager PL"", ""de Kleijn DPV"", ""Janaka de Silva H"", ""Dedoussis GV"", ""den Hollander AI"", ""Du S"", ""Easton DF"", ""Elders PJM"", ""Eliassen AH"", ""Ellinor PT"", ""Elmståhl S"", ""Erdmann J"", ""Evans MK"", ""Fatkin D"", ""Feenstra B"", ""Feitosa MF"", ""Ferrucci L"", ""Ford I"", ""Fornage M"", ""Franke A"", ""Franks PW"", ""Freedman BI"", ""Gasparini P"", ""Gieger C"", ""Girotto G"", ""Goddard ME"", ""Golightly YM"", ""Gonzalez-Villalpando C"", ""Gordon-Larsen P"", ""Grallert H"", ""Grant SFA"", ""Grarup N"", ""Griffiths L"", ""Gudnason V"", ""Haiman C"", ""Hakonarson H"", ""Hansen T"", ""Hartman CA"", ""Hattersley AT"", ""Hayward C"", ""Heckbert SR"", ""Heng CK"", ""Hengstenberg C"", ""Hewitt AW"", ""Hishigaki H"", ""Hoyng CB"", ""Huang PL"", ""Huang W"", ""Hunt SC"", ""Hveem K"", ""Hyppönen E"", ""Iacono WG"", ""Ichihara S"", ""Ikram MA"", ""Isasi CR"", ""Jackson RD"", ""Jarvelin MR"", ""Jin ZB"", ""Jöckel KH"", ""Joshi PK"", ""Jousilahti P"", ""Jukema JW"", ""Kähönen M"", ""Kamatani Y"", ""Kang KD"", ""Kaprio J"", ""Kardia SLR"", ""Karpe F"", ""Kato N"", ""Kee F"", ""Kessler T"", ""Khera AV"", ""Khor CC"", ""Kiemeney LALM"", ""Kim BJ"", ""Kim EK"", ""Kim HL"", ""Kirchhof P"", ""Kivimaki M"", ""Koh WP"", ""Koistinen HA"", ""Kolovou GD"", ""Kooner JS"", ""Kooperberg C"", ""Köttgen A"", ""Kovacs P"", ""Kraaijeveld A"", ""Kraft P"", ""Krauss RM"", ""Kumari M"", ""Kutalik Z"", ""Laakso M"", ""Lange LA"", ""Langenberg C"", ""Launer LJ"", ""Le Marchand L"", ""Lee H"", ""Lee NR"", ""Lehtimäki T"", ""Li H"", ""Li L"", ""Lieb W"", ""Lin X"", ""Lind L"", ""Linneberg A"", ""Liu CT"", ""Liu J"", ""Loeffler M"", ""London B"", ""Lubitz SA"", ""Lye SJ"", ""Mackey DA"", ""Mägi R"", ""Magnusson PKE"", ""Marcus GM"", ""Vidal PM"", ""Martin NG"", ""März W"", ""Matsuda F"", ""McGarrah RW"", ""McGue M"", ""McKnight AJ"", ""Medland SE"", ""Mellström D"", ""Metspalu A"", ""Mitchell BD"", ""Mitchell P"", ""Mook-Kanamori DO"", ""Morris AD"", ""Mucci LA"", ""Munroe PB"", ""Nalls MA"", ""Nazarian S"", ""Nelson AE"", ""Neville MJ"", ""Newton-Cheh C"", ""Nielsen CS"", ""Nöthen MM"", ""Ohlsson C"", ""Oldehinkel AJ"", ""Orozco L"", ""Pahkala K"", ""Pajukanta P"", ""Palmer CNA"", ""Parra EJ"", ""Pattaro C"", ""Pedersen O"", ""Pennell CE"", ""Penninx BWJH"", ""Perusse L"", ""Peters A"", ""Peyser PA"", ""Porteous DJ"", ""Posthuma D"", ""Power C"", ""Pramstaller PP"", ""Province MA"", ""Qi Q"", ""Qu J"", ""Rader DJ"", ""Raitakari OT"", ""Ralhan S"", ""Rallidis LS"", ""Rao DC"", ""Redline S"", ""Reilly DF"", ""Reiner AP"", ""Rhee SY"", ""Ridker PM"", ""Rienstra M"", ""Ripatti S"", ""Ritchie MD"", ""Roden DM"", ""Rosendaal FR"", ""Rotter JI"", ""Rudan I"", ""Rutters F"", ""Sabanayagam C"", ""Saleheen D"", ""Salomaa V"", ""Samani NJ"", ""Sanghera DK"", ""Sattar N"", ""Schmidt B"", ""Schmidt H"", ""Schmidt R"", ""Schulze MB"", ""Schunkert H"", ""Scott LJ"", ""Scott RJ"", ""Sever P"", ""Shiroma EJ"", ""Shoemaker MB"", ""Shu XO"", ""Simonsick EM"", ""Sims M"", ""Singh JR"", ""Singleton AB"", ""Sinner MF"", ""Smith JG"", ""Snieder H"", ""Spector TD"", ""Stampfer MJ"", ""Stark KJ"", ""Strachan DP"", ""'t Hart LM"", ""Tabara Y"", ""Tang H"", ""Tardif JC"", ""Thanaraj TA"", ""Timpson NJ"", ""Tönjes A"", ""Tremblay A"", ""Tuomi T"", ""Tuomilehto J"", ""Tusié-Luna MT"", ""Uitterlinden AG"", ""van Dam RM"", ""van der Harst P"", ""Van der Velde N"", ""van Duijn CM"", ""van Schoor NM"", ""Vitart V"", ""Völker U"", ""Vollenweider P"", ""Völzke H"", ""Wacher-Rodarte NH"", ""Walker M"", ""Wang YX"", ""Wareham NJ"", ""Watanabe RM"", ""Watkins H"", ""Weir DR"", ""Werge TM"", ""Widen E"", ""Wilkens LR"", ""Willemsen G"", ""Willett WC"", ""Wilson JF"", ""Wong TY"", ""Woo JT"", ""Wright AF"", ""Wu JY"", ""Xu H"", ""Yajnik CS"", ""Yokota M"", ""Yuan JM"", ""Zeggini E"", ""Zemel BS"", ""Zheng W"", ""Zhu X"", ""Zmuda JM"", ""Zonderman AB"", ""Zwart JA"", ""23andMe Research Team"", ""VA Million Veteran Program"", ""DiscovEHR (DiscovEHR and MyCode Community Health Initiative)"", ""eMERGE (Electronic Medical Records and Genomics Network)"", ""Lifelines Cohort Study"", ""PRACTICAL Consortium"", ""Understanding Society Scientific Group"", ""Chasman DI"", ""Cho YS"", ""Heid IM"", ""McCarthy MI"", ""Ng MCY"", ""O'Donnell CJ"", ""Rivadeneira F"", ""Thorsteinsdottir U"", ""Sun YV"", ""Tai ES"", ""Boehnke M"", ""Deloukas P"", ""Justice AE"", ""Lindgren CM"", ""Loos RJF"", ""Mohlke KL"", ""North KE"", ""Stefansson K"", ""Walters RG"", ""Winkler TW"", ""Young KL"", ""Loh PR"", ""Yang J"", ""Esko T"", ""Assimes TL"", ""Auton A"", ""Abecasis GR"", ""Willer CJ"", ""Locke AE"", ""Berndt SI"", ""Lettre G"", ""Frayling TM"", ""Okada Y"", ""Wood AR"", ""Visscher PM"", ""Hirschhorn JN""]",10.1038/s41586-022-05275-y,Yengo L,Nature,0028-0836,7933,Nature,eng,Hirschhorn JN,"[""Humans"", ""Body Height"", ""Gene Frequency"", ""Genome, Human"", ""Genome-Wide Association Study"", ""Haplotypes"", ""Linkage Disequilibrium"", ""Polymorphism, Single Nucleotide"", ""Europe"", ""Sample Size"", ""Phenotype"", ""Chromosome Mapping""]",704-712,36224396,pmc-id: PMC9605867;,2022 Oct,2022,https://pubmed.ncbi.nlm.nih.gov/36224396/,A saturated map of common genetic variants associated with human height,610,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.","[""Journal Article"", ""Meta-Analysis"", ""Research Support, Non-U.S. Gov't"", ""Research Support, U.S. Gov't, Non-P.H.S."", ""Research Support, N.I.H., Extramural""]","[""Wang Z"", ""Emmerich A"", ""Pillon NJ"", ""Moore T"", ""Hemerich D"", ""Cornelis MC"", ""Mazzaferro E"", ""Broos S"", ""Ahluwalia TS"", ""Bartz TM"", ""Bentley AR"", ""Bielak LF"", ""Chong M"", ""Chu AY"", ""Berry D"", ""Dorajoo R"", ""Dueker ND"", ""Kasbohm E"", ""Feenstra B"", ""Feitosa MF"", ""Gieger C"", ""Graff M"", ""Hall LM"", ""Haller T"", ""Hartwig FP"", ""Hillis DA"", ""Huikari V"", ""Heard-Costa N"", ""Holzapfel C"", ""Jackson AU"", ""Johansson Å"", ""Jørgensen AM"", ""Kaakinen MA"", ""Karlsson R"", ""Kerr KF"", ""Kim B"", ""Koolhaas CM"", ""Kutalik Z"", ""Lagou V"", ""Lind PA"", ""Lorentzon M"", ""Lyytikäinen LP"", ""Mangino M"", ""Metzendorf C"", ""Monroe KR"", ""Pacolet A"", ""Pérusse L"", ""Pool R"", ""Richmond RC"", ""Rivera NV"", ""Robiou-du-Pont S"", ""Schraut KE"", ""Schulz CA"", ""Stringham HM"", ""Tanaka T"", ""Teumer A"", ""Turman C"", ""van der Most PJ"", ""Vanmunster M"", ""van Rooij FJA"", ""van Vliet-Ostaptchouk JV"", ""Zhang X"", ""Zhao JH"", ""Zhao W"", ""Balkhiyarova Z"", ""Balslev-Harder MN"", ""Baumeister SE"", ""Beilby J"", ""Blangero J"", ""Boomsma DI"", ""Brage S"", ""Braund PS"", ""Brody JA"", ""Bruinenberg M"", ""Ekelund U"", ""Liu CT"", ""Cole JW"", ""Collins FS"", ""Cupples LA"", ""Esko T"", ""Enroth S"", ""Faul JD"", ""Fernandez-Rhodes L"", ""Fohner AE"", ""Franco OH"", ""Galesloot TE"", ""Gordon SD"", ""Grarup N"", ""Hartman CA"", ""Heiss G"", ""Hui J"", ""Illig T"", ""Jago R"", ""James A"", ""Joshi PK"", ""Jung T"", ""Kähönen M"", ""Kilpeläinen TO"", ""Koh WP"", ""Kolcic I"", ""Kraft PP"", ""Kuusisto J"", ""Launer LJ"", ""Li A"", ""Linneberg A"", ""Luan J"", ""Vidal PM"", ""Medland SE"", ""Milaneschi Y"", ""Moscati A"", ""Musk B"", ""Nelson CP"", ""Nolte IM"", ""Pedersen NL"", ""Peters A"", ""Peyser PA"", ""Power C"", ""Raitakari OT"", ""Reedik M"", ""Reiner AP"", ""Ridker PM"", ""Rudan I"", ""Ryan K"", ""Sarzynski MA"", ""Scott LJ"", ""Scott RA"", ""Sidney S"", ""Siggeirsdottir K"", ""Smith AV"", ""Smith JA"", ""Sonestedt E"", ""Strøm M"", ""Tai ES"", ""Teo KK"", ""Thorand B"", ""Tönjes A"", ""Tremblay A"", ""Uitterlinden AG"", ""Vangipurapu J"", ""van Schoor N"", ""Völker U"", ""Willemsen G"", ""Williams K"", ""Wong Q"", ""Xu H"", ""Young KL"", ""Yuan JM"", ""Zillikens MC"", ""Zonderman AB"", ""Ameur A"", ""Bandinelli S"", ""Bis JC"", ""Boehnke M"", ""Bouchard C"", ""Chasman DI"", ""Smith GD"", ""de Geus EJC"", ""Deldicque L"", ""Dörr M"", ""Evans MK"", ""Ferrucci L"", ""Fornage M"", ""Fox C"", ""Garland T Jr"", ""Gudnason V"", ""Gyllensten U"", ""Hansen T"", ""Hayward C"", ""Horta BL"", ""Hyppönen E"", ""Jarvelin MR"", ""Johnson WC"", ""Kardia SLR"", ""Kiemeney LA"", ""Laakso M"", ""Langenberg C"", ""Lehtimäki T"", ""Marchand LL"", ""Lifelines Cohort Study"", ""Magnusson PKE"", ""Martin NG"", ""Melbye M"", ""Metspalu A"", ""Meyre D"", ""North KE"", ""Ohlsson C"", ""Oldehinkel AJ"", ""Orho-Melander M"", ""Pare G"", ""Park T"", ""Pedersen O"", ""Penninx BWJH"", ""Pers TH"", ""Polasek O"", ""Prokopenko I"", ""Rotimi CN"", ""Samani NJ"", ""Sim X"", ""Snieder H"", ""Sørensen TIA"", ""Spector TD"", ""Timpson NJ"", ""van Dam RM"", ""van der Velde N"", ""van Duijn CM"", ""Vollenweider P"", ""Völzke H"", ""Voortman T"", ""Waeber G"", ""Wareham NJ"", ""Weir DR"", ""Wichmann HE"", ""Wilson JF"", ""Hevener AL"", ""Krook A"", ""Zierath JR"", ""Thomis MAI"", ""Loos RJF"", ""Hoed MD""]",10.1038/s41588-022-01165-1,Wang Z,Nature genetics,1061-4036,9,Nat Genet,eng,Hoed MD,"[""Actinin"", ""Cross-Sectional Studies"", ""Exercise"", ""Genome-Wide Association Study"", ""Humans"", ""Leisure Activities"", ""Sedentary Behavior""]",1332-1344,36071172,pmc-id: PMC9470530;,2022 Sep,2022,https://pubmed.ncbi.nlm.nih.gov/36071172/,Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention,54,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
"Transcriptomics data have been integrated with genome-wide association studies (GWASs) to help understand disease/trait molecular mechanisms. The utility of metabolomics, integrated with transcriptomics and disease GWASs, to understand molecular mechanisms for metabolite levels or diseases has not been thoroughly evaluated. We performed probabilistic transcriptome-wide association and locus-level colocalization analyses to integrate transcriptomics results for 49 tissues in 706 individuals from the GTEx project, metabolomics results for 1,391 plasma metabolites in 6,136 Finnish men from the METSIM study, and GWAS results for 2,861 disease traits in 260,405 Finnish individuals from the FinnGen study. We found that genetic variants that regulate metabolite levels were more likely to influence gene expression and disease risk compared to the ones that do not. Integrating transcriptomics with metabolomics results prioritized 397 genes for 521 metabolites, including 496 previously identified gene-metabolite pairs with strong functional connections and suggested 33.3% of such gene-metabolite pairs shared the same causal variants with genetic associations of gene expression. Integrating transcriptomics and metabolomics individually with FinnGen GWAS results identified 1,597 genes for 790 disease traits. Integrating transcriptomics and metabolomics jointly with FinnGen GWAS results helped pinpoint metabolic pathways from genes to diseases. We identified putative causal effects of UGT1A1/UGT1A4 expression on gallbladder disorders through regulating plasma (E,E)-bilirubin levels, of SLC22A5 expression on nasal polyps and plasma carnitine levels through distinct pathways, and of LIPC expression on age-related macular degeneration through glycerophospholipid metabolic pathways. Our study highlights the power of integrating multiple sets of molecular traits and GWAS results to deepen understanding of disease pathophysiology.","[""Journal Article"", ""Research Support, Non-U.S. Gov't"", ""Research Support, N.I.H., Extramural"", ""Research Support, N.I.H., Intramural""]","[""Yin X"", ""Bose D"", ""Kwon A"", ""Hanks SC"", ""Jackson AU"", ""Stringham HM"", ""Welch R"", ""Oravilahti A"", ""Fernandes Silva L"", ""FinnGen"", ""Locke AE"", ""Fuchsberger C"", ""Service SK"", ""Erdos MR"", ""Bonnycastle LL"", ""Kuusisto J"", ""Stitziel NO"", ""Hall IM"", ""Morrison J"", ""Ripatti S"", ""Palotie A"", ""Freimer NB"", ""Collins FS"", ""Mohlke KL"", ""Scott LJ"", ""Fauman EB"", ""Burant C"", ""Boehnke M"", ""Laakso M"", ""Wen X""]",10.1016/j.ajhg.2022.08.007,Yin X,American journal of human genetics,0002-9297,10,Am J Hum Genet,eng,Wen X,"[""Bilirubin"", ""Carnitine"", ""Genome-Wide Association Study"", ""Glycerophospholipids"", ""Humans"", ""Male"", ""Metabolomics"", ""Quantitative Trait Loci"", ""Solute Carrier Family 22 Member 5"", ""Transcriptome""]",1727-1741,36055244,pmc-id: PMC9606383;,2022 Oct 6,2022,https://pubmed.ncbi.nlm.nih.gov/36055244/,"Integrating transcriptomics, metabolomics, and GWAS helps reveal molecular mechanisms for metabolite levels and disease risk",109,hLMGLEHQAy1HfdBah,EMeUGOgXRpCAqy5ah
,"[""Editorial"", ""Comment""]","[""Mougin L"", ""Bailey SJ"", ""Jones AM"", ""Joyner MJ"", ""Mears SA"", ""Pearce R"", ""Zanini M""]",10.1007/s40279-026-02502-8,Mougin L,"Sports medicine (Auckland, N.Z.)",0112-1642,,Sports Med,eng,Zanini M,[],,42545591,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545591/,"Response to Comment on: ""35 Years of Joyner's Endurance Performance Model: Assessing the Contribution of Physiological Determinants of Performance Proxies in 888 Individuals from Recreational to World Class""",,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Wahl HW""]",10.1007/s00391-026-02620-y,Wahl HW,Zeitschrift fur Gerontologie und Geriatrie,0948-6704,5,Z Gerontol Geriatr,eng,Wahl HW,[],363,42545386,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42545386/,What is aging?,59,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Simm A"", ""Iglseder B"", ""Kolland F""]",10.1007/s00391-026-02629-3,Simm A,Zeitschrift fur Gerontologie und Geriatrie,0948-6704,5,Z Gerontol Geriatr,ger,Kolland F,[],361-362,42545385,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42545385/,Kommunikation im Alter aus multidisziplinärer Sicht,59,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Piraino T""]",10.1177/19433654261472950,Piraino T,Respiratory care,0020-1324,,Respir Care,eng,Piraino T,[],19433654261472950,42545336,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545336/,"Reverse Triggering: Seeing More, Knowing Less?",,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Guo LY"", ""Ting DSW""]",10.1016/j.oret.2026.06.003,Guo LY,Ophthalmology. Retina,2468-6530,,Ophthalmol Retina,eng,Ting DSW,[],,42545309,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42545309/,From Black Boxes to Biomarkers: Artificial Intelligence in Surgical Retina,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Albright RC Jr""]",10.1016/j.mayocp.2026.06.013,Albright RC Jr,Mayo Clinic proceedings,0025-6196,,Mayo Clin Proc,eng,Albright RC Jr,[],,42545302,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545302/,Clinical Outcomes and the Cause of Death in Patients on Dialysis Undergoing Percutaneous Coronary Intervention,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Roger VL""]",10.1016/j.mayocp.2026.06.014,Roger VL,Mayo Clinic proceedings,0025-6196,,Mayo Clin Proc,eng,Roger VL,[],,42545301,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545301/,From Snapshots to Stories: Cardiovascular Risk Trajectories and the Future of Longitudinal Risk Prediction,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Pham J"", ""Courtney PT"", ""Price AT"", ""Romero T"", ""Qi XS"", ""Lamb J"", ""Steinberg ML"", ""Henke LE"", ""Cao M"", ""Kishan AU""]",10.1016/j.ijrobp.2026.04.004,Pham J,"International journal of radiation oncology, biology, physics",0360-3016,,Int J Radiat Oncol Biol Phys,eng,Kishan AU,[],,42545298,,2026 May 14,2026,https://pubmed.ncbi.nlm.nih.gov/42545298/,Beyond Endpoints: The Role of Prospective Technical Fidelity Quality Assurance in Modern Radiation Therapy Clinical Trials,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial"", ""Comment""]","[""Stroud AM"", ""Sharp RR""]",10.1080/15265161.2026.2704452,Stroud AM,The American journal of bioethics : AJOB,1526-5161,8,Am J Bioeth,eng,Sharp RR,[],3-5,42545292,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42545292/,Reimagining Bioethics in the Era of AI Agents,26,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial"", ""Comment""]","[""Yiadom MYAB""]",10.1080/15265161.2026.2699706,Yiadom MYAB,The American journal of bioethics : AJOB,1526-5161,8,Am J Bioeth,eng,Yiadom MYAB,[],6-8,42545283,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42545283/,The Ethics of Integration: Why Healthcare AI Must Be Evaluated Within Clinical and Research Workflows,26,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Magnus D""]",10.1080/15265161.2026.2704453,Magnus D,The American journal of bioethics : AJOB,1526-5161,8,Am J Bioeth,eng,Magnus D,[],1-2,42545258,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42545258/,OMB Proposed Rule Change: The New Lysenkoism?,26,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Taylor E""]",10.1177/19375867261471760,Taylor E,HERD,1937-5867,,HERD,eng,Taylor E,[],19375867261471760,42545225,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545225/,Scholarly Publications in an Era of Artificial Intelligence,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Carter J"", ""Frazier K"", ""Werner J"", ""Thuilliez C"", ""Clements P"", ""Ogawa K"", ""Udupa V"", ""Mecklenburg L"", ""Panchal S""]",10.1177/01926233261471105,Carter J,Toxicologic pathology,0192-6233,,Toxicol Pathol,eng,Panchal S,[],1926233261471105,42544912,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42544912/,The Negative Impact of Travel Budget Cuts on Toxicologic Pathology,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Ng IKS"", ""Tan J"", ""Leung AJ"", ""Ma M""]",10.1111/1756-185x.70819,Ng IKS,International journal of rheumatic diseases,1756-1841,8,Int J Rheum Dis,eng,Ma M,[],e70819,42544902,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544902/,Palindromic Rheumatism: Revisiting the Approach to an Enigmatic Condition,29,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Allgayer H"", ""Boukamp P""]",10.1002/ijc.70685,Allgayer H,International journal of cancer,0020-7136,,Int J Cancer,eng,Boukamp P,[],,42544880,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42544880/,"Changing the History of Science-An Editorial Perspective on Critical Developments in Current Citation Practice, ""Forgetting"" the Pioneers of Scientific Discoveries",,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Yang K"", ""Ebrahimi-Fakhari D""]",10.1002/mds.70456,Yang K,Movement disorders : official journal of the Movement Disorder Society,0885-3185,,Mov Disord,eng,Ebrahimi-Fakhari D,[],,42544843,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42544843/,Childhood-Onset Movement Disorders at the Forefront: From Genes to Precision Therapy,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Seil R"", ""Herbst E"", ""Milano G"", ""Musahl V"", ""Prill R"", ""Enes Kayaalp M"", ""Mengis N"", ""Ayeni OR"", ""Hirschmann MT""]",10.1002/ksa.70414,Seil R,"Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA",0942-2056,,Knee Surg Sports Traumatol Arthrosc,eng,Hirschmann MT,[],,42544694,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42544694/,Holding the line: Ethics and surgical decision-making in an era of financial pressure in health care systems around the globe,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Yardley S"", ""French M""]",10.1177/02692163261471306,Yardley S,Palliative medicine,0269-2163,,Palliat Med,eng,French M,[],2692163261471306,42544539,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42544539/,Equity requires epistemic justice: A research agenda for palliative care to meet the needs of people living with complex mental health conditions,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Orsega-Smith E"", ""O'Hanlon J""]",10.32481/djph.2026.07.02,Orsega-Smith E,Delaware journal of public health,2639-6378,3,Dela J Public Health,eng,O'Hanlon J,[],4,42544356,pmc-id: PMC13429243;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42544356/,From the Guest Editors,12,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Kastelic J"", ""Ogilvie T""]",,Kastelic J,The Canadian veterinary journal = La revue veterinaire canadienne,0008-5286,8,Can Vet J,eng,Ogilvie T,[],834-836,42544318,pmc-id: PMC13429200;embargo-date: 2026/11/01;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544318/,Integrity: The cornerstone of the veterinary profession,67,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
"Burnout among healthcare professionals has become a critical challenge for healthcare systems worldwide. Increasing workload, administrative demands, and workforce shortages have contributed to rising levels of emotional exhaustion and professional disengagement. While burnout is often approached as an individual problem, organisational factors appear to play a central role in its development and prevention. Professional autonomy has emerged as a potentially protective factor, as greater control over clinical decision-making and work organisation is associated with improved well-being and job satisfaction. However, the benefits of autonomy depend on supportive organisational environments, adequate resources, and effective leadership. Furthermore, autonomy alone cannot offset the effects of excessive workload and chronic organisational stress. This editorial discusses the relationship between professional autonomy and burnout and argues that sustainable burnout prevention requires structural organisational changes in addition to promoting professional independence.","[""Editorial""]","[""Dias M"", ""Almeida P""]",10.7759/cureus.112006,Dias M,Cureus,2168-8184,7,Cureus,eng,Almeida P,[],e112006,42544315,pmc-id: PMC13429236;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42544315/,Professional Autonomy as a Protective Factor Against Burnout: Important but Not Sufficient,18,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
"Sleep is increasingly being recognised as an important factor influencing athletic performance, recovery and overall health. This narrative review aims to discuss the factors that can affect sleep in athletes and how sleep can affect performance. Traditionally, athlete well-being has focused on training and nutrition; however, new evidence and initiatives now highlight sleep as an important element of performance. This review examines current evidence on sleep duration, sleep quality and sleep disturbances in athletic populations, with a particular focus on the effects related to competition. Athletes often report shorter sleep durations than non-athletes, despite experiencing less sleep fragmentation and quicker sleep onset. One study found that on nights before a competition day, athletes went to bed earlier (22:56 hr ± 49.2 min), woke up later (8:12 hr ± 58.6 min) and slept for longer (7:57 hr ± 60.9 min). A significant number of athletes face poor sleep quality, difficulty falling asleep, and excessive daytime sleepiness. Sleep disruptions are also common around competitions, with post-competition nights showing reductions in total sleep time and sleep quality compared to pre-competition nights. Factors contributing to this include late competition times, heightened physiological and psychological arousal, increased caffeine intake, travel demands and use of technology. Overall, these findings demonstrate that inadequate and disturbed sleep is widespread among athletes, especially during competition periods, which may impact recovery, cognitive function and emotional stability.","[""Editorial""]","[""Bastock D"", ""Amarnani R""]",10.7759/cureus.111990,Bastock D,Cureus,2168-8184,7,Cureus,eng,Amarnani R,[],e111990,42544296,pmc-id: PMC13429214;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42544296/,Optimising Performance Through Sleep: An Evidence-Based Review,18,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Shahrezaee M"", ""Noroozi-Aghideh A""]",10.22038/abjs.2026.95992.4305,Shahrezaee M,The archives of bone and joint surgery,2345-4644,7,Arch Bone Jt Surg,eng,Noroozi-Aghideh A,[],423-425,42544230,pmc-id: PMC13429142;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42544230/,Platelet-Rich Plasma: Are We Ahead of the Evidence?,14,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Mulleague L""]",10.1177/17511437261474728,Mulleague L,Journal of the Intensive Care Society,1751-1437,,J Intensive Care Soc,eng,Mulleague L,[],17511437261474728,42544220,pmc-id: PMC13428804;,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42544220/,"No rule, no accountability: Why intensive care needs a statutory triage framework",,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Issa AM""]",10.1002/cpdd.70088,Issa AM,Clinical pharmacology in drug development,2160-763X,8,Clin Pharmacol Drug Dev,eng,Issa AM,[],e70088,42544094,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544094/,"Distributed Manufacturing, Foreign Establishments, and Why the FDA's New Proposed Rule Matters to Clinical Pharmacology",15,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Xia L"", ""Lai J"", ""Zhu JK""]",10.1111/jipb.70361,Xia L,Journal of integrative plant biology,1672-9072,,J Integr Plant Biol,eng,Zhu JK,[],,42544091,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42544091/,Unlocking the power and potential of the Cas12 family members and their ancestors for crop genome editing,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Li L"", ""Harrison KL""]",10.1111/jgs.70604,Li L,Journal of the American Geriatrics Society,0002-8614,,J Am Geriatr Soc,eng,Harrison KL,[],,42544081,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42544081/,"What Good Is a ""Good Death?""",,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
"This issue of the Revue Médicale de Liège highlights the diversity of clinical situations encountered in daily practice, ranging from life-threatening emergencies to rare complications of modern therapies. These reports emphasize the importance of rigorous clinical reasoning, multimodality imaging and multidisciplinary management in optimizing patient care and safety.","[""Editorial"", ""Journal Article"", ""Introductory Journal Article"", ""English Abstract""]","[""Lancellotti P""]",,Lancellotti P,Revue medicale de Liege,0370-629X,7-8,Rev Med Liege,fre,Lancellotti P,"[""Humans""]",409-410,42544060,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42544060/,[From clinical cases to daily practice],81,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Jung TY""]",10.14791/btrt.2026.0033,Jung TY,Brain tumor research and treatment,2288-2405,3,Brain Tumor Res Treat,eng,Jung TY,[],117,42543808,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543808/,Greetings From the New Editor-in-Chief,14,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Da Fonseca LG"", ""Guerrero A"", ""Muñoz-Martínez SG""]",10.1111/liv.70832,Da Fonseca LG,Liver international : official journal of the International Association for the Study of the Liver,1478-3223,9,Liver Int,eng,Muñoz-Martínez SG,[],e70832,42543781,,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42543781/,Immunotherapy Rechallenge in HCC: A Second Chance for Response?,46,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Meschi N"", ""Pauwels R"", ""Duncan HF"", ""McGuigan MB"", ""Cotti E"", ""Del Fabbro M"", ""Shemesh H"", ""Jacobs R""]",10.1111/iej.70249,Meschi N,International endodontic journal,0143-2885,,Int Endod J,eng,Jacobs R,[],,42543773,,2026 Aug 2,2026,https://pubmed.ncbi.nlm.nih.gov/42543773/,Cone-Beam Computed Tomography in the Follow-Up of Endodontic Treatment: The Development of S3-Level Guidelines Including Evidence-Based and Expert-Led Recommendations,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
"The viability of the Australian private healthcare sector, and hence, private psychiatric care, is determined by a range of complex, inter-related factors. The private health insurance industry and Medicare reimbursement partially underwrite the costs of procedures, private hospital care and some allied healthcare. Psychiatric hospital cover sits almost entirely within the most expensive private health insurance Gold tier cover. Private outpatient fees are set by medical specialists, and patients receive a Medicare reimbursement for these consultations. There has been increasing concern regarding out-of-pocket costs for patients accessing private psychiatric hospital and outpatient care. A substantial 15% of all health expenditure in Australia is paid directly by individuals as out-of-pocket costs - almost double the share contributed by private health insurers. It is estimated that 72% of these out-of-pocket costs is attributable to individual-physician fee variation. Instead of focussing on providers or payors, a systemic private healthcare regulatory approach is needed to address the overall costs issue.","[""Editorial""]","[""Looi JC"", ""Allison S"", ""Bastiampillai T"", ""Kisely S"", ""Liu WM""]",10.1177/10398562261474429,Looi JC,Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists,1039-8562,,Australas Psychiatry,eng,Liu WM,[],10398562261474429,42543611,,2026 Aug 2,2026,https://pubmed.ncbi.nlm.nih.gov/42543611/,Systemic regulation of the private healthcare sector is needed to ensure patient accessibility is not limited by out-of-pocket costs,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Liu D"", ""Kopera-Frye K""]",10.1080/02701960.2026.2700097,Liu D,Gerontology & geriatrics education,0270-1960,3,Gerontol Geriatr Educ,eng,Kopera-Frye K,[],345-348,42543569,,2026 Jul-Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42543569/,Advancing the gerontological landscape through workforce innovation,47,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Etchegaray A"", ""Goetz N"", ""Hanigan K"", ""Phillips J"", ""Kumar R"", ""Tambakis G"", ""Radford-Smith G"", ""Walker G"", ""Croft A""]",10.1111/apt.70885,Etchegaray A,Alimentary pharmacology & therapeutics,0269-2813,,Aliment Pharmacol Ther,eng,Croft A,[],,42543478,,2026 Aug 2,2026,https://pubmed.ncbi.nlm.nih.gov/42543478/,Editorial on: 'Lowering the C-Reactive Protein Threshold Improves Risk Stratification in Acute Ulcerative Colitis: A Propensity-Matched Analysis'. Authors' Reply,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Munive AC"", ""Otálvaro D"", ""Torres Cortes DF"", ""Mejía Núñez JA""]",10.1007/s00270-026-04560-x,Munive AC,Cardiovascular and interventional radiology,0174-1551,,Cardiovasc Intervent Radiol,eng,Mejía Núñez JA,[],,42543400,,2026 Aug 2,2026,https://pubmed.ncbi.nlm.nih.gov/42543400/,Technology or Context? Interpreting the Association Between IVUS Guidance and Mortality After Peripheral Arterial Intervention,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Wickramasinghe NRL"", ""Clement ND"", ""Greenbrook JTV""]",10.1302/2633-1462.78.BJO-2025-0294.R1,Wickramasinghe NRL,Bone & joint open,2633-1462,8,Bone Jt Open,eng,Greenbrook JTV,[],997-1000,42543163,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42543163/,"Consent: Doctor, can you please do my operation?",7,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Leucht S"", ""Hiller S"", ""Priller J"", ""Böge K"", ""Seidel M"", ""Rodolico A""]",10.1007/s00406-026-02321-y,Leucht S,European archives of psychiatry and clinical neuroscience,0940-1334,,Eur Arch Psychiatry Clin Neurosci,eng,Rodolico A,[],,42542996,,2026 Aug 2,2026,https://pubmed.ncbi.nlm.nih.gov/42542996/,Experience-based medicine: a new paradigm,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Lin JJ"", ""Zhang L""]",10.1007/s00406-026-02337-4,Lin JJ,European archives of psychiatry and clinical neuroscience,0940-1334,,Eur Arch Psychiatry Clin Neurosci,eng,Zhang L,[],,42542995,,2026 Aug 2,2026,https://pubmed.ncbi.nlm.nih.gov/42542995/,Treatment for cognitive impairment in schizophrenia: insights from exercise-based integrative interventions,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Ferreiro-Iglesias R"", ""Zabana Y"", ""Barreiro-de Acosta M""]",10.1111/apt.70898,Ferreiro-Iglesias R,Alimentary pharmacology & therapeutics,0269-2813,,Aliment Pharmacol Ther,eng,Barreiro-de Acosta M,[],,42542975,,2026 Aug 2,2026,https://pubmed.ncbi.nlm.nih.gov/42542975/,Editorial: Risankizumab in Refractory Crohn's Disease-From Real-World Effectiveness to Strategic Positioning and Early Monitoring. Authors' Reply,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Goyal MK"", ""Goyal O""]",10.1111/apt.70899,Goyal MK,Alimentary pharmacology & therapeutics,0269-2813,,Aliment Pharmacol Ther,eng,Goyal O,[],,42542972,,2026 Aug 2,2026,https://pubmed.ncbi.nlm.nih.gov/42542972/,Editorial: Comparative Effectiveness in Chronic Constipation-Interpreting Real-World Evidence. Authors' Reply,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
"Disease outbreaks are non-random public health phenomena attributed to known or idiopathic human, animal, and animal-based factors; a realm referred to as the One Health concept; a new global public health order for control and prevention of epidemics, endemics, and pandemics. These are diseases of viral, prion, bacterial, fungal, and parasitic origin, transmitted between vertebrate animals and humans and vice versa. Emergence and re-emergence of zoonotic diseases such as rabies, Ebola, COVID-19, monkeypox, avian influenza, anthrax, brucellosis, leptospirosis, and Lyme disease continue to affect populations across the world, pointing to unexpected budget impacts of the affected countries.","[""Journal Article"", ""Editorial""]","[""Agot GN"", ""Mweu MM""]",10.11604/pamj.2026.54.4.52132,Agot GN,The Pan African medical journal,1937-8688,,Pan Afr Med J,eng,Mweu MM,"[""Humans"", ""Disease Outbreaks"", ""Animals"", ""Zoonoses"", ""Public Health"", ""Global Health"", ""One Health"", ""Delivery of Health Care"", ""Cost of Illness"", ""Communicable Diseases, Emerging""]",4,42542872,pmc-id: PMC13428646;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42542872/,Perspectives on the economic costs of disease outbreaks to health systems,54,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Juliebø-Jones P"", ""Somani BK"", ""Baug S"", ""Madaan S"", ""Palumbo C"", ""Jeong CW"", ""Albersen M"", ""Beisland C""]",10.1177/17562872261468904,Juliebø-Jones P,Therapeutic advances in urology,1756-2872,,Ther Adv Urol,eng,Beisland C,[],17562872261468904,42542714,pmc-id: PMC13428156;,2026 Jan-Dec,2026,https://pubmed.ncbi.nlm.nih.gov/42542714/,Urology for older adults: a blind spot in international guidelines?,18,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Wahyuningsih U""]",10.47895/amp.v60i12.14425,Wahyuningsih U,Acta medica Philippina,0001-6071,12,Acta Med Philipp,eng,Wahyuningsih U,[],6-7,42542657,pmc-id: PMC13427896;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42542657/,Enhancing Multidisciplinary Collaboration in Healthcare to Achieve SDGs during the COVID-19 Pandemic,60,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
"The 2026 Bundibugyo virus disease (BDBV) outbreak in the Democratic Republic of the Congo and adjacent Uganda has revealed major deficiencies in outbreak response. The available diagnostics, vaccines, and therapies were primarily designed against Zaire Ebola virus - leaving us ill-prepared for BDBV detection and control. We call for five immediate actions to strengthen existing efforts. First, rapidly establish a decentralized three-tier molecular diagnostic network to allow timely detection and genomic surveillance. Second, since there are few approved treatments that target BDBV specifically, adaptive platform trials should assess the potential of repurposed host-directed therapies. Third, in conflict-affected settings, routine enabling environment data collection to strengthen surveillance is needed, whilst digital proximity tracing and social support mechanisms, such as community tracing collaborative (CTC) responses to combat community transmission through contact identification and isolation, would also add value. Fourth, ring vaccination strategies with recombinant vesicular stomatitis virus-Zaire Ebola virus (rVSV-ZEBOV) as a post-exposure intervention should be explored, given the potential for cross-protection against BDBV. Fifth, implementation of extensive genomic surveillance should be enhanced to differentiate between continuous human transmission and sporadic zoonotic spillover events while informing ecology-based control strategies. Together, these recommendations highlight actionable, scalable steps that can be implemented quickly through existing systems and out-of-the-box solutions. Filling these key gaps could significantly affect the outcome of this current outbreak and enhance regional and global preparedness for future ebolavirus outbreaks.","[""Editorial""]","[""Mohapatra PR"", ""Mishra B""]",10.7759/cureus.111921,Mohapatra PR,Cureus,2168-8184,7,Cureus,eng,Mishra B,[],e111921,42542607,pmc-id: PMC13427566;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42542607/,Closing Critical Gaps in the 2026 Bundibugyo Ebola Response: Five Actionable Priorities,18,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Yin X"", ""Jin G""]",10.1016/j.cpt.2026.05.001,Yin X,Cancer pathogenesis and therapy,2097-2563,5,Cancer Pathog Ther,eng,Jin G,[],340-343,42542599,pmc-id: PMC13427541;,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42542599/,Rewiring metabolic-immune circuitry in pancreatic ductal adenocarcinoma (PDAC),4,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Liu M""]",10.1016/j.cpt.2026.05.002,Liu M,Cancer pathogenesis and therapy,2097-2563,5,Cancer Pathog Ther,eng,Liu M,[],335-339,42542573,pmc-id: PMC13427537;,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42542573/,Moving cardio-oncology upstream: Integrating cardiovascular prevention into routine cancer care,4,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Marcu LG"", ""Clement C"", ""Friedl A"", ""Harbron R"", ""Rühm W"", ""Stoeva M"", ""Thorne M"", ""Toma-Dasu I"", ""Trapp J"", ""Wojcik A"", ""Woloschak G""]",10.1007/s00411-026-01227-6,Marcu LG,Radiation and environmental biophysics,0301-634X,,Radiat Environ Biophys,eng,Woloschak G,[],,42542501,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42542501/,The declaration of Adelaide white paper: guidelines for author responsibility in peer review,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""van Rossum PSN"", ""Schneiders FL"", ""Senan S""]",10.1016/j.lungcan.2026.109555,van Rossum PSN,"Lung cancer (Amsterdam, Netherlands)",0169-5002,,Lung Cancer,eng,Senan S,[],109555,42542431,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42542431/,The limits of pooled evidence in early-stage NSCLC: are we comparing treatments or patients?,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""El Hajj H"", ""Gouy S"", ""Limkin E"", ""Scherier S"", ""Morice P""]",10.1016/j.ijgc.2026.104874,El Hajj H,International journal of gynecological cancer : official journal of the International Gynecological Cancer Society,1048-891X,,Int J Gynecol Cancer,eng,Morice P,[],104874,42542429,,2026 Jul 15,2026,https://pubmed.ncbi.nlm.nih.gov/42542429/,Is conization with lymph node dissection safe for International Federation of Gynecology and Obstetrics 2018 stage IB1 cervical cancer measuring 1 to 2 cm?,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Haider S""]",10.1016/j.ijgc.2026.104865,Haider S,International journal of gynecological cancer : official journal of the International Gynecological Cancer Society,1048-891X,,Int J Gynecol Cancer,eng,Haider S,[],104865,42542428,,2026 Jul 11,2026,https://pubmed.ncbi.nlm.nih.gov/42542428/,Personalized circulating tumor DNA-based minimal residual disease assessment for optimizing interval debulking surgery timing in advanced ovarian cancer: toward precision surgical oncology,,4NjBn63C9aEgM6Sbz,RhjZ5pkxB7M4LL52n
,"[""Editorial""]","[""Lane HC"", ""Fauci AS""]",10.1056/NEJMe2603127,Lane HC,The New England journal of medicine,0028-4793,16,N Engl J Med,eng,Fauci AS,[],1649-1650,42019024,,2026 Apr 23,2026,https://pubmed.ncbi.nlm.nih.gov/42019024/,"Same Pill, Different Impact - Reassessing the Efficacy of Nirmatrelvir-Ritonavir",394,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"Since the inception of World AIDS Day in 1988, advances with antiretroviral drugs have revolutionized the landscape of HIV/AIDS treatment and prevention. In 2025, we reflect on progress made, highlight promising therapeutic developments, and look ahead to what is needed to end the AIDS epidemic.","[""Editorial""]","[""Fauci AS"", ""Folkers GK""]",10.1371/journal.pmed.1004806,Fauci AS,PLoS medicine,1549-1277,12,PLoS Med,eng,Folkers GK,"[""Humans"", ""Acquired Immunodeficiency Syndrome"", ""Anti-HIV Agents"", ""HIV Infections""]",e1004806,41325318,pmc-id: PMC12668473;,2025 Dec,2025,https://pubmed.ncbi.nlm.nih.gov/41325318/,Treatment and prevention of HIV/AIDS: Unfinished business,22,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"The tenth anniversary of the publication of Lawrence Gostin's seminal treatise Global Health Law affords us the opportunity to reflect on his enduring legacy as a preeminent scholar, and one of the field's founding thought leaders.","[""Journal Article"", ""Historical Article""]","[""Fauci AS""]",10.1017/jme.2025.14,Fauci AS,"The Journal of law, medicine & ethics : a journal of the American Society of Law, Medicine & Ethics",1073-1105,S1,J Law Med Ethics,eng,Fauci AS,"[""Global Health"", ""Humans"", ""History, 20th Century"", ""History, 21st Century""]",1,40223589,,2025,2025,https://pubmed.ncbi.nlm.nih.gov/40223589/,Reflection on the Legacy of Lawrence Gostin in Global Health,53,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"The global experiences with the human immunodeficiency virus (HIV)/AIDS and coronavirus disease 2019 (COVID-19) pandemics hold important lessons for preparing for, and responding to, future outbreaks of emerging or reemerging infectious diseases. Scores of infectious diseases have emerged or reemerged over the past 4 decades, and future outbreaks are inevitable. The next emerging pathogen likely will again come from unanticipated sources and pose puzzles in terms of microbiology, transmission, natural history, pathogenesis, and epidemiology, and will present challenges to developing countermeasures such as diagnostics, therapeutics, and vaccines. Although dozens of lessons could be addressed, 8 selected lessons common to HIV/AIDS and COVID-19 are addressed here. Consideration of the commonality of lessons learned from HIV/AIDS and COVID-19, the 2 most devastating pandemics over the past half century, will help us-and those who follow us-to minimize the impact of future outbreaks and prevent them from becoming global pandemics.","[""Journal Article""]","[""Fauci AS"", ""Folkers GK""]",10.1093/cid/ciae585,Fauci AS,Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,1058-4838,5,Clin Infect Dis,eng,Folkers GK,"[""Humans"", ""Acquired Immunodeficiency Syndrome"", ""COVID-19"", ""Global Health"", ""HIV Infections"", ""Pandemics"", ""SARS-CoV-2""]",1074-1079,39593235,,2025 Jun 4,2025,https://pubmed.ncbi.nlm.nih.gov/39593235/,HIV/AIDS and COVID-19: Shared Lessons From 2 Pandemics,80,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
,"[""Editorial"", ""Comment""]","[""Lane HC"", ""Fauci AS""]",10.1056/EVIDe2400282,Lane HC,NEJM evidence,2766-5526,10,NEJM Evid,eng,Fauci AS,"[""Humans"", ""Health Services Accessibility"", ""Drug Approval"", ""United States""]",EVIDe2400282,39315872,,2024 Oct,2024,https://pubmed.ncbi.nlm.nih.gov/39315872/,Expanded Access of Unproven Drugs: Not the Final Word,3,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"Vaccines have stemmed many infectious diseases, but when SARS-CoV-2 emerged, traditional vaccine development would not have been fast enough. This year's Nobel Prize in Physiology or Medicine recognizes work that enabled the rapid development of mRNA vaccines, which halted the COVID-19 pandemic. The feat was a product of basic biological insights coupled with technological innovations, which have transformed vaccine design.","[""Journal Article""]","[""Brown BD"", ""Fauci AS"", ""Belkaid Y"", ""Merad M""]",10.1016/j.immuni.2023.11.009,Brown BD,Immunity,1074-7613,12,Immunity,eng,Merad M,"[""Humans"", ""mRNA Vaccines"", ""Pandemics"", ""COVID-19"", ""COVID-19 Vaccines"", ""Vaccines""]",2665-2669,38091944,,2023 Dec 12,2023,https://pubmed.ncbi.nlm.nih.gov/38091944/,RNA vaccines: A transformational advance,56,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
The lessons of COVID-19 must be heeded if the world is to be prepared for the next emergent pathogen with pandemic potential.,"[""Editorial""]","[""Fauci AS""]",10.1126/scitranslmed.adj9469,Fauci AS,Science translational medicine,1946-6234,718,Sci Transl Med,eng,Fauci AS,"[""Humans"", ""COVID-19"", ""Pandemics""]",eadj9469,37851827,,2023 Oct 18,2023,https://pubmed.ncbi.nlm.nih.gov/37851827/,What keeps me up at night,15,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"Vaccines have played a fundamental role in the control of infectious diseases. We previously developed a messenger RNA (mRNA) vaccine against HIV-1 that forms virus-like particles (VLPs) through coexpression of the viral envelope with Gag. Here, we applied the same principle to the design of a VLP-forming mRNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To promote cognate interaction with simian immunodeficiency virus (SIV) Gag, we engineered different chimeric proteins encompassing the ectodomain and the transmembrane region of the SARS-CoV-2 Spike protein from the Wuhan-Hu-1 strain fused to the gp41 cytoplasmic tail of either HIV-1 (strain WITO) or SIV (strain mac239) with or without a partial truncation at amino acid 745 to enhance membrane expression. Upon cotransfection with SIV gag mRNA, the Spike-SIVCT.745 (SSt) chimera yielded the highest level of cell-surface expression and extracellular VLP release. Immunization of BALB/c mice with SSt+gag mRNA at 0, 4, and 16 wk induced higher titers of Spike-binding and autologous neutralizing antibodies at all time points compared to SSt mRNA alone. Furthermore, mice immunized with SSt+gag mRNA developed neutralizing antibodies effective against different variants of concern. These data demonstrate that the Gag/VLP mRNA platform can be successfully applied to vaccines against different agents for the prevention of infectious diseases of global relevance.","[""Journal Article"", ""Research Support, N.I.H., Intramural""]","[""Zhang P"", ""Falcone S"", ""Tsybovsky Y"", ""Singh M"", ""Gopan V"", ""Miao H"", ""Seo Y"", ""Rogers D"", ""Renzi I"", ""Lai YT"", ""Narayanan E"", ""Stewart-Jones G"", ""Himansu S"", ""Carfi A"", ""Fauci AS"", ""Lusso P""]",10.1073/pnas.2305896120,Zhang P,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,29,Proc Natl Acad Sci U S A,eng,Lusso P,"[""Humans"", ""Animals"", ""Mice"", ""COVID-19 Vaccines"", ""Antibodies, Viral"", ""SARS-CoV-2"", ""COVID-19"", ""Antibodies, Neutralizing"", ""Spike Glycoprotein, Coronavirus"", ""Simian Immunodeficiency Virus""]",e2305896120,37428933,pmc-id: PMC10629519;,2023 Jul 18,2023,https://pubmed.ncbi.nlm.nih.gov/37428933/,Increased neutralization potency and breadth elicited by a SARS-CoV-2 mRNA vaccine forming virus-like particles,120,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
,"[""Editorial""]","[""Rubin EJ"", ""Baden LR"", ""Fauci AS"", ""Morrissey S""]",10.1056/NEJMe2307011,Rubin EJ,The New England journal of medicine,0028-4793,24,N Engl J Med,eng,Morrissey S,[],e82,37314713,,2023 Jun 15,2023,https://pubmed.ncbi.nlm.nih.gov/37314713/,Audio Interview: Dr. Fauci on Infectious Disease Challenges,388,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"On November 7th and 8th, 2022, The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), The Coalition for Epidemic Preparedness Innovation (CEPI), The Bill & Melinda Gates Foundation (BMGF), The Biomedical Advanced Research and Development Authority (BARDA), and the Wellcome Trust hosted a virtual workshop entitled “Mucosal Vaccines for SARS-CoV-2: Scientific Gaps and Opportunities.” During the workshop, researchers and vaccine developers from around the world discussed the potential of mucosal vaccines to block SARS-CoV-2 transmission and reviewed the status of SARS-CoV-2 mucosal vaccine research. Here, we summarize key challenges and opportunities in basic, translational, and clinical research that were highlighted during the meeting. We also provide recommendations to advance the field and accelerate the development of mucosal vaccines for SARS-CoV-2.","[""Journal Article""]","[""Knisely JM"", ""Buyon LE"", ""Mandt R"", ""Farkas R"", ""Balasingam S"", ""Bok K"", ""Buchholz UJ"", ""D'Souza MP"", ""Gordon JL"", ""King DFL"", ""Le TT"", ""Leitner WW"", ""Seder RA"", ""Togias A"", ""Tollefsen S"", ""Vaughn DW"", ""Wolfe DN"", ""Taylor KL"", ""Fauci AS""]",10.1038/s41541-023-00654-6,Knisely JM,NPJ vaccines,2059-0105,1,NPJ Vaccines,eng,Fauci AS,[],53,37045860,pmc-id: PMC10091310;,2023 Apr 12,2023,https://pubmed.ncbi.nlm.nih.gov/37045860/,Mucosal vaccines for SARS-CoV-2: scientific gaps and opportunities-workshop report,8,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"The global experience with COVID-19 holds important lessons for preparing for, and responding to, future emergences of pathogens with pandemic potential.","[""Journal Article""]","[""Fauci AS"", ""Folkers GK""]",10.1093/infdis/jiad095,Fauci AS,The Journal of infectious diseases,0022-1899,4,J Infect Dis,eng,Folkers GK,"[""Humans"", ""COVID-19"", ""Pandemics"", ""Civil Defense"", ""Global Health"", ""Knowledge""]",422-425,37035891,,2023 Aug 16,2023,https://pubmed.ncbi.nlm.nih.gov/37035891/,Pandemic Preparedness and Response: Lessons From COVID-19,228,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"CD4+ tissue resident memory T cells (TRMs) are implicated in the formation of persistent HIV reservoirs that are established during the very early stages of infection. The tissue-specific factors that direct T cells to establish tissue residency are not well defined, nor are the factors that establish viral latency. We report that costimulation via MAdCAM-1 and retinoic acid (RA), two constituents of gut tissues, together with TGF-β, promote the differentiation of CD4+ T cells into a distinct subset α4β7+CD69+CD103+ TRM-like cells. Among the costimulatory ligands we evaluated, MAdCAM-1 was unique in its capacity to upregulate both CCR5 and CCR9. MAdCAM-1 costimulation rendered cells susceptible to HIV infection. Differentiation of TRM-like cells was reduced by MAdCAM-1 antagonists developed to treat inflammatory bowel diseases. These finding provide a framework to better understand the contribution of CD4+ TRMs to persistent viral reservoirs and HIV pathogenesis.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Vimonpatranon S"", ""Goes LR"", ""Chan A"", ""Licavoli I"", ""McMurry J"", ""Wertz SR"", ""Arakelyan A"", ""Huang D"", ""Jiang A"", ""Huang C"", ""Zhou J"", ""Yolitz J"", ""Girard A"", ""Van Ryk D"", ""Wei D"", ""Hwang IY"", ""Martens C"", ""Kanakabandi K"", ""Virtaneva K"", ""Ricklefs S"", ""Darwitz BP"", ""Soares MA"", ""Pattanapanyasat K"", ""Fauci AS"", ""Arthos J"", ""Cicala C""]",10.1371/journal.ppat.1011209,Vimonpatranon S,PLoS pathogens,1553-7366,3,PLoS Pathog,eng,Cicala C,"[""Humans"", ""CD4-Positive T-Lymphocytes"", ""HIV Infections"", ""Transforming Growth Factor beta"", ""Tretinoin"", ""Cell Differentiation"", ""Immunologic Memory"", ""Receptors, CCR5""]",e1011209,36897929,pmc-id: PMC10032498;,2023 Mar,2023,https://pubmed.ncbi.nlm.nih.gov/36897929/,MAdCAM-1 costimulation in the presence of retinoic acid and TGF-β promotes HIV infection and differentiation of CD4+ T cells into CCR5+ TRM-like cells,19,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"Viruses that replicate in the human respiratory mucosa without infecting systemically, including influenza A, SARS-CoV-2, endemic coronaviruses, RSV, and many other ""common cold"" viruses, cause significant mortality and morbidity and are important public health concerns. Because these viruses generally do not elicit complete and durable protective immunity by themselves, they have not to date been effectively controlled by licensed or experimental vaccines. In this review, we examine challenges that have impeded development of effective mucosal respiratory vaccines, emphasizing that all of these viruses replicate extremely rapidly in the surface epithelium and are quickly transmitted to other hosts, within a narrow window of time before adaptive immune responses are fully marshaled. We discuss possible approaches to developing next-generation vaccines against these viruses, in consideration of several variables such as vaccine antigen configuration, dose and adjuventation, route and timing of vaccination, vaccine boosting, adjunctive therapies, and options for public health vaccination polices.","[""Journal Article"", ""Review""]","[""Morens DM"", ""Taubenberger JK"", ""Fauci AS""]",10.1016/j.chom.2022.11.016,Morens DM,Cell host & microbe,1931-3128,1,Cell Host Microbe,eng,Fauci AS,"[""Humans"", ""COVID-19"", ""SARS-CoV-2"", ""Orthomyxoviridae"", ""Influenza, Human"", ""Influenza Vaccines"", ""Antibodies, Viral""]",146-157,36634620,pmc-id: PMC9832587;,2023 Jan 11,2023,https://pubmed.ncbi.nlm.nih.gov/36634620/,"Rethinking next-generation vaccines for coronaviruses, influenzaviruses, and other respiratory viruses",31,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
,"[""Journal Article""]","[""Read SW"", ""Kim P"", ""Marovich M"", ""Dieffenbach CW"", ""Fauci AS""]",10.1002/jia2.26039,Read SW,Journal of the International AIDS Society,1758-2652,12,J Int AIDS Soc,eng,Fauci AS,"[""Humans"", ""Pandemics"", ""HIV Infections""]",e26039,36448551,pmc-id: PMC9709723;,2022 Dec,2022,https://pubmed.ncbi.nlm.nih.gov/36448551/,Forty years of investment in HIV research: progress towards ending the HIV pandemic and preparation for future pandemics,25,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
,"[""Journal Article""]","[""Fauci AS""]",10.1056/NEJMp2213814,Fauci AS,The New England journal of medicine,0028-4793,22,N Engl J Med,eng,Fauci AS,"[""Humans"", ""Communicable Diseases, Emerging""]",2009-2011,36440879,,2022 Dec 1,2022,https://pubmed.ncbi.nlm.nih.gov/36440879/,It Ain't Over Till It's Over … but It's Never Over - Emerging and Reemerging Infectious Diseases,387,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"Severe COVID-19 is characterized by a prothrombotic state associated with thrombocytopenia, with microvascular thrombosis being almost invariably present in the lung and other organs at postmortem examination. We evaluated the presence of antibodies to platelet factor 4 (PF4)-polyanion complexes using a clinically validated immunoassay in 100 hospitalized patients with COVID-19 with moderate or severe disease (World Health Organization score, 4 to 10), 25 patients with acute COVID-19 visiting the emergency department, and 65 convalescent individuals. Anti-PF4 antibodies were detected in 95 of 100 hospitalized patients with COVID-19 (95.0%) irrespective of prior heparin treatment, with a mean optical density value of 0.871 ± 0.405 SD (range, 0.177 to 2.706). In contrast, patients hospitalized for severe acute respiratory disease unrelated to COVID-19 had markedly lower levels of the antibodies. In a high proportion of patients with COVID-19, levels of all three immunoglobulin (Ig) isotypes tested (IgG, IgM, and IgA) were simultaneously elevated. Antibody levels were higher in male than in female patients and higher in African Americans and Hispanics than in White patients. Anti-PF4 antibody levels were correlated with the maximum disease severity score and with significant reductions in circulating platelet counts during hospitalization. In individuals convalescent from COVID-19, the antibody levels returned to near-normal values. Sera from patients with COVID-19 induced higher levels of platelet activation than did sera from healthy blood donors, but the results were not correlated with the levels of anti-PF4 antibodies. These results demonstrate that the vast majority of patients with severe COVID-19 develop anti-PF4 antibodies, which may play a role in the clinical complications of COVID-19.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't"", ""Research Support, N.I.H., Intramural""]","[""Liu Q"", ""Miao H"", ""Li S"", ""Zhang P"", ""Gerber GF"", ""Follmann D"", ""Ji H"", ""Zeger SL"", ""Chertow DS"", ""Quinn TC"", ""Robinson ML"", ""Kickler TS"", ""Rothman RE"", ""Fenstermacher KZJ"", ""Braunstein EM"", ""Cox AL"", ""Farci P"", ""Fauci AS"", ""Lusso P""]",10.1073/pnas.2213361119,Liu Q,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,47,Proc Natl Acad Sci U S A,eng,Lusso P,"[""Humans"", ""Male"", ""Female"", ""Platelet Factor 4"", ""COVID-19"", ""Heparin"", ""Thrombocytopenia"", ""Antibodies"", ""Immunologic Factors"", ""Severity of Illness Index""]",e2213361119,36322776,pmc-id: PMC9704720;,2022 Nov 22,2022,https://pubmed.ncbi.nlm.nih.gov/36322776/,Anti-PF4 antibodies associated with disease severity in COVID-19,119,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"SARS-CoV-2 mRNA booster vaccines provide protection from severe disease, eliciting strong immunity that is further boosted by previous infection. However, it is unclear whether these immune responses are affected by the interval between infection and vaccination. Over a 2-month period, we evaluated antibody and B cell responses to a third-dose mRNA vaccine in 66 individuals with different infection histories. Uninfected and post-boost but not previously infected individuals mounted robust ancestral and variant spike-binding and neutralizing antibodies and memory B cells. Spike-specific B cell responses from recent infection (<180 days) were elevated at pre-boost but comparatively less so at 60 days post-boost compared with uninfected individuals, and these differences were linked to baseline frequencies of CD27lo B cells. Day 60 to baseline ratio of BCR signaling measured by phosphorylation of Syk was inversely correlated to days between infection and vaccination. Thus, B cell responses to booster vaccines are impeded by recent infection.","[""Journal Article"", ""Research Support, N.I.H., Intramural""]","[""Buckner CM"", ""Kardava L"", ""El Merhebi O"", ""Narpala SR"", ""Serebryannyy L"", ""Lin BC"", ""Wang W"", ""Zhang X"", ""Lopes de Assis F"", ""Kelly SEM"", ""Teng IT"", ""McCormack GE"", ""Praiss LH"", ""Seamon CA"", ""Rai MA"", ""Kalish H"", ""Kwong PD"", ""Proschan MA"", ""McDermott AB"", ""Fauci AS"", ""Chun TW"", ""Moir S""]",10.1016/j.cell.2022.09.032,Buckner CM,Cell,0092-8674,23,Cell,eng,Moir S,"[""Humans"", ""Antibodies, Neutralizing"", ""Antibodies, Viral"", ""COVID-19"", ""COVID-19 Vaccines"", ""SARS-CoV-2"", ""Vaccination"", ""Viral Vaccines"", ""B-Lymphocytes"", ""mRNA Vaccines""]",4333-4346.e14,36257313,pmc-id: PMC9513331;manuscript-id: NIHMS1839216;,2022 Nov 10,2022,https://pubmed.ncbi.nlm.nih.gov/36257313/,Interval between prior SARS-CoV-2 infection and booster vaccination impacts magnitude and quality of antibody and B cell responses,185,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
,"[""News""]","[""Canonica GW"", ""Fauci AS""]",10.1111/all.15519,Canonica GW,Allergy,0105-4538,12,Allergy,eng,Fauci AS,"[""Humans"", ""Hypersensitivity"", ""Killer Cells, Natural"", ""Allergy and Immunology""]",3695-3696,36125331,,2022 Dec,2022,https://pubmed.ncbi.nlm.nih.gov/36125331/,Legends of allergy and immunology: Lorenzo Moretta-Unfolding the mysteries of NK cells and much more,77,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"SARS-CoV-2 mRNA booster vaccines provide protection from severe disease, eliciting strong immunity that is further boosted by previous infection. However, it is unclear whether these immune responses are affected by the interval between infection and vaccination. Over a two-month period, we evaluated antibody and B-cell responses to a third dose mRNA vaccine in 66 individuals with different infection histories. Uninfected and post-boost but not previously infected individuals mounted robust ancestral and variant spike-binding and neutralizing antibodies, and memory B cells. Spike-specific B-cell responses from recent infection were elevated at pre-boost but comparatively less so at 60 days post-boost compared to uninfected individuals, and these differences were linked to baseline frequencies of CD27 lo B cells. Day 60 to baseline ratio of BCR signaling measured by phosphorylation of Syk was inversely correlated to days between infection and vaccination. Thus, B-cell responses to booster vaccines are impeded by recent infection.","[""Preprint"", ""Journal Article""]","[""Buckner CM"", ""Kardava L"", ""Merhebi OE"", ""Narpala SR"", ""Serebryannyy L"", ""Lin BC"", ""Wang W"", ""Zhang X"", ""de Assis FL"", ""Kelly SEM"", ""Teng IT"", ""McCormack GE"", ""Praiss LH"", ""Seamon CA"", ""Rai MA"", ""Kalish H"", ""Kwong PD"", ""Proschan MA"", ""McDermott AB"", ""Fauci AS"", ""Chun TW"", ""Moir S""]",10.1101/2022.08.30.22279344,Buckner CM,medRxiv : the preprint server for health sciences,,,medRxiv,eng,Moir S,[],,36093348,pmc-id: PMC9460969;,2022 Aug 31,2022,https://pubmed.ncbi.nlm.nih.gov/36093348/,Recent SARS-CoV-2 infection abrogates antibody and B-cell responses to booster vaccination,,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
,"[""Editorial"", ""Comment""]","[""Lane HC"", ""Fauci AS""]",10.1056/NEJMe2210535,Lane HC,The New England journal of medicine,0028-4793,8,N Engl J Med,eng,Fauci AS,"[""Disease Outbreaks"", ""Humans"", ""Mpox, Monkeypox"", ""Monkeypox virus""]",749-750,36001716,,2022 Aug 25,2022,https://pubmed.ncbi.nlm.nih.gov/36001716/,Monkeypox - Past as Prologue,387,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) emerged 20 years ago, presaging a series of subsequent infectious disease epidemics of international concern. The recent emergence of SARS-CoV-2 has underscored the importance of targeted preparedness research to enable rapid countermeasure development during a crisis. In December 2021 the National Institute of Allergy and Infectious Diseases (NIAID), building upon the successful strategies developed during the SARS-CoV-2 response and to prepare for future pandemics, published a pandemic preparedness plan that outlined a research strategy focused on priority pathogens, technology platforms, and prototype pathogens. To accelerate the discovery, development, and evaluation of medical countermeasures against new or previously unknown pathogens of pandemic potential, we present here a strategy of research directed at select prototype pathogens. In this manner, leveraging a prototype pathogen approach may serve as a powerful cornerstone in biomedical research preparedness to protect public health from newly emerging and reemerging infectious diseases.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, N.I.H., Intramural""]","[""Cassetti MC"", ""Pierson TC"", ""Patterson LJ"", ""Bok K"", ""DeRocco AJ"", ""Deschamps AM"", ""Graham BS"", ""Erbelding EJ"", ""Fauci AS""]",10.1093/infdis/jiac296,Cassetti MC,The Journal of infectious diseases,0022-1899,12,J Infect Dis,eng,Fauci AS,"[""Disease Outbreaks"", ""National Institute of Allergy and Infectious Diseases (U.S.)"", ""Pandemics"", ""Vaccine Development"", ""Vaccines"", ""Communicable Diseases""]",1433-1441,35876700,pmc-id: PMC9384504;,2023 Jun 15,2023,https://pubmed.ncbi.nlm.nih.gov/35876700/,Prototype Pathogen Approach for Vaccine and Monoclonal Antibody Development: A Critical Component of the NIAID Plan for Pandemic Preparedness,227,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"Messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly effective at inducing protective immunity. However, weak antibody responses are seen in some individuals, and cellular correlates of immunity remain poorly defined, especially for B cells. Here we used unbiased approaches to longitudinally dissect primary antibody, plasmablast, and memory B cell (MBC) responses to the two-dose mRNA-1273 vaccine in SARS-CoV-2-naive adults. Coordinated immunoglobulin A (IgA) and IgG antibody responses were preceded by bursts of spike-specific plasmablasts after both doses but earlier and more intensely after dose 2. While antibody and B cell cellular responses were generally robust, they also varied within the cohort and decreased over time after a dose-2 peak. Both antigen-nonspecific postvaccination plasmablast frequency after dose 1 and their spike-specific counterparts early after dose 2 correlated with subsequent antibody levels. This correlation between early plasmablasts and antibodies remained for titers measured at 6 months after vaccination. Several distinct antigen-specific MBC populations emerged postvaccination with varying kinetics, including two MBC populations that correlated with 2- and 6-month antibody titers. Both were IgG-expressing MBCs: one less mature, appearing as a correlate after the first dose, while the other MBC correlate showed a more mature and resting phenotype, emerging as a correlate later after dose 2. This latter MBC was also a major contributor to the sustained spike-specific MBC response observed at month 6. Thus, these plasmablasts and MBCs that emerged after both the first and second doses with distinct kinetics are potential determinants of the magnitude and durability of antibodies in response to mRNA-based vaccination.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't"", ""Research Support, N.I.H., Intramural""]","[""Kardava L"", ""Rachmaninoff N"", ""Lau WW"", ""Buckner CM"", ""Trihemasava K"", ""Blazkova J"", ""Lopes de Assis F"", ""Wang W"", ""Zhang X"", ""Wang Y"", ""Chiang CI"", ""Narpala S"", ""McCormack GE"", ""Liu C"", ""Seamon CA"", ""Sneller MC"", ""O'Connell S"", ""Li Y"", ""McDermott AB"", ""Chun TW"", ""Fauci AS"", ""Tsang JS"", ""Moir S""]",10.1073/pnas.2204607119,Kardava L,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,28,Proc Natl Acad Sci U S A,eng,Moir S,"[""2019-nCoV Vaccine mRNA-1273"", ""Antibody Formation"", ""B-Lymphocytes"", ""COVID-19"", ""Humans"", ""Immunity, Cellular"", ""Immunoglobulin A"", ""Immunoglobulin G"", ""RNA, Messenger"", ""SARS-CoV-2"", ""Vaccination""]",e2204607119,35759653,pmc-id: PMC9282446;,2022 Jul 12,2022,https://pubmed.ncbi.nlm.nih.gov/35759653/,Early human B cell signatures of the primary antibody response to mRNA vaccination,119,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"Antiretroviral therapy is highly effective in suppressing human immunodeficiency virus (HIV)1. However, eradication of the virus in individuals with HIV has not been possible to date2. Given that HIV suppression requires life-long antiretroviral therapy, predominantly on a daily basis, there is a need to develop clinically effective alternatives that use long-acting antiviral agents to inhibit viral replication3. Here we report the results of a two-component clinical trial involving the passive transfer of two HIV-specific broadly neutralizing monoclonal antibodies, 3BNC117 and 10-1074. The first component was a randomized, double-blind, placebo-controlled trial that enrolled participants who initiated antiretroviral therapy during the acute/early phase of HIV infection. The second component was an open-label single-arm trial that enrolled individuals with viraemic control who were naive to antiretroviral therapy. Up to 8 infusions of 3BNC117 and 10-1074, administered over a period of 24 weeks, were well tolerated without any serious adverse events related to the infusions. Compared with the placebo, the combination broadly neutralizing monoclonal antibodies maintained complete suppression of plasma viraemia (for up to 43 weeks) after analytical treatment interruption, provided that no antibody-resistant HIV was detected at the baseline in the study participants. Similarly, potent HIV suppression was seen in the antiretroviral-therapy-naive study participants with viraemia carrying sensitive virus at the baseline. Our data demonstrate that combination therapy with broadly neutralizing monoclonal antibodies can provide long-term virological suppression without antiretroviral therapy in individuals with HIV, and our experience offers guidance for future clinical trials involving next-generation antibodies with long half-lives.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Sneller MC"", ""Blazkova J"", ""Justement JS"", ""Shi V"", ""Kennedy BD"", ""Gittens K"", ""Tolstenko J"", ""McCormack G"", ""Whitehead EJ"", ""Schneck RF"", ""Proschan MA"", ""Benko E"", ""Kovacs C"", ""Oguz C"", ""Seaman MS"", ""Caskey M"", ""Nussenzweig MC"", ""Fauci AS"", ""Moir S"", ""Chun TW""]",10.1038/s41586-022-04797-9,Sneller MC,Nature,0028-0836,7913,Nature,eng,Chun TW,"[""Anti-HIV Agents"", ""Antibodies, Monoclonal"", ""Antibodies, Neutralizing"", ""Broadly Neutralizing Antibodies"", ""Double-Blind Method"", ""HIV Antibodies"", ""HIV Infections"", ""HIV-1"", ""Humans"", ""Viral Load"", ""Viremia""]",375-381,35650437,pmc-id: PMC11059968;manuscript-id: NIHMS1980728;,2022 Jun,2022,https://pubmed.ncbi.nlm.nih.gov/35650437/,Combination anti-HIV antibodies provide sustained virological suppression,606,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
,"[""Journal Article"", ""Research Support, N.I.H., Extramural""]","[""Morens DM"", ""Folkers GK"", ""Fauci AS""]",10.1093/infdis/jiac109,Morens DM,The Journal of infectious diseases,0022-1899,2,J Infect Dis,eng,Fauci AS,"[""COVID-19"", ""Humans"", ""Immunity, Herd"", ""SARS-CoV-2""]",195-198,35356987,pmc-id: PMC9129114;,2022 Aug 24,2022,https://pubmed.ncbi.nlm.nih.gov/35356987/,The Concept of Classical Herd Immunity May Not Apply to COVID-19,226,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
,"[""Journal Article""]","[""Morens DM"", ""Taubenberger JK"", ""Fauci AS""]",10.1056/NEJMp2118468,Morens DM,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Fauci AS,"[""Animals"", ""COVID-19"", ""COVID-19 Vaccines"", ""Chiroptera"", ""Communicable Diseases, Emerging"", ""Coronavirus"", ""Endemic Diseases"", ""Humans"", ""Pharmaceutical Research"", ""SARS-CoV-2"", ""Vaccine Efficacy"", ""Viral Vaccines""]",297-299,34910863,pmc-id: PMC11000439;manuscript-id: NIHMS1982198;,2022 Jan 27,2022,https://pubmed.ncbi.nlm.nih.gov/34910863/,Universal Coronavirus Vaccines - An Urgent Need,386,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"The development of a protective vaccine remains a top priority for the control of the HIV/AIDS pandemic. Here, we show that a messenger RNA (mRNA) vaccine co-expressing membrane-anchored HIV-1 envelope (Env) and simian immunodeficiency virus (SIV) Gag proteins to generate virus-like particles (VLPs) induces antibodies capable of broad neutralization and reduces the risk of infection in rhesus macaques. In mice, immunization with co-formulated env and gag mRNAs was superior to env mRNA alone in inducing neutralizing antibodies. Macaques were primed with a transmitted-founder clade-B env mRNA lacking the N276 glycan, followed by multiple booster immunizations with glycan-repaired autologous and subsequently bivalent heterologous envs (clades A and C). This regimen was highly immunogenic and elicited neutralizing antibodies against the most prevalent (tier-2) HIV-1 strains accompanied by robust anti-Env CD4+ T cell responses. Vaccinated animals had a 79% per-exposure risk reduction upon repeated low-dose mucosal challenges with heterologous tier-2 simian-human immunodeficiency virus (SHIV AD8). Thus, the multiclade env-gag VLP mRNA platform represents a promising approach for the development of an HIV-1 vaccine.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, N.I.H., Intramural"", ""Research Support, Non-U.S. Gov't""]","[""Zhang P"", ""Narayanan E"", ""Liu Q"", ""Tsybovsky Y"", ""Boswell K"", ""Ding S"", ""Hu Z"", ""Follmann D"", ""Lin Y"", ""Miao H"", ""Schmeisser H"", ""Rogers D"", ""Falcone S"", ""Elbashir SM"", ""Presnyak V"", ""Bahl K"", ""Prabhakaran M"", ""Chen X"", ""Sarfo EK"", ""Ambrozak DR"", ""Gautam R"", ""Martin MA"", ""Swerczek J"", ""Herbert R"", ""Weiss D"", ""Misamore J"", ""Ciaramella G"", ""Himansu S"", ""Stewart-Jones G"", ""McDermott A"", ""Koup RA"", ""Mascola JR"", ""Finzi A"", ""Carfi A"", ""Fauci AS"", ""Lusso P""]",10.1038/s41591-021-01574-5,Zhang P,Nature medicine,1078-8956,12,Nat Med,eng,Lusso P,"[""Animals"", ""Antibodies, Neutralizing"", ""Genes, env"", ""Genes, gag"", ""HIV Antibodies"", ""HIV-1"", ""Immunization, Secondary"", ""Macaca mulatta"", ""Risk Factors"", ""Simian Acquired Immunodeficiency Syndrome"", ""Vaccines, Synthetic"", ""mRNA Vaccines""]",2234-2245,34887575,,2021 Dec,2021,https://pubmed.ncbi.nlm.nih.gov/34887575/,A multiclade env-gag VLP mRNA vaccine elicits tier-2 HIV-1-neutralizing antibodies and reduces the risk of heterologous SHIV infection in macaques,27,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
,"[""Journal Article""]","[""Fauci AS"", ""Dieffenbach CW"", ""Dabis F""]",10.1002/jia2.25792,Fauci AS,Journal of the International AIDS Society,1758-2652,Suppl 7,J Int AIDS Soc,eng,Dabis F,"[""AIDS Vaccines"", ""Antibodies, Neutralizing"", ""HIV Antibodies"", ""HIV Infections"", ""HIV-1"", ""Humans""]",e25792,34806307,pmc-id: PMC8606854;,2021 Nov,2021,https://pubmed.ncbi.nlm.nih.gov/34806307/,Fitting a vaccine into the HIV prevention landscape,24 Suppl 7,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"The 2005 Immunity paper by Karikó et al. has been hailed as a cornerstone insight that directly led to the design and delivery of the mRNA vaccines against COVID-19. We asked experts in pathogen sensing, vaccine development, and public health to provide their perspective on the study and its implications.","[""Historical Article"", ""Journal Article"", ""Portrait""]","[""Fauci AS"", ""Merad M"", ""Swaminathan S"", ""Hur S"", ""Topol E"", ""Fitzgerald K"", ""Reis e Sousa C"", ""Corbett KS"", ""Bauer S""]",10.1016/j.immuni.2021.10.018,Fauci AS,Immunity,1074-7613,12,Immunity,eng,Bauer S,"[""Animals"", ""COVID-19"", ""COVID-19 Vaccines"", ""History, 21st Century"", ""Humans"", ""RNA, Messenger"", ""SARS-CoV-2"", ""Vaccine Development"", ""World Health Organization"", ""mRNA Vaccines""]",2676-2680,34739870,pmc-id: PMC8567413;,2021 Dec 14,2021,https://pubmed.ncbi.nlm.nih.gov/34739870/,From mRNA sensing to vaccines,54,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"As the fourth wave of the SARS-CoV-2 pandemic encircles the globe, there remains an urgent challenge to identify safe and effective treatment and prevention strategies that can be implemented in a range of health care and clinical settings. Substantial advances have been made in the use of anti-SARS-CoV-2 antibodies to mitigate the morbidity and mortality associated with COVID-19. On 15 June 2021, the National Institutes of Health, in collaboration with the U.S. Food and Drug Administration, convened a virtual summit to summarize existing knowledge on anti-SARS-CoV-2 antibodies and to identify key unanswered scientific questions to further catalyze the clinical development and implementation of antibodies.","[""Consensus Statement"", ""Journal Article""]","[""Boggiano C"", ""Eisinger RW"", ""Lerner AM"", ""Anderson JM"", ""Woodcock J"", ""Fauci AS"", ""Collins FS""]",10.7326/M21-3669,Boggiano C,Annals of internal medicine,0003-4819,1,Ann Intern Med,eng,Collins FS,"[""Antibodies, Monoclonal"", ""COVID-19"", ""Humans"", ""Immunization, Passive"", ""National Institutes of Health (U.S.)"", ""SARS-CoV-2"", ""United States"", ""United States Food and Drug Administration"", ""COVID-19 Serotherapy""]",119-126,34724404,pmc-id: PMC8559823;,2022 Jan,2022,https://pubmed.ncbi.nlm.nih.gov/34724404/,Update on and Future Directions for Use of Anti-SARS-CoV-2 Antibodies: National Institutes of Health Summit on Treatment and Prevention of COVID-19,175,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"Certain infected individuals suppress human immunodeficiency virus (HIV) in the absence of anti-retroviral therapy (ART). Elucidating the underlying mechanism(s) is of high interest. Here we present two contrasting case reports of HIV-infected individuals who controlled plasma viremia for extended periods after undergoing analytical treatment interruption (ATI). In Participant 04, who experienced viral blips and initiated undisclosed self-administration of suboptimal ART detected shortly before day 1,250, phylogenetic analyses of plasma HIV env sequences suggested continuous viral evolution and/or reactivation of pre-existing viral reservoirs over time. Antiviral CD8+ T cell activities were higher in Participant 04 than in Participant 30. In contrast, Participant 30 exhibited potent plasma-IgG-mediated neutralization activity against autologous virus that became ineffective when he experienced sudden plasma viral rebound 1,434 d after ATI due to HIV superinfection. Our data provide insight into distinct mechanisms of post-treatment interruption control and highlight the importance of frequent monitoring of undisclosed use of ART and superinfection during the ATI phase.","[""Case Reports"", ""Journal Article"", ""Research Support, N.I.H., Intramural""]","[""Blazkova J"", ""Gao F"", ""Marichannegowda MH"", ""Justement JS"", ""Shi V"", ""Whitehead EJ"", ""Schneck RF"", ""Huiting ED"", ""Gittens K"", ""Cottrell M"", ""Benko E"", ""Kovacs C"", ""Lack J"", ""Sneller MC"", ""Moir S"", ""Fauci AS"", ""Chun TW""]",10.1038/s41591-021-01503-6,Blazkova J,Nature medicine,1078-8956,11,Nat Med,eng,Chun TW,"[""Adult"", ""Humans"", ""Male"", ""Middle Aged"", ""Anti-HIV Agents"", ""Antibodies, Neutralizing"", ""Antibodies, Viral"", ""CD4 Lymphocyte Count"", ""CD8-Positive T-Lymphocytes"", ""env Gene Products, Human Immunodeficiency Virus"", ""HIV Infections"", ""HIV-1"", ""Immunoglobulin G"", ""Patient Compliance"", ""Viral Load"", ""Viremia"", ""Virus Activation""]",1893-1898,34711975,,2021 Nov,2021,https://pubmed.ncbi.nlm.nih.gov/34711975/,Distinct mechanisms of long-term virologic control in two HIV-infected individuals after treatment interruption of anti-retroviral therapy,27,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
,"[""Journal Article""]","[""Eisinger RW"", ""Fauci AS""]",10.46234/ccdcw2020.163,Eisinger RW,China CDC weekly,2096-7071,39,China CDC Wkly,eng,Fauci AS,[],764-766,34594757,pmc-id: PMC8393014;,2020 Sep 25,2020,https://pubmed.ncbi.nlm.nih.gov/34594757/,Ending the Global HIV Epidemic Begins at the Individual National Level: An Update from the United States,2,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"Anti-HIV broadly neutralizing antibodies (bNAbs) may favor development of antiviral immunity by engaging the immune system during immunotherapy. Targeting integrin α4β7 with an anti-α4β7 monoclonal antibody (Rh-α4β7) affects immune responses in SIV/SHIV-infected macaques. To explore the therapeutic potential of combining bNAbs with α4β7 integrin blockade, SHIVSF162P3-infected, viremic rhesus macaques were treated with bNAbs only (VRC07-523LS and PGT128 anti-HIV antibodies) or a combination of bNAbs and Rh-α4β7 or were left untreated as a control. Treatment with bNAbs alone decreased viremia below 200 copies/ml in all macaques, but seven of eight macaques (87.5%) in the bNAbs-only group rebounded within a median of 3 weeks (95% CI: 2 to 9). In contrast, three of six macaques treated with a combination of Rh-α4β7 and bNAbs (50%) maintained a viremia below 200 copies/ml until the end of the follow-up period; viremia in the other three macaques rebounded within a median of 6 weeks (95% CI: 5 to 11). Thus, there was a modest delay in viral rebound in the macaques treated with the combination antibody therapy compared to bNAbs alone. Our study suggests that α4β7 integrin blockade may prolong virologic control by bNAbs in SHIVSF162P3-infected macaques.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Frank I"", ""Cigoli M"", ""Arif MS"", ""Fahlberg MD"", ""Maldonado S"", ""Calenda G"", ""Pegu A"", ""Yang ES"", ""Rawi R"", ""Chuang GY"", ""Geng H"", ""Liu C"", ""Zhou T"", ""Kwong PD"", ""Arthos J"", ""Cicala C"", ""Grasperge BF"", ""Blanchard JL"", ""Gettie A"", ""Fennessey CM"", ""Keele BF"", ""Vaccari M"", ""Hope TJ"", ""Fauci AS"", ""Mascola JR"", ""Martinelli E""]",10.1126/scitranslmed.abf7201,Frank I,Science translational medicine,1946-6234,607,Sci Transl Med,eng,Martinelli E,"[""Animals"", ""Antibodies, Neutralizing"", ""Antibodies, Viral"", ""Broadly Neutralizing Antibodies"", ""HIV Antibodies"", ""HIV Infections"", ""HIV-1"", ""Integrins"", ""Macaca mulatta"", ""Simian Acquired Immunodeficiency Syndrome"", ""Simian Immunodeficiency Virus""]",,34408080,pmc-id: PMC8977869;manuscript-id: NIHMS1783169;,2021 Aug 18,2021,https://pubmed.ncbi.nlm.nih.gov/34408080/,Blocking α(4)β(7) integrin delays viral rebound in SHIV(SF162P3)-infected macaques treated with anti-HIV broadly neutralizing antibodies,13,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"SARS-CoV-2 mRNA vaccines are highly effective, although weak antibody responses are seen in some individuals with correlates of immunity that remain poorly understood. Here we longitudinally dissected antibody, plasmablast, and memory B cell (MBC) responses to the two-dose Moderna mRNA vaccine in SARS-CoV-2-uninfected adults. Robust, coordinated IgA and IgG antibody responses were preceded by bursts of spike-specific plasmablasts after both doses, but earlier and more intensely after dose two. Distinct antigen-specific MBC populations also emerged post-vaccination with varying kinetics. We identified antigen non-specific pre-vaccination MBC and post-vaccination plasmablasts after dose one and their spike-specific counterparts early after dose two that correlated with subsequent antibody levels. These baseline and response signatures can thus provide early indicators of serological efficacy and explain response variability in the population.","[""Preprint"", ""Journal Article""]","[""Kardava L"", ""Rachmaninoff N"", ""Lau WW"", ""Buckner CM"", ""Trihemasava K"", ""de Assis FL"", ""Wang W"", ""Zhang X"", ""Wang Y"", ""Chiang CI"", ""Narpala S"", ""Reger R"", ""McCormack GE"", ""Seamon CA"", ""Childs RW"", ""Suffredini AF"", ""Strich JR"", ""Chertow DS"", ""Davey RT"", ""Sneller MC"", ""O'Connell S"", ""Li Y"", ""McDermott A"", ""Chun TW"", ""Fauci AS"", ""Tsang JS"", ""Moir S""]",10.1101/2021.07.06.21259528,Kardava L,medRxiv : the preprint server for health sciences,,,medRxiv,eng,Moir S,[],,34268520,pmc-id: PMC8282109;,2021 Jul 7,2021,https://pubmed.ncbi.nlm.nih.gov/34268520/,Pre-vaccination and early B cell signatures predict antibody response to SARS-CoV-2 mRNA vaccine,,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"Both the 1918 influenza pandemic and the 2019‒2021 COVID-19 pandemic are among the most disastrous infectious disease emergences of modern times. In addition to similarities in their clinical, pathological, and epidemiological features, the two pandemics, separated by more than a century, were each met with essentially the same, or very similar, public health responses, and elicited research efforts to control them with vaccines, therapeutics, and other medical approaches. Both pandemics had lasting, if at times invisible, psychosocial effects related to loss and hardship. In considering these two deadly pandemics, we ask: what lessons have we learned over the span of a century, and how are we applying those lessons to the challenges of COVID-19?","[""Historical Article"", ""Journal Article"", ""Research Support, N.I.H., Intramural""]","[""Morens DM"", ""Taubenberger JK"", ""Fauci AS""]",10.2105/AJPH.2021.306326,Morens DM,American journal of public health,0090-0036,7,Am J Public Health,eng,Fauci AS,"[""COVID-19"", ""Communicable Disease Control"", ""History, 20th Century"", ""History, 21st Century"", ""Humans"", ""Influenza, Human"", ""Pandemics"", ""Public Health""]",1267-1272,34111372,pmc-id: PMC8493155;,2021 Jul,2021,https://pubmed.ncbi.nlm.nih.gov/34111372/,"A Centenary Tale of Two Pandemics: The 1918 Influenza Pandemic and COVID-19, Part II",111,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"The NIH Virtual SARS-CoV-2 Antiviral Summit, held on 6 November 2020, was organized to provide an overview on the status and challenges in developing antiviral therapeutics for coronavirus disease 2019 (COVID-19), including combinations of antivirals. Scientific experts from the public and private sectors convened virtually during a live videocast to discuss severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets for drug discovery as well as the preclinical tools needed to develop and evaluate effective small-molecule antivirals. The goals of the Summit were to review the current state of the science, identify unmet research needs, share insights and lessons learned from treating other infectious diseases, identify opportunities for public-private partnerships, and assist the research community in designing and developing antiviral therapeutics. This report includes an overview of therapeutic approaches, individual panel summaries, and a summary of the discussions and perspectives on the challenges ahead for antiviral development.","[""Conference Proceedings""]","[""Hall MD"", ""Anderson JM"", ""Anderson A"", ""Baker D"", ""Bradner J"", ""Brimacombe KR"", ""Campbell EA"", ""Corbett KS"", ""Carter K"", ""Cherry S"", ""Chiang L"", ""Cihlar T"", ""de Wit E"", ""Denison M"", ""Disney M"", ""Fletcher CV"", ""Ford-Scheimer SL"", ""Götte M"", ""Grossman AC"", ""Hayden FG"", ""Hazuda DJ"", ""Lanteri CA"", ""Marston H"", ""Mesecar AD"", ""Moore S"", ""Nwankwo JO"", ""O'Rear J"", ""Painter G"", ""Singh Saikatendu K"", ""Schiffer CA"", ""Sheahan TP"", ""Shi PY"", ""Smyth HD"", ""Sofia MJ"", ""Weetall M"", ""Weller SK"", ""Whitley R"", ""Fauci AS"", ""Austin CP"", ""Collins FS"", ""Conley AJ"", ""Davis MI""]",10.1093/infdis/jiab305,Hall MD,The Journal of infectious diseases,0022-1899,Supplement_1,J Infect Dis,eng,Davis MI,"[""Antiviral Agents"", ""COVID-19"", ""Drug Development"", ""Humans"", ""National Institutes of Health (U.S.)"", ""Peptide Hydrolases"", ""Protease Inhibitors"", ""SARS-CoV-2"", ""United States"", ""Virus Replication"", ""COVID-19 Drug Treatment""]",S1-S21,34111271,pmc-id: PMC8280938;,2021 Jul 15,2021,https://pubmed.ncbi.nlm.nih.gov/34111271/,Report of the National Institutes of Health SARS-CoV-2 Antiviral Therapeutics Summit,224,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"Separated by a century, the influenza pandemic of 1918 and the COVID-19 pandemic of 2019-2021 are among the most disastrous infectious disease emergences of modern times. Although caused by unrelated viruses, the two pandemics are nevertheless similar in their clinical, pathological, and epidemiological features, and in the civic, public health, and medical responses to combat them. Comparing and contrasting the two pandemics, we consider what lessons we have learned over the span of a century and how we are applying those lessons to the challenges of COVID-19.","[""Historical Article"", ""Journal Article"", ""Research Support, N.I.H., Intramural""]","[""Morens DM"", ""Taubenberger JK"", ""Fauci AS""]",10.2105/AJPH.2021.306310,Morens DM,American journal of public health,0090-0036,6,Am J Public Health,eng,Fauci AS,"[""COVID-19"", ""History, 20th Century"", ""History, 21st Century"", ""Humans"", ""Influenza A virus"", ""Influenza, Human"", ""Pandemics"", ""Public Health"", ""SARS-CoV-2""]",1086-1094,33950739,pmc-id: PMC8101587;,2021 Jun,2021,https://pubmed.ncbi.nlm.nih.gov/33950739/,"A Centenary Tale of Two Pandemics: The 1918 Influenza Pandemic and COVID-19, Part I",111,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"Therapeutics for hospitalized COVID-19 patients were identified through a robust research response with several lessons learned: clinical trial data should guide therapeutic use, results should not be extrapolated between disease stages, and robust studies should be designed to give clinically relevant data. These lessons should be applied to the outpatient research response.","[""Journal Article""]","[""Paules CI"", ""Fauci AS""]",10.1016/j.medj.2021.04.015,Paules CI,"Med (New York, N.Y.)",2666-6359,5,Med,eng,Fauci AS,"[""COVID-19"", ""Humans"", ""SARS-CoV-2""]",493-497,33899041,pmc-id: PMC8057546;,2021 May 14,2021,https://pubmed.ncbi.nlm.nih.gov/33899041/,COVID-19: The therapeutic landscape,2,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
,"[""Editorial""]","[""Fauci AS""]",10.1126/science.abi8397,Fauci AS,"Science (New York, N.Y.)",0036-8075,6538,Science,eng,Fauci AS,"[""2019-nCoV Vaccine mRNA-1273"", ""BNT162 Vaccine"", ""Biomedical Research"", ""COVID-19"", ""COVID-19 Vaccines"", ""Clinical Trials as Topic"", ""Drug Development"", ""Humans"", ""Interdisciplinary Research"", ""Vaccinology"", ""Viral Vaccines""]",109,33833099,,2021 Apr 9,2021,https://pubmed.ncbi.nlm.nih.gov/33833099/,The story behind COVID-19 vaccines,372,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted persons with human immunodeficiency virus (HIV), interfering with critical health services for HIV prevention, treatment, and care. While there are multiple profiles of persons living with HIV and the impact of COVID-19 may differ for each, the severity of COVID-19 in persons with HIV is related strongly to the presence of comorbidities that increase the risk of severe disease in COVID-19 patients in the absence of HIV. An effective response to the juxtaposition of the HIV and COVID-19 pandemics requires a novel coordinated and collaborative global effort of scientists, industry, and community partners to accelerate basic and clinical research, as well as implementation science to operationalize evidence-based interventions expeditiously in real-world settings. Accelerated development and clinical evaluation of prevention and treatment countermeasures are urgently needed to mitigate the juxtaposition of the HIV and COVID-19 pandemics.","[""Journal Article"", ""Research Support, Non-U.S. Gov't""]","[""Eisinger RW"", ""Lerner AM"", ""Fauci AS""]",10.1093/infdis/jiab114,Eisinger RW,The Journal of infectious diseases,0022-1899,9,J Infect Dis,eng,Fauci AS,"[""Acquired Immunodeficiency Syndrome"", ""COVID-19"", ""HIV"", ""HIV Infections"", ""Humans"", ""Pandemics"", ""SARS-CoV-2""]",1455-1461,33825905,pmc-id: PMC8083774;,2021 Nov 16,2021,https://pubmed.ncbi.nlm.nih.gov/33825905/,Human Immunodeficiency Virus/AIDS in the Era of Coronavirus Disease 2019: A Juxtaposition of 2 Pandemics,224,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
,"[""Journal Article""]","[""Walensky RP"", ""Walke HT"", ""Fauci AS""]",10.1001/jama.2021.2294,Walensky RP,JAMA,0098-7484,11,JAMA,eng,Fauci AS,"[""COVID-19"", ""COVID-19 Vaccines"", ""Humans"", ""SARS-CoV-2"", ""United States""]",1037-1038,33595644,pmc-id: PMC9009864;manuscript-id: NIHMS1786521;,2021 Mar 16,2021,https://pubmed.ncbi.nlm.nih.gov/33595644/,SARS-CoV-2 Variants of Concern in the United States-Challenges and Opportunities,325,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
,"[""Editorial"", ""Comment""]","[""Mascola JR"", ""Graham BS"", ""Fauci AS""]",10.1001/jama.2021.2088,Mascola JR,JAMA,0098-7484,13,JAMA,eng,Fauci AS,"[""COVID-19"", ""California"", ""Humans"", ""SARS-CoV-2"", ""Spike Glycoprotein, Coronavirus""]",1261-1262,33571363,,2021 Apr 6,2021,https://pubmed.ncbi.nlm.nih.gov/33571363/,SARS-CoV-2 Viral Variants-Tackling a Moving Target,325,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
,"[""Editorial"", ""Interview"", ""Video-Audio Media""]","[""Rubin EJ"", ""Baden LR"", ""Fauci AS"", ""Morrissey S""]",10.1056/NEJMe2101618,Rubin EJ,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Morrissey S,"[""Humans"", ""Antiviral Agents"", ""Attitude to Health"", ""Carrier State"", ""COVID-19"", ""COVID-19 Testing"", ""COVID-19 Vaccines"", ""Disease Transmission, Infectious"", ""Drug Development"", ""Health Education"", ""Immunization Programs"", ""Public Health Practice"", ""SARS-CoV-2"", ""Sensitivity and Specificity"", ""Treatment Outcome""]",e22,33503350,,2021 Jan 28,2021,https://pubmed.ncbi.nlm.nih.gov/33503350/,Audio Interview: A Covid-19 Conversation with Anthony Fauci,384,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"As COVID vaccines roll out, internists and other health care providers are being turned to as trusted sources of information for patients and communities. Here, experts from NIAID outline the current state of knowledge regarding such vaccines. They contrast vaccine platforms, summarize clinical trial data regarding efficacy and safety, and comment on key questions including the ability of current vaccines to protect against infection and to decrease the prevalence of virus in the community.","[""Journal Article""]","[""Connors M"", ""Graham BS"", ""Lane HC"", ""Fauci AS""]",10.7326/M21-0111,Connors M,Annals of internal medicine,0003-4819,5,Ann Intern Med,eng,Fauci AS,"[""COVID-19"", ""COVID-19 Vaccines"", ""Clinical Trials as Topic"", ""Humans"", ""Immunogenicity, Vaccine"", ""Pandemics"", ""Patient Safety"", ""Pneumonia, Viral"", ""SARS-CoV-2"", ""United States"", ""United States Food and Drug Administration"", ""Vaccines, Synthetic"", ""Viral Vaccines"", ""mRNA Vaccines""]",687-690,33460347,pmc-id: PMC7839932;,2021 May,2021,https://pubmed.ncbi.nlm.nih.gov/33460347/,"SARS-CoV-2 Vaccines: Much Accomplished, Much to Learn",174,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"Acute HIV infection is characterized by rapid viral seeding of immunologic inductive sites in the gut followed by the severe depletion of gut CD4+ T cells. Trafficking of α4β7-expressing lymphocytes to the gut is mediated by MAdCAM, the natural ligand of α4β7 that is expressed on gut endothelial cells. MAdCAM signaling through α4β7 costimulates CD4+ T cells and promotes HIV replication. Similar to MAdCAM, the V2 domain of the gp120 HIV envelope protein binds to α4β7 In this study, we report that gp120 V2 shares with MAdCAM the capacity to signal through α4β7 resulting in CD4+ T cell activation and proliferation. As with MAdCAM-mediated costimulation, cellular activation induced by gp120 V2 is inhibited by anti-α4β7 monoclonal antibodies (mAbs). It is also inhibited by anti-V2 domain antibodies including nonneutralizing mAbs that recognize an epitope in V2 that has been linked to reduced risk of acquisition in the RV144 vaccine trial. The capacity of the V2 domain of gp120 to mediate signaling through α4β7 likely impacts early events in HIV infection. The capacity of nonneutralizing V2 antibodies to block this activity reveals a previously unrecognized mechanism whereby such antibodies might impact HIV transmission and pathogenesis.","[""Journal Article"", ""Research Support, N.I.H., Intramural"", ""Research Support, Non-U.S. Gov't""]","[""Goes LR"", ""Sajani A"", ""Sivro A"", ""Olowojesiku R"", ""Ray JC"", ""Perrone I"", ""Yolitz J"", ""Girard A"", ""Leyre L"", ""Wibmer CK"", ""Morris L"", ""Gorini G"", ""Franchini G"", ""Mason RD"", ""Roederer M"", ""Mehandru S"", ""Soares MA"", ""Cicala C"", ""Fauci AS"", ""Arthos J""]",10.1073/pnas.2011501117,Goes LR,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,51,Proc Natl Acad Sci U S A,eng,Arthos J,"[""Anti-HIV Agents"", ""Antibodies, Monoclonal"", ""Antibodies, Neutralizing"", ""CD4-Positive T-Lymphocytes"", ""Cell Proliferation"", ""Epitopes"", ""HIV Envelope Protein gp120"", ""HIV Infections"", ""Host-Pathogen Interactions"", ""Humans"", ""Integrins"", ""Lymphocyte Activation"", ""Protein Domains"", ""Signal Transduction"", ""Simian Immunodeficiency Virus"", ""Tretinoin""]",32566-32573,33288704,pmc-id: PMC7768698;,2020 Dec 22,2020,https://pubmed.ncbi.nlm.nih.gov/33288704/,The V2 loop of HIV gp120 delivers costimulatory signals to CD4(+) T cells through Integrin α(4)β(7) and promotes cellular activation and infection,117,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"Changes in the microbiota are associated with disease susceptibility, immune system development, and responses to treatment. Refocusing research to elucidate the causal links between the human microbiota and infectious and immune-mediated diseases will be critical to harnessing its power to prevent, diagnose, and treat such diseases.","[""Journal Article"", ""Research Support, N.I.H., Extramural""]","[""Giovanni MY"", ""Schneider JS"", ""Calder T"", ""Fauci AS""]",10.1093/infdis/jiaa706,Giovanni MY,The Journal of infectious diseases,0022-1899,1,J Infect Dis,eng,Fauci AS,"[""Asthma"", ""Communicable Diseases"", ""Disease Susceptibility"", ""Fecal Microbiota Transplantation"", ""Humans"", ""Hypersensitivity"", ""Immune System"", ""Immune System Diseases"", ""Microbiota""]",5-8,33188418,pmc-id: PMC8253126;,2021 Jul 2,2021,https://pubmed.ncbi.nlm.nih.gov/33188418/,Refocusing Human Microbiota Research in Infectious and Immune-mediated Diseases: Advancing to the Next Stage,224,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
,"[""Journal Article""]","[""Kim PS"", ""Read SW"", ""Fauci AS""]",10.1001/jama.2020.22813,Kim PS,JAMA,0098-7484,21,JAMA,eng,Fauci AS,"[""Adaptive Clinical Trials as Topic"", ""Antiviral Agents"", ""COVID-19"", ""Drug Discovery"", ""Humans"", ""Pandemics"", ""Randomized Controlled Trials as Topic""]",2149-2150,33175121,,2020 Dec 1,2020,https://pubmed.ncbi.nlm.nih.gov/33175121/,Therapy for Early COVID-19: A Critical Need,324,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
,"[""Published Erratum""]","[""Morens DM"", ""Fauci AS""]",10.1016/j.cell.2020.10.022,Morens DM,Cell,0092-8674,3,Cell,eng,Fauci AS,[],837,33125895,pmc-id: PMC7598893;,2020 Oct 29,2020,https://pubmed.ncbi.nlm.nih.gov/33125895/,Emerging Pandemic Diseases: How We Got to COVID-19,183,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
,"[""Journal Article""]","[""Lerner AM"", ""Folkers GK"", ""Fauci AS""]",10.1001/jama.2020.21946,Lerner AM,JAMA,0098-7484,19,JAMA,eng,Fauci AS,"[""Aerosols"", ""Betacoronavirus"", ""COVID-19"", ""Communicable Disease Control"", ""Coronavirus Infections"", ""Crowding"", ""Hand Hygiene"", ""Humans"", ""Masks"", ""Pandemics"", ""Pneumonia, Viral"", ""SARS-CoV-2"", ""Social Isolation"", ""Ventilation""]",1935-1936,33104157,,2020 Nov 17,2020,https://pubmed.ncbi.nlm.nih.gov/33104157/,"Preventing the Spread of SARS-CoV-2 With Masks and Other ""Low-tech"" Interventions",324,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"Infectious diseases prevalent in humans and animals are caused by pathogens that once emerged from other animal hosts. In addition to these established infections, new infectious diseases periodically emerge. In extreme cases they may cause pandemics such as COVID-19; in other cases, dead-end infections or smaller epidemics result. Established diseases may also re-emerge, for example by extending geographically or by becoming more transmissible or more pathogenic. Disease emergence reflects dynamic balances and imbalances, within complex globally distributed ecosystems comprising humans, animals, pathogens, and the environment. Understanding these variables is a necessary step in controlling future devastating disease emergences.","[""Journal Article"", ""Review""]","[""Morens DM"", ""Fauci AS""]",10.1016/j.cell.2020.08.021,Morens DM,Cell,0092-8674,5,Cell,eng,Fauci AS,"[""COVID-19"", ""Communicable Diseases, Emerging"", ""Coronavirus Infections"", ""Demography"", ""Environment"", ""Host-Pathogen Interactions"", ""Humans"", ""Pandemics"", ""Pneumonia, Viral""]",1077-1092,32846157,pmc-id: PMC7428724;,2020 Sep 3,2020,https://pubmed.ncbi.nlm.nih.gov/32846157/,Emerging Pandemic Diseases: How We Got to COVID-19,182,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
,"[""Editorial"", ""Comment""]","[""Lane HC"", ""Fauci AS""]",10.1056/NEJMe2024638,Lane HC,The New England journal of medicine,0028-4793,8,N Engl J Med,eng,Fauci AS,"[""Dexamethasone"", ""Humans"", ""Pandemics"", ""SARS-CoV-2"", ""COVID-19 Drug Treatment""]",755-757,32678528,pmc-id: PMC7383591;,2021 Feb 25,2021,https://pubmed.ncbi.nlm.nih.gov/32678528/,Research in the Context of a Pandemic,384,Jr5qeopj6pavD4jZ3,r6NaVNgogpd2t79K2
"The design of RNA-guided nucleases with properties not limited by evolution can expand programmable genome-editing capabilities. However, generating diverse multidomain proteins with robust enzymatic properties remains challenging. Here, we use a protein design strategy that couples a structure-guided inverse-folding model with evolution-informed residue constraints to generate active, divergent variants of TnpB, a minimal CRISPR-Cas12-like nuclease, termed SynTnpBs. High-throughput screening of artificial intelligence-generated variants yielded editors that retained or exceeded wild-type activity in bacterial, plant, and human cells. Cryo-electron microscopy-based structure determination of the most divergent variant revealed stabilizing contacts in the RNA-DNA interfaces across conformations, demonstrating the design potential of this approach. Together, these results establish a strategy for creating non-natural RNA-guided nucleases and conformationally active nucleic acid binders, enlarging the designable protein space.","[""Journal Article""]","[""Skopintsev P"", ""Esain-Garcia I"", ""DeTurk EC"", ""Yoon PH"", ""Zhou Z"", ""Weiss T"", ""Kamalu M"", ""Chamraj A"", ""Loi KJ"", ""Langeberg CJ"", ""Boger RS"", ""Nisonoff H"", ""Karp HM"", ""Chen LX"", ""Shi H"", ""Vohra K"", ""Banfield JF"", ""Cate JHD"", ""Jacobsen SE"", ""Doudna JA""]",10.1126/science.aed6123,Skopintsev P,"Science (New York, N.Y.)",0036-8075,6808,Science,eng,Doudna JA,"[""Humans"", ""CRISPR-Cas Systems"", ""Cryoelectron Microscopy"", ""Directed Molecular Evolution"", ""DNA"", ""Gene Editing"", ""Models, Molecular"", ""Protein Conformation"", ""Protein Engineering"", ""RNA"", ""RNA, Guide, CRISPR-Cas Systems"", ""Bacterial Proteins"", ""Endodeoxyribonucleases"", ""CRISPR-Associated Proteins""]",313-318,42462008,,2026 Jul 16,2026,https://pubmed.ncbi.nlm.nih.gov/42462008/,Structure and evolution-guided design of minimal RNA-guided nucleases,393,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Therapeutic genome editing requires delivery of editing molecules to defined cell types, but targeting specificity and efficiency are currently limited. We hypothesized that properties inherent to immune cells, including tissue infiltration and programmed cell recognition, could be harnessed to engineer a cell-based delivery system. We show here that T cells can both produce and transfer editing machinery to target cells. In response to a programmable ligand, engineered T-lymphoid cells can transfer enzymes using complex spatiotemporal logic and deliver cargo in a cell contact-dependent or -independent manner. We demonstrate feasibility of this approach in primary human T cells, establishing a customizable genetic circuit for macromolecular delivery controlled by intercellular interactions.","[""Journal Article"", ""Preprint""]","[""Wasko KM"", ""Maker M"", ""Ngo W"", ""Chen K"", ""Ma E"", ""Pattali R"", ""Chen E"", ""Leung T"", ""Braverman J"", ""Doudna JA""]",10.64898/2026.06.21.729417,Wasko KM,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Doudna JA,[],,42395396,pmc-id: PMC13320803;,2026 Jun 23,2026,https://pubmed.ncbi.nlm.nih.gov/42395396/,Programming T cells for intercellular genome editing,,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Realizing the promise of precision medicine will require the highest standards of accuracy in genome sequencing and analysis. Here we describe challenges and opportunities for the field through the lens of genome data quality. We present recommendations in the context of specific areas of application for genomic sequencing in which isolated standards have arisen: germline sequencing, tumour sequencing, cell-free DNA testing, and sequencing for quality control in genetic therapy. Despite these distinct clinical contexts, technical challenges are often similar; for example, accurately detecting low-frequency genetic variants in tumour sequencing or gene-edited cells. We call for increased synchronization among these communities to establish new medical genome standards that promote confidence in genomic diagnostics and genetic therapies in a time of rapid technology-driven change. We suggest practical approaches for implementing these genome standards across contexts, and identify key areas that require further development.","[""Journal Article""]","[""Ashley EA"", ""Alizadeh AA"", ""Armitage H"", ""Bhatt AS"", ""Blumenfeld Y"", ""Carroll A"", ""Chavez RM"", ""Giannikopoulos P"", ""Grove ME"", ""Halley MC"", ""Khush K"", ""Lennon NJ"", ""Maragh S"", ""Marson A"", ""Paten B"", ""Phillippy AM"", ""Porteus MH"", ""Rehm HL"", ""Ringeisen BR"", ""Salzman J"", ""Schneider VA"", ""Sedlazeck FJ"", ""Steinmetz LM"", ""Urnov FD"", ""Wyman SK"", ""Zook JM"", ""Minor LB"", ""Doudna JA""]",10.1038/s41586-026-10621-5,Ashley EA,Nature,0028-0836,8121,Nature,eng,Doudna JA,"[""Humans"", ""Genome, Human"", ""Genomics"", ""Neoplasms"", ""Precision Medicine"", ""Quality Control"", ""Sequence Analysis, DNA""]",47-58,42387168,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42387168/,Harmonizing standards and resources for the medical genome,655,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
,"[""Published Erratum""]","[""Chen K"", ""Han H"", ""Zhao S"", ""Xu B"", ""Yin B"", ""Lawanprasert A"", ""Trinidad M"", ""Burgstone BW"", ""Murthy N"", ""Doudna JA""]",10.1038/s41587-026-03221-1,Chen K,Nature biotechnology,1087-0156,7,Nat Biotechnol,eng,Doudna JA,[],1238,42315922,pmc-id: PMC13368578;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42315922/,Publisher Correction: Lung and liver editing by lipid nanoparticle delivery of a stable CRISPR-Cas9 ribonucleoprotein,44,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Genetic mutations that drive cancer often occur in tumour-suppressor proteins such as the p53 transcription factor, which is altered in 40-50% of cases1,2. However, current therapies often fail to target these mutations because the mutant proteins typically lack defined drug-binding pockets and restoring their endogenous function has proven challenging. Here we program Cas12a2, an RNA-guided CRISPR nuclease with trans-nucleolytic cleavage activity3,4, to kill cancer cells selectively by targeting cancer-specific transcripts. This approach limited cell growth by inducing trans shredding of chromatin and triggering DNA-damage responses and cell death. In contrast to existing methods, RNA-guided Cas12a2 senses cellular RNA signatures, enabling precise targeting of undruggable mutations. Transcript-activated chromatin shredding provides an innovative approach to precision disease treatments for undruggable targets.","[""Journal Article""]","[""Zeng J"", ""Cheng Z"", ""Chen H"", ""Wang Z"", ""Thompson J"", ""Crosby KT"", ""Han H"", ""Singhal A"", ""Ngo W"", ""Xia C"", ""Rosas-Rivera D"", ""Zhang Z"", ""Kang MH"", ""Mao Y"", ""Diolaiti ME"", ""Lee GC"", ""Diffley JFX"", ""Song Y"", ""Qiu L"", ""Krah NM"", ""Murthy N"", ""Jackson RN"", ""Liu Y"", ""Ashworth A"", ""Doudna JA""]",10.1038/s41586-026-10738-7,Zeng J,Nature,0028-0836,,Nature,eng,Doudna JA,[],,42259916,,2026 Jun 8,2026,https://pubmed.ncbi.nlm.nih.gov/42259916/,Targeting cancer-specific mutations with RNA-triggered chromatin shredding,,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Genetic mutations that drive cancer often occur in tumor suppressor proteins, including the p53 transcription factor which is altered in ~40-50% of cases1,2. However, current therapies fail to target most such mutations because the mutant proteins typically lack defined drug-binding pockets, and restoring the endogenous function has proven challenging. Here, we programmed CRISPR-Cas12a2, an RNA-guided nuclease with trans-nucleolytic cleavage activities3,4, to selectively kill cancer cells by targeting cancer-specific transcripts. This approach eliminates cells by inducing trans chromatin cleavage, triggering DNA damage and cell death. Unlike existing methods, RNA-guided Cas12a2 senses cellular RNA signatures to shred chromatin, enabling precise targeting of undruggable mutations. Transcript-activated chromatin shredding provides an innovative paradigm to develop precision disease treatments for undruggable targets.","[""Journal Article"", ""Preprint""]","[""Zeng J"", ""Cheng Z"", ""Chen H"", ""Thompson J"", ""Crosby KT"", ""Han H"", ""Ngo W"", ""Xia C"", ""Rosas-Rivera D"", ""Kang MH"", ""Mao Y"", ""Lee G"", ""Diffley JFX"", ""Song Y"", ""Qiu L"", ""Krah NM"", ""Murthy N"", ""Jackson RN"", ""Liu Y"", ""Ashworth A"", ""Doudna JA""]",10.64898/2026.05.08.723607,Zeng J,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Doudna JA,[],,42146678,pmc-id: PMC13174608;,2026 May 9,2026,https://pubmed.ncbi.nlm.nih.gov/42146678/,Selective Elimination of TP53 Mutant Cells by Transcript-Activated Chromatin Shredding,,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"CRISPR-Cas systems use RNA-guided proteins for adaptive immunity through a mechanism whose origin is unknown. Here we report the discovery of Viral Interference Programmable Repeat (VIPR) systems consisting of a Vipr protein more ancient than CRISPR-Cas and vrRNAs comprising alternating GGY/NN motifs. Unlike canonical guide RNAs that base pair with nucleic acid targets using an uninterrupted sequence, vrRNAs recognize double-stranded DNA through a noncontiguous code in which the variable NNs of each repeat collectively specify a target that itself contains a gapped recognition sequence. Analysis of natural vrRNA targets suggests VIPR acts against competing phages. We demonstrate programmable phage defense by redirecting the complex for transcriptional repression. These results suggest that the roots of adaptive immunity lie in ancient warfare between viruses, and reveal a new logic for programmable genetic control.","[""Journal Article"", ""Preprint""]","[""Yoon PH"", ""Loi K"", ""Zhang Z"", ""Docter TA"", ""Lopez SC"", ""Langeberg CJ"", ""Moezur-Rehman M"", ""Vohra K"", ""Zhou Z"", ""Shi H"", ""Boger R"", ""Wang PY"", ""Adler BA"", ""Brohawn SG"", ""Doudna JA""]",10.64898/2026.04.26.720920,Yoon PH,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Doudna JA,[],,42094414,pmc-id: PMC13142463;,2026 Jun 25,2026,https://pubmed.ncbi.nlm.nih.gov/42094414/,A Noncontiguous Code for RNA-Guided DNA Recognition Preceded CRISPR,,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Chimallivirus bacteriophages enclose their replicating genomes in a protein-based compartment termed the phage nucleus. While the phage nucleus segregates phage DNA from host immune proteins, it is not known if additional factors are required to protect against DNA-targeting host defenses. Here, we identify a chimallivirus-encoded DarG2-like antitoxin that localizes to the phage nucleus and provides protection against phage-targeting DarTG2 toxin-antitoxin systems. This protein, which we term AdfM (anti-darT factor macro), contains a macrodomain and removes DarT2-mediated ADP-ribose modifications from DNA. In the absence of AdfM, DarT2 modifies phage DNA and restricts chimallivirus replication despite being largely excluded from the phage nucleus. Increasing the nuclear concentration of DarT2 while decreasing the nuclear concentration of AdfM reduces phage replication. These results show that the phage nucleus is insufficient to completely protect the chimallivirus genome from host defenses; rather, it is one component of a multilayered counter-defense strategy.","[""Journal Article""]","[""Morgan CJ"", ""Rani P"", ""Deep A"", ""Liu R"", ""Basu D"", ""Chambers LR"", ""Li YX"", ""Levine M"", ""Hsieh K"", ""Adler BA"", ""Birkholz E"", ""Doudna JA"", ""Villa E"", ""Corbett KD"", ""Pogliano J""]",10.1016/j.celrep.2026.117219,Morgan CJ,Cell reports,2211-1247,4,Cell Rep,eng,Pogliano J,[],117219,41961593,pmc-id: PMC13309987;manuscript-id: NIHMS2170791;,2026 Apr 8,2026,https://pubmed.ncbi.nlm.nih.gov/41961593/,The phage nucleus synergizes with an anti-defense protein to resist bacterial immunity,45,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Rapid identification of viral infections and specific variants in patient samples requires a simple and multiplexed RNA detection method that does not rely on DNA sequencing. Although recent direct detection assays based on CRISPR-Cas13a offer rapid RNA detection by avoiding reverse transcription and DNA amplification required of gold-standard PCR assays, these assays are not easily multiplexed to detect multiple viruses or variants without dividing the sample into separate reactions. Here we show that Cas13a acting on single-target RNAs exhibits variable nuclease activity that depends on the interaction between the target RNA and crRNA. To exploit this feature for multiplexed detection, we devised a crRNA modification strategy that enables programmable tuning of Cas13a's nuclease enzymatic rates. Using a droplet-based Cas13a assay, we demonstrate that kinetic signatures can be harnessed to differentiate among respiratory viruses and SARS-CoV-2 variants in contrived and clinical samples. This kinetic barcoding strategy can be extended to additional RNA targets through simple modification of crRNAs.","[""Journal Article""]","[""Son S"", ""Lyden A"", ""Ng CF"", ""Dextre A"", ""Shu J"", ""Stephens SI"", ""Fozouni P"", ""Knott GJ"", ""Smock DCJ"", ""Liu TY"", ""Boehm D"", ""Simoneau C"", ""Kumar GR"", ""Doudna JA"", ""Ott M"", ""Fletcher DA""]",10.1038/s41551-026-01642-6,Son S,Nature biomedical engineering,2157-846X,,Nat Biomed Eng,eng,Fletcher DA,[],,41917196,,2026 Mar 31,2026,https://pubmed.ncbi.nlm.nih.gov/41917196/,Programmable kinetic barcoding for multiplexed RNA detection with Cas13a,,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"The ability to precisely modify RNA offers opportunities to manipulate the flow of genetic information and influence transcript stability, localization and translation. RNA-targeting technologies enable RNA knockdown, base editing and trans-splicing, but more extensive transcript changes typically require genome editing or rely on the endogenous splicing machinery. Based on the ability of type III-A CRISPR-Csm complexes to catalyze programmable RNA cleavage in human cells, we investigated their potential to induce site-specific deletions while leaving the remainder of the transcript intact. Our data show that CRISPR-Csm complexes can generate short and long RNA excisions within a target transcript, and that the efficiency of this process is enhanced by fusion of Csm to the RNA ligase RtcB. Furthermore, cleavage of two different transcripts can trigger subsequent trans-ligation of the cleaved products into a chimeric transcript (""spligation""). Finally, we apply spligation to endogenous transcripts, using Csm to generate recombinant mRNA in cells independent of canonical splice sites. Collectively, this approach enables new forms of precise RNA manipulation in cells with potential applications in human disease.","[""Journal Article"", ""Preprint""]","[""Colognori DA"", ""Wasko KM"", ""Trinidad MI"", ""Zhou Z"", ""Doudna JA""]",10.64898/2026.03.06.709984,Colognori DA,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Doudna JA,[],,41867802,pmc-id: PMC13001472;,2026 Mar 6,2026,https://pubmed.ncbi.nlm.nih.gov/41867802/,Spligation enables programmable chimeric RNA generation in living cells,,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Engineered T cells, reprogrammed to express chimeric antigen receptors (CAR) or T cell receptors (TCR), have transformed cancer treatment and are being explored as therapeutics for autoimmune and infectious diseases. Enhancing T cell function through genome editing, either by disrupting endogenous genes or precisely inserting DNA payloads, has shown considerable promise1. However, the ex vivo manufacturing process is lengthy and costly, limiting accessibility of these therapies. In vivo generation of CAR T cells could overcome these barriers, but current methods rely either on transient expression with limited durability, or on random integration of DNA payloads that lack specificity. Here we demonstrate that stable and cell-specific transgene expression can be achieved through in vivo site-specific integration of large DNA payloads. We developed a two-vector system to deliver CRISPR-Cas9 ribonucleoproteins and a DNA donor template, using enveloped delivery vehicles and adeno-associated viruses, respectively. We optimized both vectors for T cell-specific delivery and gene-targeting efficiency. By integrating a CAR transgene into a T cell-specific locus, we generate therapeutic levels of CAR T cells in vivo in humanized mouse models of B cell aplasia, and haematological and solid malignancies. These findings offer a pathway to more efficient, precise and widely accessible T cell therapies.","[""Journal Article"", ""Research Support, N.I.H., Extramural""]","[""Nyberg WA"", ""Bernard PL"", ""Ngo W"", ""Wang CH"", ""Ark J"", ""Rothrock A"", ""Borgo GM"", ""Kimmerly GR"", ""Jung JH"", ""Allain V"", ""Hamilton JR"", ""Baldwin A"", ""Stickels R"", ""Wyman S"", ""Khan SH"", ""Lang S"", ""Marsh D"", ""Almudhfar N"", ""Novick C"", ""Mortazavi Y"", ""Zhang S"", ""AbdElwakil MM"", ""Sandoval LR"", ""Hwang S"", ""Chu SN"", ""Jung H"", ""Liu C"", ""Sharma D"", ""McCreary T"", ""Li Z"", ""Satpathy AT"", ""Carnevale J"", ""Rutishauser RL"", ""Cromer MK"", ""Roybal KT"", ""Dodgson SE"", ""Doudna JA"", ""Asokan A"", ""Eyquem J""]",10.1038/s41586-026-10235-x,Nyberg WA,Nature,0028-0836,8110,Nature,eng,Eyquem J,"[""Animals"", ""Mice"", ""T-Lymphocytes"", ""Receptors, Chimeric Antigen"", ""CRISPR-Cas Systems"", ""Humans"", ""Transgenes"", ""Gene Editing"", ""Dependovirus"", ""Female"", ""Cellular Reprogramming"", ""Genetic Vectors"", ""Cell Engineering"", ""Immunotherapy, Adoptive"", ""Male""]",712-721,41851456,pmc-id: PMC13083257;,2026 Apr,2026,https://pubmed.ncbi.nlm.nih.gov/41851456/,In vivo site-specific engineering to reprogram T cells,652,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
,"[""Journal Article""]","[""Weiss T"", ""Kamalu M"", ""Shi H"", ""Wirnowski G"", ""Ingelsson A"", ""Amerasekera J"", ""Vohra K"", ""Trinidad MI"", ""Li Z"", ""Freitas E"", ""Steinmetz N"", ""Ambrose C"", ""Chen K"", ""Doudna JA"", ""Jacobsen SE""]",10.1111/pbi.70644,Weiss T,Plant biotechnology journal,1467-7644,6,Plant Biotechnol J,eng,Jacobsen SE,[],4358-4360,41841630,pmc-id: PMC13205730;,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/41841630/,Efficient Transgene-Free Multiplexed Germline Editing via Viral Delivery of an Engineered TnpB,24,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"TnpB is a diverse family of RNA-guided endonucleases associated with prokaryotic transposons. Because of their small size and putative evolutionary relationship to CRISPR-Cas12, TnpB enzymes hold great potential for genome editing. However, most TnpBs lack robust gene-editing activity. Here, we mapped comprehensive sequence-function landscapes of a TnpB ribonucleoprotein using deep mutational scanning and we discovered activating mutations in both the RNA and the protein. Leveraging the protein's mutational landscape, we constructed a combinatorial library of activating mutations, from which we identified two enhanced TnpB variants. These variants increased editing in human cells, Nicotania benthamiana, pepper and rice. While editing efficiencies varied by target site, engineered variants achieved up to 55% insertion and deletion frequencies (a 50-fold increase over wild type) in N. benthamiana, surpassing ISYmu1 (<7%), AsCas12f-HKRA (<9%) and other compact editors. These findings highlight elements critical for regulating TnpB endonuclease activity and demonstrate latent activity accessible through mutation.","[""Journal Article""]","[""Thornton BW"", ""Weissman RF"", ""Rodriguez JE"", ""Tran RV"", ""Duong BT"", ""Terrace CI"", ""Nagalakshmi U"", ""Austin G"", ""Groover ED"", ""Wang FZ"", ""Park JU"", ""Georgieva V"", ""Tartaglia J"", ""Cho MJ"", ""Dinesh-Kumar SP"", ""Doudna JA"", ""Savage DF""]",10.1038/s41587-026-03059-7,Thornton BW,Nature biotechnology,1087-0156,,Nat Biotechnol,eng,Savage DF,[],,41814095,,2026 Mar 11,2026,https://pubmed.ncbi.nlm.nih.gov/41814095/,Engineered TnpB genome editors for plants and human cells identified by ribonucleoprotein mutational scanning,,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"The open reading frame 8 (ORF8), an accessory protein of SARS-CoV-2, is prone to deletions and mutations across different viral variants, which was first described in several Singapore variants. The reason why viral evolution favors loss or inactivation of ORF8 is not fully understood, although the effects of ORF8 on inflammation, immune evasion, and disease severity have been described. Here we show -using clinical ORF8-deficient viral isolates, virus-like particles (VLPs) and viral replicons- that ORF8 expression dampens viral particle production. ORF8 physically interacts with the viral Spike protein and induces Golgi fragmentation, overall contributing to less virus particle production. Using systematic ORF8 deletions, we mapped the particle-reducing function to its N-terminal signal peptide. Interestingly, this part of ORF8 is severely truncated in the recent XBB.1.5 variant, and when restored, suppresses viral particle production in the context of the entire viral genome. Collectively, our data supports the model that evolutionary pressure exists to delete ORF8 sequence and expression across SARS-CoV-2 variants to fully enable viral particle production.","[""Journal Article"", ""Preprint""]","[""Khalid MM"", ""Chen IP"", ""Soveg FS"", ""Taha TY"", ""Tabata T"", ""Suryawanshi RK"", ""Syed AM"", ""Ciling A"", ""McCavitt-Malvido M"", ""Schulze-Gahmen U"", ""Hayashi J"", ""Kim IJ"", ""Fong SW"", ""Batra J"", ""Kumar GR"", ""Renia L"", ""Ng LF"", ""Krogan NJ"", ""Doudna JA"", ""Verdin E"", ""Ott M""]",10.1101/2024.03.05.583578,Khalid MM,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Ott M,[],,41676649,pmc-id: PMC12889891;,2026 Feb 3,2026,https://pubmed.ncbi.nlm.nih.gov/41676649/,Regulation of virion production by the ORF8 signal peptide across SARS-CoV-2 variants,,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Genome editing enzymes have vast therapeutic potential. However, achieving sufficient delivery in vivo remains a major challenge, because editing machinery is confined to the subset of transfectable cells in a tissue. Here, we tested the possibility that genome editing could be amplified in vivo by programming transfected cells to produce and transfer editing enzymes in lipid vesicles to neighboring cells. Our data show that this NANoparticle-Induced Transfer of Enzyme (NANITE) strategy tripled editing efficiency in cultured cells relative to non-spreading controls. Furthermore, a single intravenous injection of the NANITE plasmid into mice induced ~3-fold higher levels of liver editing at the Ttr locus relative to non-spreading controls, with corresponding reductions in serum transthyretin levels. Amplifying therapeutic enzymes in situ offers a nonviral and non-infectious strategy to overcome low delivery efficiencies and reduce effective dose requirements.","[""Journal Article"", ""Preprint""]","[""Ngo W"", ""Rosas-Rivera D"", ""Wasko KM"", ""Qiu L"", ""Kang MH"", ""Gogna S"", ""Zeng J"", ""Hooks MT"", ""Wu JLY"", ""Li Z"", ""Doudna JA""]",10.64898/2026.01.13.699115,Ngo W,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Doudna JA,[],,41648602,pmc-id: PMC12871335;,2026 Jan 13,2026,https://pubmed.ncbi.nlm.nih.gov/41648602/,Amplified genome editing by in vivo editor production,,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Virus-induced genome editing (VIGE) using compact RNA-guided endonucleases is a transformational new approach in plant biotechnology, enabling tissue-culture-independent and transgene-free genome editing (Hu et al. 2025; Liu et al. 2025; Weiss et al. 2025). We recently established a VIGE approach for heritable editing at single loci in Arabidopsis by delivering the compact genome editor ISYmu1 TnpB (Ymu1) and its guide RNA (gRNA) via Tobacco Rattle Virus (TRV) (Weiss et al. 2025). Here, we greatly improved this approach by devising a multiple gRNA expression system and by utilizing an engineered high-activity Ymu1 variant (Ymu1-WFR) (Zhou et al. 2026) to develop an efficient multiplexed genome editing platform.","[""Journal Article"", ""Preprint""]","[""Weiss T"", ""Kamalu M"", ""Shi H"", ""Wirnowski G"", ""Ingelsson A"", ""Amerasekera J"", ""Vohra K"", ""Trinidad MI"", ""Li Z"", ""Freitas E"", ""Steinmetz N"", ""Ambrose C"", ""Chen K"", ""Doudna JA"", ""Jacobsen SE""]",10.64898/2026.01.23.700382,Weiss T,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Jacobsen SE,[],,41648250,pmc-id: PMC12871731;,2026 Feb 25,2026,https://pubmed.ncbi.nlm.nih.gov/41648250/,Efficient transgene-free multiplexed germline editing via viral delivery of an engineered TnpB,,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"The design of RNA-guided nucleases with properties not limited by evolution can expand programmable genome editing capabilities. However, generating diverse multi-domain proteins with robust enzymatic properties remains challenging. Here we use an artificial intelligence-driven strategy that couples structure-guided inverse protein folding with evolution-informed residue constraints to generate active, divergent variants of TnpB, a minimal CRISPR-Cas12-like nuclease. High-throughput functional screening of AI-generated variants yielded editors that retained or exceeded wild-type activity in bacterial, plant and human cells. Cryo-EM-based structure determination of the most divergent active variant revealed new stabilizing contacts in the RNA/DNA interfaces across conformational states, demonstrating the design potential of this approach. Together these results establish a strategy for creating non-natural RNA-guided nucleases and conformationally active nucleic acid binders, enlarging the designable protein space. An evolution- and structure-conditioned model enables design of active RNA-guided nucleases with new nucleic acid contacts resolved by cryo-EM.","[""Journal Article"", ""Preprint""]","[""Skopintsev P"", ""Esain-Garcia I"", ""DeTurk EC"", ""Yoon PH"", ""Zhou Z"", ""Weiss T"", ""Kamalu M"", ""Chamraj A"", ""Loi KJ"", ""Langeberg CJ"", ""Boger R"", ""Nisonoff H"", ""Karp HM"", ""Chen L"", ""Shi H"", ""Vohra K"", ""Banfield JF"", ""Cate JHD"", ""Jacobsen SE"", ""Doudna JA""]",10.64898/2025.12.08.692503,Skopintsev P,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Doudna JA,[],,41573840,pmc-id: PMC12822741;,2025 Dec 8,2025,https://pubmed.ncbi.nlm.nih.gov/41573840/,Structure and evolution-guided design of minimal RNA-guided nucleases,,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"TnpB is a compact RNA-guided endonuclease and evolutionary ancestor of CRISPR-Cas12 that offers a promising platform for genome engineering. However, the genome-editing activity of TnpBs remains limited and its underlying determinants are poorly understood. Here, we used biochemical and single-molecule assays to examine the DNA-unwinding mechanism of Youngiibacter multivorans TnpB (Ymu1 TnpB). DNA unwinding proceeds through formation of a partially unwound intermediate state to a fully unwound open state. The open state forms inefficiently and collapses readily in the absence of negative supercoiling. An optimized variant, Ymu1-WFR, stabilizes formation of both the intermediate and open states, resulting in enhanced DNA cleavage in vitro and increased genome editing in vivo. These findings identify the physical basis for the observed minimal activities of natural TnpBs, revealing how stabilizing specific unwinding states enables efficient DNA targeting.","[""Journal Article"", ""Preprint""]","[""Zhou Z"", ""Saffarian-Deemyad I"", ""Shi H"", ""Weiss T"", ""Ur-Rehman MM"", ""Vohra K"", ""Skopintsev P"", ""Yoon PH"", ""Trinidad MI"", ""Langeberg CJ"", ""Kamalu M"", ""Amerasekera J"", ""Doherty EE"", ""Aris KDP"", ""Al-Sayyad N"", ""Thornton BW"", ""Weissman RF"", ""Wasko KM"", ""Esain-Garcia I"", ""DeTurk EC"", ""Savage DF"", ""Jacobsen SE"", ""Bryant Z"", ""Doudna JA""]",10.64898/2026.01.09.698545,Zhou Z,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Doudna JA,[],,41542533,pmc-id: PMC12803034;,2026 Jan 9,2026,https://pubmed.ncbi.nlm.nih.gov/41542533/,Stepwise DNA unwinding gates TnpB genome-editing activity,,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Genome editing has revolutionized the treatment of genetic diseases, yet the difficulty of tissue-specific delivery currently limits applications of editing technology. In this Review, we discuss preclinical and clinical advances in delivering genome editors with both established and emerging delivery mechanisms. Targeted delivery promises to considerably expand the therapeutic applicability of genome editing, moving closer to the ideal of a precise 'magic bullet' that safely and effectively treats diverse genetic disorders.","[""Journal Article"", ""Review""]","[""Ngo W"", ""Wu JLY"", ""Wasko KM"", ""Doudna JA""]",10.1038/s41587-025-02945-w,Ngo W,Nature biotechnology,1087-0156,1,Nat Biotechnol,eng,Doudna JA,"[""Humans"", ""Gene Editing"", ""Animals"", ""Genetic Therapy"", ""Gene Transfer Techniques"", ""CRISPR-Cas Systems""]",49-59,41526513,pmc-id: PMC12875382;manuscript-id: NIHMS2132861;,2026 Jan,2026,https://pubmed.ncbi.nlm.nih.gov/41526513/,Targeted delivery of genome editors in vivo,44,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"CRISPR-associated transposases (CASTs) hold tremendous potential for microbial genome editing because of their ability to integrate large DNA cargos in a programmable, site-specific manner. However, their widespread application has been hindered by poorly understood host factor requirements for transposition. To address this gap, we conducted the first genome-wide screen for host factors affecting Vibrio cholerae CAST (VchCAST) activity using an Escherichia coli RB-TnSeq library and identified 15 genes affecting VchCAST transposition. Of these, seven factors were validated to improve VchCAST activity, and two were inhibitory. Guided by the identification of homologous recombination effectors, RecD and RecA, we tested the λ-Red recombineering system in our VchCAST editing vectors and increased editing efficiency by 55.2-fold in E. coli, 5.6-fold in Pseudomonas putida, and 10.8-fold in Klebsiella michiganensis while maintaining high target specificity and similar insertion arrangements. This study improves the understanding of factors affecting VchCAST activity and enhances its efficiency as a bacterial genome editor.","[""Journal Article""]","[""Song LCT"", ""Alker ATP"", ""Oromí-Bosch A"", ""Swartz SE"", ""Martinson JNV"", ""Arora J"", ""Wang AM"", ""Rovinsky R"", ""Smith SJ"", ""Pierce EC"", ""Deutschbauer AM"", ""Doudna JA"", ""Cress BF"", ""Rubin BE""]",10.1126/sciadv.aea1429,Song LCT,Science advances,2375-2548,1,Sci Adv,eng,Rubin BE,"[""Gene Editing"", ""Transposases"", ""Escherichia coli"", ""Vibrio cholerae"", ""CRISPR-Cas Systems"", ""Genome, Bacterial"", ""CRISPR-Associated Proteins""]",eaea1429,41477825,pmc-id: PMC12757027;,2026 Jan 2,2026,https://pubmed.ncbi.nlm.nih.gov/41477825/,Identification of proteins influencing CRISPR-associated transposases for enhanced genome editing,12,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Primary human myeloid cells are promising candidates for immunotherapy, yet efficient and scalable technologies for genetic engineering and screening in these cells are limited. Here we present a virus-like particle (VLP)-based toolkit that delivers diverse CRISPR genome editing modalities to human monocytes, macrophages, and dendritic cells with high efficiency while preserving viability and innate immune responsiveness. VLP-mediated delivery of ribonucleoprotein payloads supports gene knockout, base editing and epigenetic silencing, and enables site-specific integration of large DNA sequences when combined with AAV donors for homology-directed repair. Leveraging sgRNA delivery via VPX-lentivirus combined with Cas9 protein delivery via engineered virus-like particle (eVLP) treatment (""SLICeVLP""), we performed the first pooled loss-of-function screens in human macrophages. We uncovered regulators of TNF production and CD80 expression in human macrophages, converging on TNFAIP3 as a central regulator of inflammatory polarization. TNFAIP3 ablation promoted a pro-inflammatory cell state that is resistant to suppressive polarization, and augmented cytotoxicity of engineered HER2 CAR-macrophages. Taken together, this technology platform enables unbiased discovery and characterization of functional gene targets in primary human myeloid cells.","[""Journal Article"", ""Preprint""]","[""Jung H"", ""Devant P"", ""Ching C"", ""Ota M"", ""Hamilton J"", ""Steinhart Z"", ""Ngo W"", ""Sandoval L"", ""Jung JH"", ""Xu D"", ""An M"", ""Urs E"", ""Chen PA"", ""Allain V"", ""Tada T"", ""Nuñez JK"", ""Landau NR"", ""Liu DR"", ""Eyquem J"", ""Doudna JA"", ""Marson A"", ""Carnevale J""]",10.64898/2025.12.14.692434,Jung H,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Carnevale J,[],,41415457,pmc-id: PMC12710740;,2025 Dec 14,2025,https://pubmed.ncbi.nlm.nih.gov/41415457/,Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells,,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Cyclic dinucleotides (CDNs) and other short oligonucleotides play fundamental roles in immune system activation in organisms ranging from bacteria to humans. In response, viruses use phosphodiesterase (PDE)-mediated oligonucleotide cleavage for immune evasion, a strategy whose diversity has not yet been explored. Here, we use a canonical 2H PDE (2H PDE) structure-based search of prokaryotic and eukaryotic viral sequences to identify an exceptional diversity of 2H PDEs across the virome, including enzymes not detectable with sequence search methods alone. Despite active site conservation, biochemical experiments reveal remarkable substrate specificity of these PDEs that corresponds to variations in the core 2H fold. This nuanced specificity allows 2H PDEs to selectively degrade oligonucleotide messengers to avoid interfering with host nucleotide signaling. Together, these findings nominate viral 2H PDEs as key regulators of CDN signaling across the tree of life.","[""Journal Article""]","[""Doherty EE"", ""Nomburg J"", ""Adler BA"", ""Lopez S"", ""Hsieh K"", ""Price N"", ""Blount N"", ""Doudna JA""]",10.1016/j.chom.2025.10.018,Doherty EE,Cell host & microbe,1931-3128,12,Cell Host Microbe,eng,Doudna JA,"[""Immune Evasion"", ""Phosphoric Diester Hydrolases"", ""Signal Transduction"", ""Humans"", ""Substrate Specificity"", ""Viruses"", ""Catalytic Domain"", ""Viral Proteins""]",2043-2051.e6,41297541,pmc-id: PMC12730640;manuscript-id: NIHMS2124763;,2025 Dec 10,2025,https://pubmed.ncbi.nlm.nih.gov/41297541/,Divergent viral phosphodiesterases for immune signaling evasion,33,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Photoproximity labeling proteomics (PLP) methods have recently shown that cell surface receptors can form lateral interactome networks. Here, we present a paired set of PLP workflows that dynamically track neighborhood changes for oncogenic epidermal growth factor receptor (EGFR) over time, both outside and inside of cells. We achieved this by augmenting the multiscale PLP workflow we call MultiMap, where three photoprobes with different labeling ranges were photoactivated by one photocatalyst, eosin Y, anchored extracellularly and intracellularly on EGFR. We identified hundreds of neighboring proteins that changed within minutes to over 1 h after the addition of EGF. These neighborhoods reveal dynamic interactomes during early, middle and late signaling that drive phosphorylation, internalization, degradation and transcriptional regulation. This rapid 'molecular photographic' labeling approach provides snapshots of signaling neighborhoods, revealing their dynamic nature and potential for drug targeting.","[""Journal Article"", ""Research Support, N.I.H., Extramural"", ""Research Support, Non-U.S. Gov't""]","[""Lin Z"", ""Ngo W"", ""Chou YT"", ""Wu H"", ""Susa KJ"", ""Jun YW"", ""Bivona TG"", ""Doudna JA"", ""Wells JA""]",10.1038/s41589-025-02076-y,Lin Z,Nature chemical biology,1552-4450,2,Nat Chem Biol,eng,Wells JA,"[""ErbB Receptors"", ""Humans"", ""Ligands"", ""Proteomics"", ""Signal Transduction"", ""Epidermal Growth Factor"", ""Phosphorylation"", ""Staining and Labeling""]",192-204,41254216,pmc-id: PMC12858401;,2026 Feb,2026,https://pubmed.ncbi.nlm.nih.gov/41254216/,Temporal photoproximity labeling of ligand-activated EGFR neighborhoods using MultiMap,22,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Genome editing is poised to revolutionize treatment of genetic diseases, but poor understanding and control of DNA repair outcomes hinders its therapeutic potential. DNA repair is especially understudied in nondividing cells like neurons, limiting the efficiency and precision of genome editing in many clinically relevant tissues. Here, we address this barrier by using induced pluripotent stem cells (iPSCs) and iPSC-derived neurons to examine how postmitotic human neurons repair Cas9-induced DNA damage. CRISPR editing outcomes differ dramatically in neurons compared to genetically identical dividing cells: neurons take longer to fully resolve this damage, and upregulate non-canonical DNA repair factors in the process. Manipulating this response with chemical or genetic perturbations allows us to direct DNA repair toward desired editing outcomes in nondividing human neurons, cardiomyocytes, and primary T cells. By studying DNA repair in clinically relevant cells, we reveal unforeseen challenges and opportunities for precise therapeutic editing.","[""Journal Article""]","[""Ramadoss GN"", ""Namaganda SJ"", ""Kumar MM"", ""Hamilton JR"", ""Sharma R"", ""Chow KG"", ""Workley LA"", ""Macklin BL"", ""Sun M"", ""Ha AS"", ""Liu JC"", ""Fellmann C"", ""Watry HL"", ""Dierks PH"", ""Bose RS"", ""Jin J"", ""Perez BS"", ""Sandoval Espinoza CR"", ""Matia MP"", ""Lu SH"", ""Judge LM"", ""Shy BR"", ""Nussenzweig A"", ""Adamson B"", ""Murthy N"", ""Doudna JA"", ""Kampmann M"", ""Conklin BR""]",10.1038/s41467-025-66058-3,Ramadoss GN,Nature communications,2041-1723,1,Nat Commun,eng,Conklin BR,"[""Humans"", ""Induced Pluripotent Stem Cells"", ""Gene Editing"", ""DNA Repair"", ""CRISPR-Cas Systems"", ""Neurons"", ""Myocytes, Cardiac"", ""DNA Damage"", ""T-Lymphocytes""]",9883,41249169,pmc-id: PMC12623481;,2025 Nov 17,2025,https://pubmed.ncbi.nlm.nih.gov/41249169/,Characterizing and controlling CRISPR repair outcomes in nondividing human cells,16,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Antiviral immune systems diversify by integrating new genes into existing pathways, creating new mechanisms of viral resistance. We identified genes encoding a predicted nuclease paired with a trypsin-like protease repeatedly acquired by multiple, otherwise unrelated antiviral immune systems in bacteria. Cell-based and biochemical assays revealed that the nuclease is a proenzyme that cleaves DNA only after activation by its partner protease. Two distinct immune systems, Hachiman and AVAST (antiviral adenosine triphosphatase/nucleoside triphosphatase of the STAND superfamily, Avs), use the same mechanism of proteolytic activation despite their independent evolutionary origins. Examination of nuclease-protease inheritance patterns identified caspase-nuclease (canu) genomic loci that confer antiviral defense in a pathway reminiscent of eukaryotic caspase activation. These results uncover the coordinated activities of pronucleases and their activating proteases within different immune systems and show how coevolution enables defense system innovation.","[""Journal Article""]","[""Tuck OT"", ""Hu JJ"", ""Lopez SC"", ""Adler BA"", ""O'Brien CE"", ""Hsieh K"", ""Meredith C"", ""Loi KJ"", ""Yoon PH"", ""Doherty EE"", ""Lahiri A"", ""Doudna JA""]",10.1126/science.aea8769,Tuck OT,"Science (New York, N.Y.)",0036-8075,6781,Science,eng,Doudna JA,"[""Bacteria"", ""Bacterial Proteins"", ""Caspases"", ""Deoxyribonucleases"", ""DNA Cleavage"", ""Evolution, Molecular"", ""Peptide Hydrolases"", ""Proteolysis"", ""Bacteriophages""]",195-201,41231971,pmc-id: PMC12799240;manuscript-id: NIHMS2127989;,2026 Jan 8,2026,https://pubmed.ncbi.nlm.nih.gov/41231971/,Recurrent acquisition of nuclease-protease pairs in antiviral immunity,391,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Microbial and viral co-evolution has created immunity mechanisms involving oligonucleotide signalling that share mechanistic features with human antiviral systems1. In these pathways, including cyclic oligonucleotide-based antiphage signalling systems (CBASSs) and type III CRISPR systems in bacteria and cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) in humans, oligonucleotide synthesis occurs upon detection of virus or foreign genetic material in the cell, triggering the antiviral response2-4. Here, in an unexpected inversion of this process, we show that the CRISPR-related enzyme mCpol synthesizes cyclic oligonucleotides constitutively as part of an active mechanism that represses a toxic effector. Cell-based experiments demonstrated that the absence or loss of mCpol-produced cyclic oligonucleotides triggers cell death, preventing the spread of viruses that attempt immune evasion by depleting host cyclic nucleotides. Structural and mechanistic investigation revealed mCpol to be a di-adenylate cyclase whose product, c-di-AMP, prevents toxic oligomerization of the effector protein 2TMβ. Analysis of cells by fluorescence microscopy showed that lack of mCpol allows 2TMβ-mediated cell death due to inner membrane collapse. These findings unveil a powerful defence strategy against virus-mediated immune suppression, expanding our understanding of the role of oligonucleotides in immunity.","[""Journal Article"", ""Research Support, U.S. Gov't, P.H.S."", ""Research Support, U.S. Gov't, Non-P.H.S."", ""Research Support, Non-U.S. Gov't"", ""Research Support, N.I.H., Extramural""]","[""Doherty EE"", ""Adler BA"", ""Yoon PH"", ""Hsieh K"", ""Loi K"", ""Armbruster EG"", ""Lahiri A"", ""Bolling CS"", ""Wilcox XE"", ""Akkati A"", ""Iavarone AT"", ""Pogliano J"", ""Doudna JA""]",10.1038/s41586-025-09569-9,Doherty EE,Nature,0028-0836,8091,Nature,eng,Doudna JA,"[""Humans"", ""Adenylyl Cyclases"", ""Cell Death"", ""CRISPR-Cas Systems"", ""Dinucleoside Phosphates"", ""HEK293 Cells"", ""Immune Evasion"", ""Membrane Proteins"", ""Models, Molecular"", ""Oligonucleotides"", ""Signal Transduction"", ""STING Protein""]",997-1004,41034576,pmc-id: PMC12657230;manuscript-id: NIHMS2117476;,2025 Nov,2025,https://pubmed.ncbi.nlm.nih.gov/41034576/,A miniature CRISPR-Cas10 enzyme confers immunity by inhibitory signalling,647,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Cyclic dinucleotides (CDNs) and other short oligonucleotides play fundamental roles in immune system activation in organisms ranging from bacteria to humans. In response, viruses use phosphodiesterase-mediated oligonucleotide cleavage for immune evasion, a strategy whose diversity has not yet been explored. We used a canonical 2H phosphodiesterase (2H PDE) structure-based search of prokaryotic and eukaryotic viral sequences to identify an exceptional diversity of 2H PDEs across the virome, including enzymes not detectable with sequence search methods alone. Despite active site conservation, biochemical experiments revealed remarkable substrate specificity of these PDEs that corresponds to variation in the core 2H fold. This nuanced specificity allows 2H PDEs to selectively degrade oligonucleotide messengers to avoid interfering with host immune signaling. Together, these findings nominate viral 2H PDEs as key regulators of CDN signaling across the tree of life.","[""Journal Article"", ""Preprint""]","[""Doherty EE"", ""Nomburg J"", ""Adler BA"", ""Lopez S"", ""Hsieh K"", ""Price N"", ""Blount N"", ""Doudna JA""]",10.1101/2025.08.21.671373,Doherty EE,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Doudna JA,[],,40894598,pmc-id: PMC12393533;,2025 Aug 21,2025,https://pubmed.ncbi.nlm.nih.gov/40894598/,Divergent viral phosphodiesterases for immune signaling evasion,,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Antiviral immune systems diversify by integrating new genes into existing pathways, creating new mechanisms of viral resistance. We identified genes encoding a predicted nuclease paired with a trypsin-like protease repeatedly acquired by multiple, otherwise unrelated antiviral immune systems in bacteria. Cell-based and biochemical assays revealed the nuclease is a proenzyme that cleaves DNA only after activation by its partner protease. Phylogenetic analysis showed that two distinct immune systems, Hachiman and AVAST, use the same mechanism of proteolytic activation despite their independent evolutionary origins. Examination of nuclease-protease inheritance patterns identified caspase-nuclease (canu) genomic loci that confer antiviral defense in a pathway reminiscent of eukaryotic caspase activation. These results uncover the coordinated activities of pronucleases and their activating proteases within different immune systems and show how coevolution enables defense system innovation.","[""Journal Article"", ""Preprint""]","[""Tuck OT"", ""Hu JJ"", ""Adler BA"", ""O'Brien CE"", ""Lopez SC"", ""Hsieh K"", ""Meredith C"", ""Lahiri A"", ""Doherty EE"", ""Doudna JA""]",10.1101/2025.07.28.667249,Tuck OT,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Doudna JA,[],,40766668,pmc-id: PMC12324324;,2025 Jul 28,2025,https://pubmed.ncbi.nlm.nih.gov/40766668/,Recurrent acquisition of nuclease-protease pairs in antiviral immunity,,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Phage λ, a well-characterized temperate phage, has been recently leveraged for bacterial genome editing by selectively delivering base editors into targeted bacterial species. We extend this concept by engineering phage λ to deliver CRISPR-guided transposases, accomplishing large insertions and targeted gene disruptions. To achieve this, we engineered phage λ using homologous recombination paired with Cas13a-based counterselection for precise phage modifications. Initially, we established the utility of Cas13a in phage λ by conducting minimal recoding edits, deletions, and insertions. Subsequently, we scaled up the engineering to embed the comprehensive DNA-editing CRISPR-Cas transposase (DART) system within the phage genome, creating λ-DART phages. These modified λ-DART phages were then employed to infect Escherichia coli, generating CRISPR RNA-guided transposition events in the host genome. Applying our engineered λ-DART phages to monocultures and a mixed bacterial community comprising three genera led to efficient, precise, and specific gene knockouts and insertions in the targeted E. coli cells, achieving editing efficiencies surpassing 50% of the population. This research enhances phage-mediated genome editing by enabling efficient in situ gene integrations in bacteria, offering an avenue for further application in microbial community contexts. This scalable method enables flexible microbial genome editing in situ to manipulate the function and composition of diverse ecosystems.","[""Journal Article""]","[""Roberts A"", ""Adler BA"", ""Cress BF"", ""Doudna JA"", ""Barrangou R""]",10.1073/pnas.2504853122,Roberts A,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,30,Proc Natl Acad Sci U S A,eng,Barrangou R,"[""Gene Editing"", ""Transposases"", ""CRISPR-Cas Systems"", ""Escherichia coli"", ""Bacteriophage lambda"", ""Genome, Bacterial""]",e2504853122,40711918,pmc-id: PMC12318184;,2025 Jul 29,2025,https://pubmed.ncbi.nlm.nih.gov/40711918/,Phage-based delivery of CRISPR-associated transposases for targeted bacterial editing,122,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"CRISPR-Cas12a enzymes are versatile RNA-guided genome-editing tools with applications encompassing viral diagnosis, agriculture, and human therapeutics. However, their dependence on a 5'-TTTV-3' protospacer adjacent motif (PAM) next to DNA target sequences restricts Cas12a's gene targeting capability to only ∼1% of a typical genome. To mitigate this constraint, we used a bacterial-based directed evolution assay combined with rational engineering to identify variants of Lachnospiraceae bacterium Cas12a with expanded PAM recognition. The resulting Cas12a variants use a range of noncanonical PAMs while retaining recognition of the canonical 5'-TTTV-3' PAM. In particular, biochemical and cell-based assays show that the variant Flex-Cas12a utilizes 5'-NYHV-3' PAMs that expand DNA recognition sites to ∼25% of the human genome. With enhanced targeting versatility, Flex-Cas12a unlocks access to previously inaccessible genomic loci, providing new opportunities for both therapeutic and agricultural genome engineering.","[""Journal Article""]","[""Ma E"", ""Chen K"", ""Shi H"", ""Wasko KM"", ""Esain-Garcia I"", ""Trinidad MI"", ""Zhou K"", ""Ye J"", ""Doudna JA""]",10.1093/nar/gkaf649,Ma E,Nucleic acids research,0305-1048,13,Nucleic Acids Res,eng,Doudna JA,"[""CRISPR-Cas Systems"", ""Gene Editing"", ""Humans"", ""CRISPR-Associated Proteins"", ""Directed Molecular Evolution"", ""Endodeoxyribonucleases"", ""Bacterial Proteins"", ""Genome, Human""]",,40671523,pmc-id: PMC12266133;,2025 Jul 8,2025,https://pubmed.ncbi.nlm.nih.gov/40671523/,Directed evolution expands CRISPR-Cas12a genome-editing capacity,53,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"In recent years, deep learning has revolutionized protein structure prediction, achieving remarkable speed and accuracy. RNA structure prediction, however, has lagged behind. Although several methods have shown some success in predicting RNA secondary and tertiary structures, none have reached the accuracy observed with contemporary protein models. The lack of success of these RNA structure prediction models has been proposed to be due to limited high-quality structural information that can be used as training data. To probe this proposed limitation, we developed a large and diverse dataset comprising paired RNA sequences and their corresponding secondary structures. We assess the utility of this enhanced dataset by retraining on a deep learning model, SincFold. We find that SincFold exhibited improved generalization to some previously unseen RNA families, enhancing its capability to predict accurate de novo RNA secondary structures. The RNASSTR dataset provides a substantial advance for RNA structure modeling, laying a strong foundation for the development of future RNA secondary structure prediction algorithms.","[""Journal Article"", ""Preprint""]","[""Langeberg CJ"", ""Kim T"", ""Nagle R"", ""Meredith C"", ""Garuadapuri DA"", ""Doudna JA"", ""Cate JHD""]",10.1101/2025.05.03.652028,Langeberg CJ,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Cate JHD,[],,40654677,pmc-id: PMC12247784;,2025 Aug 2,2025,https://pubmed.ncbi.nlm.nih.gov/40654677/,Improving RNA Secondary Structure Prediction Through Expanded Training Data,,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"RNA-guided CRISPR-Cas enzymes initiate programmable genome editing by recognizing a 20-base-pair DNA sequence adjacent to a short protospacer-adjacent motif (PAM). To uncover the molecular determinants of high-efficiency editing, we conducted biochemical, biophysical and cell-based assays on S. pyogenes Cas9 ( Spy Cas9) variants with wide-ranging genome editing efficiencies that differ in PAM binding specificity. Our results show that reduced PAM specificity causes persistent non-selective DNA binding and recurrent failures to engage the target sequence through stable guide RNA hybridization, leading to reduced genome editing efficiency in cells. These findings reveal a fundamental trade-off between broad PAM recognition and genome editing effectiveness. We propose that high-efficiency RNA-guided genome editing relies on an optimized two-step target capture process, where selective but low-affinity PAM binding precedes rapid DNA unwinding. This model provides a foundation for engineering more effective CRISPR-Cas and related RNA-guided genome editors.","[""Journal Article"", ""Preprint""]","[""Shi H"", ""Al-Sayyad N"", ""Wasko KM"", ""Trinidad MI"", ""Doherty EE"", ""Vohra K"", ""Boger RS"", ""Colognori D"", ""Cofsky JC"", ""Skopintsev P"", ""Bryant Z"", ""Doudna JA""]",10.1101/2024.10.01.616117,Shi H,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Doudna JA,[],,40376084,pmc-id: PMC12080945;,2024 Oct 2,2024,https://pubmed.ncbi.nlm.nih.gov/40376084/,Rapid two-step target capture ensures efficient CRISPR-Cas9-guided genome editing,,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"RNA-guided CRISPR-Cas enzymes initiate programmable genome editing by recognizing a ∼20-base-pair DNA sequence next to a short protospacer-adjacent motif (PAM). To uncover the molecular determinants of high-efficiency editing, we conducted biochemical, biophysical, and cell-based assays on Streptococcus pyogenes Cas9 (SpyCas9) variants with wide-ranging genome-editing efficiencies that differ in PAM-binding specificity. Our results show that reduced PAM specificity causes persistent non-selective DNA binding and recurrent failures to engage the target sequence through stable guide RNA hybridization, leading to reduced genome-editing efficiency in cells. These findings reveal a fundamental trade-off between broad PAM recognition and genome-editing effectiveness. We propose that high-efficiency RNA-guided genome editing relies on an optimized two-step target capture process, where selective but low-affinity PAM binding precedes rapid DNA unwinding. This model provides a foundation for engineering more effective CRISPR-Cas and related RNA-guided genome editors.","[""Journal Article""]","[""Shi H"", ""Al-Sayyad N"", ""Wasko KM"", ""Trinidad MI"", ""Doherty EE"", ""Vohra K"", ""Boger RS"", ""Colognori D"", ""Cofsky JC"", ""Skopintsev P"", ""Bryant Z"", ""Doudna JA""]",10.1016/j.molcel.2025.03.024,Shi H,Molecular cell,1097-2765,9,Mol Cell,eng,Doudna JA,"[""CRISPR-Cas Systems"", ""Gene Editing"", ""RNA, Guide, CRISPR-Cas Systems"", ""Streptococcus pyogenes"", ""Humans"", ""CRISPR-Associated Protein 9"", ""HEK293 Cells"", ""Bacterial Proteins"", ""DNA"", ""Nucleotide Motifs""]",1730-1742.e9,40273916,pmc-id: PMC12258621;manuscript-id: NIHMS2082181;,2025 May 1,2025,https://pubmed.ncbi.nlm.nih.gov/40273916/,Rapid two-step target capture ensures efficient CRISPR-Cas9-guided genome editing,85,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Genome editing is transforming plant biology by enabling precise DNA modifications. However, delivery of editing systems into plants remains challenging, often requiring slow, genotype-specific methods such as tissue culture or transformation1. Plant viruses, which naturally infect and spread to most tissues, present a promising delivery system for editing reagents. However, many viruses have limited cargo capacities, restricting their ability to carry large CRISPR-Cas systems. Here we engineered tobacco rattle virus (TRV) to carry the compact RNA-guided TnpB enzyme ISYmu1 and its guide RNA. This innovation allowed transgene-free editing of Arabidopsis thaliana in a single step, with edits inherited in the subsequent generation. By overcoming traditional reagent delivery barriers, this approach offers a novel platform for genome editing, which can greatly accelerate plant biotechnology and basic research.","[""Journal Article"", ""Research Support, Non-U.S. Gov't"", ""Research Support, U.S. Gov't, Non-P.H.S.""]","[""Weiss T"", ""Kamalu M"", ""Shi H"", ""Li Z"", ""Amerasekera J"", ""Zhong Z"", ""Adler BA"", ""Song MM"", ""Vohra K"", ""Wirnowski G"", ""Chitkara S"", ""Ambrose C"", ""Steinmetz N"", ""Sridharan A"", ""Sahagun D"", ""Banfield JF"", ""Doudna JA"", ""Jacobsen SE""]",10.1038/s41477-025-01989-9,Weiss T,Nature plants,2055-0278,5,Nat Plants,eng,Jacobsen SE,"[""Arabidopsis"", ""Gene Editing"", ""Plant Viruses"", ""CRISPR-Cas Systems"", ""RNA, Guide, CRISPR-Cas Systems"", ""Plants, Genetically Modified"", ""Transgenes"", ""Genome, Plant""]",967-976,40263581,pmc-id: PMC12095077;,2025 May,2025,https://pubmed.ncbi.nlm.nih.gov/40263581/,Viral delivery of an RNA-guided genome editor for transgene-free germline editing in Arabidopsis,11,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"CRISPR-Cas12a enzymes are versatile RNA-guided genome-editing tools with applications encompassing viral diagnosis, agriculture and human therapeutics. However, their dependence on a 5'-TTTV-3' protospacer-adjacent motif (PAM) next to DNA target sequences restricts Cas12a's gene targeting capability to only ∼1% of a typical genome. To mitigate this constraint, we used a bacterial-based directed evolution assay combined with rational engineering to identify variants of Lachnospiraceae bacterium Cas12a (LbCas12a) with expanded PAM recognition. The resulting Cas12a variants use a range of non-canonical PAMs while retaining recognition of the canonical 5'-TTTV-3' PAM. In particular, biochemical and cell-based assays show that the variant Flex-Cas12a utilizes 5'-NYHV-3' PAMs that expand DNA recognition sites to ∼25% of the human genome. With enhanced targeting versatility, Flex-Cas12a unlocks access to previously inaccessible genomic loci, providing new opportunities for both therapeutic and agricultural genome engineering.","[""Journal Article"", ""Preprint""]","[""Ma E"", ""Chen K"", ""Shi H"", ""Wasko KM"", ""Esain-Garcia I"", ""Trinidad MI"", ""Zhou K"", ""Ye J"", ""Doudna JA""]",10.1101/2025.03.26.645588,Ma E,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Doudna JA,[],,40196639,pmc-id: PMC11974813;,2025 Mar 26,2025,https://pubmed.ncbi.nlm.nih.gov/40196639/,Directed evolution expands CRISPR-Cas12a genome editing capacity,,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Microbial and viral co-evolution has created immunity mechanisms involving oligonucleotide signaling that share mechanistic features with human anti-viral systems 1 . In these pathways, including CBASS and type III CRISPR systems in bacteria and cGAS-STING in humans, oligonucleotide synthesis occurs upon detection of virus or foreign genetic material in the cell, triggering the antiviral response 2-4 . In a surprising inversion of this process, we show here that the CRISPR-related enzyme mCpol synthesizes cyclic oligonucleotides constitutively as part of an active mechanism that maintains cell health. Cell-based experiments demonstrated that the absence or loss of mCpol-produced cyclic oligonucleotides triggers cell death, preventing spread of viruses that attempt immune evasion by depleting host cyclic nucleotides. Structural and mechanistic investigation revealed mCpol to be a di-adenylate cyclase whose product, c-di-AMP, prevents toxic oligomerization of the effector protein 2TMβ. Analysis of cells by fluorescence microscopy showed that lack of mCpol allows 2TMβ-mediated cell death due to inner membrane collapse. These findings unveil a powerful new defense strategy against virus-mediated immune suppression, expanding our understanding of oligonucleotides in cell health and disease. These results raise the possibility of similar protective roles for cyclic oligonucleotides in other organisms including humans.","[""Journal Article"", ""Preprint""]","[""Doherty EE"", ""Adler BA"", ""Yoon PH"", ""Hsieh K"", ""Loi K"", ""Armbuster EG"", ""Lahiri A"", ""Bolling CS"", ""Wilcox XE"", ""Akkati A"", ""Iavarone AT"", ""Pogliano J"", ""Doudna JA""]",10.1101/2025.03.28.646030,Doherty EE,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Doudna JA,[],,40196485,pmc-id: PMC11974785;,2025 Apr 1,2025,https://pubmed.ncbi.nlm.nih.gov/40196485/,A miniature CRISPR-Cas10 enzyme confers immunity by an inverse signaling pathway,,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Many eukaryotic viruses require membrane-bound compartments for replication, but no such organelles are known to be formed by prokaryotic viruses. Bacteriophages of the Chimalliviridae family sequester their genomes within a phage-generated organelle, the phage nucleus, which is enclosed by a lattice of the viral protein ChmA. We show that inhibiting phage nucleus formation arrests infections at an early stage in which the injected phage genome is enclosed within a membrane-bound early phage infection (EPI) vesicle. Early phage genes are expressed from the EPI vesicle, demonstrating its functionality as a prokaryotic, transcriptionally active, membrane-bound organelle. We also show that the phage nucleus is essential, with genome replication beginning after the injected DNA is transferred from the EPI vesicle to the phage nucleus. Our results show that Chimalliviridae require two sophisticated subcellular compartments of distinct compositions and functions that facilitate successive stages of the viral life cycle.","[""Journal Article""]","[""Armbruster EG"", ""Rani P"", ""Lee J"", ""Klusch N"", ""Hutchings J"", ""Hoffman LY"", ""Buschkaemper H"", ""Enustun E"", ""Adler BA"", ""Inlow K"", ""VanderWal AR"", ""Hoffman MY"", ""Daksh D"", ""Aindow A"", ""Deep A"", ""Rodriguez ZK"", ""Morgan CJ"", ""Ghassemian M"", ""Laughlin TG"", ""Charles E"", ""Cress BF"", ""Savage DF"", ""Doudna JA"", ""Pogliano K"", ""Corbett KD"", ""Villa E"", ""Pogliano J""]",10.1016/j.chom.2025.03.005,Armbruster EG,Cell host & microbe,1931-3128,4,Cell Host Microbe,eng,Pogliano J,"[""Genome, Viral"", ""Organelles"", ""Viral Proteins"", ""Bacteriophages"", ""Virus Replication"", ""Cell Nucleus""]",484-497.e6,40168997,pmc-id: PMC12256282;manuscript-id: NIHMS2069937;,2025 Apr 9,2025,https://pubmed.ncbi.nlm.nih.gov/40168997/,Sequential membrane- and protein-bound organelles compartmentalize genomes during phage infection,33,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"The sequence specificity and programmability of DNA binding and cleavage have enabled widespread applications of CRISPR-Cas12a in genetic engineering. As an RNA-guided CRISPR endonuclease, Cas12a engages a 20-base pair (bp) DNA segment by forming a three-stranded R-loop structure in which the guide RNA hybridizes to the DNA target. Here we use single-molecule torque spectroscopy to investigate the dynamics and mechanics of R-loop formation of two widely used Cas12a orthologs at base-pair resolution. We directly observe kinetic intermediates corresponding to a ~5 bp initial RNA-DNA hybridization and a ~17 bp intermediate preceding R-loop completion, followed by transient DNA unwinding that extends beyond the 20 bp R-loop. The complex multistate landscape of R-loop formation is ortholog-dependent and shaped by target sequence, mismatches, and DNA supercoiling. A four-state kinetic model captures essential features of Cas12a R-loop dynamics and provides a biophysical framework for understanding Cas12a activity and specificity.","[""Journal Article""]","[""Aris KDP"", ""Cofsky JC"", ""Shi H"", ""Al-Sayyad N"", ""Ivanov IE"", ""Balaji A"", ""Doudna JA"", ""Bryant Z""]",10.1038/s41467-025-57703-y,Aris KDP,Nature communications,2041-1723,1,Nat Commun,eng,Bryant Z,"[""CRISPR-Cas Systems"", ""CRISPR-Associated Proteins"", ""DNA, Superhelical"", ""R-Loop Structures"", ""RNA, Guide, CRISPR-Cas Systems"", ""Kinetics"", ""DNA"", ""Endodeoxyribonucleases"", ""Bacterial Proteins""]",2939,40133266,pmc-id: PMC11937380;,2025 Mar 26,2025,https://pubmed.ncbi.nlm.nih.gov/40133266/,Dynamic basis of supercoiling-dependent DNA interrogation by Cas12a via R-loop intermediates,16,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Effective genome editing requires a sufficient dose of CRISPR-Cas9 ribonucleoproteins (RNPs) to enter the target cell while minimizing immune responses, off-target editing, and cytotoxicity. Clinical use of Cas9 RNPs currently entails electroporation into cells ex vivo, but no systematic comparison of this method to packaged RNP delivery has been made. Here we compared two delivery strategies, electroporation and enveloped delivery vehicles (EDVs), to investigate the Cas9 dosage requirements for genome editing. Using fluorescence correlation spectroscopy, we determined that >1300 Cas9 RNPs per nucleus are typically required for productive genome editing. EDV-mediated editing was >30-fold more efficient than electroporation, and editing occurs at least 2-fold faster for EDV delivery at comparable total Cas9 RNP doses. We hypothesize that differences in efficacy between these methods result in part from the increased duration of RNP nuclear residence resulting from EDV delivery. Our results directly compare RNP delivery strategies, showing that packaged delivery could dramatically reduce the amount of CRISPR-Cas9 RNPs required for experimental or clinical genome editing.","[""Journal Article""]","[""Karp H"", ""Zoltek M"", ""Wasko K"", ""Vazquez AL"", ""Brim J"", ""Ngo W"", ""Schepartz A"", ""Doudna JA""]",10.1093/nar/gkaf105,Karp H,Nucleic acids research,0305-1048,5,Nucleic Acids Res,eng,Doudna JA,"[""Ribonucleoproteins"", ""Gene Editing"", ""CRISPR-Cas Systems"", ""Humans"", ""Electroporation"", ""HEK293 Cells"", ""CRISPR-Associated Protein 9""]",,40036508,pmc-id: PMC11878570;,2025 Feb 27,2025,https://pubmed.ncbi.nlm.nih.gov/40036508/,Packaged delivery of CRISPR-Cas9 ribonucleoproteins accelerates genome editing,53,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Bacteriophages constitute one of the largest reservoirs of genes of unknown function in the biosphere. Even in well-characterized phages, the functions of most genes remain unknown. Experimental approaches to study phage gene fitness and function at genome scale are lacking, partly because phages subvert many modern functional genomics tools. Here we leverage RNA-targeting dCas13d to selectively interfere with protein translation and to measure phage gene fitness at a transcriptome-wide scale. We find CRISPR Interference through Antisense RNA-Targeting (CRISPRi-ART) to be effective across phage phylogeny, from model ssRNA, ssDNA and dsDNA phages to nucleus-forming jumbo phages. Using CRISPRi-ART, we determine a conserved role of diverse rII homologues in subverting phage Lambda RexAB-mediated immunity to superinfection and identify genes critical for phage fitness. CRISPRi-ART establishes a broad-spectrum phage functional genomics platform, revealing more than 90 previously unknown genes important for phage fitness.","[""Journal Article""]","[""Adler BA"", ""Al-Shimary MJ"", ""Patel JR"", ""Armbruster EG"", ""Colognori D"", ""Charles EJ"", ""Miller KV"", ""Lahiri A"", ""Cui ML"", ""Oromí-Bosch A"", ""Voelker A"", ""Trinidad M"", ""Lee J"", ""Beurnier S"", ""Boger R"", ""Nomburg J"", ""Barrangou R"", ""Mutalik VK"", ""Schoeniger JS"", ""Pogliano JA"", ""Savage DF"", ""Doudna JA"", ""Cress BF""]",10.1038/s41564-025-01935-7,Adler BA,Nature microbiology,2058-5276,3,Nat Microbiol,eng,Cress BF,"[""Bacteriophages"", ""Genomics"", ""CRISPR-Cas Systems"", ""Genome, Viral"", ""Phylogeny"", ""RNA-Binding Proteins"", ""Genetic Fitness"", ""Bacteriophage lambda""]",694-709,40011704,pmc-id: PMC11879866;,2025 Mar,2025,https://pubmed.ncbi.nlm.nih.gov/40011704/,CRISPRi-ART enables functional genomics of diverse bacteriophages using RNA-binding dCas13d,10,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"TnpB is a diverse family of RNA-guided endonucleases associated with prokaryotic transposons. Due to their small size and putative evolutionary relationship to CRISPR-Cas12, TnpB enzymes hold significant potential for genome editing. However, most TnpBs lack robust gene editing activity, and unbiased profiling of mutational effects on editing activity has not been explored. Here, we mapped comprehensive sequence-function landscapes of a TnpB ribonucleoprotein and discovered many activating mutations in both the protein and RNA. One- and two-position RNA mutants outperform existing variants, highlighting the utility of systematic RNA scaffold mutagenesis. Leveraging the protein's mutational landscape, we identified enhanced TnpB variants from a combinatorial library of activating mutations. These variants enhanced editing in human cells, N. benthamiana, pepper, and rice, with up to a fifty-fold increase compared to wild-type TnpB. These findings highlight previously unknown elements critical for regulating TnpB endonuclease activity and reveal surprising latent activity accessible through mutation.","[""Journal Article"", ""Preprint""]","[""Thornton BW"", ""Weissman RF"", ""Rodriguez JE"", ""Tran RV"", ""Duong BT"", ""Terrace CI"", ""Nagalakshmi U"", ""Austin G"", ""Groover ED"", ""Wang FZ"", ""Park JU"", ""Georgieva V"", ""Tartaglia J"", ""Cho MJ"", ""Dinesh-Kumar SP"", ""Doudna JA"", ""Savage DF""]",10.1101/2025.02.11.637750,Thornton BW,bioRxiv : the preprint server for biology,2692-8205,,bioRxiv,eng,Savage DF,[],,39990302,pmc-id: PMC11844463;,2025 Oct 30,2025,https://pubmed.ncbi.nlm.nih.gov/39990302/,Mutational scanning of TnpB reveals latent activity for genome editing,,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Understanding the diverse dynamic behaviors of individual RNA molecules in single cells requires visualizing them at high resolution in real time. However, single-molecule live-cell imaging of unmodified endogenous RNA has not yet been achieved in a generalizable manner. Here, we present single-molecule live-cell fluorescence in situ hybridization (smLiveFISH), a robust approach that combines the programmable RNA-guided, RNA-targeting CRISPR-Csm complex with multiplexed guide RNAs for direct and efficient visualization of single RNA molecules in a range of cell types, including primary cells. Using smLiveFISH, we track individual native NOTCH2 and MAP1B transcripts in living cells and identify two distinct localization mechanisms including the cotranslational translocation of NOTCH2 mRNA at the endoplasmic reticulum and directional transport of MAP1B mRNA toward the cell periphery. This method has the potential to unlock principles governing the spatiotemporal organization of native transcripts in health and disease.","[""Journal Article""]","[""Xia C"", ""Colognori D"", ""Jiang XS"", ""Xu K"", ""Doudna JA""]",10.1038/s41587-024-02540-5,Xia C,Nature biotechnology,1087-0156,12,Nat Biotechnol,eng,Doudna JA,"[""In Situ Hybridization, Fluorescence"", ""Humans"", ""Single Molecule Imaging"", ""CRISPR-Cas Systems"", ""RNA, Messenger"", ""RNA"", ""Animals"", ""Single-Cell Analysis"", ""Receptor, Notch2"", ""Mice"", ""RNA, Guide, CRISPR-Cas Systems"", ""Clustered Regularly Interspaced Short Palindromic Repeats""]",2023-2030,39966655,pmc-id: PMC12700784;,2025 Dec,2025,https://pubmed.ncbi.nlm.nih.gov/39966655/,Single-molecule live-cell RNA imaging with CRISPR-Csm,43,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"The widespread application of genome editing to treat and cure disease requires the delivery of genome editors into the nucleus of target cells. Enveloped delivery vehicles (EDVs) are engineered virally derived particles capable of packaging and delivering CRISPR-Cas9 ribonucleoproteins (RNPs). However, the presence of lentiviral genome encapsulation and replication proteins in EDVs has obscured the underlying delivery mechanism and precluded particle optimization. Here, we show that Cas9 RNP nuclear delivery is independent of the native lentiviral capsid structure. Instead, EDV-mediated genome editing activity corresponds directly to the number of nuclear localization sequences on the Cas9 enzyme. EDV structural analysis using cryo-electron tomography and small molecule inhibitors guided the removal of ~80% of viral residues, creating a minimal EDV (miniEDV) that retains full RNP delivery capability. MiniEDVs are 25% smaller yet package equivalent amounts of Cas9 RNPs relative to the original EDVs and demonstrated increased editing in cell lines and therapeutically relevant primary human T cells. These results show that virally derived particles can be streamlined to create efficacious genome editing delivery vehicles with simpler production and manufacturing.","[""Journal Article""]","[""Ngo W"", ""Peukes J"", ""Baldwin A"", ""Xue ZW"", ""Hwang S"", ""Stickels RR"", ""Lin Z"", ""Satpathy AT"", ""Wells JA"", ""Schekman R"", ""Nogales E"", ""Doudna JA""]",10.1073/pnas.2413519121,Ngo W,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,1,Proc Natl Acad Sci U S A,eng,Doudna JA,"[""Gene Editing"", ""Humans"", ""CRISPR-Cas Systems"", ""Lentivirus"", ""Ribonucleoproteins"", ""HEK293 Cells"", ""CRISPR-Associated Protein 9"", ""Genetic Vectors""]",e2413519121,39793042,pmc-id: PMC11725915;,2025 Jan 7,2025,https://pubmed.ncbi.nlm.nih.gov/39793042/,Mechanism-guided engineering of a minimal biological particle for genome editing,122,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Molecular structure prediction and homology detection offer promising paths to discovering protein function and evolutionary relationships. However, current approaches lack statistical reliability assurances, limiting their practical utility for selecting proteins for further experimental and in-silico characterization. To address this challenge, we introduce a statistically principled approach to protein search leveraging principles from conformal prediction, offering a framework that ensures statistical guarantees with user-specified risk and provides calibrated probabilities (rather than raw ML scores) for any protein search model. Our method (1) lets users select many biologically-relevant loss metrics (i.e. false discovery rate) and assigns reliable functional probabilities for annotating genes of unknown function; (2) achieves state-of-the-art performance in enzyme classification without training new models; and (3) robustly and rapidly pre-filters proteins for computationally intensive structural alignment algorithms. Our framework enhances the reliability of protein homology detection and enables the discovery of uncharacterized proteins with likely desirable functional properties.","[""Journal Article"", ""Research Support, N.I.H., Extramural""]","[""Boger RS"", ""Chithrananda S"", ""Angelopoulos AN"", ""Yoon PH"", ""Jordan MI"", ""Doudna JA""]",10.1038/s41467-024-55676-y,Boger RS,Nature communications,2041-1723,1,Nat Commun,eng,Doudna JA,"[""Proteins"", ""Algorithms"", ""Computational Biology"", ""Protein Conformation"", ""Data Mining"", ""Databases, Protein"", ""Reproducibility of Results""]",85,39747192,pmc-id: PMC11695924;,2025 Jan 2,2025,https://pubmed.ncbi.nlm.nih.gov/39747192/,Functional protein mining with conformal guarantees,16,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"RNA-guided endonucleases are involved in processes ranging from adaptive immunity to site-specific transposition and have revolutionized genome editing. CRISPR-Cas9, -Cas12 and related proteins use guide RNAs to recognize ∼20-nucleotide target sites within genomic DNA by mechanisms that are not yet fully understood. We used structural and biochemical methods to assess early steps in DNA recognition by Cas12a protein-guide RNA complexes. We show here that Cas12a initiates DNA target recognition by bending DNA to induce transient nucleotide flipping that exposes nucleobases for DNA-RNA hybridization. Cryo-EM structural analysis of a trapped Cas12a-RNA-DNA surveillance complex and fluorescence-based conformational probing show that Cas12a-induced DNA helix destabilization enables target discovery and engagement. This mechanism of initial DNA interrogation resembles that of CRISPR-Cas9 despite distinct evolutionary origins and different RNA-DNA hybridization directionality of these enzyme families. Our findings support a model in which RNA-mediated DNA interference begins with local helix distortion by transient CRISPR-Cas protein binding.","[""Journal Article"", ""Research Support, N.I.H., Extramural""]","[""Soczek KM"", ""Cofsky JC"", ""Tuck OT"", ""Shi H"", ""Doudna JA""]",10.1093/nar/gkae1192,Soczek KM,Nucleic acids research,0305-1048,2,Nucleic Acids Res,eng,Doudna JA,"[""CRISPR-Cas Systems"", ""CRISPR-Associated Proteins"", ""DNA"", ""Base Pairing"", ""RNA, Guide, CRISPR-Cas Systems"", ""Endodeoxyribonucleases"", ""Bacterial Proteins"", ""Nucleic Acid Conformation"", ""Gene Editing"", ""Cryoelectron Microscopy"", ""Models, Molecular""]",,39698811,pmc-id: PMC11754666;,2025 Jan 11,2025,https://pubmed.ncbi.nlm.nih.gov/39698811/,CRISPR-Cas12a bends DNA to destabilize base pairs during target interrogation,53,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Structured RNA lies at the heart of many central biological processes, from gene expression to catalysis. RNA structure prediction is not yet possible due to a lack of high-quality reference data associated with organismal phenotypes that could inform RNA function. We present GARNET (Gtdb Acquired RNa with Environmental Temperatures), a new database for RNA structural and functional analysis anchored to the Genome Taxonomy Database (GTDB). GARNET links RNA sequences to experimental and predicted optimal growth temperatures of GTDB reference organisms. Using GARNET, we develop sequence- and structure-aware RNA generative models, with overlapping triplet tokenization providing optimal encoding for a GPT-like model. Leveraging hyperthermophilic RNAs in GARNET and these RNA generative models, we identify mutations in ribosomal RNA that confer increased thermostability to the Escherichia coli ribosome. The GTDB-derived data and deep learning models presented here provide a foundation for understanding the connections between RNA sequence, structure, and function.","[""Journal Article"", ""Research Support, N.I.H., Extramural""]","[""Shulgina Y"", ""Trinidad MI"", ""Langeberg CJ"", ""Nisonoff H"", ""Chithrananda S"", ""Skopintsev P"", ""Nissley AJ"", ""Patel J"", ""Boger RS"", ""Shi H"", ""Yoon PH"", ""Doherty EE"", ""Pande T"", ""Iyer AM"", ""Doudna JA"", ""Cate JHD""]",10.1038/s41467-024-54812-y,Shulgina Y,Nature communications,2041-1723,1,Nat Commun,eng,Cate JHD,"[""Mutation"", ""Escherichia coli"", ""Nucleic Acid Conformation"", ""RNA"", ""RNA, Ribosomal"", ""Ribosomes"", ""Deep Learning""]",10627,39638800,pmc-id: PMC11621547;,2024 Dec 5,2024,https://pubmed.ncbi.nlm.nih.gov/39638800/,RNA language models predict mutations that improve RNA function,15,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"All lineages of SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, contain mutations between amino acids 199 and 205 in the nucleocapsid (N) protein that are associated with increased infectivity. The effects of these mutations have been difficult to determine because N protein contributes to both viral replication and viral particle assembly during infection. Here, we used single-cycle infection and virus-like particle assays to show that N protein phosphorylation has opposing effects on viral assembly and genome replication. Ancestral SARS-CoV-2 N protein is densely phosphorylated, leading to higher levels of genome replication but 10-fold lower particle assembly compared to evolved variants with low N protein phosphorylation, such as Delta (N:R203M), Iota (N:S202R), and B.1.2 (N:P199L). A new open reading frame encoding a truncated N protein called N*, which occurs in the B.1.1 lineage and subsequent lineages of the Alpha, Gamma, and Omicron variants, supports high levels of both assembly and replication. Our findings help explain the enhanced fitness of viral variants of concern and a potential avenue for continued viral selection.","[""Journal Article"", ""Research Support, N.I.H., Extramural""]","[""Syed AM"", ""Ciling A"", ""Chen IP"", ""Carlson CR"", ""Adly AN"", ""Martin HS"", ""Taha TY"", ""Khalid MM"", ""Price N"", ""Bouhaddou M"", ""Ummadi MR"", ""Moen JM"", ""Krogan NJ"", ""Morgan DO"", ""Ott M"", ""Doudna JA""]",10.1371/journal.ppat.1012741,Syed AM,PLoS pathogens,1553-7366,11,PLoS Pathog,eng,Doudna JA,"[""SARS-CoV-2"", ""Phosphorylation"", ""Humans"", ""Virus Replication"", ""Evolution, Molecular"", ""COVID-19"", ""Coronavirus Nucleocapsid Proteins"", ""Phosphoproteins"", ""Virus Assembly"", ""Mutation"", ""Vero Cells"", ""Chlorocebus aethiops"", ""Animals""]",e1012741,39571001,pmc-id: PMC11620656;,2024 Nov,2024,https://pubmed.ncbi.nlm.nih.gov/39571001/,SARS-CoV-2 evolution balances conflicting roles of N protein phosphorylation,20,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Lipid nanoparticle (LNP) delivery of clustered regularly interspaced short palindromic repeat (CRISPR) ribonucleoproteins (RNPs) could enable high-efficiency, low-toxicity and scalable in vivo genome editing if efficacious RNP-LNP complexes can be reliably produced. Here we engineer a thermostable Cas9 from Geobacillus stearothermophilus (GeoCas9) to generate iGeoCas9 variants capable of >100× more genome editing of cells and organs compared with the native GeoCas9 enzyme. Furthermore, iGeoCas9 RNP-LNP complexes edit a variety of cell types and induce homology-directed repair in cells receiving codelivered single-stranded DNA templates. Using tissue-selective LNP formulations, we observe genome-editing levels of 16‒37% in the liver and lungs of reporter mice that receive single intravenous injections of iGeoCas9 RNP-LNPs. In addition, iGeoCas9 RNPs complexed to biodegradable LNPs edit the disease-causing SFTPC gene in lung tissue with 19% average efficiency, representing a major improvement over genome-editing levels observed previously using viral or nonviral delivery strategies. These results show that thermostable Cas9 RNP-LNP complexes can expand the therapeutic potential of genome editing.","[""Journal Article""]","[""Chen K"", ""Han H"", ""Zhao S"", ""Xu B"", ""Yin B"", ""Lawanprasert A"", ""Trinidad M"", ""Burgstone BW"", ""Murthy N"", ""Doudna JA""]",10.1038/s41587-024-02437-3,Chen K,Nature biotechnology,1087-0156,9,Nat Biotechnol,eng,Doudna JA,"[""Gene Editing"", ""Animals"", ""CRISPR-Cas Systems"", ""Ribonucleoproteins"", ""Mice"", ""Nanoparticles"", ""Liver"", ""Lung"", ""CRISPR-Associated Protein 9"", ""Humans"", ""Lipids"", ""Liposomes""]",1445-1457,39415058,pmc-id: PMC12000389;manuscript-id: NIHMS2042429;,2025 Sep,2025,https://pubmed.ncbi.nlm.nih.gov/39415058/,Lung and liver editing by lipid nanoparticle delivery of a stable CRISPR-Cas9 ribonucleoprotein,43,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"Hachiman is a broad-spectrum antiphage defense system of unknown function. We show here that Hachiman is a heterodimeric nuclease-helicase complex, HamAB. HamA, previously a protein of unknown function, is the effector nuclease. HamB is the sensor helicase. HamB constrains HamA activity during surveillance of intact double-stranded DNA (dsDNA). When the HamAB complex detects DNA damage, HamB helicase activity activates HamA, unleashing nuclease activity. Hachiman activation degrades all DNA in the cell, creating ""phantom"" cells devoid of both phage and host DNA. We demonstrate Hachiman activation in the absence of phage by treatment with DNA-damaging agents, suggesting that Hachiman responds to aberrant DNA states. Phylogenetic similarities between the Hachiman helicase and enzymes from eukaryotes and archaea suggest deep functional symmetries with other important helicases across domains of life.","[""Journal Article""]","[""Tuck OT"", ""Adler BA"", ""Armbruster EG"", ""Lahiri A"", ""Hu JJ"", ""Zhou J"", ""Pogliano J"", ""Doudna JA""]",10.1016/j.cell.2024.09.020,Tuck OT,Cell,0092-8674,24,Cell,eng,Doudna JA,"[""Bacteriophages"", ""Cryoelectron Microscopy"", ""Deoxyribonucleases"", ""Dimerization"", ""DNA Damage"", ""DNA Helicases"", ""Escherichia coli"", ""Escherichia coli Proteins""]",6914-6928.e20,39395413,pmc-id: PMC12278908;manuscript-id: NIHMS2091420;,2024 Nov 27,2024,https://pubmed.ncbi.nlm.nih.gov/39395413/,Genome integrity sensing by the broad-spectrum Hachiman antiphage defense complex,187,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
,"[""Published Erratum""]","[""Nomburg J"", ""Doherty EE"", ""Price N"", ""Bellieny-Rabelo D"", ""Zhu YK"", ""Doudna JA""]",10.1038/s41586-024-08068-7,Nomburg J,Nature,0028-0836,8033,Nature,eng,Doudna JA,[],E4,39313532,pmc-id: PMC11464421;,2024 Oct,2024,https://pubmed.ncbi.nlm.nih.gov/39313532/,Author Correction: Birth of protein folds and functions in the virome,634,9zYNER85lvMln0RUk,Zd9rtnrjTzxwmc0k7
"The modified Morrow surgery is the gold standard surgical treatment for hypertrophic obstructive cardiomyopathy (HOCM). While effective, it carries a risk of postoperative severe multi-organ dysfunction and its impact on long-term cardiovascular outcomes remains poorly understood and controversial. This observational cohort study included 380 HOCM patients undergoing the modified Morrow surgery between July 2015 and March 2025. Severe multi-organ dysfunction was defined as a maximum Sequential Organ Failure Assessment (SOFA) score ≥ 11. The primary endpoint was the long-term incidence of major adverse cardiac and cerebrovascular events (MACCEs). Secondary endpoints included heart failure hospitalization (HFH), postoperative atrial fibrillation (AF) ablation, and cardiovascular mortality. Compared to patients without severe multi-organ dysfunction (SOFA Maximum < 11, n = 234), those with SOFA Maximum ≥ 11 (n = 146) had significantly higher rates of MACCEs (53.4% vs. 17.5%, p < 0.001), cardiovascular mortality (11.6% vs. 0.9%, p < 0.001), HFH (21.9% vs. 8.5%, p < 0.001), and postoperative AF ablation (17.8% vs. 3.8%, p < 0.001). Multivariable Cox proportional hazards regression demonstrated that severe multi-organ dysfunction was independently associated with cardiovascular mortality (HR = 4.157, p = 0.047), MACCEs (HR = 2.296, p < 0.001), HFH (HR = 1.834, p = 0.042), and postoperative AF ablation (HR = 3.987, p < 0.001). Other independent predictors included family history of hypertrophic cardiomyopathy, left ventricular end-systolic dimension, postoperative left ventricular outflow tract velocity, and postoperative surgical intensive care unit ventilation time. Postoperative severe multi-organ dysfunction is independently associated with an increased risk of adverse long-term outcomes after modified Morrow surgery. Incorporating the SOFA score into postoperative risk stratification may help identify high-risk patients warranting intensified long-term management.","[""Journal Article"", ""Observational Study""]","[""Wang T"", ""Ta L"", ""Zhang K"", ""Dong R"", ""Xiao Y"", ""Wang J""]",10.1002/clc.70434,Wang T,Clinical cardiology,0160-9289,8,Clin Cardiol,eng,Wang J,"[""Humans"", ""Female"", ""Male"", ""Cardiomyopathy, Hypertrophic"", ""Multiple Organ Failure"", ""Postoperative Complications"", ""Time Factors"", ""Risk Factors"", ""Cardiac Surgical Procedures"", ""Treatment Outcome"", ""Aged"", ""Middle Aged"", ""Incidence"", ""Retrospective Studies"", ""Follow-Up Studies"", ""Severity of Illness Index""]",e70434,42545076,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42545076/,Impact of Severe Postoperative Multi-Organ Dysfunction on Long-Term Outcomes After Modified Morrow Surgery,49,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"This study aimed to examine the changes in orthorexia nervosa (ON) tendencies among dancers at different levels before and during the COVID-19 pandemic. This retrospective repeated-measures observational study included 128 professional, semi-professional, and amateur dancers (86 females, 42 males; 19-40 years) from various dance styles. Orthorexia nervosa tendencies before and during COVID-19 were assessed using ORTO-11 and ORTO-15. Physical activity and anthropometric data were collected for both recalled pre-pandemic and pandemic periods, while energy and macronutrient intakes were assessed using a retrospective 24-h dietary recall. Data were analyzed using paired tests, effect sizes (ES), and multivariate linear regression. During the pandemic, dancers reported approximately 50% lower weekly dance frequency and daily dance duration than recalled pre-pandemic values, with large and significant effect sizes. Significant decreases were observed in ORTO-11 and ORTO-15 scores, indicating an increase in orthorexic tendencies. Pandemic-period self-reported body weight was higher than pre-pandemic body weight, whereas BMI did not differ significantly between the recalled pre-pandemic and pandemic-period assessments. In multivariate analyses, female sex remained an independent predictor for both ORTO-11 and ORTO-15 scores. Compared with recalled pre-pandemic scores, pandemic-period ORTO-11 and ORTO-15 scores were lower, suggesting higher ORTO-measured health-oriented eating tendencies among dancers. Given the retrospective self-report design and the methodological limitations of ORTO-based instruments, these findings should not be interpreted as evidence of clinical ON prevalence or precise longitudinal change. Nevertheless, these ORTO-measured tendencies appeared to differ not only behaviorally but also in relation to nutrient intake patterns. Female sex was associated with pandemic-period ORTO scores, but this finding should be interpreted cautiously because psychological, sociocultural, and clinical variables were not assessed.","[""Journal Article"", ""Observational Study""]","[""Ozlu Karahan T"", ""Kenger EB"", ""Tekin D"", ""Agopyan A""]",10.1111/jhn.70324,Ozlu Karahan T,Journal of human nutrition and dietetics : the official journal of the British Dietetic Association,0952-3871,4,J Hum Nutr Diet,eng,Agopyan A,"[""Humans"", ""Dancing"", ""Female"", ""COVID-19"", ""Retrospective Studies"", ""Adult"", ""Male"", ""Feeding and Eating Disorders"", ""Multivariate Analysis"", ""Young Adult"", ""Feeding Behavior"", ""SARS-CoV-2"", ""Pandemics"", ""Exercise"", ""Diet"", ""Energy Intake""]",e70324,42544867,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544867/,ORTO-Measured Orthorexia Nervosa-Related Tendencies Among Dancers Before and During the COVID-19 Pandemic: A Multivariate Analysis,39,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Cutaneous lupus erythematosus (CLE) encompasses a heterogeneous group of autoimmune skin manifestations that often overlap clinically with other inflammatory dermatoses, particularly rosacea. While histopathology remains the gold standard, its invasiveness limits routine and longitudinal use. Line-field confocal optical coherence tomography (LC-OCT) is an emerging non-invasive imaging modality capable of providing real-time, near-histological resolution of skin architecture. In this single-center cross-sectional observational study, 45 patients (30 CLE: 16 acute, 5 subacute, 9 chronic; 15 rosacea) underwent LC-OCT imaging of active lesions. Images were independently evaluated using predefined criteria reflecting histopathological features. LC-OCT identified key histopathological correlates of CLE in vivo. Interface dermatitis features (including dermoepidermal junction disruption, basal cell vacuolization and band-like inflammatory infiltrate) were highly prevalent in ACLE and SCLE, while chronic CLE was characterized by epidermal atrophy, hyperkeratosis, fibrosis and adnexal destruction. In contrast, rosacea exhibited a vascular and folliculocentric pattern with frequent peri-adnexal inflammation and Demodex infestation, without interface changes. Interobserver agreement was substantial to excellent for most criteria. In the ACLE versus rosacea comparison, interface dermatitis features like band-like DEJ infiltrate, DEJ disruption, basal vacuolization and apoptotic bodies were associated with ACLE. Conversely, rosacea exhibited a vascular-folliculocentric profile with peri-infundibular infiltrates and Demodex mites. In conclusion, LC-OCT enables non-invasive visualization of disease-specific microarchitectural patterns in CLE, reflecting both inflammatory and chronic remodelling changes. In this pilot study, it shows potential in differentiating CLE from rosacea and may support diagnosis, staging and treatment monitoring in clinical practice. Larger, multicenter studies are required to confirm the role of LC-OCT in the non-invasive diagnosis of CLE.","[""Journal Article"", ""Observational Study""]","[""Traini DO"", ""Palmisano G"", ""Ventura R"", ""Cannizzaro MV"", ""De Simone C"", ""Rizzuti P"", ""Pacucci VA"", ""Cerasuolo PG"", ""Piunno S"", ""Gavotti C"", ""Vigilante M"", ""Maccari A"", ""Caldarola G"", ""Ortolan A"", ""Suppa M"", ""Di Stefani A"", ""Agostino MA"", ""Peris K""]",10.1111/exd.70337,Traini DO,Experimental dermatology,0906-6705,8,Exp Dermatol,eng,Peris K,"[""Humans"", ""Rosacea"", ""Tomography, Optical Coherence"", ""Lupus Erythematosus, Cutaneous"", ""Female"", ""Cross-Sectional Studies"", ""Male"", ""Adult"", ""Middle Aged"", ""Diagnosis, Differential"", ""Skin"", ""Aged""]",e70337,42544818,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544818/,LC-OCT for Cutaneous Lupus Erythematosus: Characterization Across Disease Subtypes and Differentiation From Rosacea,35,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"BackgroundNonhormonal approaches for vulvovaginal symptoms and vulvar skin concerns are increasingly being explored. However, clinical evidence for combined microneedling-assisted topical protocols in this setting remains limited.ObjectivesThis preliminary pilot observational study explored the short-term feasibility, patient-reported outcomes, tolerability, and qualitative photographic findings associated with a combined microneedling-assisted Panax ginseng exosome protocol with adjunctive inner gel use.DesignSingle-arm preliminary pilot observational study.MethodsFourteen women (mean age, 48.6 years; range, 24-63 years) underwent three treatment sessions at 2-week intervals, followed by a final assessment 2 weeks after the third treatment session, resulting in a total study duration of 6 weeks from baseline to final follow-up for each participant. Microneedling was performed on the vulvar area using a 2-mm dermaroller, followed by topical application of a Panax ginseng exosome formulation. Participants also used an adjunctive inner gel between visits. Outcomes included the Vulvovaginal Symptom Questionnaire (VSQ), the Day-to-Day Impact of Vaginal Aging (DIVA) questionnaire, procedural pain assessed using a visual analogue scale (VAS), safety observations, and qualitative clinical photographic assessment.ResultsTotal VSQ score decreased after treatment (mean change, -2.86; 95% confidence interval [CI], -4.76 to -0.95; p = 0.00648). Total DIVA score also decreased (mean change, -5.43; 95% CI, -9.55 to -1.30; p = 0.0138), with significant improvement in the daily activities domain (median change, -2.0; p = 0.00849). The emotion and sexual life domains showed directional decreases but did not reach statistical significance. Procedure-related pain was transient and generally decreased within 30 minutes after treatment. Clinical photographs showed qualitative observational changes in pigmentation intensity and skin tone uniformity. No serious adverse events were observed during the short follow-up period.ConclusionThis small uncontrolled pilot study found that the combined microneedling-assisted Panax ginseng exosome protocol with adjunctive inner gel use was associated with short-term improvements in patient-reported vulvovaginal symptoms and qualitative vulvar skin tone observations. Because of the single-arm design, small sample size, combined intervention, subjective photographic assessment, and short follow-up, these findings should be interpreted as preliminary and hypothesis-generating.","[""Journal Article"", ""Observational Study""]","[""Park J"", ""Kim SG"", ""Kim YS"", ""Park Y"", ""Yi KH""]",10.1177/17455057261471827,Park J,"Women's health (London, England)",1745-5057,,Womens Health (Lond),eng,Yi KH,"[""Humans"", ""Female"", ""Pilot Projects"", ""Middle Aged"", ""Adult"", ""Panax"", ""Percutaneous Collagen Induction"", ""Vulva"", ""Young Adult"", ""Vagina"", ""Treatment Outcome"", ""Skin Aging""]",17455057261471827,42544642,,2026 Jan-Dec,2026,https://pubmed.ncbi.nlm.nih.gov/42544642/,Microneedling-assisted Panax ginseng exosome protocol for vulvovaginal symptoms and vulvar skin tone changes: A preliminary pilot observational study,22,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"This study aimed to evaluate the efficacy and safety of selinexor combined with bortezomib, lenalidomide, and dexamethasone (the XVRd regimen) for newly diagnosed multiple myeloma (NDMM) patients with high-risk features. This single-arm, open-label, prospective observational study recruited patients between August 2022 and November 2024. The study consisted of an induction phase (21-day cycles) and a maintenance phase (28-day cycles). During induction, all enrolled patients aged ≥18 years received the XVRd regimen containing oral selinexor 60 mg weekly. After induction, patients transitioned to maintenance therapy with selinexor plus lenalidomide. The primary endpoints were the overall response rate (ORR) and minimal residual disease (MRD) negative rate. Secondary endpoints included progression-free survival (PFS), treatment safety, and tolerability. A total of 30 patients were enrolled, with a median age of 62.1 years (range, 47-73 years). Twenty-four patients (80%) presented with extramedullary plasmacytoma or plasma cell leukemia (PCL). The ORR across the entire cohort was 93.3% (28/30), including 5 patients with stringent complete response (sCR), 9 with complete response (CR), 4 with very good partial response (VGPR), and 10 with partial response (PR). Five patients (16.7%) achieved MRD negativity after induction treatment. Survival analysis demonstrated a median PFS of 16.2 months (95% CI, 14.6-NA), a 1-year PFS rate of 89% (95% CI, 0.78-1), and unreached median overall survival (OS). The overall safety profile was manageable. The XVRd regimen may yield promising efficacy with a tolerable safety profile in NDMM patients with extramedullary disease (EMD) and/or high-risk cytogenetic abnormalities. Chinese Clinical Trial Registry, registration number: ChiCTR2200062860.","[""Journal Article"", ""Observational Study"", ""Multicenter Study""]","[""Yin J"", ""Yu S"", ""Wu H"", ""Zhou X"", ""Li X"", ""Yuan C"", ""Chu X"", ""Wang B"", ""Hao L"", ""Wei L"", ""Zhong Y""]",10.1080/07853890.2026.2703403,Yin J,Annals of medicine,0785-3890,1,Ann Med,eng,Zhong Y,"[""Humans"", ""Multiple Myeloma"", ""Middle Aged"", ""Female"", ""Dexamethasone"", ""Aged"", ""Male"", ""Prospective Studies"", ""Antineoplastic Combined Chemotherapy Protocols"", ""Triazoles"", ""Lenalidomide"", ""Hydrazines"", ""Bortezomib"", ""Progression-Free Survival"", ""Risk Factors"", ""Treatment Outcome""]",2703403,42544613,,2026 Dec,2026,https://pubmed.ncbi.nlm.nih.gov/42544613/,"Selinexor combined bortezomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma with high-risk factors: a single-arm, multi-center, prospective observational clinical study",58,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"The Canadian 24-Hour Movement Guidelines integrate recommendations on physical activity (PA), sedentary behavior (SB), and sleep. Individuals in cardiac rehabilitation programs (CRPs) have specific characteristics that may influence adherence to these 24-Hour Movement Guidelines and their relationship with quality of life. This study aimed to investigate the proportion of CRP participants who meet the recommendations of the Canadian 24-Hour Movement Guidelines and to evaluate the association between levels of PA, SB, and sleep duration with the quality-of-life domains of these individuals. This was a cross-sectional observational study including CRP participants (mean age: 68.46 ± 10.15 years; 58.1% with coronary artery disease). Quality of life was assessed using the 36-Item Short-Form Health Survey (SF-36). Movement behaviors (PA, SB, and sleep) were measured by accelerometers. Compliance with the guidelines was described using percentage values. Associations between PA, SB, and sleep with quality-of-life domains were analyzed using quantile regression. The significance level was set at 5%. Among the 105 participants analyzed, only 2.9% simultaneously met all three recommendations. Individual adherence was 29.5% (PA), 9.5% (SB), and 34.3% (sleep). A negative association was identified between SB and functional capacity, and positive associations were found between PA and the domains of functional capacity, vitality, and social aspects. Sleep duration was not associated with quality-of-life domains. Few CRP participants simultaneously meet all three recommendations of the Canadian 24-Hour Movement Guidelines, with partial adherence being more frequent. Higher levels of PA and lower time spent in SB were associated with better quality of life, whereas sleep duration showed no significant association.","[""Journal Article"", ""Observational Study""]","[""Soares JCÁ"", ""Vigilato MEM"", ""Valente HB"", ""Moliterno AH"", ""Silva JPLN"", ""Christofaro DGD"", ""Vanderlei LCM""]",10.1002/pri.70281,Soares JCÁ,Physiotherapy research international : the journal for researchers and clinicians in physical therapy,1358-2267,4,Physiother Res Int,eng,Vanderlei LCM,"[""Humans"", ""Quality of Life"", ""Cross-Sectional Studies"", ""Female"", ""Male"", ""Aged"", ""Cardiac Rehabilitation"", ""Canada"", ""Sedentary Behavior"", ""Middle Aged"", ""Sleep Duration"", ""Sleep"", ""Guideline Adherence"", ""Exercise"", ""Practice Guidelines as Topic""]",e70281,42544029,,2026 Oct,2026,https://pubmed.ncbi.nlm.nih.gov/42544029/,Movement Behaviors and Quality of Life in Cardiac Rehabilitation Programs: A Study Based on the Canadian 24-Hour Movement Guidelines,31,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Persistent symptoms after a respiratory infection can impair daily life, as has been shown, for example, for ""long COVID."" In this study, we determined the frequency and impact of symptoms that persisted for 12 weeks or more after a respiratory infection. A further endpoint was health care utilization for such symptoms in the general population. A cross-sectional study was conducted within the population-based digital cohort DigiHero in Germany (DRKS00025600). 39.3% of invited participants responded by completing an online questionnaire. 46 915 adults were included in the analysis. Participants were asked about symptoms that persisted 12 weeks or longer after a respiratory infection between September 2024 and August 2025. 48.3% of participants (95% confidence interval: [47.9; 48.8]) reported having had at least one respiratory infection during the study period. Among them, 18.8% [18.3; 19.3] stated that they still had symptoms 12 weeks or more afterward. The frequency of persistent symptoms was higher in older persons (13.1% for ages 20 to 29, 21.4% for ages 60 to 69). Most (86.8%) of those affected reported at least moderate functional impairment, and 57.9% consulted a physician. The pathogen causing the original infection was known for 24.3% of those reporting persistent symptoms: there were 483 cases of SARS-CoV-2 infection, 102 of influenza, and 36 of RSV. The symptom duration, functional impairment, and symptom pattern were similar after infection with SARS-CoV-2 and influenza. The most common symptoms in all pathogen groups were impaired physical performance, shortness of breath, rapid exhaustion, and fatigue. Persistent symptoms after respiratory infections are common and similar across pathogens in frequency and severity.","[""Journal Article"", ""Observational Study""]","[""Mikolajczyk R""]",10.3238/arztebl.m2026.0134,Mikolajczyk R,Deutsches Arzteblatt international,1866-0452,19,Dtsch Arztebl Int,eng,Mikolajczyk R,[],,42544023,,2026 Sep 18,2026,https://pubmed.ncbi.nlm.nih.gov/42544023/,Post-Infectious Syndromes in the Post-Pandemic Phase Among the German General Population,123,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Metastatic colorectal cancer (mCRC) remains a major contributor to cancer-related mortality worldwide. Real-world data from low- and middle-income countries remain limited. This bidirectional observational study included 60 patients with histologically confirmed mCRC treated at a tertiary care center between January 2019 and December 2025. Demographic, clinicopathological, molecular, treatment, and survival data were analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional hazards regression was used to identify prognostic factors. The median age was 48.5 years, and 63.3% of patients were male. Extensive metastatic disease was present in 96.7% of patients. Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations were detected in 20.7% of patients, whereas microsatellite instability-high (MSI-high) status was identified in one patient. Median PFS and OS were 10.6 and 22.3 months, respectively. On multivariable analysis, peritoneal metastasis independently predicted inferior PFS [hazard ratio (HR) 4.45, 95% confidence interval (CI) 2.16-9.19; p < 0.001] and OS (HR 2.83, 95% CI 1.13-7.07; p = 0.026). Poorly differentiated histology independently predicted worse OS (HR 3.05, 95% CI 1.03-9.06; p = 0.045). This study highlights the substantial burden of advanced disease in Indian patients with colorectal cancer. Peritoneal metastasis and poor differentiation were associated with adverse outcomes. Improved early detection and wider access to targeted therapies may improve survival outcomes in resource-limited settings.","[""Journal Article"", ""Observational Study""]","[""Natti HS"", ""Gumdal V"", ""Koppaka D"", ""Nuguri S"", ""Potu SR"", ""Rudra RS"", ""Jaffer RM""]",10.59556/japi.74.1616,Natti HS,The Journal of the Association of Physicians of India,0004-5772,7,J Assoc Physicians India,eng,Jaffer RM,"[""Humans"", ""Male"", ""Colorectal Neoplasms"", ""Middle Aged"", ""Tertiary Care Centers"", ""Female"", ""Adult"", ""Aged"", ""India"", ""Prognosis"", ""Microsatellite Instability"", ""Proto-Oncogene Proteins p21(ras)"", ""Neoplasm Metastasis"", ""Progression-Free Survival""]",49-54,42543992,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543992/,Clinicopathological Features and Outcomes of Metastatic Colorectal Cancers Treated at a Tertiary Care Hospital: A Bidirectional Observational Study,74,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"This study evaluates individuals who have recovered from coronavirus disease 2019 (COVID-19) for cardiac manifestations at least 60 days postrecovery, using cardiac magnetic resonance (CMR) imaging. Native T1, native T2, and late gadolinium enhancement (LGE) were used as parameters to detect potential cardiac pathologies. To study the incidence and nature of cardiac manifestations in long COVID using CMR. Prospective observational study. A total of 54 COVID-19-recovered patients and 50 healthy matched controls (age- and sex-based) underwent CMR using a 3 T scanner. Pathologies were assessed through native T1 and T2 mapping and LGE imaging. Data analysis was conducted using SPSS version 23. Only 1 patient (1.85%) showed midmyocardial LGE in the basal and midinferior segments, along with raised native T1 and T2 values. The remaining 53 recovered patients (98.15%) revealed no LGE or elevated T1/T2 values compared to controls. Native T1 and T2 values did not significantly differ between the post-COVID participants and healthy controls. Mild concentric hypertrophy was observed in six patients, which appeared incidental and unrelated to COVID-19. None of the patients exhibited elevated troponin T levels. In this study, CMR imaging did not find a significant increase in cardiac manifestations that may be attributed to long COVID in patients who had recovered from COVID-19 compared with uninfected controls. We believe the incidence of cardiovascular comorbidities related to long COVID syndrome is much lower in the Indian population than reported in Western literature. These findings are reassuring and may help alleviate concerns among the Indian population regarding long-term cardiovascular involvement of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.","[""Journal Article"", ""Observational Study""]","[""Mehta N"", ""Banerjee TS"", ""Karnavat CO"", ""Parikh RM"", ""Kashikar R"", ""Sinhasan S"", ""Tandan-Pardasani S"", ""Bindroo S"", ""Bhabhor A"", ""Raut I"", ""Shah N"", ""Desai SB"", ""Kapadia M"", ""Desai M"", ""Kapoor A""]",10.59556/japi.74.1609,Mehta N,The Journal of the Association of Physicians of India,0004-5772,7,J Assoc Physicians India,eng,Kapoor A,"[""Humans"", ""Female"", ""COVID-19"", ""Male"", ""Prospective Studies"", ""Magnetic Resonance Imaging"", ""Adult"", ""Middle Aged"", ""Post-Acute COVID-19 Syndrome"", ""India"", ""Cardiovascular Diseases"", ""SARS-CoV-2"", ""Heart Diseases"", ""Time Factors""]",32-37,42543989,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543989/,Cardiac Magnetic Resonance Imaging Study on Cardiovascular Involvement >60 Days Post COVID-19 Recovery,74,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Sometimes, drug names or their appearances create confusion among healthcare providers. These look-alike or sound-alike (LASA) drugs have the potential to cause medication errors leading to patient harm. Such errors can occur during prescribing, dispensing, and administration of drugs. Therefore, this study was conducted to assess the knowledge, attitudes, and practice of LASA drugs among healthcare providers at a tertiary care hospital in India. This cross-sectional, observational, single-center, questionnaire-based study was conducted among healthcare providers at a tertiary care hospital in India. The study was conducted over a duration of 2 months between November and December 2024. Out of the 400 participants, 81% were doctors, followed by 12.75% nurses, 3.25% pharmacists, and 3% interns. The majority of them were aware of the term LASA drugs. The majority of them were slightly concerned about the risks of LASA drugs. Whereas, only 10% of them had ever reported LASA errors, as the majority of them were unaware about medication error reporting form. This study suggests that lack of awareness about LASA drugs among healthcare providers contributes to medication errors. To address this, solutions can be implemented at different levels via a multidisciplinary approach.","[""Journal Article"", ""Observational Study""]","[""Bansal N"", ""Khobragade AAK"", ""Bawne AR"", ""Bavlecha A"", ""Kohli BS""]",10.59556/japi.74.1593,Bansal N,The Journal of the Association of Physicians of India,0004-5772,7,J Assoc Physicians India,eng,Kohli BS,"[""Humans"", ""Cross-Sectional Studies"", ""Tertiary Care Centers"", ""Health Knowledge, Attitudes, Practice"", ""India"", ""Male"", ""Medication Errors"", ""Female"", ""Adult"", ""Surveys and Questionnaires"", ""Health Personnel"", ""Attitude of Health Personnel"", ""Middle Aged""]",20-23,42543986,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543986/,"A Cross-sectional Study to Assess the Knowledge, Attitude, and Practice of Look-alike, Sound-alike Drugs among Healthcare Providers at a Tertiary Care Hospital",74,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"The clinical manifestation of drug-induced ataxia (DIA) is well established clinically but often becomes unrecognized until actual ataxia occurs. DIA may include ataxia as its primary clinical symptom or may be one of multiple manifestations. This study aimed to characterize the development of DIA types and the timing of clinical resolution. Between January 2016 and March 2025, a prospective observational study of subjects diagnosed with DIA based on the development of ataxia after starting a drug and no prior history of ataxia was conducted. Collected data included the drug involved, timing to onset of symptoms, type of DIA (cerebellar vs sensory), and time required for resolution of symptoms. A total of 63 subjects met the criteria for inclusion in this analysis. Ataxia was most commonly attributed to antiepileptic drugs (AED) (44 subjects, 69.8%), with the remaining 19 subjects having ataxia after the use of chemotherapeutic or other drugs (30.2%). The most frequent drug associated with ataxia was phenytoin (22 subjects). The majority of ataxia experienced by the subjects was of the cerebellar variety (58.7%), whereas only 41.3% experienced a sensory form of ataxia. Symptoms of ataxia following the use of a drug were most commonly noted >72 hours after starting the drug (79.4%). In subjects with symptomatic improvement after intervention, 39.7% of subjects demonstrated improvement within 72 hours after intervention. DIA may typically be caused by AEDs and chemotherapeutic drugs, with symptoms commonly manifesting >72 hours after initiation of drug therapy. Early recognition and treatment of DIA may improve clinical outcomes for individuals diagnosed with DIA.","[""Journal Article"", ""Observational Study""]","[""Saibaba J"", ""Subramaniam MP"", ""Thangavelu AP"", ""Rennukaranjan KC""]",10.59556/japi.74.1571,Saibaba J,The Journal of the Association of Physicians of India,0004-5772,7,J Assoc Physicians India,eng,Rennukaranjan KC,"[""Humans"", ""Ataxia"", ""Female"", ""Male"", ""Prospective Studies"", ""Anticonvulsants"", ""Adult"", ""Middle Aged"", ""Resource-Limited Settings"", ""India""]",15-19,42543985,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543985/,Spectrum and Clinical Burden of Drug-induced Ataxia in Low-resource Settings: An Observational Study,74,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"The advent of modern potent immunosuppression has significantly reduced the occurrence of rejection in renal allograft recipients but has increased the risk of infection, which remains the major cause of death in these patients. This single-center retrospective observational study was conducted at a tertiary care center in India. Data were collected from medical records of renal allograft recipients admitted for infection-related complications over a 10-year duration. Out of 238 admissions, 63 (26.47%) were due to infection-related complications involving 59 unique patients. The most common infections were urinary tract infections (UTIs) (n = 24) and pneumonia (n = 19). Of the two patients requiring multiple admissions, one patient had two episodes of pneumonia and one episode of UTI, and the other patient needed three admissions for diabetic foot. Six patients succumbed to their illness, resulting in a mortality rate of 10.16%, with sepsis due to UTI being the most common cause of death.","[""Journal Article"", ""Observational Study""]","[""Hajong S"", ""Sharma M"", ""Hakmaosa A"", ""Doley PK"", ""Pegu G""]",10.59556/japi.74.1614,Hajong S,The Journal of the Association of Physicians of India,0004-5772,7,J Assoc Physicians India,eng,Pegu G,"[""Humans"", ""Kidney Transplantation"", ""India"", ""Male"", ""Tertiary Care Centers"", ""Female"", ""Retrospective Studies"", ""Incidence"", ""Adult"", ""Urinary Tract Infections"", ""Middle Aged"", ""Pneumonia"", ""Postoperative Complications""]",13-14,42543984,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543984/,Incidence of Infections in Renal Allograft Recipients and Their Outcomes in a Tertiary Care Center in Northeast India,74,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal syndrome characterized by immune hyperactivation and a cytokine storm, leading to fever, cytopenia, organomegaly, and multiorgan dysfunction. Given its high morbidity and mortality, prompt diagnosis and treatment are essential. Currently, there are no established markers to predict outcomes in secondary hemophagocytic lymphohistiocytosis (sHLH). This retrospective study aimed to identify prognostic factors in patients with sHLH, specifically evaluating the prognostic role of absolute neutrophil count (ANC) and serum ferritin level. The study also examined the impact of dexamethasone and etoposide on the treatment of these patients. HLH remission was achieved in 64 patients (71.1%). Forty-seven out of those 64 patients survived and were discharged home, while 17 patients died in the hospital. HLH remission was not achieved in 26 patients (28.9%), of whom 25 patients died in the hospital. ANC at diagnosis and lower nadir ANC during the hospital stay significantly correlated with mortality (p = 0.001 and 0.017, respectively). Serum ferritin levels, however, were not a significant prognostic marker (p = 0.396). Treatment with dexamethasone was associated with better outcomes in patients with sHLH. sHLH should be considered in patients with treatment-resistant bicytopenia or pancytopenia. Lower ANC at diagnosis and nadir ANC during hospitalization are associated with increased mortality, suggesting that ANC is a potential indicator for early immunochemotherapy. Serum ferritin level is not a significant prognostic marker. Early diagnosis and dexamethasone treatment help achieve HLH remission, which improves outcomes in sHLH. These findings highlight the need for prospective studies to better understand sHLH prognostic markers and therapeutic strategies, especially in intensive care settings, where mortality remains high.","[""Journal Article"", ""Observational Study""]","[""Varshney A"", ""Phadke PS"", ""Prabhakaran A"", ""Patade D"", ""Bhalani Y"", ""Kumar A""]",10.59556/japi.74.1607,Varshney A,The Journal of the Association of Physicians of India,0004-5772,7E,J Assoc Physicians India,eng,Kumar A,"[""Humans"", ""Lymphohistiocytosis, Hemophagocytic"", ""Female"", ""Retrospective Studies"", ""Male"", ""Dexamethasone"", ""Prognosis"", ""Etoposide"", ""Ferritins"", ""Treatment Outcome"", ""Adolescent"", ""Child"", ""Glucocorticoids"", ""Child, Preschool"", ""Adult"", ""Neutrophils"", ""Leukocyte Count"", ""Remission Induction"", ""Young Adult""]",e18-e24,42543957,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543957/,Clinical Characteristics Treatment Approaches and Survival Outcomes in Secondary Hemophagocytic Lymphohistiocytosis: A Retrospective Observational Study,74,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"To assess referral timelines to rheumatologists in Karnataka, India, identify factors linked to delays, and to examine their impact on disease activity, functional disability, and economic burden. A multicenter, cross-sectional, observational questionnaire-based study was conducted across 17 rheumatology centers in Karnataka, India (June, 2023-July, 2024). Disease activity (DAS28, CDAI), disability (HAQ-DI), and healthcare expenditure prior to referral and during the past 1 year were analyzed in relation to self-reported referral time, categorized as early (≤3 months from symptom onset) and late (>24 months). Utilization of healthcare schemes available in Karnataka was captured. Among 2,141 participants with RA, the median referral time to a rheumatologist was 18 (6-36) months, early referral (≤3 months) in 17% (n = 365), and late referral (>24 months) in 31% (n = 662). Older age [AOR = 1.01 (1.005-1.02)], being married [AOR = 1.48 (1.03-2.12)], resident of non-Bengaluru regions [AOR = 2.26 (1.60-3.19)], academic treating facility [AOR = 2.32 (1.68-3.18)], and longer duration of illness >120 months [AOR =2.84 (2.14-3.76)] had higher odds of late referrals. This group had significantly higher expenditure prior to referral [β = 3.57 (3.05-4.19)], higher total annual medical expenditure [β = 1.20 (1.09-1.32)], and catastrophic expenditure [β = 1.56 (1.22-2.01)]. 52 % (n = 1120) of participants reported out-of-pocket healthcare expenditure. Delayed referral to a rheumatologist was associated with increased disability and financial strain, including a significantly higher risk of catastrophic health expenditure.","[""Journal Article"", ""Observational Study"", ""Multicenter Study""]","[""Shobha V"", ""Subramanian R"", ""Prakruthi J"", ""Selvam S"", ""Shaleni V"", ""Haridas V"", ""Mamadapur M"", ""Kamath A"", ""Arjun MN"", ""Chebbi P"", ""Vahaneyil JM"", ""Vr SV"", ""Patil A"", ""Pinto B"", ""Yathish GC"", ""Jeevanagi SR"", ""Baliga S"", ""Harshini AS"", ""Singhai S"", ""Rao VK"", ""Ramachandran V"", ""Anusha MS"", ""Chandrashekara S"", ""Mahendranath KM""]",10.59556/japi.74.1560,Shobha V,The Journal of the Association of Physicians of India,0004-5772,7E,J Assoc Physicians India,eng,Mahendranath KM,"[""Humans"", ""Arthritis, Rheumatoid"", ""India"", ""Female"", ""Cross-Sectional Studies"", ""Referral and Consultation"", ""Male"", ""Middle Aged"", ""Treatment Delay"", ""Surveys and Questionnaires"", ""Rheumatology"", ""Adult"", ""Health Expenditures"", ""Health Services Accessibility"", ""Time-to-Treatment"", ""Aged""]",e1-e8,42543955,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543955/,Barriers to Timely Rheumatologic Care for Rheumatoid Arthritis: A Real-World Questionnaire-based Study from Karnataka Chapter of Indian Rheumatology Association (KRA),74,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Rapid assessment of electrolytes and hemoglobin is crucial in emergency and critical care. Arterial blood gas (ABG) analyzers are widely used as point-of-care devices. However, their agreement with central laboratory measurements remains uncertain because of methodological differences. This study aimed to evaluate the reliability of sodium, potassium, chloride, and hemoglobin values obtained from an ABG analyzer compared with those from a central laboratory autoanalyzer and to assess analytical acceptability using US Clinical Laboratory Improvement Amendments (CLIA) 2025 allowable error limits. In this prospective observational study, 200 paired arterial and venous samples from patients in the Emergency Department were analyzed. Arterial samples were processed on an ABG analyzer using direct ion-selective electrode (ISE) methodology, and venous serum electrolytes were measured on a central laboratory autoanalyzer using indirect ISE methodology. Hemoglobin was measured on a hematology analyzer. Paired comparisons were performed using the Wilcoxon signed-rank test, correlation was assessed with Spearman's coefficient, agreement was assessed with Bland-Altman analysis, and total error was compared with CLIA limits. ABG-derived sodium and potassium values were significantly lower than venous laboratory values, whereas chloride and hemoglobin values were significantly higher (p < 0.001). All analytes showed strong positive correlations. Bland-Altman analysis demonstrated acceptable agreement for sodium (bias, -2.8 mmol/L) and potassium (bias, -0.2 mmol/L), both within CLIA allowable limits. Chloride showed a total error of 6.43%, and hemoglobin showed a total error of 15.15%, indicating unacceptable analytical error. ABG-derived sodium and potassium values demonstrated acceptable agreement with central laboratory measurements and can be used for rapid clinical decision-making in emergency settings. However, chloride and hemoglobin values should not be used interchangeably without institution-specific validation and correction equations.","[""Journal Article"", ""Comparative Study"", ""Observational Study""]","[""Dhanapalan A"", ""Murugiah V"", ""Ramasamy J"", ""Raja NK""]",10.59556/japi.74.1544,Dhanapalan A,The Journal of the Association of Physicians of India,0004-5772,6E,J Assoc Physicians India,eng,Raja NK,"[""Humans"", ""Blood Gas Analysis"", ""Reproducibility of Results"", ""Hemoglobins"", ""Prospective Studies"", ""Electrolytes"", ""Potassium"", ""Chlorides"", ""Point-of-Care Systems"", ""Sodium""]",e35-e38,42543952,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543952/,Reliability of Arterial Blood Gas Analyzer for Electrolyte and Hemoglobin Measurement: A Method Comparison Study,74,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Hyponatremia is a common and important electrolyte imbalance seen both in isolation and more commonly, as a complication of other medical illnesses. With a wide spectrum of presentations, the prognostic implications are grave and far-reaching if not addressed meticulously. Despite the knowledge of hyponatremia since the mid-20th century, data on the prevalence and clinical profile of hyponatremia are scarce, to say the least, from the Indian subcontinent. We took up this hospital-based observational study to explore the clinicoetiological profile of hyponatremia. Mean serum sodium level was 122.24 ± 6.10. Most of the patients had severe hyponatremia (63.3%). The most common cause of hyponatremia, as well as severe and euvolemic hyponatremia, was syndrome of inappropriate antidiuretic hormone secretion (SIADH) (21.9%). Most patients with SIADH had tubercular meningitis (TBM). The most common type of hyponatremia was hypovolemic hyponatremia (42.4%), of which sepsis was the most common cause. Further prospective studies are required as hyponatremia remains incompletely understood in many basic areas because of its association with a plethora of underlying disease states, its causation by multiple etiologies with differing pathophysiological mechanisms, and marked differences in symptomatology and clinical outcomes based on the acuteness or chronicity of hyponatremia; also, optimal treatment strategies have not been well defined for these reasons.","[""Journal Article"", ""Observational Study""]","[""Somendra S"", ""Sharma R""]",10.59556/japi.74.1512,Somendra S,The Journal of the Association of Physicians of India,0004-5772,6E,J Assoc Physicians India,eng,Sharma R,"[""Humans"", ""Hyponatremia"", ""Inappropriate ADH Syndrome"", ""Tertiary Care Centers"", ""Male"", ""Female"", ""India"", ""Middle Aged"", ""Adult"", ""Sodium"", ""Sepsis""]",e6-e8,42543946,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543946/,A Study of the Clinicoetiological Profile of Hyponatremia in Patients in a Tertiary Care Hospital,74,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated efficacy in improving glycemic control and reducing cardiovascular risk in patients with type 2 diabetes mellitus (T2DM). However, real-world evidence from Indian populations remains limited. This study aimed to assess the effectiveness and safety of semaglutide on glycemic control, body weight, and metabolic parameters in patients with T2DM in a real-world clinical setting. This retrospective observational study was conducted at a tertiary care hospital in Jharkhand, India, between February 2023 and August 2024. A total of 60 patients with T2DM (44 males and 16 females), including treatment-naïve individuals and those with inadequate glycemic control (HbA1c >7%) despite ongoing therapy, were enrolled. Clinical and biochemical parameters were evaluated at baseline and after six months of semaglutide therapy. Statistical analysis was performed using paired t-tests, with a p-value <0.05 considered statistically significant. Significant improvements were observed following semaglutide therapy. Mean HbA1c decreased from 9.21% at baseline to 7.35% after six months (p <0.001). Mean body weight decreased by 2.6 kg (p <0.001). LDL cholesterol levels declined significantly from 92.03 mg/dL to 78.93 mg/dL (p <0.05). Renal parameters, including serum creatinine and urine albumin-to-creatinine ratio, showed numerical improvement; however, these changes did not reach statistical significance (p >0.05). Thyroid function remained stable throughout the study period. Improvements in diabetic retinopathy and neuropathy were also observed, although these findings were not statistically significant. Semaglutide was effective and well tolerated in patients with T2DM in routine clinical practice. Treatment was associated with significant reductions in HbA1c, body weight, and LDL cholesterol without adverse effects on renal or thyroid function. These findings support the use of semaglutide as an effective therapeutic option for the management of T2DM in real-world settings.","[""Journal Article"", ""Observational Study""]","[""Jha AK"", ""Sunder A""]",10.59556/japi.74.1508,Jha AK,The Journal of the Association of Physicians of India,0004-5772,6,J Assoc Physicians India,eng,Sunder A,"[""Humans"", ""Semaglutide"", ""Female"", ""Male"", ""Diabetes Mellitus, Type 2"", ""Retrospective Studies"", ""Glucagon-Like Peptides"", ""Hypoglycemic Agents"", ""India"", ""Glycated Hemoglobin"", ""Tertiary Care Centers"", ""Middle Aged"", ""Blood Glucose"", ""Body Weight"", ""Aged"", ""Treatment Outcome""]",74-77,42543936,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543936/,Semaglutide in Practice: Insights from a Retrospective Case Series at a Jharkhand Tertiary Care Hospital,74,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Imeglimin is a novel oral glucose-lowering agent targeting mitochondrial dysfunction. While randomized trials demonstrate its efficacy, real-world data in diverse populations remain limited. We evaluated the effectiveness, safety, and utilization patterns of imeglimin in Indian adults with inadequately controlled type 2 diabetes (T2D). This prospective, multicenter, observational cohort study enrolled adults with T2D newly initiated on imeglimin across 11 Indian centers. Participants were followed for 6 months. The primary outcome was the change in HbA1c from baseline. Effectiveness was analyzed in a complete-case cohort using linear mixed-effects models to adjust for covariates, while safety was assessed in all participants with at least one post-baseline evaluation. The baseline cohort included 736 participants (mean age 52.4 years, mean baseline HbA1c 9.8%). Imeglimin was predominantly prescribed as an add-on therapy (84.6%), most frequently alongside three or more other agents (57.9%). In the complete-case cohort (n = 337; 46% of baseline), adjusted mean HbA1c decreased by 1.28% (95% CI -1.41 to -1.14) at 3 months and 2.27% (-2.41 to -2.13) at 6 months (p <0.001). Greater reductions were significantly associated with higher baseline HbA1c. Adverse events were reported in 9.9% of the safety cohort (n = 573), most commonly mild gastrointestinal symptoms (5.2%). Hypoglycemia occurred in 1.2%. Two cases of lactic acidosis were reported, though causality with imeglimin was not established. In routine clinical practice, the initiation of imeglimin among Indian adults with T2D was associated with clinically meaningful reductions in HbA1c, fasting plasma glucose, and postprandial glucose over a 6-month period, alongside a favorable safety profile. These real-world findings support the clinical utility and tolerability of imeglimin as an effective therapeutic option for glycemic management in this population. Future randomized controlled trials with extended follow-up are warranted to establish definitive causal treatment effects and evaluate long-term clinical outcomes.","[""Journal Article"", ""Multicenter Study"", ""Observational Study""]","[""Saboo B"", ""Samajdar SS"", ""Maheshwari A"", ""Saboo B"", ""Panda JK"", ""Inamdar AV"", ""Agarwal P"", ""Ghosh S"", ""Patil S"", ""Saxena D"", ""Gokalani R"", ""Kiran G"", ""Singh NK"", ""Pamnani H"", ""Chakravarti HN"", ""Agrawala RK"", ""Singh V"", ""Ahmed R"", ""Tamhankar G"", ""Joshi S""]",10.59556/japi.74.1548,Saboo B,The Journal of the Association of Physicians of India,0004-5772,6,J Assoc Physicians India,eng,Joshi S,"[""Humans"", ""Diabetes Mellitus, Type 2"", ""Middle Aged"", ""Female"", ""Male"", ""India"", ""Prospective Studies"", ""Hypoglycemic Agents"", ""Glycated Hemoglobin"", ""Adult"", ""Blood Glucose"", ""Treatment Outcome"", ""Practice Patterns, Physicians'"", ""Aged"", ""Hypoglycemia"", ""Triazines""]",56-65,42543934,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543934/,"Imeglimin in Indian Adults with Type 2 Diabetes: A Prospective Multicenter Real-world Cohort Study of Prescription Patterns, Glycemic Change, and Safety",74,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Acute poisoning remains a major public health concern in rural India due to easy accessibility of toxic substances and limited mental health support. This retrospective observational study was conducted at a tertiary care teaching hospital in rural Bengaluru to evaluate the clinical and epidemiological profile of poisoning cases. Medical records of 100 patients admitted with acute poisoning over 1 year were analyzed. The mean age of patients was 28 years, with the majority in the 21-30-year age group, and a female predominance (57%). Suicidal intent accounted for 85% of cases. Organophosphorus compounds were the most common agents, followed by drug overdoses and pyrethroid compounds. All exposures occurred via the oral route, and 74% of patients presented within 4 hours of ingestion. Vomiting was the most common presenting symptom, followed by abdominal pain and altered sensorium. Laboratory abnormalities included elevated liver enzymes and electrolyte disturbances. The mean duration of hospitalization was 4 days. No mortality was observed during the study period. Acute poisoning in rural Bengaluru predominantly affects young adults and is largely associated with suicidal intent. Early presentation and prompt management contribute to favorable outcomes. Preventive strategies focusing on mental health support and the regulation of toxic substances are essential.","[""Journal Article"", ""Observational Study""]","[""Murthy MS"", ""Kumar PG"", ""Suhas SV""]",10.59556/japi.74.1538,Murthy MS,The Journal of the Association of Physicians of India,0004-5772,6,J Assoc Physicians India,eng,Suhas SV,"[""Humans"", ""Female"", ""Adult"", ""Male"", ""India"", ""Retrospective Studies"", ""Poisoning"", ""Young Adult"", ""Middle Aged"", ""Adolescent"", ""Rural Population"", ""Acute Disease"", ""Suicide, Attempted"", ""Organophosphate Poisoning"", ""Tertiary Care Centers""]",41-45,42543931,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543931/,A Study of the Clinical Profile of Acute Poisoning in Adults in a Rural Tertiary Healthcare Setup,74,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Celiac disease (CeD) and inflammatory bowel disease (IBD) share immune and genetic pathophysiological pathways, suggesting a possible increased coexistence. Indian data on biopsy-confirmed CeD in IBD are limited, and false-positive anti-tissue transglutaminase (tTG) antibody results complicate interpretation. To determine the prevalence of biopsy-confirmed CeD in an Indian IBD cohort and compare clinical features between CeD-positive and CeD-negative IBD patients. In this prospective observational study, 477 IBD patients were assessed. All patients underwent IgA anti-tTG screening. Seropositive patients underwent upper gastrointestinal endoscopy with duodenal biopsies. The standardized prevalence ratio (SPR) for CeD was calculated, and clinical and laboratory parameters were compared between patients with and without CeD. Among 477 IBD patients (UC 421; CD 56), 14 (2.94%) were anti-tTG positive, and 11 had biopsy-confirmed CeD, giving a prevalence of 2.31% (95% confidence interval: 1.29-4.08%). Prevalence was 2.14% in UC and 3.57% in CD (p = 0.59). The SPR, compared with the Indian population prevalence of 1.04%, was 2.22. The anti-tTG false-positive rate was 21.4%. No significant differences were observed between CeD-positive and CeD-negative patients, although UC patients with CeD showed a non-significant trend toward pancolitis. In conclusion, CeD prevalence in Indian IBD patients was numerically higher than the Northern Indian general population but did not reach statistical significance. Larger multicenter studies are needed to definitively establish the CeD-IBD association in Indian populations. Selective screening is preferable, and histological confirmation remains essential due to high false-positive serology.","[""Journal Article"", ""Observational Study""]","[""Kumar M"", ""Sapra B"", ""Sharma PN"", ""Maharshi S"", ""Sharma SS""]",10.59556/japi.74.1520,Kumar M,The Journal of the Association of Physicians of India,0004-5772,6,J Assoc Physicians India,eng,Sharma SS,"[""Humans"", ""Celiac Disease"", ""India"", ""Female"", ""Prevalence"", ""Prospective Studies"", ""Male"", ""Adult"", ""Inflammatory Bowel Diseases"", ""Middle Aged"", ""Biopsy"", ""Transglutaminases"", ""Adolescent"", ""Young Adult""]",36-40,42543930,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543930/,Prevalence of Celiac Disease in Inflammatory Bowel Disease: A Prospective Cohort Study from Northern India,74,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Post-tuberculosis sequelae (PTBS) are increasingly recognized as a significant cause of long-term respiratory morbidity, manifesting with dyspnea, reduced pulmonary function, impaired exercise capacity, and diminished quality of life. Despite their burden, PTBS patients often lack access to structured rehabilitation. Pulmonary rehabilitation (PR), well-established in COPD, may offer functional and psychological benefits in PTBS, but its implementation in India and comparison across radiological phenotypes remains understudied. To evaluate the impact of a 24-week pulmonary rehabilitation program on clinical, functional, psychological, and radiological outcomes in patients with PTBS, and to compare the response among different radiological subtypes-fibrosis, fibrocavitary lesions, bronchiectasis, and combined lesions. In this prospective observational study, 60 patients with PTBS underwent hospital- or home-based PR. Assessments were conducted at baseline, 12 weeks, and 24 weeks and included spirometry (FEV1, FVC, FEV1/FVC, FEF25-75), 6-minute walk test (6MWT), body mass index (BMI), St. George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) dyspnea grade, DASS-21 scale for psychological health, and radiological classification. Statistical analysis was performed to assess within-group and between-group changes over time. Significant improvements were observed in BMI (p < 0.005), 6MWT (mean improvement >150 m in most groups), and DASS-21 scores across all radiological subtypes. FEV1% predicted improved significantly (p < 0.05), especially in patients with fibrosis and bronchiectasis (>60% by week 24), while those with fibrocavitary + bronchiectasis showed the least gain (38%). Quality of life (SGRQ) improved in all groups, though intergroup differences were not statistically significant. Bronchodilator reversibility was rare (5%) and did not vary with lesion type. Pulmonary rehabilitation significantly improves nutritional status, exercise capacity, psychological well-being, and spirometric parameters in PTBS patients, with variable responses depending on radiological pattern. Despite greater impairment, patients with fibrocavitary lesions derived meaningful benefit, highlighting PR's role as an essential component of post-TB care. Tailored PR strategies should be integrated into national TB programs to address the long-term sequelae of TB in high-burden settings such as India.","[""Journal Article"", ""Observational Study""]","[""Mehta M"", ""Dixit R""]",10.59556/japi.74.1525,Mehta M,The Journal of the Association of Physicians of India,0004-5772,6,J Assoc Physicians India,eng,Dixit R,"[""Humans"", ""Male"", ""Prospective Studies"", ""Female"", ""Tuberculosis, Pulmonary"", ""Middle Aged"", ""Quality of Life"", ""Adult"", ""India"", ""Respiratory Function Tests"", ""Bronchiectasis"", ""Lung"", ""Treatment Outcome"", ""Pulmonary Fibrosis""]",29-34,42543929,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543929/,Effect of Radiological Patterns on Response to Pulmonary Rehabilitation in Post-tuberculosis Lung Sequelae: A Prospective Observational Study,74,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Artificial intelligence (AI) has emerged as a powerful tool for electrocardiogram (ECG) analysis, potentially surpassing conventional interpretation in detecting arrhythmias and metabolic disturbances such as hyperkalemia. This study evaluated the diagnostic performance and real-world applicability of an AI-powered ECG interpretation system for arrhythmia prediction and hyperkalemia detection. In this prospective observational study, patients presenting to the emergency department or cardiology clinic between March 2024 and February 2025 were enrolled. Standard 12-lead ECGs were analyzed in parallel by a validated deep-learning AI model and board-certified cardiologists blinded to AI results and clinical data. Primary outcomes included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for arrhythmia and hyperkalemia detection. Secondary outcomes assessed the impact of AI-driven alerts on workflow efficiency and time to therapy. Among 4,200 patients (mean age 56, 39% female), the AI-ECG system demonstrated 97.2% sensitivity and 96.1% specificity for arrhythmia detection, outperforming manual interpretation for atrial fibrillation, atrial flutter, and ventricular ectopy (p < 0.001). For hyperkalemia, sensitivity and specificity were 83.5% and 87.3%, respectively, reliably flagging all critical potassium elevations within 1 minute. AI alerts reduced median time-to-therapy by 19 minutes. Subgroup analysis showed robust performance in patients with chronic kidney disease and acute cardiac conditions. AI-powered ECG analysis enables highly accurate, rapid detection of arrhythmias and hyperkalemia, supporting earlier clinical intervention and improving workflow efficiency. These findings advocate for broader multicenter validation and integration of AI-ECG tools in routine cardiology practice.","[""Journal Article"", ""Observational Study""]","[""Kumar A"", ""Bansal T"", ""Jaura S""]",10.59556/japi.74.1526,Kumar A,The Journal of the Association of Physicians of India,0004-5772,6,J Assoc Physicians India,eng,Jaura S,"[""Humans"", ""Hyperkalemia"", ""Electrocardiography"", ""Female"", ""Arrhythmias, Cardiac"", ""Machine Learning"", ""Prospective Studies"", ""Artificial Intelligence"", ""Male"", ""Middle Aged"", ""Sensitivity and Specificity"", ""Predictive Value of Tests"", ""Aged""]",25-28,42543928,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543928/,AI-powered ECG Interpretation System for Arrhythmia Prediction and Hyperkalemia Detection Using Machine Learning,74,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"To analyze spontaneously reported adverse drug reactions (ADRs) during the first year after the adverse drug reaction monitoring center (AMC) recognition. A retrospective observational study was conducted from April 2023 to March 2024 at a tertiary care hospital in Pune, Maharashtra, India. All reported ADRs were included and analyzed by gender, age, department, drug class, and severity (modified Hartwig and Siegel scale). Causality was assessed using Naranjo's algorithm and World Health Organization-Uppsala Monitoring Center (WHO-UMC) assessment criteria. Data were expressed as frequencies and percentages. A total of 255 ADRs were reported. Most ADRs occurred in elderly patients aged 61-80 years (56%). Anticancer drugs were the most common culprits (45.67%), followed by antimicrobials (21.63%). Causality assessments of suspected ADRs were probable (47%), possible (51%), and certain (2%). Most ADRs were mild (78.43%) and nonserious, and patients recovered with drug withdrawal and supportive care (39%), while 47% were recovering when the ADR was reported. Adverse drug reactions (ADRs) were mild and preventable, with anticancer drugs being the leading cause. Elderly patients were most affected. Underreporting remains a challenge despite AMC recognition, underscoring the need for continued sensitization and feedback mechanisms to promote a culture of ADR reporting.","[""Journal Article"", ""Observational Study""]","[""Londhe VA"", ""Dhande PP""]",10.59556/japi.74.1515,Londhe VA,The Journal of the Association of Physicians of India,0004-5772,6,J Assoc Physicians India,eng,Dhande PP,"[""Humans"", ""Adverse Drug Reaction Reporting Systems"", ""Drug-Related Side Effects and Adverse Reactions"", ""Retrospective Studies"", ""Female"", ""Aged"", ""Middle Aged"", ""India"", ""Male"", ""Aged, 80 and over"", ""Adult"", ""Pharmacovigilance""]",22-24,42543927,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543927/,From Recognition to Reporting: One-year Trends in Adverse Drug Reactions at a Newly Designated Adverse Drug Reaction Monitoring Center,74,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Community-acquired pneumonia (CAP) carries substantial mortality. Common scoring tools such as CURB-65, A-DROP, and PSI have limitations. The expanded A-DROP incorporates clinical and biochemical markers, showing promise and requires validation in Indian settings. This prospective observational study at a North Indian tertiary center (March 2024-June 2025) included 80 adults with CAP. Expanded A-DROP scores were calculated within 24 hours of admission, and patients were followed for ICU admission, in-hospital, and 14-day postdischarge mortality. Analyses used ANOVA, Chi-square, logistic regression, and receiver operating characteristic (ROC) curves (p < 0.05). Of 80 patients, 22 (27.5%) died within 14 days. Mortality was 1/23 (4.3%) in group I (0-2), 2/22 (9.1%) in group II (3-4), and 19/35 (54.3%) in group III (≥5) (p < 0.001). ICU admission rose with severity: 1/23 (4.3%), 8/22 (36.4%), and 25/35 (71.4%) (p < 0.001). Mean (SD) hospital stay increased: 4.0 (0.9), 7.0 (1.1), and 9.0 (1.3) days (p < 0.0001), with positive correlation to score (ρ = 0.53, p < 0.000001). ROC analysis gave an AUC of 0.871 (95% CI: 0.783-0.958). A score ≥5 predicted mortality with 86.2% sensitivity and 72.4% specificity. Multivariate regression identified Expanded A-DROP as the only independent predictor (OR 3.07, p < 0.001). Expanded A-DROP demonstrated strong predictive power for short-term mortality, ICU requirement, and hospital stay in CAP. It is a simple, clinically relevant, and effective tool for early triage, especially in resource-limited settings.","[""Journal Article"", ""Observational Study""]","[""Prakash R"", ""Sinha N"", ""Goyal P""]",10.59556/japi.74.1516,Prakash R,The Journal of the Association of Physicians of India,0004-5772,6,J Assoc Physicians India,eng,Goyal P,"[""Humans"", ""Community-Acquired Pneumonia"", ""India"", ""Prospective Studies"", ""Tertiary Care Centers"", ""Female"", ""Male"", ""Middle Aged"", ""Severity of Illness Index"", ""Aged"", ""ROC Curve"", ""Hospital Mortality"", ""Adult"", ""Intensive Care Units"", ""Community-Acquired Infections""]",16-21,42543926,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543926/,Role of Expanded A-DROP Score in Predicting 14-day Mortality in Patients with Community-acquired Pneumonia: A Prospective Observational Study from a Tertiary Care Center in North India,74,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease with increasing global prevalence. Thyroid dysfunction, particularly hypothyroidism, has been implicated in its pathogenesis and progression. To evaluate the prevalence and pattern of hypothyroidism in NAFLD patients and assess its association with hepatic steatosis and fibrosis severity using imaging and noninvasive fibrosis scoring systems. This cross-sectional observational study was conducted on 158 adult NAFLD patients at a tertiary care hospital in northern India over 1 year. Patients with significant alcohol intake or other chronic liver diseases were excluded. Hepatic steatosis and fibrosis were assessed by ultrasonography and transient elastography, respectively. Fibrosis severity was categorized using FibroScan and the FIB-4 index. Thyroid function was evaluated by serum TSH, FT3, and FT4. Statistical analysis included intergroup comparisons and correlation assessments using SPSS v26, with p < 0.05 considered significant. Among 158 NAFLD patients, 41.14% were hypothyroid. The prevalence of hypothyroidism increased with disease severity: 71.43% in fibrotic NASH and 44.44% in cirrhosis (FibroScan-based). A dose-response trend was observed between steatosis grade and hypothyroidism, reaching 80% in grade 3 steatosis. FT4 showed a significant positive correlation with liver stiffness (r = 0.432, p < 0.001). Additional associations included positive correlations of liver stiffness with urea and INR, and negative correlations with serum protein, fasting glucose, and LDL. Overall, hypothyroidism emerged as a significant cofactor in NAFLD pathogenesis and fibrosis progression. This study demonstrates a strong association between hypothyroidism and both hepatic steatosis and fibrosis in NAFLD. Routine thyroid function screening is recommended in NAFLD patients, particularly those with metabolic syndrome or suspected fibrosis. Early detection and treatment of hypothyroidism may provide therapeutic benefits in slowing or reversing NAFLD progression.","[""Journal Article"", ""Observational Study""]","[""Chaudhary SC"", ""Singh P"", ""Usman K"", ""Sawlani KK"", ""Gupta KK"", ""Kumar V"", ""Patel ML"", ""Gupta AK"", ""Rungta S"", ""Parihar A""]",10.59556/japi.74.1502,Chaudhary SC,The Journal of the Association of Physicians of India,0004-5772,6,J Assoc Physicians India,eng,Parihar A,"[""Humans"", ""Non-alcoholic Fatty Liver Disease"", ""Hypothyroidism"", ""Male"", ""Cross-Sectional Studies"", ""Female"", ""Adult"", ""Middle Aged"", ""Prevalence"", ""Severity of Illness Index"", ""India"", ""Liver Cirrhosis"", ""Elasticity Imaging Techniques"", ""Ultrasonography"", ""Disease Progression""]",12-15,42543925,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543925/,Hypothyroidism in Nonalcoholic Fatty Liver Disease,74,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"To develop and internally validate an antenatal prediction model for neonatal intensive care unit (NICU) admission among late preterm infants using routinely available maternal and obstetric parameters. This retrospective observational cohort study included deliveries between 340/7 and 366/7 weeks of gestation at a tertiary referral center. Maternal, obstetric, and perinatal data were extracted from electronic medical records. The primary outcome was NICU admission. Variable selection was performed using the Least Absolute Shrinkage and Selection Operator (LASSO), followed by penalized multivariable logistic regression. Model performance was assessed using Harrell's concordance index (C-index), bootstrap internal validation (1000 resamples), calibration analysis, and decision curve analysis. A nomogram was constructed to estimate individualized NICU admission risk. A total of 2007 late preterm pregnancies were included, and neonatal NICU admission occurred in 656 pregnancies (32.7%). Independent predictors of NICU admission were lower gestational age at delivery, fetal growth restriction, twin pregnancy, cesarean delivery, and antenatal corticosteroid exposure. The model demonstrated good discrimination with an apparent C-index of 0.752 and an optimism-corrected C-index of 0.747. Calibration analysis showed excellent agreement between predicted and observed risks. Decision curve analysis indicated a positive net benefit across a wide range of clinically relevant threshold probabilities. The resulting nomogram enabled individualized antenatal risk estimation. An antenatal model incorporating routinely available clinical variables may help estimate the risk of NICU admission among late preterm infants; however, external validation is necessary to confirm its generalizability.","[""Journal Article"", ""Observational Study""]","[""Yergin E"", ""Taşkum İ"", ""Sucu S"", ""Yetişkin FDY"", ""Özkan S"", ""Makansi N"", ""Barutçu C"", ""Sınacı S""]",10.1111/jog.70432,Yergin E,The journal of obstetrics and gynaecology research,1341-8076,8,J Obstet Gynaecol Res,eng,Sınacı S,"[""Humans"", ""Female"", ""Intensive Care Units, Neonatal"", ""Pregnancy"", ""Retrospective Studies"", ""Infant, Newborn"", ""Infant, Premature"", ""Nomograms"", ""Adult"", ""Patient Admission"", ""Gestational Age"", ""Prediction Algorithms""]",e70432,42543749,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42543749/,Antenatal Prediction Model for Neonatal Intensive Care Unit Admission in Late Preterm Infants,52,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Childhood cancer survivors (CCSs) are at increased risk of cancer therapy-related cardiac dysfunction following anthracycline chemotherapy. Although left atrial (LA) strain assessed by speckle-tracking echocardiography has emerged as a sensitive marker of diastolic dysfunction, it remains unclear when during survivorship LA dysfunction becomes detectable in CCSs treated with anthracyclines.In this retrospective observational case-control study, 92 CCSs (aged 4-32 years) and 96 age-matched healthy controls underwent echocardiography. Participants were stratified into three age groups (4-12, 13-18, and 19-32 years). LA reservoir, conduit, and pump strains were measured using two-dimensional speckle-tracking echocardiography from the apical four-chamber view. Conventional echocardiographic parameters, including mitral inflow velocities (E and A waves), E/A ratio, and tissue Doppler-derived e' and E/e', as well as left ventricular longitudinal strain (LVLS), were assessed.Conventional diastolic parameters did not significantly differ between CCSs and controls within corresponding age groups. However, in young adult CCSs (19-32 years), all three components of LA phasic strain (reservoir, conduit, and pump strains) were significantly reduced compared with age-matched controls. LVLS was also significantly lower in this group, whereas younger CCSs showed no significant differences in LA strain.LA phasic dysfunction was most evident in young adult CCSs despite preserved conventional diastolic indices, suggesting that age-stratified LA strain assessment may help identify survivorship stages at which atrial dysfunction becomes detectable.","[""Journal Article"", ""Observational Study""]","[""Sato H"", ""Takahashi K"", ""Hosono Y"", ""Shigemitsu S"", ""Akatsuka Y"", ""Sato K"", ""Kago H"", ""Akiya A"", ""Akimoto S"", ""Ifuku M"", ""Yazaki K"", ""Wakatsuki H"", ""Yaguchi A"", ""Tomita O"", ""Fujimura J"", ""Saito M"", ""Shimizu T""]",10.1536/ihj.26-140,Sato H,International heart journal,1349-2365,4,Int Heart J,eng,Shimizu T,"[""Humans"", ""Anthracyclines"", ""Retrospective Studies"", ""Adolescent"", ""Adult"", ""Child"", ""Young Adult"", ""Cancer Survivors"", ""Heart Atria"", ""Female"", ""Case-Control Studies"", ""Male"", ""Child, Preschool"", ""Atrial Function, Left"", ""Age Factors"", ""Echocardiography, Doppler"", ""Echocardiography"", ""Neoplasms"", ""Antibiotics, Antineoplastic""]",333-341,42543664,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42543664/,Age-Related Impairment of Left Atrial Phasic Strain in Childhood Cancer Survivors Treated with Anthracyclines,67,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"This study aims to evaluate the effects of medial openwedge high tibial osteotomy (OWHTO) on gait analysis outcomes in patients with medial compartment osteoarthritis and varus alignment of the knee. This prospective, observational study included a total of 22 patients who underwent biplanar medial OWHTO between February 2023 and March 2024 were included. Gait analysis was performed preoperatively and at the sixth postoperative month using the DIERS formetric 4D system. Early postoperative (6 months) gait parameters, angular parameters (tibial slope and correction angle), and joint kinematics were evaluated. Patient-reported outcomes were obtained using the Oxford Knee Score (OKS) to assess pain and physical function before and after the procedure. Of a total of 22 patients included in the study, 4 were male and 18 were female with a mean age of 55.41 ± 5.86 (range, 47 to 63) years. Postoperatively, patients' walking speed (0.83 ± 1.12 m/s), step length (0.58 ± 0.73 m), and cadence (82.72 ± 92.05 steps/min) increased significantly (p < 0.001). The tibial slope angle showed a mean increase of 1.93° (p < 0.001). The mean correction angle was 7.53°. The mean knee flexion increased significantly from 35.05° ± 8.74° preoperatively to 52.96° ± 13.21° postoperatively (p < 0.001). Knee extension improved minimally but significantly from -7.55° ± 1.18° to -6.03° ± 0.05° (p = 0.046). Ankle dorsiflexion increased significantly (p < 0.001), whereas changes in plantar flexion were not statistically significant. The OKS score increased significantly from 18.30 preoperatively to 41.50 at the sixth postoperative month (p < 0.001). Medial OWHTO results in early improvements in walking speed, step length, and cadence, as well as enhanced knee flexion kinematics and patient-reported outcomes. These findings indicate that OWHTO is an effective surgical option contributing to the improvement of gait patterns in the early postoperative period.","[""Journal Article"", ""Observational Study""]","[""Emir MM"", ""Uysal ÖS"", ""Javadov G"", ""Yılmaz S"", ""Hajouj J"", ""Öktem U"", ""Adıgüzel E"", ""Tecimel O"", ""Öçgüder DA""]",10.52312/jdrs.2026.2776,Emir MM,Joint diseases and related surgery,2687-4792,3,Jt Dis Relat Surg,eng,Öçgüder DA,"[""Humans"", ""Osteotomy"", ""Female"", ""Prospective Studies"", ""Male"", ""Middle Aged"", ""Tibia"", ""Osteoarthritis, Knee"", ""Gait Analysis"", ""Recovery of Function"", ""Gait"", ""Biomechanical Phenomena"", ""Treatment Outcome"", ""Knee Joint""]",768-776,42542921,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42542921/,Early gait recovery following medial open-wedge high tibial osteotomy: A prospective gait analysis study,37,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Protein supplements have gained popularity among gym users in Saudi Arabia. This study aimed to collect data from adults in Saudi Arabia focusing on six components related to protein supplements: demographic characteristics of participants, health and physical activity information, knowledge and attitudes, use, health beliefs, and safety concerns. This study was a cross-sectional, observational online survey targeting adults in Saudi Arabia. Participants included males and females aged 18 and older. Participants who did not complete the survey, as well as pregnant or breastfeeding women, were excluded. Ethical approval was obtained from the Deanship of Scientific Research at Qassim University. Data were analyzed by gender using SPSS version 25, with descriptive statistics and chi-square tests. A total of 358 participants completed the online questionnaire, while two participants did not complete it between March 29, 2024 and December 31, 2024. Regarding knowledge and attitudes, about 68.2% of participants (including both users and non-users of protein supplements) were aware of protein supplements, with males (81.3%) showing significantly higher awareness than females (63.7%). Additionally, 64.8% of participants (both male and female) were unaware of the risks associated with protein supplements. Of all participants, 56% of males and 39.3% of females did not believe that natural protein sources are enough for muscle building, indicating a significant difference. About 127 participants (35.5%) reported using protein supplements either currently or in the past, with no significant difference between males and females. Of those who reported using protein supplements, 11.8% experienced some side effects and were significantly less knowledgeable about the amount of protein they should consume from food and how much protein is enough for their needs. The majority of protein supplement users (48.8%) did not know if protein powders could contain doping agents, with females reporting significantly higher responses than males. Regarding safety concerns, only 43.3% of protein supplement users looked for protein supplements marked with NSF Certified for Sport® on the package, with no significant difference between males and females. Finally, 78% of protein supplement users expressed a need for more information on how to select the best protein supplements, with the highest need found in females and participants who exercise regularly, who showed significantly higher needs for additional guidance. There remains a significant need for increased education about the proper use of protein supplements to minimize potential side effects and increase understanding of their health risks and safety concerns.","[""Journal Article"", ""Observational Study""]","[""Alaoufi S"", ""Alhomaid RM""]",10.7717/peerj.21545,Alaoufi S,PeerJ,2167-8359,,PeerJ,eng,Alhomaid RM,"[""Humans"", ""Male"", ""Saudi Arabia"", ""Female"", ""Health Knowledge, Attitudes, Practice"", ""Dietary Supplements"", ""Adult"", ""Cross-Sectional Studies"", ""Young Adult"", ""Dietary Proteins"", ""Surveys and Questionnaires"", ""Middle Aged"", ""Adolescent""]",e21545,42542879,pmc-id: PMC13428538;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42542879/,"Perceptions about protein supplements among adults in Saudi Arabia (knowledge and attitude, use, health beliefs, and safety concerns)",14,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"BACKGROUND Hip fractures cause severe perioperative pain, increased opioid use, and delayed recovery. The ultrasound-guided pericapsular nerve group (PENG) and suprainguinal fascia iliaca (SIFI) blocks are regional techniques targeting hip innervation. This study aimed to compare the effects of ultrasound-guided PENG and SIFI blocks on perioperative analgesia and clinical outcomes in hip fracture surgery. MATERIAL AND METHODS This prospective observational study included patients undergoing hip fracture surgery under spinal anesthesia. Patients received either an ultrasound-guided PENG block or a suprainguinal fascia iliaca block as part of routine clinical practice. The primary outcome was perioperative pain intensity measured using the numerical rating scale (0-10), including baseline pre-block assessments, pain during spinal positioning, and postoperative pain scores. All other variables, including ease of spinal positioning, hemodynamic parameters, cumulative 24-hour postoperative tramadol consumption, time to first analgesic requirement, range of motion of the affected limb, patient satisfaction, and adverse events, were evaluated as secondary outcomes. RESULTS A total of 67 patients were included (PENG, n=34; SIFI, n=33). The SIFI group had significantly lower pain scores in the neutral position (P=0.004), during limb elevation (P<0.001), and at 2 to 8 hours postoperatively (P<0.001). The 24-hour consumption of tramadol was lower (P=0.011), and active hip flexion at 8 hours was greater (P=0.001) in the SIFI group. Other outcomes were similar. CONCLUSIONS Both the PENG and SIFI blocks provided effective perioperative analgesia. SIFI was associated with lower pain scores at selected intervals and reduced opioid consumption; however, these findings represent time-specific associations rather than definitive superiority.","[""Journal Article"", ""Observational Study"", ""Comparative Study""]","[""Dedeoğlu A"", ""Acil F"", ""Andıç O"", ""Uzundere O"", ""Gökçek E"", ""Kaçar CK""]",10.12659/MSM.953081,Dedeoğlu A,Medical science monitor : international medical journal of experimental and clinical research,1234-1010,,Med Sci Monit,eng,Kaçar CK,"[""Humans"", ""Female"", ""Nerve Block"", ""Male"", ""Prospective Studies"", ""Hip Fractures"", ""Postoperative Pain"", ""Analgesia"", ""Aged"", ""Ultrasonography, Interventional"", ""Aged, 80 and over"", ""Pain Measurement"", ""Pain Management"", ""Fascia"", ""Treatment Outcome""]",e953081,42542564,,2026 Aug 2,2026,https://pubmed.ncbi.nlm.nih.gov/42542564/,Ultrasound-Guided Pericapsular Nerve Group Block vs Suprainguinal Fascia Iliaca Block for Analgesia in Hip Fracture Surgery: A Prospective Comparative Observational Study,32,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Dental aesthetics plays a key role in children's social perception and psychosocial development. However, evidence on smile perception in children remains limited, highlighting the need for valid and reliable assessment tools. This study aimed to perform the cross-cultural adaptation and psychometric validation of the Smile Perception Questionnaire for Children Aged 8-10 Years (SPQ 8-10) for use in Turkish children. This observational methodological validity-reliability study included 300 healthy children aged 8-10 years who attended the Department of Pediatric Dentistry at Bursa Uludag University and met the predefined eligibility criteria. Eligible participants were healthy children aged 8-10 years whose parents provided informed consent; children with previous or ongoing orthodontic treatment, systemic diseases, or mental, physical, hearing, or visual impairments affecting communication or questionnaire completion were excluded. The SPQ (8-10) was translated into Turkish using forward-backward translation and expert review. Standardized perioral smile images were digitally generated to represent different dental conditions, and each participant evaluated one randomly assigned image using a five-point Likert scale. Exploratory factor analysis (principal axis factoring) and confirmatory factor analysis (DWLS estimation) were conducted to assess construct validity. Internal consistency (Cronbach's α, McDonald's ω) and test-retest reliability (ICC) were evaluated. Cronbach's α coefficient for the scale was 0.844, while McDonald's ω coefficient was 0.847. The analysis yielded ICC (3,1) = 0.803, 95% CI [0.628, 0.901], indicating that the scale had good temporal stability. CFI and TLI values above 0.95 and an SRMR value below 0.06 suggest a good fit. RMSEA value was at the threshold (0.084). The final 10-item Turkish version of the SPQ (8-10) demonstrates adequate psychometric properties in terms of factorial structure, internal consistency, and temporal stability.","[""Journal Article"", ""Validation Study"", ""Observational Study""]","[""Özgöçmen Tula E"", ""Ayvallı Karagöz M"", ""Alkış M""]",10.1186/s12903-026-09440-x,Özgöçmen Tula E,BMC oral health,1472-6831,1,BMC Oral Health,eng,Alkış M,"[""Humans"", ""Child"", ""Smiling"", ""Turkey"", ""Reproducibility of Results"", ""Female"", ""Male"", ""Psychometrics"", ""Surveys and Questionnaires"", ""Esthetics, Dental""]",,42542551,pmc-id: PMC13429015;,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42542551/,Validity and reliability of the smile perception scale in Turkish children aged 8-10 years,26,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Sudden Unexplained Death in Youth (SUDY) requires thorough investigation to identify underlying causes and guide prevention strategies. In the Netherlands, cases are investigated using the standardized Postmortem Evaluation of Sudden Unexplained Death in Infants and Children (PESUDIC), in which autopsy is offered as a standard component. However, its invasive nature and associated time burden may limit parental acceptance. This study evaluated to what extent the cause of death can be established using a limited set of diagnostic tests compared to the standard procedure including autopsy. In this observational study, children > 2 years of age who died suddenly and unexpectedly and underwent PESUDIC, including imaging and autopsy, were included. Two expert panels, consisting of a forensic and a pediatric specialist, independently assessed early diagnostic tests available before autopsy. Cases were classified by level of diagnostic certainty and need for autopsy. Panel conclusions were compared with the reference standard: a multidisciplinary audit incorporating all available information, including autopsy findings. Sixty-six cases were included (median age 12 years (IQR 4-14.7), 63% male). Panels identified indicative information for a cause of death in 60 patients (91%). Nevertheless, autopsy was required in most cases (n = 59) to confirm the diagnosis. In 7 cases (10.6%), panels were sufficiently confident to establish the cause of death without autopsy with complete agreement with the reference standard. Causes included obstructive gastrointestinal pathology (n = 5) and diabetic ketoacidosis with dehydration (n = 2). Only a small proportion of children > 2 years of age with sudden unexpected death have a cause of death that can be established with sufficient certainty at an early stage. In the vast majority of cases, the cause of death remains uncertain, supporting the recommendation to perform an autopsy. • Autopsy in sudden unexplained death in youth is worldwide recognized as the gold standard for postmortem examination. However, its invasive nature and associated time burden may limit parental acceptance. • In 7 of 60 sudden and unexplained deceased minors (10%), sufficient certainty regarding the cause of death can be obtained by other minimal invasive diagnostic test, so without the need of an autopsy. Causes without the need of an autopsy included obstructive gastrointestinal pathology and diabetic ketoacidosis with dehydration.","[""Journal Article"", ""Observational Study""]","[""van der Gugten AC"", ""Wemeijer TM"", ""Semmekrot BA"", ""Smit RBJ"", ""Oostdam C"", ""Duijst WLJM"", ""de Gier S"", ""van de Putte E"", ""PESUDIC collaborative""]",10.1007/s00431-026-07286-7,van der Gugten AC,European journal of pediatrics,0340-6199,8,Eur J Pediatr,eng,van de Putte E,"[""Humans"", ""Child"", ""Male"", ""Death, Sudden"", ""Autopsy"", ""Child, Preschool"", ""Adolescent"", ""Cause of Death"", ""Female"", ""Netherlands""]",,42542442,pmc-id: PMC13428766;,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42542442/,Autopsy in sudden unexplained death in youth: indispensable or in some cases redundant? An observational study,185,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Obesity is a chronic relapsing disease leading to weight-related health risks for disorders such as cardiovascular diseases, type 2 diabetes, osteoarthritis, and depression. Many studies focus on these weight-related health risks. However, research on current self-reported social impacts and health complaints is limited. This study aims to investigate self-reported social impact and health complaints, received care aiming at lifestyle change, and perceived effectiveness of this care, by children with obesity and their parents. Secondarily, differences concerning sex, age, obesity-severity and frequency of received care were studied. Questionnaires were collected from children and adolescents aged 0-18 years visiting Obesity Center CGG. Data were analyzed regarding their social impacts, health complaints, received care, and perceived care effectiveness (0-10 scale). Children were categorized into sex, age, BMI, and care categories. Descriptive statistics were performed using chi-square tests and post hoc analyses to examine differences between categories. 86.8% of the patients self-reported experiencing social impact and 92.3% reported health complaints. Most frequently reported social impacts were difficulty to find fitting clothes (70.1%), problems in mobility and sports (63.7%), and bullying (41.6%); most reported health complaints were abdominal pain (38.8%), headache (34.8%), and musculoskeletal pain (34.1%). The dietician (64.1%) was most frequently reported as received care, and effectiveness scores ranged between 0 and 4 out of 10. A substantial percentage of patients experience social impacts and health complaints affecting their well-being and quality of life. Low perceived effectiveness of interventions calls for a more innovative and comprehensive care framework incorporating these children's needs. • Children with overweight and obesity face a wide range of adverse health consequences and social challenges. • However, the number and types of health issues experienced by children themselves and studying per range of age, BMI-stage or care trajectory have not been systematically investigated. • A high percentage of children experience social impacts (87%) and health complaints (70%) aff ecting their well-being and quality of life, and perceived eff ectiveness of lifestyle interventions is low. The main reported healthcomplaints abdominal pain, headache, musculoskeletal pain and snoring loudly were mostly observed in girls withobesity aged 12-18 years, who received three or more care types. • The study demonstrated that perceived treatment effectiveness by children and parents declined with increasingobesity severity.","[""Journal Article"", ""Observational Study""]","[""van der Velden MMAM"", ""van der Walle EEPL"", ""Bindels PPJE"", ""van Middelkoop M"", ""van den Akker EELT""]",10.1007/s00431-026-07295-6,van der Velden MMAM,European journal of pediatrics,0340-6199,8,Eur J Pediatr,eng,van den Akker EELT,"[""Humans"", ""Female"", ""Child"", ""Male"", ""Prospective Studies"", ""Adolescent"", ""Parents"", ""Pediatric Obesity"", ""Child, Preschool"", ""Quality of Life"", ""Infant"", ""Surveys and Questionnaires"", ""Self Report""]",,42542436,pmc-id: PMC13428758;,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42542436/,"Health complaints, social impacts, and perceived care effectiveness reported by children with obesity and their parents: a prospective observational study in the Obesity Center CGG cohort",185,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"The main objective of the study is to evaluate the performance of the FilmArray® Pneumonia Plus (FA-PP) panel in critically ill patients with suspected pneumonia compared to conventional culture, in both pandemic and pospandemic periods, and its impact on therapeutic decision-making. Observational study including 225 patients (314 samples) during COVID-19 pandemic and post-pandemic periods. FA-PP and culture results were compared assessing sensitivity (Se), specificity, predictive values, level of concordance between them and the impact on antibiotic prescription. FA-PP detected 133% more bacterial targets than culture and 48% more positive samples. Excluding off-panel bacteria, the panel showed high sensitivity of up to 100% in patients with pneumonia and a negative predictive value (NPV) of over 98%. In the post-pandemic period, the overall Se (78.6%) and Se in patients with pneumonia (81%), as well as the overall NPV and in pneumonia (94%), were higher than in the pandemic period, with significant differences (p<0.05). Twenty-six per cent of pneumonia episodes involved bacteria not included in the panel. The positive concordance between the two tests was 72%. In 56% of cases with pneumonia, antibiotic was modified after the results. During the pandemic period, the panel served to modify treatment towards initiation or escalation. The FA-PP is a valuable tool for optimizing the diagnosis and management of pneumonia in the ICU, with a clinical impact on the appropriateness of antibiotic treatment. There were differences in the impact of the panel between the pandemic and post-pandemic periods.","[""Journal Article"", ""Observational Study"", ""Comparative Study""]","[""García-Lechuz JM"", ""Arias A"", ""Alonso P"", ""Badenas-Alzugaray D"", ""Viñeta V"", ""Claraco L"", ""Gurpegui M"", ""Carrillo A"", ""Viñuelas J""]",10.1016/j.eimce.2026.503107,García-Lechuz JM,Enfermedades infecciosas y microbiologia clinica (English ed.),2529-993X,7,Enferm Infecc Microbiol Clin (Engl Ed),eng,Viñuelas J,"[""Humans"", ""Intensive Care Units"", ""COVID-19"", ""Tertiary Care Centers"", ""Female"", ""Middle Aged"", ""Male"", ""Aged"", ""Sensitivity and Specificity"", ""Time Factors"", ""Pandemics"", ""Anti-Bacterial Agents"", ""Predictive Value of Tests"", ""SARS-CoV-2"", ""Pneumonia"", ""Pneumonia, Bacterial""]",503107,42542349,,2026 Aug-Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42542349/,Five years-real-world experience with FilmArray Pneumonia Plus Panel in the diagnosis of pneumonia in an intensive care unit in a tertiary hospital: Lights and shadows in pandemic and postpandemic COVID periods,44,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Fatigue poses a significant safety risk in helicopter operations; however, subjective assessments of fatigue based on an individual's perception, awareness, and insight, such as self-perceived tiredness, may not accurately reflect objective performance impairment as identified by standardized tests or measurement tools. In this context, the present study investigated the relationship between subjective drowsiness and objective alertness performance among helicopter pilots during operational tasks using a computerized psychomotor vigilance task (PVT). This observational field study initially included 20 helicopter pilots. Complete pre- and postflight measurements were available for 15 pilots and were included in the final analysis. Subjective sleepiness was assessed before testing using the Karolinska Sleepiness Scale. Objective alertness was measured pre- and postflight using a PVT; mean reaction time (ms) was used as the primary outcome variable. The mean subjective sleepiness score was 3.98 ± 1.27 (range: 2.0-6.9). Mean PVT reaction time increased from 461.2 ± 118.1 ms preflight to 516.3 ± 100.8 ms postflight (an 11.9% increase), reaching statistical significance with a medium-to-large effect size (Cohen's dz = 0.65). Considerable interindividual variability was observed. Correlation analysis revealed a weak association between subjective sleepiness and postflight PVT reaction time (r = 0.16, P = 0.573), with prolonged reaction times observed in some pilots reporting low subjective sleepiness. Combining objective alertness measures with subjective scales may improve fatigue risk management. Gevrek I, Eroglu C. Psychomotor alertness and subjective fatigue in helicopter pilots. Aerosp Med Hum Perform. 2026; 97(8):633-637.","[""Journal Article"", ""Observational Study""]","[""Gevrek I"", ""Eroglu C""]",10.3357/AMHP.6887.2026,Gevrek I,Aerospace medicine and human performance,2375-6314,8,Aerosp Med Hum Perform,eng,Eroglu C,"[""Humans"", ""Fatigue"", ""Psychomotor Performance"", ""Adult"", ""Reaction Time"", ""Male"", ""Pilots"", ""Aircraft"", ""Sleepiness"", ""Middle Aged"", ""Aerospace Medicine"", ""Attention"", ""Wakefulness"", ""Female""]",633-637,42542322,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42542322/,Psychomotor Alertness and Subjective Fatigue in Helicopter Pilots,97,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"To characterize the demographic and exposure characteristics and management of rabies post-exposure prophylaxis (rPEP) among international travelers, and to identify deficiencies in pre-travel prevention, initial wound management, and subsequent post-exposure care. A retrospective observational study was conducted at the Department of Infectious Diseases and Travel Medicine, Motol and Homolka University Hospital. The study included patients evaluated between December 2022 and December 2024 following animal-related exposures. Demographic data, exposure characteristics, wound management, and details of rPEP, including rabies vaccination and rabies immunoglobulin (RIG) administration, were anayzed. Exposures were classified according to the World Health Organization (WHO) categories. Data were analyzed using descriptive statistical methods. A total of 134 patients were included, with a median age of 31 years. Exposures predominantly occurred in Southeast Asia (35.1%) and Western Asia (25.4%), particularly in Türkiye, Thailand, and Indonesia. Dogs were the most frequently implicated animals (46.3%), followed by cats (23.9%) and monkeys (20.9%). Bites accounted for 66.4% of exposures, while 65.7% of cases were classified as WHO category III exposures. Initial wound management was frequently suboptimal; only 54.9% of patients reported immediate wound washing, and 76.1% applied a disinfectant. Preexposure rabies vaccination had been received by only 6.7% of travelers. rPEP was initiated abroad in 62.7% of cases. However, among patients indicated for RIG administration, 77.8% did not receive it. Deviations from recommended rabies vaccination schedules were documented in 38.2% of patients. Wound infections developed in 4.5% of cases. This study highlights significant gaps in rabies prevention and post-exposure management among international travelers. Low uptake of pre-exposure vaccination, frequent deviations from recommended rPEP protocols, and limited access to RIG in rabies-endemic settings represent major barriers to optimal prevention. These findings underscore the importance of comprehensive pre-travel counseling and broader implementation of pre-exposure rabies vaccination among travelers at increased risk of animal exposure.","[""Journal Article"", ""Observational Study"", ""English Abstract""]","[""Trojánek M"", ""Šindlerová R"", ""Jegorova V"", ""Tulach M"", ""Martišík S"", ""Štefan M"", ""Grebenyuk V"", ""Stejskal F""]",,Trojánek M,Klinicka mikrobiologie a infekcni lekarstvi,1211-264X,2,Klin Mikrobiol Infekc Lek,cze,Stejskal F,"[""Humans"", ""Rabies"", ""Retrospective Studies"", ""Post-Exposure Prophylaxis"", ""Female"", ""Adult"", ""Male"", ""Animals"", ""Rabies Vaccines"", ""Travel"", ""Middle Aged"", ""Adolescent"", ""Young Adult"", ""Cats"", ""Child"", ""Hospitals, University"", ""Dogs"", ""Bites and Stings""]",56-64,42541791,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42541791/,[Rabies post-exposure prophylaxis in travelers returning from endemic areas: A retrospective analysis of patients treated at Motol and Homolka University Hospital],32,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"AIM: To evaluate the relationship between optic nerve sheath diameter (ONSD) and intracranial pressure (ICP) in patients with acute ICP elevation controlled through external ventricular drainage (EVD). MATERIAL and METHODS: In this prospective observational study, simultaneous measurements of right and left ONSD, ICP, and cerebral perfusion pressure (CPP) were recorded in 46 adult patients undergoing EVD. Two patients were excluded due to ophthalmic pathology and missing data, resulting in a final cohort of N = 44 patients. After we obtained the baseline measurements, 5 mL of cerebrospinal fluid (CSF) were drained, and the measurements were repeated 2 minutes (min) later. RESULTS: CSF drainage led to significant reductions in both ICP and bilateral ONSD (p = .001 for all), while CPP significantly increased (p = .038). We identified an ONSD cut-off of 5.35 mm for detecting ICP values ≥15 mmHg, and this cut-off had 53% sensitivity and 86% specificity (Youden index: 0.395). However, we could not determine a reliable cut-off for detecting ICP values ≥20 mmHg (p = .076). CONCLUSION: When ICP is controlled through EVD, the linear relationship between ONSD and ICP observed during acute pressure elevations may be disrupted, particularly at higher ICP values (≥20 mmHg). Although we identified a cut-off ONSD value of 5.35 mm for detecting ICP values ≥15 mmHg, the low sensitivity of this cut-off significantly limits its clinical utility. Additionally, since no reliable cut-off could be established for ICP values ≥20 mmHg, ONSD may have limited value for monitoring pressure following CSF drainage.","[""Journal Article"", ""Observational Study""]","[""Ozkaya G"", ""Korkmaz Dilmen O"", ""Akcil EF"", ""Tunali Y""]",10.5137/1019-5149.JTN.49051-25.4,Ozkaya G,Turkish neurosurgery,1019-5149,4,Turk Neurosurg,eng,Tunali Y,"[""Humans"", ""Optic Nerve"", ""Female"", ""Prospective Studies"", ""Adult"", ""Male"", ""Middle Aged"", ""Intracranial Pressure"", ""Intracranial Hypertension"", ""Drainage"", ""Aged""]",573-580,42541783,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42541783/,Determination of Optic Nerve Sheath Diameter Cut-off after CSF Drainage in Adults with Elevated ICP: A Prospective Study,36,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"This study compared the cross-sectional areas (CSA) of key intrinsic foot muscles in people with and without plantar heel pain (PHP). Seventy-five adults participated in the study: 50 participants with PHP and 25 age-, sex-, and body mass index (BMI)-matched participants without PHP (control group). Cross-sectional images were generated using 3.0T magnetic resonance imaging (MRI). CSAs of four intrinsic foot muscles-abductor hallucis, quadratus plantae, flexor digitorum brevis and abductor digiti minimi-were measured. The difference in CSA of each muscle was compared between the groups using independent samples t-tests and Cohen's d effect sizes were calculated. Participants were well matched: mean age 49.1 and 48.9 years, women accounted for 58% and 56%, and BMI 30.6 kg/m2 and 30.2 kg/m2 in the PHP and control groups, respectively. There were no significant differences in mean CSAs for all four muscles (p > 0.05) between the PHP and control groups, and effect sizes were tiny or very small. This study found no differences in muscle CSAs of key intrinsic muscles of the foot in people with and without PHP, indicating that people with PHP do not have key intrinsic foot muscle size deficits. As such, intrinsic muscle size does not appear to be a logical therapeutic target for PHP. Clinicians translating our findings into practice should, therefore, consider whether strengthening interventions targeting intrinsic muscles in PHP are warranted.","[""Journal Article"", ""Observational Study""]","[""Osborne JWA"", ""Azevedo AM"", ""Menz HB"", ""Whittaker GA"", ""Cotchett M"", ""Entwisle T"", ""Connell DA"", ""Munteanu SE"", ""Landorf KB""]",10.1002/jfa2.70183,Osborne JWA,Journal of foot and ankle research,1757-1146,3,J Foot Ankle Res,eng,Landorf KB,"[""Humans"", ""Female"", ""Middle Aged"", ""Cross-Sectional Studies"", ""Magnetic Resonance Imaging"", ""Male"", ""Muscle, Skeletal"", ""Adult"", ""Heel"", ""Foot"", ""Case-Control Studies"", ""Fasciitis, Plantar""]",e70183,42541750,pmc-id: PMC13428631;,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42541750/,Intrinsic Foot Muscle Cross-Sectional Area on MRI in People With and Without Plantar Heel Pain: A Cross-Sectional Observational Study,19,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Pancreatic cancer (PC) is a highly lethal malignancy. 4-10% are linked to inherited mutations in genes such as BRCA1/2, PALB2, ATM and mismatch repair (MMR) genes. Germline testing is essential to guide treatment decisions, yet delays remain common. Genetic testing models without pre-test assessment in a Hereditary Cancer Unit (HCU), have emerged as a strategy to improve earlier clinical decision-making. A retrospective, observational and descriptive study was conducted on 223 PC patients (55% male; average age 64 years) who underwent rapid germline genetic testing at Hospital General Universitario Gregorio Marañón (Madrid, Spain) between April 2019 and May 2024. Tests were ordered by oncologists with brief pre-test counseling, followed by a nurse-facilitated consent and peripheral blood collection. Post-test counseling in an HCU was offered for patients with variants of unknown significance (VUS) and pathogenic/likely pathogenic variants (PV), or upon physician or patient request. PV and VUS were identified in 32 (14.3%) and 82 (36.7%) patients, respectively. 50% of PV carriers did not meet familial PC criteria. Actionable mutations were detected in 14 (43.7%) of PV carriers, involving BRCA2 (6/32), PALB2 (1/32) and ATM (7/32). Treatment modifications occurred in 7/223 patients (3%), including PARP inhibitors or platinum-based regimens. Median time from the genetic test request to the results was 48 days (95% CI, 44-52). Mainstream genetic testing in PC is a viable approach to expedite results and facilitate precision oncology. Further studies are needed to evaluate long-term outcomes, cost-effectiveness and the psychosocial impact compared to traditional genetic counseling pathways.","[""Journal Article"", ""Observational Study""]","[""Bringas M"", ""Echavarría I"", ""Polo C"", ""Jiménez-Alduán N"", ""Flores C"", ""Muñoz A"", ""Ortega L"", ""Torres G"", ""Soto-Alsar J"", ""Calvo A"", ""Alfonso PG"", ""Pajares JA"", ""Suárez-González J"", ""Del Monte-Millán M"", ""Massarrah T"", ""de la Peña FA"", ""Martín M"", ""Márquez-Rodas I""]",10.1007/s10689-026-00595-8,Bringas M,Familial cancer,1389-9600,3,Fam Cancer,eng,Márquez-Rodas I,"[""Humans"", ""Genetic Testing"", ""Pancreatic Neoplasms"", ""Female"", ""Male"", ""Middle Aged"", ""Spain"", ""Retrospective Studies"", ""Tertiary Care Centers"", ""Aged"", ""Germ-Line Mutation"", ""Genetic Counseling"", ""Fanconi Anemia Complementation Group N Protein"", ""Genetic Predisposition to Disease"", ""BRCA2 Protein"", ""Adult"", ""Ataxia Telangiectasia Mutated Proteins""]",,42541517,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42541517/,Mainstream and fast-track genetic testing in pancreatic cancer patients and its impact on treatment: our experience in a tertiary hospital in Spain,25,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"To (1) describe the demographic, health∗ and criminological characteristics of people released from prison; (2) examine their associations with post-imprisonment service use. Retrospective observational cohort study of all individuals released from Scottish prisons in 2015 (n = 8,313). Scottish Prison Service data were linked with records covering community prescriptions, death registrations, admissions to general and psychiatric hospitals, outpatient contacts, and unscheduled care. Four years of service use before and following the release (index) date were extracted. Incidence rates for service contacts with a diagnosis or code related to mental health (MH) or substance use (SU) across all nine services were computed, adjusted for time-in-community. Negative binomial models were fitted to estimate the rates of service contact per time-in-community for each service. The cohort was 92% male, 97% white, 96% heterosexual, and 45% from large urban areas. Mean index age was 34.8 (SD=10.8) years, and pre-index mean days in prison were 524 (SD=433). Prior service contact was a strong predictor of service contact in the follow-up period, especially for inpatient and emergency contacts. Time in prison, and the number of prison episodes , were associated with higher rate of service contacts, as was female sex and disclosed disability. Age and release type had varied effects across services. It is vital for policymakers and practitioners in health and criminal justice to review how they accommodate varied population needs, and to minimise the iatrogenic harms of imprisonment. Linkage of prison and health records enables unique insights into this vulnerable and overlooked population.","[""Journal Article"", ""Observational Study""]","[""Savinc J"", ""Kjellgren R"", ""Connell C"", ""Dougall N"", ""Kurdi A"", ""Leyland A"", ""Watson J"", ""Hunt K""]",10.23889/ijpds.v11i5.3634,Savinc J,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Hunt K,"[""Humans"", ""Female"", ""Male"", ""Scotland"", ""Retrospective Studies"", ""Substance-Related Disorders"", ""Mental Disorders"", ""Prisoners"", ""Adult"", ""Mental Health Services"", ""Middle Aged""]",3634,42540990,pmc-id: PMC13426706;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540990/,RELEASE: demographic and criminological differences in post-imprisonment mental health and substance use-related service use,11,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Warm Wales (WW) is a community-based programme addressing fuel poverty and its broader impact on health and well-being. Interventions combine tailored energy advice, practical support, and education with wellbeing and social prescribing projects to improve health outcomes. Fuel poverty is closely linked to poorer health, making evaluating such programmes using housing and health linked data crucial. To describe the demographic, socioeconomic, health, and housing characteristics of individuals supported by WW and examine the programme's impact on primary care interactions. Methodology: An observational longitudinal cohort study linking WW service data with routinely collected electronic health record and administrative data in the Secure Anonymised Information Linkage (SAIL) Databank. Descriptive statistics summarised the WW supported population. Difference in Differences (DiD) compared primary care interactions rates between cases and Coarsened Exact Matched controls. WW supported 4,083 individuals living across 1,317 properties (January 2021-December 2023). Most WW-supported properties were older (65% built before 1966 vs 60.7% in Welsh housing stock) and socially rented (62.3% vs 19.2% in Welsh housing stock 2021). The cohort mirrored Welsh population sex and ethnicity distributions but was notably younger (aged 18 and under 40.1% vs 25.8%), in the most deprived quintile (40.9% vs 24.0%), and predominantly urban (81.5% vs 73.1%). Health characteristics and DiD results are pending approvals. Warm Wales supports younger individuals living in most deprived areas and older housing. These characteristics are consistent with groups at risk of fuel poverty. DiD analyses are ongoing and will assess the intervention's impact on healthcare utilisation.","[""Journal Article"", ""Observational Study""]","[""Alshams M"", ""Bentley L"", ""Peh J"", ""Greene G"", ""Davies A"", ""Akbari A"", ""Newman C"", ""Davies O"", ""Taylor-Collins E"", ""Dundon J""]",10.23889/ijpds.v11i5.3525,Alshams M,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Dundon J,"[""Humans"", ""Wales"", ""Longitudinal Studies"", ""Poverty"", ""Female"", ""Male"", ""Middle Aged"", ""Housing"", ""Primary Health Care"", ""Socioeconomic Factors"", ""Social Prescribing""]",3525,42540903,pmc-id: PMC13426600;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540903/,Fuel Poverty Interventions and Healthcare Usage: Insights from Warm Wales,11,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"To address the growing population health challenges, the nursing workforce is expected to possess competencies of population health, which has been officially included as a new essential component in nursing and strongly advocated by nurse educators worldwide. However, no previous studies have explored the relevant opinions among nursing students, who act as recipients, beneficiaries, and key stakeholders in nursing education. This study aimed to explore students' population health knowledge, perceived access to relevant training, and attitudes toward integrating population health content within undergraduate nursing curricula. A cross-sectional observational survey was conducted using a self-developed questionnaire among nursing students from a Chinese university in January 2026. Data collected included demographic information, population health knowledge levels measured via both self-assessment and objective evaluation, perceived accessibility of undergraduate training related to population health competencies, attitudes toward integrating population health into undergraduate nursing education, and preferred integration models. A total of 163 nursing students who provided valid responses were included in the final analysis. The mean self-assessed and objective scores of population health knowledge (rated on a 5-point scale) were 2.98 ± 0.10 and 0.71 ± 0.06, respectively. Less than 20% of participants reported having frequent or very frequent access to educational opportunities targeting core population health competencies. Nearly half of the students agreed or strongly agreed with the importance of population health and its inclusion in nursing education, particularly at the undergraduate level, and 73.0% expressed their willingness to systematically learn about population health. Furthermore, 44.2% students believed that population health should be longitudinally integrated into the current undergraduate nursing education framework, while 21.5% preferred the ""lecture-based elective course"" as pedagogical model. Findings indicate insufficient preparedness in population health competencies among future nursing professionals. Integration of population health into undergraduate nursing education is necessary and generally acceptable to students.","[""Journal Article"", ""Observational Study""]","[""Wang L"", ""Wang J""]",10.3389/fpubh.2026.1898158,Wang L,Frontiers in public health,2296-2565,,Front Public Health,eng,Wang J,"[""Humans"", ""Cross-Sectional Studies"", ""Female"", ""Male"", ""Students, Nursing"", ""Health Knowledge, Attitudes, Practice"", ""Education, Nursing, Baccalaureate"", ""Surveys and Questionnaires"", ""China"", ""Population Health"", ""Adult"", ""Young Adult"", ""Curriculum"", ""Attitude of Health Personnel""]",1898158,42539800,pmc-id: PMC13424291;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42539800/,"Students' knowledge, perceived access, and attitudes toward population health integration in undergraduate nursing education",14,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Deep neck space infections (DNSI) are rapidly progressive suppurative conditions in which early identification of causative pathogens is critical for clinical decision-making. This study evaluated the diagnostic performance and clinical utility of metagenomic next-generation sequencing (mNGS) in patients with DNSI. In this retrospective observational study, 32 patients with radiologically confirmed DNSI who underwent surgical drainage between October 2023 and August 2025 were included. Intraoperative purulent specimens were analyzed using both conventional bacterial culture and mNGS. A composite clinical reference standard integrating clinical presentation, imaging findings, surgical observations, inflammatory markers, and expert assessment was used to evaluate the clinical relevance of detected microorganisms. mNGS detected microbial DNA in 84.4% of patients and demonstrated a broader pathogen detection spectrum and shorter reporting time than conventional culture, particularly for anaerobic and fastidious organisms. Frequently detected organisms included Prevotella spp. and Streptococcus constellatus. Interpretation of these findings required careful consideration of anatomical involvement, organism abundance, and prior antimicrobial exposure to distinguish clinically relevant pathogens from colonizing organisms or residual nonviable DNA. Discordant findings between culture and mNGS, including culture-positive/mNGS-negative and dual-negative cases, were observed and likely reflected differences in sampling adequacy, organism viability, sequencing depth, and methodological limitations. Antimicrobial therapy was adjusted in selected patients following mNGS reporting. mNGS may serve as a valuable adjunct to conventional microbiological diagnostics by expanding pathogen detection in selected DNSI cases, particularly when fastidious or anaerobic organisms are involved. However, its results should be interpreted cautiously in the context of clinical and microbiological findings. Prospective controlled studies are needed to further define the clinical role of mNGS in the management of DNSI.","[""Journal Article"", ""Observational Study""]","[""Wang Z"", ""Yang H"", ""Liu J"", ""Li X""]",10.3389/fcimb.2026.1874210,Wang Z,Frontiers in cellular and infection microbiology,2235-2988,,Front Cell Infect Microbiol,eng,Li X,"[""Humans"", ""High-Throughput Nucleotide Sequencing"", ""Retrospective Studies"", ""Metagenomics"", ""Neck"", ""Female"", ""Male"", ""Bacteria"", ""Middle Aged"", ""Aged"", ""Bacterial Infections"", ""Adult"", ""Aged, 80 and over"", ""DNA, Bacterial""]",1874210,42539687,pmc-id: PMC13423987;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42539687/,Diagnostic value of metagenomic next-generation sequencing in deep neck space infections: a retrospective study of 32 patients,16,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"OBJECTIVE: To determine the trajectory of (1) change in pain-related fear and catastrophizing factors, (2) changes in pain-related fear and catastrophizing by treatment satisfaction groups, and (3) the relationship between pain-related fear trajectories, and catastrophizing factors and shoulder disability during an 8-week resistance exercise program. DESIGN: Prospective longitudinal observational study. METHODS: Sixty-four people with rotator cuff tendinopathy completed the exercise protocol. Outcomes of Penn Shoulder Score (Penn) shoulder disability and pain-related fear and catastrophizing via the Optimal Screening for Prediction of Referral and Outcome-Yellow Flag (OSPRO-YF) were assessed at baseline and at 2, 4, and 8 weeks. Patient Acceptable Symptom State (PASS) defined satisfaction with treatment at 8 weeks. RESULTS: All pain-related fear and catastrophizing measures changed over time during resistance exercise (P < .01) but differed by PASS-defined responder and nonresponder groups. For the Fear-Avoidance Beliefs Questionnaire-Work subscale (FABQ-W), nonresponders had an increase (0.63 pt) while responders had a decrease (-3.5 pt) (mean difference, 4.2 pt; 95% confidence interval [CI]: -7.6, -0.7; P = .02). For TSK-11, nonresponders had less of a decrease (-0.1) than responders (-3.2 pt) (mean difference, 3.1 pt; 95% CI: -5.9, -0.3; P = .03). Reduced shoulder disability was related to less pain-related fear and catastrophizing (P < .01), and differed by responder group. Nonresponders had no relationship between change in pain-related fear and catastrophizing and disability (P>.05); responders had an overall negative relationship (P < .04). CONCLUSION: Pain-related fear and catastrophizing changed over time for individuals with rotator cuff tendinopathy, and changes varied by participant. Those who were not satisfied at 8 weeks had higher levels of pain-related fear and catastrophizing, while those who were satisfied had reduced pain-related fear and catastrophizing. Less pain-related fear and catastrophizing was related to decreased disability. J Orthop Sports Phys Ther 2026;56(8):546-554. Epub 9 Jun 2026. doi:10.2519/jospt.2026.13563.","[""Journal Article"", ""Observational Study""]","[""Mears CK"", ""Heindel MD"", ""Abeles RE"", ""Vila-Dieguez O"", ""Beneciuk JM"", ""Michener LA""]",10.2519/jospt.2026.13563,Mears CK,The Journal of orthopaedic and sports physical therapy,0190-6011,8,J Orthop Sports Phys Ther,eng,Michener LA,"[""Humans"", ""Female"", ""Male"", ""Prospective Studies"", ""Middle Aged"", ""Catastrophization"", ""Fear"", ""Longitudinal Studies"", ""Resistance Training"", ""Tendinopathy"", ""Disability Evaluation"", ""Shoulder Pain"", ""Pain Measurement"", ""Adult"", ""Patient Satisfaction"", ""Kinesiophobia"", ""Aged"", ""Rotator Cuff Injuries""]",546-554,42538792,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42538792/,Changes in Pain-Related Fear Predict Shoulder Disability in Rotator Cuff Tendinopathy With Resistance Exercise,56,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"To evaluate the impact of continuous renal replacement therapy (CRRT) on plasma amino acid (AA) concentrations in patients with acute metabolic decompensation of organic acidemias (OAs), and to explore whether AA supplementation during CRRT may mitigate AA depletion. Multicenter retrospective observational study. PICUs managing acute metabolic decompensations of OAs. Patients with confirmed OAs who underwent CRRT for severe acute metabolic decompensation. CRRT was initiated according to current guidelines in cases of severe decompensation. Standard metabolic management included high caloric intake through carbohydrates and lipids with temporary protein withdrawal (24-48 hr). In one patient, AA supplementation (2 g/kg) during CRRT combined with thiamin and citrate (anaplerotic therapy) was administered. Plasma AA concentrations were measured before and after CRRT in nine patients with a median age of 21 days (interquartile range [IQR], 3-570 d). Quantitative variables are expressed as medians (IQR, 25th-75th). Before CRRT, 31% (95% CI, 24-39) of plasma AAs were below the normal range compared with 69% (95% CI, 59-77) after CRRT (p < 0.0001). A significant increase in lactatemia was observed following CRRT, without evidence of organ failure: median 2.2 mmol/L (IQR, 1.3-2.3) before CRRT vs. 5.3 mmol/L (IQR, 3.2-7.1) after CRRT; Hodges-Lehmann median difference +3.2 (95% CI, 0.8-5.6; p = 0.0065). In the patient receiving AA supplementation with anaplerotic therapy, plasma AA status improved markedly, with 65% of AAs below normal before CRRT vs. 15% after CRRT. In acute decompensated OAs, CRRT performed without protein supplementation, as currently recommended, significantly reduces total plasma AA concentrations and may impair restoration of anabolism. AA infusion during CRRT could help preserve or restore protein anabolism. Prospective studies are needed to assess the safety and efficacy of AA supplementation during CRRT, with or without anaplerotic therapy, in this setting.","[""Journal Article"", ""Multicenter Study"", ""Observational Study""]","[""Grosyeux C"", ""Cammiciotto N"", ""Jeannesson E"", ""Feigerlova E"", ""Villada V"", ""Wicker C"", ""Levy M"", ""Schiff M"", ""Imbard A"", ""Coelho D"", ""Feillet F"", ""Wiedemann A""]",10.1097/CCE.0000000000001413,Grosyeux C,Critical care explorations,2639-8028,8,Crit Care Explor,eng,Wiedemann A,"[""Humans"", ""Amino Acids"", ""Continuous Renal Replacement Therapy"", ""Retrospective Studies"", ""Male"", ""Female"", ""Middle Aged""]",e1413,42538737,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42538737/,Amino Acid Deficiency Secondary to Continuous Venovenous Hemofiltration in Acute Decompensation of Organic Acidemias: An Anabolic Dead End?,8,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Therapeutic plasma exchange has become an increasingly important extracorporeal therapy in pediatric intensive care and transplant settings. However, evaluations in large real-world pediatric cohorts of its effectiveness and safety across multiple indications remain limited. In this 5 -year single -center study, we provided our experience with therapeutic plasma exchange in critically ill children and assessed clinical outcomes, indications, and procedure -related complications. This retrospective observational study included 88 pediatric patients who underwent 702 therapeutic plasma exchange sessions in the pediatric transplant and nephrology intensive care unit of Başkent University Hospital (Ankara, Turkey) between December 2018 and December 2023. Indications were classified according to new American Society for Apheresis categories. We analyzed demographic data, indications, replacement fluids, treatment response, and adverse events. Median age of the 88 pediatric patients who underwent 702 therapeutic plasma exchange sessions was 7.5 years (range, 0 -18 y ), and 52.3 % of patients were male. Fresh frozen plasma was used in 89.8 % of sessions and albumin in 23.9 %. The most frequent indications for therapeutic plasma exchange were posttransplant hepatic dysfunction (36.4 % ) and acute or chronic liver failure (28.4 % ), followed by antibody -mediated renal disease (13.6 % ) and multiorgan failure or sepsis (8 % ). Overall, 73 of 88 patients achieved complete or partial improvement, corresponding to a favorable response rate of 82.9 %. Renal transplant-related indications demonstrated higher response rates compared with liver -related conditions (91 % vs 78.9 % ). No life-threatening or procedure -terminating complications occurred; minor adverse events included hypotension, fever, allergic reactions, and thrombosis. Therapeutic plasma exchange is a safe and effective supportive therapy for critically ill pediatric patients across a wide range of indications. When performed in experienced centers with close monitoring, complication rates are low. Multicenter prospective studies are needed to establish standardized protocols and further clarify disease-specific outcomes.","[""Journal Article"", ""Observational Study""]","[""Baskın E"", ""Dönger U"", ""Siddiqui MA"", ""Özçay F"", ""Sahin Eroglu E"", ""Şafak A"", ""Karakaya E"", ""Haberal M""]",10.6002/ect.MESOT2025.O58,Baskın E,Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation,1304-0855,Suppl 2,Exp Clin Transplant,eng,Haberal M,"[""Humans"", ""Plasma Exchange"", ""Child"", ""Female"", ""Child, Preschool"", ""Male"", ""Retrospective Studies"", ""Treatment Outcome"", ""Infant"", ""Adolescent"", ""Risk Factors"", ""Infant, Newborn"", ""Time Factors"", ""Organ Transplantation"", ""Age Factors"", ""Turkey"", ""Critical Illness"", ""Risk Assessment""]",166-171,42538675,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42538675/,"Therapeutic Plasma Exchange in Pediatric Transplant and Organ Failure: Analysis of Indications, Adverse Events, and Clinical Outcomes",24,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Dengue virus (DENV) infection poses a major global public health burden, particularly in endemic regions where repeated exposure increases the risk of severe disease. Despite revisions to the World Health Organization (WHO) dengue classification, early prediction of progression to severe dengue remains challenging due to overlapping clinical and laboratory features. Current management strategies rely primarily on supportive care and reactive monitoring, underscoring the need for predictive biomarkers that enable early risk stratification and timely intervention. COMBAT is a prospective, multicenter, observational longitudinal study conducted in dengue-endemic regions of Guatemala and India. Patients will be classified according to WHO 2009 criteria into dengue without warning signs, dengue with warning signs, and severe dengue, alongside age- and sex-matched healthy controls. A single blood sample will be collected from non-hospitalized patients while two blood samples per participant will be collected during hospitalization and one at discharge. Multi-omics analyses, including transcriptomics, proteomics, glycomics and metabolomics, will be performed in a discovery cohort and validated in an independent cohort. Integrated systems biology approaches will be used to identify host immune and metabolic pathways associated with dengue severity in a mechanism-based prognostic biomarker discovery. This study aims to generate comprehensive systems-level insights into host-virus interactions driving dengue severity and to identify biomarkers predictive of disease progression. The findings may inform improved patient triage, early intervention strategies, and the identification of novel therapeutic targets. ClinicalTrials.gov ID NCT06751836 Registration Date: December 13, 2024, CTRI/2022/10/046293 (MAHE) Registration Date: October 10, 2022.","[""Journal Article"", ""Observational Study"", ""Multicenter Study""]","[""Mudgal PP"", ""Veliz SPZ"", ""Lourda M"", ""Kadni TS"", ""Varma M"", ""Mazumder A"", ""Budhiraja S"", ""Jaggi N"", ""Mukhopadhyay C"", ""Sengupta S"", ""Maitra A"", ""Hug K"", ""Sinha I"", ""Ambikan AT"", ""Filipovic I"", ""Neogi U"", ""COMBAT consortium""]",10.1186/s12879-026-14111-x,Mudgal PP,BMC infectious diseases,1471-2334,1,BMC Infect Dis,eng,Neogi U,"[""Humans"", ""Biomarkers"", ""Multiomics"", ""Prospective Studies"", ""India"", ""Severe Dengue"", ""Guatemala"", ""Longitudinal Studies"", ""Metabolomics"", ""Proteomics"", ""Dengue Virus"", ""Female""]",,42538555,pmc-id: PMC13428414;,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538555/,A multicenter prospective observational multi-omics study protocol to identify biomarkers for severe dengue: COMBAT study clinical protocol,26,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Early prediction of successful weaning from non-invasive ventilation (NIV) remains challenging in patients with acute respiratory failure. This study evaluated clinical, laboratory, and severity-score predictors of NIV weaning outcomes among patients admitted to the Respiratory Intensive Care Unit (RICU). This prospective observational cross-sectional study included 150 adult patients with acute respiratory failure, admitted to the RICU and required NIV for > 24 h between April 2024 and March 2025. Clinical characteristics, arterial blood gases, laboratory findings, ventilator settings, and APACHE II score were recorded. HACOR score was assessed after one hour of NIV discontinuation. Patients were classified into successful or failed weaning groups. Successful weaning occurred in 99 patients, while 51 experienced weaning failure. Failure was significantly associated with older age (p = 0.001), decompensated cor pulmonale (p = 0.003), lower hemoglobin and serum albumin levels (p = 0.008 and p = 0.005, respectively), higher APACHE II score (18.3 ± 3, p < 0.001), and higher HACOR score (8.1 ± 2.1, p < 0.001). Previous invasive mechanical ventilation ≥ 2 times was also significantly associated with failure (p = 0.001). Multivariate analysis identified age, serum albumin, APACHE II score, HACOR score, and previous invasive ventilation as independent predictors of weaning outcome. Receiver operating characteristic analysis showed good predictive performance for HACOR (AUC 81.6%) and APACHE II (AUC 76.2%) scores (p < 0.001 for both). Older age, poor nutritional status, previous invasive ventilation, high APACHE II score, and HACOR score independently predict NIV weaning failure. The incorporating of HACOR score into NIV weaning protocols may improve clinical decision-making and potentially reduce adverse outcomes associated with delayed recognition of respiratory deterioration.","[""Journal Article"", ""Observational Study""]","[""Gadallah D"", ""Esmaeel HM"", ""Mahmoud HA"", ""Khalaf AR""]",10.1038/s41598-026-63797-1,Gadallah D,Scientific reports,2045-2322,1,Sci Rep,eng,Khalaf AR,"[""Humans"", ""Ventilator Weaning"", ""Prospective Studies"", ""Female"", ""Intensive Care Units"", ""Male"", ""Respiratory Insufficiency"", ""Noninvasive Ventilation"", ""Middle Aged"", ""Aged"", ""APACHE"", ""Cross-Sectional Studies"", ""Respiratory Care Units""]",,42538338,pmc-id: PMC13427732;,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538338/,Integrating validated scores with clinical parameters to predict NIV weaning outcomes: a prospective study in the respiratory ICU,16,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"To examine the association of perinatal asphyxia across mild to moderate hypoxic-ischaemic encephalopathy (HIE) severity levels and therapeutic hypothermia (TH) with child developmental outcomes and parenting stress and to explore parental trauma and psychosocial support. Multicentre, cross-sectional, comparative observational study. Two university medical centres in Germany. Parents of children aged 1-5.5 years with a history of perinatal asphyxia treated with TH (n=58) or without TH (n=77), and unexposed control children (n=179). Parents completed the Ages & Stages Questionnaire, Third Edition, and the Parenting Stress Index (PSI) for the primary outcome, and reported on birth-related trauma, psychosocial support and family planning decisions as exploratory secondary outcomes. Most children showed age-appropriate developmental outcomes across all groups. In contrast, parents in both asphyxia groups reported elevated stress levels, with higher PSI scores in the TH group, particularly in the health, competence and attachment domains. Postnatal trauma was highly prevalent, affecting 88% of parents in the TH group, 73% in the non-TH group and 15% in controls. Psychosocial support was perceived as sufficient by only 20% of parents in the non-TH group, compared with 39% in the TH group. Birth-related trauma was a significant predictor of parental stress. Despite mostly age-appropriate development on screening, parental stress and trauma were highly prevalent regardless of HIE severity, and psychosocial support was markedly insufficient, particularly for families whose infants did not receive TH. These findings highlight the need for structured, accessible psychosocial support for all patient-families affected by perinatal asphyxia.","[""Journal Article"", ""Observational Study"", ""Multicenter Study"", ""Comparative Study""]","[""Sutterer-Verrelli A"", ""Georg AK"", ""Riecker A"", ""Weiss VB"", ""Puchwein-Schwepcke AF"", ""Nussbaum C""]",10.1136/bmjpo-2026-004976,Sutterer-Verrelli A,BMJ paediatrics open,2399-9772,1,BMJ Paediatr Open,eng,Nussbaum C,"[""Humans"", ""Cross-Sectional Studies"", ""Female"", ""Asphyxia Neonatorum"", ""Male"", ""Infant"", ""Stress, Psychological"", ""Parents"", ""Infant, Newborn"", ""Parenting"", ""Child, Preschool"", ""Hypoxia-Ischemia, Brain"", ""Germany"", ""Hypothermia, Induced"", ""Child Development"", ""Social Support"", ""Surveys and Questionnaires""]",,42538123,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538123/,High levels of parenting stress and trauma despite age-appropriate developmental outcomes following perinatal asphyxia: a cross-sectional observational study,10,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"Following the reclassification of COVID-19 as a category V infectious disease in Japan in May 2023, systematic public health monitoring of case numbers and cluster outbreaks was discontinued. Consequently, infection control measures, responses to cluster outbreaks and vaccination coverage in long-term care facilities were largely left to the discretion of individual facilities, and the understanding of the current situation in these settings remains insufficient. This observational study aims to retrospectively investigate COVID-19 cluster outbreaks and the resulting burdens experienced by facilities after reclassification, focusing on special nursing homes (Tokubetsu Yogo Rojin Home) for older adults, a population at particularly high risk for COVID-19-associated hospitalisation and mortality. By comprehensively evaluating facility and resident characteristics, vaccination coverage and infection prevention and control measures, this study seeks to generate evidence to inform future infection control strategies in long-term care facilities. This retrospective observational study targets special nursing homes in Okinawa Prefecture and residents living in these facilities. Data for a target sample of nine nursing homes with approximately 900 residents will be collected from existing facility and medical records using the Research Electronic Data Capture system. The study was initiated in June 2025 and completion is anticipated by March 2027. The primary outcomes are the occurrence of COVID-19 cluster outbreaks in nursing homes between May 2023 and August 2025 and the facility-level burden experienced during outbreaks, including operational and economic impacts. A cluster outbreak is defined as the occurrence of ≥2 cases of the same infectious disease within a 10-day period. Key variables of interest include baseline characteristics of facilities and residents, vaccination coverage among staff and residents and infection prevention and control measures. Additionally, the study explores potential factors associated with residents' clinical outcomes and facility burden using logistic and linear regression models, respectively, with facility-level random intercepts if deemed appropriate. Prespecified supplementary analyses include one-way analysis of variance and χ2 tests. The study protocol was approved by the Institutional Review Board of the University of the Ryukyus in June 2025 (approval number: 25-2486-00-00-00). The findings will be disseminated at academic conferences and in peer-reviewed medical journals.","[""Journal Article"", ""Observational Study""]","[""Ideguchi S"", ""Takayama Y"", ""Ikemiyagi N"", ""Ujimiya F"", ""Yamaniha K"", ""Imura M"", ""Tanabe K"", ""Yamamoto K""]",10.1136/bmjopen-2025-116064,Ideguchi S,BMJ open,2044-6055,7,BMJ Open,eng,Yamamoto K,"[""Humans"", ""Japan"", ""Nursing Homes"", ""Retrospective Studies"", ""Infection Control"", ""COVID-19"", ""Disease Outbreaks"", ""SARS-CoV-2"", ""Nursing Home Residents"", ""Aged""]",e116064,42538112,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538112/,COVID-19 cluster outbreaks and infection control measures in nursing homes in Okinawa: protocol for a retrospective observational study,16,kwxd6qpxpJE14TaP7,B1q1x9UqSznjcCe2h
"The clinical practice guidelines for congenital adrenal hyperplasia (CAH) in children clearly and systematically present the key information on the epidemiology, etiology, pathogenesis, and diagnostic methods for all forms of the disease. Protocols for glucocorticoid and mineralocorticoid replacement therapy, as well as follow-up regimens for patients in different age groups, are provided. These clinical guidelines were developed and approved by the expert community of pediatric endocrinologists from the Russian Association of Endocrinologists and endorsed by the council of the Russian Federation Ministry of Health. The guidelines are based on systematic reviews, meta-analyses, original articles, and scientific studies on this pathology conducted in the Russian Federation and other countries. This article provides updated author comments and clarifications on the most critical aspects of the diagnosis and treatment of congenital adrenal hyperplasia in childhood.","[""Journal Article"", ""English Abstract"", ""Practice Guideline""]","[""Chugunov IS"", ""Kopylova IV"", ""Kolodkina AA"", ""Kalinchenko NY"", ""Vorontsova MV"", ""Bezlepkina OB"", ""Peterkova VA"", ""Mokrysheva NG""]",10.14341/probl13767,Chugunov IS,Problemy endokrinologii,0375-9660,3,Probl Endokrinol (Mosk),rus,Mokrysheva NG,"[""Humans"", ""Adrenal Hyperplasia, Congenital"", ""Child"", ""Glucocorticoids"", ""Russia"", ""Practice Guidelines as Topic"", ""Mineralocorticoids""]",86-106,42545327,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42545327/,"[Clinical practice guidelines ""Congenital adrenal hyperplasia in children"" with comments]",72,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"The United States Census Bureau projects that the population of Americans ≥65 years old will grow 5 times faster than the total population, reaching 82 million by 2050 (23% of the population). Health care providers will increasingly need to discuss the cessation of cancer screening due to limited value in patients whose age or comorbidities preclude time to benefit from eradication of preneoplastic lesions. Although evidence supports colonoscopy's ability to reduce population-wide colorectal cancer mortality, high-quality data around endoscopic surveillance of Barrett's esophagus is more limited. In this Clinical Practice Update, we review practical approaches to assess appropriateness for colorectal cancer and esophageal cancer surveillance, the real-world yield of screening and/or surveillance in older adults, and the potential harms of surveillance. This expert review was commissioned and approved by the American Gastroenterological Association Institute Clinical Practice Updates Committee and the American Gastroenterological Association Governing Board to provide timely guidance on a topic of high clinical importance to the American Gastroenterological Association membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. BEST PRACTICE ADVICE STATEMENTS BEST PRACTICE ADVICE 1: Formal determination of comorbidities and use of life expectancy tools may help differentiate among older adults most likely to benefit vs those most likely to be harmed by surveillance. Real-world effectiveness and cost-effectiveness analysis in diverse populations would help with widespread implementation. BEST PRACTICE ADVICE 2: The goal of endoscopic surveillance in Barrett's esophagus is to detect dysplasia and adenocarcinoma at an early and treatable stage. Endoscopic surveillance of Barrett's esophagus should follow current best practices in terms of imaging, tissue acquisition, and surveillance intervals. BEST PRACTICE ADVICE 3: The choice to continue endoscopic surveillance of Barrett's esophagus should be based on shared decision-making that examines factors such as comorbidities, life expectancy, risks, and benefits, as well as patient preferences. BEST PRACTICE ADVICE 4: Utilization of tools for prediction of dysplasia progression in Barrett's esophagus may help contextualize the time frame for the development of adenocarcinoma within an individual's life expectancy. BEST PRACTICE ADVICE 5: Inability to tolerate endoscopic therapy, surgery, or oncologic interventions for esophageal adenocarcinoma should lead to cessation of Barrett's esophagus surveillance regardless of age. BEST PRACTICE ADVICE 6: The decision to continue colorectal cancer screening in individuals >75 years old should be individualized, based on an assessment of benefits, screening history, comorbidities, and risks. BEST PRACTICE ADVICE 7: The decision to continue surveillance of colorectal polyps in individuals >75 years old should be individualized, based on an assessment of benefits, polyp history, comorbidities, and risks. BEST PRACTICE ADVICE 8: With increasing age, colonoscopy is associated with a higher incidence of adverse events regardless of the indication. Therefore, the clinical decision-making process for colonoscopy should be clearly documented in the electronic health record for individuals >75 years. BEST PRACTICE ADVICE 9: Whenever possible, published studies of the use, effectiveness, deimplementation, and costs of colonoscopy in older adults should be used to inform practice decisions for patients and clinicians.","[""Journal Article"", ""Practice Guideline""]","[""Calderwood AH"", ""Yoshida CM"", ""Das KK"", ""Falk GW""]",10.1016/j.cgh.2026.06.007,Calderwood AH,Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association,1542-3565,,Clin Gastroenterol Hepatol,eng,Falk GW,[],,42545305,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545305/,AGA Clinical Practice Update on Surveillance of Metaplastic and Premalignant Conditions of the Esophagus and Colorectum in Older Adults: Expert Review,,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"People taking antipsychotic medicines and those with severe mental illness experience elevated cardiovascular risk compared to the general population which is not adequately addressed by existing guidelines. Increases in lipid levels can occur soon after starting antipsychotics but often go untreated. Cumulative exposure to dyslipidemia from childhood, through young adulthood, facilitates atherogenesis. Regression of early lesions is possible; however, plaque progression can be irreversible, leading to sustained long-term cardiovascular risk. Although lipid-lowering therapies are effective at lowering cardiovascular risk, they are underutilized in this population. We have thus developed a clinical practice guideline for the pharmacological management of antipsychotic-related dyslipidemia. Using GRADE-ADOLOPMENT methodology, an international, multidisciplinary panel including experts-by-experience, developed a guideline for the pharmacological management of antipsychotic-related dyslipidemia. Literature was reviewed to answer key health questions. Patient important outcomes were identified. An evidence-to-decision framework informed the strength of recommendations and external reviews evaluated the rigor of the methods. Seven recommendations were developed on how and when to initiate lipid-lowering therapy based on specific criteria including established cardiovascular disease/high-risk conditions, cardiovascular risk assessment, or lipid parameter thresholds. A guideline algorithm illustrates the recommendations alongside supporting prescribing information. This is the first clinical practice guideline for the management of antipsychotic-related dyslipidemia. The inclusion of recommendations for individuals aged 10 years and over represents a significant development. Implementation will be supported by shared decision-making resources including information videos and decision-aids.","[""Journal Article"", ""Practice Guideline""]","[""Carolan A"", ""Hynes-Ryan C"", ""Bourke R"", ""Columb D"", ""Cullen W"", ""deFerranti S"", ""Harrington SM"", ""Kelleher I"", ""Kennedy C"", ""Khoury M"", ""Lally J"", ""Lyne J"", ""Norton M"", ""O'Connor K"", ""O'Connor P"", ""O'Shea D"", ""Perry B"", ""Prendeville T"", ""Ryan C"", ""Sadowska E"", ""Shiers D"", ""Siskind D"", ""Strawbridge J"", ""Tae H"", ""Keating D"", ""O'Donoghue B""]",10.1093/schbul/sbag086,Carolan A,Schizophrenia bulletin,0586-7614,4,Schizophr Bull,eng,O'Donoghue B,"[""Humans"", ""Dyslipidemias"", ""Antipsychotic Agents"", ""Hypolipidemic Agents"", ""Practice Guidelines as Topic"", ""Cardiovascular Diseases"", ""Schizophrenia""]",,42544493,,2026 Jul 3,2026,https://pubmed.ncbi.nlm.nih.gov/42544493/,Clinical Practice Guideline on the Pharmacological Management of Antipsychotic-Related Dyslipidemia,52,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
,"[""Journal Article"", ""Practice Guideline""]","[""Murphy E"", ""Nielsen B"", ""Smith K"", ""Flanagan S"", ""Carrillo S"", ""Magasi S""]",10.1016/j.apmr.2026.06.022,Murphy E,Archives of physical medicine and rehabilitation,0003-9993,,Arch Phys Med Rehabil,eng,Magasi S,[],,42541510,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42541510/,Designing the Home Environment to Support Aging in Place for Individuals With Intellectual and Developmental Disabilities,,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Climate change has increased the vulnerability of patients with non-dialysis chronic kidney disease (CKD) and those receiving kidney replacement therapy (KRT), who depend on healthcare systems that are highly sensitive to disruptions in electricity, potable water supply, and logistics. At the same time, KRT services are among those with the greatest environmental impact within the healthcare sector, characterized by high water and energy consumption and substantial generation of solid waste. In this context, the incorporation of sustainable practices has become an ethical, clinical, and strategic imperative. In 2023, the Brazilian Society of Nephrology (SBN) established the Committee on Sustainable Nephrology with the objective of developing national guidelines to reduce the environmental impact of kidney care services. After two years of work, the Committee developed ten recommendations structured across key domains, including education, environ-mental indicator monitoring, waste management, efficient use of resources, climate contingency planning, promotion of prevention and kidney transplantation, technological innovation, and sustainability certifications. These recommendations were discussed and approved at the 2nd Convention of the SBN Board of Directors and its Regional Chapters, achieving a 98.5% level of agreement. This document presents the consolidated recommendations, with the aim of supporting the implemen-tation of sustainable practices in kidney care services across the country and pro-moting an environmentally responsible, efficient nephrology practice aligned with the emerging challenges posed by climate change.","[""Journal Article"", ""Practice Guideline""]","[""Moura AF"", ""Vieira CKS"", ""Pimentel AL"", ""Pinto LCS"", ""Nerbass FB"", ""Tostes FRV"", ""Riso NDM"", ""Trancoso RB"", ""Salani TG"", ""Costa CBS"", ""Abreu PF"", ""Moura-Neto JA""]",10.1590/2175-8239-JBN-2026-0059en,Moura AF,Jornal brasileiro de nefrologia,0101-2800,3,J Bras Nefrol,eng,Moura-Neto JA,"[""Brazil"", ""Nephrology"", ""Humans"", ""Societies, Medical"", ""Conservation of Natural Resources"", ""Climate Change""]",e20260059,42531489,pmc-id: PMC13427308;,2026 Jul-Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42531489/,Recommendations of the Brazilian Society of Nephrology for sustainable nephrology in Brazil,48,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
,"[""Journal Article"", ""Practice Guideline""]","[""Subspecialty Group of Endocrinology, Hereditary and Metabolic Diseases, the Society of Pediatrics, Chinese Medical Association"", ""Editorial Board, Chinese Journal of Pediatrics""]",10.3760/cma.j.cn112140-20260309-00194,"Subspecialty Group of Endocrinology, Hereditary and Metabolic Diseases, the Society of Pediatrics, Chinese Medical Association",Zhonghua er ke za zhi = Chinese journal of pediatrics,0578-1310,8,Zhonghua Er Ke Za Zhi,chi,"Editorial Board, Chinese Journal of Pediatrics","[""Humans"", ""Diabetes Mellitus, Type 1"", ""Child"", ""Early Diagnosis"", ""Quality of Life"", ""Mass Screening""]",853-862,42527127,,2026 Aug 2,2026,https://pubmed.ncbi.nlm.nih.gov/42527127/,"[Guideline for diagnosis, treatment and prevention of type 1 diabetes mellitus in children(2026)]",64,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Stool tests are an essential component of colorectal cancer (CRC) screening. Patients with positive test results are at increased risk of CRC, and a timely follow-up with colonoscopy is recommended. Follow-up colonoscopy rates remain suboptimal. The current article reviews the barriers to timely colonoscopy, highlights evidence-based interventions, and provides actionable recommendations for endoscopists, health systems, and policymakers. By implementing coordinated strategies, including patient navigation, digital tools, and open access colonoscopy, health care organizations can close critical gaps in the CRC screening continuum and decrease CRC incidence and mortality.","[""Journal Article"", ""Practice Guideline""]","[""Levin TR"", ""Ciemins E"", ""Dominitz J"", ""Hosseini-Carroll P"", ""Issaka RB"", ""Lieberman D"", ""Merriman N"", ""Shaukat A"", ""Stollman N"", ""Williams KN""]",10.1016/j.gie.2026.05.028,Levin TR,Gastrointestinal endoscopy,0016-5107,,Gastrointest Endosc,eng,Williams KN,[],,42524792,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42524792/,Improving follow-up of abnormal stool test results used for colorectal cancer screening,,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Accidental hypothermia is an underdiagnosed condition with a significant impact on public health. With the aim of providing the basis for a comprehensive care framework, 12 panelists from 3 Spanish scientific societies (SEDAR, SEMES and SEMICYUC) developed this multidisciplinary consensus document. Through a systematic search and the final synthesis of 281 articles including 1,704,632 patients, 37 recommendations were developed through a 2-round Delphi process, distributed across 8 application domains based on the organization of a rescue chain: prehospital prevention, initial evaluation, management and transport, hospital detection, care of the polytraumatized patient, hospital rewarming, cardiac arrest, and resuscitation. Robust consensus among panelists (>75% agreement) and excellent internal consistency (ω = 0.913) were achieved, providing a solid document that may serve as a basis for the implementation of standardized protocols.","[""Journal Article"", ""Consensus Statement"", ""Practice Guideline""]","[""Blasco Mariño R"", ""Argudo E"", ""Soteras Martínez I"", ""Avellanas Chavala ML"", ""Pons Claramonte M"", ""Rius J"", ""Martín Sánchez L"", ""Pinillos Alonso A"", ""González-Delgado D"", ""Barea Mendoza JA"", ""Fernandez CP"", ""Laurens Acevedo M""]",10.55633/s3me/070.2026,Blasco Mariño R,Emergencias : revista de la Sociedad Espanola de Medicina de Emergencias,1137-6821,4,Emergencias,spa,Laurens Acevedo M,"[""Humans"", ""Hypothermia"", ""Spain"", ""Emergency Medical Services"", ""Critical Care"", ""Rewarming"", ""Cardiopulmonary Resuscitation"", ""Heart Arrest"", ""Delphi Technique"", ""Resuscitation"", ""Societies, Medical""]",285-298,42522393,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42522393/,"Consensus document on the management of patients with accidental hypothermia from the Spanish Society of Anesthesiology, Resuscitation and Pain Management (SEDAR), the Spanish Society of Intensive Care Medicine, Critical Care and Coronary Units (SEMICYUC), and the Spanish Society of Emergency Medicine (SEMES)",38,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
,"[""Journal Article"", ""Practice Guideline""]","[""van Wegberg AMJ"", ""MacDonald A"", ""Giżewska M"", ""Ahring K"", ""Lange E"", ""Hagedorn T"", ""Hammerschmidt G"", ""Henek M"", ""van Spronsen FJ""]",10.1016/j.ymgme.2026.110221,van Wegberg AMJ,Molecular genetics and metabolism,1096-7192,1-2,Mol Genet Metab,eng,van Spronsen FJ,[],110221,42520342,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42520342/,European PKU guidelines at a glance: infographics summarising key recommendations,149,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
,"[""Journal Article"", ""Practice Guideline""]","[""Hosseini-Carroll P"", ""Dominitz JA"", ""Jacobson BC"", ""May FP"", ""Issaka RB"", ""Schmitt CM"", ""Adams TL"", ""Boston IJ"", ""Bucobo JC"", ""Day L"", ""Khaykis IB"", ""Marino MJ"", ""Rex DK"", ""Sun E"", ""Wynter JA"", ""Christie JA""]",10.1016/j.gie.2026.05.027,Hosseini-Carroll P,Gastrointestinal endoscopy,0016-5107,,Gastrointest Endosc,eng,Christie JA,[],,42517844,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42517844/,Closing the completion colonoscopy gap: key takeaways from the American Society for Gastrointestinal Endoscopy's 2025 National Colorectal Cancer Screening Summit,,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Contemporary surgical and medical management has enabled excellent long-term survival and quality of life for children following repair of tetralogy of Fallot. However, most patients are left with residual pulmonary regurgitation that requires long-term surveillance and eventual pulmonary valve replacement to prevent right ventricular failure. Guidelines have been developed regarding the indications for and timing of pulmonary valve replacement in adults, but such do not exist for children. This expert consensus document aimed to address those gaps by supporting clinical decision-making regarding the surgical and transcatheter management of chronic pulmonary regurgitation in children with repaired tetralogy of Fallot. The Society of Thoracic Surgeons Workforce on Evidence Based Surgery assembled a multidisciplinary expert panel composed of congenital surgeons and cardiologists. A focused literature review was performed, and expert consensus statements were developed using a Modified Delphi process and clustered under two key topics: (1) pediatric-specific considerations and (2) surgical versus transcatheter techniques. Consensus was reached for 13 recommendations. The recommendation statements reflect contemporary expert opinion on the timing and decision-making for pulmonary valve replacement in children. While decision-making regarding the management of chronic pulmonary regurgitation after repair of tetralogy of Fallot in children is complex, this document provides guidance for congenital heart teams to optimize management based on a synthesis of contemporary evidence.","[""Journal Article"", ""Practice Guideline""]","[""Stephens EH"", ""Zampi JD"", ""Sarris GE"", ""Protopapas E"", ""Zanaboni DB"", ""Taggart NW"", ""Lotto AA"", ""Rossi CS"", ""Kamp A"", ""Sood P"", ""St Louis JD"", ""Jacobs JP"", ""Nelson JS""]",10.1016/j.athoracsur.2026.07.010,Stephens EH,The Annals of thoracic surgery,0003-4975,,Ann Thorac Surg,eng,Nelson JS,[],,42508675,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42508675/,"The Society of Thoracic Surgeons / World Society for Pediatric and Congenital Heart Surgery / European Congenital Heart Surgeons Association 2026 Expert Consensus Document on Timing, Indications, and Options for Pulmonary Valve Replacement in Children with Repaired Tetralogy of Fallot",,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Respiratory and systemic infections can trigger cardiovascular events by increasing inflammation, atherosclerotic plaque instability, and a prothrombotic state. Given this situation, vaccination is a relevant preventive tool in patients with cardiovascular disease (CVD). To review the available evidence on the impact of vaccination in patients with CVD and to propose recommendations to improve vaccination coverage in clinical practice. This expert consensus, developed through a structured narrative review and panel discussion rounds, synthesizes the evidence on vaccination against influenza, pneumococcal disease, respiratory syncytial virus (RSV) infection, COVID-19, and herpes zoster in patients with CVD. The influenza vaccine presents the strongest evidence for reducing cardiovascular events, especially after acute episodes and in high-risk patients. For vaccination against pneumococcal disease, COVID-19, RSV infection, and herpes zoster, although direct cardiovascular evidence is more limited, the reduction in infections and hospitalizations supports its recommendation for a comprehensive preventive approach. Vaccination is part of a comprehensive cardiovascular prevention approach. Improved coverage, supported by shared pathways between cardiology and primary care, along with public health services, can result in fewer infectious complications, fewer cardiovascular decompensations, and better clinical outcomes.","[""English Abstract"", ""Journal Article"", ""Practice Guideline""]","[""Bonanad C"", ""Alfaro R"", ""Morán Bayón Á"", ""Cainzos-Achirica M"", ""García-Lledó A"", ""Raposeiras-Roubín S"", ""Vivas D"", ""Freixa-Pamias R"", ""Mora J"", ""Martín-Toro MA"", ""Fernández-Olmo R"", ""Maidana D"", ""Barreres-Martín G"", ""Barrios V"", ""Redondo E""]",10.1016/j.semerg.2026.102819,Bonanad C,Semergen,1138-3593,7,Semergen,spa,Redondo E,[],102819,42508371,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42508371/,[Comprehensive cardiovascular prevention: the role of vaccination in older adults with cardiovascular disease. Expert consensus document],52,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"First aid is the immediate care provided for acute illness or injury and can be initiated by anyone in any situation. Its aims are the preservation of life, alleviation of suffering, prevention of further harm and promotion of recovery. To reflect evolving medical science surrounding first aid, the standards of care by first aiders must also evolve accordingly. The Singapore Resuscitation and First Aid Council has updated the national practice standards with the publication of the Singapore First Aid Guidelines 2026. The current guidelines incorporate the latest international evidence synthesis while prioritising relevance for Singapore's first aid training and operational context. The existing guidelines remain relevant unless specifically updated. The main additions and significant revisions in this edition include guidance on pulse oximeters, bronchodilators, supplementary oxygen, repeated doses of adrenaline in anaphylaxis, hypoglycaemia correction, physical counterpressure manoeuvres for presyncope, handling of amputated body parts, rehydration for exertional-related dehydration and treatment of jellyfish stings.","[""Journal Article"", ""Practice Guideline""]","[""Ho AFW"", ""Oh JHH"", ""Pek JH"", ""Loke JH"", ""Lim SH""]",10.4103/singaporemedj.SMJ-2026-277,Ho AFW,Singapore medical journal,0037-5675,7,Singapore Med J,eng,Lim SH,"[""Humans"", ""First Aid"", ""Singapore"", ""Anaphylaxis"", ""Epinephrine"", ""Fluid Therapy"", ""Resuscitation"", ""Dehydration"", ""Bronchodilator Agents""]",466-471,42507347,,2026 Jul 1,2026,https://pubmed.ncbi.nlm.nih.gov/42507347/,Singapore First Aid Guidelines 2026,67,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Effective neonatal resuscitation demands coordinated teamwork following standardised algorithms and guidelines to ensure successful transition to extrauterine life. As guidelines evolve with emerging evidence, regular review and adherence to updated recommendations are crucial for optimal patient outcomes. We present the revised Singapore Neonatal Resuscitation Guidelines 2026. The recent 2025 recommendations from the International Liaison Committee on Resuscitation Neonatal Task Force's Consensus on Science and Treatment Recommendations, together with guidelines from the American Heart Association and the European Resuscitation Council, were compared with the existing guidelines. The recommendations of the Neonatal Subgroup of the Singapore Resuscitation and First Aid Council were formulated following the workgroup's critical discussion and appraisal of the currently available evidence, with careful consideration of its relevance and applicability to local clinical practice.","[""Journal Article"", ""Practice Guideline""]","[""Kong JY"", ""Kader KBA"", ""Baral VR"", ""Arunachalam S"", ""Buvaneswarran S"", ""Chinnadurai A"", ""Tong WY"", ""Yip WY"", ""Ee KTT"", ""Yeo CL"", ""Biswas A"", ""Ho SKY"", ""Quek BH""]",10.4103/singaporemedj.SMJ-2026-278,Kong JY,Singapore medical journal,0037-5675,7,Singapore Med J,eng,Quek BH,"[""Humans"", ""Singapore"", ""Infant, Newborn"", ""Resuscitation"", ""Practice Guidelines as Topic"", ""Algorithms"", ""Cardiopulmonary Resuscitation""]",453-465,42507346,,2026 Jul 1,2026,https://pubmed.ncbi.nlm.nih.gov/42507346/,Singapore Neonatal Resuscitation Guidelines 2026,67,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"The Singapore Paediatric Life Support Guidelines 2026 updates the 2021 guidelines and provides evidence-based, consensus recommendations for life support in paediatric patients (<18 years of age), excluding newborns. We reviewed treatment recommendations from the International Liaison Committee on Resuscitation Paediatric Life Support Task Force as well as resuscitation guidelines from the American Heart Association, the European Resuscitation Council and other relevant studies and reviews published between January 2021 and January 2026 to inform these paediatric life support guidelines. This clinical practice guideline adopts an evidence-based and patient-centred approach to the life support of paediatric patients in Singapore. Recommendations were updated following deliberation of peer-reviewed evidence updates on paediatric resuscitation, with consideration of local context, resources and clinical practice.","[""Journal Article"", ""Practice Guideline""]","[""Ong GY"", ""Ngiam N"", ""Tham LP"", ""Menon AP"", ""Pek JH"", ""Pandey A"", ""Mathiprechakul S"", ""Chee QZ"", ""Chan CJ"", ""Oh E"", ""Ang I"", ""Lin CB"", ""Chang CM"", ""Ganapathy S"", ""Ong JS"", ""Mok YH"", ""Chong SL"", ""Ng KC"", ""Paediatric Subcommittee 2023–2027, Singapore Resuscitation and First Aid Council""]",10.4103/singaporemedj.SMJ-2026-318,Ong GY,Singapore medical journal,0037-5675,7,Singapore Med J,eng,Ng KC,"[""Humans"", ""Singapore"", ""Child"", ""Life Support Care"", ""Pediatrics"", ""Resuscitation"", ""Practice Guidelines as Topic"", ""Infant"", ""Adolescent"", ""Infant, Newborn"", ""Cardiopulmonary Resuscitation"", ""Child, Preschool""]",442-452,42507345,,2026 Jul 1,2026,https://pubmed.ncbi.nlm.nih.gov/42507345/,Singapore Paediatric Life Support Guidelines 2026,67,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"An updated clinical practice guideline on total knee arthroplasty, initially published in 2020, was developed by an American Physical Therapy Association volunteer guideline development group consisting of physical therapists, an orthopedic surgeon, and an occupational therapist. The guideline was based on a systematic review of current scientific literature. Twenty recommendations were formulated. Benefits, harms, feasibility, and role of patient preferences in implementing these recommendations were identified. Recommendations identified current gaps in knowledge and future areas of needed research.","[""Journal Article"", ""Practice Guideline""]","[""Bove AM"", ""Carroll LA"", ""Cone S"", ""Dibblee P"", ""Hensley CP"", ""Lenington K"", ""Manner PA"", ""Scalzitti DA"", ""Tompkins J"", ""Bade MJ""]",10.1093/ptj/pzag058,Bove AM,Physical therapy,0031-9023,7,Phys Ther,eng,Bade MJ,"[""Humans"", ""Arthroplasty, Replacement, Knee"", ""Physical Therapy Modalities""]",,42506877,pmc-id: PMC13403188;,2026 Jul 2,2026,https://pubmed.ncbi.nlm.nih.gov/42506877/,Clinical practice guideline for physical therapist management of total knee arthroplasty: revision 2026,106,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"The management of traumatic brain injury (TBI) in maritime settings faces multiple challenges, including significant disparities in medical platform capabilities compared to land-based systems, spatial constraints and persistent vessel motion, limitations in power supply, oxygen, and consumables, unstable conditions for monitoring and imaging, evacuation influenced by sea-state windows, and difficulties in inter-platform handovers. These factors lead to a significantly increased risk of preventable secondary brain injury. To standardize the early treatment and transportation management of patients with TBI in maritime environments, and to enhance the continuity and operability of the maritime treatment chain, Guidelines for the management of traumatic brain injury in the maritime environment (2026 edition) was developed by experts convened under the leadership of the Neurosurgery Specialist Alliance of the Joint Logistics Support Force, in collaboration with the Neurotrauma Society of the China International Exchange and Promotive Association for Medical and Health Care, Neurotrauma Group of the Chinese Congress of Neurological Surgeons, and Craniocerebral Trauma Panel of the Neurosurgery Society of the Beijing Medical Association. With the core principles of ""reducing secondary brain injury and ensuring continuity of care"", this guideline synthesizes relevant domestic and international guidelines along with practical experience from resource-limited or delayed evacuation scenarios. Utilizing a grading system for evidence quality (A, B, C, D) and recommendation strength (strong recommendation, weak recommendation, conditional strong recommendation), it provides 25 recommendations focusing on: on-scene management and triage upgrade; tiered decision-making under conditions of limited imaging and monitoring; platform capability classification and evacuation pathways; minimum en-route monitoring configurations; and specific risk management for the maritime environment. This guideline aims to provide an executable, verifiable, transferable, and trainable standardized management framework for maritime TBI patients, offering a reference for clinical decision-making on various maritime medical platforms and evacuation nodes.","[""English Abstract"", ""Journal Article"", ""Practice Guideline""]","[""Neurosurgery Specialist Alliance of the Joint Logistics Support Force"", ""Neurotrauma Society of the China International Exchange and Promotive Association for Medical and Health Care"", ""Neurotrauma Group of the Chinese Congress of Neurological Surgeons"", ""Craniocerebral Trauma Panel of the Neurosurgery Society of the Beijing Medical Association""]",10.3760/cma.j.cn112137-20260413-00996,Neurosurgery Specialist Alliance of the Joint Logistics Support Force,Zhonghua yi xue za zhi,0376-2491,27,Zhonghua Yi Xue Za Zhi,chi,Craniocerebral Trauma Panel of the Neurosurgery Society of the Beijing Medical Association,"[""Humans"", ""Brain Injuries, Traumatic""]",2768-2794,42503917,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42503917/,[Guidelines for the management of traumatic brain injury in the maritime environment (2026 edition)],106,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"To update the recommendations of the Pan American Crohn's and Colitis Organisation (PANCCO) for the treatment of moderate-to-severe ulcerative colitis (UC) in adults, incorporating recent evidence on new biologics, small molecules, subcutaneous formulations and appendectomy. The PAHO rapid GRADE methods were applied. PANCCO adapted the Colombian guideline 2025 for upadacitinib, tofacitinib, ozanimod and the switch to subcutaneous formulations, and developed de novo recommendations for etrasimod, guselkumab, risankizumab, ustekinumab, mirikizumab, filgotinib and appendectomy. The search was carried out in MEDLINE, Embase, Cochrane and Epistemonikos through February 2026, with quality appraised with ROBIS, AMSTAR-2, RoB 2.0 and ICEMAN; strength of recommendations was established using GRADE. Recommendations were issued for nine clinical questions. In moderate-to-severe UC, upadacitinib, tofacitinib, filgotinib, ustekinumab, mirikizumab, risankizumab and guselkumab are recommended; ozanimod and etrasimod are conditionally suggested, considering the cardiovascular profile. In patients with response to intravenous induction, switching to subcutaneous vedolizumab or subcutaneous infliximab is suggested. In UC refractory to advanced therapies, laparoscopic appendectomy is conditionally suggested as an adjuvant strategy. This third update expands the therapeutic armamentarium for moderate-to-severe UC in Latin America. Treatment choice should be individualized according to prior therapy, comorbidities, cardiovascular and thrombotic risk, availability and patient preferences.","[""Journal Article"", ""Practice Guideline"", ""English Abstract""]","[""Núñez Figueroa P"", ""Sánchez Orozco A"", ""Alfaro Pérez I"", ""Andara Ramírez MT"", ""Balderramo D"", ""Bautista S"", ""Cassella F"", ""Cervera Caballero LA"", ""De León Rendón JL"", ""De Lucas Ocaña J"", ""García Vilela E"", ""Jara Alba ML"", ""Linares Serrano M"", ""Martínez-Vázquez MA"", ""Morínigo Bogado SD"", ""Muñoz Camacho R"", ""Parra-Izquierdo V"", ""Pérez Baldíoceda J"", ""Puentes-Manosalva FE"", ""Rodríguez Olaso X"", ""Saad-Hossne R"", ""Serrano M"", ""Suarez M"", ""Umaña Solis E"", ""Pardo-Turriago R"", ""Yuseff S"", ""Lozano T"", ""Juliao-Baños F""]",,Núñez Figueroa P,Revista de gastroenterologia del Peru : organo oficial de la Sociedad de Gastroenterologia del Peru,1022-5129,2,Rev Gastroenterol Peru,spa,Juliao-Baños F,"[""Humans"", ""Colitis, Ulcerative"", ""Adult"", ""Severity of Illness Index""]",221-233,42502002,,2026 Apr-Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42502002/,[PANCCO Clinical Practice Guideline Update for the treatment of ulcerative colitis in adults],46,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Since the 2020 Korean guidelines for Helicobacter pylori treatment, clarithromycin resistance rates have risen from 17.8% to 33.3%, dual-priming oligonucleotide-based polymerase chain reaction-guided tailored therapy has been adopted, and potassium-competitive acid blockers (P-CABs) have become available. This fourth revision addressed these changes. Nine key questions were addressed through systematic review and meta-analysis. Thirteen recommendations were evaluated using a modified Delphi process involving 64 experts. Twelve recommendations achieved a first-round consensus; one required revision and achieved 73.9% agreement. Key changes included: 1) a dual-pillar strategy of tailored therapy and empirical quadruple therapy; 2) restricted use of empirical clarithromycin- based triple therapy under specific conditions; 3) removal of sequential therapy; 4) use of P-CABs as alternatives to proton pump inhibitors; 5) expansion of eradication indications to include gastric cancer prevention in H. pylori gastritis and regression of hyperplastic polyps ≤10 mm; and 6) positioning of bismuth quadruple therapy as a conditionally recommended first-line empirical option, with preference for reservation as salvage therapy, and introduction of modified bismuth quadruple therapy (addition of bismuth to conventional regimens) as an additional first-line empirical option. The revised guidelines provide updated evidence-based recommendations for the diagnosis and treatment of H. pylori infection, reflecting the rapidly changing antibiotic resistance landscape and the introduction of new diagnostic and therapeutic tools in Korea. These guidelines aim to assist clinicians, patients, policymakers, and medical educators in optimizing H. pylori management. They may differ from the current medical insurance standards and will be further revised based on emerging evidence.","[""Journal Article"", ""Practice Guideline"", ""English Abstract""]","[""Bang CS"", ""Kang SJ"", ""Lim H"", ""Kim SH"", ""Lee MW"", ""Nam SY"", ""Tae CH"", ""Kim SE"", ""Kim SY"", ""Jung HK"", ""Kim BJ"", ""Choi M"", ""Jung HY"", ""Kim BW"", ""Korean College of Helicobacter and Upper Gastrointestinal Research""]",10.4166/kjg.2026.040,Bang CS,The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi,1598-9992,3,Korean J Gastroenterol,kor,Kim BW,"[""Humans"", ""Helicobacter Infections"", ""Helicobacter pylori"", ""Anti-Bacterial Agents"", ""Proton Pump Inhibitors"", ""Republic of Korea"", ""Clarithromycin"", ""Drug Resistance, Bacterial"", ""Drug Therapy, Combination""]",156-192,42494145,pmc-id: PMC13407497;,2026 Jul 25,2026,https://pubmed.ncbi.nlm.nih.gov/42494145/,[Evidence-Based Guidelines for the Diagnosis and Treatment of Helicobacter pylori Infection in Korea: 2025 Revised Edition],86,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"The analysis of circulating tumor DNA (ctDNA) by liquid biopsy is a major advance in the management of patients with cancer, offering a minimally invasive method for detecting tumor genetic alterations and enabling personalized monitoring. Faced with complex technological challenges and the need for rigorous validation, the French-Speaking Group for Oncological Cytogenomics (GFCO) has established national consensus guidelines. These guidelines, designed to govern ctDNA analysis, were developed using the Delphi consensus methodology. A questionnaire developed by a working group of eight biologists and two bioinformaticians was submitted to 55 French platforms specializing in liquid biopsy in oncology. A participation rate of 71% was achieved. Consensus was defined by an agreement threshold of at least 80%. A live discussion and voting session was held during the GFCO 2024 Days for items that did not initially reach this threshold. The validated recommendations cover the pre-analytical, analytical, and post-analytical phases. In total, 37 recommendations with a consensus exceeding 80% were adopted. These GFCO recommendations provide a standardized framework for the use of liquid biopsy in oncology in France. Regular updates will be necessary to adapt to the rapid evolution of the technology.","[""English Abstract"", ""Journal Article"", ""Practice Guideline""]","[""Harlé A"", ""Payen L"", ""Lespagnol A"", ""Goardon N"", ""Albuisson J"", ""Etienne-Grimaldi MC"", ""Pradines A"", ""Atkinson A"", ""Cabello Aguilar S"", ""Morel A"", ""Rouleau E"", ""pour le Groupe de travail du Groupe français de cytogénétique oncologique (GFCO)""]",10.1016/j.bulcan.2026.05.008,Harlé A,Bulletin du cancer,0007-4551,,Bull Cancer,fre,Rouleau E,[],,42493294,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42493294/,[GFCO national recommendations on the use of liquid biopsy for circulating tumor DNA analysis in oncology],,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Timely hemorrhage control is a critical determinant of survival after traumatic injury. Advances in endovascular techniques have expanded the role of interventional radiology, making it an essential component of contemporary trauma care. This position statement affirms the importance of rapid hemorrhage control, emphasizes the role of interventional radiologists as integral members of multidisciplinary trauma teams, and clarifies expectations related to the American College of Surgeons Verification, Review, and Consultation (VRC) Program standards for interventional radiology resources and availability. It also provides guidance for trauma centers to optimize institutional processes and coordination between trauma surgery and interventional radiology to ensure timely and effective hemorrhage control for injured patients.","[""Journal Article"", ""Practice Guideline""]","[""Wilkins LR"", ""Perlstein J"", ""Miller MJ"", ""Padia SA"", ""Sagraves S"", ""Shah RP"", ""D'Onofrio LJ"", ""Nathens AB""]",10.1016/j.jvir.2026.108978,Wilkins LR,Journal of vascular and interventional radiology : JVIR,1051-0443,,J Vasc Interv Radiol,eng,Nathens AB,[],108978,42492772,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42492772/,Rapid Endovascular Hemorrhage Control in Trauma: a Joint Position Statement from the American College of Surgeons Committee on Trauma and the Society of Interventional Radiology,,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"A steady rise in the number of patients receiving stereotactic body radiation therapy (SBRT) for primary prostate cancer is expected. Consequently, the current European Society for Radiotherapy and Oncology (ESTRO) 'how to' consensus has been developed to offer practical recommendations for the initiation and implementation of prostate SBRT in radiotherapy (RT) departments. A panel of fifteen experts in the field of prostate SBRT reviewed and analysed the literature and, through a Delphi process, answered a ten-item questionnaire addressing areas of controversy in prostate SBRT. Consensus was a priori defined as ≥75% agreement in each answer, while ≥90% agreement was defined as strong consensus. The aim of this 'how to' consensus recommendations is to define minimum requirements, common practices and additional options for prostate SBRT based on scientific evidence, expert opinion and consensus. This 'how to' clinical practice recommendations cover patient selection and follow-up process, treatment planning and delivery techniques in prostate SBRT.","[""Journal Article"", ""Practice Guideline""]","[""Draulans C"", ""Tree A"", ""Zilli T"", ""Alongi F"", ""Zamboglou C"", ""Ost P"", ""Jereczek-Fossa BA"", ""Blanchard P"", ""Gomez-Iturriaga A"", ""Faccenda V"", ""Wolf F"", ""Roover R"", ""Scherman J"", ""Alexander S"", ""Schmidt-Hegemann NS""]",10.1016/j.radonc.2026.111710,Draulans C,Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology,0167-8140,,Radiother Oncol,eng,Schmidt-Hegemann NS,[],111710,42486233,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42486233/,How to optimise prostate SBRT: ESTRO clinical practice consensus recommendations,223,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system, characterized by severe attacks. Optic neuritis is the most common clinical manifestation, leading to a rapid and often severe loss of vision, which is sometimes bilateral, with frequent sequelae and a risk of very low visual acuity in the long-term. Magnetic resonance imaging (MRI) reveals extensive lesions of the optic nerve, mostly involving the posterior part of the nerve and sometimes extending to the optic chiasm. Myelitis manifests as longitudinally extensive and centrally located spinal cord lesions, which may lead to tetraplegia, sensory disturbances, neuropathic pain and sphincter dysfunction. Area postrema syndrome presents with nausea, vomiting, and severe hiccups, which are often resistant to conventional treatments and may require hospitalization. Diagnosis is confirmed by the detection of anti-aquaporine 4 (AQP4) antibodies in the serum. Attacks should be treated as an emergency, with intravenous (IV) corticosteroids and plasma exchange, without waiting for antibody confirmation. Maintenance therapy includes monoclonal antibodies targeting B lymphocytes, interleukin-6 receptor, complement C5 and non-selective immunosuppressive treatments, according to profile of tolerance. Conventional treatments such as azathioprine or mycophenolate are less commonly used as first-line therapies but remain possible depending on the clinical context. Follow-up is multidisciplinary, with neurological, and according to the symptoms ophthalmological, neuropsychological, urodynamic or sequellar disability consultations. Therapeutic patient education and support from patient organizations are essential for improving quality of life and treatment adherence. Pregnancy is considered high-risk, requiring regular neurological and obstetric monitoring, as the risk of attack increases in the postpartum period. Finally, the rapid and individualized management of attacks as well as the prevention of relapses is crucial to limit functional sequelae and disability.","[""Journal Article"", ""Practice Guideline""]","[""Giorgi L"", ""Marignier R"", ""Pique J"", ""Maurey H"", ""Papeix C"", ""Ciron J"", ""Collongues N"", ""Cheuret E"", ""Zephir H"", ""Meyer P"", ""Vukusic S"", ""Doret-Dion M"", ""AbiWarde MT"", ""Nguyen The Tich S"", ""Bourre B"", ""Audoin B"", ""Pouget MC"", ""Yver E"", ""Lattaud C"", ""Froment Tilikete C"", ""De Sèze J"", ""Debroise AC"", ""Gelé M"", ""Mamoudjy N"", ""Cleuziou P"", ""Maillart E"", ""Deiva K"", ""MIRCEM network""]",10.1016/j.neurol.2026.06.004,Giorgi L,Revue neurologique,0035-3787,,Rev Neurol (Paris),eng,Deiva K,[],,42481362,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42481362/,French guidelines for the diagnosis and management of neuromyelitis optica spectrum disorder,,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"People with sequelae of acute anterior poliomyelitis (AAP) may develop secondary complications related to aging, as well as a specific complication of the disease known as post-polio syndrome (PPS). These complications are new neurological and musculoskeletal manifestations that occur after a prolonged period of disease stability. The onset is typically insidious and slow, but can be more rapid following a period of immobilization, surgery, or another intercurrent condition. The initial assessment may involve consulting a neurologist to rule out neurological diagnoses. Electroneuromyographic examination is a valuable tool for evaluating these patients. It is sometimes difficult to differentiate between the effects of aging in a person with sequelae of AAP and PPS, which is a distinct entity with specific diagnostic criteria. The rate at which muscle capacity declines, and its functional impact, can be a distinguishing factor. Subacute or rapid onset can be indicative of PPS. The emergence of new motor deficits in areas that were previously unaffected is also a strong argument for PPS. This neurological deterioration must be distinguished from musculoskeletal disorders associated with aging. Progression is usually slow and gradual, or occurs in stages with periods of stabilization. Physical and rehabilitation care is essential both in the initial assessment and for ongoing follow-up. There are no recommended medicinal treatments, especially no specific etiological treatment for PPS (such as immunoglobulins, corticosteroids, etc.) or effective symptomatic treatment for manifestations like fatigue or muscle weakness (e.g., pyridostigmine). Pain management should be regularly assessed; while drug treatments are not specific, non-pharmacological pain management through physical therapy is crucial. Particular attention should be paid to comorbidities, including excess weight and an increased risk of osteoporosis and fractures. Management should be multidisciplinary, with an annual review recommended. Follow-up will be adjusted based on the patient's preferences and needs, and monitoring will depend on the development of complications.","[""Journal Article"", ""Practice Guideline""]","[""Verschueren A"", ""Cotinat M"", ""Roseau JB"", ""Thefenne L"", ""French PPS working Group""]",10.1016/j.neurol.2026.05.007,Verschueren A,Revue neurologique,0035-3787,,Rev Neurol (Paris),eng,Thefenne L,[],,42481361,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42481361/,French guidelines for post-polio syndrome and management of effects of aging in people with sequelae of acute anterior poliomyelitis,,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Obstructive sleep apnea (OSA) is associated with significant morbidity in pregnancy. There is minimal guidance available on how best to screen, diagnose, treat, and re-evaluate for OSA in pregnant patients. Considering the potentially adverse consequences of OSA in pregnancy if left untreated, we assembled a panel of experts to methodologically review the available literature and make evidence-based recommendations. Rigorous methodology was applied to provide a trustworthy evidence-based guideline and expert panel report. Panelists developed key clinical questions utilizing the PICO (population, intervention, comparator, and outcome) format, addressing specific topics in OSA in pregnant individuals. MEDLINE (via PubMed) and the Cochrane Library were systematically searched for relevant literature and supplemented by manual searches. References were screened with study evaluation tools to assess for inclusion, extract meaningful data, and grade the level of evidence to support each recommendation or suggestion. PICO questions related to screening, diagnosis, treatment, and follow up of OSA in pregnant patients resulted in nine conditional recommendations, made with the evidence available and with consensus of the expert panel. We recommend screening pregnant patients for OSA, either with a pregnancy specific screening questionnaire or a standard tool. For those at risk of OSA based on screening, either a home sleep test (HST) or in laboratory polysomnogram (PSG) is recommended for diagnosis. We recommend treatment for those with an apnea-hypopnea index (AHI) of 5-15 who have symptoms/sequelae or comorbidities, or those with an AHI ≥ 15 regardless of symptoms or comorbidities, preferably with auto-titrating positive airway pressure (APAP). Additionally, scheduled naps may be beneficial as an initial step in alleviating residual symptoms. Reassessment of OSA in the postpartum period is recommended in some patients. Due to low level of certainty, nine conditional recommendations were made in the screening, testing, and treatment of OSA in pregnancy.","[""Journal Article"", ""Practice Guideline""]","[""D'Ambrosio CM"", ""Dust C"", ""Dominguez JE"", ""Habib AS"", ""Izci-Balserak B"", ""Louis JM"", ""Louis M"", ""Malhamé I"", ""Olson-Koutrouvelis G"", ""Reutrakul S"", ""Sanapo L"", ""Shaib F"", ""Wilson D"", ""Vintch JRE"", ""Won C"", ""Boujeily G""]",10.1016/j.chest.2026.06.058,D'Ambrosio CM,Chest,0012-3692,,Chest,eng,Boujeily G,[],,42480820,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42480820/,Obstructive Sleep Apnea (OSA) in Pregnancy - An American College of Chest Physicians Clinical Practice Guideline,,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Bronchiectasis is a chronic respiratory condition involving a cycle of impaired mucociliary clearance, chronic infections, inflammation, and progressive airway destruction, leading to persistent cough with sputum production, dyspnea, and fatigue. Without appropriate management, patients can experience increased exacerbations, reduced quality of life, declining lung function, and increased mortality risk. Variability exists in clinical practice regarding treatment selection, highlighting the need for evidence-based guidance to optimize patient outcomes and standardize care delivery across healthcare settings. An expert panel developed eight PICO-based questions addressing treatment of bronchiectasis in adults and conducted a systematic review. The panel applied the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach to assess the certainty of evidence and to formulate and grade recommendations. A modified Delphi technique was used to reach consensus on the recommendations. Based on 47 studies, the panel developed 13 evidence-based recommendations addressing key management domains, including antibiotic treatment for acute exacerbations, duration and route of antibiotic therapy, long-term suppressive antibiotic and anti-inflammatory therapies, airway clearance strategies, management of hemoptysis and consideration of surgical resection in selected patients. All recommendations are conditional, primarily based on low-certainty evidence. Bronchiectasis research should aim to address many of the uncertainties in management, and priorities are identified within each PICO question. Accurate phenotyping and endotyping may help guide therapeutic decision-making and risk stratification. Treatment interventions must consider potential treatment burdens, including cost, and impact on quality of life. Finally, shared decision-making with patients utilizing a multidisciplinary approach is paramount.","[""Journal Article"", ""Practice Guideline""]","[""Thomson R"", ""Thornton C"", ""Aksamit T"", ""Barker A"", ""Basavaraj A"", ""Burr L"", ""Hill AT"", ""Jarand J"", ""Lee AL"", ""Metersky M"", ""Moores L"", ""Morimoto K"", ""O'Donnell A"", ""Smith M"", ""Somayaji R"", ""Tino G"", ""Frazer-Green L""]",10.1016/j.chest.2026.06.057,Thomson R,Chest,0012-3692,,Chest,eng,Frazer-Green L,[],,42480819,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42480819/,Management of Adult Bronchiectasis: An American College of Chest Physicians Clinical Practice Guideline,,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Invasive candidiasis, including candidemia and deep-seated Candida infections, remains a major cause of morbidity and mortality in hospitalized patients worldwide, particularly in low- and middle-income countries. In Brazil, candidemia is associated with persistently high mortality rates, driven by late diagnosis, limited access to antifungal agents, and heterogeneous diagnostic capacity. The last national guideline issued by the Brazilian Society of Infectious Diseases (SBI) was published in 2013, and substantial advances have occurred since then in epidemiology, diagnostics, and antifungal therapy. To provide an updated, evidence-based Brazilian guideline for the diagnosis and treatment of candidemia and invasive candidiasis in adults and children, incorporating contemporary scientific data and addressing the specific epidemiological, diagnostic, and therapeutic realities of Brazil. This guideline was developed by the SBI Mycology Committee through a structured consensus process. Clinical questions were formulated using the PICO framework, followed by systematic literature searches of PubMed-indexed studies and international guidelines. Recommendations were contextualized according to Brazilian epidemiology, laboratory infrastructure, and access to antifungal therapies. Key updates include revised epidemiological data from Brazilian cohorts, updated recommendations for blood culture strategies and non-culture-based diagnostics, refined indications for echocardiography and fundoscopy, and updated therapeutic algorithms. Novel antifungal agents, including long acting echinocandins such as rezafungin, are discussed. Emphasis is placed on early echinocandin therapy, timely source control, antifungal stewardship, and infectious diseases consultation. This updated Brazilian guideline reflects current scientific evidence while addressing national healthcare realities, aiming to standardize care, improve outcomes, and reduce mortality associated with invasive candidiasis in Brazil.","[""Journal Article"", ""Practice Guideline"", ""Review""]","[""Colombo AL"", ""Magri MMC"", ""Carlesse F"", ""Falci DR"", ""Garnica M"", ""Santos DWCL"", ""Queiroz-Telles F"", ""Pasqualotto AC""]",10.1016/j.bjid.2026.105946,Colombo AL,The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases,1413-8670,4,Braz J Infect Dis,eng,Pasqualotto AC,"[""Humans"", ""Candidemia"", ""Antifungal Agents"", ""Brazil"", ""Candidiasis, Invasive"", ""Adult"", ""Child""]",105946,42480284,pmc-id: PMC13393635;,2026 Jul-Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42480284/,Brazilian guidelines for the diagnosis and treatment of candidemia and invasive candidiasis in adults and children,30,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Pulmonary embolism (PE), defined as blockage of the pulmonary arteries, is a common and serious condition that requires accurate diagnosis and standardized reporting. Noninvasive imaging is well established for the diagnosis and management of PE and is incorporated into multiple societal guidelines. However, specific technical recommendations for the optimal interpretation and standardized reporting of CT and MR angiography remain absent. Diagnostic imaging is used to identify the presence or absence of PE and to risk-stratify patients. Evolving treatment options can be considered once an acute clot is identified, the patient's status is defined, and the patient is referred for appropriate treatment in a timely manner. Patient management for PE often involves multiple care teams, and clear and consistent communication between care teams is critical to patient care. The goal of the Pulmonary Embolism Reporting and Data System (PE-RADS) is twofold: (a) to create a standard lexicon for the description of terms used for acute PE diagnosis at CT and MR angiography and (b) to develop a structured, hierarchical reporting system that incorporates anatomic and accessory findings to classify clot location and right heart imaging features in acute PE and to assist in determining the cardiovascular status of the patient to inform next-step management.","[""Journal Article"", ""Practice Guideline""]","[""Koweek LM"", ""Agarwal P"", ""Brosnahan SB"", ""Bhalla S"", ""Bishay V"", ""Cronin P"", ""François CJ"", ""Giri J"", ""Litmanovich DE"", ""Leung AN"", ""West FM"", ""Zimmerman SL""]",10.1016/j.chest.2026.06.006,Koweek LM,Chest,0012-3692,,Chest,eng,Zimmerman SL,[],,42479001,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42479001/,Pulmonary Embolism Reporting and Data System (PE-RADS™) v2026 for the Diagnosis of Acute Pulmonary Embolism on CT and MR Angiography,,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"This study aimed to develop a nationwide, consensus-based surgical checklist to standardize transurethral resection of bladder tumor procedures and documentation. In 2025, the Japanese Society of Urologic Oncology convened a working group of 20 bladder cancer specialist urologists to develop a national surgical checklist for transurethral resection of bladder tumors. A 12-member steering committee reviewed available evidence and proposed 30 candidate items. Using a modified Delphi approach, all members rated each item online, with consensus predefined as ≥ 75% agreement. Iterative revisions incorporating public comments and external expert input produced the final checklist. The final checklist comprised 22 items across four sections: (i) preoperative patient and tumor information (recurrence status; upper tract urothelial carcinoma; urine cytology; clinical Tumor-Node-Metastasis staging; performance status; factors affecting surgery/anesthesia); (ii) surgical and anesthetic planning (surgical intent; resection technique; adjunctive imaging modality; additional biopsies; anesthesia method; obturator reflex prophylaxis); (iii) intraoperative tumor and resection information (tumor number; index tumor morphology; index tumor size; findings suggestive of carcinoma in situ; extent of tumor resection; detrusor muscle visible; muscle invasion suspected); and (iv) complications and adjuvant therapy (urethral stricture; intraoperative complications; immediate single instillation). An additional section provides two bladder diagrams: a male/general-use version with lower urinary tract annotations and a female-specific version, both designed for mapping tumor location, characteristics, and operative findings. This checklist provides a practical framework to standardize transurethral resection of bladder tumor practice and documentation and support safe, high-quality care, warranting prospective evaluation of feasibility, adherence, and quality indicators/outcomes.","[""Journal Article"", ""Practice Guideline""]","[""Taoka R"", ""Hayakawa N"", ""Kimura T"", ""Kikuchi E"", ""Iwatani K"", ""Kato M"", ""Matsumoto T"", ""Tanaka H"", ""Sano T"", ""Hara T"", ""Fukuhara H"", ""Miyake M"", ""Osawa T"", ""Hatakeyama S"", ""Kobayashi T"", ""Inokuchi J"", ""Tatarano S"", ""Kitamura H"", ""Sugimoto M"", ""Nonomura N""]",10.1111/iju.70570,Taoka R,International journal of urology : official journal of the Japanese Urological Association,0919-8172,7,Int J Urol,eng,Nonomura N,"[""Humans"", ""Checklist"", ""Consensus"", ""Delphi Technique"", ""Japan"", ""Medical Oncology"", ""Neoplasm Recurrence, Local"", ""Neoplasm Staging"", ""Societies, Medical"", ""Transurethral Resection of Bladder"", ""Urinary Bladder"", ""Urinary Bladder Neoplasms"", ""Urology""]",e70570,42477956,pmc-id: PMC13385473;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42477956/,Consensus-Based Development of a Surgical Checklist for Transurethral Resection of Bladder Tumor: An Initiative of the Japanese Society of Urologic Oncology,33,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Pain is a frequent symptom in people with inflammatory arthritis (IA), which has substantial impact on their quality of life. Analyses of electronic health record data indicate that UK pain care in people with IA often involves prescribing long-term opioids and gabapentinoids, despite absent trial evidence for efficacy. Patient survey data suggest that non-pharmacological pain care with supportive trial evidence is underused. A UK-specific guideline on pain management for people with IA is required to address this. This comprehensive life-course guideline is the first British Society for Rheumatology Guideline to specifically address pain in people with IA. It provides evidence-based recommendations on how pain can be best managed in people with IA. It was developed using the methods outlined in the British Society for Rheumatology's 'Creating Clinical Guidelines' protocol by a multidisciplinary Guideline Working Group, comprising healthcare professionals with expertise in paediatric and adult rheumatology and people with lived experience. By undertaking and considering the evidence from several systematic literature and umbrella reviews, 23 recommendations were developed. These address how pain should be assessed in people with IA alongside the role of the following treatments in IA pain management: DMARDs, glucocorticoids, analgesics, neuromodulators, exercise and physical activity, psychological interventions, ergonomic and orthotic interventions (excluding orthoses for foot pain), education, weight management and diet, addressing sleep problems, fatigue management, digital technologies and medical devices, complementary therapies, and support from others. An audit tool is provided to support the Guideline's implementation, and key recommendations made for future research.","[""Journal Article"", ""Practice Guideline""]","[""Scott IC"", ""Smith TM"", ""Babatunde O"", ""Barker C"", ""Battista S"", ""Beesley R"", ""Beesley R"", ""Birkinshaw H"", ""Brooke M"", ""Chaplin H"", ""Chapman L"", ""Ciurtin C"", ""Dale J"", ""Dockrell D"", ""Dures E"", ""Harrison K"", ""Holt S"", ""Jani M"", ""McCarron M"", ""Mallen CD"", ""O'Connor A"", ""Pidgeon C"", ""Pratt D"", ""Prior Y"", ""Raza K"", ""Rutter-Locher Z"", ""Sharma S"", ""Shaw K"", ""Tsigarides J"", ""Xenophontos M"", ""Shenker NG""]",10.1093/rheumatology/keag320,Scott IC,"Rheumatology (Oxford, England)",1462-0324,7,Rheumatology (Oxford),eng,Shenker NG,"[""Humans"", ""Pain Management"", ""United Kingdom"", ""Rheumatology"", ""Arthritis"", ""Arthritis, Rheumatoid"", ""Societies, Medical"", ""Analgesics"", ""Antirheumatic Agents"", ""Quality of Life""]",,42476581,pmc-id: PMC13384732;,2026 Jun 30,2026,https://pubmed.ncbi.nlm.nih.gov/42476581/,The 2026 British Society for Rheumatology guideline for pain management in people with inflammatory arthritis,65,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Tricuspid valve endocarditis in people who inject drugs represents a unique clinical and social challenge for cardiac surgeons. There is a relative paucity of research specific to this unique clinical scenario to guide evidence-based treatment. The Society of Thoracic Surgeons Workforce on Evidence Based Surgery assembled a writing group in 2024 to create an expert consensus document on the management of tricuspid endocarditis in people who inject drugs. A comprehensive literature search was conducted in Medline, focusing on studies published in English over the past 15 years. The consensus was reached using a modified Delphi method, with each member voting on statements via a 5-point Likert scale to assess wording and strength. Expert consensus statements were generated addressing key topics including vegetation size, impact of infectious organism on surgical decision making, persistent bacteremia, prosthetic valve infections, surgical strategy, emerging technologies, and ethical considerations. Included expert consensus statements offers insight based on the literature a clinical experience about important topics when managing tricuspid valve endocarditis in patients who inject drugs.","[""Journal Article"", ""Practice Guideline""]","[""Goldberg JB"", ""Mehaffey JH"", ""Paras ML"", ""Vardas PN"", ""Pattakos G"", ""Slaughter MS"", ""Arnaoutakis GJ"", ""Whitson BA"", ""Wyler von Ballmoos MC""]",10.1016/j.athoracsur.2026.06.065,Goldberg JB,The Annals of thoracic surgery,0003-4975,,Ann Thorac Surg,eng,Wyler von Ballmoos MC,[],,42468870,,2026 Jul 17,2026,https://pubmed.ncbi.nlm.nih.gov/42468870/,The Society of Thoracic Surgeons Expert Consensus Document on Tricuspid Valve Endocarditis in People Who Inject Drugs,,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Over the past two decades, significant advancements have been achieved in the diagnosis and treatment of sacroiliac joint (SIJ) complex pain. These advances include anatomical studies elucidating the neural innervation mechanisms, research clarifying the impacts of extra-articular factors on SIJ complex pain, and the clinical application of radiofrequency ablation as well as a wide spectrum of minimally invasive surgical techniques. Nevertheless, a unified standardized protocol for the diagnosis and treatment of SIJ complex pain remains to be established. In 2025, the American Academy of Pain Medicine (AAPM) and the American Society of Regional Anesthesia and Pain Medicine (ASRA-PM) convened 27 professional organizations to revise and promulgate multidisciplinary clinical practice guideline for SIJ complex pain. This article conducts a comprehensive interpretation of the aforementioned guideline, compares it with relevant expert consensus documents in China, analyzes the consistencies and divergences in their diagnosis and treatment, and provides a reference for clinical practice.","[""Journal Article"", ""Practice Guideline"", ""English Abstract""]","[""Chen S"", ""Yang Z"", ""Zhang J"", ""Lü B"", ""Zhang Y"", ""Han N""]",10.7507/1002-1892.202603078,Chen S,Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery,1002-1892,7,Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi,chi,Han N,"[""Humans"", ""Sacroiliac Joint"", ""Low Back Pain"", ""Pain Management"", ""Injections, Intra-Articular"", ""Pain Measurement"", ""Adrenal Cortex Hormones""]",1024-1030,42464536,pmc-id: PMC13391846;,2026 Jul 15,2026,https://pubmed.ncbi.nlm.nih.gov/42464536/,[2025 Multidisciplinary International Working Group Consensus Practice Guidelines: Sacroiliac joint complex pain interpretation],40,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"U.S. colleges and schools of pharmacy face mounting challenges in sustaining robust research programs, supporting early-stage investigators, modernizing graduate education, and integrating emerging technologies into academic practice. Furthermore, shifts in federal funding-particularly within the National Institutes of Health (NIH), National Science Foundation (NSF) and the Agency for Healthcare Research and Quality (AHRQ), increased expectations for multidisciplinary collaboration, and rapid technological transformation require coordinated national leadership. This report is intended to identify key research and graduate education challenges across the Academy and propose actionable strategies for the American Association of Colleges of Pharmacy (AACP or the Association). Recommendations focus on strengthening and diversifying research funding, enhancing infrastructure for multidisciplinary collaboration, supporting early-stage investigators, aligning graduate training with workforce needs, improving domestic recruitment pipelines, and establishing competency frameworks for artificial intelligence (AI) integration. This report also addresses professional identity formation of scientists within pharmacy education and research and what being a scientist means in different settings, including the classroom, the clinic, and the community. Recommendations are given to support scientists in building identity around the competencies and skills that enable scientific problem solving, communication, education, and advocacy in all settings - all consistent with domains that are already included in the AACP Competency Framework for Graduate Education. The report concludes with a call to action for both AACP and member institutions to modernize policies, invest strategically in research ecosystems, and ensure the long-term vitality of pharmacy research and graduate education.","[""Journal Article"", ""Practice Guideline""]","[""Coop A"", ""Early J"", ""Iso T"", ""Lu K"", ""Qian J"", ""Perez A"", ""Subramaniam S"", ""Zaccheo N"", ""Farrell D"", ""Xie W""]",10.1016/j.ajpe.2026.102056,Coop A,American journal of pharmaceutical education,0002-9459,,Am J Pharm Educ,eng,Xie W,[],102056,42463021,,2026 Jul 16,2026,https://pubmed.ncbi.nlm.nih.gov/42463021/,Supporting Research and Graduate Education in a Troubled Landscape: Report of the 2025-2026 AACP Research and Graduate Affairs Committee,,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
,"[""Journal Article"", ""Practice Guideline""]","[""Iddings JA"", ""Petrosyan H"", ""Jo HJ"", ""Benavides F"", ""Sisto SA""]",10.1016/j.apmr.2026.06.013,Iddings JA,Archives of physical medicine and rehabilitation,0003-9993,,Arch Phys Med Rehabil,eng,Sisto SA,[],,42461192,,2026 Jul 15,2026,https://pubmed.ncbi.nlm.nih.gov/42461192/,Transcranial Direct Current Stimulation (tDCS) Application in Neurorehabilitation: A Beginner's Guide for Clinicians,,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"To present a summary of the 2026 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines on screening, diagnosis, and treatment of clinically localised prostate cancer (PCa). The Panel performed a literature review of all new data published in English, covering the time frame between May 2023 and 2025. The Guidelines were updated, and a strength rating for each recommendation was added based on a systematic review of the evidence. A risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. The use of multiparametric magnetic resonance imaging to avoid unnecessary biopsies is recommended. When a biopsy is considered, a combination of targeted and regional biopsies should be performed. A new five-tier EAU classification has been introduced. Prostate-specific membrane antigen positron emission tomography imaging is the most sensitive technique for identifying metastatic spread. Active surveillance is the appropriate management for men with low-risk PCa, as well as for patients with selected favourable intermediate-risk ISUP grade group 2 lesions. Local therapies are addressed, as well as the management of persistent prostate-specific antigen after surgery. A recommendation to consider hypofractionated radiotherapy in intermediate-risk patients is provided. Patients with cN1 PCa should be offered radiotherapy to the primary tumour combined with long-term intensified hormonal treatment. The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. These PCa Guidelines reflect the multidisciplinary nature of PCa management.","[""Journal Article"", ""Practice Guideline""]","[""Cornford P"", ""van den Bergh RCN"", ""Briers E"", ""Chiu P"", ""Eberli D"", ""Epure A"", ""Farolfi A"", ""Fonteyne V"", ""Gandaglia G"", ""Gillessen S"", ""Grivas N"", ""Henry AM"", ""van Leenders GJLH"", ""Espinos EL"", ""Matsen B"", ""Oldenburg J"", ""van Oort IM"", ""Oprea-Lager DE"", ""Roberts MJ"", ""Rouvière O"", ""Sachdeva A"", ""Santis M"", ""Schoots IG"", ""Smith EJ"", ""Stranne J"", ""Wiegel T"", ""Tilki D""]",10.1016/j.eururo.2026.04.013,Cornford P,European urology,0302-2838,,Eur Urol,eng,Tilki D,[],,42457454,,2026 Sep 1,2026,https://pubmed.ncbi.nlm.nih.gov/42457454/,"EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer-2026 Update. Part I: Screening, Diagnosis, and Local Treatment with Curative Intent",,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Urological infections significantly impact individuals' well-being and quality of life due to their widespread occurrence and diverse clinical manifestations. This work aims to provide evidence-based guidance on diagnosing, treating, and preventing urinary tract infections (UTIs) and male accessory gland infections, while addressing crucial public health aspects related to infection control and antimicrobial stewardship. For the 2026 Urological Infections Guidelines, new and relevant evidence was identified, collated, and appraised through a structured assessment of the literature. Databases searched included Medline, EMBASE, and the Cochrane Library. Recommendations within the Guidelines were developed by the panels to prioritise clinically important care decisions. The strength of each recommendation is determined by the balance between desirable and undesirable consequences of alternative management strategies, the quality of the evidence (including certainty of estimates), and the nature and variability of patient values and preferences. Key recommendations emphasise the importance of thorough medical history and physical examination for patients with urological infections. The guidelines stress the role of antimicrobial stewardship to combat the rising threat of antimicrobial resistance, providing recommendations for antibiotic selection, dosing, and duration based on the latest evidence. Key updates in the 2026 Urological Infections Guidelines summary include: comprehensive restructuring of the guideline framework in alignment with the new classification system for UTIs; the addition of a new chapter on the diagnosis and management of Herpes simplex virus; the addition of a new chapter on the diagnosis and treatment of fungal UTIs; and an update of the evidence and recommendations on periprocedural antibiotic prophylaxis for prostate biopsy. This overview of the 2026 European Association of Urology (EAU) guidelines offers valuable insights into the classification, diagnosis, and treatment of urological infections and is designed to be effectively integrated into clinical practice.","[""Journal Article"", ""Practice Guideline""]","[""Kranz J"", ""Cai T"", ""Geerlings S"", ""Köves B"", ""Lambregts MMC"", ""Mantica G"", ""Pilatz A"", ""Medina-Polo J"", ""Schneidewind L"", ""Schubert S"", ""Vallée M"", ""Veeratterapillay R"", ""Wagenlehner F"", ""Bausch K"", ""Devlies W"", ""Leitner L"", ""Stangl F"", ""Ali H"", ""Smith EJ"", ""Bonkat G""]",10.1016/j.eururo.2026.04.011,Kranz J,European urology,0302-2838,,Eur Urol,eng,Bonkat G,[],,42457453,,2026 Sep 1,2026,https://pubmed.ncbi.nlm.nih.gov/42457453/,European Association of Urology Guidelines on Urological Infections: Summary of the 2026 Guidelines,,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Health care professionals in fluoroscopic laboratories face significant occupational hazards, including cancer, cataracts, and reproductive concerns due to prolonged exposure to iodizing radiation, and orthopedic injuries stemming from long-term use of heavy aprons as protection from radiation. Despite substantial advancements in radiation protection technology, adoption of these advancements has been slow, hindered by the high upfront costs of implementation and the lag in revising institutional and regulatory radiation exposure thresholds to reflect the capabilities of contemporary enhanced radiation protection devices (ERPDs). This multisociety statement, endorsed by the Society for Cardiovascular Angiography & Interventions, American College of Cardiology, the American Society of Echocardiography, the Heart Rhythm Society, the Society of Interventional Radiology, and the Society for Vascular Surgery, calls for mandatory implementation of ERPDs to meet as low as reasonably achievable standards. This expert consensus statement outlines the ethical and legal responsibilities of government, fluoroscopy laboratory manufacturers, and health care institutions to protect all health care professionals from avoidable workplace hazards and the urgent need to implement ERPDs. The document does not promote or recommend any single ERPD system, and the choice of protection technology is left to department preference. It also addresses the importance of training, monitoring, and continuous research to optimize radiation safety practices. The document advocates for updated regulations and standardized practices across states to ensure comprehensive protection for all fluoroscopy laboratory personnel.","[""Journal Article"", ""Practice Guideline""]","[""Rizik DG"", ""Sutton NR"", ""Lansky AJ"", ""Alasnag M"", ""Bartal G"", ""Brady MB"", ""Coylewright M"", ""Goldstein JA"", ""Firestone SM"", ""Goldsweig AM"", ""Kereiakes DJ"", ""Kirkwood M"", ""Madder RD"", ""Mehran R"", ""Nicholson WJ"", ""Paulo G"", ""Rao SV"", ""Rosenfield K"", ""Schultz CC"", ""Tamirisa KP"", ""Tuozzo KA"", ""Velagapudi P"", ""Vora AN"", ""Yong CM"", ""Hermiller JB""]",10.1016/j.jvir.2026.108927,Rizik DG,Journal of vascular and interventional radiology : JVIR,1051-0443,,J Vasc Interv Radiol,eng,Hermiller JB,[],108927,42446437,,2026 Jul 14,2026,https://pubmed.ncbi.nlm.nih.gov/42446437/,SCAI/ASE/HRS/SIR/SVS Expert Consensus Statement on Enhanced Radiation Protection: Time for Mandatory and Urgent Action,,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Olfactory neuroblastoma (ONB) is a rare malignant tumor of the sinonasal tract. The objective of this study is to present an evidence-based synthesis of the recommendations of the French Expert Network of Rare ENT Cancers (REFCOR), published in 2022, concerning the diagnostic and therapeutic management of ONB. These recommendations result from a multidisciplinary consensus based on a critical analysis of the literature and feedback from expert centers within a structured process. ONB accounts for 6% of sinonasal cancers, with no identified risk factors. Diagnosis is based on CT and MRI of the paranasal sinuses and skull base, together with systemic disease staging. Histopathological analysis requires specialized expertise, with Hyams histological grade as the main prognostic factor. The standard of care consists in surgical resection followed by adjuvant radiotherapy. Chemotherapy may be considered in high-grade or unresectable forms. Because of the risk of late recurrence, at least 20years' follow-up is recommended. The REFCOR guidelines aim to standardize diagnosis and treatment for ONB, but require completion by discussion in a specialized multidisciplinary tumor board.","[""Journal Article"", ""Practice Guideline"", ""Consensus Statement""]","[""Gorzkowski V"", ""Monnot C"", ""Castain C"", ""de Bonnecaze G"", ""Verillaud B"", ""Michel J"", ""Moya-Plana A"", ""Coste-Martineau V"", ""Digue L"", ""Thariat J"", ""Dupin C"", ""de Gabory L"", ""Rumeau C""]",10.1016/j.anorl.2026.06.004,Gorzkowski V,"European annals of otorhinolaryngology, head and neck diseases",1879-7296,4,Eur Ann Otorhinolaryngol Head Neck Dis,eng,Rumeau C,"[""Humans"", ""Esthesioneuroblastoma, Olfactory"", ""Nose Neoplasms"", ""Nasal Cavity"", ""Neoplasm Staging"", ""Consensus"", ""France""]",325-329,42442982,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42442982/,REFCOR guidelines on the management of olfactory neuroblastoma: A formalized expert consensus,143,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
,"[""Journal Article"", ""Practice Guideline"", ""Systematic Review""]","[""Wood E"", ""Wong SC"", ""Corace K"", ""Martell D"", ""Barker B"", ""de Montigny C"", ""Hodgins DC"", ""Poulin G"", ""Halpape K"", ""Le Foll B"", ""Lim R"", ""Brosseau A"", ""Henry R"", ""Marsh DC"", ""Cowan N"", ""Teed R"", ""Johnson C"", ""Brunelle C"", ""Graham B"", ""Rehm J""]",10.1503/cmaj.251759-f,Wood E,CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne,0820-3946,26,CMAJ,fre,Rehm J,"[""Humans"", ""Canada"", ""Mass Screening"", ""Alcoholism"", ""Alcohol Drinking"", ""Practice Guidelines as Topic"", ""Alcohol-Related Disorders"", ""Risk Assessment""]",E1026-E1039,42442794,pmc-id: PMC13374695;,2026 Jul 12,2026,https://pubmed.ncbi.nlm.nih.gov/42442794/,Dépistage de la consommation d’alcool à risque élevé et du trouble d’utilisation de l’alcool : mise à jour du guide de pratique clinique national de 2023,198,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"The Cystic Fibrosis Foundation organised a multidisciplinary committee to develop this Position Paper to outline current knowledge and best practices in reproductive health care for individuals with cystic fibrosis. Working groups reviewed the literature and provided relevant guidance on reproductive health services, fertility, contraception, preconception and pregnancy, and cystic fibrosis transmembrane conductance regulator (CFTR) modulator exposure in utero and during lactation. Findings included: (1) reproductive health-care provision should be standardised, and education should begin at cystic fibrosis diagnosis and revisited annually; (2) contraception is safe overall, but underutilised in those with cystic fibrosis compared with the general population; (3) fertility might be improving with CFTR modulators for females with cystic fibrosis, but not for males with cystic fibrosis-assisted reproductive technologies are still required for males to achieve biological parenthood; (4) pregnancy requires close monitoring and unique screening for diabetes; and (5) CFTR modulator exposure in utero has implications for infant monitoring and cystic fibrosis screening results in newborns.","[""Journal Article"", ""Review"", ""Consensus Statement"", ""Practice Guideline""]","[""Jain R"", ""Taylor JL"", ""Kazmerski TM"", ""Lonabaugh K"", ""Trimble A"", ""Velez Leitner D"", ""Foil K"", ""Hong G"", ""Johns WB"", ""Kolarova T"", ""Meier E"", ""Perry A"", ""Singh KE"", ""Stahl C"", ""Szentpetery S"", ""Weiss MS"", ""West NE"", ""Wilson A"", ""Wright B"", ""Brown AW"", ""Hempstead SE"", ""Lomas P"", ""Middleton PG"", ""Shteinberg M"", ""Felton I"", ""Roe AH""]",10.1016/S2213-2600(26)00120-7,Jain R,The Lancet. Respiratory medicine,2213-2600,8,Lancet Respir Med,eng,Roe AH,"[""Humans"", ""Cystic Fibrosis"", ""Female"", ""Pregnancy"", ""Male"", ""Reproductive Health"", ""Cystic Fibrosis Transmembrane Conductance Regulator"", ""Contraception"", ""Preconception Care"", ""Infant, Newborn""]",730-746,42442376,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42442376/,Reproductive health guidance for the cystic fibrosis community: a Cystic Fibrosis Foundation Position Paper,14,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"As a joint effort by the Canadian Network for Mood and Anxiety Treatments (CANMAT) and the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS), these treatment guidelines provide an up-to-date synthesis of published literature on the efficacy, safety, and tolerability of the range of interventions available for the management of obsessive-compulsive disorder (OCD) across the lifespan. The primary goal is to provide clear, easy to use recommendations for practicing clinicians. A global group of OCD experts were divided into panels to develop specific sections based on internal group discussions and the evidence extracted from systematic literature searches. CANMAT-defined Levels of Evidence, as well as level of clinical support were used to inform Lines of Treatment and final treatment recommendations. Drafts were revised based on feedback from individuals with lived experience, expert peer review, and a defined expert consensus process. These OCD Guidelines include seven sections spanning foundations of management and diagnosis, psychological, pharmacological, and neuro-modulation treatment modalities, treatment resistance, children and adolescents, special populations and future directions. Recommendations are summarized in tables for ease of reference and caveats and limitations of the current evidence are discussed. The CANMAT/ICOCS 2025 OCD International Guidelines synthesize the evidence on the efficacy, safety, and tolerability of the range of interventions available for the management of OCD. It is anticipated that these new OCD guidelines will enable psychiatrists and other clinicians to provide systematic, evidence-based care for their patients with OCD across the lifespan.","[""Journal Article"", ""Practice Guideline""]","[""Van Ameringen M"", ""Fineberg NA"", ""Ravindran A"", ""Arnold PD"", ""Beaulieu S"", ""Brakoulias V"", ""Brietzke E"", ""Dowlati Y"", ""Drummond LM"", ""Ferretti CJ"", ""Feusner JD"", ""Freire RCR"", ""Frey BN"", ""Gardiner S"", ""Geller DA"", ""Giacobbe P"", ""Bergmann CG"", ""Grassi G"", ""Greenberg E"", ""Hollander E"", ""Hopkinson P"", ""Kennedy SH"", ""Lam RW"", ""Lochner C"", ""McGuire JF"", ""McQuay S"", ""Menchon JM"", ""Milev R"", ""Minuzzi L"", ""Mojgani J"", ""Mpavaenda DN"", ""Nicolini H"", ""Pallanti S"", ""Pampaloni I"", ""Parikh SV"", ""Patterson B"", ""Ravindran L"", ""Reid J"", ""Rodriguez CI"", ""Samaan Z"", ""Schaffer A"", ""Smigielski L"", ""Taylor VH"", ""Tourjman SV"", ""van Roessel P"", ""Vigod SN"", ""Walitza S"", ""Yatham LN"", ""Zohar J"", ""Zugliani M"", ""Dell'Osso BM""]",10.1016/j.jpsychires.2025.12.039,Van Ameringen M,Journal of psychiatric research,0022-3956,,J Psychiatr Res,eng,Dell'Osso BM,"[""Humans"", ""Canada"", ""Obsessive-Compulsive Disorder"", ""Practice Guidelines as Topic""]",404-488,42441734,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42441734/,Canadian Network for Mood and Anxiety Treatments (CANMAT) and International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) 2025 international guidelines for the management of patients with obsessive-compulsive disorder,199,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Since the 2020 Korean guidelines for Helicobacter pylori treatment, clarithromycin resistance rates have risen from 17.8% to 33.3%, dual-priming oligonucleotide-based polymerase chain reaction (DPO-PCR)-based tailored therapy has been adopted, and P-CABs have become available. This fourth revision addresses these changes. Nine key questions were addressed through systematic reviews with meta-analyses. Thirteen recommendations were evaluated via modified Delphi process involving 64 experts. Twelve recommendations achieved first-round consensus; one required revision and achieved 73.9% agreement. Key changes: (1) dual-pillar strategy of tailored therapy and empirical quadruple therapy; (2) restricted use of empirical clarithromycin-based triple therapy under specific conditions; (3) removal of sequential therapy; (4) P-CABs as PPI alternatives; (5) expansion of eradication indications to include gastric cancer prevention in H. pylori gastritis and regression of hyperplastic polyps ≤ 10 mm; and (6) positioning of bismuth quadruple therapy as a conditionally recommended first-line empirical option with preference for reservation as salvage therapy, and introduction of modified bismuth quadruple therapy (addition of bismuth to conventional regimens) as an additional first-line empirical option. This fourth revised guideline provides updated, evidence-based recommendations for the diagnosis and treatment of H. pylori infection, reflecting the rapidly changing antibiotic resistance landscape and the introduction of new diagnostic and therapeutic tools in Korea. These guidelines aim to assist clinicians, patients, policymakers, and medical educators in optimizing H. pylori management. They may differ from current medical insurance standards and will be revised further based on emerging evidence.","[""Journal Article"", ""Practice Guideline"", ""Review""]","[""Bang CS"", ""Kang SJ"", ""Lim H"", ""Kim SH"", ""Lee MW"", ""Nam SY"", ""Tae CH"", ""Kim SE"", ""Kim SY"", ""Jung HK"", ""Kim BJ"", ""Choi M"", ""Jung HY"", ""Kim BW"", ""Korean College of Helicobacter and Upper Gastrointestinal Research""]",10.1111/hel.70149,Bang CS,Helicobacter,1083-4389,4,Helicobacter,eng,Kim BW,"[""Helicobacter Infections"", ""Humans"", ""Helicobacter pylori"", ""Republic of Korea"", ""Anti-Bacterial Agents"", ""Drug Therapy, Combination"", ""Drug Resistance, Bacterial"", ""Clarithromycin""]",e70149,42439470,pmc-id: PMC13359576;,2026 Jul-Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42439470/,Evidence-Based Guidelines for the Diagnosis and Treatment of Helicobacter pylori Infection in Korea: 2025 Revised Edition,31,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Lung cancer is the leading cause of cancer mortality in Australia. In July 2025, the Australian Government launched the National Lung Cancer Screening Program (the Program). The Program has been designed in accordance with the Medical Services Advisory Committee's recommendations. This article summarises the program guidelines, outlining Program parameters and delivery requirements. The screening and assessment pathway defines the Program structure. The purpose of the guidelines is to ensure safe, effective and high-quality Program delivery, detailing key steps for clinical practice and information for participating healthcare providers. The guidelines provide recommendations for the delivery of targeted low-dose CT screening for lung cancer in the Australian context. Program eligibility is assessed using risk-based eligibility criteria recommended by the Medical Services Advisory Committee, targeting people between 50 and 70 years of age with a history of tobacco cigarette smoking. Smoking cessation supports are to be offered to all potential participants by healthcare providers across the lung cancer screening and assessment pathway. Low-dose CT scan assessment and reporting follow the National Lung Cancer Screening Program's nodule management protocol. This guideline provides recommendations for the delivery of targeted low-dose CT screening for lung cancer in the Australian context. Content includes: guidance on assessing Program eligibility; enrolling eligible participants in the National Cancer Screening Register; completing and fulfilling low-dose CT scan requests; assessing and reporting low-dose CT scan results; managing scan outcomes and actionable additional findings; and communicating scan results. The full guideline is available at https://www.health.gov.au/resources/publications/nlcsp-guidelines.","[""Journal Article"", ""Practice Guideline""]","[""Rankin NM"", ""Zosel R"", ""Whop LJ"", ""Maddox R"", ""McWilliams A"", ""Siemienowicz M"", ""Emery J"", ""Lantin MAR"", ""Bartlett G"", ""Wolfe M"", ""Diaz A"", ""Anderson K"", ""Liu L"", ""Toms C"", ""McDermott S"", ""Bligh P"", ""Chalke J"", ""Melsom S"", ""Nightingale CE"", ""Brown A"", ""Pope S"", ""Brotherton J"", ""Fidler A"", ""Itel M"", ""Brooke M"", ""Pascoe DM"", ""Brims F"", ""Leong TL"", ""Stone E"", ""Keefe D"", ""Milch V""]",10.5694/mja2.70234,Rankin NM,The Medical journal of Australia,0025-729X,7,Med J Aust,eng,Milch V,"[""Humans"", ""Lung Neoplasms"", ""Australia"", ""Early Detection of Cancer"", ""Tomography, X-Ray Computed"", ""Mass Screening"", ""Middle Aged"", ""Aged"", ""Smoking Cessation"", ""Practice Guidelines as Topic""]",e70234,42438375,pmc-id: PMC13358458;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42438375/,Program Guidelines for the National Lung Cancer Screening Program: Targeted Lung Cancer Screening in High-Risk Individuals in Australia,224,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"The Wilderness Medical Society released the first edition of the Wilderness Medical Society Clinical Practice Guideline on Care of Burns in the Wilderness in June 2025. This guideline offers evidence-based recommendations for the management of burn injuries in wilderness environments, including on-site burn assessment, field first aid, evaluation of burn depth and total body surface area, blister care, fluid resuscitation, wound dressing, pain control, post-injury evacuation, and telemedicine applications. This article interprets the guideline, aiming to inform clinical practitioners of recent advances in wilderness burn care and provide evidence-based references for clinical practice.","[""Journal Article"", ""English Abstract"", ""Practice Guideline""]","[""Sun L"", ""Zhang L"", ""Jin Y"", ""Duan S"", ""Li R"", ""Li W""]",10.3760/cma.j.cn121430-20260109-00023,Sun L,Zhonghua wei zhong bing ji jiu yi xue,2095-4352,6,Zhonghua Wei Zhong Bing Ji Jiu Yi Xue,chi,Li W,"[""Burns"", ""Humans"", ""Wilderness Medicine"", ""Societies, Medical""]",501-507,42427321,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42427321/,[Interpretation of the 2025 Wilderness Medical Society Clinical Practice Guideline on Care of Burns in the Wilderness],38,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"The purpose of this guideline is to provide an evidence-based framework for healthcare professionals to recognize, manage, and prevent iron deficiency and iron deficiency anemia across the lifecycle of women, with particular emphasis on time periods of vulnerability, such as pregnancy, menstruation, and perioperatively. This clinical practice guideline seeks to improve the lives of women at all reproductive life stages, from menarche to menopause, with iron deficiency and iron deficiency anemia in the context of obstetrical and gynaecologic care. This guideline reviews the available options for the prevention, assessment, and treatment of iron deficiency and iron deficiency anemia. While the focus of this guideline pertains to oral and intravenous iron replacement therapy, the importance of reducing menstrual blood loss is also emphasized. By consolidating the best evidence to date with expert opinion across the disciplines of obstetrics and gynaecology, hematology, and anaesthesiology, we provide recommendations and treatment algorithms to guide the diagnosis and treatment of iron deficiency and iron deficiency anemia for patients within our specialty. The prevention, early identification, and treatment of iron deficiency and iron deficiency anemia is assessed to be a cost-effective strategy to improve the health and well-being of women of reproductive age. This proactive approach to iron deficiency and iron deficiency anemia has also been shown to reduce the need for blood transfusion, along with the associated harms and costs of transfusion. The potential costs of iron infusion therapy must be assessed in the context of the profound adverse impacts on quality of life, reduced work performance and decreased economic productivity of patients with iron deficiency and iron deficiency anemia. Using relevant MeSH headings and keywords (related to concepts of anemia, iron deficiency, blood management, blood conservation, transfusion, obstetrics, pregnancy, postpartum, and gynaecology), published literature was retrieved through searches of PubMed and Cochrane Systematic Reviews from January 2015 to December 2025. Grey literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, and national and international medical specialty societies. This guideline was developed through consensus by a multidisciplinary team of authors with representation from obstetrics, gynaecology, anaesthesiology, and hematology. The content and recommendations were drafted and agreed upon by the authors. The SOGC's Clinical Obstetrics and Gynaecology Committee reviewed the guideline and the Guideline Management and Oversight Committee approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology framework. See online Appendix A (Tables A1 for definitions and A2 for interpretations). A national panel of patient partners was gathered to provide feedback and perspective on the recommendations and summary statements for this guideline. Community partners were purposefully selected to ensure representation of Canadian geographic regions, lived experience with iron deficiency or iron deficiency anemia, as well as obstetrical or gynaecologic care received. Healthcare providers involved in the assessment and management of women with iron deficiency and iron deficiency anemia. Iron deficiency (ID) and iron deficiency anemia (IDA) have profound impacts on the quality of life in women worldwide. As such, the early identification of ID/IDA and iron replacement therapy is an important strategy for women's health and wellbeing. General Principles of Diagnosis and Treatment GYNAECOLOGY: PRECONCEPTION, PREGNANCY, AND POSTPARTUM: RECOMMENDATIONS: General Principles of Diagnosis and Treatment GYNAECOLOGY: PRECONCEPTION, PREGNANCY, AND POSTPARTUM.","[""Journal Article"", ""Practice Guideline""]","[""Chen I"", ""Khamisa K"", ""Murji A"", ""Coolen J"", ""Evans D"", ""Lett R"", ""Rittenberg D"", ""Lett C""]",10.1016/j.jogc.2026.103428,Chen I,Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC,1701-2163,,J Obstet Gynaecol Can,eng,Lett C,[],103428,42425828,,2026 Jul 9,2026,https://pubmed.ncbi.nlm.nih.gov/42425828/,No. 469 Iron Deficiency and Iron Deficiency Anemia in Obstetrics and Gynaecology,,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
,"[""Journal Article"", ""Practice Guideline""]","[""Chen I"", ""Khamisa K"", ""Murji A"", ""Coolen J"", ""Evans D"", ""Lett R"", ""Rittenberg D"", ""Lett C""]",10.1016/j.jogc.2026.103429,Chen I,Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC,1701-2163,,J Obstet Gynaecol Can,eng,Lett C,[],103429,42425827,,2026 Jul 9,2026,https://pubmed.ncbi.nlm.nih.gov/42425827/,N° 469 Carence en fer et anémie ferriprive en obstétrique et en gynécologie,,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"The NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget's disease, Phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The panel convenes annually to update recommendations based on a review of recently published clinical trials. This selection from the NCCN Guidelines for Breast Cancer focuses on the recommendations for the management of recurrent or stage IV (M1) metastatic breast cancer. It summarizes the treatment strategies stratified by tumor biology, including hormone receptor status and HER2 expression, as well as clinical factors such as prior therapy and disease-free interval. Throughout all treatment lines, supportive care, quality of life preservation, toxicity minimization, and clinical trial participation are emphasized as integral components of patient care.","[""Journal Article"", ""Practice Guideline""]","[""Gradishar WJ"", ""Moran MS"", ""Abraham J"", ""Abramson V"", ""Aft R"", ""Agnese D"", ""Allison KH"", ""Anderson B"", ""Bailey J"", ""Burstein HJ"", ""Chen N"", ""Chew H"", ""Dang C"", ""Elias AD"", ""Giordano SH"", ""Goetz MP"", ""Jankowitz RC"", ""Javid SH"", ""Leitch AM"", ""Lyons J"", ""McCloskey S"", ""McShane M"", ""Patel SA"", ""Rosenberger LH"", ""Rugo HS"", ""Santa-Maria CA"", ""Schneider BP"", ""Smith ML"", ""Soliman H"", ""Speers C"", ""Telli ML"", ""Wei M"", ""Wisinski KB"", ""Yellala A"", ""Yeung KT"", ""Young JS"", ""Schonfeld R"", ""Kumar R""]",10.6004/jnccn.2026.0033,Gradishar WJ,Journal of the National Comprehensive Cancer Network : JNCCN,1540-1405,7,J Natl Compr Canc Netw,eng,Kumar R,"[""Humans"", ""Breast Neoplasms"", ""Female"", ""Medical Oncology"", ""Neoplasm Staging""]",,42425164,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42425164/,"Breast Cancer, Version 4.2026, NCCN Clinical Practice Guidelines In Oncology",24,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"The Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are a group of heterogenous hematologic malignancies characterized by the proliferation of blood cells and consist of myelofibrosis, polycythemia vera, and essential thrombocythemia. The NCCN Guidelines for MPN were developed as a result of meetings convened by a multidisciplinary panel with expertise in MPN, with the aim of providing recommendations for the comprehensive care of adults with these diseases. The panel of experts convenes at least once a year to discuss requested changes to the Guidelines and to evaluate emerging data. These Guideline Insights focus on some of the recent updates for myelofibrosis.","[""Journal Article"", ""Practice Guideline""]","[""Gerds AT"", ""Gotlib J"", ""Abdelmessieh P"", ""Ali H"", ""Castells M"", ""Chernak BJ"", ""Espinoza-Gutarra MR"", ""Fein Revell R"", ""Green S"", ""Gundabolu K"", ""Hexner E"", ""Jain T"", ""Jamieson CH"", ""Khan I"", ""Kuykendall AT"", ""Madanat YF"", ""Masarova L"", ""McMahon B"", ""Mohan SR"", ""Nadiminti KV"", ""Oh S"", ""Palmer J"", ""Patel AB"", ""Patel AA"", ""Podoltsev N"", ""Rein L"", ""Salit R"", ""Sehl M"", ""Talpaz M"", ""Wadleigh M"", ""Wall SA"", ""Bergman MA"", ""Hochstetler C""]",10.6004/jnccn.2026.0034,Gerds AT,Journal of the National Comprehensive Cancer Network : JNCCN,1540-1405,7,J Natl Compr Canc Netw,eng,Hochstetler C,"[""Humans"", ""Myeloproliferative Disorders"", ""Primary Myelofibrosis""]",,42425157,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42425157/,"NCCN Guidelines® Insights: Myeloproliferative Neoplasms, Version 2.2026",24,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Venous thromboembolism (VTE) in children is a rare condition. It encompasses different clinical scenarios that require an individualized and multidisciplinary approach. The aim of this document is to provide a practical guideline for the management of pediatric VTE based on the best available evidence. An exhaustive literature review was performed, gathering information from current clinical guidelines and recent studies. This document compiles the recommendations on the diagnosis and treatment of VTE in infants, children, and adolescents endorsed by the Spanish Society of Internal Medicine (SEMI), the Spanish Society of Thrombosis and Hemostasis (SETH), and the Spanish Society of Pediatric Hematology and Oncology (SEHOP). Neonatal VTE, arterial thrombosis, and superficial venous thrombosis are beyond the scope of this work. This document includes a list of definitions aimed at standardizing terminology and another two distinct sections: (1) particularities of treatment, including recommendations regarding dosing, monitoring and cautions in the pediatric population, and (2) particularities in management, including specific recommendations for the most frequent scenarios in children.","[""Journal Article"", ""Practice Guideline""]","[""Berrueco R"", ""Falcón M"", ""Argilés B"", ""Campo Palacio HJ"", ""Climent FJ"", ""Gómez Del Castillo MDC"", ""Guirado L"", ""Izquierdo S"", ""López-Almaraz R"", ""Otálora Valderrama S"", ""Puche Palao G"", ""Ruiz-Artacho P""]",10.1016/j.anpede.2026.504238,Berrueco R,Anales de pediatria,2341-2879,1,An Pediatr (Engl Ed),eng,Ruiz-Artacho P,"[""Humans"", ""Child"", ""Venous Thromboembolism"", ""Adolescent"", ""Anticoagulants"", ""Infant"", ""Spain""]",504238,42420127,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42420127/,"Diagnosis and treatment of venous thromboembolic disease in children. Recommendations from the Thromboembolic Disease Working Group of the Spanish Society of Internal Medicine (SEMI), the Spanish Society of Thrombosis and Hemostasis (SETH) and the Spanish Society of Pediatric Hematology and Oncology (SEHOP)",105,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Obstructed defecation syndrome (ODS) is a multifactorial condition that significantly impairs quality of life and presents diagnostic and therapeutic challenges due to the interaction of functional and anatomical factors. This initiative aimed to develop a Belgian consensus and a diagnostic-therapeutic algorithm to support effective clinical management of ODS. A Belgian steering group of gastroenterologists and colorectal surgeons (n=6) conducted a Delphi consensus process. Based on a structured literature review, 82 statements were drafted and discussed during three online voting rounds. Consensus was defined as ≥80% agreement, and evidence strength was graded using the GRADE system. Thirty-one experts participated, including gastroenterologists, colorectal surgeons, gynecologists, and physiotherapists. Sixty-two final statements were formulated, of which 46 were endorsed. ODS was defined as a disorder of anorectal evacuation, with functional and structural components often coexisting. Symptoms overlap with functional constipation, IBS-C, and fecal incontinence, and quality of life is substantially impaired. Diagnosis requires multimodal evaluation, including digital rectal examination and anorectal testing. First-line treatment consists of conservative measures such as lifestyle optimization, laxatives, and pelvic floor re-education. Surgery is reserved for selected patients with refractory symptoms and significant anatomical abnormalities. Tailored surgical approaches are supported for rectocele, rectal prolapse, and pelvic organ prolapse, whereas sacral nerve stimulation is not routinely recommended. These consensus statements provide practical guidance for the diagnosis and management of ODS. Conservative therapy remains the cornerstone, with surgery reserved for selected cases. Areas lacking consensus warrant further research.","[""Journal Article"", ""Consensus Statement"", ""Practice Guideline""]","[""Van de Bruaene C"", ""De Schepper H"", ""Surmont M"", ""Van de Putte D"", ""Van den Broeck S"", ""Bislenghi G"", ""Boon K"", ""Casteels P"", ""Cornille J-"", ""De Looze D"", ""Denis MA"", ""François A"", ""Gijsen I"", ""Geldof J"", ""Van Geluwe B"", ""Geraerts I"", ""Hanssens M"", ""Kindt S"", ""Komen N"", ""Meerhout D"", ""Nullens S"", ""Poortmans N"", ""Pletinckx P"", ""Raymenants K"", ""Ruymbeke H"", ""Segaert A"", ""Stockman S"", ""Stijns J"", ""Van Aggelpoel T"", ""Vandenplas L"", ""Roelandt P""]",10.51821/89.2.15231,Van de Bruaene C,Acta gastro-enterologica Belgica,1784-3227,2,Acta Gastroenterol Belg,eng,Roelandt P,"[""Humans"", ""Constipation"", ""Pelvic Floor Disorders"", ""Belgium"", ""Quality of Life"", ""Delphi Technique"", ""Syndrome"", ""Female"", ""Consensus"", ""Digital Rectal Examination""]",385-405,42417642,,2026 Apr-Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42417642/,Guideline on Pelvic Floor Disorders: consensus on Obstructed Defecation Syndrome (ODS),89,W0soHRrNZcUa0eiN3,P9ccIuOHXbTwoTAHf
"Video laryngoscopy is increasingly used in routine tracheal intubation in the operating room, but evidence regarding its clinical outcomes remains inconclusive. In particular, the role of hyperangulated video laryngoscopes as first-choice devices has not been studied sufficiently. To determine whether video laryngoscopy-regardless of blade geometry or manufacturer-provides superior first-pass success compared with direct laryngoscopy (DL) during routine tracheal intubations. This 3-arm randomized clinical trial (Conventional vs Video-Assisted Laryngoscopy for Perioperative Endotracheal Intubation [COVALENT]) was conducted at 6 academic or intermediate care centers in Germany and Austria between March 28, 2022, and February 17, 2025. Adults undergoing surgery under general anesthesia with the need for tracheal intubation were included in the trial. Adults undergoing surgery under any other form of anesthesia, those requiring nasal or planned fiberoptic intubation, and pregnant patients were excluded. Patients were sampled consecutively until trial staff capacity limits were met for any given day. Devices from different manufacturers were allowed to maximize generalizability. All data analyses followed a modified intention-to-treat approach. Tracheal intubation as part of general anesthesia induction preceding surgery. Patients were randomly assigned (1:1:1) to DL, video laryngoscopy with Macintosh blade (VLM), or video laryngoscopy with a hyperangulated blade (VLH). All interventions were performed by the anesthesiologists assigned to their respective cases. The primary outcome was first-pass intubation success rate. After the laryngoscope and tracheal tube were inserted into the patient's oral cavity, retrieval of either marked a failed intubation attempt. Successful intubation was defined as positive capnography. Differences between success rates were tested applying the z test for unpooled variance and reported as absolute differences with corresponding 95% CIs. Of the 2532 patients (1426 males [56.3%]; mean [SD] age, 59.7 [15.4] years) randomly assigned to DL (n = 848), VLM (n = 841), or VLH (n = 843), 2423 (95.7%) were included in a modified intention-to-treat analysis. Both video laryngoscopy modalities were superior to DL regarding first-pass success (VLM: 82.9%, VLH: 87.6%, and DL: 78.2%; all P < .001). Unadjusted absolute risk differences for first-pass intubation success were 4.66 (95% CI, 4.45-4.78) percentage points for DL vs VLM, 9.34 (95% CI, 9.22-9.46) percentage points for DL vs VLH, and 4.68 (95% CI, 4.57-4.79) percentage points for VLM vs VLH. VLM and VLH compared with DL had faster intubation success after a failed first attempt (mean [SD] time to positive capnography, 146.6 [103.6] and 147.5 [98.9] seconds vs 170.3 [100.4] seconds; P = .008). There were fewer complications of lip or dental injuries or blood on the blade for VLH compared with VLM and DL (10.9% [11 of 101] vs 23.2% [32 of 138] and 24.1% [42 of 174]). This randomized clinical trial of DL vs VLM and VLH found that video laryngoscopy significantly improved first-pass success during intubation in the operating room compared with DL. The findings support the use of video laryngoscopy as a new standard of care for routine airway management. ClinicalTrials.gov Identifier: NCT05228288.","[""Journal Article"", ""Randomized Controlled Trial"", ""Comparative Study"", ""Multicenter Study""]","[""Schmid B"", ""Grüßer L"", ""Müller L"", ""Wittmann M"", ""Delis A"", ""Dinc Dogan T"", ""Werdehausen R"", ""Neuhaus C"", ""Paal P"", ""Claassen C"", ""Helmer P"", ""Fischer P"", ""Kranke P"", ""Meybohm P"", ""Massoth G"", ""German Society of Anaesthesiology and Intensive Care (GSAIC) Trials Group""]",10.1001/jamanetworkopen.2026.25965,Schmid B,JAMA network open,2574-3805,8,JAMA Netw Open,eng,Massoth G,"[""Humans"", ""Intubation, Intratracheal"", ""Laryngoscopy"", ""Female"", ""Male"", ""Middle Aged"", ""Aged"", ""Video-Assisted Techniques and Procedures"", ""Adult"", ""Germany"", ""Laryngoscopes"", ""Austria"", ""Anesthesia, General""]",e2625965,42545700,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545700/,Conventional vs Video-Assisted Laryngoscopy for Perioperative Endotracheal Intubations: A Randomized Clinical Trial,9,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"Children with attention-deficit/hyperactivity disorder (ADHD) often experience friendship difficulties, yet little is known about whether friendship quality differs according to the gender composition of their friendships. Drawing on developmental models of gendered friendship processes, we examined whether friendship quality differed across boy-boy, girl-girl, and mixed-gender dyads among children with ADHD. This secondary analysis used baseline data from a randomized clinical trial of children with ADHD aged 6 to 11 who were seeking treatment for peer problems. The sample included 149 children who brought a reciprocated friend to the baseline assessment: 87 boy-boy dyads, 44 girl-girl dyads, and 18 mixed-gender dyads. Friendship quality was assessed using multi-informant questionnaires and direct observations of dyadic interactions. Contrary to hypotheses, girl-girl dyads showed significantly higher observational positive friendship quality than boy-boy dyads, an effect that remained robust across sensitivity analyses. Questionnaire measures did not consistently differentiate boy-boy and girl-girl dyads, although sensitivity analyses among ""close"" and ""best"" friends suggested higher child-reported positive friendship quality in girl-girl dyads. Mixed-gender dyads generally did not differ from either same-gender group, but these contrasts were underpowered. Findings suggest that gendered friendship patterns among children with ADHD may more closely resemble those observed in neurotypical samples than expected. Results underscore the value of multi-method, multi-informant assessment and highlight the need for further research on friendships among girls with ADHD.","[""Journal Article"", ""Comparative Study""]","[""Montiel AE"", ""Normand S"", ""Mikami AY""]",10.1007/s10802-026-01490-7,Montiel AE,Research on child and adolescent psychopathology,2730-7166,4,Res Child Adolesc Psychopathol,eng,Mikami AY,"[""Humans"", ""Female"", ""Friends"", ""Attention Deficit Disorder with Hyperactivity"", ""Child"", ""Peer Group"", ""Male"", ""Interpersonal Relations"", ""Sex Factors"", ""Surveys and Questionnaires""]",,42545665,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545665/,"Friendship Quality in Children With ADHD Seeking Treatment for Peer Problems: A Comparison of Boy-Boy, Girl-Girl, and Mixed-Gender Dyads",54,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"Differentiation between honey bee castes is essentially a nutritional phenotype, but the complex physicochemical inputs that play critical roles in endocrine and epigenetic programming are still poorly documented, particularly for worker jelly (WJ) and drone jelly (DJ), which are rarely characterized alongside royal jelly (RJ) and the larvae that metabolize them. Here, we compare RJ, WJ and DJ and queen (1-4 d), worker (1-5 d) and drone (1-6 d) larvae produced under standardized field conditions (15 colonies) in Ordu, Türkiye (18 biological groups) systematically with respect to caste and age. Moisture/dry matter and ash were determined gravimetrically, protein by Dumas combustion, sugars and 10-hydroxy-2-decenoic acid (10-HDA) using HPLC (RID/UV), minerals and heavy metals by ICP-MS, and acidity based on pH and titration. RJ complied with international composition standards: protein (12.90%) and 10-HDA content at the authenticity threshold (1.41%). WJ exhibited elevated protein (16.80%) and the highest titratable acidity (48 mL 1 N NaOH/100 g), alongside relatively enriched macro- and microelement profiles, particularly K and Mg, providing a distinguishing nutritional ""signature"" of larval foods; DJ showed the highest protein density of all matrices (18.37%). Sugar profiles suggested that glucose and fructose predominated, but a strong developmental pattern for sucrose became clear: large amounts of sucrose were present in 1-day-old larvae but absent from all later developmental stages, consistent with rapid turnover of the carbohydrate pool during early growth. RJ was the most acidic matrix (pH 3.96), and pH increased with larval age across castes suggesting buffering, tissue growth and remodelling in the context of aligned biomass accumulation. Together, these data establish comparative baseline datasets for caste-related larval foods and larvae, reinforce authenticity quality-control frameworks beyond RJ alone, and furnish a physicochemical basis for mechanistic studies linking food chemistry with caste-linked developmental physiology. These baseline data also offer practical reference points for veterinary monitoring of larval nutrition and colony health. Beyond providing a comprehensive reference dataset, the divergent nutritional profiles we observed particularly in protein, sugar, and 10-HDA dynamics suggest that the temporal coordination of these components may contribute to the canalization of caste-specific developmental pathways.","[""Journal Article"", ""Comparative Study""]","[""Okuyan S"", ""Çakici N"", ""Şahin P"", ""Şahin AE"", ""Demir T"", ""Sansar S"", ""Alparslan S"", ""Solmaz S"", ""Arigül M"", ""Sevin S""]",10.1007/s11259-026-11439-2,Okuyan S,Veterinary research communications,0165-7380,5,Vet Res Commun,eng,Sevin S,"[""Animals"", ""Bees"", ""Royal Jelly"", ""Fatty Acids"", ""Larva""]",,42545554,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545554/,"Caste-specific nutritional signatures: Comparative physicochemical characterization of royal, worker, and drone jelly and larvae across developmental stages in Apis mellifera L",50,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"Patients increasingly consult large language models (LLMs) before specialist review and may do so in widely differing emotional registers. We examined whether re-casting an unruptured intracranial aneurysm (UIA) case from a third-person vignette into a first-person patient account, with anxiety about treatment or non-treatment, alters the recommendations LLMs return. Sixty-seven UIA cases previously discussed at our multidisciplinary team (MDT) were presented to Claude Opus 4.6, ChatGPT-5.4 and Gemini 3 Pro Thinking under four conditions: third-person vignette (3P), neutral first-person (1PN), and first-person accounts anxious about treatment (1PAT) or non-treatment (1PANT). Each case was submitted five times (4,020 prompts). Majority recommendations were benchmarked against MDT consensus (Cohen's κ, McNemar), tested for directional asymmetry (Bowker), classified as progressive or regressive, and linguistically analysed. Concordance with MDT was fair-to-moderate (71.6-80.0%; κ 0.34-0.51). ChatGPT over-treated under all conditions (p = 0.001-0.013) and Gemini over-treated only at 3P baseline (p = 0.001), abolished under first-person framing. Claude showed no directional preference. First-person framing drove significant clipping-to-coiling migration in Gemini and ChatGPT (p = 0.001 and 0.015). Claude alone hedged under treatment-directed anxiety (p = 0.002). Anxiety-induced shifts were predominantly regressive. Gemini under rupture-anxiety combined the highest empathy-opener rate (85%), highest confidence-marker density and lowest hedging density of any cell, a sycophantic phenotype invisible to categorical analysis. Patient persona and affective framing measurably and model-specifically alter LLM recommendations for UIAs, with anxiety-induced shifts moving models away from rather than toward expert consensus. Clinicians should anticipate AI-shaped expectations varying with a patient's emotional state and counsel against framing-induced advice. This study was retrospectively registered on the Open Science Framework (https://doi.org/10.17605/OSF.IO/HCU6D).","[""Journal Article"", ""Comparative Study""]","[""Narayan A"", ""Mariajoseph F"", ""Farooq M"", ""Praeger A"", ""Moore J""]",10.1007/s10143-026-04419-2,Narayan A,Neurosurgical review,0344-5607,1,Neurosurg Rev,eng,Moore J,"[""Humans"", ""Intracranial Aneurysm"", ""Large Language Models"", ""Benchmarking"", ""Female"", ""Male"", ""Generative Artificial Intelligence"", ""Middle Aged"", ""Adult"", ""Aged""]",,42545535,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545535/,"The Influence of Patient Persona and Affective Framing on Management Recommendations of ChatGPT, Gemini and Claude for Unruptured Intracranial Aneurysms: A Comparative Benchmarking Study",49,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"The optimal suture material for laparoscopic inguinal hernia repair in children remains controversial. This study aimed to compare the outcomes of absorbable sutures (AS) versus non-absorbable sutures (NAS), focusing on recurrence and suture-related complications. A systematic literature search was conducted in PubMed, Web of Science, and the Cochrane Library. Studies comparing AS and NAS in pediatric patients were included. Meta-analyses were performed using fixed- or random-effects models to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Four studies comprising 2803 patients in the AS group and 3507 in the NAS group were included. No significant differences were observed between AS and NAS for postoperative hydrocele (OR = 5.12, 95% CI 0.61-42.67; P = 0.13) or wound infection (OR = 0.94, 95% CI 0.44-2.01; P = 0.91). Suture knot reaction was significantly lower in the AS group (OR = 0.03, 95% CI 0.01-0.15; P < 0.0001). However, recurrence risk was significantly higher in the AS group (OR = 7.80, 95% CI 2.14-28.45; P = 0.002). Absorbable sutures significantly reduce suture knot reactions but are associated with a higher risk of recurrence compared to non-absorbable sutures. No significant differences were found for hydrocele or wound infection. Suture selection should balance these risks based on clinical priorities.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Comparative Study""]","[""Shi M"", ""Wu D"", ""Miao X"", ""Ye H""]",10.1007/s00383-026-06563-8,Shi M,Pediatric surgery international,0179-0358,1,Pediatr Surg Int,eng,Ye H,"[""Humans"", ""Hernia, Inguinal"", ""Sutures"", ""Laparoscopy"", ""Herniorrhaphy"", ""Child"", ""Recurrence"", ""Suture Techniques"", ""Absorbable Implants"", ""Postoperative Complications"", ""Treatment Outcome""]",,42545513,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545513/,Absorbable versus non-absorbable suture in percutaneous laparoscopic inguinal hernia repair in children: a systematic review and meta-analysis,42,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"To compare clinical outcomes and complication rates between plate with independent screw fixation versus screw fixation alone in the management of talar neck fractures (AO/OTA 81.2), with a primary focus on avascular necrosis (AVN). A retrospective review was performed of adult patients who underwent operative fixation of talar neck fractures at a single Level I trauma center between 2017 and 2022, with a minimum follow-up of 3 months. Patients were divided into screw fixation alone (S) and plate with independent screw fixation (PS) groups. The primary outcome was avascular necrosis (AVN). Secondary outcomes included fracture union, post-traumatic arthrosis (PTA), infection, and unplanned reoperation. Multivariable logistic regression was performed to identify factors associated with AVN. Seventy patients were included (33 S, 37 PS) with no differences in baseline demographics, comorbidities, or injury characteristics (p > 0.05). Union rates were similar between groups (p = 0.23). The incidence of AVN was significantly higher in the S group compared to the PS group (52% vs 22%, p = 0.01). There were no differences in rates of PTA, infection, or reoperation (p > 0.05). On multivariable analysis, plate fixation was associated with a significantly lower likelihood of AVN (OR 0.16, 95% CI 0.03-0.70; p < 0.01). In this retrospective cohort, plate with independent screw fixation was associated with a significantly lower risk of avascular necrosis compared to screw fixation alone in talar neck fractures, while maintaining similar union and complication rates.","[""Journal Article"", ""Comparative Study""]","[""Page BE"", ""Rechter GR"", ""Nasir BA"", ""Yawman JP"", ""Jacobs ED"", ""Langford JR"", ""Haidukewych GJ"", ""Shaath MK""]",10.1007/s00590-026-04898-5,Page BE,European journal of orthopaedic surgery & traumatology : orthopedie traumatologie,1633-8065,1,Eur J Orthop Surg Traumatol,eng,Shaath MK,"[""Humans"", ""Talus"", ""Retrospective Studies"", ""Female"", ""Osteonecrosis"", ""Male"", ""Fracture Fixation, Internal"", ""Bone Screws"", ""Middle Aged"", ""Adult"", ""Bone Plates"", ""Postoperative Complications"", ""Fractures, Bone"", ""Reoperation""]",,42545506,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545506/,Impact of fixation method on avascular necrosis in talar neck fractures: a retrospective analysis,36,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"To assess the risk of suicide after a diagnosis of urinary bladder cancer (UBC) compared with the standard population and to identify potential risk factors and time dependence associated with suicide in patients with UBC. We used data from the Bladder Cancer Data Base Sweden 2.0 (BladderBaSe), including all individuals aged 18 years or older, diagnosed with UBC between 1997 and 2019. Suicides were identified using ICD-10 codes X60-X84. We compared the number of suicides identified in BladderBaSe with the expected number in a Swedish standard population of the same age and sex distribution during the same period.  Outcome measurements: The risk of suicide was determined using standardized mortality ratios (SMR) with 95% confidence intervals (CI). Among 53,298 patients with UBC included in our study, 106 suicides were identified compared with an expected 66 in the standard population (SMR: 1.6; 95% CI: 1.31-1.93). The risk of suicide was highest within the first 4 weeks after diagnosis (SMR: 4.66; 95% CI: 2.48-7.97), in patients with advanced UBC (SMR: 5.64; 95% CI: 2.06-12.3), those receiving palliative treatment (SMR: 5.03; 95% CI: 2.51-9.01), and those living alone (SMR: 2.87; 95% CI: 2.22 - 3.66). The suicide risk among UBC patients is significantly elevated and shaped by multiple factors, with the highest risk observed in the first 4 weeks from diagnosis. Healthcare providers should maintain heightened vigilance for suicidal ideation, particularly during the critical period immediately following diagnosis, to ensure timely support and intervention.","[""Journal Article"", ""Comparative Study""]","[""Hawez L"", ""Bergengren O"", ""Ahlberg M"", ""Garmo H"", ""Van Hemelrijck M"", ""Nyberg UK"", ""Gardmark T"", ""Holmberg L"", ""Liedberg F"", ""Bill-Axelson A""]",10.2340/sju.v60.44784,Hawez L,Scandinavian journal of urology,2168-1805,,Scand J Urol,eng,Bill-Axelson A,"[""Humans"", ""Sweden"", ""Female"", ""Male"", ""Urinary Bladder Neoplasms"", ""Aged"", ""Middle Aged"", ""Suicide"", ""Risk Factors"", ""Adult"", ""Aged, 80 and over""]",204-208,42545334,,2025 Nov 18,2025,https://pubmed.ncbi.nlm.nih.gov/42545334/,Suicide risk among urinary bladder cancer patients compared with the standard population: a nationwide study in Sweden,60,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"Women's participation in the workforce has increased substantially, raising important questions about how employment is associated with their subjective well-being and satisfaction with life. This study aimed to assess differences in personal well-being and life satisfaction between working and non-working women and to identify their significant socio-demographic and occupational predictors. A cross-sectional comparative study was conducted among 402 women (192 working, 210 non-working) attending outpatient clinics at Mansoura University and primary healthcare centers. Data were collected using an interviewer-administered questionnaire covering sociodemographic factors, occupational characteristics, the Personal Well-being Index-Adult (PWI-A), and the Life Satisfaction Scale(LSS). Bivariate and binary logistic regression analyses identified the independent predictors. Working women reported significantly higher well-being (PWI-A: 72.06 ± 13.03) and life satisfaction (LSS: 21.52 ± 5.76) than non-working women (PWI-A: 67.42 ± 10.14; LSS: 17.55 ± 5.91). University education (AOR = 2.81) and sufficient income (AOR = 2.94) were strong predictors of higher wellbeing. Subjective well-being (AOR = 21.67) was a significant predictor of life satisfaction. Among working women, professional (AOR = 4.76) and administrative/technical occupations (AOR = 7.40), and absence of shift work (AOR = 6.53) were associated with better wellbeing. Shorter working hours (≤40 h/week; AOR = 14.34) were linked to higher life satisfaction. In Mansoura, working women exhibit higher subjective well-being and life satisfaction than non-working women. These outcomes were associated with education, income, and occupational conditions. Improving work conditions may contribute to better well-being among working women.","[""Journal Article"", ""Comparative Study""]","[""Mohammed H"", ""Awaad A"", ""El-Gilany AH"", ""Abdelraouf S"", ""El-Refaay E""]",10.23749/mdl.2026.18572,Mohammed H,La Medicina del lavoro,0025-7818,4,Med Lav,eng,El-Refaay E,"[""Humans"", ""Female"", ""Cross-Sectional Studies"", ""Personal Satisfaction"", ""Adult"", ""Psychological Well-Being"", ""Women, Working"", ""Middle Aged"", ""Surveys and Questionnaires"", ""Employment"", ""Working Conditions""]",18572,42545246,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545246/,Women's Work and its Effects on Personal Wellbeing and Satisfaction with Life: A Cross-Sectional Comparative Study,117,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"To compare the diagnostic performance of two anterior segment optical coherence tomography devices, REVO FC130 and REVO HR, in patients with Fuchs endothelial corneal dystrophy (FECD). This prospective cross-sectional study included 33 patients with FECD. Each patient was imaged with both devices. Eleven corneal features were graded independently by two evaluators. A third grader resolved disagreements. Agreement between graders and between devices was quantified by calculating the proportion of concordant assessments, including agreement for both detected and non-detected features, with corresponding 95% confidence intervals. REVO HR provided better visualization of key corneal structures, including Descemet's membrane, Bowman's layer, and hyperreflective basal changes. Hyperreflective basal features were detected 11 times more often with REVO HR. Bowman's layer was identified 2.06 times more frequently with REVO HR compared to REVO FC130. Interoperator agreement was high for REVO HR (PropOverall ≥ 0.97 in 10 of 11 features). FC130 showed lower and more variable agreement, especially in low-contrast regions. Interdevice comparisons indicated systematic differences in detection capability. REVO HR showed higher sensitivity and reproducibility in detecting corneal microstructural changes in FECD. Improved image resolution allows better identification of subtle abnormalities, which may support more accurate disease staging and better timing of surgical intervention. For follow-up, the same OCT device should be used consistently. This study demonstrates that improved OCT resolution enhances detection of corneal microstructural abnormalities in Fuchs endothelial corneal dystrophy, improving diagnostic precision, disease staging, and clinical decision-making in routine clinical practice.","[""Journal Article"", ""Comparative Study""]","[""Szkodny D"", ""Wylegala A"", ""Potrawa P"", ""Wylegala E""]",10.1167/tvst.15.8.1,Szkodny D,Translational vision science & technology,2164-2591,8,Transl Vis Sci Technol,eng,Wylegala E,"[""Humans"", ""Tomography, Optical Coherence"", ""Fuchs' Endothelial Dystrophy"", ""Cross-Sectional Studies"", ""Female"", ""Prospective Studies"", ""Male"", ""Aged"", ""Middle Aged"", ""Reproducibility of Results"", ""Cornea""]",1,42545073,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545073/,Enhancing Diagnostic Precision in Fuchs Dystrophy: Comparative Evaluation of REVO HR and FC130 OCT Systems,15,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"Systematic intra-saccadic displacements of the saccade target object induce oculomotor learning. This type of manipulation remains undetected because of saccadic suppression of displacement. The subtle intra-saccadic manipulation causes the target object to appear at a retinal position that is inconsistent with the computed displacement of visual space during the saccade, leading to the computation of a postdicted motor error and corresponding adaptive changes to the saccade amplitude and the perceived location of objects in space. Adaptive changes to the saccade amplitude or direction have also been observed following obvious intra-saccadic manipulations, but very little is known about the characteristics of this learning process or its underlying mechanisms. The current study therefore compares oculomotor learning in response to subtle and obvious changes of the stimulus display. By measuring their effect on object localization and saccade gain, we were able to show that two different kinds of sensory error can induce oculomotor learning: a global spatial error and a local feature error. While experiencing the former leads to the typical adaptation-induced shift in perceived object location, experiencing the latter does not. On top of that, we demonstrate that adaptive adjustments to the oculomotor behavior do not necessarily rely on those sensory errors. Instead, the overt oculomotor behavior minimizes a task error.","[""Journal Article"", ""Comparative Study""]","[""Heins F"", ""Lappe M""]",10.1167/jov.26.8.3,Heins F,Journal of vision,1534-7362,8,J Vis,eng,Lappe M,"[""Humans"", ""Saccades"", ""Photic Stimulation"", ""Space Perception"", ""Learning"", ""Adaptation, Physiological"", ""Male"", ""Adult""]",3,42545065,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545065/,Global spatial errors and local feature errors drive oculomotor learning,26,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"Continuous glucose monitoring (CGM) is central to diabetes care, but explaining CGM patterns consistently and empathetically remains time-intensive in clinical practice. Large language model (LLM)-based systems may support patient-facing interpretation of CGM data, but evidence remains limited for retrieval-grounded tools evaluated against clinician-authored responses in counseling scenarios. The system was intended for CGM interpretation and communication support rather than autonomous therapeutic decision-making. This study aimed to evaluate whether a retrieval-grounded LLM-based conversational agent (CA) could support patient understanding of CGM data and preparation for diabetes consultations by generating responses to questions arising during CGM-informed diabetes counseling, with quality comparable to clinician-authored responses. We developed a scaffolded LLM-based CA for CGM interpretation and diabetes counseling support. The system was designed to provide plain-language explanations of CGM patterns and responses to diabetes management questions while avoiding directive or individualized medical advice, such as recommending medication initiation, dose adjustment, or regimen changes. Around 12 CGM-informed cases, each comprising a deidentified CGM trace, a synthetic patient vignette, and accompanying CGM visual materials, were constructed from using available clinical datasets. Between October 2025 and February 2026, 6 senior UK diabetes clinicians each reviewed 2 assigned cases and answered 24 questions (12 per case). In a source-masked multirater evaluation, each CA-generated and clinician-authored response was independently rated by 3 clinicians on 6 quality dimensions, including clinical accuracy, guideline adherence, actionability, personalization, communication clarity, and empathy. Safety flags and perceived source labels were also recorded. The primary analysis used linear mixed effects models with random intercepts for case and rater. A total of 288 unique responses (144 CA and 144 clinician responses) were evaluated, generating 864 ratings. CA-generated responses received higher quality scores than clinician-authored responses under controlled vignette-based conditions, with mean scores of 4.37 (SD 0.57) versus 3.58 (SD 0.90) and an estimated mean difference of 0.782 points on a 5-point scale (95% CI 0.692-0.872; P<.001). This pattern was observed across all 6 categories of patient questions. The largest estimated differences were for empathy (mean difference 1.062, 95% CI 0.948-1.177) and actionability (0.992, 95% CI 0.877-1.106). Safety flag distributions were similar between CA and clinician responses, with major concerns rare in both groups (n=3, 0.7% each). Although CA responses were longer, additional analyses adjusting for word count did not indicate that response length explained the overall quality difference. Scaffolded LLM-based systems may have value as adjunct tools for CGM review, patient education, and preconsultation preparation by supporting standardized explanatory tasks. However, these findings should be interpreted in light of the vignette-based design, restricted datasets, and a small clinician panel, and they do not establish suitability for autonomous therapeutic decision-making, medication adjustment, or unsupervised real-world use. Prospective validation in clinical workflows is needed before implementation.","[""Journal Article"", ""Comparative Study""]","[""Guo Z"", ""Lai A"", ""Korakas E"", ""Vagenas A"", ""Ahamed I"", ""Albor C"", ""Zhang H"", ""Healy J"", ""Li K""]",10.2196/98519,Guo Z,Journal of medical Internet research,1438-8871,,J Med Internet Res,eng,Li K,"[""Humans"", ""Large Language Models"", ""Continuous Glucose Monitoring"", ""Diabetes Mellitus"", ""Counseling""]",e98519,42544991,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42544991/,Retrieval-Augmented Large Language Model Counseling for Continuous Glucose Monitoring in Diabetes: Source-Masked Multirater Comparative Evaluation,28,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"This study compared radiographic spinopelvic alignment parameters and clinical outcomes after multisegment posterior lumbar interbody fusion (PLIF) with different degrees of sagittal correction in multilevel degenerative lumbar spine disease. We retrospectively reviewed adults who underwent three-segment PLIF (L2-L5 or L3-S1) between January 2020 and August 2021. Patients were stratified post hoc by achieved change in fused-segment lordosis (ΔSL) from preoperative to early postoperative radiographs (ΔSL ≤5° vs >5°). Spinopelvic parameters (SL, lumbar lordosis [LL], pelvic tilt [PT], sacral slope [SS], pelvic incidence [PI], PI-LL) and patient-reported outcomes (Visual Analog Scale [VAS], Oswestry Disability Index [ODI]) were assessed preoperatively and at follow-up (≥2 years). A total of 157 patients were included (Group A, n = 85; Group B, n = 72) with comparable baseline parameters. At 1 month and 1 year, SL was higher in Group B. At final follow-up, Group B showed more favorable alignment (higher SL/LL and lower PT/PI-LL) and better VAS/ODI than Group A (all p < 0.05). Postoperative complications were similar, except for a higher ileus rate in Group B (p = 0.024). A larger achieved ΔSL was associated with improved mid-to long-term spinopelvic alignment parameters and better final follow-up patient-reported outcomes. This potential benefit may occur at the expense of worse early postoperative symptoms; prospective studies with predefined correction targets are warranted.","[""Journal Article"", ""Comparative Study""]","[""Wang C"", ""Sun H"", ""Fang T"", ""Liu H""]",10.1080/08941939.2026.2696123,Wang C,Journal of investigative surgery : the official journal of the Academy of Surgical Research,0894-1939,1,J Invest Surg,eng,Liu H,"[""Humans"", ""Retrospective Studies"", ""Spinal Fusion"", ""Female"", ""Lumbar Vertebrae"", ""Lordosis"", ""Male"", ""Middle Aged"", ""Treatment Outcome"", ""Aged"", ""Follow-Up Studies"", ""Radiography"", ""Patient Reported Outcome Measures"", ""Time Factors"", ""Postoperative Complications""]",2696123,42544946,,2026 Dec,2026,https://pubmed.ncbi.nlm.nih.gov/42544946/,A Retrospective Comparative Study of Early and Mid-to Long-Term Clinical Efficacy and Spinopelvic Sagittal Alignment After Multisegment PLIF with Different Degrees of Sagittal Correction,39,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"This study addresses the need for an examination of the criterion validity of a highly popular self-report instrument which is used to gain a quick first impression of personality dysfunction: the Level of Personality Functioning Scale-Brief Form 2.0 (LPFS-BF 2.0). To this end, the relationship between LPFS-BF 2.0 scores and SCID-5-AMPD-I scores rated by trained clinicians was investigated in a clinical Norwegian sample (N = 155). Moreover, we investigated the relationship between the Norwegian version of the LPFS-BF 2.0 and other self-report instruments (the WSAS, GAD-7, and PHQ-9). Correlations, a linear regression model, as well as sensitivity and specificity for cut-off values proposed in the literature, were estimated. The results of the linear regression analysis with SCID-5-AMPD-I scores as the dependent variable, showed a strong and significant relationship between LPFS-BF 2.0 scores and SCID-5-AMPD-I scores, also when controlling for other variables. The LPFS-BF 2.0 showed moderate to high correlations with all other instruments. The sensitivity values for cut-off scores suggested in the literature for the LPFS-BF 2.0 were too low. In sum, we found support for the concurrent and criterion validity of the LPFS-BF 2.0. Additionally, we tentatively suggest that the cut-off values currently in use may need to be lowered.","[""Journal Article"", ""Comparative Study""]","[""Paap MCS"", ""Germans Selvik S"", ""Buer Christensen T"", ""Nysæter TE"", ""Eikenaes I"", ""Hummelen B""]",10.1002/pmh.70093,Paap MCS,Personality and mental health,1932-8621,3,Personal Ment Health,eng,Hummelen B,"[""Humans"", ""Female"", ""Male"", ""Personality Disorders"", ""Self Report"", ""Adult"", ""Norway"", ""Middle Aged"", ""Psychometrics"", ""Interview, Psychological"", ""Reproducibility of Results"", ""Young Adult"", ""Sensitivity and Specificity"", ""Adolescent"", ""Psychiatric Status Rating Scales"", ""Aged""]",e70093,42544898,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544898/,Comparison of Self-Report and Structured Clinical Interview Scores for the Assessment of the Level of Personality Functioning Scale,20,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"Obese parturients are at increased risk of spinal anesthesia-induced hypotension during cesarean delivery, but optimal prophylactic norepinephrine dosing remains unclear. In this randomized, double-blind, dose-response study, 200 parturients undergoing elective cesarean delivery were stratified into obese (BMI ≥30 kg/m²) and normal weight (BMI 18.5-24.9 kg/m²) groups. Within each group, patients received norepinephrine infusion at 0.02-0.06 µg·kg⁻¹·min⁻¹. Standardized combined spinal-epidural anesthesia with 16 mg hyperbaric ropivacaine was used, and infusion was started immediately after spinal injection. Hypotension was defined as SBP <90 mmHg or >20% decrease from baseline, and success as absence of hypotension. Probit regression was used to estimate ED50 and ED95. ED50 and ED95 were 0.022 (95% CI 0.015-0.029) and 0.051 (0.041-0.061) µg·kg⁻¹·min⁻¹ in normal weight, compared with 0.036 (0.029-0.043) and 0.080 (0.058-0.102) µg·kg⁻¹·min⁻¹ in obese parturients. The relative potency ratio was 1.597 (95% CI 1.007-2.187; P=0.013). Neonatal outcomes and maternal adverse effects were comparable. Obese parturients require higher weight-adjusted norepinephrine infusion rates to prevent spinal anesthesia-induced hypotension during cesarean delivery.","[""Journal Article"", ""Randomized Controlled Trial"", ""Comparative Study""]","[""Chen X"", ""Gao Z"", ""Jiao C"", ""Wang J"", ""Sun L"", ""Qian X"", ""Liu S""]",10.29063/ajrh2026/v30i14.8,Chen X,African journal of reproductive health,1118-4841,14,Afr J Reprod Health,eng,Liu S,"[""Humans"", ""Female"", ""Cesarean Section"", ""Pregnancy"", ""Anesthesia, Spinal"", ""Norepinephrine"", ""Adult"", ""Hypotension"", ""Double-Blind Method"", ""Obesity"", ""Dose-Response Relationship, Drug"", ""Vasoconstrictor Agents"", ""Anesthesia, Obstetrical""]",,42544724,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42544724/,Dose-response relationship of prophylactic norepinephrine infusion for prevention of spinal anesthesia-induced hypotension during caesarean delivery: A comparative study of normal weight and obese parturients,30,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"To compare the effects of high-intensity focused ultrasound (HIFU) ablation and laparoscopic myomectomy on ovarian function and endometrial receptivity in patients with uterine fibroids. In this prospective, non-randomized cohort study, 60 patients with uterine fibroids were either treated with HIFU (n = 30) or laparoscopic myomectomy (n = 30) based on patient preference after standardized counseling. Ovarian function and endometrial receptivity were evaluated preoperatively and at 1, 3, and 6 months post‑treatment. Ovarian reserve was assessed using anti‑Müllerian hormone (AMH), sex hormone levels of luteinizing hormone (LH), follicle‑stimulating hormone (FSH), estradiol (E2), and antral follicle count (AFC). Endometrial receptivity was evaluated using endometrial thickness and vascular indices, including endometrial artery resistance index (RI), pulsatility index (PI), and the systolic/diastolic velocity ratio (S/D). Regarding endometrial receptivity, the HIFU group exhibited significantly greater endometrial thickness at the 1‑month follow‑up compared to the laparoscopic group (mean difference: 1.5 mm, 95% CI: 0.6 to 2.4 mm; Cohen's d = 0.72, p < 0.05). Both groups showed a reduction in PI after treatment, though the change was not statistically significant. RI and S/D ratios were comparable between the two groups at any time point (p > 0.05). Both HIFU and laparoscopic myomectomy preserved ovarian function in patients with uterine fibroids. HIFU was associated with faster short-term endometrial recovery at 1 month post-treatment, but no differences in ovarian function or other receptivity markers were observed between the two groups of patients. Randomized trials with pregnancy outcomes are needed before clinical recommendations can be made.","[""Journal Article"", ""Comparative Study""]","[""Huang R"", ""Wang Y"", ""Song Y"", ""Duan X"", ""Wu S"", ""Zhang X"", ""Wu S"", ""Guo H""]",10.1080/02656736.2026.2703617,Huang R,"International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group",0265-6736,1,Int J Hyperthermia,eng,Guo H,"[""Humans"", ""Female"", ""Leiomyoma"", ""Adult"", ""Laparoscopy"", ""Uterine Myomectomy"", ""High-Intensity Focused Ultrasound Ablation"", ""Endometrium"", ""Ovary"", ""Prospective Studies""]",2703617,42544600,,2026 Dec,2026,https://pubmed.ncbi.nlm.nih.gov/42544600/,Comparative study on the effects of high-intensity focused ultrasound (HIFU) and laparoscopic myomectomy on ovarian function and endometrial receptivity in patients with uterine fibroids,43,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"Cyst enucleation is a common procedure performed in oral and maxillofacial surgery to remove cystic lesions. Conventional surgical techniques have traditionally been used for this purpose. However, piezosurgery, a relatively new technology, has gained popularity in recent years. This systematic review aims to compare the efficacy, safety and clinical outcomes of piezosurgery and conventional surgery for cyst enucleation.A comprehensive literature search was conducted using electronic databases, including PubMed, EBSCOhost, Scopus, ProQuest, and ScienceDirect. Studies published from inception up to May 2023 were included. Randomized controlled trials (RCTs) comparing piezosurgery with conventional surgery for cyst enucleation were considered. The primary outcomes included surgical duration, intraoperative bleeding, postoperative complications, and healing outcomes. Secondary outcomes comprised postoperative pain, edema and recurrence. The quality of the included studies was assessed using the revised Cochrane risk of bias tool for RCTs (RoB 2.0).The initial search identified 160 relevant articles, of which 6 studies met the inclusion criteria. Piezosurgery was shown to have a longer operation time, but higher visibility and a similar ease of operation. Clinical outcomes showed less postoperative pain, swelling and trismus in the piezosurgery group.This systematic review suggests that piezosurgery is a promising alternative to conventional surgery for cyst enucleation, offering advantages in terms of reduced surgical duration, intraoperative bleeding, postoperative pain, and edema, as well as proven not to cause any recurrence. However, further well-designed RCTs with larger sample sizes are warranted to validate these findings and evaluate long-term outcomes.","[""Journal Article"", ""Systematic Review"", ""Comparative Study"", ""Review""]","[""Ghassani UP"", ""Lintong LA"", ""Paramita S"", ""Sulistyani LD"", ""Latief MA""]",10.17219/dmp/171845,Ghassani UP,Dental and medical problems,1644-387X,3,Dent Med Probl,eng,Latief MA,"[""Humans"", ""Piezosurgery"", ""Treatment Outcome"", ""Cysts"", ""Postoperative Complications""]",805-812,42544597,,2026 May-Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42544597/,Clinical outcomes and efficacy of piezosurgery compared to conventional surgery for cyst enucleation: A systematic review,63,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"BackgroundSplit-thickness skin grafting (STSG) is commonly used for traumatic soft-tissue defects; however, graft instability and suboptimal scar outcomes remain concerns. Negative pressure wound therapy (NPWT) has emerged as an alternative fixation method to the conventional tie-over dressing. This study compared clinical outcomes between NPWT and tie-over fixation and evaluated whether defect size influenced their comparative effectiveness.MethodsSeventy-five patients who underwent STSG for traumatic soft-tissue defects between March 2020 and February 2025 were retrospectively reviewed. Patients were divided according to fixation method into NPWT (n = 38) and tie-over dressing groups (n = 37). Outcomes included operative time, complete graft-take rate, postoperative complications, and Vancouver Scar Scale (VSS) scores at 2 weeks and 6 months. Subgroup analysis was performed according to defect size (<100 cm2 vs ≥100 cm2).ResultsAt 2 weeks postoperatively, the NPWT group demonstrated significantly lower VSS scores for vascularity, pliability, and height compared with the tie-over group (p < 0.05). At 6 months, significantly lower pliability scores were observed in the NPWT group; in the ≥100 cm2 subgroup, NPWT also showed a significantly lower height score (p < 0.05). Operative time was significantly shorter in the NPWT group than in the tie-over group (p < 0.001). Complete graft-take rates were comparable overall; however, in defects ≥100 cm2, NPWT achieved a significantly higher complete graft-take rate (p = 0.048).ConclusionsNPWT was associated with shorter operative time and early scar-related outcomes, particularly in larger defects. However, given the retrospective design and limited subgroup size, these findings should be interpreted cautiously, and NPWT may be considered as a useful option in selected mechanically demanding cases rather than a universal fixation method.","[""Journal Article"", ""Comparative Study""]","[""Jang HJ"", ""Lee SK""]",10.1177/10225536261475728,Jang HJ,Journal of orthopaedic surgery (Hong Kong),1022-5536,2,J Orthop Surg (Hong Kong),eng,Lee SK,"[""Humans"", ""Negative-Pressure Wound Therapy"", ""Retrospective Studies"", ""Skin Transplantation"", ""Female"", ""Male"", ""Adult"", ""Middle Aged"", ""Bandages"", ""Soft Tissue Injuries"", ""Treatment Outcome""]",10225536261475728,42544524,,2026 May-Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544524/,Negative pressure wound therapy versus conventional tie-over dressing for split-thickness skin graft fixation: A retrospective comparative study with defect size-based subgroup analysis,34,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"Meniscal tears are a common cause of knee morbidity and a frequent indication for arthroscopy. Whether clinical examination, magnetic resonance imaging (MRI), or both should be the first-line diagnostic test remains contested. We searched PubMed, CINAHL Complete, Medline, and Web of Science for paired-design studies in adults in which every patient underwent both composite clinical examination and MRI, with arthroscopy as the reference standard. Ten studies (1643 knees) met our inclusion criteria. Risk of bias was assessed with QUADAS-2; estimates were pooled with a random-effects model. For medial meniscal tears, MRI achieved pooled sensitivity of 90% and specificity of 91%; composite clinical examination achieved 85% sensitivity and 95% specificity. For lateral meniscal tears, MRI yielded 81% sensitivity and 82% specificity; composite clinical examination yielded 75% sensitivity and 93% specificity. Whether composite clinical examination is interchangeable with MRI as a first-line test; reduced MRI specificity in degenerative meniscal lesions and osteoarthritic knees; and the operator-dependence of clinical examination and the lack of a standardized composite-examination protocol. Composite clinical examination by an experienced clinician retains diagnostic value alongside MRI. Paired-design synthesis with arthroscopic verification gives less biased estimates of comparative accuracy than unpaired designs. Standardization of composite clinical examination protocols; consistent reporting of examiner experience; stratification of MRI accuracy by field strength and pulse sequence; and cost-effectiveness evaluation of clinical-examination-first diagnostic pathways.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Comparative Study""]","[""Rana R"", ""Mehan N"", ""Hassan R"", ""Gohil Y"", ""Tyagi A"", ""Maffulli N""]",10.1093/bmb/ldag023,Rana R,British medical bulletin,0007-1420,1,Br Med Bull,eng,Maffulli N,"[""Humans"", ""Magnetic Resonance Imaging"", ""Tibial Meniscus Injuries"", ""Physical Examination"", ""Sensitivity and Specificity"", ""Arthroscopy"", ""Knee Injuries"", ""Menisci, Tibial""]",,42544509,,2026 Jul 3,2026,https://pubmed.ncbi.nlm.nih.gov/42544509/,Diagnostic accuracy of clinical examination versus MRI for meniscal tears: a systematic review and meta-analysis,159,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"To evaluate the impact of blue-filtering intraocular lenses (BFIOLs) on retinal oxidative stress by comparing 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the macular retina and submacular retinal pigment epithelium (RPE) of donor eyes with BFIOLs and non-BFIOLs. Cross-sectional laboratory study using postmortem human donor eyes. Fifty-eight eyes from 39 donors were categorized as BFIOL (n = 16), non-BFIOL (n = 24), or phakic (n = 18). Macular retina and submacular RPE were dissected, genomic DNA extracted, and 8-OHdG quantified using ELISA. 8-OHdG levels were compared across lens groups, and associations with age and sex were examined. Submacular RPE had higher 8-OHdG levels than the macular retina (0.95 vs 0.44 ng/mL; P < 0.0001). No significant differences in 8-OHdG were observed between BFIOL and non-BFIOL eyes in either tissue (all P ≥ 0.09). Age was not associated with 8-OHdG, whereas male donors showed higher RPE 8-OHdG levels than female donors (P = 0.03). Macular retinal and RPE 8-OHdG levels did not differ significantly by IOL type. These biochemical observations, considered alongside existing clinical data, suggest that any retinal protective effect of BFIOLs on oxidative DNA damage is likely to be modest.","[""Journal Article"", ""Comparative Study""]","[""Sevugamurthi K"", ""Sivashanmugam P"", ""Jaju S"", ""Janani PS"", ""Sakthivel V"", ""Kumar N"", ""Elamurugan V"", ""Pandian J"", ""Amarakoon S"", ""Berendschot TTJM"", ""Narendran S""]",10.4103/IJO.IJO_3121_25,Sevugamurthi K,Indian journal of ophthalmology,0301-4738,Suppl 2,Indian J Ophthalmol,eng,Narendran S,"[""Humans"", ""Oxidative Stress"", ""Male"", ""Female"", ""8-Hydroxy-2'-Deoxyguanosine"", ""Cross-Sectional Studies"", ""Tissue Donors"", ""Middle Aged"", ""Lenses, Intraocular"", ""Aged"", ""Retinal Pigment Epithelium"", ""Enzyme-Linked Immunosorbent Assay"", ""Blue Light"", ""Macula Lutea"", ""Deoxyguanosine"", ""Adult"", ""Biomarkers""]",S215-S220,42544414,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42544414/,Evaluating the impact of blue-filtering intraocular lenses on macular oxidative stress: A comparative analysis of 8-hydroxy-2'-deoxyguanosine levels in the retinal tissue of donor eyes,74,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"In the AQuIRE trial, most cases (83.6%) did not involve transbronchial needle aspiration (TBNA), often underutilized due to challenges in accessing peripheral pulmonary lesions (PPLs). Advances in robotic bronchoscopy with shape-sensing technology (ssRAB) have mitigated these challenges, but the optimal number of needle and cryoprobe passes for reliable diagnosis remains undefined. This retrospective study compares the diagnostic yield (DY) of TBNA and transbronchial cryoprobe biopsy (TBCB) and their adequacy for molecular testing in PPLs. We performed a retrospective analysis of 166 patients who underwent ssRAB with both TBNA and TBCB from May to August 2024. Fisher exact tests and McNemar χ2 tests were used to compare prevalence differences in DY and molecular testing adequacy between discordant cases. Odds ratios (OR) and 95% CIs of associations between the number of passes and diagnostic yield and rates of obtaining adequate samples for molecular testing were obtained using generalized linear mixed models (GLMMs) with a logit link. TBCB demonstrated a higher diagnostic rate than TBNA (89% vs. 80%, OR=2.04, 95% CI=1.06-4.03; P=0.032), as well as better rates of obtaining samples adequate for molecular testing (60% vs. 20%, OR=5.94, 95% CI=2.31-16.38, P<0.001). TBCB provided diagnostic yields in 55% (χ2=9.33, P=0.002) of cases where TBNA failed to provide a diagnosis and was able to obtain adequate samples for molecular testing in 42% (χ2=15.06, P<0.001) of cases where TBNA was unable to. TBCB suggests a higher diagnostic yield and higher cellular adequacy for molecular testing compared with TBNA, underscoring its potential value as a reliable and versatile diagnostic tool in PPLs.","[""Journal Article"", ""Comparative Study""]","[""Odeh T"", ""Hegde V"", ""Chen M"", ""Haworth S"", ""Postigo M""]",10.1097/LBR.0000000000001088,Odeh T,Journal of bronchology & interventional pulmonology,1948-8270,4,J Bronchology Interv Pulmonol,eng,Postigo M,"[""Humans"", ""Bronchoscopy"", ""Retrospective Studies"", ""Female"", ""Male"", ""Middle Aged"", ""Aged"", ""Robotic Surgical Procedures"", ""Biopsy, Needle"", ""Lung Neoplasms""]",,42544013,,2026 Oct 1,2026,https://pubmed.ncbi.nlm.nih.gov/42544013/,Diagnostic Yield and Molecular Testing Adequacy of Transbronchial Cryoprobe Biopsy Versus Needle Aspiration in Robotic Bronchoscopy,33,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"Depression and insomnia are common yet under-recognized comorbidities in end-stage kidney disease (ESKD) patients on dialysis. Comparative data on their prevalence between hemodialysis (HD) and peritoneal dialysis (PD) are limited. To compare the prevalence and severity of depression and insomnia in patients undergoing HD and PD and identify clinical and biochemical correlates. A multicenter, cross-sectional study was conducted across armed forces hospitals in Northern India from November 2024 to January 2025. Adult ESKD patients on HD or PD were assessed using the Patient Health Questionnaire-9 (PHQ-9) for depression. Insomnia was assessed using a response to a battery of questions. Demographic, clinical, and laboratory data were analyzed. Of 188 patients screened (HD 105, PD 83), 51 HD (48.6%) and 37 PD (44.6%) patients had PHQ-9 scores ≥5, indicating depression. Most had mild depression (HD 25.7%; PD 22.6%). Moderately severe depression was present in a small number, with no difference between the dialysis modalities. Insomnia prevalence was comparable (HD 24.7%; PD 22.6%). Severe depression was associated with lower hemoglobin and albumin, especially in PD (albumin: 2.38 vs 3.10 gm/dL, p = 0.03). Depression and insomnia are highly prevalent but underrecognized in dialysis patients. Dialysis modality did not affect the prevalence of depression or insomnia. Lower hemoglobin and albumin correlate with severe depressive symptoms.","[""Journal Article"", ""Comparative Study"", ""Multicenter Study""]","[""Singh JI"", ""Sangha SS"", ""Datt B"", ""Kumar S"", ""Batta G"", ""Akal RS"", ""Ghosh I"", ""Srivastava S"", ""Dogra PM"", ""Pannu KK""]",10.59556/japi.74.1518,Singh JI,The Journal of the Association of Physicians of India,0004-5772,6,J Assoc Physicians India,eng,Pannu KK,"[""Humans"", ""Sleep Initiation and Maintenance Disorders"", ""Female"", ""Cross-Sectional Studies"", ""Male"", ""Kidney Failure, Chronic"", ""Middle Aged"", ""Prevalence"", ""Depression"", ""Renal Dialysis"", ""India"", ""Adult"", ""Peritoneal Dialysis, Continuous Ambulatory"", ""Severity of Illness Index""]",46-49,42543932,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543932/,A Comparative Study of Depression and Insomnia among Patients on Continuous Ambulatory Peritoneal Dialysis versus Hemodialysis,74,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"Comparative randomized evidence specifically evaluating totally extraperitoneal (TEP) and Lichtenstein repair is limited. This study compared sex-related and general health-related quality of life following these two techniques. In this prospective randomized controlled trial, sexually active adult men with primary uncomplicated inguinal hernias were randomized to TEP or open Lichtenstein repair. The primary endpoint was pain during sexual activity at 1 year, measured using the Sexual Inguinal Hernia Questionnaire (SexIHQ). Secondary outcomes included additional SexIHQ domains and health-related quality of life measured by the 36-Item Short Form Health Survey (SF-36). A total of 105 patients were analyzed, including 50 undergoing TEP and 55 undergoing open repair. Baseline demographic, clinical, SF-36, and SexIHQ measures were comparable between groups. At 1 year, pain during sexual activity was reported less frequently after TEP than after open repair (16.0% vs. 43.6%; risk ratio 0.37, 95% CI 0.18-0.74; p = 0.003). Among patients reporting pain during sexual activity, the degree of impairment in sexual activity did not differ significantly between groups. SF-36 scores at 1 year were significantly higher after TEP across all measured domains. TEP repair was associated with a lower rate of pain during sexual activity at 1 year compared with Lichtenstein repair. However, other SexIHQ domains were not significantly different. These findings suggest a possible benefit of avoiding anterior inguinal canal dissection, but do not establish broad superiority of TEP for overall sexual function.","[""Journal Article"", ""Randomized Controlled Trial"", ""Comparative Study""]","[""Maurya S"", ""Silodia A"", ""Kothiya P"", ""Yadav SK"", ""Sharma D""]",10.1111/ases.70365,Maurya S,Asian journal of endoscopic surgery,1758-5902,1,Asian J Endosc Surg,eng,Sharma D,"[""Humans"", ""Hernia, Inguinal"", ""Quality of Life"", ""Male"", ""Prospective Studies"", ""Middle Aged"", ""Herniorrhaphy"", ""Adult"", ""Postoperative Pain"", ""Treatment Outcome"", ""Sexual Behavior"", ""Aged"", ""Surveys and Questionnaires""]",e70365,42543880,,2026 Jan-Dec,2026,https://pubmed.ncbi.nlm.nih.gov/42543880/,Sex-Related Quality of Life After Totally Extraperitoneal Versus Lichtenstein Inguinal Hernia Repair: A Randomized Controlled Trial,19,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"Robotic right hemicolectomy has been widely adopted, but the impact of extraction-site location on postoperative pain in single-port (SP) surgery remains unclear. We aimed to compare short-term outcomes between SP and multiport robotic surgery and to evaluate postoperative wound pain according to extraction-site location. This retrospective single-center study included 49 consecutive patients who underwent robotic right hemicolectomy (January 2024-December 2025): 25 in the SP group and 24 in the Xi group. Postoperative pain was assessed using the cumulative pain score (sum of daily maximum NRS values, POD1-POD7). Pain outcomes were compared among SP_P (Pfannenstiel, n = 13), SP_Umb (umbilical, n = 12), and Xi_P (Pfannenstiel, n = 22). Perioperative and oncological outcomes were comparable between the groups. The SP group had significantly shorter operative time (244 vs. 309 min, p = 0.0013) and console time (167 vs. 239 min, p = 0.0014). Postoperative pain differed significantly among the three subgroups (p = 0.0049). Pairwise comparisons showed significantly lower pain in SP_P than in SP_Umb (p = 0.0062), with no significant difference for the other two comparisons. The difference between SP_P and SP_Umb remained significant after adjusting for anastomotic technique and surgical procedure in multiple regression analysis. SP-assisted right hemicolectomy was safe, with short-term outcomes comparable to the Xi platform. These findings suggest that postoperative pain following robotic right hemicolectomy may be influenced not only by the number of abdominal ports but also by the location of the extraction incision.","[""Journal Article"", ""Comparative Study""]","[""Nishikawa Y"", ""Mori T"", ""Hara M"", ""Kageyama Y"", ""Bando Y"", ""Jikihara S"", ""Nishigori T"", ""Hata K""]",10.1111/ases.70364,Nishikawa Y,Asian journal of endoscopic surgery,1758-5902,1,Asian J Endosc Surg,eng,Hata K,"[""Humans"", ""Colectomy"", ""Robotic Surgical Procedures"", ""Retrospective Studies"", ""Postoperative Pain"", ""Female"", ""Male"", ""Middle Aged"", ""Aged"", ""Treatment Outcome"", ""Operative Time"", ""Colonic Neoplasms"", ""Pain Measurement""]",e70364,42543847,,2026 Jan-Dec,2026,https://pubmed.ncbi.nlm.nih.gov/42543847/,Single-Port Versus Multiport Robotic Right Colectomy: Short-Term Outcomes and Impact of Extraction-Site Location on Postoperative Pain,19,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"Objective To compare research hotspots and development trends regarding freezing of gait in Parkinson's disease between Chinese and English articles,thus providing reference for related studies in China. Methods The articles about freezing of gait in Parkinson's disease that were published from 2001 to 2025 was retrieved from the China National Knowledge Infrastructure,Wanfang Data,VIP,and Web of Science Core Collection.Visual analyses were conducted on the distribution of countries,authors,institutions,and keywords. Results A total of 177 Chinese articles and 1 095 English articles were included.The global annual number of published articles showed an overall upward trend with fluctuations.The articles in Chinese maintained steady growth while those in English slightly declined over the past three years.The United States led in the number of published articles,followed by China and Italy.The authors and institutions of Chinese articles exhibited greater independence than those of English articles.Current research hotspots on freezing of gait in Parkinson's disease focus on pathogenesis,assessment methods,and treatment strategies.Chinese articles emphasize clinical interventions,while English articles prioritize mechanism exploration and emerging physical therapies. Conclusions The research on freezing of gait in Parkinson's disease remains active,though differences exist in research focus between Chinese and English articles.Compared with Chinese articles,English articles reported early on freezing of gait in Parkinson's disease.In the future,China should deepen international exchanges and cooperation to actively draw on advanced findings and experience and work jointly to achieve breakthrough progress in both research and clinical practice,ultimately improving patients' quality of life.","[""Journal Article"", ""Comparative Study""]","[""Liu J"", ""Wang QQ"", ""Chen MY"", ""Zhang XY"", ""Wang Q"", ""Weng H"", ""Chen JP"", ""Xu GH""]",10.3881/j.issn.1000-503X.16937,Liu J,Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae,1000-503X,3,Zhongguo Yi Xue Ke Xue Yuan Xue Bao,eng,Xu GH,"[""Parkinson Disease"", ""Humans"", ""Bibliometrics"", ""China"", ""Gait Disorders, Neurologic"", ""Gait"", ""East Asian People""]",498-509,42543832,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543832/,Comparative Bibliometric Analysis of Chinese and English Articles on Freezing of Gait in Parkinson's Disease,48,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"There is morphological overlap between nodular necrotizing fibroblastic sarcoma (NNFS) and myxoinflammatory fibroblastic sarcoma (MIFS). Whether they represent neoplasms within the same tumor spectrum remains unclear. We performed a comparative clinicopathological, molecular, and epigenetic study of these two tumors. We analyzed the clinicopathological features, immunophenotypes, and molecular profiles of three cases each of NNFS and MIFS. DNA methylation profiling was also performed. All three NNFS cases were located in the trunk, presenting as well-circumscribed subcutaneous nodules with central necrosis, whereas the three MIFS cases all arose in acral sites with an infiltrative or ill-defined growth pattern. Morphologically, both NNFS and MIFS were characterized by large polygonal to epithelioid cells with virocyte-like, ganglion cell-like, or Reed-Sternberg-like appearance. Unlike MIFS, NNFS did not exhibit prominent myxoid stroma or vacuolated pseudolipoblasts. On immunohistochemistry, NNFS cases uniformly showed focal positivity for pancytokeratin (AE1/AE3), whereas MIFS cases exhibited variable CD34 expression. Molecular analysis identified YAP1::MAML2 fusions in all three NNFS cases, while a BRAF rearrangement was detected in one of the three MIFS cases. DNA methylation profiling demonstrated that NNFS and MIFS cases clustered together forming a distinct group. Although NNFS and MIFS each harbor unique genetic alterations, our DNA methylation profiling demonstrates a potential relationship between these two morphologically similar entities.","[""Journal Article"", ""Comparative Study""]","[""Zhu P"", ""Han D"", ""Sun Y"", ""Bai Q"", ""Zhou X"", ""Wang J""]",10.1002/gcc.70158,Zhu P,"Genes, chromosomes & cancer",1045-2257,8,Genes Chromosomes Cancer,eng,Wang J,"[""Humans"", ""Fibrosarcoma"", ""Female"", ""DNA Methylation"", ""Male"", ""Epigenesis, Genetic"", ""Middle Aged"", ""Myxosarcoma"", ""Aged"", ""Adult""]",e70158,42543785,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42543785/,"Nodular Necrotizing Fibroblastic Sarcoma and Myxoinflammatory Fibroblastic Sarcoma: A Comparative Clinicopathological, Molecular, and Epigenetic Study",65,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"To compare the effects of hemodialysis (HD) and peritoneal dialysis (PD) on peripheral nervous system function and frailty in non-diabetic end-stage renal disease (ESRD) patients. This prospective, single-center, cross-sectional study consecutively enrolled 88 non-diabetic ESRD patients (HD: n = 45, PD: n = 43) receiving dialysis for ≥3 months at Bursa City Hospital between 1 May and 16 September 2025. All underwent neurological examination and nerve conduction studies. Frailty was assessed using the Fried Frailty Phenotype (FFP), classifying patients as robust (0), pre-frail (1-2) or frail (≥3). Multivariable linear regression identified independent correlates of frailty score. Median age was 57 (HD) versus 52 years (PD) (p = 0.077). HD patients had higher potassium (5.1 ± 0.7 vs 4.7 ± 0.6 mmol/L, p = 0.025) and ferritin (763 vs 406.5 ng/mL, p < 0.001) and a trend toward higher CRP (8.1 vs 3.2 mg/L, p = 0.075). PD patients showed better dialysis adequacy (Kt/V 1.9 vs 1.6, p < 0.001) and a trend toward higher sural sensory conduction velocity (54 vs 48 m/s, p = 0.052). Axonal polyneuropathy predominated (37.5%), without difference between modalities. Median FFP score was 1 in both groups (p = 0.705), but frailty-category distribution differed (frail: HD 20.0% vs PD 6.9%, p = 0.047). Univariately, CRP correlated with frailty in HD (rs = 0.31, p = 0.038); age (rs = 0.34, p = 0.041), hemoglobin (rs = 0.39, p = 0.014) and Kt/V (rs = -0.37, p = 0.027) correlated in PD. In multivariable regression, CRP remained an independent correlate (B = 0.017, 95% CI 0.001-0.033, p = 0.042). Although median FFP scores were similar, frailty distribution and its correlates differed by modality - inflammation in HD, age, and dialysis adequacy in PD. These hypothesis-generating findings warrant larger multicenter evaluation.","[""Journal Article"", ""Comparative Study""]","[""Usta M"", ""Şeker A"", ""Gönüllü S"", ""Hüzmeli C"", ""Ortaç H""]",10.1080/0886022X.2026.2702239,Usta M,Renal failure,0886-022X,1,Ren Fail,eng,Ortaç H,"[""Humans"", ""Female"", ""Male"", ""Peritoneal Dialysis"", ""Middle Aged"", ""Kidney Failure, Chronic"", ""Cross-Sectional Studies"", ""Renal Dialysis"", ""Prospective Studies"", ""Frailty"", ""Electromyography"", ""Nerve Conduction Studies"", ""Adult"", ""Aged"", ""Neural Conduction""]",2702239,42543753,,2026 Dec,2026,https://pubmed.ncbi.nlm.nih.gov/42543753/,Electromyographic findings and frailty in hemodialysis vs peritoneal dialysis patients,48,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"Bruton tyrosine kinase inhibitors are central to the treatment of relapsed or refractory mantle cell lymphoma, but cardiovascular and bleeding toxicities influence treatment selection. Ibrutinib has been associated with atrial fibrillation/flutter and other cardiovascular adverse events, whereas second-generation covalent BTK inhibitors were developed to improve kinase selectivity and tolerability. Mantle cell lymphoma-specific real-world comparative safety data across ibrutinib, acalabrutinib, and zanubrutinib remain limited. To compare cardiovascular and bleeding outcomes among patients with mantle cell lymphoma treated with ibrutinib, acalabrutinib, or zanubrutinib. We conducted a retrospective propensity score-matched TriNetX cohort study of patients with mantle cell lymphoma treated with ibrutinib, acalabrutinib, or zanubrutinib. Alternate BTK inhibitor exposure and prior recorded outcomes were excluded. Outcomes included newly recorded atrial fibrillation/flutter, heart failure, and gastrointestinal bleeding. Matching included demographics, comorbidities, cardiovascular risk factors, anthracycline exposure, and antithrombotic use. After matching, the 365-day cohorts included 738 patients per group for acalabrutinib versus ibrutinib, 522 per group for zanubrutinib versus ibrutinib, and 532 per group for acalabrutinib versus zanubrutinib. Newly recorded atrial fibrillation/flutter was lower with acalabrutinib than ibrutinib, 4.5% versus 12.0%, RR 0.371, HR 0.387, and with zanubrutinib than ibrutinib, 5.0% versus 12.3%, RR 0.408, HR 0.421. Atrial fibrillation/flutter rates were similar between acalabrutinib and zanubrutinib, 4.0% versus 5.7%, RR 0.704, HR 0.714. Heart failure did not differ statistically, and 180-day sensitivity analyses were consistent. Exploratory gastrointestinal bleeding was higher with ibrutinib than acalabrutinib, 4.3% versus 2.2%, and numerically higher with ibrutinib than zanubrutinib, 4.7% versus 3.3%; acalabrutinib-versus-zanubrutinib gastrointestinal bleeding output was unavailable. Ibrutinib was associated with a higher risk of atrial fibrillation/flutter than acalabrutinib or zanubrutinib. These findings may support individualized BTK inhibitor selection, particularly among patients with baseline cardiovascular risk.","[""Journal Article"", ""Comparative Study""]","[""Homeniuk A"", ""Sandhu A"", ""Abdalla L"", ""Atrash A""]",10.1002/cam4.72111,Homeniuk A,Cancer medicine,2045-7634,8,Cancer Med,eng,Atrash A,"[""Humans"", ""Adenine"", ""Piperidines"", ""Benzamides"", ""Lymphoma, Mantle-Cell"", ""Pyrazines"", ""Female"", ""Male"", ""Retrospective Studies"", ""Propensity Score"", ""Aged"", ""Hemorrhage"", ""Pyrimidines"", ""Pyrazoles"", ""Middle Aged"", ""Atrial Fibrillation"", ""Protein Kinase Inhibitors"", ""Cardiovascular Diseases""]",e72111,42543719,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42543719/,"Comparative Cardiovascular Safety and Exploratory Bleeding Outcomes of Ibrutinib, Acalabrutinib, and Zanubrutinib in Mantle Cell Lymphoma: A Propensity Score-Matched Real-World Analysis",15,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"Rectal prolapse (RP) and pelvic organ prolapse (POP) frequently coexist, yet are often evaluated and treated separately. This study aimed to compare patient-reported outcomes and cost-effectiveness of combined versus isolated robotic prolapse repair. We conducted a prospective multicentre cohort study across three tertiary pelvic floor centres. Women undergoing robotic rectal prolapse repair (rRP), robotic pelvic organ prolapse repair (rPOP) or combined robotic repair (rRP + rPOP) were included. Validated patient-reported outcome measures were collected at baseline and 12 months. Health utility was derived from EQ-5D-3L and used to calculate quality-adjusted life years (QALYs). A trial-based cost-effectiveness analysis was performed from the healthcare sector perspective. A theoretical cohort was modelled to examine staged versus combined repair in patients with multicompartment prolapse. Forty-seven patients were included (rRP n = 14, rPOP n = 16, rRP + rPOP n = 17). All groups demonstrated significant improvement in pelvic floor symptoms and quality of life at 12 months. Improvements across bowel, bladder and prolapse-related domains were greatest in the combined repair group. Health utility gains were observed in all cohorts. In patients with multicompartment prolapse, combined robotic repair was cost-effective, whereas staged procedures were associated with higher cumulative costs without proportional gains in QALYs. Within robotic prolapse surgery, combined rectal and pelvic organ prolapse repair provides the most comprehensive symptom improvement and represents a cost-effective strategy when both compartments are symptomatic. These findings support systematic evaluation for multicompartment prolapse and multidisciplinary surgical planning.","[""Journal Article"", ""Multicenter Study"", ""Comparative Study""]","[""Wallace SL"", ""Ogilvie JW Jr"", ""Bordeianou L"", ""Earley M"", ""Platte R"", ""Weinstein MM"", ""Sokol ER"", ""Enemchukwu EA"", ""Mishra K"", ""Gurland BH""]",10.1111/codi.70570,Wallace SL,Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland,1462-8910,8,Colorectal Dis,eng,Gurland BH,"[""Humans"", ""Female"", ""Pelvic Organ Prolapse"", ""Patient Reported Outcome Measures"", ""Prospective Studies"", ""Rectal Prolapse"", ""Cost-Benefit Analysis"", ""Robotic Surgical Procedures"", ""Aged"", ""Middle Aged"", ""Cost-Effectiveness Analysis"", ""Quality of Life"", ""Quality-Adjusted Life Years"", ""Treatment Outcome"", ""Colorectal Surgical Procedures""]",e70570,42543563,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42543563/,Cost-effectiveness and patient-reported outcomes of combined versus isolated robotic rectal and pelvic organ prolapse repair: A multicentre prospective cohort study,28,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"The genus Passiflora L. comprises approximately 650 species, and exhibits high diversity in the Neotropics, especially the subgenus Passiflora. Several species of this subgenus have an abundant repetitive fraction, consistent with their increased genome sizes. However, the repetitive DNA fraction of Passiflora foetida (n = 10), sister to the other species of the subgenus (n = 9) and the species with the smallest genome, has not yet been described in detail. In addition, this species comprises a complex of morphological varieties with a wide geographical distribution. The aim of this study was to characterize its repeatome variability in comparison to other species in section Dysosmia and other sections in the same subgenus, and to investigate whether it may reflect the high variability reported for this species complex. The results showed that P. foetida has a proportion of repetitive DNA fraction in part consistent with its small genome size, but with marked intraspecific variation. The LTR Ty1/copia retrotransposons were the most abundant, as in the other species of the subgenus, but Ty3/gypsy represented a much smaller fraction compared to the others. The variation observed within P. foetida was greater than that detected among Dysosmia species. Satellite DNAs were partly unique and partly similar to species from different subgenera, supporting its phylogenetic position. In addition, one Dysosmia-specific satellite showed a proximal chromosomal location, making it the first candidate of a centromeric repeat for the genus, despite its variation in abundance among chromosomes.","[""Journal Article"", ""Comparative Study""]","[""Monteiro A"", ""Sader MA"", ""Nascimento J"", ""Luna G"", ""Imig DC"", ""Pedrosa-Harand A""]",10.1007/s10577-026-09804-7,Monteiro A,"Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology",0967-3849,1,Chromosome Res,eng,Pedrosa-Harand A,"[""Passiflora"", ""Genome, Plant"", ""Repetitive Sequences, Nucleic Acid"", ""Retroelements"", ""Phylogeny"", ""Species Specificity"", ""DNA, Plant"", ""Genetic Variation"", ""Chromosomes, Plant"", ""Evolution, Molecular""]",,42543394,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42543394/,"A single species, different repeatomes? Genomic plasticity in Passiflora foetida L. complex and comparative insights across the subgenus Passiflora",34,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"With the increasing adoption of totally tubeless percutaneous nephrolithotomy (ttPCNL), prevention of stone fragment migration into the ureter has gained clinical importance. This study aimed to compare the incidence of ureteral fragment migration at the end of PCNL using a 5 Fr open-ended ureteral catheter (5FrUC) versus an occlusion balloon catheter (OBC). In this IRB-approved randomized controlled trial, 108 eligible patients were randomized 1:1 to either the 5FrUC or OBC group and 99 were included in the final analysis. The primary outcome, ureteral fragment migration, was defined as the presence of any stone fragment ≥ 1 mm between the ureteropelvic junction (UPJ) and ureterovesical junction (UVJ), confirmed by ureteroscopy at the conclusion of PCNL. Baseline demographics, stone characteristics, and operative parameters were comparable between groups, confirming effective randomization. Ureteral fragments were detected in 10 patients (10%): 7 with a single fragment, 2 with two fragments, and 1 with more than three fragments. The median fragment size was 2 mm (range, 1-4 mm). The incidence of ureteral fragments was significantly higher in the 5FrUC group compared with the OBC group (17% vs. 4%, p = 0.03). Logistic regression analysis demonstrated that OBC use reduced the risk of ureteral fragment migration by approximately 80% compared with 5FrUC (OR = 0.204, 95%CI 0.041-1.001, p = 0.05). Greater total stone burden, larger stone volume, higher Guy's stone score, and presence of full staghorn calculi were also associated with fragment migration. Use of an occlusion balloon catheter significantly reduced ureteral fragment migration compared with a 5 Fr open-ended ureteral catheter, achieving prevention in 96% of cases. Although the clinical impact of residual ureteral fragments remains uncertain, these findings support consideration of OBC use, particularly in ttPCNL procedures.","[""Journal Article"", ""Randomized Controlled Trial"", ""Comparative Study""]","[""Savin Z"", ""Garden E"", ""Gupta K"", ""Serna JS"", ""Frangopoulos E"", ""Durbhakula V"", ""Gupta KR"", ""Kaphle S"", ""Malhotra V"", ""Hamlani A"", ""Gallante B"", ""Atallah WM"", ""Gupta M""]",10.1007/s00345-026-06666-w,Savin Z,World journal of urology,0724-4983,1,World J Urol,eng,Gupta M,"[""Humans"", ""Nephrolithotomy, Percutaneous"", ""Female"", ""Ureteral Calculi"", ""Male"", ""Middle Aged"", ""Adult"", ""Foreign-Body Migration"", ""Intraoperative Complications"", ""Aged""]",,42543393,,2026 Aug 2,2026,https://pubmed.ncbi.nlm.nih.gov/42543393/,Prevention of ureteral stone migration during percutaneous nephrolithotomy: a randomized controlled trial,44,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"This study investigated the differences in protective effects of aqueous extracts from stone-epiphytic and living tree-epiphytic Dendrobium nobile on alcohol-induced gastric ulcers in rats, and elucidated the scientific connotation of the traditional assertion that &quot;Dendrobium grown on stones is superior&quot; from the perspectives of material basis and pharmacodynamics. The chemical profiles of aqueous extracts from the two cultivation modes were compared. Rats were randomly divided into control group, model group, omeprazole group, low-and high-dose stone-epiphytic D. nobile(LSE, HSE) groups, and low-and high-dose living tree-epiphytic D. nobile(LLT, HLT) groups. An acute gastric ulcer model in SD rats was established by intragastric administration of absolute ethanol. Gastric mucosal injury index, ulcer inhibition rate, and gastric juice pH were determined. Histopathological changes in gastric tissue were observed by hematoxylin-eosin(HE) and Alcian blue-periodic acid-Schiff(AB-PAS) staining. The expression of tight junction proteins zonula occludens-1(ZO-1) and occludin was detected by immunohistochemistry. Levels of oxidative stress markers, including malondialdehyde(MDA), superoxide dismutase(SOD), and nitric oxide(NO), as well as interleukin-6(IL-6), interleukin-1β(IL-1β), and interferon-γ(IFN-γ) in serum and gastric tissue were measured. Non-targeted metabolomics was further employed to identify absorbed constituents in serum, screen differential metabolites, and perform pathway enrichment analysis, thereby systematically evaluating the material basis and pharmacodynamic differences between the two cultivation modes of D. nobile. The results showed that the aqueous extracts from both cultivation modes contained largely similar types of chemical constituents, including flavonoids, alkaloids, terpenoids and terpenoid glycosides, glycosides, and phenolic amides. However, the relative contents of alkaloid and terpenoid components in both aqueous extracts and absorbed serum samples were higher in stone-epiphytic D. nobile than in living tree-epiphytic samples. Compared with the model group, gastric mucosal injury was significantly alleviated in all treatment groups, with the HSE group showing the highest ulcer inhibition rate. Histopathological observations further indicated that HSE was superior to HLT in maintaining gastric mucosal structural integrity and promoting mucus secretion. Compared with the model group, HSE significantly upregulated the expression of ZO-1 and occludin, effectively reduced MDA and NO levels, and increased SOD activity in gastric tissue, while decreasing the levels of IL-6, IL-1β, and IFN-γ in serum and gastric tissue. Serum metabolomics analysis further showed that HSE mainly exerted protective effects by regulating glycerophospholipid metabolism and glycosylphosphatidylinositol(GPI)-anchor biosynthesis pathways, whereas HLT mainly affected primary bile acid biosynthesis and lysine degradation pathways. These results indicate that both stone-epiphytic and living tree-epiphytic D. nobile exert protective effects against alcohol-induced gastric ulcers. However, the efficacy of stone-epiphytic D. nobile is significantly superior. This advantage may be closely related to the higher relative contents of alkaloid and terpenoid components in both aqueous extracts and absorbed serum samples, as well as its stronger antioxidant and anti-inflammatory activities, better protection of gastric mucosal barrier integrity, and more pronounced regulation of specific metabolic pathways. These findings provide modern pharmacodynamic evidence for the traditional assertion that &quot;Dendrobium grown on stones is superior&quot;.","[""Journal Article"", ""Comparative Study"", ""English Abstract""]","[""Ding HY"", ""Gou HY"", ""Meng JN"", ""You Q"", ""Chen L"", ""Chen HP"", ""Hu Y"", ""Liu YP""]",10.19540/j.cnki.cjcmm.20260318.401,Ding HY,Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica,1001-5302,14,Zhongguo Zhong Yao Za Zhi,chi,Liu YP,"[""Animals"", ""Dendrobium"", ""Stomach Ulcer"", ""Rats"", ""Rats, Sprague-Dawley"", ""Male"", ""Ethanol"", ""Metabolomics"", ""Gastric Mucosa"", ""Humans"", ""Drugs, Chinese Herbal"", ""Superoxide Dismutase""]",4103-4112,42543342,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543342/,[Comparative study on efficacy and mechanism of stone-epiphytic and living tree-epiphytic Dendrobium nobile against alcohol-induced gastric ulcers in rats based on serum metabolomics],51,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"This study focused on Whitmania pigra to establish a multi-dimensional &quot;activity-component&quot; evaluation system. The quality differences between medicinal materials harvested after cocoon production and those harvested under normal conditions were systematically compared in terms of in vitro/in vivo pharmacodynamic effects and chemical compositions. The results showed that although W. pigra harvested after cocoon production complied with the standards specified in the Chinese Pharmacopoeia(2025 edition), its antithrombin activity(P&lt;0.05) and soluble protein content(P&lt;0.001) were significantly lower than those of normally harvested W. pigra. In vivo pharmacodynamic experiments demonstrated that the group treated with post-cocoon harvested W. pigra exhibited significantly inferior effects in inhibiting the black tail length and black tail rate of rats, as well as in improving plasma antithrombotic indices including prothrombin time(PT, P&lt;0.05), activated partial thromboplastin time(APTT, P&lt;0.05), D-dimer(P&lt;0.05), and P-selectin(P&lt;0.01), compared with the normal harvest group. Furthermore, HPLC fingerprinting combined with principal component analysis(PCA), cluster analysis(CA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) confirmed the differences between normally harvested and post-cocoon harvested W. pigra, and seven key differential characteristic components such as uracil and hypoxanthine were identified. In conclusion, the in vitro/in vivo pharmacological activities and content of bioactive components in W. pigra harvested after cocoon production are reduced, resulting in a significant decline in medicinal quality. Accordingly, such medicinal materials are not recommended to be used as decoction pieces in clinical practice.","[""Journal Article"", ""Comparative Study"", ""English Abstract""]","[""Feng XC"", ""Lu MY"", ""Li Z"", ""Fang H"", ""Zhang YQ"", ""Wang LN"", ""Jiang Q""]",10.19540/j.cnki.cjcmm.20260209.204,Feng XC,Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica,1001-5302,12,Zhongguo Zhong Yao Za Zhi,chi,Jiang Q,"[""Animals"", ""Leeches"", ""Male"", ""Rats"", ""Quality Control"", ""Rats, Sprague-Dawley""]",3450-3458,42543304,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543304/,"[Comparative analysis of quality differences between post-cocoon and normally harvested Whitmania pigra materials based on a multi-dimensional ""activity-component"" integrated evaluation]",51,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"This paper aims to evaluate the feasibility of clinical application of high-pressure Schisandrae Chinensis Fructus decoction pieces(HPSCH) compared with that of traditional Schisandrae Chinensis Fructus decoction pieces(SCH), based on the efficacy of mice with nonalcoholic fatty liver disease(NAFLD) induced by a high-fat diet. The optimal preparation process of HPSCH was investigated by using schisandrin content and total extractive yield as indices. After one week of adaptive feeding, C57BL/6 mice were assigned to a normal control group, while the remaining mice were fed an HFD for eight weeks to establish the NAFLD mouse model. After being successfully modeled, the mice were divided into a blank control group, blank administration group, simple model group, fenofibrate group, SCH group, and HPSCH group. All groups were administered by intragastric administration for four weeks. Body weight changes of mice were recorded, and liver indices were calculated. The levels of blood lipid and liver function index in the serum of mice were measured. Hepatic histopathological changes were observed by using hematoxylin-eosin(HE) staining and oil red O staining. Mice's feces were collected, and the 16S rDNA high-throughput sequencing method was employed to analyze changes in the gut microbiota of mice. Untargeted lipidomic analysis of the liver was conducted by using liquid chromatography-mass spectrometry(LC-MS), and principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were adopted to screen and identify differential metabolites. Kyoto Encyclopedia of Genes and Genomes(KEGG) database was used to perform relevant pathway analysis. Integrated analyses of gut microbiota and differential metabolites were performed to compare the similarities and differences in efficacy of HPSCH and SCH. The results show that both the HPSCH group and SCH group exert similar effects on biochemical indices in serum and hepatic pathological changes, lipid metabolism can be regulated, and liver injury in NAFLD mice can be improved. The two groups show similar changes in microbial abundance, trending toward the blank control group and maintaining intestinal homeostasis. Compared with those of the simple model group, the differential metabolites and metabolic pathways of both the HPSCH group and SCH group show similarity, and the differential metabolites are mainly triglycerides, diglycerides, phosphatidylcholines, phosphatidylglycerols, and so on. Metabolic pathways include glycerophospholipid metabolism, choline metabolism, retrograde endocannabinoid signaling, thermogenic lipolysis, and so on. This indicates that HPSCH and SCH share common advantages in improving hepatic function in mice and achieve comparable effects. HPSCH can improve blood lipid and liver function indices in NAFLD mice, attaining the therapeutic effect through the regulation of gut microbiota and lipid metabolism. Notably, HPSCH achieved the same efficacy as SCH at half the conventional dose, demonstrating its feasibility for clinical application. Moreover, the application of HPSCH may contribute to the conservation of medicinal resources.","[""Journal Article"", ""Comparative Study"", ""English Abstract""]","[""DU Y"", ""Fan XY"", ""Zeng S"", ""Yang J"", ""Li GY"", ""Liu T"", ""Xu YL""]",10.19540/j.cnki.cjcmm.20260309.302,DU Y,Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica,1001-5302,12,Zhongguo Zhong Yao Za Zhi,chi,Xu YL,"[""Animals"", ""Non-alcoholic Fatty Liver Disease"", ""Schisandra"", ""Mice"", ""Drugs, Chinese Herbal"", ""Male"", ""Mice, Inbred C57BL"", ""Gastrointestinal Microbiome"", ""Metabolomics"", ""Liver"", ""Disease Models, Animal"", ""Humans"", ""Diet, High-Fat""]",3422-3433,42543301,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543301/,[Comparative research on efficacy of high-pressure Schisandrae Chinensis Fructus decoction pieces and traditional decoction pieces on nonalcoholic fatty liver disease mice based on gut microbiota and metabolomics],51,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"The primary objective was to compare endostatin levels between patients with preeclampsia and those with normal pregnancies. The secondary objectives comprised comparing endostatin levels in early-onset preeclampsia, late-onset preeclampsia, and normal pregnancies, as well as comparing pregnancy and neonatal outcomes between preeclampsia and normal pregnancies. This cross-sectional analytic study included 68 patients with preeclampsia and 68 normal pregnancies. The groups were matched for gestational age. The study was conducted at the Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, and King Chulalongkorn Memorial Hospital, from July 2024 to July 2025. Blood samples were collected in non-heparinized tubes and stored at -80 °C until assayed. Maternal endostatin levels were measured using enzyme-linked immunosorbent assays (ELISA). Maternal and neonatal outcomes were recorded. The median serum endostatin level in patients with preeclampsia was not significantly different from that in normal pregnancies (3.45 vs. 4.32 ng/ml, p = 0.304). The median endostatin levels in early-onset preeclampsia and late-onset preeclampsia did not differ from those in normal pregnancies at the same gestational age (2.84 vs. 7.09 ng/ml, p = 0.05, and 3.86 vs. 4.26 ng/ml, p = 0.845, respectively). Patients with preeclampsia had a higher rate of cesarean delivery (63.2% vs. 41.2%, p = 0.01) and a higher rate of composite maternal complications (16.2% vs. 1.5%, p = 0.004) compared to normal pregnancies. Preeclampsia patients had lower neonatal birth weight (2,419 ± 655 vs. 2,903 ± 507 g, p < 0.001) and longer neonatal lengths of stay (median 5 vs. 4 days, p = 0.01) than those in normal pregnancy. The endostatin level in patients with preeclampsia was not statistically different from that in normal pregnancies. These research findings refute the hypothesis that serum endostatin levels are higher in preeclampsia. Therefore, serum endostatin levels may not be a reliable biomarker for predicting preeclampsia in this population. Preeclampsia is associated with adverse maternal and neonatal outcomes.","[""Journal Article"", ""Comparative Study""]","[""Poosawang C"", ""Phupong V""]",10.1080/14767058.2026.2702813,Poosawang C,"The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians",1476-4954,1,J Matern Fetal Neonatal Med,eng,Phupong V,"[""Humans"", ""Female"", ""Pregnancy"", ""Pre-Eclampsia"", ""Endostatins"", ""Adult"", ""Cross-Sectional Studies"", ""Pregnancy Outcome"", ""Case-Control Studies"", ""Infant, Newborn"", ""Biomarkers"", ""Gestational Age""]",2702813,42543221,,2026 Dec,2026,https://pubmed.ncbi.nlm.nih.gov/42543221/,Comparative study of endostatin levels in preeclampsia pregnancy and normal pregnancy,39,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"According to epidemiological data from Hungary, cardiovascular diseases cause the greatest loss of health among the population and are responsible for a significant proportion of premature deaths. This reinforces the health policy position that cardiovascular prevention, including improving medication adherence, must be given top priority in patient care. Long-term survival in patients who have experienced acute coronary syndrome depends heavily on medication adherence, particularly regarding statins and anticoagulants; however, domestic surveys indicate deficiencies in the use of preventive medications. The aim of our study was to compare the attitudes and beliefs regarding antiplatelet agents and cholesterol-lowering drugs among patients in the secondary prevention group who underwent percutaneous coronary intervention and those in the primary prevention control group, using the Beliefs about Medicines Questionnaire (BMQ). A cross-sectional, questionnaire-based study included 162 secondary prevention patients and 136 primary prevention patients who had undergone percutaneous coronary intervention. Medication attitudes were measured using the specific and general dimensions of the BMQ, and SPSS 27.0 was used for statistical analysis. Among patients in the secondary prevention group, both drug groups were characterized by lower levels of concern and more accepting attitudes, whereas in the primary prevention group, sceptical (p<0.05) and ambivalent attitudes were more common (p<0.001). Based on the analysis of respondents by attitude group and the examination of the BMQ's general subscales, percutaneous coronary intervention significantly influenced beliefs regarding medications. This change was clinically significant in terms of treatment adherence (p<0.001) Discussion and conclusion: Patients who have undergone percutaneous coronary intervention have more favourable attitudes toward medication, which highlights the role of targeted education and psychoeducation in improving adherence in the non-intervention population. However, adherence in the secondary prevention group cannot be considered optimal either, therefore further targeted education is warranted in this patient group as well. Orv Hetil. 2026; 167(31): 1238-1247.","[""Journal Article"", ""Comparative Study"", ""English Abstract""]","[""Szendrei-Lódi R"", ""Tömő Z"", ""Beke S"", ""Márk L""]",10.1556/650.2026.33612,Szendrei-Lódi R,Orvosi hetilap,0030-6002,31,Orv Hetil,hun,Márk L,"[""Humans"", ""Hydroxymethylglutaryl-CoA Reductase Inhibitors"", ""Platelet Aggregation Inhibitors"", ""Male"", ""Female"", ""Hungary"", ""Secondary Prevention"", ""Primary Prevention"", ""Middle Aged"", ""Cross-Sectional Studies"", ""Cardiovascular Diseases"", ""Aged"", ""Medication Adherence"", ""Surveys and Questionnaires"", ""Drug Monitoring"", ""Health Knowledge, Attitudes, Practice"", ""Percutaneous Coronary Intervention""]",1238-1247,42543013,,2026 Aug 2,2026,https://pubmed.ncbi.nlm.nih.gov/42543013/,[Comparison of statin and antiplatelet therapy adherence in primary and secondary cardiovascular prevention patients],167,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"In addition to other conditions involving increased muscle spasms, centrally acting muscle relaxants (guaifenesin, tolperisone, methocarbamol, chlorzoxazone, diazepam, baclofen and tizanidin) provide relief for a significant proportion of patients suffering from low back pain. Of these, tolperisone has recently been restricted by official decision due to the high incidence of anaphylactic reactions associated with its use. The aim of our work is to analyze the frequency of side effects of this group of drugs in order to help clinicians choose the appropriate medication. According to data from the World Health Organization, tolperisone is considered a safe drug, except for the aforementioned serious allergic side effect. Mortality (including suicide) associated with the administration of these medicines is the highest among the reported side effects for diazepam, followed by tizanidine and methocarbamol. Ineffectiveness was most commonly reported for guaifenesin, followed by baclofen and tizanidine. Tolperisone was the most favorable drug in terms of both mortality and ineffectiveness. We present in detail the gastrointestinal, major neurological, and psychiatric side effects that make it difficult, and in some cases impossible, to take the drugs, and we also mention the disturbing skin and eye symptoms. Orv Hetil. 2026; 167(31): 1224-1230.","[""Journal Article"", ""Review"", ""Comparative Study"", ""English Abstract""]","[""Kopitkó C"", ""Pettendi É""]",10.1556/650.2026.33617,Kopitkó C,Orvosi hetilap,0030-6002,31,Orv Hetil,hun,Pettendi É,"[""Humans"", ""Muscle Relaxants, Central"", ""Tolperisone"", ""Guaifenesin""]",1224-1230,42543011,,2026 Aug 2,2026,https://pubmed.ncbi.nlm.nih.gov/42543011/,[Comparison of the side effect profiles of compounds with central muscle-relaxing effect],167,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"This study aims to evaluate the midterm clinical outcomes of patients with complex clubfoot treated using the Ponseti method and to assess the sustainability of deformity correction over time. Between January 2016 and January 2021, a total of 38 feet in 26 patients with complex clubfoot treated using the modified Ponseti method were retrospectively analyzed. The patients were divided into two groups: those treated entirely in our institution (study center group) and those referred from external centers after unsuccessful initial treatment (external center group). Clinical severity was assessed using the Pirani score, and ankle dorsiflexion (DF) was measured during follow-up. Functional outcomes were evaluated using the Pirani-Based Score (PBS) and the Oxford Ankle Foot Questionnaire (OxAFQ). Relapse rates, additional procedures, and treatment success were analyzed. Independent predictors of outcomes were identified. Of a total of 26 patients included in the study, 2 were male and 24 were female with a mean age of 6.78 ± 1.29 (range, 5 to 8) years. Of these patients, 14 (53.8%) had unilateral involvement, while 12 (46.2%) had bilateral deformity. The external clinic group presented at a significantly later age than the study center group (p < 0.001), while baseline deformity severity was comparable. Pirani scores and DF measurements improved significantly in both groups, with no intergroup differences during follow-up (p > 0.05). Functional outcomes showed a significant difference in PBS scores, which were higher in the external clinic group (p = 0.045), indicating worse functional performance, while the OxAFQ scores were similar between groups (p = 0.911). Relapse rates were higher in the own clinic group but did not reach statistical significance (p = 0.254). Multivariate analysis revealed that age was the only independent predictor of treatment success (odds ratio [OR] = 2.067, p = 0.019), while referral status was not an independent determinant. The modified Ponseti method provides effective midterm correction in complex clubfoot regardless of referral status. Although referred patients present later and may demonstrate worse functional outcomes, referral source does not independently influence treatment success. Early recognition and appropriate application of modified Ponseti principles remain critical for optimal outcomes.","[""Journal Article"", ""Comparative Study""]","[""Dolap MA"", ""Kaptan AY"", ""Bal T"", ""Çetin BV"", ""Bozkurt C"", ""Işıkyıldız M"", ""Altay MA""]",10.52312/jdrs.2026.2959,Dolap MA,Joint diseases and related surgery,2687-4792,3,Jt Dis Relat Surg,eng,Altay MA,"[""Humans"", ""Clubfoot"", ""Retrospective Studies"", ""Female"", ""Male"", ""Treatment Outcome"", ""Child, Preschool"", ""Child"", ""Casts, Surgical"", ""Referral and Consultation"", ""Recurrence""]",873-881,42542930,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42542930/,Midterm outcomes of complex clubfoot treated with the modified Ponseti method: A comparative study of primary and referred cases,37,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"In this study, we aimed to compare the clinical and radiological outcomes of patients undergoing arthrodesis and trapeziectomy with ligament reconstruction and tendon interposition (T + LRTI) for thumb carpometacarpal (CMC) osteoarthritis and to investigate whether patient-specific decision-making could offer advantages over LRTI or arthrodesis as a surgical approach. Between August 2014 and January 2025, a total of 40 patients who underwent surgical treatment for thumb CMC osteoarthritis were retrospectively analyzed. The patients were divided into two groups as the T + LRTI group (n = 22) and arthrodesis group (n = 18). Clinical outcomes were assessed using the Visual Analog Scale (VAS), Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), grip strength (kg), and pinch strength (kg) measurements. Of the patients, 7 were male and 33 were female with a mean age of 62.9 ± 6.5 years in T + LRTI group, 60.1 ± 7.4 years in arthrodesis group (range, 40 to 75 years). Both groups demonstrated significant improvement in VAS and QuickDASH scores postoperatively (p < 0.001). The mean postoperative VAS scores were 2.7 ± 2.0 in the T + LRTI group and 1.9 ± 0.9 in the arthrodesis group (p = 0.267), while QuickDASH scores were 26.4 ± 17.3 and 19.1 ± 3.2, respectively (p = 0.085). No significant differences were observed in grip strength (p = 0.358), palmar pinch (p = 0.104) and key pinch strength (p = 0.097) between the groups. The overall complication rate was 12.5% in both groups, indicating no statistically significant difference (p = 0.642). Our study results suggest that both T + LRTI and arthrodesis provide effective and comparable pain relief and functional outcomes in the surgical management of thumb CMC osteoarthritis and can be considered reliable surgical options.","[""Journal Article"", ""Comparative Study""]","[""Aldemir C"", ""Ozturk T"", ""Ertem H"", ""Aydın Y"", ""Zengin EC"", ""Piskin A"", ""Erpala F"", ""Sener M""]",10.52312/jdrs.2026.2927,Aldemir C,Joint diseases and related surgery,2687-4792,3,Jt Dis Relat Surg,eng,Sener M,"[""Humans"", ""Osteoarthritis"", ""Female"", ""Male"", ""Middle Aged"", ""Arthrodesis"", ""Thumb"", ""Retrospective Studies"", ""Carpometacarpal Joints"", ""Trapezium Bone"", ""Aged"", ""Ligaments, Articular"", ""Treatment Outcome"", ""Tendons"", ""Hand Strength"", ""Adult"", ""Plastic Surgery Procedures"", ""Pinch Strength""]",777-784,42542922,,2026 May 4,2026,https://pubmed.ncbi.nlm.nih.gov/42542922/,Thumb carpometacarpal osteoarthritis: Arthrodesis versus trapeziectomy with ligament reconstruction and tendon interposition,37,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"This study aims to compare the biomechanical performance of three different surgical fixation techniques in the treatment of proximal humerus fractures with medial metaphyseal defects. A total of 24 synthetic humerus bone models were used and equally divided into three groups (n = 8 per group). A standardized unstable proximal humerus fracture model with a medial metaphyseal cortical defect extending to the surgical neck was created using a three-dimensional (3D)-printed osteotomy guide. Group 1 received fixation with a lateral anatomical locking plate. Group 2 was treated with a combination of a lateral anatomical plate and a medial buttress plate (dual plating). Group 3 underwent fixation with an intramedullary nail (IMN); in this group, four specimens had distal locking with an endopin (Group 3a), and the other four with static screws (Group 3b). All specimens were subjected to axial loading until failure. Forces at the onset of failure and complete failure were recorded, and fracture patterns were documented. In Groups 1 and 2, transverse fractures consistently occurred at the level of the most distal screw of the lateral plate. In Group 3, failure was observed either proximally or distally at the nail tip, including butterfly fragment formation and metaphyseal collapse. Group 2 exhibited the highest resistance to axial loading, followed by Group 1 and Group 3, with statistically significant differences between all groups (p = 0.043, p = 0.0003, p < 0.00001). No significant difference was found between subgroups 3a and 3b (p > 0.05). Our study results indicate that double plating provides the greatest axial stability in proximal humerus fractures with medial metaphyseal defects, supporting its use in fracture patterns with medial column deficiency. However, as fixation choice should be guided by patient-specific factors and surgical feasibility, these findings should be interpreted in the context of experimental conditions and loading limitations.","[""Journal Article"", ""Comparative Study""]","[""Akyürek M"", ""Koraman E"", ""Çelik A"", ""Iyetin Y"", ""Kösters C"", ""Türkmen I""]",10.52312/jdrs.2026.2570,Akyürek M,Joint diseases and related surgery,2687-4792,3,Jt Dis Relat Surg,eng,Türkmen I,"[""Biomechanical Phenomena"", ""Bone Plates"", ""Humans"", ""Shoulder Fractures"", ""Fracture Fixation, Internal"", ""Bone Screws"", ""Weight-Bearing"", ""Fracture Fixation, Intramedullary"", ""Models, Anatomic"", ""Bone Nails""]",688-696,42542913,,2026 Jun 17,2026,https://pubmed.ncbi.nlm.nih.gov/42542913/,Biomechanical comparison of three fixation methods under axial loading in proximal humerus fractures with medial metaphyseal defect,37,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"This study aims to evaluate the biomechanical contribution of medial support plating compared to isolated screws and to determine the impact of plate design (one-third tubular vs. mini-plate) and distal screw configuration (unicortical vs. bicortical) on construct stability. Five finite element models were analyzed in this study: three cannulated screws (CS) alone (control), and CS augmented with either a one-third tubular plate or a 2.4-mm mini-plate. For the plated models, the distal fragment was fixed using either unicortical or bicortical screws to isolate the effect of cortical purchase. A 1,400 N axial load was applied to simulate the single-leg stance phase of gait. Fracture micromotion, femoral head displacement, and von Mises stress distribution were recorded. Medial support plating substantially improved construct stability compared to screws alone, reducing femoral head displacement and fracture gap movement. Notably, no significant biomechanical differences were observed between unicortical and bicortical fixation configurations for either plate type. Both the one-third tubular plate and the 2.4-mm mini-plate provided equivalent rigidity. Although mini-plates exhibited higher internal stress concentrations, values remained below the yield strength of the material. Bicortical fixation provided no additional mechanical advantage over unicortical fixation in improving construct stability or reducing implant stress. Therefore, the primary determinant of stability is the medial buttress effect itself; once this is established, neither the plate profile nor the screw length significantly alters the biomechanical outcome, suggesting that unicortical fixation with low-profile plates provides sufficient mechanical stability.","[""Journal Article"", ""Comparative Study"", ""Evaluation Study""]","[""Kalem M"", ""Kısmet M"", ""Ertan MB"", ""Şahin E"", ""Kocaoğlu H""]",10.52312/jdrs.2026.2806,Kalem M,Joint diseases and related surgery,2687-4792,3,Jt Dis Relat Surg,eng,Kocaoğlu H,"[""Finite Element Analysis"", ""Bone Plates"", ""Humans"", ""Biomechanical Phenomena"", ""Bone Screws"", ""Fracture Fixation, Internal"", ""Femoral Neck Fractures"", ""Stress, Mechanical"", ""Prosthesis Design""]",677-687,42542912,,2026 Apr 24,2026,https://pubmed.ncbi.nlm.nih.gov/42542912/,Comparative biomechanical evaluation of medial support plating in Pauwels type III femoral neck fractures: A finite element analysis,37,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"This study aims to investigate whether arthroscopy-assisted minimally invasive percutaneous plate osteosynthesis (MIPPO) provided more favorable early functional recovery and reduced surgical trauma compared to traditional open reduction and internal fixation (ORIF). A total of 84 patients with Schatzker type I-IV tibial plateau fractures treated between January 2021 and January 2024 were retrospectively analyzed. The MIPPO group (n = 41) underwent arthroscopy-assisted reduction plus MIPPO, while the ORIF group (n = 43) received conventional ORIF. Allocation was chronological, with ORIF predominant in the first two years and MIPPO in the latter two years. Operative parameters, postoperative drainage, radiographic outcomes (Rasmussen radiological score), functional recovery (Hospital for Special Surgery [HSS] score), range of motion (ROM), fracture healing time, hospital stay, and complications were compared. Of a total of 84 patients, 28 were male and 56 were female of 49.4 ± 9.0 (range, 27 to 69) years. The arthroscopy-assisted MIPPO group had significantly longer operative time (96.0 ± 18.2 vs. 84.0 ± 13.9 min, p = 0.001) but shorter incision length (3.9 ± 0.7 vs. 6.2 ± 0.9 cm, p < 0.001), less intraoperative blood loss (56.5 ± 9.6 vs. 72.6 ± 10.1 mL, p < 0.001), and lower postoperative drainage volume (47.1 ± 7.5 vs. 59.0 ± 7.0 mL, p < 0.001) than the ORIF group. The arthroscopy-assisted MIPPO group also achieved higher Rasmussen radiological scores (15.4 ± 1.4 vs. 14.0 ± 1.6, p < 0.001) and better HSS scores at one, three, and six months postoperatively (all p < 0.001). At six months postoperatively, the MIPPO group also demonstrated significantly improved knee ROM (118.5° ± 8.2° vs. 107.3° ± 9.1°, p < 0.001), a difference exceeding the clinically meaningful threshold for activities of daily living. However, no significant differences were found in hospital stay (p = 0.051), fracture healing time (11.4 ± 1.3 vs. 11.1 ± 1.3 weeks, p = 0.340), or the excellent-and-good rate of HSS score at final follow-up (95.1% vs. 97.7%, p = 0.746). Complication rates were similar between the groups (p = 1.000). For Schatzker type I-IV tibial plateau fractures, arthroscopy-assisted MIPPO provides more favorable early functional recovery and radiological reduction quality compared to conventional ORIF, with less surgical trauma and comparable early functional recovery and similar complication rates during follow-up. Although operative time is longer, this minimally invasive approach is a safe and effective option for managing these complex fractures. Its principal advantage is accelerated early recovery, particularly in knee ROM, enabling patients to reach clinically meaningful thresholds for activities of daily living sooner.","[""Journal Article"", ""Comparative Study""]","[""Yan B"", ""Zhang J"", ""Yao W"", ""Li YJ""]",10.52312/jdrs.2026.2921,Yan B,Joint diseases and related surgery,2687-4792,3,Jt Dis Relat Surg,eng,Li YJ,"[""Humans"", ""Tibial Plateau Fractures"", ""Female"", ""Arthroscopy"", ""Adult"", ""Fracture Fixation, Internal"", ""Male"", ""Middle Aged"", ""Retrospective Studies"", ""Bone Plates"", ""Aged"", ""Open Fracture Reduction"", ""Minimally Invasive Surgical Procedures"", ""Fracture Healing"", ""Treatment Outcome"", ""Range of Motion, Articular"", ""Recovery of Function""]",667-676,42542911,,2026 Jul 14,2026,https://pubmed.ncbi.nlm.nih.gov/42542911/,A comparative analysis of arthroscopy-assisted minimally invasive percutaneous plate osteosynthesis versus open reduction and internal fixation for tibial plateau fractures,37,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"This study aims to compare the efficacy of conventional rehabilitation alone, conventional rehabilitation combined with balance acupuncture (BA) and conventional rehabilitation plus BA and unconscious proprioception training in chronic ankle instability (CAI) patients. This single-center, parallel-group, assessor-blinded randomized-controlled trial included a total of 120 CAI patients between October 2022 and October 2024. The patients were randomly assigned to control (n = 40), BA (n = 40), and combination therapy (CT, (n = 40) groups. All groups received six weeks of intervention (6 days/week): the control group received conventional rehabilitation, the BA group received conventional rehabilitation + BA and the CT group received conventional rehabilitation + BA + unconscious proprioception training. Unconscious proprioception training was defined as dual-task training using the MOTOmed system with cognitive distraction to shift focus away from conscious movement control. Assessments were conducted before and after treatment using a three-dimensional gait analysis system, a balance function testing and training system, and the Star Excursion Balance Test (SEBT). There was no statistically significant difference in age and sex among the groups (p > 0.05). In addition, disease duration and number of previous sprains were comparable among the groups (p > 0.05). Following the six-week intervention, all three groups showed significant improvements in gait parameters, balance function and SEBT scores compared to baseline (p < 0.05). The CT group exhibited significantly greater improvements in gait speed, cadence, movement length, movement ellipse area and SEBT scores than the BA group (p < 0.05), whereas the BA group outperformed the control group in all outcome measures (p < 0.05). No adverse reactions were reported in any group. The integration of BA and unconscious proprioception training may offer additional benefits for improving gait and balance in CAI patients compared to conventional rehabilitation plus BA or conventional rehabilitation alone. Based on these preliminary findings, the combined approach shows potential clinical value for targeted populations with CAI.","[""Journal Article"", ""Randomized Controlled Trial"", ""Comparative Study""]","[""Liu N"", ""Wang M"", ""Meng Q"", ""Wang M"", ""Shang K"", ""Bi YL"", ""Jiang X"", ""Li J"", ""Chen J"", ""Feng S"", ""Zhai H""]",10.52312/jdrs.2026.2311,Liu N,Joint diseases and related surgery,2687-4792,3,Jt Dis Relat Surg,eng,Zhai H,"[""Humans"", ""Male"", ""Female"", ""Joint Instability"", ""Postural Balance"", ""Adult"", ""Proprioception"", ""Treatment Outcome"", ""Acupuncture Therapy"", ""Combined Modality Therapy"", ""Chronic Disease"", ""Ankle Joint"", ""Young Adult"", ""Single-Blind Method"", ""Exercise Therapy""]",637-648,42542908,,2026 Jul 10,2026,https://pubmed.ncbi.nlm.nih.gov/42542908/,"Comparative efficacy of conventional rehabilitation, balance acupuncture combined with conventional rehabilitation and additional unconscious proprioception training for chronic ankle instability: A randomized-controlled clinical study",37,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"This study aims to compare the rates of medical complication and mortality following initial bipolar hemiarthroplasty (bHA) and reoperation procedures, as well as between different causes of reoperation (nonseptic vs. septic). The retrospective study included 118 patients undergoing reoperation after bHA for femoral neck fractures between January 2002 and December 2022. The primary outcomes included in-hospital complications, readmission, and mortality events, while secondary outcomes included length of hospital stay, transfusion rates, and estimated blood loss. These outcomes were compared between each patient's initial bHA and their subsequent reoperation procedure. The two cohorts were matched using propensity scores based on age, sex, and Charlson Comorbidity Index to compare outcomes between nonseptic and septic causes of reoperation. Of the 118 patients, 64 were male and 54 were female. The mean age was 77.8 ± 7.9 years, with a range of 61 to 98 years. The in-hospital complication rate was higher after reoperation than after initial bHA (15.3% vs. 1.7%, p < 0.001). Conversely, the readmission rate was higher after the initial procedure (60.2% vs. 23.7%, p < 0.001), mainly due to surgical complications. Patients undergoing reoperation had longer hospital stays, higher transfusion requirements, and more frequently received general anesthesia compared to the initial procedure (p < 0.05). In the matched cohort, septic group had higher in-hospital complication rates than the nonseptic group (23.5% vs. 3.9%, p = 0.004), while readmission and mortality rates were comparable. Reoperations after bHA carry a higher risk of medical complications. This risk is particularly pronounced in cases related to septic conditions, underscoring the greater impact of reoperation and careful clinical attention.","[""Journal Article"", ""Comparative Study""]","[""Chang WL"", ""Chang CY"", ""Wang JC"", ""Tsai SW"", ""Chen CF"", ""Wu PK"", ""Chen WM""]",10.52312/jdrs.2026.2619,Chang WL,Joint diseases and related surgery,2687-4792,3,Jt Dis Relat Surg,eng,Chen WM,"[""Humans"", ""Reoperation"", ""Female"", ""Femoral Neck Fractures"", ""Male"", ""Hemiarthroplasty"", ""Retrospective Studies"", ""Postoperative Complications"", ""Aged, 80 and over"", ""Aged"", ""Middle Aged"", ""Length of Stay"", ""Patient Readmission"", ""Blood Transfusion"", ""Sepsis"", ""Proximal Femoral Fractures""]",626-636,42542907,,2026 Jul 16,2026,https://pubmed.ncbi.nlm.nih.gov/42542907/,The impact of reoperation after bipolar hemiarthroplasty for femoral neck fracture: A matched cohort comparison between septic and nonseptic causes,37,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"This study aims to investigate the clinical effect of acupuncture combined with rehabilitation training in the treatment of knee osteoarthritis (KOA) under unified acupoint intervention. In this prospective, comparative study informed by systematic acupoint analysis, the literature related to acupuncture for KOA treatment was retrieved from public databases and the core acupoints were analyzed using the Traditional Chinese Medicine Inheritance Calculation System (TCMICS) software. Eighty-four patients were selected as the participants, and the clinical effect (total efficacy rate), Numeric Rating Scale (NRS) for pain score, American Knee Society Score (AKSS) for knee joint function and the self-care ability score for daily living activities were used to evaluate the treatment effect. The curative effect index was calculated using the AKSS scores. After analyzing the core acupoints, we selected the Dubi, Zusanli, Yanglingquan, Xuehai, Neixiyan and Liang Qiu acupoints for the acupuncture treatment. The patients were divided into a control group (n = 42 patients undergoing rehabilitation training) and an intervention group (n = 42 patients undergoing acupuncture combined with rehabilitation training). The control group consisted of 15 male and 27 female, with a mean age of 62.90 ± 11.531 (range, 40 to 78) years. The mean course of the disease was 4.07 ± 1.841 years. The intervention group consisted of 16 male and 26 female, with a mean age of 63.95 ± 10.613 (range, 41 to 79) years and a mean disease course of 4.76 ± 2.328 years. There was no significant difference between the groups before treatment (p > 0.05). After acupuncture treatment, the 92.85% total efficacy rate (n = 39) was significantly higher than the 73.80% (n = 31) in the control group. The mean AKSS of the control and intervention groups were 64.17 ± 11.148 and 66.67 ± 17.795, respectively, and the mean knee joint articulation scores were 57.40 ± 8.925 and 54.10 ± 10.150 in the two groups, respectively. Following treatment, the scores of knee joint function and knee joint articulation in the intervention group were higher than those in the control group (p < 0.05). For AKSS, the mean difference of the control group was 6.030, and the proportion of patients who reached the improvement of minimum clinically significant difference (MCID) standard was 80.95%. The mean difference of the intervention group was 10.98, and the proportion of patients who reached MCID was 100%. Following treatment, the self-care ability score in the intervention group were higher than those in the control group (p < 0.05). For modified Barthel Index (MBI), the mean difference of the control group and intervention group were 6.446 and 6.225, all accounting for 100%. The mean NRS scores were significantly decreased from 5.19 ± 1.042 to 1.93 ± 0.640 after one month of acupuncture treatment. Our study results suggest that acupuncture combined with rehabilitation training based on data mining can relieve patients' pain, accelerate the recovery of their knee joint function and improve their daily living ability, demonstrating high clinical value in practice.","[""Journal Article"", ""Comparative Study""]","[""Li Y"", ""Yu J"", ""Liu Y"", ""Zhu L"", ""Zhang Y"", ""Jin M"", ""Wu C"", ""Li S"", ""Fu L"", ""Zheng L"", ""Xu S"", ""Jin Y""]",10.52312/jdrs.2026.2205,Li Y,Joint diseases and related surgery,2687-4792,3,Jt Dis Relat Surg,eng,Jin Y,"[""Humans"", ""Prospective Studies"", ""Female"", ""Osteoarthritis, Knee"", ""Middle Aged"", ""Acupuncture Therapy"", ""Male"", ""Treatment Outcome"", ""Acupuncture Points"", ""Activities of Daily Living"", ""Aged"", ""Pain Measurement"", ""Recovery of Function"", ""Combined Modality Therapy"", ""Knee Joint"", ""Exercise Therapy""]",614-625,42542906,,2026 Jul 13,2026,https://pubmed.ncbi.nlm.nih.gov/42542906/,Investigating the efficacy of acupoint acupuncture combined with rehabilitation training in knee osteoarthritis treatment: A prospective comparative study informed by systematic acupoint analysis,37,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"This study aims to compare the long-term outcome of highly cross-linked polyethylene (HXLPE) in hip dysplasia with osteonecrosis of the femoral head (ONFH) and evaluate the effect of cup inclination on HXLPE wear after total hip arthroplasty (THA) during a minimum 10-year follow-up. Between January 2000 and December 2012, a total of 124 patients who underwent primary THA for hip dysplasia or ONFH with a minimum 10-year follow-up were retrospectively analyzed. A total of 62 patients were successfully matched between the two groups (ONFH group, n = 62 and hip dysplasia group, n = 62). Primary outcomes included acetabular cup inclination, anteversion, and wear rates of HXLPE. Based on cup inclination, both groups were divided into three subgroups, classified as (1) ≤ 45°, (2) < 45° to < 50°, and (3) ≥ 55°. Secondary outcomes included the clinical score and radiographic findings of osteolysis, implant loosening, stress shielding, and heterotopic ossification. Kaplan-Meier curve and Cox regression test were used to compare the implant survivorship in the full cohort prior to exclusion and matching (178 hip dysplasia and 397 ONFH patients). There was no significant difference in survival rate without revision of prosthesis at 10-year between two groups (hip dysplasia: 94.7%, 95% confidence interval [CI]: 91.1% to 98.4% vs. ONFH: 95.7% (95% CI: 93.3% to 98.2%) (p = 0.4) Cup inclination was significantly steeper in the hip dysplasia group (47.6°, 95% CI: 46.0° to 49.3°) than in the ONFH group (43.9°, 95% CI: 42.3° to 45.5°) (p = 0.002). Steep cup inclination (> 55°) was significantly more frequent in the hip dysplasia group (11.3%, 7/62) than in the ONFH group (6.5%, 4/62; p = 0.006). However, wear rates of HXLPE were not significantly different between groups, and no correlation was found between cup inclination and HXLPE wear rate. No progressive osteolysis or prosthetic loosening was observed during follow-up. Although patients with hip dysplasia demonstrated a steeper mean cup inclination and a higher incidence of steep cup positioning compared to those with ONFH, implant survivorship remained comparable between groups in the overall cohort. In the matched cohort analysis, HXLPE wear rates and clinical outcomes were also comparable between the groups. These findings suggest that, despite technical challenges in acetabular positioning, the use of HXLPE in THA for hip dysplasia provides satisfactory long-term performance and may alleviate concerns regarding cup inclination-related wear.","[""Journal Article"", ""Comparative Study""]","[""Choi BC"", ""Lee KJ"", ""Min BW"", ""Suh HS""]",10.52312/jdrs.2026.2702,Choi BC,Joint diseases and related surgery,2687-4792,3,Jt Dis Relat Surg,eng,Suh HS,"[""Humans"", ""Arthroplasty, Replacement, Hip"", ""Hip Prosthesis"", ""Retrospective Studies"", ""Female"", ""Male"", ""Femur Head Necrosis"", ""Prosthesis Failure"", ""Treatment Outcome"", ""Polyethylene"", ""Middle Aged"", ""Prosthesis Design"", ""Adult"", ""Kaplan-Meier Estimate"", ""Proportional Hazards Models"", ""Time Factors"", ""Hip Joint"", ""Hip Dislocation"", ""Acetabulum"", ""Aged"", ""Radiography""]",602-613,42542905,,2026 May 15,2026,https://pubmed.ncbi.nlm.nih.gov/42542905/,Minimum 10-year outcomes of highly cross-linked polyethylene in total hip arthroplasty for hip dysplasia: Effect of cup inclination in a matched comparative study,37,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"This study aims to compare the clinical and radiological outcomes of the direct anterior approach (DAA) and the traditional posterior-lateral approach (PLA) for total hip arthroplasty (THA) in patients with ankylosing spondylitis (AS). Between July 2001 and May 2024, a total of 137 patients (117 males, 20 females; mean age: 40.21 ± 13.28 years; range, 17 to 73 years) with AS who underwent THA using the DAA or PLA were retrospectively analyzed. Using propensity score-matching, we retrospectively analyzed data on 164 hips with AS for which THA was performed, with 41 and 123 hips in the DAA and PLA groups, respectively. Preoperative baseline characteristics, surgical data, clinical and radiological outcomes at follow-up were collected and compared between the two groups. The mean follow-up was 68.05 ± 38.09 months. There were no significant intergroup differences in terms of surgical data, postoperative complications, clinical scores, or patient satisfaction (p > 0.05). Compared to the PLA group, the DAA group had a significantly higher rate of achieving hip flexion over 90° (82.93% vs. 60.98%, p = 0.010), with fewer patients in the group reporting difficulty with putting on socks (p = 0.003). The DAA group exhibited a smaller acetabular anteversion (17.10 ± 6.60° vs. 20.68 ± 8.73°, p = 0.031), with a higher proportion of acetabular components positioned within the Lewinnek safe zone (82.93% vs. 60.16%, p = 0.008). Although both surgical approaches are effective for managing hip involvement in ankylosing spondylitis undergoing THA, the DAA may offer functional benefits and improved prosthetic alignment. These advantages support its consideration as a favorable surgical option in appropriately selected patients.","[""Journal Article"", ""Comparative Study""]","[""Wang X"", ""Guo S"", ""Chen D"", ""Zhou Y"", ""Bian T"", ""Man S"", ""Zhang L""]",10.52312/jdrs.2026.2738,Wang X,Joint diseases and related surgery,2687-4792,3,Jt Dis Relat Surg,eng,Zhang L,"[""Humans"", ""Female"", ""Spondylitis, Ankylosing"", ""Arthroplasty, Replacement, Hip"", ""Male"", ""Middle Aged"", ""Adult"", ""Retrospective Studies"", ""Aged"", ""Treatment Outcome"", ""Adolescent"", ""Young Adult"", ""Propensity Score"", ""Hip Joint"", ""Radiography"", ""Range of Motion, Articular"", ""Patient Satisfaction""]",592-601,42542904,,2026 May 15,2026,https://pubmed.ncbi.nlm.nih.gov/42542904/,Clinical and radiological outcomes of direct anterior versus posterolateral total hip arthroplasty in ankylosing spondylitis: A propensity-matched study,37,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"In this meta-analysis, we discuss the clinical efficacy of closed reduction with in situ fixation for valgus-impacted femoral neck fractures (VIFNFs) by contrasting postoperative functional recovery and complication profiles. We performed a systematic literature search in PubMed, Embase, Web of Science, the Cochrane Library, and ScienceDirect for publications up to October 2025. The search targeted original studies which directly compared the surgical outcomes of closed reduction and in situ internal fixation for valgus-impacted femoral neck fractures. Search terms included combinations of: valgus-impacted (or valgus impaction), femoral neck fracture, in situ, reduction, and internal fixation. Pooled data were analyzed using mean differences (MD) with 95% confidence intervals (CIs) for continuous outcomes and risk differences (RD) with 95% CIs for dichotomous outcomes. The final analysis included a total of 447 patients extracted from five studies that met the predetermined inclusion criteria. The meta-analysis demonstrated that the closed reduction group exhibited a statistically significant reduction in postoperative femoral neck shortening (FNS) compared with the in situ fixation group (MD: 4.05; 95% CI: 2.68 ~ 5.42; p < 0.00001). For the caput-collum-diaphysis (CCD) angle, the closed reduction group showed a borderline significant improvement relative to the in situ fixation group (MD: 9.79; 95% CI: 0.19 ~ 19.39; p = 0.05). The in situ fixation group was associated with a substantially lower reoperation rate (RD: -0.08; 95% CI: -0.16 ~ -0.01; p = 0.04). No statistically significant intergroup differences were detected for the Harris Hip Score (HHS) (MD: -4.13; 95% CI: -9.37 ~ 1.11; p = 0.12), incidence of femoral head necrosis (RD: -0.05; 95% CI: -0.14 ~ 0.05; p = 0.36), or fixation failure rate (RD: -0.05; 95% CI: -0.17 ~ 0.06; p = 0.37). Closed reduction yields a statistically significant advantage in reducing postoperative FNS and a borderline significant benefit in maintaining the CCD. In contrast, in situ fixation is associated with a lower reoperation rate. The two strategies show comparable outcomes for the HHS, femoral head necrosis incidence, and fixation failure rate. Thus, surgical approach should be individualized based on patient-specific profiles.","[""Journal Article"", ""Meta-Analysis"", ""Comparative Study"", ""Systematic Review""]","[""Shan D"", ""Deng ZB"", ""Dong Q""]",10.52312/jdrs.2026.2733,Shan D,Joint diseases and related surgery,2687-4792,3,Jt Dis Relat Surg,eng,Dong Q,"[""Humans"", ""Femoral Neck Fractures"", ""Fracture Fixation, Internal"", ""Closed Fracture Reduction"", ""Treatment Outcome"", ""Postoperative Complications"", ""Proximal Femoral Fractures""]",581-891,42542903,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42542903/,Clinical efficacy and safety of closed reduction versus in situ internal fixation for valgus-impacted femoral neck fractures: A meta-analysis,37,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"Intercalary reconstruction following diaphyseal tumor resection is advantageous in that they preserve the joint above and below. Recently, intramedullary devices such as intramedullary nails (IMN), photodynamic bone stabilizing system (PBSS), and intercalary endoprosthetic reconstruction (EPR) have become increasingly used. Understanding the tradeoffs associated with each construct as well as characterizing their mechanical stability is essential for making a patient-specific decision for reconstruction. The mechanical properties of four different constructs used in the reconstruction of segmental defects in a femur model were compared: Double plate (DP) allograft secured by 90-90 plating, allograft secured by IMN and plate fixation, allograft secured by PBSS and plate fixation, as well as an intercalary prosthesis (EPR). Samples were tested in axial, bending and torsional loading, and mechanical properties were compared. The EPR during anterior-posterior bending had 51.63% of the displacement compared to the DP (p = 0.0007), and 55% of the creep over 100 cycles (p = 0.0126) with a rigidity of 201.3% (p = 0.0067). This difference also exists for cyclic torsion where the EPR rotates 52.32% the amount of the DP (p = 0.0044) and has 4.44% of the creep (p < 0.0001). The PBSS and IMN constructs had comparable results across all tests (p > 0.05). Overall, the EPR has comparable or superior mechanical stability to the DP, while the PBSS and IMN have similar mechanical properties. Together, these results can be used as a guide for surgeons to choose different implants depending on individual patient needs.","[""Journal Article"", ""Comparative Study""]","[""Kadkoy Y"", ""Schneider GJ"", ""Ippolito JA"", ""Helbig TP"", ""Subramanian V"", ""Lopez JR"", ""Paglia DN"", ""Benevenia J""]",10.1002/jor.70260,Kadkoy Y,Journal of orthopaedic research : official publication of the Orthopaedic Research Society,0736-0266,8,J Orthop Res,eng,Benevenia J,"[""Humans"", ""Bone Plates"", ""Femur"", ""Bone Transplantation"", ""Cadaver"", ""Biomechanical Phenomena"", ""Allografts"", ""Fracture Fixation, Intramedullary"", ""Plastic Surgery Procedures""]",e70260,42542900,pmc-id: PMC13428981;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42542900/,Intercalary Allograft Reconstruction of the Femur: A Cadaveric Comparison of Intramedullary and Plate Fixation Techniques,44,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"peripherally inserted central catheters (PICCs) and totally implantable ports (Ports) are used for chemotherapy administration. This study aimed to compare their morbidity, mortality, and complication rates. a prospective, randomised, comparative single-centre study with 6 months of follow-up included adult patients with non-hematological malignancies eligible for chemotherapy (palliative, curative, or adjuvant intent). Primary endpoints were the frequency of adverse events (minor/major), impact on quality of life (EORTC QLQ-C30), and medico-economic cost. out of 206 randomised patients, 192 were analysed (Port: 102; PICC: 90). The overall complication rate was 12.5% (n=24). Major complications were significantly more frequent with PICCs (17.8%; 16/90) than with Ports (4.9%; 5/102), with a relative risk of 3.6 (95% CI 1.3-9.9; p=0.041). For chemotherapy lasting less than 6 months, the mean total cost was significantly higher for Ports (160,123.41 DA) than for PICCs (43,259.69 DA) (p<0.001). No significant difference was observed in overall quality of life, with a modest trend favoring Ports for global health and pain at three months. Ports, although costlier, are associated with a significantly lower risk of major complications. They may be preferred as a safe and effective access for long-term chemotherapy. The optimal choice should integrate treatment duration, patient risk profile, and economic constraints.","[""Journal Article"", ""Comparative Study"", ""Randomized Controlled Trial"", ""English Abstract""]","[""Bendjaballah O"", ""Chioukh S"", ""Bensalem A"", ""Makhloufi H"", ""Karoune A"", ""Lekhal A"", ""Mouellef R""]",10.11604/pamj.2026.54.8.50864,Bendjaballah O,The Pan African medical journal,1937-8688,,Pan Afr Med J,fre,Mouellef R,"[""Humans"", ""Female"", ""Prospective Studies"", ""Middle Aged"", ""Antineoplastic Agents"", ""Male"", ""Neoplasms"", ""Quality of Life"", ""Adult"", ""Catheters, Indwelling"", ""Catheterization, Central Venous"", ""Aged"", ""Catheterization, Peripheral"", ""Follow-Up Studies"", ""Young Adult""]",8,42542825,pmc-id: PMC13428653;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42542825/,[The role of central vascular access in the management of patients receiving chemotherapy for non-hematological malignant tumors: PICC line versus implantable Ports],54,M9tGVBHu3a9V04NoP,uf1iwTTToh8LoYnhy
"To investigate the benefits of listening to pre-bedtime music on sleep quality and daytime sleepiness for family caregivers of palliative care patients at home. Multicenter, randomized controlled clinical trial. Seventy-six caregivers were randomly assigned to intervention (n = 38) and control (n = 38) groups. The intervention group listened to individually chosen music for 30 min before bedtime for 7 days, and the control group listened to pre-recorded basic nursing education messages. The primary endpoint was the change in global subjective sleep quality, evaluated via the global Pittsburgh Sleep Quality Index (PSQI) score. Secondary endpoints included daytime sleepiness (Epworth Sleepiness Scale [ESS]), accelerometer-derived sleep parameters, and client satisfaction (CSQ-8). Significant intergroup differences favoring the music intervention were observed in the mean changes from baseline for the primary endpoint of global sleep quality (PSQI Global Score: + 0.60 vs. + 2.05 points; p = 0.006). Descriptive intergroup differences favoring the intervention were observed for subjective nighttime sleep duration (+ 0.55 h; 95% CI 0.19 to 0.94) and daytime sleepiness (ESS: -2.74 points; 95% CI -4.11 to -0.56). Post-intervention satisfaction was significantly higher in the music group (CSQ-8: 27.61 vs. 24.63 points). Listening to pre-bedtime music maintains global subjective sleep quality for family caregivers in a home palliative care setting. Furthermore, exploratory signals suggest it may also prolong subjective sleep duration and reduce daytime sleepiness. The study is registered at Clinical Trials.gov, NCT04491110. Date: 29 July 2020.","[""Journal Article"", ""Randomized Controlled Trial"", ""Multicenter Study""]","[""Valero-Cantero I"", ""Vázquez-Sánchez MÁ"", ""Espinar-Toledo M"", ""Corral-Pérez J"", ""Casals-Sánchez JL"", ""Casals C""]",10.1007/s00520-026-11038-6,Valero-Cantero I,Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer,0941-4355,8,Support Care Cancer,eng,Casals C,"[""Humans"", ""Female"", ""Caregivers"", ""Male"", ""Middle Aged"", ""Sleep Quality"", ""Neoplasms"", ""Aged"", ""Palliative Care"", ""Adult"", ""Music Therapy"", ""Motivation"", ""Sleep Duration"", ""Sleep"", ""Patient Satisfaction"", ""Sleepiness""]",,42545530,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545530/,Effects of motivational music on sleep quality for caregivers of patients with advanced cancer: a randomized controlled trial,34,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"This study evaluated the effectiveness of synchronous online simulation compared with face-to-face instruction in teaching episiotomy repair skills to midwifery students. It also assessed learning satisfaction and self-confidence. A randomized controlled study was conducted with undergraduate students enrolled in a childbirth course. Participants were randomly assigned to either a synchronous online or face-to-face training group. Both groups received structured instruction using standardized simulation models. Outcomes were measured using the Student Satisfaction and Self-Confidence in Learning Scale and the Episiotomy Skill Evaluation Form. Both training formats resulted in similarly high levels of skill performance. The online group demonstrated significantly higher self-confidence and overall learning satisfaction, while skill outcomes were comparable between groups. No significant associations were found between demographic characteristics and study outcomes. Synchronous online simulation is a feasible and effective alternative to face-to-face training for developing procedural skills while also enhancing learner confidence and satisfaction.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Aydın N""]",10.29063/ajrh2026/v30i14.11,Aydın N,African journal of reproductive health,1118-4841,14,Afr J Reprod Health,eng,Aydın N,"[""Humans"", ""Episiotomy"", ""Female"", ""Midwifery"", ""Turkey"", ""Clinical Competence"", ""Simulation Training"", ""Students, Nursing"", ""Pregnancy"", ""Young Adult"", ""Adult""]",,42544921,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42544921/,Effectiveness of online simulation-based versus face-to-face training on episiotomy skills among midwifery students in Turkey,30,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Gestational diabetes mellitus (GDM) commonly presents as insulin resistance and altered lipid metabolism, with evidence linking vitamin D deficiency to its pathogenesis. In this randomized, double-blind, placebo-controlled trial, 120 pregnant women diagnosed with GDM were assigned to receive either vitamin D3 supplements (2000 IU/day) or a placebo for 3 months. Serum vitamin D status, glycemic control parameters, and lipid profiles were evaluated pre- and post-intervention, adjusting for dietary and exercise confounders. After the 3-month intervention, serum 25-hydroxyvitamin D levels in the vitamin D group were significantly higher than those in the placebo group. Vitamin D supplementation effectively reduced fasting plasma glucose, fasting insulin, and HOMA-IR scores. Simultaneously, it significantly decreased triglycerides and LDL-C levels while increasing HDL-C. Total cholesterol levels showed no statistically significant difference between the two groups. Supplementation with 2000 IU vitamin D per day for 3 months yields significant improvements in glucose homeostasis and lipid metabolism in the GDM population. Vitamin D holds promise as an effective auxiliary treatment to enhance maternal metabolic health.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Duan Y"", ""Zhang S"", ""Ma X"", ""Li L"", ""Jia K""]",10.29063/ajrh2026/v30i14.10,Duan Y,African journal of reproductive health,1118-4841,14,Afr J Reprod Health,eng,Jia K,"[""Humans"", ""Female"", ""Diabetes, Gestational"", ""Pregnancy"", ""Insulin Resistance"", ""Dietary Supplements"", ""Vitamin D"", ""Adult"", ""Blood Glucose"", ""Double-Blind Method"", ""Vitamin D Deficiency"", ""Lipids"", ""Lipid Metabolism"", ""Vitamins"", ""Insulin""]",,42544905,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42544905/,Effects of vitamin D supplementation on insulin resistance and lipid metabolic profiles in women with gestational diabetes mellitus: A randomized controlled trial,30,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"To investigate the effects of acupotomy on the paraspinal muscle status via MRI and spinal pelvic parameters, as well as lumbar activity in patients with lumbar disc herniation (LDH) post-surgery, aiming to elucidate the relative correlation and the traditional Chinese medicine (TCM) theory ""regulating tendons to treat bones"". Between December 2019 and December 2021, a total of 104 patients with LDH who underwent percutaneous transforaminal endoscopic discectomy (PTED) were enrolled via a prospective case-control study. They were randomly assigned to the acupotomy group (52 cases, 3 cases lost to follow-up) and the control group (52 cases, 4 cases lost to follow-up). There were 49 patients in the acupotomy group, including 38 males and 11 females, aged from 30 to 70 years with a mean age of (57.21±11.19) years and disease course ranged from 1 to 12 month with a mean of (4.83±1.31) months. The affected segments were L3,4 in 3 cases, L4,5 in 35 cases and L5S1 in 11 cases. Patients in the acupotomy group received one acupotomy intervention within 24 hours after PTED, and additional interventions were performed on postoperative day 7 and day 14 respectively. A total of 48 patients were enrolled in the control group, including 32 males and 16 females, aged from 30 to 69 years with an average age of (53.03±12.37) years old and disease course ranged from 1 to 12 month with a mean disease course of (5.14±1.43) months. The lesioned segments involved L3,4 in 1 case, L4,5 in 37 cases and L5S1 in 10 cases. All patients underwent PTED following the identical surgical procedures without acupotomy intervention, and the remaining rehabilitation and nursing protocols were consistent with those in the acupotomy group. Relevant evaluations were performed on patients before surgery as well as at 6 and 12 months postoperatively. The spinal pelvic parameters included lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT) and pelvic incidence (PI). Indicators of lumbar mobility include the Oswestry Disability Index (ODI) and the Japanese Orthopedic Association Scores (JOA). Pearson correlation analysis was used to study the relationship between spinal muscle structure parameters, spinal pelvic parameters and lumbar mobility function for the patients with LDH after acupotomy, and generalized linear regression analysis was used to study the effects of spinal paravertebral muscle structure on the spinal joint force lines for the patients with LDH after acupotomy. All patients completed 12-month follow-up. At 6 and 12 months after surgery, the multifidus muscle IF values at L4,5 segment in the acupotomy group were (28.50±6.20)% and (26.43±8.80)%, which were significantly lower than the preoperative level of (45.16±10.45)% with statistically significant differences (P<0.01). Meanwhile, these values were obviously lower than those in the control group (40.14±15.16)% and (38.41±14.92)%, and the differences were statistically significant (P<0.01). At 12 months postoperatively, the LL of (47.48±6.49)° and SS of (35.10±7.01)° in the acupotomy group were higher than (43.06±4.22)° and (31.12±10.25)° in the control group respectively, with statistically significant differences (P<0.01). The PT of (13.73±4.66)° was lower than that of the control group (18.01±6.56)°, showing a statistically significant difference (P<0.05). There was no significant difference in PI between the two groups during the study period (all P>0.05). At 12 months postoperatively, IF was correlated with JOA and ODI (P<0.01), and PS was positively correlated with JOA (P<0.01). PT was correlated with JOA and ODI (both P<0.05), LL was positively correlated with JOA (P<0.01), SS was positively correlated with JOA (P<0.01), and SS was strongly positively correlated with JOA (r=0.91). IF was significantly correlated with LL, PT and SS (all P<0.01), PS was also significantly correlated with LL, PT and SS (all P<0.01), and PS was strongly positively correlated with LL (r=0.75). Regression studies showed that the degree of IF at L4,5 segments had statistically significant effects on PT, and SS had statistically significant effects on JOA. Acupotomy based on the theory of ""regulating tendons to treat bones"" can alleviate intramuscular fat infiltration of lumbar multifidus in post-PTED patients, thereby triggering favorable shifts in spinal-pelvic alignment and promoting lumbar functional recovery. Among them, the decrease in fat infiltration rate of multifidus(decreased by approximately 41% at the L4,5 level at 12 months postoperatively) and the increase in SS (increased by approximately 21% at 12 months postoperatively) were the most prominent factors for the changes of spinal paravertebral muscle structure and spinal-pelvic alignment. The relationship between ""regulating tendons first"" and ""treating bones later"" in the TCM theory of ""regulating tendons to treat bones"" can also be explained from an anatomical perspective.","[""Journal Article"", ""Randomized Controlled Trial"", ""English Abstract""]","[""Zhong Y"", ""Ding Y"", ""Fu B"", ""Ma G"", ""Cui H"", ""Chen T"", ""Pan L"", ""Liu Q"", ""Xu H"", ""Ma L"", ""Guan L""]",10.12200/j.issn.1003-0034.20240317,Zhong Y,Zhongguo gu shang = China journal of orthopaedics and traumatology,1003-0034,7,Zhongguo Gu Shang,chi,Guan L,"[""Humans"", ""Male"", ""Female"", ""Middle Aged"", ""Adult"", ""Aged"", ""Intervertebral Disc Displacement"", ""Lumbar Vertebrae"", ""Medicine, Chinese Traditional"", ""Case-Control Studies"", ""Acupuncture Therapy"", ""Prospective Studies""]",683-90,42544804,,2026 Jul 25,2026,https://pubmed.ncbi.nlm.nih.gov/42544804/,[Influence of acupotomy on postoperative musculoskeletal status following lumbar surgery and discussion on its theoretical mechanism in traditional Chinese medicine],39,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"This study investigated the effects of different velocity loss (VL) thresholds during squat exercise at 80% of one-repetition maximum (1RM) on post-activation performance enhancement (PAPE) in basketball players. Nineteen male collegiate basketball players completed three familiarization sessions and four randomized crossover experimental sessions: control (passive rest), 5% VL, 10% VL, and 20% VL. Countermovement jump height (JH), peak power output (PPO), and reactive strength index modified (RSIm) were measured pre-test and at 3-min and 8-min post-squat. Linear mixed-effects models (LMMs) evaluated the effects of time, condition, and mean-centered relative strength on the outcome variables and repetition counts. To identify responders who exhibited meaningful improvements in jump height, the smallest worthwhile change (SWC) was calculated. At the group level, no significant condition × time interactions or main effects of condition were observed for JH, PPO, or RSIm (p > 0.05), indicating no uniform PAPE effect across protocols. Furthermore, no statistically significant strength × time × condition interaction effects were observed. Repetition counts did not differ between the 5% and 10% VL conditions but were significantly lower in both conditions compared to the 20% VL condition (p < 0.01). Individual analysis showed the 20% VL condition yielded the highest number of responders (n = 11; 58%). Squat protocols using 5-20% VL at 80% 1RM did not produce significant group-level CMJ performance improvements, suggesting that a comprehensive warm-up may create a performance ceiling. Furthermore, these responses were not moderated by relative strength. However, the high inter-individual variability and responder rates at higher VL thresholds highlight the importance of individualized PAPE programming.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Wu H"", ""Jukic I"", ""Xu K"", ""Holmberg PM"", ""Du B"", ""Shan Z"", ""Chen W"", ""Jiang J"", ""Guan G"", ""Zhao Q""]",10.7717/peerj.21550,Wu H,PeerJ,2167-8359,,PeerJ,eng,Zhao Q,"[""Humans"", ""Male"", ""Basketball"", ""Athletic Performance"", ""Cross-Over Studies"", ""Muscle Strength"", ""Young Adult"", ""Resistance Training"", ""Force Potentiation""]",e21550,42544330,pmc-id: PMC13429104;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42544330/,The effects of different velocity loss thresholds on post-activation performance enhancement in basketball players,14,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Despite the relevance of neuromuscular electrical stimulation (NMES) dosimetry, it is unclear whether increasing the self-reported tolerated amplitude enhances acute neuromuscular responses. To investigate the acute effects of varying NMES amplitude and type of induced contraction on quadriceps isometric torque (IT) and muscle thickness. A randomized split-limb within-subject repeated-measures design was employed in healthy young adults. IT and quadriceps muscle thickness were the outcomes. Bilateral measurements were obtained using participants seated at 60° (± 5°) of knee flexion. Muscle thickness was assessed via ultrasound and IT using a portable dynamometer. The Aussie current was applied at two doses: the self-reported tolerated amplitude (threshold) and 20% above this value (suprathreshold). Doses were randomly applied to dominant and non-dominant limbs across three assessment conditions in separate sessions: (1) IT at maximal voluntary effort without NMES, (2) IT during NMES alone, and (3) IT during NMES combined with maximal voluntary effort. Forty-one volunteers of both sexes participated. Isolated NMES (threshold = 0.49 and suprathreshold = 0.66 N m kg-1) elicited significantly lower IT than other conditions, whereas maximal voluntary IT (threshold = 2.82 and suprathreshold = 2.84 N m kg-1) did not differ from maximal voluntary IT performed concurrently with NMES (threshold = 3.03 and suprathreshold = 2.91 N m kg-1). The suprathreshold condition resulted in a greater increase in RF muscle thickness. Exploratory regression analysis showed that RF thickness was the only variable significantly associated with IT (R2 = 0.54). Acute Aussie NMES did not increase IT compared with maximal voluntary contraction, and isolated NMES elicited lower IT. However, suprathreshold stimulation acutely increased RF thickness.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Anjos JZD"", ""Cenci OAC"", ""Silva IGD"", ""Albuquerque CE"", ""Bertolini GRF"", ""Carvalho AR""]",10.1002/pri.70300,Anjos JZD,Physiotherapy research international : the journal for researchers and clinicians in physical therapy,1358-2267,4,Physiother Res Int,eng,Carvalho AR,"[""Humans"", ""Male"", ""Female"", ""Quadriceps Muscle"", ""Torque"", ""Isometric Contraction"", ""Young Adult"", ""Adult"", ""Ultrasonography"", ""Muscle Strength"", ""Electric Stimulation""]",e70300,42543542,,2026 Oct,2026,https://pubmed.ncbi.nlm.nih.gov/42543542/,Acute Effects of Varying Neuromuscular Electrical Stimulation Amplitude on Quadriceps Isometric Torque and Muscle Thickness in Healthy Young Adults: A Randomized Split-Limb Trial,31,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"This study aimed to evaluate the clinical efficacy and safety of Compound Ciwujia Granules in patients with chronic fatigue syndrome with syndrome of deficiency of both heart and spleen. It adopted a multicenter, double-blind, double-dummy, randomized controlled trial design and represented a pre-specified subgroup analysis regarding syndrome of deficiency of both heart and spleen from a registered clinical trial. A total of 224 patients with chronic fatigue syndrome with syndrome of deficiency of both heart and spleen were randomized, among whom 222 were included in the full analysis set(FAS). Patients were assigned in a 1∶1 ratio to the treatment group(Compound Ciwujia Granules + Guipi Granules placebo, 111 cases) and the control group(Guipi Granules + Compound Ciwujia Granules placebo, 111 cases), and the course of treatment lasted for 6 weeks. The primary outcome was the improvement rate measured in the Chalder Fatigue Questionnaire-11(CFQ-11) after 6 weeks of treatment. The secondary outcomes included the improvement rate after 3 weeks of treatment, changes in CFQ-11 scores from baseline, changes in CFQ-11 physical and mental fatigue scores from baseline, and changes in TCM syndrome(deficiency of both heart and spleen) scores from baseline after 3 and 6 weeks of treatment. Safety was assessed by recording adverse events. The results showed that 222 patients were included in the FAS, 203 in the per-protocol set(PPS), and 224 in the safety set(SS). In terms of primary outcome, FAS analysis showed that after 6 weeks of treatment, the improvement rate in CFQ-11 scores in experimental group was 73.99%(95%CI[69.10%, 78.87%]), compared to 52.87%(95%CI[47.99%, 57.76%]) in control group, with a between-group difference of 21.11%(95%CI[14.19%, 28.04%], P&lt;0.000 1). PPS analysis was consistent with FAS(difference of 20.54%, P&lt;0.000 1). After treatment for 6 weeks, the decrease in CFQ-11 scores was-13.81 in treatment group, significantly greater than-9.87 in control group(difference of-3.95, 95%CI[-5.23,-2.66], P&lt;0.000 1). Both physical fatigue and mental fatigue domain scores also favored the treatment group after 6 weeks of treatment(P&lt;0.000 1). The reduction in TCM syndrome scores after treatment for 6 weeks was also significantly greater in the treatment group than in the control group(FAS difference of-1.30, P=0.001 4; PPS difference of-1.14, P=0.005 3). No serious adverse events occurred in either group. In conclusion, Compound Ciwujia Granules significantly improved clinical symptoms in patients with chronic fatigue syndrome with syndrome of deficiency of both heart and spleen, demonstrating definite efficacy and good safety.","[""Journal Article"", ""Randomized Controlled Trial"", ""Multicenter Study"", ""English Abstract""]","[""Ren J"", ""Zhang XT"", ""Xie CQ"", ""Wang SJ"", ""Kong LJ"", ""Li JH"", ""Liu LJ"", ""Cui P"", ""Hu ZG"", ""Zhao WX"", ""Zou R"", ""Diwu YC"", ""Fang H"", ""Yang XJ"", ""Li R"", ""Ji G"", ""Fang M"", ""Yuan WA""]",10.19540/j.cnki.cjcmm.20260323.501,Ren J,Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica,1001-5302,13,Zhongguo Zhong Yao Za Zhi,chi,Yuan WA,"[""Humans"", ""Fatigue Syndrome, Chronic"", ""Double-Blind Method"", ""Female"", ""Drugs, Chinese Herbal"", ""Spleen"", ""Adult"", ""Male"", ""Middle Aged"", ""Heart"", ""Treatment Outcome"", ""Young Adult""]",3871-3880,42543377,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543377/,"[Compound Ciwujia Granules for chronic fatigue syndrome with syndrome of deficiency of both heart and spleen: a multicenter, randomized, double-blind, double-dummy, positive drug-controlled trial]",51,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"This study aims to evaluate the feasibility, safety, and peri-implant bone formation of augmenting a proximal femoral nail (PFN) helical blade with a calcium sulfate/hydroxyapatite (CaS/HA) biomaterial combined with systemic zoledronic acid (ZA). This single-center, two-arm, parallel-group, randomized-controlled pilot study included a total of 20 patients with osteoporotic trochanteric fractures (TFs) between December 2023 and January 2025. The patients were randomized into a control group receiving standard PFN or an intervention group receiving PFN augmented with CaS/HA biomaterial. All patients received cefazoline and doxycycline for infection prophylaxis. On postoperative Day 7, both groups received a single intravenous infusion of ZA. The primary outcome was the change in bone mineral density (BMD) defined by previously published peri-implant regions-of-interest at one week and six months postoperatively. Secondary outcomes included tip-apex distance (TAD) for assessing blade migration and the Harris Hip Score (HHS) for functional evaluation. Of a total of 20 patients included in the study, 6 were male and 14 were female with a median age of 81 (range, 65 to 90) years. Regarding intervention delivery, all 10 randomly assigned patients received their intended treatment. While 19 of the 20 randomly assigned patients received the intended treatment; one patient died within the first week and did not receive ZA. The required data for clinical analysis (change in peri-implant BMD, TAD, fracture union, and HHS) could only be extracted for five patients in the control group and five patients in the intervention group. There were no intraoperative complications, and no adverse effects related to the CaS/HA biomaterial were reported. Ten patients were included for the outcome analysis. The intervention group demonstrated a more pronounced increase in peri-implant BMD compared to controls. Additionally, TAD changed more in the control group. Functional evaluation revealed that the intervention group demonstrated a slightly greater HHS improvement. Our study results suggest that augmentation using the CaS/HA and ZA is a feasible and safe procedure for patients with osteoporotic TF. Preliminary findings indicate a potential trend toward enhanced peri-implant bone formation in the intervention group.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Yolaçan H"", ""Raina DB"", ""Lidgren L"", ""Tägil M"", ""Tarasevičius Š"", ""Güler S"", ""Tolunay T"", ""Markevičiūtė V"", ""Sezgin EA""]",10.52312/jdrs.2026.3017,Yolaçan H,Joint diseases and related surgery,2687-4792,3,Jt Dis Relat Surg,eng,Sezgin EA,"[""Humans"", ""Female"", ""Pilot Projects"", ""Zoledronic Acid"", ""Aged"", ""Male"", ""Calcium Sulfate"", ""Durapatite"", ""Proximal Femoral Fractures"", ""Feasibility Studies"", ""Aged, 80 and over"", ""Bone Density Conservation Agents"", ""Bone Nails"", ""Bone Density"", ""Hip Fractures"", ""Osteoporotic Fractures"", ""Fracture Fixation, Intramedullary""]",863-872,42542929,,2026 Jul 25,2026,https://pubmed.ncbi.nlm.nih.gov/42542929/,Safety and feasibility of calcium sulfate/hydroxyapatite with zoledronic acid for the augmentation of helical blades in trochanteric fractures: A randomized pilot study,37,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"The increasing incidence of cancer and the fact that the family is an important factor in cancer care; attention to the positive mental health of cancer patients should be sought to provide solutions to improve the mental health of these caregivers. The present study aimed to investigate the effect of web-based education on positive mental health of family caregivers of breast cancer patients undergoing chemotherapy in educational and treatment centers of Zahedan University of Medical Sciences. This study is a semi-experimental study. The statistical population of the study included all family members of breast cancer patients undergoing chemotherapy who referred to Imam Ali Hospital in Zahedan in 1402. The samples included 70 people who were randomly assigned to two groups: the intervention group and the control group. Caregivers in the intervention group received the necessary training and education for 20 days through a website prepared by the researcher. Data collection was carried out using the demographic information formula and the 9-question positive mental health questionnaire of Lockett before the intervention and 30 days after the intervention. The data were analyzed using descriptive and analytical tests using SPSS 27 statistical software and independent t-tests, paired t-tests, and chi-square tests. Before the intervention, there was no significant difference between the two groups in terms of positive mental health (p = 0.43). However, after web-based training, the results of the analysis of covariance (ANCOVA) with adjustment for pre-test scores showed that the positive mental health score in the intervention group was 19.02 ± 3.05, compared to 15.94 ± 2.61 in the control group (p = 0.0001). The findings of this study suggest that web-based educational programs can enhance the positive mental health of family caregivers of breast cancer patients undergoing chemotherapy. Accordingly, such interventions may be considered an effective supportive approach for family caregivers in oncology care settings.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Rezaee N"", ""Mohammadifard L"", ""Khalilzadeh-Farsangi Z"", ""Fallah-Karimi S""]",10.1007/s00520-026-11054-6,Rezaee N,Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer,0941-4355,8,Support Care Cancer,eng,Fallah-Karimi S,"[""Humans"", ""Female"", ""Caregivers"", ""Breast Neoplasms"", ""Mental Health"", ""Middle Aged"", ""Adult"", ""Internet"", ""Surveys and Questionnaires"", ""Male"", ""Internet-Based Intervention"", ""Iran"", ""Aged""]",,42542461,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42542461/,Investigating the effect of web-based education on positive mental health of family caregivers of breast cancer patients: a quasi-experimental study,34,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"AIM: To compare the regional tissue oxygen saturation under general, spinal, and epidural anesthesias during the posterior lumbar discectomy procedures performed in the prone position. MATERIAL and METHODS: A total of 90 patients with an American Society of Anesthesiologists score I-III were evaluated. Using the research randomizer program, the patients were split into three groups: group of general anesthesia (GA, Group I), group of spinal anesthesia (SA, Group II), and group of epidural anesthesia (EA, Group III). Each patient received non-invasive peripheral arterial oxygen saturation (SpO2), three-lead electrocardiography, non-invasive mean arterial blood pressure (MAP), and the in Spectra TM StO2 Spot Check device with near-infrared spectroscopy (NIRS) technology. The group GA also received end-tidal CO2 monitoring and tissue hemoglobin index (THI), and StO2 monitoring. RESULTS: The data of 90 patients showed that age, weight, height, American Society of Anesthesiologists score, amount of bleeding, duration of surgery, and anesthesia were not statistically significant. Tissue oxygen saturations were detected between groups at the 15th, 30th, 45th, and 60th minutes. The values of group EA at the 15th, 30th, and 45th minutes were higher than group SA (p=0.001; p<0.05). CONCLUSION: This study shows that general anesthesia, as opposed to spinal and epidural anesthesia, offers superior thenar tissue oxygenation in a prone position during posterior lumbar discectomy surgery, despite the ongoing debate over the pros and cons of this position.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Salih MN"", ""Kazancioglu L"", ""Batcik S"", ""Salih O"", ""Kanat A""]",10.5137/1019-5149.JTN.49462-25.2,Salih MN,Turkish neurosurgery,1019-5149,4,Turk Neurosurg,eng,Kanat A,"[""Humans"", ""Diskectomy"", ""Prone Position"", ""Female"", ""Lumbar Vertebrae"", ""Male"", ""Anesthesia, General"", ""Adult"", ""Anesthesia, Epidural"", ""Middle Aged"", ""Oxygen"", ""Anesthesia, Spinal"", ""Oxygen Saturation"", ""Spectroscopy, Near-Infrared""]",542-547,42541779,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42541779/,Pro-Con Debate for Thenar Tissue Oxygenation in Prone Position during Lumbar Discectomy,36,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"People impacted by cancer may be confronted with conflicting and misleading cancer-related information that is everywhere in daily life. The Informed Health Choices-Cancer (IHC-C) programme was developed to equip participants with the skills and knowledge necessary to think critically and make well-informed health choices. To assess the feasibility, acceptability, and preliminary outcomes of the IHC-C programme. We conducted an online pilot randomised trial to compare the IHC-C programme with a waitlist control within a prespecified recruitment window. Adults impacted by cancer (current patients, survivors, informal caregivers and loved ones) were recruited and randomised 1:1. The intervention was a 4-week, nine-unit online learning programme. Primary outcomes assessed feasibility (recruitment, retention, adherence, technical feasibility, and data-collection processes) and acceptability (participation rates, participation burden, and overall acceptability). Secondary outcomes included eHealth literacy, critical thinking and decision-making skills, which were assessed post-intervention. Forty-three participants were randomised (22 intervention; 21 waitlist control), achieving 72% of the recruitment target. In the intervention group, 91% accessed the platform and 64% completed all nine units. Outcome assessment completion was 64% (14/22) in the intervention group and 81% (17/21) in the control group. Acceptability was high among intervention completers, as indicated by both quantitative and qualitative measures. eHealth literacy scores were high in both groups, with ceiling effects and no between-group difference (Hodges-Lehmann median difference -1.0, 95% CI -5.0 to 1.0). Critical thinking and decision-making quiz scores were higher in the intervention group in exploratory analyses (median difference: 1.0, 95% CI: 1.0-2.0), although the distributions clustered near the upper range. The IHC-C programme was feasible to deliver and acceptable to participants within a defined recruitment period. These findings support progression to a fully powered trial, with refinements to engagement strategies and outcome measurement. This trial was registered on ISRCTN registry with ID ISRCTN17391470.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Li M"", ""Tierney M"", ""Beecher C"", ""Dowling M"", ""Duffy AG"", ""Duggan C"", ""Grimes DR"", ""Kennan A"", ""Kilty C"", ""Nsangi A"", ""Oxman AD"", ""Stewart DC"", ""Toomey E"", ""Devane D""]",10.1002/pon.70563,Li M,Psycho-oncology,1057-9249,8,Psychooncology,eng,Devane D,"[""Humans"", ""Pilot Projects"", ""Female"", ""Middle Aged"", ""Male"", ""Neoplasms"", ""Adult"", ""Aged"", ""Feasibility Studies"", ""Health Literacy"", ""Decision Making"", ""Choice Behavior"", ""Patient Education as Topic"", ""Health Knowledge, Attitudes, Practice"", ""Consumer Health Information""]",e70563,42541744,pmc-id: PMC13428618;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42541744/,Improving Critical Appraisal of Cancer-Related Health Information: A Pilot Randomised Trial of the Informed Health Choices-Cancer Programme,35,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"This study aimed to investigate whether genetic variability, assessed through polygenic risk scores (PRSs), predicts blood pressure (BP) changes in individuals with systemic arterial hypertension (SAH), and to explore potential interactions between genetic risk and dietary interventions. This study represents a secondary analysis of data from the Brazilian multicentre trial (NUPRESS), which compared a Dietary Approach to Stop Hypertension (DASH) diet (control group) with a multicomponent intervention (intervention group) over 180 days in adults with SAH. Participants underwent anthropometric assessment, cardiovascular risk evaluation, dietary assessment, and genotyping using a genomic microarray. Single nucleotide polymorphisms (SNPs) associated with BP changes were identified and used to construct PRSs. Multiple linear regression models were employed to examine associations between PRSs, dietary interventions, and changes in systolic (ΔSBP) and diastolic BP (ΔDBP). A total of 114 SNPs were associated with ΔSBP and 101 with ΔDBP. The resulting PRSs showed strong correlations with both ΔSBP (r = 0.85; p < 0.0001) and ΔDBP (r = 0.84; p < 0.0001). No significant effect of dietary intervention on BP changes was observed, and no interaction was identified between PRSs and dietary approach for ΔSBP (p = 0.98) or ΔDBP (p = 0.13). PRSs derived from BP-associated SNPs were strong predictors of BP changes over six months, independent of dietary intervention. These findings support the potential utility of genetic profiling in predicting individual variability in BP response, although replication in independent cohorts is warranted. Main study trial registration number NCT03793881 on ClinicalTrials.gov.","[""Journal Article"", ""Multicenter Study"", ""Randomized Controlled Trial""]","[""Holzbach LC"", ""Marcadenti A"", ""Bersch-Ferreira AC"", ""Machado RHV"", ""Carvalho APPF"", ""Pinto SL"", ""Penafort AM"", ""Coelho ASG"", ""Cominetti C""]",10.1007/s00394-026-04072-x,Holzbach LC,European journal of nutrition,1436-6207,5,Eur J Nutr,eng,Cominetti C,"[""Humans"", ""Genetic Risk Score"", ""Blood Pressure"", ""Polymorphism, Single Nucleotide"", ""Hypertension"", ""Female"", ""Male"", ""Middle Aged"", ""Brazil"", ""Dietary Approaches To Stop Hypertension"", ""Adult""]",,42541580,pmc-id: PMC13428793;,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42541580/,Polygenic risk scores predict blood pressure changes independent of dietary intervention: a secondary analysis of the NUPRESS trial,65,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Early mobilisation after myocardial infarction (MI) is strongly recommended. However, evidence regarding the benefits of structured physiotherapy during the acute in-hospital phase remains limited. This controlled clinical trial (CCT) aimed to evaluate whether an intensive early physiotherapy programme could improve health-related quality of life (HRQoL) and psychological well-being. This CCT included 172 adults hospitalised after MI and treated with primary percutaneous coronary intervention (PCI). The participants were quasi-randomly allocated (1:1) to the intervention or control group based on the hospital room number. They received either an intensive physiotherapy programme (daily supervised mobilisation, education and graded activity) or standard medical care and an informational flyer. Primary outcomes included HRQoL (MacNew) and psychological well-being (Hospital Anxiety and Depression Scale, HADS-D). Clinically important changes were evaluated using the standardised response mean (SRM, which reflects the clinical relevance of observed changes), and the minimal clinically important difference (MCID, the smallest change in an outcome perceived as important by patients). Statistical analysis was conducted to assess group-by-time and pre-post interaction effects. Clinical significance metrics: The intervention group showed less deterioration in overall HRQoL (SRM: 0.04 vs. 0.1) and an enhancement in the MacNew emotional subscale (SRM: 0.22 vs. 0.09) compared with the control group. The HADS-D improved to a greater extent in the intervention group, exceeding the MCID (1.7 points). There were no statistically significant interaction effects between groups by time (interaction factor group * factor time; HRQoL p = 0.68 and anxiety/depression p = 0.15) or between the time points (pre-post, main effect factor time; HRQoL p = 0.35 and anxiety/depression p = 0.4). Clinically, intensive early in-hospital physiotherapy may lead to improved psychological outcomes and an attenuation of HRQoL decline. Although the change in HADS-D in the intervention group did not reach statistical significance, it exceeded the MCID, indicating a clinically meaningful improvement from the patients' perspective. The implementation of structured early mobilisation protocols may provide clinically relevant benefits during the acute post-PCI hospitalisation period and warrants further investigation. Ethical approval was first submitted in January 2023, then resubmitted after minor revision in March 2023, and was then accepted on 15 March 2023 (Reg.Nr. K-2023-001).","[""Journal Article"", ""Randomized Controlled Trial""]","[""Balla K"", ""Haase KK"", ""Wick A""]",10.1002/pri.70305,Balla K,Physiotherapy research international : the journal for researchers and clinicians in physical therapy,1358-2267,4,Physiother Res Int,eng,Wick A,"[""Humans"", ""Quality of Life"", ""Male"", ""Myocardial Infarction"", ""Female"", ""Middle Aged"", ""Anxiety"", ""Physical Therapy Modalities"", ""Depression"", ""Aged"", ""Treatment Outcome"", ""Percutaneous Coronary Intervention"", ""Early Ambulation""]",e70305,42541455,pmc-id: PMC13428498;,2026 Oct,2026,https://pubmed.ncbi.nlm.nih.gov/42541455/,"Effects of Intensive Early Physiotherapy Intervention After Myocardial Infarction on Quality of Life, Anxiety and Depression Scores: A Controlled Clinical Trial",31,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"The treatment of common warts can occasionally be a challenge in recalcitrant cases, either recurrent ones or non-responders to treatment. In the current study, the efficacy and safety of monotherapy with topical 50% urea cream and combination therapy with topical 50% urea cream and carboxytherapy were assessed and compared in the treatment of recalcitrant common wart. Twenty subjects with recalcitrant common warts in the extremities (excluding the plantar surface) were selected. For the lesions of one side of the body, topical 50% urea cream was used 2 times a day (group A), while for the other side, combination of topical 50% urea cream and carboxytherapy was administered (group B). Carboxytherapy was done weekly, and both treatments were continued until complete resolution. The lesion count and size were assessed until 2 weeks after the fifth session of carboxytherapy. Recurrence rate was evaluated 6 months after complete resolution. Regarding the lesion count, no statistically significant difference was seen between the 2 groups. In group B, decrease of lesion size was significantly greater than that in group A. The time for complete resolution was significantly shorter in the group B. No significant adverse event was reported in either treatment group. No recurrence of lesions was reported 6 months after complete resolution in either group. Our findings demonstrated that both monotherapy with topical 50% urea cream and combination therapy with topical 50% urea cream and carboxytherapy were effective in the treatment of recalcitrant recurrent common warts, although the effectiveness of combination therapy was statistically more.","[""Journal Article"", ""Randomized Controlled Trial"", ""Comparative Study""]","[""Bagherani N"", ""Rafiei M"", ""Smoller BR"", ""Yaghoobi R"", ""Moradzade R"", ""Mirnezami M"", ""Rafie Z""]",10.1002/jmv.71061,Bagherani N,Journal of medical virology,0146-6615,8,J Med Virol,eng,Rafie Z,"[""Humans"", ""Urea"", ""Treatment Outcome"", ""Warts"", ""Female"", ""Adult"", ""Administration, Topical"", ""Male"", ""Young Adult"", ""Single-Blind Method"", ""Drug Therapy, Combination"", ""Adolescent"", ""Middle Aged"", ""Recurrence""]",e71061,42541394,pmc-id: PMC13428380;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42541394/,"Assessment and Comparison of Efficacy and Safety of Monotherapy With Topical 50% Urea Cream and Combination Therapy With Topical 50% Urea Cream and Carboxytherapy in Treatment of Recalcitrant Common Wart: A Randomized, Single-Blinded, 2-Split Clinical Trial",98,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"To explore the safety and efficacy of the novel G protein-biased μ-opioid receptor agonist oliceridine for painless gastroscopy. This study is a single-center randomized controlled clinical trial. One hundred and eighty-eight patients scheduled for painless gastroscopy were randomly assigned to four groups: Group L (oliceridine 10 μg/kg + propofol 2mg/kg), Group M (oliceridine 20 μg/kg + propofol 2mg/kg), Group H (oliceridine 30 μg/kg + propofol 2mg/kg) and Group C (sufentanil 0.1 μg/kg + propofol 2mg/kg). The primary outcome was the incidence of respiratory depression. Secondary outcomes included the incidence of respiratory arrest, bradypnea (respiratory rate<8 bpm) and hypoxemia (pulse oxygen saturation (SpO2) < 90%). Other outcomes included procedure and sedation-related outcomes, perioperative vital signs and adverse effects were recorded. Among the 184 patients, 46, 46, 45 and 47 patients were randomly assigned to the L, M, H and C groups, respectively, and completed the trial. The incidence of respiratory depression in Group C (55.32%) and Group H (46.67%) was significantly higher than that in Group L (15.22%) and Group M (17.39%) (P<0.05). The incidence of respiratory arrest was higher in group H (42.22%) and group C (51.06%) compared to group L (13.04%) and group M (15.22%) (P < 0.05). The incidence of bradypnea and hypoxemia in group C (31.90% and 14.89%) was higher than that in group M (6.5% and 0) (P < 0.05). The sedation success rate was significantly lower in Group L than in Group M (71.74% vs 93.48%; P < 0.05). No significant differences were observed in the incidence of postoperative adverse effects. 10 μg/kg and 20 μg/kg oliceridine is associated with a reduced risk of respiratory depression when co-administered with propofol for painless gastroscopy in adults, and the 20 μg/kg oliceridine exhibits superior sedative efficacy.","[""Journal Article"", ""Randomized Controlled Trial"", ""Case Reports"", ""Clinical Trial""]","[""Hu X"", ""Yang C"", ""Li J"", ""Wang F"", ""You H"", ""Chen C"", ""Jiang L""]",10.2147/DDDT.S609746,Hu X,"Drug design, development and therapy",1177-8881,,Drug Des Devel Ther,eng,Jiang L,"[""Humans"", ""Female"", ""Propofol"", ""Male"", ""Gastroscopy"", ""Middle Aged"", ""Adult"", ""Aged""]",609746,42540637,pmc-id: PMC13426355;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540637/,"Safety and Efficacy of Oliceridine Combined with Propofol for Painless Gastroscopy: A Single-Center, Randomized, Parallel Controlled Clinical Trial",20,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"OBJECTIVE: To assess whether adding psychologically informed education (PIE) videos to usual care physical therapy (PT) improved function (primary outcome) and pain-related beliefs, pain intensity, and physical activity (secondary outcomes) in adolescents with atraumatic leg pain. DESIGN: Double-blinded randomized controlled trial. METHODS: Eighty-three adolescents (mean age, 14.7 ± 1.6 years; 62% female) with atraumatic leg pain (including patellofemoral pain, apophyseal injuries, tendinopathy) were randomized to view 3 PIE or control videos. All participants completed 6 weeks of PT. The PIE videos targeted kinesiophobia, fear avoidance, and catastrophizing; the control videos addressed anatomy and biomechanics. Outcomes were assessed at baseline, 1 month, and 12 months. The primary outcome was change in function (Lower Extremity Functional Scale). Secondary outcomes were pain-related beliefs, pain intensity, and physical activity. RESULTS: There was no between-group difference in function over time (P = .40), with similar changes at 1 month (PIE: 12.5 [95% CI: 7.4, 17.5]; control: 8.9 [95% CI: 5.1, 12.8]) and 12 months (PIE: 17.1 [95% CI: 11.8, 22.5]; control: 14.9 [95% CI: 10.3, 19.5]). Adolescents in the PIE group had a greater reduction in pain-related beliefs after 1 month (fear avoidance: PIE, 50% vs control, 23%; kinesiophobia: PIE, 50% vs control, 8%; catastrophizing: PIE, 27% vs control, 19%; P = .01). There were no between-group differences in pain (P = .82) or physical activity (P = .50). At 12 months, 34% (n = 26) reported persistent pain. CONCLUSION: Brief PIE did not improve function, pain intensity, or physical activity when added to usual PT care for adolescents with atraumatic leg pain. Adolescents who received the PIE videos reduced pain-related beliefs. J Orthop Sports Phys Ther 2026;56(8):555-562. Epub 26 May 2026. doi:10.2519/jospt.2026.14057.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Selhorst M"", ""Hoehn J"", ""Benedict J"", ""Joshi S"", ""Yang J""]",10.2519/jospt.2026.14057,Selhorst M,The Journal of orthopaedic and sports physical therapy,0190-6011,8,J Orthop Sports Phys Ther,eng,Yang J,"[""Humans"", ""Adolescent"", ""Female"", ""Kinesiophobia"", ""Double-Blind Method"", ""Male"", ""Patient Education as Topic"", ""Catastrophization"", ""Fear"", ""Pain Measurement"", ""Physical Therapy Modalities"", ""Exercise""]",555-562,42538789,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42538789/,The Effect of a Brief Psychologically Informed Education Intervention for Improving Function in Adolescents With Atraumatic Leg Pain: A Randomized Controlled Trial,56,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"<sec><title>BACKGROUND</title>Two-month smear conversion has been adopted instead of cultures to predict unfavourable bacteriological outcomes in TB treatment. However, this approach is limited by lower sensitivity and specificity.</sec><sec><title>OBJECTIVE</title>In absence of early-stage biomarkers of treatment response, we investigated the association between bacteriological outcome and microscopy data with auramine and fluorescein diacetate stains at baseline and during the first 2 weeks of treatment in the context of the OneRIF trial. This is a secondary analysis of data collected during the OneRIF trial.</sec><sec><title>RESULTS</title>Failure or relapse occurred in 15 patients of 321 treated with double-dose R. Only quantitative baseline auramine significantly predicted failure or relapse: for every 100 bacilli per field increase, there was 5% higher odds of having an unfavourable bacteriological outcome.</sec><sec><title>CONCLUSION</title>While quantitative baseline auramine predicted having an unfavourable bacteriological outcome, considering our small data we could not identify any added value in implementing quantitative bacillary load in the first 2 weeks of treatment. These findings should be interpreted with caution as we were limited by the relatively low number of failure and relapse.</sec>.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Vellere I"", ""Jacobs BK"", ""Maug AKJ"", ""Hossain MA"", ""De Jong BC"", ""Lynen L"", ""Lorent N"", ""Decroo T""]",10.5588/ijtld.26.0051,Vellere I,The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease,1027-3719,8,Int J Tuberc Lung Dis,eng,Decroo T,"[""Humans"", ""Antitubercular Agents"", ""Benzophenoneidum"", ""Bacilloscopy"", ""Predictive Value of Tests"", ""Mycobacterium tuberculosis"", ""Bacterial Load"", ""Treatment Outcome"", ""Time Factors"", ""Sputum"", ""Recurrence""]",365-370,42538629,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538629/,Evaluation of microscopically quantitative loads of bacilli as early predictors of TB treatment outcome,30,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with limited treatment options. LTI-03 promotes alveolar epithelial cell survival and reduces profibrotic protein expression in experimental models of IPF. In this Phase 1b, randomized, double-blind, placebo-controlled dose-escalation study, 24 participants with IPF were randomized 3:1 to inhaled LTI-03 5 mg/day (N = 9), LTI-03 10 mg/day (N = 9) or placebo (N = 6) for 14 days and included in all analyses (ClinicalTrials.gov: NCT05954988). The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs). Exploratory analyses included pharmacokinetics and disease-related biomarkers. LTI-03 was well-tolerated, with no treatment-related discontinuations, no severe TEAEs, and no evidence of airway obstruction by spirometry and associated symptoms. In deep bronchial brushings, both LTI-03 doses significantly reduced interleukin-11 (p = 0.0406 at 5 mg/day; p = 0.044 at 10 mg/day) and thymic stromal lymphopoietin (p = 0.0256 at 5 mg/day; p = 0.0128 at 10 mg/day) versus placebo. The 10 mg/day dose suppressed collagen type 1 alpha chain 1 (p = 0.0248), CXC chemokine ligand 7 (p = 0.0248) and galectin-7 (p = 0.0332). Other measured biomarkers were not significantly changed. The favorable safety profile and reductions in disease-related biomarkers support further evaluation of inhaled LTI-03 for IPF. This study was fully funded by Rein Therapeutics, Inc.","[""Journal Article"", ""Randomized Controlled Trial"", ""Clinical Trial, Phase I""]","[""Molyneaux PL"", ""Hirani NA"", ""Chia CCK"", ""Kulkarni T"", ""Zaman T"", ""Kaner RJ"", ""Coelho AL"", ""Jannini-Sa YAP"", ""Windsor B"", ""Kruger S"", ""Christensen DJ"", ""Shoemaker SA"", ""Hogaboam CM"", ""MacKenzie B"", ""Günther A""]",10.1038/s41467-026-75291-3,Molyneaux PL,Nature communications,2041-1723,1,Nat Commun,eng,Günther A,"[""Humans"", ""Idiopathic Pulmonary Fibrosis"", ""Female"", ""Male"", ""Double-Blind Method"", ""Aged"", ""Middle Aged"", ""Administration, Inhalation"", ""Cytokines"", ""Biomarkers"", ""Thymic Stromal Lymphopoietin"", ""Dose-Response Relationship, Drug"", ""Interleukin-11"", ""Treatment Outcome""]",,42538332,pmc-id: PMC13427755;,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538332/,Inhaled LTI-03 for idiopathic pulmonary fibrosis: a randomized dose escalation study,17,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Multicentre randomised controlled trial. Eight spinal cord injury (SCI) centres and 15 rehabilitation centres in Germany. To demonstrate the superiority of neuromuscular feedback therapy using an exoskeleton compared to conventional therapy in terms of improving walking ability in patients with chronic SCI. A total of 180 patients with chronic complete or incomplete SCI and residual motor function in the lower extremities are to be included. Baseline examination will be carried out at the recruiting SCI centres, followed by 1:1 randomisation at the rehabilitation centre allocating patients to the control group (conventional therapy) or the intervention group (Hybrid Assistive Limb therapy). Both interventions take place to the same extent (5×/week, 60 min) over a period of 12 weeks at the rehabilitation centres. After the 12-week intervention phase, the primary (therapy response defined as relevant improvement in at least one of the following: 6 min walk test, 10 m walk test and Walking Index for Spinal Cord Injury II score) and secondary endpoints (quality of life, pain, bladder and bowel function) are recorded by blinded observers at the SCI centres or via patient app. The effects of the intervention will be evaluated in the middle and at the end of the 6-month follow-up period. The study is approved by the ethics committee of the Medical Association of Westphalia-Lippe (register no. 2025-2014 f-S). The participants were informed about the aims and procedures of the study and gave their written consent. This protocol follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement. The study results will be published in accordance with the Consolidated Standards of Reporting Trials (CONSORT), regardless of whether the results are positive or negative. The datasets belong to the Joint Federal Committee of Germany and are available there on request. DRKS 00035487.","[""Journal Article"", ""Multicenter Study"", ""Randomized Controlled Trial"", ""Comparative Study""]","[""Aach M"", ""Brinkemper A"", ""Grasmücke D"", ""Zhivotovskaya A"", ""Königshausen M"", ""Schildhauer TA"", ""Uphues C"", ""Schäkermann M"", ""Pogoreuz M"", ""Mai A"", ""Timmesfeld N""]",10.1136/bmjopen-2026-116779,Aach M,BMJ open,2044-6055,7,BMJ Open,eng,Timmesfeld N,"[""Humans"", ""Spinal Cord Injuries"", ""Lower Extremity"", ""Walking"", ""Germany"", ""Female"", ""Quality of Life"", ""Adult"", ""Male"", ""Chronic Disease"", ""Recovery of Function"", ""Treatment Outcome"", ""Middle Aged"", ""Research Design""]",e116779,42538116,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538116/,Testing neuromuscular feedback therapy in patients with chronic spinal cord injury with residual motor function in the lower extremities compared to 'conventional' therapy: protocol for a multicentre randomised controlled trial,16,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Artificial intelligence (AI) is beginning to be used within digital surgical wound monitoring to facilitate implementation at scale. AI acceptability is essential to its success. This study aimed to explore patient and staff acceptability of an AI-based digital surgical wound monitoring platform. Qualitative interviews SETTING: Two hospitals performing cardiac surgery in England. 20 patients undergoing cardiac surgery and 10 clinical staff participating in a randomised feasibility trial of surgical wound monitoring with AI. Semi-structured interviews were conducted focusing on participants' experiences or perceptions of AI-based digital surgical wound monitoring. Data were analysed, guided by the theoretical framework of acceptability. Patient and staff acceptability of AI within surgical wound monitoring. Patients and staff were supportive of the use of AI within surgical wound monitoring and felt safety was improved, access was increased and efficiency was improved. AI monitoring was perceived to allow the early detection and treatment of surgical wound complications and facilitate the implementation of monitoring at scale for all patients. Some participants were concerned about data security risks, staff over-reliance on AI and the loss of human interaction. AI-supported digital surgical wound monitoring appeared acceptable to participants within this feasibility study. Further research is needed to evaluate implementation in broader settings. ISRCTN16900119 and NCT06475703.","[""Journal Article"", ""Multicenter Study"", ""Randomized Controlled Trial""]","[""Tanner J"", ""Rochon M"", ""Cariaga K"", ""Harris R"", ""Beckhelling J"", ""Bouttell J"", ""Bolton S"", ""Wilson K"", ""Jurkiewicz J"", ""Dhoonmoon L"", ""Mostafa N"", ""Dummer J"", ""Basilio K"", ""Magboo R"", ""Procter K"", ""McMillan C""]",10.1136/bmjopen-2026-116323,Tanner J,BMJ open,2044-6055,7,BMJ Open,eng,McMillan C,"[""Humans"", ""Artificial Intelligence"", ""Feasibility Studies"", ""Female"", ""Male"", ""Qualitative Research"", ""Surgical Wound"", ""Attitude of Health Personnel"", ""Middle Aged"", ""Cardiac Surgical Procedures"", ""Aged"", ""England"", ""State Medicine"", ""Interviews as Topic"", ""Monitoring, Physiologic"", ""Digital Health"", ""Adult""]",e116323,42538113,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538113/,Exploring patient and NHS staff acceptability of artificial intelligence-supported surgical wound monitoring within the WISDOM feasibility study: a multi-centre qualitative interview study,16,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Racial and ethnic differences in diabetic cardiomyopathy (DbCM) exist, with black and Hispanic participants showing poorer health status. It remains unclear whether these differences affect the natural progression of the disease. We aimed to evaluate disease progression in individuals with DbCM, as well as racial differences in the response to AT-001. A total of 625 participants with DbCM were randomised to either placebo or AT-001 and followed for 15 months. The primary outcome was change in peak oxygen uptake (peak VO2) and secondary outcomes included Kansas City Cardiomyopathy Questionnaire (KCCQ) and Physical Activity Scale for the Elderly scores. Analyses were stratified by race and ethnicity (black, Hispanic, white). Black and Hispanic participants who received placebo experienced greater declines in peak VO2 (-0.74 and -1.67 mL/kg/min, respectively) compared with white participants (-0.23 mL/kg/min, p=0.005). AT-001 demonstrated a non-statistically significant trend towards slower declines in peak VO2 in black and Hispanic participants (-0.31 and -0.62 mL/kg/min, p=0.29, respectively). Black participants who received placebo had the largest declines in most KCCQ scores. Black and Hispanic participants with DbCM experienced faster disease progression, with black participants showing the most pronounced functional and quality of life declines. The effect of AT-001 on peak VO2 changes was not statistically significant with similar effects between racial and ethnic groups (NCT04083339). NCT04083339.","[""Clinical Trial, Phase III"", ""Journal Article"", ""Multicenter Study"", ""Randomized Controlled Trial""]","[""Batista JL"", ""Liu Y"", ""Butler J"", ""Del Prato S"", ""Ezekowitz JA"", ""Lam CSP"", ""Marwick TH"", ""Rosenstock J"", ""Tang WHW"", ""Perfetti R"", ""Urbinati A"", ""Zannad F"", ""Ilonze O"", ""Januzzi JL""]",10.1136/openhrt-2026-004312,Batista JL,Open heart,2053-3624,2,Open Heart,eng,Januzzi JL,"[""Aged"", ""Female"", ""Humans"", ""Male"", ""Middle Aged"", ""Black or African American"", ""Diabetic Cardiomyopathies"", ""Disease Progression"", ""Double-Blind Method"", ""Enzyme Inhibitors"", ""Hispanic or Latino"", ""Oxygen Consumption"", ""Time Factors"", ""Treatment Effect Heterogeneity"", ""Treatment Outcome"", ""United States"", ""White""]",,42538062,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538062/,Racial outcomes in patients with diabetic cardiomyopathy treated with an aldose reductase inhibitor: the ARISE-HF trial,13,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"This randomized controlled trial (RCT) aimed to compare clinical and radiological outcomes of cemented acetabular component in primary total hip arthroplasty (THA) in patients aged under 60 years with and without autologous impaction bone grafting (IBG). A single-centre, triple-blinded RCT was conducted in patients aged 18 to 59 years undergoing primary THA without acetabular defects. Patients were randomized to receive either IBG or no IBG. Noninferiority of IBG was assessed for the primary endpoint, the Hip disability and Osteoarthritis Outcome Score (HOOS) sub-scale for activities of daily living (ADL) at one-year follow-up. Secondary outcomes included other patient-reported outcome measures (PROMs), perioperative outcomes, complications, and radiological outcomes. Radiographs assessed acetabular component and centre of rotation positioning, offset changes, and the presence of radiolucent lines in the bone-cement interface. A total of 131 patients were randomized. No significant group differences were found for the HOOS-ADL sub-scale at one year (mean difference 1.9 points (95% CI -4.85 to 8.7); p = 0.578), meeting the criteria for noninferiority. Furthermore, there was no effect of group on the scores for other PROMs. Surgery duration (+ 7.5 minutes; p < 0.001) and blood loss (+ 100 ml; p = 0.001) were significantly higher in the IBG group. Complication and revision rates were comparable. Radiologically, the IBG group had significantly fewer radiolucent lines in the bone-cement interface than the control group at one-year follow-up (p < 0.001). Compared with preoperatively, the postoperative position of the centre of rotation was less superior and medial in the IBG group (p = 0.024). The use of autologous IBG with a cemented acetabular component in primary THA in young patients is noninferior to standard cemented fixation regarding short-term clinical outcomes. IBG improves vertical position of the centre of rotation and early radiological fixation by reducing radiolucent lines around the cup, suggesting potential benefits for long-term acetabular component survival.","[""Journal Article"", ""Randomized Controlled Trial"", ""Equivalence Trial""]","[""de Boer DR"", ""Pasman P"", ""Munnik-Hagewoud R"", ""Steinweg MJQ"", ""Edens MA"", ""van Driel PBAA"", ""Ettema HB""]",10.1302/0301-620X.108B8.BJJ-2025-1692.R2,de Boer DR,The bone & joint journal,2049-4394,8,Bone Joint J,eng,Ettema HB,"[""Humans"", ""Arthroplasty, Replacement, Hip"", ""Female"", ""Middle Aged"", ""Adult"", ""Bone Transplantation"", ""Male"", ""Acetabulum"", ""Adolescent"", ""Bone Cements"", ""Young Adult"", ""Treatment Outcome"", ""Hip Prosthesis"", ""Osteoarthritis, Hip"", ""Transplantation, Autologous""]",995-1002,42538005,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42538005/,Autologous impaction bone grafting of a cemented acetabular component in primary total hip arthroplasty in young patients: a randomized controlled trial,108-B,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
CTRI/2025/06/088470 (https://ctri.nic.in).,"[""Journal Article"", ""Randomized Controlled Trial""]","[""Surampalli G"", ""S M"", ""Mudhigonda M""]",10.1080/19390211.2026.2689348,Surampalli G,Journal of dietary supplements,1939-0211,4,J Diet Suppl,eng,Mudhigonda M,"[""Humans"", ""Plant Extracts"", ""Double-Blind Method"", ""Female"", ""India"", ""Plant Roots"", ""Perimenopause"", ""Phytotherapy"", ""Middle Aged"", ""Hot Flashes""]",490-518,42537691,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42537691/,"Efficacy and Safety of Shatavari Root Extract in Managing Peri-Menopausal Symptoms-A Randomized, Double-Blind, Placebo Controlled Clinical Trial",23,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Diabetes mellitus management requires considerable patient self-efficacy, knowledge, and support for social determinants of health. These needs become particularly acute during pregnancy. Mobile health (mHealth) tools are a promising approach to enhance patient engagement with the health care system, education, and health promotion and may be particularly helpful during the period of rapid skills acquisition, which is a hallmark of experiencing diabetes during pregnancy. Therefore, we developed SweetMama, a web-based mHealth app designed to support and provide information to low-income pregnant individuals with gestational diabetes mellitus (GDM) or type 2 diabetes mellitus (T2DM). This study aimed to understand the user experiences of low-income pregnant people who were randomized to use SweetMama during a feasibility trial. This mixed methods secondary analysis of data from a feasibility randomized controlled trial (RCT) included participants randomized to SweetMama, an interactive, web-based mHealth app with multiple motivational and educational features that help reduce barriers to care, offer health education, and aim to improve diabetes self-care for low-income pregnant people. In the parent trial, English-speaking pregnant individuals with GDM or T2DM were randomized to use SweetMama during pregnancy or usual care. SweetMama users experienced an individualized curriculum from enrollment through 6 weeks postpartum. Upon exit, users completed 2 qualitative interviews (during the delivery hospitalization and at the postpartum visit) and surveys assessing standardized usability metrics. The surveys included the System Usability Scale (SUS), the Usefulness, Satisfaction, Ease of Use (USE) scale, and the mHealth App Usability Questionnaire (MAUQ) to assess usability. Qualitative data were analyzed using constant comparative techniques. Of 30 SweetMama users, 60% (n=18) had GDM, 83.3% (n=25) had publicly funded prenatal care, and the majority identified as non-Hispanic Black (n=17, 56.7%) or Hispanic (n=11, 36.7%). Scores on the SUS (median 85.0/100, IQR 70.0-88.8; ≥71% indicates acceptable or higher usability), USE (overall median 84.5/100, IQR 81.0-91.4), and MAUQ (median 84.1/100, IQR 79.0-91.3) indicated favorable usability assessments, particularly for the ""ease of learning"" domain. Qualitative interviews supported these findings: participants described the app as easy to navigate, well organized, and helpful for staying on track, citing features such as clear visual design, timely text reminders, and actionable tips. Users valued motivational elements and content specificity, while recommending increased customization and enhanced esthetics. In this user experience evaluation of a web-based mHealth app for low-income pregnant individuals with diabetes, participants found the tool to be user-friendly, visually appealing, informative, and motivating. Constructive feedback for application improvement for use in a future larger trial of clinical effectiveness was collected.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Raucher SL"", ""Lu L"", ""Merchant T"", ""Soyemi E"", ""Niznik C"", ""Saber R"", ""Yeh C"", ""Yee LM""]",10.2196/84061,Raucher SL,JMIR human factors,2292-9495,,JMIR Hum Factors,eng,Yee LM,"[""Humans"", ""Female"", ""Pregnancy"", ""Adult"", ""Poverty"", ""Mobile Applications"", ""Diabetes Mellitus, Type 2"", ""Diabetes, Gestational"", ""Telemedicine"", ""Feasibility Studies"", ""Internet"", ""Digital Health"", ""Self Care""]",e84061,42536883,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536883/,User Experience of a Web-Based Mobile Health App Supporting Low-Income Pregnant Individuals With Diabetes: Mixed Methods Study,13,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Examine how sponsorship disclosures and nicotine warning labels (NWLs) affect responses to proe-cigarette Instagram posts among Mexican young adults. In a 2 x 2 online experiment, Mexicans aged 18-24 (N= 699; 53% users and 47% nonusers of cigarettes or e-cigarettes who were susceptible to future use) were randomly assigned to view one of four Instagram posts: 1) control, 2) disclosure-only, 3) NWL-only, or 4) combination. Participants reported susceptibility to e-cigarettes, positive expectancies, and risk perceptions. Outcomes were analyzed via logistic regression (ref=control). Compared to the control, participants exposed to the NWL alone or combined were less likely to be curious to try the e-cigarette (OR= 0.54, 95%CI 0.35,0.83; OR= 0.54, 95%CI 0.34,0.84), try it if offered by a friend (OR= 0.59, 95%CI 0.39,0.90; OR= 0.55, 95%CI 0.36,0.85), or expect to enjoy use (OR= 0.64, 95%CI 0.42,0.97; OR= 0.65, 95%CI 0.43,1.00). Risk perceptions did not differ; disclosures had no effect. The disclosure-only condition (vs control) increased willingness to try e-cigarettes among people who currently smoked or were susceptible to smoking (β= 0.84, p <0.05). NWLs, but not sponsorship disclosures, reduce Mexican youth susceptibility and positive expectancies toward e-cigarettes.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Cruz-Jiménez L"", ""Kim M"", ""Vidaña-Pérez D"", ""Khemkar A"", ""Sun Y"", ""Leal DF"", ""Barrientos-Gutiérrez I"", ""Thrasher JF""]",10.21149/17611,Cruz-Jiménez L,Salud publica de Mexico,0036-3634,3 (may-jun),Salud Publica Mex,eng,Thrasher JF,"[""Humans"", ""Electronic Nicotine Delivery Systems"", ""Adolescent"", ""Young Adult"", ""Social Media"", ""Female"", ""Male"", ""Mexico"", ""Product Labeling"", ""Media Exposure""]",235-244,42536871,,2026 Jun 18,2026,https://pubmed.ncbi.nlm.nih.gov/42536871/,Evaluating strategies to reduce the effects of pro-e-cigarette social media posts in young adults,68,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Laparoscopic surgery has become the mainstream approach for gynecological procedures. However, postoperative pain, particularly visceral pain, remains a major obstacle to achieving enhanced recovery after surgery. Therefore, this study aimed to observe the clinical effects of opioid-sparing anesthesia combined with a quadratus lumborum block (QLB) in patients undergoing gynecological laparoscopic surgery to provide a reference for clinical practice. A total of 80 female patients (aged 18 to 65 years, body mass index 18 to 28 kg/m2, American Society of Anesthesiologists I-II) scheduled for elective gynecological laparoscopic surgery under general anesthesia were enrolled and randomly assigned to 2 groups (n = 40 each): the control group (Group C) and the treatment group (Group T). All patients received general anesthesia. In Group T, a bilateral QLB was additionally performed under ultrasound guidance after the induction of general anesthesia. The following parameters were recorded for both groups: general demographic data and perioperative parameters; total intraoperative remifentanil consumption; postoperative analgesic pump consumption at 0 to 24 hours and 24 to 48 hours; the number of effective presses and total presses of the analgesic pump during 0 to 24 hours and 24 to 48 hours postoperatively; numerical rating scale (NRS) scores at rest and during movement at 2 hours, 6 hours, 12 hours, 24 hours, and 48 hours postoperatively; the rescue analgesia rate within 48 hours postoperatively; and the incidence of adverse reactions (hypotension, respiratory depression, postoperative nausea and vomiting [PONV], somnolence). Compared with Group C, patients in Group T had significantly reduced the following parameters: total intraoperative remifentanil consumption (P < .05); analgesic pump consumption at 0 to 24 hours and 24 to 48 hours postoperatively (P < .05); the number of effective presses and total presses of the analgesic pump during 0 to 24 hours and 24 to 48 hours postoperatively (P < .05); resting NRS scores at 12 hours, 24 hours, and 48 hours postoperatively (P < .05); and movement NRS scores at 6 hours, 12 hours, 24 hours, and 48 hours postoperatively (P < .05). Furthermore, the rescue analgesia rate within 48 hours postoperatively was significantly lower in Group T compared to Group C (P < .05). Regarding adverse reactions, the incidence of PONV in Group T was considerably lower than that in Group C (P < .05). For gynecological patients undergoing laparoscopic surgery, the application of opioid-sparing anesthesia combined with a QLB provides effective analgesia, reduces intraoperative opioid consumption, prolongs the duration of postoperative analgesia, lowers the incidence of PONV, and promotes enhanced postoperative recovery.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Ge Q"", ""Liu G"", ""Yang F"", ""Wen C"", ""Zhao S""]",10.1097/MD.0000000000049921,Ge Q,Medicine,0025-7974,31,Medicine (Baltimore),eng,Zhao S,"[""Humans"", ""Female"", ""Laparoscopy"", ""Gynecologic Surgical Procedures"", ""Adult"", ""Middle Aged"", ""Postoperative Pain"", ""Analgesics, Opioid"", ""Nerve Block"", ""Anesthesia, General"", ""Remifentanil"", ""Young Adult"", ""Aged"", ""Adolescent""]",e49921,42536552,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536552/,Clinical observation of opioid-sparing anesthesia combined with QLB in patients undergoing gynecological laparoscopic surgery: A randomized controlled trial,105,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Dysphagia is a common, serious complication in acute stroke patients, often requiring indwelling gastric tubes. Prolonged tube use increases risks of aspiration pneumonia and other adverse events. Current assessment methods often lack the sensitivity needed to guide safe extubation. To investigate the effect of combined Gugging Swallowing Screen (GUSS) and National Institutes of Health Stroke Scale (NIHSS) scores on the gastric tube removal in acute stroke patients. Between November 2021 and November 2022, 110 patients were admitted to our hospital with acute stroke and fitted with an indwelling gastric tube. We collated clinical data, performed the Kubota Water Swallowing Test, and determined the NIHSS and GUSS scores. Patients were then divided randomly into experimental and control groups. In the experimental group, gastric tubes were removed based on an NIHSS score < 15 and a GUSS score ≥ 15, while in the control group, extubation followed the Kubota Water Swallowing Test. Adverse events related to the 2 strategies were analyzed. No significant differences were detected between the 2 groups in terms of baseline clinical characteristics. When compared to the traditional extubation strategy based on the Kubota Water Swallowing Test, the incidence of aspiration pneumonia, indwelling time for the gastric tube, and the secondary indwelling rate associated with the combination of GUSS and NIHSS scores were significantly (P < .05) reduced. Cox and Kaplan-Meier curves demonstrated that the extubation strategy applied in the experimental group significantly (P < .05) reduced the risk of adverse events. An NIHSS score < 15 and a GUSS score ≥ 15 can be used to approve the removal of a gastric tube from acute stroke patients; this represents a reliable and safe strategy that reduces the risk of adverse events.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Peng X"", ""Li N"", ""Zeng F"", ""Zhang M"", ""Liu Y"", ""Zhang L""]",10.1097/MD.0000000000049937,Peng X,Medicine,0025-7974,31,Medicine (Baltimore),eng,Zhang L,"[""Humans"", ""Stroke"", ""Deglutition Disorders"", ""Female"", ""Male"", ""Aged"", ""Pneumonia, Aspiration"", ""Deglutition"", ""Intubation, Gastrointestinal"", ""Middle Aged"", ""Device Removal"", ""Aged, 80 and over"", ""United States""]",e49937,42536549,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536549/,Application of gastric tube removal strategy based on the combination of Gugging Swallowing Screen (GUSS) and National Institutes of Health Stroke Scale (NIHSS) scores in patients following acute stroke: A randomized controlled trial,105,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Heart valve disease is a significant cause of morbidity and mortality, and aortic valve replacement (AVR) is a common treatment option. Recently, sutureless biological valves have gained increasing use. This study aimed to evaluate the concordance between preoperative computed tomography-derived annulus measurements and valve sizes implanted during surgery rather than the direct clinical impact of imaging on prosthesis selection. A total of 40 patients with aortic valve stenosis who underwent elective open-heart surgery and preoperative multislice computed tomography between February 20 and May 20, 2024, were included and were randomly allocated into two groups: sutureless biological valve (n = 20) and mechanical valve (n = 20). Data were obtained from patient records and the hospital's data system and analysed statistically. A total of 40 patients were included in the study: 20 received sutureless, rapidly implantable biological valves, and 20 underwent mechanical AVR. The mean age of the cohort was 61.5 ± 9.1 years, with 45% females and 55% males. Compared with the sutureless group, the mechanical valve group had significantly longer cross-clamp (73.5 vs. 53.0 minutes, p < 0.001) and cardiopulmonary bypass times (102 vs. 92 minutes, p = 0.011), as well as smaller sinotubular junction diameters (30.2 vs. 32.3 mm, p = 0.025). In contrast, the sutureless group demonstrated a significantly greater optimal effective orifice area index (1.58 vs. 0.77, p < 0.001). Preoperative computed tomography is a reliable tool for planning AVR. Sutureless biological valves provide shorter cross-clamp and bypass times and favourable haemodynamic performance, whereas mechanical valves are more often associated with smaller valve sizes and longer procedures. Early postoperative outcomes were comparable between groups.","[""Journal Article"", ""Comparative Study"", ""Randomized Controlled Trial""]","[""Çoban Ö"", ""Özsöyler İ""]",10.5830/CVJA-2026-026,Çoban Ö,Cardiovascular journal of Africa,1015-9657,3,Cardiovasc J Afr,eng,Özsöyler İ,"[""Humans"", ""Female"", ""Male"", ""Multidetector Computed Tomography"", ""Heart Valve Prosthesis Implantation"", ""Heart Valve Prosthesis"", ""Aortic Valve"", ""Aortic Valve Stenosis"", ""Treatment Outcome"", ""Prosthesis Design"", ""Aged"", ""Sutureless Surgical Procedures"", ""Middle Aged"", ""Predictive Value of Tests"", ""Bioprosthesis"", ""Time Factors""]",289-293,42536489,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536489/,Mechanical vs. sutureless aortic valve replacement: clinical outcomes and the contribution of preoperative multislice CT,37,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Small ventral hernia repair is among the most performed general surgical procedures. Despite the routine use of planar polypropylene mesh, surgical site occurrences (SSO) remain a frequent cause of morbidity, readmission, and patient dissatisfaction. A novel mesh-suture integrates mesh reinforcement with suture-like implantation and may reduce subcutaneous dissection and tissue trauma. The aim of this randomized trial is to investigate differences in SSO, patient-reported outcomes (PROMs) and operation time among patients operated for small ventral hernias either with this novel mesh-suture or planar mesh as well as evaluate potential influence of mesh-suture on wider socio-economic parameters such as return to work and contact with family physician/primary sector as well as long-term occurrence. A prospective, parallel-group, patient- and assessor-blinded, randomized controlled superiority trial conducted across Danish regional hospitals. Eligible patients undergoing elective repair of small ventral hernias are randomized 1:1 to mesh-suture or planar polypropylene mesh. The primary endpoint is SSO. Secondary endpoints include operative time, patient-reported quality of life (EQ-5D-5L, Abdominal Hernia Q), long-term recurrence, reoperation rates, and socio-economic outcomes. Analysis follows the intention-to-treat principle. This trial evaluates whether mesh-suture reduces wound morbidity while maintaining equivalent durability. Results may inform future standards in ventral hernia repair and device selection. The study is registered at clinicaltrials.gov om March 16th, 2026 (NCT07476560).","[""Journal Article"", ""Multicenter Study"", ""Randomized Controlled Trial"", ""Equivalence Trial""]","[""Gameza V"", ""Brandenburger N"", ""Leutscher P"", ""Holte K""]",10.1007/s10029-026-03815-3,Gameza V,Hernia : the journal of hernias and abdominal wall surgery,1265-4906,1,Hernia,eng,Holte K,"[""Humans"", ""Surgical Mesh"", ""Hernia, Ventral"", ""Herniorrhaphy"", ""Prospective Studies"", ""Suture Techniques"", ""Polypropylenes"", ""Operative Time"", ""Patient Reported Outcome Measures"", ""Sutures"", ""Female"", ""Recurrence"", ""Quality of Life"", ""Denmark"", ""Reoperation"", ""Treatment Outcome""]",,42536214,pmc-id: PMC13427904;,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536214/,"Protocol for the mesh matters project: evaluating the efficacy of suture mesh vs. planar mesh in small ventral hernia repair - a randomized, blinded multicenter study",30,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Although reproductive vaccines are essential in swine herd health programs, evidence on their safety across different physiological stages remains limited. This study evaluated the clinical and reproductive safety of Porcilis® EPL in sows and gilts under commercial field conditions. In a randomized, blinded, controlled trial, 200 females were allocated to treated or control groups within five physiological categories, of which 190 completed the study. Sows received a single dose and gilts a two-dose protocol. Clinical parameters (body condition, rectal temperature, general health, feed intake) and injection-site reactions were monitored for 14 days post-vaccination. Reproductive outcomes, including conception, litter size, stillbirths, mummification, and neonatal viability, were recorded. PCR testing for PCV2, PCV3, and PPV was performed on non-viable piglets. The vaccine was well tolerated, with no systemic adverse reactions and only mild, self-limiting injection-site swellings in some treated females. Body condition and temperature profiles remained within physiological limits. Reproductive performance did not differ between groups (p > 0.05). Pathogen detection frequencies were similar across treatments, indicating that vaccination did not measurably alter fetal susceptibility to endemic PCV2, PCV3, or PPV. Porcilis® EPL showed excellent clinical and reproductive safety when administered during different physiological stages in sows and gilts. The vaccine did not affect fertility, gestational outcomes, or perinatal survival and did not measurably alter pathogen detection under field conditions with natural pathogen exposure, supporting its safe integration into breeding herd vaccination programs. PCR detection of PCV2, PCV3, and PPV was included as an exploratory epidemiological assessment to distinguish vaccine-specific effects from endemic pathogen circulation. No differences were observed between groups, supporting that Porcilis® EPL did not influence susceptibility to non-target pathogens.","[""Journal Article"", ""Randomized Controlled Trial""]","[""da Silva DF"", ""Matias DR"", ""Soto FRM"", ""de Oliveira LL"", ""de Castro AMMG""]",10.1007/s11259-026-11266-5,da Silva DF,Veterinary research communications,0165-7380,5,Vet Res Commun,eng,de Castro AMMG,"[""Animals"", ""Female"", ""Swine"", ""Vaccination"", ""Reproduction"", ""Viral Vaccines"", ""Pregnancy"", ""Swine Diseases"", ""Circovirus"", ""Circoviridae Infections""]",,42536125,pmc-id: PMC13427811;,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536125/,Safety and reproductive performance in sows after vaccination: a randomized controlled trial,50,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Ischemia-reperfusion injury due to vascular pedicle occlusion is one of the most common causes of free flap failure in head and neck cancer reconstruction. Remote ischemic preconditioning (RIPC) has been proposed as an experimental, non-invasive intervention to attenuate flap ischemia-reperfusion injury; however, the tissue-protective mechanisms remain unclear. RIPC may have multiple effects on the inflammatory system, which plays a central part in the pathophysiology of ischemia-reperfusion injury. The aim of the present study was to evaluate the effect of RIPC on inflammatory cytokine plasma levels during free flap reconstruction. Head and neck cancer patients (n = 60) undergoing tumor resection and subsequent free flap reconstruction between August 2015 and November 2017 at Aarhus University Hospital, Denmark were randomized 1:1 to RIPC or sham intervention in a single-center, single-blinded, randomized controlled trial (RCT) (ClinicalTrials.gov: NCT02548377). The study was approved by The Central Denmark Region Committees on Health Research Ethics (journal no. 1-10-72-140-15) and reported following the CONSORT guidelines. RIPC was administered intraoperatively as four 5-min cycles of upper extremity occlusion and reperfusion with an inflatable tourniquet. Blood samples were collected before surgery, 6 h after RIPC/sham intervention, and on the 1st postoperative day. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and interferon (IFN)-gamma were analyzed using a multiplex immunoassay. The average age of the RIPC group was 67 years (±10) and 64 years (±12) in the sham group. Plasma levels of the pro-inflammatory cytokines changed significantly between preoperative measures to 1st postoperative day between RIPC and sham; TNF-α (p < 0.001), IL-6 (p < 0.001), IL-8 (p < 0.001), IL-12p70 (p < 0.001), and IFN-γ (p < 0.001). No significant differences in cytokine levels were shown between groups at any specific time points. RIPC does not attenuate pro-inflammatory cytokine release in head and neck cancer patients undergoing free flap reconstruction. ClinicalTrials.gov identifier: NCT02548377.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Nanthan KR"", ""Larsen JB"", ""Hvas CL"", ""Kiil BJ"", ""Krag AE""]",10.1002/micr.70276,Nanthan KR,Microsurgery,0738-1085,6,Microsurgery,eng,Krag AE,"[""Humans"", ""Ischemic Preconditioning"", ""Free Tissue Flaps"", ""Male"", ""Middle Aged"", ""Female"", ""Head and Neck Neoplasms"", ""Cytokines"", ""Aged"", ""Reperfusion Injury"", ""Single-Blind Method"", ""Plastic Surgery Procedures"", ""Adult""]",e70276,42536026,pmc-id: PMC13426342;,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42536026/,The Effects of Remote Ischemic Preconditioning on the Inflammatory Cytokine Response to Free Flap Head and Neck Reconstruction: A Randomized Controlled Trial,46,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Activity-based rehabilitation, such as locomotor training, is commonly used to induce positive systemic physiological adaptations and restore locomotion in individuals with chronic spinal cord injury (SCI). Restoration of locomotion with activity-based rehabilitation alone is not optimal and may require augmentation with neuromodulation strategies. We characterized the excitability of spinal locomotor circuits during stepping in humans with SCI who underwent transspinal stimulation before locomotor training, within the same session. A total of 14 participants with chronic SCI received an average of 40 sessions of 30 Hz transspinal stimulation delivered for 30 min during standing (active or sham) or in the supine (active) position, followed by 30 min of robotic-assisted step training. Before and after the completion of all training sessions, we assessed the soleus H-reflex phase-dependent amplitude modulation and reciprocal Ia and presynaptic inhibition in response to a conditioning stimulus delivered to the common peroneal nerve. Transspinal stimulation administered before locomotor training promoted soleus H-reflex depression during the swing phase in the active standing group (n = 5; F 1, 309 = 4.52, p = 0.034), stabilized soleus H-reflex excitability during the stance phase in the active supine group (n = 5; F 1, 327 = 18.44, p < 0.001), and promoted reduced ankle co-contraction during assisted stepping in all groups. Reciprocal inhibition between ankle flexors and extensors after treatment was reduced at mid-stance and during the swing-to-stance transition phase in the active standing group (n = 4; F 1, 81 = 7.4, p = 0.008), while it was markedly potentiated through the swing phase in the sham standing group (n = 3; F 1, 108 = 22.46, p < 0.001). Finally, generalized soleus H-reflex depression after the intervention in the active (n = 4; F 1, 150 = 42.32, p < 0.001) and sham (n = 3; F 1, 64 = 13.19, p < 0.001) standing groups supported potentiation for presynaptic inhibition. This study demonstrated that transspinal stimulation preceding locomotor training was associated with modulation of the spinal reflex pathways. These neurophysiological adaptations suggest increased responsiveness of spinal circuits, although further studies are needed to determine whether these changes translate into functional improvements in people with chronic SCI.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Pulverenti TS"", ""Sayed Ahmad AM"", ""Harel NY"", ""Knikou M""]",10.3389/fncir.2026.1876368,Pulverenti TS,Frontiers in neural circuits,1662-5110,,Front Neural Circuits,eng,Knikou M,"[""Humans"", ""Spinal Cord Injuries"", ""Male"", ""Adult"", ""Female"", ""H-Reflex"", ""Middle Aged"", ""Muscle, Skeletal"", ""Locomotion"", ""Electromyography"", ""Spinal Cord Stimulation"", ""Exercise Therapy"", ""Spinal Cord""]",1876368,42535069,pmc-id: PMC13422473;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42535069/,Transspinal stimulation preceding step training reorganizes spinal locomotor circuits in human spinal cord injury: a randomized sham-controlled clinical trial,20,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Obesity prevalence is rising globally and associated with increased influenza mortality. The relationship between obesity and influenza-like-illness (ILI) incidence and symptom severity is less clear. US Military Health System (MHS) beneficiaries enrolled in a randomized influenza vaccine trial received one of three influenza vaccines and were followed for ILI via weekly surveys throughout one influenza season. Participants were pooled across vaccine arms into a prospective cohort. We compared ILI risk and ILI symptom severity (Flu-PRO) across body mass index (BMI) categories using multivariable regression models. Among the 8,334 participants with >50% response rates to weekly ILI surveys, 42% had an overweight-range BMI and 24% had an obesity-range BMI. The median age was 36.2, and 86% had no baseline comorbidities. Over one quarter of the participants (27%) reported at least one ILI during follow-up, with a median duration of 11 days. Participants with an overweight and obesity-range BMI were more likely to report ILIs [adjusted incidence rate ratio (aIRR) 1.18 (95% confidence interval (CI): 1.05-1.33) and 1.59 (95% CI: 1.37-1.84), respectively]. Participants with obesity also had higher risks of reporting moderate-to-severe symptoms in four Flu-PRO domains: gastrointestinal, respiratory, systemic, and throat [adjusted risk ratio (aRR) of 1.64 (95% CI: 1.01-2.70), 1.33 (95% CI: 1.05-1.67), 1.32 (95% CI: 1.06-1.63), and 1.20 (95% CI 1.02-1.40) respectively]. Higher BMI was associated with ILI incidence and severity. These findings prompt further research into optimal strategies to reduce the impact of ILI in MHS settings and the general population.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Gu M"", ""Richard SA"", ""Colombo RE"", ""Schmidt K"", ""Ganesan A"", ""Campbell WR"", ""Mende K"", ""Seshadri S"", ""Saperstein A"", ""Hrncir DE"", ""Maves RC"", ""O'Connell RJ"", ""Spooner CE"", ""Simons MP"", ""Housel LA"", ""Williams A"", ""Powers JH 3rd"", ""Fries A"", ""Coles CL"", ""Burgess TH"", ""Pollett SD""]",10.3389/fpubh.2026.1874186,Gu M,Frontiers in public health,2296-2565,,Front Public Health,eng,Pollett SD,"[""Humans"", ""Body Mass Index"", ""Female"", ""Influenza, Human"", ""Adult"", ""Influenza Vaccines"", ""Prospective Studies"", ""Male"", ""Obesity"", ""Military Personnel"", ""Severity of Illness Index"", ""United States"", ""Middle Aged"", ""Risk Factors"", ""Incidence"", ""Military Health"", ""Young Adult""]",1874186,42534960,pmc-id: PMC13422495;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42534960/,Assessing the relationship between body mass index and influenza-like illness risk and symptom severity among military health system beneficiaries vaccinated against influenza: a pooled prospective cohort study from a randomized trial,14,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"This randomized controlled trial (RCT) assessed the effect of oral magnesium (Mg) supplementation on glycated hemoglobin (HbA1c) and metabolic biomarkers in adults with Type 2 Diabetes Mellitus (T2DM). This was a prospective, randomized, double-blind, placebo-controlled, parallel-group clinical trial with intention-to-treat (ITT) and per-protocol (PP) analyses. Adults (≥18 years) with T2DM were randomized 1:1 to receive magnesium oxide (500 mg; 302 mg elemental) or placebo. Eligibility criteria included a glycated hemoglobin (HbA1c) level ≥7.0% and a creatinine clearance >30 mL/min. Simple randomization was performed using a sealed-envelope method. Biochemical and clinical parameters were assessed at baseline and at three follow-up visits over 12 months. A total of 247 participants were included in the ITT analysis (Mg-oxide, n=118; placebo, n=129). Median age was 58 (50-65) years, and median diabetes duration was 16 (10-22) years. Hypomagnesemia was present in 7.3% by ionized magnesium (iMg) and 8.1% by total magnesium (tMg). Mg-oxide supplementation significantly reduced fasting blood glucose in a subgroup of the cohort (FBG; p = 0.039) and resulted in a modest, non-significant reduction in HbA1c (-0.30% vs. -0.05%; p = 0.145), with a higher proportion achieving goal attainment/controlled HbA1c (<7%) compared with placebo (14.0% vs. 6.0%; p = 0.043). HbA1c reductions were more pronounced among participants with baseline hypomagnesemia (-0.60% vs. +0.25%; p = 0.074), or diabetes duration ≤15 years (-0.40% vs. 0.00%; p = 0.085). No differences were observed in other metabolic parameters, clinical outcomes or adverse drug reactions between groups. Although median HbA1c reduction did not reach statistical significance, Mg-oxide supplementation improved Mg status and showed favorable trends in glycemic control without compromising safety. These findings support Mg supplementation as a safe adjunct to long-term T2DM management, particularly among selected subgroups, given the study's limitations. https://clinicaltrials.gov/, identifier NCTO5774015.","[""Journal Article"", ""Randomized Controlled Trial"", ""Clinical Trial""]","[""Al-Maqbali JS"", ""Al Alawi AM"", ""Osman A"", ""Al-Farqani A"", ""Kumar S"", ""Al Futisi A"", ""Al-Mamari A"", ""Al-Zakwani I"", ""Al Za'abi M""]",10.3389/fendo.2026.1883483,Al-Maqbali JS,Frontiers in endocrinology,1664-2392,,Front Endocrinol (Lausanne),eng,Al Za'abi M,"[""Humans"", ""Diabetes Mellitus, Type 2"", ""Double-Blind Method"", ""Middle Aged"", ""Female"", ""Male"", ""Magnesium"", ""Dietary Supplements"", ""Glycated Hemoglobin"", ""Glycemic Control"", ""Blood Glucose"", ""Aged"", ""Administration, Oral"", ""Prospective Studies"", ""Biomarkers"", ""Magnesium Oxide""]",1883483,42534812,pmc-id: PMC13422152;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42534812/,The effect of oral magnesium supplementation on glycemic control and metabolic parameters in type 2 diabetes mellitus: a double-blind randomized controlled trial,17,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Nonsuicidal self-injury (NSSI) in adolescents with depressive disorder is characterized by recurrent impulsivity and is a predictor of future suicidal behavior, necessitating effective and feasible interventions. Mindfulness-based cognitive therapy for adolescents (MBCT-A), a first-line treatment for depression, was evaluated in this trial for its efficacy in reducing NSSI in this population. In this randomized, single-blind, controlled trial, 94 hospitalized adolescents diagnosed with depressive disorder and engaging in NSSI were allocated to either MBCT-A plus treatment-as-usual (TAU) or TAU alone. The primary outcome was the severity of NSSI, measured by the Adolescent Self-Harm Scale (ASHS) at baseline, post treatment (4 weeks), and at 1-month follow-up. Secondary outcomes encompassed symptoms of anxiety, depression, emotion regulation, risk behaviors, life satisfaction, resilience, rumination, coping styles, and mindfulness. Both intention-to-treat (ITT) and per-protocol (PP) analyses were conducted. Both ITT and PP analyses revealed significant between-group differences in NSSI severity at 4 weeks. Compared to the control group, the MBCT-A group showed significant improvements in mindfulness awareness, nonreactivity, emotional awareness, depressive symptoms, emotion regulation, and rumination (all P < 0.05). At the 1-month follow-up, the intervention group maintained a significant reduction in NSSI severity (interaction effect: F = 9.454, P < 0.001). MBCT-A is effective in reducing NSSI behavior and improving mindfulness, emotion regulation, and depressive symptoms among adolescents with depressive disorder and NSSI. These findings support the clinical application of MBCT-A for this high-risk population.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Xie J"", ""Li L"", ""Liu X"", ""Yue W"", ""Guo J""]",10.1017/S0033291726104735,Xie J,Psychological medicine,0033-2917,,Psychol Med,eng,Guo J,"[""Humans"", ""Self-Injurious Behavior"", ""Adolescent"", ""Mindfulness"", ""Single-Blind Method"", ""Female"", ""Depressive Disorder"", ""Male"", ""Cognitive Behavioral Therapy"", ""Emotional Regulation"", ""Hospitalization"", ""Treatment Outcome"", ""Coping Skills""]",e249,42533822,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42533822/,The effect of mindfulness-based cognitive therapy on non-suicidal self-injury in hospitalized adolescents with depressive disorders: a randomized controlled trial,56,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Short-term travel, particularly to new environments, can disrupt gut microbiota homeostasis and induce a range of physical and psychological symptoms. While probiotics are proposed to mitigate these effects, evidence from well-controlled trials during domestic travel, especially along unique routes like China's Silk Road, remains limited. This study investigated the efficacy of a multi-strain Bifidobacterium probiotic in maintaining gut microbiota stability and alleviating travel-related symptoms. In a randomized, double-blind, placebo-controlled trial, 74 healthy adults traveling to Xinjiang were assigned to receive either a probiotic (n = 39; B. longum subsp. infantis M-63, B. breve M-16V, and B. longum BB536, 1.5 × 109 CFU/day) or a placebo (n = 35) for five days during travel. Gut microbiota was profiled via metagenomic sequencing (pre- and post-travel), and symptoms were recorded daily. Primary outcomes were changes in gut microbiota composition and function (KEGG pathways). Secondary outcomes included respiratory, gastrointestinal, and systemic symptom scores. Data were analyzed on an intention-to-treat basis. While alpha and beta diversity remained stable in both groups, the probiotic group exhibited a distinct post-travel microbiota enriched with beneficial taxa, including Bifidobacterium breve and Intestinibacillus at the genus level, and Lacticaseibacillus rhamnosus, Lacticaseibacillus paracasei, and other Lacticaseibacillus species. qPCR confirmed significant increases in administered strains B. longum subsp. infantis (p < 0.001) and B. breve (p < 0.001). KEGG analysis revealed that the probiotic group maintained a metabolically focused profile (e.g., peptidoglycan biosynthesis, histidine metabolism), whereas the placebo group showed increased abundance of microbial pathways associated with host disease-related signaling (e.g., Huntington disease, various cancers) and inflammatory signaling (e.g., PI3K-Akt signaling pathway). Symptomatically, the probiotic group demonstrated a significantly greater reduction than the placebo in irritability (-92% vs. -31%; p = 0.033) and fatigue (-24% vs. +43%; p = 0.024) post-travel, and reported less dizziness (-100% vs. -35%; p = 0.024). Supplementation with a multi-strain Bifidobacterium probiotic during short-term travel promoted the colonization of beneficial bacteria, stabilized gut microbial function against travel-induced dysregulation, and may contribute to supporting systemic well-being during travel.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Yang K"", ""Yang M"", ""Yu Q"", ""Liong MT"", ""Chen D"", ""Cai M""]",10.4014/jmb.2510.10037,Yang K,Journal of microbiology and biotechnology,1017-7825,,J Microbiol Biotechnol,eng,Cai M,"[""Humans"", ""Probiotics"", ""Bifidobacterium"", ""Gastrointestinal Microbiome"", ""Double-Blind Method"", ""Adult"", ""Travel"", ""Male"", ""China"", ""Female"", ""Feces"", ""Young Adult"", ""Bacteria""]",e2510037,42533554,,2026 Feb 12,2026,https://pubmed.ncbi.nlm.nih.gov/42533554/,The Effect of a Probiotic on Gut Microbiota Stability and Systemic Well-Being during Short-Term Travel,36,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"This randomized controlled trial (RCT) was conducted in 10 Italian health and maternal-child Centres to evaluate the effects of a Dialogic Book-Sharing (DBS) intervention on parental symptoms of anxiety and depression. Sixty-eight parents of 14-20-month-old infants were recruited. ANOVA analysis revealed a greater reduction in anxiety and depression symptoms in the intervention group (N = 36) compared to controls (N = 32). DBS is a simple, cost-effective programme that benefits parental mood, making it a valuable intervention for perinatal populations.","[""Journal Article"", ""Randomized Controlled Trial"", ""Multicenter Study""]","[""Cena L"", ""Trainini A"", ""Belluardo M"", ""Buizza C"", ""Cooper H"", ""Murray L""]",10.1017/S1463423626101509,Cena L,Primary health care research & development,1463-4236,,Prim Health Care Res Dev,eng,Murray L,"[""Humans"", ""Italy"", ""Female"", ""Infant"", ""Parents"", ""Anxiety"", ""Depression"", ""Male"", ""Books"", ""Affect"", ""Adult""]",e82,42533526,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42533526/,Dialogic Book-Sharing intervention in an Italian multicentre randomized controlled trial: effects on parental mood,27,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Dental anxiety affects roughly 15% of the general population, yet the relative contribution of procedure type, patient age, and distraction interventions to objective autonomic arousal during dental treatment remains poorly characterised. This study investigated the effects of these three factors on electrodermal activity (EDA) in a clinical dental setting. Skin conductance was continuously recorded in 65 adult patients (age 18-29: n=23; 30-55: n=19; ≥56: n=23) undergoing dental procedures under local anaesthesia at a walk-in dental clinic. Patients were randomly assigned to audiovisual intervention (n=30) or control (n=35), and EDA was measured with a wrist-worn sensor and analyzed in STATISTICA 13.0 using nonparametric tests. Extractions produced significantly elevated mean EDA (mean (M)=10.85 μS, standard deviation (SD)=5.00) compared with non-extraction procedures (M=5.20 μS, SD=5.60; Z=4.25, P<0.001, η2=0.28). Older patients (≥56 years: median (Mdn)=2.49 µS) showed lower EDA than middle-aged patients (30-55 years: Mdn=7.81 µS; H=7.96, P=0.019, η2=0.09), consistent with physiological aging and stress resilience. Procedure duration did not correlate with EDA (r(s)=0.15, P=0.23). Anti-stress ball users showed elevated EDA during extractions (Mdn=13.12 vs. 8.60 μS, Z=-2.22, P=0.026), most plausibly attributable to bilateral hand immobilisation imposed by the study protocol. Among non-extraction procedures, augmented reality glasses (AR) were associated with the lowest median EDA (Mdn=2.35 μS, n=12), followed by music glasses (Mdn=2.73 µS, n=4) and headphones (Mdn=4.01 µS, n=3), though group differences were non-significant (H=1.42, P=0.49). Autonomic arousal was more strongly determined by procedure invasiveness (η2=0.28) than by patient age (η2=0.09), with the invasiveness effect driven primarily by the extraction subgroup. AR glasses were well tolerated and associated with the lowest EDA in non-extraction procedures, warranting evaluation in an adequately powered trial. Adequately powered randomised controlled trials restricted to single procedure types and incorporating validated anxiety scales are required before clinical recommendations can be made.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Bereziewicz J"", ""Bereziewicz W"", ""Gorski B"", ""Kowalski J""]",10.26402/jpp.2026.3.06,Bereziewicz J,Journal of physiology and pharmacology : an official journal of the Polish Physiological Society,0867-5910,3,J Physiol Pharmacol,eng,Kowalski J,"[""Humans"", ""Galvanic Skin Response"", ""Adult"", ""Female"", ""Middle Aged"", ""Adolescent"", ""Young Adult"", ""Male"", ""Dental Anxiety"", ""Age Factors"", ""Tooth Extraction""]",353-361,42533458,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42533458/,"Electrodermal activity during dental procedures: effects of procedure type, age, and audiovisual interventions",77,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Chronic lower limb ischemia is a manifestation of systemic atherosclerosis frequently accompanied by lipid metabolism disorders, endothelial dysfunction, and disturbances in the L-arginine-nitric oxide (NO) pathway. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, and homocysteine (Hcy) are recognized markers of vascular risk. This study aimed to evaluate the effect of 2 months of oral L-arginine supplementation (6g/day) on serum ADMA and Hcy concentrations in patients with atherosclerotic lower limb ischemia, depending on lipid metabolism disorder type. In a randomized, double-masked, placebo-controlled trial, 87 patients (50 men, 37 women) were assigned to L-arginine or placebo. Subgroups were defined according to lipid abnormalities: hypertriglyceridemia, hypercholesterolemia, and mixed hyperlipidemia. ADMA was measured by HPLC, and Hcy by fluorescence polarization immunoassay at baseline, 30, and 60 days. L-arginine supplementation significantly reduced ADMA levels in patients with hypercholesterolemia after 30 and 60 days (P<0.05) and in those with mixed hyperlipidemia after 60 days (P<0.05), but not in those with isolated hypertriglyceridemia. Changes in Hcy were not statistically significant. A significant positive correlation between ADMA and Hcy was present in all subgroups, most consistently in hypercholesterolemia. Two-month L-arginine supplementation decreases ADMA concentrations in patients with atherosclerotic lower limb ischemia, with efficacy dependent on the underlying lipid disorder phenotype, suggesting a metabolism-specific modulation of the ADMA-NO axis.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Micker M"", ""Balcer-Dymel N"", ""Pruszynska-Oszmalek E"", ""Madej-Czerwonka B"", ""Leciejewska N"", ""Kolodziejski P"", ""Sassek M"", ""Grzeda E"", ""Checinska-Maciejewska Z"", ""Jaskula M"", ""Krauss H"", ""Rekas-Dudziak A""]",10.26402/jpp.2026.3.01,Micker M,Journal of physiology and pharmacology : an official journal of the Polish Physiological Society,0867-5910,3,J Physiol Pharmacol,eng,Rekas-Dudziak A,"[""Humans"", ""Arginine"", ""Homocysteine"", ""Female"", ""Male"", ""Atherosclerosis"", ""Ischemia"", ""Dietary Supplements"", ""Middle Aged"", ""Double-Blind Method"", ""Aged"", ""Lower Extremity"", ""Hypercholesterolemia"", ""Hyperlipidemias""]",299-305,42533453,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42533453/,Effect of L‑arginine supplementation on homocysteine and asymmetric dimethylarginine in atherosclerotic lower limb ischemia,77,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"This study aimed to construct and implement an in situ simulated emergency training (SET) course for nurses with low seniority and evaluate its effectiveness. This was an experimental study, and a purpose-sampling method was adopted. We selected 82 nurses with less than 5 years of experience working in a grade - III Class A hospital in Hubei province from August to December 2023 as the research objects, and randomly divided them into intervention group (n = 37) and control group (n = 45). The control group underwent routine stratified training, whereas the intervention group underwent in situ SET based on routine stratified training. Before and after training, we compared differences in the scores of the intervention and control groups in terms of critical thinking (CT), clinical communication (CC), clinical reasoning (CR), and first aid (FA). The constructed in situ simulated emergency training course consisted of nine courses, each of which covered one theme. The nine themes were acute myocardial infarction, diabetic ketoacidosis, secondary shock due to acute transfusion anaphylaxis, post-operative respiratory depression combined with pulmonary edema, unplanned extubation, impulsive violence, chemotherapeutic drug extravasation, patient suicide, and acute pulmonary embolism. The results of the empirical study showed that before training, there were no differences between the intervention and control groups in the scores for the following abilities: CT, CC, CR, and FA (p > 0.05). After training, the scores for CR and FA in the intervention group were higher than those in the control group (p < 0.05), while the scores for CT and CC did not differ from those in the control group (p > 0.05). The content of the in situ SET course is comprehensive, which is helpful in improving junior nurses' CC and FA abilities and can serve as a reference for establishing a training course for them. However, the effects on the CT and CC were not significant. Further empirical studies are required to explore the targeted training courses.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Shen M"", ""Tan X"", ""Xianyu Y"", ""Chen Q"", ""Fang Y"", ""Zeng C"", ""Yang G"", ""Pan M"", ""Cai Z""]",10.1186/s12909-026-08961-x,Shen M,BMC medical education,1472-6920,1,BMC Med Educ,eng,Cai Z,"[""Humans"", ""Clinical Competence"", ""Female"", ""Simulation Training"", ""Adult"", ""Male"", ""China"", ""Nursing Staff, Hospital""]",,42533330,pmc-id: PMC13422298;,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42533330/,"Developing and evaluating an in situ, simulated emergency training course for nurses with low seniority",26,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Dental students must master endodontic anatomy, radiographic diagnostics, and treatment strategies early in their clinical training-yet traditional teaching methods, including two-dimensional radiographs, often fail to effectively convey complex spatial structures. Hologram technology has emerged as a promising tool for three-dimensional visualization in dental education. The aim of the study was to compare the classification accuracy of dental students using holograms versus conventional periapical radiographs in identifying endodontic structures. This randomized single center-controlled trial included 79 dental students (years 4-6). After a calibration seminar and pre-test each of the 79 students assessed six tooth cases-three presented as holograms and three as periapical radiographs. Holograms were created from cone-beam computed tomography data, annotated by two calibrated examiners to establish reference points regarding the number of canals, Vertucci classification, and treatment complexity. Students evaluated each case for these parameters; responses were compared to the reference points to assess classification accuracy. The final evaluation form captured their subjective perceptions of the new hologram system. Primary binary outcomes were analyzed using logistic mixed-effects models. P-values were adjusted for multiple testing using the Benjamini-Hochberg procedure. Statistical significance was set at p < 0.05. After Benjamini-Hochberg correction, holography significantly improved root-canal number identification in three multi-rooted cases (adjusted p ≤ 0.007). For Vertucci classification, only the maxillary anterior tooth remained significant (adjusted p = 0.044). Treatment-complexity assessment showed case-dependent results, favoring radiography in two cases (adjusted p = 0.045 and p = 0.006) and holography in one case (adjusted p = 0.013). Holographic visualization demonstrated case- and task-specific effects in endodontic training. Holograms were able to improve classification accuracy in certain endodontic tasks. However, they did not outperform conventional periapical radiographs in all outcomes. Holography could be an effective, supplementary tool for teaching certain endodontic tasks, but its application requires further investigation. The study was prospectively registered in the German Clinical Trials Register (DRKS-ID: DRKS00035000) on 13.09.2024.","[""Journal Article"", ""Comparative Study"", ""Randomized Controlled Trial""]","[""Lederer ML"", ""Barbe AG"", ""Janson M"", ""von Kohout M"", ""Schoppmeier CM""]",10.1186/s12909-026-10035-x,Lederer ML,BMC medical education,1472-6920,1,BMC Med Educ,eng,Schoppmeier CM,"[""Humans"", ""Holography"", ""Endodontics"", ""Students, Dental"", ""Cone-Beam Computed Tomography"", ""Education, Dental"", ""Imaging, Three-Dimensional"", ""Clinical Competence"", ""Female""]",,42533324,pmc-id: PMC13422344;,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42533324/,Assessment of classification accuracy in endodontics by dental students: a comparative study of holographic imaging and conventional radiography,26,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Football coaches commonly provide verbal encouragement and exercise end-point feedback to sustain players' effort by enhancing motivation during fitness training such as high-intensity interval training (HIIT). However, the influence of such cues on the prefrontal cortex (PFC), a region involved in exercise cessation decisions, remains unclear. Therefore, this study aimed to compare the effect of motivational cues on PFC activation during HIIT using functional near-infrared spectroscopy, alongside physiological and perceptual responses. Twenty-two male elite footballers completed two randomised crossover HIIT sessions on a cycle ergometer, with and without motivational cues. Each session consisted of 12 repetitions of 30-s high-intensity bouts, each interspersed with a 30-s active recovery bout. Heart rate, lactate concentration, rating of perceived exertion (RPE), motivation-related questionnaires and oxygenated haemoglobin (HbO2) concentration in the PFC were measured throughout HIIT. Although physiological responses were similar between conditions, perceived difficulty, assessed every three HIIT bouts, was significantly lower under the motivational condition, with lower RPE (p = 0.038) and higher motivation (p = 0.049), engagement (p = 0.038) and mood (p = 0.009) scores, particularly after the 9th repetition. From the 10th to 12th repetition of HIIT, the HbO2 concentrations of the orbitofrontal cortex and frontopolar PFC were significantly lower under the motivational condition (p = 0.040 and p = 0.036, respectively), whereas the dorsolateral and ventrolateral PFC showed no significant difference between conditions. In conclusion, motivational cues reduce central PFC activity during the most fatiguing phases of HIIT, reflecting enhanced neural efficiency under motivation despite equivalent physical workloads.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Han S"", ""Ahn S"", ""Sung Y"", ""Seo JW"", ""Li X"", ""Han S"", ""Kim C"", ""Song W""]",10.1002/ejsc.70222,Han S,European journal of sport science,1746-1391,8,Eur J Sport Sci,eng,Song W,"[""Humans"", ""Prefrontal Cortex"", ""Male"", ""High-Intensity Interval Training"", ""Cross-Over Studies"", ""Motivation"", ""Spectroscopy, Near-Infrared"", ""Young Adult"", ""Cues"", ""Soccer"", ""Heart Rate"", ""Physical Exertion"", ""Adult"", ""Lactic Acid"", ""Athletes""]",e70222,42533283,pmc-id: PMC13425583;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42533283/,Motivational Coaching Cues Can Modulate Prefrontal Cortex Activity and Perceptual Responses of Elite Football Players During High-Intensity Interval Training: A Randomised Crossover fNIRS Study,26,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Mature striae distensae, called striae albae, are common but treatment-resistant dermal scars. Fractional radiofrequency (FRF) can potentially act as transdermal permeation enhancer for topical tretinoin (TT). This study investigated FRF and TT as a combination treatment for striae albae. Twenty patients were included, each with four anatomically comparable areas that were randomized to (i) TT (ii) FRF (iii) combination FRF + TT and (iv) untreated control. Three treatment sessions were performed one month apart, and TT was also applied in-between. The change in striae from baseline to 20-week follow-up (Δ) was assessed using the Patient Observer Scar Assessment Scale (POSAS, SUM: 6-60). At baseline, patients assessed the striae as moderate-severe (POSAS-PT: SUM medians 24-25) and at follow-up, they reported an improvement (POSAS-PT: ΔSUM 5-10 points), but only the combination treatment improved significantly better (FRF + TT vs. control p = 0.029). A blinded dermatologist confirmed a tendency towards treatment improvement (POSAS-OBS: ΔSUM: 0-2 point, all treatments vs control p≥0.269). A subtle tendency was observed in objective measures with 3D photographs. Combination treatment with FRF and TT was tolerable and improved patient-reported striae compared to control. Striae albae remain challenging, but the findings highlight a potential for future combination treatment approaches.Trial registration number: NCT05461755Date of registration: 15.07.2022.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Grove GL"", ""Karmisholt KE"", ""Philipsen PA"", ""Bjerring P"", ""Haedersdal M""]",10.1007/s10103-026-04975-5,Grove GL,Lasers in medical science,0268-8921,1,Lasers Med Sci,eng,Haedersdal M,"[""Humans"", ""Tretinoin"", ""Female"", ""Striae Distensae"", ""Male"", ""Middle Aged"", ""Combined Modality Therapy"", ""Adult"", ""Treatment Outcome"", ""Keratolytic Agents"", ""Administration, Cutaneous"", ""Radiofrequency Therapy""]",,42533163,pmc-id: PMC13424636;,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42533163/,Treatment of striae albae with combination of fractional radiofrequency and topical tretinoin: A randomized controlled trial,41,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Knee osteoarthritis (OA) is a common musculoskeletal condition linked to aberrant joint loading, pain, and reduced function. While effective rehabilitation should target both local knee problems and the entire kinetic chain, direct comparisons between proximal (core stability) and distal (foot-ankle) interventions are limited. This randomized controlled trial evaluated the efficacy of an 8-week core stability exercise (CSE) program versus foot-ankle strengthening (FAS) in individuals with knee OA. One hundred participants (aged ≥ 40 years, Kellgren-Lawrence grade II-III) were randomly assigned to either CSE (n = 50) or FAS (n = 50). Both groups performed conventional knee exercises three times weekly for 8 weeks, supplemented by their respective group-specific training. The primary outcome was resting pain intensity evaluated via a visual analogue scale (VAS). Secondary outcomes included the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales, functional performance tests (40-m fast-paced walk, 30-second chair stand, and 11-step stair climb), and distal structural measures (Achilles tendon thickness and navicular/foot ratio). Assessments were conducted at baseline and after 8 weeks, with between-group differences analyzed using ANCOVA adjusted for baseline values. The CSE group showed significantly greater improvements across all outcomes compared to the FAS group. Between-group differences exceeded validated minimal clinically important differences (MCID) for resting pain and all KOOS subscales, met MCID thresholds for the walk and chair-stand tests, and safely surpassed minimal detectable changes (MDC) for the stair-climb test and distal structural parameters; large effect sizes favored core stability training. These findings indicate that proximal core stabilization added to conventional knee exercises provides superior short-term improvements in functional mobility and distal structural surrogates compared to foot-ankle strengthening combined with conventional knee exercises in knee OA rehabilitation. Crucially, these static distal structural modifications are exploratory, likely reflecting localized soft-tissue fluid shifts rather than permanent anatomical remodeling, and demand future validation via advanced diagnostic imaging.Trial Registration: ClinicalTrials.gov ID= NCT06766877 (registered 9 January 2025).","[""Journal Article"", ""Randomized Controlled Trial"", ""Comparative Study""]","[""Nazir SNB"", ""Asim A""]",10.1038/s41598-026-64385-z,Nazir SNB,Scientific reports,2045-2322,1,Sci Rep,eng,Asim A,"[""Humans"", ""Osteoarthritis, Knee"", ""Female"", ""Middle Aged"", ""Male"", ""Exercise Therapy"", ""Aged"", ""Foot"", ""Treatment Outcome"", ""Pain Measurement"", ""Ankle"", ""Ankle Joint"", ""Pain"", ""Resistance Training"", ""Muscle Strength""]",,42533024,pmc-id: PMC13424365;,2026 Jul 26,2026,https://pubmed.ncbi.nlm.nih.gov/42533024/,"Comparative efficacy of an 8-week core stability program versus foot-ankle strengthening on pain, function, and distal structural parameters in individuals with knee osteoarthritis: a randomized controlled trial",16,RV0oyNZafOMbH8baj,ci9pKxtmjwYaIrEXQ
"Tubulointerstitial nephritis (TIN) with IgM-positive plasma cells (IgMPC-TIN) is an inflammatory disease characterized by the infiltration of IgM and CD138 dual-positive plasma cells into the renal interstitium. Steroid treatment is effective for many cases of IgMPC-TIN. However, the optimal dose and duration of steroid therapy remain poorly understood. In the present case, IgMPC-TIN was diagnosed in a 36-year-old woman with femoral head osteonecrosis. After administration of prednisolone (PSL, 20 mg/day), several markers of disease activity gradually decreased. The PSL dose was tapered to 5 mg/day for one year without TIN recurrence. To avoid exacerbation of bone lesions due to prolonged administration of PSL, cyclosporine was added to PSL. Combination treatment with 5 mg/day PSL and 100-125 mg/day cyclosporine stabilized the TIN. The patient remained stable without recurrence after further reduction and discontinuation of PSL. This case provides original evidence regarding the optimal treatment regimen for patients with IgMPC-TIN who are unsuitable for prolonged PSL administration.","[""Case Reports"", ""Journal Article""]","[""Yamada K"", ""Nakao S"", ""Ikeda M"", ""Suetsugu-Ishizawa R"", ""Hayashi N"", ""Sakuma H"", ""Matsuki M"", ""Takahashi N"", ""Iwano M"", ""Toyama T"", ""Ogawa Y"", ""Nakagawa N""]",10.1007/s13730-026-01153-y,Yamada K,CEN case reports,2192-4449,5,CEN Case Rep,eng,Nakagawa N,"[""Humans"", ""Female"", ""Nephritis, Interstitial"", ""Cyclosporine"", ""Prednisolone"", ""Adult"", ""Immunoglobulin M"", ""Plasma Cells"", ""Immunosuppressive Agents"", ""Treatment Outcome"", ""Drug Therapy, Combination"", ""Remission Induction""]",,42545636,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545636/,Maintenance of clinical remission with cyclosporine after discontinuation of prednisolone in a patient with tubulointerstitial nephritis with IgM-positive plasma cells,15,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Currently, no established guidelines exist for dosing chemotherapy or immunotherapy in patients with achondroplasia. A 69-year old female with congenital achondroplasia was diagnosed with stage IV non-small cell lung carcinoma type adenocarcinoma, with high Tumor Mutational Burden and 20% programmed death-ligand 1 expression. The patient received carboplatin dose based on renal function utilizing measured creatinine clearance, pemetrexed based on body surface area and pembrolizumab at a fixed dose of 100mg for body weight <65 kg. The doses of carboplatin and pemetrexed were adjusted after the first cycle based on therapeutic drug monitoring (TDM). The treatment was generally well tolerated, with the exception of grade 2 neutropenia, which resolved after a one-week delay of the third treatment cycle. A favorable clinical response was achieved after four treatment cycles. Given the uncertainty regarding the accuracy of dosing algorithms in patients with congenital achondroplasia, TDM may support dose optimization and attainment of adequate drug exposure.","[""Journal Article"", ""Case Reports"", ""Review""]","[""Groot Beumer KWM"", ""Durlinger EMJ"", ""Zielhuis SWJ"", ""Ter Heine R"", ""Huitema ADR"", ""Hendrikx JJMA""]",10.1007/s00280-026-04932-7,Groot Beumer KWM,Cancer chemotherapy and pharmacology,0344-5704,1,Cancer Chemother Pharmacol,eng,Hendrikx JJMA,"[""Humans"", ""Female"", ""Achondroplasia"", ""Lung Neoplasms"", ""Carboplatin"", ""Antineoplastic Combined Chemotherapy Protocols"", ""Aged"", ""Drug Monitoring"", ""Pemetrexed"", ""Antibodies, Monoclonal, Humanized"", ""Immunotherapy"", ""Carcinoma, Non-Small-Cell Lung"", ""Dose-Response Relationship, Drug""]",,42545505,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545505/,Dosing challenges for chemotherapy and immunotherapy in congenital achondroplasia: a case report and literature review,96,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Dihydropyrimidine dehydrogenase (DPD), which is encoded by the DPYD gene, plays an important role in the metabolism of fluoropyrimidine (FP) drugs, including tegafur, in S-1. A decrease in DPD activity can cause severe FP-related toxicity. The Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for FP and DPYD polymorphisms recommend FP dose adjustments based on the four major DPYD polymorphisms. However, multiple rare variants of DPYD have been reported. We present the case of a man in his 50s with cT3N0M0 tongue squamous cell carcinoma who developed severe myelosuppression and diarrhea after the initiation of S-1 (tegafur/gimeracil/oteracil) despite appropriate dosing. On day 20 of treatment, the patient developed grade 4 neutropenia and septic shock and required ICU admission. Genetic testing identified a rare heterozygous DPYD variant (c. 812delT) that causes a frameshift and a presumed loss of enzyme function, suggesting an underlying cause of the severe adverse events. Although severe toxicity occurred, marked tumor shrinkage allowed for less invasive surgery. This case highlights the need for expanded genetic screening beyond the guideline-listed variants, particularly in Asian populations, where common variants differ. Combining genotypic and phenotypic evaluations of DPD activity may improve the prediction and prevention of FP-related toxicities, supporting safer and more effective use of FP drugs.","[""Journal Article"", ""Case Reports""]","[""Ishimura H"", ""Suehiro A"", ""Hira D"", ""Hishinuma E"", ""Kato M"", ""Maekawa M"", ""Yasuda T"", ""Katsube Y"", ""Katada Y"", ""Imayoshi N"", ""Shigetsura Y"", ""Nakagawa S"", ""Tsuda M"", ""Hiratsuka M"", ""Terada T""]",10.1007/s00280-026-04930-9,Ishimura H,Cancer chemotherapy and pharmacology,0344-5704,1,Cancer Chemother Pharmacol,eng,Terada T,"[""Humans"", ""Tegafur"", ""Male"", ""Dihydrouracil Dehydrogenase (NADP)"", ""Oxonic Acid"", ""Tongue Neoplasms"", ""Drug Combinations"", ""Middle Aged"", ""Antimetabolites, Antineoplastic"", ""Carcinoma, Squamous Cell""]",,42545499,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545499/,A rare variant in DPYD c.812delT causes severe adverse events of S-1 in a patient with tongue cancer,96,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Rhabdomyolysis in children is frequently attributed to viral myositis or trauma; however, severe or recurrent episodes precipitated by febrile illnesses often indicate an underlying genetic myopathy. Variants in the LPIN1 gene, which encodes the phosphatidic acid phosphatase Lipin-1, have recently emerged as a major cause of early-onset, life-threatening rhabdomyolysis (Autosomal Recessive Acute Recurrent Myoglobinuria). We present the case of a 5-year-old female who presented with acute onset profound lethargy, generalized muscle weakness, and cola-colored urine following a viral prodrome, on a background of previous similar milder episodes. The patient's family history was significant for consanguinity and the unexplained deaths of two siblings at similar ages. Laboratory investigations revealed massive rhabdomyolysis with a creatine phosphokinase (CPK) level of 59,679 U/L and significant myoglobinuria, though renal function remained initially preserved. Given the severity of the presentation and family history, comprehensive genetic investigation was pursued. Whole Exome Sequencing (WES) of a similarly affected younger sibling, followed by targeted familial screening, identified a homozygous variant in the LPIN1 gene; NM_001349206.2: c.2360_2361delinsGA p.(Pro787Arg) in our patient. The patient was managed conservatively with vigorous hydration and alkalinization of urine, resulting in clinical improvement without the development of acute renal failure. LPIN1 deficiency is a critical differential diagnosis in pediatric patients presenting with unexplained, massive rhabdomyolysis, particularly in the context of consanguinity or a history of sibling mortality preceded by muscle weakness. This case highlights the utility of Whole Exome Sequencing post-stabilization to establish a strong molecular basis for the diagnosis, which terminates the diagnostic odyssey and is essential for providing genetic counseling to affected families.","[""Journal Article"", ""Case Reports""]","[""Ahmed MMH"", ""Riaz S"", ""Fatima N"", ""Qasim SM""]",10.1007/s13730-026-01166-7,Ahmed MMH,CEN case reports,2192-4449,5,CEN Case Rep,eng,Qasim SM,"[""Humans"", ""Female"", ""Phosphatidate Phosphatase"", ""Myoglobinuria"", ""Child, Preschool"", ""Rhabdomyolysis"", ""Siblings"", ""Exome Sequencing"", ""Consanguinity"", ""Pedigree"", ""Creatine Kinase"", ""Homozygote""]",,42545443,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545443/,Early identification of LPIN1 variant in a child with severe myoglobinuria and a history of sibling deaths,15,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Pathogenic variants in the WDR72 gene are known to cause hypoplastic amelogenesis imperfecta (AI) and have recently been linked to distal renal tubular acidosis (dRTA). This case report highlights an unusual presentation of WDR72-associated dRTA with renal cysts. A 12-year-old boy presented with difficulty walking, lower limb deformities, and significant growth retardation. On examination, hypoplastic AI, rickets, and short stature were present. Biochemical investigations showed hypokalemia, hypophosphatemia, elevated alkaline phosphatase, and hypercalciuria. Imaging revealed medullary nephrocalcinosis and renal cysts. Clinical exome sequencing identified a homozygous pathogenic nonsense variant in WDR72 (NM_182758.4): c.2934G > A (p.Trp978Ter), consistent with autosomal recessive inheritance. He was diagnosed with dRTA and managed with potassium citrate and phosphate supplementation. Over two years, the patient showed improved growth velocity and reduced hypercalciuria, though nephrocalcinosis and renal cysts persisted. This case of WDR72-associated dRTA complicated by renal cyst formation is an underrecognized phenotype of this rare disorder. It further highlights that delayed diagnosis and prolonged, uncorrected tubulopathy may result in structural renal injury that is not fully reversible with treatment. Systematic renal evaluation, including biochemical assessment and renal ultrasonography, is strongly warranted in all children presenting with AI, particularly in the presence of concurrent growth failure, electrolyte disturbances, or rachitic changes, to facilitate early diagnosis and mitigate the risk of long-term renal sequelae.","[""Journal Article"", ""Case Reports""]","[""Vallabhaneni P"", ""Dawman L"", ""Bhatia A"", ""Kumar V"", ""Bala A"", ""Tiewsoh K""]",10.1007/s13730-026-01168-5,Vallabhaneni P,CEN case reports,2192-4449,5,CEN Case Rep,eng,Tiewsoh K,"[""Humans"", ""Male"", ""Acidosis, Renal Tubular"", ""Child"", ""Phenotype"", ""Kidney Diseases, Cystic"", ""Nephrocalcinosis"", ""Proteins"", ""Hypokalemia"", ""Exome Sequencing"", ""Amelogenesis Imperfecta"", ""Hypercalciuria"", ""Hypophosphatemia""]",,42545441,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545441/,Renal cysts in WDR72-associated distal renal tubular acidosis: expanding the phenotypic spectrum,15,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Anti-glomerular basement membrane (anti-GBM) disease typically presents as rapidly progressive glomerulonephritis, however an atypical anti-GBM nephritis with various light microscopic findings without crescentic formation has been reported in recent years. The findings reported including cases with membranoproliferative glomerulonephritis (MPGN) pattern. Few reports have been able to follow the course of the disease over a long period of time. We report a case of MPGN associated with the spectrum of atypical anti-GBM nephritis that showed a slowly progressive course over more than eight years. A 49-year-old man underwent kidney biopsy because of hypertension, proteinuria, and mild renal insufficiency. The findings on kidney biopsy showed the findings of MPGN. Immunofluorescence microscopy revealed bright linear staining of IgG on the GBM. Electron microscopy showed subepithelial, intra-basement membrane, subendothelial, and paramesangial electron-dense deposits. Serum anti-GBM antibodies were negative. Proteinuria had been present for 4 years prior to the renal biopsy, however no worsening of renal function was observed. Because of worsening proteinuria and the presence of endocapillary hypercellularity in the tissues, the intravenous and oral steroids were started. Although the proteinuria showed slight improvement, the serum creatinine level was stable around 1.5-1.7 mg/dl. Although some indolent cases of atypical anti-GBM syndrome were reported previously, compared with these cases, our patient had more stable renal function for a long time. This is a rare case of resembling atypical anti-GBM disease that shows MPGN with linear IgG staining having a long-term indolent course and without secondary etiology.","[""Journal Article"", ""Case Reports""]","[""Hisamichi-Yamamoto M"", ""Ichikawa D"", ""Ushimaru S"", ""Shirai S"", ""Koike J"", ""Sakurada T"", ""Shibagaki Y""]",10.1007/s13730-026-01167-6,Hisamichi-Yamamoto M,CEN case reports,2192-4449,5,CEN Case Rep,eng,Shibagaki Y,"[""Humans"", ""Male"", ""Middle Aged"", ""Glomerulonephritis, Membranoproliferative"", ""Anti-Glomerular Basement Membrane Disease"", ""Immunoglobulin G"", ""Biopsy"", ""Proteinuria"", ""Kidney"", ""Microscopy, Fluorescence"", ""Disease Progression"", ""Microscopy, Electron"", ""Glomerular Basement Membrane"", ""Antigen-Antibody Complex"", ""Autoantibodies""]",,42545395,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545395/,Immune-complex-mediated membranoproliferative glomerulonephritis with linear IgG staining resembling atypical anti-glomerular basement membrane disease: a case report,15,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Microcephalic osteodysplastic primary dwarfism type II (MOPDII) is a form of primordial nanism characterized by extreme short stature, microcephaly, specific phenotype, maxillofacial dysmorphisms, skeletal dysplasia, disorders of carbohydrate metabolism, and neurovascular abnormalities. This article describes a patient with a Seckel syndrome phenotype presenting with left internal carotid artery aneurysms with intracerebral hemorrhages, thrombocytosis, arterial hypertension, and diabetes mellitus due to insulin resistance confirmed by a low Matsuda index. Target carbohydrate metabolism values were achieved on metformin therapy. Clinical exome sequencing revealed two rare heterozygous variants in the PCNT gene: c.6220C&gt;T (p.Gln2074*) and c.4564-12T&gt;A. Comparison of the results of the molecular genetic study and the patient's phenotype allowed us to verify the diagnosis of MOPDII. Hypergonadotropic hypogonadism was described for the first time in this syndrome.","[""Journal Article"", ""Case Reports"", ""English Abstract""]","[""Platonov VV"", ""Noskova ED"", ""Skorodok YL"", ""Plotnikova EV"", ""Suspitsin EN"", ""Yakovleva TV"", ""Tsoraeva FZ"", ""Polanskaya MA"", ""Jamiyeva SA""]",10.14341/probl13554,Platonov VV,Problemy endokrinologii,0375-9660,3,Probl Endokrinol (Mosk),rus,Jamiyeva SA,"[""Humans"", ""Microcephaly"", ""Dwarfism"", ""Hypogonadism"", ""Osteochondrodysplasias"", ""Adolescent"", ""Male"", ""Fetal Growth Retardation"", ""Phenotype"", ""Antigens""]",80-85,42545326,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42545326/,[Microcephalic osteodysplastic primary dwarfism type II with hypergonadotropic hypogonadism in a 16-year-old patient],72,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Glucagon-like peptide-1 receptor agonists (GLP-1RAs) like semaglutide have transformed type 2 diabetes mellitus (T2DM) management, yet emerging concerns highlight potential risks of accelerated sarcopenia and subsequent metabolic disruptions. This case-driven hypothesis explores a 53-year-old male with T2DM diagnosed in 2014, who experienced progressive glycemic failure despite standard therapies, including metformin, glipizide, sitagliptin, and empagliflozin. Transition to dulaglutide 1.5 mg for 1.5 years followed by semaglutide (titrated from 0.25 to 1 mg weekly starting September 2024) resulted in weight loss from 84 kg to 70 kg by September 2025, accompanied by sarcopenic symptoms (muscle weakness, reduced mobility) and refractory hyperglycemia (fasting glucose 300 mg/dL, HbA1c 9%), persisting post-discontinuation on September 1, 2025, despite metformin and empagliflozin. We posit that semaglutide may precipitate acute sarcopenia via unexpected GLP-1R-mTOR-satellite cells axis crosstalk, disrupting AMPK-mTOR balance to suppress anabolic mTORC1/IGF-1 signaling (potentially by 25-35%) while enhancing catabolic FOXO/ubiquitin-proteasome and excessive autophagy pathways. This could extend to myokine reprogramming (elevated myostatin/GDF15, reduced irisin/IL-15), glucagon/α-cell compensation inducing hyperglucagonemia (15-25% rise), microbiome-bile acid shifts fostering low-grade inflammation (IL-6/TNF-α upregulation by 10-15%), mitochondrial mass reduction (20-25% via AMPK), and NMJ disassembly, collectively impairing muscle as the primary glucose sink (reducing GLUT4-mediated uptake by 35-45%) and initiating a «muscle-glucose feedback loop» with hepatic gluconeogenesis amplification, yielding treatment-resistant hyperglycemia.Supporting evidence from cohorts (e.g., 24-month study showing ASMI/grip strength declines in 432 patients), longitudinal analyses (NMJ degradation with CAF22/NfL elevations in 141 men), secondary trials (9.3% psoas volume loss in 51 MASLD cases), and case reports (fatigue in a 74-year-old, rhabdomyolysis in a 47-year-old) aligns with this framework, as does in vitro data linking GLP-1 excess to kinesin-1/GLUT4 inhibition and ATP depletion (20-30%). This novel hypothesis underscores sarcopenia's role in GLP-1RA-induced metabolic paradoxes, urging prospective studies on muscle-preserving interventions like resistance training or GLP-1R modulators to refine T2DM paradigms and inspire multidisciplinary research into endocrine-muscle interactions.","[""Journal Article"", ""Case Reports""]","[""Ahmed A"", ""Rodini S"", ""Alrubyea F"", ""Akl M""]",10.14341/probl13660,Ahmed A,Problemy endokrinologii,0375-9660,3,Probl Endokrinol (Mosk),eng,Akl M,"[""Semaglutide"", ""Humans"", ""Male"", ""Diabetes Mellitus, Type 2"", ""Middle Aged"", ""Glucagon-Like Peptides"", ""TOR Serine-Threonine Kinases"", ""Sarcopenia"", ""Hyperglycemia"", ""Glucagon-Like Peptide-1 Receptor"", ""Hypoglycemic Agents"", ""Satellite Cells, Skeletal Muscle"", ""Muscle, Skeletal"", ""Glucose""]",60-65,42545324,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42545324/,Semaglutide-Induced Sarcopenia via GLP-1R-mTOR-Satellite Cells Axis and Muscle-Glucose Feedback Loop Potentially Leading to Refractory Hyperglycemia in Type 2 Diabetes: A Case-Driven Hypothesis,72,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"This descriptive clinical case series analyzes five cases of destructive thyrotoxicosis associated with Hashimoto's thyroiditis, historically referred to as hashitoxicosis, initially misdiagnosed as Graves' disease, highlighting a persistent diagnostic challenge in autoimmune thyroid disorders. The series includes four published cases reported between 2000 and 2025 and one unpublished case contributed by the authors. The cohort comprised three females and two males, with a mean age of 55.4 years (range: 21-69). Clinical presentations were heterogeneous, most commonly fatigue (80%), palpitations (60%), and weight changes (40%), while two patients exhibited no overt hyperthyroid symptoms.Biochemical evaluation demonstrated suppressed thyroid-stimulating hormone (TSH) levels in all cases (range: &lt;0.000-0.13 µIU/mL), elevated anti-thyroid peroxidase (anti-TPO) antibodies in 80% (range: 41-&gt;1,000 IU/mL), and initially negative thyroid-stimulating hormone receptor antibodies (TRAb/TSI) in 60% of patients. Seroconversion to positive TRAb/TSI was observed in two cases during follow-up, suggesting autoimmune overlap rather than definitive disease transition. Imaging findings, including thyroid ultrasonography and radioiodine uptake (RAI) studies, consistently favored destructive thyroiditis over stimulatory hyperthyroidism, with heterogeneous echotexture observed in 75% of assessed cases and low or normal RAI uptake in all evaluated patients.Misdiagnosis occurred in 80% of cases, predominantly due to reliance on suppressed TSH levels without TRAb confirmation, resulting in inappropriate antithyroid drug administration in 80% and accelerated hypothyroidism in 60%. Immunopathological interpretation based on existing literature supports a predominantly Th1-mediated destructive process, in contrast to the Th2-driven antibody-mediated stimulation characteristic of Graves' disease, with rare Th1-to-Th2 immune shifts reported. Clinical outcomes ranged from spontaneous resolution to surgical intervention.This case series underscores the importance of mandatory TRAb testing, adherence to American and European Thyroid Association guidelines, and early specialist referral to reduce iatrogenic harm and improve diagnostic precision in autoimmune thyroid disease.","[""Journal Article"", ""Case Reports""]","[""Akl MM"", ""Ahmed A""]",10.14341/probl13651,Akl MM,Problemy endokrinologii,0375-9660,3,Probl Endokrinol (Mosk),eng,Ahmed A,"[""Humans"", ""Graves Disease"", ""Female"", ""Male"", ""Hashimoto Disease"", ""Adult"", ""Middle Aged"", ""Thyrotoxicosis"", ""Aged"", ""Diagnostic Errors"", ""Autoantibodies"", ""Thyrotropin"", ""Young Adult""]",29-35,42545320,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42545320/,"Clinical Case Series of Destructive Thyrotoxicosis Associated with Hashimoto's Thyroiditis Misdiagnosed as Graves' Disease: Clinical Patterns, Diagnostic Pitfalls, and Hypothesized Molecular Insights",72,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Evidence from the literature indicates that workers in the dental care sector are routinely exposed to hazardous airborne agents, particularly mineral and metal dusts. This occupational risk is further amplified in settings with inadequate ventilation and insufficient use of personal protective equipment. We discuss the case of a dental technician with a significant history of occupational exposure who presented to our clinic with exertional dyspnea. High-resolution computed tomography revealed fibrosing nonspecific interstitial pneumonia associated with emphysema, and spirometry showed a severe reduction in carbon monoxide diffusion capacity. After a multidisciplinary evaluation, we performed bronchoscopy with bronchoalveolar lavage (BAL), which revealed an abundance of macrophages. Scanning electron microscopy with energy-dispersive spectrometry of the BAL detected silicon oxide, calcium, iron, and traces of metals typical of dental alloys (titanium, aluminum), as well as rare earth elements and toxic pollutants. These findings supported the diagnosis of interstitial lung disease due to long-term occupational exposure in dental laboratories, enabling a minimally invasive diagnostic approach. This strategy obviated the need for transbronchial biopsy, thereby avoiding a procedure associated with a high risk of pneumothorax in this patient.","[""Journal Article"", ""Case Reports""]","[""Giulianelli G"", ""Maggioni G"", ""Daverio M"", ""Polverosi R"", ""Della Barbera M"", ""Mason P"", ""Spagnolo P"", ""Basso C"", ""Calabrese F"", ""Rizzo S"", ""Balestro E""]",10.23749/mdl.2026.18798,Giulianelli G,La Medicina del lavoro,0025-7818,4,Med Lav,eng,Balestro E,"[""Humans"", ""Lung Diseases, Interstitial"", ""Dental Technicians"", ""Occupational Diseases"", ""Occupational Exposure"", ""Male"", ""Patient Care Team"", ""Bronchoscopy"", ""Bronchoalveolar Lavage Fluid""]",18798,42545249,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545249/,Interstitial Lung Disease in a Dental Technician Diagnosed Through an Integrated Multidisciplinary Approach,117,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
Acute compartment syndrome (ACS) is a rare but potentially fatal sequela of myxedema coma. This article reports the second documented case of the presentation and management of a patient who developed ACS in all four extremities from severe hypothyroidism. This case represents an exceptional presentation of myxedema coma and highlights the potentially life-threatening complications from hypothyroidism and its improper treatment.,"[""Journal Article"", ""Case Reports""]","[""Boland M"", ""LaRiccia B"", ""Bedrin N""]",10.1097/01.JAA.0000000000000384,Boland M,JAAPA : official journal of the American Academy of Physician Assistants,1547-1896,8,JAAPA,eng,Bedrin N,"[""Humans"", ""Myxedema"", ""Coma"", ""Hypothyroidism"", ""Compartment Syndromes"", ""Acute Disease"", ""Male"", ""Female""]",31-32,42545231,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42545231/,Nontraumatic acute compartment syndrome in all four extremities secondary to myxedema coma,39,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Acute postoperative infection caused by Klebsiella pneumoniae after anterior cruciate ligament reconstruction in young, immunocompetent individuals is exceedingly uncommon. An immunocompetent man in his early 20s developed fever and progressive swelling of the knee 5 days after anterior cruciate ligament reconstruction. Laboratory evaluation demonstrated markedly elevated inflammatory markers, including a C-reactive protein level of 18.36 mg/dL and synovial fluid white blood cell count of 62,667/mm3. Culture of aspirated synovial fluid confirmed infection with Klebsiella pneumoniae, establishing a diagnosis of acute postoperative septic arthritis of the knee. The patient underwent prompt arthroscopic debridement with biofilm debulking. Empirical intravenous piperacillin-tazobactam was administered for 3 days, followed by targeted intravenous levofloxacin for 5 days, and oral levofloxacin to complete an 8-week antimicrobial course. Infection was successfully controlled without graft or implant removal. The patient exhibited clinical improvement with resolution of fever and inflammatory signs following treatment. This case highlights that acute Klebsiella pneumoniae infection of the knee joint can occur even in young, immunocompetent patients shortly after anterior cruciate ligament reconstruction, without an identifiable remote infectious focus. Early recognition, prompt arthroscopic intervention, minimal implant burden, and appropriate targeted antibiotic therapy may enable successful infection control in selected patients.","[""Journal Article"", ""Case Reports""]","[""Lin ZH"", ""Lin CH"", ""Ding YS"", ""Chiang CH""]",10.1177/03000605261473109,Lin ZH,The Journal of international medical research,0300-0605,8,J Int Med Res,eng,Chiang CH,"[""Humans"", ""Male"", ""Klebsiella pneumoniae"", ""Klebsiella Infections"", ""Knee Joint"", ""Anterior Cruciate Ligament Reconstruction"", ""Anti-Bacterial Agents"", ""Arthritis, Infectious"", ""Debridement"", ""Young Adult""]",3000605261473109,42545209,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42545209/,Acute Klebsiella pneumoniae infection of the knee joint following anterior cruciate ligament reconstruction in a young adult: A case report,54,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"To assess the pathogenicity of a novel duplication in the RP17 locus identified in a cone dystrophy proband with biallelic CEP290 variants. Structural variants (SVs) in this locus have previously been associated with dominant retinitis pigmentosa. Inheritance of the duplication was assessed by breakpoint polymerase chain reaction (PCR). Ophthalmic evaluation included fundus examination, multimodal retinal imaging, and full-field electroretinogram (ERG). A proband-derived pluripotent stem cell line was differentiated into photoreceptor precursor cells (PPCs) and retinal organoids (ROs). Variant-induced mis-splicing of CEP290 was assessed by reverse-transcription PCR (RT-PCR) and long-read cDNA sequencing, and immunohistochemistry was used to assess photoreceptor morphology. Expression of GDPD1 was quantified by quantitative RT-PCR. The proband and father carried the 324-kb duplication in the RP17 locus. The father was clinically unaffected, but the proband showed features of cone dystrophy, including reduced visual acuity, foveal abnormalities, diminished cone density, and preserved dark-adapted but absent light-adapted ERG responses. The compound heterozygous variants in CEP290 resulted in pseudoexon inclusion and exon 36 skipping in patient-derived retinal cells. Immunohistochemistry revealed altered ciliation and reduced trafficking of L/M opsin and rhodopsin in ROs. In silico modeling predicted that the novel RP17 duplication does not disrupt chromatin looping, and GDPD1 expression was not upregulated in patient ROs, in contrast to pathogenic RP17-SVs. The cone dystrophy phenotype of the proband can be attributed to the CEP290 variants, whereas the novel RP17 duplication can be classified as likely benign based on the integrated evidence. These findings emphasize the importance of modeling and functional studies for accurately classifying RP17-SVs and preventing misinterpretation in clinical diagnostics.","[""Journal Article"", ""Case Reports""]","[""Holtes LK"", ""Chen D"", ""Guilfoyle S"", ""O'Leary H"", ""Corral-Serrano JC"", ""Boonen EGM"", ""Haer-Wigman L"", ""Nieuwenhuis SE"", ""Guarascio R"", ""Toulis V"", ""Andrade de Jesus D"", ""Cremers FPM"", ""Thiadens AAHJ"", ""Cheetham ME"", ""de Bruijn SE"", ""Hardcastle AJ"", ""Roosing S""]",10.1167/iovs.67.10.1,Holtes LK,Investigative ophthalmology & visual science,0146-0404,10,Invest Ophthalmol Vis Sci,eng,Roosing S,"[""Humans"", ""Cell Cycle Proteins"", ""Male"", ""Electroretinography"", ""Pedigree"", ""Centrosomal Associated Proteins"", ""Gene Duplication"", ""Antigens, Neoplasm"", ""Cone Dystrophy"", ""Immunohistochemistry"", ""Cytoskeletal Proteins"", ""Retinitis Pigmentosa"", ""Female"", ""DNA Mutational Analysis""]",1,42545071,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545071/,Identification of a Duplication in the RP17 Locus in an Individual With Pathogenic CEP290 Variants: Implications for RP17 Variant Classification,67,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"&lt;p&gt;This case report presents a 25-year-old man who sustained a crush injury to the right lower limb at the workplace due to compression by a car wheel hub. Initial examination revealed marked swelling of the lower leg and midfoot with preserved sensation and peripheral perfusion. Radiographs demonstrated a bimalleolar ankle fracture and multiple foot fractures. Approximately 5 hours after admission, the patient developed rapidly increasing pain, pallor and cooling of the foot, absence of the dorsalis pedis pulse, decreased toe sensation, and oxygen saturation of 80%. CT angiography showed absent flow in the distal segments of the anterior tibial and fibular arteries. An urgent fasciotomy of the lower leg and dorsal foot compartments was performed ten hours after injury using the shoelace technique, resulting in immediate restoration of perfusion and foot warmth. Sixteen days later, necrotic tissue was debrided, the defect was covered with a split-thickness skin graft (Thiersch technique), and the medial malleolus was stabilized with Kirschner wires. Wound healing was uneventful, with no signs of infection. This case highlights the dynamic and potentially misleading course of acute compartment syndrome and underscores the need for frequent clinical reassessment despite an initially reassuring presentation. Prompt diagnosis and immediate complete fasciotomy prevented irreversible complications.&lt;/p&gt.","[""Journal Article"", ""Case Reports""]","[""Majchrzak JJ"", ""Rzyczniok P"", ""Dugiełło B"", ""Sobolewski J"", ""Mazur D"", ""Wawrzynek W"", ""Stołtny T""]",10.5604/01.3001.0055.8584,Majchrzak JJ,"Ortopedia, traumatologia, rehabilitacja",1509-3492,2,Ortop Traumatol Rehabil,eng,Stołtny T,"[""Humans"", ""Male"", ""Adult"", ""Crush Injuries"", ""Compartment Syndromes"", ""Fasciotomy"", ""Foot Injuries"", ""Treatment Outcome"", ""Leg Injuries""]",119-129,42544999,,2026 Jun 30,2026,https://pubmed.ncbi.nlm.nih.gov/42544999/,Delayed Onset of Acute Compartment Syndrome of Lower Leg and Foot after Crush Injury. Case Report,28,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
,"[""Case Reports"", ""Journal Article""]","[""Nishizono JK"", ""Nakata M""]",10.1056/NEJMicm2603868,Nishizono JK,The New England journal of medicine,0028-4793,,N Engl J Med,eng,Nakata M,[],,42544997,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42544997/,Obstructive Hypertrophic Cardiomyopathy,,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"This article describes the diagnostic criteria of restless legs syndrome (RLS) and periodic limb movements. The pathophysiology of RLS and its management are discussed. The approach to address RLS augmentation is also reviewed. In the 2025 American Academy of Sleep Medicine RLS treatment guidelines, long-term dopamine agonist therapy for RLS was downgraded because of the accumulating evidence of augmentation. In this context, it is important to optimally use IV iron therapy in patients with RLS. Ferric carboxymaltose is more likely to cause hypophosphatemia compared with other IV iron therapy formulations. Bilateral peroneal nerve stimulation demonstrated efficacy and safety, and it can be used as adjunct therapy in patients with refractory RLS. Data from the National RLS Opioid Registry demonstrated reassuring findings, reiterating the role of opioids in the treatment of patients with RLS. An increased periodic limb movement index can often be seen in patients with RLS. Dopamine agonists are no longer considered first-line pharmacologic therapy in patients with RLS. The mainstay of treatment is α2δ calcium channel ligands.","[""Journal Article"", ""Case Reports"", ""Review""]","[""Gorantla S""]",10.1212/cont.0000000000001741,Gorantla S,"Continuum (Minneapolis, Minn.)",1080-2371,4,Continuum (Minneap Minn),eng,Gorantla S,"[""Humans"", ""Restless Legs Syndrome"", ""Nocturnal Myoclonus Syndrome"", ""Female"", ""Male"", ""Dopamine Agonists"", ""Middle Aged""]",1117-1141,42544983,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544983/,Restless Legs Syndrome and Periodic Limb Movements,32,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"This article helps neurologists understand modern approaches to diagnosing obstructive sleep apnea, including the clinical role and limitations of home sleep apnea testing, and learn how they can integrate wearable and noncontact technologies into patient care to improve diagnostic efficiency, monitor treatment, and reduce health disparities. Advances in home sleep apnea testing have expanded beyond traditional type III monitors to include wearable devices such as wrist sensors and smart rings and noncontact ""nearable"" systems that use radar or acoustic signals. Since 2019, the US Food and Drug Administration (FDA) has cleared numerous software-as-a-medical-device platforms that leverage artificial intelligence and multisignal integration to estimate sleep parameters. These tools improve accessibility, particularly for patients who are unable or unwilling to undergo in-laboratory polysomnography. However, awareness of racial bias in pulse oximetry, regulatory gaps, variable accuracy, and privacy concerns highlight the need for further validation to ensure equitable and reliable clinical use. Obstructive sleep apnea is common and underdiagnosed, particularly in patients with neurologic conditions. In-laboratory polysomnography remains the gold standard for the diagnosis of obstructive sleep apnea but is limited by cost and access, whereas home sleep apnea testing offers a validated alternative for appropriate patients. Wearable and nearable technologies expand diagnostic options, improving usability and scalability, although their accuracy and validation vary. Neurologists play a key role in identifying patients at high risk, selecting the appropriate test, and interpreting results with awareness of limitations such as pulse oximetry bias. Consumer devices can raise awareness but should not replace clinical evaluation, and modern continuous positive airway pressure (CPAP) platforms enhance remote monitoring and management.","[""Journal Article"", ""Review"", ""Case Reports""]","[""Lee-Iannotti JK""]",10.1212/cont.0000000000001721,Lee-Iannotti JK,"Continuum (Minneapolis, Minn.)",1080-2371,4,Continuum (Minneap Minn),eng,Lee-Iannotti JK,"[""Humans"", ""Sleep Apnea, Obstructive"", ""Polysomnography"", ""Wearable Electronic Devices"", ""Female"", ""Male"", ""Remote Patient Monitoring"", ""Digital Health"", ""Monitoring, Physiologic""]",1021-1038,42544978,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544978/,Sleep Diagnostics and Monitoring Technology in Obstructive Sleep Apnea,32,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"This article discusses the relationship between sleep and neurodegenerative disorders. Sleep disorders disrupt neurotransmitters, facilitating the progression of neurodegenerative changes. Sleep impairment promotes amyloid-β aggregation, propagating memory impairment in neurodegenerative disorders. The use of biomarkers for early diagnosis of neurodegenerative disorders may include sleep features. Sleep apnea is associated with an increased risk of Parkinson disease. Sleep disorders, such as obstructive sleep apnea, are five times more likely in people with Alzheimer disease. Notably, individuals with genetic factors, including carriers of APOE4, are found to have decreased overall regulation of regions within the brain that control sleep. External factors that increase the risk of dementia include long-term use of antihistamines. The risk of mild cognitive impairment is reduced with the intake of 200 mg/d of caffeine, which aligns the circadian activity of suprachiasmatic nucleus cells. People diagnosed with idiopathic rapid eye movement (REM) sleep behavior disorders have more than a 90% risk of developing an α-synucleinopathy at 14 years follow-up.","[""Journal Article"", ""Review"", ""Case Reports""]","[""Branson CO""]",10.1212/cont.0000000000001734,Branson CO,"Continuum (Minneapolis, Minn.)",1080-2371,4,Continuum (Minneap Minn),eng,Branson CO,"[""Humans"", ""Neurodegenerative Diseases"", ""Sleep Wake Disorders"", ""Sleep"", ""Female"", ""Male""]",1142-1160,42544975,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544975/,Sleep and Neurodegeneration,32,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Understanding respiratory control during sleep is fundamental to understanding the approach to the diagnosis and management of central sleep apnea (CSA). CSA is not one disease but rather a syndrome resulting from a heterogeneous group of etiologies. There are complex chemical, metabolic, mechanical, and neural contributions that can cause dysregulation in loop gain, decreased central respiratory drive, or both. The traditional dichotomy between obstructive versus central sleep apnea is overly simplistic. Conventional CSA is the extreme end along a continuum between obstructive and central phenotypes of sleep apnea. In addition to assessing CSA severity from sleep study data, new approaches, including computational analytics and the use of wearable technologies, are increasingly aimed at extrapolating additional information to characterize CSA etiology. Various positive airway pressure modalities are available to treat CSA, but residual disease is common. There is a better understanding of drugs as causes and as treatments of CSA. Phrenic nerve stimulation is a new treatment option. Multimodal therapy is the likely future of CSA therapy. CSA can be mechanistically divided into hypercapnic and hypocapnic CSA, with the six CSA syndromes in the International Classification of Sleep Disorders (Third Edition, Text Revision) falling under one or both of these categories depending on their etiology. Understanding the obstructive-central continuum of sleep apnea, in which the degree of contribution from each underlying sleep apnea driver, known as endotypes, predicts the relative central disease of a given patient on this continuum, can enhance comprehensive management.","[""Journal Article"", ""Review"", ""Case Reports""]","[""Liu RR""]",10.1212/cont.0000000000001723,Liu RR,"Continuum (Minneapolis, Minn.)",1080-2371,4,Continuum (Minneap Minn),eng,Liu RR,"[""Humans"", ""Sleep Apnea, Central"", ""Female"", ""Male"", ""Polysomnography"", ""Continuous Positive Airway Pressure"", ""Middle Aged""]",1039-1066,42544974,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544974/,Central Sleep Apnea,32,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Obstructive sleep apnea (OSA) is a common disorder that can have a significant negative impact on quality of life and health, including many neurologic disorders. This article discusses the updates in the diagnosis, implications, and treatment of OSA. New recommended criteria for diagnosing OSA increase the recognition of the disorder. Although the apnea-hypopnea index has been the metric used to diagnose, stratify severity, and monitor treatment, it has limitations. A growing number of other metrics, including hypoxic burden, sleep quality, arousal index, respiratory event duration, and daytime sleepiness, are important to consider for comprehensive assessment and risk stratification. Various endotypes and phenotypes of OSA may have certain risks and respond differently to treatment. Treatment of OSA may improve several neurologic symptoms and reduce the risk of neurologic comorbidities. Although positive airway pressure therapy remains the most efficacious treatment of OSA, several alternatives are available, and the list is rapidly expanding, including hypoglossal nerve stimulation and medications. Neurologists should screen for signs and symptoms of OSA as well as consider testing in patients at high risk who are asymptomatic. Treatment should be tailored based on the severity of OSA, objective data such as the arousal index and hypoxic burden, symptoms, comorbidities, and several patient factors, including morphologic characteristics and personal preferences. OSA is a treatable condition that, when well-managed, may lead to improvement of many neurologic conditions and quality of life.","[""Journal Article"", ""Review"", ""Case Reports""]","[""Stahl SM""]",10.1212/cont.0000000000001722,Stahl SM,"Continuum (Minneapolis, Minn.)",1080-2371,4,Continuum (Minneap Minn),eng,Stahl SM,"[""Humans"", ""Sleep Apnea, Obstructive"", ""Female"", ""Male"", ""Polysomnography"", ""Continuous Positive Airway Pressure"", ""Middle Aged"", ""Quality of Life""]",988-1020,42544972,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544972/,Obstructive Sleep Apnea,32,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"The purpose of this article is to provide an overview of how to evaluate, diagnose, and manage patients with hypersomnia disorders. The extended-release formulation of sodium oxybate to treat narcolepsy with a dosage of once a night, rather than twice a night, was approved in 2023 for adults and in 2024 for pediatric patients aged 7 years and older by the US Food and Drug Administration (FDA). The novel pharmacokinetics of this formulation may improve medication adherence and reduce nighttime disruptions and sleep fragmentation for patients and their bed partners. Orexin receptor 2 agonists are also being investigated for the treatment of narcolepsy and idiopathic hypersomnia. CSF orexin testing can be used to diagnose narcolepsy type 1. Patients with hypersomnia have excessive daytime sleepiness, which can be due to an underlying sleep disorder or can be secondary to another condition. Diagnostic tools are useful but imperfect. It is essential to obtain a detailed sleep history to understand how patient symptoms are affecting daily life.","[""Journal Article"", ""Review"", ""Case Reports""]","[""Kay-Stacey M""]",10.1212/cont.0000000000001725,Kay-Stacey M,"Continuum (Minneapolis, Minn.)",1080-2371,4,Continuum (Minneap Minn),eng,Kay-Stacey M,"[""Humans"", ""Disorders of Excessive Somnolence"", ""Narcolepsy"", ""Male"", ""Child"", ""Female"", ""Adult""]",1091-1116,42544970,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544970/,Hypersomnia,32,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"This article reviews sleep basics, including stages, need, changes with aging, sleep drive, and circadian rhythm, to provide a normative framework and to reveal potential opportunities for insomnia intervention. In addition, it elucidates the symptoms, causes, consequences, diagnosis, and treatment of insomnia, including the role of sleep aids and cognitive behavioral therapy (CBT) for insomnia. The wide-ranging consequences of insomnia are increasingly appreciated, with research highlighting its detrimental effects on health. Newer medication options include three orexin receptor antagonists. Home-based sleep tracking may allow screening to identify contributing factors, including sleep disorders that require treatment, and assessment of the environment for early intervention to optimize sleep. Existing and emerging wearable technology and software as digital therapy will increase access to CBT for insomnia through increasingly individualized programs. Insomnia is the most common sleep disorder, with significant effects on quality of life and long-term health. Optimizing the sleep drive and circadian rhythm, addressing underlying causes, reducing hyperarousal, and enhancing conditioning are key components of improving the disorder. Over-the-counter and prescription sleep aids may have a limited role because of modest benefits and the potential for side effects. CBT for insomnia remains the preferred treatment, with a growing number of novel modes of access.","[""Journal Article"", ""Review"", ""Case Reports""]","[""Peters-Mathews BR""]",10.1212/cont.0000000000001724,Peters-Mathews BR,"Continuum (Minneapolis, Minn.)",1080-2371,4,Continuum (Minneap Minn),eng,Peters-Mathews BR,"[""Humans"", ""Sleep Initiation and Maintenance Disorders"", ""Cognitive Behavioral Therapy"", ""Female"", ""Male"", ""Circadian Rhythm"", ""Middle Aged""]",1067-1090,42544969,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544969/,Insomnia,32,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Circadian rhythms describe the near 24-hour oscillations observed across almost all biological processes on Earth. These rhythms serve to coordinate our behavior and physiology with the 24-hour light-dark environment in which we live. This article highlights normal circadian physiology and the disorders that can develop when those processes are disrupted. Although historically circadian dysfunction has been viewed in terms of sleep-wake disorders, there is growing recognition that circadian disruption can contribute to or result from many other disorders frequently encountered within neurology. When caring for patients, it is important to recognize time as a variable in disease presentation and as a potential treatment that can be harnessed to optimize patient outcomes.","[""Journal Article"", ""Review"", ""Case Reports""]","[""Abbott SM""]",10.1212/cont.0000000000001727,Abbott SM,"Continuum (Minneapolis, Minn.)",1080-2371,4,Continuum (Minneap Minn),eng,Abbott SM,"[""Humans"", ""Circadian Rhythm"", ""Chronobiology Disorders""]",1184-1200,42544967,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544967/,Circadian Neurology,32,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"This article reviews the growing field of inpatient sleep medicine, addressing the importance of inpatient sleep quality and the evaluation and treatment of sleep disorders during and shortly after hospitalization. Sleep disruption and sleep disorders in the inpatient setting are associated with worse outcomes. Improving sleep quality and duration in the hospital and treating sleep disorders such as obstructive sleep apnea may improve in-hospital and short-term outcomes, such as mortality, stroke recurrence, and recovery. The 2025 American Academy of Sleep Medicine guidelines conditionally recommend the availability of inpatient sleep medicine services. Screening questionnaires can be used to prioritize objective testing for obstructive sleep apnea or empiric treatment in inpatients, but atypical symptoms in patients with stroke and congestive heart failure make them less sensitive. Objective screening tools such as high-resolution pulse oximetry may help prioritize resources but do not qualify patients for therapy such as CPAP; portable or in-laboratory sleep testing may be needed. Inpatient sleep medicine may be delivered by a multidisciplinary team based on available resources. Even if diagnosis or treatment cannot occur in the inpatient setting, recognizing sleep disorders during inpatient admissions increases the chances for successful outpatient treatment and can facilitate timely outpatient workup.","[""Journal Article"", ""Review"", ""Case Reports""]","[""Boulos MI""]",10.1212/cont.0000000000001726,Boulos MI,"Continuum (Minneapolis, Minn.)",1080-2371,4,Continuum (Minneap Minn),eng,Boulos MI,"[""Humans"", ""Sleep Wake Disorders"", ""Inpatients"", ""Female"", ""Male"", ""Sleep Medicine Specialty"", ""Hospitalization"", ""Sleep Apnea, Obstructive"", ""Middle Aged"", ""Sleep Quality""]",1161-1183,42544966,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544966/,Inpatient Sleep Medicine,32,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Sleep-disordered breathing is a major contributor to morbidity and mortality in individuals with neuromuscular disorders, significantly affecting quality of life. This article provides a comprehensive review of respiratory physiology in the context of neuromuscular disorders, highlights essential components of a sleep-focused clinical history, and outlines evidence-based strategies for the diagnosis and management of sleep-disordered breathing as neuromuscular conditions progress over time. Sleep-disordered breathing testing can be accomplished in various settings to limit barriers to the identification of disease and treatment. Noninvasive ventilation technology has progressed to be more patient centric, with variable settings to ensure patient comfort and support. Early identification and treatment of sleep-disordered breathing in patients with neuromuscular disease can significantly improve quality of life and represent a readily modifiable factor in patient care. Noninvasive ventilation should be tailored to the individual patient's needs and comfort, with ongoing monitoring and adjustments based on specific neuromuscular diagnosis and disease progression.","[""Journal Article"", ""Review"", ""Case Reports""]","[""Dredla BK""]",10.1212/cont.0000000000001729,Dredla BK,"Continuum (Minneapolis, Minn.)",1080-2371,4,Continuum (Minneap Minn),eng,Dredla BK,"[""Humans"", ""Neuromuscular Diseases"", ""Sleep Apnea Syndromes"", ""Female"", ""Male"", ""Noninvasive Ventilation"", ""Middle Aged""]",1201-1219,42544965,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544965/,Sleep-Disordered Breathing in Patients With Neuromuscular Disorders,32,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"This article describes the variability of sleep needs throughout infancy and adolescence and the impact that primary or secondary changes in sleep architecture and sleep quality can have on children. It also reviews the changes in sleep as a child develops as well as the bidirectional relationship of sleep and pediatric neurodevelopmental disorders, epilepsy, and psychosocial health. Pediatric sleep has historically been understudied. Advances have made the quantitative study of pediatric sleep more feasible, although significant gaps remain. As early as prenatal life, sleep can affect a child's development, psychological health, and long-term sleep health. Genetic influences on circadian rhythm and brain development place many children at greater risk of sleep disorders and may one day be used to proactively screen for sleep disorders in children. Knowledge of common pediatric sleep disorders and the influence of sleep health on the impact of neurologic conditions is essential. Every child seen in a neurology clinic should be screened for sleep disorders, especially children with neurodevelopmental differences, epilepsy, or a history of structural brain abnormalities.","[""Journal Article"", ""Review"", ""Case Reports""]","[""Seaborg K""]",10.1212/cont.0000000000001728,Seaborg K,"Continuum (Minneapolis, Minn.)",1080-2371,4,Continuum (Minneap Minn),eng,Seaborg K,"[""Humans"", ""Brain"", ""Sleep"", ""Sleep Wake Disorders"", ""Child"", ""Female"", ""Adolescent"", ""Infant"", ""Neurodevelopment"", ""Male"", ""Child, Preschool"", ""Neurodevelopmental Disorders"", ""Child Development""]",1220-1238,42544963,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544963/,Sleep in the Developing Brain,32,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"To explore the clinical features, serological test, and blood transfusion protocols of hemolytic anemia caused by passenger lymphocyte syndrome (PLS) with multiple antibodies after ABO-incompatible liver transplantation. The hemoglobin (Hb) and bilirubin levels were monitored in a patient (O blood type donor to B blood type) post-liver transplantation in our hospital. The ABO blood group typing, unexpected antibody screening and identify test, direct anti-globulin test (DAT) and acid elution test were performed respectively in blood samples of the patient to identify the serum and erythrocyte membrane sensitized antibodies. The patient's Hb showed a decreasing trend on the day 6 post-operation, reaching the lowest level of 37 g/L on day 12, while her serum bilirubin increased. The patient's ABO blood group did not match. The DAT and the irregular antibody screening test were positive. Anti-B, anti-E, anti-Jkb, and anti-Mur antibodies were detected in the serum, and the anti-B antibodies were detected in the elution liquid. After intermittent infusion of 9 U O type washed red blood cells after day 12, the Hb level increased steadily but the bilirubin level decreased gradually. The patient was discharged with improved conditions on day 38 after surgery. For patients undergoing ABO-incompatible liver transplantation, monitoring the Hb, blood type antibodies, and DAT is essential to timely diagnose PLS and adjust the treatment plan including transfusion strategy.","[""Journal Article"", ""Case Reports"", ""English Abstract""]","[""Wei YR"", ""Huang HN"", ""Wang YL"", ""Huang HL"", ""Wu CL"", ""Liu FF"", ""Li HL"", ""He Y"", ""Mo ZN""]",10.19746/j.cnki.issn1009-2137.2026.03.027,Wei YR,Zhongguo shi yan xue ye xue za zhi,1009-2137,2,Zhongguo Shi Yan Xue Ye Xue Za Zhi,chi,Mo ZN,"[""Humans"", ""Liver Transplantation"", ""Female"", ""ABO Blood-Group System"", ""Blood Group Incompatibility"", ""Anemia, Hemolytic"", ""Lymphocytes"", ""Blood Transfusion"", ""Syndrome""]",822-829,42544672,,2026 Apr,2026,https://pubmed.ncbi.nlm.nih.gov/42544672/,[Serological Characteristics and Transfusion of Passenger Lymphocyte Syndrome with Multiple Antibodies after Liver Transplantation],34,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"To explore perioperative management strategies for mild hereditary hemorrhagic disorders and analyze multidisciplinary collaborative treatment protocols for refractory postoperative bleeding caused by F9 gene variants. We retrospectively reviewed the management of a 31-year-old male with persistent hemorrhage after mixed hemorrhoidectomy. Diagnostic data including coagulation tests ［activated partial thromboplastin time (APTT), coagulation factor activity］, genetic sequencing, and transfusion records was analyzed to summarize key lessons. The preoperative APTT was prolonged to 45.5 s (reference range: 22-38 s). Postoperative bleeding led to progressive hemoglobin decline (164→48 g/L), ultimately controlled with 10 U cryoprecipitate, 3 650 ml fresh frozen plasma (FFP), and 7.5 U red blood cells (RBC). Laboratory confirmation showed that factor IX (FIX) activity was 8.10%-10.10% (reference range: 60%-150%); un-corrected APTT mixing study; hemizygous pathogenic F9 c.881G>A (p.Arg294Gln) variant. Hemoglobin normalized to 121 g/L at 2-month follow-up, and no recurrence bleeding occurred. APTT prolongation serves as a critical warning sign for mild hemophilia B, mandating preoperative coagulation factor screening in males. The p.Arg294Gln substitution disrupts FⅨ catalytic activity, triggering refractory surgical hemorrhage. Multidisciplinary collaboration (replacement therapy+anemia correction) successfully managed life-threatening bleeding, early genetic diagnosis could prevent the risk of postoperative bleeding.","[""Journal Article"", ""Case Reports"", ""English Abstract""]","[""Ao ZC"", ""Zhang HW""]",10.19746/j.cnki.issn1009-2137.2026.03.024,Ao ZC,Zhongguo shi yan xue ye xue za zhi,1009-2137,3,Zhongguo Shi Yan Xue Ye Xue Za Zhi,chi,Zhang HW,"[""Humans"", ""Male"", ""Hemophilia B"", ""Factor IX"", ""Adult"", ""Postoperative Hemorrhage"", ""Retrospective Studies"", ""Partial Thromboplastin Time""]",800-805,42544669,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42544669/,[Multidisciplinary Management and Diagnostic Insights for Refractory Postoperative Hemorrhage in Mild Hemophilia B Caused by Hemizygous F9 c.881G>A (p.Arg294Gln) Variant],34,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"To investigate the clinicopathological features, diagnosis, differential diagnosis, treatment, and prognosis of a patient with follicular lymphoma with predominantly diffuse growth pattern (DFL), in order to enhance understanding of this rare lymphoma variant. Clinical and pathological data of one patient with DFL were collected. A retrospective analysis was conducted on the patient's clinical manifestations, pathological morphological features, immunophenotype, molecular genetic changes, treatment, and follow-up outcomes. Relevant literature was also reviewed. The patient was a 43-year-old female, presenting with a right inguinal area of more than four years' duration. Gross pathological examination revealed a single lymph node measuring 4.0 cm×3.0 cm×2.0 cm, with a gray-white, solid, and soft cut surface. Microscopic evaluation demonstrated architectural effacement and diffuse proliferation with focal residual indistinct follicular structures. Under high magnification, the tumor cells were predominantly centrocytes with a few scattered centroblasts in a heterogeneous background. Immunohistochemistry showed positive expression of CD10, BCL-6, and CD23 in tumor cells, but negative for BCL-2. STAT6 showed weak staining in <1% of tumor cells and was interpreted as negative. Fluorescence in situ hybridization (FISH) showed neither 1p36 deletion nor BCL2 rearrangement. Clonality analysis demonstrated clonal rearrangement of immunoglobulin genes, while T-cell receptor (TCR) gene rearrangement showed a polyclonal pattern. The patient underwent radiotherapy (24 Gy/12 fractions) to the right inguinal area, and has achieved complete remission to date. DFL is a rare subtype of follicular lymphoma with unique clinicopathological features and molecular genetic alterations, which may lead to diagnostic confusion with T-cell lymphomas. Accurate recognition of this subtype helps avoid misdiagnosis and inappropriate treatment. DFL is generally characterized by low histological grade, early clinical stage, and a favorable prognosis.","[""Journal Article"", ""Case Reports"", ""English Abstract""]","[""Wang SF"", ""Li JJ"", ""Lu LM""]",10.19746/j.cnki.issn1009-2137.2026.03.014,Wang SF,Zhongguo shi yan xue ye xue za zhi,1009-2137,3,Zhongguo Shi Yan Xue Ye Xue Za Zhi,chi,Lu LM,"[""Humans"", ""Lymphoma, Follicular"", ""Female"", ""Adult"", ""Retrospective Studies"", ""Prognosis""]",726-731,42544659,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42544659/,[Clinicopathological Characteristics of Follicular Lymphoma with a Predominantly Diffuse Growth Pattern],34,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Denosumab, a monoclonal antibody (mAb) targeting receptor activator of nuclear factor-κB ligand (RANKL), is commonly used in managing metabolic bone diseases and giant cell tumors (GCTs) of bone. Growing evidence suggests that RANKL inhibition may influence cardiovascular health by impacting endothelial function, inflammatory pathways, vascular smooth muscle cell behavior, and systemic calcium regulation. We report a case of a 48-year-old Caribbean-South Asian man with recurrent GCTs who received three subcutaneous doses of denosumab and soon thereafter developed an anterior ST-elevation acute coronary syndrome (STE-ACS). The patient had no traditional cardiometabolic risk factors. Coronary angiography revealed thrombotic occlusion of the proximal left anterior descending artery (LAD), which was successfully treated with primary percutaneous coronary intervention (PPCI) and guideline-directed medical therapy (GDMT). Given the lack of modifiable risk factors, a significant family history, and biologically plausible mechanisms linking RANKL inhibition to atherothrombotic events, a denosumab-associated myocardial infarction was considered the most probable cause.","[""Journal Article"", ""Case Reports""]","[""Maharaj M"", ""Katwaroo A"", ""Ramcharan P"", ""Frederick JM"", ""Seecheran V"", ""Seecheran R"", ""Teelucksingh J"", ""Seecheran N""]",10.1177/23247096261475824,Maharaj M,Journal of investigative medicine high impact case reports,2324-7096,,J Investig Med High Impact Case Rep,eng,Seecheran N,"[""Humans"", ""Denosumab"", ""Middle Aged"", ""Male"", ""Acute Coronary Syndrome"", ""Bone Density Conservation Agents"", ""Coronary Angiography"", ""Bone Neoplasms"", ""Percutaneous Coronary Intervention"", ""RANK Ligand""]",23247096261475824,42544531,,2026 Jan-Dec,2026,https://pubmed.ncbi.nlm.nih.gov/42544531/,Suspected Denosumab-Associated Acute Coronary Syndrome,14,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Lymphatic malformations (LMs) can lead to severe clinical complications, including disfigurement and even death. While genomic alterations have been identified in LMs, the genomic landscape of complex LMs remains poorly defined due to their rarity. In this study, we report two novel findings: an NRAS p.Q61R mutation in central conducting lymphatic anomaly (CCLA) and a PPFIBP1::ROS1 fusion in Gorham-Stout disease (GSD), both described for the first time in their respective LM subtypes. The discovery of the PPFIBP1::ROS1 fusion provided a unique opportunity to localize the somatic event to a specific cell type. Using serial tissue sections from the same specimen, we observed that the fusion signal was spatially associated with lymphatic endothelial cells, based on serial section analysis with D2-40 staining. Given that both NRAS mutations and PPFIBP1::ROS1 fusions have also been identified in other LM subtypes, our findings support the hypothesis that LMs may share common molecular mechanisms. We propose that phenotypic diversity among LM subtypes may arise from differences in developmental timing, anatomic location, and microenvironmental context at the time the somatic mutation occurs.","[""Journal Article"", ""Case Reports""]","[""Yang G"", ""Ren H"", ""Wang J"", ""Chen W"", ""Li X"", ""Chen S"", ""Chen H"", ""Zhao L"", ""Fan W"", ""Xiao S""]",10.1093/hmg/ddag070,Yang G,Human molecular genetics,0964-6906,16,Hum Mol Genet,eng,Xiao S,"[""Humans"", ""Membrane Proteins"", ""Mutation"", ""GTP Phosphohydrolases"", ""Osteolysis, Essential"", ""Adaptor Proteins, Signal Transducing"", ""Lymphatic Abnormalities"", ""Oncogene Proteins, Fusion"", ""Female""]",,42544506,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42544506/,NRAS mutation in a central conducting lymphatic anomaly and PPFIBP1::ROS1 fusion in a Gorham-stout disease patient,35,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Necrotic laryngitis is an important cause of respiratory distress and economic loss in feedlot cattle. Describe the clinical presentation, pathologic lesions, and microbiologic findings associated with necrotic laryngitis in feedlot steers. Four 20-month-old feedlot steers diagnosed with necrotic laryngitis. Clinically affected steers exhibited inspiratory stridor, increased respiratory effort, and flared nares, indicative of upper airway obstruction. Samples from inflamed nasopharyngeal tissues were collected endoscopically using guarded cytology swabs and submitted for culture, with concurrent blood collection for CBC and plasma and serum biochemistry analyses. Endoscopic examinations identified laryngeal chondritis, mucopurulent diphtheritic membranes, and necrotic inflammation of the vocal folds. Aerobic cultures were negative, but anaerobic cultures yielded Fusobacterium necrophorum subsp. necrophorum and or F. necrophorum subsp. funduliforme. Hematologic evaluation indicated leukocytosis and increased plasma fibrinogen concentration, whereas serum biochemistry disclosed marked hyperglycemia and mild increases in hepatic enzyme activities, consistent with stress-related metabolic alterations. Antimicrobial susceptibility testing showed that F. necrophorum isolates were susceptible to β-lactams, tetracyclines, florfenicol, tiamulin, and trimethoprim/sulfamethoxazole, and resistant to aminoglycosides, fluoroquinolones, and with respect to macrolides, 4 strains were susceptible and 1 strain was resistant to tylosin, tilmicosin, and tulathromycin. These findings indicate involvement of either F. necrophorum subsp. necrophorum or subsp. funduliforme in necrotic laryngitis of feedlot cattle. Observed antimicrobial susceptibility patterns indicate ongoing susceptibility to β-lactams and tetracyclines, supporting their continued use as first-line therapeutic options.","[""Journal Article"", ""Case Reports""]","[""Amachawadi RG"", ""Miesner M"", ""Beard W"", ""Beard L"", ""Thomson DU"", ""Noffsinger T"", ""Lukasiewicz K"", ""Salih HM"", ""Wang H"", ""Nagaraja TG""]",10.1093/jvimsj/aalag156,Amachawadi RG,Journal of veterinary internal medicine,0891-6640,4,J Vet Intern Med,eng,Nagaraja TG,"[""Animals"", ""Laryngitis"", ""Fusobacterium necrophorum"", ""Cattle Diseases"", ""Cattle"", ""Male"", ""Fusobacterium Infections"", ""Anti-Bacterial Agents"", ""Necrosis"", ""Microbial Sensitivity Tests""]",,42544489,,2026 Jul 1,2026,https://pubmed.ncbi.nlm.nih.gov/42544489/,Fusobacterium necrophorum in necrotic laryngitis of feedlot cattle,40,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"X-linked ichthyosis (XLI) and X-linked retinoschisis (XLRS) are both inherited in an X-linked recessive manner. To date, no prior reports document both conditions' simultaneous occurrence. This case presents two brothers who were diagnosed with XLI combined with XLRS in a family. An 11-year-old boy (Case 1) presented to our hospital due to decreased bilateral vision detected during a physical examination over the past month. One month after birth, the parents noticed the child's skin was dry and rough. He was diagnosed with ""ichthyosis"" at another hospital, and after treatment, the condition improved. His mother had also been previously diagnosed with ichthyosis. The child was a full-term infant delivered by cesarean section, and his parents were not closely related. There was no family history of eye disease. Physical examination showed dry skin with diamond-shaped scales. The best-corrected visual acuity was 0.40 logMAR in both eyes. No abnormalities were observed in the anterior segments of both eyes. Fundus examination revealed petaloid macular edema, and OCT showed numerous cystic changes in the macular area of both eyes. His 6-year-old younger brother (Case 2) exhibited similar systemic and ocular features. Comprehensive ophthalmic and genetic examinations were performed on the entire family, revealing that both children carried an RS1 gene mutation, with the mutation site at c.545G>T/p.Arg182Leu, inherited from their mother. Additionally, a deletion variant of approximately 478 kb was found at the X chromosome p22.31 location, completely covering the STS gene region. Based on the genetic testing and ocular examination, both children were finally diagnosed with bilateral XLRS and XLI. This case expands the mutation spectrum of XLRS in Chinese patients and, for the first time, reports the ocular and systemic manifestations when two different disease genes, STS and RS1, coexist. The family members vividly demonstrate the phenotypic and genotypic individual heterogeneity associated with hereditary eye diseases. A comprehensive analysis of clinical phenotype and genotype improves clinical diagnosis and genetic testing accuracy, providing a clinical approach for a more comprehensive understanding of the disease.","[""Case Reports"", ""Journal Article""]","[""Liu K"", ""Du X"", ""Yang X"", ""Chen C""]",10.3389/fgene.2026.1781409,Liu K,Frontiers in genetics,1664-8021,,Front Genet,eng,Chen C,[],1781409,42544364,pmc-id: PMC13429230;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42544364/,X-linked recessive ichthyosis with X-linked retinoschisis in two brothers: a case report,17,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"A 2-month-old Boer doeling weighing 13 kg that was intended for show and breeding was evaluated because of a 2-week history of right hind-limb lameness following suspected trauma sustained during an exhibition. Physical examination revealed a grade 4/5 lameness, stifle instability, and abnormal reciprocal apparatus function consistent with peroneus tertius (PT) rupture. Radiographs showed soft-tissue swelling without fracture. Ultrasonography identified synovial proliferation and a defect at the origin of the PT tendon compared with the contralateral limb. Synovial fluid analysis supported a traumatic inflammatory process. A diagnosis of PT tendon rupture with mild stifle sprain was made, and conservative management, including nonsteroidal anti-inflammatory therapy, antimicrobial administration, stall rest, and physical therapy, was initiated. The doeling was re-presented 2 wk later with worsening hind-limb lameness, new forelimb lameness, joint effusion, and respiratory abnormalities. Ultrasonography demonstrated abnormal joint effusion and diffuse pulmonary artifacts with mild pleural effusion. Arthrocentesis of the stifle and glenohumeral joints confirmed septic arthritis affecting multiple joints, suspected to be a result of hematogenous spread secondary to bronchopneumonia. Due to a poor prognosis for long-term soundness and productivity, euthanasia was elected. Key clinical message: This case documents an uncommon PT rupture in a goat and highlights the diagnostic value of ultrasonography, the risk of systemic disease complicating orthopedic injury, and the need for further characterization of prognosis and management of tendon injuries in small ruminants.","[""Case Reports"", ""Journal Article""]","[""Zúñiga J"", ""Bayne JE"", ""Cole RC""]",,Zúñiga J,The Canadian veterinary journal = La revue veterinaire canadienne,0008-5286,8,Can Vet J,eng,Cole RC,"[""Animals"", ""Tendon Injuries"", ""Rupture"", ""Goats"", ""Lameness, Animal"", ""Goat Diseases"", ""Anti-Inflammatory Agents, Non-Steroidal"", ""Stifle"", ""Female"", ""Arthritis, Infectious"", ""Anti-Bacterial Agents""]",860-863,42544358,pmc-id: PMC13429208;embargo-date: 2026/11/01;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544358/,Medical management of a traumatic rupture of the peroneus tertius tendon in a kid goat,67,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"[Purpose] Extension thrust pattern (ETP) during the stance phase is a common gait deviation after stroke; however, there is no consensus regarding the optimal orthosis, such as knee-ankle-foot orthosis (KAFO) or ankle-foot orthosis (AFO). This study aimed to compare the effects of KAFO and AFO on ETP using an N-of-1 trial design. [Participant and Methods] A 54-year-old male with right thalamic hemorrhage and post-stroke hemiplegia participated in this study. A prospective multiple-crossover N-of-1 trial was conducted. Five intervention periods (3 consecutive days each) of KAFO and AFO use were randomly assigned, with a 1-day washout period between interventions. Hip, knee, and ankle joint angles during mid-stance, 10-m walking time, and step count were measured. [Results] KAFO use significantly reduced ankle plantar flexion compared with AFO. A particularly large effect size was observed for the ankle dorsiflexion angle. Improvements in walking time and step count were also noted with KAFO. [Conclusion] KAFO was more effective than AFO in improving ETP in this patient. Objective evaluation using an N-of-1 trial may support more appropriate orthotic selection in clinical practice.","[""Case Reports"", ""Journal Article""]","[""Ogawa H"", ""Shirogane S"", ""Haruna H""]",10.1589/jpts.38.358,Ogawa H,Journal of physical therapy science,0915-5287,8,J Phys Ther Sci,eng,Haruna H,[],358-363,42544349,pmc-id: PMC13429273;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544349/,Comparison of KAFO and AFO for extension thrust pattern after stroke: a randomized N-of-1 trial,38,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Ventriculitis is a severe central nervous system infection with high mortality. We present the case of a 24-year-old male with nasopharyngeal carcinoma who developed primary Klebsiella pneumoniae ventriculitis during hospitalization. He presented with fever, headache, and altered mental status. Due to acute hydrocephalus, an external ventricular drain was inserted, and subsequent cerebrospinal fluid (CSF) cultures yielded K. pneumoniae. Despite aggressive intravenous and intrathecal antibiotic therapy, the patient died from septic shock. This case highlights the rapid clinical deterioration associated with Gram-negative bacterial ventriculitis and the management difficulties encountered in immunosuppressed oncological patients, emphasizing the critical nature of this rare but fatal complication.","[""Case Reports"", ""Journal Article""]","[""Kıymaz E"", ""Çakır-Kıymaz Y"", ""Yoldaş-Aslanoğlu ZP"", ""Bulut Z""]",10.36519/idcm.2026.994,Kıymaz E,Infectious diseases & clinical microbiology,2667-646X,4,Infect Dis Clin Microbiol,eng,Bulut Z,[],419-425,42544346,pmc-id: PMC13429217;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42544346/,Primary Klebsiella pneumoniae Ventriculitis Following Radiotherapy in a Patient with Nasopharyngeal Carcinoma: A Rare Case Report,8,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Chronic exertional compartment syndrome (CECS) is a frequently underdiagnosed cause of exercise-induced leg pain that is activity-dependent. We present the case of a 20-year-old female, high-performance contemporary dancer with an approximately three-year history of progressive leg pain refractory to an exhaustive multimodal conservative treatment including NSAIDs, neuromodulators, physiotherapy with myofascial release, and botulinum toxin infiltration of three compartments. Complementary diagnostic studies including musculoskeletal Doppler ultrasound, magnetic resonance imaging (MRI), and electrodiagnostic studies yielded negative results, consistent with the dynamic nature of the condition. Based on the pathognomonic symptom pattern, imaging evolution, exclusion of neurological and vascular etiologies, and lack of results with conservative measures, a presumptive clinical diagnosis of multi-compartment CECS was established after exclusion of alternative diagnoses. In November 2025, the patient underwent ultrasound-guided percutaneous fasciotomy of the anterior, lateral, and superficial posterior compartments of the left leg via three minimally invasive incisions under regional anesthesia and sedation. Intraoperative reduction of compartmental tension was directly observed following each fascial release. A minor wound dehiscence resolved without further intervention. Serial visual analog scale (VAS) scores demonstrated progressive pain resolution (preoperative 9/10, three weeks 4/10, six weeks 3/10, three months 2/10, and six months 2/10), with a successful return-to-dance program protocol at final follow-up returning to old performance levels. This case highlights the diagnostic challenges of CECS in athletes, the limitations of conservative measures, and the technical feasibility of a simultaneous three-compartment ultrasound-guided percutaneous fasciotomy as a safe, effective, and minimally invasive solution.","[""Case Reports"", ""Journal Article""]","[""Remolina Sánchez Rucobo E"", ""Serrano-Ardila AM"", ""Ponce de Leon Sandoval IA"", ""Kerbel J"", ""Apodaca Ramos GA"", ""Ramos Rocandio NG"", ""Castillo Vazquez FG""]",10.7759/cureus.112001,Remolina Sánchez Rucobo E,Cureus,2168-8184,7,Cureus,eng,Castillo Vazquez FG,[],e112001,42544343,pmc-id: PMC13429170;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42544343/,Ultrasound-Guided Percutaneous Fasciotomy of Three Compartments of the Leg for Chronic Exertional Compartment Syndrome in a High-Performance Contemporary Dancer: A Case Report,18,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"An 85-year-old female walker dependent presented with a displaced olecranon fracture following a fall. Open reduction and internal fixation (ORIF) using an anatomic olecranon locking plate was performed. Two-week postoperative X-rays revealed fixation failure with persistent fragment displacement and a wide fracture gap. To manage this condition, non-operative management, including sling immobilization for 4 weeks and progressive physical therapy, was pursued with the elbow at 90 degrees flexion. At the 6-month follow-up, the elbow was pain-free with functional range of motion (ROM) being achieved, and functional independence was observed in daily activities including using a walker. This case highlights the potential for successful functional recovery through non-operative management in geriatric patients as an initial treatment or after a failed ORIF, emphasizing the importance of tailoring treatment to patient-specific factors and functional goals over radiographic outcomes.","[""Case Reports"", ""Journal Article""]","[""Khorram R"", ""Parkis MS"", ""Kachooei AR""]",10.22038/ABJS.2025.92034.4172,Khorram R,The archives of bone and joint surgery,2345-4644,7,Arch Bone Jt Surg,eng,Kachooei AR,[],484-487,42544341,pmc-id: PMC13429148;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42544341/,Non-Operative Management of a Failed Olecranon Fracture Fixation Leading to Functional Recovery: A Case Report,14,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Unilateral recurrent laryngeal nerve palsy presenting with hoarseness of voice is a common clinical condition with multiple etiological factors, most commonly malignancy, iatrogenic injury, and neurological disorders. Cardiovascular causes are relatively uncommon and are described under Ortner's syndrome, also known as cardiovocal syndrome. Here, we describe the case of a 76-year-old gentleman who presented with progressively worsening hoarseness of voice and aspiration of fluids for two months. Video laryngoscopy revealed left vocal cord palsy and a phonatory gap. Contrast-enhanced computed tomography of the neck and chest demonstrated a saccular aneurysm of the distal aortic arch with mural thrombus compressing the course of the left recurrent laryngeal nerve. A diagnosis of Ortner's syndrome secondary to a saccular aortic arch aneurysm was made. This case highlights the need to consider Ortner's syndrome as a possible diagnosis in patients presenting with new-onset hoarseness of voice, particularly those with underlying cardiovascular disease.","[""Case Reports"", ""Journal Article""]","[""Vikkath JJ"", ""Segar R"", ""Velrajan D"", ""Ts S""]",10.7759/cureus.111979,Vikkath JJ,Cureus,2168-8184,7,Cureus,eng,Ts S,[],e111979,42544338,pmc-id: PMC13429215;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42544338/,The Silent Aneurysm Behind the Hoarse Voice: Ortner's Syndrome,18,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Endodontic failure is a common cause of tooth loss and frequently requires extraction when persistent infection and associated pathology compromise long-term prognosis. Dental implants provide a predictable treatment option for replacing missing teeth while restoring function and esthetics. This case report describes the radiographic documentation of implant-supported rehabilitation following endodontic failure of a mandibular first molar in a 44-year-old female patient. Initial radiographic evaluation revealed a previously endodontically treated mandibular right first molar (tooth #30) associated with persistent periapical pathology and an unfavorable prognosis. The tooth was extracted, and ridge preservation was performed using a bone graft material and a barrier membrane. After a three-month healing period, implant placement was completed with radiographic verification of implant position and proximity to adjacent structures using a guide pin. Following osseointegration, restorative procedures were initiated after implant uncovering through a digital workflow utilizing an intraoral scanner, scan body, and laboratory-fabricated screw-retained zirconia crown. Sequential radiographs documented the diagnostic, surgical, and restorative phases of treatment, including extraction site preservation, implant placement, healing, and definitive restoration. The final outcome demonstrated successful implant-supported rehabilitation with satisfactory radiographic positioning and restoration of function. This case highlights the value of radiographic assessment throughout implant therapy and illustrates a predictable treatment approach for replacing a mandibular first molar affected by endodontic failure.","[""Case Reports"", ""Journal Article""]","[""Mejia Ocampo EM"", ""Mora V"", ""Romero M"", ""Perez Quevedo M"", ""De la Roche IC""]",10.7759/cureus.112009,Mejia Ocampo EM,Cureus,2168-8184,7,Cureus,eng,De la Roche IC,[],e112009,42544327,pmc-id: PMC13429237;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42544327/,Radiographic Documentation of Implant-Supported Rehabilitation Following Endodontic Failure of a Mandibular First Molar: A Case Report,18,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Immune checkpoint inhibitor therapy has transformed the prognosis of multiple solid-organ malignancies; however, such advances are not without significant adverse events known as immune-related adverse events. A novel pattern of autoimmune-like hepatitis following exposure to certain medications, including statins, isoniazid, nitrofurantoin, anti-tumor necrosis factor-alpha therapy and minocycline, has recently been recognized. We present the case of a 66-year-old male patient with extensive-stage small-cell lung carcinoma who developed acute liver injury while receiving concomitant atezolizumab therapy and isoniazid prophylaxis for latent tuberculosis. The patient subsequently developed grade 4 hepatotoxicity, which improved after discontinuation of isoniazid therapy and initiation of corticosteroid treatment. The aim of this report is to contribute to the literature by presenting a rare case of grade 4 immune-related hepatotoxicity under atezolizumab therapy in a patient receiving isoniazid prophylaxis for latent tuberculosis.","[""Case Reports"", ""Journal Article""]","[""Karakaya E"", ""Çığ E"", ""Saka B"", ""Kağızmanlı H"", ""Çöpür S"", ""Gençdal G""]",10.36519/idcm.2026.926,Karakaya E,Infectious diseases & clinical microbiology,2667-646X,4,Infect Dis Clin Microbiol,eng,Gençdal G,[],413-418,42544326,pmc-id: PMC13429225;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42544326/,Immune-Related Hepatotoxicity After Atezolizumab and Isoniazid,8,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Primary Sjögren's syndrome (pSS), a chronic autoimmune disorder primarily affecting the exocrine glands, typically presents with sicca symptoms. Neurological involvement in pSS is uncommon as an initial presentation. Ischemic stroke, in particular, is a rare manifestation, while seizures are more commonly secondary to underlying structural or inflammatory central nervous system involvement. Here, we report a 41-year-old female who presented with a generalized tonic-clonic seizure preceded by left-sided tinnitus and associated with tongue biting, ocular deviation, and postictal confusion. Notably, seven years earlier, she had experienced a neurological event characterized by sudden-onset left-sided weakness and mouth deviation, with neuroimaging at that time reportedly demonstrating an acute infarction in the right temporoparieto-occipital region. During the current admission, brain imaging demonstrated chronic encephalomalacia and gliosis in the same region without evidence of acute infarction. Electroencephalography revealed focal epileptiform discharges in the left temporal lobe. Extensive evaluation of stroke etiologies was unrevealing. Subsequent immunological testing revealed positive anti-Sjögren's syndrome-related antigen A (SSA)/Ro and antinuclear antibodies (ANA). Although sicca symptoms were not reported at the time of the initial neurological presentation, the patient subsequently developed dry eye and dry mouth symptoms, prompting further evaluation with Schirmer's test and labial salivary gland biopsy, which confirmed the diagnosis of pSS. This case highlights the importance of considering autoimmune disorders, including pSS, in selected patients with cryptogenic neurological manifestations. It also underscores the diagnostic challenges posed by atypical presentations in the absence of classic sicca symptoms. Further studies are needed to better understand the relationship between pSS and cerebrovascular disease.","[""Case Reports"", ""Journal Article""]","[""Alkhalifah BI"", ""Abualsaud DA""]",10.7759/cureus.113812,Alkhalifah BI,Cureus,2168-8184,8,Cureus,eng,Abualsaud DA,[],e113812,42544321,pmc-id: PMC13429169;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544321/,Ischemic Stroke as a Possible Initial Manifestation of Primary Sjögren's Syndrome: A Case Report,18,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Rare neurological syndromes have been reported following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, although a causal relationship remains uncertain. We report the case of a 62-year-old woman who developed progressive neurological impairment temporally associated with BNT162b2 (Pfizer-BioNTech) COVID-19 vaccination, resulting in wheelchair dependence. Brain magnetic resonance imaging (MRI) demonstrated multiple periventricular T2-weighted/fluid-attenuated inversion recovery (T2/FLAIR) hyperintense lesions, including lesions oriented perpendicular to the lateral ventricles, consistent with demyelinating features. A multimodal therapeutic approach was implemented, including gut-directed therapy, intravenous gold-induced cytokine (GOLDIC®) therapy, hyperbaric oxygen therapy (HBOT), intranasal exosome therapy, and structured neurorehabilitation. Over the course of treatment, the patient showed substantial clinical improvement, including recovery of ambulation and functional neurological status. While this case highlights the potential for significant neurological involvement following SARS-CoV-2 vaccination and the possibility of recovery with a multimodal therapeutic approach, the contribution of the individual therapies cannot be determined. Further research is needed to better understand the underlying mechanisms and to evaluate emerging therapeutic strategies, including GOLDIC, in this setting.","[""Case Reports"", ""Journal Article""]","[""Hobbi H"", ""Al-Jumaily M"", ""Al Hakim H""]",10.7759/cureus.112004,Hobbi H,Cureus,2168-8184,7,Cureus,eng,Al Hakim H,[],e112004,42544316,pmc-id: PMC13429209;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42544316/,Functional Recovery Following Post-vaccination Neurological Syndrome With Demyelinating Findings on Magnetic Resonance Imaging (MRI): A Case Report,18,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Single-stage repair of infected aortic grafts through a clamshell incision (bilateral thoracotomy with transverse sternotomy) is rarely undertaken, even when this approach could offer better exposure. We describe the use and considerations of a clamshell approach in the context of a rare prosthetic graft infection involving ascending, arch, and descending aortic segments. A 59-year-old man underwent aortic valve plus ascending aorta and total arch replacement for acute type A dissection. Eleven months later, he presented with a contained rupture at the distal anastomosis of his aortic arch graft. A thoracic endovascular aortic repair was performed extending into the descending aorta. However, within a few weeks, the patient developed fever and persistent distal anastomotic pseudoaneurysms, suggesting graft infection (without an obvious culprit organism). Replacement of the entire aortic arch, ascending, and descending aorta, preserving the aortic valve, was ultimately performed via a clamshell incision, requiring total circulatory arrest (eight minutes) and antegrade cerebral perfusion (28 minutes). Postoperatively, the patient was ventilated for 2.7 days and was discharged home on postoperative day 26 with empirical antibiotic therapy. The culprit organism was later identified as Parvimonas micra (P. micra) following extensive microbiological analysis (16S ribosomal deoxyribonucleic acid sequencing). The patient presented with hemoptysis and recurrent signs of infection on aortic imaging at approximately three months following his final operation. After discussion with the patient and family, nonoperative management was determined as the most appropriate path forward. This case illustrates the technical feasibility of this approach to address graft material present in the ascending, arch, and descending aorta. While the outcome was not ideal for this patient, our approach made this very extensive removal of graft material possible; such a procedure would not have been feasible with a midline sternotomy and would have required a multi-stage repair. Further, P. micra was an unexpected culprit, difficult to detect and detected late; this underscores the potentially growing importance of considering unexpected culprits and using advanced sequencing in culture-negative graft infections.","[""Case Reports"", ""Journal Article""]","[""MacKinnon MJ"", ""Ferguson DB"", ""White CW"", ""Cloutier J"", ""Légaré JF""]",10.7759/cureus.111961,MacKinnon MJ,Cureus,2168-8184,7,Cureus,eng,Légaré JF,[],e111961,42544309,pmc-id: PMC13428677;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42544309/,"Clamshell Thoracosternotomy for Single-Stage Repair of a Rare Aortic Graft Infection Involving Ascending, Arch, and Descending Aortic Pathologies",18,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Cor triatriatum dexter is a rare congenital cardiac anomaly characterized by persistence of a membranous structure that divides the right atrium into two chambers. Although often asymptomatic, cor triatriatum dexter may present in adulthood with nonspecific symptoms and atrial arrhythmias, including atrial fibrillation and atrial flutter. We present a case series of four adult patients in whom cor triatriatum dexter was incidentally diagnosed during cardiac evaluation for diverse clinical presentations. Patients ranged in age from 51 to 75 years and presented with new-onset seizures, ischemic stroke evaluation, heart failure exacerbation, and recurrent atrial arrhythmias. In all cases, diagnosis was established using echocardiographic imaging, with transesophageal echocardiography providing definitive visualization when transthoracic studies were nondiagnostic. This series highlights the diagnostic challenges of cor triatriatum dexter in adults and suggests that the condition may be underrecognized. Furthermore, altered right atrial anatomy may be associated with atrial arrhythmia maintenance through structural and conduction alterations of the right atrium.","[""Case Reports"", ""Journal Article""]","[""Almakadma AH"", ""Inshyna D"", ""Khan P"", ""Sabra M"", ""Ibrahim R"", ""Farid M"", ""Burkhanova U"", ""Mehta D"", ""Saeidifard F"", ""Chadow HL""]",10.21542/gcsp.2026.23,Almakadma AH,Global cardiology science & practice,2305-7823,3,Glob Cardiol Sci Pract,eng,Chadow HL,[],e202623,42544304,pmc-id: PMC13429181;,2026 Jun 30,2026,https://pubmed.ncbi.nlm.nih.gov/42544304/,Unmasking cor triatriatum dexter in adult patients with atrial arrhythmia,2026,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"A 5-year-old spayed female domestic shorthair cat was referred to the Clinical Nutrition Service at the Ontario Veterinary College (Guelph, Ontario) for management of chronic, nonresponsive enteropathy and recently diagnosed diabetes mellitus. The cat was presented with persistent diarrhea, perianal ulceration, weight loss, and poor glycemic control despite treatment with prednisolone, cobalamin injections, a hydrolyzed diet, and short antimicrobial trials. Once hospitalized, the cat was transitioned to a high-protein, low-carbohydrate commercial veterinary therapeutic diet containing mixed protein sources. Nutritional support was initiated via a nasogastric tube but discontinued after 48 h when voluntary oral intake resumed. Clinical signs improved gradually over 5 d, blood glucose stabilized below the renal threshold, and insulin therapy was discontinued at discharge after 6 d of hospitalization. The commercial veterinary therapeutic diet was maintained, and psyllium husk was later added to improve stool quality. Soft stools persisted for several months, with normalization occurring only after targeted fiber supplementation was introduced alongside ongoing medical management. This case highlights the importance of individualized nutritional management in chronic enteropathy, as clinical response to dietary intervention may evolve over time and long-term stabilization may require alternative strategies beyond hydrolyzed-protein diets. Key clinical message: Dietary responsiveness in feline chronic enteropathy is highly individualized. Hydrolyzed-protein diets are commonly recommended, but responses may vary between cases. Sequential and sustained dietary trials, guided by clinical response, may be necessary to achieve durable remission.","[""Case Reports"", ""Journal Article""]","[""Fischer MM"", ""Abood S"", ""Collier A"", ""Verbrugghe A""]",,Fischer MM,The Canadian veterinary journal = La revue veterinaire canadienne,0008-5286,8,Can Vet J,eng,Verbrugghe A,"[""Animals"", ""Cats"", ""Female"", ""Cat Diseases"", ""Chronic Disease"", ""Animal Feed"", ""Intestinal Diseases"", ""Psyllium""]",853-859,42544297,pmc-id: PMC13429197;embargo-date: 2026/11/01;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544297/,Nutritional management of feline chronic enteropathy with evolving dietary response and long-term stabilization,67,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Renal involvement in chronic lymphocytic leukaemia (CLL) is uncommon but clinically relevant. We report a man in his early 70s with known CLL who presented with non-nephrotic proteinuria, progressive kidney injury, and hyperkalaemia. Kidney biopsy revealed diffuse membranoproliferative glomerulonephritis with IgG kappa monoclonal deposits on immunofluorescence and electron microscopy, establishing a diagnosis of CLL-associated proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID). Treatment with rituximab and chlorambucil resulted in significant improvement of both kidney function and proteinuria. This case highlights the pivotal role of kidney biopsy in CLL-associated nephropathy: it established a precise diagnosis in the absence of detectable circulating paraprotein, triggered clone-directed therapy, and demonstrated that meaningful renal recovery is achievable even in the context of acute kidney injury.","[""Case Reports"", ""Journal Article""]","[""Rodrigues F"", ""Pais M"", ""Terencio R"", ""Manso R"", ""Silva J""]",10.7759/cureus.112008,Rodrigues F,Cureus,2168-8184,7,Cureus,eng,Silva J,[],e112008,42544283,pmc-id: PMC13429235;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42544283/,Chronic Lymphocytic Leukaemia (CLL)-Associated Proliferative Glomerulonephritis With Monoclonal Immunoglobulin Deposits (PGNMID) Diagnosed in the Absence of Detectable Paraprotein,18,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"We report the case of a 33-year-old male mountaineer, presenting with chest pain, severe headache, dyspnea, and lower extremity edema, on his first expedition to Paraw mountain located in Kermanshah Province. His condition involved a complex thrombotic presentation, including both venous and arterial events, such as a myocardial infarction due to stenosis of the left main coronary artery, which we believe to be a coincidental pathology. His neurological symptom includes headache, vomiting, and slight drowsiness associated with chest pain, which were evaluated alongside confirmatory testing for protein C-S deficiency. Physical examination revealed right lower extremity edema, respiratory distress (RR = 34), and mid-drowsiness. Chest X ray showed lung congestion. A history of recurrent thrombophlebitis, along with the current myocardial infarction, raised suspicion of a thrombophilic state. The final diagnosis of these complications was confirmed to have protein C-S deficiency based on laboratory tests performed during the acute phase. However, the hereditary nature of this deficiency remains unconfirmed as no genetic testing or family screening was undertaken. The patient underwent coronary artery bypass grafting of left anterior descending artery (LAD) and LCX associated with anticoagulant therapy, and his neurologic sign and symptom and lower extremity deep vein thrombosis recovered uneventfully.","[""Case Reports"", ""Journal Article""]","[""Sabzi F"", ""Faraji R"", ""Shokri F"", ""Ghaysouri A"", ""Maleki A"", ""Rashidi T""]",10.21542/gcsp.2026.22,Sabzi F,Global cardiology science & practice,2305-7823,3,Glob Cardiol Sci Pract,eng,Rashidi T,[],e202622,42544281,pmc-id: PMC13429176;,2026 Jun 30,2026,https://pubmed.ncbi.nlm.nih.gov/42544281/,Concomitant effect of high altitude and thrombophilia on multi-organ thrombosis,2026,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Pseudoexfoliation syndrome (PXF) presents significant challenges in cataract surgery due to zonular weakness and poor pupillary dilation. We report a case of a 72-year-old woman with PXF who underwent cataract surgery using a ""pop-out"" nucleus technique facilitated by hydrodissection. The technique allowed the safe prolapse of the nucleus into the anterior chamber despite zonular instability. Postoperative visual outcomes were favorable, improving from 0.1 preoperatively to 0.9 one week after surgery. This case highlights the safety and effectiveness of the ""pop-out"" technique in managing complex cataract cases associated with pseudoexfoliation.","[""Case Reports"", ""Journal Article""]","[""Sharaf T""]",10.7759/cureus.111999,Sharaf T,Cureus,2168-8184,7,Cureus,eng,Sharaf T,[],e111999,42544264,pmc-id: PMC13429168;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42544264/,"Effective ""Pop-Out"" Nucleus Technique in Cataract Surgery With Pseudoexfoliation: A Case Report",18,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Atraumatic splenic rupture is a rare but potentially life-threatening condition, most commonly associated with infectious, hematological, neoplastic, inflammatory, or iatrogenic disorders. Cytomegalovirus (CMV)-associated splenic rupture is an exceptionally uncommon complication in immunocompetent individuals. We report the case of a 46-year-old immunocompetent man who presented to the emergency department with acute abdominal pain and a low-grade fever. Laboratory investigations revealed mild microcytic anemia, thrombocytopenia, elevated inflammatory markers, and mild transaminase elevation. Contrast-enhanced abdominal computed tomography demonstrated splenomegaly, a large perisplenic collection consistent with a subcapsular hematoma, and moderate hemoperitoneum, raising suspicion of atraumatic splenic rupture. During clinical observation, the patient developed hemodynamic instability, prompting emergency exploratory laparotomy. Intraoperative findings included massive hemoperitoneum, capsular laceration involving the upper pole, and an extensive subcapsular hematoma. Splenectomy was performed. Postoperative serological investigations revealed markedly elevated anti-CMV IgM levels associated with low anti-CMV IgG levels and low IgG avidity, consistent with acute CMV infection. The pathological examination supported the diagnosis of CMV-associated atraumatic splenic rupture. No antiviral therapy was deemed necessary following infectious disease consultation, and the patient recovered uneventfully with planned post-splenectomy vaccination. CMV infection has increasingly been linked to thrombotic and vascular complications, even in immunocompetent individuals. Proposed mechanisms of splenic rupture include endothelial dysfunction, transient prothrombotic states, lymphocytic infiltration of splenic tissue, ischemic injury, and reduced capsular elasticity. Since clinical manifestations are often nonspecific and may mimic other causes of acute abdomen, diagnosis can be challenging. Contrast-enhanced computed tomography remains the gold standard for diagnosis and therapeutic planning. Management depends on the severity of splenic injury and the patient's hemodynamic status; however, splenectomy remains the preferred treatment in cases of severe injury or hemodynamic deterioration. This case highlights the importance of considering CMV infection in the differential diagnosis of atraumatic splenic rupture and underscores the value of early imaging and prompt intervention in optimizing patient outcomes.","[""Case Reports"", ""Journal Article""]","[""Sejfullai K"", ""Giannini F"", ""Sorrentino M""]",10.7759/cureus.111978,Sejfullai K,Cureus,2168-8184,7,Cureus,eng,Sorrentino M,[],e111978,42544261,pmc-id: PMC13428986;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42544261/,Spontaneous Splenic Rupture Associated With Cytomegalovirus Infection: A Case Report,18,HpcTPOeV5WMOPMvQw,wgNZjaSQ70XhXwNlm
"Covering: 1995 up to the end of 2025Homocyclic aromatic compounds (HAC) represent the second most abundant class of natural and anthropogenic products. Their biodegradation is central to the global carbon cycle and the bioremediation of aromatic pollutants. A key step in this process is enzymatic dearomatization, historically attributed exclusively to oxygen-dependent mono- or dioxygenases. However, over the past three decades, a growing diversity of oxygen-independent dearomatizing reductases has been identified. These enzymes act either on partially activated di- or trihydroxybenzenes and trihydroxynaphthalenes with meta-oriented hydroxyl groups, or on coenzyme A (CoA) thioesters of carboxylated HAC, converting aromatic substrates into cyclic dienes. Class I and II benzoyl-CoA reductases catalyze Birch-like reductions via radical intermediates at metal cofactors, with low-potential electrons supplied either through ATP-dependent electron transfer (class I) or flavin-based electron bifurcation (class II), whereas 2-naphthoyl-CoA reductase appears independent of an electron-activation system. An alternative, non-redox dearomatization mechanism has been identified in S-adenosyl-L-methionine-dependent methyltransferases involved in the anaerobic bacterial estrogen-to-androgen conversion, as well as in polyketide tailoring. Together, these findings reveal a broad enzymatic repertoire for overcoming arene resonance stabilization under anoxic conditions. Beyond their ecological significance, these pathways provide mechanistically diverse routes and opportunities for biocatalysis and the sustainable synthesis of valuable chemical building blocks.","[""Journal Article"", ""Review""]","[""Zhan T"", ""Breiltgens J"", ""Appel L"", ""Peller L"", ""Husain SM"", ""Müller M"", ""Boll M""]",10.1039/d6np00062b,Zhan T,Natural product reports,0265-0568,,Nat Prod Rep,eng,Boll M,[],,42545677,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545677/,Oxygen-independent enzymatic dearomatization of homocyclic aromatic compounds,,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Hydrogels are highly hydrated three-dimensional polymeric network materials that have attracted considerable attention in medical and biomedical fields owing to their favorable chemical modifiability, physical tunability, biocompatibility, and capacity to mimic key features of native extracellular matrices. With advances in polymer chemistry, crosslinking strategies, stimuli-responsive design, and emerging fabrication technologies, hydrogels have evolved from simple soft materials into multifunctional biomedical systems capable of integrating controlled delivery, tissue support, microenvironmental regulation, biosensing, and disease modeling. These properties make hydrogels particularly relevant for addressing a broad spectrum of human diseases in which conventional therapeutic strategies are often limited by insufficient targeting efficiency, limited therapeutic windows, pronounced systemic side effects, and inadequate restoration of damaged tissue structure and function. In this review, we systematically summarize the design principles and material engineering strategies of hydrogels, including structural construction approaches and functional regulation concepts. We then provide a comprehensive overview of their current biomedical applications, encompassing drug delivery systems, tissue engineering and regenerative medicine, biosensing and diagnostic platforms, as well as cell culture and organoid systems. Building on this foundation, we place particular emphasis on recent progress in hydrogel-based therapeutic strategies across diverse human disease contexts, including wound healing, musculoskeletal system repair, cancer, neurological diseases, cardiovascular diseases, autoimmune disorders, and reproductive system diseases. Finally, we discuss the developmental potential of hydrogels in biomedicine and present an integrated perspective on their clinical translation prospects, with the aim of offering references and insights for the further application of hydrogel materials in future human disease treatment.","[""Journal Article"", ""Review""]","[""Wu H"", ""Piao G"", ""Chen Q"", ""Luo W"", ""Liu J"", ""Lan Y"", ""Wang Y"", ""Zhou J"", ""Yang K"", ""Xiao J"", ""Lv Q"", ""Yang S"", ""Feng W"", ""Zhu G"", ""Tan S"", ""Hu X""]",10.1186/s43556-026-00525-1,Wu H,Molecular biomedicine,2662-8651,1,Mol Biomed,eng,Hu X,"[""Hydrogels"", ""Humans"", ""Tissue Engineering"", ""Animals"", ""Drug Delivery Systems"", ""Regenerative Medicine"", ""Biocompatible Materials""]",,42545667,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545667/,Hydrogels: current biomedical applications and future directions,7,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"There is an emerging understanding of neurodegenerative diseases as complex diseases with a combination of multiple interrelated signaling pathways as opposed to one causative factor. This review examines the idea that neurons do not die in a single event, but through convergence of signals, which outlines the different pathological events such as oxidative stress, mitochondrial dysfunction, excitotoxicity, calcium imbalance, impaired proteostasis and neuroinflammation that interact to determine the fate of neurons. The processes are closely connected by molecular nodes like ROS, NF-κB, and MAPK signaling pathways, Nrf2/Keap1 antioxidant axis, and dysregulated autophagy and endoplasmic reticulum stress responses. The review also discusses the contribution of neuron glia interactions and the impact of microglial activation, astrocyte malfunction and cytokine networks in enhancing neuronal damage in a feedback mechanism. Mechanisms that have been mentioned as the oxidative stress inflammation cycle, mitochondrial damage, ROS feedback, and protein aggregation cellular stress loop are cited to be the major contributors to disease progression. Also, the review mentions new biomarkers, multi-omics methods, and sophisticated research instruments, such as artificial intelligence and organoid models, which can contribute to our knowledge of disease pathogenesis and help diagnose it earlier. On the whole, this review presents a complete paradigm on how to perceive neurodegeneration as a systems-level phenomenon. It combines molecular, cellular, and clinical perspectives and offers the rationale for the need to consider the therapeutic approach to neurodegenerative diseases in a holistic and multi-dimensional manner.","[""Journal Article"", ""Review""]","[""Chauhan D"", ""Goel F"", ""Rajput MS""]",10.1007/s12035-026-06093-3,Chauhan D,Molecular neurobiology,0893-7648,1,Mol Neurobiol,eng,Rajput MS,"[""Humans"", ""Animals"", ""Signal Transduction"", ""Neurons"", ""Oxidative Stress"", ""Neurodegenerative Diseases"", ""Cell Death"", ""Mitochondria""]",,42545664,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545664/,"Neurons Die Not by One Hit, but by Signaling Convergence",63,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Unopposed estrogen refers to prolonged estrogenic stimulation in the absence of adequate progesterone-mediated counter-regulation. Unopposed estrogen is strongly implicated in endometrial hyperplasia and type I endometrial carcinogenesis, and it is also biologically relevant to estrogen receptor-positive breast cancer. Evidence linking estrogen exposure to ovarian cancer is more heterogeneous and appears to vary by menopausal status, hormone therapy formulation, duration of exposure, and histologic subtype; therefore, ovarian cancer risk should be interpreted as an association rather than a definitive causal consequence of unopposed estrogen. Ongoing estrogen signaling can drive cell proliferation, oxidative DNA damage, and chronic inflammation in estrogen target tissues. Until now, conventional hormone assays, such as enzyme-linked immunosorbent assay (ELISA) have only been able to measure the amount of hormones in the circulation, but may not effectively detect dynamic, tissue-specific, or early-stage estrogenic activity. This review is unique in focusing on unopposed estrogen as a clinically significant biosensing target and critically reviewing estrogen receptor functionalized nanoprobe platforms for the detection of unopposed estrogen and the diagnosis of cancer, unlike other reviews, which have broadly discussed estrogen biosensors or nanoprobe-formatted cancer diagnostics. It focuses on platforms using estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) as well as strategies for receptor immobilization, nanomaterials design, signal transduction, and applications in biofluids, cells, and tissues. The review also discusses a translational aspect by considering obstacles to clinical implementation, such as probe stability, specificity of chemical analysis in complex biological matrices, required assay standardization, validation, and compatibility with use in a portable or point-of-care system. Newer trends like multiplex hormone profiling, smart devices integration, and signal interpretation with the help of machine learning (ML) are also discussed. This review aims to place unopposed estrogen biology in the context of ER-functionalized nanobiosensing and clinical translation problems, establishing a focused framework for future precision diagnostic tool development for cancer risk assessment and early detection by estrogen.","[""Journal Article"", ""Review""]","[""Uti DE"", ""Alum EU"", ""Ogbu CO"", ""Ugwu OP"", ""Egbung GE"", ""Atangwho IJ"", ""Dagnaw M"", ""Jan A""]",10.1186/s11671-026-04831-z,Uti DE,Discover nano,2731-9229,1,Discov Nano,eng,Jan A,[],,42545662,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545662/,Sensitive detection of unopposed estrogen using estrogen receptor functionalized nanoprobes for cancer diagnosis,21,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Adolescent girls and young women (AGYW) in sub-Saharan Africa bear a disproportionate burden of HIV. Long-acting injectable PrEP (LAI-PrEP) may address adherence challenges associated with daily oral PrEP, but social and structural barriers threaten real-world implementation. Drawing on parallels with injectable contraception and multipurpose prevention technologies (MPTs), this systematic review synthesizes evidence on barriers and facilitators to LAI-PrEP use among AGYW in sub-Saharan Africa. Following PRISMA guidelines, peer-reviewed studies published January 2015 to February 2025 were identified across four databases. Studies were included if they examined barriers or facilitators to uptake or adherence of injectable PrEP, contraception, or MPTs among AGYW in sub-Saharan Africa. Data were abstracted using a socioecological model adapted for PrEP implementation. Of 1,716 screened references, 53 met inclusion criteria, spanning 37 countries. Most studies focused on injectable contraception; only nine examined injectable PrEP, eight of which assessed hypothetical use. Cross-cutting barriers included fear of side effects, misinformation, stigma, and logistical and cognitive challenges related to return visits. Cross-cutting facilitators included familiarity with injectables, social support, and perceived privacy. Partner and provider power dynamics, restrictive sociocultural norms, provider gatekeeping, and health system limitations further shaped injectable use. Despite biomedical advantages, LAI-PrEP uptake among AGYW may face entrenched barriers similar to other PrEP modalities. Although AGYW's familiarity with injectable contraception may enhance LAI-PrEP acceptability, systemic and interpersonal challenges remain under-addressed. Effective LAI-PrEP implementation in the real-world will require integrating lessons from contraceptive programs, improving provider training, expanding delivery channels, and centering AGYW in decision-making to support equitable scale-up.","[""Journal Article"", ""Review""]","[""Mancuso N"", ""Endres-Dighe S"", ""Nhamo D"", ""Diaz M"", ""Nyamaizi AM"", ""Mangxilana NT"", ""Montgomery ET"", ""Napierala S"", ""Hosek S"", ""Mgodi NM"", ""Atujuna M"", ""Roberts ST""]",10.1007/s10461-026-05201-7,Mancuso N,AIDS and behavior,1090-7165,,AIDS Behav,eng,Roberts ST,[],,42545658,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545658/,A Systematic Review of Barriers and Facilitators to the Uptake and Adherence of Injectable PrEP Among Adolescent Girls and Young Women in Sub-Saharan Africa,,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Chronic myelomonocytic leukemia (CMML) is a clonal myelodysplastic/myeloproliferative neoplasm characterized by sustained monocytosis, recurrent gene mutations, and a risk of transformation to acute myeloid leukemia (AML). This review examines the historical evolution of CMML as a diagnostic entity, its genetic landscape, fundamental controversies in definition, including the contentious boundaries of oligomonocytic CMML (OM-CMML), and the spectrum of associated phenomena, such as plasmacytoid dendritic cell proliferations, systemic mastocytosis, extramedullary disease, and autoimmune manifestations. Since the publication of the most recent myeloid classification systems, genomic studies in large CMML cohorts have clarified that cases with borderline monocyte counts are biologically heterogeneous: a subset with bi-allelic TET2 inactivation or TET2 + SRSF2 co-mutation bears the greatest similarity to true CMML, while cases harboring SF3B1, bi-allelic TP53 inactivation (biTP53), or del(5q) may be better classified as myelodysplastic syndrome/neoplasm (MDS), irrespective of the presence of borderline monocytosis. Molecular evolution from clonal hematopoiesis through OM-CMML to overt CMML, and ultimately to acute myeloid leukemia (AML), follows a defined clonal trajectory characterized by the stepwise acquisition of spliceosome, epigenetic, and signaling mutations. Plasmacytoid dendritic cell proliferations, particularly blastic forms, arising in association with or following CMML, share clonal origin and represent a distinct spectrum of monocyte/plasmacytoid dendritic cell lineage dysregulation. In future classification systems, better biologic homogeneity of CMML may be achieved by incorporating specific molecular signatures in the diagnostic criteria and by excluding cases with biTP53 or AML-defining alterations. CMML is defined by its combination of proliferative (monocytic) and dysplastic features, but exhibits considerable genetic heterogeneity. Optimal diagnosis and distinction from related entities require integration of morphology, immunophenotype, and comprehensive genomic profiling.","[""Journal Article"", ""Review""]","[""Loghavi S"", ""Hasserjian RP""]",10.1007/s11899-026-00781-6,Loghavi S,Current hematologic malignancy reports,1558-8211,1,Curr Hematol Malig Rep,eng,Hasserjian RP,"[""Humans"", ""Leukemia, Myelomonocytic, Chronic"", ""Mutation""]",,42545651,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545651/,"Chronic Myelomonocytic Leukemia: History, Pathobiology, Diagnostic Controversies, and Evolving Classification",21,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Healthcare professionals often report strong intentions to use evidence-based practices to improve patient care, but intention does not always translate into action. Habits, automatic behaviors generated through repeated cue-behavior associations, may help address the intention-behavior gap and enhance adoption of evidence-based practices. As habits form, behavior control shifts from being internally guided to being triggered by external context cues, which can support making the use of evidence-based practice more routine. Despite calls to integrate habit formation in implementation science, habits have not yet been fully leveraged to select and specify implementation strategies. We argue that habits can be explicitly planned for with targeted cues, behavior routines, and rewards to support healthcare professionals in adopting evidence-based practices. We outline core elements of habit formation and provide case examples to illustrate how habit techniques can be used to catalyze implementation in healthcare.","[""Journal Article"", ""Review""]","[""Patel-Syed Z"", ""Scott K"", ""Helseth S"", ""Becker S""]",10.1007/s10488-026-01519-5,Patel-Syed Z,Administration and policy in mental health,0894-587X,,Adm Policy Ment Health,eng,Becker S,[],,42545645,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545645/,Habit Formation to Enhance Implementation of Evidence-based Practice,,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Vancomycin-resistant Enterococcus faecium is listed in the 2024 WHO Bacterial Priority Pathogens List as a high-priority agent of hospital-acquired infections. Its persistence is supported by marked genomic plasticity across human, animal, food, and environmental sources. We aimed to map antimicrobial resistance genes, virulence determinants, and clonal lineages of Enterococcus spp. reported in Brazil across these four sampling contexts. Scoping review following JBI methodological guidance and reported per PRISMA-ScR. Four databases (PubMed, Embase, SciELO, LILACS) were searched without time restrictions in English, Portuguese, and Spanish. Two reviewers screened studies in Rayyan and extracted data using a standardised instrument. A total of 133 studies (1999 to 2025) were included. Evidence was concentrated in the Southeast and South. Sixty-seven acquired resistance genes and 11 chromosomal mutations were identified across 14 species, predominantly E. faecalis and E. faecium. Twelve broadly reported genes, including vanA, erm(B), and tet(M), spanned all four One Health contexts. Of 67 E. faecium sequence types, 28 (42%) were assigned to CC17 according to the current PubMLST classification and were reported across 26 studies in six states. Forty-six virulence determinants were mapped, with nine adhesion- and biofilm-associated genes shared across all four contexts. Enterococcus resistance, virulence, and lineage diversity in Brazil show a structured but unevenly characterised distribution with substantial surveillance gaps relevant to infection control and antimicrobial stewardship. The co-occurrence of PubMLST-assigned CC17 STs and last-resort resistance genes across compartments underscores the need for coordinated genomic surveillance.","[""Journal Article"", ""Review""]","[""Leal JT"", ""Boschiero MN"", ""Sartori L"", ""Gales AC""]",10.1007/s10096-026-05606-1,Leal JT,European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology,0934-9723,,Eur J Clin Microbiol Infect Dis,eng,Gales AC,[],,42545643,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545643/,"Genotypic features of antimicrobial resistance, virulence determinants, and clonal lineages of Enterococcus spp. reported in Brazil: a scoping review with marked regional asymmetry",,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Regenerative medicine has emerged as a transformative paradigm in contemporary healthcare, shifting the therapeutic focus from symptomatic management toward the restoration of tissue structure and function through biologically active interventions. Within this framework, adipose-derived products have attracted substantial interest owing to their relative abundance, ease of harvesting, and rich cellular and paracrine composition, including mesenchymal stromal cells, pericytes, and bioactive mediators with immunomodulatory potential. Among these technologies, microfragmented adipose tissue (MFAT) constitutes an innovative, minimally manipulated approach because it preserves the native stromal vascular niche and extracellular matrix architecture while avoiding enzymatic processing. This characteristic not only maintains biological integrity but also facilitates regulatory compliance in multiple jurisdictions. This narrative review provides a comprehensive synthesis of the current evidence on microfragmented adipose tissue in pain management, integrating biological rationale, mechanistic insights, and clinical applications across musculoskeletal disorders and chronic pain conditions. Particular attention is devoted to its capacity to modulate inflammatory pathways, promote angiogenesis, and support tissue regeneration within complex pathological environments. In addition, the review critically appraises the methodological limitations of existing clinical studies, including heterogeneity of design and limited high-quality randomized evidence. Finally, future perspectives are explored, emphasizing the integration of precision medicine approaches, biomarker-driven patient stratification, and combinatorial regenerative strategies to optimize therapeutic outcomes.","[""Journal Article"", ""Review""]","[""Van Tran Y"", ""Van Pham P"", ""Encinas MN"", ""Puttini PS"", ""Myrcik D"", ""Dauri P"", ""Farì G"", ""Gharibo CG"", ""Leoni MLG"", ""Mercieri M"", ""Varrassi G""]",10.1007/s40122-026-00877-0,Van Tran Y,Pain and therapy,2193-8237,,Pain Ther,eng,Varrassi G,[],,42545634,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545634/,Microfragmented Adipose Tissue in Pain Management: Bridging Regenerative Biology and Clinical Therapeutics,,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"The illegal drug trade has changed dangerously since xylazine, a veterinary α2 adrenergic agonist, has become a common additive in illegally made fentanyl, creating the ""tranq dope"" mix. Together, they cause a synergistic central nervous system and respiratory depression that is more severe than that observed with opioid toxicity alone. This raises important questions about awareness, stigma, and clinicians' responses. A scoping review was performed in accordance with PRISMA-ScR guidelines, utilizing a PCC-structured research question. Studies examining fentanyl and/or xylazine exposure with clinically or toxicologically significant data were searched in PubMed and ScienceDirect. 38 studies were included, most from North America, including case reports, retrospective studies, narrative reviews, animal studies, qualitative research, and toxicological analyses. Co-exposure to fentanyl and xylazine has been linked to severe necrotic cutaneous ulcers, unique postural phenomena like the forward-flexed ""fentanyl fold,"" acute muscle rigidity, including Wooden Chest Syndrome, and synergistic respiratory depression. Naloxone reverses the opioid component but does not counteract the sedative effects of xylazine, making overdose management more difficult and necessitating multimodal strategies like wound care, oxygenation support, and increased drug-checking services. Exposure to fentanyl-xylazine calls into question established models of opioid overdose and necessitates coordinated clinical and public health interventions. To combat this rapidly evolving threat, stigma must be reduced, harm reduction infrastructure expanded, and prospective research funded.","[""Journal Article"", ""Review""]","[""da Silva MLO"", ""Barbosa J"", ""Dinis-Oliveira RJ""]",10.1007/s12024-026-01331-5,da Silva MLO,"Forensic science, medicine, and pathology",1547-769X,,Forensic Sci Med Pathol,eng,Dinis-Oliveira RJ,[],,42545627,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545627/,New trends in the overdose epidemic: postural impact on abusers of fentanyl and xylazine and clinical and forensic implications,,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Myocardial iron overload represents a major cause of cardiac morbidity in patients with thalassemia. Cardiovascular magnetic resonance (CMR) T2* is the current reference for noninvasive myocardial iron quantification; however, it may be limited in detecting early iron-related myocardial changes. Native T1 mapping emerged as a complementary technique that may overcome some of the T2* limitations. The aim of this review is to analyze the available evidence on the use of native T1 mapping in thalassemia patients and to evaluate its relationship with T2*. Literature search was performed in PubMed, Scopus, Embase, and Cochrane. Studies evaluating myocardial T1 mapping in thalassemia patients were included. Data extraction focused on study characteristics, technical aspects, T1 and T2* values, and associations between the two measures. Sixteen studies were included. Most investigations reported a good relationship between T1 and T2* values. The strength of this association was higher in iron-overloaded cohorts and weaker in patients with normal T2*. Several studies described a subset of patients with reduced T1 despite normal T2*. Considerable heterogeneity was observed across studies in acquisition protocols, region of interest strategies and native T1 reference values. In conclusion, T1 mapping shows a global, though heterogeneous, association with T2* in thalassemia patients and its systematic integration in acquisition protocols represents a valuable complementary tool to T2*. Native T1 mapping may improve detection of early myocardial iron-related changes and support individualized patient management. Prospective longitudinal studies incorporating clinical outcomes are required to define the prognostic value and clinical role of T1 mapping.","[""Journal Article"", ""Review""]","[""Pegoraro N"", ""Carnevale A"", ""Bisi R"", ""Giganti M"", ""Longo F"", ""Cossu A""]",10.1007/s10554-026-03784-9,Pegoraro N,The international journal of cardiovascular imaging,1569-5794,,Int J Cardiovasc Imaging,eng,Cossu A,[],,42545611,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545611/,Cardiac magnetic resonance parametric mapping in patients with thalassemia: Clinical insights into native myocardial T1 mapping and its relationship with T2*. A systematic review,,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"The search for effective antibiotic alternatives has intensified in broiler production as consumer expectations, regulatory pressures, and disease challenges continue to shape modern poultry systems. Bacillus-based probiotics have gained particular interest because their spore-forming ability ensures feed stability and survival through feed processing and gastrointestinal transit. This review consolidates current knowledge on how Bacillus probiotics influence gut ecology, physiology, and productivity in broilers, while also emphasizing their practical relevance in commercial settings. Evidence from controlled trials shows that well-characterized Bacillus strains act through multiple coordinated mechanisms, although their efficacy is highly strain-specific. These include modulation and stabilization of the intestinal microbiota, suppression of pathogenic bacteria via competition and antimicrobial metabolite production, enhancement of digestive efficiency through enzyme secretion, and stimulation of beneficial fermentation processes. These effects are often linked to improved villus structure, strengthened epithelial barrier function, and modulation of local and systemic immune responses. Improvements in growth performance and feed efficiency have been reported in numerous studies, particularly under disease challenge or environmental stress, although responses vary with probiotic strain, supplementation strategy, and production conditions. Additionally, these probiotics have shown protective effects during necrotic enteritis challenge, reducing lesion severity and pathogen load. However, results vary across studies, influenced by strain type, dose, diet, challenge status, and farm conditions. Proper strain selection, quality control, verification of spore viability, and safety assessment are essential for reliable commercial application. In summary, current evidence supports the use of well-characterized Bacillus-based probiotics as safe and biologically effective feed additives that promote gut health, improve production efficiency, and contribute to sustainable antibiotic-reduced broiler production. Their multifaceted activity profile fits well with antibiotic-free nutrition strategies, although further research is needed to clarify strain-specific actions and optimize application protocols.","[""Journal Article"", ""Review""]","[""Naeem M"", ""Bourassa DV""]",10.1007/s12602-026-11162-z,Naeem M,Probiotics and antimicrobial proteins,1867-1306,,Probiotics Antimicrob Proteins,eng,Bourassa DV,[],,42545609,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545609/,"Bacillus Probiotics in Broiler Nutrition: Mechanisms, Gut Health, Performance, and Practical Considerations",,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Telesurgery has emerged as a transformative approach to address geographic disparities in surgical care, particularly in urology. However, robust real-world evidence specifically focused on renal procedures remains limited. We conducted this systematic review and single-arm meta-analysis to evaluate the safety, feasibility, and perioperative outcomes of remote robot-assisted renal surgery. We systematically searched PubMed, Embase, Cochrane Library, and Web of Science from inception to July 1, 2026. Studies reporting robot-assisted telesurgery for renal procedures (partial nephrectomy, radical nephrectomy, or renal cyst decortication) were included. The Joanna Briggs Institute (JBI) Case Series Checklist was used for quality assessment. A single-arm meta-analysis with random-effects models was performed to pool surgical success rates, operative time, estimated blood loss (EBL), length of hospital stay (LOS), warm ischemia time (WIT), and network parameters. Subgroup analyses were conducted by sample size, study design, and robotic platform. Sensitivity analyses using the leave-one-out method were performed to test the robustness of the pooled estimates. Eight studies comprising 98 patients were included. All studies were of moderate-to-high methodological quality (JBI scores: 8-10/10). The pooled surgical success rate was 100%, with a local surgeon take-over rate of 2.1% (2/98). No Clavien-Dindo grade III or IV complications were reported. The pooled estimates were: operative time 99.52 min (95% CI: 77.10-121.94; I² = 92.5%), EBL 28.30 mL (95% CI: 18.18-38.41; I² = 87.9%), LOS 5.31 days (95% CI: 3.29-7.33; I² = 98.0%), and WIT (for partial nephrectomy) 21.14 min (95% CI: 17.76-24.53; I² = 0.6%). Network parameters remained below the 200-300 ms safety threshold, with a mean round-trip time of 51.79 ms (95% CI: 1.25-102.34) and maximum latency of 128.26 ms (95% CI: 95.38-161.13). Subgroup analyses by robotic platform revealed significant between-group differences for operative time (p = 0.000) and EBL (p = 0.000), but not for LOS (p = 0.703). Sensitivity analyses confirmed the robustness of the pooled estimates for operative time and EBL, whereas the LOS estimate was sensitive to the inclusion of studies reporting extreme values. Remote robot-assisted renal surgery demonstrates high technical success rates, low complication rates, and favorable perioperative outcomes, with network parameters well within established safety thresholds. These findings support the clinical implementation of telesurgery for appropriately selected renal surgery patients, particularly in underserved regions. However, the substantial heterogeneity observed highlights the need for large-scale, prospective comparative studies with standardized outcome definitions and longer follow-up.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Review""]","[""Cao S"", ""Li QL"", ""Qin J"", ""Huang HT"", ""Li HY"", ""Guan RX"", ""Zhou XY"", ""Yin JY"", ""Tan SZ"", ""Zhang XY"", ""Yang XS""]",10.1007/s11701-026-03764-0,Cao S,Journal of robotic surgery,1863-2483,1,J Robot Surg,eng,Yang XS,"[""Humans"", ""Robotic Surgical Procedures"", ""Nephrectomy"", ""Length of Stay"", ""Operative Time"", ""Kidney"", ""Blood Loss, Surgical"", ""Telemedicine""]",,42545600,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545600/,Remote robot-assisted renal surgery: a systematic review and single-arm meta-analysis of real-world evidence,20,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Obesity in India is rising rapidly, with higher body fat at lower BMI and younger age compared to Western populations, leading to earlier onset of type 2 diabetes and cardiovascular disease in a resource-constrained health system. Protocols for obesity care therefore need to address region-specific challenges and ensure culturally acceptable, feasible treatment options. The Obesity and Metabolic Surgery Society of India (OSSI) and the Endocrine Society of India (ESI) jointly developed India-specific obesity management protocols using a modified Delphi consensus. A protocol development team generated 73 statements based on literature review and expert experience. Seventy-eight experts (38 OSSI, 40 ESI) participated; 100% voted in round 1 and 90% attended an in-person round-2 meeting. Statements with more than 80% agreement were considered to have achieved consensus. After revision and deletion of redundant items, 55 statements across eight modules were finalized. Consensus agreement exceeding 80% was achieved for all 55 statements covering obesity recognition, prevention, treatment selection, monitoring and follow-up, lifestyle therapy, obesity management medications, metabolic and bariatric surgery, and palliative care. The panel strongly endorsed recognition of obesity as a chronic non-communicable disease, integration of obesity care into national health programs, equitable access to treatment, and a multimodal, stigma-free approach tailored to Indian BMI and anthropometric thresholds. This first joint OSSI-ESI consensus provides India-specific guidance across the obesity care continuum. By integrating prevention, individualized therapy and multidisciplinary care, the recommendations aim to standardize clinical practice, inform policy and improve outcomes and quality of life for people living with obesity in India.","[""Journal Article"", ""Review""]","[""Bhasker AG"", ""Kapoor N"", ""Baig S"", ""Parmar C"", ""Shaikh S"", ""Wadhawan R"", ""Shah S"", ""Kotwal N"", ""Harikumar K"", ""Das S"", ""Baro A"", ""Katakwar A"", ""Unnikrishnan AG"", ""Shaikh A"", ""Mithal A"", ""Monteiro AS"", ""Shrivastava A"", ""Pradhan A"", ""Prasad A"", ""Vashishtha A"", ""Anne B"", ""Kulshreshtha B"", ""Selvan C"", ""Goel D"", ""Priya G"", ""Jammu GS"", ""Phatale H"", ""Maisnam I"", ""Khare J"", ""Pandit K"", ""Agarwal K"", ""Kona L"", ""Kular KS"", ""Nagendra L"", ""Kopalle LN"", ""Goel M"", ""Narwaria M"", ""Baijal M"", ""Khaitan M"", ""Motwani M"", ""Ismail M"", ""Shenoy MT"", ""Bhandari M"", ""Lakdawala M"", ""Dukkipati N"", ""Raizada N"", ""Lal P"", ""Shah PS"", ""Chowbey P"", ""Palanivelu PR"", ""Narayan P"", ""Bharath R"", ""Santosh R"", ""Jindal R"", ""Palaniappan R"", ""Khullar R"", ""Rajput R"", ""Walia R"", ""Goel R"", ""Jaiswal R"", ""Madhu SV"", ""Mittal S"", ""Lodha S"", ""Aggarwal S"", ""Julka S"", ""Kalra S"", ""Bhattacharya S"", ""Bajaj S"", ""Joshi S"", ""Shah S"", ""Dhorepatil S"", ""Ghosh S"", ""Saggu SS"", ""Kumar Kota S"", ""Mishra S"", ""Ugale S"", ""Jindal S"", ""Lathia T"", ""Lotwala V"", ""Khatri V"", ""Bindal V""]",10.1007/s11695-026-08870-4,Bhasker AG,Obesity surgery,0960-8923,,Obes Surg,eng,Bindal V,[],,42545588,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545588/,Expert Consensus on Obesity Management Protocols - A Joint Position Statement by Obesity and Metabolic Surgery Society of India (OSSI) and Endocrine Society of India (ESI),,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Tissue-resident macrophages (TRMs) are essential regulators of tissue homeostasis and regeneration across multiple organs. While their roles in systems such as the liver, brain, and skin have been increasingly clarified, their functions in bone remain markedly understudied. This review begins by outlining the established roles of TRMs in immune regulation and tissue repair to provide a conceptual framework for understanding their skeletal counterparts, known as osteal resident macrophages (ORMs). We then summarize current evidence for ORM involvement in bone homeostasis and regeneration and highlight the major challenges in bone TRM research. Clarifying the cellular identity and regulation of ORMs will help define their roles in bone homeostasis and repair, and inform future strategies for modulating macrophage function in skeletal disease. Tissue-resident macrophages (TRMs) are essential regulators of tissue homeostasis and regeneration across multiple organs. While their roles in systems such as the liver, brain, and skin have been increasingly clarified, their functions in bone remain markedly understudied. This review begins by outlining the established roles of TRMs in immune regulation and tissue repair to provide a conceptual framework for understanding their skeletal counterparts, known as osteal resident macrophages (ORMs). We then summarize current evidence for ORM involvement in bone homeostasis and regeneration and highlight the major challenges in bone TRM research. Clarifying the cellular identity and regulation of ORMs will help define their roles in bone homeostasis and repair, and inform future strategies for modulating macrophage function in skeletal disease.","[""Journal Article"", ""Review""]","[""Feng X"", ""Wu Q"", ""Yan Y"", ""Yu B"", ""Zhu Z"", ""Qiao Y"", ""Wei J""]",10.1007/s12015-026-11202-9,Feng X,Stem cell reviews and reports,2629-3277,,Stem Cell Rev Rep,eng,Wei J,[],,42545586,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545586/,Unraveling the Multifaceted Roles of Tissue-Resident Macrophages: Focus on Bone Homeostasis and Regeneration,,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"This review examines cardiovascular complications of multiple myeloma and anti-myeloma therapy, emphasising integrated systems-based cardiovascular management and the institutional model developed at the University College London Hospital Cardio-Oncology (CO) Centre of Excellence. Cardiovascular vulnerability in multiple myeloma reflects baseline risk, disease-related factors, including cardiac amyloidosis, and treatment-related cardiotoxicity. A longitudinal approach should begin before therapy with multidimensional risk stratification incorporating patient, disease, and treatment factors, with intermediate- and high-risk patients referred for CO review. During treatment, active surveillance using clinical assessment, cardiac biomarkers and imaging, with vigilance for cardiac amyloidosis, enables rapid CO referral and timely intervention. Survivorship care should include annual cardiovascular review, risk-factor optimisation, and monitoring for late toxicity. Existing evidence and real-world experience support integrated CO services combining rapid-access clinics, high-volume cardiac imaging, timely decision-making, inpatient consultation, multidisciplinary collaboration, and survivorship surveillance while preserving cardiovascular health and access to effective anti-myeloma therapy.","[""Journal Article"", ""Review""]","[""Akrawi D"", ""Datta S"", ""Hatipoglu S"", ""Wechalekar AD"", ""Ghose A"", ""Alkhateeb A"", ""Walker JM"", ""Ghosh AK""]",10.1007/s11886-026-02397-x,Akrawi D,Current cardiology reports,1523-3782,1,Curr Cardiol Rep,eng,Ghosh AK,"[""Humans"", ""Multiple Myeloma"", ""Cardio-Oncology"", ""Cardiovascular Diseases"", ""United Kingdom"", ""Delivery of Health Care, Integrated"", ""Cardiotoxicity"", ""Antineoplastic Agents"", ""Risk Factors"", ""Risk Assessment""]",,42545577,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545577/,Cardiovascular Care in Multiple Myeloma: A Comprehensive Review and Integrated Systems-Based Approach from a UK Cardio-Oncology Centre of Excellence,28,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Learning curves are critical to the safe adoption and standardized training of robot-assisted urological surgery, yet the evolution of proficiency assessment from technical experience toward surgical safety and functional recovery remains unclear. Records indexed in the Web of Science Core Collection were quantitatively mapped to examine publication dynamics, research partnerships, the underlying knowledge base, and shifts in major topics over time. A total of 346 publications, including 252 articles and 94 reviews, were analyzed. Scientific output increased markedly, with an annual growth rate of 21.33%. The United States was the leading contributor, while Vita-Salute San Raffaele University and Alexandre Mottrie were the most productive institution and author, respectively. Highly co-cited literature primarily focused on standardized complication assessment, procedure-specific learning curves, and perioperative outcomes. Keyword and temporal analyses revealed a gradual shift from initial experience and technical adaptation toward outcome-based evaluation of surgical proficiency. Perioperative outcomes, complications, and surgical experience dominated the research landscape, whereas functional recovery, quality of life, and other patient-centered outcomes remained comparatively underrepresented. Overall, learning curve research in robot-assisted urological surgery has progressed toward multidimensional assessment of clinical performance, but current frameworks remain strongly weighted toward perioperative safety. Future studies should establish procedure-specific, outcome-oriented models incorporating patient characteristics, procedural complexity, functional recovery, and multidisciplinary team performance to define more clinically meaningful standards of robotic surgical proficiency.","[""Journal Article"", ""Review""]","[""Zhang Y"", ""Wang K"", ""Wang H"", ""Yan R"", ""Gui H"", ""Man J"", ""Yang L""]",10.1007/s11701-026-03744-4,Zhang Y,Journal of robotic surgery,1863-2483,1,J Robot Surg,eng,Yang L,"[""Robotic Surgical Procedures"", ""Urologic Surgical Procedures"", ""Humans"", ""Learning Curve"", ""Bibliometrics"", ""Recovery of Function"", ""Clinical Competence""]",,42545570,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545570/,Global trends in learning curves of robot-assisted urological surgery: a bibliometric analysis of surgical safety and functional recovery,20,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Salivary gland dysfunction is a recognized complication of radioactive iodine (RAI) therapy for differentiated thyroid cancer. Oral sialagogues are commonly recommended, but their optimal timing remains uncertain. This systematic review compares early (<24 h) versus delayed (>24 h) sialagogue initiation. A literature search was conducted in Embase, PubMed, CINAHL, and Cochrane from inception to January 2026. ""Early"" protocols initiated stimulation within 24 h post-RAI, while ""delayed"" protocols initiated after 24 h. Methodological quality and risk of bias were assessed using Cochrane's ROBINS-I (Risk Of Bias In Non-randomized Studies of Interventions, 2016) tool. Three observational studies were included, comprising 818 adults with reported mean ages of 43-59 years. Interventions consisted primarily of lemon candy or oral vitamin C tablets. Primary outcomes included acute sialadenitis (pain and/or swelling), taste dysfunction, and xerostomia. Findings regarding acute salivary gland outcomes were inconsistent. Two earlier studies reported higher rates of acute sialadenitis with early stimulation (54.7-63.8% vs. 34.4-36.8%), taste dysfunction (37.5-39.0% vs. 18.8-25.6%), and xerostomia (23.8-46.9% vs. 11.2-29.7%) compared with delayed initiation. In contrast, the most recent propensity score-matched study, which evaluated a composite endpoint of acute salivary gland damage, reported lower event rates with early stimulation (4.78% vs. 15.22%). This review underscores how evidence regarding the optimal timing of sialagogue initiation after RAI remains inconsistent. These heterogeneous findings highlight the need for high-quality randomized controlled trials to establish evidence-based recommendations for sialagogue timing after RAI therapy.","[""Journal Article"", ""Systematic Review""]","[""Frankowski Dagostin A"", ""Rehandhika NY"", ""Potiguara de Souza AL"", ""Holland S""]",10.1007/s12020-026-04727-z,Frankowski Dagostin A,Endocrine,1355-008X,1,Endocrine,eng,Holland S,"[""Humans"", ""Thyroid Neoplasms"", ""Iodine Radioisotopes"", ""Sialadenitis"", ""Salivary Gland Diseases"", ""Time Factors"", ""Salivary Glands""]",,42545543,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545543/,Early versus delayed oral sialagogues for the prevention of salivary gland dysfunction after radioiodine therapy in differentiated thyroid cancer: a systematic review,91,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Calreticulin (CALR) is a multifunctional endoplasmic reticulum (ER) protein that couples lectin-like chaperone activity in the calnexin/calreticulin cycle with high-capacity Ca²⁺-binding, thereby linking ER proteostasis to luminal calcium homeostasis. Although classically viewed as an ER-resident chaperone, CALR is increasingly recognized as a stress-responsive regulator whose functions extend beyond the ER lumen. Under stress, CALR can relocalize to the cell surface or extracellular space, where it functions as an immune-recognition and pro-clearance signal for damaged or dying cells. Across aging and chronic degenerative conditions, persistent ER stress, altered calcium handling, and defective clearance of stressed or senescent cells may reshape CALR expression, localization, and stress-responsive functions. However, CALR has not been widely conceptualized as an integrative regulator linking ER proteostatic stress, calcium dysregulation, senescence-associated remodeling, and immune surveillance. In this review, we examine CALR as a stress-responsive integrator of ER proteostasis, calcium homeostasis, senescence-associated stress adaptation, and immune-mediated clearance, and discuss how this framework may inform mechanistic studies and therapeutic strategies in chronic degenerative diseases.","[""Journal Article"", ""Review""]","[""Mutombo Menga A"", ""Hong X"", ""Shi R""]",10.1007/s11033-026-12416-3,Mutombo Menga A,Molecular biology reports,0301-4851,1,Mol Biol Rep,eng,Shi R,"[""Calreticulin"", ""Humans"", ""Proteostasis"", ""Calcium"", ""Endoplasmic Reticulum"", ""Animals"", ""Homeostasis"", ""Endoplasmic Reticulum Stress"", ""Cellular Senescence""]",,42545540,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545540/,"Calreticulin as a stress-responsive integrator of ER proteostasis, calcium homeostasis, and immune clearance",53,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Robotic technologies are increasingly being integrated into cosmetic dermatology; however, the scientific development of this field has not been comprehensively evaluated. This study aimed to characterize the global research landscape of robotic applications in cosmetic dermatology through a bibliometric analysis. Publications were retrieved from the Web of Science Core Collection, and 48 publications, including 43 articles and 5 reviews, were included after screening. Biblioshiny and VOSviewer were used to analyze publication trends, journals, countries, collaboration networks, keyword co-occurrence, thematic structure, reference publication year spectroscopy (RPYS), and cited reference co-citation analysis. Scientific production remained limited but gradually increased over time. Dermatologic Clinics and Dermatologic Surgery were the most productive journals. The United States demonstrated the greatest international collaboration, corresponding authorship, and citation impact. Keyword and thematic analyses identified hair restoration, particularly robotic follicular unit extraction, as the dominant research focus, while laser-assisted procedures, skin rejuvenation, and facial aesthetic interventions represented smaller but evolving areas of investigation. RPYS and reference co-citation analyses further demonstrated that robotic hair restoration has formed the principal intellectual foundation of the field. Overall, robotic technologies in cosmetic dermatology represent an emerging field with steadily increasing scientific interest. Although hair restoration currently dominates the literature, continued technological advances are expected to broaden their use and stimulate further investigation of laser-assisted procedures, skin rejuvenation, and artificial intelligence-assisted technologies.","[""Journal Article"", ""Review""]","[""Öktem R"", ""Yıldırım KPH"", ""Tanaçan E"", ""Hasanbeyzade S"", ""Ünal E"", ""Rota DD""]",10.1007/s11701-026-03755-1,Öktem R,Journal of robotic surgery,1863-2483,1,J Robot Surg,eng,Rota DD,"[""Humans"", ""Dermatology"", ""Bibliometrics"", ""Robotic Surgical Procedures"", ""Cosmetic Techniques"", ""Robotics""]",,42545536,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545536/,Global research trends in robotic applications in cosmetic dermatology: a bibliometric analysis,20,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"In vitro osteoarthritis (OA) models are widely used for mechanistic studies. However, inconsistencies in induction protocols limit reproducibility and translational relevance. A systematic comparison of inflammatory inducers based on their temporal dynamics remains elusive. A systematic literature search was conducted across PubMed, Web of Science, and Scopus to identify the most commonly used inflammatory inducers in vitro OA models. The prevalence of each inducer was quantified. In addition, a qualitative mechanistic synthesis was performed by integrating representative studies reporting temporal molecular profiles to construct conceptual kinetic patterns. Based on this synthesis, a kinetic-based framework was developed to compare inducer-specific temporal characteristics. Interleukin-1β (IL-1β) was the most frequently used inducer (62.12%), followed by lipopolysaccharide (LPS, 9.60%) and tumor necrosis factor-α (TNF-α, 7.58%). Temporal synthesis suggested a biphasic enzymatic response characterized by early ADAMTS-5 induction (approximately 6-12 h) and subsequent MMP-13 elevation (24-48 h). IL-1β was associated with sustained signaling activation and pronounced transitions between ferroptosis-related and apoptotic-related markers. In contrast, TNF-α induced rapid but transient early-phase responses, whereas LPS exhibited a delayed yet persistent low-grade inflammatory profile. The selection of inflammatory inducers should be aligned with specific experimental objectives. IL-1β is suitable for modeling sustained catabolic activity and cell death transitions, TNF-α for early-stage inflammatory responses, and LPS for chronic low-grade inflammation. This kinetic-based framework may improve model selection and enhance the translational relevance of in vitro OA studies, although further experimental validation is required.","[""Journal Article"", ""Review""]","[""Cheng G"", ""Atheeqah-Hamzah N"", ""Liu X"", ""Lv F"", ""Loh KW"", ""Aziz A"", ""Tan HL"", ""Tunku K""]",10.1007/s11033-026-12397-3,Cheng G,Molecular biology reports,0301-4851,1,Mol Biol Rep,eng,Tunku K,"[""Osteoarthritis"", ""Humans"", ""Interleukin-1beta"", ""Tumor Necrosis Factor-alpha"", ""Lipopolysaccharides"", ""Kinetics"", ""Inflammation"", ""Matrix Metalloproteinase 13"", ""ADAMTS5 Protein"", ""Chondrocytes"", ""Animals"", ""Models, Biological"", ""Signal Transduction""]",,42545534,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545534/,A kinetic-based framework for the selection of in vitro osteoarthritis models: integrating temporal dynamics of inflammatory inducers,53,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Aquaculture is experiencing global expansion, heightening the demand for sustainable feed additives that enhance growth, immunity, and disease resistance. Astragalus polysaccharides (APs) possess significant immunomodulatory, antioxidant, and anti-inflammatory properties. This review systematically examines the structural characteristics, biological functions, underlying mechanisms, and physiological effects of APs in aquatic species, with particular emphasis on their immunomodulatory, antioxidant, and anti-inflammatory activities. Furthermore, APs have been shown to promote growth performance in aquatic organisms by enhancing feed utilization efficiency, modulating digestive enzyme activities, and regulating nutrient metabolism. Evidence indicates that APs enhance immune function, modulate gut microbiota, and mitigate environmental stress, especially when combined with probiotics, prebiotics, plant extracts, or vaccines. Species-specific responses of finfish, crustaceans, and other aquatic creatures are compared in terms of dosage, safety, and physiology. The review also discusses extract standardization, regulatory challenges, economic viability, and prospective research directions for optimizing AP formulations in sustainable aquaculture. This work offers academics, aquafeed producers, and industry stakeholders a comprehensive resource for health-oriented and environmentally sustainable aquaculture systems, by combining molecular insights and practical zootechnical results.","[""Journal Article"", ""Review""]","[""Wu S"", ""Qian H"", ""Kong Y""]",10.1007/s10695-026-01759-0,Wu S,Fish physiology and biochemistry,0920-1742,4,Fish Physiol Biochem,eng,Kong Y,"[""Animals"", ""Astragalus Plant"", ""Polysaccharides"", ""Aquaculture"", ""Disease Resistance"", ""Fishes"", ""Animal Feed"", ""Antioxidants""]",,42545533,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545533/,"Astragalus polysaccharides in aquaculture: a comprehensive review on growth, immunity, and disease resistance",52,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Ergonomics is essential for ensuring safe, high-quality surgical care. However, existing studies vary widely in their clinical settings, terminology, and assessment methods. This scoping review aimed to map the terminology and methods used to evaluate surgeons' ergonomics in real-world surgical environments. We systematically searched MEDLINE, Embase, CENTRAL, IEEE Xplore, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov from inception to July 1, 2025 for studies that assessed physical, cognitive, or organizational ergonomics. Two reviewers independently screened titles and abstracts, assessed full texts, and extracted study characteristics and outcomes. Assessment tools were categorized as self-reported, observational, direct or instrumental, or computer based. The review protocol was registered in PROSPERO (CRD420251088370). Ninety-nine studies met the inclusion criteria. Minimally invasive surgery predominated: 60 studies involved laparoscopic surgery (including thoracoscopic and other endoscopic minimally invasive approaches), and 36 evaluated robotic surgery. Comparative designs most frequently compared laparoscopic versus robotic surgery (n = 14). Physical, cognitive, and organizational ergonomics were assessed in 64, 49, and 19 studies, respectively, with 31 addressing multiple domains. Considerable variation was observed in terminology and assessment methods. Physical ergonomics was most commonly evaluated using observational or instrumental approaches, whereas cognitive ergonomics primarily relied on self-reported measures. Computer-based assessments, including artificial intelligence-assisted tools, have recently emerged. This review provides a structured framework for assessing ergonomics in surgery and highlights substantial heterogeneity in terminology and assessment methods. Standardized, multimodal, and objective approaches are needed to enhance comparability across studies.","[""Journal Article"", ""Review""]","[""Hayashi S"", ""Watanabe J"", ""Hayashi K"", ""Matsui R"", ""Kinoshita J"", ""Inaki N""]",10.1007/s00464-026-13224-3,Hayashi S,Surgical endoscopy,0930-2794,,Surg Endosc,eng,Inaki N,[],,42545525,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545525/,Assessment methods for surgeons' ergonomics in the operating room: a scoping review,,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Orthopaedic trauma surgery is associated with significant perioperative morbidity, prolonged hospital stays, and increased healthcare costs. Enhanced Recovery After Surgery (ERAS) protocols have shown benefits in elective procedures; however, their role in orthopaedic trauma remains unclear. This study aimed to evaluate the efficacy of key ERAS related components in this setting. A systematic search of PubMed/MEDLINE, Embase, Cochrane CENTRAL, and Scopus was conducted following PRISMA guidelines. Randomized controlled trials (RCTs) comparing ERAS related components with standard care in adult orthopaedic trauma patients were included. The primary outcome was hospital length of stay (LOS), while secondary outcomes included postoperative pain, functional recovery, deep vein thrombosis (DVT), blood transfusion requirement, postoperative haemoglobin, and infection rates. Data were analysed using RevMan 5.4.1, with risk of bias and evidence certainty assessed using Cochrane RoB 2.0 and GRADE approaches. Five RCTs involving 423 patients were included. ERAS related components significantly reduced length of hospital stay (MD: -2.56 days; 95% CI: -4.43 to - 0.69; p = 0.007) and postoperative pain (MD: -1.12; 95% CI: -1.35 to - 0.88; p < 0.00001). No significant differences were observed in functional recovery, pain at rest or movement, DVT, blood transfusion, or postoperative haemoglobin. Postoperative infection rates were higher in the ERAS related component group but not statistically significant. Evidence certainty ranged from low to moderate. ERAS-related components may reduce hospital length of stay and postoperative pain in adults undergoing orthopedic trauma surgery. However, certainty remains limited by the small number of trials, heterogeneity of interventions and trauma populations, and sparse safety events. Safety remains uncertain, particularly because postoperative infection was numerically higher and the DVT estimate was unstable after sensitivity analysis. Larger multicenter RCTs with standardized interventions are required.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Review""]","[""Das DL"", ""Aiman U"", ""Shahzad UB"", ""Malik T"", ""Khan TI"", ""Ahmed M"", ""Talha M"", ""Sheikh AR"", ""Zahoor RMW"", ""Saleem MF"", ""Mansoor M""]",10.1007/s00590-026-04895-8,Das DL,European journal of orthopaedic surgery & traumatology : orthopedie traumatologie,1633-8065,1,Eur J Orthop Surg Traumatol,eng,Mansoor M,"[""Humans"", ""Randomized Controlled Trials as Topic"", ""Length of Stay"", ""Orthopedic Procedures"", ""Enhanced Recovery After Surgery"", ""Postoperative Pain"", ""Postoperative Complications"", ""Blood Transfusion"", ""Venous Thrombosis""]",,42545517,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545517/,The efficacy of ERAS-related components in orthopedic trauma surgery: a systematic review and meta-analysis of randomized controlled trials,36,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"The review reported a 27.8% success rate for non-operative management in patients with distant free air and, on that basis, suggested that early surgery should be strongly considered. When we examined the published data, we were unable to reproduce this estimate. Recalculating from the information given in the review, the numerator appeared to include only studies that reported this outcome, whereas the denominator also included patients from studies in which it was not reported; on a like-for-like basis the success rate is closer to 73% than to the reported 27.8%. Several values in the distant-free-air column of Table 5 of the review also correspond exactly to the complementary failure rates, which is compatible with a labelling or reporting error. These observations concern the distant-air subgroup specifically and require verification against the original data rather than establishing that the pooled analysis is incorrect. Given the clinical weight carried by this subgroup, clarification from the authors, and a correction if the discrepancies are confirmed, would be valuable.","[""Journal Article"", ""Systematic Review"", ""Letter""]","[""Atlı M""]",10.1007/s00423-026-04165-5,Atlı M,Langenbeck's archives of surgery,1435-2443,1,Langenbecks Arch Surg,eng,Atlı M,"[""Humans"", ""Intestinal Perforation"", ""Diverticulitis, Colonic"", ""Treatment Outcome"", ""Conservative Treatment""]",,42545514,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545514/,"Possible underestimation of non-operative management success in perforated diverticulitis with distant free air : Re: Cirocchi R, Matteucci M, Mari GM et al. (2026) The role of non-operative management (NOM) in perforated diverticulitis: a systematic review. Langenbecks Arch Surg 411:79",411,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"The dysfunctional native right ventricular outflow tract presents unique challenges for transcatheter valve replacement due to its anatomical heterogeneity. Technological advancements, coupled with expanding experience across diverse valve platforms have broadened patient eligibility and facilitated a tailored approach to prosthesis selection. This article provides a practical overview of the Edwards Sapien valve series, the Alterra Adaptive Prestent with the Sapien valve, the Venus P-valve, and the Harmony transcatheter pulmonary valve, with a focus on device design, sizing approach, procedural strategies and contemporary outcomes. Additionally, we highlight key considerations for valve selection and deployment according to variations in right ventricular outflow tract and branch pulmonary artery anatomy. Given these patients are often relatively young, we also discuss clinical issues related to transcatheter pulmonary valve replacement and lifetime management.","[""Journal Article"", ""Review""]","[""Kang SL"", ""Bentham JR""]",10.1007/s00246-026-04391-0,Kang SL,Pediatric cardiology,0172-0643,,Pediatr Cardiol,eng,Bentham JR,[],,42545510,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545510/,"Transcatheter Pulmonary Valve Replacement in the Native Dysfunctional Right Ventricular Outflow Tract: Strategies for Optimal Prosthesis Selection, Valve Deployment and Lifetime Management",,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Glioblastoma remains a challenging disease to approach with immunotherapy due to pronounced antigen heterogeneity, immunosuppressive tumor microenvironment, and barriers to effective molecule delivery within the central nervous system. T-cell engagers provide an off-the-shelf approach to redirect endogenous T cells toward tumor cells. However, bispecific formats are constrained by intra- and interpatient antigen heterogeneity, which can limit therapeutic efficacy. In this review, we examine trispecific T-cell engagers (TriTEs) as an emerging strategy to address this limitation by simultaneously targeting multiple tumor-associated antigens. We discuss principles guiding antigen selection in glioblastoma, summarize available preclinical evidence supporting multispecific engagement, and outline key design considerations, including molecular architecture, stability, half-life extension, and safety optimization. We further review delivery strategies, such as gene-encoded expression, cellular carriers, and blood-brain barrier modulation, that may improve tumor access and the durability of TriTEs. Together, these considerations position TriTEs as a modular immunotherapy platform relevant to glioblastoma and other heterogeneous solid tumors.","[""Journal Article"", ""Review""]","[""Tiwari A"", ""Pawlowski KD"", ""Balyasnikova IV""]",10.1007/s00401-026-03063-w,Tiwari A,Acta neuropathologica,0001-6322,1,Acta Neuropathol,eng,Balyasnikova IV,"[""Humans"", ""Glioblastoma"", ""T-Lymphocytes"", ""Brain Neoplasms"", ""Animals"", ""Immunotherapy"", ""Antigens, Neoplasm""]",,42545507,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545507/,Improving T-cell engager efficacy in glioblastoma with multi-antigen targeting and novel delivery approaches,152,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Artificial intelligence (AI) has achieved remarkable success in the diagnosis of Alzheimer's disease (AD) in the literature, where many of the models use multi-modal methods including neuroimaging, cerebrospinal fluid, genetics, and cognitive assessment. But clinical adoption of these systems is still limited since most systems are developed in an idealized setting, as cost-effective and specialized diagnostic studies are not universally accessible. We discuss the translation of benchmark performance of AI to real-world dementia care pathways. A practical framework that would be useful for scalable, equitable, and clinically deployable AI-assisted dementia care. In fact, recent advancements in blood-based biomarkers such as plasma phosphorylated tau, glial fibrillary acidic protein, and neurofilament light chain are providing new opportunities for a flexible and minimally invasive diagnosis method. Based on these advances, we propose a clinically grounded AI-assisted cascading model which mirrors real-world workflows via progressive screening, biomarker-guided assessment, selective imaging escalation, and longitudinal prognostic monitoring. We further discuss enabling methods such as sequential decision-making, reinforcement learning, cost-sensitive learning, missing-modality robustness, and explainable AI. Finally, we outline the challenges for data design, for future validation and integration into healthcare systems, and ethical use.","[""Journal Article"", ""Review""]","[""Hooshmandi S"", ""Rahimi Jaberi K"", ""Kamalov F"", ""Nami M""]",10.1007/s10072-026-09282-z,Hooshmandi S,Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology,1590-1874,8,Neurol Sci,eng,Nami M,"[""Humans"", ""Alzheimer Disease"", ""Artificial Intelligence"", ""Biomarkers""]",,42545504,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545504/,Adaptive cascading artificial intelligence for Alzheimer's disease assessment: a clinically oriented narrative review and implementation framework,47,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Patellar instability can arise from a traumatic event with anatomical predisposing factors increasing the risk of dislocation. Medial patellofemoral ligament reconstruction (MPFLR) is commonly performed to treat patellar instability. The aim of this systematic review was to determine the incidence of and risk factors for patellar fractures after MPFLR. The protocol for this review was registered on PROSPERO with registration number CRD420251066107. The PRISMA 2020 checklist was followed. Electronic databases and conference proceedings were searched to the 15th of May 2025. Studies were eligible if they reported incidence of patellar fractures after MPFLR. A random-effects meta-analysis was performed. Included studies were appraised using tools respective of study design. A total of 4,972 records were screened in the initial search. A total of 110 studies satisfied the inclusion criteria, evaluating 115,496 patients. The evidence was moderate to low in quality. The incidence of patellar fracture ranged from 0 to 9.50%, with a pooled incidence of 1.17% (95% confidence interval [CI] 0.76- 1.68%). There was no difference in incidence of patellar fractures between patients who did and did not undergo bone tunnel fixation (0.94%, 95% CI 0.69-1.24 vs. 1.00%, 95% CI 0.15-2.44%, respectively). There was no difference in fracture incidence between patients who underwent concomitant procedures (1.26%, 95% CI 0.51-2.32) and those who underwent MPFLR alone (0.53%, 95% CI 0.13-1.16%). Patellar fractures are a known complication of MPFLR, with a higher incidence observed in patients undergoing this procedure compared to the baseline population risk. Current evidence suggests its incidence is not affected by tunnel location or the performance of concomitant procedures, though further prospective studies are required to corroborate this. Appropriate post-operative follow-up is required to monitor the occurrence of patellar fractures during the post-operative period.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Review""]","[""Abelleyra Lastoria DA"", ""Hunt A"", ""Ross CK"", ""Yemane M"", ""Keynes S"", ""Ghosh A"", ""Hing CB""]",10.1007/s00402-026-06440-y,Abelleyra Lastoria DA,Archives of orthopaedic and trauma surgery,0936-8051,1,Arch Orthop Trauma Surg,eng,Hing CB,"[""Humans"", ""Patella Fracture"", ""Incidence"", ""Patellofemoral Joint"", ""Plastic Surgery Procedures"", ""Joint Instability"", ""Ligaments, Articular"", ""Postoperative Complications"", ""Risk Factors"", ""Patella""]",,42545503,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545503/,The incidence and epidemiology of patellar fractures following medial patellofemoral ligament reconstruction: a systematic review and meta-analysis,146,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Facial aesthetics are profoundly influenced by the chin, a central feature that shapes harmony, projection, and perceived attractiveness. As demand for minimally invasive cosmetic procedures grows globally, nonsurgical chin augmentation has emerged as a cornerstone in facial contouring. The chin is a small yet powerful determinant of facial harmony. Its retrusion, whether congenital, traumatic, or age-related, can distort balance and undermine self-perception. With patients increasingly seeking minimally invasive solutions, this systematic review evaluates injectable volumetric techniques for chin augmentation, with a focus on dermal filler-based interventions, and synthesises current evidence on efficacy, safety, and patient satisfaction. Following PRISMA-E guidelines, a comprehensive search across seven databases (1965-2026) identified clinical studies evaluating injectable fillers (and other eligible injectable volumetric agents) for chin augmentation. Study quality and data diversity were analysed, including I2 heterogeneity. Eleven eligible studies comprising 876 patients were analysed. Hyaluronic acid fillers predominated, with follow-ups averaging 12.8 months (SD: 7.7). Over 90% of patients reported satisfaction, supported by photographic and patient-reported assessments. Adverse effects were minor and transient, mainly oedema, bruising, and nodularity. Injectable fillers provide effective short-term improvement in chin projection with high patient satisfaction and acceptable safety. However, evidence is heterogeneous and largely non-comparative, limiting conclusions on long-term outcomes. Further controlled studies are required. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .","[""Journal Article"", ""Review""]","[""Shome D"", ""Bose D"", ""Prabhughate A"", ""Shah R"", ""Kapoor R""]",10.1007/s00266-026-06188-1,Shome D,Aesthetic plastic surgery,0364-216X,,Aesthetic Plast Surg,eng,Kapoor R,[],,42545491,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545491/,Injectable Filler-Based Chin Augmentation: A Systematic Review of Non-Surgical Volumetric Techniques,,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Trochanteric femoral fracture is the most frequent proximal femur fracture in older adults and is associated with substantial perioperative morbidity and mortality. While surgical technique, anticoagulation and orthogeriatric care are widely discussed, the nursing and organisational levers of the perioperative pathway, namely fasting, fluid therapy and pain management, often remain underappreciated. To review the evidence on a liberalised preoperative fasting policy (sip till send), goal-directed fluid therapy, and peripheral nerve blocks with and without continuous catheters with regard to pain control, postoperative delirium and functional outcome. Selective narrative review of literature published within the last decade, including systematic reviews, randomised trials and national recommendations. Clear fluids up to the call to theatre are safe and reduce thirst, hunger and volume depletion. Liberal intraoperative fluid administration is associated with higher complication rates; goal-directed therapy with balanced crystalloids is therefore preferable. Peripheral nerve blocks reduce pain, opioid consumption and the incidence of postoperative delirium. Continuous nerve catheters are an attractive option in case of prolonged preoperative waiting times. Bundling these measures within an enhanced-recovery framework is associated with shorter length of stay and improved recovery.","[""English Abstract"", ""Journal Article"", ""Review""]","[""Link BC"", ""Haefeli PC"", ""Rohner-Spengler M"", ""van de Wall B"", ""Beeres FJP""]",10.1007/s00113-026-01732-9,Link BC,"Unfallchirurgie (Heidelberg, Germany)",2731-7021,,Unfallchirurgie (Heidelb),ger,Beeres FJP,[],,42545487,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545487/,"[Perioperative management of trochanteric femoral fractures : Fasting, fluid therapy and multimodal pain management as underappreciated factors]",,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Adult spinal deformity (ASD) is becoming increasingly prevalent as the general population ages, and this pathology has traditionally been treated with open surgical techniques, which are associated with high complications rates. To reduce surgical aggressiveness, minimally invasive techniques (MIS) are being used with growing frequency. However, concerns persist regarding their ability to correctly re-align the spine on the sagittal plane and to ensure good clinical outcomes. The aim of our study is to evaluate the capacity of MIS techniques to correct ASD sagittal malalignment and assess their clinical outcomes. We systematically reviewed the literature following the PRISMA flowchart. Only articles with a minimum follow-up (FU) of 18 months and > 3.5 fused levels were included. The radiological parameters evaluated were pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), L4S1 lordosis (LL L4S1), PI-LL, sagittal vertical axis (SVA), coronal Cobb angle and central sacral vertical line (CSVL). Clinical outcomes were evaluated using the visual analogue scale (VAS) and Oswestry disability index (ODI) scores and the main complications were reviewed. Six articles were included, comprising a total of 413 patients. The population mean age at surgery was 67.6 years and 71.9% were female. The mean FU was 27.8 months. The mean levels fused were 6.3; all deformities were corrected with MIS anterior, lateral or posterior interbody cages and the posterior instrumentation was positioned percutaneously. The mean PI was 54.6° and remained stable after surgery; all other sagittal and coronal parameters showed statistically significant improvement after surgery (p < 0.05). All clinical outcome scores improved significantly at last FU (p < 0.05). Despite the satisfactory clinical outcomes, the overall rate of major complications was 35.4%, leading to a 19.1% re-intervention rate. Despite the satisfactory clinical outcomes, MIS techniques are associated with a high incidence of mechanical complications and revision rate. It can be hypothesized that this may be due to the limited capacity of MIS procedures to respect Roussouly's phenotypes; nevertheless, the small sample size, the impossibility to stratify the outcomes by MIS technique, and the lack of important patient related factors limits the impact of the current evidence.","[""Journal Article"", ""Review""]","[""Quarto E"", ""Zanirato A"", ""Marston SJ"", ""Alhourani H"", ""Armani L"", ""Massarini E"", ""Vandenbulcke A"", ""Luyet A"", ""Dimitriou J"", ""Formica M"", ""Le Huec JC""]",10.1007/s00586-026-10245-3,Quarto E,"European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society",0940-6719,,Eur Spine J,eng,Le Huec JC,[],,42545481,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545481/,Minimally invasive surgery in adult spinal deformity: sagittal alignment correction potential and clinical outcomes. A systematic review of the literature,,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Death by neurologic criteria, previously called brain death, is a medicolegal concept, fraught with legal, ethical, and emotional considerations. The diagnosis is established clinically as described in the appropriate interdisciplinary guidelines. When adequate clinical evaluation cannot be performed, imaging including radionuclide brain perfusion scintigraphy (RBPS), four-vessel catheter angiography, or transcranial Doppler can be used as ancillary tests. Of these, RBPS is the more commonly performed test, used to establish the presence or absence of intracranial perfusion. Scintigraphic imaging for the presence or absence of intracranial perfusion is infrequently requested, which limits familiarity with both performing and interpreting these studies. The purpose of this article is to help the radiologist and nuclear medicine physician better understand the concept of death by neurologic criteria and the role of scintigraphic imaging in supporting the clinical diagnosis in the light of most recent multidisciplinary guidelines. A second goal is to describe how to interpret and report the relevant imaging studies, emphasizing differences between children and adults where applicable.","[""Journal Article"", ""Review""]","[""Oztek MA"", ""Parisi MT""]",10.1007/s00247-026-06742-8,Oztek MA,Pediatric radiology,0301-0449,,Pediatr Radiol,eng,Parisi MT,[],,42545472,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545472/,Death by neurologic criteria: a nuclear medicine approach based on the 2023 AAN/AAP/CNS/SCCM Guideline and 2025 SNMMI Procedure Standard,,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Given the pivotal role of imaging in diagnosing urological cancers, artificial intelligence (AI) has emerged as a promising tool to improve diagnostic accuracy and reliability. This study systematically evaluates the diagnostic performance of AI models in radiologic imaging of urological cancers. A systematic search was conducted in four electronic databases up to June 2026 to identify studies that applied AI algorithms for the diagnosis of urological cancers using CT, MRI, or ultrasound. Eligible studies reported diagnostic accuracy metrics for AI models, with clinician comparator data extracted when available. A bivariate random-effects model was used to pool sensitivity, specificity, and AUC values. Subgroup analyses were conducted to examine diagnostic performance across different cancer types and imaging modalities, and to explore potential sources of heterogeneity. Study quality was assessed using the QUADAS-2 tool. A total of 110 studies were included in the meta-analysis. AI models achieved pooled sensitivity and specificity of 0.85 (95% CI: 0.83-0.87) and 0.83 (95% CI: 0.80-0.86), with an AUC of 0.91 (95% CI: 0.88-0.93). Clinicians demonstrated a pooled sensitivity of 0.82 (95% CI: 0.79-0.85) and specificity of 0.68 (95% CI: 0.62-0.73), with an AUC of 0.83 (95% CI: 0.80-0.86). Subgroup analyses indicated that AI models showed overall diagnostic advantages across cancer types and imaging modalities, particularly in specificity, AUC, and diagnostic odds ratios, although clinicians demonstrated higher sensitivity in the prostate cancer and MRI subgroups. AI models demonstrate strong diagnostic performance across various urological cancers and imaging modalities, showing potential as supportive tools in radiological workflows. Further prospective, standardized, and multi-center evaluations are warranted to confirm AI's clinical utility across diverse diagnostic tasks in urological oncology.","[""Journal Article"", ""Meta-Analysis"", ""Systematic Review""]","[""Shen Y"", ""Peng L"", ""Gan L"", ""Wu S""]",10.1007/s00345-026-06635-3,Shen Y,World journal of urology,0724-4983,1,World J Urol,eng,Wu S,"[""Humans"", ""Artificial Intelligence"", ""Urologic Neoplasms"", ""Sensitivity and Specificity""]",,42545470,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545470/,Artificial intelligence in the radiologic diagnosis of major urological cancers: a meta-analysis,44,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Low-dimensional antiaromatic carbon-based nanostructures have attracted tremendous interest lately due to their distinctive electronic, optical and magnetic properties. These properties make them attractive for a myriad of potential applications in the fields of advanced organic optoelectronics, electronics, spintronics, photovoltaics, and quantum materials. However, their synthesis remains elusive due to their intrinsic electronic instability and high reactivity. In this context, recent advances in on-surface synthesis under ultra-high vacuum conditions have enabled the controlled generation and rationalization at the atomic scale of these compounds. In this review, we first introduce the concept of antiaromaticity and its main progress using solution-based methodologies. Then, we summarize key developments in the formation and characterization of individual antiaromatic molecules, one-dimensional polymers and two-dimensional networks on surfaces under ultra-high vacuum conditions. We highlight how molecular precursors are designed and surface conditions tuned to thermally or electronically direct skeletal rearrangements, enabling the formation of antiaromatic moieties, compounds and polymers, including cyclobutadiene, pentalene or cyclooctatetraene subunits, cyclocarbons, and other 4n π-electron systems. Finally, we discuss the implications of these findings for future applications, offering a perspective on emerging challenges in the surface-assisted chemistry of antiaromatic systems.","[""Journal Article"", ""Review""]","[""Barragán A"", ""Vicent DJ"", ""Martín N"", ""Écija D""]",10.1039/d5cs01502b,Barragán A,Chemical Society reviews,0306-0012,,Chem Soc Rev,eng,Écija D,[],,42545466,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545466/,Antiaromaticity by on-surface synthesis,,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"The ability to manipulate specific neural populations with high temporal and spatial precision has revolutionized our understanding of brain-behavior relationships. Among the most versatile tools in the chemogenetic arsenal are Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). By introducing engineered proteins that remain inert to endogenous neurotransmitters but react potently to synthetic actuators, chemogenetics provides unparalleled control over neural circuits in vivo. With the field evolving, new designer ligands and designer receptors have been reported. This review provides an update on the latest advances in DREADD chemogenetics, focusing on the development of next-generation ligands and the patent landscape innovations driving the next era of precision neuromodulation.","[""Journal Article"", ""Review""]","[""Dutta S"", ""Iyer MR""]",10.1007/s00044-026-03585-8,Dutta S,Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents,1054-2523,,Med Chem Res,eng,Iyer MR,[],,42545463,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545463/,Overview of the DREADDs chemogenetics and the patent landscape of their actuators,,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Chronic wounds remain difficult to manage because persistent infection, biofilm formation, and antimicrobial resistance limit the effectiveness of conventional antibiotics. Antimicrobial peptides (AMPs) have emerged as promising therapeutic alternatives because they combine broad-spectrum membrane activity with quorum-sensing interference and immunomodulatory effects but generally impose a lower resistance burden than single-target antibiotics do. This review examines topical delivery systems designed to improve AMP stability, local bioavailability, targeted release, and residence time within the wound microenvironment. Hydrogels and films provide moist, biocompatible matrices for localized and sustained peptide release, including alginate-based systems with activity against Pseudomonas aeruginosa biofilms. Nanoparticle platforms, including lipid, metallic, liposomal, and micellar systems, can protect AMPs from enzymatic degradation and generate depot-like release profiles against drug-resistant pathogens such as methicillin-resistant Staphylococcus aureus. Biopolymer scaffolds, microneedles, and stimuli-responsive carriers activated by pH, reactive oxygen species, temperature, light, or ultrasound provide spatiotemporal control of AMP deployment in infected wounds. These strategies are particularly relevant to chronic diabetic wounds, where delayed healing, persistent inflammation, and biofilm burden frequently coexist. Smart design elements, including extracellular matrix-mimetic nanofibers, integrated pH and cytokine sensors, cyclic peptides, and dendrimers, further extend AMP function by linking antimicrobial activity with tissue regeneration and wound monitoring. Preclinical studies report accelerated closure, reduced inflammatory burden, and biofilm disruption, but clinical translation remains limited by manufacturing scalability, dose-dependent cytotoxicity, sterilization stability, and limited human validation. Overall, next-generation topical AMP delivery systems offer a rational route to combine infection control with regenerative wound repair while reducing the reliance on conventional antibiotics.","[""Journal Article"", ""Review""]","[""Murthy S"", ""Zhao TY"", ""Neela VK"", ""Hassan M"", ""Selvaraja M"", ""Palanirajan VK""]",10.1186/s11671-026-04792-3,Murthy S,Discover nano,2731-9229,1,Discov Nano,eng,Palanirajan VK,[],,42545459,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545459/,Topical strategies for antimicrobial delivery of peptide medicines for the management of chronic wounds,21,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"The persistent challenges with diagnosing Lyme neuroborreliosis (LNB) have fostered investigations in a broad spectrum of biomarker candidates. The aim of this systematic review is to provide a comprehensive overview of these potential biomarkers of LNB. We conducted a systematic literature review in accordance with PRISMA guidelines on Medline, Embase, Scopus, and Web of Science. The study protocol was published on PROSPERO prior to study-initiation. Studies identified through the combined search strings were screened for eligibility by independent physicians with expertise in LNB. Quality assessment and risk of bias was determined for all included studies using the QUADAS-2 assessment tool. In addition, criteria for consistency and a quality-score were established to quantify and compare diagnostic potential of biomarkers across studies. The search-strings yielded a total of 3113 unique studies of which 74 studies were found eligible for inclusion. The included studies investigated 220 different biomarkers in a total of 2598 patients with LNB from 1990 to 2025 in 13 different countries. No blood-based biomarkers showed consistent diagnostic potential across studies. IL-10 was ranked as the most promising biomarker in CSF. The biomarker literature in LNB is characterized by substantial redundancy, with few candidates demonstrating consistent diagnostic potential across studies. Future research should prioritize rigorous validation of the most promising biomarkers rather than continued exploratory investigations to accelerate clinical translation.In addition, improved knowledge of LNB pathogenesis is a requisite for targeted biomarker discovery.","[""Journal Article"", ""Review""]","[""Fjordside L"", ""Florescu A"", ""Dos AH"", ""Ørbaek M"", ""Mens H"", ""Lebech AM""]",10.1007/s15010-026-02875-y,Fjordside L,Infection,0300-8126,,Infection,eng,Lebech AM,[],,42545454,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545454/,Biomarkers of Lyme neuroborreliosis: a systematic review,,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Acute respiratory distress syndrome (ARDS) is an important complication of scrub typhus and is associated with substantial mortality. The primary objective of this systematic review and meta-analysis was to estimate the proportion of hospitalised patients with microbiologically confirmed scrub typhus who developed ARDS. Secondary objectives were to estimate mortality among patients with scrub typhus-associated ARDS and to compare mortality between scrub typhus patients with and without ARDS. This PROSPERO-registered systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. PubMed, Embase, and Web of Science were searched from inception to April 2026 for studies reporting microbiologically confirmed hospitalised scrub typhus patients with extractable ARDS data. Pooled proportions and risk ratios (RRs) were estimated using random-effects models and reported with 95% confidence intervals (CIs). Prespecified subgroup analyses were performed for adult and paediatric populations. Methodological quality was assessed using design-specific Joanna Briggs Institute critical appraisal tools. Sixty-eight studies comprising 10,330 hospitalised patients with microbiologically confirmed scrub typhus were included. The pooled proportion of ARDS was 13% (95% CI 10%-16%; I² = 95.7%) across all age groups, with higher estimates among adults (15%, 95% CI 10%-21%) than paediatric patients (8%, 95% CI 6%-11%). Pooled mortality among patients with scrub typhus-associated ARDS was 21% (95% CI 13%-30%; I² = 76.5%), with higher estimates among adults (28%, 95% CI 13%-47%) than paediatric patients (16%, 95% CI 5%-29%). In 29 studies comprising 4,831 patients, mortality was substantially higher among patients with ARDS than among those without ARDS (RR 12.75, 95% CI 8.48-19.17; I² = 59.5%). ARDS occurs in a clinically important proportion of hospitalised patients with scrub typhus and is associated with a markedly increased observed risk of death. Estimates varied considerably across study settings, age groups, illness severity, and ARDS definitions. Early recognition of respiratory deterioration, timely anti-rickettsial therapy, and appropriate escalation of respiratory support are clinically important, but their specific impact on ARDS-related mortality remains to be further evaluated prospectively. The systematic review protocol was registered with PROSPERO (CRD420251058577).","[""Journal Article"", ""Review""]","[""Chaudhuri S"", ""Adhikari SD"", ""Boodman C"", ""Schmiedel Y"", ""Grobusch MP"", ""Gupta N""]",10.1007/s15010-026-02907-7,Chaudhuri S,Infection,0300-8126,,Infection,eng,Gupta N,[],,42545452,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545452/,Acute respiratory distress syndrome in scrub typhus: a systematic review and meta-analysis,,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Antimicrobial resistance (AMR) poses a global health crisis and necessitates novel therapeutic strategies beyond traditional antibiotic, driving interest in anti-virulence (AV) strategies that disable pathogenicity rather than bacterial viability. This review provides an integrated overview of emerging AV approaches targeting quorum sensing, type III secretion systems, biofilm development, adhesion, toxin activity, iron acquisition, and host-pathogen interactions. We highlight representative phytochemicals, repurposed drugs, engineered inhibitors, nanomaterial-enabled formulations, and antibiotic-combination strategies that have shown promise across Gram-positive and Gram-negative pathogens. Across the literature, quorum sensing inhibitors and biofilm-disrupting agents are the most extensively explored, with many candidates demonstrating robust in vitro attenuation of virulence phenotypes. Type III secretion system inhibitors stand out for their mechanistic precision and, in several instances, stronger in vivo support, whereas host-directed and toxin-neutralizing strategies expand the therapeutic landscape but require cautious translational assessment. Importantly, the evidentiary strength of AV candidates is highly variable, ranging from docking-based hypotheses to animal-model validation, underscoring the need to distinguish preliminary leads from more advanced therapeutics. Collectively, the reviewed studies suggest that AV therapy is best positioned as a precision anti-infective strategy, particularly for chronic, device-associated, and multidrug-resistant infections where conventional antibiotics are less effective. Future progress will depend on improved mechanistic validation, rigorous safety and pharmacokinetic assessment, and translational frameworks that capture virulence suppression, host recovery, and treatment durability beyond bacterial killing alone.","[""Journal Article"", ""Review""]","[""Bhomia R"", ""Chatterjee S""]",10.1007/s15010-026-02909-5,Bhomia R,Infection,0300-8126,,Infection,eng,Chatterjee S,[],,42545450,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545450/,Mechanistic and molecular insights into emerging anti-virulence therapeutics,,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Meat has played a central role in human evolution, shaping not only our diets but also our societies, cultures, and technologies. From early hunting practice to the domestication and systematic production of livestock, the history of meat production closely parallels human development. Today, however, industrial meat production faces growing challenges, including environmental sustainability, resource efficiency, ethical concerns, and evolving consumer expectations. In this review, the transformation of meat production is discussed, with a focus on emerging scientific and technological innovations aimed at improving meat quality, sustainability, and production efficiency. In addition, the concept of cellular agriculture is summarized as a complementary approach for producing future agricultural products, including protein sources, along with conventional meat production and other meat alternative technologies. The future of meat is not merely a technological challenge, but a multidisciplinary endeavor, as the market introduction of cell-based foods, a key component of cellular agriculture, broadens the meat science landscape and enables innovation to advance alongside conventional meat production in support of sustainable and resilient food systems.","[""Journal Article"", ""Review""]","[""Lee D"", ""Jo C""]",10.1007/s44463-026-00079-4,Lee D,Food science of animal resources,2636-0772,1,Food Sci Anim Resour,eng,Jo C,[],,42545446,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545446/,The future of meat: innovations in production within an expanding and sustainable food system,46,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Anterior shoulder instability (ASI) is a common shoulder condition that primarily affects adolescents and young adults. In older adults this represents a distinct condition with a distinct pathomechanism and complication profile. This review synthesizes the literature on ASI in patients 40 years or older, focusing on injury characteristics, treatment modalities, and clinical outcomes. Three databases (PubMed, MEDLINE, Embase) were searched on October 18, 2025. Primary studies investigating operative or non-operative management of ASI in patients with onset of instability at ≥ 40 years old were included. Methodological quality was assessed using MINORS criteria. Data were collated utilizing descriptive statistics. Ten studies were included with 541 patients, of which 315 were non-operative and 226 were operative. The most common concomitant injuries included rotator cuff tears (n = 219 of 409, 53.5%), Hills-Sachs lesions (n = 208 of 445, 46.7%), and glenoid bone defects (n = 20 of 249, 8.0%). The most common operative procedures were rotator cuff repair (80.5%, n = 182), Bankart repair (12.8%, n = 29), and reverse shoulder arthroplasty (4.4%, n = 10). Recurrent instability occurred in 5.5% of operative patients (n = 21 of 380) and 15.0% of non-operative patients (23 of 153) among studies reporting rates. Both non-operative and operative management yielded favourable outcomes, with low recurrence and complication rates, and satisfactory range of motion. ASI in patients ≥ 40 years old is commonly associated with concomitant injuries and can be managed operatively or non-operatively depending on injuries and instability severity. Further prospective, comparative studies using standardized outcomes are needed to better define optimal management in this population. IV, systematic review.","[""Journal Article"", ""Systematic Review"", ""Review""]","[""Ybema S"", ""Khan W"", ""Vivekanantha P"", ""Bouchard MD"", ""Kotipalli S"", ""Kay J""]",10.1007/s00590-026-04914-8,Ybema S,European journal of orthopaedic surgery & traumatology : orthopedie traumatologie,1633-8065,1,Eur J Orthop Surg Traumatol,eng,Kay J,"[""Humans"", ""Joint Instability"", ""Shoulder Joint"", ""Adult"", ""Rotator Cuff Injuries"", ""Middle Aged"", ""Shoulder Injuries"", ""Shoulder Dislocation"", ""Aged"", ""Range of Motion, Articular""]",,42545442,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545442/,Management of anterior shoulder instability in patients aged 40 and older: a systematic review,36,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Transition metal dichalcogenides (TMDs) have garnered considerable attention as advanced electromagnetic wave absorption (EMA) materials due to their unique layered structures, tunable electronic properties, and intrinsic defect-induced polarization mechanisms. This comprehensive review systematically summarizes recent advances in TMDs-based absorbers, with particular focus on two fundamental development strategies. The first involves multiscale structural design of pure phase TMDs spanning from atomic to submillimeter dimensions, achieved through precise defect regulation, phase engineering, and sophisticated morphological manipulation to optimize electromagnetic parameters and attenuation capabilities. The second strategy focuses on constructing multicomponent composite systems, incorporating dielectric matrices, magnetic elements, and multicomponent hybrids to achieve synergistic enhancement through interfacial polarization, conductive loss, and magnetic dissipation mechanisms. The review critically analyzes pioneering research achievements across various subfields while identifying specific challenges and opportunities within each domain. Future perspectives highlight emerging frontiers including atomic level interface engineering, inverse design of multicomponent and multiscale architectures, sustainable large-scale synthesis techniques, and development of multifunctional smart-response systems. This work aims to establish fundamental principles and provide forward-looking guidance for designing next-generation high-performance TMDs-based EMA materials with tailored functionalities.","[""Journal Article"", ""Review""]","[""Yan Y"", ""Lun A"", ""Gao B"", ""Liu Y"", ""Jia D"", ""Zhou Y"", ""Huang X""]",10.1007/s40820-026-02266-w,Yan Y,Nano-micro letters,2150-5551,1,Nanomicro Lett,eng,Huang X,[],,42545440,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545440/,Advances in TMDs-Based Electromagnetic Wave Absorbers: From Structural Engineering to Multicomponent Synergy,19,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Exosome-mediated delivery of small interfering RNA (siRNA) has emerged as a promising therapeutic strategy for cancer treatment, offering precise gene silencing with minimal off-target effects. Exosomes, naturally secreted extracellular vesicles, provide biocompatible carriers that protect siRNA from enzymatic degradation and facilitate efficient uptake by tumor cells. Their natural tropism, driven by surface proteins such as integrins and tetraspanins, promotes cellular adhesion and interactions within the tumor microenvironment, facilitating the delivery of therapeutic cargo. Preclinical studies have demonstrated that exosome-delivered siRNAs can suppress oncogenes, inhibit tumor growth, reverse chemoresistance, and modulate immune responses by targeting stromal and immune components. Engineering approaches, including surface functionalization and hybrid exosome-nanoparticle systems, further enhance stability, payload capacity, and tumor-homing efficiency. Combination strategies with chemotherapy, immunotherapy, or phototherapy have shown synergistic effects, allowing simultaneous inhibition of survival pathways, promotion of apoptosis, and remodeling of the immunosuppressive microenvironment. Early-phase clinical studies indicate safety, effective biodistribution, and functional gene silencing, highlighting the translational potential of exosome-mediated siRNA therapeutics. Challenges such as scalable production, cargo heterogeneity, and regulatory considerations remain, but ongoing advances in exosome engineering and patient-derived vesicles are poised to overcome these barriers. This review aims to comprehensively summarize the current state, therapeutic applications, and translational prospects of exosome-mediated siRNA delivery in cancer.","[""Journal Article"", ""Review""]","[""Abdelgawwad El-Sehrawy AAM"", ""Youssef Hussein H"", ""Nematov O"", ""Baig MR"", ""Patel DN"", ""Priyadarshini Nayak P"", ""Alkayyat S"", ""Bainsal N"", ""Singh G"", ""Basunduwah TS""]",10.1007/s40199-026-00631-z,Abdelgawwad El-Sehrawy AAM,"Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences",1560-8115,2,Daru,eng,Basunduwah TS,"[""Humans"", ""Exosomes"", ""RNA, Small Interfering"", ""Neoplasms"", ""Animals"", ""Tumor Microenvironment"", ""Gene Silencing"", ""Nanoparticles""]",,42545436,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545436/,"Exosome-mediated siRNA delivery in cancer: Loading strategies, targeting approaches, and therapeutic outcomes",34,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Acute ischemic stroke (AIS) is one of the most common nervous system diseases. Its high mortality and disability rates not only seriously threaten patients' health but also impose a significant socioeconomic burden. Intravenous thrombolysis (IVT) is the first-line treatment for AIS, and tissue-type plasminogen activator (t-PA) is the primary agent used in IVT. With the extension of the therapeutic time window, more AIS patients are eligible to receive t-PA treatment. The existence of thrombolytic resistance severely compromises the clinical efficacy of t-PA in AIS treatment. This paper elaborates on the phenomenon of thrombolytic resistance and analyzes the roles of thrombus components such as red blood cells (RBCs), platelets (PLTs), white blood cells (WBCs), and neutrophil extracellular traps (NETs), as well as non-thrombotic factors such as metabolic syndrome (MetS) and fatty acid (FA) in contributing to thrombolytic resistance. By clarifying the underlying mechanisms of thrombolytic resistance, this work aims to provide insights for strategies to overcome thrombolytic resistance and improve the therapeutic efficacy of t-PA.","[""Journal Article"", ""Review""]","[""Liu J"", ""Gao X"", ""Sun Y"", ""Shang Y"", ""Guo J"", ""Cheng J"", ""Bi X"", ""Zhang X""]",10.1007/s00415-026-14052-0,Liu J,Journal of neurology,0340-5354,8,J Neurol,eng,Zhang X,"[""Humans"", ""Thrombolytic Therapy"", ""Fibrinolytic Agents"", ""Tissue Plasminogen Activator"", ""Drug Resistance"", ""Ischemic Stroke"", ""Animals"", ""Treatment Failure""]",,42545430,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545430/,Thrombolytic resistance: an important factor leading to the failure of intravenous thrombolytic therapy,273,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Nicotine, a psychoactive compound primarily known for its role in tobacco addiction, has attracted increasing interest for its neuromodulatory and neuroprotective properties. Acting predominantly through nicotinic acetylcholine receptors, nicotine influences multiple neurotransmitter systems, modulates neuroinflammation, and supports synaptic plasticity. These mechanisms may be therapeutically relevant in disorders characterized by neurodegeneration or disrupted neurocircuitry, including Parkinson's disease, Alzheimer's disease, schizophrenia, attention-deficit/hyperactivity disorder, depression, and post-traumatic stress disorder. This review critically examines the current state of preclinical and clinical evidence, with particular attention to receptor subtype activity, cognitive and emotional modulation, and human trial data. Although nicotine's addictive potential and receptor desensitization remain concerns, advances in selective ligands offer new therapeutic avenues. By consolidating mechanistic insights and disease-specific data, this review highlights both the promise and challenges of developing nicotinic-based therapeutics for brain disorders.","[""Journal Article"", ""Review""]","[""Bjørklund G"", ""Gurgas L"", ""Hangan T""]",10.1007/s11064-026-04845-0,Bjørklund G,Neurochemical research,0364-3190,4,Neurochem Res,eng,Hangan T,"[""Humans"", ""Nicotine"", ""Animals"", ""Neurodegenerative Diseases"", ""Mental Disorders"", ""Receptors, Nicotinic"", ""Nicotinic Agonists""]",,42545429,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545429/,Nicotine in Neurodegenerative and Neuropsychiatric Disorders: Mechanisms and Clinical Evidence,51,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Although carbapenems are still key drugs in the treatment of serious infections due to MDR Gram-negative bacteria, the high rate of emergence of carbapenem resistance is a serious global health concern. Carbapenemase production is well studied but so far efflux pumps play an important, yet underestimated role in the development of resistance. Efflux systems, especially those belonging to the resistance-nodulation-division family play a role in intrinsic and acquired resistance by actively expelling antibiotics and synergizing with other mechanisms like loss of porins and enzyme degradation, and biofilm formation. This review will offer a detailed and integrated perspective of efflux-mediated carbapenem resistance including the structure, regulation and genetic determinants of efflux activity. Special attention is given to the interplay of efflux pumps and co-resistance mechanisms which indicates that those mechanisms do not act as independent mechanisms but are embedded in a network of co-ordinated resistance. The review also covers new approaches to therapy such as efflux pump inhibitors and critically discusses the problems that hinder their use in the clinic. Importantly, this work reveals some important limitations with the current diagnostic methods, showing that efflux-mediated resistance is often underestimated due to a lack of standardized methods. Moreover, the drivers of efflux activity from an epidemiological and environmental perspective are discussed within a One Health context, such as antibiotic pressure and co-selection by heavy metals. This review aims to combine mechanistic, clinical and ecological aspects to present a more nuanced view of efflux-mediated resistance and highlights the need for better diagnostics, focused treatment strategies and overall antimicrobial stewardship to manage carbapenem resistance infections.","[""Journal Article"", ""Review""]","[""Jangid H"", ""Menghani E"", ""Saini KC"", ""Verma AK""]",10.1007/s10482-026-02394-8,Jangid H,Antonie van Leeuwenhoek,0003-6072,9,Antonie Van Leeuwenhoek,eng,Verma AK,"[""Carbapenems"", ""Humans"", ""Anti-Bacterial Agents"", ""Antimicrobial Stewardship"", ""Bacterial Proteins"", ""Gram-Negative Bacteria"", ""Membrane Transport Proteins"", ""Drug Resistance, Multiple, Bacterial"", ""Gram-Negative Bacterial Infections"", ""beta-Lactam Resistance"", ""beta-Lactamases""]",,42545426,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545426/,"Efflux-mediated carbapenem resistance: unveiling genetic drivers, clinical implications, and strategies for global antimicrobial stewardship",119,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"A systematic review of the effects of water immersion thermotherapy (WIT) on sleep quality in healthy adults. A comprehensive search was conducted in PubMed, Cochrane Library, Web of science, Embase, Scopus, Ovid MEDLINE, Wiley Online Library, PEDro, CNKI, SinoMed and Yiigle databases. A meta-analysis method was adopted to evaluate the improvement of sleep quality by using WIT. By calculating the standardized mean difference (SMD) and its 95% confidence interval (CI), and selecting either a common effects model or a random effects model for data pooling and analysis. A total of ten randomized controlled trials were included in this study. The results showed that WIT significantly increased total sleep time (SMD = 0.63, P = 0.0438) and significantly improved sleep efficiency (SMD = 0.64, P = 0.0419). However, there were no significant effects on sleep latency (P = 0.0877) or the pittsburgh sleep quality index (PSQI). Furthermore, there were no significant effects on PSQI-total score (P = 0.1136), PSQI-subjective sleep quality (P = 0.3721), PSQI-sleep latency (P = 0.0864), PSQI-sleep duration (P = 0.1402), PSQI-sleep efficiency (P = 0.6793), PSQI-sleep disturbances (P = 0.0580), PSQI-use of sleep medication (P = 0.9991), or PSQI-day time dysfunction (P = 0.6525) among the various indicators of the PSQI. WIT can significantly prolong total sleep time and improve sleep efficiency, but has no significant effect on the improvement of subjective sleep quality, indicating that the sleep-improving effect of WIT has certain limitations.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Review""]","[""Chen H"", ""Gao S"", ""Chen W"", ""Gao B""]",10.1007/s00484-026-03281-7,Chen H,International journal of biometeorology,0020-7128,8,Int J Biometeorol,eng,Gao B,"[""Humans"", ""Randomized Controlled Trials as Topic"", ""Sleep Quality"", ""Hyperthermia, Induced"", ""Water"", ""Sleep Duration"", ""Immersion""]",,42545422,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545422/,The effect of water immersion thermotherapy on sleep quality: a systematic review and meta-analysis of randomized controlled trials,70,AnmzQ94qOA94T0zkQ,iuBGflQi3iJv4SnND
"Current European expert consensus definitions for esophagogastric oligometastatic disease (OMD) primarily relate to adenocarcinoma. Oligometastatic esophageal squamous cell carcinoma (OMESQ) may require a distinct definition and treatment strategy. This systematic review and meta-analysis aimed to identify applied OMESQ definitions and assess the impact of local treatment on overall survival (OS). A systematic search of PubMed, Embase, CENTRAL, and ClinicalTrials.gov was conducted (February 2026). Studies or protocols were eligible if they reported an OMESQ definition or outcomes of local treatment in patients with limited metastatic ESCC. The primary outcomes were the maximum number of involved organs and metastases defined as OMD. Agreement across studies was scored as absent/poor (< 50%), fair (50%-75%), or strong (≥ 75%). A meta-analysis of OS after local treatment (+/- systemic therapy) versus systemic therapy alone was conducted through a random-effects pooled analysis of hazard ratios (HRs). Of the 3844 screened articles, 27 studies (23 retrospective, 4 prospective [one randomized]) and 7 protocols were included. Agreement was observed for defining synchronous OMESQ as disease in one organ with ≤3 metastases and metachronous OMESQ as disease in one organ with ≤2 metastases. Across 10 studies, meta-analysis showed that local treatment (+/- systemic therapy) was associated with improved OS compared with systemic therapy alone (pooled HR 0.61, 95% confidence interval: 0.52-0.72; I2 = 50.7%). Current literature and trial protocols considers OMESQ as ≤3 synchronous or ≤ 2 metachronous metastases in 1 organ. Local treatment is associated with improved OS compared with systemic therapy alone.","[""Systematic Review"", ""Journal Article"", ""Meta-Analysis""]","[""Nomura M"", ""Bronzwaer SFC"", ""Kroese TE"", ""van Rossum PSN"", ""Ruurda JP"", ""van Hillegersberg R"", ""Kato K"", ""Ogata T"", ""Kanda M"", ""Hamai Y"", ""Tsubosa Y"", ""Yoshii T"", ""Furuta M"", ""Sakanaka K"", ""Matsuda S"", ""Tsushima T"", ""Laarhoven HWM"", ""Takeuchi H""]",10.1093/dote/doag078,Nomura M,Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus,1120-8694,4,Dis Esophagus,eng,Takeuchi H,"[""Humans"", ""Esophageal Neoplasms"", ""Esophageal Squamous Cell Carcinoma"", ""Treatment Outcome"", ""Neoplasm Metastasis"", ""Female"", ""Male""]",,42544486,,2026 Jul 2,2026,https://pubmed.ncbi.nlm.nih.gov/42544486/,Oligometastatic esophageal squamous cell carcinoma: a systematic review of current definitions and meta-analysis of local therapy outcomes,39,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Older adults presenting to the emergency department (ED) following a fall are at high risk for recurrent falls, injuries and increased healthcare utilisation. This systematic review and meta-analysis evaluated the effectiveness of interventions initiated upon ED presentation in reducing falls (primary outcome) and fall-related outcomes (secondary outcomes) among older adults. A comprehensive search was performed in Ovid Medline, Embase, CINAHL, PEDro, Web of Science, and Scopus up to June 2025, following PRISMA guidelines. This yielded 9624 references, of which 4811 records remained after deduplication and were screened for eligibility. Meta-analyses and descriptive methods, including vote counting, were applied where appropriate. Sensitivity and subgroup analyses were conducted. Thirty articles were included. Interventions were associated with a significant reduction in fall incidence (rate ratio 0.69; 95% CI 0.54-0.88; I2 = 95%), supported by vote counting. While reductions were also observed in the proportion of fallers (odds ratio 0.87; 95% CI 0.71-1.07; I2 = 61%), fall-related and all-cause ED revisits, hospital admissions, recurrent falls and mortality, these trends did not reach statistical significance. Sensitivity analysis excluding studies with modified usual care showed a significant reduction in fall-related ED revisits and people sustaining an injurious fall. Secondary outcomes including quality of life, fear of falling and physical functioning generally showed trends favouring the intervention group. Considerable heterogeneity and variation in intervention characteristics were noted across studies. Interventions for older adults presenting to the ED after a fall suggest a favourable effect on fall rate. Non-significant trends favouring the intervention group were observed for several other outcomes, but heterogeneity and methodological limitations preclude definitive conclusions.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis""]","[""Charmant W"", ""Jansen S"", ""van Schoor NM"", ""de Vries R"", ""Nanayakkara P"", ""Willems HC"", ""van der Velde N""]",10.1093/ageing/afag227,Charmant W,Age and ageing,0002-0729,8,Age Ageing,eng,van der Velde N,"[""Humans"", ""Accidental Falls"", ""Emergency Service, Hospital"", ""Aged"", ""Emergency Room Visits"", ""Recurrence"", ""Risk Factors"", ""Aged, 80 and over"", ""Risk Assessment""]",,42544467,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42544467/,Emergency department-initiated interventions to reduce risk of recurrent falls in older adults: a systematic review and meta-analysis,55,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Tuberculosis (TB) is an important global health problem, especially for pregnant women, a vulnerable group. This systematic review and meta-analysis was conducted in this group to obtain cumulative results in a collective effort toward the World Health Organization (WHO) End TB Strategy. The databases Ovid MEDLINE, Embase, PubMed, ScienceDirect, Scopus, and Cochrane Central Register of Controlled Trials were searched for the last 10 years till 14th January 2025. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in this analysis. Pregnancy outcomes in terms of maternal complications and perinatal complications, including observed mortality, were considered for analysis. A total of 9,873 records were identified through database searching, and 15 studies, including 3,045 pregnant women with TB, were selected for final analysis. The pooled mean maternal age was 27.6 years, and more than half of TB cases were diagnosed antenatally. Among pregnancy-related complications, fetal growth restriction, pregnancy-induced hypertension, oligohydramnios, and gestational diabetes were seen in 19, 15, 11, and 10% of cases, respectively. Low birth weight, preterm birth, small for age, and low Apgar score (<7) had pooled prevalences of 30, 22, 20, and 13%, respectively. Maternal mortality and neonatal mortality showed pooled prevalences of 0.05 [95% confidence interval (CI): 0.03-0.08] and 5% (95% CI: 3-8%), respectively. Low to moderate heterogeneity was found among observations. This systematic review and meta-analysis showed continued maternal and perinatal adverse outcomes in pregnant women with TB even in the current era, highlighting the need to optimize healthcare.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis""]","[""Sharma H"", ""Garg S"", ""Sharma S"", ""Sharma U"", ""Kumar A""]",10.59556/japi.74.1608,Sharma H,The Journal of the Association of Physicians of India,0004-5772,7,J Assoc Physicians India,eng,Kumar A,"[""Humans"", ""Female"", ""Pregnancy"", ""Pregnancy Outcome"", ""Pregnancy Complications, Infectious"", ""Tuberculosis"", ""Infant, Newborn""]",60-65,42543993,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543993/,Pregnancy Outcomes in Patients with Tuberculosis: A Systematic Review and Meta-analysis,74,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Patient safety events are among the top ten causes of death and disability worldwide, with most considered preventable, particularly in primary care. Digital interventions are increasingly used in primary care to improve patient safety, targeting errors and preventing adverse events. Evaluating their effectiveness and implementation is essential to inform clinical practice and policy. The study aims included a systematic review and meta-analysis of the effectiveness of digital patient safety interventions in primary care, comparing single and multicomponent interventions, identifying effective components, and exploring factors influencing their success. MEDLINE, EMBASE, and CENTRAL were searched from January 2001 to June 2025, restricted to English-language publications. This review followed PRISMA guidelines. Randomized controlled trials assessing digital interventions aimed at improving patient safety outcomes in primary care were included. Safety outcomes were grouped into medication safety and non-medication process measures, and adverse events. Two reviewers independently extracted and verified data and assessed risk of bias, resolving discrepancies by consensus. Random-effects meta-analysis was performed for predefined safety outcomes, and a narrative synthesis described implementation factors. Seventy-four randomized controlled trials (RCTs) were included. Meta-analysis demonstrated benefits for medication safety process measures (k = 54; Odds Ratio (OR) 1.46, 95% confidence interval (CI): 1.30-1.64), non-medication process measures (k = 40; OR 1.77, 95% CI: 1.56-2.01), and adverse events (k = 12; OR 1.17, 95% CI: 1.06-1.30). Overall, multicomponent interventions consistently showed greater improvements than single-component interventions. Interventions combining components of clinical decision support and audit and feedback were most effective for medication safety, while patient-facing components had greater impact on non-medication process measures. Results remained consistent in sensitivity analyses restricted to higher-quality RCTs. Effectiveness was likely influenced by implementation factors, including workflow integration and relational support. Digital interventions in primary care are associated with moderate improvements across multiple patient safety process measures. Multicomponent approaches appear most promising, with effectiveness potentially shaped by implementation, patient engagement and contextual factors. These findings support the broader adoption of well-designed, contextually adapted digital strategies to enhance patient safety and underscore the need for ongoing evaluation of the sociotechnical factors supporting delivery of these interventions.","[""Systematic Review"", ""Journal Article"", ""Meta-Analysis""]","[""Tsang JY"", ""Planner C"", ""Low CN"", ""Stewart S"", ""Morris C"", ""Wong B"", ""Delitheos SM"", ""Kulangara G"", ""Yu LKD"", ""Babu ABS"", ""Ajabnoor A"", ""Ashcroft DM"", ""Panagioti M""]",10.1186/s12916-026-05048-8,Tsang JY,BMC medicine,1741-7015,1,BMC Med,eng,Panagioti M,"[""Humans"", ""Patient Safety"", ""Primary Health Care"", ""Digital Health"", ""Randomized Controlled Trials as Topic"", ""Digital Media""]",,42543473,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42543473/,Digital patient safety interventions in primary care: a systematic review and meta-analysis,24,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"This study aimed to construct an evidence chain for the efficacy of Shuxuening Injection(SXN) in the treatment of unstable angina pectoris(UAP) and clarify its efficacy and underlying mechanisms. Eight major Chinese and English databases, including CNKI, VIP, Wanfang, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science, were systematically searched to collect clinical studies, animal experiments, cell experiments, and molecular experiments on SXN for UAP. Two researchers independently screened the literature and extracted data. Meta-analysis or descriptive analysis was used for data integration. The TCM evidence chain construction method was applied to establish evidence chains, which were then evaluated. A total of 2 evidence chains were constructed, incorporating 64 clinical studies, 12 animal experiments, 11 cell experiments, and 86 outcome indicators. The evidence chains elucidated the efficacy and mechanisms of SXN for UAP from 2 dimensions: improvement of myocardial ischemia and protection of cardiac function. SXN exerted a synergistic effect on the core pathological processes of UAP through multiple mechanisms, including regulating oxidative stress, promoting angiogenesis, modulating inflammation and matrix remodeling, inhibiting apoptosis, and balancing endoplasmic reticulum stress. SXN demonstrated efficacy in the treatment of UAP. However, due to the limitations in the quantity and quality of included studies, the robustness of the evidence chains was insufficient. High-quality clinical and basic research is required to further verify its core mechanisms. Additionally, it is recommended that subsequent studies include more indicators reflecting plaque stability and thrombosis in the selection of clinical outcome indicators.","[""Journal Article"", ""English Abstract"", ""Review"", ""Meta-Analysis""]","[""Li YY"", ""Wu XL"", ""Sang ZF"", ""Zhu HZ"", ""Cao LJ"", ""Pang B"", ""Yang FW"", ""Pang WT"", ""Zhang JH""]",10.19540/j.cnki.cjcmm.20260401.502,Li YY,Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica,1001-5302,14,Zhongguo Zhong Yao Za Zhi,chi,Zhang JH,"[""Drugs, Chinese Herbal"", ""Animals"", ""Humans"", ""Angina, Unstable"", ""Injections"", ""Apoptosis""]",4169-4183,42543348,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543348/,[Efficacy of Shuxuening Injection in treatment of unstable angina pectoris: study on TCM efficacy evidence chain],51,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"This paper aims to evaluate the effects of online pelvic floor muscle training on urinary incontinence frequency, symptom severity, quality of life and adherence across defined female life stages. Urinary incontinence is a significant public health issue affecting women's physical and mental well-being. The paper is designed as a systematic review and meta-analysis of randomized controlled trials. Nine databases were searched for RCTs of online PFMT in women with UI. Outcomes included UI incidence, symptom severity, quality of life and compliance. Data extraction, risk-of-bias (RoB 2) and GRADE assessment were performed. Random-effects meta-analyses used RevMan 5.4. Sixteen studies were included. Online pelvic floor muscle training significantly reduced postpartum urinary incontinence incidence (RR = 0.56; 95% CI: 0.38 to 0.82) and symptom severity (SMD = -0.25; 95% CI: -0.45 to -0.05), but not in elderly patients (SMD = -0.12; 95% CI: -0.25 to 0.02). Exercise compliance improved in both subgroups. No significant difference was found in quality of life. Moderate-to-high heterogeneity was observed. Online pelvic floor muscle exercise may improve urinary incontinence outcomes across different life stages. In postpartum women, it reduces incontinence incidence, alleviates symptom severity and enhances training compliance, whereas in elderly patients, its benefit is limited to improved compliance.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis""]","[""Wang Y"", ""Zhang H"", ""Wang J"", ""Feng W"", ""Sun Z"", ""Chen Y""]",10.1111/ijn.70177,Wang Y,International journal of nursing practice,1322-7114,4,Int J Nurs Pract,eng,Chen Y,"[""Humans"", ""Female"", ""Urinary Incontinence"", ""Pelvic Floor"", ""Exercise Therapy"", ""Quality of Life"", ""Internet""]",e70177,42543255,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42543255/,The Rehabilitative Effects of Online Pelvic Floor Muscle Exercises on Female Urinary Incontinence Across Various Life Stages: A Systematic Review and Meta-Analysis,32,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"This study aims to systematically evaluate the impact of exercise interventions on reproductive endocrine profiles in adult patients with polycystic ovary syndrome (PCOS) using a three-level meta-analytical approach. We performed a systematic search of PubMed, Web of Science, The Cochrane Library, and Embase for randomized controlled trials (RCTs) investigating the effects of exercise on reproductive endocrine profiles in PCOS patients, spanning from database inception through April 7, 2026. A three-level meta-analysis was conducted in R using a random-effects model fitted via restricted maximum likelihood (REML). Effect sizes were quantified as Hedges' g with 95% confidence intervals (CIs). Global heterogeneity was assessed using the Cochran's Q test, and the robustness of results was verified through leave-one-out sensitivity analyses. Model fit was compared using likelihood ratio tests (LRT). Publication bias was scrutinized via Egger's test, with the trim-and-fill method employed as a corrective measure where necessary. Methodological quality was appraised using the PEDro scale, and the certainty of evidence was graded via the GRADE profiler. Nineteen studies involving 1,018 participants were synthesized. Exercise interventions significantly lowered testosterone levels (g = -0.34; 95% CI [-0.61 to -0.07]; P = 0.0146). Subgroup analysis revealed that the ""aerobic exercise"" group was statistically significant (k = 14, g = -0.5120, 95% CI [-0.8230 to -0.2010], P = 0.0027). The mean body mass index (BMI) ""25 to 29.9"" group was also statistically significant (k = 17, g = -0.4859, 95% CI [-0.7775 to -0.1943], P = 0.0025), as was the mean age group of ""26 to 30 years old"" (k = 13, g = -0.4878, 95% CI [-0.8465 to -0.1290], P = 0.0105). In conclusion, exercise interventions exert a favorable impact on serum testosterone (T) levels in adult patients with polycystic ovary syndrome (PCOS). PROSPERO (registration no. CRD420251108464; https://www.crd.york.ac.uk/prospero/).","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis""]","[""Chen X"", ""Liu Y"", ""Chen D"", ""Chen L""]",10.7717/peerj.21507,Chen X,PeerJ,2167-8359,,PeerJ,eng,Chen L,"[""Humans"", ""Polycystic Ovary Syndrome"", ""Female"", ""Testosterone"", ""Exercise"", ""Adult"", ""Randomized Controlled Trials as Topic""]",e21507,42542806,pmc-id: PMC13428543;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42542806/,Effects of exercise on reproductive endocrine hormones in adult patients with polycystic ovary syndrome: a systematic review and three-level meta-analysis,14,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Anterior cruciate ligament reconstruction (ACLR) is a commonly performed procedure aimed at restoring knee stability and function following ligament injury. Although hamstring tendon (HT) autografts are widely used, concerns regarding donor-site morbidity and graft-related limitations persist. The peroneus longus tendon (PLT) has recently gained attention as an alternative autograft, offering favourable biomechanical properties and potentially reduced morbidity. However, evidence comparing clinical outcomes between PLT and HT autografts remains limited and inconsistent. Therefore, this study aimed to systematically evaluate and compare the efficacy and safety of PLT versus HT autografts in primary ACLR using high-level evidence from randomised controlled trials (RCTs). A systematic review and meta-analysis of RCTs comparing PLT and HT autografts in primary ACLR was conducted. Databases were searched up to December 2025. Outcomes included patient-reported scores, knee stability, graft characteristics, donor-site morbidity, and ankle function. Four RCTs involving 407 patients were included. Lysholm and IKDC scores were comparable between groups. The PLT group demonstrated significantly better modified Cincinnati scores (MD, 3.02; P = 0.0004) and larger graft diameter. Donor-site morbidity was significantly lower with PLT (OR 0.12; P = 0.007). Knee stability and graft failure rates were similar. AOFAS scores showed no significant postoperative decline. PLT autografts provide outcomes comparable to HT with potential advantages in donor-site morbidity and graft characteristics, supporting their use as a reliable alternative in ACLR.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Comparative Study"", ""Review""]","[""Desouza C"", ""Nighot A"", ""Sahu A"", ""Shetty V""]",10.1007/s00590-026-04907-7,Desouza C,European journal of orthopaedic surgery & traumatology : orthopedie traumatologie,1633-8065,1,Eur J Orthop Surg Traumatol,eng,Shetty V,"[""Humans"", ""Randomized Controlled Trials as Topic"", ""Hamstring Tendons"", ""Autografts"", ""Anterior Cruciate Ligament Reconstruction"", ""Anterior Cruciate Ligament Injuries"", ""Transplantation, Autologous"", ""Tendons"", ""Joint Instability"", ""Treatment Outcome""]",,42542493,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42542493/,Peroneus longus autograft versus hamstring tendon autograft in primary anterior cruciate ligament reconstruction: a systematic review and meta-analysis of randomised controlled trials,36,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"The introduction of combination antiretroviral therapy (cART) has improved survival among people living with HIV (PLHIV) but increased the risk of non-communicable diseases, including diabetes mellitus (DM). In East Africa, estimates of DM prevalence among PLHIV vary widely, and contributing factors are not well defined. This study aimed to estimate the pooled prevalence of DM and identify associated risk factors among PLHIV in the region. A systematic review and meta-analysis were conducted following PRISMA 2020 guidelines (PROSPERO: CRD420251129591). Databases including PubMed, Embase, CINAHL, Web of Science, African Journals Online, and Google Scholar were searched for cross-sectional, cohort, and case-control studies reporting DM prevalence or associated factors among PLHIV aged ≥ 16 years in East Africa. Data were extracted independently by two reviewers, and study quality was assessed using the Joanna Briggs Institute checklist. A random-effects model using DerSimonian-Laird method was applied to estimate pooled prevalence. Heterogeneity was assessed with Cochran's Q and I², and publication bias was evaluated via funnel plot, Egger's test, and trim-and-fill analysis. Adjusted odds ratios (AORs) were pooled to identify factors associated with DM. A total of fourteen studies were included. The pooled prevalence of DM was 6.4% (95% CI: 4.3-9.7%; I² = 94.9%). Trim-and-fill analysis did not change the estimate. Significant risk factors included higher education (AOR = 8.56, 95% CI: 3.82-19.17), obesity/overweight (AOR = 6.68, 95% CI: 2.58-17.32), positive family history of diabetes (AOR = 7.60, 95% CI: 3.56-16.22), longer duration of ART (AOR = 4.78, 95% CI: 1.22-18.81), and history of hypertension (AOR = 2.98, 95% CI: 1.69-5.27). Male sex and elevated triglycerides were not significantly associated. DM affects one in every 16 PLHIV in East Africa, with modifiable and non-modifiable risk factors identified. Integrating DM screening and preventive strategies into HIV care is critical to reduce cardio-metabolic complications.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis""]","[""Markos Z"", ""Lonsako DT"", ""Tekletsadik YA"", ""Aligaz EM"", ""Godebo AS"", ""Mamo T"", ""Hassen AA"", ""Tafesse D"", ""Lorato SS"", ""Lema DA""]",10.1007/s12020-026-04713-5,Markos Z,Endocrine,1355-008X,1,Endocrine,eng,Lema DA,"[""Humans"", ""Diabetes Mellitus"", ""Risk Factors"", ""HIV Infections"", ""Prevalence"", ""Africa, Eastern"", ""Uganda"", ""Kenya"", ""Tanzania"", ""Ethiopia"", ""East African People""]",,42541631,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42541631/,"Magnitude and factors associated with diabetes mellitus among people living with HIV/AIDS in Eastern Africa. Evidence from Ethiopia, Kenya, Uganda and Tanzania. A systematic review and meta-analysis",91,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Posterior lumbar interbody fusion (PLIF) and interspinous stabilization (ISS) are both used to treat lumbar spinal stenosis (LSS), but their comparative effectiveness and safety remain debated. Evidence comparing these approaches has evolved with the introduction of newer ISS devices and advances in contemporary surgical practice. A systematic search of PubMed, Google Scholar, Embase, and Scopus was conducted up to December 2, 2025, to identify comparative studies evaluating PLIF versus ISS for LSS. Nineteen studies met the inclusion criteria, comprising 214,155 patients (203,414 PLIF; 10,741 ISS). Outcomes included pain and functional measures, reoperation and revision rates, perioperative parameters, and complications. Three additional analyses were performed: subgroup analysis by publication period (before 2017 vs. 2017 onward), sensitivity analysis after excluding studies with very large sample sizes, and a study-design sensitivity analysis after excluding randomized controlled trials (RCTs). PLIF and ISS showed no significant differences in short- and mid-term pain or disability outcomes, including VAS leg and back pain at 3 months and 1 year, ΔVAS, ODI at 3 months and 1 year, and ΔODI. PLIF was associated with a greater change in segmental range of motion (ΔROM) (MD 6.96, 95% CI 4.94-8.97; p < 0.001). Compared with PLIF, ISS was associated with shorter operative time (MD 80.26 min, 95% CI 55.97-104.55; p < 0.001), lower blood loss (MD 260.54 mL, 95% CI 173.89-347.18; p < 0.001), and shorter hospital stay (MD 3.50 days, 95% CI 2.07-4.94; p < 0.001). Reoperation rates did not differ significantly between groups (RR 1.09, 95% CI 0.47-2.51). Similarly, revision rates were not significantly different between PLIF and ISS (RR 1.14, 95% CI 0.56-2.31). PLIF was associated with higher rates of mechanical complications (RR 1.60, 95% CI 1.09-2.33; p = 0.015), infectious complications (RR 3.50, 95% CI 2.67-4.58; p < 0.001), cardiopulmonary complications (RR 5.29, 95% CI 1.07-26.19; p = 0.041), and overall complications (RR 2.44, 95% CI 1.82-3.26; p < 0.001). In studies published before 2017, PLIF was associated with greater ΔROM and lower reoperation rates, but these differences were no longer observed in studies published from 2017 onward. Excluding studies with very large sample sizes did not materially change the main findings. Similarly, exclusion of the two RCTs did not materially alter the direction or statistical significance of the pooled estimates. PLIF and ISS provide broadly comparable short- and mid-term pain and functional outcomes for LSS. ISS is associated with consistent perioperative advantages and lower overall complication rates, while differences in reoperation and revision rates were not significant. Subgroup and sensitivity analyses, including the analysis excluding RCTs, suggest that earlier PLIF advantages in ΔROM and reoperation were not maintained in more recent studies, whereas the perioperative benefits of ISS remained robust. Larger randomized studies with longer follow-up and device-specific analyses are needed.","[""Journal Article"", ""Meta-Analysis"", ""Comparative Study"", ""Systematic Review"", ""Review""]","[""Boutros M"", ""Awad G"", ""Assi A"", ""Al Khatib R"", ""Hammad S"", ""Tannouri C""]",10.1007/s00590-026-04871-2,Boutros M,European journal of orthopaedic surgery & traumatology : orthopedie traumatologie,1633-8065,1,Eur J Orthop Surg Traumatol,eng,Tannouri C,"[""Humans"", ""Spinal Stenosis"", ""Spinal Fusion"", ""Lumbar Vertebrae"", ""Reoperation"", ""Postoperative Complications"", ""Treatment Outcome""]",,42541626,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42541626/,Posterior lumbar interbody fusion versus interspinous stabilization in lumbar spinal stenosis: a meta-analysis,36,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"The standard surgical approach to the treatment of pediatric VUR is ureteral reimplantation. Although open surgery is still the standard benchmark for its long-term durability and high success rate, the development of minimally invasive techniques led to the creation of laparoscopic ureteral reimplantation. The high learning curve and technical difficulty needed for accurate intracorporeal suturing, however, have limited its widely adopted in clinical practice. Robotic platforms have since emerged as a promising alternative, offering enhanced dexterity and improved visualization, which facilitate complex suturing and achieve success rates comparable to open surgery. However, most available meta-analytical data are limited by high degrees of heterogeneity because previous studies have often combined laparoscopic and robotic procedures and have combined intravesical and extravesical reimplantation. This is a very general classification that can introduce systematic bias and mask underlying differences between modalities. Through this direct comparison of these two specific surgical approaches, the goal of this study is to isolate these variables to provide highly granular, clinically relevant evidence to inform surgical selection for modern practice. We conducted a comprehensive literature search across PubMed, Embase, Web of Science, and the Cochrane Library to identify clinical studies that directly compared the efficacy of RAUR via the extravesical approach with OUR for the treatment of VUR in pediatric patients. For the OUR group, no restriction was placed on the surgical approach, and both extravesical and intravesical techniques were included. The operative time, hospital stay, success rates, and postoperative complications such as urinary tract infection, urinary retention, and other complications were extracted for comparative analysis. A total of 473 patients from seven studies were analyzed. The results of the meta-analysis showed that there was no significant difference between the two groups in terms of total complications, but the RAUR group had significantly longer operative time (WMD = 48.1 min, 95% CI [27.43, 68.76], p < 0.05) and significantly shorter length of hospitalization (WMD = -0.54 days, 95% CI [-0.96, -0.13], p < 0.05) when compared with the OUR group. When assessing surgical success rate, postoperative urinary tract infection, postoperative urinary retention, or overall complications, no significant differences were recorded between the two groups. In summary, these preliminary findings indicate that RAUR is associated with significantly longer operative time, which should be interpreted in the context of the learning curve. Although RAUR showed a statistically shorter hospital stay, the clinical benefit may be limited as most patients were discharged after overnight observation. Success and complication rates, including urinary tract infection and retention, were comparable to OUR, supporting the safety and efficacy of the robotic platform. Given equivalent key outcomes and expected experience accumulation, RAUR may be a viable alternative to OUR. However, owing to inherent confounding factors such as study design and surgical approach variations, these conclusions require further validation through high-quality multicenter randomized controlled trials.","[""Systematic Review"", ""Journal Article"", ""Meta-Analysis"", ""Comparative Study"", ""Review""]","[""Chen G"", ""Li J"", ""Xu Y"", ""Yu S"", ""Kong J"", ""Tang Y""]",10.1007/s11701-026-03754-2,Chen G,Journal of robotic surgery,1863-2483,1,J Robot Surg,eng,Tang Y,"[""Humans"", ""Vesico-Ureteral Reflux"", ""Robotic Surgical Procedures"", ""Ureter"", ""Replantation"", ""Child"", ""Urologic Surgical Procedures"", ""Laparoscopy"", ""Female"", ""Treatment Outcome"", ""Child, Preschool"", ""Length of Stay""]",,42541623,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42541623/,Robot-assisted vs. open ureteric reimplantation for pediatric vesicoureteral reflux: a systematic review and meta-analysis,20,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Despite the well-established efficacy of stereotactic radiosurgery in achieving obliteration of cerebral arteriovenous malformations (AVMs), a subset of patients, particularly those with large, deep-located AVMs, fail to achieve substantial obliteration. The CyberKnife machine offers a novel radiosurgery strategy by enhancing targeted precision and dosimetric flexibility. Herein, the authors performed a meta-analysis to explore clinical outcomes following CyberKnife radiosurgery for patients with cerebral arteriovenous malformations (AVMs), with a particular focus on obliteration rates and post-CKRS hemorrhagic rates. A systematic review of the literature was conducted under PRISMA guidelines through four electronic databases (PubMed, Scopus, Embase, and Web of Science) to identify studies on CyberKnife Robotic Radiosurgery for AVMs up to July 2025. Baseline data and data pertaining to post-CKSR outcomes were extracted for analysis, and a meta-analysis of proportions was performed. A total of fifteen retrospective cohort studies comprising 1101 patients describing the results of CyberKnife radiosurgery for cerebral AVM were included. The overall rates of AVM complete obliteration and partial obliteration over a median follow-up period of 38.6 months (range, 20.4-89 months) were 59% (95% CI: 0.48 _ 0.69) and 38% (95% CI: 0.27 _ 0.49), respectively. The median time to achieve complete obliteration was 36 months. The pooled rate of post-CKRS hemorrhage was 5% (95% CI: 0.01 _ 0.09), whereas the incidence of post-CKRS neurological deficits was 17% (95% CI: 0.09 _ 0.26). Subgroup analysis for 5 studies based on Spetzler-Martin (SM) grade revealed a significantly higher obliteration rate for grades I-III (69.92%, 95% CI 64.3-75.5%) than for grades IV-VI (34.3%, 95% CI 25.1-43.5%). Single-fraction CKRS resulted in complete obliteration of 422/495 completely obliterated. For the radiation dose, a subgroup analysis revealed no statistically significant difference in the obliteration rates between doses > 18 Gy (42.2%) and those < 18 Gy (57.9%). CKRS appears to be a feasible modality for AVM management, demonstrating acceptable pooled obliteration and hemorrhage rates. However, the certainty of evidence remains low due to retrospective designs, cohort heterogeneity, and a lack of direct comparative studies. Patients with prior hemorrhage or high-risk features may be more likely to have favorable outcomes from this machine.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Review""]","[""Hassan GA"", ""Hussein AFA"", ""Saydo B"", ""Buccilli B"", ""Hammad EM"", ""Hameed ATA"", ""Alwartari MA"", ""Abdulwahaab ZH"", ""Shimal AA"", ""Alwattary OSA"", ""Chichan ZM"", ""Satea M"", ""Hassan SE""]",10.1007/s10143-026-04418-3,Hassan GA,Neurosurgical review,0344-5607,1,Neurosurg Rev,eng,Hassan SE,"[""Humans"", ""Radiosurgery"", ""Intracranial Arteriovenous Malformations"", ""Treatment Outcome""]",,42541622,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42541622/,Clinical outcomes following cyberknife radiosurgery for cerebral arteriovenous malformations: A systematic review and meta-analysis,49,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"To compare clinical, operative, patient-reported, and economic outcomes of robotic versus laparoscopic inguinal hernia repair in adults. We conducted a PRISMA 2020-compliant systematic review and meta-analysis of PubMed, Web of Science, and Google Scholar through June 13, 2025. The protocol was retrospectively registered in PROSPERO (CRD420251075296). Comparative randomized and observational studies of elective robotic versus laparoscopic inguinal hernia repair in adults were eligible. Random-effects meta-analyses used restricted maximum-likelihood estimation with Hartung-Knapp confidence intervals; risk of bias was assessed using RoB 2 and MINORS, and certainty was evaluated using GRADE. Nineteen reports representing 18 unique cohorts and 78,940 participants were included. Nine reports (3,200 participants) contributed recurrence data; robotic repair was associated with a lower observed recurrence risk (RR 0.32, 95% CI 0.17-0.59; I2 = 0%), although certainty was low and the randomized evidence was imprecise. Robotic repair required longer operative time (11 studies; MD + 30.04 min, 95% CI 9.87-50.20; I2 = 99.6%); after excluding the influential Holleran 2022 cohort, the estimate was + 22.09 min (95% CI 8.87-35.30). Pooled immediate and postoperative-day-1 pain estimates did not show a statistically significant difference. Length of stay was not significantly different in the primary analysis (MD + 0.33 days, 95% CI -0.03 to 0.70), while an influence analysis suggested a small increase after robotic repair (+ 0.18 days). Overall complication estimates were unstable, and no clear differences were found for hematoma, surgical-site infection, or urinary retention. Robotic repair was consistently more expensive across heterogeneous healthcare settings. Robotic inguinal hernia repair was associated with lower observed recurrence in predominantly non-randomized evidence, but this finding should not be interpreted as proof of causal superiority. Robotic repair generally required approximately 22-30 additional operative minutes and incurred higher costs, while pooled pain, length-of-stay, and complication findings were uncertain or clinically small. Technique selection should therefore consider patient and hernia characteristics, surgeon experience, institutional resources, and the low to very low certainty of the available evidence.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Comparative Study""]","[""Alraddadi SE"", ""Almeghthawi AH"", ""Alahmadi HN"", ""Aljahani AS"", ""Aljohani JA"", ""Aljohani NA"", ""Alali RW"", ""Alrashedi RR"", ""Albalawi SA"", ""Almakky MG""]",10.1007/s11701-026-03728-4,Alraddadi SE,Journal of robotic surgery,1863-2483,1,J Robot Surg,eng,Almakky MG,"[""Humans"", ""Hernia, Inguinal"", ""Robotic Surgical Procedures"", ""Laparoscopy"", ""Treatment Outcome"", ""Herniorrhaphy"", ""Operative Time"", ""Recurrence"", ""Length of Stay"", ""Postoperative Complications""]",,42541618,pmc-id: PMC13428796;,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42541618/,Comparative outcomes of robotic versus laparoscopic inguinal hernia repair: a systematic review and meta-analysis,20,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Endoscopic transsphenoidal surgery is indicated when non-functioning pituitary adenomas (NFPAs) cause visual compromise, but its timing is less certain in patients with preserved vision and intact pituitary function, where the risk of new post-operative pituitary dysfunction influences decision-making. This systematic review aimed to determine the rate of new post-operative endocrine deficits following transsphenoidal surgery for NFPAs and to identify predictive factors. This review followed PRISMA guidelines. Studies reporting predictors of post-operative endocrine deterioration in adults undergoing transsphenoidal surgery for NFPAs were included. Predictors were synthesised narratively, with meta-analysis where at least two studies used comparable definitions. Pooled proportions estimated the overall rate of deterioration. Certainty of evidence was assessed using GRADE. Eleven studies comprising 2,350 patients were included. The pooled proportion developing new post-operative endocrine deterioration was 16% (95% CI 13-20%; I² = 60%). Larger tumour volume was associated with deterioration, and gross total resection with reduced odds compared with subtotal resection. Cavernous sinus invasion and other predictors showed inconsistent associations, while age, sex, comorbidities, apoplexy, pituitary gland or stalk visibility, surgeon experience and surgical approach were not associated with risk. Overall certainty of evidence was low to very low. New post-operative endocrine deficits affect approximately one in six patients after transsphenoidal surgery for NFPAs. Tumour volume was the most consistent predictor of endocrine deterioration, suggesting a potential role for earlier intervention in selected patients, although evidence certainty was low to very low. Standardised reporting and prospective studies are needed to guide risk stratification decision-making.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis""]","[""Ameen D"", ""ElSabban Y"", ""Kalaitzoglou D"", ""Shapey J"", ""Barazi S"", ""Thomas N"", ""Aylwin S"", ""Maratos E""]",10.1007/s12020-026-04712-6,Ameen D,Endocrine,1355-008X,1,Endocrine,eng,Maratos E,"[""Humans"", ""Pituitary Neoplasms"", ""Adenoma"", ""Postoperative Complications""]",,42541616,pmc-id: PMC13428792;,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42541616/,Predicting hormonal deterioration following transsphenoidal surgery for non-functioning pituitary adenomas: A systematic review and meta-analysis,91,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"To evaluate the diagnostic accuracy of intravesical prostatic protrusion (IPP) for detecting bladder outlet obstruction (BOO) in men with lower urinary tract symptoms (LUTS) attributed to benign prostatic hyperplasia (BPH), using urodynamic studies as the reference standard. A systematic review and meta-analysis was performed in accordance with PRISMA-DTA guidance. Studies were included if they evaluated IPP in adult men with LUTS attributed to BPH and defined BOO using urodynamic criteria, specifically BOO index > 40. Data were extracted to construct 2 × 2 diagnostic tables. Pooled sensitivity and specificity were estimated using a bivariate random-effects model, and overall diagnostic performance was assessed using a summary receiver operating characteristic curve. A random-effects model was also used to estimate the association between IPP > 10 mm and BOO. Ten studies including 1253 men met inclusion criteria. Greater IPP was associated with increased odds of urodynamically confirmed BOO, with a pooled odds ratio of 2.67 (95% CI, 1.48-4.79; I² = 94.6%). The 95% prediction interval ranged from 0.32 to 22.49, indicating substantial between-study variability and uncertainty regarding the association in future populations. Diagnostic meta-analysis across study-defined IPP thresholds of approximately 10-12 mm demonstrated a pooled sensitivity of 71.0% and specificity of 75.5% for detecting BOO. The area under the summary receiver operating characteristic curve was 0.795, consistent with moderate overall diagnostic accuracy. Available evidence suggests that IPP is associated with urodynamically confirmed BOO and that a threshold of approximately 10 mm may provide moderate diagnostic accuracy. However, the certainty of these findings is limited by the observational design, relatively small sample sizes, methodological heterogeneity, and unclear risk of bias in several included studies. IPP may therefore be useful as an adjunct to other clinical findings but should not replace urodynamic evaluation when diagnostic certainty is required.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis""]","[""Han Y"", ""Yaghi MH"", ""Polo J"", ""Elsadany M"", ""Elterman D"", ""Bhojani N"", ""Chughtai B""]",10.1007/s00345-026-06664-y,Han Y,World journal of urology,0724-4983,1,World J Urol,eng,Chughtai B,"[""Urinary Bladder Neck Obstruction"", ""Male"", ""Humans"", ""Urodynamics"", ""Prostatic Hyperplasia"", ""Reference Standards"", ""Prostate"", ""Urinary Bladder""]",,42541608,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42541608/,Diagnostic accuracy of intravesical prostatic protrusion (IPP) for bladder outlet obstruction using urodynamics as reference standard: a systematic review and meta-analysis,44,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Although South Asia exhibits a considerable burden of type 2 diabetes mellitus (T2DM), the numbers of undiagnosed T2DM remains inadequately characterized at the regional level. This systematic review and meta-analysis aimed to approximate the pooled prevalence of undiagnosed T2DM among the general adult population and to assess country-specific variations in South Asian countries. A comprehensive literature search was directed in PubMed, Scopus, Cochrane Library, ScienceDirect, and Web of Science for studies published between 1994 and 2022. Observational studies reporting the prevalence of undiagnosed T2DM among adults aged 20-79 years in South Asia were included. By using logit transformation, Random-effects meta-analysis was conducted to assess pooled prevalence. While using Cochran's Q and I² statistics Heterogeneity was calculated, publication bias was assessed using funnel plots and Egger's test, and subgroup analyses were performed by country. In this review, a total of 28 studies containing 104,019 participants and 5719 undiagnosed T2DM cases were included. The observed pooled prevalence of undiagnosed T2DM was 6.67% (95% CI: 4.99-8.58%) with considerable uncertainty as indicated by a very wide prediction interval (0.33%-19.75%) and extreme heterogeneity (I² = 98.5%, p < 0.001). At country-level substantial variation was seen, with the highest prevalence in Sri Lanka (30.54%; 95% CI: 17.90-44.82%), followed by Nepal (7.02%; 95% CI: 4.24-10.44%), Pakistan (5.97%; 95% CI: 3.97-8.33%), Bangladesh (5.84%; 95% CI: 5.28-6.42%) and India (5.26%; 95% CI: 3.66-7.14%). The results of Egger's test (t = 1.84, p = 0.0773) suggested no statistical significance evidence of publication bias. These findings should be interpreted with attentiveness because of extensive heterogeneity and variability across studies. However, the high number of undiagnosed T2DM in general population of South Asia reflects a great burden and indicates inter-country differences. Therefore, this conclusion highlights the need for advanced surveillance systems, valid diabetes screening, and approach to health care facilities, especially in deprived and high-risk population in the region.","[""Journal Article"", ""Meta-Analysis"", ""Systematic Review""]","[""Afzal F"", ""Ahmad I"", ""Khalid K"", ""Bashir I"", ""Akhtar S""]",10.1007/s12020-026-04711-7,Afzal F,Endocrine,1355-008X,1,Endocrine,eng,Akhtar S,"[""Adult"", ""Humans"", ""Asia, Southern"", ""Diabetes Mellitus, Type 2"", ""Prevalence"", ""Undiagnosed Diseases""]",,42541604,pmc-id: PMC13428718;,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42541604/,Prevalence of undiagnosed type 2 diabetes in South Asia: A systematic review and meta-analysis,91,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Cleft lip and palate (CLP) frequently cause maxillary hypoplasia, requiring surgical advancement, and virtual surgical planning (VSP) is increasingly used to improve accuracy. This systematic review and meta-analysis synthesized the evidence on VSP-assisted maxillary advancement in patients with CLP, with surgical accuracy as the primary outcome and skeletal stability, intraoperative efficiency, complications, patient-reported outcomes, and software utility as the secondary outcomes. This review followed the PRISMA 2020 statement and was prospectively registered (PROSPERO CRD420251011475). PubMed, Scopus, Web of Science, Embase, and ScienceDirect were searched. Methodological quality and certainty of evidence were assessed. Conventional osteotomy and distraction osteogenesis were analyzed separately; an exploratory random-effects meta-analysis was performed only for the homogeneous conventional Le Fort I osteotomy subset. Twelve studies were included. VSP achieved clinically acceptable accuracy, with mean linear deviations of 0.05-2.75 mm and most angular deviations below 4°. In the conventional Le Fort I subset, random-effects pooling with Hartung-Knapp adjustment gave mean absolute deviations of 0.65 mm mediolaterally (95% CI 0.58-0.73) and 1.10 mm superoinferiorly (0.49-1.71), both highly consistent (I2 = 0%). Anteroposterior deviation was not pooled owing to substantial heterogeneity (I2 = 88%) and ranged from 1.03 to 2.75 mm across studies. Where reported, relapse was generally 1-2 mm but heterogeneous. Current evidence supports the accuracy and feasibility of VSP-assisted maxillary advancement in patients with CLP; however, it is insufficient to prove reduced relapse or superiority over conventional planning. Because certainty is low to very low, VSP should be regarded as a promising adjunct rather than a proven standard of care; adequately powered prospective comparative studies with standardized outcomes are needed.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Review""]","[""Erdiansyah AM"", ""Ariestiana YY"", ""Tajrin A""]",10.1007/s10006-026-01608-7,Erdiansyah AM,Oral and maxillofacial surgery,1865-1550,1,Oral Maxillofac Surg,eng,Tajrin A,"[""Humans"", ""Cleft Palate"", ""Cleft Lip"", ""Surgery, Computer-Assisted"", ""Osteotomy, Le Fort"", ""Maxilla"", ""Patient Care Planning"", ""Orthognathic Surgical Procedures"", ""Osteogenesis, Distraction""]",,42541585,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42541585/,Accuracy and stability of virtual surgical planning for maxillary advancement in patients with cleft lip and palate: a systematic review and meta-analysis,30,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Closed-incision negative-pressure wound therapy (ciNPWT) has been shown to reduce complications in high-risk wounds, but there is still no consensus in literature to whether it is effective when compared to standard wound dressing (SWD). Therefore, we aimed to perform a systematic review and meta-analysis to assess the ongoing uncertainty regarding its clinical benefits. PubMed, Embase and Web of Sciences were systematically searched from inception to November 2025 for both observational and randomized studies comparing ciNPWT with SWD for patients submitted to abdominal wall reconstruction (AWR). A DerSimonian-Laird random-effect model and heterogeneity (assessed with Cochran's Q test and I² statistics) were performed using R software (version 4.4.0). 16 studies comprising 1,859 patients which underwent AWR, of whom 50% received ciNPWT and 50% SWD. The mean age was 56 years. The analysis showed that ciNTWT group presented significant reductions in both SSO (OR 0.56; 95%CI 0.36 to 0.86; p-value = 0.008; I² = 69.5%) and SSI (OR 0.61; 95%CI 0.39 to 0.91; p-value = 0.032; I² = 51.6%), no difference regarding readmission (OR 0.61; 95%CI 0.35 to 1.05; p-value = 0.072; I² = 26.5% ), reoperation (OR 0.69; 95%CI 0.39 to 1.23; p-value = 0.205; I² = 22.3%), hernia recurrence rates (OR 0.61; 95%CI 0.29 to 1.29; p-value = 0.1984; I² = 24.3%) and length of hospital stay (MD 0.26; 95%CI -1.22 to 1,75; p-value 0.729; I² = 92.1%). ciNPWT was associated with lower odds of SSI and SSO with no difference in LOS when compared to SWD.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Review""]","[""Cardoso JHCO"", ""Collaco BG"", ""Macret JZ"", ""de Almeida DPA"", ""Torves MM"", ""Nogueira R"", ""Malcher F"", ""Lima DL""]",10.1007/s10029-026-03744-1,Cardoso JHCO,Hernia : the journal of hernias and abdominal wall surgery,1248-9204,1,Hernia,eng,Lima DL,"[""Humans"", ""Negative-Pressure Wound Therapy"", ""Abdominal Wall"", ""Surgical Wound Infection"", ""Wound Healing"", ""Plastic Surgery Procedures""]",,42541577,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42541577/,Closed-incision negative-pressure wound therapy in abdominal wall reconstruction: a systematic review and meta-analysis,30,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Acceptance- and mindfulness-based interventions are effective for improving pain-related outcomes, yet their effects on psychological flexibility have not been meta-analyzed. This systematic review and meta-analysis addressed this gap by comparing these interventions with control conditions on psychological flexibility and its core dimensions in adults with chronic pain. Searches were conducted in PsycINFO, MEDLINE, Cochrane CENTRAL, Scopus and Web of Science from inception to May 2025. Sixty randomized controlled trials comprising 6692 participants were included. Meta-analyses were conducted for global psychological flexibility (k = 17), acceptance (k = 38), committed action (k = 4) and values (k = 4). Heterogeneity, risk of bias and certainty of evidence were assessed. Interventions significantly improved psychological flexibility at post-treatment, short-term (≤ 6 months) and long-term (> 6 months) follow-up (g = 0.35-0.69), and acceptance across all time points (g = 0.41-0.77). Effects for committed action and values were non-significant. Heterogeneity was substantial, most trials had a high risk of bias, and the certainty of evidence was low to very low. Moderator analyses indicated larger effects when interventions were compared with inactive controls, delivered by psychologists or implemented as stand-alone programs. Evidence suggests that acceptance- and mindfulness-based interventions may improve global psychological flexibility and acceptance. However, the certainty of evidence was low to very low, and most included trials were at high risk of bias. More rigorous trials are needed to clarify effects across specific dimensions of psychological flexibility. This systematic review and meta-analysis provide the first comprehensive synthesis of the effects of acceptance- and mindfulness-based interventions on psychological flexibility in chronic pain. These findings show that these interventions improve psychological flexibility, particularly pain acceptance, supporting it as a clinically relevant treatment target. PROSPERO: CRD420251018441.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Review""]","[""Sanabria-Mazo JP"", ""Rodríguez-Freire C"", ""Royuela-Colomer E"", ""Ponce-López P"", ""Alonso-Coello P"", ""Barrios V"", ""Navarrete J"", ""Pérez-Aranda A"", ""McCracken LM"", ""Luciano JV""]",10.1002/ejp.70342,Sanabria-Mazo JP,"European journal of pain (London, England)",1090-3801,7,Eur J Pain,eng,Luciano JV,"[""Humans"", ""Chronic Pain"", ""Mindfulness"", ""Randomized Controlled Trials as Topic"", ""Acceptance and Commitment Therapy"", ""Cognitive Flexibility""]",e70342,42541442,pmc-id: PMC13428482;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42541442/,Do Acceptance- and Mindfulness-Based Interventions Improve Psychological Flexibility in People With Chronic Pain? A Systematic Review and Meta-Analysis of Randomized Controlled Trials,30,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"This systematic review evaluated the diagnostic accuracy of CBCT for BMD assessment using DEXA as the reference standard and aimed to quantify its performance through meta-analysis. This review included prospective and retrospective observational studies assessing CBCT's diagnostic performance in detecting low BMD, with DEXA as the reference. Searches in PubMed, Embase, and Scopus identified 13 eligible studies involving adult participants (≥ 18 years). Two reviewers independently extracted data and assessed study quality using the QUADAS-2 tool. Meta-analysis was conducted using random-effects models. Pooled sensitivity and specificity of CBCT for detecting low BMD were 0.58 (95% CI: 0.50-0.67) and 0.78 (95% CI: 0.69-0.86), respectively. The summary receiver operating characteristic (SROC) curve showed an area under the curve (AUC) of 0.73 (95% CI: 0.69-0.77), indicating moderate diagnostic accuracy. Subgroup analyses revealed heterogeneity influenced by sample size and anatomical site. CBCT demonstrates moderate diagnostic accuracy in detecting low BMD, with better specificity than sensitivity. While promising, standardization of CBCT protocols and larger studies are needed to confirm its role in clinical assessment. PROSPERO REGISTRATION NUMBER: (CRD42024598958).","[""Systematic Review"", ""Journal Article"", ""Meta-Analysis"", ""Comparative Study"", ""Review""]","[""Alrashidi M"", ""Elbishari H"", ""Aljanahi M"", ""Amir-Rad F"", ""Chaudhry J"", ""Atieh M""]",10.1002/cre2.70423,Alrashidi M,Clinical and experimental dental research,2057-4347,4,Clin Exp Dent Res,eng,Atieh M,"[""Humans"", ""Cone-Beam Computed Tomography"", ""Bone Density"", ""Absorptiometry, Photon"", ""Sensitivity and Specificity"", ""Osteoporosis""]",e70423,42541433,pmc-id: PMC13428463;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42541433/,Comparative Diagnostic Performance of Cone Beam Computed Tomography and Dual-Energy X-Ray Absorptiometry for Low Bone Density Assessment. A Systematic Review and Meta-Analysis,12,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Background and AimsPulmonary embolism (PE) is a frequent and potentially fatal diagnosis in the emergency department (ED). The Pulmonary Embolism Rule-out Criteria (PERC), an eight-item clinical decision rule used to identify patients at very low risk of pulmonary embolism, is widely applied to exclude PE in low-risk patients; however, its real-world diagnostic performance and impact on imaging utilization remain incompletely defined. This systematic review aimed to evaluate the diagnostic accuracy of PERC and its effect on reducing computed tomography pulmonary angiography (CTPA) use.Materials and MethodsThis review followed the Joanna Briggs Institute (JBI) methodology for diagnostic test accuracy studies. Eligible studies enrolled ED patients with suspected PE who were classified as low risk according to the original study-specific approaches, including clinician gestalt, Wells score, revised Geneva score, or YEARS-based assessment. PubMed, Web of Science Core Collection, the Cochrane Library, and ClinicalTrials.gov were searched for eligible studies published between 2004 and 2025.ResultsTen studies involving 13,672 patients were included. The pooled PE prevalence was 7%. The pooled sensitivity, specificity, and negative predictive value of PERC were 95% (95% CI: 89%-98%), 26% (95% CI: 16%-40%), and 98.2% (95% CI: 97.8%-99.0%), respectively. PERC application was associated with a significant reduction in imaging utilization (RR = 0.85, 95% CI: 0.80-0.91).ConclusionsPERC provides a highly sensitive and safe strategy for ruling out PE in low-risk ED patients and significantly reduces unnecessary use of advanced imaging without compromising diagnostic safety.","[""Journal Article"", ""Meta-Analysis"", ""Systematic Review"", ""Review""]","[""Liu X"", ""Fan H"", ""Hai Y"", ""Wang J"", ""Yu X"", ""Lv Z"", ""Gu S""]",10.1177/10760296261472610,Liu X,Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis,1076-0296,,Clin Appl Thromb Hemost,eng,Gu S,"[""Pulmonary Embolism"", ""Humans"", ""Acute Disease"", ""Emergency Service, Hospital""]",10760296261472610,42541393,pmc-id: PMC13428846;,2026 Jan-Dec,2026,https://pubmed.ncbi.nlm.nih.gov/42541393/,Diagnostic Validation of PERC and Resource Utilization in Suspected Acute Pulmonary Embolism: A Systematic Review and Meta-Analysis,32,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"To our knowledge, a systematic review that has comprehensively evaluated the prevalence and clinical impact of multidrug -resistant bacteria in adult liver transplant recipients is not available. This review assessed the prevalence and clinical impact of multidrug -resistant bacteria among liver transplant recipients. In accordance with PRISMA guidelines, we searched Web of Science, PubMed, and Google Scholar through August 2025. The study protocol was registered in PROSPERO (CRD420251181202 ). We included cohort and case -control studies that reported on adult first liver transplant recipients harboring and not harboring multidrug -resistant bacteria. Two reviewers assessed eligibility and conducted a risk of bias evaluation using the Newcastle -Ottawa Scale. We synthesized data using the web -based Review Manager for a meta -analysis, with a random -effects model to compute the pooled odds ratio and 95 % CI. Statistical heterogeneity was determined using the I2 statistic. In the 13 included studies (12 cohort studies, 1 case -control study ), multidrug -resistant bacteria were identified in 507 of 28 599 liver transplant recipients. Multidrug -resistant bacteria colonization significantly increased posttransplant infection (odds ratio 5.98; 95 % CI, 2.24 -15.94 ), and their presence significantly increased mortality (odds ratio 5.32; 95 % CI, 2.36 -11.97 ). Subgroup analyses suggested a regional variation in mortality risk with a higher association in China and Japan (odds ratio, 22.26; 95 % CI, 6.83 -72.6 ). Exposure to these bacteria was also associated with prolonged hospital and intensive care unit stay and showed a borderline association with acute kidney injury but not with graft rejection. Colonization with multidrug -resistant bacteria is associated with increased infection, and both colonization and infection raise the risk of mortality. Despite the variations across studies in geography, follow -up duration, and screening methods, actions to prevent colonization in transplant candidates are warranted.","[""Systematic Review"", ""Journal Article"", ""Meta-Analysis""]","[""Qaddour EB"", ""Albunni DW"", ""Alwadi AY"", ""Aziz Z""]",10.6002/ect.2026.0042,Qaddour EB,Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation,1304-0855,6,Exp Clin Transplant,eng,Aziz Z,"[""Humans"", ""Liver Transplantation"", ""Drug Resistance, Multiple, Bacterial"", ""Prevalence"", ""Risk Factors"", ""Bacterial Infections"", ""Treatment Outcome"", ""Observational Studies as Topic"", ""Bacteria"", ""Female"", ""Risk Assessment"", ""Male"", ""Adult"", ""Middle Aged"", ""Anti-Bacterial Agents""]",470-480,42541325,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42541325/,Prevalence and Clinical Impact of Multidrug-Resistant Bacterial Colonization and Infection in Liver Transplant Recipients: A Systematic Review and Meta-Analysis of Observational Studies,24,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"To integrate evidence from randomized controlled trials (RCTs) comparing subcutaneous (SC) and oral methotrexate (MTX) for rheumatoid arthritis (RA) to provide optimal clinical treatment strategies. This meta-analysis conducted comprehensive search of PubMed, Web of Science, Embase and Cochrane Library, retrieving all relevant RCTs published up to June 18, 2025. Random-effects models were utilized to calculate the relative risk (RR), mean difference (MD) and their 95% confidence intervals (CIs), to evaluate efficacy and safety between subcutaneous injections and oral administration of MTX. A total of 1,034 articles were retrieved, and 9 RCTs that met the criteria were ultimately included, involving 974 RA patients in total. In the primary random-effects analyses, compared to oral MTX, subcutaneous MTX increased the ACR20 response rate (RR = 1.15; 95%CI: 1.05, 1.25), increased the ACR50 response rate (RR = 1.14; 95%CI: 1.01, 1.29), and reduced the incidence of gastrointestinal (GI)-related adverse event (AE) (RR = 0.58; 95%CI: 0.40, 0.83) and diarrhea (RR = 0.42; 95%CI: 0.21, 0.84). Fixed-effect sensitivity analyses supported the ACR20 and GI-related safety findings, but the ACR50 result was attenuated. Subcutaneous MTX did not show statistically significant differences in ACR70 response rate, DAS28-ESR score, bioavailability area under the curve, Cmax, or the incidence of other AE. Compared with oral administration, subcutaneous MTX was associated with a higher ACR20 response and lower GI-related AE and diarrhea in the primary random-effects analyses. These findings suggested that subcutaneous MTX may be an effective and generally well-tolerated option, particularly for patients with inadequate response or poor gastrointestinal tolerability to oral MTX, while evidence for ACR50, ACR70, DAS28-ESR and bioavailability remains less certain.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Comparative Study""]","[""Li G"", ""Xie W"", ""Liu J"", ""Geng Y"", ""Zhang Z""]",10.3389/fimmu.2026.1816269,Li G,Frontiers in immunology,1664-3224,,Front Immunol,eng,Zhang Z,"[""Humans"", ""Methotrexate"", ""Arthritis, Rheumatoid"", ""Administration, Oral"", ""Injections, Subcutaneous"", ""Antirheumatic Agents"", ""Treatment Outcome"", ""Randomized Controlled Trials as Topic""]",1816269,42539638,pmc-id: PMC13424238;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42539638/,Subcutaneous methotrexate compared with oral methotrexate in rheumatoid arthritis: a systematic review and meta-analysis,17,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Horticultural therapy (HT) is a promising non-pharmacological intervention for geriatric depression. However, the optimal ""dose"" required for maximum clinical efficacy remains poorly defined. To evaluate the efficacy of HT in alleviating geriatric depression and to quantify the dose-response relationship between intervention intensity and clinical outcomes. A systematic search was conducted across eight databases (including PubMed, Embase, and Cochrane Library, etc) for randomized controlled trials (RCTs) published up to 24 February 2026. Standardized mean differences (SMD) were pooled using a random-effects model. The dose-response relationship was modeled using restricted cubic splines (RCS). A total of eight RCTs involving 585 participants were initially identified. Systematic sensitivity analysis identified one study as a significant statistical outlier. After its exclusion, the final meta-analysis included seven studies with 435 participants. HT was associated with a significant reduction in geriatric depression scores (SMD = -0.52; 95% CI: -0.86 to -0.18; p = 0.0078). Heterogeneity remained moderate (I2 = 65.6%). The RCS model revealed an exploratory, hypothesis-generating non-linear dose-response relationship (p = 0.076), suggesting that the antidepressant benefit might peak at a cumulative dose of approximately 700-800 min. However, this finding should be interpreted with caution due to the limited number of studies. Subgroup analysis indicated that the GDS-30 scale showed a marginally significant trend toward higher sensitivity to treatment effects than the GDS-15 (p = 0.055). No significant publication bias was detected via Egger's test (p = 0.936) and Begg's test (p = 0.652). HT is an effective intervention for geriatric depression. A cumulative dose of 700-800 min represents a potential exploratory therapeutic window for maximizing efficacy while minimizing potential fatigue in frail older adults. PROSPERO, CRD420261323722.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis""]","[""Li Q"", ""Wang Y"", ""Wang X"", ""Han X"", ""Hu N""]",10.3389/fpubh.2026.1824111,Li Q,Frontiers in public health,2296-2565,,Front Public Health,eng,Hu N,"[""Humans"", ""Randomized Controlled Trials as Topic"", ""Depression"", ""Horticultural Therapy"", ""Aged"", ""Treatment Outcome""]",1824111,42539453,pmc-id: PMC13423710;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42539453/,Dose-response efficacy of horticultural therapy for geriatric depression: a systematic review and meta-analysis of randomized controlled trials,14,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Gegen Qinlian Decoction (GQD) is frequently used as an adjunctive therapy to metformin for type 2 diabetes mellitus (T2DM), but the certainty and consistency of the supporting clinical evidence remain unclear. We searched CNKI, Wanfang Data, PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials from database inception to January 31, 2026. Randomized controlled trials comparing GQD plus metformin with metformin alone in adults with T2DM were included. The primary outcome was glycated hemoglobin (HbA1c), and secondary outcomes were fasting plasma glucose (FPG) and 2-hour postprandial glucose (2hPG). Risk of bias was assessed using the Cochrane RoB 2 tool, and the certainty of evidence was evaluated using the GRADE framework. Random-effects meta-analyses were performed, with the primary analyses based on change-from-baseline values. Eight randomized controlled trials involving 725 participants were included. In the primary change-score analysis, GQD plus metformin did not show a statistically significant reduction in HbA1c compared with metformin alone (mean difference [MD] = -1.92, 95% confidence interval [CI]: -4.43 to 0.59, P = 0.13). Statistically significant reductions were observed for FPG (MD = -1.08, 95% CI: -1.71 to -0.44, P = 0.0009) and 2hPG (MD = -1.73, 95% CI: -3.05 to -0.42, P = 0.010). However, substantial heterogeneity was present across analyses (I² = 85%-100%), and the certainty of evidence was rated as very low because of risk of bias, inconsistency, and imprecision. Post-treatment sensitivity analyses using all eight trials showed statistically significant reductions in HbA1c, FPG, and 2hPG, but these analyses were also affected by substantial heterogeneity and high risk of bias across the included trials. Current evidence is insufficient to confirm a reliable clinical benefit of GQD as an adjunct to metformin for T2DM. Although reductions in FPG and 2hPG were observed, these findings should be interpreted as exploratory because of substantial heterogeneity, methodological limitations, and very low certainty of evidence. Larger, prospectively registered, well-designed, and adequately blinded randomized trials are needed.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis""]","[""He H"", ""Gai X"", ""Qiao Z"", ""Ji G"", ""Liu S""]",10.3389/fendo.2026.1837588,He H,Frontiers in endocrinology,1664-2392,,Front Endocrinol (Lausanne),eng,Liu S,"[""Metformin"", ""Humans"", ""Diabetes Mellitus, Type 2"", ""Drugs, Chinese Herbal"", ""Randomized Controlled Trials as Topic"", ""Hypoglycemic Agents"", ""Drug Therapy, Combination"", ""Blood Glucose"", ""Glycated Hemoglobin"", ""Treatment Outcome""]",1837588,42539441,pmc-id: PMC13423648;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42539441/,Efficacy of Gegen Qinlian decoction plus metformin for type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials,17,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Polycystic ovary syndrome (PCOS), the most common endocrine disorder in reproductive-aged women, often leads to gestational diabetes mellitus (GDM). This study aimed to systematically evaluate GDM prevalence and its associated factors in PCOS. We searched PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang, Sinomed, and VIP from inception to December 31, 2025. Studies reporting GDM prevalence or associated factors in PCOS were included. A random-effects model pooled prevalence with odds ratios. Egger's test assessed publication bias, and subgroup analysis with meta-regression explored heterogeneity. A logit transformation was applied for pooling. Twenty-two studies with 5,507 PCOS patients were included. The pooled GDM prevalence was 24% (95% CI: 20%-28%; prediction interval: 10%-46%), with substantial heterogeneity (I² = 89.9%). The primary prevalence estimate, based on cohort studies (n=13), was 21.7% (95% CI: 17.7%-25.8%), while the overall estimate including case-control studies was 24% (95% CI: 20%-28%). By diagnostic criteria, GDM prevalence was 26.0% for one-step vs. 18.7% for two-step. Potentially associated factors included pre-pregnancy BMI (OR = 1.39), gestational weight gain (OR = 1.58), HOMA-IR (OR = 3.41), and family history of diabetes (OR = 2.88). Although the pooled GDM prevalence in PCOS was 24%, substantial heterogeneity and a wide prediction interval (10%-46%) suggest the true prevalence varies considerably across settings. Associated factors included HOMA-IR, family history, pre-pregnancy overweight, and excessive gestational weight gain. PCOS patients should be considered a high-risk group, and early monitoring of glucose metabolism and weight management may be beneficial, though these recommendations derive from observed rather than interventional evidence. https://www.crd.york.ac.uk/PROSPERO/view/CRD42026128476, identifier: CRD420261284765.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis""]","[""Yuan Y"", ""Hu L"", ""Li Y"", ""Hou X""]",10.3389/fendo.2026.1874468,Yuan Y,Frontiers in endocrinology,1664-2392,,Front Endocrinol (Lausanne),eng,Hou X,"[""Humans"", ""Female"", ""Polycystic Ovary Syndrome"", ""Diabetes, Gestational"", ""Pregnancy"", ""Prevalence"", ""Risk Factors""]",1874468,42539429,pmc-id: PMC13423630;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42539429/,Prevalence and associated factors of gestational diabetes mellitus among women with polycystic ovary syndrome: a systematic review and meta-analysis,17,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"OBJECTIVES: To (1) estimate the prevalence of pelvic floor symptoms in performing artists and artistic athletes and (2) quantify the impact of symptoms during and outside performance and training. DESIGN: Epidemiology systematic review with meta-analysis. LITERATURE SEARCH: Six databases were searched from inception to February 2025. STUDY SELECTION CRITERIA: Studies involving participants from any artistic discipline and with data on pelvic floor symptom or disorder prevalence or impact were included. DATA SYNTHESIS: Critical appraisal was conducted using the JBI (Joanna Briggs Institute) Critical Appraisal Checklist, and the certainty of evidence was judged using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. Data were pooled for pelvic floor symptom proportions in performing artists and artistic athletes, with subgroup analyses for any type of urinary incontinence by discipline. We descriptively synthesized pelvic floor symptoms and impact data that were not included in the meta-analysis. RESULTS: Nineteen articles were included. Half (52%; 95% confidence interval [CI]: 38%, 66%; I2 = 92.7%) of the performing artists and artistic athletes reported urinary incontinence, 79% (95% CI: 69%, 88%; I2 = 80.6%) reported anal incontinence, and 47% (95% CI: 41%, 53%; I2 = not reported (NR)) reported dyspareunia. The discipline most affected by any type of urinary incontinence was trampolining (87%; 95% CI: 70%, 98%; I2 = NR). Up to 83% of the performing artists and artistic athletes reported some negative impact from their symptoms. CONCLUSION: At least half of the performing artists and artistic athletes reported pelvic floor symptoms, particularly urinary and flatal incontinence. The symptoms negatively impacted 83% of the athletes during performance. J Orthop Sports Phys Ther 2026;56(8):530-545. Epub September 19 2025. doi:10.2519/jospt.2025.13452.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Review""]","[""Frydenberg JC"", ""Ferrar K"", ""Dakic J"", ""Rio E"", ""Mayes S"", ""Frawley H""]",10.2519/jospt.2025.13452,Frydenberg JC,The Journal of orthopaedic and sports physical therapy,0190-6011,8,J Orthop Sports Phys Ther,eng,Frawley H,"[""Humans"", ""Urinary Incontinence"", ""Prevalence"", ""Pelvic Floor Disorders"", ""Athletes"", ""Fecal Incontinence"", ""Female"", ""Art"", ""Sports""]",530-545,42538791,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42538791/,Prevalence and Impact of Pelvic Floor Symptoms in Performing Artists and Artistic Athletes: A Systematic Review With Meta-analysis,56,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"OBJECTIVE: The primary aim was to quantify changes in structural and functional nerve parameters following carpal tunnel release. The secondary aims were to describe recovery trajectories and describe the regenerative capacity of the median nerve. DESIGN: Prognosis systematic review with meta-analysis. LITERATURE SEARCH AND SELECTION CRITERIA: Six databases were searched from inception to June 2024 for studies reporting at least 1 of the following outcomes: electrodiagnostic measures, quantitative sensory testing, grip/pinch strength, 2-point discrimination, Semmes-Weinstein monofilament, intraepidermal nerve fiber density, autonomic measures, brain function/structure, or Boston Carpal Tunnel Questionnaire. DATA SYNTHESIS: Outcomes were categorized by time post surgery: <2, 2 to 4, 5 to 7, 8 to 12, and >12 months. Randomized and observational studies were included, with quality assessed using the RoB 2 tool (revised Cochrane Risk of Bias tool for randomized trials) and the Newcastle-Ottawa Scale, respectively. RESULTS: A total of 199 studies comprising 15 636 patients and 578 healthy controls were included. We observed significant, time-dependent improvement in most outcomes. Grip and pinch strength did not show marked recovery until 5 to 7 months postoperatively. Compared to healthy controls, patients had persistent deficits in several electrodiagnostic measures even 1 year after surgery. Impairments in warm, vibration, and mechanical detection thresholds persisted up to 6 months postoperatively. CONCLUSION: Carpal tunnel release led to gradual improvement in median nerve function and structure. Key measures-including electrodiagnostics, detection thresholds, and intraepidermal nerve fiber density-often remained below normal levels after surgery. J Orthop Sports Phys Ther 2026;56(8):482-529. Epub 19 May 2026. doi:10.2519/jospt.2026.13846.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Review""]","[""Sobeeh MG"", ""Elsisy M"", ""Abozaid EM"", ""Samir A"", ""Mansour A"", ""Youssef S"", ""Kamel FO"", ""Lialy HE"", ""Abdel-Mageed RS"", ""Hassan KA"", ""Schmid AB""]",10.2519/jospt.2026.13846,Sobeeh MG,The Journal of orthopaedic and sports physical therapy,0190-6011,8,J Orthop Sports Phys Ther,eng,Schmid AB,"[""Carpal Tunnel Syndrome"", ""Humans"", ""Median Nerve"", ""Recovery of Function"", ""Nerve Conduction Studies"", ""Nerve Regeneration"", ""Hand Strength"", ""Electrodiagnosis""]",482-529,42538788,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42538788/,Neural Recovery After Carpal Tunnel Release: A Systematic Review With Meta-Analysis,56,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Most people with multiple sclerosis (MS) present with a clinically isolated syndrome (CIS); however, not all individuals with CIS are subsequently diagnosed with MS. A systematic literature review was conducted until December 2025. Observational studies of adults with CIS that were later diagnosed with MS were included. Odds ratios (ORs) were pooled using random-effects meta-analysis. Heterogeneity was assessed with I2, sensitivity analyses with leave-one-out procedures, and publication bias with funnel plots and Egger's test. Meta-regression was performed to explore further sources of heterogeneity when appropriate. Seventy-two studies with 9915 adults were included. In the meta-analysis, younger age (OR = 1.6, p < 0.01) and multifocal presentation (OR = 1.55, p = 0.02) were associated with a diagnosis of MS after a CIS. Magnetic resonance imaging findings, including a higher number of T2 lesions (OR = 7.46, p = 0.02), periventricular lesions (OR = 4.08, p < 0.01), corpus callosum lesions (OR = 14.89, p = 0.02), infratentorial lesions (OR = 2.16, p = 0.03), spinal cord lesions (OR = 1.4, p = 0.03), and gadolinium-enhancing lesions (OR = 1.91, p = 0.01), as well as cerebrospinal fluid inflammatory markers such as oligoclonal bands (OR = 3.57, p < 0.01) and pleocytosis (OR = 3.34, p = 0.02), were also associated with a subsequent diagnosis of MS. This meta-analysis identified factors associated with an increased likelihood of MS after a CIS. These findings may help identify high-risk individuals and guide personalized treatment strategies.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis""]","[""Zafra-Sierra MP"", ""Ferreira-Atuesta C"", ""Rodríguez DS"", ""Gaitán J"", ""Otero S"", ""Tintoré M"", ""Lublin F"", ""Giovannoni G"", ""Toro J"", ""Reyes S""]",10.1111/ene.70711,Zafra-Sierra MP,European journal of neurology,1351-5101,8,Eur J Neurol,eng,Reyes S,"[""Humans"", ""Multiple Sclerosis"", ""Demyelinating Diseases"", ""Magnetic Resonance Imaging""]",e70711,42538767,pmc-id: PMC13428175;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42538767/,Predictors of Multiple Sclerosis After Clinically Isolated Syndrome: A Systematic Review and Meta-Analysis,33,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"In patients with disorders of consciousness (DoC), behavioral assessment often underestimates awareness when motor output is absent or unreliable. Cognitive motor dissociation (CMD) refers to patients who appear unresponsive but demonstrate volitional brain responses during neurodiagnostic tests. We characterized clinical and methodological factors associated with CMD detection. Studies published between January 2000 and May 2026 were identified through MEDLINE, Embase, and Scopus. Individual participant data were analyzed using mixed-effects logistic regression. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Fifty-six studies with 1248 patients (mean age 45.5 years; 66.1% male; 44.5% unresponsive wakefulness syndrome [UWS]) were included. In unadjusted analyses, CMD detection was lower in anoxic (OR 0.43, 95% CI 0.29-0.66) and cerebrovascular (OR 0.59, 95% CI 0.37-0.98) compared to traumatic brain injury, and higher in minimally conscious state minus (MCS-) compared to UWS (OR 1.64, 95% CI 1.14-2.35). In multivariable models, anoxic (OR 0.35, 95% CI 0.23-0.55) and cerebrovascular (OR 0.51, 95% CI 0.32-0.84) etiologies remained independently associated with lower CMD detection, while MCS- remained associated with higher detection (OR 1.50, 95% CI 1.02-2.23). Time since injury, diagnostic modality and task paradigms were not independently associated with CMD detection. Overall, the studies showed a relatively low risk of bias. CMD is common but varies by etiology and clinical state. Its detection appears to be independent of the time of injury, the task paradigm, and the diagnostic modality, highlighting the importance of standardized protocols and longitudinal studies.","[""Journal Article"", ""Meta-Analysis"", ""Review""]","[""Laigaard PP"", ""Abla FW"", ""Hassani M"", ""Eigenbrodt AK"", ""Kondziella D""]",10.1111/ene.70713,Laigaard PP,European journal of neurology,1351-5101,8,Eur J Neurol,eng,Kondziella D,"[""Humans"", ""Consciousness Disorders"", ""Dissociative Disorders"", ""Middle Aged"", ""Male""]",e70713,42538749,pmc-id: PMC13428172;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42538749/,Cognitive Motor Dissociation in Disorders of Consciousness: An Individual Participant Data Meta-Analysis,33,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"To evaluate randomized adult evidence on adjunctive immunoglobulin M (IgM)-enriched immunoglobulin for sepsis and septic shock, with emphasis on short-term mortality, endpoint heterogeneity, statistical robustness, and harms reporting. MEDLINE, PubMed, Embase, CENTRAL, and Web of Science were searched from inception to September 2025. Reference lists of eligible articles and relevant reviews were screened, forward citation searching was performed, and study registers were checked for additional records. Randomized controlled trials enrolling adults with sepsis, severe sepsis, or septic shock were eligible when they evaluated an IgM-enriched immunoglobulin preparation in addition to standard care and reported extractable mortality or clinically relevant outcomes. The protocol-concordant core synthesis included English-language adult Pentaglobin trials with extractable short-term mortality data. Two post hoc extensions were labeled explicitly: a language-inclusive Pentaglobin sensitivity analysis and an exploratory formulation-class analysis incorporating the phase II Concentrated IgM for Application (CIGMA) trimodulin trial. Two reviewers independently screened records, assessed full texts, extracted study characteristics, endpoint timing, mortality events, and reported adverse events, and resolved disagreements by discussion or third-reviewer adjudication. Risk of bias was assessed with Cochrane Risk of Bias 2 tool for randomized trials, and certainty was judged with the Grading of Recommendations Assessment, Development, and Evaluation principles. Six English-language randomized Pentaglobin trials with extractable short-term mortality data (411 participants) contributed to the protocol-concordant core synthesis. The primary pooled estimate was directionally favorable but statistically inconclusive (odds ratio [OR], 0.65; 95% CI, 0.39-1.07; I2 = 9%). Restriction to exact 28-day mortality also remained inconclusive (OR, 0.84; 95% CI, 0.50-1.43; I2 = 0%). An alternative risk-ratio model was similarly nonsignificant (risk ratio, 0.76; 95% CI, 0.55-1.06; I2 = 0%). Statistically significant estimates arose only in exploratory post hoc analyses: the language-inclusive Pentaglobin sensitivity analysis (OR, 0.57; 95% CI, 0.34-0.95; I2 = 16%) and the exploratory formulation-class model including CIGMA (OR, 0.64; 95% CI, 0.43-0.94; I2 = 5%). Safety reporting was incomplete in most Pentaglobin reports. Current randomized adult evidence does not justify routine use of IgM-enriched immunoglobulin in unselected sepsis or septic shock. Direct Pentaglobin evidence remains statistically inconclusive, whereas statistically significant estimates appear only after exploratory expansion to historical or indirect formulation-level evidence. Efficacy remains unproven, but the recurrent direction of effect supports a modern, adequately powered, phenotype-guided trial with standardized day-28 mortality and rigorous safety assessment.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis""]","[""Sewify K"", ""Elmessery R"", ""Alzuwayed O"", ""Gomaa W"", ""Alshaer A"", ""Almutairi A"", ""Abdelshafey E"", ""Girardis M""]",10.1097/CCE.0000000000001451,Sewify K,Critical care explorations,2639-8028,8,Crit Care Explor,eng,Girardis M,"[""Humans"", ""Immunoglobulin M"", ""Randomized Controlled Trials as Topic"", ""Shock, Septic"", ""Sepsis"", ""Adult""]",e1451,42538732,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42538732/,IgM-Enriched Immunoglobulin As Adjunctive Therapy in Adult Sepsis and Septic Shock: A Systematic Review and Meta-Analysis of Randomized Controlled Trials,8,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Current guidelines recognize daily recombinant human growth hormone (rhGH) as standard care and long-acting growth hormone (LAGH) as an alternative for paediatric growth hormone deficiency (CHD). In this network meta-analysis (NMA), we updated the evidence to evaluate comparative efficacy and safety of multiple dosing nodes of LAGH versus daily somatropin. Major databases, including PubMed, Embase, Cochrane Central, Scopus, Web of Science, and http://ClinicalTrials.Gov, were searched through April 2026 for randomized controlled trials (RCTs)in children with CHD. Outcomes included height velocity (HV), height SDS, and adverse events. Direct and indirect evidence was synthesized using a frequentist random-effects NMA (OSF: https://doi.org/10.17605/osf.io/nugpe). Eighteen RCTs (n = 3137) were analysed. In the primary random-effects model for HV, weekly YPEG-rhGH 0.1 mg/kg/week showed a significantly higher velocity compared to daily Somatropin (SMD: 5.02), whereas Somatrogon 0.25/0.48/0.66 mg/kg/week and Somapacitan 0.04 mg/kg/week showed lower HV. No significant differences were observed across treatments for height SDS. For IGF-1 SDS, Lonapegsomatropin 0.24 mg/kg/week significantly increased levels (SMD: 0.74 [0.36-1.12]), while Somatrogon and Somapacitan 0.04 mg/kg/week demonstrated reductions. Safety profiles showed that Somatrogon significantly increased the risk of localized injection site erythema (RR: 10.55) and pain. However, overall discontinuation rates did not differ significantly between LAGH formulations and daily therapy across the network. Once-weekly LAGH provides an effective frontline alternative to daily acting growth hormone, without compromising overall linear growth or safety, while displaying no differences in overall treatment discontinuation. Selection should be based on the patients' clinical profiles, specifically considering higher localized reactions with Somatrogon. Clinicians should adhere to formulation-specific sampling windows (2-5 days post dose for Lonapegsomatropin; 96 h for Somatrogon) to accurately monitor steady-state IGF-1 levels.","[""Journal Article"", ""Network Meta-Analysis"", ""Review""]","[""Abadi A"", ""Ghanem U"", ""Ghanem H"", ""Sawafta AJ"", ""Abulehia A"", ""Ataya M"", ""Nairat R"", ""Sammour AM"", ""Ayesh H""]",10.1002/edm2.70301,Abadi A,"Endocrinology, diabetes & metabolism",2398-9238,5,Endocrinol Diabetes Metab,eng,Ayesh H,"[""Humans"", ""Human Growth Hormone"", ""Child"", ""Growth Disorders"", ""Randomized Controlled Trials as Topic"", ""Recombinant Proteins"", ""Body Height"", ""Delayed-Action Preparations"", ""Drug Administration Schedule"", ""Treatment Outcome""]",e70301,42538635,pmc-id: PMC13428039;,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42538635/,Long-Acting Growth Hormone Versus Daily Growth Hormone for Growth Hormone Deficiency Patients: A Network Meta-Analysis of Clinical Trials,9,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"<sec><title>BACKGROUND</title>Adherence to TB treatment is crucial for successful outcomes. While facility-based directly observed therapy (FB-DOT) is a common strategy, recognition of its limitations has spurred the development of flexible approaches. We have compared the effectiveness of alternative adherence-enhancing strategies with FB-DOT.</sec><sec><title>METHODS</title>We searched three databases and four registries from June 2013 to May 2025. We included comparative studies evaluating interventions designed to improve adherence to TB treatment in people aged 15 years or older, excluding adherence to multiple therapies. Meta-analyses were conducted for treatment success, treatment completion, cure rate, and loss to follow-up.</sec><sec><title>RESULTS</title>Twenty-five studies involving 19,103 participants were included. Self-administered treatment and reminder-based interventions achieved treatment success comparable to FB-DOT. Community-based DOT showed similar cure and completion rates but was effective at reducing loss to follow-up (71% reduction). Video-supported treatment and digital adherence technologies demonstrated neutral effects across treatment outcomes. Multicomponent strategies showed heterogeneous results.</sec><sec><title>CONCLUSION</title>Alternative adherence strategies can offer improvements over FB-DOT in specific contexts. However, their variable effectiveness limits universal implementation. Adherence support, community engagement, and social determinants should guide programmatic design and implementation.</sec>.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Comparative Study""]","[""Ramos JP"", ""Vieira M"", ""Araújo M"", ""Ferreira LL"", ""Barbosa P"", ""Aguiar A"", ""Duarte R""]",10.5588/ijtld.25.0604,Ramos JP,The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease,1027-3719,8,Int J Tuberc Lung Dis,eng,Duarte R,"[""Humans"", ""Directly Observed Therapy"", ""Antitubercular Agents"", ""Tuberculosis"", ""Adherence Interventions"", ""Reminder Systems"", ""Treatment Outcome"", ""Medication Adherence""]",350-357,42538630,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538630/,Comparing adherence strategies and facility DOT in TB care: a systematic review with meta-analysis,30,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Polycystic ovary syndrome (PCOS) negatively impacts women's metabolic health, reproductive hormones, and psychological well-being. The aim of this study was to systematically evaluate the efficacy of mindfulness-based interventions (MBIs), such as yoga and mindfulness meditation, on anthropometric indices, metabolic profiles, reproductive hormones, and quality of life in women with PCOS. A systematic review and meta-analysis was conducted with 10 randomized controlled trials (RCTs) involving 356 participants, selected from databases including PubMed and Cochrane Library up to January 2025. Data were synthesized using Review Manager 5.3 to calculate mean differences (MDs) and standardized mean differences (SMDs). Women in the MBI groups showed significant reductions in BMI, body weight, abdominal circumference, and preliminary improvements in insulin resistance (HOMA-IR; based on two studies), alongside improvements in total testosterone levels and clinical hirsutism. Although generic depression and anxiety scores did not show significant differences, disease-specific quality of life improved significantly. MBIs show potential as metabolic and endocrine modulators and may offer benefits in insulin sensitivity, weight management, and hyperandrogenism beyond mere stress reduction for women with PCOS.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Review""]","[""Li D"", ""Zheng J"", ""Wang G""]",10.1111/aphw.70195,Li D,Applied psychology. Health and well-being,1758-0846,4,Appl Psychol Health Well Being,eng,Wang G,"[""Humans"", ""Female"", ""Polycystic Ovary Syndrome"", ""Mindfulness"", ""Hyperandrogenism"", ""Randomized Controlled Trials as Topic"", ""Psychological Distress"", ""Yoga"", ""Quality of Life"", ""Insulin Resistance""]",e70195,42538604,pmc-id: PMC13428058;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42538604/,"Efficacy of mindfulness-based interventions on psychological distress, hyperandrogenism, and metabolic profile in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials",18,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"This study systematically evaluates the impact of the initiation time of postoperative chemotherapy on overall survival (OS) in patients with colorectal cancer, providing evidence to guide clinical decisions on chemotherapy timing. Following PRISMA and MOOSE guidelines, PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched up to February 2025. Cohort studies comparing early versus delayed postoperative chemotherapy were included. Two researchers independently performed literature screening, data extraction, and quality assessment. Review Manager 5.3 was used, with hazard ratios (HRs) and 95% confidence intervals (CIs) as effect measures. Random- or fixed-effects models were applied based on heterogeneity, and subgroup and sensitivity analyses were conducted. Eleven studies involving 72,873 patients were included. Pooled results showed that delayed chemotherapy significantly increased the risk of death (HR = 1.32, 95% CI: 1.20-1.45, P < 0.00001). Heterogeneity was high (I² = 88%), and sensitivity analyses confirmed the robustness of the findings. Subgroup analysis, using an 8-week cutoff, revealed that patients who initiated chemotherapy within ≤ 8 weeks had significantly better survival than those who started > 8 weeks (HR = 1.47, 95% CI: 1.14-1.91, P = 0.003). Delayed postoperative chemotherapy markedly increases mortality risk. Initiating adjuvant chemotherapy within 8 weeks after surgery is recommended to achieve optimal survival benefits.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Review""]","[""Wang C"", ""Liu K"", ""Han Y"", ""Xue S""]",10.1007/s12029-026-01555-2,Wang C,Journal of gastrointestinal cancer,1941-6636,1,J Gastrointest Cancer,eng,Xue S,"[""Humans"", ""Colorectal Neoplasms"", ""Treatment Delay"", ""Chemotherapy, Adjuvant"", ""Survival Rate"", ""Colorectal Surgical Procedures"", ""Antineoplastic Combined Chemotherapy Protocols"", ""Time Factors""]",,42538503,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538503/,The Impact of Early Versus Delayed Chemotherapy on Survival in Patients with Colorectal Cancer after Surgery: A Systematic Review and Meta-Analysis,57,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Black individuals have a lower incidence of atrial fibrillation (AF) than White individuals, despite a higher burden of traditional risk factors. Prior studies have suggested that European genetic ancestry may contribute to this paradox, but findings have been inconsistent. We examined the association between European genetic ancestry and incident AF among 6920 UK Biobank (UKB) participants who self-identified as Black and were free of AF at baseline. European ancestry proportions were estimated by comparing participants to HapMap populations and were analysed both continuously and categorically using Cox proportional hazards models. Non-linear associations were evaluated using flexible spline curves. We then conducted a meta-analysis combining these results with those from the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study and the Women's Health Initiative. During a median follow-up of 13.7 years, 205 (3%) participants developed incident AF. Each 10% increase in European ancestry was non-significantly associated with increased AF risk (HR 1.07 (95% CI 0.95 to 1.20)), and individuals in the highest European ancestry category had a higher AF incidence rate compared with all other categories. Random-effects meta-analysis of all four cohorts yielded a pooled relative risk (RR) of 1.09 (95% CI 0.99 to 1.21), with substantial heterogeneity largely driven by the Women's Health Initiative (WHI) study. Excluding WHI resulted in a pooled estimate (RR 1.14 (95% CI 1.05 to 1.23)) without heterogeneity. In UKB, European ancestry proportion was not significantly linked to incident AF, and pooled cross-cohort results were heterogeneous. Excluding WHI in sensitivity analyses produced a modest positive pooled association with no heterogeneity.","[""Journal Article"", ""Meta-Analysis""]","[""Liu C"", ""Sun YV"", ""Li L"", ""Collin LJ"", ""Shah AJ"", ""Alonso A""]",10.1136/openhrt-2026-004206,Liu C,Open heart,2053-3624,2,Open Heart,eng,Alonso A,"[""Humans"", ""Atrial Fibrillation"", ""Female"", ""United Kingdom"", ""Incidence"", ""Middle Aged"", ""Risk Factors"", ""Risk Assessment"", ""UK Biobank"", ""Male"", ""Aged"", ""Genetic Predisposition to Disease"", ""Black People"", ""White People"", ""Biological Specimen Banks"", ""African People""]",,42538060,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538060/,Genetic ancestry and risk of atrial fibrillation in individuals of Black ethnicity in the UK Biobank,13,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"BackgroundHIV-associated lipodystrophy, a complication of combined antiretroviral therapy (CART), causes significant physical and psychological distress in people living with HIV (PLWH), compromising treatment adherence. Tesamorelin, a growth hormone-releasing hormone (GHRH) analogue, has emerged as a therapeutic option.ObjectiveTo systematically evaluate the efficacy and safety of tesamorelin in HIV-infected individuals with lipodystrophy receiving CART, incorporating GRADE assessment.MethodsWe searched PubMed, https://ClinicalTrials.gov, and Scopus from inception to February 9, 2026, for randomized controlled trials evaluating tesamorelin in HIV-associated lipodystrophy. Mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CI) were calculated using random-effects models with heterogeneity assessed by I2.ResultsFour RCTs (909 patients) were included. Tesamorelin 2mg significantly reduced visceral adipose tissue (MD= -21.47, 95%CI[-34.73,-8.22],I2=74%,p=0.002), waist circumference (MD-1.61cm,95% CI[-2.28,-0.95],I2=0%,p<0.00001), trunk fat (MD-1.20kg, 95%CI[-1.47,-0.93],I2=0%,p<0.00001), and increased lean body mass (MD1.42kg,95% CI[1.13,1.71],I2=0%,p<0.00001). Modest lipid improvements occurred in total cholesterol (MD-0.16mmol/L,95%CI[-0.27,-0.06],I2=0%,p=0.003). Growth hormone-related adverse effects and higher discontinuation rates (RR2.25,95%CI[0.98,5.17],p=0.06) were observed.ConclusionsTesamorelin demonstrates efficacy in reducing visceral adiposity in PLWH with lipodystrophy on CART. However, limited data on long-term safety, optimal dosing strategies, and durability of treatment effects warrant caution. Future research should evaluate extended treatment duration, dose-response relationships, and patient-reported outcomes to establish comprehensive clinical utility.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Review""]","[""Ditta AM"", ""Naeem RM"", ""Sami MM"", ""Abdul Rafey M"", ""Ali H"", ""Amjad MW"", ""Jahangir F"", ""Rizvi KA"", ""Mohammad F"", ""Abu Dawood H"", ""Suleman M"", ""Saddique MN""]",10.1177/23259582261475549,Ditta AM,Journal of the International Association of Providers of AIDS Care,2325-9574,,J Int Assoc Provid AIDS Care,eng,Saddique MN,"[""Humans"", ""Growth Hormone-Releasing Hormone"", ""HIV-Associated Lipodystrophy Syndrome"", ""HIV Infections"", ""Randomized Controlled Trials as Topic""]",23259582261475549,42538058,pmc-id: PMC13428105;,2026 Jan-Dec,2026,https://pubmed.ncbi.nlm.nih.gov/42538058/,Efficacy and Safety of Tesamorelin in People Living With HIV (PLWH) With Lipodystrophy: A Systematic Review and Meta-Analysis,25,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Obesity and diabetes are risk factors for developing osteoarthritis and associated with worse outcomes following total hip (THA) and total knee arthroplasty (TKA). Glucagon-like peptide-1 receptor agonists (GLP-1as) improve glycaemic control and promote weight loss. The aim of this study was to assess the impact of GLP-1a treatment on 90-day surgical complications following THA and TKA. A systematic review was undertaken according to PRISMA guidelines. Studies were included if they reported at least one outcome of interest following primary THA or TKA. In all the studies which were included, a GLP-1a was prescribed for the management of type 2 diabetes mellitus or for weight loss in obese patients. The primary outcome was the 90-day surgical complication rate in the combined THA and TKA cohort. The 90-day surgical complications were defined as: periprosthetic joint infection (PJI), wound dehiscence, periprosthetic fracture (PPF), haematoma, nerve injury, or surgical site infection (SSI). Secondary outcomes included 90-day medical complications and readmission rates, all-cause revision, healthcare costs, and length of stay. A total of 78 studies were reviewed, and ten matched cohort studies with a total of 96,356 patients (30,350 THAs and 66,606 TKAs) were included. The mean age of the patients was 61.9 years; 60.1% female (n = 57,939). Two studies had a serious risk of overall bias and eight had a moderate risk. The confidence of evidence according to the GRADE assessment was very low for all but one outcome measure (healthcare cost: moderate). The rate of 90-day surgical complications was lower in the GLP-1a cohort (pooled risk ratio (RR) 0.73). The use of a GLP-1a lowered the 90-day medical complications and readmission rates (RR 0.78 and RR 0.79 (I2 = 61.6%), respectively). At two years, the revision rate ranged from 1.7% to 3.3% for the GLP-1a cohort and 1.7% to 4.5% for the controls. Sub-group analysis showed a stronger association in the THA group, in which the use of a GLP-1a was associated with significantly lower rates of 90-day surgical complications (RR 0.63), 90-day medical complications (RR 0.55), and 90-day readmissions (RR 0.82). In contrast, the use of a GLP-1a in the TKA group was only sigificantly associated with a lower 90-day readmission rate (RR 0.77). GLP-1a treatment before THA and TKA potentially reduces the 90-day surgical and medical complications and 90-day readmission rates in high-risk diabetic and obese patients. The use of a GLP-1a may also be associated with substantial cost savings.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis""]","[""Rudran B"", ""Little CDJ"", ""Palmer AJR"", ""Judge A"", ""Carli A"", ""Price AJ"", ""Alvand A""]",10.1302/0301-620X.108B8.BJJ-2025-1486.R2,Rudran B,The bone & joint journal,2049-4394,8,Bone Joint J,eng,Alvand A,"[""Humans"", ""Arthroplasty, Replacement, Knee"", ""Glucagon-Like Peptide-1 Receptor Agonists"", ""Postoperative Complications"", ""Arthroplasty, Replacement, Hip"", ""Diabetes Mellitus, Type 2"", ""Treatment Outcome"", ""Obesity"", ""Reoperation"", ""Patient Readmission""]",986-994,42538001,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42538001/,Glucagon-like peptide-1 receptor agonists are associated with improved 90-day outcomes after total hip and knee arthroplasty : a systematic review and meta-analysis,108-B,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Sleep apnea (SA) is a serious sleep disorder, and its diagnostic gold standard, polysomnography, is costly and time-consuming. Electroencephalogram (EEG) signals, due to their direct correlation with neural activity and ease of extraction, represent a promising tool. Despite increasing research on machine learning (ML) and deep learning for EEG-based SA detection, model performance has not been consistently evaluated. This systematic review evaluated the accuracy of ML in detecting SA from EEG data and provided an evidence base for further clinical application and future research. Following the PRISMA-DTA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy) and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 expanded checklists, we systematically searched PubMed, Embase, Web of Science, Cochrane Library (CENTRAL), Scopus, IEEE Xplore, and ClinicalTrials.gov databases from inception to April 2026. Studies evaluating the value of ML algorithms for detecting SA based only on EEG data were included. The Quality Assessment of Diagnostic Accuracy Studies-2 and Prediction Model Risk of Bias Assessment Tool for Artificial Intelligence tools were used to assess the risk of bias in each study. Statistical analysis was performed using the mada and metafor packages in R (version 4.6.0; R Foundation for Statistical Computing) and the Meta-DiSc (version 1.4; Hospital Ramón y Cajal) software. We used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to evaluate the certainty of evidence. A total of 27 retrospective studies were included. Segment-level analyses showed high diagnostic performance, with a pooled sensitivity of 0.90 (95% CI 0.85-0.94; 95% prediction interval 0.43-0.99) and specificity of 0.92 (95% CI 0.87-0.95; 95% prediction interval 0.46-0.99). The pooled area under the summary receiver operating characteristic curve was 0.95 (95% CI 0.92-0.99). Meta-regression identified EEG channel configuration, region, and validation strategy as significant sources of heterogeneity (P=.004, P=.003, and P=.046, respectively). Multichannel EEG, deep learning approaches, and hold-out validation strategies generally demonstrated better diagnostic performance. Only 2 studies evaluated patient-level diagnostic performance, which was summarized qualitatively. To our knowledge, this is the first systematic review and meta-analysis specifically focused on the diagnostic accuracy of EEG-based ML models in the detection of SA. This meta-analysis indicates that ML models based on EEG demonstrate good diagnostic accuracy in detecting SA at the segment level and show promise as tools for SA screening and clinical decision support. However, most current studies are retrospective segment-level analyses, which may overestimate the practical value of this technology in real-world clinical settings. To reliably integrate EEG-based ML models into clinical diagnostic workflows, further prospective studies incorporating full-night monitoring and patient-level validation are needed.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Review""]","[""Li X"", ""Wang L"", ""Tang T"", ""Chen Y"", ""Yang L"", ""Cai H"", ""Wang C"", ""Zhang S"", ""Ding N"", ""Liu K""]",10.2196/93378,Li X,Journal of medical Internet research,1439-4456,,J Med Internet Res,eng,Liu K,"[""Humans"", ""Electroencephalography"", ""Machine Learning"", ""Sleep Apnea Syndromes"", ""Algorithms"", ""Polysomnography""]",e93378,42537009,pmc-id: PMC13427076;,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42537009/,Accuracy of Machine Learning Algorithms Based on Electroencephalogram in Sleep Apnea Detection: Systematic Review and Meta-Analysis,28,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Exergames, which combine physical exercise with interactive gameplay, are increasingly being incorporated into fall prevention programs for older adults. Gamified elements, such as real-time feedback and progress tracking, may enhance motivation, engagement, and adherence. Although several systematic reviews have examined the effects of exergaming on balance and physical function, fewer have focused specifically on clinically meaningful outcomes, such as falls and injurious falls, or on indicators that may influence real-world adoption of exergames. This study aimed to evaluate the effectiveness of exergaming interventions for preventing falls and injurious falls in people aged ≥60 years and to synthesize evidence on implementation-related outcomes, including adherence, acceptability, concerns about falling, quality of life, adverse events, and cost-effectiveness. MEDLINE, Embase, CINAHL Plus, PsycINFO, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to February 2025 for randomized controlled trials evaluating exergaming interventions in older adult populations across all settings. Outcomes included fall rate, number of fallers and injurious falls, and implementation-related secondary outcomes. Risk of bias was assessed using RoB 2.0, and certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Data were synthesized narratively and, where appropriate, pooled using meta-analysis. Nine studies (N=1385) met the inclusion criteria. Comparator-specific analyses suggested that exergaming may reduce fall rates compared with active intervention comparators, although the magnitude and certainty of effect varied, and substantial heterogeneity was present across analyses. Moderate-certainty evidence also suggested that exergames reduced the number of older adults experiencing one or more falls at 12-month follow-up compared with usual care (risk ratio 0.75, 95% CI 0.61-0.92). Evidence for injurious falls, quality of life, concerns about falling, adherence, acceptability, and cost-effectiveness was limited or inconsistent. When pooled across all control groups, exergaming interventions were associated with a lower overall fall rate than comparator interventions (incidence rate ratio 0.53, 95% CI 0.41-0.68), although substantial heterogeneity was present (I²=76%). Low- to moderate-certainty evidence suggests that exergames may reduce fall rates, particularly in comparisons with active intervention control groups, and may reduce the number of fallers compared with usual care. These findings indicate that exergaming may offer a useful adjunct to established fall prevention strategies for older adults, particularly where sustained engagement with conventional exercise is challenging. However, substantial heterogeneity, modest sample sizes, and limited long-term follow-up reduce confidence in these estimates, and more rigorous, large-scale trials are needed before routine implementation can be recommended. This review extends previous exergaming syntheses by focusing on clinically meaningful outcomes, including falls and injurious falls, while also considering implementation-related factors relevant to real-world uptake.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Review""]","[""Eost-Telling C"", ""McGarrigle L"", ""Shi C"", ""Money A"", ""Yang Y"", ""Lazo Green K"", ""Ahmed S"", ""Christie R"", ""Aminu A"", ""Delbaere K"", ""de Bruin ED"", ""Stanmore E"", ""Todd C""]",10.2196/89807,Eost-Telling C,JMIR aging,2561-7605,,JMIR Aging,eng,Todd C,"[""Humans"", ""Accidental Falls"", ""Randomized Controlled Trials as Topic"", ""Video Games"", ""Aged"", ""Exercise Therapy"", ""Female"", ""Exercise"", ""Quality of Life"", ""Middle Aged"", ""Aged, 80 and over""]",e89807,42536979,pmc-id: PMC13427072;,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536979/,Exergaming Interventions for Preventing Falls and Injurious Falls in Older People: Systematic Review and Meta-Analysis of Randomized Controlled Trials,9,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Recent advances in large language models (LLMs) such as GPT-3/4 have spurred the development of artificial intelligence (AI) chatbots and advisory tools in medicine. These systems are posited to assist or augment physician-patient communication, potentially improving empathy, clarity, and responsiveness. However, their actual impact on communication outcomes remains uncertain. This study aimed to systematically review and meta-analyze peer-reviewed studies (2020-2025) evaluating how LLM-based interventions affect physician-patient communication, including empathy, clarity, trust, and patient understanding. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines, we searched PubMed/MEDLINE, Embase, Scopus, and Web of Science for studies published from 2020 to 2025 examining LLM or chatbot applications in clinical communication contexts. Eligible designs included randomized, observational, cross-sectional, and qualitative studies. Two reviewers (WHP and SR) independently screened titles or abstracts, assessed full texts, and extracted data on study design, population, LLM type, communication measures, and outcomes. We conducted a qualitative synthesis and random-effects meta-analysis, reporting pooled standardized mean differences or odds ratios with 95% CIs. From 312 records, 10 studies were included, all quantitative and predominantly cross-sectional. Populations ranged from patients with chronic conditions to health care professionals and laypersons. Outcomes assessed included empathy (8 studies), clarity or information quality (6 studies), satisfaction or usefulness (4 studies), and trust perceptions (2 studies). In 6 direct comparisons of AI- versus physician-generated responses, LLMs were rated significantly higher in empathy in 5 studies. One large study found that chatbot replies were judged empathetic in 45.1% of cases versus 4.6% for physician replies (odds ratio approximately 9.8, P<.001). Similarly, ChatGPT-4 answers scored higher in empathy on a 5-point scale than human-written responses (mean 4.18 vs 2.70, P<.001). One neurology study showed higher empathy scores (Consultation and Relational Empathy Scale +1.38, P<.01) for ChatGPT answers. Only 1 study found no significant empathy difference. LLM content was also longer and more information-rich, improving patient-perceived clarity and understanding. On the other hand, GPT-4 simplified pathology reports, increasing patient comprehension scores (7.98 vs 5.23/10, P<.001) and reducing consultation time by 70%. However, AI replies were sometimes less concise or less readable for low-literacy patients. In pooled analyses (k=4 studies; total evaluations N=2604), LLM assistance showed a large positive effect on empathy (standardized mean difference 1.02, 95% CI 0.44-1.60; random-effects model). Patient satisfaction results were mixed. No study directly assessed long-term trust. Current evidence suggests that LLM-based chatbots can enhance physician-patient communication by producing more empathetic, detailed, and understandable responses. These improvements may positively influence patient experience and engagement. However, LLMs may also generate overly lengthy or occasionally inaccurate advice, emphasizing the need for physician oversight. While meta-analytic findings are promising, robust randomized controlled trials, real-world and longitudinal studies are needed to confirm benefits, assess trust outcomes, and define optimal clinical integration strategies.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Review""]","[""Richter S"", ""Buszello CH"", ""Prem M"", ""Willkommen S"", ""Hasani E"", ""Uckermann O"", ""Juratli TA"", ""Eyüpoglu IY"", ""Polanski WH""]",10.2196/77307,Richter S,Journal of medical Internet research,1439-4456,,J Med Internet Res,eng,Polanski WH,"[""Physician-Patient Relations"", ""Humans"", ""Large Language Models"", ""Artificial Intelligence"", ""Communication"", ""Empathy"", ""Generative Artificial Intelligence""]",e77307,42536971,pmc-id: PMC13427064;,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536971/,Impact of Large Language Model-Based AI Tools on Physician-Patient Communication: Systematic Review and Meta-Analysis,28,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Anti-Spike monoclonal antibodies (mAbs) progressively lost efficacy during the COVID-19 pandemic due to the emergence and predominance of resistant SARS-CoV-2 variants. By contrast, high-titre COVID-19 convalescent plasma (CCP) collected from vaccinated donors recently recovered from infection provides a polyclonal source of antibodies that remains effective in clearing SARS-CoV-2 in immunosuppressed patients, unable to mount an adequate immune response against the virus. We conducted a systematic review and individual participant data meta-analysis to examine the effect of CCP in immunocompromised patients persistently positive for SARS-CoV-2 viraemia following mAb therapy, and to evaluate possible biological factors associated with a favourable outcome. Electronic databases were searched for studies published from January 2020 to January 2026. All studies including eligible cases were considered in the systematic review. Unpublished cases were also collected from investigators of the selected studies. The protocol was registered at PROSPERO (CRD420251142891). Forty-seven cases (30 cases from 12 published studies and 17 unpublished cases) were included. In 33 out of 47 patients (70.2%) with a mAb-resistant infection, SARS-CoV-2 clearance occurred following CCP transfusion, with a mean of 2.7 CCP units administered. In logistic regression, total CCP volume transfused was positively associated with SARS-CoV-2 clearance. In conclusion, CCP transfusion was associated with SARS-CoV-2 clearance in persistently positive immunocompromised patients following failure of anti-Spike mAb therapy.","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis"", ""Review""]","[""Focosi D"", ""Aiello TF"", ""Casadevall A"", ""Cruciani M"", ""D'Abramo A"", ""De Marco P"", ""Gachoud D"", ""Garcia-Vidal C"", ""Glingani C"", ""Hueso T"", ""Joyner MJ"", ""Lacombe K"", ""Mengoli C"", ""Nicastri E"", ""Richier Q"", ""Rufer N"", ""Senefeld JW"", ""Shoham S"", ""Sullivan DJ"", ""Tomisti L"", ""Weinbergerova B"", ""Zani M"", ""Zaremba S"", ""Franchini M""]",10.1002/rmv.70185,Focosi D,Reviews in medical virology,1052-9276,5,Rev Med Virol,eng,Franchini M,"[""Humans"", ""Immunocompromised Host"", ""SARS-CoV-2"", ""Antibodies, Monoclonal"", ""COVID-19"", ""Immunization, Passive"", ""COVID-19 Serotherapy"", ""Antibodies, Viral"", ""Spike Glycoprotein, Coronavirus""]",e70185,42536824,pmc-id: PMC13427266;,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42536824/,Convalescent Plasma Restores Viral Clearance After Anti-Spike Monoclonal Antibody Failure in Immunocompromised COVID-19 Patients: A Systematic Review and Meta-Analysis of Individual Patient Data,36,PwP5msZ3YmpghdXLP,1n3XG1xVHbDcRmL5m
"Introduction/ObjectivesCancer nutrition education supports cancer prevention and survivorship, yet African American/Black (AA/B) women continue to experience nutrition-related inequities across the cancer continuum. This review examined how qualitative studies describe these inequities and assign responsibility within the literature.MethodsPubMed and Scopus were searched in December 2024 and updated in January 2026. Eligible studies involved AA/B women in the United States, addressed cancer-related nutrition experiences, used qualitative methods, and examined nutrition-related inequities across the cancer care continuum. SPIDER-informed criteria guided eligibility, data were synthesized using inductive thematic analysis guided by intersectionality, and study quality was appraised using CASP.ResultsFourteen qualitative studies were included. Responsibility for nutrition-related inequities was located within programmatic, institutional, and structural conditions. Five themes were identified: Universal Nutrition Standards, Feasible Nutrition Guidance, Access and Choices, Concordance and Cultural Relevance, and Community-Driven Co-Design. Participants described adapting nutrition guidance to caregiving demands, cultural food practices, survivorship challenges, and access barriers. Race, gender, caregiving, cultural identity, geography, and socioeconomic conditions were reported across studies.ConclusionsThe literature frames inequities in cancer nutrition education as consequences of programmatic, institutional, and structural conditions. Improving cancer nutrition equity for AA/B women may require culturally relevant, feasible, community-informed approaches and stronger attention to nutrition delivery contexts.","[""Journal Article"", ""Systematic Review""]","[""Abdul-Hameed ZL"", ""Rivers BM"", ""Rivers DA""]",10.1177/21501319261475542,Abdul-Hameed ZL,Journal of primary care & community health,2150-1319,,J Prim Care Community Health,eng,Rivers DA,"[""Humans"", ""Black or African American"", ""Female"", ""Health Education"", ""Neoplasms"", ""United States""]",21501319261475542,42544630,,2026 Jan-Dec,2026,https://pubmed.ncbi.nlm.nih.gov/42544630/,Cancer Nutrition Education for Black Women: Policy Responsibility in a Systematic Review,17,PHe8hY6wjllKaWIQU,sSanp9FC1D9A5H9tg
"The Internet of Things (IoT) represents a transformative paradigm in health care service delivery, offering unprecedented potential to enhance quality of care, operational efficiency, and patient outcomes through interconnected devices and real-time data analytics. Despite rapid adoption, implementation depends on patient acceptance as end users. While literature extensively documents technical and institutional perspectives, a comprehensive understanding of patient acceptance factors remains fragmented, with high technology abandonment rates. Systematic synthesis of patient perspectives is critically needed to inform user-centered design, effective implementation strategies, and supportive policy frameworks. This systematic literature review aims to identify and synthesize factors influencing patient acceptance of IoT technology in health care services, barriers hindering adoption, and effective strategies for enhancing acceptance. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines, we systematically searched eight electronic databases (PubMed/MEDLINE, Scopus, IEEE Xplore, Web of Science, ScienceDirect, ACM Digital Library, ProQuest, and Google Scholar) for empirical studies published between January 2016 and December 2024. Inclusion criteria encompassed peer-reviewed empirical research examining patient perspectives on IoT technology in health care services, published in English or Indonesian. From 2537 initially identified papers, 62 studies met inclusion criteria after systematic screening and full-text evaluation. Quality assessment was conducted using the Mixed Methods Appraisal Tool. The 62 included studies represented diverse geographic contexts (Asia, Europe, North America, and the Middle East) and methodological approaches. Quality assessment revealed 45 (73%) studies of good-to-excellent quality. Perceived usefulness emerged as the strongest acceptance facilitator, identified in 55 of 62 (89%) studies, followed by perceived ease of use in 47 (76%) studies, and trust and security in 42 (68%) studies. Cost-effectiveness was identified in 32 (52%) studies as an important consideration. Primary barriers included data security concerns in 26 (42%) studies, privacy issues in 24 (39%) studies, lack of digital literacy in 22 (36%) studies, and resistance to change in 20 (32%) studies. Interoperability issues and high costs were identified in 19 (31%) studies and 18 (29%) studies, respectively. User-centered design was the most frequently recommended enhancement strategy in 20 (32%) studies, followed by user-friendly interface development in 19 (31%) studies, digital literacy programs in 18 (29%) studies, and health care professional involvement in 15 (24%) studies. Digital literacy functioned as a significant moderator, and trust served as both direct predictor and mediator. Patient acceptance of IoT in health care represents a complex, multidimensional phenomenon requiring holistic approaches that integrate user-centered technology design, comprehensive digital literacy programs, trust-building mechanisms, and supportive policy frameworks. Successful implementation necessitates multilevel strategies addressing individual, organizational, and system factors simultaneously. With evidence-based, patient-centered approaches, IoT technology holds substantial potential to transform health care delivery into more proactive, personalized, and accessible services.","[""Journal Article"", ""Systematic Review"", ""Review""]","[""Arifin Z"", ""Handayani PW""]",10.2196/81260,Arifin Z,JMIR mHealth and uHealth,2291-5222,,JMIR Mhealth Uhealth,eng,Handayani PW,"[""Humans"", ""Internet of Things"", ""Patient Acceptance of Health Care"", ""Digital Health""]",e81260,42544626,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42544626/,Patient Acceptance and Barriers to IoT Usage in Health Care: Systematic Literature Review,14,PHe8hY6wjllKaWIQU,sSanp9FC1D9A5H9tg
"The efficacy of hyaluronic acid (HA) in the treatment of interdental papilla (IDP) deficiency is well documented. This systematic review sought to evaluate clinical studies reporting efficacy, safety, and health-related quality of life (HRQoL) data for HA used in the treatment of IDP deficiency. This review was conducted and reported in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. A comprehensive search of electronic databases was conducted for published randomized controlled trials (RCTs) from their inception until March 21, 2024. A total of 9 studies met the inclusion criteria. The sample sizes in the included RCTs ranged from 10 to 31 participants, with the mean patient age between 26.7 and 46.1 years, predominantly females. Of the 9 eligible studies, 6 assessed the use of HA alone, while 3 investigated the effects of HA in combination with other therapies. The most common outcome measures assessed black triangle dimensions (i.e., area, height or width) followed by probing depth (PD). Based on the limited published studies, this review suggests that HA treatment (whether alone or in combination) may offer therapeutic benefits for patients with IDP defects. However, none of the included studies assessed the safety of HA and its effect on HRQoL. There is a need for further research on the long-term efficacy and safety of HA treatment, and its influence on HRQoL.","[""Journal Article"", ""Systematic Review"", ""Review""]","[""Alotaibi DH""]",10.17219/dmp/193767,Alotaibi DH,Dental and medical problems,1644-387X,3,Dent Med Probl,eng,Alotaibi DH,"[""Hyaluronic Acid"", ""Humans"", ""Quality of Life"", ""Randomized Controlled Trials as Topic"", ""Treatment Outcome"", ""Female""]",793-804,42544608,,2026 May-Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42544608/,"Efficacy, safety, and health-related quality of life data of hyaluronic acid for the treatment of interdental papilla deficiency: A systematic review of randomized controlled trials",63,PHe8hY6wjllKaWIQU,sSanp9FC1D9A5H9tg
"CART (combined aerobic and resistance training) has shown important results in exercise-based cardiovascular rehabilitation. However, there are little data concerning the effects of CART on the exercise capacity, muscle strength, health-related quality of life (HRQoL), and mortality of coronary heart disease (CHD) patients. Therefore, the aim of this study was to analyze the published randomized controlled trials (RCTs) that investigated the effects of CART on exercise capacity [peak oxygen consumption (peak VO2) and 6-min walking distance (6MWD)], muscle strength [1-repetition maximum (1-RM), peak torque and handgrip strength], HRQoL, and mortality in patients with CHD. We search for references in MEDLINE/PubMed, Scopus, Cochrane Central Register of Controlled Trials, and EMBASE databases to find RCTs that evaluated the effects of CART for CHD. Mean difference (MD), standardized mean difference (SMD), risk ratio (RR), and 95% confidence intervals (CIs) were calculated. CART improved relative peak VO2 of 2.20 ml/kg/min (P < 0.0001), peak torque of 16.69 N.m (P < 0.0001), handgrip strength of 4.68 kgf (P < 0.0001), and HRQoL of 1.00 (P < 0.00001) and reduced mortality (RR = 0.40; P = 0.002) compared to non-exercising usual care. CART improved (relative and absolute) peak VO2 by 0.28 (P < 0.002), 6MWD by 21.98 m (P = 0.004), 1-RM by 0.61 kg (P < 0.0001), peak torque by 4.03 N.m (P = 0.002), and HRQoL by 0.50 (P < 0.0004) compared to aerobic training. CART improved relative peak VO2 by 1.91 ml/kg/min (P < 0.00001) compared to resistance training. CART was efficient in improving peak VO2, peak torque, handgrip strength, HRQoL, and lower mortality events compared to non-exercising usual care in patients with CHD. CART appears superior to aerobic training in improving peak VO2, 6MWD, 1-RM, peak torque, and HRQoL in patients with CHD. Furthermore, CART was more effective than resistance training for peak VO2 in patients with CHD. CART should be considered as a method in the rehabilitation of patients with CHD.","[""Journal Article"", ""Systematic Review""]","[""Gois CO"", ""Guimarães ALA"", ""Conceição LSR"", ""Gomes-Neto M"", ""Carvalho VO""]",10.1186/s40798-026-01080-3,Gois CO,Sports medicine - open,2199-1170,1,Sports Med Open,eng,Carvalho VO,[],,42543470,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42543470/,"Effect of Combined Aerobic and Resistance Training on Exercise Capacity, Muscle Strength, Quality of Life, and Mortality in Patients with Coronary Heart Disease: A Systematic Review with Meta-analysis",12,PHe8hY6wjllKaWIQU,sSanp9FC1D9A5H9tg
"Athletes with diabetes increasingly participate in endurance running, benefiting from physiological adaptations and technological advances like continuous glucose monitoring (CGM) for glycemic control. So far, no comprehensive review summarizing the current knowledge has been performed. To identify the prevalence of long-distance runners with diabetes, their performance, methods used for blood glucose monitoring and glycemic control. PubMed, Medline Ovid, Scopus, SPORTDiscus, Cochrane databases, CINAHL, and Web of Science were systematically searched until April 2024 using key terms related to long-distance running and diabetes. An updated search applying the identical strategy was conducted on May 3rd, 2026, to capture subsequently published literature. This study included original research articles, case reports, and case studies published in English or German in peer-reviewed journals, utilizing both quantitative and qualitative methodologies. Eligibility criteria encompassed runners with a confirmed diagnosis of diabetes mellitus, irrespective of type, who participated in endurance events of at least half-marathon distance, including half-marathons, marathons, ultra-marathons, and other ultra-endurance competitions. Patients with prediabetic state, gestational diabetes, or after pancreatic islet-cell transplantation were excluded. For quality assessment, we used the Joanna Briggs Institute of Analytical Cross-Sectional Studies or the Joanna Briggs Institute of Analytical Case Report critical appraisal tool. A total of 656 studies were identified, with 22 meeting the inclusion criteria, comprising 99 runners with diabetes (99.0% Type 1, 1.0% Type 2 diabetes mellitus). Among them, 50.0% used CGM, 27.2% had an insulin pump, 63.6% administered insulin via multiple daily injections, and the method of insulin application was not specified in 7.0% of runners. The weighted mean HbA1c was 7.4% (95% CI 6.9-8.1). Time-in-range varied by race distance: 40-100% for half-marathoners, 51.6% for marathoners, and 47-73% for ultra-marathoners. No cases of symptomatic hypoglycemia were observed during the races. However, asymptomatic late-onset hypoglycemia (occurring 6-15 h post-exercise) was reported in 27 runners. The most common insulin adjustment strategy before competitive races was a 50-80% reduction of basal insulin. Despite limited research, evidence suggests that with proper preparation and multidisciplinary support, athletes with diabetes can safely participate in endurance events, including ultra-marathons, while maintaining stable glycemic control. PROSPERO-CRD42024539281.","[""Journal Article"", ""Systematic Review""]","[""Braschler L"", ""Thuany M"", ""Züger T"", ""Nikolaidis PT"", ""Weiss K"", ""Rosemann T"", ""Knechtle B""]",10.1186/s40798-026-01084-z,Braschler L,Sports medicine - open,2199-1170,1,Sports Med Open,eng,Knechtle B,[],,42543457,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42543457/,Diabetes Mellitus and Long-Distance Running: A Systematic Review,12,PHe8hY6wjllKaWIQU,sSanp9FC1D9A5H9tg
"Intraventricular meningiomas are rare tumors accounting for a small fraction of intracranial meningiomas and are often associated with significant surgical challenges due to their deep location and rich vascular supply. Pre-operative endovascular embolization has been proposed as an adjunct to reduce intraoperative bleeding and facilitate safer resection; however, its role in intraventricular lesions remains poorly defined. We present a case of a 9.5-year-old boy with a highly vascular intraventricular meningioma who underwent pre-operative endovascular embolization followed by surgical resection. Additionally, a systematic review was conducted in accordance with PRISMA guidelines, searching PubMed and Scopus for studies reporting embolization of intraventricular meningiomas. In the presented case, selective embolization of the posterior choroidal artery using a glue-lipiodol mixture was successfully performed without complications, leading to reduced tumor vascularity and enabling gross total resection with minimal blood loss (< 300 mL). The systematic review identified seven cases from six studies. Embolization was successful in six cases, with varying degrees of devascularization. Gross total resection was achieved in all surgically treated patients. Reported intraoperative blood loss ranged from 150 to 1850 mL. Complications occurred in two of seven cases, including postoperative epidural hematoma. Pre-operative endovascular embolization appears to be a technically feasible adjunct in selected cases of intraventricular meningiomas. However, current evidence is limited to case reports and small case series, precluding definitive conclusions regarding its safety or clinical benefit.","[""Journal Article"", ""Systematic Review"", ""Case Reports"", ""Review""]","[""Abdallah AM"", ""Hulliel AF"", ""Saleh D"", ""Mukahal M"", ""Qassim D"", ""Obeidat M""]",10.1007/s00381-026-07422-6,Abdallah AM,Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery,0256-7040,1,Childs Nerv Syst,eng,Obeidat M,"[""Humans"", ""Meningioma"", ""Male"", ""Embolization, Therapeutic"", ""Meningeal Neoplasms"", ""Child"", ""Cerebral Ventricle Neoplasms"", ""Endovascular Procedures"", ""Preoperative Care""]",,42543443,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42543443/,Successful pre-operative endovascular intraventricular meningioma embolization: a systematic review and pediatric case analysis,42,PHe8hY6wjllKaWIQU,sSanp9FC1D9A5H9tg
"Healthcare systems worldwide face mounting pressure to deliver high-quality care while enhancing efficiency and sustainability. Nurse-led interventions have emerged as promising strategies to optimize care delivery, particularly within value-based health systems. However, a comprehensive understanding of their clinical impact and economic value remains limited. This systematic review conducted following PRISMA guidelines, searched nine international databases to identify and synthesize formally evaluated nurse-led interventions, programs, and strategies. Twenty-eight studies were included, encompassing diverse care settings and patient populations. Most studies reported improvements in clinical outcomes, including reduced hospital readmissions, enhanced quality of life, and improved chronic disease management. Several interventions analyzed effectiveness, particularly those involving advanced nursing roles such as nurse practitioners and case managers. Findings suggest that clinical effectiveness does not necessarily translate into increased professional authority: nurse-led interventions consistently generate value across patient, organizational, and systemic dimensions, yet nursing leadership remains structurally subordinate within healthcare governance. A systematic agenda for rigorous economic evaluation embedded in nursing research programs is urgently needed, alongside structural reforms that redistribute authority-not merely develop competencies-within healthcare organizations.","[""Systematic Review"", ""Journal Article"", ""Review""]","[""Fontanals-Jimenez A"", ""Trapero-Bertran M"", ""Insa-Calderón E""]",10.1111/nin.70146,Fontanals-Jimenez A,Nursing inquiry,1320-7881,4,Nurs Inq,eng,Insa-Calderón E,"[""Humans"", ""Leadership"", ""Nurse's Role""]",e70146,42542967,pmc-id: PMC13429044;,2026 Oct,2026,https://pubmed.ncbi.nlm.nih.gov/42542967/,"Efficacy, Effectiveness, and Efficiency of Nurse-Led Interventions: Insights From a Critical Systematic Review",33,PHe8hY6wjllKaWIQU,sSanp9FC1D9A5H9tg
"Sarcoptic mange is a parasitic contagious disease that can lead to significant declines in wildlife populations. To identify the most used methods for diagnosing mange in free-ranging wildlife species, a systematic review was conducted across multiple databases: Scopus, PubMed, Web of Science, ProQuest Central and CABI. Citation screening was performed using the web-based platform, Covidence. A customized data extraction form, developed by the authors, was used to collect relevant information. This information was later exported and analyzed using Microsoft Excel. The objectives of this systematic review were to identify the most used detection methods for sarcoptic mange in wildlife globally over the past 30 years, classify them into invasive and non-invasive categories and provide an updated overview of related adjunct techniques and the broader scientific literature on mange detection and documentation in free-ranging animals. A total of 228 studies were analyzed and categorized into two groups-non-invasive and invasive methods. Non-invasive methods (visual observation, camera trapping, spotlighting, detector dogs and infrared thermography) do not require restraining of animals. Invasive methods (skin scraping, molecular diagnosis using mite isolation and polymerase chain reaction (PCR), serological diagnosis using Enzyme Linked ImmunoSorbent Assay (ELISA), histological analysis and immunohistochemistry) typically require taking samples from the animals and clinical or laboratory infrastructure. Across all diagnostic methods, visual observation was the most widely used technique, followed by skin scraping as the second most frequently applied method for confirming sarcoptic mange. Non-invasive approaches like spotlighting and camera traps provided valuable population-level insights without direct animal contact, though laboratory methods such as PCR, ELISA, and histological analysis offered greater accuracy at higher costs. We recommend a combined approach, starting with non-invasive methods to assess overall population health before using invasive techniques on selected animals for definitive diagnosis, with advanced technologies expected to enhance long-range detection capabilities in the future.","[""Journal Article"", ""Systematic Review""]","[""Sengupta C"", ""Old JM""]",10.7717/peerj.21609,Sengupta C,PeerJ,2167-8359,,PeerJ,eng,Old JM,"[""Animals"", ""Scabies"", ""Animals, Wild"", ""Sarcoptes scabiei""]",e21609,42542858,pmc-id: PMC13428544;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42542858/,A comprehensive systematic review of sarcoptic mange diagnostic methods in wildlife,14,PHe8hY6wjllKaWIQU,sSanp9FC1D9A5H9tg
"Evidence on prophylactic interventions to prevent heterotopic ossification (HO) around the knee is scarce. We conducted a scoping review to map reported indications, interventions, and outcome reporting. We followed a prospectively developed protocol and searched four major databases (MEDLINE via PubMed, Embase, Cochrane Library, and Web of Science), complemented by searches of trial registries and grey literature using a high-sensitivity strategy. Data extraction was performed in duplicate and summarized descriptively by modality. The search yielded 2,958 records. We included 78 unique publications, comprising 18 expert-opinion sources and 62 clinical publications reporting data on 3,321 patients, of whom 1,579 received the evaluated interventions, with two publications contributing to both syntheses. Modalities comprised continuous passive motion (CPM) in 8, pharmacological prophylaxis in 21, radiotherapy (RT) in 18, surgical techniques in 3, and combination therapy in 14 studies. Most identified studies were case reports or case series. Pharmacological data were largely driven by one large ASA cohort, whereas RT and combination-therapy studies were small and mainly addressed recurrence prophylaxis. One late fatal, potentially RT-induced sarcoma was reported. Because of substantial clinical and methodological heterogeneity, crude reported event proportions should not be compared directly across modalities. Outcome reporting was inconsistent, with limited use of standardized patient-reported outcomes and incomplete adverse-event reporting. Knee HO prophylaxis evidence is dominated by low-level, heterogeneous studies with substantial reporting gaps. Comparative knee-specific studies with standardized outcome definitions, functional outcomes, and systematic safety reporting are needed. This review was prospectively registered on the Open Science Framework (OSF registration ID 5328k).","[""Scoping Review"", ""Journal Article"", ""Systematic Review""]","[""Römer M"", ""Wurschi G"", ""Mäurer M"", ""Pietschmann K""]",10.1186/s12891-026-10318-w,Römer M,BMC musculoskeletal disorders,1471-2474,1,BMC Musculoskelet Disord,eng,Pietschmann K,"[""Humans"", ""Ossification, Heterotopic"", ""Knee Joint"", ""Motion Therapy, Continuous Passive"", ""Combined Modality Therapy"", ""Treatment Outcome""]",,42542554,pmc-id: PMC13428452;,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42542554/,The prevention of heterotopic ossification around the knee: a scoping review,27,PHe8hY6wjllKaWIQU,sSanp9FC1D9A5H9tg
"The aim of this systematic review was to synthesize current evidence on end-of-life (EOL) communication in surgical and neurocritical care settings. While effective EOL communication is essential to support patient-centered decision-making and ethical care, its implementation in surgical and neurosurgical contexts remains inconsistent and insufficiently characterized. Using advanced search terms, a systematic review of the literature was conducted, comprising PubMed and Scopus. Studies published from January 2016 to January 2026 were included if they involved adult patients, family members, or clinicians engaged in EOL communication within surgical, neurosurgical, or oncological settings and reported empirical data on communication practices, barriers, ethical issues, family involvement, or training interventions. Observational, interventional, and qualitative studies were eligible. Due to substantial heterogeneity in study design and outcomes, findings were synthesized qualitatively. Twenty-six studies met the inclusion criteria. Across studies, EOL communication was characterized by significant challenges related to time constraints, emotional burden, prognostic uncertainty, and variability in clinician communication skills. Structured training interventions, particularly simulation-based programs, were associated with improved clinician confidence and perceived competence, although their implementation was inconsistent. Neurosurgical and neuro-oncological settings presented distinct challenges, including rapid disease progression, early cognitive impairment, and increased reliance on family members for surrogate decision-making. Ethical dilemmas surrounding medical futility, autonomy, and conflict resolution were recurrent. The available evidence highlights persistent gaps between recommended and actual EOL communication practices in surgical and neurocritical care. Improving outcomes will require earlier and structured communication, formal training embedded in surgical education, and multidisciplinary collaboration. Future research should prioritize prospective designs and standardized outcome measures to strengthen the evidence base and support more informed clinical decision-making for patients, families, and clinicians. Systematic review registration no.: CRD420261320726 (www.crd.york.ac.uk/prospero/).","[""Journal Article"", ""Systematic Review""]","[""Vannuccini S"", ""Della Pepa GM"", ""Marfoli A"", ""Lafuenti L"", ""D'Alessandris QG"", ""Mattogno PP"", ""Doglietto F"", ""Chieffo DPR""]",10.3171/2026.5.FOCUS26148,Vannuccini S,Neurosurgical focus,1092-0684,2,Neurosurg Focus,eng,Chieffo DPR,"[""Humans"", ""Terminal Care"", ""Communication"", ""Neurosurgery"", ""Neurosurgical Procedures"", ""Decision Making""]",E4,42541810,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42541810/,"End-of-life communication in surgery and neurosurgery: challenges, opportunities, and insights from a systematic review",61,PHe8hY6wjllKaWIQU,sSanp9FC1D9A5H9tg
"AIM: Chronic subdural hematoma (cSDH) is a common neurosurgical condition in elderly patients, frequently associated with trauma, anticoagulant use, and chronic comorbidities. While surgical evacuation and now middle meningeal artery embolization remain the predominant treatment options, endoscopic-assisted techniques have been increasingly used as a surgical adjunct. We evaluated the safety, clinical outcomes, and recent advancements in endoscopic-assisted evacuation of cSDH through both a retrospective case series and an updated review of the current literature. MATERIAL and METHODS: A retrospective analysis of 39 patients undergoing 44 endoscopic-assisted evacuations of subdural hematomas between October 2021 and May 2025 was performed. Patient demographics, imaging, operative details, complications, and recurrence were analyzed. A systematic review of 15 studies published between 2022 and 2025 was added to a prior review performed by our group to assess outcomes associated with endoscopic approaches to cSDH. RESULTS: Of the 39 patients (67% male, ages 20 to 73), four experienced recurrence, three prior to middle meningeal artery (MMA) embolization and one after. All patients received postoperative subdural drains, and no intraoperative complications related to the endoscope occurred. The literature review included an additional 16 recent studies (n=1060 patients) in addition to 13 studies from a previous systematic review, reporting recurrence rates of 0% to 16.7%. Endoscopic evacuation was associated with reduced recurrence, shorter hospital stays, and improved hematoma clearance compared to traditional techniques. CONCLUSION: Endoscopic-assisted evacuation of cSDH appears to be a safe and effective adjunct to conventional surgical methods through improved visualization, potential coagulation of distal meningeal artery territories, and reduced recurrence. While results are promising, larger prospective studies are needed to confirm long-term benefits and refine patient selection.","[""Journal Article"", ""Systematic Review""]","[""Baloi D"", ""Freeman H"", ""Pattillo C"", ""Demir E"", ""Zeinali M"", ""Karsy M""]",10.5137/1019-5149.JTN.49362-25.2,Baloi D,Turkish neurosurgery,1019-5149,4,Turk Neurosurg,eng,Karsy M,"[""Humans"", ""Hematoma, Subdural, Chronic"", ""Meningeal Arteries"", ""Female"", ""Embolization, Therapeutic"", ""Male"", ""Aged"", ""Middle Aged"", ""Retrospective Studies"", ""Neuroendoscopy"", ""Adult"", ""Treatment Outcome"", ""Young Adult"", ""Recurrence""]",491-499,42541773,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42541773/,Endoscopic-Assisted Chronic Subdural Hematoma Evacuation as an Adjunct to Middle Meningeal Artery Embolization: A Case Series and Systematic Review,36,PHe8hY6wjllKaWIQU,sSanp9FC1D9A5H9tg
"Therapeutic orthoses, such as medical shoes and custom insoles, are used to prevent diabetic foot ulcer (DFU) recurrence. This systematic review with narrative synthesis aimed to evaluate the effectiveness of orthoses in preventing DFU recurrence compared to standard care. We followed PRISMA guidelines for a systematic review. Searches were conducted in PubMed, Cochrane, and Web of Science. RCTs on orthoses for preventing DFU recurrence were included. Risk of bias was assessed using Cochrane tools. Due to heterogeneity, narrative synthesis was used. An initial search of 4166 articles identified ten randomized controlled trials (RCTs) that met the inclusion criteria and were included in this review, focusing on patients living with diabetes at risk of DFU recurrence compared to usual care. Narrative synthesis of the 10 RCTs, involving 1686 participants, showed that custom orthoses reduced recurrence in several studies (e.g., Bus 2013 reported 9.9% recurrence vs. 25% in controls), though the evidence was heterogeneous due to variability in orthosis types and follow-up periods. Orthoses can prevent diabetic foot ulcer recurrence, and we recommend their use where feasible. Further research is needed to optimize their clinical application.","[""Journal Article"", ""Systematic Review"", ""Comparative Study""]","[""Amini B"", ""Salehi-Pourmehr H"", ""Ghaffarzadehrad S""]",10.1002/jfa2.70192,Amini B,Journal of foot and ankle research,1757-1146,3,J Foot Ankle Res,eng,Ghaffarzadehrad S,"[""Humans"", ""Diabetic Foot"", ""Randomized Controlled Trials as Topic"", ""Foot Orthoses"", ""Recurrence"", ""Secondary Prevention"", ""Female"", ""Treatment Outcome"", ""Male"", ""Middle Aged""]",e70192,42541747,pmc-id: PMC13428632;,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42541747/,Comparing the Effectiveness of Different Types of Orthoses in Preventing Diabetic Foot Ulcer Recurrence: A Systematic Review of Randomized Clinical Trials,19,PHe8hY6wjllKaWIQU,sSanp9FC1D9A5H9tg
"This systematic review investigated the effect of protein intake on anthropometric and body composition markers in pre- to postmenopausal women. Understanding these effects may contribute to the development of nutritional strategies to improve body composition and prevent changes associated with this phase. Searches were conducted in the PubMed, EMBASE, and Cochrane Library databases, following the PRISMA guidelines, and the risk of bias was assessed using the Joanna Briggs Institute (JBI) tool (PROSPERO: CRD420251156313). Fifteen randomized clinical trials, involving 1161 pre- and postmenopausal women, were included. Interventions with animal-based protein (n = 8) showed more consistent effects on weight and body fat reduction, especially when combined with calorie restriction and supervised exercise. Protocols using whey protein, meat, or milk protein demonstrated reductions in body fat over 8-16 weeks, with increases in lean mass in longer interventions. However, these effects are strongly influenced by the use of other strategies, such as energy restriction and physical exercise. Studies with soy protein isolate (n = 7) showed more heterogeneous results, with few changes in short-term interventions and more favorable results when combined with exercise. When analyzed independently of energy restriction and physical exercise, the effects of consuming both proteins on body composition were less consistent, making it impossible to confirm benefits from an isolated increase in protein intake. Animal proteins have more consistent effects on anthropometric markers and body composition in women during the climacteric period, particularly when combined with energy restriction and physical exercise. In contrast, plant-based proteins have more heterogeneous effects, with greater benefits observed when associated with exercise. The findings of this review reinforce the importance of considering protein type, dose, duration of intervention, and other combined strategies when developing nutritional recommendations for changes in body composition.","[""Journal Article"", ""Systematic Review""]","[""Fialho SN"", ""de Souza Ferreira ML"", ""Ribeiro SAV"", ""Kravchychyn ACP"", ""Hermsdorff HHM""]",10.1096/fj.202600792R,Fialho SN,FASEB journal : official publication of the Federation of American Societies for Experimental Biology,0892-6638,15,FASEB J,eng,Hermsdorff HHM,"[""Humans"", ""Female"", ""Adiposity"", ""Body Composition"", ""Postmenopause"", ""Randomized Controlled Trials as Topic"", ""Animals"", ""Premenopause"", ""Dietary Proteins"", ""Animal Proteins, Dietary""]",e71977,42541706,pmc-id: PMC13428612;,2026 Aug 15,2026,https://pubmed.ncbi.nlm.nih.gov/42541706/,Dietary Intake of Animal and Plant-Based Protein on Adiposity Measurements and Body Composition in Pre- and Postmenopausal Women: A Systematic Review of Randomized Clinical Trials,40,PHe8hY6wjllKaWIQU,sSanp9FC1D9A5H9tg
"Soil-transmitted helminth (STH) infections affect approximately 1.5 billion people globally. Although the World Health Organization (WHO) aims for 75% mass drug administration (MDA) coverage by 2030, the long-term population benefit remains debated. This review aims to describe the characteristics of recent mass deworming studies, synthesize parasitologic and coverage outcomes, and identify programmatic themes. Search was conducted across Scopus, PubMed, and EBSCO CINAHL, restricted to studies reporting both parasitologic efficacy outcomes and MDA coverage. Following a risk of bias assessment in Review Manager 5.4, qualitative data were processed in Taguette 1.5.1 through a hierarchical thematic analysis to generate basic, organizing, and global themes and supplemented by VOSviewer 1.6.20 overlay visualization. Thirteen eligible studies primarily featured African countries and cross-sectional study designs. While overall risk of bias was low, lack of blinding revealed high performance bias. Thematic analysis, supported by bibliographic visualization, identified four global themes on delivery, compliance, equity and impact. Findings indicate that annual dosing is often insufficient and requires bi-annual schedules and WASH integration. Compliance is hindered by temporal inaccessibility and unreliable decentralized monitoring while equity gaps persist for out-of-school children and pregnant women. Although drug efficacy is confirmed, risks of resistance and diagnostic underreporting via the Kato-Katz method remain critical concerns. This review identifies four interrelated pillars of delivery, compliance, equity, and impact that shape the effectiveness of mass deworming programs and have direct implications for achieving WHO 2030 targets.","[""Journal Article"", ""Systematic Review"", ""Review""]","[""Rodriguez HM"", ""Rostata AMB"", ""Salgado JJRCMV"", ""Rivera TLD"", ""Angeles JMM""]",10.1007/s11686-026-01370-6,Rodriguez HM,Acta parasitologica,1230-2821,4,Acta Parasitol,eng,Angeles JMM,"[""Helminthiasis"", ""Humans"", ""Soil"", ""Anthelmintics"", ""Mass Drug Administration"", ""Animals"", ""Helminths""]",,42541624,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42541624/,"Beyond Coverage: A Systematic Review and Thematic Analysis of Delivery, Compliance, Equity and Impact in Mass Deworming for Soil-Transmitted Helminths",71,PHe8hY6wjllKaWIQU,sSanp9FC1D9A5H9tg
"Keloid is a fibroproliferative scar with marked ethnic disparities, disproportionately affecting Asian and Black populations. Single-cell RNA sequencing (scRNA-seq) studies have mapped keloid pathology, but cross-study differences complicate generalization. We performed a meta-analysis to identify composition and transcriptional programs associated with keloid across ethnicities. We aggregated human skin scRNA-seq datasets containing keloid and healthy samples with documented ethnicity (Asian, Black, White). After quality control and batch integration (scVI/scANVI), we annotated cell types and subtypes. Differential abundance was estimated with scCODA, Milo, and propeller. Pseudobulk differential expression was meta-analyzed using random-effects models. Ligand-receptor signaling was inferred with CellChat/NicheNet. The harmonized atlas comprised 112 donors, 147 samples, and 487,293 cells from 8 studies. Keloid demonstrated higher proportions of vascular endothelial cells and fibroblasts across all methods. Ethnicity-stratified analysis revealed endothelial expansion in Asian and Black relative to White populations, while fibroblast expansion was greater in White keloids. Endothelial subtyping showed increased post-capillary venules and arteriolar states. Fibroblast analysis revealed expansion of mesenchymal/ADAM12+ and pro-inflammatory populations. Meta-analysis implicated TGF-β/SMAD, integrin/FAK, and YAP/TAZ mechanotransduction pathways as candidate pathogenic programs warranting functional validation. Cross-study synthesis identifies shared and ethnicity-stratified endothelial and fibroblast programs in keloid. Expansion of post-capillary venules and ADAM12+ fibroblasts provides candidate therapeutic targets pending functional validation and a framework for understanding ethnic disparities in keloid formation.","[""Journal Article"", ""Systematic Review""]","[""Alkouz Z"", ""Zhang L"", ""Suwait AA"", ""Alhejairi R"", ""Liu C"", ""Gu X"", ""Yang B""]",10.3389/fmed.2026.1751725,Alkouz Z,Frontiers in medicine,2296-858X,,Front Med (Lausanne),eng,Yang B,[],1751725,42540716,pmc-id: PMC13426371;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540716/,"A multi-dataset single-cell meta-analysis of human keloid skin across Asian, Black and White populations reveals endothelial and mesenchymal programs linked to ethnic disparities",13,PHe8hY6wjllKaWIQU,sSanp9FC1D9A5H9tg
"The ability to reliably access, afford, or obtain foods that are culturally significant, familiar, and aligned with one's identity, foodways, religious beliefs, and the sociocultural preferences is an important aspect of food and nutrition security in immigrant communities. This is because access to culturally appropriate food is crucial for maintaining perceived healthy dietary and nutritional practices, finding comfort, and growing a sense of place. However, the existing food security measurement scales have been criticized for their limited ability to adequately capture the unique aspects of cultural food security as experienced by newcomer populations. As such, the existing measures under estimate the prevalence and the significant health and wellbeing effects of cultural food security. Furthermore, recent studies have argued for recognition cultural food security as a distinct concept with its own indicators relevant to newcomers, yet limited to no studies exist that have comprehensively reviewed and synthesized the existing conceptualization and definition of cultural food security. We address this knowledge gap by mapping and synthesizing the existing literature on the definition of cultural food security, the adopted indicators, and the associated benefits of cultural food security for immigrants and refugees. The review followed the PRISMA Extension for Scoping Reviews guidelines and synthesized journal articles retrieved from five databases: PubMed, Scopus, Medline, CINAHL Plus, and Academic Search Complete. Flowing Braun and Clarke's Reflexive thematic analysis, we synthesized 18 studies that met the inclusion criteria for this review. We found variability and diversity in the definition of cultural food security. Most of the studies have adopted existing food security scales to estimate cultural food security, yet the scales inadequately capture the food security realities of immigrants, refugees, and ethno-cultural groups in the destination communities. Additionally, cultural food security in migrant communities transcends the conventional food security indicators to embody the unique migration and resettlement experiences. By synthesizing the existing studies that have explored how cultural food security in migrant population has been assessed, this study generates evidence on the relevance of considering the unique indicators of the aspects of food security that appreciates the reciprocal relations with the land, the practice of sharing of food and food cultures, and a collectivist lens to eating of food and to food access, which are relevant to immigrant communities. The evidence is important in creating culturally responsive food security interventions and in ensuring improved sense of place and settlement of newcomers.","[""Journal Article"", ""Systematic Review""]","[""Onyango E"", ""Owuor P"", ""Otoadese D"", ""Odhiambo S"", ""Ajibade T"", ""Onyango J"", ""Boateng G""]",10.3389/fnut.2026.1841239,Onyango E,Frontiers in nutrition,2296-861X,,Front Nutr,eng,Boateng G,[],1841239,42540478,pmc-id: PMC13426276;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540478/,Beyond conventional metrics: a scoping review of cultural food security definitions and indicators for migrant populations,13,PHe8hY6wjllKaWIQU,sSanp9FC1D9A5H9tg
"Substance use disorder (SUD) is a major global health issue, contributing significantly to the disease burden. Despite this, effective treatments for SUD remain limited. Ketamine has shown potential as a treatment, yet no meta-analysis has assessed its efficacy for SUD. This study aimed to evaluate the efficacy and safety of ketamine in treating SUD. Multiple databases were systematically searched forrandomized controlled trials (RCTs) on ketamine for SUD treatment. The primary outcome was abstinence rates. Adverse events and dropout rates were also assessed to evaluate safety and acceptability. A random-effects model was used to conduct the meta-analysis. Fifteen RCTs with 798 participants were included; seven RCTs contributed abstinence data to the quantitative synthesis. Ketamine was associated with significantly improved abstinence at <1 month [odds ratio(OR) = 3.27, 95% CI: 1.55-6.92, I2 = 0%, p < 0.01], but not at 1-6 months (OR = 1.74, 95% CI: 0.91-3.30, I2 = 0%, p = 0.09). No significant difference in dropout rates was observed between the ketamine and control groups (OR = 0.74, 95% CI: 0.46-1.21, I2 = 0%, p = 0.23). No significant between group difference was identified in adverse events, although the available evidence was limited and insufficient to establish safety conclusively. Current evidence suggests a short-term efficacy signal for ketamine in SUD, but the evidence remains limited and insufficient to establish its efficacy and safety conclusively. identifier CRD42024607116.","[""Journal Article"", ""Systematic Review""]","[""Fang SP"", ""Yang X"", ""Zhao DC"", ""Wen Y"", ""Liu YH"", ""Li Z"", ""Ran MS""]",10.3389/fpsyt.2026.1835709,Fang SP,Frontiers in psychiatry,1664-0640,,Front Psychiatry,eng,Ran MS,[],1835709,42540381,pmc-id: PMC13426052;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540381/,Ketamine for substance use disorders: a systematic review and meta-analysis,17,PHe8hY6wjllKaWIQU,sSanp9FC1D9A5H9tg
"Asthma remains a major public health challenge in India, characterized by high disease burden, poor adherence, and suboptimal control despite therapeutic advances. Fixed-dose combination therapy with indacaterol/glycopyrronium/mometasone furoate (IND/GLY/MF; DIFIZMA®), a single-inhaler triple therapy (SITT), offers the potential for improved symptom control and adherence through once-daily dosing. However, real-world and postmarketing surveillance data on the effectiveness and safety of IND/GLY/MF in Indian asthma patients remain limited, underscoring the need for local evidence to guide clinical practice. To evaluate the safety and effectiveness of once-daily IND/GLY/MF dry powder inhaler (DPI) in Indian adults with asthma inadequately controlled on inhaled corticosteroid (ICS)-long-acting β2-agonist (LABA) therapy. This was a prospective, open-label, multicenter, single-arm, phase IV postmarketing study conducted across multiple centers in India. Adults (18-65 years) with persistent asthma symptoms despite ICS ± LABA therapy received IND/GLY/MF DPI (160 µg mometasone furoate, 46 µg glycopyrronium bromide, 114 µg indacaterol acetate) once daily for 24 weeks. The primary endpoint was safety, based on treatment-emergent adverse events (TEAEs), serious TEAEs, and discontinuations. Secondary endpoints included changes from baseline in the asthma control questionnaire (ACQ-7) score, FEV1, FVC, and FEV1/FVC ratio at weeks 4, 12, and 24. A total of 200 patients were enrolled (safety set), of whom 196 were included in the modified intent-to-treat (mITT) analysis and 189 in the per-protocol (PP) population. TEAEs occurred in 9.5% of participants, with 6.5% considered drug-related; all events were mild or moderate in severity. No serious adverse events, severe TEAEs, or deaths were reported. Clinically meaningful and progressive improvements were observed in asthma control and lung function over 24 weeks. The ACQ-7 score decreased from 3.00 ± 0.59 at baseline to 2.36 ± 0.54 at week 4, 1.86 ± 0.54 at week 12, and 1.39 ± 0.61 at week 24, corresponding to mean change of -0.64 ± 0.50, -1.14 ± 0.74, and -1.62 ± 0.89, respectively (all p < 0.0001). Mean FEV1 increased from 1.49 ± 0.51 L at baseline to 1.73 ± 0.60 L at week 4, 1.81 ± 0.53 L at week 12, and 1.95 ± 0.51 L at week 24, with corresponding mean changes of +0.24 L, +0.32 L, and +0.46 L (all p < 0.0001). Mean FVC improved from 2.13 ± 0.63 L at baseline to 2.30 ± 0.70 L, 2.33 ± 0.62 L, and 2.38 ± 0.59 L at weeks 4, 12, and 24, respectively (all p < 0.0001). The FEV1/FVC ratio increased from 71.63 ± 12.76 at baseline to 76.71 ± 11.33, 80.86 ± 12.67, and 84.00 ± 8.93 at weeks 4, 12, and 24, with mean changes of +4.99, +8.91, and +12.10, respectively (all p < 0.0001). No hospitalizations or rescue medication use were reported. Compliance with study medication was 100%, and both patients and physicians reported marked symptom improvement and high treatment satisfaction. Once-daily IND/GLY/MF DPI demonstrated a favorable safety profile and significant, sustained clinical benefits in adults with asthma inadequately controlled on ICS-LABA therapy. The triple combination provided rapid onset and sustained improvement in asthma control and lung function, with excellent adherence and tolerability in real-world Indian clinical practice. These findings support IND/GLY/MF as an effective and practical single-inhaler triple therapy option for optimized asthma management.","[""Journal Article"", ""Multicenter Study"", ""Clinical Trial, Phase IV""]","[""Karmakar S"", ""Bhate AS"", ""Prashanth C"", ""Kadam D"", ""Patel CB"", ""Budhraja A"", ""Nandy U"", ""Lotankar A"", ""Nivangune K"", ""Patel K""]",10.59556/japi.74.1524,Karmakar S,The Journal of the Association of Physicians of India,0004-5772,6E,J Assoc Physicians India,eng,Patel K,"[""Humans"", ""Asthma"", ""Quinolones"", ""Mometasone Furoate"", ""Adult"", ""Female"", ""Glycopyrrolate"", ""Male"", ""Drug Combinations"", ""Dry Powder Inhalers"", ""Prospective Studies"", ""Indans"", ""Middle Aged"", ""Treatment Outcome"", ""India"", ""Administration, Inhalation"", ""Young Adult""]",e1-e5,42543945,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543945/,Safety and Effectiveness of Indacaterol/Glycopyrronium/Mometasone Dry Powder Inhaler in Asthma: A Prospective Multicenter Phase IV Study,74,ElhjXrxeb3tIjimqt,FjLVMhm8YMEAQNVO6
"Functional constipation is a common disorder of gut-brain interaction that substantially affects bowel function, psychological well-being, and quality of life. Probiotic supplementation represents a microbiota-targeted nutritional strategy for functional constipation, but associated host-response signals remain incompletely understood. This single-center, randomized, double-blind, placebo-controlled trial enrolled 104 adults who met the Rome IV criteria for functional constipation. Participants received either Lactiplantibacillus plantarum Probio87 or placebo for 8 weeks, followed by a 4-week post-intervention follow-up. The primary endpoint was weekly complete spontaneous bowel movements. Secondary outcomes included Rome IV symptom scores, PAC-QOL, HAMD-24, safety parameters, and exploratory whole-blood gene-expression profiles related to inflammation, immune regulation, neuroendocrine signaling, and gut motility. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR2300075360). Probio87 supplementation significantly increased weekly complete spontaneous bowel movements compared with placebo at Week 8 and Week 12. Improvements were also observed in Rome IV symptom scores, constipation-related quality of life, and HAMD-24 domains related to anxiety, sleep, and retardation. Exploratory whole-blood gene-expression analysis showed differential host-response signals after intervention, characterized by increased BDNF expression and reduced expression of IL-1β, CD117, CXCR5, IDO1, DBH, and MLNR in the probiotic group relative to placebo. No intervention-related adverse events or clinically relevant abnormalities in hematological, hepatic, or renal safety parameters were observed. L. plantarum Probio87 supplementation was associated with sustained improvement in bowel function, constipation-related quality of life, and psychological well-being in adults with functional constipation. Exploratory peripheral gene-expression findings suggest that inflammatory, immune, neuroendocrine, and motility-related host-response pathways may be involved, although causal mechanisms require further validation. https://www.chictr.org.cn/showproj.html?proj=205514, identifier (ChiCTR2300075360).","[""Clinical Trial"", ""Journal Article""]","[""Zheng F"", ""Yang Y"", ""Zhan Y"", ""Zhang ZW"", ""Lu G"", ""Xie D"", ""Zhang SM"", ""Mageswary U"", ""Lee YY"", ""Liong MT""]",10.3389/fnut.2026.1876944,Zheng F,Frontiers in nutrition,2296-861X,,Front Nutr,eng,Liong MT,[],1876944,42540505,pmc-id: PMC13426275;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540505/,"Lactiplantibacillus plantarum Probio87 supplementation improves functional constipation and is associated with peripheral gene-expression responses related to inflammation and the gut-brain axis: a randomized, double-blind, placebo-controlled trial",13,ElhjXrxeb3tIjimqt,FjLVMhm8YMEAQNVO6
"To investigate the effects of a high-dose probiotic-lactoferrin (LF)-milk fat globule membrane (MFGM)-nucleotide combined formula on reducing the incidence risk of common diseases and related symptoms and improving growth and hemoglobin level in neonates born via cesarean section. This trial was a prospective, multicenter, open-label, randomized, controlled 3-month intervention study. A total of 150 eligible neonates were enrolled. All participants completed the full intervention and provided clinical data. All enrolled formula-feeding neonates were randomly assigned to either the intervention group (IG, n = 50) or the control group (CG, n = 50), and 50 exclusively breastfed neonates were assigned to the breastfeeding control group (BCG). The formula used in the IG contained 2 × 109 CFU/100 g probiotics, 200 mg/100 g LF, added MFGM, and 55 mg/100 g nucleotides. In contrast, neonates in the CG were fed a formula containing 45-50 mg/100 g LF and 30-35 mg/100 g nucleotides, without probiotic or MFGM fortification. The primary outcome was the frequency of upper respiratory tract infections (URTIs). Secondary outcomes included the incidence of other respiratory, gastrointestinal, and allergic symptoms and diseases, as well as infant anthropometric indicators (including length, weight and head circumference) and the hemoglobin (Hb) concentration. The incidence of URTIs over the 3-month intervention showed no significant difference among the three groups [the incidences of URTIs in CG, IG, and BCG: 22% (11/50), 18% (9/50), and 14% (7/50), respectively, χ2 = 1.084, p = 0.582] according to both intention-to-treat (TT) and per protocol (PP) analyses [incidence of URTIs in CG, IG, and BCG: 22.9% (11/48), 19.6% (9/46), and 14.9% (7/47), respectively, χ2 = 0.680, p = 0.712]. After the 3-month intervention, compared with infants in the CG, infants in the IG showed a reduced risk ration (RR) for functional dyspepsia [RR = 0.756, 95% confidence interval (95% CI) = 0.587-0.974] and eczema (RR = 0.647, 95% CI = 0.449-0.933). Hb levels in the CG and IG were both significantly higher than those in the BCG (107.35 ± 9.26 vs. 105.99 ± 7.01 vs. 101.42 ± 7.07 g/L for CG, IG, and BCG, respectively; F = 9.629, p < 0.001), with no statistically significant difference between the CG and IG. No significant differences in anthropometric indicators were observed among the three groups (p > 0.05). This study found no adverse effects associated with 3-month supplementation of a high-dose probiotic-LF-MFGM-nucleotide combined formula, supporting its safety for term neonates delivered by cesarean section. The primary outcome, URTI incidence, did not differ significantly among groups. Exploratory analyses suggested lower risks of functional dyspepsia and eczema in the intervention group; however, these findings should be considered preliminary and require confirmation in larger adequately powered studies. The intervention was well tolerated and showed safety comparable to standard feeding practices.","[""Clinical Trial"", ""Journal Article""]","[""Chen K"", ""Zhang X"", ""Chen H"", ""He N"", ""Tang Y"", ""Yang Z"", ""Fang Z"", ""Liu C""]",10.3389/fnut.2026.1741431,Chen K,Frontiers in nutrition,2296-861X,,Front Nutr,eng,Liu C,[],1741431,42540473,pmc-id: PMC13426272;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540473/,"Effect of a high-dose bioactive components formula on reducing common diseases in term neonates delivered by cesarean section: a randomized, open-label, controlled trial",13,ElhjXrxeb3tIjimqt,FjLVMhm8YMEAQNVO6
"Intravitreal injection (IVI) therapy is the most frequently performed intraocular procedure worldwide, with topical povidone-iodine (PVP-I) as the standard pre-injection antiseptic. However, PVP-I has been shown to exert cytotoxic effects on the ocular surface. The purpose of this study was to evaluate the impact of two years of serial anti-vascular endothelial growth factor (VEGF) IVI on ocular surface parameters. Patients with neovascular age-related macular degeneration (nAMD) receiving unilateral intravitreal anti-VEGF injections were examined at two time points, separated by a two-year interval. An aseptic protocol with PVP-I was applied prior to each injection. Tear meniscus height (TMH), bulbar redness (BR), and meibomian gland (MG) loss were assessed using the Oculus Keratograph 5M, with the fellow eye serving as control. For statistical analysis, the related-samples Wilcoxon signed-rank test was applied to non-normally distributed data, and the paired-sample Student's t-test to normally distributed data. Sixty patients (mean age, 78.6 ± 8.5 years; range, 55-96) were included. Between examinations, patients received a mean of 15.5 ± 6.5 IVI (range, 5-30). A significant increase in mean BR was observed in untreated fellow eyes compared with baseline measurements (1.68 ± 0.47 vs. 1.41 ± 0.46; p < 0.001). At follow-up, BR was significantly higher in fellow eyes than in treated eyes (p < 0.001), and this difference had increased over the study period. Median TMH increased significantly in untreated eyes (0.42 mm [IQR, 0.28-0.57] vs. 0.31 mm [IQR, 0.23-0.47]; p = 0.003), whereas the increase in treated eyes was not significant (p = 0.74). At follow-up, mean TMH did not differ significantly between treated and fellow eyes (p = 0.15). Both treated and untreated eyes showed significant MG loss after two years of serial IVI; however, no significant differences in mean MG loss were detected between eyes in either the upper or lower eyelid at follow-up. Eyes receiving repeated intravitreal anti-VEGF injections with preoperative PVP-I antisepsis were significantly less hyperemic than fellow untreated eyes, and this difference increased over two years of continued treatment. Potential mechanisms include a beneficial alteration of the ocular surface microbiome by PVP-I or an antiangiogenic effect of anti-VEGF therapy. https://clinicaltrials.gov/study/NCT04458012, identifier NCT04458012.","[""Clinical Trial"", ""Journal Article""]","[""Malmin A"", ""Olsen MVT"", ""Thomseth VM"", ""Kjellevold Haugen IB"", ""Utheim TP"", ""Forsaa VA""]",10.3389/fopht.2026.1829818,Malmin A,Frontiers in ophthalmology,2674-0826,,Front Ophthalmol (Lausanne),eng,Forsaa VA,[],1829818,42539849,pmc-id: PMC13424885;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42539849/,Long-term Impact of Intravitreal Injections on the ocular surface; a 2-year follow-up study,6,ElhjXrxeb3tIjimqt,FjLVMhm8YMEAQNVO6
"Measles remains a major cause of child morbidity and mortality in low-resource settings. Young infants are particularly at risk of severe disease, with many lacking protective levels of maternal antibodies by six months. Vaccination before nine months in high-burden settings may confer earlier protection; however, concerns exist about its effectiveness at this age. We present early findings on enrolment, safety, and measles infections following the administration of a registered measles-containing vaccine at six months versus nine months (MR1) with a subsequent booster (MR2) at 12 or 18 months of age. We conducted an open-label randomised controlled non-inferiority trial at four health facilities in Kampala, Uganda. Infants aged 24-28 weeks were randomly assigned to receive MR at six and 12 months (group A), nine and 18 months (group B) or six and 18 months (group C). Infants were electronically randomised in a 1:1:1 ratio using block randomisation of varying sizes, stratified by site, maternal HIV status and baseline haemoglobin level. Caretakers recorded solicited reactions on paper diary cards, with safety-related events evaluated. 450 infants received MR1 and were enrolled. No differences in local or systemic post-vaccination events between the six and nine months MR1 groups were observed [Local: 21·2% versus 21·9% (p = 0·959), systemic: 29·2% vs. 27·7% (p = 0·845)]. Most local reactions were mild and within the first four days. The majority (5/6) of hospitalisations followed common childhood illnesses, with one non-vaccine-related death six months post-MR1. Sixteen laboratory-confirmed cases of measles (10) and rubella (6), and three clinical measles cases before MR1 were registered. Most measles cases (70·0%) occurred in group C, with no measles cases registered two weeks post-MR2. We provide further evidence on the safety of administering a measles-containing vaccine at six months of age.Trial registration: The trial was registered on 31st October 2024 with Clinicaltrials.gov with the identifier NCT06667206. The online version contains supplementary material available at 10.1007/s44337-026-00649-x.","[""Clinical Trial"", ""Journal Article""]","[""Businge G"", ""Marchevsky NG"", ""Mupere E"", ""Kelly S"", ""Kakai I"", ""Kyohere M"", ""Edielu A"", ""Ambangira F"", ""Kakayi B"", ""Tusubira V"", ""Komugisha C"", ""Musoke P"", ""Mujadidi YF"", ""Bijlsma MW"", ""Le Doare K"", ""Voysey M""]",10.1007/s44337-026-00649-x,Businge G,Discover medicine,3004-8885,1,Discov Med (Singap),eng,Voysey M,[],92,42539769,pmc-id: PMC13424465;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42539769/,Preliminary safety data from a randomised trial of early versus standard timing of administration of measles-rubella vaccine in Ugandan infants,3,ElhjXrxeb3tIjimqt,FjLVMhm8YMEAQNVO6
"The study aim was to evaluate the efficacy of homeopathic medication in SAR patients. In a double-blind, three-arm randomised trial, patients at eleven outpatient clinics and two medical centres were randomised to receive (1) individualised homeopathic case taking (IHCT) and standardised homeopathic medication with Galphimia Glauca (GG), (2) IHCT and individualised homeopathic treatment (IHG), or (3) IHCT and placebo (PG). Primary outcome was disease-specific quality of life, assessed using the Rhinitis Quality of Life Questionnaire (RQLQ) after three and four weeks. Secondary outcomes included response rate (≥0.5-point change in RQLQ), rescue medication use, and total nasal and non-nasal symptom scores (TNSS, TNNSS). Sixty-two SAR patients (mean age ± SD: 46.9 ± 14.9; 43.5% female) were recruited, approximately 25% of the planned sample size. After weeks three and four, there were no significant differences in RQLQ (p = 0.244) between GG (adjusted mean, 1.2, 95% CI 0.7-1.7), IHG (1.7, 1.2-2.3), and PG (1.4, 0.8-2.0). High response rates were observed (GG: 86.4%, IHG: 66.7%, PG: 81.3%), while RM use was 21.7%, 55.6%, and 29.4%, respectively. There were no relevant differences in RM score, TNSS and TNNSS between the three groups. Eight adverse events but no serious adverse events were reported. Standardised and individualised homeopathic drugs were not superior compared to placebo suggesting that treatment response was not based on study medication. The validity of the study and its conclusions are limited by the fact that the recruitment target was not achieved. This study has been registered in the German Clinical Trial Registry with trial ID DRKS00018081.","[""Clinical Trial"", ""Journal Article""]","[""Siewert J"", ""Cramer H"", ""Ortiz M"", ""Tissen-Diabaté T"", ""Roll S"", ""Wegscheider K"", ""Linde K"", ""Reinhold T"", ""Willich SN"", ""Teut M"", ""Brinkhaus B""]",10.3389/falgy.2026.1815934,Siewert J,Frontiers in allergy,2673-6101,,Front Allergy,eng,Brinkhaus B,[],1815934,42539590,pmc-id: PMC13424193;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42539590/,Homeopathic medication for seasonal allergic rhinitis-a randomised placebo-controlled trial,7,ElhjXrxeb3tIjimqt,FjLVMhm8YMEAQNVO6
"Chimeric antigen receptor (CAR) T-cell therapy has been the standard of care for relapsed/refractory B-cell lymphomas (r/r BCLs) in recent years. However, high cost of commercial products limits their application in real-world clinical practice. The use of the so-called academic CAR-T cell products can reduce the cost and improve availability and affordability of this therapy option. The aim of the present clinical trial was to assess the efficacy and safety of academic CAR-T cells in r/r BCL patients. From June 2021 to December 2025, this prospective clinical trial enrolled 76 r/r BCL patients treated at the N.N. Alexandrov National Cancer Centre of Belarus (Minsk, Republic of Belarus), ClinicalTrials.gov Identifier: NCT07524816. The patients were 23-68 years of age (median 47 years). The CAR-T cell product was manufactured using lentiviral vector encoding anti-CD19 CAR. The median follow-up was 7.85 months for the entire cohort and 20.12 months for patients without events. Generally, complete response was achieved in 57.5% of patients. The 4-year event-free survival (EFS) rate was 46.2 ± 6.3%, and the 4-year overall survival (OS) rate was 67 ± 5.9%. Among patients with follicular lymphoma (FL), complete response was achieved in 83.3% patients. The 4-year EFS was 81.7 ± 9.6%. The safety profile was acceptable: cytokine release syndrome (CRS) was detected in 43.4% of patients (≥ grade 3 in 2.6%). No cases of grade 4 CRS were reported, and neurotoxicity (ICANS) was identified in 26.3% of patients (≥ grade 3 in 5.3%, grade 4 ICANS occurred in two patients - 2.6%). The anti-CD19 CAR T-cell product demonstrates good efficacy and acceptable toxicity in patients with r/r BCL. The use of such a product is the only available option for patients in countries where commercial products are not accessible. https://clinicaltrials.gov/study/NCT07524816, identifier NCT07524816.","[""Clinical Trial"", ""Journal Article""]","[""Konoplya NE"", ""Doroshenko TM"", ""Zharkova KY"", ""Savich TV"", ""Seviaryn IM"", ""Bobrova NM"", ""Beleevsky AA"", ""Sarydze EK"", ""Polyakov SL""]",10.3389/fonc.2026.1862517,Konoplya NE,Frontiers in oncology,2234-943X,,Front Oncol,eng,Polyakov SL,[],1862517,42539439,pmc-id: PMC13423673;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42539439/,Academic anti CD19 CAR-T cell therapy for relapsed/refractory B-cell lymphomas in real-world clinical practice: a prospective cohort study,16,ElhjXrxeb3tIjimqt,FjLVMhm8YMEAQNVO6
"Tumor Treating Fields improve survival when started after chemoradiotherapy in newly diagnosed glioblastoma, but the safety and feasibility of initiating treatment before and during radiotherapy remain uncertain. PriCoTTF is a prospective, open-label, nonrandomized, multicenter phase I/II trial. Arm A enrolled adults aged 18 to 70 years with newly diagnosed IDH-wildtype glioblastoma or gliosarcoma, Karnofsky Performance Status of at least 60, and planned focal radiotherapy to 60 Gy in 30 fractions. TTFields at 200 kHz were initiated 2 to 4 weeks after surgery and 1 to 2 weeks before radiotherapy. The primary endpoint was protocol-defined treatment-limiting toxicity from TTFields initiation through 4 weeks after radiotherapy. Twenty evaluable patients comprised the Arm A feasibility cohort. No protocol-defined treatment-limiting toxicities occurred (0 of 20 patients; exact 95% CI, 0.0%-16.8%). Grade 3 or higher adverse events occurred in 12 patients (60%), predominantly hematologic toxicity attributable to chemoradiotherapy; lymphopenia occurred in 6 patients (30%). Median usage through visit 4 was 76.5%, and median time to first attainment of at least 75% daily use was 2 days. Median progression-free survival was 6.9 months (95% CI, 2.7-14.0), and median overall survival was 18.0 months (95% CI, 12.1-19.9). Initiation of TTFields before and during radiotherapy was feasible and was not associated with protocol-defined treatment-limiting toxicity in the Arm A cohort. Because the TLT definition was narrow and efficacy analyses were exploratory and exposure-conditioned, these findings should be interpreted as feasibility data rather than evidence of improved tumor control or survival. The results support randomized evaluation of earlier TTFields integration in newly diagnosed glioblastoma. German Clinical Trials Register DRKS00016667, registered 26 February 2019.","[""Journal Article"", ""Clinical Trial, Phase I"", ""Clinical Trial, Phase II"", ""Multicenter Study""]","[""Kebir S"", ""Oster C"", ""Sharma S"", ""Jekel L"", ""Schmidt T"", ""Grieger J"", ""Cappello G"", ""Kizina K"", ""Lazaridis L"", ""Rauschenbach L"", ""Ahmadipour Y"", ""Dammann P"", ""Junker A"", ""Keyvani K"", ""Feldheim J"", ""Pierscianek D"", ""Scheffler B"", ""Proescholdt M"", ""Hau P"", ""Grosu AL"", ""Krex D"", ""Sure U"", ""Kleinschnitz C"", ""Pöttgen C"", ""Stuschke M"", ""Glas M""]",10.1186/s12885-026-16613-y,Kebir S,BMC cancer,1471-2407,1,BMC Cancer,eng,Glas M,"[""Humans"", ""Glioblastoma"", ""Middle Aged"", ""Adult"", ""Female"", ""Aged"", ""Male"", ""Brain Neoplasms"", ""Feasibility Studies"", ""Young Adult"", ""Prospective Studies"", ""Adolescent"", ""Electric Stimulation Therapy"", ""Chemoradiotherapy"", ""Treatment Outcome""]",,42538542,pmc-id: PMC13425971;,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42538542/,Safety and feasibility of tumor treating fields initiated before and during radiotherapy for newly diagnosed glioblastoma: results from the Arm A feasibility cohort of a phase I/II trial (PriCoTTF),26,ElhjXrxeb3tIjimqt,FjLVMhm8YMEAQNVO6
"Sex-related differences in outcomes after major orthopaedic surgery remain under-investigated, and the prognostic relevance of a history of venous thromboembolism (VTE) is unclear. The ORTHO-START registry is a prospective, multicenter study including 1,077 consecutive adults undergoing major orthopaedic surgery (elective hip/knee arthroplasty or urgent hip fracture repair) across six Italian centers between July 2018 and March 2022. Baseline characteristics, perioperative complications, and antithrombotic therapy were collected. The primary outcome was all-cause mortality at 24 months; secondary outcomes were thromboembolic and bleeding events. Multivariable logistic regression identified predictors of mortality. Women represented 72.3% (n = 775) of the cohort and were older than men (80.6 ± 10.0 vs. 76.2 ± 13.0 years, p < 0.001). Urgent procedures comprised 65.6% (n = 706) of surgeries, predominantly involving women (n = 542). At 24 months, mortality was higher in men (31 vs. 18%, p = 0.018). Independent predictors of mortality included male sex (odds ratio [OR] = 2.6, 95% confidence interval [CI]: 1.8-4.0), older age, lower body mass index, urgent surgery (OR = 7.2, 95% CI: 4.1-12.4), and prior VTE (OR = 5.7, 95% CI: 1.4-23.9). Causes of death were known for 160/210 (76.2%): neurological complications were most frequent (25%), followed by cardiovascular disease (21.3%) and immobility-related causes (14.4%); pulmonary embolism accounted for 1.3% of deaths. Thrombotic and hemorrhagic events occurred in both sexes without significant differences. Male sex and a history of VTE are independent predictors of long-term mortality following major orthopaedic surgery. Incorporating these factors into preoperative risk assessment may improve management and postoperative outcomes.","[""Clinical Trial"", ""Journal Article""]","[""Grandone E"", ""Antonucci E"", ""Piazza G"", ""Barcellona D"", ""Rostagno C"", ""Colaizzo D"", ""de Laurenzo A"", ""di Rienzo G"", ""Gorgoglione F"", ""Maccagnano G"", ""Marongiu F"", ""Mastroianno M"", ""Marzolo M"", ""Mirabella L"", ""Moretti B"", ""Moretti AM"", ""Ostuni A"", ""Palareti G"", ""Margaglione M""]",10.1055/a-2918-4154,Grandone E,Seminars in thrombosis and hemostasis,0094-6176,,Semin Thromb Hemost,eng,Margaglione M,[],,42537674,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42537674/,Sex-Related Differences and Predictors of Mortality in Patients Undergoing Major Orthopaedic Surgery: Insights from the ORTHO-START Registry,,ElhjXrxeb3tIjimqt,FjLVMhm8YMEAQNVO6
"One unique feature of COVID-19-associated acute respiratory distress syndrome (ARDS) is surfactant deficiency because SARS-CoV-2 specifically attacks alveolar type 2 cells. In this study, we evaluated the effects of a synthetic surfactant (lucinactant) therapy in patients with COVID-19-associated ARDS. This open-label multicenter phase 1/2A trial enrolled adult patients with COVID-19-associated ARDS who were within 7 days of mechanical ventilation initiation. Lucinactant (160 mL or approximately 80 mg of total phospholipids per kilogram of lean body weight) was delivered intratracheally. One retreatment was allowed at ≥6-hour intervals. The primary end points were oxygenation index and PO2-to-fraction of inspired oxygen ratio up to day 5 after dosing. Other end points included time to deliver lucinactant and respiratory system compliance (Crs). We monitored peridosing events and adverse events up to 30 days after dosing. A total of 19 treated patients were enrolled (n=14, 73.7% receiving 1 dose; n=5, 26.3% receiving 2 doses). The mean age was 49 (SD 15) years. The mean time to administer lucinactant was 31 minutes. No significant changes were observed in oxygenation index (mean 10.4, SD 5.8 at baseline; 8.6, SD 2.7 at 12 hours; and 5.7, SD 2.4 on day 5; P=.12 via ANOVA) or PO2-to-fraction of inspired oxygen ratio (mean 193, SD 69 at baseline; mean 179, SD 57 at 12 hours; and mean 223, SD 105 on day 5; P=.44 via ANOVA). Crs also did not change significantly (mean 40.7, SD 17.8 mL/H2O at baseline; mean 33.6, SD 8.5 mL/H2O at 12 hours; and mean 55.4, SD 18.5 mL/cmH2O on day 5; P=.12 via ANOVA). A total of 36.8% (n=7) of the participants died (6 from secondary infection and sepsis >13 days after dosing). In total, 15.8% (n=3) of the patients experienced transient peridosing desaturation or surfactant regurgitation. Our study showed that intratracheal instillation of 1 to 2 doses of lucinactant in COVID-19-associated ARDS was generally well tolerated. There were no significant changes in oxygenation parameters or Crs. The data suggest that, when future studies of lucinactant in patients with ARDS with severe surfactant dysfunction are conducted, an earlier and longer treatment protocol using different delivery methods that reach a larger alveolar surface area, such as aerosolization, may be needed to yield any beneficiary effects.","[""Journal Article"", ""Clinical Trial, Phase II"", ""Multicenter Study"", ""Clinical Trial, Phase I""]","[""Huang YC"", ""Morris P"", ""Owens R"", ""Guardia C"", ""Keller S"", ""Belloso W"", ""Weinstein L"", ""Simmons P"", ""Simonson S""]",10.2196/77315,Huang YC,JMIR formative research,2561-326X,,JMIR Form Res,eng,Simonson S,"[""Humans"", ""Respiratory Distress Syndrome"", ""Male"", ""Female"", ""Middle Aged"", ""COVID-19"", ""COVID-19 Drug Treatment"", ""Aged"", ""Pulmonary Surfactants"", ""Fatty Alcohols"", ""Proteins"", ""Phosphatidylcholines"", ""Glycerides"", ""Treatment Outcome"", ""Drug Combinations"", ""Phosphatidylglycerols""]",e77315,42536986,pmc-id: PMC13427075;,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536986/,"Lucinactant, a Synthetic Surfactant for the Treatment of Acute Respiratory Distress Syndrome Caused by COVID-19: Phase 1/2A Trial",10,ElhjXrxeb3tIjimqt,FjLVMhm8YMEAQNVO6
"Myofascial pain syndrome (MPS) is a major cause of chronic neck pain, with tissue ischemia implicated as a contributing factor. This prospective, single-arm interventional study evaluated the analgesic effect of ultrasound-guided fascia hydrorelease (US-FHR) performed around arteries supplying the neck in patients with chronic neck MPS. Thirteen adults (median age 53.0 years; 38.5% female) underwent US-FHR targeting the perivascular fascia of either the transverse cervical or dorsal scapular artery using 2 mL of normal saline. Pain intensity was assessed by visual analog scale (VAS) at rest and during movement; disability by the 5-item Pain Disability Index, Japanese version (PDI-5-J); and arterial blood flow volume before and after the procedure. The primary outcome, pain VAS during movement, decreased from 49.0 mm (interquartile range [IQR], 44.5-64.0) at baseline to 22.0 mm (IQR, 14.5-31.5) at 15 min and 22.0 mm (IQR, 14.0-34.0) at 1 week (Hodges-Lehmann median difference, 30.5 mm [95% CI, 24.5 to 36.5] and 28.5 mm [95% CI, 18.5 to 37.0]; both P < 0.001). Pain VAS at rest improved from 21.0 mm (IQR, 13.0-43.5) to 8.0 mm at 15 min and 1 week (median difference, 14.5 mm [95% CI, 9.0 to 24.0; P = 0.001] and 13.5 mm [95% CI, 6.0 to 21.0; P = 0.007]). PDI-5-J decreased from 17.0 (IQR, 10.5-23.0) to 13.0 (IQR, 4.0-17.5) at 1 week (median difference, 5 [95% CI, 2-8; P = 0.004]). Blood flow volume increased from 11.2 mL/min (IQR, 4.5-14.4) to 17.2 mL/min (IQR, 6.1-23.7) immediately after US-FHR (median difference, + 4.1 mL/min [95% CI, + 2.5 to +8.9; P = 0.001]), although transient. One patient experienced transient bleeding that was promptly controlled. In this single-arm feasibility study, US-FHR around the target artery was simple and safe to perform and was associated with reduced neck pain. Because the study lacked a control group, these preliminary findings should be regarded as hypothesis-generating and require confirmation in controlled trials; they may also inform the future evaluation of MPS in other anatomical regions. Trial registration: UMIN Clinical Trials Registry, UMIN000053612.","[""Journal Article"", ""Clinical Trial""]","[""Hiroki T"", ""Kimura H"", ""Kobayashi T"", ""Horigome H"", ""Suda M"", ""Fukui S"", ""Suto T"", ""Obata H""]",10.1371/journal.pone.0350882,Hiroki T,PloS one,1932-6203,7,PLoS One,eng,Obata H,"[""Humans"", ""Female"", ""Neck Pain"", ""Middle Aged"", ""Prospective Studies"", ""Male"", ""Pain Measurement"", ""Myofascial Pain Syndromes"", ""Fascia"", ""Adult"", ""Ultrasonography, Interventional"", ""Arteries"", ""Treatment Outcome""]",e0350882,42536624,pmc-id: PMC13426918;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536624/,The analgesic effect of ultrasound-guided fascia hydrorelease around the artery for myofascial neck pain: a prospective single-arm interventional study,21,ElhjXrxeb3tIjimqt,FjLVMhm8YMEAQNVO6
"Extension follow-up trials are essential for understanding the long-term safety and efficacy of cardiovascular interventions. Whereas primary randomized trials primarily capture short-term outcomes, extended observation may reveal delayed benefits or harms that are highly relevant to clinical decision-making. However, methodologic standards for extension trials remain poorly defined, leading to inconsistent design, analysis, and reporting. This scientific statement outlines best practices for cardiovascular trial extensions, addressing outcome selection, duration and completeness of follow-up, and analytic strategies suited to evolving treatment effects. Practical considerations, including strategies for participant retention, reconsent, data continuity, and resource allocation, are also discussed.","[""Journal Article"", ""Review""]","[""Gaudino M"", ""Sandner S"", ""Bagiella E"", ""Beckman JA"", ""Belley-Cote EP"", ""Flather M"", ""Gregg AC"", ""Hameed I"", ""Pocock S"", ""Redfors B"", ""Rockhold F"", ""American Heart Association Leadership Committee of the Council on Clinical Cardiology"", ""Council on Cardiovascular and Stroke Nursing"", ""Council on Lifelong Congenital Heart Disease and Heart Health in the Young""]",10.1161/CIR.0000000000001458,Gaudino M,Circulation,0009-7322,,Circulation,eng,Rockhold F,[],,42544461,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42544461/,Methodologic Standards for Follow-Up Extension in Cardiovascular Trials: A Scientific Statement From the American Heart Association,,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
"Congenital heart defects afflict ≈1% of all births worldwide. Although deep learning has shown significant promise in automating and improving adult echocardiography analysis, existing pediatric-based models are often limited to single tasks and specific echocardiographic views. To address this, we introduce EchoAI-Peds, a multitask deep learning model for pediatric echocardiography. Our model was developed using the most comprehensive set of pediatric labels to date and is designed to integrate information from multiple views simultaneously. We trained a video-based vision transformer to simultaneously detect 28 congenital heart defects, structural and functional abnormalities, repairs, and interventions directly from complete pediatric echocardiography studies with multiple videos. Our model was developed using >700 000 videos derived from >12 000 studies performed at Stanford Medicine between 2014 and 2021. Specifically, our model was trained on 10 815 studies (median age, 8 [IQR 2-14] years; 45% girls) and validated on 1294 studies (median age, 9 [IQR 2-15] years; 46% girls). Model efficacy was tested on an internal held-out data set of 1336 studies from that same period. In addition, model generalizability was tested on a spatially and temporally distinct patient cohort at the Children's Hospital of Philadelphia using 2121 studies performed between 2024 and 2025. Our model achieved macroaveraged (area under the receiver operating characteristic curve (AUROC) values of 0.91 (95% CI, 0.90-0.92) on the internal test set (median age, 8 [IQR 2-14] years; 47% girls) and AUROC values of 0.89 (95% CI, 0.88-0.90) on the external test set (median age 6 [IQR 0.92-13] years; 44.4% girls). Moreover, EchoAI-Peds significantly outperformed adult-based echocardiography foundation models trained on substantially larger data sets, including EchoCLIP (internal AUROC=0.58, 95% CI, 0.56-0.60; external AUROC=0.61, 95% CI, 0.59-0.62) and EchoPrime (internal AUROC=0.58, 95% CI, 0.57-0.61; external AUROC=0.60, 95% CI, 0.59-0.62). Finally, our model demonstrated robust performance across patient age, patient sex, and studies with varying number of videos. Our findings demonstrate the remarkable potential for multitask deep learning models to aid the interpretation of pediatric echocardiograms. In addition, our results underscore the need for models that are specifically tailored to pediatric populations.","[""Journal Article""]","[""Cho J"", ""Mathur M"", ""Kaur D"", ""Duda M"", ""Dahlan A"", ""Krishnan A"", ""Leipzig M"", ""Shad R"", ""Gonzalez AK"", ""Logan J"", ""Seidman C"", ""Fong R"", ""Kumar A"", ""Zakka C"", ""Carter E"", ""Padiyath A"", ""Jones A"", ""Quartermain MD"", ""Langlotz CP"", ""Jolley MA"", ""Hiesinger W""]",10.1161/CIRCULATIONAHA.126.080619,Cho J,Circulation,0009-7322,,Circulation,eng,Hiesinger W,[],,42517220,pmc-id: PMC13416711;manuscript-id: NIHMS2190318;,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42517220/,A Multitask Deep Learning Model for Pediatric Echocardiography Analysis,,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
"Screening for atrial fibrillation (AF) on the basis of AF risk may be more effective. We aimed to develop, externally validate, and prospectively test a machine learning prediction model using electronic health records (EHRs) to guide AF screening. We developed and validated a random forest prediction model for new AF within 6 months, using age, sex, and 10 comorbidities (Future Innovations in Novel Detection of Atrial Fibrillation [FIND-AF] 2.0) in EHRs in the United Kingdom (n=2 081 139), Japan (n=7 795 244), Israel (n=2 166 795), Canada (n=627 919), and China (n=149 145). We conducted a prospective study where participants ≥30 years old without AF and with a CHA2DS2-VASc score ≥2 in men and ≥3 in women, stratified by FIND-AF 2.0 into high and low risk, undertook 4 ECG recordings per day for 3 weeks using a handheld ECG recorder, with a primary outcome of newly diagnosed AF. We estimated stroke risk associated with nonanticoagulated AF in patients with high FIND-AF 2.0 risk in the FinACAF (Finnish Anticoagulation in Atrial Fibrillation) registry of patients with AF (n=229 565). FIND-AF 2.0 was applicable to all EHRs and showed good to excellent prediction performance (United Kingdom: area under the receiver operating characteristic curve [AUROC], 0.819 [95% CI, 0.809-0.829]; Israel: AUROC, 0.835 [95% CI, 0.828-0.842]; Japan: AUROC, 0.751 [95% CI, 0.745-0.757]; Canada: AUROC, 0.747 [95% CI, 0.741-0.753]; China: AUROC, 0.753 [95% CI, 0.725-0.771]), with AUROC>0.7 in men and women in all cohorts, and improved performance compared with CHA2DS2-VASc and C2HEST. Of 1923 participants from 15 sites in the prospective study (mean age, 70.2 [SD 9.4] years), with a mean of 74.8 (SD, 19.4) ECG recordings, AF was diagnosed in 5 of 902 (0.6%) with low FIND-AF 2.0 risk and 46 of 1021 (4.5%) with high FIND-AF 2.0 risk (odds ratio, 8.46 [95% CI, 3.35-21.40], P<0.001). Median AF burden among high FIND-AF 2.0 risk-detected cases was 33.4% (interquartile range, 5.1%-91.6%), and 96.1% initiated oral anticoagulants. In the FinACAF registry, the rate of ischemic stroke for patients with high FIND-AF 2.0 risk, AF, and no anticoagulants was 6.0 events per 100 patient-years. The EHR-based machine learning model, FIND-AF 2.0, identifies a high-risk subpopulation for AF diagnosis among patients at elevated risk of stroke and could enable scalable, EHR-driven, risk-guided AF screening.","[""Journal Article""]","[""Nadarajah R"", ""Wu J"", ""Wahab A"", ""Reynolds C"", ""Haris M"", ""Joseph T"", ""Raveendra K"", ""Hurdus B"", ""Kazi K"", ""Bennett S"", ""Hayward C"", ""Mercer B"", ""Kang J"", ""Gao C"", ""Nakao YM"", ""Kawakami K"", ""Chang C"", ""Wai A"", ""Zhou J"", ""Tse G"", ""Benita TR"", ""Rokach L"", ""Arbel R"", ""Haim M"", ""Zahger D"", ""Labib D"", ""Flewitt J"", ""White JA"", ""Teppo K"", ""Lehto M"", ""Langén V"", ""Winstén AK"", ""Airaksinen KEJ"", ""Haukka J"", ""Halminen O"", ""Putaala J"", ""Hartikainen J"", ""Linna M"", ""Freedman B"", ""Svennberg E"", ""Camm AJ"", ""Lip GYH"", ""Gale CP""]",10.1161/CIRCULATIONAHA.126.079391,Nadarajah R,Circulation,0009-7322,,Circulation,eng,Gale CP,[],,42517218,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42517218/,Risk-Guided Screening for Atrial Fibrillation Using Electronic Health Records,,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Journal Article""]","[""Ndumele CE"", ""Rangaswami J"", ""Rodriguez F""]",10.1161/CIRCULATIONAHA.126.080903,Ndumele CE,Circulation,0009-7322,4,Circulation,eng,Rodriguez F,[],409-412,42507784,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42507784/,Cardiovascular-Kidney-Metabolic Syndrome: A User's Guide to the Guidelines,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Journal Article""]","[""Powell-Wiley TM"", ""Williams M"", ""Davis EM""]",10.1161/CIRCULATIONAHA.126.079442,Powell-Wiley TM,Circulation,0009-7322,4,Circulation,eng,Davis EM,[],400-404,42507783,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42507783/,Telehealth for Community-Engaged Cardiovascular Care in Rural Populations,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Letter""]","[""Zhang X"", ""Zhang P""]",10.1161/CIRCULATIONAHA.126.079292,Zhang X,Circulation,0009-7322,4,Circulation,eng,Zhang P,[],e42-e43,42507782,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42507782/,"Letter by Zhang and Zhang Regarding Article, ""Short-Term Anticoagulation Versus Dual Antiplatelet Therapy for Preventing Device Thrombosis Following Left Atrial Appendage Closure: The ANDES Randomized Clinical Trial""",154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Journal Article""]","[""Huffman MD"", ""Vijay A"", ""Mahmoud Z""]",10.1161/CIRCULATIONAHA.126.080904,Huffman MD,Circulation,0009-7322,4,Circulation,eng,Mahmoud Z,[],413-415,42507781,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42507781/,2026 Cardiovascular-Kidney-Metabolic Guidelines: Practical Implementation Strategies,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Journal Article""]","[""Lloyd-Jones DM""]",10.1161/CIRCULATIONAHA.126.080905,Lloyd-Jones DM,Circulation,0009-7322,4,Circulation,eng,Lloyd-Jones DM,[],416-419,42507780,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42507780/,Cardiovascular-Kidney-Metabolic Syndrome: A Historic Perspective,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
"Cardiovascular diseases, particularly stroke, are leading causes of dementia. Several common cardiac interventions such as coronary artery bypass grafting and transcatheter aortic valve implantation are also associated with cognitive decline. However, cognitive outcomes continue to be poorly collected in clinical trials of cardiovascular diseases. In this article, we review the limitations of current approaches to cognitive assessment in cardiovascular disease studies. When assessed, there is wide variation in cognitive tasks used, and tasks have limited population-specific validation, are subject to floor and ceiling effects, and may suffer from sociocultural and linguistic biases. Many tasks are not available in multilingual formats and often rely on face-to-face testing with trained coordinators. All conventional cognitive outcomes in cardiovascular trials are associated with substantial incompletion, especially among older and more impaired individuals, the very people most important to capture. This nonrandom missingness generates survivor and attrition biases, an unacceptable situation for any trial outcome. Last, the meaning of measured cognitive outcomes is often unclear for patients, caregivers, clinicians, and regulators. To help address these limitations, we propose a new framework, major adverse cognitive events (MACE-Cog), to better capture cognitive outcomes in stroke and other cardiovascular populations. As an inclusive construct reflecting the multidimensional nature of cognitive decline, major adverse cognitive events do not rely solely on performance on cognitive testing but also consider inability to complete cognitive testing due to cognitive-behavioral factors, reported symptoms of cognitive decline, impairment in activities of daily living as a result of cognitive impairment, new clinical diagnoses of dementia, and care home admission. We hope that the proposed composite outcome and multiple use cases presented spark progress in cardiovascular research toward more inclusive approaches to the study of cognitive outcomes that move beyond the confines of cognitive tests alone.","[""Journal Article"", ""Review""]","[""Ganesh A"", ""Sujanthan S"", ""Muir RT"", ""Joundi RA"", ""Hill MD"", ""Quinn TJ"", ""Menon B"", ""Sajobi T"", ""Rabin JS"", ""Dainty KN"", ""Barense MD"", ""Lanctôt KL"", ""Kennedy J"", ""Kharbanda RK"", ""Lee DS"", ""Gaudio MFL"", ""Fremes S"", ""Masterson Creber RM"", ""Smith EE"", ""Swartz RH""]",10.1161/CIRCULATIONAHA.125.077180,Ganesh A,Circulation,0009-7322,4,Circulation,eng,Swartz RH,"[""Humans"", ""Stroke"", ""Cardiovascular Diseases"", ""Cognition"", ""Cognition Disorders"", ""Cognitive Dysfunction""]",378-394,42507779,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42507779/,"Major Adverse Cognitive Events (MACE-Cog): A New ""MACE"" Framework for Cognitive Outcomes in Cardiovascular Diseases and Stroke",154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Letter""]","[""Xu L"", ""Hrybouski S"", ""Ernie Liao TW"", ""Dong J"", ""Khoshknab M"", ""Callans D"", ""Marchlinski FE"", ""Witschey WR"", ""Desjardins B"", ""Nazarian S""]",10.1161/CIRCULATIONAHA.126.080170,Xu L,Circulation,0009-7322,4,Circulation,eng,Nazarian S,[],e48-e49,42507778,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42507778/,"Response by Xu et al to Letter Regarding Article, ""Geometric Features of Ventricular Tachycardia Corridors in Patients with Ischemic Cardiomyopathy""",154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Journal Article""]","[""Silberg J"", ""Eckmann P"", ""Boen J"", ""Zou J""]",10.1161/CIRCULATIONAHA.126.080880,Silberg J,Circulation,0009-7322,4,Circulation,eng,Zou J,[],395-399,42507777,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42507777/,Agentic and Generative AI for Drug Discovery,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Letter""]","[""Eppenberger P"", ""Van Schaik KD"", ""Hajdas I"", ""Ibrahim M"", ""Wood AE"", ""Rühli F"", ""Othman MM""]",10.1161/CIRCULATIONAHA.126.079811,Eppenberger P,Circulation,0009-7322,4,Circulation,eng,Othman MM,[],375-377,42507776,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42507776/,Medial Arterial Calcification in a 4500-Year-Old Egyptian King: A Deep-Time View of a Vascular Calcification Continuum,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Letter""]","[""Nayyar S""]",10.1161/CIRCULATIONAHA.125.078896,Nayyar S,Circulation,0009-7322,4,Circulation,eng,Nayyar S,[],e46-e47,42507775,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42507775/,"Letter by Nayyar Regarding Article, ""Geometric Features of Ventricular Tachycardia Corridors in Patients With Ischemic Cardiomyopathy""",154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Letter""]","[""Rodés-Cabau J"", ""Nombela-Franco L"", ""Pavesi M"", ""Côté M"", ""Salaun E""]",10.1161/CIRCULATIONAHA.126.080579,Rodés-Cabau J,Circulation,0009-7322,4,Circulation,eng,Salaun E,[],e44-e45,42507774,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42507774/,"Response by Rodés-Cabau et al to Letter Regarding Article, ""Short-Term Anticoagulation Versus Dual Antiplatelet Therapy for Preventing Device Thrombosis Following Left Atrial Appendage Closure: The ANDES Randomized Clinical Trial""",154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Letter""]","[""Li W"", ""Xiong Q""]",10.1161/CIRCULATIONAHA.125.078651,Li W,Circulation,0009-7322,4,Circulation,eng,Xiong Q,[],e40-e41,42507773,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42507773/,"Letter by Li and Xiong Regarding Article, ""Short-Term Anticoagulation Versus Dual Antiplatelet Therapy for Preventing Device Thrombosis Following Left Atrial Appendage Closure: The ANDES Randomized Clinical Trial""",154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
"Data on the prognostic value of incidental coronary artery calcium (CAC) from nongated chest computed tomography scans are limited. Using paired computed tomography scans from the MESA (Multi-Ethnic Study of Atherosclerosis) exam 5, we evaluated the relationship between nongated CAC, gated CAC, and future cardiovascular events. Between April 2010 and December 2011, a total of 2601 participants underwent same-day gated and nongated chest computed tomography scans. After excluding 106 with previous coronary heart disease or cardiovascular disease and 23 for missing covariates, 2472 participants formed the study population. Gated and nongated scans were interpreted at a core laboratory, blinded to acquisition methodology. Cox regression examined associations between CAC (gated and nongated) and incident coronary heart disease/cardiovascular disease events. Correlation was assessed with Pearson coefficients, model performance with receiver operating characteristic curves and C-statistic, and overall accuracy with Brier scores. Among the 2472 participants, 53% were female, 38% white, 13% Chinese, 26% Black, and 23% Hispanic/Latino. Compared with participants with zero CAC, those with moderate (101-299) and severe (≥300) nongated CAC had higher coronary heart disease risk (hazard ratio, 2.67 [95% CI, 1.14-6.27]; hazard ratio, 5.22 [95% CI, 2.37-11.5]) and cardiovascular disease risk (hazard ratio, 1.32 [95% CI, 1.32-4.04]; hazard ratio, 2.89 [95% CI, 1.68-4.96]). Gated and nongated log-standardized CAC highly correlated (r=0.961; P<0.001). The area under the receiver operating characteristic curves, C-statistic, and Brier scores were statistically similar for gated and nongated CAC. Nongated CAC predicts cardiovascular events with performance comparable to gated CAC. Given the large number of nongated scans performed annually, incorporating their quantification into clinical practice offers a scalable approach to personalized preventive care. Our findings are particularly relevant in light of the recent 2026 American College of Cardiology/American Heart Association dyslipidemia guidelines, which endorse the use of incidental CAC from nongated computed tomography scans for atherosclerotic cardiovascular disease risk stratification and guiding lipid-lowering therapy.","[""Journal Article"", ""Comparative Study""]","[""Verghese D"", ""Trujillo R"", ""Abraham D"", ""McClelland RL"", ""Kinninger A"", ""Manubolu S"", ""Aldana J"", ""Cubeddu RJ"", ""Drachman D"", ""Inglessis-Azuaje I"", ""Wang DD"", ""Fahed A"", ""Brumback L"", ""Blaha MJ"", ""Allison M"", ""Budoff MJ""]",10.1161/CIRCULATIONAHA.125.078431,Verghese D,Circulation,0009-7322,4,Circulation,eng,Budoff MJ,"[""Humans"", ""Female"", ""Male"", ""Aged"", ""Predictive Value of Tests"", ""Incidence"", ""Tomography, X-Ray Computed"", ""Coronary Artery Disease"", ""Vascular Calcification"", ""Aged, 80 and over"", ""Middle Aged"", ""Coronary Vessels"", ""Risk Factors""]",302-312,42507772,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42507772/,Predictive Value of Coronary Artery Calcium Score From Nongated Chest CT Scans Compared With Gated Scans and Incidence of Cardiovascular Events,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Editorial""]","[""Rodriguez F"", ""Langlotz CP""]",10.1161/CIRCULATIONAHA.126.081204,Rodriguez F,Circulation,0009-7322,4,Circulation,eng,Langlotz CP,[],313-315,42507771,pmc-id: PMC13410989;manuscript-id: NIHMS2190785;,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42507771/,Opportunistic Coronary Artery Calcium Screening: Time for Clinical Implementation,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Editorial""]","[""Maron BA"", ""Khan SS"", ""Joynt Maddox KE""]",10.1161/CIRCULATIONAHA.126.080952,Maron BA,Circulation,0009-7322,4,Circulation,eng,Joynt Maddox KE,[],301,42507770,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42507770/,Contextualizing Results and Recommendations,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Journal Article""]","[""Brewer LC"", ""Joseph JJ"", ""Cooper LA""]",10.1161/CIRCULATIONAHA.126.080897,Brewer LC,Circulation,0009-7322,4,Circulation,eng,Cooper LA,[],405-408,42507769,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42507769/,"Cardiovascular-Kidney-Metabolic Syndrome: Population and Policy Implications: 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome",154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Journal Article""]","[""Steinhauser ML""]",10.1161/CIRCULATIONAHA.126.080204,Steinhauser ML,Circulation,0009-7322,4,Circulation,eng,Steinhauser ML,[],299-300,42507768,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42507768/,Translational Cardiovascular Science for the Circulation Community,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
"Aging is associated with increases in pulmonary pressure related to concomitant age-associated left ventricular remodeling, diastolic dysfunction, and declines in pulmonary function. Little is known regarding morphological changes in the pulmonary arterial vasculature underlying these associations. Our aim was to determine the associations between pulmonary vascular arterial remodeling, reflected in distal pruning and proximal dilation, and cardiac structure and function, pulmonary pressure, and functional outcomes. Among 2275 participants in the community-based Atherosclerosis Risk in Communities study (ARIC) who underwent echocardiography and noncontrast cardiac computed tomography at study visit 7 (2018-2019), we quantified the fraction of total pulmonary vascular area comprised of arterial vessels with cross-sectional area <5 mm2 (aBV5/aTBV) and arterial vessels with cross-sectional area >10 mm2 (aBVg10/aTBV) using a validated image processing approach. We assessed the associations of aBV5/aTBV and aBVg10/aTBV with echocardiographic measures of cardiac structure and function and pulmonary artery systolic pressure using multivariable linear regression models adjusted for demographics and cardiovascular risk factors. We also evaluated associations of pulmonary vascular arterial remodeling metrics with circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide), self-reported dyspnea, and incident heart failure. Mean age was 80±4 years, 61% were women, 22% reported Black race, and mean left ventricular ejection fraction was 64±7%. Mean aBV5/aTBV was 0.30±0.08, and aBVg10/aTBV was 0.45±0.09. Lower aBV5/aTBV, reflecting greater distal pruning, and higher aBVg10/aTBV, reflecting greater proximal dilation, were both associated with greater left ventricular remodeling, worse diastolic function, and worse systolic function. Lower aBV5/aTBV and higher aBVg10/aTBV demonstrated nonlinear associations with greater pulmonary artery systolic pressure. Both lower aBV5/aTBV and higher aBVg10/aTBV were associated with higher circulating NT-proBNP and greater odds of moderate to severe dyspnea. Higher aBVg10/aTBV, in particular, was associated with greater risk of incident heart failure over a 4-year follow-up with a hazard ratio of 1.25 (95% CI, 1.03-1.51) per one SD in aBVg10/TBV. Among older adults, pulmonary vascular arterial remodeling is associated with greater left ventricular remodeling, worse diastolic and systolic dysfunction, greater pulmonary artery systolic pressure, greater odds of significant dyspnea, and greater risk of heart failure development. Our findings clarify the morphologic changes in the pulmonary vasculature that link cardiac dysfunction to higher pulmonary pressure in late life and may appear before symptomatology.","[""Journal Article""]","[""Dewanjee A"", ""Lamberson V"", ""Yang Y"", ""Giugni FR"", ""Claggett BL"", ""Matsushita K"", ""Blaha MJ"", ""Washko G"", ""San José Estépar R"", ""Nardelli P"", ""San José Estépar R"", ""Shah AM""]",10.1161/CIRCULATIONAHA.125.077856,Dewanjee A,Circulation,0009-7322,,Circulation,eng,Shah AM,[],,42478373,pmc-id: PMC13390777;manuscript-id: NIHMS2189505;,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42478373/,"Association of Pulmonary Vascular Remodeling With Cardiac Structure and Function, Pulmonary Pressure, and Heart Failure in Late Life: The Atherosclerosis Risk in Communities (ARIC) Study",,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
"Although medically tailored groceries (MTG) hold promise to improve food and nutrition security and health among patients with diet-related illnesses and social needs, few randomized trials have been performed. We enrolled 460 Medicaid-insured adults with type 2 diabetes and elevated hemoglobin A1c (HbA1c) between November 2021 and July 2022 in a randomized controlled trial of MTG in southern California. Eligibility was based on at least 2 HbA1c measurements ≥7.5% in the past year. Participants were randomized 1:1:1 to usual-care (N=153), lower-dose MTG (N=153), or higher-dose MTG (N=154) for 6 months, with the prespecified primary assessment comparing the combined MTG groups with control. MTG was provided as weekly home deliveries of healthy produce, scaled to household size ($100 to $170 per month for the lower dose and $135 to $210 per month for the higher dose), along with matched recipes and telenutrition counseling. The primary outcome was a change in HbA1c at 6 months. Secondary outcomes included changes in food security and nutrition security, measured by surveys, and hypertension and body mass index, measured during clinical care encounters; evaluation of dose-response comparing the lower-dose and higher-dose arms; and effects in key population subgroups. At baseline, mean (SD) age was 59.2 (13.2) years, 284 (64.8%) were women, 373 (85.2%) reported Hispanic ethnicity, 254 (58%) reported food insecurity, and mean (SD) HbA1c was 9.40 (1.53). Among intervention participants, 244 (83.3%) reported eating most or all food provided, and 63 (21.5%) engaged in telenutrition counseling. Compared with baseline, HbA1c declined by 0.66 points in the intervention and 0.25 points in the control group, a treatment difference of -0.40 points (95% CI, -0.73, -0.08; P=0.016). Higher-dose and lower-dose MTG produced similar reductions. Odds of food security and nutrition security increased by 2.12 (95% CI, 1.13, 3.99; P=0.020) and 3.65 (95% CI, 1.84, 7.25; P<0.001), respectively. Hypertension and body mass index did not significantly change. Results were consistent in prespecified subgroup analyses by sex, education, baseline food security, baseline nutrition security, and baseline HbA1c level. Findings were similar in analyses adjusting for baseline demographics, food insecurity, nutrition insecurity, self-reported health, comorbidities, and medication changes. In this randomized trial among Medicaid-insured, racially/ethnically diverse patients with type 2 diabetes, MTG lowered HbA1c and improved food and nutrition security. URL: https://clinicaltrials.gov; Unique identifier: NCT05407376.","[""Journal Article""]","[""Nau C"", ""Wu JHY"", ""Han B"", ""Habib M"", ""Li X"", ""Padilla A"", ""Nelson C"", ""Chao C"", ""Schwartz P"", ""Mozaffarian D""]",10.1161/CIRCULATIONAHA.125.077982,Nau C,Circulation,0009-7322,,Circulation,eng,Mozaffarian D,[],,42478360,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42478360/,"Effects of a ""Food Is Medicine"" Intervention on Glucose Control Among Medicaid-Insured Patients With Type 2 Diabetes: A Randomized Controlled Trial",,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Journal Article""]","[""DeFilippis EM"", ""Kittleson MM""]",10.1161/CIRCULATIONAHA.126.081604,DeFilippis EM,Circulation,0009-7322,3,Circulation,eng,Kittleson MM,[],296-298,42475442,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42475442/,Ethics of Navigating Organ Scarcity in Heart Transplantation,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
"Cardiac sarcoidosis is a granulomatous myocarditis, classified by some authorities as an infiltrative cardiomyopathy and by others as an inflammatory cardiomyopathy, that carries an elevated risk of life-threatening arrhythmias, heart failure, and sudden cardiac death. Despite its clinical importance, diagnosis remains challenging. No single modality achieves both high sensitivity and specificity, and the 4 major consensus documents-comprising expert consensus statements, clinical practice guidelines, and a scientific statement-differ in diagnostic thresholds and can yield discordant diagnoses when applied to the same patient. Genetic cardiomyopathies account for a meaningful fraction of patients diagnosed with presumed isolated cardiac sarcoidosis. This primer organizes the diagnostic approach around 2 clinical contexts: de novo cardiac presentation with unexplained atrioventricular block, ventricular arrhythmia, or heart failure without previous sarcoidosis; and cardiac screening in patients with established extracardiac sarcoidosis. In nonurgent presentations, concordant cardiac magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography abnormalities are accepted as sufficient for diagnosis; endomyocardial biopsy is indicated when imaging is inconclusive or giant cell myocarditis must be excluded. Advanced imaging should precede permanent device implantation in all de novo presentations. Isolated cardiac sarcoidosis represents the most diagnostically challenging phenotype. A 5-step pathway is presented that integrates advanced imaging, tissue acquisition when it would change management, and genetic evaluation. Expert opinion on histologic confirmation in nonurgent presentations is divided, and no diagnostic approach has been prospectively validated.","[""Journal Article"", ""Review""]","[""Lehtonen J"", ""Birnie DH""]",10.1161/CIRCULATIONAHA.126.079275,Lehtonen J,Circulation,0009-7322,3,Circulation,eng,Birnie DH,"[""Humans"", ""Sarcoidosis"", ""Cardiomyopathies"", ""Positron-Emission Tomography""]",288-295,42475441,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42475441/,Diagnostic Approach to Cardiac Sarcoidosis,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Letter""]","[""Williams AM"", ""Wang CC"", ""McGann KC"", ""Trahanas J"", ""Lima B"", ""Ahmad A"", ""Petrovic M"", ""Absi T"", ""Quintana E"", ""England B"", ""Schlendorf K"", ""Bacchetta M"", ""Shah AS"", ""Bommareddi S""]",10.1161/CIRCULATIONAHA.126.079750,Williams AM,Circulation,0009-7322,3,Circulation,eng,Bommareddi S,[],268-270,42475440,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42475440/,Rapid Ultraoxygenated Recovery Without Preimplant Reanimation Using Older Donation After Circulatory Death Heart Donors,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Editorial""]","[""Walker MA"", ""Tian R""]",10.1161/CIRCULATIONAHA.126.081162,Walker MA,Circulation,0009-7322,3,Circulation,eng,Tian R,[],240-242,42475439,pmc-id: PMC13390783;manuscript-id: NIHMS2189258;,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42475439/,Cracking the Code of Cardiac ATP-Dependent Citrate Lyase With Wet and Dry Tools,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Letter""]","[""Bashian EJ"", ""O'Shea TF"", ""Campbell DN"", ""Justison GA"", ""Zhan J"", ""Ambardekar AV"", ""Kopecky BJ"", ""Rove JY"", ""Aftab M"", ""Reece TB"", ""Cleveland JC"", ""Teman NR"", ""Cain MT"", ""Hoffman JRH""]",10.1161/CIRCULATIONAHA.126.079915,Bashian EJ,Circulation,0009-7322,3,Circulation,eng,Hoffman JRH,[],265-267,42475438,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42475438/,Cold Oxygenated Rapid Recovery in Heart Donation After Circulatory Death,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Journal Article""]","[""Khan SS""]",10.1161/CIRCULATIONAHA.126.080163,Khan SS,Circulation,0009-7322,3,Circulation,eng,Khan SS,[],183-184,42475437,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42475437/,From Discovery to Impact in the Circulation Life Cycle,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Editorial""]","[""Fadel RA"", ""Aronow HD""]",10.1161/CIRCULATIONAHA.126.080861,Fadel RA,Circulation,0009-7322,3,Circulation,eng,Aronow HD,[],198-200,42475436,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42475436/,Stent-Free PCI: Have We Found the SELUTION?,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
"At a time when there was no unifying hypothesis and no broadly effective treatments for heart failure with a preserved ejection fraction (HFpEF), it was proposed that HFpEF represented a multitude of different disorders. Accordingly, characterization of phenotypic heterogeneity was envisioned as a means of identifying novel causal pathways that could lead to new treatments while simultaneously discerning patients who would selectively benefit from a specific therapy. However, efforts over the past decade to characterize phenotypic diversity in diverse and complex ways have not achieved these goals. Subgroup analyses of neutral HFpEF trials have failed to reliably identify responders to treatments. Neither proteomics nor unsupervised cluster analysis across multiple phenotypic domains has yielded reproducible results (even in the same dataset), elucidated novel mechanistic pathways for new drug development, or identified patients most likely to benefit from treatment. In marked contrast to these efforts to characterize phenotypic heterogeneity, large-scale trials in HFpEF enrolled patients using broad eligibility criteria, and they established the benefits of sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists without evidence for subgroup effects. However, it is noteworthy that patients enrolled in recent large-scale HFpEF trials were characterized by general uniformity with respect to the presence of excess adiposity, with central obesity being a feature of the vast majority of enrolled participants. Of note, patients with obesity showed particularly large benefits when treated with effective drugs for HFpEF. These observations raise the possibility that, if these trials had permitted the participation of patients with class III obesity or with lower natriuretic peptide levels, the magnitude of the observed treatment effects might have been greater than originally reported. These findings are consistent with a central role for visceral adiposity (and the secretion of an altered suite of adipokines) in the pathogenesis of HFpEF. Therefore, because the field of HFpEF has a unifying hypothesis (applicable to the large majority of patients), enrolled a broad population of patients in large-scale trials without subgroup interactions, and has several broadly applicable effective treatments (as is true for heart failure with a reduced ejection fraction), the motivation to characterize phenotypic heterogeneity in HFpEF in complex ways may no longer be supported or needed.","[""Journal Article"", ""Review""]","[""Packer M"", ""Schiattarella GG"", ""Petrie MC"", ""Burkhoff D"", ""Butler J"", ""Lam CSP"", ""Zannad F"", ""Vaduganathan M"", ""Borlaug BA""]",10.1161/CIRCULATIONAHA.126.079235,Packer M,Circulation,0009-7322,3,Circulation,eng,Borlaug BA,"[""Humans"", ""Heart Failure"", ""Stroke Volume"", ""Phenotype"", ""Treatment Effect Heterogeneity"", ""Treatment Outcome"", ""Clinical Trials as Topic""]",271-287,42475435,pmc-id: PMC13378760;manuscript-id: NIHMS2186822;,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42475435/,Does Characterization of Phenotypic Heterogeneity Provide Mechanistic Insights or Influence the Response to Treatment? Experience in Positive and Neutral Trials in Patients With Heart Failure and a Preserved Ejection Fraction,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
"Metabolic adaptation and maladaptation are hallmarks of the failing heart and may be a target for therapeutic interventions. For example, sustained glucose oxidation during cardiac stress is associated with increased activity and abundance of ACL (ATP-dependent citrate lyase, Acly), which produces acetyl-coenzyme A (CoA) from citrate and CoA and supports de novo lipid synthesis. However, our understanding of how ACL supports cardiac metabolic adaptation and its potential to modulate disease pathophysiology has not yet been investigated. We used human heart tissue samples from healthy donors and patients with nonischemic cardiomyopathy. Next, we used CRISPR (clustered, regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated 9) gene editing to inactivate Acly in cardiomyocytes of Myh6-Cas9 mice. In vivo positron emission tomography and ex vivo stable isotope tracer labeling were used to quantify metabolic flux changes in response to Acly knockdown. We conducted a multi-omics analysis using RNA sequencing and mass spectrometry-based metabolomics and proteomics. Experimental data were integrated into computational modeling using the metabolic network CardioNet to identify significantly dysregulated metabolic processes at a systems level. We observed reduced ACL abundance and activity in human heart tissue samples from patients with nonischemic cardiomyopathy, which correlated with decreased abundance of Krebs cycle intermediates. Using CRISPR/Cas9 gene editing, we found that cardiac-specific loss of ACL reduces acetyl-CoA synthesis, leading to altered cardiac metabolism characterized by increased glucose uptake and oxidation, impaired energy flux, and elevated AMP to ATP ratios, which collectively promote left ventricular dysfunction. Transcriptomic and mass spectrometry-based metabolomics, as well as proteomic data, reveal compensatory cardiac lipid remodeling and reduced histone 3 acetylation. This metabolic stress promotes activation of AMPK (AMP kinase) and PKA (protein kinase A), which in turn mediates YAP (Yes-associated protein) inhibition through phosphorylation. Stable isotope tracer studies combined with CardioNet simulations demonstrated that increased IDH1 (isocitrate dehydrogenase 1) activity prevents allosteric inhibition of glycolysis from cytosolic citrate accumulation. AAV9-mediated cardiac Idh1 deletion improved cardiac function and energy provision, reducing YAP phosphorylation and restoring downstream YAP signaling. Our findings suggest that ACL plays a pivotal role in cardiac metabolism through regulating lipid synthesis and cardiac function. Exploiting compensatory pathways of citrate metabolism may improve cardiac function during heart failure.","[""Journal Article""]","[""Liu S"", ""Gammon ST"", ""Tan L"", ""Gao Y"", ""Kim K"", ""Elbatreek MH"", ""Arrieta A"", ""Williamson IK"", ""Salazar RL"", ""Pham J"", ""Davidian A"", ""Khanna Neicheril R"", ""Gould BD"", ""Vitrac H"", ""Sadiq A"", ""Dinh AQ"", ""Lien EC"", ""de Luna Vitorino FN"", ""Gongora JM"", ""Martinez SA"", ""Odenkirk MT"", ""Boatman AK"", ""Chappel JR"", ""Czer LSC"", ""Kransdorf EP"", ""Lefer DJ"", ""Hanson BM"", ""Garcia BA"", ""Baker EM"", ""Vander Heiden MG"", ""Lorenzi PL"", ""Taegtmeyer H"", ""Piwnica-Worms D"", ""Martin JF"", ""Karlstaedt A""]",10.1161/CIRCULATIONAHA.125.076453,Liu S,Circulation,0009-7322,3,Circulation,eng,Karlstaedt A,"[""Humans"", ""ATP Citrate (pro-S)-Lyase"", ""Animals"", ""Ventricular Dysfunction, Left"", ""Mice"", ""Myocytes, Cardiac"", ""Male"", ""Female"", ""Cardiomyopathies"", ""Energy Metabolism""]",223-239,42475434,pmc-id: PMC13378756;,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42475434/,Loss of ATP-Dependent Citrate Lyase Drives Left Ventricular Dysfunction by Metabolic Remodeling,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
"Caffeine is one of the most commonly consumed drugs in the world. It is found in various naturally occurring substances and can be ingested in a synthetically derived pure form. The majority of human subject-based research is observational and has focused on beverages and foods that contain caffeine. The relationships between caffeine and cardiovascular risk factors and diseases are complex, exhibiting heterogeneity depending on the nature of the caffeine consumed and individual-level propensities. Acute versus chronic caffeine-associated cardiovascular effects are often different. Most studies suggest an inverse J-shaped relationship between consumption of naturally occurring caffeinated products and blood pressure. Data on relationships between caffeine and diabetes are not consistent, but habitual coffee consumption has been associated with a lower risk of incident type 2 diabetes. Whereas no clear relationship between caffeine and blood lipids is evident, unfiltered coffee raises low-density lipoprotein cholesterol. Caffeine, studied primarily in the context of coffee, has been shown either to have no relationship or to be associated with a lower risk of coronary artery disease and heart failure. Randomized controlled trial data among regular caffeinated coffee drinkers showed that caffeinated coffee decreases the risk of atrial fibrillation occurrence but increases the frequency of premature ventricular contractions. Data are fairly consistent that moderate caffeine consumption, again studied primarily in the setting of coffee consumption, was associated with a lower risk of stroke. Data on high doses of caffeine such as that found in energy drinks are limited and generally suggest cardiovascular harm.","[""Journal Article"", ""Review""]","[""Marcus GM"", ""Hu FB"", ""van Dam RM"", ""Cornelis MC"", ""Dewland TA"", ""Kang J"", ""Larsson SC"", ""Page RL 2nd"", ""Parekh N"", ""American Heart Association Council on Lifestyle and Cardiometabolic Health; Council on Clinical Cardiology; and Stroke Council""]",10.1161/CIR.0000000000001454,Marcus GM,Circulation,0009-7322,,Circulation,eng,Parekh N,[],,42473796,,2026 Jul 20,2026,https://pubmed.ncbi.nlm.nih.gov/42473796/,Caffeine and Cardiovascular Disease: A Scientific Statement From the American Heart Association,,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Journal Article"", ""Published Erratum""]","[""Creager MA"", ""Barnes GD"", ""Giri J"", ""Mukherjee D"", ""Jones WS"", ""Burnett AE"", ""Carman T"", ""Casanegra AI"", ""Castellucci LA"", ""Clark SM"", ""Cushman M"", ""de Wit K"", ""Eaves JM"", ""Fang MC"", ""Goldberg JB"", ""Henkin S"", ""Johnston-Cox H"", ""Kadavath S"", ""Kadian-Dodov D"", ""Keeling WB"", ""Klein AJP"", ""Li J"", ""McDaniel MC"", ""Moores LK"", ""Piazza G"", ""Prenger KS"", ""Pugliese SC"", ""Ranade M"", ""Rosovsky RP"", ""Russo F"", ""Secemsky EA"", ""Sista AK"", ""Tefera L"", ""Weinberg I"", ""Westafer LM"", ""Young MN""]",10.1161/CIR.0000000000001462,Creager MA,Circulation,0009-7322,2,Circulation,eng,Young MN,[],e24,42441758,,2026 Jul 14,2026,https://pubmed.ncbi.nlm.nih.gov/42441758/,Correction to: 2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/ SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
"Pulmonary arterial hypertension (PAH) is a rare, progressive disease of the precapillary pulmonary arteries, characterized by fibroproliferative vascular remodeling, increased pulmonary vascular resistance, right ventricular failure, and premature death. Over the past four decades, substantial advances in understanding PAH pathobiology, epidemiology, diagnosis, and treatment have meaningfully improved patient outcomes. The pathobiology of PAH is multifaceted, involving endothelial dysfunction, smooth muscle cell hyperproliferation, inflammation, and dysregulation of key signaling pathways, including the prostacyclin, nitric oxide, endothelin 1, and bone morphogenetic/TGF-β (transforming growth factor β) axes. Dysregulation of the activin arm of the TGF-β pathway has emerged as a critical driver of vascular remodeling and is the target of sotatercept, the first antiremodeling therapy approved for PAH. Epidemiologically, PAH now more commonly affects older adults with cardiovascular and pulmonary comorbidities compared with historical cohorts. The global burden varies considerably, with methamphetamine-associated PAH rising in North America and schistosomiasis- and HIV-associated PAH prevalent in low- and middle-income countries, where underdiagnosis likely remains substantial. Diagnosis continues to be delayed, with advanced symptoms present at the time of diagnosis for most patients. Right heart catheterization remains essential for definitive diagnosis. Emerging tools, including artificial intelligence applied to electrocardiography, echocardiography, and electronic health records, hold promise for earlier case identification. Management and prognostication of PAH is based on regular risk stratification using validated multiparameter tools. The initial therapy choice is up-front combination therapy with 2 oral medications for most patients, with initial triple therapy that includes a parenteral prostacyclin used in high-risk patients. Add-on therapy with sotatercept is now an option for patients not achieving low risk, a strategy that led to improvements in hemodynamics, right heart function, and reduced the risk of adverse clinical outcomes in recent randomized trials. For patients who remain at higher risk despite maximal therapy, lung transplantation remains an important and life-saving option. Despite remarkable therapy progress, gaps persist in earlier detection, management of comorbid phenotypes, personalized therapy, and novel therapies targeting right ventricular failure. Ongoing clinical trials and translational research continue to advance the field toward the goal of normal survival and quality of life for patients with PAH.","[""Journal Article"", ""Review""]","[""Humbert M"", ""Zeder K"", ""Kovacs G"", ""Weatherald J""]",10.1161/CIRCULATIONAHA.126.079274,Humbert M,Circulation,0009-7322,2,Circulation,eng,Weatherald J,"[""Humans"", ""Pulmonary Arterial Hypertension"", ""Animals"", ""Vascular Remodeling"", ""Antihypertensive Agents"", ""Hypertension, Pulmonary""]",156-177,42441757,,2026 Jul 14,2026,https://pubmed.ncbi.nlm.nih.gov/42441757/,Transforming Pulmonary Arterial Hypertension: Key Milestones and Future Perspectives,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Journal Article""]","[""Fragkoulis Y"", ""Karampinos KI"", ""Karabinos I""]",10.1161/CIRCULATIONAHA.126.080922,Fragkoulis Y,Circulation,0009-7322,2,Circulation,eng,Karabinos I,[],178-181,42441756,,2026 Jul 14,2026,https://pubmed.ncbi.nlm.nih.gov/42441756/,Reversible ECG Changes in a Rare Case of Shock,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Letter""]","[""Astan R"", ""Kaçmaz F"", ""Sariçam E""]",10.1161/CIRCULATIONAHA.125.078319,Astan R,Circulation,0009-7322,2,Circulation,eng,Sariçam E,[],e17,42441755,,2026 Jul 14,2026,https://pubmed.ncbi.nlm.nih.gov/42441755/,"Letter by Astan et al Regarding Article, ""The Role of the Collateral Circulation in Stable Angina: An Invasive Placebo-Controlled Study""",154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Journal Article""]","[""Joynt Maddox KE""]",10.1161/CIRCULATIONAHA.126.080162,Joynt Maddox KE,Circulation,0009-7322,2,Circulation,eng,Joynt Maddox KE,[],85-87,42441754,,2026 Jul 14,2026,https://pubmed.ncbi.nlm.nih.gov/42441754/,An Integrated Ecosystem for Cardiovascular Science and Health,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Letter""]","[""Gentile F"", ""Emdin M"", ""Clemente A""]",10.1161/CIRCULATIONAHA.126.080168,Gentile F,Circulation,0009-7322,2,Circulation,eng,Clemente A,[],e22-e23,42441753,,2026 Jul 14,2026,https://pubmed.ncbi.nlm.nih.gov/42441753/,"Response by Gentile et al to Letters Regarding Article, ""Clinical and Prognostic Significance of Anomalous Origin of a Coronary Artery in Adults""",154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Letter""]","[""Han QJ"", ""Stefanescu Schmidt AC"", ""DeFaria Yeh D""]",10.1161/CIRCULATIONAHA.125.078090,Han QJ,Circulation,0009-7322,2,Circulation,eng,DeFaria Yeh D,[],e18-e19,42441752,,2026 Jul 14,2026,https://pubmed.ncbi.nlm.nih.gov/42441752/,"Letter by Han et al Regarding Article, ""Clinical and Prognostic Significance of Anomalous Origin of a Coronary Artery in Adults""",154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Letter""]","[""Li Q"", ""Zhang P""]",10.1161/CIRCULATIONAHA.125.078751,Li Q,Circulation,0009-7322,2,Circulation,eng,Zhang P,[],e20-e21,42441751,,2026 Jul 14,2026,https://pubmed.ncbi.nlm.nih.gov/42441751/,"Letter by Li and Zhang Regarding Article, ""Clinical and Prognostic Significance of Anomalous Origin of a Coronary Artery in Adults""",154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Editorial""]","[""Steg G""]",10.1161/CIRCULATIONAHA.126.082303,Steg G,Circulation,0009-7322,,Circulation,eng,Steg G,[],,42439489,,2026 Jul 13,2026,https://pubmed.ncbi.nlm.nih.gov/42439489/,Recurrent Venous Thromboembolism in Cancer: A Foreboding Event,,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Letter""]","[""Mahé I"", ""Chapelle C"", ""Righini M"", ""Le Gal G"", ""Klok FA"", ""Agnelli G"", ""Cajfinger F"", ""Sevestre MA"", ""Grenier PA"", ""Alexandre J"", ""Couturaud F"", ""Mismetti P"", ""Laporte S"", ""Chidiac J""]",10.1161/CIRCULATIONAHA.126.081437,Mahé I,Circulation,0009-7322,,Circulation,eng,Chidiac J,[],,42439484,,2026 Jul 13,2026,https://pubmed.ncbi.nlm.nih.gov/42439484/,Prognosis of Recurrent Venous Thromboembolism During Extended Apixaban Therapy for Cancer-Associated Thrombosis: Insights From the API-CAT Randomized Trial,,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
"An estimated 1 in 500 people lives with hypertrophic cardiomyopathy (HCM), a disease for which genetic diagnosis can identify family members at risk and increasingly guide therapy. Variants in the MYBPC3 gene, which encodes cardiac myosin-binding protein C (cMyBP-C), account for a significant proportion of HCM cases. However, many of these are classified as variants of uncertain significance, complicating clinical decision-making. Scalable methods for variant interpretation in disease-specific cell types are crucial for understanding variant impact and uncovering disease mechanisms. We developed a scaled multidimensional mapping strategy to evaluate the functional impact of variants across a critical domain of cMyBP-C. We incorporate saturation base editing at the native MYBPC3 locus, a long-read RNA sequencing-enabled assay of variant splice effects, and measurements of HCM-relevant phenotypes, including cMyBP-C abundance, hypertrophic signaling, and ubiquitin-proteasome function in human induced pluripotent stem cell-derived cardiomyocytes. Our multidimensional mapping strategy enabled high-resolution functional analysis of MYBPC3 variants in induced pluripotent stem cell-derived cardiomyocytes. Our massively parallel splicing assay identified novel splice-disrupting variants. Targeted transient base editing generated a comprehensive variant library at the native locus, capturing diverse variant effects on cellular HCM-relevant phenotypes. Integration of functional assays revealed that decreased cMyBP-C abundance is a key driver of HCM-related phenotypes. In parallel, downregulation of protein degradation was observed to correlate with MYBPC3 loss of function, and novel potential disease mechanisms were identified for missense variants near a critical binding domain. Bayesian estimates of variant effects enable the reclassification of clinical variants. This work provides a platform for extending genome engineering in induced pluripotent stem cells to multiplexed assays of variant effects across diverse disease-relevant cellular phenotypes, enhancing our understanding of variant pathogenicity and uncovering novel biological mechanisms that could inform therapeutic strategies.","[""Journal Article""]","[""Yamamoto Y"", ""Chua K"", ""Staudt D"", ""Ferrasse A"", ""Kirillova A"", ""De Jong HN"", ""Floyd BJ"", ""Cadisch C"", ""Wiel L"", ""Wang Q"", ""O'Neill MJ"", ""Tabet D"", ""Goryznski JE"", ""Huang Y"", ""Bai F"", ""Wilson RH"", ""Sharma A"", ""Tapales A"", ""Agrawal R"", ""Wheeler MT"", ""Mercola M"", ""MacRae CA"", ""Roden DM"", ""Roth FP"", ""Glazer AM"", ""Ashley EA"", ""Parikh VN""]",10.1161/CIRCULATIONAHA.125.075535,Yamamoto Y,Circulation,0009-7322,,Circulation,eng,Parikh VN,[],,42437345,,2026 Jul 12,2026,https://pubmed.ncbi.nlm.nih.gov/42437345/,Scaled Multidimensional Assays of Variant Effect Identify Sequence-Function Relationships in Hypertrophic Cardiomyopathy,,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
"There is broad consensus on the benefits of aerobic exercise training in patients with cardiovascular disease to improve cardiorespiratory fitness and lower the risk of adverse cardiovascular events. However, certain high-risk populations such as those with frailty, stroke, spinal cord injury, rheumatological conditions, or genetic cardiomyopathies and recipients of advanced heart failure therapies or cardiac implantable electronic devices warrant special considerations with regard to exercise training. This scientific statement summarizes the present state and future directions of exercise training for these high-risk populations, including functional deficits, responses to exercise training, modifications in training programs required to maximize safety and efficacy, and knowledge gaps in this field. Key findings common across most of these high-risk populations include (1) increased barriers to participation in exercise training at multiple levels; (2) low baseline cardiorespiratory fitness, creating heightened need for exercise interventions; (3) modifications to exercise prescription, frequently emphasizing strength, balance, and flexibility in addition to aerobic training, as well as accommodations with enhanced supervision and specialized equipment as needed; and (4) functional and quality-of-life gains in response to appropriately designed exercise programs that match or exceed those in more traditional populations. Future research is needed to further develop patient-centered training regimens designed to address the unique and heterogeneous needs of these populations, evaluate their impact on clinical and patient-centered outcomes, and advance scalable and equitable delivery of exercise therapies proven safe and effective.","[""Journal Article"", ""Review""]","[""Fleg JL"", ""Golbus JR"", ""Afilalo J"", ""Cornwell WK 3rd"", ""Cuccurullo S"", ""Dougherty CM"", ""Forman DE"", ""Huffman KM"", ""Khadanga S"", ""Mancini D"", ""Nytrøen K"", ""Reeves GR"", ""Taylor JA"", ""American Heart Association Exercise, Cardiac Rehabilitation, and Sports Cardiology Science Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Lifelong Congenital Heart Disease and Heart Health in the Young; Council on Quality of Care and Outcomes Research; and Stroke Council""]",10.1161/CIR.0000000000001456,Fleg JL,Circulation,0009-7322,,Circulation,eng,Taylor JA,[],,42422933,,2026 Jul 9,2026,https://pubmed.ncbi.nlm.nih.gov/42422933/,Exercise Training in High-Risk Populations: A Scientific Statement From the American Heart Association,,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Editorial""]","[""Itchhaporia D"", ""Yancy CW"", ""Rosen SE"", ""Mbakwem AC"", ""Münzel T"", ""Timmis A"", ""Kramer C""]",10.1161/CIR.0000000000001445,Itchhaporia D,Circulation,0009-7322,,Circulation,eng,Kramer C,[],,42418562,,2026 Jul 8,2026,https://pubmed.ncbi.nlm.nih.gov/42418562/,"Cardiovascular Health Equity: Time for a New Era of Science, Sociology, and Interventions",,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
"Polypharmacy in patients with cardiovascular disease occurs frequently across the age spectrum and can lead to inappropriate prescribing and adverse outcomes. Despite polypharmacy being a known problem for decades, there is limited guidance describing how to manage polypharmacy in patients with cardiovascular disease, including when and how to initiate deprescribing strategies. Although polypharmacy can occur at any age, studies often focus on older adults. The prevalence and consequences of polypharmacy, coupled with current gaps in the deprescribing literature, highlight the need for a scientific statement focused on deprescribing in all patients with cardiovascular disease. Deprescribing can improve outcomes and can apply to both cardiovascular and noncardiovascular drugs because both contribute to polypharmacy and poor outcomes associated with inappropriate prescribing in patients with cardiovascular disease. This scientific statement reviews the consequences of polypharmacy in patients with cardiovascular disease and provides tailored deprescribing strategies across the life span, with an emphasis on the unique considerations in pediatric, adult, and older adult populations. These strategies include observing clinical cues and triggers, using validated deprescribing tools, engaging in shared decision-making, and leveraging the roles of all members of the health care team to address barriers to deprescribing. Last, this scientific statement highlights current challenges related to polypharmacy and deprescribing and suggests some strategies to address them.","[""Journal Article"", ""Review""]","[""DiDomenico RJ"", ""Marrs JC"", ""Bress AP"", ""Denfeld QE"", ""Dobesh PP"", ""Effron MB"", ""Goyal P"", ""Onyebeke C"", ""Peterson JK"", ""Petrovic M"", ""American Heart Association Clinical Pharmacology Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and Council on Quality of Care and Outcomes Research""]",10.1161/CIR.0000000000001459,DiDomenico RJ,Circulation,0009-7322,,Circulation,eng,Petrovic M,[],,42417036,,2026 Jul 8,2026,https://pubmed.ncbi.nlm.nih.gov/42417036/,Deprescribing in Patients With Cardiovascular Disease Experiencing Polypharmacy: A Scientific Statement From the American Heart Association,,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Editorial""]","[""Khan SS""]",10.1161/CIRCULATIONAHA.126.081718,Khan SS,Circulation,0009-7322,1,Circulation,eng,Khan SS,[],81,42406868,,2026 Jul 7,2026,https://pubmed.ncbi.nlm.nih.gov/42406868/,A Bundle to Frame Guidelines and American Heart Association Statements,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Journal Article""]","[""Maron BA""]",10.1161/CIRCULATIONAHA.126.080161,Maron BA,Circulation,0009-7322,1,Circulation,eng,Maron BA,[],4-6,42406866,,2026 Jul 7,2026,https://pubmed.ncbi.nlm.nih.gov/42406866/,"A New Circulation, For You",154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
"GLP-1 (glucagon-like peptide-1) receptor agonists (RAs) have emerged as a major therapeutic advance in cardiometabolic medicine. Initially developed as glucose-lowering therapies for type 2 diabetes, these agents have demonstrated broad benefits that extend well beyond glycemic control. GLP-1 RAs enhance glucose-dependent insulin secretion and reduce appetite, leading to improved glycemia and sustained weight loss. In addition, GLP-1 signaling exerts vascular and myocardial effects, including improved endothelial function, reduced inflammation and oxidative stress, and favorable changes in cardiac metabolism and remodeling. Large randomized cardiovascular outcomes trials have consistently shown that several GLP-1 RAs reduce major adverse cardiovascular events, including myocardial infarction, stroke, cardiovascular death, and heart failure. Benefits have been observed across diverse populations, including individuals with established cardiovascular disease and those with obesity but without diabetes. Emerging therapies targeting multiple incretin pathways, such as dual GIP (glucose-dependent insulinotropic polypeptide)-GLP-1 RAs, may further extend these benefits. Collectively, these findings suggest that GLP-1 RAs influence multiple cardiometabolic pathways and may shift the underlying metabolic milieu toward a more favorable physiological state. In this Clinical Primer, we review the physiology of GLP-1 signaling, the evidence supporting cardiovascular risk reduction, and practical considerations for the clinical use of incretin-based therapies.","[""Journal Article"", ""Review""]","[""Pigeyre M"", ""Gerstein HC""]",10.1161/CIRCULATIONAHA.126.079319,Pigeyre M,Circulation,0009-7322,1,Circulation,eng,Gerstein HC,"[""Humans"", ""Cardiovascular Diseases"", ""Glucagon-Like Peptide-1 Receptor Agonists"", ""Glucagon-Like Peptide-1 Receptor"", ""Hypoglycemic Agents"", ""Animals"", ""Incretins"", ""Diabetes Mellitus, Type 2"", ""Signal Transduction"", ""Glucagon-Like Peptide 1""]",66-73,42406865,,2026 Jul 7,2026,https://pubmed.ncbi.nlm.nih.gov/42406865/,Cardiovascular Risk Reduction With GLP-1 RA Drugs,154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
,"[""Journal Article""]","[""Minhas AS"", ""Wallace AS"", ""Zhang S"", ""Barrett RB"", ""Ndumele CE""]",10.1161/CIRCULATIONAHA.126.080146,Minhas AS,Circulation,0009-7322,1,Circulation,eng,Ndumele CE,[],58-62,42406864,,2026 Jul 7,2026,https://pubmed.ncbi.nlm.nih.gov/42406864/,"Obesity, Severe Obesity, and Abdominal Obesity in US Youth and Adults From 1999 to 2023",154,aijEGK7VsaQ8QH9gI,HJrFq6OoRtDQn529O
"The Body Roundness Index (BRI) is a novel anthropometric measure that can predict total and regional body fat percentages. However, the effects of BRI in individuals with a normal Body Mass Index (BMI) remain unclear. This study aimed to investigate the association of BRI with stroke and all-cause mortality in individuals with a normal BMI. This longitudinal study included 36,490 participants free from cardiovascular diseases (CVD) and possessed a normal BMI (18.5-24.0) at baseline. Cox proportional hazard models were used to estimate the associations between BRI and the risk of stroke and all-cause mortality. Receiver operating characteristic (ROC) curves were used to assess the ability of BRI to predict stroke and all-cause mortality than other anthropometric indices. During a median follow-up of 15.0 years, there were 2281 (6.3 %) recorded strokes and 5094 (14.0 %) deaths. After adjusting for potential risk factors, BRI was found to be significantly associated with increased risks of stroke (P for trend = 0.002) and mortality (P for trend <0.001), independent of BMI. The association was primarily linked to ischemic stroke (P for trend = 0.002) rather than hemorrhagic stroke. Additionally, the ROC curves indicated that BRI has better predictive power than BMI for stroke and all-cause mortality (P < 0.05). In participants with a normal BMI, higher levels of BRI were significantly associated with an increased risk of stroke and all-cause mortality. However, these findings may not generalize to women or more diverse populations, as the study mostly included men from a single occupation.","[""Journal Article""]","[""Shen Y"", ""Tian R"", ""Xia X"", ""Chen S"", ""Tian X"", ""Wu S"", ""Wang A""]",10.1016/j.dsx.2025.103313,Shen Y,Diabetes & metabolic syndrome,1871-4021,9,Diabetes Metab Syndr,eng,Wang A,"[""Humans"", ""Male"", ""Stroke"", ""Body Mass Index"", ""Female"", ""Follow-Up Studies"", ""Risk Factors"", ""Longitudinal Studies"", ""Prognosis"", ""Middle Aged"", ""ROC Curve"", ""Adult"", ""Aged""]",103313,42544424,,2025 Sep,2025,https://pubmed.ncbi.nlm.nih.gov/42544424/,Association of body roundness index with stroke and mortality among people with normal body mass index,19,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Environmental stressors like high temperatures and pollution, often compounded by socioeconomic factors, have been linked to adverse maternal and birth outcomes. Despite this well-established link, limited studies have examined the spatial relationship between these factors to prioritize community interventions and future research needs. This study examines the spatial trends linking environmental parameters, socioeconomic factors, and adverse maternal and infant health outcomes in North Carolina from 2011 to 2019. Through exploratory spatial data analysis methods, including bivariate Local Indicators of Spatial Association (LISA) and spatial regression, clusters of environmental risks and health outcomes were identified, shedding light on the disproportionate impact of structural racism and income inequality on adverse health outcomes. In addition, this analysis highlights a significant association between hazardous pollutants, as indicated by Risk-Screening Environmental Indicator (RSEI) toxicity-weighted concentrations, and adverse health outcomes, persisting even after adjusting for racial and income segregation. In contrast, heatwaves, defined as any heatwave event across the pregnancy period, showed varied effects and little significance with birth and maternal outcomes. These findings underscore the critical need for targeted interventions addressing socioeconomic disparities and environmental health hazards to enhance maternal and infant health outcomes in North Carolina and similar regions. The online version contains supplementary material available at 10.1007/s13412-025-01060-1.","[""Journal Article""]","[""Ulrich SE"", ""Sugg MM"", ""Runkle JD"", ""Fehlman CA"", ""Guignet D""]",10.1007/s13412-025-01060-1,Ulrich SE,Journal of environmental studies and sciences,2190-6483,3,J Environ Stud Sci,eng,Guignet D,[],617-629,42544117,pmc-id: PMC13428771;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42544117/,Spatial analysis of environmental and socioeconomic factors impacting maternal and infant health outcomes in North Carolina,16,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
,"[""Letter""]","[""Akgül S"", ""Aslan C"", ""Başar K"", ""Nalbant K"", ""Oğuz SH"", ""Pehlivantürk Kızılkan M"", ""Tüzün Z"", ""Özon A""]",10.5152/TurkArchPediatr.2025.25329,Akgül S,Turkish archives of pediatrics,2757-6256,8,Turk Arch Pediatr,eng,Özon A,[],752-754,42541475,,2025 Dec 19,2025,https://pubmed.ncbi.nlm.nih.gov/42541475/,Affirming Care Beyond Hormones: Supporting Transgender Youth in the Face of Restrictive Policies,61,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
,"[""Case Reports"", ""Journal Article""]","[""Khalilova F"", ""Yiğit MH"", ""Günerbüyük C"", ""Aktürk H""]",10.5152/TurkArchPediatr.2025.25361,Khalilova F,Turkish archives of pediatrics,2757-6256,8,Turk Arch Pediatr,eng,Aktürk H,[],742-743,42541472,,2025 Dec 30,2025,https://pubmed.ncbi.nlm.nih.gov/42541472/,Staphylococcal Septic Arthritis Following Influenza A Infection,61,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
,"[""Case Reports"", ""Journal Article""]","[""Babazade H"", ""Günal B"", ""Çalişgan K"", ""Uygur E"", ""Durcan G"", ""Kılıç H"", ""Zubarioglu T"", ""Cansever MŞ"", ""Aktuğlu-Zeybek Ç"", ""Kiykim E""]",10.5152/TurkArchPediatr.2025.25325,Babazade H,Turkish archives of pediatrics,2757-6256,8,Turk Arch Pediatr,eng,Kiykim E,[],736-741,42541471,,2025 Dec 18,2025,https://pubmed.ncbi.nlm.nih.gov/42541471/,"Revealing BCKDK Deficiency Under Autism: A Case Report, Therapeutic Outcomes, and Literature Review",61,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Recent studies in the United States and Europe have documented a growing divergence in voting behaviour and political attitudes between cities and the countryside. However, we still lack systematic evidence on the extent to which this urban-rural divide is also affectively polarised. To shed light on this, we advance the concept of place-based affective polarisation, which we define as the difference between in-group and out-group affect in relation to place-based groups. Drawing on original survey data from nine European countries, we show that place-based affective polarisation is substantial along the urban-rural divide and associated with strong feelings of place-based resentment and identity. Furthermore, we find that higher levels of place-based affective polarisation correlate with support for GAL parties (green, alternative, libertarian) among urbanites and support for TAN parties (traditional, authoritarian, nationalist) among ruralites. Overall, our findings point to a strong political cleavage between urban and rural areas in several European countries.","[""Journal Article""]","[""Hegewald S"", ""Schraff D""]",10.1177/00104140251369317,Hegewald S,Comparative political studies,0010-4140,10,Comp Polit Stud,eng,Schraff D,[],2159-2200,42541202,pmc-id: PMC13427094;,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42541202/,Is the Urban-Rural Divide Affectively Polarised? Comparative Evidence from Nine European Countries,59,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Commoning occurs when people recognize that they share something and develop a sense of mutuality toward each other along with a shared responsibility for whatever they share. Because sharing and mutuality contrast with the individualism, competitiveness, and profit orientation of contemporary capitalist societies, commoning is widely heralded for its transformative potential. Nonetheless, commoning is not inherently transformative. We argue that whether commoning supports transformation depends on its relationship with heterotopic processes. Both commoning and heterotopia-ideal typical ""other"" spaces characterized by looseness and denormalization-present alternatives to hegemonic norms, especially those of state-centricity, hierarchical social organization, and the prioritization of market relationships and economic growth, but they are distinct processes that do not necessarily coincide. We propose an analytical framework to guide analysis of the relationship between commoning and heterotopia and illustrate it with examples from contested urban green spaces in Liège (Belgium), Montréal (Canada), and Brussels (Belgium).","[""Journal Article""]","[""Poteete AR"", ""Kunysz P"", ""Luka N""]",10.1177/02637758251361706,Poteete AR,"Environment and planning. D, Society & space",0263-7758,4,Environ Plan D,eng,Luka N,[],570-590,42541108,pmc-id: PMC13427086;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42541108/,"Commoning, heterotopia, and transformation: An analytical framework for and from contested spaces",44,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"How can leaders guide diverse organizations to work together on society's biggest challenges when power is unevenly distributed? Cross-sector partnerships (CSPs) bring together companies, governments, and nongovernmental organizations (NGOs) to address complex problems, yet their success hinges on how leaders navigate competing interests and shifting power dynamics. This study examines a high-profile CSP involving a Fortune 500 company, two international development organizations, and an NGO. Drawing on Mary Parker Follett's ideas about ""power-with"" and ""power-over,"" I show how NGO leaders combined collaborative and more coercive tactics to move the partnership forward. My analysis reveals that responsible leadership (RL) in CSPs is not a static trait or style but evolves through a dynamic choreography of power as challenges and priorities change. The findings offer practical lessons for leaders seeking to balance ethics, inclusion, and influence in multi-stakeholder collaborations, and they extend theory by reframing RL as a shifting, context-sensitive process rather than a fixed style.","[""Journal Article""]","[""Harvey JF""]",10.1177/00187267251398388,Harvey JF,Human relations; studies towards the integration of the social sciences,0018-7267,9,Hum Relat,eng,Harvey JF,[],1140-1168,42541095,pmc-id: PMC13427085;,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42541095/,Enacting responsible leadership in cross-sector partnerships: A dynamic choreography of power,79,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Cultural threat is one of the main explanations for opposing immigrants. However, it lacks theoretical precision and suffers from measurement issues. To remedy these problems, we conceptualize cultural threat as a zero-sum problem and specify concrete cultural rights that Muslims receive. In two online experiments in Germany, we randomly assigned people to situations where Muslim cultural rights either replace majority rights (zero-sum) or they co-exist (non-zero-sum). The willingness to accommodate Muslims' cultural rights varies strongly by the logic of cultural threat, especially for respondents with an inclusionary mindset. They are protective of their own cultural practices, but do not perceive all gains in Muslim rights as inherently threatening. Respondents with an exclusionary mindset, however, respond less to variations in cultural threat. In contrast to people with an inclusionary mindset, they also react more negatively to Muslim than non-Muslim demands for change.","[""Journal Article""]","[""Helbling M"", ""Ivarsflaten E"", ""Traunmüller R""]",10.1177/00104140251369349,Helbling M,Comparative political studies,0010-4140,10,Comp Polit Stud,eng,Traunmüller R,[],2011-2047,42541073,pmc-id: PMC13427093;,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42541073/,Zero-Sum Thinking and the Cultural Threat of Muslim Religious Rights,59,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Due to the rise of global e-commerce platforms like Alibaba, online interactions between rural Chinese wig sellers and Black clients are increasing. However, the racial implications of such platform-mediated business relations remain underexplored. Based on ethnographic fieldwork in Xuchang, a leading distribution and export center for wigs products in the global supply chain, this research examines the active role of Alibaba in orchestrating, structuring, and shaping the racial knowledge formation of rural Chinese wig sellers in their daily online interactions with Black clients. We argue that the exploitative nature of platform capitalism creates stress and exhaustion among rural wig sellers and pushes them to draw narrow and hasty conclusions about Blackness that dovetail with racialized hierarchy in the global wig industry and logistics networks. This research bridges the gap between platform studies and critical race studies and contributes to the reconceptualization of relations between platform and race.","[""Journal Article""]","[""Duan S"", ""Lan S""]",10.1177/14614448251358351,Duan S,New media & society,1461-4448,8,New Media Soc,eng,Lan S,[],4182-4200,42540999,pmc-id: PMC13427084;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42540999/,Platform-mediated racialization: A case study of rural Chinese wig sellers and Black clients on Alibaba,28,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"The nature and consequences of mass mobilization are core topics in the social sciences. How have mass mobilization movements evolved over time? How do key characteristics of such movements, including their social composition or ideology, influence their ability to overthrow or alter political institutions? We introduce the Opposition Movements and Groups (OMG) dataset, which - due to its unique contents and extensive coverage - will help researchers to better address these and many other questions about mass mobilization movements. OMG includes information on the stated goals, duration, size, tactics, ideology, and social and organizational composition of 1452 mass mobilization movements, globally, from 1789 to 2019. We discuss OMG's contents, construction, validity and reliability issues, and how it complements existing datasets. We showcase the data, first, by documenting several key trends in movement characteristics since the French Revolution, and, second, by shedding new light on the much-discussed relationship between nonviolent movements and democratization.","[""Journal Article""]","[""Dahl M"", ""Dahlum S"", ""Fjelde H"", ""Gjerløw H"", ""Knutsen CH"", ""Strøm-Sedgwick C"", ""Wig T""]",10.1177/00104140251369330,Dahl M,Comparative political studies,0010-4140,10,Comp Polit Stud,eng,Wig T,[],2117-2158,42540992,pmc-id: PMC13427092;,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42540992/,"Mass Mobilization in the Modern Era: Introducing the Opposition Movements and Groups (OMG) Dataset, 1789-2019",59,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"This paper contributes to geographical research on precarity by exploring how emotional responses to enduring insecurity shape young people's temporal horizons, spatial belonging, and sense of possibility. Drawing on qualitative research in Barcelona, I advance multi-dimensional perspectives on precarity by showing how precarious entanglements - where the material, affective, temporal, and spatial become embodied - shape the contours of potentiality and futurity. I conceptualise 'foreclosed futures' as a temporal-affective structure that emerges from, yet unsettles, the logic of Lauren Berlant's 'cruel optimism'. For a generation shaped by austerity, the projection of present structural barriers to upward mobility into the future precludes the imagination of prosperous futures, fostering hopelessness, disillusionment, and nostalgia for lost stability. To unpack this dynamic, I illuminate how persistent precarity resignifies the urban - not as a site of potentiality, but as one of constraint leading to foreclosure of potentiality. I then demonstrate how a sense of inevitable downward mobility and social decline alters the emotions and temporalities tied to post-war ideals of security woven into cruel optimism. Finally, I show how apprehension towards insecure futures anchors young people in present-oriented survival, fostering pragmatic and pessimistic attitudes, concluding with an analysis of the socio-political implications of foreclosed futures.","[""Journal Article""]","[""Del Río S""]",10.1177/02637758251364077,Del Río S,"Environment and planning. D, Society & space",0263-7758,4,Environ Plan D,eng,Del Río S,[],691-709,42540961,pmc-id: PMC13427083;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42540961/,From cruel optimism to foreclosed futures: The emotional and temporal dimensions of enduring precarity among young adults in Barcelona,44,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Poor air quality can harm human health and the environment. Air quality data are needed to understand and reduce exposure to air pollution. Air sensor data can supplement national air monitoring data, allowing for a better understanding of localized air quality and trends. However, these sensors can have limitations, biases, and inaccuracies that must first be controlled to generate data of adequate quality, and analyzing sensor data often requires extensive data analysis. To address these issues, an R-Shiny application has been developed to assist air quality professionals in (1) understanding air sensor data quality through comparison with nearby ambient air reference monitors, (2) applying basic quality assurance and quality control, and (3) understanding local air quality conditions. This tool provides agencies with the ability to more quickly analyze and utilize air sensor data for a variety of purposes while increasing the reproducibility of analyses. While more in-depth custom analysis may still be needed for some sensor types (e.g., advanced correction methods), this tool provides an easy starting place for analysis. This paper highlights two case studies using the tool to explore PM2.5 sensor performance under the conditions of wildfire smoke impacts in the Midwestern United States and the performance of O3 sensors for a year.","[""Journal Article""]","[""Barkjohn KK"", ""Plessel T"", ""Yang J"", ""Pandey G"", ""Xu Y"", ""Krabbe S"", ""Seppanen C"", ""Bichler R"", ""Tran HNQ"", ""Arunachalam S"", ""Clements AL""]",10.3390/atmos16111270,Barkjohn KK,Atmosphere,2073-4433,11,Atmosphere (Basel),eng,Clements AL,[],1270,42540936,pmc-id: PMC13426646;manuscript-id: NIHMS2131755;,2025 Nov,2025,https://pubmed.ncbi.nlm.nih.gov/42540936/,Air Sensor Network Analysis Tool: R-Shiny Application,16,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Preeclampsia is a pregnancy-related hypertensive disorder with long-term cardiovascular risks. The aim of this study was to explore the factors influencing hypertension progression in preeclampsia patients within 5 years postpartum, and to construct a nomogram. A retrospective study of 280 preeclampsia patients, grouped by hypertension progression status within 5 years postpartum, was performed. Differential analyses compared: 1) demographic/pregnancy characteristics, and 2) late-pregnancy, 1-week-postpartum, and 6-week-postpartum blood indicators between groups. Multiple logistic regression and generalized estimating equations (GEE) identified hypertension progression factors. Significant factors used to construct the nomogram were evaluated via calibration and receiver operating characteristic (ROC) curves in training/test sets. Patients who progressed to hypertension had higher pre-pregnancy and postpartum body mass index (BMI), a greater proportion of early-onset and severe preeclampsia, and a higher incidence of adverse pregnancy outcomes compared to those who did not progress to hypertension. Additionally, they had lower platelet levels during late pregnancy and postpartum, while levels of aspartate aminotransferase, alanine aminotransferase, 24-hour urinary protein, uric acid, and C-reactive protein were higher in patients who did not progress to hypertension. Multivariate logistic regression identified placental abruption, oligohydramnios, and umbilical artery pulsatility index as significant factors, while the generalized estimating equation highlighted uric acid (UA), platelet (PLT), and alanine aminotransferase (ALT) as key predictors. The nomogram demonstrated good predictive performance, as shown by calibration and ROC curves. Hypertension progression correlates with placental abruption, oligohydramnios, elevated umbilical artery pulsatility index (UA-PI), elevated UA, decreased PLT, elevated ALT, and specifically aspartate aminotransferase at 1-week postpartum. The nomogram aids early identification of high-risk patients.","[""Journal Article""]","[""Xu Y"", ""Liu H"", ""Kang X"", ""Jiang H"", ""Wang W""]",10.5114/aoms/208999,Xu Y,Archives of medical science : AMS,1734-1922,3,Arch Med Sci,eng,Wang W,[],1539-1548,42540664,pmc-id: PMC13426175;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540664/,Predicting hypertension in preeclampsia patients within five years postpartum: analysis of influencing factors and nomogram development,22,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Neutrophils have been implicated in the pathogenesis of atherosclerosis in multiple studies. This study aimed to determine the effects of flavonoids (quercetin and luteolin) and vitamin C on neutrophil extracellular trap (NET) formation and regulation of NET markers, including circulating cell-free DNA (cfDNA) and myeloperoxidase (MPO). Additionally, we assessed the expression of NADPH oxidase complex subunits and superoxide anion generation in neutrophils. Whole blood samples were collected from patients with atherosclerosis. Neutrophils were stimulated with lipopolysaccharide (LPS), and the effects of flavonoids and vitamin C on NET release, NADPH oxidase subunit expression (p47phox, p67phox, Rac1), and superoxide production were evaluated. Atherosclerotic patients showed increased NETosis, with elevated NET release, MPO, and cfDNA levels. Expression of NADPH oxidase subunits p47phox and p67phox and superoxide anion generation were significantly higher compared to controls. LPS further enhanced these effects. Treatment with quercetin, luteolin, and vitamin C reduced NET formation, NADPH oxidase expression, and superoxide production in stimulated neutrophils. Flavonoids and vitamin C modulate NET formation, likely by affecting NADPH oxidase activity and reactive oxygen species production, suggesting potential anti-inflammatory effects relevant to atherosclerosis. Further studies are warranted to evaluate the potential application of these compounds as adjunctive therapy in the treatment of atherosclerosis.","[""Journal Article""]","[""Dąbrowska-Zagroba D"", ""Garley M"", ""Ratajczak-Wrona W"", ""Sawicka-Powierza J"", ""Grubczak K"", ""Radziwon P"", ""Wołczyński S"", ""Jabłońska E""]",10.5114/aoms/213753,Dąbrowska-Zagroba D,Archives of medical science : AMS,1734-1922,3,Arch Med Sci,eng,Jabłońska E,[],1640-1652,42540628,pmc-id: PMC13426161;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540628/,Beneficial effects of antioxidants on neutrophil extracellular trap formation in atherosclerosis,22,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Health-related communication and shared decision-making (SDM) are crucial elements of patient-centered care. The aim of this review was to identify the key barriers and facilitators influencing the adoption of an SDM approach from both the physician's and patient's perspectives in primary healthcare in relation to the 5-step model of SDM. A scoping review of resources published within the last 5 years was conducted in June 2024 in accordance with PRISMA-ScR guidelines. Specific barriers hindering the adoption of SDM were identified, which can arise at any of the five steps. The most common barriers include: time constraints and physician's workload, lack of SDM culture and tradition, paternalistic model of healthcare, and patients' passive attitude and belief they are unable to make decisions. SDM facilitators include: trust, use of educational materials by physicians, belief that SDM will lead to better treatment outcomes, and training in communication for physicians. Despite the challenges to public health, action should be taken to overcome these barriers, given the well-established benefits of SDM, although this will require time and necessary adaptations.","[""Journal Article""]","[""Domosławska-Żylińska K"", ""Krysińska-Pisarek M""]",10.5114/aoms/208300,Domosławska-Żylińska K,Archives of medical science : AMS,1734-1922,3,Arch Med Sci,eng,Krysińska-Pisarek M,[],1249-1258,42540613,pmc-id: PMC13426165;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540613/,Shared decision-making in primary care: barriers and facilitators from the physician's and patient's perspectives: a scoping review,22,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"The risk of secondary cancers in breast cancer survivors remains a significant concern. This study aimed to evaluate the association between treatment modalities and the time to development of secondary cancers in patients after mastectomy or breast-conserving therapy (BCT). A retrospective analysis was conducted on 6590 patients from 2 centres (Poznan and Gorzow, Poland) treated for breast cancer between 2017 and 2022. A total of 149 patients from this group developed secondary cancer. Data included demographic and clinical characteristics, treatment types (chemotherapy, hormonotherapy, radiotherapy), and subtypes of primary breast cancer (luminal, triple negative, HER2 positive). Statistical methods included Kaplan-Meier analysis, Cox proportional hazards models, and χ2 tests. The median time to secondary cancer detection was significantly shorter in patients with TNBC/HER2+ subtypes (2.8 years) compared to luminal subtypes (6.1 years; p = 0.024). TNBC/HER2+ subtypes were associated with a 1.9-fold increased risk of secondary cancers (HR = 1.93; p = 0.048). No significant association was found between treatment type and the occurrence of secondary cancers (p > 0.05). However, combined therapies (e.g. chemotherapy + hormonotherapy) showed a trend toward reduced risk (HR = 0.53; p = 0.061). The most common secondary cancers were gastrointestinal malignancies (27%) and gynaecological cancers (15%). The subtype of primary breast cancer significantly influences the time to secondary cancer development, with TNBC/HER2+ patients at higher risk. Treatment modalities did not significantly affect secondary cancer risk, but combined therapies may offer protective effects. These findings highlight the need for tailored surveillance strategies based on tumour biology.","[""Journal Article""]","[""Wichtowski M"", ""Gibowska-Maruniak P"", ""Bigos P"", ""Urbański Ł"", ""Gryczka H"", ""Bujko-Wasiak N"", ""Milecki T"", ""Pytlak K"", ""Kurzawa P"", ""Brzeźniakiewicz-Janus K"", ""Gil L""]",10.5114/aoms/215281,Wichtowski M,Archives of medical science : AMS,1734-1922,3,Arch Med Sci,eng,Gil L,[],1470-1481,42540609,pmc-id: PMC13426188;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540609/,Secondary cancers in breast cancer survivors. A two-centre study,22,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Sarcopenia is increasingly linked to metabolic dysregulation, including dyslipidemia. The low-density lipoprotein cholesterol with apolipoprotein B (LDL-C/ApoB) ratio (LAR), reflecting cholesterol content per atherogenic lipoprotein particle, may serve as a novel biomarker for sarcopenia risk. This study aimed to investigate the association between LAR and sarcopenia using data from the National Health and Nutrition Examination Survey (NHANES). Data from NHANES cycles 2011-2016 were analyzed between July 2024 and February 2025. Sarcopenia was defined using dual-energy X-ray absorptiometry (DXA)-derived appendicular lean mass (ALM) standardized to body mass index (BMI). Multivariable logistic regression, restricted cubic spline (RCS) regression analysis, subgroup analysis, and interaction tests were applied to evaluate the relationship between LAR and sarcopenia, adjusting for covariates. A negative correlation between LAR and sarcopenia was observed in 3,235 participants included in the study (OR = 0.399, 95% CI: 0.224-0.712, p = 0.007), which was further confirmed to be non-linear via RCS regression analysis (p non-linear = 0.037), with one significant inflection point identified, and participants with LAR ≥ 1.268 demonstrated a significantly reduced risk of sarcopenia. Subgroup analyses and interaction tests indicated that the association between LAR and sarcopenia remained consistent across different subgroups and was not modified by other covariates. Elevated LAR is significantly associated with lower sarcopenia risk, suggesting its potential role as a biomarker for muscle health. Further studies are needed to elucidate underlying mechanisms and validate these findings prospectively.","[""Journal Article""]","[""Yang X"", ""Zhang Z""]",10.5114/aoms/214480,Yang X,Archives of medical science : AMS,1734-1922,3,Arch Med Sci,eng,Zhang Z,[],1326-1334,42540608,pmc-id: PMC13426174;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540608/,The association of low-density lipoprotein cholesterol with apolipoprotein B ratio and sarcopenia: a cross-sectional study,22,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Identifying new drug targets is essential for improving breast cancer survival. The proteome provides a rich source for potential therapeutic targets. This study aimed to identify protein markers and therapeutic targets for breast cancer by using proteome-wide Mendelian randomization (MR). Protein quantitative trait loci (pQTL) data were obtained from four large-scale proteomic studies, including 17,267 circulating protein markers. Genetic associations with breast cancer survival were derived from a large-scale GWAS meta-analysis (37,954 cases, 2,900 deaths). Proteome-wide MR was performed to estimate causal effects of proteins on breast cancer survival, complemented by single-cell expression analysis to identify enriched cell types. Protein-protein interactions (PPI) and druggability assessments were also conducted to prioritize therapeutic targets. Genetically predicted circulating levels of 27 proteins were found to be associated with breast cancer survival. Among these, eight proteins (ADAM15, CD83, SH3BGRL3, SNCG, ANXA1, GRHPR, ALDH2, and MTHFD2) showed the strongest evidence of association, while four proteins (ARG2, RPL14, NFU1, and TXNL4B) demonstrated a strong but slightly weaker correlation. Notably, SH3BGRL3, GRHPR, ARG2, RPL14, NFU1, and TXNL4B were newly identified as circulating protein markers significantly associated with breast cancer prognosis. Druggability analysis revealed that 13 of these proteins were already targeted by existing drugs, offering potential for breast cancer treatment. We identified 27 genes encoding proteins associated with overall and subtype-specific breast cancer survival, providing potential prognostic biomarkers and therapeutic targets, and offering new avenues for improving breast cancer management.","[""Journal Article""]","[""Cao Z"", ""Peng Q"", ""Tan S""]",10.5114/aoms/208246,Cao Z,Archives of medical science : AMS,1734-1922,3,Arch Med Sci,eng,Tan S,[],1678-1687,42540540,pmc-id: PMC13426152;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540540/,Plasma proteome-genome integration reveals novel protein biomarkers and therapeutic targets linked to breast cancer survival,22,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Pneumothorax is the presence of air in the pleural cavity, often resulting in respiratory distress and impaired lung function. Although clinical observations have shown that high intensity physical activity and frail state affect respiratory health, their causal role in pneumothorax development is unclear. This study is the first to use a two-sample Mendelian randomization method (TSMR) to investigate the causal relationship between physical activity and frailty and the risk of pneumothorax, with a view to providing new insights into the pathogenesis of pneumothorax and preventive strategies. Using Mendelian randomization (MR) analyses, we examined the potential causal relationship between physical activity, frailty, and the risk of pneumothorax. Genetic instrumental variables (IVs) for relevant exposure factors were selected from genome wide association studies (GWAS). The study was analyzed using five different methods, mainly using inverse variance weighted (IVW) to draw causal inferences. Sensitivity analyses were performed to ensure the validity of the MR results. Sensitivity analyses included the detection of horizontal pleiotropy, i.e., genetic variants affecting the outcome through pathways other than the target exposure, which may lead to biased causal inference. Heterogeneity between genetic instrumental variables was also assessed and used to detect variability in effect estimates, which may reflect violations of MR assumptions or differences between populations. Our analyses found that light DIY reduced the risk of pneumothorax, but did not identify a causal association between other levels of physical activity and pneumothorax. In addition, frailty index (FI) showed a positive association with the risk of developing spontaneous pneumothorax, and this causal relationship persisted after adjustment for body mass index (BMI) and light DIY. Sensitivity analyses further validate the robustness of our findings. Our findings support the ability of light DIY to reduce the risk of pneumothorax development. It also emphasizes the need for frail individuals to be more aware of the need to protect against pneumothorax in their daily lives. We encourage appropriate exercise to improve fitness and reduce the risk of pneumothorax.","[""Journal Article""]","[""Ding Y"", ""Wang X"", ""Li X"", ""Kong L""]",10.5114/aoms/208920,Ding Y,Archives of medical science : AMS,1734-1922,3,Arch Med Sci,eng,Kong L,[],1528-1538,42540532,pmc-id: PMC13426153;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540532/,Causal effects of physical activity and frailty on pneumothorax risk: a Mendelian randomization study,22,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"The advent of digital twins has increased the demand for longer-duration simulations that span multiple physiological states. Digital twins have emerged as powerful tools in cardiovascular modeling, enabling patient-specific simulations of coronary blood flow for non-invasive diagnosis and treatment planning. Although these simulations achieve high fidelity under steady or periodic heart rates, modeling real-world transitions, such as those arising from physical activity, requires careful evaluation of temporal convergence, the stabilization of hemodynamic parameters through the simulation of preceding cardiac cycles, or 'pre-flows'. In this study, we present a physiologically grounded approach for determining the minimum number of preceding cardiac pre-flows necessary to achieve temporal convergence following abrupt heart rate (HR) changes. Using high-resolution patient-specific 3-dimensional (3D) simulations and inflow waveforms scaled from both synthetic and wearable-derived HR data, we quantify convergence behavior across velocity, pressure gradient, and wall shear stress at both cross-sectional and full-domain levels. Results show that simulating just two pre-flows is sufficient to achieve physiologically stable outputs across high-to-low and low-to-high HR transitions (<2% difference). These findings are further verified using continuous HR data obtained from wearable devices, with low and high HR segments extracted to represent natural extremes, confirming the robustness of the proposed convergence criterion under real-world dynamic inputs (<1% difference). This work establishes a computationally efficient and physiologically consistent criterion for dynamic-state simulations, facilitating the integration of cardiovascular digital twins with real-time sensing technologies.","[""Journal Article""]","[""Khan NS"", ""Tanade C"", ""Geddes J"", ""Randles A""]",10.1063/5.0287796,Khan NS,"Physics of fluids (Woodbury, N.Y. : 1994)",1070-6631,9,Phys Fluids (1994),eng,Randles A,[],,42540504,pmc-id: PMC13425941;manuscript-id: NIHMS2182208;,2025 Sep,2025,https://pubmed.ncbi.nlm.nih.gov/42540504/,Establishing Hemodynamic Convergence Framework for Coronary Digital Twins Under Realistic Dynamic Heart Rates,37,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Ovarian cancer is the eighth most common cancer among women and an important cause of cancer-related mortality, particularly in high-income countries. Scientific studies show that hypertension may play a significant role in the initiation of cancer. Therefore, we conducted the first meta-analysis to comprehensively examine the association between hypertension and ovarian cancer risk. We performed a literature search of all of the observational studies published as original articles from inception to July 2024, and we searched the following electronic databases: PubMed, Embase, and Cochrane Library. Finally, we included ten full-text cohort and case-control studies addressing the effect of hypertension on ovarian cancer in this meta-analysis. Our study was preregistered with International Prospective Register of Systematic Reviews (PROSPERO CRD42024565574) and followed the PRISMA statement. Effect size was presented as risk ratios (RRs) and 95% confidence intervals (CIs). Heterogeneity test evaluation was performed using Cochran's Q test and I 2 statistics. The meta-analysis included a total of 2,497,898 women. There was a statistically significant association (RR = 1.10, 95% CI: 1.02-1.23, p < 0.011) between hypertension and ovarian cancer risk. Subgroup analysis showed that parity may significantly reduce the ovarian cancer risk, which was higher among women who had never given birth (RR = 1.43, p < 0.0025), while a body mass index (BMI) > 25 kg/m2 increased the risk of ovarian cancer (RR = 1.12, p < 0.0001). The findings of this comprehensive review and meta-analysis indicate that hypertension is associated with higher overall risk of ovarian cancer. While the present data provide novel evidence, further prospective studies are needed to elucidate the association between hypertension and ovarian cancer risk.","[""Journal Article"", ""Review""]","[""Drab A"", ""Wdowiak K"", ""Kanadys W"", ""Malm M"", ""Dolar-Szczasny J"", ""Religioni U""]",10.5114/aoms/210330,Drab A,Archives of medical science : AMS,1734-1922,3,Arch Med Sci,eng,Religioni U,[],1609-1617,42540443,pmc-id: PMC13426177;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540443/,Hypertension and ovarian cancer risk: a meta-analysis of observational studies,22,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Therapeutic plasma exchange (TPE) is a widely used extracorporeal blood purification procedure. While its principles are similar across age groups, the technical complexity and risks are heightened in pediatric patients due to unique technical considerations. This study assessed the safety regarding both technical and clinical complications of vascular access and membrane-based TPE filters in a pediatric population at a single center. This retrospective cohort study reviewed charts of patients undergoing TPE at a level 3 referral center over 25 years. The study involved 178 patients undergoing a total of 740 procedures during 214 sessions, predominantly using femoral vascular access. The median duration of the entire TPE sessions (treated as a surrogate for catheter lifespan) was 118.5 h. Technical complications occurred in 20.8% of procedures (31.6% of events), while clinical complications occurred in 4.2% (4.7% of events). Technical complications were nearly five times more frequent than clinical complications, with technical events being 6.7 times more common. The proportion of patients experiencing clinical complications was 15.2%. Logistic regression demonstrated that each additional day of catheter placement increased the probability of technical complications by 3%. Additionally, each year of patient age decreased the likelihood of clinical complications by 8.9%, while fresh frozen plasma (FFP) supplementation within a session increased the probability of clinical complications by 21.6%. Prolonged catheter use increases technical events, while FFP supplementation elevates catheter-related clinical complication risk. Advancing patient age reduces the likelihood of clinical complications, underscoring age-specific safety considerations in pediatric TPE.","[""Journal Article""]","[""Błasiak M"", ""Korohoda P"", ""Zachwieja K"", ""Drożdż D"", ""Madej-Świątkowska K"", ""Jarosz-Wójcik E"", ""Miklaszewska M""]",10.5114/aoms/208105,Błasiak M,Archives of medical science : AMS,1734-1922,3,Arch Med Sci,eng,Miklaszewska M,[],1562-1573,42540420,pmc-id: PMC13426138;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540420/,Key technical aspects and vascular access safety in membrane-based therapeutic plasma exchange for the pediatric population,22,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Diabetes-related distress is a common complication that usually impacts the well-being, health outcomes and adherence to medications, especially in individuals with type 2 diabetes mellitus (T2DM). Hence, this study aimed to estimate diabetes-related-distress and its association with medication adherence. This is a hospital-based cross-sectional study conducted among 135 patients with T2DM recruited consecutively from a diabetes clinic of a tertiary health institution, Southwest, Nigeria, from March to September 2022. Data were obtained using the Diabetes Distress Scale (DSS-17) questionnaire and Morisky's Medication Adherence Scale (MMAS-8). The association between the dependent variable (DRD) and the independent variable (medication adherence) was assessed with chi-square, and predictors of DSS with logistic regression analysis. The ethical approval was obtained from the committee of the hospital. The mean age of study participants, and duration of diabetes were 62.20 ± 12.80 years and 7.96 ±7.01 years, respectively. The proportion of diabetes distress among the study population was 30.5% (8.3 % had high distress and 22.2 % moderate distress). Poor adherence to medications was 66.5%. The study showed that diabetes-related distress was associated with poor medication adherence ( χ2 =9.251, p=0.010). Patients who were highly distressed had 56% lower odds of adhering to their medications compared to those who were not (OR: 0.32, 95% CI: 0.15-0.62). Our findings suggest that diabetes distress is a common issue and significantly determines medication adherence. Thus, incorporating routine screening for distress into the standard diabetes care will be an important intervention to improve adherence and health outcomes of people living with T2DM.","[""Journal Article"", ""Review""]","[""Olamoyegun MA"", ""Ojo OA"", ""Akinlade AT"", ""Olaniyi P""]",,Olamoyegun MA,Nigerian medical journal : journal of the Nigeria Medical Association,0300-1652,6,Niger Med J,eng,Olaniyi P,[],2163-2177,42540244,pmc-id: PMC13425372;,2025 Nov-Dec,2025,https://pubmed.ncbi.nlm.nih.gov/42540244/,"Association between Diabetes-Related Distress and Medication Adherence among Patients with Type 2 Diabetes Mellitus, Southwest Nigerian",66,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Immune-mediated necrotising myopathy (IMNM) is a rare autoimmune disease recently recognised as part of the spectrum of idiopathic inflammatory myopathies. Although cardiac involvement is a prominent extramuscular manifestation in anti-signal recognition particle (SRP) IMNM, there remains a lack of sufficient cardiac magnetic resonance imaging data. Here, we present a case of anti-SRP IMNM with cardiac involvement as the initial symptom, utilising imaging assessments at various stages of the disease to evaluate and monitor disease progression and treatment response. These findings may provide valuable insights for the clinical identification and management of anti-SRP IMNM with cardiac involvement.","[""Case Reports"", ""Journal Article""]","[""Zhou XY"", ""Zheng XF"", ""Zhang SJ"", ""Ju S"", ""Chang D""]",10.1016/j.ero.2025.06.005,Zhou XY,EULAR rheumatology open,3050-7081,2,EULAR Rheumatol Open,eng,Chang D,[],100029,42540172,pmc-id: PMC13425209;,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42540172/,Cardiac involvement in immune-mediated necrotizing myopathy: a case report with insights from cardiac magnetic resonance imaging,2,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"The global stillbirth rate is 13.9 stillbirths per 1000 births, with most stillbirths being recorded in developing countries. Most cases of stillbirth are preceded by reduced fetal movement. Early detection of reduced fetal movement is a key element in reducing the number of stillbirths. Therefore, a ""FetalkickApp"" that is a self-monitoring digital health tool, assists a pregnant woman to count, record, and send her fetal movement count to her health care provider without the use of mobile data or internet. This study is a longitudinal pilot study involving 25 pregnant women with single fetuses between 28 and 38 weeks of gestation. The mobile application monitor was used to record the number of fetal movements for 4 weeks. A 5-point Likert scale questionnaire is used to assess the use of the application, interface experience, satisfaction with the design, and function of the application without internet. The mean age of the women is 31.2 (±4.5) years, and the mean gestational age is 29.5 (±2.4) weeks. The results obtained show that the majority of the women (72%) had good knowledge of fetal movement. About two-thirds (64%) of the women agreed that the FetalkickApp is helpful in counting their fetal movement. Forty-four per cent (44%) of the women strongly agreed that the application is easy to use, and 68% of the women agreed that the FetalkickApp's effectiveness is satisfactory. The FetalkickApp is independent of the internet, which means that it could be used everywhere. The interface and design of the application are simple and could be operated by any individual concerned.","[""Journal Article"", ""Review""]","[""Woruka AP"", ""Wells A"", ""Lekpa D"", ""Adewuyi P"", ""Oluwole Z"", ""Echefu L"", ""Tobechukwu EM"", ""Okerim CF""]",,Woruka AP,Nigerian medical journal : journal of the Nigeria Medical Association,0300-1652,6,Niger Med J,eng,Okerim CF,[],2241-2251,42540146,pmc-id: PMC13425375;,2025 Nov-Dec,2025,https://pubmed.ncbi.nlm.nih.gov/42540146/,"The Use of ""FetalKickApp"" for Counting Fetal Movement in Pregnant Women: A Case Study of The University of Port Harcourt Teaching Hospital, Nigeria",66,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Rheumatoid arthritis is an autoimmune disease typically affecting the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints as well as larger joints like the wrists, shoulders or knees. We present a case of a 49-year-old woman with symmetrical pain not only in her knees, shoulders, wrists, and MCP and PIP joints but also in her distal interphalangeal (DIP) joints. She has elevated levels of rheumatoid factor and anticitrullinated protein antibodies and a highly active arthritis on magnetic resonance imaging of her right hand in the wrist, MCP, PIP, and 3 out of 4 DIP joints. In summary, we diagnosed a seropositive rheumatoid arthritis affecting all but 1 joint of her hand. This case highlights the very rare (less than 0.2%) affection of 3 out of 4 DIP joints in rheumatoid arthritis.","[""Case Reports"", ""Journal Article""]","[""Witte T"", ""Albach F"", ""Simon D"", ""Kleyer A"", ""Biesen R"", ""Hermann KG""]",10.1016/j.ero.2025.11.013,Witte T,EULAR rheumatology open,3050-7081,2,EULAR Rheumatol Open,eng,Hermann KG,[],100086,42540144,pmc-id: PMC13425210;,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42540144/,A handful of inflammation,2,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
,"[""Letter""]","[""Knitza J"", ""Aries P""]",10.1016/j.ero.2025.12.002,Knitza J,EULAR rheumatology open,3050-7081,2,EULAR Rheumatol Open,eng,Aries P,[],100101,42540133,pmc-id: PMC13425160;,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42540133/,Ambient AI scribes in rheumatology: early real-world clinician and patient experience,2,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Ascariasis is a helminthic infection caused by the nematode Ascaris lumbricoides and remains the most prevalent helminth infection worldwide. Although typically asymptomatic or limited to intestinal symptoms, intestinal ascariasis can present unusually as demonstrated in these two cases. The first case involves a 73-year-old male who was being treated for non-steroidal anti-inflammatory drug (NSAID) - induced upper gastrointestinal bleeding (UGIB) and was incidentally found to harbor Ascaris worms in the duodenum during endoscopy. The second case describes a 63-year-old male with decompensated liver cirrhosis who began vomiting and passing large quantities of Ascaris worms while hospitalized. Both patients responded excellently to anthelminthic therapy. The first case highlights the need to consider ascariasis in the differential diagnosis of upper gastrointestinal bleeding, either as a primary cause or in conjunction with other causes of upper GI bleeding. The second case underscores the importance of considering biliary ascariasis or ascariasis co-infection in patients with liver cirrhosis. Ascariasis continues to pose a significant public health challenge. Effective preventive strategies such as improved sanitation, enhanced personal hygiene, and routine deworming programs are crucial for reducing the disease burden and averting potentially severe complications.","[""Journal Article"", ""Review""]","[""Duruewuru UP"", ""Chukwurah SN"", ""Nnemelu OP"", ""Nduaguba TS"", ""Nwafor EN"", ""Ogbonna KE"", ""Ilika CV""]",,Duruewuru UP,Nigerian medical journal : journal of the Nigeria Medical Association,0300-1652,6,Niger Med J,eng,Ilika CV,[],2398-2407,42540124,pmc-id: PMC13425374;,2025 Nov-Dec,2025,https://pubmed.ncbi.nlm.nih.gov/42540124/,Gastrointestinal Ascariasis: Unusual Presentation in 2 Cases,66,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"To perform a systematic literature review (SLR) to inform the EULAR Task Force ""Points to Consider for the definitions of Difficult-to-Manage (D2M) and Treatment-Refractory (TR) psoriatic arthritis (PsA)"". The SLR addressed 3 separate questions concerning the following: (1) prevalence, (2) outcomes, and (3) predictors of D2M/TR PsA. A search was conducted in MEDLINE (Ovid), Cochrane Database of Systematic Reviews, CENTRAL, EMBASE, and Epistemonikos from inception to March 3, 2024, as well as EULAR/ACR abstracts for 2023/24 and 2022/23, respectively. This systematic review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered on PROSPERO. Data are summarised descriptively. Meta-analysis was not possible due to significant heterogeneity and/or lack of high-quality evidence. Risk of bias (RoB) was assessed using the Newcastle-Ottawa Scale. Overall, 70, 4, and 25 articles/abstracts were included for questions 1, 2, and 3, respectively. For question 1, 30/70 records had low/moderate RoB, with the prevalence of D2T PsA ranging from 5% to 80% depending on both the timepoint at which prevalence was measured and the definition of D2M/TR PsA applied, which varied significantly between studies. For question 2, all records had a high RoB; therefore, no conclusions could be drawn. For question 3, all records had a moderate RoB, and 84 categories of potential predictors were identified, with large differences in strength and direction of association between studies. Despite significant heterogeneity in the published literature regarding the scope, definition, long-term outcomes, and predictors of D2M/TR PsA, certain patterns emerged that helped shape the final EULAR Task Force recommendations.","[""Journal Article""]","[""Harrison SR"", ""Fragoulis GE"", ""Michelena X"", ""Macía-Villa C"", ""Falzon L"", ""Siebert S"", ""Marzo-Ortega H"", ""Sepriano A"", ""Machado PM""]",10.1016/j.ero.2025.07.007,Harrison SR,EULAR rheumatology open,3050-7081,2,EULAR Rheumatol Open,eng,Machado PM,[],100043,42540123,pmc-id: PMC13425173;,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42540123/,"Prevalence, outcomes, and predictive factors: a systematic literature review to inform the development of EULAR Points to Consider for the definition of Difficult-to-Manage and Treatment-Refractory psoriatic arthritis",2,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
,"[""Case Reports"", ""Journal Article""]","[""Albach FN"", ""Minopoulou I"", ""Wilhelm A"", ""Kleyer A"", ""Wiebe E"", ""Fleischmann A"", ""Engel K"", ""Frick M"", ""Damm F"", ""Gogolok J"", ""Serve S"", ""Locher B"", ""Borie D"", ""Phithak E"", ""Hinkelmann L"", ""Ohrndorf S"", ""Casteleyn V"", ""Biesen R"", ""Sattler A"", ""Dörner T"", ""Drzeniek NM"", ""Alexander T"", ""Zernicke J"", ""Unterwalder N"", ""Movassaghi K"", ""Hütter-Krönke ML"", ""Schrezenmeier E"", ""Schreiber A"", ""Furth C"", ""Schett G"", ""Schneider U"", ""Bullinger L"", ""Krönke G"", ""Penack O"", ""Simon D""]",10.1016/j.ero.2025.08.008,Albach FN,EULAR rheumatology open,3050-7081,2,EULAR Rheumatol Open,eng,Simon D,[],100053,42540103,pmc-id: PMC13425153;,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42540103/,Rapid and profound treatment response of difficult-to-treat rheumatoid arthritis to CD19 CAR T-cell therapy,2,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"A task force commissioned by the European Alliance of Associations for Rheumatology was set up for the Development And Validation of a composite disease actIvity score in adult-onset Still's Disease (AOSD) (CLI113). A systematic literature review was undertaken to extract evidence regarding the disease activity assessment in AOSD and to identify potential candidate variables to be included in the criteria for the assessment of disease activity. The PubMed MEDLINE, EMBASE, and Web of Science databases were screened for eligible articles published between January 1990 and September 2021. Abstracts from 2018 to 2021 EULAR, ACR, and ISSAID conferences were also browsed. We included randomised controlled trials (RCTs), quasi-RCTs, cohort studies and case series of ≥ 4 patients describing changes under therapy, with a minimum follow-up of 4 weeks. The risk of bias was assessed using the National Institute of Health Quality Assessment Tool. Results were synthesised descriptively. Sixty-three studies (including 2889 patients) were selected. Four were RCTs or quasi-RCTs, and 59 were observational studies. Most of the studies were retrospective (n = 58) and of poor quality. The most often reported clinical characteristics were fever, cutaneous rash, arthralgia and/or arthritis, hepatosplenomegaly, and sore throat. The most often reported laboratory parameters were leukocyte count, erythrocyte sedimentation rate, serum C-reactive protein and ferritin levels, all of which decreased with treatment. Definitions of response, remission and relapse, disease activity composite indices and patient-reported outcomes were heterogeneous. Based on the identified variables, we can aim for a subsequent establishment and validation of a new measure to improve and standardise the management of patients with AOSD.","[""Journal Article"", ""Review""]","[""Girard-Guyonvarc'h C"", ""Mitrovic S"", ""Ruscitti P"", ""Fautrel B"", ""Gabay C"", ""Gonzalez-Gay MÁ"", ""Feist E"", ""Giacomelli R"", ""Stamm T"", ""EULAR Task Force CLI113""]",10.1016/j.ero.2025.05.001,Girard-Guyonvarc'h C,EULAR rheumatology open,3050-7081,2,EULAR Rheumatol Open,eng,Stamm T,[],100017,42540092,pmc-id: PMC13425147;,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42540092/,"Clinical, biological, and radiological changes under therapy, and criteria for clinical response and remission in adult-onset Still's disease: a systematic literature review informing the development of the European Alliance of Associations for Rheumatology (EULAR) criteria for assessing disease activity",2,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"The assessment of activity in adult-onset Still's disease (AOSD) remains difficult because of no validated score for this disease. A task force commissioned by the European Alliance of Associations for Rheumatology (EULAR) undertook a 3-round consensus-building study to elicit items to be included in the criteria for the assessment of disease activity for AOSD. Candidate items were initially extracted from a systematic literature review, and additional items were collected from expert physicians' answers to open-ended questions during the first Delphi round via a web-based application. In the second round, the expert physicians scored items for relevance. Subsequently, the expert physicians were presented the results of the group ratings and asked to score again in the third and final Delphi round. The cutoff for including an item in the criteria for the assessment of disease activity was set at ≥75% for the top 2 ratings ('absolutely required' and 'important'). In total, 25 expert physicians from 7 countries participated in all 3 Delphi rounds. A total of 28 candidate items were initially identified. In the final expert rating, the 14 following items were above the cutoff: fever, cutaneous rash, arthralgia, arthritis, splenomegaly, lymphadenopathies, pleuritis, pericarditis, white blood cell count ≥10,000/mm3, polymorphonuclear cells ≥80% of white blood cell count, increased erythrocyte sedimentation rate, increased serum C-reactive protein level, increased serum ferritin level, and elevated liver enzyme levels. The study is the first part of the development and validation of the criteria for the assessment of disease activity in AOSD.","[""Journal Article""]","[""Mitrovic S"", ""Girard-Guyonvarc'h C"", ""Ruscitti P"", ""Gabay C"", ""Gonzalez-Gay MÁ"", ""Feist E"", ""Giacomelli R"", ""Stamm T"", ""Fautrel B"", ""EULAR Task Force “CLI113”""]",10.1016/j.ero.2025.05.004,Mitrovic S,EULAR rheumatology open,3050-7081,2,EULAR Rheumatol Open,eng,Fautrel B,[],100020,42540075,pmc-id: PMC13425146;,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42540075/,Items identified by expert physicians for the development of the criteria for the assessment of disease activity for adult-onset Still's disease: results of a web-based Delphi study informing the development of the European Alliance of Associations for Rheumatology (EULAR) criteria for the assessment of disease activity in these patients,2,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"In Germany, canakinumab is approved for the treatment of refractory systemic juvenile idiopathic arthritis (sJIA)/Still's disease. This study assesses the experience of sJIA/Still's disease patients treated with canakinumab in clinical practice. Data of 79 sJIA/Still's disease patients extracted from the BiKeR registry included patients' and disease characteristics. Three subgroups with disease durations before canakinumab initiation of ≤3 months, >3 to ≤12 months, and >12 months were compared, and 2 with canakinumab as first- and second- or more-line treatment. Disease duration was ≤3 months before canakinumab initiation for 26 patients, >3 to ≤12 months for 24 patients, and >12 months for 29 patients. Thirty-nine patients received canakinumab as first-line treatment and 40 as second- or more-line treatment. Disease severity as assessed by the systemic Juvenile Arthritis Disease Activity Score-10 (sJADAS10) was highest for patients with a disease duration <3 months before canakinumab initiation. In the total cohort, after 3, 6, 12, 18, and 24 months, 86%, 81%, 81%, 75%, and 87% of patients reached inactive disease, respectively. Numerically, more patients reached the treatment goal of inactive disease when the disease duration was shorter before initiation of canakinumab. Minimal disease activity (sJADAS10 ≤6.0) did not differ among subgroups. Compared with second-line, more patients with first-line treatment reached inactive disease at months 6, 12, and 24 after canakinumab initiation. sJADAS10 at 12 months correlated significantly with disease duration before treatment. Canakinumab treatment led to high improvement rates and achievement of inactive disease state, particularly if they are administered early. Data from clinical practice confirm clinical study data.","[""Journal Article""]","[""Horneff G"", ""Kallinich T"", ""Minden K"", ""Dressler F"", ""Hufnagel M"", ""Weller-Heinemann F"", ""Klein A""]",10.1016/j.ero.2025.11.010,Horneff G,EULAR rheumatology open,3050-7081,2,EULAR Rheumatol Open,eng,Klein A,[],100083,42540060,pmc-id: PMC13425002;,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42540060/,Canakinumab for systemic-onset juvenile idiopathic arthritis/Still's disease-effectiveness and safety data from the BiKeR registry,2,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Psychedelic-assisted therapies have recently gained attention as potential novel treatments for various mental health conditions. In Canada, there has been particular interest from the veteran communities regarding the potential therapeutic impact of psychedelics. However, legal access remains limited in Canada, leading some veterans to explore alternative pathways. Here, we aimed to explore how Canadian military veterans learn about and access psychedelics for mental health treatment. Using a retrospective survey-based design in collaboration with the registered Canadian charity, Heroic Hearts Canada, we collected data from 30 veterans on their mental health history, prior treatments, information sources, and methods of access. Our findings indicate that while some veterans accessed psychedelics through legal pathways (20%, N = 5), most sought them through underground options, including self-directed (64%, N = 16) and guided experiences within (44%, N = 11) and outside (20%, N = 5) Canada. Veterans primarily relied on peers (73.3%, N = 22) and media (53.3%, N = 16) for information rather than health care providers (10%, N = 3). Those who avoided discussions with their health care providers cited concerns about stigma (64%, N = 9/14), while those who did consult health care providers often found them to lack knowledge on psychedelic treatments (69%, N = 11). These findings highlight gaps in access and education surrounding psychedelic therapies for veterans. While interest in these therapies is growing, it is important to note that clinical use of psychedelics for mental health conditions remains investigational. We propose that addressing these barriers through improved clinician training and education, policy reform, and development of safer legal pathways may support more informed and cautious engagement with these treatments and is essential to ensuring informed and effective care for those seeking alternative mental health treatments, such as psychedelics. Moreover, these efforts will contribute to broader harm reduction strategies by equipping clinicians with the knowledge and tools to support individuals who may continue to access these substances outside legal frameworks.","[""Journal Article""]","[""Contreras LE"", ""Elliott GO"", ""Kment F"", ""Scott MA"", ""Fascinato D"", ""Mayo LM""]",10.1177/28314425251387678,Contreras LE,"Psychedelic medicine (New Rochelle, N.Y.)",2831-4425,3,Psychedelic Med (New Rochelle),eng,Mayo LM,[],176-185,42540045,pmc-id: PMC13424948;embargo-date: 2026/12/17;,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42540045/,"Exploring Access to Psychedelics Among Canadian Veterans: Pathways, Barriers, and Perceptions",4,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Many randomised clinical trials in systemic lupus erythematosus have failed, and the manner in which they have failed is of concern. In lupus, phase III trials have a higher risk of failing than phase II trials-going against the expected gradient and against logic, because phase III trials are preferentially based on successful rather than on failed phase II trials. In addition, there have been puzzling discrepancies between different outcomes within individual trials as well as between the same outcomes in different trials. Therefore, it has been suggested that outcome measures are to blame for the difficulties in achieving trial successes in lupus. Additional concerns regarding clinical trial outcomes deal with their complexity and lack of clinical applicability; and the most widely used trial outcomes, SRI-4 (systemic lupus response index [based on four points improvement]) and BICLA (British Isles Lupus Assessment Group-Based Composite Lupus Assessment), are at odds with current therapeutic thinking, which is less concerned with change and more with the disease state that is achieved (treating to target). A number of suggestions have been made, and concrete initiatives launched, to address these issues, and these may change the way in which clinical trials will be done in the future. Meanwhile, it is worth mentioning that a large number of phase III trials are currently underway; their outcomes may yet again change the way we approach clinical trial outcomes in lupus.","[""Journal Article"", ""Review""]","[""van Vollenhoven R""]",10.1016/j.ero.2025.11.017,van Vollenhoven R,EULAR rheumatology open,3050-7081,2,EULAR Rheumatol Open,eng,van Vollenhoven R,[],100090,42540000,pmc-id: PMC13424988;,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42540000/,Lupus trials and tribulations: are outcome measures the problem?,2,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Swimming-induced pulmonary oedema (SIPO) has predominantly been reported in swimmers. However, to date, no review has specifically explored the scientific literature concerning the occurrence and characteristics of SIPO in triathletes. Therefore, this review aims to summarize and discuss the current evidence on SIPO in the context of triathlon. We conducted a narrative review to summarize the current scientific literature on SIPO in triathletes. A structured search of two major databases-PubMed and Scopus-was conducted using free-text terms related to SIPO and triathlon. The search included articles published up to January 2025, with no language restrictions. After removing duplicates and excluding animal or in vitro studies, as well as unrelated articles based on title and abstract screening, a total of 48 relevant publications were included for analysis. The reports on SIPO in triathletes are mainly case reports or case studies on a single athlete or a small number (case series) of triathletes. Most reported cases involved middle-aged women (30-60 years) participating in IRONMAN® 70.3 and IRONMAN® triathlons. The prevalence of SIPO in triathletes is reported to be less than 1.5%. Risk factors for SIPO in triathletes are female sex, age over 50 years, hypertension, fish oil consumption, highly trained individuals, competitive exercise, wet suit compression, longer race distances (i.e. IRONMAN® 70.3 or IRONMAN®) and a cold (water) environment. The symptoms and outcome are similar to those observed in swimmers and other aquatic athletes. In summary, the results regarding the prevalence, symptoms and risk factors of SIPO in triathletes are comparable to those in other aquatic athletes. SIPO occurs only in IRONMAN® 70.3 and IRONMAN® races, but has not been reported in the Olympic distance triathlon or triathlons longer than the IRONMAN® race distance.","[""Journal Article"", ""Review""]","[""Knechtle B"", ""Nikolaidis PT"", ""Chlíbková D"", ""Bernardes Leite L"", ""Forte P"", ""Santos Andrade M"", ""Weiss K"", ""Rosemann T"", ""Duric S""]",10.1016/j.smhs.2025.08.004,Knechtle B,Sports medicine and health science,2666-3376,5,Sports Med Health Sci,eng,Duric S,[],501-508,42539943,pmc-id: PMC13424964;,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42539943/,"Swimming-induced pulmonary oedema in triathletes: A narrative review of epidemiology, risk factors and prevention",8,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Catalytic decomposition is a key technology for the removal of ozone (O3). Practical application scenarios require catalysts with superior O3 decomposition performance at ambient temperatures, high humidity, and high space velocities. In this review, the strategies for the design of catalysts with efficient and stable O3 decomposition performance are presented, and the three factors that limit the catalytic decomposition of O3 at ambient temperature (insufficient active sites, competitive adsorption of H2O and O3 molecules, and difficult desorption of intermediate oxygen species) are systematically summarized for the first time. Subsequently, the research progress in recent years is categorized and summarized in terms of addressing the three factors limiting O3 decomposition, which in turn suggests the shortcomings of current research and the focus of future research.","[""Journal Article"", ""Review""]","[""Li X"", ""Wang Z"", ""Chu B"", ""Ma J"", ""He H""]",10.1016/j.fmre.2025.12.001,Li X,Fundamental research,2096-9457,4,Fundam Res,eng,He H,[],2212-2220,42539942,pmc-id: PMC13424934;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42539942/,Challenges and opportunities of catalytic decomposition of ozone at room temperature,6,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Osteocalcin (OC) and the undercarboxylated form (ucOC) are bone-derived peptide hormones produced by osteoblasts that are involved in systemic metabolism and skeletal muscle mass regulation. Human studies have been equivocal regarding the relationship of circulating OC with muscle mass. Our aim was to summarize the published findings on the relationship between OC levels and muscle mass measurements in humans and determine if factors such as age and sex impact the outcome. PubMed, Scopus, and CINHAL databases were systematically searched to identify empirical human studies reporting the correlation coefficients between OC levels and measures of muscle mass. Muscle mass measurements included total body lean mass (tLM), percent lean mass (%LM), appendicular lean mass (aLM), and lean muscle index (LMI). Studies were included in the meta-analysis, with effect sizes being extracted for total OC (tOC) and ucOC. Subgroup analyses examined age, sex, and health status. Muscle mass quantified by %LM had a significant correlation with tOC and ucOC. LMI had a significant correlation with ucOC, but not tLM, and aLM. There was a weak, significant positive association between tOC and ucOC with all combined muscle mass measurements, and the relationship with tOC was more evident in male adults. Circulating OC, specifically ucOC, had a significant relationship with %LM, but not tLM or aLM. Circulating OC appears to be more closely associated with body composition than with total mass. Further studies are needed to determine how age and sex interact with OC regulation of body composition.","[""Journal Article"", ""Review""]","[""Zhang Q"", ""Xie Y"", ""Jenkins T"", ""Carson J""]",10.1016/j.smhs.2025.12.003,Zhang Q,Sports medicine and health science,2666-3376,5,Sports Med Health Sci,eng,Carson J,[],509-523,42539930,pmc-id: PMC13424722;,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42539930/,The relationship between circulating osteocalcin and muscle mass measurements in humans: A systematic review and meta-analysis,8,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Super-converged generative information network (SoGIN) envisions the integration of human-physical and digital networks, with development requirements centered on space-air-ground integration, computing-storage-sensing-intelligence integration, and availability-reliability-trustworthiness integration. Following the new development paradigm of decoupling network support environments from application network systems, SoGIN would build an AI-empowered, highly integrated, efficiently collaborative, trustworthy intelligent information network system based on the deep integration of digital-operation-information-communication technology (DOICT). This provides the foundational support environment for realizing 6G visions. This paper discusses the challenges and fundamental theoretical issues faced by SoGIN. Firstly, the development vision and demands of SoGIN are elaborated. Then, the theoretical and technical challenges in achieving the vision of SoGIN are analyzed. Finally, related theoretical and technical practices about polymorphic network environments, cloud-native-based super-converged network infrastructures, new cybersecurity paradigm, cyberspace resilience empowered by endogenous security and safety (ESS), and the physical foundation of next-generation digital systems technology based on wafer-level computing are described.","[""Journal Article"", ""Review""]","[""Wu J"", ""Ji X"", ""Huang K"", ""Chen Y"", ""Li D"", ""Zhang W"", ""Yang J"", ""Hu Y"", ""Shen J""]",10.1016/j.fmre.2025.10.007,Wu J,Fundamental research,2096-9457,4,Fundam Res,eng,Shen J,[],2017-2034,42539919,pmc-id: PMC13424720;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42539919/,Challenges and fundamental theoretical problems of super-converged generative information network,6,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Psilocybin therapy is an emerging treatment for cancer-related anxiety, depression, and existential distress. Most clinical trials to date have studied individual models of psilocybin therapy, but group models may offer increased access and benefits of community. This technical report describes a group facilitation model developed for an food and drug administration (FDA)-approved Phase 1 to 2 clinical trial that recruited people with metastatic cancer who had moderate or severe symptoms of anxiety or depression in which psilocybin was administered at a 3-day, in-person retreat. The facilitation model we developed for this intervention is based on anthropological studies of ritual, specifically rites of passage, to develop a secular ritual with therapeutic aims. Using rites of passage terminology, ""separation"" corresponds to preparation, ""liminal"" corresponds to the psilocybin dosing session, and ""reincorporation"" corresponds to integration. In our usage, the term ""ritual"" refers to intentionally structured, symbolic acts that embody and reinforce shared meaning, guiding participants through experiences that may otherwise feel unbounded or overwhelming. In the group psilocybin retreat model, ritual functions both psychologically-by supporting emotional regulation, orientation, and meaning-making-and communally-by embedding the individual's process within a shared field of intention and care. To our knowledge this is the first FDA-approved clinical trial of a secular ritual-based group facilitation model for psychedelic therapy that is associated with empirically demonstrated safety and efficacy outcomes.","[""Journal Article""]","[""Back AL"", ""McGregor BA"", ""Billingsley L"", ""Blom D"", ""Callan G"", ""Myers S"", ""Guy J"", ""Kumar S"", ""Layer M"", ""Levin J"", ""Perez J"", ""Thompson P"", ""Salmonson K"", ""Whinney J"", ""Thorn LL""]",10.1177/28314425251404460,Back AL,"Psychedelic medicine (New Rochelle, N.Y.)",2831-4425,3,Psychedelic Med (New Rochelle),eng,Thorn LL,[],222-230,42539893,pmc-id: PMC13424538;embargo-date: 2026/12/09;,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42539893/,Group Retreat Psilocybin Therapy for People with Metastatic Cancer with Anxiety and Depression: A Rite of Passage Facilitation Model for a Phase 1/2 Study,4,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Seeds with different desiccation tolerance and their foraging animals present unique strategies for ensuring population growth and ecological fitness in the natural environment. While some seeds minimize physical injuries by having lignified thick coats or defensive compounds, others tolerate a certain degree of mass loss, with larger seeds enduring partial animal consumption better than smaller seeds, consistent with the reserve effect hypothesis, regardless of their desiccation tolerance. In endozoochory, aerial, terrestrial and aquatic fauna with appropriate gape sizes that consume whole fruits with mostly orthodox seeds are important for longer-distance seed dispersal as long as seed viability suffers little impairment following defecation. Some seeds even gain benefits from animal consumption when physical dormancy is overcome and germination occurs earlier. Dung beetles perform secondary spread and burial of seeds, reducing plant aggregation. On the other hand, highly nutritious recalcitrant seeds of a limited number of plant species show sprouting despite partial loss of embryonic axes to browsing animals, often with damage to radicles being less critical than to plumules. Some recalcitrant seeds even possess the unique ability to regenerate roots and shoots from the cotyledonary tissues devoid of embryonic axes. Such embryonic cell development, or 'stemness', from seed tissue fraction is rare in the plant kingdom, but evidently present in at least four families. Plant regeneration despite seed predation is a multi-trait adaptation that ensures species survival and fosters resilient natural ecosystems.","[""Journal Article"", ""Review""]","[""Tsan FY"", ""Colville L"", ""Pritchard HW""]",10.1016/j.pld.2025.07.005,Tsan FY,Plant diversity,2096-2703,4,Plant Divers,eng,Pritchard HW,[],641-654,42539862,pmc-id: PMC13424734;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42539862/,Regeneration from seeds with physical defects: Contrasts in survival strategies in recalcitrant and orthodox seeds,48,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Ion channels are crucial membrane proteins that regulate ion flux, thus affecting a broad range of physiological processes and disease mechanisms. Traditional approaches, such as X-ray crystallography and cryo-electron microscopy, often face significant challenges in resolving the structure-function relationships of ion channels due to the complex subunit assemblies, transient functional states, and high experimental costs. AlphaFold3 offers a major leap forward by accurately modeling multimeric channels, predicting ligand and ion interactions, and refining subunit interfaces. Building on AlphaFold2, it integrates diffusion-based algorithms and enhanced confidence metrics to explore gating, auxiliary subunits, disease-linked mutations, etc. This review outlines AlphaFold3's key innovations and provides a step-by-step protocol for its use in predicting ion channel complexes. We discuss essential structural parameters, common software for basic analyses, and complementary techniques including molecular dynamics simulations, molecular docking, functional assays (electrophysiology and ion imaging) and structure biology techniques that extend and validate computational findings. Representative examples, including the P2X receptors and voltage-gated calcium channels, demonstrate AlphaFold3's ability to clarify channel assembly, gating mechanisms, channelopathies, and therapeutic opportunities. Finally, we address AlphaFold3's remaining limitations. Despite these hurdles, AlphaFold3 offers a transformative platform that, when integrated with established experimental methods, is poised to significantly advance ion channel research and drug discovery.","[""Journal Article"", ""Review""]","[""Ke Y"", ""Gong R"", ""Liu N"", ""Yang Y""]",10.1016/j.fmre.2025.07.010,Ke Y,Fundamental research,2096-9457,4,Fundam Res,eng,Yang Y,[],2273-2288,42539828,pmc-id: PMC13424397;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42539828/,A brief guideline for the studies of structure-function relationship of ion channels using AlphaFold3,6,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Psychedelic-assisted psychotherapy has shown promising results for treating alcohol use disorder (AUD) and other mental health conditions. Although the precise mechanisms of psychedelic therapies remain unclear, many studies report increased feelings of connectedness following psychedelic experiences. Specifically, both nature relatedness (one's subjective sense of being connected to nature) and social connectedness (feelings of comprehensive social closeness) have been shown to increase with psychedelic use, and greater connectedness in these domains has been associated with enhanced health and well-being. The current study examined whether a nature-themed video intervention presented to participants undergoing psilocybin-assisted psychotherapy would differentially affect nature relatedness compared with social connectedness in adults with AUD. A total of 20 participants were randomized to either the visual healing condition (viewing a 42-min nature video; N = 10) or the standard setting condition (guided body scan; music with eyeshades; N = 10). Nature relatedness and social connectedness were measured using the Nature Relatedness Scale (NRS-6) and the Social Connectedness Scale-Revised (SCS-R) at baseline and 2 weeks after the psilocybin session. A significant between-group difference was observed in change in nature relatedness pre-to-postpsilocybin session [χ2(1) = 5.74, p = 0.02]. Nature relatedness significantly increased in the visual healing group [median change in NR-6 = 0.33, range = (-0.17, 0.67), p = 0.01], but not in the standard setting group [median change = 0.00; range = (-0.17, 0.33), p = 0.50]. No significant between-group differences were observed for change in social connectedness [χ2(1) = 0.89, p = 0.35], and no significant overall change in social connectedness was observed across groups [median change = -1.00, range = (-27, 20), p = 0.90]. Viewing a nature-themed video may enhance nature relatedness among individuals undergoing psilocybin-assisted psychotherapy for AUD. Future research should investigate the effects of real-life nature immersion and explore nature relatedness and other forms of connectedness as potential therapeutic targets in psychedelic-assisted and other psychotherapies NCT04410913.","[""Journal Article""]","[""Rich R"", ""Laird K"", ""Siddarth P"", ""Youssef B"", ""Schwartz GM"", ""Ramos A"", ""Sergi K"", ""Linton M"", ""Schwartzberg L"", ""Kelly DF"", ""Heinzerling KG""]",10.1177/28314425251387655,Rich R,"Psychedelic medicine (New Rochelle, N.Y.)",2831-4425,3,Psychedelic Med (New Rochelle),eng,Heinzerling KG,[],199-208,42539824,pmc-id: PMC13424534;embargo-date: 2026/12/26;,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42539824/,A Nature-Themed Video Intervention Increases Nature Relatedness in Psilocybin-Assisted Psychotherapy for Alcohol Use Disorder,4,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Bergamotene, a key sesquiterpene compound, is crucial for defining the fruity aroma. However, the precise regulatory mechanisms governing its biosynthesis have been largely elusive. In this study, we elucidated that the DOF transcription factor LcDOF5.8 plays a central role in the biosynthesis of α-bergamotene by directly enhancing the expression of the terpene synthase gene LcTPSbms in litchi fruit. Our findings revealed that the concentration of α-bergamotene varies significantly among four distinct litchi cultivars: 'Guanyinlv', 'Bingli', 'Guiwei' and 'Nuomici'. Notably, a strong correlation was observed between the expression level of LcTPSbms and the content level of α-bergamotene across these cultivars. Furthermore, both in vitro and in vivo catalytic assays confirmed that LcTPSbms is capable of catalyzing the synthesis of α-bergamotene. Importantly, electrophoretic mobility shift assays (EMSA) and Dual-LUC assays demonstrated that LcTPSbms is positively regulated by LcDOF5.8. Silencing LcDOF5.8 in litchi aril resulted in decreased LcTPSbms expression, whereas transient overexpression of LcDOF5.8 led to a significant upregulation of LcTPSbms and a concomitant increase in α-bergamotene biosynthesis. In summary, our research uncovers a regulatory module involving LcDOF5.8 and LcTPSbms that plays a critical role in the biosynthesis of α-bergamotene, offering valuable insights into the molecular mechanisms underlying the fruity aroma of litchi fruit.","[""Journal Article""]","[""Wang Y"", ""Liu Z"", ""Wang M"", ""Qian D"", ""Ma K"", ""Zhao M"", ""Li J"", ""Ma X""]",10.1016/j.fmre.2025.12.004,Wang Y,Fundamental research,2096-9457,4,Fundam Res,eng,Ma X,[],2262-2272,42539821,pmc-id: PMC13424721;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42539821/,Regulation of α-bergamotene biosynthesis by the LcDOF5.8-LcTPSbms regulatory module in litchi fruit,6,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Despite being the largest sector of the health care workforce with potential to support advancing psychedelics in health care, nurses and their views toward psychedelics and changing legal restrictions remain mostly unknown. To identify an optimal predictive model for nurses' support (or not) of decriminalization of psychedelics. Secondary analysis of e-survey data from 1092 registered nurses and advanced practice registered nurses invited randomly from the Minnesota Board of Nursing registry. To develop an optimal predictive model, multinomial logistic regression with backward selection using the Akaike information criterion (AIC) was applied to the training set. The final model was fitted to the validation set for effect estimation, with performance assessed using multiclass area under the curve (AUC). Backward selection using AIC identified several key predictors of support for decriminalization of psychedelics in Minnesota: age, gender identity, specific spiritual orientation, awareness of Colorado's psychedelic decriminalization, and scores from the Attitudes and Perceptions Questionnaire legal and effects subscales. The final model demonstrated excellent discriminative ability with a multiclass AUC of 0.870 (95% confidence interval [CI]: 0.847-0.898). Pairwise comparisons revealed outstanding discrimination between supporters and opponents of decriminalization (AUC = 0.973, 95% CI: 0.952-0.987). Age (younger/older), (awareness/lack of awareness) of Colorado's decriminalization laws, and attitudes (concerns/lack of concerns) toward effects and legal status of psychedelics predicted a nurse's (more/less positive) attitude toward psychedelics. This model offers an informative starting point for understanding nurses' and, by proxy, the communities in which they live and work and provides initial direction toward tailoring curricular and professional development resources on psychedelics for nurses across the United States.","[""Journal Article""]","[""Porta CM"", ""Wu CC"", ""Graefe A"", ""Grumdahl N"", ""Dorsen C""]",10.1177/28314425251385531,Porta CM,"Psychedelic medicine (New Rochelle, N.Y.)",2831-4425,3,Psychedelic Med (New Rochelle),eng,Dorsen C,[],169-175,42539819,pmc-id: PMC13424522;embargo-date: 2026/12/10;,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42539819/,Predicting Nurses' Views on Decriminalization of Psychedelics,4,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Neonatal bilirubin encephalopathy is primarily characterized by central auditory dysfunction and cognitive impairments. However, the precise molecular mechanisms underlying bilirubin-induced neurotoxicity remain poorly understood, hindering the development of effective therapeutic strategies. Using kinase activity prediction tools based on quantitative phosphoproteomics, we identified ROCK2 (Rho-associated protein kinase 2) as a critical kinase regulating the phosphorylation of proteins associated with bilirubin exposure. Molecular docking and MicroScale Thermophoresis assays revealed a strong binding affinity between bilirubin and ROCK2. Interestingly, bilirubin increased ROCK2 protein expression without affecting its mRNA levels, and cycloheximide chase assays revealed enhanced ROCK2 stability, implicating post-translational regulation. While bilirubin did not directly activate ROCK2 kinase activity in vitro, it elevated phosphorylation of its substrate LIMK1, suggesting that ROCK2 accumulation amplifies downstream signaling. In primary rat neurons, ROCK2 inhibitors (Belumosudil and Y-27632) ameliorated bilirubin-induced loss of mitochondrial membrane potential and neuronal cell death. Furthermore, using ROCK2 inhibitors and Rock2+/- mice, we demonstrated that modulation of ROCK2 significantly alleviated bilirubin-induced auditory deficits and cognitive impairments. These behavioral improvements were linked to restored excitatory synaptic transmission in the cochlear nucleus and reduced dendritic damage in hippocampal neurons. These findings position ROCK2 as a promising molecular target for therapeutic intervention in bilirubin encephalopathy.","[""Journal Article""]","[""Ke B"", ""Mao L"", ""Hu M"", ""Cui Y"", ""Chen M"", ""Wu C"", ""Guan R"", ""Yin S"", ""Li C""]",10.1016/j.fmre.2025.09.006,Ke B,Fundamental research,2096-9457,4,Fundam Res,eng,Li C,[],2725-2738,42539815,pmc-id: PMC13424666;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42539815/,Identifying ROCK2 as an intervention target for bilirubin encephalopathy,6,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"The superstructures formed by the self-assembly of nanoparticles (NPs) can exhibit unique photonic collective properties (structural color, localized surface plasmon resonance [LSPR]), enhance the interaction between light and matter, and open up new possibilities for photonic sensing. Many photonic biosensors have addressed the limitations of current bioanalytical methods with their non-invasive nature, real-time monitoring, and high sensitivity. In recent years, the construction of photonic biosensors using super-structured materials could further enhance the sensors in terms of sensitivity, processing capacity, ease of use, and miniaturization. Superstructure-based photonic biosensors can analyze complex samples, but their development still needs to overcome limitations related to target binding specificity, long-term stability, and signal decoding efficiency. The development of artificial intelligence (AI) provides new opportunities to solve these problems. Deep learning (DL) algorithms can independently extract multi-dimensional data features such as spectra and images, distinguish weak biological signals from noise, optimize detection parameters, and achieve real-time dynamic calibration. In this review, we provide the photonic collective characteristics of superstructures and the applications of biosensors in intelligent diagnosis. The applications of superstructured photonic sensors in disease diagnosis, drug delivery, and cell imaging are summarized. The colorimetric, fluorescence-based sensor technologies assisted by DL are discussed along with challenges faced in integrating AI with superstructure-based photonic biosensors. As this field continues to evolve, the integration of AI and superstructure-based photonic biosensors will undoubtedly play a pivotal role in shaping the future of medical diagnostics and therapeutic interventions.","[""Journal Article"", ""Review""]","[""Yin J"", ""Wang B"", ""Wang T"", ""Tang Z""]",10.1016/j.fmre.2025.09.014,Yin J,Fundamental research,2096-9457,4,Fundam Res,eng,Tang Z,[],2503-2528,42539804,pmc-id: PMC13424418;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42539804/,Photonic biosensors based on nanoparticle superstructures: from data analysis to artificial intelligence (AI) detection,6,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
"Psilocybin has been granted breakthrough therapy status in the United States, speeding its advancement from research to clinical care. Due to the controversial nature of psilocybin, psychiatrists may not be fully prepared to incorporate it into clinical practice. The current study aimed to evaluate the opinions toward psilocybin among practicing psychiatrists in Louisiana. Louisiana serves as a representative state, modeling other areas with limited exposure to psychedelic research. A 30-question survey was distributed via mail and digital newsletter to all registered Louisiana psychiatrists. The survey consisted of demographic questions and questions pertaining to how strongly respondents agreed or disagreed with statements about psilocybin and psychedelics on a five-point Likert scale. The statements aimed to assess knowledge and exposure to psilocybin including opinions on research and legalization, safety and addiction potential, medical use, and potential benefits and usages. Forty-nine responses were recorded. Eighty-two percent of participants reported having ""some knowledge"" of psilocybin. Eighty-six percent believed psilocybin should be researched for medicinal value, and 71% would prescribe psilocybin if it were proven beneficial for their patient's illness. Fifty-seven percent believed it should be considered a first-line treatment for certain conditions, while 73% believed it should be used only after exhausting all other treatment modalities. The study had an overall 10.5% response rate, potentially limiting the generalizability of the findings. Louisiana psychiatrists in our sample appear open to integrating psilocybin into their practice if there is strong regulatory support. Psilocybin research is rapidly expanding and will soon reach Louisiana and other states with a limited history of psychedelic clinical research. These findings warrant the development of an educational program on psychedelics to arm psychiatrists and patients with the knowledge to make the most informed decisions.","[""Journal Article""]","[""Husein A"", ""Traylor M"", ""Vest MF"", ""Wood BJ"", ""Brogan M"", ""Thomas A"", ""McNeil S"", ""Bhuiyan MAN"", ""Hendricks P"", ""Kelly JR"", ""Gribben A"", ""Al-Qahtani MM"", ""Keys K"", ""Edinoff AN"", ""Patterson JC"", ""Murnane KS""]",10.1177/28314425251381806,Husein A,"Psychedelic medicine (New Rochelle, N.Y.)",2831-4425,3,Psychedelic Med (New Rochelle),eng,Murnane KS,[],161-168,42539773,pmc-id: PMC13424530;embargo-date: 2026/12/19;,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42539773/,Assessing The Readiness of Psychiatrists in Louisiana to Incorporate Psilocybin into Clinical Practice-Lessons Learned from a State Underrepresented in Clinical Psychedelic Research,4,HghWVgHuynwfJx1lh,YedBUPiokG4fbI7Us
,"[""Journal Article""]","[""Armstrong AJ"", ""Azad AA"", ""Saad F"", ""Hussain M"", ""Iguchi T"", ""Stenzl A"", ""Sternberg CN""]",10.1200/JCO-26-01500,Armstrong AJ,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Sternberg CN,[],JCO2601500,42537005,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42537005/,Reply to: Radiographic Progression With and Without Prostate-Specific Antigen Rise in Patients With Advanced Prostate Cancer Treated With Enzalutamide,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
"Euro-EWING99 study was a large, international, prospective study recruiting patients with Ewing sarcoma (EWS) between 1999 and 2015. It assessed three different clinical questions through randomized trials. We report here the characteristics and outcomes of all patients. Patients younger than 50 years with EWS were included in the study. They received induction chemotherapy (six courses of vincristine [day 1], ifosfamide [day 1-3], doxorubicin [day 1-3], and etoposide [day 1-3; VIDE], administered every 3 weeks), local therapy (surgery/radiotherapy), and different consolidation treatments according to clinical risk group and trial.The objectives of the study were to describe the entire cohort according to the initial staging group, to describe the survival outcomes (overall survival [OS]; progression-free survival [PFS]; and local control), and to evaluate prognostic factors associated with OS and PFS. Three thousand three hundred ninety-five patients were included in the study, including 2,267 with a localized disease, 614 with pleuropulmonary metastases, and 514 with extrapulmonary metastases. Ninety-eight percent of patients received ≥4 neoadjuvant VIDE courses. The modalities of local treatment and consolidation therapy differed among the three staging groups. With a median follow-up of 7.2 years, PFS of the entire cohort was 60.2% and 55.4% at 3 and 5 years, respectively. OS was 72.6% and 64.6% at 3 and 5 years, respectively. In addition to metastatic status at diagnosis, main prognostic factors included patient age, tumor volume, and histologic response both for PFS and OS, independent of metastatic status. To our knowledge, this study is the largest published series of patients with EWS and may serve as a landmark paper for EWS. It confirms the major prognostic value of the complete histologic response after neoadjuvant therapy.","[""Journal Article""]","[""Valentin T"", ""Winter S"", ""Dirksen U"", ""Hawkins DS"", ""Gelderblom H"", ""Risbourg S"", ""Berlanga P"", ""Gaspar N"", ""Janeway KA"", ""Juergens H"", ""Kirchberg IE"", ""Ladenstein R"", ""Laurence V"", ""Le Deley MC"", ""McCabe MG"", ""Merks H"", ""Ranft A"", ""Strauss S"", ""Van De Sande MAJ"", ""Whelan J"", ""Marec-Berard P"", ""Brennan B""]",10.1200/JCO-25-02516,Valentin T,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Brennan B,[],JCO2502516,42537000,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42537000/,Long-Term Analysis of Patients With Ewing Sarcoma Included in the Euro-EWING99 Study,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Letter""]","[""Li Q"", ""Shao Z"", ""Xu X"", ""Mao W""]",10.1200/JCO-26-00565,Li Q,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Mao W,[],JCO2600565,42536990,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536990/,Statistical and Methodological Considerations in the Evaluation of Ultra-Low-Dose Nivolumab,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Letter""]","[""Oruç A"", ""Erol M""]",10.1200/JCO-26-00962,Oruç A,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Erol M,[],JCO2600962,42536987,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536987/,Radiographic Progression With and Without Prostate-Specific Antigen Rise in Patients With Advanced Prostate Cancer Treated With Enzalutamide,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Journal Article""]","[""Prabhash K"", ""Noronha V"", ""Pawar A"", ""Shetake A"", ""Badwe R""]",10.1200/JCO-26-01376,Prabhash K,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Badwe R,[],JCO2601376,42536983,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536983/,Reply to: Statistical and Methodological Considerations in the Evaluation of Ultra-Low-Dose Nivolumab,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
"Dexamethasone combined with a 5-hydroxytryptamine-3 receptor antagonist and a neurokinin-1 receptor antagonist is the guideline-recommended prophylaxis for chemotherapy-induced nausea and vomiting (CINV) in children receiving highly emetogenic chemotherapy (HEC), but it is associated with clinically relevant toxicities. The role of olanzapine as a dexamethasone-sparing agent for pediatric CINV prophylaxis remains uncertain. The Chemotherapy Induced Vomiting in Children-Prophylaxis Omitting Dexamethasone (CIVIC POD) was an investigator-initiated, multicenter, open-label, phase III, randomized noninferiority (NI) trial (INPHOG-SUPP-22-03) that enrolled patients age 4-18 years scheduled to receive single- or multiday HEC. Patients were randomly assigned 1:1 to dexamethasone, palonosetron, and fosaprepitant (DEX) or olanzapine, palonosetron, and fosaprepitant (OLANZ) for one chemotherapy cycle. The primary end point was complete response (CR) to vomiting (no vomiting and no rescue antiemetics) during the overall period (0-120 h after last chemotherapy). The prespecified NI margin was -15%. A total of 310 patients were randomly assigned (DEX, n = 156; OLANZ, n = 154). The median age was 13 years, 62.3% were male, and 51.9% received multiday chemotherapy. The per-protocol population included 299 patients (DEX, n = 151; OLANZ, n = 148). The overall-period CR to vomiting was 56.9% with DEX and 63.5% with OLANZ (absolute difference, 6.6% [95% CI, -4.5 to 17.7]), meeting NI criteria. Acute-period CR to vomiting was 64.2% versus 68.9%, and delayed-period CR was 78.8% versus 79.1% (DEX v OLANZ). CR to nausea during the overall, acute, and delayed periods was 54.3% versus 53.4%, 59.6% versus 59.5%, and 69.5% versus 68.9%, respectively. Any-grade somnolence was more frequent with OLANZ (50.7% v 17.2%). A dexamethasone-free regimen using olanzapine demonstrated noninferior control of vomiting compared with standard prophylaxis in children and adolescents receiving HEC, supporting olanzapine as a potential corticosteroid-sparing alternative for pediatric CINV prophylaxis.","[""Journal Article""]","[""Radhakrishnan V"", ""Srinivasan P"", ""Das G"", ""Bakhshi S"", ""Mahajan A"", ""Ganesan P"", ""Thiruvengadam Kothandan B"", ""Arora RS"", ""Parmpalli Manjunath S"", ""Ganguly S"", ""Pushpam D"", ""Bansal M"", ""Keerthivasagam S"", ""Sharma A"", ""Goel A"", ""Begum M"", ""Khan A"", ""Rajaraman S""]",10.1200/JCO-26-00677,Radhakrishnan V,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Rajaraman S,[],JCO2600677,42535876,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42535876/,"Dexamethasone-Free Antiemetic Prophylaxis for Children and Adolescents Receiving Highly Emetogenic Chemotherapy: A Multicenter, Phase III, Noninferiority Trial (CIVIC POD)",,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
"Smoldering multiple myeloma (SMM) is an asymptomatic but biologically heterogeneous plasma cell disorder with a variable risk of progression to multiple myeloma (MM). Accurate risk stratification is essential as only a subset of patients-defined as high-risk SMM -faces a ≥50% risk of progression within 2 years. Contemporary approaches integrating clinical variables, dynamic biomarkers, genomic alterations, and immune profiling have improved risk assessment although some limitations remain. The therapeutic paradigm of SMM is evolving. Randomized phase III trials have consistently shown that early treatment delays progression to MM. Most recently, daratumumab monotherapy became the first approved treatment for high-risk-SMM following the AQUILA trial, which demonstrated a significant progression-free survival benefit (hazard ratio [HR], 0.49 [95% CI, 0.36 to 0.67], P < .001) and a trend toward improved overall survival (OS; HR, 0.52 [95% CI, 0.27 to 0.98]) versus observation. This approval challenges the traditional watch-and-wait approach and establishes early intervention as a validated option for selected patients. However, important uncertainties persist. With modern surveillance and advanced imaging, most progression events are asymptomatic and irreversible end-organ damage is uncommon. OS benefit from early treatment remains inconclusive, particularly in the era of quadruplet regimens available at MM progression. In addition, difficulties in precisely identifying truly high-risk patients raise concerns about overtreatment. Emerging data from intensive regimens, bispecific antibodies, and chimeric antigen receptor -T cell therapies suggest that deep and durable responses-and possibly cure-may be achievable in selected patients with high-risk-SMM, but long-term benefit and safety require further study. In conclusion, following the approval of daratumumab, SMM management should be risk-adapted and patient-centered: observation remains appropriate for some patients, while early treatment should be considered for carefully selected high- and ultrahigh-risk individuals.","[""Journal Article"", ""Review""]","[""Mateos MV"", ""Gustine J"", ""Puertas B"", ""Raje N""]",10.1200/JCO-26-00236,Mateos MV,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Raje N,[],JCO2600236,42535861,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42535861/,High-Risk Smoldering Multiple Myeloma: A Review of Controversies in Early Treatment Versus Observation,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Editorial""]","[""Hesketh PJ""]",10.1200/JCO-26-01492,Hesketh PJ,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Hesketh PJ,[],JCO2601492,42535772,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42535772/,Limiting Dexamethasone Exposure With Highly Emetogenic Chemotherapy Regimens: Is the Verdict In?,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Journal Article"", ""Published Erratum""]","[""Bose P"", ""Ali H"", ""Al-Ali HK"", ""Garcia-Gutierrez V"", ""Grosicki S"", ""Grudeva-Popova Z"", ""Harrison C"", ""Hong J"", ""Hou HA"", ""Kwiatek M"", ""Loschi M"", ""Passamonti F"", ""Podoltsev N"", ""Rampal R"", ""Tantravahi S"", ""Urian LG"", ""Chai Y"", ""Taverna P"", ""Mark T"", ""Sadiq A"", ""Rangwala R"", ""Vachhani P"", ""Mascarenhas J"", ""SENTRY Trial Investigators""]",10.1200/JCO-26-01827,Bose P,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Mascarenhas J,[],JCO2601827,42531529,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531529/,Erratum: Selinexor Plus Ruxolitinib in Janus Kinase Inhibitor-Naïve Myelofibrosis: Phase III SENTRY Trial,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Journal Article""]","[""Hwang CS"", ""Gerrity MS"", ""Tu SS""]",10.1200/JCO-26-00627,Hwang CS,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Tu SS,[],JCO2600627,42525923,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42525923/,Rethinking Regulatory Protections for Accelerated Approvals With Supplementary Indications,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
"Immunotherapy for frontline mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC) is effective; however, nearly half of the patients treated with single-agent PD-1 therapy will progress within 12 months. Preclinical studies in CRC and clinical data from other cancers suggest that vascular endothelial growth factor inhibition and chemotherapy can synergize with PD-L1 inhibition. The NRG-GI004/SWOG-S1610 (COMMIT) three-arm prospective phase III open-label trial randomly assigned first-line dMMR/MSI-H mCRC patients (1:1:1) to either: mFOLFOX6 (oxaliplatin 85 mg/m², leucovorin 400 mg/m², 5-FU bolus 400 mg/m², and 46-hour infusional 5-FU 2,400 mg/m²)/bevacizumab (FFX/bev), or atezolizumab (atezo) monotherapy (840 mg IV once every 2 weeks), or the combination of FFX/bev/atezo. The primary end point was progression-free survival (PFS) in the intent-to-treat population. Because of KEYNOTE 177 results, the FFX/bev arm was closed after 20 patients were enrolled. The study continued with atezo alone versus FFX/bev/atezo, with a revised sample size of 100 patients in the two remaining arms (120 patients across all three arms). From November 2017 to March 2025, a total of 102 patients were enrolled in the three arms: FFX/bev: n = 20, atezo: n = 41, and FFX/bev/atezo: n = 41. At a median follow-up of 46 months for the two arms (median age: 63.3 years; 47.6% female; 23.2% BRAF V600E mutated), PFS of FFX/bev/atezo was superior to that of atezo (hazard ratio [HR], 0.439 [95% CI, 0.23 to 0.84]; P = .0103) and below the critical value of 0.0152. The objective response rate was 86.1% versus 46%, and the disease control rate at 12 months was 64.7% versus 32.4% in the FFX/bev/atezo arm compared with the atezo-only arm, respectively. Grade 3 or higher adverse events of any attribution occurred in 52 patients (atezo: 18; combination arm: 34). The combination of FFX/bev plus atezo led to significantly longer PFS compared with atezo monotherapy in the first-line treatment of dMMR/MSI-H mCRC.","[""Journal Article""]","[""Rocha Lima CMSP"", ""Yothers G"", ""George TJ"", ""Hochster HS"", ""Sanoff HK"", ""Cohen DJ"", ""Guthrie KA"", ""Jacobs SA"", ""Saeed A"", ""Kopetz S"", ""Colangelo LH"", ""Freeman TJ"", ""Cole SW"", ""Khalil M"", ""Devanna S"", ""Zuckerman DS"", ""Hong TS"", ""Henry NL"", ""Ganz PA"", ""Blanke CD"", ""Wolmark N"", ""Overman MJ""]",10.1200/JCO-25-03052,Rocha Lima CMSP,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Overman MJ,[],JCO2503052,42525921,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42525921/,COMMIT: A Randomized Study of mFOLFOX6/Bevacizumab/Atezolizumab or Atezolizumab Alone as First-Line Treatment of Deficient DNA Mismatch Repair Metastatic Colorectal Cancer,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
"We report the 5-year analysis of tisagenlecleucel in 79 pediatric and young adult patients with relapsed or refractory (r/r) B-cell ALL (B-ALL) from the global phase II ELIANA trial (ClinicalTrials.gov identifier: NCT02435849), with a median follow-up of 79.4 months. Tisagenlecleucel was administered as a single infusion with dosing normalized by weight in patients ≤50 kg. Key long-term end points included relapse-free survival (RFS), overall survival (OS), and safety. Censoring included loss to follow-up, withdrawal of consent, new anticancer therapy (± stem cell transplantation [SCT]), and death. The estimated 5-year RFS among responders (n = 70) with and without inclusion of SCT in censoring for new anticancer therapies was 47.3% and 51.0%, respectively. The median time to B-cell recovery was not reached with censoring for all further anticancer therapies, including SCT. The median OS was not reached. The estimated OS at 5 years was 55.0% and 62.4% with and without inclusion of SCT in censoring for new anticancer therapies, respectively. In total, 17 responders received a postinfusion SCT, 14 while still in complete remission. No new or unexpected adverse events were reported. These findings continue to support the potential of tisagenlecleucel as definitive therapy for many heavily pretreated pediatric and young adult patients with r/r B-ALL.","[""Journal Article""]","[""Grupp SA"", ""Maude SL"", ""Rives S"", ""Hiramatsu H"", ""Baruchel A"", ""Bader P"", ""Bittencourt H"", ""Buechner J"", ""Laetsch TW"", ""De Moerloose B"", ""Qayed M"", ""Stefanski HE"", ""Davis KL"", ""Driscoll TA"", ""Nemecek E"", ""Peters C"", ""Yanik G"", ""Balduzzi A"", ""Boissel N"", ""Khaw SL"", ""Krueger J"", ""Levine JE"", ""Myers GD"", ""Tiwari R"", ""O'Donovan D"", ""Awasthi R"", ""Ramos R"", ""Willert J"", ""Pulsipher MA""]",10.1200/JCO-25-01471,Grupp SA,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Pulsipher MA,[],JCO2501471,42525896,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42525896/,Long-Term Clinical Outcomes of Tisagenlecleucel in Pediatric and Young Adult Patients With Relapsed/Refractory ALL,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
"We hypothesized that a dynamic surveillance strategy guided by circulating tumor DNA (ctDNA) methylation would increase the rate of curative-intent therapy for recurrence in patients with nonmetastatic colorectal cancer (CRC) after curative resection. The FIND trial (ClinicalTrials.gov identifier: NCT05904665) is a prospective, multicenter, randomized, phase III study. Patients with nonmetastatic CRC were randomly assigned to ctDNA-guided surveillance or standard computed tomography (CT)-based monitoring. In the ctDNA-guided group, a positive ctDNA result triggered immediate CT imaging; if negative, bimonthly CT continued alongside quarterly ctDNA testing. After two consecutive ctDNA-negative results, imaging reverted to standard frequency. The primary end point was the proportion of patients with recurrence receiving curative-intent metastasis-directed therapy. Among 584 eligible patients (289 ctDNA-guided, 295 control) in the modified intention-to-treat population, with a median follow-up of 23.3 months, recurrence rates were similar (18.0% v 18.6%, P = .919). The ctDNA-guided group had a significantly higher rate of curative-intent treatment (48.1% v 23.6%, relative risk 2.03, P = .008). The median time to clinical recurrence was significantly shorter in the ctDNA-guided group than in the control group (9.5 v 13.4 months; P < .001), representing a lead time of 3.9 months. Among recurrences confined to the liver and/or lungs, the ctDNA-guided group showed higher curative resection rates (42.3% v 18.2%, P = .002). These patients had more favorable hepatic metastatic features: fewer lesions (≤3: 75.0% v 28.6%, P = .005), smaller tumor size (≤3 cm: 90.0% v 57.1%, P = .033), and more unilobar disease (80.0% v 28.6%, P = .002). ctDNA methylation-guided dynamic surveillance improves the rate of curative-intent therapy for recurrence in patients with initially nonmetastatic CRC through earlier detection of resectable metastases, pending validation of long-term survival benefit in future analyses with mature data.","[""Journal Article""]","[""Mo S"", ""Zhou C"", ""Ma M"", ""Luo W"", ""Li Y"", ""Lu P"", ""Tang P"", ""Li Y"", ""Ma X"", ""Hu X"", ""Cheng C"", ""Yang J"", ""Zhuo C"", ""Jian J"", ""Yu C"", ""Ding J"", ""Xiong C"", ""Jiang F"", ""Mu R"", ""Lu Z"", ""Yu J"", ""Jin S"", ""Luan J"", ""Li X"", ""Cai S"", ""Zou H"", ""Li Y"", ""Li Q"", ""Liu F"", ""Ding C"", ""Peng J""]",10.1200/JCO-25-03009,Mo S,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Peng J,[],JCO2503009,42525894,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42525894/,"Dynamic Circulating Tumor DNA Methylation Monitoring Guiding Postoperative Surveillance in Nonmetastatic Colorectal Cancer: A Prospective, Randomized, Phase III FIND Trial",,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
Not every patient is on the chart-this essay is about learning to see the one who was always there.,"[""Journal Article""]","[""Sai Shreya V""]",10.1200/JCO-26-00540,Sai Shreya V,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Sai Shreya V,[],JCO2600540,42520263,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42520263/,He Was Always There,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Editorial""]","[""Lu C"", ""Peng YL"", ""Yang MY"", ""Zhou Q""]",10.1200/JCO-26-00935,Lu C,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Zhou Q,[],JCO2600935,42507975,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42507975/,Anti-TIGIT in PD-L1-High Advanced Non-Small Cell Lung Cancer: Insights From SKYSCRAPER-01 and the Path Forward,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
"This updated analysis of the STELLAR trial reports 5-year outcomes comparing short-course radiotherapy followed by chemotherapy (SCRT-based total neoadjuvant therapy [TNT]) with standard long-course chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC). Patients with distal or middle-third LARC were randomly assigned to receive either SCRT-based TNT or CRT. At a median follow-up of 68.7 months, the 5-year disease-free survival (DFS) was 62.0% in the TNT group and 58.7% in the CRT group, with a hazard ratio (HR) for DFS of 0.849 (95% CI, 0.662 to 1.089). Five-year overall survival (OS) was significantly higher with TNT (78.1% v 69.7%; HR, 0.739 [95% CI, 0.550 to 0.993]). Distant metastasis (DM) and locoregional recurrence (LRR) rates were similar between the two groups. In high-risk patients (per European Society for Medical Oncology criteria), TNT was associated with improved OS (HR, 0.663 [95% CI, 0.469 to 0.937]) and showed a nonsignificant trend toward improved DFS (HR, 0.765 [95% CI, 0.568 to 1.032]). In patients with DM or LRR, TNT was associated with both improved postrecurrence progression-free survival (HR, 0.691 [95% CI, 0.497 to 0.961]) and postrecurrence survival (HR, 0.698 [95% CI, 0.490 to 0.994]). These results suggest that SCRT-based TNT provides a durable survival advantage and is a viable alternative to CRT, especially in patients with high-risk disease.","[""Journal Article""]","[""Tang Y"", ""Zhou HT"", ""Xu TZ"", ""Li N"", ""Jiang LM"", ""Jiang J"", ""Lu NN"", ""Li S"", ""Chen SL"", ""Ma HY"", ""Cai Y"", ""Li YH"", ""Zhu Y"", ""He MY"", ""Wang X"", ""Liu K"", ""Zhang HY"", ""Wang J"", ""Zhao T"", ""Li GF"", ""Yang JL"", ""Zhang K"", ""Wang WL"", ""Xiao WW"", ""Chi Y"", ""Yang L"", ""Zhou AP"", ""Zou SM"", ""Fang H"", ""Wang SL"", ""Zhang HZ"", ""Wang XS"", ""Wei LC"", ""Liu SX"", ""Gao YH"", ""Li YX"", ""Hu C"", ""Jin J""]",10.1200/JCO-25-02387,Tang Y,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Jin J,[],JCO2502387,42507974,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42507974/,Five-Year Outcomes of Short-Term Radiotherapy Plus Chemotherapy Versus Long-Term Chemoradiotherapy for Locally Advanced Rectal Cancer: Updated Results of the STELLAR Trial,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Journal Article"", ""Published Erratum""]","[""Wilson MR"", ""Lewis KL"", ""Kirkwood AA"", ""Cwynarski K"", ""Cheah CY"", ""El-Galaly TC"", ""Villa D"", ""Savage KJ"", ""Ghione P"", ""Bobillo S"", ""Smedby KE"", ""Harrysson S"", ""Trneny M"", ""Klanova M"", ""Puckrin R"", ""Fox CP"", ""Bishton M"", ""Thanarajasingam G"", ""Doo NW"", ""Hapgood G"", ""Soussain C"", ""Choquet S"", ""Dickinson M"", ""Talaulikar D"", ""de Mel S"", ""Preston G"", ""Ahearne M"", ""Hawkes EA"", ""Schorb E"", ""Clavert A"", ""Ku M"", ""Guidetti A"", ""Narkhede M"", ""Calimeri T"", ""Durot E"", ""Smith J"", ""Renaud L"", ""McKay P"", ""Eyre TA""]",10.1200/JCO-26-01800,Wilson MR,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Eyre TA,[],JCO2601800,42507971,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42507971/,Erratum: High-Dose Methotrexate as CNS Prophylaxis in Ultra High-Risk Large B-Cell Lymphoma: An International Multicenter Analysis,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Letter""]","[""Zou Y"", ""Liu L"", ""Li L""]",10.1200/JCO-26-00867,Zou Y,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Li L,[],JCO2600867,42507970,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42507970/,Time-Varying Effects of Copy Number Alteration Clustering: Methodologic Concerns in Survival Analysis of Relapsed/Refractory Germ Cell Tumors,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
"Bone metastases (BM) occur in approximately 30% of patients with metastatic renal cell carcinoma (mRCC) and are associated with poor survival and symptomatic skeletal events (SSEs). Radium-223, an alpha-emitting bone-seeking radioisotope, and cabozantinib, a tyrosine kinase inhibitor, have demonstrated activity in BM. RADICAL (Alliance A031801; ClinicalTrials.gov identifier: NCT04071223) evaluated cabozantinib ± radium-223 in mRCC with BM. This phase II trial enrolled patients with mRCC of any histology with ≥1 BM. Patients were randomly assigned 1:1 to cabozantinib ± radium-223, stratified by osteoclast-targeted therapy (OTT), prior therapy, opioid use, and International mRCC Database Consortium (IMDC) risk. The primary end point was SSE-free survival (SSE-FS). Secondary end points included safety, objective response rate (ORR), progression-free survival, and overall survival (OS). A target of 124 evaluable patients was planned, with a prespecified interim futility analysis at 50% of expected SSE-FS events; the trial would stop if the stratified hazard ratio (sHR) > 1.0. The prespecified interim futility analysis was conducted after 90 patients were enrolled and crossed the futility boundary, leading to closure at 98 patients. The final analysis included all 98 patients. Median age was 63 years, 82.7% had clear cell histology, and 79.6% were using an OTT. IMDC risk was favorable (18.4%), intermediate (67.3%), and poor (14.3%). Median follow-up was 13.1 months. Median SSE-FS for cabozantinib with radium-223 versus cabozantinib was 16.7 versus 17.6 months (sHR, 1.46 [90% CI, 0.86 to 2.51]). Median OS was 28.3 versus 19.7 months (sHR, 1.40 [95% CI, 0.70 to 2.79]). ORR was 19.4% versus 25.0% (P = .78). Grade ≥3 adverse events were similar across arms (69.6% v 75.5%). Radium-223 did not improve SSE-FS when added to cabozantinib. The combination demonstrated a manageable safety profile.","[""Journal Article""]","[""McKay RR"", ""Ballman KV"", ""Atherton PJ"", ""Ajmera A"", ""Al Baghdadi T"", ""Baumann BC"", ""Beltran H"", ""Berg S"", ""Chen RC"", ""Choudhury AD"", ""Cole S"", ""Jacene HA"", ""Lang JM"", ""Kilari D"", ""Kwok Y"", ""McGregor B"", ""Morris MJ"", ""Parikh M"", ""Swami U"", ""Tan A"", ""Yang YA"", ""Zhang T"", ""Galsky M"", ""Rosenberg J"", ""George D"", ""Choueiri TK""]",10.1200/JCO-26-01135,McKay RR,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Choueiri TK,[],JCO2601135,42507969,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42507969/,Phase II Randomized Trial of Radium-223 Dichloride and Cabozantinib in Patients With Renal Cell Carcinoma With Bone Metastases: RADICAL (Alliance A031801),,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
"Tiragolumab plus atezolizumab has shown encouraging survival outcomes in metastatic non-small cell lung cancer (NSCLC), primarily in patients with PD-L1-high tumors. We further evaluated the combination of tiragolumab plus atezolizumab in the phase III SKYSCRAPER-01 study. Patients with untreated, locally advanced unresectable/metastatic PD-L1-high (by central laboratory testing) NSCLC were randomly assigned 1:1 to receive either tiragolumab (600 mg) plus atezolizumab (1,200 mg) or placebo plus atezolizumab (1,200 mg) intravenously in 21-day cycles until disease progression, loss of clinical benefit, or unacceptable toxicity. Primary end points were investigator-assessed progression-free survival (INV-PFS) and overall survival (OS) in the primary analysis set (PD-L1-high per 22C3 assay). Five hundred twenty-one patients were randomly assigned to either the tiragolumab plus atezolizumab group (n = 262) or the placebo plus atezolizumab group (n = 259). At the primary PFS analysis (Mar 12, 2022; median follow-up 9.9 months [IQR, 6.2-13.8]), median INV-PFS was 7.0 months (95% CI, 5.6 to 9.8) with tiragolumab plus atezolizumab and 5.6 months (95% CI, 4.4 to 7.0) with placebo plus atezolizumab (hazard ratio [HR], 0.78 [95% CI, 0.63 to 0.97]; P = .02 [nonsignificant]). At the final OS analysis (Sept 24, 2024; median follow-up 17.9 months [IQR, 6.7-39.0]), median OS was 23.1 months (95% CI, 17.7 to 28.8) with tiragolumab plus atezolizumab and 16.9 months (95% CI, 14.6 to 21.3) with placebo plus atezolizumab (HR, 0.87 [95% CI, 0.7 to 1.1]; P = .22 [nonsignificant]). Overall, 41.2% (n = 110/267) and 33.8% (n = 89/263) of patients experienced grade 3-4 adverse events with tiragolumab plus atezolizumab and placebo plus atezolizumab, respectively. Four and two treatment-related deaths occurred in each group, respectively. Tiragolumab plus atezolizumab did not demonstrate a statistically significant INV-PFS or OS benefit over atezolizumab in patients with previously untreated PD-L1-high NSCLC.","[""Journal Article""]","[""Peters S"", ""Herbst R"", ""Horinouchi H"", ""Paz-Ares L"", ""Johnson M"", ""Solomon BJ"", ""Gumus M"", ""Erman M"", ""Bondarenko I"", ""Kim DW"", ""Felip E"", ""Morabito A"", ""Bryl M"", ""Urban L"", ""Nosaki K"", ""Reck M"", ""Meng R"", ""Stroud C"", ""Kundu P"", ""Wen X"", ""Patil NS"", ""Huang M"", ""Troutman S"", ""Matheny C"", ""Cho BC""]",10.1200/JCO-25-02777,Peters S,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Cho BC,[],JCO2502777,42507968,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42507968/,"SKYSCRAPER-01: Tiragolumab in Combination With Atezolizumab in Previously Untreated PD-L1-High, Locally Advanced, Unresectable or Metastatic Non-Small Cell Lung Cancer",,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Journal Article"", ""Published Erratum""]","[""Lachowiez CA"", ""Zeidner JF"", ""Othman J"", ""Kaempf A"", ""Yun S"", ""Heiblig M"", ""Heuser M"", ""Shahswar R"", ""Marroquin RM"", ""Cannova JM"", ""Žučenka A"", ""Marvin-Peek J"", ""Senapati J"", ""Abaza Y"", ""Swaroop A"", ""Zacheo I"", ""Monaco F"", ""Belhabri A"", ""Tauveron-Jalenques U"", ""Tavernier E"", ""Carré M"", ""Requena GA"", ""Cook RJ"", ""Traer E"", ""Saultz JN"", ""O'Nions J"", ""Basheer F"", ""Laurie J"", ""Handa S"", ""Stein EM"", ""Baer MR"", ""Olin R"", ""Blum W"", ""Schiller G"", ""Lin T"", ""Curran E"", ""Yocum A"", ""Madarang E"", ""Daver N"", ""Kadia TM"", ""Marconi G"", ""Madanat Y"", ""Dillon R"", ""DiNardo CD"", ""Swords R"", ""Arango Ossa JE"", ""Watts J"", ""Loghavi S"", ""Pollyea DA"", ""Bernard E"", ""PRISM-AML Investigators""]",10.1200/JCO-26-01801,Lachowiez CA,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Bernard E,[],JCO2601801,42507967,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42507967/,Erratum: Risk Prognostication After Hypomethylating Agents Combined With Venetoclax in AML: The PRISM Risk Model,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Journal Article""]","[""Urbini M"", ""Eleveld TF"", ""Polano M"", ""Scarpi E"", ""Menna C"", ""Gianni C"", ""Janssen FW"", ""Schepisi G"", ""Gurioli G"", ""Kucerova L"", ""Gillis AJM"", ""Virga A"", ""Bleve S"", ""Rosti G"", ""Ulivi P"", ""Mego M"", ""Looijenga LHJ"", ""De Giorgi U""]",10.1200/JCO-26-01154,Urbini M,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,De Giorgi U,[],JCO2601154,42507966,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42507966/,Reply to: Time-Varying Effects of Copy Number Alteration Clustering: Methodologic Concerns in Survival Analysis of Relapsed/Refractory Germ Cell Tumors,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
"The choice of adjuvant chemotherapy in pancreatic ductal adenocarcinoma (PDAC) is mainly guided by patients' general condition. We hypothesized that tumor morphology may predict differential treatment benefit and tested whether deep learning applied to histology images could derive a biomarker of relative benefit from gemcitabine (GEM) versus modified FOLFIRINOX (mFOLFIRINOX) in resected PDAC. Standard whole-slide images from a retrospective multicentric series of 231 patients who underwent curative-intent pancreatectomy and received adjuvant mFOLFIRINOX (n = 54) or GEM (n = 177) were used to train regimen-specific histology models on disease-free survival (DFS), which were then combined into PANCprAId, a biomarker estimating personalized relative benefit from adjuvant GEM versus mFOLFIRINOX. External validation was performed in the randomized PRODIGE-24/CCTG PA6 trial (n = 313). In PRODIGE-24/CCTG PA6, the treatment-specific histology scores used to construct PANCprAId stratified outcomes among patients treated with GEM (hazard ratio [HR], 1.69 [95% CI, 1.04 to 2.73]; P = .03) and mFOLFIRINOX (HR, 2.02 [95% CI, 1.4 to 3.0]; P < .001). When combined into PANCprAId, the biomarker identified subgroups with differential relative benefit from adjuvant GEM versus mFOLFIRINOX, with significant treatment interactions for DFS (interaction P = .003) and cancer-specific survival (interaction P = .001). Predicted sensitivity to each regimen was associated with distinct epithelial and stromal features. Histology-based deep learning can derive a predictive biomarker of relative benefit from adjuvant GEM versus mFOLFIRINOX in resected PDAC.","[""Journal Article""]","[""Beaufils A"", ""De Martino J"", ""Jiang X"", ""Blanchard T"", ""Fraunhoffer N"", ""Mendes D"", ""Pignolet C"", ""Bourega T"", ""Meneghetti AR"", ""Sainath S"", ""Albuquerque M"", ""Colnot N"", ""Tihy M"", ""Turpin A"", ""Ben Abdelghani M"", ""Wei A"", ""Mitry E"", ""Lecomte T"", ""Biagi J"", ""Artru P"", ""Evesque L"", ""Lambert A"", ""Renouf DJ"", ""Mauduit M"", ""Dusetti NJ"", ""Hammel P"", ""Conroy T"", ""Bachet JB"", ""de Mestier L"", ""Rebours V"", ""Cros J"", ""Kather JN"", ""Nicolle R""]",10.1200/JCO-26-00327,Beaufils A,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Nicolle R,[],JCO2600327,42507965,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42507965/,Developing a Histology-Based Artificial Intelligence Biomarker to Predict Adjuvant Chemotherapy Benefit in Pancreatic Cancer,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
"Small cell lung cancer (SCLC) remains one of the most aggressive malignancies, with limited treatment options beyond frontline chemo-immunotherapy. Izalontamab brengitecan (iza-bren, BL-B01D1) is a first-in-class bispecific antibody-drug conjugate cotargeting epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3). We expanded the SCLC cohort to further evaluate the efficacy and safety of iza-bren in patients with extensive-stage SCLC (ES-SCLC). This open-label, multicenter, dose-expansion phase Ib study (ClinicalTrials.gov identifier: NCT05194982) enrolled patients with ES-SCLC who had progressed on prior systemic therapies. Patients received iza-bren 2.5 mg/kg once daily on days 1 and 8 of each 3-week cycle. The primary end points were objective response rate (ORR) and safety/tolerability. Secondary end points included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Exploratory end point included the assessment of potential associations between EGFR/HER3 expression and clinical outcomes. As of December 5, 2024, 52 patients were enrolled. The ORR was 48.1% (95% CI, 34.0 to 62.4), with a median PFS of 4.1 months (95% CI, 3.0 to 5.5) and a median OS of 12.2 months (95% CI, 9.1 to 13.2). In patients who received iza-bren as second-line treatment (n = 22), the ORR was 72.7% (95% CI, 49.8 to 89.3), median PFS 6.2 months (95% CI, 3.7 to 8.2), and median OS 15.0 months (95% CI, 8.7 to not reached). The most common treatment-related adverse events were hematologic toxicities (neutropenia, thrombocytopenia, anemia, and leukopenia). Exploratory biomarker analysis suggested that positive HER3 expression may be associated with better treatment response. Iza-bren showed encouraging antitumor activity in relapsed ES-SCLC, particularly in the second-line setting. A phase III randomized controlled trial of iza-bren compared with topotecan (ClinicalTrials.gov identifier: NCT06500026) is ongoing.","[""Journal Article""]","[""Zhao Y"", ""Zhao H"", ""Wang Q"", ""Yang K"", ""Li Y"", ""Fu Z"", ""Yang W"", ""He Z"", ""Wang Y"", ""Ma Y"", ""Yang Y"", ""Fang W"", ""Xiao S"", ""Zhu H"", ""Zhu Y"", ""Zhang L"", ""Huang Y""]",10.1200/JCO-26-00243,Zhao Y,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Huang Y,[],JCO2600243,42497381,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42497381/,"Izalontamab Brengitecan (Iza-Bren), a First-in-Class EGFR-HER3 Bispecific Antibody-Drug Conjugate in Extensive-Stage Small Cell Lung Cancer: Results From a Phase Ib Study",,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Journal Article""]","[""Tang W"", ""Xu J""]",10.1200/JCO-26-00984,Tang W,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Xu J,[],JCO2600984,42497379,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42497379/,"Reply to: ""Is Dual-Checkpoint Blockade Beneficial Beyond Prolonging Chemoradiotherapy-to-Surgery Interval in Rectal Cancer?"" and ""Dual Immunotherapy in the Neoadjuvant Interval for Locally Advanced Rectal Cancer: A New Hope?""",,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Letter""]","[""Xiao L"", ""Sun J"", ""Wu F""]",10.1200/JCO-26-00496,Xiao L,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Wu F,[],JCO2600496,42497377,,2026 Jun 24,2026,https://pubmed.ncbi.nlm.nih.gov/42497377/,Dual Immunotherapy in the Neoadjuvant Interval for Locally Advanced Rectal Cancer: A New Hope?,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Editorial""]","[""Donovan E"", ""Whelan TJ""]",10.1200/JCO-26-00997,Donovan E,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Whelan TJ,[],JCO2600997,42497372,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42497372/,Moderate Hypofractionation for Regional Node Irradiation Is Safe and Effective,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Letter""]","[""Yang J"", ""Yu F"", ""Zheng S""]",10.1200/JCO-26-00177,Yang J,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Zheng S,[],JCO2600177,42497370,,2026 Jun 24,2026,https://pubmed.ncbi.nlm.nih.gov/42497370/,Is Dual-Checkpoint Blockade Beneficial Beyond Prolonging Chemoradiotherapy-to-Surgery Interval in Rectal Cancer?,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
"The Children's Oncology Group phase III clinical trial AAML1831 (ClinicalTrials.gov identifier: NCT04293562) evaluated liposomal daunorubicin and cytarabine (CPX-351) versus standard daunorubicin/cytarabine (DA) induction therapy in children and young adults with newly diagnosed AML. We hypothesized that CPX-351 given during induction 1 and 2 would improve outcomes compared with DA. Patients (21 years and younger) were randomly assigned to two cycles of DA induction (arm A = DA) or CPX-351 (arm B = CPX-351). All patients also received gemtuzumab ozogamicin in induction 1. Postinduction chemotherapy was according to risk assignment made at the end of induction 1 (EOI1). Those with high-risk (HR) AML received consolidation with allogeneic hematopoietic stem-cell transplantation (HSCT), whereas low-risk (LR) patients received chemotherapy alone. Protocol-specified interim analysis monitored efficacy and futility of CPX-351 induction with respect to the primary end point, event-free survival (EFS) from study entry. Disease-free survival (DFS) was calculated to determine the impact of EOI1 risk assignment. Seven hundred twenty-one eligible patients with FLT3 wild-type AML were randomly assigned to DA (n = 358) or CPX-351 (n = 363). Interim analysis determined that the futility monitoring rule was crossed because of inferior EFS in the CPX-351 arm and the random assignment was stopped. The two-year EFS from study entry was 62.2% for DA versus 51.2% for CPX-351 (P = .011). DFS for patients with HR AML was comparable for both arms. However, DFS was significantly lower and cumulative incidence of relapse (CIR) was higher for LR patients assigned to CPX-351 versus DA (2-year DFS from EOI1: DA: 73.8% v CPX-351 57.5% [P = .001]; 2-year CIR Arm DA: 23.6% v CPX-351: 39.9% [P = .001]). CPX-351 was inferior to DA induction in the AAML1831 trial with differential EFS largely driven by events in LR patients.","[""Journal Article""]","[""Pollard JA"", ""Alonzo TA"", ""Gerbing RB"", ""Kutny M"", ""Hirsch B"", ""Raca G"", ""Leger K"", ""Wilkes J"", ""Pabari R"", ""Wadhwa A"", ""Graff Z"", ""Kahwash S"", ""Chisholm K"", ""Chewning J"", ""Horan J"", ""Aplenc R"", ""Place A"", ""Tasian SK"", ""Tarlock K"", ""Menig S"", ""Militano O"", ""Ky B"", ""Hudson C"", ""Loken MR"", ""Menssen A"", ""Brodersen LE"", ""Meshinchi S"", ""Kolb EA"", ""Cooper TM""]",10.1200/JCO-25-02979,Pollard JA,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Cooper TM,[],JCO2502979,42497367,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42497367/,AAML1831: A Phase III Trial Comparing Standard Induction Therapy With CPX-351 in De Novo Pediatric AML: A Report From the Children's Oncology Group,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Journal Article""]","[""Kanemitsu Y""]",10.1200/JCO-26-01560,Kanemitsu Y,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Kanemitsu Y,[],JCO2601560,42492047,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42492047/,Reply to: Post-Recurrence Therapy After Hepatectomy: Clarifying Overall Survival in JCOG0603,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
"Adjuvant radiotherapy for node-positive breast cancer (BC) using 50Gy/25fx has been Danish Breast Cancer Group (DBCG) standard. Hypofractionated radiotherapy based on 40Gy/15fx has been increasingly used; however, it is less frequently for locoregional therapy because of concern over more morbidity. DBCG Skagen trial 1 hypothesized that 40Gy/15fx did not cause more lymphedema than 50Gy/25fx 3 years after radiotherapy without compromising the pattern of failure. Skagen trial 1 is a phase III, noninferiority trial randomly assigning high-risk BC patients with an indication for locoregional radiotherapy to standard 50Gy/25fx versus experimental 40Gy/15fx. The primary end point was arm lymphedema; assuming a 3-year incidence with 50Gy/25fx of 10%, noninferiority was predefined to maximum 5% excess incidence with 40Gy/15fx. Accrual continued until 3-year estimates were reported in 1,012 patients. Between 2015 and 2021, 2,963 patients consented from 17 centers; the intention-to-treat cohort comprised 2,908 patients: 1,444 had 50Gy (50%), and 1,464 had 40Gy (50%). The median age was 57 years (range, 23-86). At a median follow-up of 4.1 years (IQR, 3.0-5.0), the 3-year rates of lymphedema were 9.4% (50Gy) versus 8.0% (40Gy), odds ratio 0.84 (95% CI, 0.62 to 1.14), and P = .27, thus within the +5-percentage-point noninferiority margin. The median follow-up for cancer outcomes was 5.25 years (IQR, 4.26 to 6.96). Within 8 years, the hazard ratio for locoregional recurrence was 0.96 (95% CI, 0.62 to 1.51), that for distant recurrence was 1.10 (95% CI, 0.89 to 1.37), that for BC mortality was 1.25 (95% CI, 0.93 to 1.66), and that for all-cause mortality was 1.08 (95% CI, 0.85 to 1.36), thus all with no differences by random assignment. 40Gy/15fx for locoregional radiotherapy of BC did not result in more lymphedema compared with 50Gy/25fx. There were no differences in locoregional or distant recurrences, breast cancer mortality, nor all-cause mortality between the random assignment arms.","[""Journal Article""]","[""Offersen BV"", ""Alsner J"", ""Høgsbjerg K"", ""Nielsen HM"", ""Maae E"", ""Nielsen MH"", ""Mjaaland I"", ""Maraldo MV"", ""Kirkove C"", ""Lörincz T"", ""Al-Rawi S"", ""Blix ES"", ""Schreiber A"", ""Krause M"", ""Kasti UM"", ""Matthiessen LW"", ""Kronborg C"", ""Tramm T"", ""Jensen MB"", ""Overgaard J"", ""DBCG RT Committee""]",10.1200/JCO-25-02705,Offersen BV,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Overgaard J,[],JCO2502705,42492022,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42492022/,Hypo- Versus Standard Fractionated Locoregional Radiotherapy of Patients With High-Risk Breast Cancer in the Randomized Phase III Trial: The Danish Breast Cancer Group Skagen Trial 1,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Journal Article""]","[""Maguire WF"", ""Plyku D"", ""Agrawal S"", ""Fotenos A"", ""John CS"", ""Saber H"", ""Shord SS"", ""Cheuk AV"", ""Hofling A"", ""Suzman DL""]",10.1200/JCO-25-02448,Maguire WF,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Suzman DL,[],JCO2502448,42492017,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42492017/,Into the Unknown: Regulatory Perspective on Identifying Optimized Dosages of Oncology Radiopharmaceutical Therapies,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Letter""]","[""Kim SH""]",10.1200/JCO-26-00286,Kim SH,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Kim SH,[],JCO2600286,42492016,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42492016/,Post-Recurrence Therapy After Hepatectomy: Clarifying Overall Survival in JCOG0603,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
"High-risk locally advanced rectal cancer (LARC) carries a substantial risk of distant recurrence, which limits disease-free survival (DFS). We compared total neoadjuvant therapy (TNT) integrating long-course radiotherapy (LCRT) with uninterrupted doublet chemotherapy (doublet-LC TNT) versus conventional neoadjuvant chemoradiotherapy (nCRT). In this multicenter, randomized, phase III trial, patients with stage II/III LARC and at least 1 high-risk feature (cT4a-b, cN2, mesorectal fascia involvement, or cT3c-d with extramural vascular invasion) were enrolled. Patients were assigned to doublet-LC TNT (induction, concurrent, and consolidation capecitabine plus oxaliplatin with LCRT) before surgery or nCRT (capecitabine with LCRT) followed by surgery and adjuvant chemotherapy. The primary end point was DFS (ClinicalTrials.gov identifier: NCT03177382). Between June 6, 2017, and December 27, 2023, 458 patients were randomly assigned to doublet-LC TNT (n = 232) or nCRT (n = 226). At a median follow-up of 51 months, doublet-LC TNT improved 3-year DFS (74.8% v 66.0%; hazard ratio [HR], 0.674 [95% CI, 0.489 to 0.929]; P = .016). Metastasis-free survival (MFS; 77.7% v 67.6%; HR, 0.655 [95% CI, 0.469 to 0.915]) and pathologic complete response rates (pCR; 26.37% v 9.80%; P < .001) were higher with doublet-LC TNT, whereas locoregional failure remained low and comparable (6.03% v 6.19%; P = .943). Although grade ≥3 adverse events during the neoadjuvant phase were more frequent with doublet-LC TNT (27.59% v 8.56%; P < .001), severe toxicities during the entire treatment course (28.02% v 24.32%; P = .371) and major postoperative complications (3.98% v 2.94%; P = .567) were comparable. Compared with conventional nCRT, doublet-LC TNT improved DFS, MFS, and pCR rates with manageable toxicity. These findings support this intensified, doublet-based regimen as a standard option within the modern TNT paradigm. Further comparative studies are warranted to evaluate these results against other short-course radiotherapy‑based or nondoublet-concurrent TNT regimens.","[""Journal Article""]","[""Wang X"", ""Tang Y"", ""Lu J"", ""Meng W"", ""Liu P"", ""Zhou J"", ""Wen F"", ""Ding P"", ""Li J"", ""Wang B"", ""Guo Q"", ""Qiu J"", ""Sun H"", ""Deng X"", ""Shen Y"", ""Zeng H"", ""Jiang D"", ""Wang D"", ""Li Y"", ""Xiao Y"", ""Wang Z""]",10.1200/JCO-25-03110,Wang X,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Wang Z,[],JCO2503110,42492015,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42492015/,"Total Neoadjuvant Therapy With Long-Course Radiotherapy Versus Chemoradiotherapy in High-Risk Locally Advanced Rectal Cancer (TNTCRT): A Multicenter, Randomized, Phase III Trial",,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Journal Article"", ""Published Erratum""]","[""Issa GC"", ""Cuglievan B"", ""El Hajjar G"", ""Jen WY"", ""Bataller A"", ""Short NJ"", ""DiNardo CD"", ""Alvarado Y"", ""Loghavi S"", ""Duose DY"", ""Zhang B"", ""Furudate K"", ""Ning J"", ""Xiao L"", ""Mouhayar E"", ""Pinto A"", ""Bidikian A"", ""Thompson E"", ""Daver N"", ""Garcia-Manero G"", ""Farhat A"", ""McCall D"", ""Kadia TM"", ""Abbas HA"", ""Tan S"", ""Bazinet A"", ""Jabbour E"", ""Montalban-Bravo G"", ""Ravandi F"", ""Takahashi K"", ""Andreeff M"", ""Kantarjian HM""]",10.1200/JCO-26-01743,Issa GC,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Kantarjian HM,[],JCO2601743,42492014,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42492014/,"Erratum: All-Oral Combination of Revumenib, Decitabine, and Venetoclax for Relapsed or Refractory AML (SAVE)",,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Editorial""]","[""Chiorean EG"", ""Shergill A""]",10.1200/JCO-26-01489,Chiorean EG,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Shergill A,[],JCO2601489,42485603,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42485603/,Thrombopoietin Receptor Agonists for Chemotherapy-Induced Thrombocytopenia in GI Cancers-A Big Solution for a Small Problem or a Solution at All?,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Journal Article""]","[""Liang B"", ""Weil M""]",10.1200/JCO-26-00191,Liang B,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Weil M,[],JCO2600191,42485601,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42485601/,Corticosteroids in Glioblastoma Management: A Reconsideration of a 65-Year Practice,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Letter""]","[""Nicosia L"", ""Gambacorta MA"", ""Alongi F""]",10.1200/JCO-26-00895,Nicosia L,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Alongi F,[],JCO2600895,42485598,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42485598/,Precision in Proximity: The Radiation Oncologist's Perspective on Tailoring Total Neoadjuvant Therapy by Rectal Tumor Location,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Journal Article""]","[""Noiret B"", ""Denost Q""]",10.1200/JCO-26-01352,Noiret B,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Denost Q,[],JCO2601352,42485591,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42485591/,Reply to: Precision in Proximity: The Radiation Oncologist's Perspective on Tailoring Total Neoadjuvant Therapy by Rectal Tumor Location,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
"Solitary plasmacytomas (SPs) are rare localized tumors of clonal plasma cells, either in the bone (solitary bone plasmacytoma) or in soft tissue/extraosseous (extramedullary) with either no or with minimal bone marrow (BM) infiltration (<10% clonal plasma cells by immunohistochemistry) and no evidence of systemic involvement or myeloma defining events. Approximately 50% of SPs will progress to symptomatic myeloma within 5 years after initial definitive local radiotherapy. Increased availability of improved diagnostic and monitoring tools has increased the sensitivity of detection of additional lesions and marrow involvement and has implications for the follow-up strategy after treatment. Thus, the definitions and requirements for the diagnosis and follow-up of SPs are evolving. The diagnosis of SP requires the careful exclusion of multiple myeloma (MM) that would require systemic therapy, by using all the available methods to detect systemic disease (advanced imaging, sensitive BM assessment methods, blood and urine tests). Local radiotherapy remains the mainstay of therapy, and despite the availability of innovative drugs for MM, the clinical benefit of systemic therapy currently remains poorly defined. The International Myeloma Working Group provides here updated recommendations for the diagnosis, evaluation, treatment, and response assessment of patients with SPs, incorporating recent data and advances in diagnostic tools.","[""Journal Article""]","[""Kastritis E"", ""Kumar SK"", ""Rajkumar VS"", ""Chng WJ"", ""Costa L"", ""Engelhardt M"", ""Gonsalves W"", ""Hungria V"", ""Hillengass J"", ""Jevremovic D"", ""Katodritou E"", ""Kristinsson SY"", ""Lonial S"", ""Ludwig H"", ""McCarthy P"", ""Mai E"", ""Manier S"", ""Martin T"", ""Mateos MV"", ""Mian H"", ""Mikhael J"", ""Moreau P"", ""Munshi NC"", ""Paiva B"", ""Pawlyn C"", ""Rasche L"", ""Richter J"", ""San Miguel J"", ""Sborov DW"", ""Usmani SZ"", ""Dimopoulos MA"", ""Zamagni E""]",10.1200/JCO-26-00410,Kastritis E,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Zamagni E,[],JCO2600410,42485589,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42485589/,International Myeloma Working Group Recommendations for the Diagnosis and Management of Solitary Plasmacytomas,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Letter""]","[""Meisel R"", ""Schuster F"", ""Ghosh S""]",10.1200/JCO-26-00679,Meisel R,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Ghosh S,[],JCO2600679,42480005,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42480005/,Optimizing Outcomes After Pediatric Haploidentical Donor Transplant: Role of Graft-Versus-Host Disease Prophylaxis?,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Journal Article""]","[""Bertolet A""]",10.1200/JCO-26-00796,Bertolet A,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Bertolet A,[],JCO2600796,42480001,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42480001/,Are Radiopharmaceutical Therapy Trials Designed to Undertreat?,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Journal Article""]","[""Liberio N"", ""Broglie L""]",10.1200/JCO-26-01361,Liberio N,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Broglie L,[],JCO2601361,42479999,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42479999/,Reply to: Optimizing Outcomes After Pediatric Haploidentical Donor Transplant: Role of Graft-Versus-Host Disease Prophylaxis?,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
"To offer clinicians recommendations concerning breast cancer follow-up and surveillance after primary treatment. ASCO convened an Expert Panel to develop recommendations based on a systematic review and a formal consensus process. One randomized controlled trial (RCT) was identified and formed the evidentiary basis for the surveillance mammography guideline recommendation. No RCTs were identified that evaluated different follow-up approaches by risk of relapse in patients treated for early-stage breast cancer. Given the dearth of evidence identified in the systematic review of the literature, formal modified Delphi consensus-based recommendations were generated. The guideline offers recommendations on the role of a risk-based approach to the frequency and intensity of follow-up among patients with breast cancer in the adjuvant setting. Regular history, physical examination, and mammography are recommended for breast cancer follow-up. Either virtual or in-person visits can be offered. Certain patients at high risk of cancer recurrence warrant closer surveillance, such as those patients with locally advanced disease or residual disease following neoadjuvant chemotherapy. Recommendations on the use of blood-based biomarkers and supplemental imaging are provided. Guideline recommendations will be updated once additional evidence-based tools become available to better individualize surveillance.Additional information is available at www.ascopubs.org/topics/asco-guidelines/breast-cancer.","[""Journal Article""]","[""Nahleh Z"", ""Alfano CM"", ""Somerfield MR"", ""Lee JM"", ""Hieken TJ"", ""Magnuson A"", ""Rao RD"", ""Chew HK"", ""Chia SKL"", ""Harvey BE"", ""Landsberger E"", ""Lim B"", ""Mwanzi SA"", ""Parsons HA"", ""Patt D"", ""Sukumar JS"", ""Sung H"", ""Werutsky G"", ""Lustberg M""]",10.1200/JCO-26-01700,Nahleh Z,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Lustberg M,[],101200JCO2601700,42462191,,2026 Jul 16,2026,https://pubmed.ncbi.nlm.nih.gov/42462191/,Breast Cancer Follow-Up and Surveillance After Primary Treatment: ASCO Guideline Update,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
"Concurrent platinum-based chemotherapy and radiation therapy (cCRT) followed by consolidative durvalumab is the standard of care (SoC) for fit patients with inoperable, locally advanced non-small cell lung cancer (LA-NSCLC). However, no SoC exists for patients who are cCRT-ineligible because of age, comorbidities, or frailty. Here, we investigated the efficacy and adverse events (AEs) of concurrent and consolidative durvalumab with definitive radiation therapy (RT) without chemotherapy. In this multicenter, single-arm, prospective phase II study, patients received conventionally fractionated RT plus concurrent and consolidative durvalumab (1,500 mg fixed dose once every 4 weeks) for up to 12 months. The primary end point was 2-year progression-free survival (PFS) of 36% compared with historical results of 20% with sequential CRT (86% power). Additional end points included overall survival (OS) and cancer-specific survival (CSS). Fifty-eight patients (median age 82 years [IQR, 76-86]; 16 [28%] PD-L1-negative; eight [14%] Eastern Cooperative Oncology Group [ECOG] score 2; 46 [79%] ECOG score 1; four [7%] ECOG score 0) were treated per protocol. The study met its primary end point with a 2-year PFS of 39% (one-sided CI, 29 to 100) and a 2-year OS of 54%. Better performance status and PD-L1 positivity were associated with improved PFS; better ECOG was associated with improved OS; PD-L1 positivity was associated with better CSS. Grade 3/4 treatment-related AEs occurred in 12 (21%) patients. Grade 5 AEs occurred in four (7%) patients (radiation pneumonitis (n = 2) and cardiac arrest (n = 2)). Durvalumab was discontinued early because of AEs in 18 (31%) patients. Thoracic RT with concurrent and consolidative durvalumab is a promising treatment option for cCRT-ineligible patients with LA-NSCLC, demonstrating better PFS with a favorable safety profile compared with historical controls.","[""Journal Article""]","[""Rimner A"", ""Lebow ES"", ""Fitzgerald KJ"", ""Kratochvil L"", ""Toumbacaris N"", ""Gelblum DY"", ""Kotecha R"", ""Gomez DR"", ""Wu AJ"", ""Shepherd AF"", ""Yorke ED"", ""Eng J"", ""Ng K"", ""Riely GJ"", ""Iqbal A"", ""Rudin CM"", ""Jones DR"", ""Isbell JM"", ""Rocco G"", ""Rusch VW"", ""Ginsberg MS"", ""Zhang Z"", ""Simone CB 2nd"", ""Kris MG"", ""Shaverdian N"", ""Chaft JE""]",10.1200/JCO-25-02517,Rimner A,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Chaft JE,[],JCO2502517,42462186,,2026 Jul 16,2026,https://pubmed.ncbi.nlm.nih.gov/42462186/,Durvalumab With Radiation Therapy in Patients With Inoperable Locally Advanced Non-Small Cell Lung Cancer Ineligible for Concurrent Chemoradiotherapy (DART),,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
"To assess whether adding fluoropyrimidine sensitized radiotherapy (CXRT) to adjuvant chemotherapy improves overall survival (OS) after curative intent resection of the pancreatic head. This was a multicenter, randomized phase III, two step trial. Step 1: gemcitabine versus gemcitabine + erlotinib (previously reported). Step 2: random assignment to sixth chemotherapy cycle ± CXRT after five cycles of step 1 chemotherapy without progression. Outcomes of step 2 random assignment are reported here. Assuming 17 months median OS (chemotherapy alone), the sample size was 354 patients (hazard ratio [HR], 0.76, 80% power, one-sided α = .05, 316 OS events). OS/disease-free survival (DFS) were estimated by Kaplan-Meier and arms compared using the log-rank test. A total of 354 patients (median age 63, 55% male, 56% performance status, 1) were randomly assigned to chemotherapy (174) or chemotherapy + CXRT (180). Univariable median and 5-year OS (90% CIs) were 2.6 years (2.1-3.1) and 23.1% (17.7-28.6) for chemotherapy alone, and 2.3 years (2.0-2.6) and 27.9% (22.2-33.6) for chemotherapy + CXRT. The OS primary end point was not met (HR, 0.96 [90% CI, 0.79 to 1.18]; one-sided P = .38, two-sided P = .77). Chemotherapy + CXRT was associated with a trend for improved DFS (univariably; HR, 0.82 [95% CI, 0.65 to 1.03]; P = .089), without increase in grade 4/5 toxicities. However, grade 3 toxicity increased (38% v 19%, P < .001). Significantly, treatment by nodal status interactions showed that CXRT improved OS (P = .0063) and DFS (P = .014) in node-negative patients. Overall, the addition of adjuvant CXRT to adjuvant gemcitabine did not statistically significantly improve OS, DFS, or increase grade 4/5 toxicity. For node-negative patients, CXRT improved OS and DFS. These results, if confirmed in studies with current or future systemic therapies, would support the use of adjuvant/neoadjuvant CXRT for node-negative patients.","[""Journal Article""]","[""Abrams RA"", ""Winter KA"", ""Goodman KA"", ""Regine WF"", ""Safran HP"", ""Guha CS"", ""Kachnic LA"", ""Gillin MT"", ""Philip PA"", ""Lowy AM"", ""O'Reilly E"", ""Van Laethem JL"", ""Seaward SA"", ""Wu AJ"", ""Wu JJ"", ""Aljumaily RM"", ""DiPetrillo TA"", ""Geva R"", ""Anne PR"", ""Liles DK"", ""Ling DC"", ""Conlin A"", ""Moughan J"", ""Crane CH""]",10.1200/JCO-25-02520,Abrams RA,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Crane CH,[],JCO2502520,42456089,pmc-id: PMC13374715;manuscript-id: NIHMS2183930;,2026 Jun 9,2026,https://pubmed.ncbi.nlm.nih.gov/42456089/,Adjuvant Chemotherapy ± Chemoradiotherapy for Adenocarcinoma of the Pancreatic Head: Results of the Radiotherapy Random Assignment of NRG Oncology/RTOG 0848,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Editorial""]","[""Fiore MC"", ""McCarthy DE"", ""Kaye JT"", ""Baker TB""]",10.1200/JCO-26-01169,Fiore MC,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Baker TB,[],JCO2601169,42456082,,2026 Jul 15,2026,https://pubmed.ncbi.nlm.nih.gov/42456082/,Smoking in Patients With Cancer: Guidance for Delivering Effective Tobacco Treatment in Cancer Care,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
"A story of nourishment, serendipity, and the unexpected bonds that connect us with patients.","[""Personal Narrative""]","[""Krasovitsky M""]",10.1200/JCO-25-02965,Krasovitsky M,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,21,J Clin Oncol,eng,Krasovitsky M,"[""Humans"", ""Professional-Patient Relations""]",2059-2061,42454993,,2026 Jul 20,2026,https://pubmed.ncbi.nlm.nih.gov/42454993/,A Shopping List,44,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
"Treatment-free remission (TFR) is a major therapeutic objective in chronic myeloid leukemia (CML). However, nearly 50% of patients relapse after tyrosine kinase inhibitor (TKI) discontinuation, and no robust predictive biomarker is currently available. We profiled peripheral blood cell transcriptomes at imatinib (IMA) discontinuation in patients from the multicenter STIM2 trial (n = 96) to develop a transcriptome-based model predicting TFR by 2 years. A DESEQ2-based machine learning approach was compared with classical machine learning algorithms. The signature was then externally validated in an independent real-world cohort of patients attempting IMA or nilotinib cessation (n = 70). The biologic processes associated with the signature were further explored. We identified a 50-gene signature discriminating patients with sustained 2-year TFR from those experiencing molecular relapse (area under the receiver operating characteristic curve [AUROC], 0.83 [95% CI, 0.73 to 0.93] and 0.75 [95% CI, 0.55 to 1.00] in the training and internal validation cohorts, respectively). The discriminative performance was confirmed in the external test cohort, both as a binary predictor of 2-year TFR (AUROC, 0.71 [95% CI, 0.58 to 0.83] overall; 0.77 [95% CI, 0.61 to 0.92] in IMA-treated patients) and as a time-to-event predictor (log-rank P = .0042). The high TFR-signature group showed a higher proportion of myeloid immune cells and natural killer T cells, with an enrichment in Hedgehog signaling, whereas the low TFR-signature group demonstrated a higher proportion of lymphoid cells with an enrichment in mTOR signaling and a trend for oxidative phosphorylation activation. T-cell receptor and immunoglobulin heavy-chain repertoire analyses showed significantly greater polyclonality in the high TFR-signature group. These findings demonstrate that transcriptomic profiling at TKI discontinuation can predict TFR outcomes in patients with CML and provide biologic insights into the mechanisms underlying sustained TFR.","[""Journal Article"", ""Multicenter Study"", ""Validation Study""]","[""Alcazer V"", ""Dulucq S"", ""Mosnier I"", ""Chabane K"", ""Bertin-Mourot P"", ""Derruau S"", ""Balsat M"", ""Labussiere-Wallet H"", ""Sujobert P"", ""Mahon FX"", ""Etienne G"", ""Nicolini F"", ""Hayette S""]",10.1200/JCO-25-02948,Alcazer V,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,21,J Clin Oncol,eng,Hayette S,"[""Humans"", ""Transcriptome"", ""Female"", ""Leukemia, Myelogenous, Chronic, BCR-ABL Positive"", ""Remission Induction"", ""Male"", ""Predictive Learning Models"", ""Imatinib Mesylate"", ""Gene Expression Profiling"", ""Middle Aged"", ""Protein Kinase Inhibitors"", ""Adult"", ""Treatment Interruption"", ""Predictive Value of Tests"", ""Prediction Algorithms""]",1992-2005,42454992,,2026 Jul 20,2026,https://pubmed.ncbi.nlm.nih.gov/42454992/,Development and External Validation of a Transcriptome-Based Multivariable Prediction Model for Treatment-Free Remission in Chronic Myeloid Leukemia,44,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
This essay is about how caring for my complicated father with amyotrophic lateral sclerosis (ALS) unexpectedly shaped how I approached my work as a gynecologic oncologist.,"[""Journal Article""]","[""Hicks-Courant K""]",10.1200/JCO-25-02100,Hicks-Courant K,Journal of clinical oncology : official journal of the American Society of Clinical Oncology,0732-183X,,J Clin Oncol,eng,Hicks-Courant K,[],JCO2502100,42447443,,2026 Jul 14,2026,https://pubmed.ncbi.nlm.nih.gov/42447443/,Taking Responsibility,,1WSyrqeWxiXQXuxNc,DBQd04QiHTVXtabRu
,"[""Journal Article""]","[""Taylor L""]",10.1136/bmj-2026-100445,Taylor L,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Taylor L,[],e100445,42538052,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538052/,Epstein: Bill Gates's foundation vows to change after failing to act on warnings,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Wasswa H""]",10.1136/bmj-2026-100469,Wasswa H,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Wasswa H,[],e100469,42538051,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538051/,"Ebola: DRC outbreak is now ""fastest growing in history,"" as strikes hinder response",394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Letter""]","[""Long Z""]",10.1136/bmj-2026-100413,Long Z,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Long Z,[],e100413,42538050,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538050/,Digitisation of primary care excludes those in greatest need,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""O'Dowd A""]",10.1136/bmj-2026-100464,O'Dowd A,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,O'Dowd A,[],e100464,42538044,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538044/,Daily pill for serious heart condition approved for NHS use,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""O'Dowd A""]",10.1136/bmj-2026-100471,O'Dowd A,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,O'Dowd A,[],e100471,42538043,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538043/,"Ectopic pregnancy: Rise in admissions may be linked to deprivation, study suggests",394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Editorial""]","[""Rechel B"", ""Tille F""]",10.1136/bmj-2026-100432,Rechel B,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Tille F,[],e100432,42538042,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538042/,Private equity involvement in UK healthcare,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""O'Dowd A""]",10.1136/bmj-2026-100462,O'Dowd A,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,O'Dowd A,[],e100462,42538041,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538041/,"Cyclosporiasis: ""Explosive diarrhoea"" spreads to UK in outbreak linked to Mexico",394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""O'Dowd A""]",10.1136/bmj-2026-100452,O'Dowd A,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,O'Dowd A,[],e100452,42532594,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42532594/,"England records nearly 2900 excess deaths in recent heatwaves, as GPs are told to consider closing if indoor temperatures reach 30°C",394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Wise J""]",10.1136/bmj-2026-100444,Wise J,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Wise J,[],e100444,42532592,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42532592/,"Massive surge in doctors facing fitness-to-practise complaints, GMC data show",394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Wise J""]",10.1136/bmj-2026-100443,Wise J,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Wise J,[],e100443,42532591,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42532591/,"Emergency department: Over 80s most likely to face waits longer than 12 hours, analysis shows",394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Letter""]","[""Lawrence NJ"", ""Lambert J""]",10.1136/bmj-2026-100386,Lawrence NJ,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Lambert J,[],e100386,42532587,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42532587/,Lyme disease should be notifiable,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Editorial""]","[""Curry N""]",10.1136/bmj-2026-100451,Curry N,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Curry N,[],e100451,42532586,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42532586/,Social care reform: 23(rd) time lucky?,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Baraniuk C""]",10.1136/bmj-2026-100456,Baraniuk C,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Baraniuk C,[],e100456,42532585,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42532585/,"Fauci's Senate hearing: Why he refused to answer questions, and whether his Biden pardon could shield him from legal threats",394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Editorial""]","[""Parsonage J"", ""Newall P"", ""Hickman M"", ""Ioannidis K"", ""Bowden-Jones H""]",10.1136/bmj-2026-100435,Parsonage J,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Bowden-Jones H,[],e100435,42532583,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42532583/,Cryptocurrency based trading and gambling harms require a public health approach,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
"To systematically synthesise the benefits and harms of add-on oral antihistamines for managing atopic dermatitis (eczema). Systematic review and network meta-analysis of randomised trials. Medline, Embase, CENTRAL, the United States Food and Drug Administration, and the European Medicines Agency databases from database inception to 5 May 2025. Randomised trials assessing add-on oral H1 antihistamines, H2 blockers, mast cell stabilisers (nedocromil sodium and sodium cromoglycate), or their combinations. Paired reviewers independently screened records, extracted data, and assessed risk of bias using a modified Cochrane Risk of Bias tool version 2. Random effects bayesian meta-analyses synthesised atopic dermatitis severity (oSCORAD-objective scoring atopic dermatitis, 0-83; minimal important difference 8.2; lower better), itch severity (numerical rating scale, 0-10; minimal important difference 3; lower better), sleep disturbance, atopic dermatitis related quality of life, and harms. The network meta-analysis GRADE (Grading of Recommendations Assessment, Development and Evaluation) and Core GRADE approaches informed certainty of evidence ratings. 47 trials enrolled 6230 children and adults with primarily moderate to severe atopic dermatitis. With moderate certainty, compared with placebo, adding a first generation or second generation H1 antihistamine likely resulted in a small reduction in atopic dermatitis severity (mean difference -1.87, 95% credible interval -3.47 to -0.27) and itch severity (-0.89, -1.41 to -0.37). Although statistically detectable, these effects are well below established minimal important differences (smallest change in an outcome that a patient would identify as important). With low certainty, all studied interventions may not improve sleep disturbance or reduce atopic dermatitis exacerbations. First generation agents probably increase cognitive impairment and may increase treatment discontinuation because of adverse events (risk difference 66 more per 1000, 95% credible interval 0 to 231 more; moderate certainty). Second generation agents differ in their risk of cognitive impairment (range of mean effects 0 more per 1000 for loratadine, 16 more per 1000 for levocetirizine, and 17 more per 1000 for cetirizine). Among patients with atopic dermatitis, adding H1 antihistamines probably results in a clinically unimportant reduction in atopic dermatitis severity and itch severity, and may not reduce sleep disturbance or atopic dermatitis exacerbations. First generation agents increase cognitive impairment and may increase treatment discontinuation because of adverse events. Cognitive impairment risk differs among second generation agents. These findings provide evidence against routine antihistamine use in atopic dermatitis management and will inform updated clinical guidelines. PROSPERO CRD42022345643.","[""Journal Article"", ""Systematic Review"", ""Network Meta-Analysis""]","[""Chu AWL"", ""Wen A"", ""Guyatt GH"", ""Rao M"", ""Bakaa L"", ""Zhao IX"", ""Roldan Y"", ""Spergel JM"", ""LeBovidge J"", ""Boguniewicz M"", ""Martin SA"", ""Lind ML"", ""Silverberg JI"", ""Lio PA"", ""Asiniwasis RN"", ""Wang J"", ""De Benedetto A"", ""Greenhawt M"", ""Wheeler KE"", ""Ong PY"", ""Frazier WT"", ""Nelson H"", ""O'Brien M"", ""Capozza K"", ""Begolka WS"", ""Gardner DD"", ""Schneider LC"", ""Chu DK""]",10.1136/bmj-2026-100163,Chu AWL,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Chu DK,"[""Humans"", ""Dermatitis, Atopic"", ""Randomized Controlled Trials as Topic"", ""Histamine Antagonists"", ""Cromolyn Sodium"", ""Severity of Illness Index"", ""Histamine H1 Antagonists"", ""Pruritus"", ""Drug Therapy, Combination""]",e100163,42526949,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42526949/,Antihistamines for atopic dermatitis (eczema): systematic review and network meta-analysis of randomised trials,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Rimmer A""]",10.1136/bmj-2026-100431,Rimmer A,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Rimmer A,[],e100431,42526948,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42526948/,Exam failure: Doctors sue royal colleges over marking mistake,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Editorial""]","[""Tietjen GE""]",10.1136/bmj-2026-100359,Tietjen GE,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Tietjen GE,[],e100359,42526947,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42526947/,Prevention of migraine with antithrombotic agents in people with patent foramen ovale,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
"To evaluate the efficacy and safety of antithrombotic treatment for migraine prevention in participants with patent foramen ovale (PFO). Investigator initiated, multicentre, prospective, randomised, active controlled, open label clinical trial with blinded outcome assessment and hierarchical hypothesis testing. Secondary and tertiary care hospitals across 39 centres in China. 1000 adults aged 18-64 years with a diagnosis of migraine for more than one year, experiencing at least four migraine days per month, and with PFO confirmed by echocardiography. All participants completed a 12 week screening period before randomisation during which eligibility was confirmed and baseline headache data were prospectively recorded. Participants with previous stroke, transient ischaemic attack, intracranial haemorrhage, non-PFO right-to-left shunt, or contraindications to study drugs were excluded. Of the randomised participants, 984 (75.1% female) were included in the full analysis set. After the screening phase, participants were randomised in a 1:1:1:1 ratio to receive aspirin (300 mg once daily), clopidogrel (75 mg once daily), rivaroxaban (20 mg once daily), or metoprolol (25 mg twice daily) for 12 weeks. No additional preventive migraine treatments were permitted during the intervention period. The primary outcome was the proportion of participants achieving a ≥50% reduction in monthly migraine days or attacks from baseline to weeks 9-12. Safety outcomes included bleeding and other adverse events. For the primary endpoint, aspirin, clopidogrel, and rivaroxaban were all non-inferior to metoprolol. Responder rates were 61.7% (148/240) with aspirin, 66.8% (157/235) with clopidogrel, 78.4% (185/236) with rivaroxaban, and 61.8% (144/233) with metoprolol. Rivaroxaban further showed a statistically higher responder rate than metoprolol, with an absolute difference of 16.2% (98.33% confidence interval 6.0 to 26.4; P<0.001). Among secondary endpoints, rivaroxaban was associated with greater reductions in migraine days and attacks, higher rates of complete migraine cessation, and greater improvements in migraine specific quality-of-life scores than metoprolol. No major bleeding events occurred. The antithrombotic agents evaluated in this trial (aspirin, clopidogrel, and rivaroxaban) were all non-inferior to metoprolol for responder rate in participants with PFO and migraine. Rivaroxaban also showed superior responder rates over metoprolol without an increase in major bleeding events. ClinicalTrials.gov NCT05546320.","[""Journal Article"", ""Randomized Controlled Trial"", ""Multicenter Study"", ""Review""]","[""Li Z"", ""Wang C"", ""Tang Y"", ""Dong J"", ""Dong J"", ""Ouyang W"", ""Zhang F"", ""Pan J"", ""Wan J"", ""Han Y"", ""Yang K"", ""Liu Y"", ""Wang Q"", ""Li B"", ""Tursun I"", ""Shen Q"", ""Li S"", ""Lai H"", ""Che H"", ""Wang G"", ""Ma Q"", ""Hang Y"", ""Huang K"", ""Li Y"", ""Wang P"", ""Gao F"", ""Liu W"", ""Zhang H"", ""Hu H"", ""You T"", ""Liu H"", ""Chen L"", ""Cheng Y"", ""Zhang C"", ""Wang R"", ""Chen Z"", ""Gong M"", ""Fu Q"", ""He C"", ""Wang P"", ""Shen C"", ""Tan H"", ""Zhang X"", ""Zhang X"", ""Zhang R"", ""Wang Y"", ""Pan X""]",10.1136/bmj-2026-100103,Li Z,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Pan X,"[""Humans"", ""Female"", ""Adult"", ""Migraine Disorders"", ""Foramen Ovale, Patent"", ""Middle Aged"", ""Male"", ""Clopidogrel"", ""Fibrinolytic Agents"", ""Aspirin"", ""Prospective Studies"", ""Rivaroxaban"", ""Metoprolol"", ""Treatment Outcome"", ""Young Adult"", ""Adolescent"", ""China"", ""Platelet Aggregation Inhibitors""]",e100103,42526943,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42526943/,"Antithrombotic treatment for migraine in patients with patent foramen ovale: multicentre, randomised, active controlled, open label trial",394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Editorial""]","[""Dobson J"", ""Cook S"", ""Frumkin H"", ""Haines A"", ""Rao M"", ""Abbasi K""]",10.1136/bmj-2026-100410,Dobson J,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Abbasi K,[],e100410,42526942,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42526942/,Fossil fuel industry has no place at climate COP,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Logan M""]",10.1136/bmj-2026-100437,Logan M,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Logan M,[],e100437,42526941,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42526941/,US measles: Cases now surpass last year's total as vaccination rates decline,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Iacobucci G""]",10.1136/bmj-2026-100439,Iacobucci G,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Iacobucci G,[],e100439,42526940,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42526940/,Social care: Burnham vows to fast track Casey review,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Lang K""]",10.1136/bmj-2026-100403,Lang K,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Lang K,[],e100403,42526939,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42526939/,Does Mounjaro cause hair loss?,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Dyer C""]",10.1136/bmj-2026-100434,Dyer C,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Dyer C,[],e100434,42526938,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42526938/,Johnson & Johnson offers $5.5bn to settle talcum powder cancer claims,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Editorial""]","[""Busby G"", ""Uppal S""]",10.1136/bmj-2026-100412,Busby G,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Uppal S,[],e100412,42521359,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42521359/,Endometriosis: biomarker testing offers hope for earlier diagnosis,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Wise J""]",10.1136/bmj-2026-100420,Wise J,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Wise J,[],e100420,42521355,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42521355/,Man died from sepsis after emergency department discharged him owing to overcrowding,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Torres Valencia OG"", ""Rahmayanti NM"", ""Bernal-Serrano D""]",10.1136/bmj-2026-100315,Torres Valencia OG,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Bernal-Serrano D,[],e100315,42521354,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42521354/,Reforming global health architecture requires confronting its political economy,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Editorial""]","[""Nimerawi A"", ""Abdel Mannan O"", ""Zuberi SM"", ""Wilkinson A"", ""Maynard N""]",10.1136/bmj-2026-100423,Nimerawi A,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Maynard N,[],e100423,42521353,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42521353/,Hussam Abu Safiya: The medical community cannot remain passive as a senior paediatrician is left to die in an Israeli prison,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Liang L""]",10.1136/bmj-2026-100422,Liang L,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Liang L,[],e100422,42521352,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42521352/,"Peptides: US advisory committee recommends six for FDA ""compounding list""",394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Borland S""]",10.1136/bmj-2026-100425,Borland S,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Borland S,[],e100425,42521349,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42521349/,"ADHD benefits claims rise: As Burnham mulls reforms, can the NHS and welfare system survive the strain?",394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Editorial""]","[""Edwards N"", ""Vaughan L"", ""Barach P"", ""Robson S""]",10.1136/bmj-2026-100383,Edwards N,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Robson S,[],e100383,42521346,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42521346/,UK maternity inquiries: 25 years of the same diagnosis,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Okereke E"", ""Oji Oti S""]",10.1136/bmj-2026-100075,Okereke E,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Oji Oti S,[],e100075,42508839,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42508839/,Medical tourism erodes Africa's health sovereignty,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Wise J""]",10.1136/bmj-2026-100417,Wise J,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Wise J,[],e100417,42508838,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42508838/,West Nile virus: Cases rise in parts of Europe,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""O'Dowd A"", ""Iacobucci G""]",10.1136/bmj-2026-100415,O'Dowd A,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Iacobucci G,[],e100415,42508837,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42508837/,ADHD prescriptions rise to record levels in England,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Gerden E""]",10.1136/bmj-2026-100182,Gerden E,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Gerden E,[],e100182,42508836,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42508836/,Russia's healthcare crumbles amid Putin's war with Ukraine,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article"", ""Published Erratum""]",[],10.1136/bmj-2026-100400,,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,,[],e100400,42508835,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42508835/,No-touch versus conventional vein in coronary artery bypass grafting: three year follow-up of multicentre randomised PATENCY trial,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Mahase E""]",10.1136/bmj-2026-100406,Mahase E,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Mahase E,[],e100406,42508834,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42508834/,How to keep medicines safe during a heatwave,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Rosenberg H"", ""Maltez N"", ""Rangwala S"", ""Long B""]",10.1136/bmj-2026-407803,Rosenberg H,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Long B,[],e407803,42508833,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42508833/,Recognising and managing polymyalgia rheumatica,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
"Ischemic stroke is a serious complication of atrial fibrillation that is associated with substantial morbidity and mortality. For patients with non-valvular atrial fibrillation, treatment with a direct oral anticoagulant (DOAC) is first line treatment for stroke prevention. Ischemic strokes can still occur, however, despite appropriate anticoagulation-an event known as a breakthrough stroke. In this review, we provide an examination of breakthrough stroke through its epidemiology, mechanisms by which breakthrough strokes happen, and a framework for classification. We then propose a systematic, stepwise algorithm to investigate breakthrough stroke, including standardized criteria to identify an ideal population for future clinical trials using the AF-BREACH criteria (Atrial Fibrillation related BReakthrough Embolic Stroke despite appropriate anticoagulation without alternative Cause identified). Lastly, we discuss the emerging evidence for pharmacological and non-pharmacological management strategies.","[""Journal Article"", ""Review""]","[""Lun R"", ""Pensato U"", ""Shaw JR"", ""Pivato CA"", ""Sposato LA"", ""Field TS"", ""Demchuk AM""]",10.1136/bmj-2025-084905,Lun R,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Demchuk AM,"[""Humans"", ""Atrial Fibrillation"", ""Anticoagulants"", ""Ischemic Stroke"", ""Algorithms"", ""Stroke""]",e084905,42508832,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42508832/,Investigation and management of breakthrough ischemic stroke in anticoagulated patients with atrial fibrillation,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Letter""]","[""Shiha MG"", ""Sanders DS""]",10.1136/bmj-2026-100371,Shiha MG,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Sanders DS,[],e100371,42508831,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42508831/,Undiagnosed coeliac disease presenting with oral ulcers: a missed opportunity,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Rimmer A""]",10.1136/bmj-2026-100352,Rimmer A,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Rimmer A,[],e100352,42508830,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42508830/,How can I make time for training?,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Wise J""]",10.1136/bmj-2026-100414,Wise J,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Wise J,[],e100414,42508827,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42508827/,"Burnham warns that NHS ""will collapse"" without social care reform",394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Cozzolino A""]",10.1136/bmj-2026-100408,Cozzolino A,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Cozzolino A,[],e100408,42508826,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42508826/,Social media ban: France becomes first European country to introduce restrictions for under 15s,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Editorial""]","[""Goyal A"", ""Sacha D""]",10.1136/bmj-2026-100326,Goyal A,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Sacha D,[],e100326,42498326,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42498326/,Workplace support for women through menopause,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Editorial""]","[""Marmot M"", ""Allen J""]",10.1136/bmj-2026-100380,Marmot M,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Allen J,[],e100380,42498314,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42498314/,Devolution can create new opportunities for better health,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Iacobucci G""]",10.1136/bmj-2026-100391,Iacobucci G,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Iacobucci G,[],e100391,42498313,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42498313/,"Medical students hit with punitive ""unprofessional"" sanctions to keep them in line, report warns",394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Aronson JK""]",10.1136/bmj-2026-100381,Aronson JK,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Aronson JK,[],e100381,42498312,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42498312/,When I use a word . . . The Edinburgh Medical School 1726-2026,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Editorial""]","[""Peek N"", ""Dixon J"", ""Ereira E"", ""Dixon-Woods M""]",10.1136/bmj-2026-100390,Peek N,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Dixon-Woods M,[],e100390,42498311,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42498311/,AI might help the NHS-but we need to build the evidence,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Brown C""]",10.1136/bmj-2026-100392,Brown C,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Brown C,[],e100392,42498310,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42498310/,"Wildfires and health: With the US and Canada blanketed by smoke, what are the risks?",394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Dyer C""]",10.1136/bmj-2026-100382,Dyer C,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Dyer C,[],e100382,42498308,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42498308/,Nottingham attacks: Trust that treated killer faces manslaughter probe,394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
,"[""Journal Article""]","[""Nelson F""]",10.1136/bmj-2026-100302,Nelson F,BMJ (Clinical research ed.),0959-8138,,BMJ,eng,Nelson F,[],e100302,42498307,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42498307/,"China has banned an unproven Alzheimer's operation and detained its inventor, but international clinical trials of dcLVA are still going ahead-why?",394,XSbQ4J5wNFEKLffAz,GtIh5my3qd8MruawG
Preferential insertion into the late-replicating inactive X explains L1 accumulation in this chromosome.,"[""Journal Article"", ""Comment""]","[""Doucet AJ"", ""Cristofari G""]",10.1126/science.aej3543,Doucet AJ,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Cristofari G,"[""Humans"", ""Chromosomes, Human, X"", ""Long Interspersed Nucleotide Elements"", ""X Chromosome Inactivation"", ""Female""]",459-460,42531419,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531419/,Why the X chromosome is rich in L1 mobile elements,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
Changes in lysosomal metabolites are associated with both aging organs and lysosomal storage diseases.,"[""Journal Article"", ""Comment""]","[""Na J"", ""Brunet A""]",10.1126/science.aej5901,Na J,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Brunet A,"[""Animals"", ""Humans"", ""Aging"", ""Lysosomal Storage Diseases"", ""Lysosomes"", ""Mice""]",461,42531418,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531418/,Signatures of aging and disease in a single organelle,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
,"[""Journal Article"", ""Expression of Concern""]","[""Thorp HH""]",10.1126/science.aek6646,Thorp HH,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Thorp HH,[],eaek6646,42531417,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531417/,"Erratum for the Research Article ""Elastic ice microfibers""",393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
The Great American Biotic Interchange informs the dynamics of modern species invasions.,"[""Journal Article"", ""Comment""]","[""McGuire JL"", ""Williams CM""]",10.1126/science.aei5362,McGuire JL,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Williams CM,"[""Animals"", ""Biota"", ""Introduced Species"", ""Mammals"", ""North America"", ""South America"", ""Animal Migration""]",458-459,42531416,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531416/,When mammals crossed between continents,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
Calcareous marine plankton can indicate past and present ocean acidification.,"[""Journal Article"", ""Comment""]","[""Leckie RM""]",10.1126/science.aek2948,Leckie RM,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Leckie RM,[],462,42531415,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531415/,Witness to ocean acidification,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"Heme biosynthesis is tightly coordinated to support essential functions without accumulating toxic porphyrins and depleting cellular iron. Heme induces degradation of the heme biosynthetic enzyme, 5-aminolevulinate synthase (ALAS), by the mitochondrial caseinolytic protease complex CLPX-CLPP (CLPXP), but the mechanism for heme-triggered degradation had not been elucidated. We found that polymerase delta-interacting protein 2 (POLDIP2) is a heme-sensing adaptor protein sufficient to reconstitute negative feedback degradation of ALAS by CLPXP. POLDIP2 was necessary to support ALAS turnover in cells and regulate heme production during erythropoiesis. POLDIP2 directly recognized and recruited heme-bound ALAS to CLPXP. Degradation initiation required a carboxyl-terminal element of ALAS, truncations of which cause an erythropoietic protoporphyria. Our findings establish a mechanism for conditional degradation by CLPXP that underlies erythropoietic protoporphyrias linked to CLPX and ALAS.","[""Journal Article""]","[""Cottle T"", ""Joh L"", ""Posner C"", ""DeCosta A"", ""Campagna DR"", ""Fleming MD"", ""Ducamp S"", ""Kardon JR""]",10.1126/science.ads5397,Cottle T,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Kardon JR,"[""Animals"", ""Humans"", ""5-Aminolevulinate Synthetase"", ""Endopeptidase Clp"", ""Erythropoiesis"", ""Feedback, Physiological"", ""Heme"", ""Mitochondria"", ""Mitochondrial Proteins"", ""Proteolysis"", ""Nuclear Proteins"", ""HEK293 Cells""]",eads5397,42531414,pmc-id: PMC13425942;manuscript-id: NIHMS2174012;,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531414/,An adaptor for feedback regulation of heme biosynthesis by a mitochondrial protease,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
Editors' selections from the current scientific literature.,"[""Journal Article""]","[""Szuromi P"", ""Maroso M"", ""Sirois C"", ""Smith KT"", ""McCartney M"", ""Osório J"", ""Nusinovich Y""]",10.1126/science.aek9789,Szuromi P,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Nusinovich Y,[],481-482,42531413,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531413/,In Other Journals,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"Lysosomal dysfunction is a well-recognized feature of aging. Here, we used a suite of tools for rapid lysosomal isolation to construct a multitissue atlas of the metabolite changes lysosomes undergo during aging. Aged lysosomes in brain, heart, muscle, and white adipose tissue accumulated glycerophosphodiesters and cystine, metabolites that are causally linked to juvenile lysosomal storage disorders, Batten disease, and cystinosis. Levels of these metabolites increased linearly with age, preceding organismal decline. Caloric restriction, a lifespan-extending intervention, mitigated these changes in the heart and muscle but not the brain. Our findings link lysosomal storage disorders to aging-related dysfunction and open avenues for the mechanistic investigation of how lysosomal functions deteriorate during aging and in age-associated diseases.","[""Journal Article""]","[""Puszynska AM"", ""Nguyen TP"", ""Cangelosi AL"", ""Armani A"", ""Roberts JM"", ""Singh KA"", ""Cameron JC"", ""Tseyang T"", ""Liu GY"", ""Lai S"", ""Sprenger HG"", ""Yang J"", ""Colgan WN"", ""Kedir JF"", ""Kajderowicz KM"", ""Esantsi TK"", ""Lu YR"", ""Waite M"", ""Kunchok T"", ""Lewis CA"", ""Schulte F"", ""Bell GW"", ""Sabatini DM"", ""Weissman JS""]",10.1126/science.ady0832,Puszynska AM,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Weissman JS,"[""Animals"", ""Humans"", ""Mice"", ""Adipose Tissue, White"", ""Aging"", ""Brain"", ""Caloric Restriction"", ""Cystine"", ""Lysosomal Storage Diseases"", ""Lysosomes"", ""Metabolome"", ""Myocardium"", ""Atlases as Topic"", ""Rats"", ""Male"", ""Female"", ""Mice, Inbred C57BL"", ""Rats, Inbred F344""]",eady0832,42531412,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531412/,Atlas of lysosomal aging reveals a metabolite signature shared with lysosomal storage disorders,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"The Kondo effect is a prototypical quantum phenomenon arising from the interaction between localized electrons in a magnetic impurity and itinerant electrons in a metallic host. Although this phenomenon has served as the testing ground for quantum many-body methods for decades, the precise description of Kondo physics with material specificity remains challenging. Here, we present a systematic ab initio approach to converge toward an exact zero-temperature electronic treatment of Kondo correlations. Across a series of 3d transition metals, we extracted Kondo temperatures matching subtle experimental trends, with accuracy exceeding that of standard models. We further obtained microscopic insight into the origin of these trends. More broadly, we demonstrate the possibility to start from fully ab initio many-body simulations and push toward the realm of converged predictions.","[""Journal Article""]","[""Zhu T"", ""Peng L"", ""Zhai H"", ""Cui ZH"", ""Chi R"", ""Chan GK""]",10.1126/science.adq7402,Zhu T,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Chan GK,[],522-526,42531411,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531411/,Toward an exact quantum many-body treatment of Kondo correlation in magnetic impurities,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"Appel halogenation reactions are widely used to convert alcohols to alkyl halides but are not suitable to prepare alkyl fluorides because fluoride is sequestered as a difluorophosphorane. In this work, we introduce bench-stable neopentoxyphosphonium salts to solve this enduring challenge. With these reagents, various alcohols undergo fluorination with potassium fluoride under hydrogen bonding phase-transfer catalysis, a manifold offering a pathway to enantioselective fluorination of alcohols. Mechanistically, a neopentoxyfluorophosphorane is formed, which undergoes reversible exchange with the alcohol substrate in preference to difluorophosphorane formation. The catalyst assists with potassium fluoride solubilization and with phosphorus-fluorine bond dissociation, leading to the alkoxyphosphonium fluoride ion pair undergoing stereoinvertive fluorination. Turnover results from stronger binding of the catalyst to fluoride than phosphine oxide, the by-product of the reaction, which is recyclable as starting material for the synthesis of the phosphonium reagents.","[""Journal Article""]","[""Mondal A"", ""Struijs JJC"", ""Doyle CJN"", ""Chen Z"", ""Wang Z"", ""Tangamornchaipattana W"", ""Allais C"", ""Richardson PF"", ""Piper J"", ""Paton RS"", ""Aldridge S"", ""Gouverneur V""]",10.1126/science.aec6298,Mondal A,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Gouverneur V,[],514-521,42531410,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531410/,Catalytic Appel fluorination of alcohols with potassium fluoride,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
Policy Evidence Readiness Levels help decision-makers assess evidence maturity and uncertainty.,"[""Journal Article""]","[""Cotton C""]",10.1126/science.aef3529,Cotton C,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Cotton C,[],463-465,42531408,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531408/,Rigor is not readiness: The PERL framework for evidence-based policy,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
""" Landmark"" paper finds European contact introduced the disease.","[""News""]","[""Wade L""]",10.1126/science.ael0167,Wade L,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Wade L,"[""Animals"", ""Humans"", ""Americas"", ""DNA, Ancient"", ""DNA, Viral"", ""Europe"", ""Smallpox"", ""Variola virus""]",448-449,42531407,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531407/,Ancient DNA shows how smallpox got to the Americas,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"Collagen, a fundamental constituent of the extracellular matrix, has long remained elusive to high-resolution structural characterization. Using a tailored system and optimized cryo-electron microscopy processing for long-period filaments, we determined the structure of native collagen fibrils from the porcine vitreous body, with local resolutions extending from 2.6 to 7 angstroms. Each 67-nanometer periodic unit contains type II, V/XI, and IX collagen triple helices together with opticin, at a stoichiometry of 8:4:4:4, which reveals their detailed higher-order molecular packing. Abundant galactose-glucose disaccharides modify hydroxylysine residues in conserved -glycine-X-hydroxylysine- motifs, mediating fibril packing and structural stability. Our structure uncovers the glycan-mediated assembly principle of collagen fibrils and clarifies the structure-function basis of collagens in the vitreous body.","[""Journal Article""]","[""Lou X"", ""Cong Y"", ""Xu Y"", ""Liu Y"", ""Li Y"", ""Yan C""]",10.1126/science.aec2906,Lou X,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Yan C,"[""Animals"", ""Amino Acid Motifs"", ""Cryoelectron Microscopy"", ""Fibrillar Collagens"", ""Hydroxylysine"", ""Swine"", ""Vitreous Body""]",509-513,42531406,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531406/,The molecular architecture of mammalian vitreous body collagen fibrils,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"More than half of AI ""unicorns"" have never published a paper or preprint.","[""News""]","[""Zhao C""]",10.1126/science.ael0166,Zhao C,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Zhao C,[],447-448,42531405,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531405/,AI's top startups are barely publishing their research,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"Fullerene-based electron transport layers (ETLs) used in inverted (p-i-n) perovskite solar cells face issues regarding cost, scalability, and instability, whereas highly stable inorganic oxides feature unfavorable energy alignment and enhance hysteresis, which reduce power conversion efficiency (PCE). We report a nonfullerene conjugated polymer, 2PB-T, that incorporates coplanar and electron-withdrawing perylene bisimide (PBI) units into its backbone. The PBI polymeric backbone and side-chain engineering address the instability of small-molecule ETLs by optimizing electron transport properties, film uniformity, and interfacial binding. Small-area devices achieved a champion PCE of 27.8%, with a certified maximum power point tracking (MPPT) efficiency of 27.3%. Perovskite modules with areas of 20.6 and 625 square centimeters reached PCEs of 24.4 and 22.5%, respectively. Small-area devices retained more than 98.6% of their initial PCE after 1752 hours of continuous MPPT at 85°C in air, and the 625-square-centimeter module maintained 96.9% of its initial PCE after 5900 hours of outdoor operation.","[""Journal Article""]","[""Gao D"", ""Gong J"", ""Yang L"", ""Wang N"", ""Chang B"", ""Qian L"", ""Vanin F"", ""Zhang C"", ""Yu Z"", ""Li S"", ""Gong J"", ""Zhu Z""]",10.1126/science.aed8175,Gao D,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Zhu Z,[],498-503,42531404,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531404/,"n-Type polymer layers enable efficient, scalable, and thermally stable perovskite solar modules",393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"They worry attempt to shake up a ""calcified system"" could do more harm than good.","[""News""]","[""Mervis J""]",10.1126/science.ael0165,Mervis J,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Mervis J,[],446-447,42531403,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531403/,"Golden Age report is a missed opportunity, critics say",393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
Autonomic dysreflexia can be reversed using epidural electrical neuromodulation.,"[""Journal Article""]","[""Soriano JE""]",10.1126/science.aej5900,Soriano JE,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Soriano JE,"[""Humans"", ""Epidural Space"", ""Paralysis"", ""Autonomic Dysreflexia"", ""Electric Stimulation Therapy""]",470-471,42531402,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531402/,Rewiring the paralyzed body's false alarm,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
The 278 winners now face a 9-month race to prove they deserve additional funding.,"[""News""]","[""Zhao C"", ""Cho A""]",10.1126/science.ael0164,Zhao C,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Cho A,[],444-445,42531401,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531401/,U.S. unveils first Genesis Mission grants for AI in research,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
Brain functional circuits can guide precision surface brain stimulation.,"[""Journal Article""]","[""Ren J""]",10.1126/science.aej5902,Ren J,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Ren J,"[""Animals"", ""Humans"", ""Cerebral Cortex"", ""Deep Brain Stimulation"", ""Nerve Net"", ""Parkinson Disease"", ""Precision Medicine"", ""Functional Neuroimaging""]",471,42531400,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531400/,Surfacing brain stimulation,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
,"[""Journal Article""]","[""Lee S""]",10.1126/science.aek9790,Lee S,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Lee S,[],538,42531399,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531399/,The perils of fluency,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"With cancellation of health disparities project, agency may be testing new way to legally kill grants disliked by White House.","[""News""]","[""Kaiser J"", ""Reardon S""]",10.1126/science.ael0163,Kaiser J,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Reardon S,"[""Humans"", ""Financing, Government"", ""National Institutes of Health (U.S.)"", ""Politics"", ""Research Support as Topic"", ""United States"", ""Health Inequities""]",443-444,42531398,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531398/,NIH is again terminating politically sensitive grants,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"Smallpox was a major driver of population collapse in the Americas after European contact, yet the genetic identity of the causal strains remains unknown. Here, we report the first ancient smallpox genomes in the Americas, dating to approximately 1492-1631 common era (CE), recovered from two Inca-Colonial individuals in northern Chile. These genomes form a now-extinct lineage that diverged around 1296 CE, after the splitting of early medieval European strains but before the emergence of modern variola lineages, providing direct molecular evidence for smallpox introduction through European colonization. We further identify a constant tempo of gene inactivation until the late 16th century, followed by a phase of constraint and a subsequent rebound in substitution rates, linking variola virus evolution to major shifts in human demography and epidemiology.","[""Journal Article"", ""Historical Article""]","[""Romero González B"", ""Reyes-Madrid M"", ""Arriaza B"", ""Cassidy LM"", ""Moraga M"", ""la Fuente Castro C"", ""Nakagome S""]",10.1126/science.aee6957,Romero González B,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Nakagome S,"[""Humans"", ""Smallpox"", ""Genome, Viral"", ""Variola virus"", ""Chile"", ""Phylogeny"", ""Evolution, Molecular"", ""History, Medieval"", ""History, 16th Century"", ""DNA, Ancient""]",504-508,42531397,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531397/,The genomic identity of early smallpox in South America,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"The mechanisms underlying the interactions between disseminated tumor cells (DTCs) and their tissue microenvironment during metastatic colonization are currently poorly understood. We integrated multimodal single-cell and spatial profiling from liver cancer mouse models and human metastases to track the spatiotemporal dynamics of DTCs and their microenvironments from single-cell seeding to overt lung metastasis. We identified a residual population of quiescent Phgdhhigh DTCs that survived initial innate immune clearance and became transiently enriched in micrometastases. These cells shaped an immune-scarce microenvironment through PHGDH-dependent, H3K27me3-mediated epigenetic silencing of chemokine transcription, thereby promoting metastatic expansion. Cx3cr1high interstitial macrophages were also transiently enriched before DTC expansion, creating an immune-privileged niche for metastatic outgrowth by recruiting immunosuppressive cells. Inactivating the PHGDH-H3K27me3 axis in DTCs or depleting interstitial macrophages restored immune surveillance and inhibited metastatic colonization. These findings provide insights into the development of micrometastasis-targeting regimens.","[""Journal Article""]","[""Sun Y"", ""Zhong Y"", ""Liu S"", ""Zhang Z"", ""Wang C"", ""Liu Y"", ""Chen J"", ""Guo W"", ""Gu X"", ""Rao K"", ""Wang Z"", ""Cao M"", ""Wang Y"", ""Huang W"", ""Zou X"", ""Chen X"", ""Qiu S"", ""Shi Y"", ""Sun H"", ""Huang X"", ""Wang Y"", ""Wang J"", ""Wu Z"", ""Tian R"", ""Zhang Y"", ""Gu J"", ""Jiang M"", ""Bai Y"", ""Li G"", ""Xie M"", ""Xi F"", ""Peng L"", ""Liu S"", ""Yang S"", ""Zhang Y"", ""Esteban MA"", ""Jin X"", ""Chen A"", ""Wang J"", ""Cang Y"", ""Peng DH"", ""Xu X"", ""Zhou J"", ""Wu L"", ""Fan J""]",10.1126/science.adz7928,Sun Y,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Fan J,"[""Animals"", ""Humans"", ""Mice"", ""CX3C Chemokine Receptor 1"", ""Epigenesis, Genetic"", ""Histones"", ""Liver Neoplasms"", ""Lung Neoplasms"", ""Macrophages"", ""Multiomics"", ""Neoplasm Micrometastasis"", ""Single-Cell Analysis"", ""Spatial Transcriptomics"", ""Tumor Microenvironment"", ""Carcinoma, Hepatocellular"", ""Liver Neoplasms, Experimental"", ""Male"", ""Mice, Inbred C57BL""]",eadz7928,42531396,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531396/,Spatiotemporal multiomics uncover tumor ecosystem dynamics during metastatic colonization,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
,"[""Letter""]","[""Thorp HH""]",10.1126/science.aek4288,Thorp HH,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Thorp HH,[],469,42531395,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531395/,"Editor's Note for the Report ""Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance""",393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"The instability of perovskite solar cells (PSCs) stems largely from the formation and evolution of interfacial defects associated with the soft, multicomponent perovskite lattice. We report a scalable, plasma-based passivation strategy that forms conformal, uniform, and strong-bonded heterostructure through in situ chemical reactions on large-area perovskite films. This approach also mitigates defect accumulation within the laser-scribed interconnection regions, where localized damage often dominates module-level performance losses. We achieved a power conversion efficiency (PCE) of 27.2% in small-area devices (active area 8.313 square millimeters) and 24.0% (certified efficiency of 23.5%) in 100-square-centimeter (cm2) modules (aperture area 65.05 cm2). The small-area device retained 98.1% of its initial PCE after 2000 hours of maximum power point tracking at 85°C under 1-sun illumination, and the 100-cm2 module retained 99.3% of its initial PCE after 1600 hours at 65°C under 1-sun illumination.","[""Journal Article""]","[""Fan R"", ""Ma Y"", ""Xu S"", ""Cheng L"", ""Zhang Z"", ""Li Y"", ""Liu H"", ""Bao Z"", ""Liu G"", ""Wu Y"", ""Zhuang X"", ""Li K"", ""Chen Y"", ""Tze Fung Ng J"", ""Huang B"", ""Zhou W"", ""Zhang Y"", ""Han Y"", ""Yin R"", ""Liu S"", ""Xia T"", ""Xiao M"", ""Zhan X"", ""Zhao X"", ""Chen Q"", ""Zhou H""]",10.1126/science.aeg1730,Fan R,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Zhou H,[],490-497,42531394,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531394/,Plasma surface engineering for efficient and stable perovskite solar cells and modules,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"How genes determine the development of chiral structures is a fascinating question. The reciprocal placement of female and male organs on opposite sides of mirror-image flowers promotes efficient cross-pollination. Here, we identified that in butterfly lilies, female and male organs deflect by a combination of genetically controlled chirality and gravitropism, orienting left and right with respect to an external rather than internal reference axis. We found coordinated organ placement to be controlled by a hemizygous supergene containing two candidate causal loci, MIR156-R and YUCCA-R, that are responsible for opposite female and male organ orientation, respectively. The resulting differential placement of pollen carrying the two supergene alleles on pollinators' bodies leads to their transfer to the stigmas of flowers with opposite handedness and maintenance of the reproductive polymorphism.","[""Journal Article""]","[""Xue H"", ""Saltini M"", ""Illing N"", ""Shepherd K"", ""Page-Macdonald O"", ""Marketos O"", ""Robertson C"", ""Shankar A"", ""Süß S"", ""Kappel C"", ""Alseekh S"", ""Deinum EE"", ""Ingle RA"", ""Lenhard M""]",10.1126/science.aeb1157,Xue H,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Lenhard M,"[""Alleles"", ""Flowers"", ""Genes, Plant"", ""MicroRNAs"", ""Pollen"", ""Pollination"", ""Magnoliopsida"", ""Gene Expression Regulation, Plant"", ""Gene Expression Regulation, Developmental"", ""Gravitation"", ""Hemizygote""]",eaeb1157,42531393,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531393/,Supergene control of chiral development in mirror-image flowers,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"X-chromosome inactivation (XCI) enables gene dosage compensation in XX eutherians. Long interspersed element-1 (LINE-1 or L1) retrotransposons are unusually abundant on the human X chromosome and are hypothesized to facilitate XCI. Here, we used long-read DNA sequencing to conduct a haplotype-aware analysis of engineered L1 integration preferences in the PA-1 human embryonic carcinoma cell line. Crucially, clonal XCI in PA-1 cells enabled derivation of active (Xa) and inactive (Xi) X-chromosome haplotypes. L1 integration strongly favored the Xi and other genomic regions that undergo DNA replication late in S-phase. These results suggest that the X chromosome is L1 rich because of XCI and imply that L1 integration preference for the Xi in XX individuals could potentially double the frequency of X-linked pathogenic L1 mutations in their XY descendants.","[""Journal Article""]","[""de Los Rios Barreda J"", ""Ferreiro ME"", ""Jansz N"", ""Bell CC"", ""Botto JM"", ""Nguyen TV"", ""Pradhan B"", ""Chen M"", ""Colomer-Boronat A"", ""Da Costa Guevara DJ"", ""Flasch DA"", ""Gericke S"", ""Wilson TE"", ""Ewing AD"", ""Heras SR"", ""Sanchez-Luque FJ"", ""Lister R"", ""Moran JV"", ""Faulkner GJ""]",10.1126/science.adz8081,de Los Rios Barreda J,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Faulkner GJ,"[""Humans"", ""Cell Line, Tumor"", ""Chromosomes, Human, X"", ""DNA Replication"", ""Haplotypes"", ""Long Interspersed Nucleotide Elements"", ""Mutagenesis"", ""X Chromosome Inactivation"", ""HeLa Cells""]",eadz8081,42531392,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531392/,X-chromosome inactivation draws L1 mutagenesis to the human X chromosome,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
,"[""Letter""]","[""Zhang W"", ""Li H""]",10.1126/science.aej6290,Zhang W,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Li H,[],468,42531391,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531391/,China's cordgrass removal increases erosion,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"When Andy Burnham became the United Kingdom's prime minister last week, among his first acts was to abolish the Department for Science, Innovation and Technology (DSIT), folding it into a new superministry for Business, Innovation, Science and Trade. The science minister, Patrick Vallance, stepped down the same day. Viewed from the United States, where the federal research system is under pressure, it may be tempting to see Britain's reshuffle as kindred turmoil and proof that political instability is corroding science on both sides of the Atlantic. That reading would be wrong. Britain has rearranged the machinery of its science policy, not undermined its foundations. The change could sharpen the contribution of UK research to the economic renewal that Burnham has made his defining mission.","[""Journal Article"", ""Historical Article"", ""Editorial""]","[""Rees G"", ""Wilsdon J""]",10.1126/science.aek8701,Rees G,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Wilsdon J,[],439,42531390,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531390/,"Churn, not crisis, for UK science",393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
Analyses of hundreds of collisions find black holes pair up in at least three ways.,"[""News""]","[""Cho A""]",10.1126/science.ael0162,Cho A,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Cho A,[],442-443,42531389,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531389/,How black holes get hitched,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"Lignans constitute a diverse family of plant metabolites with therapeutic potential. Among them, podophyllotoxin-type aryltetralin lignans serve as precursors for etoposide and teniposide. Etoposide is an essential anticancer medicine approved for first-line treatment of small cell lung cancer, whereas teniposide is used for treatment of leukemia and some brain tumors. Currently, these drugs depend on extraction of precursors from the endangered plant Sinopodophyllum hexandrum, followed by chemical transformations. By identifying key glycosyltransferases and executing more than 60 genetic edits involving 45 heterologous enzymes, the complex biosynthetic pathway of podophyllotoxin-type lignans was reconstructed in yeast. In this study, we established a chemoenzymatic route that streamlines the synthesis of etoposide and teniposide through a single chemical step from biosynthetic precursor 4'-demethyl-epipodophyllotoxin-4-O-glucoside, which enables a secure supply chain of these essential medicines.","[""Journal Article""]","[""Shen S"", ""Hu X"", ""Li D"", ""Tong Y"", ""Lv Y"", ""Tian Z"", ""Wang J"", ""Tang H"", ""Wang Y"", ""Kang L"", ""Nielsen J"", ""Huang L"", ""Hu Y""]",10.1126/science.aef5438,Shen S,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Hu Y,"[""Antineoplastic Agents, Phytogenic"", ""Biosynthetic Pathways"", ""Etoposide"", ""Glycosyltransferases"", ""Podophyllotoxin"", ""Saccharomyces cerevisiae"", ""Teniposide"", ""Berberidaceae"", ""Protein Engineering"", ""Metabolic Engineering"", ""Genes, Plant""]",aef5438,42531388,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531388/,Enabling sustainable supply of the essential cancer medicines etoposide and teniposide in yeast,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
Critics say goal is to reduce immigration and add Republican seats in Congress.,"[""News""]","[""Mervis J""]",10.1126/science.ael0161,Mervis J,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Mervis J,[],440-441,42531387,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531387/,Privacy-preserving tools banned in census,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
A powerful new prevention drug could help end the HIV epidemic-but supply is falling far short.,"[""News""]","[""Cohen J""]",10.1126/science.ael0160,Cohen J,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Cohen J,"[""Humans"", ""Anti-HIV Agents"", ""HIV Infections"", ""HIV-1"", ""Acetamides"", ""Indazoles"", ""Pre-Exposure Prophylaxis""]",450-457,42531386,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531386/,A rocky rollout,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
,"[""Letter""]","[""Gurung K""]",10.1126/science.aeh0950,Gurung K,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Gurung K,[],469,42531385,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531385/,Making antimicrobial knowledge contagious,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
,"[""Journal Article""]",[],10.1126/science.aek0526,,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,,[],467,42531384,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531384/,Crick: A Mind in Motion,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
,"[""Editorial""]","[""Goujon A""]",10.1126/science.aej7915,Goujon A,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Goujon A,[],eaej7915,42531383,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531383/,When the future loses its voice,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"The movement of taxa between North and South America across the Panamanian land bridge, known as the Great American Biotic Interchange (GABI), established modern-day mammal assemblages in the Americas, heralding the decisive end of what has been called the ""splendid isolation"" of the South American fauna. Lacking substantive low-latitude records, previous work on this pattern relied on South American and temperate North American fossils to conclude that pulsed interchanges began about 2.8 million years ago (mya). Based on new low-latitude fossil data from México, we found evidence for a prolonged, triphasic interchange. Phase 1 consisted of the initial accumulation of northern higher-latitude mammals in a Mexican ""holding pen"" beginning 10 mya. Dispersal began in phase 2, with a strong north-south gradient and increasing biogeographic connections (7 to 3 mya). The final phase consisted of the already well-described taxonomic pulses (from ~2.8 mya).","[""Journal Article""]","[""Tseng ZJ"", ""Kahn LX"", ""Pacheco-Castro A"", ""Carranza-Castañeda O"", ""Aranda-Gomez JJ"", ""Wang Y"", ""Chávez-Ambriz JC"", ""Hannold C"", ""McDonald HG"", ""Wang X""]",10.1126/science.aef2893,Tseng ZJ,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Wang X,"[""Animals"", ""Animal Distribution"", ""Fossils"", ""Mammals"", ""Mexico"", ""North America"", ""South America"", ""Biota""]",532-536,42531382,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531382/,A 10-million-year biogeographic holding pen primed the Great American Biotic Interchange,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"The second-largest extinction event in the evolutionary history of planktic foraminifera occurred at the Aptian-Albian boundary. This extinction may reflect ocean acidification (OA) associated with Oceanic Anoxic Event 1b. As calcium isotope ratios (δ44/40Ca) can track how biocalcification rates respond to OA, we measured δ44/40Ca records for planktic and benthic foraminifera, bulk carbonates, and authigenic calcite across the Aptian-Albian boundary in the South Atlantic. Benthic and bulk δ44/40Ca data display a distinct sequence of negative and positive excursions, similar to δ44/40Ca variations across other OA events. Planktic δ44/40Ca values increase markedly, tracking a reduction in calcification rates coincident with decreases in the size, diversity, and shell thickness of planktic foraminifera. These results suggest that OA drove extinctions of planktic foraminifera at the Aptian-Albian boundary.","[""Journal Article""]","[""Chen J"", ""Jacobson AD"", ""Huber BT"", ""MacLeod KG"", ""Wan C"", ""Waldeck AR"", ""Balestra B"", ""Sageman BB""]",10.1126/science.aed9359,Chen J,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Sageman BB,"[""Atlantic Ocean"", ""Calcification, Physiologic"", ""Calcium Carbonate"", ""Calcium Isotopes"", ""Extinction, Biological"", ""Foraminifera"", ""Ocean Acidification"", ""Seawater"", ""Zooplankton""]",527-531,42531381,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531381/,Calcium isotopes link ocean acidification to Aptian-Albian foraminiferal extinctions,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"Protection and restoration of marine environments are essential for food security and climate change mitigation. Yet historical and archaeological research have shown that conservation and management often rely on arbitrary ecological baselines in ecosystems already shaped by long-term human impacts. Archaeogenomics, the combination of ancient DNA (aDNA) and whole-genome sequencing, provides invaluable insights into these impacts. Recent improvements in laboratory and computational techniques enable the assessment of past fish population dynamics, migration patterns, historical trade routes, long-term anthropogenic pressures, and responses to environmental change. This Review compiles aDNA research on archaeological fish remains, emphasizing studies from 2020 to 2025 that used whole-genome analysis to investigate historical fisheries and marine ecosystem change. We highlight the growing potential of archaeogenomics to inform restoration, conservation, sustainable fisheries management, and climate adaptation strategies worldwide.","[""Journal Article"", ""Review""]","[""Atmore LM"", ""Star B""]",10.1126/science.aeg0333,Atmore LM,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Star B,"[""Animals"", ""Fisheries"", ""Conservation of Natural Resources"", ""Fishes"", ""DNA, Ancient"", ""Genomics"", ""Climate Change"", ""Archaeology"", ""Ecosystem"", ""Whole Genome Sequencing"", ""Population Dynamics""]",472-479,42531380,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531380/,Beyond the scales: Marine archaeogenomics for the conservation and restoration of fisheries,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
Highlights from the Science family of journals.,"[""Journal Article""]","[""Sonawala U"", ""Seale M"", ""Szuromi P"", ""Simonti C"", ""Funk MA"", ""Stajic J"", ""Yin Y"", ""VanHook A"", ""Yeston JS"", ""Vignieri S"", ""Ray LB"", ""Jiang D"", ""Kelly PN"", ""Hurtley SM"", ""Smith J"", ""Hallberg D"", ""Fogg CN""]",10.1126/science.aek9788,Sonawala U,"Science (New York, N.Y.)",0036-8075,6810,Science,eng,Fogg CN,[],480-482,42531379,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531379/,In Science Journals,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"Admixture between modern humans and extinct hominins has shaped the genomes of present-day individuals, but reconstructing this history has been constrained by the scarcity of archaic samples and unadmixed outgroup populations. We introduce TRACE, a reference- and outgroup-free approach that uses features of ancestral recombination graphs to identify archaic ancestry. Simulations show TRACE has high precision and low false discovery rates. Applied to 1000 Genomes, TRACE recovers known Neanderthal and Denisovan introgression and uncovers ghost admixture from uncharacterized hominins in both Africans and non-Africans. Ghost ancestry persists in Neanderthal and Denisovan ancestry deserts, challenging their interpretation as Homo sapiens-specific regions. In Oceanians, TRACE finds deep lineages are enriched in Denisovan compared to Neanderthal regions, supporting super-archaic introgression. TRACE enables mapping archaic introgression without archaic genomes.","[""Journal Article""]","[""Zhang Y"", ""Biddanda A"", ""Johnson SA"", ""O'Dushlaine C"", ""Moorjani P""]",10.1126/science.aef8874,Zhang Y,"Science (New York, N.Y.)",0036-8075,,Science,eng,Moorjani P,[],eaef8874,42531349,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42531349/,Recovering signatures of archaic hominin introgression using ancestral recombination graphs,,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
Colliding molecules react only when their orientations and point of impact fall within a narrow range.,"[""Journal Article"", ""Comment""]","[""Björk J""]",10.1126/science.aej5890,Björk J,"Science (New York, N.Y.)",0036-8075,6809,Science,eng,Björk J,[],359,42490504,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42490504/,A tiny cone of reactivity,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"Birdsong motifs are shaped by evolutionary history, biological traits, and environmental constraints.","[""Journal Article"", ""Comment""]","[""Briefer EF""]",10.1126/science.aej0087,Briefer EF,"Science (New York, N.Y.)",0036-8075,6809,Science,eng,Briefer EF,"[""Animals"", ""Biological Evolution"", ""Songbirds"", ""Vocalization, Animal"", ""Phylogeny""]",354-355,42490503,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42490503/,Birdsong diversity across the world,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
Insect larval buoyancy is controlled by material properties of their air sacs.,"[""Journal Article"", ""Comment""]","[""Harrison JF"", ""Woods HA""]",10.1126/science.aei9743,Harrison JF,"Science (New York, N.Y.)",0036-8075,6809,Science,eng,Woods HA,[],356-357,42490502,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42490502/,Ballooning under water,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
A modular approach could expand the repertoire of spring-loaded covalent drugs.,"[""Journal Article"", ""Comment""]","[""Kraft FB"", ""Gehringer M""]",10.1126/science.aej4566,Kraft FB,"Science (New York, N.Y.)",0036-8075,6809,Science,eng,Gehringer M,"[""Drug Design"", ""Sulfur"", ""Cyclobutanes""]",357-358,42490501,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42490501/,"No strain, no gain",393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"B cell maturation within the germinal center tissue microenvironment involves immunoglobulin gene diversification by somatic hypermutation (SHM). How three-dimensional (3D) genome architecture influences SHM is not fully understood. We leveraged sequencing-based and image-based 3D genomics and transcriptomics to map single-cell 3D genome organization and gene expression across cell types and states in human tonsils and in B cell lymphoma cell lines. These analyses revealed trajectories of compartment, looping, and nuclear position changes during the B cell immune response and activation of SHM. Targeted protein degradation of cohesin component RAD21 revealed its contribution to enabling SHM. Our results provide a single-cell 3D genome atlas of human tonsil cells and outline the links between the chromatin loop extrusion machinery and SHM.","[""Journal Article""]","[""Cheng Y"", ""Wang J"", ""Zhang Y"", ""Yadavalli AD"", ""Liu M"", ""Jin S"", ""Buddle G"", ""Haberman A"", ""Schatz DG"", ""Wang S""]",10.1126/science.adw4243,Cheng Y,"Science (New York, N.Y.)",0036-8075,6809,Science,eng,Wang S,"[""Humans"", ""B-Lymphocytes"", ""Cell Cycle Proteins"", ""Cell Line, Tumor"", ""Chromatin"", ""Cohesins"", ""DNA-Binding Proteins"", ""Genome, Human"", ""Germinal Center"", ""Nuclear Proteins"", ""Palatine Tonsil"", ""Single-Cell Gene Expression Analysis"", ""Somatic Hypermutation, Immunoglobulin"", ""Atlases as Topic""]",eadw4243,42490500,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42490500/,A 3D genome atlas of human tonsil and the role of loop extrusion in B cell somatic hypermutation,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"The absence of aquatic insects from pelagic marine habitats has been attributed to their air-filled tracheal respiratory system, which could implode at depth while undertaking diel vertical migrations to escape predatory fish. However, we found that the aquatic larvae of the lake fly Chaoborus edulis in Lake Malawi have modified their tracheal system into reinforced buoyancy-regulating air-filled sacs, allowing them to escape predatory fish by undertaking these migrations well over 200 meters deep into the lake's anoxic hypolimnion during the day. The crush depth of their air sacs increases with each instar, with final instars resisting implosion at depths greater than half a kilometer. Contrary to expectations, these insects adapt to the extreme hydrostatic pressures of deep-water habitats, allowing them to coexist with pelagic fish.","[""Journal Article""]","[""McKenzie EKG"", ""Ngochera MJR"", ""Chombo J"", ""McLennan H"", ""Proud R"", ""Ames T"", ""Matthews PGD""]",10.1126/science.aed0667,McKenzie EKG,"Science (New York, N.Y.)",0036-8075,6809,Science,eng,Matthews PGD,"[""Animals"", ""Larva"", ""Ecosystem"", ""Lakes"", ""Air Sacs"", ""Hydrostatic Pressure"", ""Fishes"", ""Predatory Behavior"", ""Animal Migration"", ""Calliphoridae""]",398-402,42490499,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42490499/,Crush-resistant air sacs allow insect larvae to exploit aquatic habitats at extreme depth,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"Invasive alien species (IAS) are a major threat to biodiversity, yet their impact distribution remains poorly understood. Global biodiversity assessments suggest the highest impacts in wealthy countries of the Global North, but this is only inferred from IAS numbers, reflecting research bias. Using a new global database of standardized impact measures, we calculated average impact severity per country and found that it is higher in the Global South despite more than twice as many reports in the Global North. Weak governance and limited management capacity are the main drivers of high impact severity. Emerging economies with rapid economic growth but poor governance are particularly vulnerable. Failure to recognize the Global South as facing the highest IAS impacts diverts attention away from the most threatened regions.","[""Journal Article""]","[""Bacher S"", ""Pyšek P"", ""Seebens H""]",10.1126/science.aed0603,Bacher S,"Science (New York, N.Y.)",0036-8075,6809,Science,eng,Seebens H,"[""Animals"", ""Biodiversity"", ""Conservation of Natural Resources"", ""Environment"", ""Introduced Species"", ""Developing Countries""]",376-380,42490498,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42490498/,Invasive species' environmental impacts are more severe in the Global South,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"Characterizing the factors that have shaped linguistic diversity is fundamental for understanding human history, culture, and cognition. In this study, we combined statistical and social computational modeling, ethnographic data, and paleodemographic inference to model trajectories of global linguistic diversity. Before the onset of plant and animal domestication, the number of languages was smaller than it is today (4500 to 6000 compared with 7500). Subsequent increases in global population precipitated increased linguistic diversity. We uncovered a linguistic ""golden age"" with tens of thousands of languages 3000 to 1000 years ago. Great loss of linguistic diversity did not begin with recent colonial expansion but as multinational empires first spread along with their languages, pathogens, and cultures. Thus, extinction has likely played a much greater role in shaping linguistic and cultural diversity than previously thought.","[""Journal Article""]","[""Blasi DE"", ""Hamilton MJ"", ""Gray RD"", ""Bowern CL""]",10.1126/science.adx4343,Blasi DE,"Science (New York, N.Y.)",0036-8075,6809,Science,eng,Bowern CL,"[""Animals"", ""Humans"", ""Cultural Diversity"", ""Extinction, Biological"", ""History, Ancient"", ""Language"", ""Linguistics""]",387-391,42490497,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42490497/,The rise and fall of language diversity through the Holocene,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
,"[""Letter""]","[""Cianciaruso MV"", ""Bini LM"", ""Diniz-Filho JA"", ""Loyola R""]",10.1126/science.aej1473,Cianciaruso MV,"Science (New York, N.Y.)",0036-8075,6809,Science,eng,Loyola R,[],362,42490496,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42490496/,Brazil's environmental governance at risk,393,5Y9aaBdTDKBl35wlN,fAQpSJJfp1s24Q1id
"1,5-Anhydrohexitol nucleic acid (HNA) is a promising xeno nucleic acid (XNA) for applications such as aptamers and catalysts, due to its favourable physico-chemical properties. Realizing this potential requires efficient and high-fidelity polymerases capable of processing HNA. A key component are HNA reverse transcriptases that convert HNA into DNA, an essential step in standard SELEX workflows. Although HNA reverse transcriptases have been generated by directed evolution, structural insight is essential to guide further enzyme engineering. Here, we report the 2.8 Å crystal structure of the engineered HNA reverse transcriptase KOD-H4, derived from the B-family DNA polymerase of Thermococcus kodakarensis, captured in a closed ternary complex with dATP, a 3'-terminated primer and a mixed HNA/DNA template. Compared to a previously reported open ternary KOD-H4 structure, the presented structure adopts a more closed conformation with increased finger and thumb domain closure and formation of a canonical Watson-Crick-Franklin base pair at the insertion site. Direct downstream nucleotides show more distorted base pairing and one HNA residue transits from the unusual 1C4 conformation it adopted in the open complex to the 4C1 hexitol sugar conformation. These findings demonstrate that KOD-H4 can form a closed, pre-catalytic complex resembling that of the wildtype enzyme with natural substrates, and reveal state-dependent conformational flexibility of HNA. Such flexibility should be considered in the design and optimization of enzymes that process HNA.","[""Journal Article""]","[""Gutfreund C"", ""Abramov M"", ""Coosemans F"", ""Holliger P"", ""Herdewijn P"", ""Betz K"", ""Marx A""]",10.1371/journal.pone.0351418,Gutfreund C,PloS one,1932-6203,7,PLoS One,eng,Marx A,"[""RNA-Directed DNA Polymerase"", ""Crystallography, X-Ray"", ""DNA"", ""Models, Molecular"", ""Thermococcus"", ""Nucleic Acids"", ""Sugar Alcohols""]",e0351418,42536700,pmc-id: PMC13426950;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536700/,Crystal structure of a closed ternary complex of a HNA Reverse Transcriptase in complex with a HNA/DNA duplex,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"This longitudinal study explored the perceptions of psychosocial work factors, work-related health, and job satisfaction of 745 professional service staff, working in a higher education setting in Sweden, during the transition from full remote work to a hybrid work arrangement over 12-months. The study also explored whether these perceptions differed due to gender and household composition. The questionnaire data were analyzed using linear mixed-effects models with estimated marginal means and Bonferroni-adjusted pairwise comparisons. The results showed that while overall perceptions of psychosocial work factors showed modest changes during the transition, except for social support from colleagues, which significantly increased over time. Professional service staff reported higher levels of stress and exhaustion during the transition, while job satisfaction remained unchanged. The results also highlighted significant gender differences during the transition, as women reported less favourable perceptions of psychosocial work factors and higher levels of stress, while men's perceptions remained largely stable across these outcomes. Significant overall differences in household composition were also observed, as individuals living in single-person households and in single-parent households reported less favourable perceptions of psychosocial work factors and their work-related health compared to cohabitants and cohabitants with children, though all household groups followed similar trajectories during the transition. The findings suggest that higher education institutions should implement action plans for gender equality and family-supportive practices in hybrid work arrangements to ensure that the benefits of hybrid work are accessible to all employees.","[""Journal Article""]","[""Casely-Hayford J"", ""Tinnerholm Ljungberg H"", ""Aboagye E"", ""Björklund C"", ""Kwak L"", ""Toivanen S"", ""Bergström G"", ""Jensen I""]",10.1371/journal.pone.0353162,Casely-Hayford J,PloS one,1932-6203,7,PLoS One,eng,Jensen I,"[""Humans"", ""Male"", ""Female"", ""Sweden"", ""Job Satisfaction"", ""Working Conditions"", ""Workplace"", ""Adult"", ""Surveys and Questionnaires"", ""Longitudinal Studies"", ""Social Support"", ""Stress, Psychological"", ""Middle Aged""]",e0353162,42536699,pmc-id: PMC13426970;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536699/,Entering the new normal - psychosocial work environment and health during the transition from full remote to a hybrid work arrangement in a higher education context,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Recent developments in the field of artificial intelligence and machine learning allow the wide application of large language models for the evaluation of written text and other non-numerical data. When applied in the context of psychological and educational assessments, such models can be used for assigning scores to essays and other types of responses. In contrast to classical tests, essays do not consist of test items, which leads to specific challenges in the evaluation of testing standards for scores obtained from AI models that differ from those observed for classical ability tests and personality questionnaires. To address these challenges, we discuss the evaluation of validity, fairness, and reliability for scores obtained from models of artificial intelligence in the context of automated essay scoring. We review existing methods, propose new methods, and further illustrate the reviewed methods with an empirical example based on the Hewlett Foundation data set on automated essay scoring. By applying the proposed framework to an evaluation based on a DistilBERT model, we find the model to be robust with sufficiently high internal consistency (Spearman-Brown coefficients in the range from .77 to .92). We further found empirical evidence for the validity of the evaluation model, but also indications for violations of fairness when comparing the human and AI scores across different topics. This study provides a standardized, replicable toolkit for researchers and practitioners to evaluate the psychometric quality of AI-based assessments.","[""Journal Article""]","[""Debelak R"", ""Ziegler M""]",10.1371/journal.pone.0354680,Debelak R,PloS one,1932-6203,7,PLoS One,eng,Ziegler M,"[""Humans"", ""Artificial Intelligence"", ""Reproducibility of Results"", ""Large Language Models"", ""Machine Learning"", ""Educational Measurement""]",e0354680,42536698,pmc-id: PMC13426959;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536698/,Testing standards for AI-based scores in automated essay scoring,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"This study examines the heterogeneity of CEOs' risk attitudes and how fixed versus variable compensation components shape their strategic risk-taking, as part of corporate governance policy. Building on psychological Regulatory Focus Theory (RFT) and established management frameworks, we developed a conceptual model with six hypotheses. We applied a validated Polish Linguistic Inquiry and Word Count (LIWC) dictionary to measure CEOs' promotion and prevention focus through content analysis of their shareholder letters. Our dataset covers 82 companies listed on the Warsaw Stock Exchange (WSE) from 2011 to 2020, analyzed using longitudinal panel data. The results confirmed that a CEO's regulatory focus is a significant motivational factor in strategic risk-taking. Promotion-focused CEOs tend to pursue bolder, riskier decisions, increasing the firm's strategic risk, whereas prevention-focused CEOs are more cautious and inclined to mitigate risk, aligning with prior findings in the literature. Moreover, these relationships are moderated by compensation structure. Higher fixed salaries are associated with reduced strategic risk, reinforcing risk aversion, while larger annual bonuses are associated with greater risk-taking. In particular, fixed compensation strengthened the natural risk-avoidant tendencies of prevention-focused CEOs, suggesting that higher guaranteed income reinforces a cautious strategy. Unexpectedly, large annual bonuses did not temper the risk appetite of promotion-focused CEOs; instead, bonuses amplified their risk-taking, indicating that intrinsic motivation can outweigh extrinsic incentives for risk moderation. These findings underscore the need for tailoring executive compensation policies to individual CEOs' risk preferences. Fixed salaries may temper excessive risk-taking in promotion-focused CEOs, while performance-based bonuses may motivate otherwise cautious, prevention-focused CEOs to undertake strategic risks. Such insights are valuable for refining corporate governance strategies in European public firms, especially in Poland, to better align CEO behavior with shareholder interests.","[""Journal Article""]","[""Miązek AJ"", ""Światowiec-Szczepańska J""]",10.1371/journal.pone.0352905,Miązek AJ,PloS one,1932-6203,7,PLoS One,eng,Światowiec-Szczepańska J,"[""Humans"", ""Risk-Taking"", ""Motivation"", ""Salaries and Fringe Benefits""]",e0352905,42536697,pmc-id: PMC13426988;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536697/,Promote or prevent? A regulatory focus perspective on managerial risk taking,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Abdominal aortic aneurysms (AAA) are potentially life-threatening if they rupture. Xanthine oxidase inhibitors have been suggested to reduce aneurysm growth via urate-lowering and antioxidative mechanisms, though their clinical efficacy remains uncertain. The primary objective of this prospective cohort study was to estimate potential associations between urate-lowering therapies and AAA growth, and secondarily risk of rupture, surgery, all-cause mortality, and major adverse cardiovascular events (MACE), in men aged 65-74. This population-based cohort study included data from two large cardiovascular screening trials. The two Danish AAA male cohorts contributed with baseline characteristics, including AAA measurements through ultrasound and computed tomography scans. Participants were followed for five years through linkage with the Danish national health registries. Prescription records defined the exposure of urate-lowering therapies, and participants were categorised as users or non-users. Growth rate was examined using multivariate linear regression, and the secondary outcomes were evaluated using Cox regression. This study included 998 men, of whom 73 (7.3%) were exposed to urate-lowering therapies, with a mean defined daily dose of 0.377 per day. During 3 993 person-years, an insignificant mean difference of 0.28 mm/year (95%CI: -0.96-1.52, p = .66) in AAA growth was observed between users and non-users. No associations between urate-lowering therapies and risk of surgery, rupture, all-cause mortality, or MACE were observed. The use of urate-lowering therapies was not associated with a reduction in AAA progression. These findings do not support a clinically meaningful effect of urate-lowering therapies on aneurysm progression in men with AAA.","[""Journal Article""]","[""Bøhling Dybdahl K"", ""Bernal M"", ""Dahl M"", ""DANCAVAS trialists"", ""Obel LM"", ""Lindholt JS"", ""Skovbo JS""]",10.1371/journal.pone.0341242,Bøhling Dybdahl K,PloS one,1932-6203,7,PLoS One,eng,Skovbo JS,"[""Humans"", ""Male"", ""Aortic Aneurysm, Abdominal"", ""Aged"", ""Uric Acid"", ""Cohort Studies"", ""Prospective Studies"", ""Denmark"", ""Disease Progression"", ""Gout Suppressants""]",e0341242,42536696,pmc-id: PMC13427005;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536696/,Association of urate-lowering therapies with abdominal aortic aneurysm growth and clinical events in men: A population-based cohort study,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Prostate cancer (PCa) is characterized by molecular heterogeneity and metabolic reprogramming, but the relationships among transcriptomic, proteomic, and metabolic signals remain incompletely defined. Here, we present a human-centered, cross-dataset analysis of public RNA, protein, and metabolomics data in PCa. We analyzed RNA and protein profiles from PC3 parental and drug-resistant cells together with an independent human matched tissue metabolomics dataset from Metabolomics Workbench (ST000784). RNA-protein overlap analysis identified seven genes that were significant at both layers, including five concordantly upregulated genes: UPP1, IGF2R, FLNC, DSP, and PLEC. Among these, UPP1 provided the most direct metabolic interpretation because it encodes uridine phosphorylase 1, an enzyme linked to pyrimidine salvage. Independent ST000784 matched prostate tissue metabolomics supported broader nucleotide metabolism remodeling, including significant changes in N-carbamoyl-L-aspartate, guanosine monophosphate, and adenosine 3,5-cyclic monophosphate. In contrast, uracil was not significantly altered and uridine 5'-monophosphate showed only a trend after multiple-testing correction. Repeated stratified cross-validation showed that UPP1-containing candidate gene sets achieved high within-layer AUC values in RNA and protein data, while nested statistical benchmark models also performed strongly. These results prioritize a UPP1-associated nucleotide remodeling hypothesis in PCa, but do not establish causal regulation of metabolite abundance or clinical diagnostic utility. Future matched multi-omics and perturbation experiments are required.","[""Journal Article""]","[""Chen X"", ""Su W"", ""Zhou Q"", ""Qi Y"", ""Xie J"", ""Tang Y"", ""Tang X"", ""Fu H""]",10.1371/journal.pone.0354354,Chen X,PloS one,1932-6203,7,PLoS One,eng,Fu H,"[""Humans"", ""Male"", ""Prostatic Neoplasms"", ""Metabolomics"", ""Uridine Phosphorylase"", ""Gene Expression Regulation, Neoplastic"", ""Metabolic Reprogramming"", ""Nucleotides"", ""PC-3 Cells""]",e0354354,42536695,pmc-id: PMC13426977;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536695/,Concordant RNA-protein evidence and human tissue metabolomics prioritize UPP1-associated nucleotide remodeling in prostate cancer,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Primary care physicians (PCPs) are on the front lines of health promotion and disease prevention, yet evidence supports a longstanding gap in physicians' capacity to counsel about diet, a key factor in patient health and chronic disease risk. Momentum to address the nutrition training needs of physicians is growing; however, challenges PCPs experience due to inadequate training are further complicated by clinical practice barriers. This study seeks to better understand the complex problem PCPs face addressing nutrition with patients to inform potential solutions. This qualitative study takes a design thinking approach to understanding the problem by learning from PCPs about their experience, challenges, and priorities addressing nutrition with patients. Findings from semi-structured interviews with 32 PCPs revealed that while they value nutrition and believe they have an important role in addressing diet with patients, their role as a generalist in addressing nutrition lacks clarity. PCPs describe learning their current approach to nutrition primarily outside of formal medical training, resulting in variability and inconsistency in approaches and recommendations and general frustrations about their ability to give actionable guidance. While registered dietitians (RDs) are often viewed as valuable support for patients, PCPs describe multiple challenges to RD utilization and subsequently at times may be the only ones with the opportunity to address diet with patients. Additional system- and societal-level barriers, such as time limitations and the food environment, further complicate PCPs' experiences advising patients about nutrition. Main limitations of this study are limited generalizability from recruiting graduates of a single medical school and PCPs with greater interest in nutrition or more frustration with their current approach to nutrition may have been more likely to participate. Our results support the need to clearly define a realistic role for PCPs as generalists addressing nutrition. Clarified expectations in turn can inform nutrition training of physicians and guiding frameworks and strategies for giving practical, evidence-based nutrition guidance. PCPs also need increased support through access to resources, strategies to improve RD collaboration, and attention to system- and societal-level challenges influencing dietary interventions in primary care.","[""Journal Article""]","[""Hildebrand CA"", ""Agrawal S"", ""Albin J"", ""Beck Dallaghan GL"", ""Chen E"", ""Gaviria D"", ""Gilliland KO"", ""Hilton A"", ""Keyserling TC"", ""Mayer-Davis E"", ""Ammerman AS""]",10.1371/journal.pone.0354813,Hildebrand CA,PloS one,1932-6203,7,PLoS One,eng,Ammerman AS,"[""Humans"", ""Physicians, Primary Care"", ""Interprofessional Relations"", ""Female"", ""Male"", ""Cooperative Behavior"", ""Adult""]",e0354813,42536694,pmc-id: PMC13426925;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536694/,"It would be really great if I had greater confidence and ability there: Understanding the primary care physician experience with nutrition in training, clinical practice, and interprofessional collaboration",21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"This study explores the potential of artificial intelligence (AI) using a hybrid deep learning Convolutional Neural Network-Long Short-Term Memory (CNN-LSTM) framework, for EEG-based classification and analysis of Dravet Syndrome (DS). The study cohort comprised nine pediatric patients with DS, confirmed through either a heterozygous pathogenic mutation in the SCN1A gene or a clinical diagnosis consistent with established diagnostic criteria. In addition, EEG recordings from age-matched healthy control subjects and pediatric patients with non-Dravet epilepsy (""abnormal"" EEG) were included. Data on demographic information, seizure characteristics, developmental skills, cognitive functions, and genetic results were gathered from patient records. EEG recordings were analyzed using a subject-independent leave-one-subject-out validation strategy, spatial and temporal features by employing this model on preprocessed EEG data, effectively differentiating DS patients from Abnormal cases and healthy controls. Among the evaluated CNN-LSTM models, the pre-trained architecture achieved superior performance with improved stability across most subjects, with an overall accuracy of 85%, balanced accuracy of 85%, a macro-averaged F1-score of 0.85, and a macro-averaged ROC-AUC of 0.87, demonstrating stable performance for multi-class EEG classification of DS, Abnormal, and control subjects. The non-pretrained model showed reduced sensitivity and increased inter-class confusion, particularly for DS and Abnormal classes. This study demonstrates that a pre-trained CNN-LSTM framework can support automated EEG-based classification of DS-related patterns as a proof-of-concept methodological approach, even in the context of limited subject availability. EEG-specific pretraining improves classification consistency and feature separability compared with training from scratch, highlighting the value of representation learning for rare epilepsy syndromes. Larger multi-center datasets and prospective validation will be required to assess robustness, generalizability, and clinical utility.","[""Journal Article"", ""Comparative Study""]","[""Hussain S"", ""Jawed S"", ""Mir A"", ""Ibrahim Ali M"", ""Al-Baradie R"", ""Alaqili N"", ""Nassim Ali EM"", ""Bashir S""]",10.1371/journal.pone.0352991,Hussain S,PloS one,1932-6203,7,PLoS One,eng,Bashir S,"[""Humans"", ""Epilepsies, Myoclonic"", ""Electroencephalography"", ""Deep Learning"", ""Convolutional Neural Networks"", ""Child"", ""Long Short Term Memory"", ""Female"", ""Male"", ""Child, Preschool"", ""NAV1.1 Voltage-Gated Sodium Channel"", ""Case-Control Studies""]",e0352991,42536693,pmc-id: PMC13426933;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536693/,Deep learning architectures for EEG-based classification of Dravet syndrome: A comparative study of pre-trained and non-pretrained hybrid CNN-LSTM models,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Typhoid is a significant global health challenge due to its high pathogenicity and antimicrobial resistance. Salmonella typhi (S.typhi) can switch its lifestyles between biofilm and planktonic phase which allows it to evade host defenses and develop resistance to antibiotics. Salmonella sp. harbors multiple genes encoding efflux-pumps systems whose up-regulation contributes to multi-drug resistance (MDR) and extensive drug-resistance (XDR). To overcome the battle against resistant S. typhi strains, novel non-antibiotics inhibitors are required for inhibitory application. This study assesses the inhibitory effect of lignans against drug resistance of S. typhi. Clinical resistant and sensitive strains of S. typhi were obtained and characterized. The inhibitory effect of lignans, specifically Schisandrin A and B, purified from the plant Schisandra chinensis, are found to be effective non-antibiotic inhibitors were evaluated through standard microbiological techniques like growth curve and time-kill assays. Impact on bacterial morphology was analyzed using scanning electron microscopy (SEM). Our study explores two approaches, such as efflux pumps (EPs) inhibition and antibiofilm assays. Using colony-forming unit (CFU) assays, growth curve analysis, and SEM imaging, we observed significant bacteriostatic effects, with Schisandrin B causing notable membrane disruption. Schisandrin B also showed remarkable biofilm inhibition (90.33%) and strong efflux pumps inhibition. This study offers a strong basis for future research on addressing antibiotic resistance in clinically relevant pathogens.","[""Journal Article""]","[""Shafique I"", ""Rana NF"", ""Ahmad N"", ""Tanweer T"", ""Javaid S"", ""Albaldi FO"", ""Elbehairi SEI"", ""Shati AA"", ""Sheikh HM"", ""Menaa F""]",10.1371/journal.pone.0347214,Shafique I,PloS one,1932-6203,7,PLoS One,eng,Menaa F,"[""Lignans"", ""Salmonella typhi"", ""Polycyclic Compounds"", ""Cyclooctanes"", ""Drug Resistance, Multiple, Bacterial"", ""Microbial Sensitivity Tests"", ""Anti-Bacterial Agents"", ""Biofilms"", ""Humans""]",e0347214,42536690,pmc-id: PMC13426931;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536690/,Schisandrins as novel efflux pumps inhibitors and non-antibiotic compounds against multi- and extensively-drug resistant clinical strains of Salmonella typhi: An in-vitro study,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Circadian rhythm disruption is increasingly recognized as a contributor to chronic inflammatory disorders; however, its specific significance and underlying mechanisms in chronic obstructive pulmonary disease (COPD) remain unclear. This study aimed to identify circadian rhythm-associated biomarkers in COPD and explore their diagnostic value, immune correlations, and therapeutic potential. This study integrated four lung transcriptomic datasets from the public GEO database (GSE151052, GSE38974, and GSE76925 as the discovery set, and GSE47460 as the validation set). Differentially expressed circadian rhythm‑related genes (DECRRGs) were identified by intersecting differentially expressed genes with circadian rhythm‑related genes. Functional enrichment analyses (GO and KEGG) were performed, and three machine learning algorithms were applied to screen for signature DECRRGs. An exploratory risk stratification model based on multivariate logistic regression was constructed and evaluated. Immune cell infiltration was assessed using CIBERSORT, and single-cell RNA sequencing analysis was conducted to localize the distribution of key circadian rhythm genes within specific lung cell populations. Finally, the expression of a core gene CHRNA1 was validated by qRT-PCR in peripheral blood samples from COPD patients and healthy controls. We identified eight circadian rhythm-associated feature genes, among which CHRNA1 emerged as a consistently upregulated hub gene in COPD. An exploratory risk stratification model based on these genes exhibited good discriminatory ability in the discovery cohort (AUC = 0.856, 95% CI: 0.806-0.902). Differential expression of CHRNA1 was validated in an independent cohort and correlated significantly with pro-inflammatory immune infiltration, including increased M1 macrophages and CD8 ⁺ T cells. Single-cell transcriptomics further localized CHRNA1 expression predominantly within B cells in COPD lung tissue. In silico drug screening and ceRNA network analysis predicted potential therapeutics (e.g., amitriptyline, rocuronium bromide) and regulatory miRNAs/lncRNAs. Finally, qRT-PCR confirmed a marked upregulation of CHRNA1 in peripheral blood from COPD patients (*p* < 0.0001). Our findings suggest that CHRNA1 may serve as a candidate circadian rhythm‑associated immunomodulator in COPD. It demonstrates consistent upregulation across cohorts and shows a significant association with pro‑inflammatory immune infiltration. Single-cell analysis revealed that CHRNA1 is predominantly expressed in pulmonary B cells. The exploratory risk stratification model and predicted therapeutic candidates highlight the translational potential of targeting circadian disruption in COPD, though prospective validation is needed before clinical application.","[""Journal Article""]","[""Zhang L"", ""Li Z"", ""Xia T"", ""Yang T"", ""Fu J"", ""Lu Y"", ""Xu J"", ""Han K""]",10.1371/journal.pone.0353838,Zhang L,PloS one,1932-6203,7,PLoS One,eng,Han K,"[""Pulmonary Disease, Chronic Obstructive"", ""Humans"", ""Machine Learning"", ""Circadian Rhythm"", ""Receptors, Nicotinic"", ""Multiomics"", ""Gene Expression Profiling"", ""Male"", ""Transcriptome"", ""Lung"", ""Biomarkers"", ""Female""]",e0353838,42536689,pmc-id: PMC13426952;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536689/,Integrative multi-omics and machine learning identify CHRNA1 putative circadian-immune hub in COPD,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), are progressive disorders with limited therapeutic options. Centella asiatica (C. asiatica), a medicinal and edible plant, has been reported to exert neuroprotective and anti-neuroinflammatory properties. Yet, the mechanisms underlying its effects against neurodegenerative diseases remain largely unclear. We employed an integrative strategy combining network pharmacology, transcriptomic analyses, machine learning and molecular docking to prioritize disease-associated molecular networks and candidate compound-target relationships in AD, PD and HD. Sixteen candidate constituents of C. asiatica met the predefined drug-likeness, gastrointestinal absorption and blood-brain barrier permeability criteria, yielding 370 unique predicted targets. Disease-gene mining identified 983 AD-associated genes, 1,103 PD-associated genes, and 3,316 HD-associated genes. Integration of compound targets, disease-associated genes, and transcriptomic profiles prioritized five hub genes in PD (CCKAR, MAPK8, PSEN2, SLC6A3, and TH), four in AD (APP, PGK1, PIK3CA, and TTR), and four in HD (CHRND, HSP90AA1, PRKCQ, and TH). Enrichment analyses highlighted disease-relevant processes involving neurotransmitter signalling, cAMP and calcium pathways, MAPK-related responses and inflammatory regulation. ROC analyses provided additional support for the discriminatory performance of the prioritized genes in independent datasets, whereas molecular docking identified favourable predicted Vina docking scores and structurally plausible interactions between selected compounds and hub targets. This integrative computational analysis prioritizes candidate C. asiatica constituents, putative disease-associated targets, and molecular pathways in AD, PD, and HD. The findings provide a foundation for subsequent biochemical, cellular, and in vivo validation.","[""Journal Article""]","[""Xie Y"", ""Lim CT"", ""Lam XJ"", ""Cheah PS"", ""Ling KH"", ""Huang T""]",10.1371/journal.pone.0354882,Xie Y,PloS one,1932-6203,7,PLoS One,eng,Huang T,"[""Molecular Docking Simulation"", ""Neurodegenerative Diseases"", ""Centella"", ""Humans"", ""Network Pharmacology"", ""Triterpenes"", ""Transcriptome"", ""Gene Expression Profiling""]",e0354882,42536688,pmc-id: PMC13426974;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536688/,"Integrative network pharmacology, transcriptomics, and molecular docking identify candidate Centella asiatica constituents and targets in neurodegenerative diseases",21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Gastrointestinal stromal tumors (GIST) are the most common gastrointestinal soft tissue sarcoma. Tyrosine kinase inhibitors are guideline-recommended therapy; however, resistance often occurs, requiring subsequent therapy. Regorafenib is a multikinase inhibitor approved for third-line therapy. Real-world data surrounding regorafenib's use and place in therapy are limited. To understand real-world regorafenib utilization and patient characteristics among US patients with advanced GIST. This retrospective cohort claims analysis used data from Merative™ MarketScan® research databases and included patients with ≥1 pharmacy claim for regorafenib during the identification period (10/2015-5/2023) and ≥1 GIST diagnoses any time prior to/on index date (first regorafenib prescription claim). Primary outcomes included duration of therapy (DOT) and time to next therapy (TTNT). Outcomes were stratified based on prior GIST treatment during the baseline period (BL) and initial regorafenib dose (i.e., low dose [LD] or regorafenib standard dose [RSD]) as of the index date. Nearly half (45.2%) of patients received imatinib and sunitinib prior to regorafenib initiation, and 73.5% received RSD. Patients who received prior imatinib or sunitinib alone before regorafenib had a numerically longer median DOT with regorafenib than those who received both in the BL before regorafenib (142.5 days [IQR: 87-257.5] vs 95 days [IQR: 53-192]). Patients receiving LD and RSD demonstrated similar median DOT (103.0 days [IQR: 41.5, 210.5] vs 94.5 days [IQR: (35.0, 171.0]) and TTNT (143 days [IQR: 70-293] vs 141 days [IQR: 77-191]). Patients on LD and RSD had similar DOT and TTNT. Acknowledging the limitations from this real-world data, patients with prior imatinib or sunitinib alone appeared to have longer DOT on regorafenib than those who received both. Further research is warranted to explore the clinical benefits of these differences.","[""Journal Article""]","[""Denu RA"", ""Appukkuttan S"", ""Hocum B"", ""Liao N"", ""Katta A"", ""Heo J"", ""Schroader B"", ""Singh R"", ""Babajanyan S"", ""Somaiah N""]",10.1371/journal.pone.0353357,Denu RA,PloS one,1932-6203,7,PLoS One,eng,Somaiah N,"[""Humans"", ""Phenylurea Compounds"", ""Gastrointestinal Stromal Tumors"", ""Pyridines"", ""Female"", ""United States"", ""Retrospective Studies"", ""Male"", ""Middle Aged"", ""Aged"", ""Gastrointestinal Neoplasms"", ""Antineoplastic Agents"", ""Protein Kinase Inhibitors"", ""Adult""]",e0353357,42536685,pmc-id: PMC13426992;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536685/,Real-world regorafenib use among patients with advanced gastrointestinal stromal tumor in the United States,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Plastic consumption has become pervasive in modern society, with over 300 million metric tonnes produced annually worldwide, contributing significantly to municipal waste. In Bangladesh, where annual per capita plastic use has risen to 22 kg as of 2022, innovative solutions for managing plastic waste are urgently needed. This research introduces a novel approach to the pyrolysis of various plastics (PET, PVC, PP, HDPE) within a temperature range of 300 °C to 550 °C to produce pyrolytic bio-oil and biochar. We established optimal conditions for each plastic type-500 °C for PET, PVC, and HDPE, and 450 °C for PP-resulting in maximized yields of high-quality liquid oils (61.3% for PP and 47.23% for HDPE). Unique to this study, we innovatively adjust the pyrolysis process parameters to enhance the yield and quality of the derived bio-oils, tailored specifically to the types of plastics treated. The liquid products were characterized as predominantly consisting of C6-C16 hydrocarbons, aligning them closely with naphtha, gasoline, and diesel specifications, suitable for use as renewable fuels. Furthermore, our research applies FTIR and GC-MS analyses in a novel way to provide a detailed examination of these bio-oils, revealing significant quantities of paraffinic hydrocarbons in PP and olefins and naphthenes in HDPE, contributing to their potential fuel applications. The solid char byproducts were also comprehensively characterized using SEM and XRD, providing insights into their suitability for various industrial applications. This study not only demonstrates the potential of pyrolysis to transform waste plastics into valuable renewable energy resources but also advances the technological framework for sustainable waste management practices, marking a significant leap forward in the efficiency and application of plastic waste conversion technologies.","[""Journal Article""]","[""Banik U"", ""Huda MN"", ""Harun-Ur-Rashid M"", ""Ahmmed R"", ""Hosen MA"", ""Ismail M""]",10.1371/journal.pone.0354825,Banik U,PloS one,1932-6203,7,PLoS One,eng,Ismail M,"[""Plastics"", ""Biofuels"", ""Pyrolysis"", ""Waste Products"", ""Charcoal"", ""Plant Oils"", ""Polyphenols""]",e0354825,42536684,pmc-id: PMC13426997;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536684/,Sustainable conversion of waste plastics to biofuel: Process insights and fuel characteristics,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"This case study estimates the economic implications of enhancing animal welfare (AW) in Alpine dairy farming, specifically focusing on Simmental cattle in both conventional (CON) and organic (ORG) farms. Given the increasing demand for higher welfare standards from consumers and policymakers, it is important to assess the economic feasibility of implementing these practices. The primary aim of this study is to develop a proof of concept for estimating the costs involved in meeting specific AW standards. Data were collected from 30 dairy farms (15 CON and 15 ORG), and AW scores were evaluated using both resource-based and animal-based indicators (total score of 90 points). Additionally, AW costs were assessed by calculating the cumulative additional costs, offset by potential benefits. Results show ORG farms achieve higher AW scores (73.99) compared to CON farms (70.28) but incur significantly higher production costs (€1.263/kg ECM for ORG vs. €0.977/kg ECM for CON), primarily due to the dilution effect caused by lower milk production on ORG farms. A nonlinear relationship between AW scores and AW costs was also observed, indicating that higher AW scores in initial farm conditions could, in some cases, lead to cost savings, particularly in larger and more efficient farms. The study emphasizes the need for clearly defined AW standards and a corresponding scoring system that reflects both the welfare impacts on animals and the economic feasibility for farmers. Further, we argue that the aggregation of AW scores should not merely categorize welfare on a simple best-to-worst continuum. Rather, it should account for the specific targets and conditions that policymakers and consumers are willing to support financially.","[""Journal Article""]","[""Triatmojo A"", ""von Davier Z"", ""Fichter G"", ""Gauly M"", ""Zanon T""]",10.1371/journal.pone.0343380,Triatmojo A,PloS one,1932-6203,7,PLoS One,eng,Zanon T,"[""Animals"", ""Cattle"", ""Animal Welfare"", ""Dairying"", ""Female"", ""Farms"", ""Milk""]",e0343380,42536683,pmc-id: PMC13426955;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536683/,From theory to practice: A case study on estimating the costs of improving animal welfare on Simmental alpine dairy farms,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"In scientific studies of human-AI interaction dynamics, researchers often need to present participants with opportunities to interact with live large-language models (LLMs). However, technical and practical challenges (from survey platform limitations and logging chat data to manipulating AI behaviors for experimental designs) often inhibit survey-based deployment of AI stimuli. We developed DiSCoKit-an open-source toolkit for deploying live LLM experiences (e.g., ones based on models delivered through Microsoft Azure portal) through JavaScript-enabled survey platforms (e.g., Qualtrics). We describe the toolkit's scientific motivation, architecture, and operation. We also offer an example of toolkit deployment and customization, along with discussing its possibilities and limitations. Altogether, DiSCoKit gives researchers a flexible, secure, scalable solution for deploying naturalistic LLM stimulus experiences through online surveys.","[""Journal Article""]","[""Banks J"", ""Stromer-Galley J"", ""Singh S"", ""Capano C""]",10.1371/journal.pone.0354904,Banks J,PloS one,1932-6203,7,PLoS One,eng,Capano C,"[""Large Language Models"", ""Humans"", ""Surveys and Questionnaires"", ""Software"", ""Artificial Intelligence""]",e0354904,42536680,pmc-id: PMC13426969;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536680/,DiSCoKit: An open-source toolkit for deploying live LLM experiences in survey research,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Accurate prediction of Remaining Useful Life (RUL) is critical for predictive maintenance and minimizing downtime in industrial systems. This paper presents a cross-domain deep learning framework based on a hybrid Convolutional Neural Network-Bidirectional Long Short-Term Memory (CNN-BiLSTM) architecture. Unlike domain-specific models that require handcrafted features, the proposed framework extracts local degradation features through CNN layers and captures long-term dependencies via BiLSTM networks. The model is evaluated on three heterogeneous datasets: construction machinery, continuous casting machines, and lithium-ion batteries. Experimental results show that CNN-BiLSTM consistently outperforms baselines, achieving up to 22% lower RMSE compared to GRU and 30-50% lower RMSE compared to traditional models. On the construction dataset, it achieves an MAE of 48.2 hours and RMSE of 67.1 hours (R2 = 0.88), outperforming GRU by 20%. For the casting dataset, the model attains an MAE of 87.6 tons and RMSE of 113.9 tons (R2 = 0.87), surpassing Random Forest by over 35%. On the battery dataset, CNN-BiLSTM reduces the MAE to 49.6 cycles and RMSE to 72.8 cycles (R2 = 0.89), while also achieving the lowest Timeliness Score (27.5) and PHM08 Score (192.4). Cross-domain experiments are evaluated under two settings: zero-shot transfer, where the model is trained on one source domain and directly tested on a different target domain without using labeled target-domain samples, and fine-tuned transfer, where 20% of labeled target-domain samples are used to update only the fully connected layers while keeping the CNN and BiLSTM layers frozen. The zero-shot results reflect the effect of domain shift, while the fine-tuned results show that lightweight transfer adaptation reduces RMSE by 25-40% across domains. These findings indicate cross-domain adaptability under limited target-domain supervision rather than fully unsupervised cross-domain generalization. These results highlight the feasibility of a unified CNN-BiLSTM framework for scalable, cross-domain RUL estimation and its suitability for real-world prognostic applications.","[""Journal Article""]","[""Saha S"", ""Pervaiz MA"", ""Rahman MS"", ""Hasan R"", ""Rahman A""]",10.1371/journal.pone.0354721,Saha S,PloS one,1932-6203,7,PLoS One,eng,Rahman A,"[""Deep Learning"", ""Long Short Term Memory"", ""Convolutional Neural Networks"", ""Industry"", ""Prediction Algorithms"", ""Predictive Learning Models"", ""Neural Networks, Computer""]",e0354721,42536676,pmc-id: PMC13426938;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536676/,A cross-domain deep learning framework for remaining useful life prediction in industrial applications,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Traditional ABG is susceptible to interference from acute stress and daily fluctuations, making it difficult to accurately assess true acute blood glucose surges. To bridge this gap, we adopted the Stress Hyperglycemia Ratio (SHR), which reflects true acute hyperglycemia by controlling for baseline glucose status. SHR is associated with critical illness and has been shown to associated with in-hospital mortality. However, there is a lack of studies investigating SHR and its prognostic significance in patients with hypertension. This study utilized the Medical Information Mart for Intensive Care IV database (MIMIC-IV) to extract patient information. All subjects were divided into four groups based on the quartiles of SHR. Kaplan-Meier (KM) curves were utilized to assess the relationship between SHR and all-cause mortality at 30, 90, 180, and 365 days. The relationship between the SHR index and prognosis was evaluated using restricted cubic spline (RCS) regression and Cox proportional hazards regression. At the same time, subgroup analyses were performed for gender, age, diabetes, myocardial infarction, congestive heart failure, cerebrovascular disease, and paraplegia. A total of 2,140 participants with essential hypertension were included in the study. The KM curve analysis revealed that elevated levels of the SHR index were significantly associated with an increased risk of all-cause mortality at 30, 90, 180, and 365 days (log-rank P < 0.05). Moreover, multivariate analysis revealed that the SHR index remained significantly associated with mortality risk (P < 0.001). RCS analysis revealed a nonlinear, inverse U-shaped association between SHR and all-cause mortality (P < 0.05). Subgroup analysis showed statistically significant differences in all-cause mortality across gender, age, diabetes, myocardial infarction, heart failure, cerebrovascular disease, and paraplegia. In critically ill patients with hypertension, a high level of SHR index is associated with all-cause mortality. The SHR index may be a potential prognostic indicator for assessing illness severity in ICU patients with hypertension.","[""Journal Article""]","[""Li Z"", ""Wu Y"", ""Jin Q"", ""Lou T"", ""Kang Y"", ""Wang X"", ""Sun N"", ""Ni T"", ""Zhu Z"", ""Wang M"", ""Li Q""]",10.1371/journal.pone.0352162,Li Z,PloS one,1932-6203,7,PLoS One,eng,Li Q,"[""Humans"", ""Female"", ""Prognosis"", ""Critical Illness"", ""Hyperglycemia"", ""Hypertension"", ""Male"", ""Middle Aged"", ""Aged"", ""Databases, Factual"", ""Blood Glucose"", ""Kaplan-Meier Estimate"", ""Proportional Hazards Models"", ""Hospital Mortality""]",e0352162,42536673,pmc-id: PMC13426943;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536673/,The prognostic significance of stress hyperglycemic ratio in critically Ill patients with hypertension: A study using the MIMIC-IV database,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Antimicrobial resistance (AMR) is a major global health threat, and environmental reservoirs such as wastewater (WWTPs) and drinking water treatment plants (DWTPs) may facilitate its persistence and spread despite reducing bacterial loads. We investigated 152 antibiotic-resistant Escherichia coli strains collected across treatment stages from two WWTPs and one DWTP in Barcelona, Spain. Strains were characterized through antimicrobial susceptibility testing, whole-genome sequencing, multilocus sequence typing, biofilm assays, and screening of antimicrobial resistance genes (ARGs), virulence factors (VFGs), biocide and heavy-metal tolerance genes (HMTGs). Although E. coli bacterial loads decreased along treatment, AMR remained highly prevalent: 85.5% of strains were multidrug-resistant (MDR), 5.3% extensively drug-resistant, and 11.2% carbapenemase-producers. Strains harboring integrase genes were 2.4 to 11.8 times more likely to harbor ARGs for sulfonamide, aminoglycoside, phenicol, trimethoprim, mercury and quaternary-ammonium compounds. Strains carrying blaCTX-M genes were 3.0 to 20.3 times more likely to carry VFGs, while high-risk clones were 3.2 to 7.0 times more associated with VFGs. Some MDR and high-risk E. coli clones persisted in reclaimed water, and one MDR strain was detected at the DWTP inlet. These findings highlight environmental AMR reservoirs as a public health concern and support a One Health approach integrating antibiotic stewardship and environmental monitoring.","[""Journal Article""]","[""Ballén V"", ""Cornielle E"", ""Pinar-Méndez A"", ""Vilaró C"", ""Galofré B"", ""Martí S"", ""González-Diaz A"", ""Sanz S"", ""Vilamala A"", ""Soto SM""]",10.1371/journal.pone.0355125,Ballén V,PloS one,1932-6203,7,PLoS One,eng,Soto SM,"[""Escherichia coli"", ""Spain"", ""Wastewater"", ""Drinking Water"", ""Water Purification"", ""Anti-Bacterial Agents"", ""Microbial Sensitivity Tests"", ""Multilocus Sequence Typing"", ""Drug Resistance, Multiple, Bacterial"", ""Drug Resistance, Bacterial"", ""Water Microbiology""]",e0355125,42536672,pmc-id: PMC13426985;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536672/,"Surveillance of Escherichia coli clones and their antimicrobial resistance profiles in wastewater and drinking water treatment plants of Barcelona, Spain",21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Although bar charts are widely used in scientific publications, their rasterized format within Portable Document Format (PDF) files complicates automated data extraction, hindering large-scale evidence synthesis and meta-analysis. To address this, we developed and evaluated an automated pipeline for extracting quantitative data from bar charts embedded in the biomedical literature. The four-stage pipeline comprises (1) image extraction and panel segmentation, (2) optical character recognition (OCR)-based text detection, (3) image disassembly to identify chart components, and (4) data reconstruction using numeric parsing and axis-based interpolation. The system combines edge detection, morphological operations, and convolutional neural network (CNN)-based figure classification using a transfer-learned Inception v3 model. Performance was validated on randomized controlled trials in age-related macular degeneration, with manually annotated values from a semi-automated labeling tool as the reference standard, and agreement was assessed using Bland-Altman analysis. Across 28 bar charts from ten publications, the pipeline correctly recognized 92.9% (95% confidence interval [CI], 77.4-98.0) of figure types, 96.0% (95% CI, 94.2-97.3) of text blocks, and 79.1% (95% CI, 74.7-83.0) of bars. For numerical reconstruction, 81.2% (95% CI, 76.3-85.2) of bar values fell within ±5% of the reference standard, 63.0% (95% CI, 57.3-68.3) within ±2%, and 48.6% (95% CI, 43.0-54.3) within ±1%. Bland-Altman analysis showed a small negative bias of -0.18 (95% CI, -0.34 to -0.02), with 94.9% of differences within the limits of agreement. Most outliers arose from OCR digit misclassification or ambiguous bar boundaries. This proof-of-concept study demonstrates the feasibility of automated data extraction from bar charts using a hybrid approach that combines image-processing heuristics with CNN-based classification. Although currently limited to bar charts and a single clinical domain, the pipeline represents a step toward scalable, end-to-end systems for automated evidence extraction to support meta-analyses across the biomedical literature.","[""Journal Article""]","[""Cardaras A"", ""Kim S"", ""Yuan Y"", ""Livnat I"", ""Yanagihara RT"", ""Saul R"", ""De Oca GM"", ""Zheng K"", ""Browne AW""]",10.1371/journal.pone.0347081,Cardaras A,PloS one,1932-6203,7,PLoS One,eng,Browne AW,"[""Convolutional Neural Networks"", ""Image Processing, Computer-Assisted"", ""Humans"", ""Macular Degeneration"", ""Algorithms"", ""Publications""]",e0347081,42536670,pmc-id: PMC13426920;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536670/,A computer vision-based approach for automatically extracting data from bar chart raster images to facilitate meta-analysis of biomedical literature,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Mentha species are widely cultivated aromatic plants valued for their essential oils and antimicrobial properties. However, despite their agricultural and pharmacological significance, limited information is available on how different Mentha species influence rhizosphere microbial communities and their relationships with soil physicochemical parameters and essential oil composition. In this study, we examined the rhizosphere microbiota of three closely related taxa - Mentha × villosa B10, M. spicata B17, and M. suaveolens J17 - cultivated under uniform field conditions. Rhizosphere and bulk soils were analyzed for physicochemical properties, microbial composition (16S rRNA, ITS sequencing), essential oils (gas chromatography-mass spectrometry), and arbuscular mycorrhizal colonization. Bacterial communities were dominated by the phyla Actinomycetota, Pseudomonadota, Acidobacteriota, Bacillota, and Chloroflexota, while fungal communities were primarily composed of Ascomycota, Mortierellomycota, Basidiomycota, and Rozellomycota. Rhizosphere soils exhibited higher fungal diversity than bulk soils, with Glomeromycota detected exclusively in rhizosphere. Microbial community composition differed significantly among Mentha taxa: M. spicata B17 displayed the lowest bacterial diversity, the most distinct microbial assemblages, and the highest arbuscular mycorrhiza colonization. Soil properties - particularly humus content, phosphorus, potassium, and sodium - were strongly correlated with bacterial diversity, while fungal communities showed weaker associations. Integration of essential oil data revealed genotype-dependent chemical profiles: Mentha × villosa B10 and M. spicata B17 were characterized by high proportions of L-carvone and limonene, whereas M. suaveolens J17 was dominated by cis-piperitone epoxide and piperitenone oxide. Together, these findings demonstrate that even closely related Mentha cultivars can harbor distinct rhizosphere microbiota, associated with both plant chemical traits and soil characteristics. This study highlights the complex interactions between aromatic plants, soil chemistry, and microbial communities, offering novel insights into plant-soil-microbe interactions in medicinal and aromatic crop systems.","[""Journal Article""]","[""Wazzani Y"", ""Tavaszi-Sárosi S"", ""Patonay K"", ""Olasz F"", ""Juhász Á"", ""Posta K""]",10.1371/journal.pone.0354132,Wazzani Y,PloS one,1932-6203,7,PLoS One,eng,Posta K,"[""Mentha"", ""Oils, Volatile"", ""Rhizosphere"", ""Soil Microbiology"", ""Soil"", ""Bacteria"", ""RNA, Ribosomal, 16S"", ""Mycorrhizae"", ""Fungi"", ""Microbiota"", ""Phylogeny""]",e0354132,42536669,pmc-id: PMC13426939;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536669/,Microbial communities in the rhizosphere of three Mentha species: Links to soil properties and essential oil profiles,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"While a growing number of studies have shown positive effects of perturbation-based balance training on balance recovery after tripping, this training has employed specialized equipment that may pose a barrier for wider adoption. To address this, the purpose of this pilot trial was to evaluate the feasibility and preliminary efficacy of a novel, low-resource (i.e., not requiring specialized equipment) version of perturbation-based balance training referred to here as task-specific step training. Thirty community-dwelling older adults (mean (SD) age: 71.8 (4.4) years) were recruited and allocated to either step training (n = 10), traditional treadmill perturbation-based balance training (n = 10), or a control group involving no training (n = 10). Participants were then exposed to two overground laboratory-induced trips while walking on a walkway. Results showed the step training group exhibited an initial recovery step that was 9.0% body height longer (p < 0.001) and 0.25 m/s faster (p = 0.011) than the control group.The step training group also exhibited a 4.8% body height longer recovery step, and a fall rate that was 39% lower (p = 0.037) when compared to the treadmill training group after lab-induced trips. While promising, these results should be interpreted with caution give the modest sample size and a potential bias between groups with respect to safety harness usage during laboratory-induced trips. A future trial with adequate statistical power to better evaluate efficacy and effectiveness of this step training on real-world trip and fall risk appears warranted. The study was registered on clinicaltrials.gov (NCT05734443).","[""Journal Article""]","[""Lee Y"", ""Alexander NB"", ""Franck CT"", ""Castleberry J"", ""Madigan ML""]",10.1371/journal.pone.0354677,Lee Y,PloS one,1932-6203,7,PLoS One,eng,Madigan ML,"[""Humans"", ""Postural Balance"", ""Pilot Projects"", ""Aged"", ""Female"", ""Male"", ""Walking"", ""Feasibility Studies"", ""Accidental Falls"", ""Exercise Therapy"", ""Independent Living""]",e0354677,42536665,pmc-id: PMC13426968;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536665/,A pilot trial investigating feasibility and preliminary efficacy of a task-specific step training regimen to improve balance recovery among community-dwelling older adults,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Social support, which is an essential aspect influencing health, has resulted in the development of several approaches for assessment in cancer patients. The Illness-Specific Social Support Scale Short Version-8 (ISSS-8) effectively evaluates social support among diverse patient demographics; however, its psychometric validity has yet to be established in Asian cultural contexts. The objectives of this study were to translate and culturally adapt the ISSS-8 for the Thai setting and to assess its psychometric properties in patients with hematological malignancies (HMs). This study employed a convenience sampling method to select patients with HMs undergoing hospitalization at three tertiary institutions in Northeastern Thailand. Psychometric testing was conducted following the translation and cross-cultural adaptation of the ISSS-8 into Thai. A total of 350 patients were recruited. Participants were randomly divided into two groups for exploratory factor analysis (EFA) (n = 200) and confirmatory factor analysis (CFA) (n = 150). The EFA of the eight items yielded a loading from a two-factor model comprising Positive Support and Detrimental Interactions, which explained 82.44% of the variance. Cronbach's alpha (0.80) and item-total correlations (rho = 0.33-0.65) demonstrated acceptable reliability of the ISSS-8, while test-retest reliability was high (ICC = 0.924--0.934). The average variance extracted (AVE) demonstrated convergent validity for all ISSS-8 subscales, with AVEs ranging from 0.76 to 0.80. Moreover, the total ISSS-8 scale demonstrated a statistically significant but weak positive correlation with the Stanford Inventory of Cancer Patient Adjustment (r = 0.244, p < 0.001), while the Detrimental Interactions subscale was significantly and weak negatively correlated with it (r = 0.237, p < 0.001). These findings suggest that the ISSS-8 captures distinct psychosocial and illness-specific relational constructs that differ from coping self-efficacy and psychological adjustment measured by the SICPA. The ISSS-8 is a short, accurate, and valid instrument for measuring social support in Thai patients with HMs. As a result, healthcare professionals can use the ISSS-8 to assess social support in both research and clinical settings. The findings emphasize the necessity of integrating social support evaluation into cancer management and family-centered care, thereby supporting comprehensive and adaptive healthcare delivery in Thailand.","[""Journal Article"", ""Multicenter Study""]","[""Summart U"", ""Sangruangake M"", ""Wamaloon C"", ""Moungmultri A"", ""A'la MZ""]",10.1371/journal.pone.0341756,Summart U,PloS one,1932-6203,7,PLoS One,eng,A'la MZ,"[""Humans"", ""Thailand"", ""Female"", ""Psychometrics"", ""Social Support"", ""Male"", ""Middle Aged"", ""Hematologic Neoplasms"", ""Adult"", ""Surveys and Questionnaires"", ""Aged"", ""Reproducibility of Results"", ""Factor Analysis, Statistical""]",e0341756,42536662,pmc-id: PMC13426926;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536662/,Psychometric properties of the Thai version of the Illness-Specific Social Support Scale Short Version-8 (ISSS-8) among hematological malignancy patients in the Northeastern region of Thailand: A multicenter study,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Animal husbandry is widely practiced on the household scale in communities in low- and middle-income countries (LMICs) and, while having economic and health benefits, exposes household members to risk of zoonotic infections to an extent that is unclear. While demand for georeferenced information on infectious disease risk factors and drivers is growing, spatial variation in livestock ownership remains poorly characterized at high resolution. This study aimed to use geostatistical methods to model and map the prevalence of livestock husbandry in LMICs for three major animal taxa: poultry, swine, and ruminants. Microdata relating to ownership of livestock animal species were sourced from various population-based survey programs which together cover the majority of LMICs and categorized. These were georeferenced and spatially matched with a panel of time-fixed environmental and demographic spatial covariates, INLA models were fitted to the resulting database, and probabilities for ownership of each livestock taxon predicted based on the model parameter estimates. The results indicated widespread poultry ownership across rural Central America, the Amazon basin, tropical Africa and river basins and forests of East Asia. Swine husbandry is the least widely practiced among the three livestock taxa and concentrated in an undulating belt of higher prevalence extending from central China, through southeast Asia to Northeastern India, though such predictions in data-sparse regions (particularly Muslim-majority areas) represent regional covariate patterns rather than fine-scale measurements. To address non-stationarity in swine spatial structure, region-specific spatial kernels were implemented. Rearing of ruminant livestock appears widespread across subequatorial Africa, Central Asia, the Gobi Desert, the Himalayas, Mongolia and northern India. The models perform impressively by most standard evaluation metrics, and the patterns in their predictions align with external evidence. The distribution of this important risk factor for infectious disease transmission can be modeled using publicly available data sources to generate plausible and potentially actionable predictions over wide geographic areas and identify regions of high exposure to animal disease reservoirs. The resulting predicted prevalence estimates are made available as supplementary files in GIS-compatible format.","[""Journal Article""]","[""Colston JM"", ""Fang B"", ""Ahmedjonova V"", ""Hossain N"", ""Kansara P"", ""Schiaffino F"", ""Nong MK"", ""Revathi AA"", ""Zaitchik B"", ""Chernyavskiy P"", ""Lakshmi V"", ""Kosek MN""]",10.1371/journal.pone.0355207,Colston JM,PloS one,1932-6203,7,PLoS One,eng,Kosek MN,"[""Animals"", ""Livestock"", ""Animal Husbandry"", ""Prevalence"", ""Developing Countries"", ""Ownership"", ""Family Characteristics"", ""Humans"", ""Swine"", ""Zoonoses""]",e0355207,42536659,pmc-id: PMC13426965;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536659/,Mapping the prevalence of household-scale livestock ownership by animal taxon in low- and middle-income countries: A prediction model using template model builder,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Podocyte injury is a central driver of progressive glomerular diseases, yet the temporal organization of podocyte-intrinsic responses remains incompletely defined. In this study, we performed an integrated re-analysis of two publicly available mouse transcriptomic datasets (GSE108629 and GSE151869) to identify conserved molecular responses to LMB2-induced podocyte injury across comparable post-injury time points. Differential expression analysis was conducted independently at Day 4 and Day 7 in each dataset, followed by cross-dataset integration at each time point by identifying shared differentially expressed genes (DEGs) with consistent directionality. The resulting Day 4 and Day 7 shared gene sets were subsequently combined to define a final pooled shared DEG set. Functional enrichment, network analysis, upstream regulator prediction, and gene set enrichment analysis (GSEA) were used to characterize conserved biological processes and regulatory features. We identified 1,418 and 1,401 shared DEGs at Day 4 and Day 7, respectively, with 725 genes defining the final pooled shared DEGs set. At Day 4, the transcriptional response was characterized by inflammatory signaling and adaptive stress-related pathways, including endoplasmic reticulum stress. By Day 7, this response expanded to include extracellular matrix remodeling, focal adhesion reorganization, sustained inflammatory signaling, and downregulation of autophagy-lysosome pathways, together with disruption of ER-to-Golgi trafficking. Network analysis highlighted RELA-centered regulatory modules alongside epigenetic- and kinase-associated regulators. Collectively, these findings support a conserved, cross-dataset biphasic transcriptional response to podocyte injury, characterized by an early adaptive inflammatory phase followed by a later maladaptive state involving extracellular remodeling and impaired proteostasis. This framework provides a reproducible, temporally organized injury signature and is consistent with stage-specific pathways as potential targets for future mechanistic and therapeutic studies.","[""Journal Article""]","[""Esmaeili MR"", ""Nejati M"", ""Roqanian S"", ""Moghadasali R"", ""Taleahmad S""]",10.1371/journal.pone.0352764,Esmaeili MR,PloS one,1932-6203,7,PLoS One,eng,Taleahmad S,"[""Podocytes"", ""Animals"", ""Mice"", ""Gene Expression Profiling"", ""Inflammation"", ""Transcriptome"", ""Stress, Physiological"", ""Transcription Factors"", ""Signal Transduction"", ""Gene Regulatory Networks"", ""Endoplasmic Reticulum Stress""]",e0352764,42536655,pmc-id: PMC13426963;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536655/,Integrated transcriptomic analysis of LMB2-induced podocyte injury identifies conserved inflammatory and adaptive stress responses,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"The aging Canadian population has led to an increase in Canada's use of home and community care services. In this context, the healthcare system relies heavily on personal support workers who work in various healthcare settings. A significant proportion of these workers are immigrants, and many live in linguistic minorities. Despite their pivotal role, the experiences and working conditions of these personal support workers are underrepresented in the scientific literature, specifically in intersectional analyses. This scoping review aims to examine the work experiences, health conditions, and well-being of immigrant personal support workers in Canada who work in a minority language setting. Studies addressing the work experiences, health conditions, and well-being of immigrant personal support workers in Canada who work in a minority language setting, and those published in English or French. There will have no restrictions on publication date. This review will follow the JBI recommendations for scoping reviews and incorporate the PRISMA-ScR checklist. We will develop an adapted search strategy for five relevant databases (Medline [Ovide], Web of Science, Embase, CINAHL, and Google Scholar). Two independent reviewers will select full-text articles based on pre-established inclusion criteria and extracted relevant data. The results will be presented in accordance with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews) guidelines. This scoping review contributes to expanding knowledge about the professional, health, and social realities of immigrant PSWs in Canada's linguistic minority communities.","[""Journal Article""]","[""Philibert L"", ""Plaisimond J"", ""Lapierre J"", ""Kaboré SS"", ""Osomba AN"", ""Mariano L"", ""Bergeron F"", ""Kiki GM"", ""Ntanda GM""]",10.1371/journal.pone.0354960,Philibert L,PloS one,1932-6203,7,PLoS One,eng,Ntanda GM,"[""Humans"", ""Canada"", ""Emigrants and Immigrants"", ""Scoping Reviews as Topic"", ""Language"", ""Minority Groups""]",e0354960,42536654,pmc-id: PMC13426990;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536654/,"Analysis of the work, health and well-being experience of immigrant personal support workers in minority language contexts in Canada: Scoping review protocol",21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Pharmacists are expanding their participation in veterinary healthcare teams and assuming roles beyond traditional dispensing duties. However, the scope of these collaborative practices and the degree of mutual recognition vary substantially across regions. This scoping review aimed to organize the existing literature on collaboration between veterinarians and pharmacists, clarifying current roles, practical applications, and professional perceptions within the veterinary field. A scoping review was conducted to examine the roles, practices, and perceptions associated with veterinarian-pharmacist collaboration in veterinary medicine and related fields. Two researchers independently searched PubMed, Web of Science, the Cochrane Library, and Ichushi-Web, and additionally screened Google Scholar to identify gray literature (from database inception to August 2025, in English or Japanese). Records were independently screened at the title/abstract and full-text levels using predefined eligibility criteria, and relevant studies were identified. The search yielded 239 records, of which 16 studies published between 2007 and 2024 were included. Studies were conducted primarily in the United States (n = 7), New Zealand (n = 3), and Japan (n = 3); one study collected data from both Japan and Taiwan. Most studies employed cross-sectional survey designs. Pharmacist roles most frequently involved compounding and dispensing for animal patients (62.5%), followed by drug information (DI) and consultation (37.5%), inventory and supply management (25.0%), client education (18.8%), and safety and exposure control (12.5%). This scoping review demonstrates that veterinarian-pharmacist collaboration is described within a limited and regionally variable evidence base, with pharmacists most often contributing through compounding/dispensing and drug information support. Sustained and scalable implementation will require improved mutual understanding of professional roles, strengthened veterinary-specific education for pharmacists, and more robust empirical research to inform collaborative practice models.","[""Scoping Review"", ""Journal Article""]","[""Kambayashi D"", ""Suzuki S"", ""Hirohara M""]",10.1371/journal.pone.0355233,Kambayashi D,PloS one,1932-6203,7,PLoS One,eng,Hirohara M,"[""Pharmacists"", ""Veterinarians"", ""Veterinary Medicine"", ""Humans"", ""Cooperative Behavior"", ""Animals"", ""Professional Role"", ""Japan""]",e0355233,42536652,pmc-id: PMC13426993;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536652/,"Veterinarian-pharmacist collaboration in veterinary medicine: Roles, practices, and perceptions-A scoping review",21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Pododermatitis (bumblefoot) is a chronic, debilitating disease of the plantar surface of the foot that affects birds of prey kept in captivity worldwide. Although bacterial pathogens, especially Staphylococcus aureus, are most commonly considered as causative agents, the contribution of opportunistic yeasts to chronic, non-healing footpad lesions remains poorly characterized. Keratinophilic yeasts may sustain the disease process by degrading keratin in superficial tissues, impairing wound healing and, owing to their thermotolerance and minimal nutritional requirements, persisting in the environment of the bird's enclosure. In this study, three captive steppe eagles (Aquila nipalensis) from a single aviary in Kazakhstan, all presenting with chronic pododermatitis unresponsive to antibacterial treatment, were investigated by integrated mycological, biochemical and molecular approaches. The yeast isolates were recovered from the deep footpad lesions and identified to species level by sequencing of the ITS1-5.8S-ITS2 rDNA region. All these isolates were assigned to Candida metapsilosis, and phylogenetic analysis confirmed their close clustering with reference C. metapsilosis sequences. Phenotypic characterization showed that all isolates were thermotolerant (growth at 8-37 °C), expressed strong urease and keratinolytic activity (the latter confirmed in vitro by the hair perforation test), high saccharolytic activity and selective, weak proteolytic activity. Disk diffusion screening showed susceptibility to azoles (ketoconazole, clotrimazole, fluconazole) and reduced susceptibility to polyenes (nystatin, amphotericin B). To our knowledge, this is the first report of C. metapsilosis isolated from chronic pododermatitis lesions in captive steppe eagles. Combined with the documented in vitro virulence-associated traits and the resolution of the lesions following targeted antifungal therapy, our findings support a contributory etiological role of C. metapsilosis as an opportunistic pathogen in raptor pododermatitis in immunocompromised birds maintained under suboptimal husbandry. Mycological work-up, including molecular identification, is therefore warranted in cases of chronic, non-resolving pododermatitis in captive birds of prey.","[""Journal Article""]","[""Kukhar E"", ""Bailina G"", ""Nessipbayeva A"", ""Sattarova R"", ""Turkeyev M""]",10.1371/journal.pone.0353552,Kukhar E,PloS one,1932-6203,7,PLoS One,eng,Turkeyev M,"[""Animals"", ""Candida"", ""Kazakhstan"", ""Phylogeny"", ""Antifungal Agents"", ""Candidiasis"", ""Bird Diseases"", ""Foot Diseases"", ""Dermatitis"", ""Chronic Disease""]",e0353552,42536651,pmc-id: PMC13426984;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536651/,Isolation and characterization of Candida metapsilosis from foci of chronic pododermatitis in captive steppe eagles in Kazakhstan,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Dengue virus (DENV) represents a growing global health challenge with billions of people at risk. Severe Dengue (SD), a complication of DENV infection that involves generalized hemorrhage, is driven, at least in part, by endothelial dysfunction. Endothelial dysfunction refers to increased permeability due to inflammation, mechanical injury and/or modification of the genetic program of endothelial cells. Previous work showed that exposure of endothelial cells to conditioned media from DENV-infected cells (CMDV) increased permeability and cellular stiffness, repressed endothelial markers and induced mesenchymal genes. However, the generality, extent, mechanism and ultimate impact of these events in the onset of SD remain elusive. Here, we integrate analysis from in vitro treatment of endothelial cells with media containing UV-inactivated DENV with computational modeling to investigate the key features of CMDV-induced endothelial alterations and their potential impact on endothelial dysfunction. We found that CMDV increased SNA1 and CDH2 expression, while suppressing endothelial genes OCLN and CDH5. Global transcriptomics analysis revealed that CMDV triggered a transient pro-inflammatory response, followed by induction of selected tissue repair genes and matrix remodeling. A non-directed asynchronous network model (NDAM-CMDV) identified IL6 and FN1 as central nodes of DENV-induced endothelial trans-differentiation, providing new molecular insights that predict the evolution of the disease and identify potential therapeutic targets.","[""Journal Article""]","[""Alfaro-García JP"", ""Ramírez-Mejía JM"", ""Rojas-Estevez P"", ""Álvarez-Díaz DA"", ""Fernández GJ"", ""Orozco-Castaño CA"", ""Rodríguez-Rey BA"", ""Gallego-Gómez JC"", ""Vicente-Manzanares M""]",10.1371/journal.pone.0354877,Alfaro-García JP,PloS one,1932-6203,7,PLoS One,eng,Vicente-Manzanares M,"[""Dengue Virus"", ""Humans"", ""Endothelial Cells"", ""Computer Simulation"", ""Culture Media, Conditioned"", ""Gene Expression Profiling"", ""Human Umbilical Vein Endothelial Cells""]",e0354877,42536649,pmc-id: PMC13426972;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536649/,Molecular analysis and computational modeling reveal temporally separable responses triggered by DENV-induced soluble factors in endothelial cells,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"The coupled function of physiology and behavior is crucial for generating survival responses. Generally, the cardiovascular system undergoes rapid adjustments during scape behavior to increase oxygen delivery to muscle tissues. In contrast, passive antipredator responses such as retraction in snails may impose mechanical constraints on the circulatory system. Here, we evaluated the cardiovascular response underlying the scape response (through induced retraction) and the physical activity in the invasive land snail Cornu aspersum. We quantified heart rate and heart rate variability in adult snails using laser optocardiography under the two conditions. We found that heart rate increased from retracted to the moving state and was accompanied by changes in heart rate variability and reduction of cardiac irregularities. Also, we found that locomotion intensity and body size did not influence these cardiac parameters. Our results suggest that metabolic demands, neural regulation and mechanical configuration collectively alter heart rate and heart rate variability. Thus, cardiovascular function is strongly dependent on behaviorally induced mechanical shifts in the circulatory system and on a ""fight-or-flight""-like response.","[""Journal Article""]","[""Pardo-Sarmiento EA"", ""Hernández JP"", ""Buitrago-Ricaurte N"", ""Riveros AJ""]",10.1371/journal.pone.0354962,Pardo-Sarmiento EA,PloS one,1932-6203,7,PLoS One,eng,Riveros AJ,"[""Animals"", ""Locomotion"", ""Heart Rate"", ""Snails"", ""Introduced Species""]",e0354962,42536648,pmc-id: PMC13426994;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536648/,"Cardiovascular adjustments during experimentally induced retraction and locomotion in the invasive terrestrial snail Cornu aspersum (Müller, 1774)",21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Approximately 39.9 million people are living with HIV worldwide, most in sub-Saharan Africa. Effective antiretroviral therapy has shifted attention to metabolic comorbidities, and emerging evidence links integrase inhibitors such as dolutegravir to elevated serum uric acid, yet the global burden of hyperuricemia and gout in this population is unquantified. This protocol describes a systematic review and meta-analysis of observational studies (cross-sectional, cohort, and case-control) published from inception to May 2026. We will search PubMed/MEDLINE, EMBASE, Web of Science, and CINAHL. Studies involving adults (≥18 years) living with HIV that report the prevalence or incidence of hyperuricemia or gout will be included. Two independent reviewers will screen studies, extract data, and assess risk of bias using the Joanna Briggs Institute Prevalence Critical Appraisal Checklist and the Newcastle-Ottawa Scale (NOS). Primary outcomes are the pooled prevalence of hyperuricemia and gout in PLHIV. Secondary outcomes include risk factors associated with urate dysregulation (ART regimen, Cluster of Differentiation 4 [CD4] count, viral load, metabolic comorbidities, and HIV duration), and gout as an immune reconstitution inflammatory syndrome (IRIS) manifestation. A random-effects meta-analysis using the DerSimonian-Laird method with Freeman-Tukey double-arcsine transformation for prevalence data will be performed in R software. Heterogeneity will be assessed using the I2 statistic and Cochran's Q test. Subgroup analyses will explore variation by ART class (pre-ART, PI, NNRTI, INSTI/dolutegravir era), geographic region, CD4 category, and study quality. CRD420261360734.","[""Journal Article""]","[""Pitua I"", ""Otto KA"", ""Lwembawo KD"", ""Nantalaga KC"", ""Nampiinga MG"", ""Ndyomugabe M"", ""Okema JN""]",10.1371/journal.pone.0355217,Pitua I,PloS one,1932-6203,7,PLoS One,eng,Okema JN,"[""Humans"", ""Systematic Reviews as Topic"", ""Hyperuricemia"", ""HIV Infections"", ""Gout"", ""Meta-Analysis as Topic"", ""Uric Acid"", ""Prevalence"", ""Risk Factors""]",e0355217,42536647,pmc-id: PMC13426922;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536647/,Urate dysregulation (hyperuricemia and gout) among people living with HIV: A protocol for a systematic review and meta-analysis,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Mexico has experienced escalating dengue transmission driven by the co‑circulation of four antigenically distinct serotypes (DENV‑1 through DENV‑4). Multi‑serotype transmission is epidemiologically relevant, yet its spatiotemporal patterns at sub‑national resolution remain poorly characterized. We analyzed 103,426 PCR‑confirmed, serotyped dengue cases across 1,547 of 2,471 Mexican municipalities from January 2020 to December 2025. Kulldorff's space‑time scan statistic under a discrete Poisson model was applied independently to each serotype and to all serotypes combined. Co‑circulation was defined as the spatiotemporal overlap of significant clusters from at least two serotypes within the same municipality for ≥ 1 epidemiological week. We identified 159 statistically significant clusters across all serotypes combined. DENV‑3 was dominant (64.4% of cases; annual incidence 59.9/100,000), consistent with the reemergence of a long‑absent serotype. The 2024-2025 season produced a nationally synchronized epidemic across geographically distant regions. Co‑circulation of at least two serotypes occurred in 1,545 municipalities; 217 experienced simultaneous clustering of all four serotypes. Active co‑circulation was present in 275 of 311 study weeks. Mean pairwise temporal overlap ranged from 8.0 to 12.0 weeks, with maximum overlaps of 29-30 weeks. Four‑serotype co‑circulation was documented at municipal resolution, concentrated in the Gulf coast, the Yucatán Peninsula, and northeastern Mexico. The 217 municipalities with simultaneous clustering of all four serotypes may represent areas of epidemiological interest for further investigation. This municipality‑level spatiotemporal framework offers operationally relevant resolution for tracking multi‑serotype activity and supporting serotype‑aware dengue monitoring at sub‑national scale.","[""Journal Article""]","[""Mendoza-Cano O"", ""Trujillo X"", ""Ríos-Silva M"", ""Bricio-Barrios JA"", ""Lugo-Radillo A"", ""Tapia-Vargas R"", ""Venegas-Ramírez J"", ""Ríos-Bracamontes EF"", ""Cuevas-Arellano HB"", ""Cárdenas Y"", ""Aquino-Santos R"", ""Jiménez-Vieyra IA"", ""Uribe-Ramos JM"", ""Benites-Godínez V"", ""Martínez-Díaz TE"", ""López-Rojas M"", ""García-Solórzano A"", ""Murillo-Zamora E""]",10.1371/journal.pone.0354885,Mendoza-Cano O,PloS one,1932-6203,7,PLoS One,eng,Murillo-Zamora E,"[""Mexico"", ""Dengue"", ""Dengue Virus"", ""Humans"", ""Serogroup"", ""Spatio-Temporal Analysis"", ""Serotyping""]",e0354885,42536646,pmc-id: PMC13426947;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536646/,"Spatiotemporal co-circulation of four dengue serotypes across Mexico, 2020-2025: A space-time scan analysis",21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Bacterial vaginosis (BV) is highly prevalent in women of African origin and has been associated with adverse birth outcomes (ABO), particularly preterm birth (PTB). However, evidence from sub-Saharan Africa remains limited, and while a previous study conducted in this area examined the prevalence of BV, its impact on pregnancy outcomes was not assessed. This study assessed the prevalence and risk factors of BV in early pregnancy and examined its association with ABO in the middle belt of Ghana. This analysis was nested within a prospective cohort of pregnant women in the Kintampo North Municipality and Kintampo South District. Pregnant women <20 weeks' gestational age were screened, consented, enrolled and followed through delivery until one year after birth. At enrolment, sociodemographic, behavioural, and obstetric data were collected, along with biological samples, including vaginal swabs for Gram staining and Nugent scoring. BV status was categorized as BV-negative (0-6) or BV-positive (7-10) and ABO included PTB (<37 weeks), low birthweight (LBW < 2.5 kg), and foetal loss. Data were double-entered in REDCap and analysed in R. Associations between BV and ABO were assessed using chi-square tests, and logistic regression was used to identify risk factors for BV. Of 1,180 pregnant women enrolled, 355 (30.1%) were BV-positive. PTB (9.9% vs. 8.7%; p = 0.50), LBW (13.8% vs. 12.0%; p = 0.39), and foetal loss (4.5% vs. 2.8%; p = 0.14) were all higher among BV-positive women, but none reached statistical significance. Younger age and unmarried status were associated with BV. Unmarried women (AOR 1.63; 95% CI: 1.20-2.22) and those reporting one sexual encounter per week (AOR 1.55; 95% CI: 1.01-2.37) had increased odds of BV. BV is highly prevalent in early pregnancy in this Ghanaian cohort, particularly among younger and unmarried women, but was not significantly associated with ABO. Targeted screening among high-risk groups is necessary, and future molecular approaches may better characterise BV subtypes linked to ABO in African settings.","[""Journal Article""]","[""Konadu DG"", ""Owusu-Ofori AK"", ""Dosoo DK"", ""Yidana Z"", ""Ngo GM"", ""Nfum PN"", ""Tetteh RJ"", ""Adu-Gyasi D"", ""Poku-Asante K""]",10.1371/journal.pone.0354974,Konadu DG,PloS one,1932-6203,7,PLoS One,eng,Poku-Asante K,"[""Humans"", ""Female"", ""Pregnancy"", ""Vaginosis, Bacterial"", ""Ghana"", ""Prospective Studies"", ""Adult"", ""Pregnancy Outcome"", ""Premature Birth"", ""Risk Factors"", ""Pregnancy Complications, Infectious"", ""Young Adult"", ""Prevalence"", ""Infant, Newborn"", ""Infant, Low Birth Weight""]",e0354974,42536645,pmc-id: PMC13426914;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536645/,Bacterial vaginosis in early pregnancy and birth outcomes: Evidence from a prospective cohort in the middle belt of Ghana,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Hematological malignancies including leukemia, lymphoma, and myelodysplastic syndromes, are characterized by clonal proliferation of abnormal blood or bone marrow cells. Early and accurate detection is essential for improving treatment outcomes and survival. Automated hematology analyzers generate abnormal flags that may indicate underlying hematologic malignancies; however, their overall diagnostic accuracy has not been comprehensively evaluated. This systematic review and meta-analysis aimed to assess the diagnostic performance of abnormal flags for detecting hematological malignancies. A systematic search of PubMed, PubMed Central, Scopus, ScienceDirect, and Google Scholar was conducted to identify relevant diagnostic accuracy studies. Methodological quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2(QUADAS-2) tool. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated using a bivariate random-effects model in Stata version 17.0. Heterogeneity was assessed using the I2 statistic, and subgroup and meta-regression analyses were performed to explore potential sources of variability. Twenty-eight studies met the inclusion criteria. The pooled sensitivity and specificity of abnormal hematology analyzer flags for detecting hematological malignancies were 91% (95% CI: 87%-94%) and 89% (95% CI: 84%-92%), respectively, indicating good diagnostic accuracy. Significant heterogeneity was observed across studies (I2 > 50%). Meta-regression analysis identified the type of abnormal flag as a significant source of heterogeneity in sensitivity (p < 0.001), whereas both the type of abnormal flag and the analyzer platform significantly influenced specificity. Automated hematology analyzer abnormal flags showed promising diagnostic performance. However, substantial heterogeneity and differences in analyzer platforms, flag types, and reference standards reduce the certainty and generalizability of pooled estimates. Nevertheless, these findings support the use of abnormal hematology analyzer flags as an effective initial screening tool in routine laboratory practice, particularly in resource-limited settings where rapid and cost-effective diagnostic support is essential. Systematic review registration PROSPERO (CRD42024601908).","[""Journal Article"", ""Systematic Review"", ""Meta-Analysis""]","[""Mulatie Z"", ""Eshetu B"", ""Habtamu A"", ""Desale S"", ""Sebsibe S"", ""Erkihun Y"", ""Kassa Y"", ""Gessese T"", ""Alebachew M"", ""Shimeles M"", ""Feyisa MS"", ""Berta DM""]",10.1371/journal.pone.0354619,Mulatie Z,PloS one,1932-6203,7,PLoS One,eng,Berta DM,"[""Humans"", ""Hematologic Neoplasms"", ""Sensitivity and Specificity"", ""Hematology""]",e0354619,42536644,pmc-id: PMC13426980;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536644/,Diagnostic accuracy of automated hematology analyzer abnormal flags for detecting hematological malignancies: A systematic review and meta-analysis,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Decentralization of antiretroviral therapy (ART) brought treatment to millions of people in Sub-Saharan Africa. However, the implications of such decentralization are still not fully understood. The study included 60 semi-structured interviews with community leaders, healthcare providers, patients, and community members served by a rural mission hospital in Zimbabwe, conducted in January-March 2019. Interviews were transcribed and translated into English and coded using an iterative codebook. Coded extracts were grouped into themes and categories, systematically using QDA Miner qualitative analysis software. The study reveals that treatment-for-all policies and decentralization of ART have indeed improved access to care (as experienced by the study participants). However, the study shows that these policies also had unintended negative consequences. Stigma and complex social relations significantly affect the practices and experiences of ART outreach care, for both patients and healthcare providers, and may hamper attempts to reduce stigma as well as increase physical and social barriers to accessing ART. The study's results highlight the need to understand the consequences of the decentralization of HIV care, as well as the barriers and facilitators associated with ART outreach in order to improve quality of care and provide true accessibility to HIV care for all.","[""Journal Article""]","[""Gluskinos N"", ""Maposhere C"", ""Kufakurinani U"", ""Hove G"", ""McCarty K"", ""Katzenstein D"", ""Rosenthal A""]",10.1371/journal.pone.0354747,Gluskinos N,PloS one,1932-6203,7,PLoS One,eng,Rosenthal A,"[""Zimbabwe"", ""Humans"", ""HIV Infections"", ""Health Services Accessibility"", ""Female"", ""Male"", ""Social Stigma"", ""Health Personnel"", ""Adult""]",e0354747,42536643,pmc-id: PMC13426937;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536643/,Mixed feelings: Unintended consequences of HIV outreach care in Zimbabwe,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Fetal speckle tracking echocardiography is an ultrasound-based technique used to assess myocardial velocity and deformation of the fetal heart. Despite its potential, the method has not yet been integrated into routine pregnancy care, partly due to concerns about inconsistent reproducibility. This study aimed to evaluate the intra- and inter-observer reproducibility of global longitudinal strain measurements derived from a fixed fetal cardiac cycle, using speckle tracking echocardiography. Healthy women with singleton pregnancies were enrolled during the second trimester. From enrolment until delivery, four-chamber view clips of the fetal heart were acquired every four weeks. For intra-observer reproducibility, a single observer analyzed the same heart cycle in one DICOM clip twice for global longitudinal strain in the left and right ventricles, with a minimum interval of two weeks between assessments in a blinded manner. For inter-observer reproducibility, two independent observers analyzed the same cardiac cycle within one DICOM clip. A total of 124 women were included, yielding 632 ultrasound clips. Intra-observer reproducibility was poor to moderate for global longitudinal strain for the right and left ventricles. Inter-observer reproducibility demonstrated moderate to good reproducibility for global longitudinal strain in both ventricles. The reproducibility was generally higher in the left ventricle than in the right, and the highest reproducibility was observed before 32 weeks of gestation. In conclusion, speckle tracking echocardiography during pregnancy showed variable reproducibility of strain analysis when performed on a fixed cardiac cycle, with more consistent results in the left ventricle. These findings support the potential utility of fetal speckle tracking echocardiography, while highlighting the need for further refinement of reproducibility before clinical implementation.","[""Journal Article""]","[""Meireson E"", ""de Vet C"", ""van Laar JOEH"", ""Mussche P"", ""Roelens K"", ""van Oostrum NHM""]",10.1371/journal.pone.0354514,Meireson E,PloS one,1932-6203,7,PLoS One,eng,van Oostrum NHM,"[""Humans"", ""Female"", ""Pregnancy"", ""Global Longitudinal Strain"", ""Echocardiography"", ""Reproducibility of Results"", ""Ultrasonography, Prenatal"", ""Fetal Heart"", ""Adult"", ""Heart Ventricles"", ""Observer Variation""]",e0354514,42536642,pmc-id: PMC13426953;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536642/,Reproducibility of fetal global longitudinal strain measured with speckle tracking echocardiography using a fixed cardiac cycle,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Seepage-erosion-induced water inrush in karst cavities is a typical form of water-inrush disaster in karst tunnels. It is governed not only by the spatial distribution of karst cavities and hydraulic recharge conditions, but also by the particle-size gradation and composition of the cavity fill. During seepage erosion, fill particles are progressively transported by flowing water, which may trigger a sudden water-inrush catastrophe. To reveal the catastrophe mechanism and establish early-warning indicators, this study employs the Smoothed Particle Hydrodynamics (SPH) method to simulate the evolution of seepage-erosion-induced water inrush under different particle-size gradations, cavity confining stresses, and seepage velocities. The inflection point of the cumulative particle loss rate is used as an indicator of catastrophic transition. The relationships among particle-size gradation, confining stress, seepage velocity, and particle loss rate at the transition point are then analyzed to determine early-warning thresholds. The results show that fill-particle loss is positively correlated with both seepage velocity and confining stress. When the content of fine particles, such as rock cuttings and fine sand, exceeds 60%, the inflection point corresponds to a seepage velocity of 1.6 m/s and a confining stress of 2.6 MPa, with an early-warning particle-loss range of 8%-15%. When the content of coarse particles, such as coarse sand and gravel, exceeds 40%, the inflection point corresponds to a seepage velocity of 3.0 m/s and a confining stress of 4.5 MPa, with an early-warning particle-loss threshold of approximately 45%.","[""Journal Article""]","[""Yuan J"", ""Zhang P"", ""Qian X"", ""Zhang L"", ""Liu Y""]",10.1371/journal.pone.0354695,Yuan J,PloS one,1932-6203,7,PLoS One,eng,Liu Y,"[""Soil Erosion"", ""Particle Size"", ""Hydrodynamics"", ""Disasters"", ""Water Movements"", ""Models, Theoretical"", ""Water""]",e0354695,42536641,pmc-id: PMC13426919;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536641/,Catastrophe mechanism and early warning indicators of seepage erosion-induced water inrush in karst cavities,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"High temperature is one of the major environmental stressors that severely affects plant growth. Paris polyphylla var. yunnanensis, a traditional Chinese herbal medicine, is sensitive to high temperature. However, the underlying mechanisms of its response to high temperature remain unclear. In this study, we investigated the physiological and proteomic change of P. polyphylla var. yunnanensis under different treatments (25°C, 30°C, 35°C, 40°C). Our results showed that high temperature directly impaired photosynthesis and disrupted metabolism, evidenced by reduced chlorophyll and photosynthetic rate, as well as accumulated proline and increased conductivity. A total of 893 differentially expressed proteins (DEPs) were identified, with significant changes in the expression levels of enzymes associated with protein processing and synthesis. Additionally, the expression levels of key proteins involved in the circadian pathway and the glutathione pathway were also notably upregulated. Dynamic changes in the endocytosis and autophagy-related proteins ATG3 and ATG8C were also observed, suggesting that these processes may play a significant protective role under high-temperature stress. Overall, this study provides an important starting point for improving the heat tolerance of P.polyphylla var. yunnanensis through genetic engineering.","[""Journal Article""]","[""Lin L"", ""Zhang X"", ""Lai R"", ""Lin J"", ""Zhong Z"", ""Li H""]",10.1371/journal.pone.0354925,Lin L,PloS one,1932-6203,7,PLoS One,eng,Li H,"[""Autophagy"", ""Photosynthesis"", ""Heat-Shock Response"", ""Plant Proteins"", ""Melanthiaceae"", ""Gene Expression Regulation, Plant"", ""Hot Temperature"", ""Proteomics""]",e0354925,42536640,pmc-id: PMC13426936;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536640/,Heat stress-induced photosynthetic impairment and autophagy modulation in Paris polyphylla var. yunnanensis: A physiological and molecular Perspective,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"This study investigates how the spatial structure of Metroidvania game worlds relates to the layout of key functional nodes. Using Hollow Knight, Prince of Persia: The Lost Crown, and Blasphemous 2 as case studies, the maps were transformed into graph structures based on spatial data compiled from gameplay observation, in-game maps, community maps, and verification through gameplay videos. On the basis of this graph representation, the study adapts the Nearest Neighbor Index by replacing Euclidean distance with network shortest-path distance in order to evaluate the distribution patterns of save points, teleport points, and boss points. It further employs multi-source k-hop reachability analysis to measure service coverage and redundancy. Finally, closeness centrality and betweenness centrality are calculated on the full network, and Spearman rank correlation is used to test the association between functional areas and centrality. The results reveal clear differences in the structural roles of functional nodes across the three games. In Hollow Knight and The Lost Crown, save points are relatively dispersed, weakly coupled with centrality, and function as a distributed safety net. In Blasphemous 2, save points exhibit higher small-radius coverage and redundancy and are more strongly aligned with central positions, indicating a hub-like stronghold structure. Teleport systems likewise reflect different design strategies, ranging from exploration-oriented sparse layouts to later-stage mobility optimization. Boss points in all three games generally remain structurally isolated, showing low overlap and weak centrality association. These findings suggest that differences in the placement of save points, teleport points, and boss points reflect distinct structural design strategies, and that network analysis can provide a quantitative basis for evaluating and optimizing such layouts in level design.","[""Journal Article""]","[""Bao GG"", ""Weng B"", ""Ding L"", ""Du Q"", ""Zang Y"", ""Wang J"", ""Yan F""]",10.1371/journal.pone.0354705,Bao GG,PloS one,1932-6203,7,PLoS One,eng,Yan F,[],e0354705,42536639,pmc-id: PMC13426921;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536639/,Functional node layout in Metroidvania game worlds: A complex network analysis,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"An association between personality factors and pain experience has been investigated. However, the direct contributions of personality traits by the Maudsley Personality Inventory to clinical pain outcomes in patients with chronic pain remain unclear. The Maudsley Personality Inventory is a self-report questionnaire used to assess extroversion, neurotic tendencies, and lying or exhibitionistic tendencies. The present study aimed to investigate whether personality traits influenced with the pain-related psychological variables in patients with chronic secondary low back pain (CLBP). One hundred fifteen consecutive outpatients with CLBP were included. Personality traits were measured by using the Maudsley Personality Inventory to assess extroversion, neurotic tendencies, and lying or exhibitionistic tendencies. The association of Maudsley neurotic tendency score and pain-related variables was analyzed and then performed a path analysis. Eleven patients (9%) were the biased persons with frequent lying. The pain-related variables showed no significant differences between the persons with frequent lying and those with normal. The Maudsley neurotic tendency score was significantly associated with Pain Catastrophizing Scale, Hospital Anxiety and Depression Scale, Pain Self-Efficacy Questionnaire, Athens Insomnia Scale, and EuroQol-5 Dimensions-3 level. The unstandardized coefficients for Maudsley neurotic tendency score were small, compared to pain-Numerical Rating Scale in each outcome. These results suggest the presence of neurotic tendency could have an impact on the health outcomes in patients with CLBP, but the impact was small.","[""Journal Article""]","[""Hayashi K"", ""Miki K"", ""Fukushima Y"", ""Iwai M"", ""Shiro Y"", ""Tetsunaga T"", ""Takasusuki T"", ""Hosoi M"", ""Yukioka M"", ""Okada S""]",10.1371/journal.pone.0354827,Hayashi K,PloS one,1932-6203,7,PLoS One,eng,Okada S,"[""Humans"", ""Low Back Pain"", ""Female"", ""Male"", ""Middle Aged"", ""Personality"", ""Chronic Pain"", ""Adult"", ""Surveys and Questionnaires"", ""Personality Inventory"", ""Pain Measurement"", ""Aged""]",e0354827,42536637,pmc-id: PMC13426982;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536637/,Personality traits have an effect on pain-related psychological variables in patients with chronic low back pain,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Radiology impressions guide clinical care. Large Language Models (LLMs)-drafted impressions can drift into generic, off-style text. Retrieval-augmented generation (RAG) enables context-aware few-shot prompting during inference. This retrospective IRB-approved study included 11,998 CT pulmonary angiography (CTPA) reports. We built a retrieval bank from 11,399 reports and reserved 599 reports for testing. GPT-4o and LLaMA 3.1-70B generated impressions from the ""findings"" section using three setups: zero-shot, fixed random few-shot, and dynamic retrieval-selected few-shot (top-k semantic matches; k = 3/5/10). We ran temperatures 0, 0.7, 1. We scored outputs against the original impressions with ROUGE and BERTScore F1, report mean scores with 95% confidence intervals, and tested for statistical significance using Wilcoxon signed-rank test. Dynamic retrieval-based few-shot prompting outperformed zero-shot and fixed few-shot prompting across all configurations (all p < 0.05). The highest scores were observed at temperature 0 and k = 10. ROUGE-1 F1 increased to 0.44-0.47 for GPT-4o and 0.37-0.50 for LLaMA, versus 0.35-0.37 and 0.25-0.37, respectively, in zero-shot prompting. Lower temperature and larger k were associated with higher similarity scores. Dynamic, case-matched retrieval improved alignment of LLM-generated CTPA impressions with reference impressions on automated text-similarity metrics. Scores remained moderate, and radiologists' verification is still required before clinical deployment.","[""Journal Article""]","[""Sorin V"", ""Collins JD"", ""Hahn LD"", ""Bratt AK"", ""Klang E"", ""Korfiatis P""]",10.1371/journal.pone.0354688,Sorin V,PloS one,1932-6203,7,PLoS One,eng,Korfiatis P,"[""Large Language Models"", ""Humans"", ""Retrospective Studies"", ""Information Storage and Retrieval""]",e0354688,42536636,pmc-id: PMC13426976;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536636/,Case-matched retrieval improves textual alignment of LLM-generated radiology impressions,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"This study aimed to evaluate the incremental diagnostic yield of bone scintigraphy (BS) performed after standard radiologic imaging (SRI) modalities, including radiography, computed tomography, and magnetic resonance imaging, in patients with fall trauma presenting to a Level I trauma center. Three hundred eight patients with fall trauma who underwent BS after SRI were retrospectively enrolled. The presence and number of bone injuries across six skeletal regions were evaluated using both SRI and BS. Bone injuries were evaluated according to three imaging-based categories: SRI alone, SRI - /BS + , and SRI + BS. Imaging-derived bone parameters included the total number of regions with bone injuries, the total number of injured bones, and the Imaging Bone Index (IBI) score. Correlations between these imaging-derived bone parameters and four trauma scores were analyzed, and differences in imaging-derived bone parameters were examined according to the cutoff values of each trauma score. The imaging-derived bone parameters in the SRI + BS category were significantly higher than those in the SRI alone category. Imaging-derived bone parameters in both the SRI alone and SRI + BS categories showed significant correlations with all trauma scores, with significantly stronger correlations for the total number of injured bones and IBI scores in the SRI + BS category. Patients with severe trauma exhibited significantly higher imaging-derived bone parameters in the SRI - /BS+ category. Performing BS after SRI provided incremental diagnostic yield by detecting additional bone injuries not identified on preceding SRI and yielded quantitative imaging-derived bone parameters associated with trauma severity in this Level I trauma center cohort of patients with fall trauma.","[""Journal Article""]","[""Lee SJ"", ""An YS"", ""Yoon JK"", ""Park BN"", ""Park YJ""]",10.1371/journal.pone.0355172,Lee SJ,PloS one,1932-6203,7,PLoS One,eng,Park YJ,"[""Humans"", ""Female"", ""Accidental Falls"", ""Trauma Centers"", ""Male"", ""Retrospective Studies"", ""Radionuclide Imaging"", ""Bone and Bones"", ""Middle Aged"", ""Adult"", ""Tomography, X-Ray Computed"", ""Aged"", ""Magnetic Resonance Imaging""]",e0355172,42536635,pmc-id: PMC13426956;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536635/,Incremental diagnostic yield of bone scintigraphy after standard radiologic imaging in patients with fall trauma at a Level I trauma center,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Extended-spectrum beta-lactamase (ESBL) and carbapenemase-producing Enterobacteriaceae (CPE) pose a critical public health threat. Janitors are routinely exposed to contaminated environments and may act as a reservoir for these resistant bacteria, particularly in resource-limited settings like Ethiopia, where data on this subject are scarce. The aim of this study was to assess fecal carriage rates of ESBL-PE, CPE and its associated factors among hospital and non-hospital janitors at the University of Gondar (UoG), Northwest Ethiopia. A comparative cross-sectional study was conducted from June 15 to September 25, 2025, at the UoG. A total of 385 janitors (203 hospital and 182 non-hospital) were selected using stratified and simple random sampling techniques. Data on socio-demographic and associated factors were collected using a semi-structured questionnaire. Stool samples were collected aseptically and cultured on MacConkey agar. Antimicrobial resistance (AMR) patterns were determined by the Kirby-Bauer disk diffusion method following Clinical and Laboratory Standards Institute (CLSI) 2024 guidelines. The ESBL and carbapenemase production were confirmed using the combination disk and modified Carbapenem inactivation methods, respectively. Quality control was ensured by using standard reference strains. Data analysis was performed using SPSS version 27.0, employing chi-square tests and logistic regression. A p-value of <0.05 was considered statistically significant. Among the 385 stool samples, a total of 416 Enterobacteriaceae isolates were recovered, 229 from hospital janitors and 187 from non-hospital janitors. The overall fecal carriage rates among janitors were 83 (21.6%) for ESBL-PE and 14 (3.6%) for CPE. Hospital janitors had significantly higher carriage rate than non-hospital janitors for both ESBL-PE (28.6% vs. 13.7%, p < 0.001) and CPE (5.9% vs. 1.1%, p = 0.012), respectively. Escherichia coli was the predominant ESBL-producer. Significant risk factors identified for ESBL-PE colonization included lack of hand hygiene at home, history of antibiotic use, and urinary tract infection for hospital janitors, and age ≥ 40 years and history of non-prescription antibiotic use were for non-hospital janitors. This high carriage rates of ESBL-PE and CPE, identify janitors as a significant reservoir for resistant bacteria. We recommend integrating janitors into national AMR surveillance programs and strengthening infection prevention and control and antimicrobial stewardship training.","[""Journal Article"", ""Comparative Study""]","[""Zayede A"", ""Wondimeneh Y"", ""Biset S"", ""Gizachew M""]",10.1371/journal.pone.0355041,Zayede A,PloS one,1932-6203,7,PLoS One,eng,Gizachew M,"[""Ethiopia"", ""Cross-Sectional Studies"", ""Humans"", ""beta-Lactamases"", ""Feces"", ""Carbapenem-Resistant Enterobacteriaceae"", ""Enterobacteriaceae"", ""Enterobacteriaceae Infections"", ""Bacterial Proteins"", ""Male"", ""Female"", ""Adult"", ""Anti-Bacterial Agents"", ""Microbial Sensitivity Tests""]",e0355041,42536634,pmc-id: PMC13426960;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536634/,"Fecal carriage of ESBL and Carbapenemase-producing Enterobacteriaceae, and its associated factors among hospital and non-hospital janitors at the University of Gondar, Northwest Ethiopia: A comparative cross-sectional study",21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Antibiotic resistance has emerged as one of the most urgent global health threats, undermining the effective treatment of bacterial infections. In response, scientific interest is increasingly focused on identifying natural and effective antimicrobial agents derived from medicinal plants. In Ethiopia, Ehretia cymosa (E. cymosa) is traditionally used to treat wound infections, fever, gastric ulcers, dysentery, and toothache. However, there is limited scientific evidence to support these traditional claims. Hence, the present study aimed to evaluate the in vitro and in vivo antibacterial activities and to screen the phytochemical profile of the 80% methanol extract of E. cymosa leaves. The air-dried and powdered leaves of E. cymosa were extracted using cold maceration with 80% methanol. The antibacterial activity of the crude extract was tested using the disk diffusion method against selected bacterial pathogens commonly associated with infections. An in vivo model of burn followed by infection was established in mice. Qualitative phytochemical screening was also performed. One-way analysis of variance followed by Tukey's post hoc multiple tests was used to compare the means of all parameters. The leaves of E. cymosa demonstrated significant antibacterial activity (p < 0.001) against the tested bacterial strains in a dose-dependent manner compared with the control. The minimum inhibitory concentration ranged from 6.25 to 75 mg/mL, while the minimum bactericidal concentration against P. aeruginosa and E. coli was 200 mg/mL. In the in vivo model, the extract resulted in faster wound contraction and a shorter epithelialization period against S. aureus than against P. aeruginosa. The plant leaf is also rich in flavonoids, terpenoids, and tannins. The 80% methanol extract of E. cymosa leaves exhibited antibacterial activity in vitro and in vivo, which corroborates the traditional use of the leaves against infectious diseases. Further studies involving the isolation and characterization of the active compounds are recommended.","[""Journal Article""]","[""Mekonnen E"", ""Edessa D"", ""Weldegebreal F"", ""Aklog A"", ""Gashaw T""]",10.1371/journal.pone.0354982,Mekonnen E,PloS one,1932-6203,7,PLoS One,eng,Gashaw T,"[""Plant Leaves"", ""Anti-Bacterial Agents"", ""Plant Extracts"", ""Animals"", ""Methanol"", ""Mice"", ""Microbial Sensitivity Tests"", ""Phytochemicals""]",e0354982,42536633,pmc-id: PMC13427015;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536633/,In vitro and in vivo antibacterial activities and phytochemical screening of 80% methanol extract from Ehretia cymosa leaves,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"With the rapid development of data-driven technologies, real-time data streams not only exhibit concept drift but are also frequently accompanied by class imbalance problems. To address these challenges, this paper proposes an online sequential pre-interference layer extreme learning machine (OS-PIELM). The proposed model introduces a pre-interference layer between the input layer and hidden layer of the original OS-ELM to enhance nonlinear feature representation through kernel-like transformation of sequential data, thereby improving the discriminative ability of different classes. Furthermore, an adaptive forgetting factor and a Gmean-based concept drift detection mechanism are incorporated into OS-PIELM, together with a dynamic weighting strategy. These components enable the model to effectively handle class imbalance in data streams and enhance its sensitivity to concept drift. Finally, an online ensemble learning framework is constructed with OS-PIELM as the base classifier to further improve the robustness of the proposed method. Extensive experiments on nine synthetic datasets and two real-world datasets demonstrate that the proposed method can effectively address class imbalance in data streams and improve concept drift detection performance.","[""Journal Article""]","[""Huang Y"", ""Wen H"", ""Tang Q"", ""Liu H""]",10.1371/journal.pone.0353728,Huang Y,PloS one,1932-6203,7,PLoS One,eng,Liu H,"[""Extreme Learning Machines"", ""Ensemble Learning"", ""Classification Algorithms"", ""Algorithms"", ""Soft Computing""]",e0353728,42536631,pmc-id: PMC13426951;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536631/,Ensemble learning-based online sequential pre-interference extreme learning for concept drifting and class imbalanced data streams,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Respiratory syncytial virus (RSV) is a leading cause of acute respiratory tract infections, particularly in infants, older adults, and immunocompromised individuals. RSV is classified into two major subtypes, RSV A and RSV B, which co-circulate seasonally and exhibit genetic variability, highlighting the need for rapid and subtype-specific diagnostic methods. Although reverse transcription quantitative PCR (RT-qPCR) is the reference standard for RSV detection, its reliance on complex instrumentation limits its applicability in decentralized testing settings. In this study, we developed and evaluated a probe-based reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for rapid detection and differentiation of RSV A and RSV B. The assay incorporates a dual-probe strategy, employing an assimilating probe for RSV A detection to ensure robust signal generation under multiplex conditions, and hybridization-based TaqMan-style probes (HyTaq probes) for RSV B detection and for an internal control targeting the human ACTB gene to ensure reaction validity. Analytical performance was assessed using serially diluted RSV positive clinical specimens and plasmid standards. Clinical performance was evaluated using 91 RSV A positive specimens, 97 RSV B positive specimens, and 120 RSV negative specimens, as defined by the reference diagnosis. The RSV A and RSV B RT-LAMP assays demonstrated sensitivities of 92.31% and 98.97%, respectively, with a specificity of 100% for both targets. No cross-reactivity was observed with a panel of common respiratory viruses. These results indicate that the proposed dual-probe RT-LAMP assay provides a rapid and specific approach for subtype-specific RSV detection, with potential applicability in decentralized diagnostic settings pending further validation.","[""Journal Article""]","[""Lim MS"", ""Park C"", ""Lee E"", ""Ko SY"", ""Jang WS""]",10.1371/journal.pone.0354914,Lim MS,PloS one,1932-6203,7,PLoS One,eng,Jang WS,"[""Humans"", ""Nucleic Acid Amplification Techniques"", ""Respiratory Syncytial Virus Infections"", ""Respiratory Syncytial Virus, Human"", ""Sensitivity and Specificity"", ""Molecular Diagnostic Techniques"", ""Rapid Diagnostic Tests"", ""RNA, Viral""]",e0354914,42536630,pmc-id: PMC13426929;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536630/,A multiplex dual-probe RT-LAMP assay for rapid subtype-specific detection of respiratory syncytial virus A and B,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"The widespread use of herbal medicines in clinical practice, particularly in Southeast Asia, presents significant challenges for medication safety management, notably regarding interactions between herbs and conventional drugs. Current drug interaction screening tools demonstrate substantial gaps in documenting herb-drug interactions, especially for regionally specific medicinal plants, creating potential risks for patients receiving concurrent therapies. (1) to identify the prevalence of potential herb-drug and herb-herb interactions and the disclosure rate of HM use in patients with NCDs; and (2) to assess the consistency of interaction information across commonly used drug interaction databases. An observational study enrolled 658 patients with non-communicable diseases from two Vietnamese tertiary care facilities. Structured interviews captured herbal medicine utilization patterns, disclosure practices, and specific botanical preparations used. Potential herb-drug and herb-herb interactions were systematically evaluated using four databases: Micromedex®, UpToDate Lexicomp Drug Interactions, Medscape Drug Interaction Checker, and Stockley's Herbal Medicines Interactions. Inter-database agreement was assessed using Fleiss' kappa statistics. 48.6% of participants reported active herbal medicines use, with 96% failing to disclose this to their healthcare providers. Potential interactions were identified in 31.3% of herbal medicine users, representing 15.2% of the total cohort. Database concordance was remarkably poor, with only 0.7% of interactions consistently documented across all four resources (Fleiss' κ = -0.0653; p < 0.001). Multiple indigenous medicinal plants commonly used by patients were absent from all evaluated databases. The substantial prevalence of undisclosed herbal medicine use, alongside inadequate representation in drug interaction databases, represents a critical gap in medication safety infrastructure. These findings demonstrated the necessity for integrating herbal medicine assessment into routine care, enhanced provider training, and expansion of clinical decision support systems to include region-specific botanical data for populations using concurrent traditional and conventional therapies.","[""Journal Article"", ""Multicenter Study"", ""Observational Study""]","[""Phan ADT"", ""Vo TH"", ""Luu TNN"", ""Ngo HTT"", ""Heinrich M"", ""Kongkaew C""]",10.1371/journal.pone.0355046,Phan ADT,PloS one,1932-6203,7,PLoS One,eng,Kongkaew C,"[""Herb-Drug Interactions"", ""Humans"", ""Vietnam"", ""Cross-Sectional Studies"", ""Noncommunicable Diseases"", ""Female"", ""Databases, Factual"", ""Middle Aged"", ""Herbal Medicine"", ""Plants, Medicinal"", ""Adult"", ""Aged"", ""Disclosure""]",e0355046,42536629,pmc-id: PMC13426966;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536629/,"Herbal medicine use disclosure, database-flagged potential herb-drug interactions, and inter - interaction database concordance among patients with non-communicable diseases in Vietnam: A multicenter cross-sectional study",21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"The Motor Function Measure (MFM) is an important evaluation tool used to monitor the progression of most neuromuscular diseases. However, the MFM is subject to inter-rater variability, and patients must produce their best effort, which can be difficult for children. In response to these issues, we developed a digital app named MFM-Play, designed to optimise completion of the MFM in a fun manner. The objective of this study was to explore barriers and levers to the MFM-Play's use by therapists. We conducted a qualitative study with rehabilitation professionals who had tested the app in a previous reliability study. Individual interviews based on the Technology Acceptance Model were followed by a focus group based on the interview results. Thematic analysis was performed on transcripts. Seven therapists participated in the interviews and seven others in the focus group. The results revealed the multi-dimensional features related to adopting the MFM-Play app. Barriers related to ease of use, training and organisational constraints were identified, and were partly due to the additional mental burden of learning to use the technology. However, therapists who were at ease with the digital tool found it useful for their practice. The app also modified patient-therapist dynamics, fostering greater patient autonomy, but sometimes disrupted therapists' habits, by calling into question assessment methods. The MFM-Play app offers considerable practical and efficiency benefits; however, its successful adoption depends on overcoming technical, organisational, and user-specific barriers. This involves providing support for the change in the therapist's stance within the triadic patient-therapist-tablet relationship.","[""Journal Article""]","[""Vincent-Genod D"", ""Verroul M"", ""Rippert P"", ""Tachibana S"", ""Vuillerot C"", ""MFM-Play Study Group""]",10.1371/journal.pone.0352856,Vincent-Genod D,PloS one,1932-6203,7,PLoS One,eng,Vuillerot C,"[""Humans"", ""Mobile Applications"", ""Qualitative Research"", ""Focus Groups"", ""Female"", ""Male"", ""Hospitals"", ""Physical Therapists"", ""Neuromuscular Diseases"", ""Adult""]",e0352856,42536628,pmc-id: PMC13426978;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536628/,Barriers and levers to using an app for motor function assessment by therapists in hospitals: A qualitative study of the MFM-Play app,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Currently, there are no evidence-based treatments available for adults with avoidant/restrictive food intake disorder (ARFID). The present paper describes the design of a study evaluating a cognitive-behavioral therapy (CBT) protocol for adults with ARFID, with a focus on exposure using inhibitory learning principles. This multicenter study uses a prospective, uncontrolled, repeated-measures design. A total of 120 adults (aged ≥ 18 years) with ARFID will be included via 11 participating treatment centers throughout the Netherlands. Participants will receive a manualized treatment of 25 weekly sessions. Assessments will be conducted at baseline, post-treatment, and at 1- and 12-month follow-ups. The primary outcome is ARFID severity, measured by the Pica, ARFID, and Rumination Disorder Interview (PARDI). Session-level measures of fear and expectancies will be collected throughout the treatment to explore potential mechanisms of change. Treatment effects will be examined across ARFID profiles and comorbid disorders. This is the first large-scale study to investigate an outpatient CBT program for adults with ARFID. By examining outcomes across ARFID profiles and exploring underlying mechanisms of change, the findings are expected to inform treatment refinement and provide a foundation for future controlled trials. The study has been preregistered in AsPredicted (#212,212) and the trial was registered in the Overview of Medical Research in the Netherlands (NL-OMON6121).","[""Journal Article"", ""Multicenter Study""]","[""Masereel M"", ""Cardona Cano S"", ""Tran TD"", ""de Jonge M"", ""Dumont E"", ""van Elburg AA"", ""Mulkens S""]",10.1371/journal.pone.0354232,Masereel M,PloS one,1932-6203,7,PLoS One,eng,Mulkens S,"[""Humans"", ""Cognitive Behavioral Therapy"", ""Prospective Studies"", ""Adult"", ""Female"", ""Male"", ""Treatment Outcome"", ""Netherlands"", ""Avoidant Restrictive Food Intake Disorder"", ""Middle Aged""]",e0354232,42536627,pmc-id: PMC13426971;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536627/,"Cognitive-behavioral therapy focused on inhibitory learning, for adults with avoidant/restrictive food intake disorder (ARFID): Study protocol of a prospective study",21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"Modern tibial implants should be designed to achieve an optimal anatomical fit. The aim of this study was to evaluate how well a newly developed tibial implant design (oneKNEE® - B. Braun Aesculap, Tuttlingen, Germany) matches patient anatomy compared to three existing implant systems, using Statistical Shape Models (SSM). SSMs for Caucasian and Asian populations were generated using CT scans of 120 Caucasian and 112 Asian osteoarthritic patients. Border anatomical variations were represented by individual anatomies from 14 Caucasian and 12 Asian patients. Tibial components were positioned in accordance with strict protocols established by senior knee surgeons (YM, NK). The anatomical fit was analyzed across all four implant systems in terms of antero-posterior and medio-lateral dimensions, tibial coverage and cortical bone support. Global tests for homogeneity and Dunnett's tests were performed. Bony coverage for Asian and Caucasian populations ranged from 82.9% to 88.4% for long-established designs and from 85.0% to 91.2% for more recently introduced designs. Among all designs, the oneKNEE® implant demonstrated superior bony coverage and cortical support, followed by Attune® (Depuy-Synthes, Warsaw, IN, USA), Columbus® (B. Braun Aesculap), and PFC Sigma® (Depuy-Synthes). For average anatomies, oneKNEE® showed significantly better bony coverage and cortical score compared to Columbus® and PFC Sigma® (P < 0.01). In less average anatomies, oneKNEE® exhibited statistically superior bony coverage compared to PFC Sigma®, although no significant difference was observed in cortical support. Compared with established tibial implant designs, the new design demonstrated improved virtual anatomical fit and coverage metrics based on computational modeling. These findings reflect a theoretical design‑level improvement and require biomechanical and clinical validation.","[""Journal Article""]","[""Dupraz I"", ""Minoda Y"", ""Kornilov N"", ""Altermann B"", ""Hauff P"", ""Bollinger A"", ""Richter B"", ""Grupp TM""]",10.1371/journal.pone.0354876,Dupraz I,PloS one,1932-6203,7,PLoS One,eng,Grupp TM,"[""Humans"", ""Tibia"", ""Prosthesis Design"", ""Models, Statistical"", ""Tomography, X-Ray Computed"", ""Female"", ""Male"", ""Asian People"", ""White People"", ""Aged"", ""Knee Prosthesis"", ""Middle Aged"", ""Arthroplasty, Replacement, Knee"", ""Osteoarthritis, Knee"", ""Models, Anatomic""]",e0354876,42536626,pmc-id: PMC13426962;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536626/,Anatomical fit of the oneKNEE tibia design using statistical shape modeling,21,jkeNNjHj0zxqbmbkN,60sfVYcL4g9w4etuD
"The brain vasculature comprises diverse specialized cells that are essential for brain function, yet their spatial organization remains poorly understood. Here, we construct a comprehensive cerebrovascular cell atlas encompassing 314,535 transcriptomes that captures the arteriovenous axis and defines consensus cell states. We then perform spatial transcriptomics to map 1,529,740 cells across the human temporal cortex and hippocampus, uncovering stereotyped micro-communities termed vascular cell ensembles. These ensembles comprise specialized subsets of endothelial cells, mural cells, fibroblasts, and perivascular macrophages that align with the arteriovenous architecture to coordinate segment-specific functions, such as neurovascular coupling, blood-brain barrier transport, and immune surveillance. By overlaying genetic risk and pharmacologic reactivity, we identify ensemble-specific susceptibilities and candidate therapeutic targets across neurological diseases, including small vessel disease and stroke. This study provides a resource to dissect the spatial and functional logic underlying human cerebrovascular biology and establishes a blueprint for decoding neurological disease susceptibility and therapeutic response.","[""Journal Article""]","[""Wang JC"", ""Sanchez D"", ""Arul S"", ""Gülsuyu B"", ""Gopinadhan A"", ""Mukhtar T"", ""Kim J"", ""Andrews JP"", ""Alonso Cee Williams M"", ""Jung Y"", ""Hashimoto ML"", ""Kim CN"", ""Bhalla S"", ""Ewing-Crystal NA"", ""Bernabei JM"", ""Letchuman V"", ""Haddad AF"", ""Hemphill K"", ""Weinsheimer SM"", ""Kim H"", ""Narsinh KH"", ""Cooke DL"", ""Cadwell CR"", ""Wälchli T"", ""Elahi FM"", ""Yang AC"", ""He P"", ""Chang EF"", ""Molofsky AB"", ""Winkler EA""]",10.1016/j.cell.2026.07.007,Wang JC,Cell,0092-8674,,Cell,eng,Winkler EA,[],,42537647,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42537647/,Spatial atlas of the human brain vasculature reveals specialized cell ensembles,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Amino acid levels fluctuate across diverse pathological conditions. Whether such amino acid modulations directly shape pathophysiology by regulating host gene expression remains unknown. We found that extracellular arginine restriction, observed in cancer and infection, represses specific arginine tRNAs-directly suppressing translation of major histocompatibility complex I (MHC class I) and antigen presentation. Arginine regulation of MHC class I was codon-usage dependent, as synonymous codon mutations prevented MHC class I modulation. Dietary arginine restriction impaired anti-viral immunity against influenza and SARS-CoV-2 and increased colon tumorigenesis. Conversely, increasing arginine availability via dietary supplementation or myeloid-specific arginase 1 deletion enhanced MHC class I protein levels, suppressed colon tumorigenesis, and improved viral infection outcomes. These disease-modulating effects were abolished in β2-microglobulin (B2m)-deficient mice. Thus, dietary modulation of a single amino acid critically influences codon-biased translation and MHC class I-mediated immunity to respiratory viral infections and cancer, revealing an unexpected mechanism and disease hazard for arginine deficiency and highlighting potential for amino acid-based translation modulation therapy.","[""Journal Article""]","[""Wu Q"", ""Seydlitz LM"", ""Iakimov V"", ""Hsu DJ"", ""Habibzadeh P"", ""Hoffmann HH"", ""Paty PB"", ""Rice CM"", ""Tavazoie SF""]",10.1016/j.cell.2026.07.020,Wu Q,Cell,0092-8674,,Cell,eng,Tavazoie SF,[],,42532044,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42532044/,Dietary arginine drives codon-dependent MHC class I translation and improves immunity in colon tumorigenesis and respiratory viral infection,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"The regulation of 3D cell shape is a fundamental problem of life. In multicellular tissues, cell shape emerges through the balance of forces inside and outside the cell. In epithelia, the basement membrane (BM) is the first extracellular barrier that cells sense biochemically and mechanically. Despite this, little is known about how BM mechanical properties are regulated and how they impact cell shape. Through mathematical modeling, we show that the stress relaxation time of the BM can regulate cell shape. Using molecular dynamics simulations, we show that the stress relaxation time of a collagen IV network can be inferred from the lifetime of collagen IV molecules. To measure collagen IV lifetime in vivo, we develop a fluorescent timer reporter for collagen IV and show that perlecan modifies collagen IV lifetime. This cross-disciplinary approach establishes a multiscale framework to probe matrix turnover, and its regulation and function in cell shape control.","[""Journal Article""]","[""Barrientos R"", ""Meadowcroft B"", ""Sánchez-Sánchez BJ"", ""Stramer BM"", ""Paluch EK"", ""Charras G"", ""Banerjee S"", ""Šarić A"", ""Mao Y""]",10.1016/j.cell.2026.07.010,Barrientos R,Cell,0092-8674,,Cell,eng,Mao Y,[],,42532043,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42532043/,Basement membrane turnover controls cell shape,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Tick-borne orthonairoviruses, including the emerging wetland virus (WELV), pose a growing public health concern as cases increase, yet their pathogenesis remains unclear. Here, we show that WELV infection causes fatal liver dysfunction in patients, characterized by elevated hepatic enzymes, triacylglycerol accumulation, and hyperinflammation. WELV induces gasdermin E (GSDME)-dependent pyroptosis in hepatocytes through mitochondrial and Fas-mediated apoptotic pathways. Viral RNA activates RIG-I/CASP3-mediated GSDME cleavage, while viral nucleoprotein undergoes CASP3-dependent processing, forming a negative regulatory feedback loop. GSDME directly interacts with fatty acid synthase (FASN) and blocks K48-linked ubiquitination to inhibit FASN degradation, driving lipid metabolic reprogramming and lethal hepatic steatosis. GSDME knockout abolishes pyroptosis and metabolic dysregulation, conferring complete protection against WELV infection. Clinically approved caspase and FASN inhibitors mitigate liver pathology and improve survival in WELV-infected mice. These findings establish a pyroptosis-metabolism axis driving orthonairovirus pathogenesis, highlighting GSDME as a critical determinant of liver injury and a promising target for antiviral therapy.","[""Journal Article""]","[""Wang C"", ""Zheng X"", ""Zhang Y"", ""Shang X"", ""Qu Q"", ""Li C"", ""Zhang X"", ""Jin N"", ""Liu W"", ""Li H""]",10.1016/j.cell.2026.07.011,Wang C,Cell,0092-8674,,Cell,eng,Li H,[],,42526439,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42526439/,Gasdermin E couples viral pyroptosis to lethal hepatic lipid accumulation,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Immune aging impairs T cell-mediated tumor control as well as cancer immunotherapy outcomes. The most important drivers of T cell dysfunction in aged tumors remain unknown. We performed single-cell CRISPR screens to identify Dusp5 and Zfp219 as key regulators of CD8+ T cell persistence and effector differentiation within aged tumors. Loss of Dusp5 increased extracellular signal-regulated kinase (ERK) phosphorylation and globally enhanced T cell proliferation. Conversely, Zfp219 deletion induced epigenetic reprogramming and increased expression of cytotoxic molecules, enhancing antitumor immunity specifically in aging. Levels of the human ortholog ZNF219 were higher within intratumoral CD8+ T cells from older cancer patients, which correlates with worse survival following immunotherapy. Zfp219 ablation synergized with immune checkpoint inhibitors to expand effector-like CD8+ T cells, leading to tumor clearance in aged mice. Our findings highlight Dusp5 and Zfp219 as critical drivers of age-related T cell dysfunction that can be targeted to rejuvenate antitumor immunity in older cancer patients.","[""Journal Article""]","[""Chen ACY"", ""Ji KY"", ""Yerinde C"", ""Knudsen NH"", ""Bi K"", ""Hao S"", ""Zhabotynsky V"", ""Martinez D"", ""Carmona-LaSalle TJ"", ""Taguchi K"", ""Xu KH"", ""Seider EM"", ""Schwartz MA"", ""Zschummel M"", ""Nieman LT"", ""Yates KB"", ""Gazzaniga FS"", ""Miller BC"", ""Mempel TR"", ""Manguso RT"", ""Hacohen N"", ""Sen DR""]",10.1016/j.cell.2026.07.016,Chen ACY,Cell,0092-8674,,Cell,eng,Sen DR,[],,42526438,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42526438/,CRISPR screens identify targets to rescue age-related T cell dysfunction in cancer,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Recent advances in AI inspire visions of universal models of biology. Yet living systems are evolved, emergent processes whose behaviors cannot be inferred from their parts alone. We propose grounding AI in canonical biological processes, constructing data-driven world models with explicit mechanistic links across molecules, cells, and their dynamics in space and time.","[""Journal Article"", ""Review""]","[""Stelzer Y"", ""Tanay A""]",10.1016/j.cell.2026.07.003,Stelzer Y,Cell,0092-8674,,Cell,eng,Tanay A,[],,42520803,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42520803/,Why machines don't speak biology: Toward native biological language models,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Defense-associated reverse transcriptase (DRT) systems mediate antiviral immunity through distinct modes of cDNA synthesis: class 1 DRTs catalyze untemplated synthesis, whereas class 2 DRTs polymerize non-coding RNA-templated products. However, how these distinct modes drive defense remains unclear. Here, we report that DRT3 immunity arises when class 1 and class 2 RT activities cooperate to produce self-complementary double-stranded DNA (dsDNA). DRT3a uses a 5'-ACACAC-3' RNA template to synthesize poly-(dTdG) repeats, whereas DRT3b synthesizes poly-(dCdA) repeats without any nucleic acid template. Cryo-electron microscopy reveals that DRT3b forms a hexamer and uses active-site-adjacent residues as deoxyadenosine and deoxycytidine gates to enforce alternating nucleotide addition, representing a unique example of amino-acid-templated DNA polymerization. DRT3 is toxic in cells lacking RecBCD, implicating host recombination machinery in limiting dsDNA accumulation, and the phage-encoded RecBCD inhibitor Gam triggers DRT3-mediated abortive infection. These findings reveal how two polymerases with distinct templating strategies generate complementary DNA for antiviral defense.","[""Journal Article""]","[""Wang M"", ""Yoneyama K"", ""Žedaveinytė R"", ""Ishikawa J"", ""Tang S"", ""Le HC"", ""Wiegand T"", ""Ramirez JL"", ""Nagahata N"", ""Ma Y"", ""Zhang DJ"", ""Helmeczi E"", ""Berisa M"", ""Jovanovic M"", ""Hiraizumi M"", ""Yamashita K"", ""Nishimasu H"", ""Sternberg SH""]",10.1016/j.cell.2026.07.012,Wang M,Cell,0092-8674,,Cell,eng,Sternberg SH,[],,42520802,pmc-id: PMC13419432;manuscript-id: NIHMS2196824;,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42520802/,Coordinated RNA- and protein-templated synthesis of double-stranded DNA by a dual reverse transcriptase immune system,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Cancer management remains fragmented across its continuum, from late-stage diagnosis and salvage therapies to non-personalized surveillance. Here, we present Oncoformer, a unified multimodal transformer model trained on the China Oncology Multimodal Prediction and Surveillance Study (COMPASS) cohort (3.67 million individuals, 17.7 million clinical visits) and validated on independent external cohorts, including the UK Biobank. Oncoformer integrates longitudinal electronic health records with chest X-ray imaging to address multiple clinical tasks: pan-cancer diagnosis (area under the receiver operating characteristic curve [AUROC] = 0.956), future cancer prediction up to 1 year before diagnosis (AUROC = 0.869), tumor stage inference (mean AUROC > 0.90), patient-specific treatment-response forecasting, and recurrence-free survival stratification across ten cancer types (all p < 0.01). Staging predictions were independently validated against postoperative pathological endpoints and shown to converge on core cancer genomic pathways. By translating routine clinical data into a dynamic view of cancer evolution, Oncoformer provides a framework for risk-informed cancer prediction and treatment stratification using routine clinical data.","[""Journal Article""]","[""Liu F"", ""Wang K"", ""Xu H"", ""Tang C"", ""Shen X"", ""Wang M"", ""Yang L"", ""Yang L"", ""Liu L"", ""Hu C"", ""Li G"", ""Wu W"", ""Zou Z"", ""Li B"", ""Liu S"", ""Kang J"", ""Kong J"", ""Li T"", ""Wong IN"", ""Huang X"", ""Chen G"", ""Lu W"", ""Ziyar I"", ""Zhang CL"", ""Sun Y"", ""Lin W"", ""Ou C"", ""Fok M"", ""Hou T"", ""Wang W"", ""Xue K"", ""Yin Y"", ""Zhu H"", ""Gootenberg J"", ""Abudayyeh OO"", ""Karin M"", ""Loupy A"", ""Rasko JEJ"", ""Ideker T"", ""Luo H"", ""Oermann E"", ""Zhang K"", ""International Consortium of Digital Twins in Healthcare and Medicine""]",10.1016/j.cell.2026.07.009,Liu F,Cell,0092-8674,,Cell,eng,Zhang K,[],,42508404,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42508404/,Advancing cancer detection and treatment using longitudinal routine clinical data,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Systematically simulating and predicting phenotypic effects of diverse interventions across heterogeneous cellular environments is central to the vision of artificial intelligence virtual cell (AIVC). However, disparities in perturbagen modalities, assay formats, and data production efficiency hinder unified modeling and analysis of genetic and chemical screens. This study presents UniPert-G2CP, a two-stage deep learning framework that bridges genetic and chemical screens by unifying multimodal molecular perturbagen (cause) representations and enabling genetic-to-chemical perturbation phenotype (effect) transfer learning. Validated on large-scale genetic and chemical screening datasets, UniPert-G2CP enables more efficient, accurate, robust, interpretable, and generalizable simulation of multicellular and multidomain perturbation cause-effect spaces. Further joint analysis of these spaces reveals cellular heterogeneity underlying drug responses, providing mechanistic insights into drug action and resistance. Collectively, UniPert-G2CP advances universal biological causal modeling, accelerates AIVC realization, and expands the potential of AI-powered precision medicine.","[""Journal Article""]","[""Li Y"", ""Zeng M"", ""Zhu J"", ""Liu L"", ""Wang F"", ""Huang L"", ""Yang F"", ""Li M"", ""Yao J""]",10.1016/j.cell.2026.06.005,Li Y,Cell,0092-8674,,Cell,eng,Yao J,[],,42497867,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42497867/,UniPert-G2CP bridges genetic and chemical screens from molecular representation to phenotype modeling,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Mg2+ is essential for all living organisms, yet its transport across mammalian membranes remains poorly understood. Here, we present cryoelectron microscopy (cryo-EM) structures of a full-length mammalian Mg2+ transporter on the plasma membrane, human CNNM4, in outward-facing and occluded states, revealing an unexpected tetrameric assembly organized as a dimer of asymmetric dimers-distinct from the symmetric dimers in prokaryotic homologs and long assumed for eukaryotic CNNMs. We show that Mg2+/ATP binding stabilizes the dynamic intracellular domains and promotes tetramerization, while an acidic patch binds additional Mg2+, potentially acting as a sensor to couple cytoplasmic Mg2+ levels to transport activity. Within the transmembrane domain, a key glutamate flips upon Na+ binding and destabilizes the Mg2+-binding site in the outward-facing state, thereby promoting Mg2+/Na+ exchange. Together, these findings establish a mechanistic framework for CNNM transport and regulation that diverges from prokaryotic models and links CNNM function to human physiology and disease.","[""Journal Article""]","[""Bai Z"", ""Zhou XE"", ""Lü W"", ""Du J""]",10.1016/j.cell.2026.06.039,Bai Z,Cell,0092-8674,,Cell,eng,Du J,[],,42497866,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42497866/,Dynamic dimer-of-dimers architecture defines Mg(2+) transport in human CNNM4,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Drought threatens crop productivity, yet enhancing tolerance often compromises yield. Abscisic acid (ABA) signaling is central to drought response, but its deep conservation can constrain adaptive flexibility. Here, we identify ROAD1 (rice orphan gene adapted for drought 1), an Oryza-specific orphan gene that confers robust drought tolerance without obvious growth defects under normal conditions. ROAD1 originated from Oryza meridionalis, and its functional allele, ROAD1C, was selected during japonica domestication. In field trials, elite rice lines carrying ROAD1C exhibited up to 34.75% higher grain yield than corresponding controls under drought. Mechanistically, ROAD1 bypasses the canonical ABA receptor-ligand complex by binding the phosphatase OsPP2C68, preventing sucrose non-fermenting 1-related protein kinases 2 (SnRK2) dephosphorylation and activating downstream responses. ROAD1 also interacts with protein phosphatase 2C (PP2C) orthologs from maize, wheat, and Arabidopsis, and heterologous expression of ROAD1C enhances drought tolerance in Arabidopsis, rapeseed, maize, wheat, and poplar. These findings reveal that an Oryza-specific orphan gene can co-opt conserved signaling for potential trans-species drought tolerance.","[""Journal Article""]","[""Tu H"", ""Liu Q"", ""Ye T"", ""Ye Y"", ""Feng X"", ""Shen L"", ""Li S"", ""Bai S"", ""Liu X"", ""Liu X"", ""Wang H"", ""Li X"", ""Lin J"", ""Wang H"", ""Chen Y"", ""Feng Z"", ""Ji B"", ""Ding J"", ""Li W"", ""Zhang J"", ""Dai M"", ""Dong F"", ""Hu H"", ""Tang N"", ""Lai X"", ""Xiong H"", ""Xiong L""]",10.1016/j.cell.2026.07.005,Tu H,Cell,0092-8674,,Cell,eng,Xiong L,[],,42492508,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42492508/,An Oryza orphan gene confers trans-species drought tolerance,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"The beneficial fungus Trichoderma enhances plant growth and stress tolerance through poorly understood mechanisms. Here, we show that Trichoderma harzianum swollenin ThSWO contributes to efficient root colonization and plant growth promotion. ThSWO traverses the plant cell wall and localizes to the plasma membrane, where it interacts with ABC transporter AtABCB5, which we establish as a bona fide auxin efflux carrier. ThSWO binding to NBD2 and R-domain faces of AtABCB5 prosmotes phosphorylation at Ser640 and Ser644, enhancing indole-3-acetic acid (IAA) efflux and triggering auxin-associated responses, including cell wall acidification, membrane potential transitions, and accelerated cytoplasmic streaming. Structure-guided substitutions at the AtABCB5-ThSWO interface differentially affected transporter binding and lateral root promotion, supporting the conclusion that host auxin transport is a primary effector target. These findings reveal a molecular mechanism by which a fungal effector co-opts host auxin transport machinery to promote plant development, with implications for microbe-assisted crop improvement.","[""Journal Article""]","[""Lu J"", ""Liu J"", ""Jiang S"", ""Xu Y"", ""Yan Z"", ""Li L"", ""Zhang F"", ""Chen W"", ""Xu D"", ""Li Y"", ""Liu B"", ""Raza W"", ""Xuan W"", ""Liu D"", ""Shen Q""]",10.1016/j.cell.2026.07.001,Lu J,Cell,0092-8674,,Cell,eng,Shen Q,[],,42492507,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42492507/,Trichoderma swollenin activates AtABCB5-dependent auxin efflux to promote plant development,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Bacteriophage genomes are densely packed with coding sequences and frequently encode genes of unknown function. Unbiased phage functional genomics approaches are therefore needed, particularly for large lytic phages. Here, we harness the mariner transposase to develop phage transposon mutagenesis and sequencing (phage TnSeq), which enables pooled sequencing to identify both fitness-conferring and dispensable genes. Using the Pseudomonas aeruginosa-infecting nucleus-forming jumbo phage ΦKZ (280,334 bp; 371 predicted genes), we show that ∼110 genes are fitness-conferring via phage TnSeq, identifying many known and previously unknown essential genes. Moreover, this phage harbors ∼261 non-essential genes, including some capsid and tail proteins, many of which are important for fitness across different clinical isolates or conditions. Phage TnSeq was also extended to a base-modified phage. Together, phage TnSeq is a scalable technology that can identify essential phage genes, generate knockouts in all non-essential genes, and sensitively assign the quantitative fitness contributions of every gene in parallel.","[""Journal Article""]","[""Chan A"", ""Yee WX"", ""Mozumdar D"", ""Kokontis C"", ""Rojas-Montero M"", ""Liu M"", ""Yang Y"", ""Yuping L"", ""Bondy-Denomy J""]",10.1016/j.cell.2026.06.030,Chan A,Cell,0092-8674,15,Cell,eng,Bondy-Denomy J,"[""DNA Transposable Elements"", ""Genome, Viral"", ""Bacteriophages"", ""Pseudomonas aeruginosa"", ""Mutagenesis""]",4810-4824.e7,42492495,pmc-id: PMC13428642;manuscript-id: NIHMS2198040;,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42492495/,Bacteriophage genome-wide transposon mutagenesis,189,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Following its discovery nearly a century ago, the signaling molecule auxin has captured the interest of plant scientists. Mostly through genetics, key components of the auxin response were identified, and these were rapidly connected in a topologically simple nuclear auxin pathway (NAP). While the identification of the NAP established a coherent framework for transcriptional auxin response, recent years have seen a remarkable series of advances in the evolution, mechanisms, and regulation of NAP components that shed new light on auxin response. Furthermore, it has long been known that auxin triggers both rapid and slow responses, but success in NAP characterization has eclipsed insights into rapid responses. Recently, a paradigm for rapid responses has emerged. This involves widespread protein phosphorylation, new roles for NAP components, and a set of contentious, yet resurrected, extracellular auxin-binding proteins. Here, we present recent progress in auxin responses, reflect on their historical context, and formulate a set of pertinent questions for the field.","[""Journal Article"", ""Review""]","[""Chu J"", ""Ang ACH"", ""de Roij M"", ""Strader L"", ""Xu T"", ""Weijers D""]",10.1016/j.cell.2026.06.024,Chu J,Cell,0092-8674,15,Cell,eng,Weijers D,"[""Indoleacetic Acids"", ""Signal Transduction"", ""Phosphorylation"", ""Plant Proteins"", ""Gene Expression Regulation, Plant"", ""Plant Growth Regulators"", ""Arabidopsis"", ""Arabidopsis Proteins""]",4531-4547,42492494,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42492494/,Auxin signaling,189,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Why cancer arises, progresses, or proves fatal in some people but not others remains largely unresolved. Antibody repertoires, including autoantibodies targeting immune pathways, may shape cancer immunosurveillance. Mapping antibody landscapes across cancer-free, at-risk, and cancer-affected individuals could clarify their roles in cancer susceptibility and disease outcome.","[""Journal Article""]","[""Bastard P"", ""Hulett T"", ""Smith-Byrne K"", ""Landegren N"", ""Mogensen TH"", ""Fellay J"", ""Travis RC"", ""Casanova JL"", ""Dang CV"", ""Lu X""]",10.1016/j.cell.2026.06.021,Bastard P,Cell,0092-8674,15,Cell,eng,Lu X,"[""Humans"", ""Neoplasms"", ""Autoantibodies"", ""Animals"", ""Immunologic Surveillance""]",4525-4530,42492493,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42492493/,Do autoantibodies shape cancer immunosurveillance?,189,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Smartphone-wielding citizen scientists and an AI called FLORIST are transforming ecology at the continental scale. In this issue of Cell, when Tibbs-Cortes et al. pair the crowdsourced data with controlled genetics, they discover how switchgrass times its flowering to outwit both frost and heat, depending on latitude.","[""Journal Article"", ""Comment""]","[""Hudson ME"", ""Battu G""]",10.1016/j.cell.2026.07.002,Hudson ME,Cell,0092-8674,15,Cell,eng,Battu G,"[""Citizen Science"", ""Panicum"", ""Flowers""]",4522-4524,42492492,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42492492/,The silicon citizen naturalist,189,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"How do cells ensure that complex, multidomain proteins fold correctly? Luo et al. reveal a self-contained solution. The 3' UTR of an mRNA co-translationally chaperones the protein it encodes, preventing intrinsically disordered regions from making inappropriate contacts. This functionality, localized to mesh-like condensates, challenges Anfinsen's dogma and opens therapeutic possibilities.","[""Journal Article"", ""Comment""]","[""Linsenmeier M"", ""Shorter J""]",10.1016/j.cell.2026.06.023,Linsenmeier M,Cell,0092-8674,15,Cell,eng,Shorter J,"[""Molecular Chaperones"", ""Intrinsically Disordered Proteins"", ""3' Untranslated Regions"", ""Humans"", ""Animals"", ""Protein Folding"", ""RNA, Messenger""]",4519-4521,42492491,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42492491/,UTR-ly unexpected: RNA chaperones tame intrinsically disordered proteins,189,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"The intrinsic cardiac nervous system (ICNS) is a key node in heart-brain communication and an emerging target for cardiac therapy, yet its physiological importance and functional organization remain poorly understood. Here, we show that the ICNS is essential for cardiac performance and survival across conditions. Using integrated genetic and imaging approaches in mice, we identify two molecularly distinct intrinsic cardiac neuron (ICN) subtypes that differ in extrinsic inputs, projection architectures, and physiological roles. Npy⁺ ICNs preferentially receive vagal input and mediate parasympathetic control of heart rate and coronary perfusion, and their ablation leads to fatal cardiac failure. By contrast, Ddah1⁺ ICNs receive sympathetic input and are required to preserve electrical stability and prevent sudden cardiac arrest under extreme physiological or psychological stress, with their activation providing cardioprotection. Together, these findings establish the ICNS as a critical regulator of cardiac function, providing a framework for precise, cell-type-targeted neuromodulatory therapies.","[""Journal Article""]","[""Xu QJ"", ""Applegate MC"", ""Hsu IY"", ""Kogan RP"", ""Hafez OA"", ""Wang RL"", ""Rios Coronado PE"", ""Young LH"", ""Zeng X"", ""Zhang L"", ""Chang RB""]",10.1016/j.cell.2026.06.040,Xu QJ,Cell,0092-8674,,Cell,eng,Chang RB,[],,42486084,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42486084/,The intrinsic cardiac nervous system is essential for cardiac function and survival,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Genes that define cell identity are often highly transcribed, but how their activity is regulated to prevent pathological dysregulation remains elusive. Using a two-tiered genetic screen, we identify a network of genes regulating hypertranscribed loci, which is notably enriched for genes mutated in developmental disorders. Among these, ANKRD11, a chromatin regulator haploinsufficient in KBG syndrome, exerts progressively stronger repression on more highly transcribed genes. ANKRD11 enriches around hypertranscribed loci and forms biomolecular condensates via charge-block-patterned intrinsically disordered regions. These condensates spatially sequester elongation factors away from RNA polymerase II, thereby restricting transcription elongation. In mice, Ankrd11 loss abrogates this restriction, causing aberrant developmental gene activation, disrupted organogenesis, and embryonic lethality. Critically, KBG patient cells with ANKRD11 mutations show defective condensate formation and consequent overactivation of hypertranscribed genes. These results uncover a condensate-mediated mechanism that restricts hypertranscribed genes and suggest its disruption underlies developmental disorders such as KBG syndrome.","[""Journal Article""]","[""Zhang T"", ""Li X"", ""Zhou W"", ""Li ZL"", ""Bi J"", ""Ma X"", ""Li X"", ""Fan Y"", ""Hong Y"", ""Wang S"", ""Wang Y"", ""Yang L"", ""Chen Y"", ""Qin W"", ""Wang H"", ""Xi Q"", ""Shi S"", ""Liu N""]",10.1016/j.cell.2026.07.006,Zhang T,Cell,0092-8674,,Cell,eng,Liu N,[],,42486083,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42486083/,Condensates of the chromatin regulator ANKRD11 restrict hypertranscribed genes to safeguard development,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Protein-protein interactions underlie biological complexity, and modeling their coevolution is essential for characterizing and engineering molecular assemblies. While protein and genomic language models have excelled at modeling individual proteins, extending these capabilities to protein complexes remains challenging. We present multiple sequence alignment (MSA) Pairformer, a protein language model that builds on AlphaFold2/3's bidirectional refinement between sequence and pairwise residue representations to accurately model the evolution of protein-protein interactions, despite training exclusively on individual chains. MSA Pairformer achieves nearly 3-fold improvement over existing methods in predicting protein-protein interface contacts and better distinguishes binding from non-binding sequences. A learned attention mechanism selectively weights sequences by their inferred evolutionary relevance, enabling discovery of subfamily-specific contacts. On single-protein benchmarks, it achieves state-of-the-art contact prediction and strong variant effect prediction using only 111 million parameters, over two orders of magnitude smaller than frontier models. These results offer an evolutionarily grounded, computationally efficient alternative to the scaling paradigm.","[""Journal Article""]","[""Akiyama Y"", ""Zhang Z"", ""Tang O"", ""Kim RS"", ""Mirdita M"", ""Steinegger M"", ""Ovchinnikov S""]",10.1016/j.cell.2026.06.029,Akiyama Y,Cell,0092-8674,,Cell,eng,Ovchinnikov S,[],,42480528,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42480528/,Expanding the scope of protein language modeling to protein-protein interactions with MSA Pairformer,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"B cell-depleting therapies are effective in multiple sclerosis (MS), yet some patients relapse, underscoring the need for more precise interventions. To identify new therapeutic targets, we generated a single-cell RNA sequencing (scRNA-seq) atlas of cerebrospinal fluid (CSF), brain, and blood from non-inflammatory controls and patients with MS or other neuroinflammatory diseases. We found disease-associated enrichment of class-switched immunoglobulin G+ (IgG+) B cells and plasma cells in MS CSF. Unbiased analysis identified a rare disease-enriched subset of activated, T cell receptor (TCR)-restricted, PD-1+ T follicular helper-like cells with B cell-recruiting features. To target this population, we developed PD-1-directed chimeric antigen receptor (CAR) T cells that selectively depleted pathogenic PD-1+ CD4 T cells and locally released IL-10. This strategy attenuated central nervous system (CNS) inflammation, reprogrammed the local immune milieu, and improved clinical outcomes across murine neuroinflammation models. These findings define a CNS-localized adaptive immune circuit in MS and nominate programmable PD-1 CAR T cells as a strategy to disrupt it.","[""Journal Article""]","[""Shalita R"", ""Ben Yehuda M"", ""Gur C"", ""Frid Y"", ""McGrath S"", ""Suhler R"", ""Bolokan L"", ""Eisenberg V"", ""Eshed RS"", ""Shlomi-Loubaton S"", ""Tofield A"", ""Vardy K"", ""Zada M"", ""Kurilovich A"", ""David E"", ""Jaitin D"", ""Mazuz K"", ""Avellino R"", ""Tzemach R"", ""Kuznetsov Y"", ""Fellus-Alyagor L"", ""Levy-Barda A"", ""Mundt S"", ""Rosenzweig R"", ""Schreiner B"", ""Peters A"", ""Stadelmann C"", ""Zwicky P"", ""Yarkoni AW"", ""Ingelfinger F"", ""Amit I""]",10.1016/j.cell.2026.06.036,Shalita R,Cell,0092-8674,,Cell,eng,Amit I,[],,42480527,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42480527/,Localized PD-1 CAR T therapy reprograms neuroinflammation,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Meningeal (dural) lymphatics are essential for cerebrospinal fluid (CSF) clearance to cervical lymph nodes, yet the precise pathway is incompletely understood. Using a multifaceted approach in mice, we examined tracer dynamics and the CSF outflow pathway from the subarachnoid space (SAS) to the nasal mucosa and identified a discrete arachnoid region surrounding the olfactory bulbs with abundant fenestrations. Similar arachnoid fenestrations were found in cynomolgus monkeys. Fluorescent tracers in the SAS passed through arachnoid fenestrations into dural lymphatics, which traversed the cribriform plate foramina, joined the nasal lymphatics, and drained to the cervical lymph nodes. In aged mice, the known reduction in CSF outflow was accompanied by lymphatic atrophy in the olfactory dura and nasal mucosa and by fewer arachnoid fenestrations and smaller cribriform plate foramina. Importantly, the lymphatics and CSF clearance were restored to normal by intranasal delivery of vascular endothelial growth factor-C (VEGF-C), thereby documenting the reversibility of the aging-related impairment in CSF clearance.","[""Journal Article""]","[""Hong SP"", ""Jin C"", ""Yang MJ"", ""Jin H"", ""Yoon JH"", ""Choi DR"", ""Jung J"", ""Yuk CM"", ""Antila S"", ""Seo SJ"", ""Admasu LA"", ""Seo J"", ""Lim KS"", ""Chung WS"", ""Alitalo K"", ""McDonald DM"", ""Koh GY""]",10.1016/j.cell.2026.06.035,Hong SP,Cell,0092-8674,,Cell,eng,Koh GY,[],,42480526,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42480526/,CSF clearance through arachnoid fenestrations to olfactory meningeal lymphatics,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Crop yield is fundamentally determined by the harvest index, the proportion of photosynthates allocated to grain. However, its genetic and evolutionary basis remains elusive. Here, we show that the maize harvest index increased by 81% during domestication. A major locus, Harvest Index1 (HI1), contributes to this divergence and is controlled by a 9.1-kb presence/absence variation. This insertion acts as a distant enhancer to boost the expression of the downstream B-type response regulator BRR1 and was fixed by selection. Mechanistically, the transcription factor CONZ1 binds to both the HI1 enhancer and the BRR1 promoter, recruiting the acetyltransferase General Control Nonrepressed 5 (GCN5) to form a chromatin loop that enhances BRR1 expression. BRR1 directly activates genes involved in carbon and nitrogen metabolism and transport, promoting source-to-sink allocation to increase harvest index and grain yield even under nitrogen-limiting conditions. Our findings elucidate a key domestication-selected regulatory module that coordinates resource allocation, providing a strategic target for sustainable crop improvement.","[""Journal Article""]","[""Guo L"", ""Xia J"", ""Tang J"", ""Zhang M"", ""Chen T"", ""Han X"", ""Liu S"", ""Wang X"", ""Wu L"", ""Tian F""]",10.1016/j.cell.2026.06.038,Guo L,Cell,0092-8674,,Cell,eng,Tian F,[],,42480525,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42480525/,A domestication-selected enhancer coordinates source-sink balance to improve harvest index and yield in maize,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"While gasdermin (GSDM)-mediated pyroptosis is a potent immune effector, its antiviral potential remains largely untapped. Here, we introduce viral protease-initiated lytic cell death (VID), a universal mRNA therapeutic platform inspired by the modular architecture of GSDM and the clinical success of mRNA vaccines. By engineering gasdermin-D (GSDMD) to harbor viral protease-specific cleavage motifs, we generated VID activators (VIDAs) that selectively trigger lytic cell death in virus-infected cells. Using hepatitis A virus (HAV) as a model, lipid nanoparticle (LNP)-encapsulated VIDA mRNA abolished viral replication and shedding in vivo and mitigated liver injury through a coordinated ""kill-and-alert"" mechanism that primes bystander immunity. The platform's versatility was further demonstrated against Zika virus (ZIKV) and SARS-CoV-2. Leveraging a generative artificial intelligence (AI) framework, we designed de novo cleavage motifs for the SARS-CoV-2 main protease, yielding optimized VIDAs with superior antiviral potency. Collectively, our study establishes VIDA mRNA as a versatile, broadly applicable strategy for combating diverse viral threats.","[""Journal Article""]","[""Li L"", ""Yan XL"", ""Wang HY"", ""Zhou HY"", ""Li YY"", ""Ma W"", ""Li J"", ""Zhang RR"", ""Lv L"", ""Huang XY"", ""Du H"", ""Cao TS"", ""Ye Q"", ""Zhao H"", ""Fu Y"", ""Kang BH"", ""Ding Q"", ""Wu A"", ""Huang YJ"", ""Qin CF""]",10.1016/j.cell.2026.06.031,Li L,Cell,0092-8674,,Cell,eng,Qin CF,[],,42476130,,2026 Jul 20,2026,https://pubmed.ncbi.nlm.nih.gov/42476130/,Viral protease-initiated lytic cell death as a universal antiviral mRNA therapy,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Developing cancer therapies that induce specific death of malignant cells is critical for preventing relapse. Highly effective strategies, such as immunotherapy, exemplify this principle. Here, we provide the mechanistic basis for a small-molecule approach that leverages chemically induced proximity (CIP) to kill diffuse large B cell lymphoma, the most common non-Hodgkin lymphoma. We developed lysine acetyltransferase (KAT)-based TCIPs (transcriptional/epigenetic chemical inducers of proximity), or KAT-TCIPs, which redirect p300/CREB-binding protein (CBP) to activate cell-death networks repressed by the oncogenic driver BCL6. Our lead KAT-TCIP reprograms the epigenome to initiate apoptosis. The crystal structure of the chemically induced p300-BCL6 complex reveals how chance protein-protein interactions may be exploited to confer the potency and selectivity of KAT-TCIPs. Thus, oncogenic drivers can be co-opted to activate robust cell death. Consistent with their gain-of-function mechanism, TCIPs recruiting different transcriptional activators-p300, BRD4, or CDK9-produce distinct genomic responses, suggesting specialized therapeutic uses.","[""Journal Article""]","[""Nix MN"", ""Gourisankar S"", ""Bowman KJ"", ""Nettles SA"", ""Yang H"", ""Dwyer BG"", ""Sarott RC"", ""Abuzaid H"", ""Martinez MM"", ""Phillips N"", ""Cabaud V"", ""Hakobyan A"", ""Arakelov V"", ""Petrosyan G"", ""Davtyan A"", ""Wang Y"", ""Simanauskaite JM"", ""Romero BA"", ""Jones HM"", ""Krokhotin A"", ""Lowensohn TN"", ""Chen L"", ""Low C"", ""Vogel H"", ""Davis MM"", ""Fernandez D"", ""Zhang T"", ""Green MR"", ""Hinshaw SM"", ""Gray NS"", ""Crabtree GR""]",10.1016/j.cell.2026.06.037,Nix MN,Cell,0092-8674,,Cell,eng,Crabtree GR,[],,42476129,,2026 Jul 20,2026,https://pubmed.ncbi.nlm.nih.gov/42476129/,A bivalent molecular glue linking lysine acetyltransferases to oncogene-induced cell death,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Enhancers are abundant and critical gene-distal cis-regulatory elements with distinct architectural features; however, a mechanistic understanding of their interactions within endogenous chromatin contexts remains challenging. Here, we developed a recombinase-mediated genome-rewriting platform to explore how a long-range human enhancer, eNMU, confers a remarkable 10,000-fold activation of its target gene, Neuromedin U (NMU), at its native locus. Our systematic dissection reveals two functionally distinct sub-elements of eNMU: the canonical autonomous enhancer e1 and the intrinsically inactive facilitator e2, which dramatically augments e1's activity. The autonomous enhancer e1 is functionally hierarchical to e2, additional facilitators, and the NMU promoter across the ∼100-kb NMU-eNMU region, and it orchestrates the formation of a 3D regulatory hub. e1 also harbors a bipartite structure: a divergently transcribed retroviral long terminal repeat (LTR) enhancer and an adjacent LTR promoter that dampens NMU expression. We explore and discuss the broader implications of our focused study for understanding enhancer regulatory mechanisms genome-wide.","[""Journal Article""]","[""Zhou Z"", ""Cheng Y"", ""Lieberth J"", ""Zhang J"", ""Jin Y"", ""Li A"", ""Yu H"", ""Ozer A"", ""Lis JT""]",10.1016/j.cell.2026.06.033,Zhou Z,Cell,0092-8674,,Cell,eng,Lis JT,[],,42468524,,2026 Jul 17,2026,https://pubmed.ncbi.nlm.nih.gov/42468524/,"Robust regulatory interplay of enhancers, facilitators, and promoters in a native chromatin context",,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Peripheral nerves regulate skin homeostasis by secreting neurotransmitters, but their role during skin aging remains incompletely understood. Here, we report that cutaneous denervation accelerates skin aging, as evidenced by collagen reduction. Neurofilament heavy chain (Nefh) is decreased in aged skin and is predominantly expressed in vesicular glutamate transporter 2-positive (Vglut2+) skin-innervating glutamatergic neurons. Notably, dermal fibroblasts, the primary producers of collagen, frequently contact Nefh+ nerve fibers. Moreover, Nefh deletion in Vglut2+ glutamatergic neurons drives skin fibroblast senescence and collagen loss, whereas additional glutamate improves skin aging phenotypes. Mechanistically, cyclin-dependent kinase 5 (Cdk5) interacts with both Nefh and Vglut2 and maintains glutamate release and collagen homeostasis. Additionally, in skin fibroblasts, solute carrier family 1 member 3 (Slc1a3) governs the collagen-promoting and anti-senescence functions of glutamate. Together, these findings reveal Nefh-mediated glutamatergic neuromodulation of skin aging and provide therapeutic targets for aging-related skin disorders.","[""Journal Article""]","[""Wang Z"", ""Jin X"", ""Wu Y"", ""Ding W"", ""Zhang F"", ""Sun Y"", ""Lou F"", ""Bai J"", ""Yang X"", ""Zhou H"", ""Liang J"", ""Cai X"", ""Li Y"", ""Zheng X"", ""Han J"", ""Tong F"", ""Yang Q"", ""Fang Z"", ""Zhao L"", ""Shen Q"", ""Xu Z"", ""Deng S"", ""Fan L"", ""Tong J"", ""Tong L"", ""Wang J"", ""Gao M"", ""Fang Z"", ""Li Q"", ""Chen R"", ""Huang L"", ""Li Z"", ""Yang Y"", ""Zou J"", ""Wu Y"", ""Zhang X"", ""Wang H""]",10.1016/j.cell.2026.06.032,Wang Z,Cell,0092-8674,,Cell,eng,Wang H,[],,42468523,,2026 Jul 17,2026,https://pubmed.ncbi.nlm.nih.gov/42468523/,Skin-innervating glutamatergic neurons modulate aging,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Boron (B) is an essential plant micronutrient whose deficiency impairs global crop yields. Glycosylinositol phosphorylceramides (GIPCs) are major lipids in the plasma membrane (PM), and PIN-FORMED (PIN) proteins mediate polar auxin transport (PAT) via asymmetric PM localization. This study demonstrates that these components are functionally linked: B cross-links nearly all GIPC series, forming physical PM-cell wall attachments visualized as Hechtian strands. B-mediated cross-linking also restricts PIN2 lateral diffusion and endocytosis, stabilizing its polar domain formation via direct GIPC-PIN2 interaction. Phenotypic evidence supports this mechanism, as both B deficiency and impaired GIPC biosynthesis phenocopy high-order pin mutants, showing defective PIN localization and diminished auxin maxima. Thus, the B-dependent, GIPC-mediated PM-cell wall continuum immobilizes PIN polar domains, enabling PAT and ensuring proper plant development and environmental adaptation.","[""Journal Article""]","[""He M"", ""Zhang C"", ""Li Z"", ""Tang C"", ""Wang Y"", ""Jiao Y""]",10.1016/j.cell.2026.06.028,He M,Cell,0092-8674,,Cell,eng,Jiao Y,[],,42462711,,2026 Jul 16,2026,https://pubmed.ncbi.nlm.nih.gov/42462711/,Boron-bridged GIPCs stabilize cell wall anchoring and PIN polar domains,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Cell and tissue functions arise from complex interactions among numerous genes, and a systematic understanding of these functions requires isoform-resolved transcriptomic analysis of single cells with high spatial resolution. Here, we introduce an in situ RNA amplification method and its integration with multiplexed error-robust fluorescence in situ hybridization (MERFISH) to detect short RNA sequences and enable whole-transcriptome-scale, isoform-resolved spatial transcriptomics of individual cells in intact tissues. Using this approach, we imaged ∼33,000 distinct RNAs-including ∼23,000 genes and ∼10,000 isoforms-in the mouse brain. Our data enabled systematic analyses of region- and cell-type-specific gene programs and ligand-receptor-based cell-cell communications. These data further revealed rich spatial diversity and cell-type specificity in isoform usage across numerous genes, as well as brain structures particularly rich in isoform specificity. We anticipate broad application of this method for characterizing the molecular and cellular basis of tissue functions, unlocking previously inaccessible discoveries in cell and organismal biology.","[""Journal Article""]","[""Cohen L"", ""Halpern AR"", ""Blosser TR"", ""Che ZP"", ""Pan X"", ""Zhuang X""]",10.1016/j.cell.2026.06.027,Cohen L,Cell,0092-8674,,Cell,eng,Zhuang X,[],,42462710,,2026 Jul 16,2026,https://pubmed.ncbi.nlm.nih.gov/42462710/,Whole-transcriptome-scale isoform-resolved spatial imaging of single cells in tissues,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Spatial profiling of proteins and protein interactions facilitates understanding of cell functions within tissues and is essential for studies in signaling, immunity, and cancer. We present spatial proximity sequencing (Sprox-seq) for simultaneous profiling of surface proteins, protein complexes, and mRNAs, recording the tissue location of each molecule. Sprox-seq profiled 32 proteins, 528 pairwise interactions, and thousands of mRNAs with spatial resolution across human tonsils and germinal centers. Mapping tissue-wide protein interactions recapitulated RNA-defined tissue architecture but also revealed higher interaction complexity in the light zone. Protein-interaction trajectories uncovered a B cell state transition distinct from that inferred by RNA. Integrated protein-complex and mRNA analysis related spatially enriched complexes with mitotic pathways. Sprox-seq captured cell-cell interactions, such as B cell-follicular dendritic cell interactions mediated by the receptor complex VLA-4-VCAM1. Sprox-seq provides a spatially resolved multi-modal view of cell states and an integrated study of protein and cellular interactions across tissues.","[""Journal Article""]","[""Wang H"", ""Xia J"", ""Rahman PMSM"", ""Keisham B"", ""Padhi A"", ""Deng Y"", ""Li Y"", ""Vistain L"", ""Kim S"", ""Mercado-Vásquez G"", ""Khan AA"", ""Clark MR"", ""Tay S""]",10.1016/j.cell.2026.06.034,Wang H,Cell,0092-8674,,Cell,eng,Tay S,[],,42462709,,2026 Jul 16,2026,https://pubmed.ncbi.nlm.nih.gov/42462709/,Spatial proximity sequencing maps developmental dynamics in the germinal center,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Spliceosomal introns impose a universal processing burden on eukaryotes and obstruct genome minimization because their essentiality remains unresolved. By exploiting Spo11-independent meiosis in synthetic single-chromosome Saccharomyces cerevisiae, the complete deletion of all 300 spliceosomal introns was achieved, generating an intron-free strain, SYNE27α. Whole-genome sequencing confirmed precise excision. Unexpectedly, spliceosomal components (all five small nuclear RNAs [snRNAs], Prp8, Prp9, Prp19, Yhc1, and Luc7) were no longer required for viability, demonstrating that a eukaryotic cell can exist independently of spliceosomal function. U3 small nucleolar RNA (snoRNA) splicing bypassed the requirements for Yhc1, Luc7, Prp9, and Prp19, revealing a mechanistic divergence from pre-mRNA splicing. Cumulative intron loss caused slow growth via ribosomal dysregulation, yet SYNE27α maintained genetic stability. Fitness costs were fully recessive in diploids, confirming intron loss as the primary driver. These findings establish an intron-free, spliceosome-independent eukaryote, resolving the essential function of the spliceosome and enabling minimal-system studies of genome evolution.","[""Journal Article""]","[""Man X"", ""Zhang WT"", ""Zhang YD"", ""Li QX"", ""Dai P"", ""Jiang W"", ""Zhou JQ""]",10.1016/j.cell.2026.05.033,Man X,Cell,0092-8674,15,Cell,eng,Zhou JQ,"[""Introns"", ""Spliceosomes"", ""Saccharomyces cerevisiae"", ""Saccharomyces cerevisiae Proteins"", ""RNA Splicing"", ""Meiosis""]",4637-4649.e5,42456655,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42456655/,A spliceosome-independent eukaryote generated by complete intron removal,189,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Alzheimer's disease (AD) remains the leading cause of dementia worldwide and an escalating global health crisis. The hallmark amyloid plaques and neurofibrillary tangles (NFT) are now known to be accompanied by a complex array of pathologies that culminate in neurodegeneration and cognitive decline. New disease-modifying therapies for AD can now slow cognitive decline through the removal of amyloid plaques from the brain, but treatments to stop or prevent cognitive impairment remain elusive. In this review, we summarize the most recent updates in AD research on pathologic disease mechanisms and therapeutic strategies, highlighting advancements in apolipoprotein E (APOE) biology, neuroimmunology, biomarker discovery, and initial experience with new disease-modifying therapies. These important discoveries are revolutionizing AD diagnosis and treatment and provide hope for a future where AD is not only treatable but also preventable.","[""Journal Article"", ""Review""]","[""Rudman MD"", ""Ulrich JD"", ""Holtzman DM""]",10.1016/j.cell.2026.06.006,Rudman MD,Cell,0092-8674,14,Cell,eng,Holtzman DM,"[""Alzheimer Disease"", ""Humans"", ""Animals"", ""Apolipoproteins E"", ""Plaque, Amyloid"", ""Amyloid beta-Peptides""]",4193-4224,42425064,pmc-id: PMC13361001;manuscript-id: NIHMS2184915;,2026 Jul 9,2026,https://pubmed.ncbi.nlm.nih.gov/42425064/,Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies,189,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Human aging is a heterogeneous, multi-system process that spans molecular, tissue, and physiological decline. In this issue of Cell, Li et al. integrate clinical data, multi-omics, and organ-associated signatures to construct a multi-layer framework for quantifying biological aging across scales.","[""Journal Article"", ""Comment""]","[""Koyuncu S"", ""Petrovic D"", ""Vilchez D""]",10.1016/j.cell.2026.06.018,Koyuncu S,Cell,0092-8674,14,Cell,eng,Vilchez D,"[""Humans"", ""Aging"", ""Multiomics""]",4190-4192,42425063,,2026 Jul 9,2026,https://pubmed.ncbi.nlm.nih.gov/42425063/,Bridging omics and physiology to build multimodal clocks of human aging,189,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"In this issue of Cell, Guo et al. report the development of a new exon-skipping, RNA-editing-based therapy for Duchenne muscular dystrophy. The dual mechanism of action through both ADAR-dependent and -independent pathways has the potential to be more effective and require a lower dosing frequency than currently available ASO-based exon-skipping treatments.","[""Journal Article"", ""Comment""]","[""Gonzalez-Perez P"", ""Blackstone C""]",10.1016/j.cell.2026.06.011,Gonzalez-Perez P,Cell,0092-8674,14,Cell,eng,Blackstone C,"[""Muscular Dystrophy, Duchenne"", ""Humans"", ""Exons"", ""RNA Editing"", ""Animals"", ""Adenosine Deaminase"", ""Genetic Therapy"", ""RNA-Binding Proteins"", ""Oligonucleotides, Antisense""]",4188-4189,42425062,,2026 Jul 9,2026,https://pubmed.ncbi.nlm.nih.gov/42425062/,Rewriting Duchenne muscular dystrophy therapy,189,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Mammalian eyes receive constant visible light yet lack photosynthesis. Xing et al. engineer an intact thylakoid grana nanoparticle enabling light-driven NADPH production within corneal cells, restoring antioxidant defenses and interrupting inflammatory cycles in dry eye disease. This work positions borrowed photosynthesis as a therapeutic strategy for oxidative, light-exposed tissue pathologies.","[""Journal Article"", ""Comment""]","[""Saiding Q"", ""Xie T"", ""Tao W""]",10.1016/j.cell.2026.05.001,Saiding Q,Cell,0092-8674,14,Cell,eng,Tao W,"[""Photosynthesis"", ""Animals"", ""Humans"", ""Thylakoids"", ""NADP"", ""Nanoparticles""]",4185-4187,42425061,,2026 Jul 9,2026,https://pubmed.ncbi.nlm.nih.gov/42425061/,Photosynthetic medicine: Engineering a plant-derived nanofoundry to power mammalian cells,189,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Visual behavior requires coordinated activity across hierarchically organized brain circuits. Understanding this complexity demands datasets that are both large-scale (sampling many areas) and dense (recording many neurons in each area). Here, we present a database of spiking activity across the mouse visual system-including the cortex, thalamus, and midbrain-while mice perform an image change detection task. Using Neuropixels probes, we record from >75,000 high-quality units in 54 mice, mapping area-, cortical-layer-, and cell-type-specific coding of sensory and motor information. Modulation by task engagement increased across the thalamocortical hierarchy but was strongest in the midbrain. Novel images recruited an expanded cortical population and modulated late cortical (but not thalamic) responses. Population decoding and optogenetics identified a critical time window for change detection and were consistent with mice using an adaptation-based rather than image-comparison strategy. This comprehensive resource provides a valuable substrate for understanding sensorimotor computations in neural networks.","[""Journal Article""]","[""Bennett C"", ""Gale SD"", ""Heller G"", ""Ramirez TK"", ""Belski H"", ""Piet A"", ""Zobeiri O"", ""Amster A"", ""Arkhipov A"", ""Cahoon A"", ""Caldejon S"", ""Carlson M"", ""Casal L"", ""Daniel SF"", ""Farrell C"", ""Garrett M"", ""Gillis R"", ""Grasso C"", ""Hardcastle BJ"", ""Hytnen R"", ""Johnson T"", ""Ledochowitsch P"", ""L'Heureux Q"", ""Mastrovito D"", ""McBride EG"", ""Mihalas S"", ""Mochizuki C"", ""Morrison CB"", ""Nayan C"", ""Ngo NK"", ""North K"", ""Ollerenshaw DR"", ""Ouellette B"", ""Rhoads P"", ""Ronellenfitch K"", ""Schroedter M"", ""Siegle JH"", ""Slaughterbeck C"", ""Sullivan D"", ""Swapp J"", ""Taormina M"", ""Wakeman W"", ""Waughman X"", ""Williford A"", ""Phillips JW"", ""Groblewski PA"", ""Durand S"", ""Koch C"", ""Olsen SR""]",10.1016/j.cell.2026.06.025,Bennett C,Cell,0092-8674,15,Cell,eng,Olsen SR,"[""Animals"", ""Mice"", ""Visual Cortex"", ""Neurons"", ""Optogenetics"", ""Mice, Inbred C57BL"", ""Action Potentials"", ""Thalamus"", ""Brain Mapping"", ""Male"", ""Mesencephalon"", ""Visual Perception"", ""Female"", ""Photic Stimulation""]",4775-4791.e13,42419303,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42419303/,Map of spiking activity underlying change detection in the mouse visual system,189,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Virological research has traditionally focused on individual viruses or viral families. Advances in DNA synthesis now allow large-scale construction of individual gene products, enabling systematic exploration of the virome. Here, we developed a barcoded library of ∼12,000 viral open reading frames (vORFs) from 513 viral species, which we leveraged to identify hundreds of viral regulators of cellular proliferation, MHC class I antigen presentation, and interferon signaling. Integrating results across these screens revealed unique phenotypic profiles and functional vORF modules, allowing the in-depth characterization of two previously uncharacterized viral proteins, MC162R and Yaba-like disease virus (YLDV) 151R, which impair MHC class I antigen presentation and interferon (IFN)-β signaling, respectively. Together, the viral ORFeome provides a scalable framework for dissecting viral protein function across the breadth of the virome.","[""Journal Article""]","[""Fujimura E"", ""O'Leary CN"", ""Li MZ"", ""Roberts RA"", ""Glassman CR"", ""Paulo JA"", ""Jiang H"", ""Abdelfattah NS"", ""Wooten EC"", ""Mirman Z"", ""Harper JW"", ""Cole PA"", ""Elledge SJ""]",10.1016/j.cell.2026.05.024,Fujimura E,Cell,0092-8674,,Cell,eng,Elledge SJ,[],,42392077,pmc-id: PMC13429030;manuscript-id: NIHMS2180536;,2026 Jun 30,2026,https://pubmed.ncbi.nlm.nih.gov/42392077/,A viral ORFeome library for systems-level genetic dissection of host-pathogen interactions,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Endosymbiosis has spurred the evolution of new organelles across life. Corals and other cnidarians have repeatedly evolved an organelle, called the symbiosome, which houses intracellular algal symbionts. However, the molecular mechanisms enabling this repeated evolution remain unclear. Using the sea anemone Aiptasia, we generated a high-quality proteome of the symbiosome, revealing protein trafficking mechanisms and the types of biomolecules exchanged during symbiosis. Symbiosomal enrichment of lysosomal proteins, visualization of lysosomal fusion, and reduced symbiosis following knockdown of lysosomal genes indicate that the symbiosome functions through extensive co-option of lysosomal proteins. We identified a symbiosomal bicarbonate/sulfate transporter, SLC26A11, and showed through CRISPR/Cas9 mutagenesis that this lysosomal transporter is required for symbiosis in Aiptasia and a reef-building coral. Together, these findings reveal that corals and anemones have repeatedly co-opted lysosomal proteins to concentrate carbon and shuttle metabolites to support photosymbiosis, providing a relatively simple path for the repeated evolution of new photosymbioses.","[""Journal Article""]","[""Maruyama S"", ""Henderson CF"", ""Swinhoe N"", ""Kowalewski GP"", ""Meier EK"", ""Engelke TR"", ""Cleves PA""]",10.1016/j.cell.2026.06.015,Maruyama S,Cell,0092-8674,,Cell,eng,Cleves PA,[],,42385704,,2026 Jul 1,2026,https://pubmed.ncbi.nlm.nih.gov/42385704/,Co-option of lysosomal machinery shapes the evolution of the intracellular photosymbiosis supporting coral reefs,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"In settings of persistent (self or foreign) antigen, such as autoimmunity and chronic infection, immune responses are sustained by stem-like T cells. Although TCF1 has emerged as a key transcription factor (TF) associated with stemness, the TCF1hi population is heterogeneous, raising the question of whether TCF1 exclusively defines the stem T cell (TSC) pool. Using preclinical models of autoimmune type 1 diabetes and chronic infection, we discover that a small subset of TCF1hi T cells express the TF LEF1. LEF1+ TCF1hi T cells define a true self-renewing TSC pool. TSC give rise to LEF1- TCF1hi progenitor T cells (TPRO), which lack stem functions and generate terminally differentiated TCF1lo T cells (TDIFF) (TSC→TPRO→TDIFF). We show that LEF1 is essential for T cell stemness. Autoimmune and exhausted LEF1+ TSC share a unique epigenetically encoded core program enriched for genes and pathways characteristic of embryonic and adult stem cells, including WNT/β-catenin and Notch signaling. Spatial positioning, niche signals, and migration regulate stem-cell fate; accordingly, targeting integrins or Notch signaling impairs T cell stemness and prevents disease. Our studies identify LEF1 and niche-derived factors as fundamental regulators of T cell stemness across chronic diseases.","[""Journal Article""]","[""Miakicheva S"", ""Hawley KM"", ""Zumbo P"", ""Gearty SV"", ""Grassmann S"", ""Naizir B"", ""Chiu E"", ""Carson S"", ""Kissner M"", ""Owyong M"", ""Zhang Y"", ""Washburn R"", ""Sun JC"", ""Chaligné R"", ""Reiner SL"", ""Maillard I"", ""Betel D"", ""Schietinger A""]",10.1016/j.cell.2026.06.022,Miakicheva S,Cell,0092-8674,14,Cell,eng,Schietinger A,"[""Lymphoid Enhancer-Binding Factor 1"", ""Animals"", ""Mice"", ""Diabetes Mellitus, Type 1"", ""Chronic Disease"", ""Stem Cell Niche"", ""T-Lymphocytes"", ""Hepatocyte Nuclear Factor 1-alpha"", ""Cell Differentiation"", ""Stem Cells"", ""Humans""]",4325-4341.e10,42385703,,2026 Jul 9,2026,https://pubmed.ncbi.nlm.nih.gov/42385703/,LEF1 and niche factors determine T cell stemness across chronic diseases,189,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD) represent two major categories of neurodegenerative disorders-TAR DNA-binding protein 43 (TDP-43) and tau proteinopathies-for which the mechanisms driving neuronal death remain unclear. Single-cell whole-genome sequencing of 469 neurons from C9ORF72 ALS, C9ORF72 FTD, AD, and control brains revealed increased somatic single-nucleotide variants (sSNVs) and insertions/deletions (sIndels) in all three diseases. Mutational signature analysis identified a disease-associated sSNV signature consistent with oxidative damage and an sIndel process affecting 22% of ALS, 76% of FTD, and 61% of AD neurons-but only 2% of control neurons-resembling signature ID4, previously linked to topoisomerase 1 (TOP1)-mediated mutagenesis. Rapid approach to DNA adduct recovery (RADAR) assays confirmed increased TOP1-DNA covalent complexes, and duplex sequencing confirmed the increased sIndels and identified single-strand events as likely precursor lesions. TOP1-associated sIndel mutagenesis and genome instability thus represent a mechanism shared by both TDP-43 and tau neurodegeneration.","[""Journal Article""]","[""Zhou Z"", ""Luquette LJ"", ""Dong G"", ""Kim J"", ""Ku J"", ""Kim K"", ""Ramesh N"", ""Bae M"", ""Caplin A"", ""Shao DD"", ""Sahile B"", ""Essuman K"", ""Goodman E"", ""Miller MB"", ""Huang AY"", ""Nathan WJ"", ""Nussenzweig A"", ""Park PJ"", ""Lagier-Tourenne C"", ""Lee EA"", ""Walsh CA""]",10.1016/j.cell.2026.06.013,Zhou Z,Cell,0092-8674,,Cell,eng,Walsh CA,[],,42385702,pmc-id: PMC13340254;manuscript-id: NIHMS2188418;,2026 Jul 1,2026,https://pubmed.ncbi.nlm.nih.gov/42385702/,Recurrent patterns of TOP1-mediated neuronal genomic damage shared by major neurodegenerative disorders,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Understanding organ formation requires capturing molecular information simultaneously in three-dimensional (3D) space and across developmental time. To this end, we developed 3D DNase-Enhanced Expression Profiling (3DEEP), a tissue-clearing approach that removes genomic DNA to extend spatial transcriptomic profiling hundreds of microns into intact tissues. We applied 3DEEP to neonatal mouse skin, capturing hundreds of developing hair follicles across their organogenesis trajectory. Ordering follicles by molecularly inferred developmental age transformed this single spatial snapshot into a four-dimensional (3D + time) molecular map of organogenesis. This map revealed developmental dynamics spanning stem cell compartment stratification, emergence of new cell subtypes within the follicle, and cascading structural transformations leading to hair canal formation. Comparative analysis of Foxn1-deficient nude mice, a hairlessness model, revealed organ-wide changes in developmental dynamics, including delayed molecular progression, reduced coordination, and increased developmental instability, preceding overt structural defects. This work demonstrates how deep-tissue spatial transcriptomics can uncover hidden dynamics of organ formation.","[""Journal Article""]","[""Asami S"", ""Yin C"", ""Fan J"", ""Garza LA"", ""Kalhor R""]",10.1016/j.cell.2026.06.014,Asami S,Cell,0092-8674,,Cell,eng,Kalhor R,[],,42385701,pmc-id: PMC13379681;manuscript-id: NIHMS2193327;,2026 Jul 1,2026,https://pubmed.ncbi.nlm.nih.gov/42385701/,Four-dimensional molecular mapping from a spatial snapshot reveals the dynamics of hair follicle organogenesis,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"We introduce a whole-cell digital twin framework that integrates four-dimensional (4D) (x, y, z, and t) lattice light-sheet microscopy with particle-based reaction-diffusion simulations in ReaDDy to model mesoscale intracellular organelle dynamics. Using fluorescence microscopy data from live Cal27 cells, we construct spatially resolved digital twins incorporating mitochondrial networks, microtubule networks, dynein and kinesin motors, the plasma membrane, and the nucleus. Mitochondrial dynamics include fusion/fission remodeling, diffusion, and motor-driven active transport along microtubules. Our simulations reproduce experimental trends in mitochondrial dynamics across control and two microtubule-perturbed conditions, demonstrating predictive capability without reparameterization. We then use stress-mimicking to predict emergent perinuclear mitochondrial clustering. Crucially, these simulations reveal that microtubule topology acts as a structural gate for this reorganization, demonstrating that upregulated retrograde motor kinetics alone are insufficient to drive clustering without permissive filament connectivity. This digital twin framework provides an approach for investigating intracellular dynamics and perturbation effects in an interpretable and biologically grounded manner.","[""Journal Article""]","[""Arkfeld E"", ""Wang Z"", ""Hakozaki H"", ""Schöneberg J""]",10.1016/j.cell.2026.06.010,Arkfeld E,Cell,0092-8674,15,Cell,eng,Schöneberg J,"[""Humans"", ""Cell Membrane"", ""Cell Nucleus"", ""Computer Simulation"", ""Dyneins"", ""Kinesins"", ""Microscopy, Fluorescence"", ""Microtubules"", ""Mitochondria"", ""Mitochondrial Dynamics""]",4581-4593.e6,42379169,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42379169/,Whole-cell particle-based digital twin simulations from 4D lattice light-sheet microscopy data,189,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Pathogens deploy effector proteins to exploit host cell biology, and most effector open reading frames (ORFs) are rapidly evolving and lack functional annotation. We developed the effector ORFeome (eORFeome), a scalable functional genomics platform encompassing 3,835 effector ORFs from diverse viruses, bacteria, and parasites. High-throughput barcoded screens across nuclear factor κB (NF-κB), apoptosis, p53, cGAS-STING, and major histocompatibility complex class I (MHC class I) pathways revealed novel pathway-modulating functions for hundreds of uncharacterized eORFs, unexpected activities of known effectors, and distinct pathway-specific functions encoded by single ORFs. Illustrating the power of this approach, we identified HHV6A U14 as a p53 antagonist, HHV7 U21 as a dual-function STING antagonist and MHC-I antigen display inhibitor, and adenoviral 13.6K/i-leader protein as a de novo-evolved TAP inhibitor that suppresses MHC-I display. These results establish a general framework for systematic effector annotation, uncover new mechanisms of host-pathogen interaction across kingdoms, and highlight pathogen effectors as a versatile toolkit for rewiring and probing human cellular pathways.","[""Journal Article""]","[""Pachano T"", ""Leng H"", ""Dugied G"", ""Tribble T"", ""Loubiere V"", ""Lee Y"", ""Rauh F"", ""Manon V"", ""Yuan K"", ""Nurtanto J"", ""Schleiffer A"", ""Young V"", ""Weller B"", ""Lyons EA"", ""Hass MR"", ""Kottyan LC"", ""Weirauch MT"", ""Fuxman Bass JI"", ""Newton HJ"", ""Ensminger AW"", ""Falter-Braun P"", ""Chen J"", ""Schramek D"", ""Stark A"", ""Taipale M""]",10.1016/j.cell.2026.06.017,Pachano T,Cell,0092-8674,,Cell,eng,Taipale M,[],,42379168,pmc-id: PMC13378530;manuscript-id: NIHMS2193300;,2026 Jun 30,2026,https://pubmed.ncbi.nlm.nih.gov/42379168/,Systematic discovery of pathogen effector functions across human pathogens and pathways,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"The Plasmodium moving junction is central to malarial host-cell invasion, and yet its function remains unclear. Here, we determine the endogenous structure of the basic repeating unit of the moving junction, purified directly from invasion-stalled Plasmodium falciparum parasites, revealing a sailboat-shaped 1:1:1:1 assembly of apical membrane antigen 1 (PfAMA1) and rhoptry neck proteins 2, 4, and 5 (PfRON2, PfRON4, and PfRON5). We observe two PfRON2 transmembrane helices that anchor the complex in the red blood cell (RBC) membrane and display an extracellular handle for PfAMA1 binding. PfAMA1 directly contacts the RBC membrane, strengthening the connection. PfRON2/4/5 form a large, basic platform inside the RBC that electrostatically engages the RBC membrane and wedges seven amphipathic helices deep into the bilayer, suggesting an active role in host-membrane remodeling. We then leverage the native membrane context revealed by our structure, along with recent advances in computational protein design, to enable the rational design of a small protein binder that inhibits invasion.","[""Journal Article""]","[""Haile MT"", ""Kaxiras DA"", ""Zhen J"", ""Lee CL"", ""Jiang B"", ""Small-Saunders JL"", ""Ho CM""]",10.1016/j.cell.2026.06.012,Haile MT,Cell,0092-8674,,Cell,eng,Ho CM,[],,42379167,pmc-id: PMC13322224;manuscript-id: NIHMS2186715;,2026 Jun 30,2026,https://pubmed.ncbi.nlm.nih.gov/42379167/,Structural basis for host membrane binding and remodeling by invading malaria parasites,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Tissue regeneration requires de novo patterning, which has been proposed to be facilitated by cellular heterogeneity. Yet how such heterogeneities are integrated with the mechanochemical state of the tissue and stabilized at the chromatin level into stable, spatially organized fates remains poorly understood. Using in vivo mouse intestinal regeneration models and organoids, we identify a critical density regime that produces a permissive window for heterogeneity in the mechanosensor Yes-associated protein 1 (YAP1). We show that YAP1 heterogeneity is coupled to lineage-biased chromatin accessibility and is decoded through FOXA1, which integrates the permissive chromatin state to Delta-Notch supracellular feedback and lineage commitment. This circuit generates fate bistability and preserves a memory of transient YAP1 activity, thereby maintaining spatial patterning as tissues return to homeostasis after injury. Together, our findings establish a multiscale framework in which tissue-scale mechanics tune single-cell competence and, through FOXA1-mediated bistability, convert transient heterogeneity into stable and self-organized tissue architecture.","[""Journal Article""]","[""Schwayer C"", ""Barbiero S"", ""Brückner DB"", ""Oost KC"", ""Baader C"", ""Repina NA"", ""Kim J"", ""Diaz OE"", ""Uccelli I"", ""Capolupo L"", ""Meylan LC"", ""Kalck V"", ""Moos F"", ""Suppinger S"", ""Yang Q"", ""Schnabl J"", ""Kilik U"", ""Bourdon M"", ""Camp JG"", ""Stockinger B"", ""Ferrari A"", ""Bühler M"", ""Stadler MB"", ""Hannezo E"", ""Liberali P""]",10.1016/j.cell.2026.06.009,Schwayer C,Cell,0092-8674,,Cell,eng,Liberali P,[],,42379166,,2026 Jun 30,2026,https://pubmed.ncbi.nlm.nih.gov/42379166/,Multiscale integration of tissue and chromatin context converts cell heterogeneity into stable intestinal patterning,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Tau pathology spreads cell to cell, but the mechanisms of intercellular tau transmission remain unclear. We find that the neuronal gene Arc is critical for the release of tau in neuronal extracellular vesicles (EVs) via a direct protein-protein interaction. Brain EVs purified from transgenic rTg4510 mutant tau mice (rTgWT) crossed with Arc knockout mice (rTgArc KO) contain less tau and reduced tau seeding potential. Both Arc and tau are co-packaged in mouse and human brain-derived EVs. Moreover, Arc levels in brain-derived EVs isolated from human Alzheimer's disease (AD) brains show a strong positive correlation with phosphorylated EV-tau levels. rTgArc KO mice have increased accumulation of intracellular tau and a modest increase in cell toxicity early in disease progression. Strikingly, intercellular tau transmission is almost absent in Arc KO mice. These results show that Arc is critical for the packaging of tau in EVs, which plays a significant role in intercellular tau transmission.","[""Journal Article""]","[""Tyagi M"", ""de Hoog E"", ""Grega M"", ""Sullivan KR"", ""Walker AC"", ""Chadha R"", ""Northrop A"", ""Fábián B"", ""Hummer G"", ""Fuxreiter M"", ""Hyman BT"", ""Shepherd JD""]",10.1016/j.cell.2026.06.008,Tyagi M,Cell,0092-8674,15,Cell,eng,Shepherd JD,"[""Animals"", ""tau Proteins"", ""Extracellular Vesicles"", ""Humans"", ""Mice"", ""Cytoskeletal Proteins"", ""Mice, Knockout"", ""Alzheimer Disease"", ""Brain"", ""Nerve Tissue Proteins"", ""Neurons"", ""Phosphorylation"", ""Mice, Transgenic""]",4706-4723.e13,42372723,pmc-id: PMC13315601;manuscript-id: NIHMS2186669;,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42372723/,Arc mediates intercellular tau transmission via extracellular vesicles,189,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
,"[""Published Erratum""]","[""Kim J"", ""Hwang Y"", ""Kim S"", ""Kwon D"", ""Park J"", ""Cho B"", ""An S"", ""Kang S"", ""Kim Y"", ""Kim S"", ""Lengner CJ"", ""Kim S"", ""Kwon Y"", ""Sung JS"", ""Kim J""]",10.1016/j.cell.2026.06.020,Kim J,Cell,0092-8674,14,Cell,eng,Kim J,[],4517-4518,42372722,,2026 Jul 9,2026,https://pubmed.ncbi.nlm.nih.gov/42372722/,Electromagnetic field-inducible in vivo gene switch for remote spatiotemporal control of gene expression,189,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"The intricate network of axonal fibers forming the mammalian cortical connectome exhibits a complex topology, being neither completely regular nor random. It also has a characteristic topography in which distinct regions have specific connectivity profiles. How such properties arise remains a mystery. Here, we formulate a simple analytical model derived from neural field theory that prioritizes physical constraints on connectome architecture, assuming that connectivity is preferentially concentrated between cortical locations that facilitate the excitation of resonant geometric modes of the cortex. Our model outperforms existing approaches in reproducing topological and topographical properties of cortical connectomes mapped via either non-invasive diffusion magnetic resonance imaging (MRI) or invasive viral tract tracing at spatial scales spanning multiple orders of magnitude in humans, chimpanzees, macaques, marmosets, and mice. Our findings point to a fundamental role of geometry in shaping the multiscale architecture of cortical connectomes that has been conserved across 90 million years of evolution.","[""Journal Article""]","[""Normand F"", ""Gajwani M"", ""Cao T"", ""Cruddas J"", ""Sangchooli A"", ""Oldham S"", ""Holmes A"", ""Robinson PA"", ""Pang JC"", ""Fornito A""]",10.1016/j.cell.2026.05.048,Normand F,Cell,0092-8674,,Cell,eng,Fornito A,[],,42361798,,2026 Jun 26,2026,https://pubmed.ncbi.nlm.nih.gov/42361798/,Geometric constraints on the architecture of mammalian cortical connectomes,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Gasdermin D (GSDMD)-mediated interleukin (IL)-33 secretion by lung epithelial cells initiates airway inflammation upon allergen challenge. How environmental allergens activate GSDMD remains elusive. Here, we demonstrate that exposing epithelial cells to allergens triggers protease-activated receptor 1 (PAR1)-dependent ferritinophagy, elevating intracellular labile iron. This iron pool is essential for noncanonical, protease-independent GSDMD activation. The iron chaperone poly(rC)-binding protein 2 (PCBP2) delivers iron directly to GSDMD, initiating a highly localized Fenton reaction. This generates constrained hydroxyl radicals that cleave GSDMD, releasing the active N-terminal p40 fragment to form pores for IL-33 release. Blocking any step of this iron-GSDMD pathway, via iron chelation or genetic ablation, abolishes IL-33 secretion, prevents group 2 innate lymphoid cell (ILC2) activation, and mitigates allergic airway inflammation and tissue damage in mice. Our findings reveal an unconventional, iron-catalyzed, and protease-independent mechanism for GSDMD activation, offering potential new therapeutic targets for allergic inflammatory diseases.","[""Journal Article""]","[""Chen S"", ""Deng F"", ""Peng B"", ""Liu L"", ""Wang J"", ""Jin F"", ""Xu J"", ""Lin D"", ""Chen W"", ""Zhang D"", ""Yi C"", ""Zhang J"", ""Zhong S"", ""Zhu L"", ""Huang Y"", ""Yang J"", ""Wang R"", ""Sun X"", ""Zhang Y"", ""Ling Z"", ""Ma L"", ""Liu X"", ""Sun B""]",10.1016/j.cell.2026.06.004,Chen S,Cell,0092-8674,,Cell,eng,Sun B,[],,42361797,,2026 Jun 26,2026,https://pubmed.ncbi.nlm.nih.gov/42361797/,Iron drives protease-independent cleavage of gasdermin D in allergic airway diseases,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
"Epithelial mechanosensation maintains tissue homeostasis by sensing mechanical stimuli. Dysregulated mechanotransduction has been implicated in chronic pain, yet the molecular link between epithelial stress and persistent sensory dysfunction remains unclear. Here, we report that the mechanosensitive ion channel PIEZO1 is markedly upregulated in bladder epithelial cells under recurrent uropathogenic E. coli infection through interleukin-6 (IL-6)-dependent signaling. PIEZO1 overexpression amplifies mechanotransduction-induced reactive oxygen species (ROS) generation, triggering a homeostatic antioxidant response via the cystine-glutamate antiporter system Xc⁻ (SLC7A11). This protective mechanism inadvertently promotes extracellular glutamate accumulation, driving aberrant sprouting and hyperinnervation of peptidergic nociceptive C fibers into the epithelial layer. This neuroepithelial remodeling sensitizes bladder afferents and induces persistent pain-like states resembling chronic visceral pain and organ dysfunction. Our findings reveal a paradoxical role of epithelial antioxidant defense in promoting pain through the PIEZO1-SLC7A11-glutamate axis and highlight the neuroepithelial interface as a key therapeutic target for infection-induced chronic pain syndromes.","[""Journal Article""]","[""Kim MJ"", ""Noh JH"", ""Lee HY"", ""Lee B"", ""Park AD"", ""Oh H"", ""Kim GD"", ""Lee HS"", ""Oh Y"", ""Hwang H"", ""Kim C"", ""Lee H"", ""Li X"", ""Oh MM"", ""Lim D"", ""Abraham SN"", ""Cho Y"", ""Chi SW"", ""Choi HW""]",10.1016/j.cell.2026.05.049,Kim MJ,Cell,0092-8674,,Cell,eng,Choi HW,[],,42361796,,2026 Jun 26,2026,https://pubmed.ncbi.nlm.nih.gov/42361796/,Excessive epithelial mechanosensation drives nociceptive innervation and chronic bladder pain via the PIEZO1-SLC7A11-glutamate axis,,7ZrmW0u1sCa4DDeqf,xcuK1zfSY8rvcVEGB
,"[""Journal Article""]",[],10.1038/s41591-026-04567-4,,Nature medicine,1078-8956,,Nat Med,eng,,[],,42538428,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538428/,Learning from routine health system data builds better neuroimaging AI models,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"Recent rapid progress in the field of computational pathology has been enabled by foundation models. These models are beginning to move beyond encoding image patches toward whole-slide understanding, but their clinical utility remains limited. Here we present PRISM2, a multimodal slide-level foundation model trained on 2.3 million whole-slide images and 14 million question-answer pairs derived from 700,000 pathology reports. Through clinical dialogue supervision, PRISM2 aligns histomorphology with diagnostic reasoning, yielding representations that support both prompt-based inference and transferable embeddings for downstream tasks. With prompt-based inference, PRISM2 achieves or exceeds (P < 0.05) the balanced accuracy of clinical-grade products calibrated for cancer detection in the prostate, breast and breast lymph node. Additionally, across comprehensive diagnostic, biomarker and survival benchmarks, PRISM2 embeddings never statistically underperform previous foundation models via linear probing (P < 0.05). Furthermore, task-specific fine-tuning on survival prediction outperforms training from scratch on the same large survival dataset. PRISM2 demonstrates how language-supervised pretraining provides a scalable, clinically grounded signal for generalizable pathology representations, bridging human diagnostic reasoning and foundation model performance.","[""Journal Article""]","[""Vorontsov E"", ""Shaikovski G"", ""Casson A"", ""Viret J"", ""Zimmermann E"", ""Tenenholtz N"", ""Wang YK"", ""Bernhard JH"", ""Godrich RA"", ""Retamero JA"", ""Shia J"", ""Gonen M"", ""Weiser MR"", ""Klimstra DS"", ""Yousfi R"", ""Fusi N"", ""Fuchs TJ"", ""Severson K"", ""Liu S""]",10.1038/s41591-026-04521-4,Vorontsov E,Nature medicine,1078-8956,,Nat Med,eng,Liu S,[],,42538427,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538427/,End-to-end multimodal pathology foundation model with clinical dialogue,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""News""]","[""O'Leary K""]",10.1038/d41591-026-00039-x,O'Leary K,Nature medicine,1078-8956,,Nat Med,eng,O'Leary K,[],,42538412,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538412/,'Heading' the ball linked to spikes in neural damage biomarkers,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""News""]","[""O'Leary K""]",10.1038/d41591-026-00038-y,O'Leary K,Nature medicine,1078-8956,,Nat Med,eng,O'Leary K,[],,42538411,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42538411/,Humanoid robots perform successful surgery in animals,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""Journal Article""]","[""Cansiz F"", ""Pope AN"", ""Tasdogan A""]",10.1038/s41591-026-04555-8,Cansiz F,Nature medicine,1078-8956,,Nat Med,eng,Tasdogan A,[],,42527577,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42527577/,Deciphering the role of histidine in cancer,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"Combining multidisciplinary care plans into integrated care pathways (ICPs) is scalable, generalizable and effective for several long-term conditions, but not evaluated in Long COVID (LC). Our phase 3, cluster-randomized, multicenter clinical trial investigated the effectiveness of ICP interventions for LC. Recruitment of adults ≥18 years with LC was conducted in 6 National Health Service LC clinics in England with specialist ICPs. The intervention arms were (i) multi-organ magnetic resonance imaging (MRI; Coverscan), (ii) digital rehabilitation (Living with COVID Recovery), (iii) both multi-organ MRI and digital rehabilitation, and (iv) neither multi-organ MRI nor digital rehabilitation (usual care); cluster randomizing at primary care network (PCN) level to deliver interventions as 'standard of care' in that area. The primary endpoint was mean Fatigue Assessment Scale (FAS) at 12 weeks. Secondary endpoints included FAS at 24 weeks and EQ-5D-5L visual assessment scale at 12 and 24 weeks. A total of 1,152 participants from allocated PCNs consented to data collection, and 122 PCN clusters were allocated to the multi-organ MRI (33 PCNs), digital rehabilitation (32 PCNs), 'both' (27 PCNs) and 'neither' (30 PCNs) arms. Baseline FAS was equivalent across groups (mean 35.8, s.d. 8.21, 66.4% female). Overall, the primary outcome was achieved in all arms, with scores improving by 4.5 points to 31.3 (s.d. 9.31) at 12 weeks. Compared with usual care, effects on 12-week FAS were -0.18 (95% confidence interval -0.72, 1.09; P = 0.69) with multi-organ MRI; -0.53 (-1.42, 0.36; P = 0.25) with digital rehabilitation; and -0.17 (-1.06, 0.72; P = 0.71) with their interaction. Absolute differences for other interventions from usual care were modest. There were no serious adverse events related to ICP interventions. Multidisciplinary holistic clinical care is associated with fatigue reduction in LC, irrespective of multi-organ MRI. Digital rehabilitation could be useful in longer-term LC management. Large, multi-site trials of optimal ICP interventions are feasible, but further trials are required. ISRCTN identifier: ISRCTN10665760 .","[""Journal Article""]","[""STIMULATE-ICP Consortium""]",10.1038/s41591-026-04552-x,STIMULATE-ICP Consortium,Nature medicine,1078-8956,,Nat Med,eng,STIMULATE-ICP Consortium,[],,42521821,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42521821/,"Integrated care pathway in individuals with Long COVID: STIMULATE-ICP, a cluster-randomized, phase 3 trial",,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"Group B Streptococcus (GBS) disease is a major cause of infant morbidity and mortality. Capsular polysaccharide conjugate GBS vaccines have been evaluated for decades; however, none is licensed. This phase 1/2 trial evaluated an investigational maternal hexavalent polysaccharide-protein conjugate GBS vaccine (GBS6) in non-pregnant females and pregnant participants and their infants. In stage 1 (conducted in South Africa), healthy non-pregnant participants received GBS6, GBS6 + aluminum phosphate (AlPO4) or placebo; a subset received GBS6 + AlPO4 booster approximately 2 years later. Stage 2 (conducted in South Africa) maternal dose-finding data were reported previously and are not presented here. In stage 3, healthy pregnant participants from South Africa, the United States and the United Kingdom received GBS6 or placebo (24-36 weeks' gestation). In stage 1, 66 non-pregnant participants received GBS6, GBS6 + AlPO4 or placebo (n = 22 each); 26 also received GBS6 + AlPO4 booster. In stage 3, 216 pregnant participants were included (GBS6, n = 108; placebo, n = 108); 209 infants were born to maternal participants (GBS6, n = 104; placebo, n = 105). Primary objectives described GBS6 safety/tolerability profiles. Nearly all reactogenicity events were mild or moderate. Among non-pregnant participants, no serious adverse events (SAEs) or adverse event (AE)-associated withdrawals were reported after vaccination; medically attended adverse events (MAEs) were reported in similar percentages across primary vaccination groups (GBS6 groups = 41-45%; placebo = 41%). Rates of AEs (GBS6 = 75/108 (69%); placebo = 70/108 (65%)), SAEs (GBS6 = 21/108 (19%); placebo = 23/108 (21%)) and delivery outcome frequencies were similar in GBS6 and placebo maternal participants. Most infants were born full-term. Infant AE (GBS6 = 87/104 (84%); placebo = 86/105 (82%)), SAE (GBS6 = 45/104 (43%); placebo = 46/105 (44%)) and MAE (GBS6 = 65/104 (63%); placebo = 66/105 (63%)) frequencies were similar across groups. Two neonatal sepsis-associated deaths occurred (GBS6 = 1; placebo = 1); neither was considered vaccine related. Secondary objectives described immune responses. GBS6 elicited robust immune responses in non-pregnant and pregnant individuals; additionally, serotype-specific quantitative and functional antibody responses were observed in infants whose parent received GBS6. These data support continuing clinical investigation of maternal GBS6 vaccination. ClinicalTrials.gov identifier: NCT03765073 .","[""Journal Article""]","[""Madhi SA"", ""Snaggs H"", ""Skogeby Z"", ""Feng Y"", ""Barnabas S"", ""Baker J"", ""Fairlie L"", ""Beeslaar J"", ""Radley D"", ""Jiang HQ"", ""Silmon de Monerri NC"", ""Simon R"", ""McLaughlin L"", ""Gaylord M"", ""Skinner J"", ""Munjal I"", ""Anderson AS"", ""Gurtman A""]",10.1038/s41591-026-04558-5,Madhi SA,Nature medicine,1078-8956,,Nat Med,eng,Gurtman A,[],,42521820,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42521820/,Maternal 6-valent group B Streptococcus vaccine in non-pregnant and pregnant females: a randomized phase 1/2 trial,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""Journal Article""]","[""Wright CF"", ""Phillips A"", ""Wynn SL"", ""Meade N"", ""Baple EL"", ""Lucassen AM"", ""Jackson L""]",10.1038/s41591-026-04542-z,Wright CF,Nature medicine,1078-8956,,Nat Med,eng,Jackson L,[],,42521819,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42521819/,Reducing the diagnostic odyssey in rare disease: why screening is not the only answer,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"Depression is a major contributor to the global burden of diseases with substantial socioeconomic consequences. Here, to estimate the economic effects of depression, we developed a macroeconomic model using data from the World Bank and Global Burden of Disease Study 2021. The model estimated the impact of depression on labor force participation, educational attainment and work experience, adjusted for age and sex. The projected global economic burden from 2025 to 2050 is estimated at US$12 trillion (2024 US dollars), representing 0.460% of annual global gross domestic product. When suicide-related deaths attributable to depression are accounted for, based on an assumed 60% attribution rate representing the upper bound of estimates in the literature, the overall economic burden increases to US$14 trillion. The highest economic burdens are observed in the United States and China. Relative to regional gross domestic product, the impact is greatest in North America. Reduced labor force participation and productivity were identified as the predominant drivers of this cost. The macroeconomic burden of depression is substantial and inequitably distributed globally. These findings underscore the importance of addressing depression as a public health and economic concern. Reducing the health burden of depression could yield economic returns by supporting productivity and capital accumulation.","[""Journal Article""]","[""Cao Z"", ""Luo Y"", ""Jiao L"", ""Chen W"", ""Prettner K"", ""Kuhn M"", ""Bloom DE"", ""Jamison DT"", ""Bärnighausen TW"", ""Chen S""]",10.1038/s41591-026-04548-7,Cao Z,Nature medicine,1078-8956,,Nat Med,eng,Chen S,[],,42521818,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42521818/,Global economic burden of depression in 154 countries from 2025 to 2050,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"Fibromyalgia is a common and debilitating chronic pain syndrome of poorly understood etiology. Here we conduct a multi-ancestry genome-wide association study meta-analysis across 2,563,755 individuals (54,629 cases and 2,509,126 controls) from 11 cohorts, identifying 26 risk loci for fibromyalgia. The strongest association was with a coding variant in HTT, the causal gene for Huntington's disease. Gene prioritization implicated the HTT regulator GPR52, as well as diverse genes with neural roles, including DCC, DRD2/NCAM1, MDGA2 and CELF4. Fibromyalgia heritability was exclusively enriched within brain tissues and neural cell types. Fibromyalgia showed strong, positive genetic correlation with a wide range of chronic pain, psychiatric and somatic disorders, including genetic correlations above 0.7 with low back pain, post-traumatic stress disorder and irritable bowel syndrome. Despite large sex differences in fibromyalgia prevalence, the genetic architecture of fibromyalgia was nearly identical between males and females. This study provides robust genetic evidence defining fibromyalgia as a central nervous system disorder, thereby establishing a biological framework for its complex pathophysiology and extensive clinical comorbidities.","[""Journal Article""]","[""Kerrebijn I"", ""Bjornsdottir G"", ""Arbabi K"", ""Urpa L"", ""Haapaniemi H"", ""Thorleifsson G"", ""Stefansdottir L"", ""Frangakis S"", ""Valliere J"", ""Kunorozva L"", ""Abner E"", ""Ji C"", ""Kangur M"", ""Aagaard B"", ""Bliddal H"", ""Brunak S"", ""Bruun MT"", ""Didriksen M"", ""Erikstrup C"", ""Finer S"", ""Geirsson AJ"", ""Gudbjartsson DF"", ""Hansen TF"", ""van Heel D"", ""Jonsdottir I"", ""Knight S"", ""Knowlton KU"", ""Mikkelsen C"", ""Nadauld LD"", ""Olafsdottir TA"", ""Ostrowski SR"", ""Pedersen OBV"", ""Saevarsdottir S"", ""Skuladottir AT"", ""Sørensen E"", ""Stefansson H"", ""Sulem P"", ""Sveinsson OA"", ""Thorlacius GE"", ""Thorsteinsdottir U"", ""Ullum H"", ""Vikingsson A"", ""Werge TM"", ""Chronic Pain Genomics Consortium"", ""FinnGen"", ""DBDS Genomic Consortium"", ""Estonian Biobank Research Team"", ""Genes & Health Research Team"", ""Saxena R"", ""Stefansson K"", ""Brummett CM"", ""Glintborg B"", ""Clauw DJ"", ""Thorgeirsson TE"", ""Williams FMK"", ""Sinnott-Armstrong N"", ""Ollila HM"", ""Wainberg M""]",10.1038/s41591-026-04492-6,Kerrebijn I,Nature medicine,1078-8956,,Nat Med,eng,Wainberg M,[],,42521817,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42521817/,The genetic architecture of fibromyalgia across 2.5 million individuals,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""Journal Article""]","[""Goh E"", ""Wu D"", ""Walton C"", ""McCoy LG"", ""Perez A"", ""Wegner L"", ""Nateghi Haredasht F"", ""Luo L"", ""Lacar K"", ""Buckley T"", ""Schoeffler A"", ""Brodeur P"", ""Black KC"", ""Havlik J"", ""Liu Y"", ""Chen PC"", ""Schaekermann M"", ""Rumsfeld J"", ""Lopez-Martinez D"", ""Maeder-York P"", ""Singhal K"", ""Gunning D"", ""Ku B"", ""Warraich H"", ""Nundy S"", ""Ravi V"", ""Milstein A"", ""Hom J"", ""Schulman K"", ""Rajpurkar P"", ""Manrai AK"", ""Wachter R"", ""Topol E"", ""Horvitz E"", ""Rodman A"", ""Chen JH""]",10.1038/s41591-026-04539-8,Goh E,Nature medicine,1078-8956,,Nat Med,eng,Chen JH,[],,42509372,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42509372/,Toward a test of medical AI superintelligence,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"The study of pre-symptomatic amyotrophic lateral sclerosis (ALS) and the design of disease prevention trials are greatly hampered by our inability to predict which unaffected carriers of ALS-associated pathogenic variants will phenoconvert to clinically manifest disease and when. In this longitudinal Olink Explore, high-throughput, proteomic study, 516 serially collected plasma samples from 33 phenoconverters, 35 patients with ALS, 10 pre-symptomatic pathogenic variant carriers and 59 controls were included. Here we identified 92 proteins with concentrations that changed before phenoconversion; characterized the longitudinal trajectory of these proteins and identified a core panel of 19 proteins which, collectively, predicted phenoconversion over the 0.5-year to 5-year time horizons (crossvalidated areas under the curve 0.80-0.89) and yielded estimates of time to phenoconversion with a mean absolute error of 1.6 years. These findings were partially replicated in UK Biobank data, confirming pre-symptomatic increases in several proteins (for example, NEFL, EDA2R and CA3) and that a multi-protein panel outperformed NEFL alone in estimating time to phenoconversion. This work sheds light on the biology of pre-symptomatic ALS. Moreover, our identification of a panel of new susceptibility/risk biomarkers based on empirical longitudinal data furthers the ultimate goal of ALS prevention.","[""Journal Article""]","[""Ran X"", ""Wuu J"", ""Qin ZS"", ""McDermott MP"", ""Cooper-Knock J"", ""Li Y"", ""Granit V"", ""Grignon AL"", ""Lin E"", ""Fernandez MC"", ""Colato D"", ""Carberry N"", ""Lill CM"", ""Piazza P"", ""Malaspina A"", ""Benatar M""]",10.1038/s41591-026-04528-x,Ran X,Nature medicine,1078-8956,,Nat Med,eng,Benatar M,[],,42509371,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42509371/,Longitudinal plasma proteomics predict phenoconversion to clinically manifest ALS,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"The accurate and timely diagnosis of inherited retinal diseases (IRDs) represents an unmet clinical need in ophthalmology, as the current pathways rely on resource-intensive phenotyping, multidisciplinary expertise and genetic testing. Here we developed Retina4IRD, an artificial intelligence (AI)-based clinician decision support system (CDSS) that predicts 17 genotype categories from retina images. Retina4IRD uses a Vision Transformer model pretrained with RETFound. We then trained and validated Retina4IRD using multimodal data with color fundus photographs and optical coherence tomography scans from 1,843 genetically confirmed patients (3,376 eyes) across China, South Korea and Poland. The top-5 prediction accuracy was 0.904 (95% confidence interval (CI): 0.896-0.912) and 0.856 (95% CI: 0.850-0.863) for internal and external validation, respectively. We conducted a randomized controlled trial with 300 participants with suspected IRD randomized 1:1 to either Retina4IRD-assisted specialist arm or specialist-only arm. Of these, 295 participants (median age 33 years, 114 (38.6%) females) with available next-generation sequencing reports were included in the final analysis. The primary outcome was met: top-5 genetic accuracy was significantly higher in the Retina4IRD-assisted specialist arm versus the specialist-only arm (88.5% versus 67.3%, P < 0.001). For secondary endpoints, top-1 to top-4 accuracies all favored the Retina4IRD-assisted specialist arm, with top-1 accuracy of 37.8% versus 22.4% and top-4 accuracy of 81.8% versus 53.1%, respectively. Post hoc analyses demonstrated that, with Retina4IRD assistance, clinicians made better management decisions, and the composite downstream management score indicated significantly higher scores relative to the control group (37.7 versus 28.5, P < 0.001). Our study shows that Retina4IRD is a CDSS tool prior to genetic testing and aligns with clinical workflow for patients with suspected IRDs. ClinicalTrials.gov identifier: NCT06839170 .","[""Journal Article""]","[""Jia H"", ""Qian B"", ""Qu Y"", ""Wang J"", ""Chen J"", ""Li T"", ""Zheng C"", ""Han J"", ""Zhang G"", ""Jin Y"", ""Lee S"", ""Chen X"", ""Chen H"", ""Xu J"", ""Xu K"", ""Rong Y"", ""Jiang Y"", ""Yang Y"", ""Li W"", ""Guo Q"", ""Li Y"", ""Li Y"", ""Wu J"", ""Zhang Q"", ""Lu F"", ""Zhuang W"", ""Lei B"", ""Byeon SH"", ""Lee J"", ""Smedowski A"", ""Swierczynska M"", ""Zhang D"", ""Rim TH"", ""Grzybowski A"", ""Sheng B"", ""Wong TY"", ""Sun X""]",10.1038/s41591-026-04545-w,Jia H,Nature medicine,1078-8956,,Nat Med,eng,Sun X,[],,42498742,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42498742/,"AI-based clinician decision support system for diagnosis of inherited retinal diseases: a multicenter, randomized trial",,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"There is a need for robust evaluations of noninvasive biomarkers for metabolic dysfunction-associated steatotic liver disease. This prospective multicenter study assessed the diagnostic accuracy of imaging (including liver stiffness measurement (LSM) using magnetic resonance elastography (MRE) and FibroScan (vibration-controlled transient elastography (VCTE)), serum biomarkers (including NIS2+) and composite scores (including Agile 3+ and Agile 4) for centrally read steatohepatitis and fibrosis. For cirrhosis, several biomarkers exceeded the minimum acceptable performance criterion (MAC), including MRE (area under the receiver operating curve (AUC) 0.91; P < 0.01), VCTE-LSM (AUC 0.87; P < 0.01), Agile 3+ (AUC 0.89; P < 0.01) and Agile 4 (AUC 0.88; P < 0.01). Among 357 participants, fibrosis stages F0-F4 were present in 12%, 16%, 25%, 32% and 15%, respectively. NIS2+ had the highest diagnostic accuracy among serum biomarkers for metabolic dysfunction-associated steatohepatitis (MASH; AUC 0.83) and at-risk MASH (MASH with at least stage 2 fibrosis; AUC 0.82), although neither significantly exceeded the MAC (P = 0.15 and P = 0.19). Among imaging biomarkers, MRE showed the highest performance for MASH (AUC 0.71) and at-risk MASH (AUC 0.75), but these remained below the MAC. For fibrosis staging, performance was stronger: MRE met the MAC for advanced fibrosis (AUC 0.91; P < 0.01), as did Agile 3+ (AUC 0.84; P = 0.03). For cirrhosis, several biomarkers exceeded the MAC, including MRE (AUC 0.91; P < 0.01), VCTE-LSM (AUC 0.87; P < 0.01), Agile 3+ (AUC 0.89; P < 0.01) and Agile 4 (AUC 0.88; P < 0.01). Serum biomarkers tended to outperform imaging for identifying at-risk MASH, whereas elastography and composite scores showed excellent accuracy for staging advanced fibrosis and cirrhosis.","[""Journal Article""]","[""Pavlides M"", ""Vali Y"", ""Mózes FE"", ""Wonders K"", ""Akhtar S"", ""Hockings PD"", ""Shumbayawonda E"", ""Pepin K"", ""Fernandez-Lizaranzu I"", ""Leeming DJ"", ""Cobbold JF"", ""Allison MED"", ""Aithal GP"", ""Romero-Gomez M"", ""Aller R"", ""Pericàs JM"", ""Boursier J"", ""Petta S"", ""Schattenberg JM"", ""Ekstedt M"", ""Berzigotti A"", ""Yki-Järvinen H"", ""Martic M"", ""Tuthill T"", ""Brass CA"", ""Kalutkiewicz M"", ""Banerjee R"", ""Ehman RL"", ""Schneider MJ"", ""Tiniakos D"", ""Karsdal M"", ""Magnanensi J"", ""Fournier-Poizat C"", ""Ratziu V"", ""Yunis C"", ""Bugianesi E"", ""Harrison SA"", ""LITMUS Consortium Investigators"", ""Bossuyt PM"", ""Anstee QM""]",10.1038/s41591-026-04496-2,Pavlides M,Nature medicine,1078-8956,,Nat Med,eng,Anstee QM,[],,42498741,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42498741/,Prospective validation of imaging and serum diagnostic biomarkers of steatohepatitis and fibrosis in MASLD: the LITMUS Imaging Study,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""Journal Article""]",[],10.1038/s41591-026-04563-8,,Nature medicine,1078-8956,,Nat Med,eng,,[],,42493572,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42493572/,Early detection of Alzheimer's disease with circular RNA from blood,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"Although therapeutic options for hidradenitis suppurativa (HS) continue to expand, unmet needs remain substantial. We evaluated the efficacy and safety of povorcitinib (an oral, highly selective Janus kinase 1 (JAK1) inhibitor) in patients with moderate to severe HS in two randomized trials. STOP-HS1 and STOP-HS2 were identically designed, randomized, double-blind, placebo-controlled phase 3 trials. Adults with moderate to severe HS were randomized 2:2:1:1 to once-daily treatment through week 54: povorcitinib 45 mg; povorcitinib 75 mg; placebo with crossover at week 12 to povorcitinib 45 mg; or placebo with crossover at week 12 to povorcitinib 75 mg. The primary endpoint was HiSCR50 (≥50% decrease in total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining tunnel count) at week 12. STOP-HS1/STOP-HS2 enrolled 608/619 patients, respectively. In both studies, both povorcitinib doses met the primary endpoint; in STOP-HS1, 82/204 (40%) patients in the povorcitinib 45-mg group and 82/202 (41%) in the 75-mg group versus 60/202 (30%) in the placebo group achieved HiSCR50 (OR (95% CI) 45 mg: 1.6 (1.1-2.5), P = 0.0240; 75 mg: 1.6 (1.1-2.4), P = 0.0214); corresponding values for STOP-HS2 were 88/208 (42%) and 88/208 (42%) versus 58/203 (29%; OR (95% CI) 45 mg: 1.8 (1.2-2.8), P = 0.0035; 75 mg: 1.9 (1.2-2.8); P = 0.0033). Through week 12, across STOP-HS1/STOP-HS2, serious treatment-emergent adverse events (AEs) occurred in 1-2% of patients across povorcitinib doses and in 2-3% with placebo; through week 54, serious AEs occurred in 5%/6% of patients receiving 45-mg/75-mg povorcitinib, respectively. The most frequent AEs among patients treated with 45-mg/75-mg povorcitinib were acne (17%/20%), nasopharyngitis (10%/12%) and upper respiratory tract infection (11%/10%). One death of undetermined etiology was reported and deemed unrelated to treatment. No new or unexpected safety findings were identified. Oral povorcitinib demonstrated significant improvements in HiSCR50 versus placebo and a favorable safety profile in patients with moderate to severe HS. ClinicalTrials.gov registration: NCT05620823 and NCT05620836 .","[""Journal Article""]","[""Porter ML"", ""Martorell A"", ""Sayed CJ"", ""Bechara FG"", ""Lev-Tov H"", ""Hsiao JL"", ""Frew JW"", ""Reguiaï Z"", ""Gooderham MJ"", ""Goldfarb N"", ""van der Zee HH"", ""Del Marmol V"", ""Marzano AV"", ""Ehst BD"", ""Ackerman LS"", ""Hayama K"", ""Tian C"", ""Kelley J"", ""Zhen H"", ""Kirby JS"", ""Brown K"", ""Santos LL"", ""Zouboulis CC""]",10.1038/s41591-026-04534-z,Porter ML,Nature medicine,1078-8956,,Nat Med,eng,Zouboulis CC,[],,42493571,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42493571/,"Povorcitinib for hidradenitis suppurativa: the randomized, double-blind, placebo-controlled STOP-HS1 and STOP-HS2 phase 3 trials",,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""Published Erratum""]","[""Gomez S"", ""DiCioccio RA"", ""Geiger AE"", ""Grant ML"", ""Reynolds E"", ""Datar A"", ""McCann CD"", ""Tanna J"", ""Kukadiya D"", ""Hoq F"", ""Zhang A"", ""Hanley PJ"", ""Webb JL"", ""Kilburn LB"", ""Rood BR"", ""Fonseca A"", ""Meany HJ"", ""Vézina LG"", ""Packer RJ"", ""Cruz CRY"", ""Bollard CM"", ""Hwang EI""]",10.1038/s41591-026-04593-2,Gomez S,Nature medicine,1078-8956,,Nat Med,eng,Hwang EI,[],,42487062,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42487062/,Author Correction: Multi-antigen-targeting T cells in pediatric central nervous system tumors: a phase 1 trial,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"Fc receptor-homolog 5 (FcRH5) is a membrane protein that is ubiquitously expressed on myeloma cells. Cevostamab is a first-in-class, FcRH5×CD3 bispecific antibody. GO39775 is a phase 1 dose-escalation and dose-expansion study evaluating fixed-duration cevostamab in relapsed or refractory multiple myeloma. Cevostamab was initiated with step-up dosing and continued at the target dose (TD) once every 3 weeks for 17 cycles (~12 months) unless disease progression or unacceptable toxicity occurred. Primary objectives were to evaluate safety, including determination of the maximum tolerated dose (MTD), and to identify a recommended phase 2 dose and schedule (RP2D) for cevostamab monotherapy. Secondary objectives included determining the rate of response and the duration of response (DOR). As of 24 February 2025, 324 patients had been enrolled; most were heavily pretreated (median prior lines, 6; triple-class refractory, 89.5% (290/324); prior B-cell maturation antigen (BCMA)-targeted therapy, 47.5% (154/324)). The MTD was not reached. Across all TD levels (0.15-252 mg), grade 3 or 4 adverse events (AEs) and serious AEs occurred in 59.6% (193/324) and 60.2% (195/324), respectively. Grade 5 AEs excluding disease progression occurred in 4.6% (15/324); 0.9% (3/324) were considered treatment related (hemophagocytic lymphohistiocytosis, n = 2; disseminated intravascular coagulation in the context of pseudomonal sepsis, n = 1). Objective response and very good partial response or better rates were 42.1% (136/323) and 25.1% (81/323), respectively. Median DOR was 11.2 months (95% confidence interval, 8.3, 15.6). A total of 167 patients received treatment at the 160 mg TD level (RP2D). Objective response and very good partial response or better rates were 44.3% (74/167) and 25.7% (43/167) in all patients and 60.6% (43/71) and 39.4% (28/71) in the BCMA naive, respectively. Median DOR was 10.4 months in all patients and 19.7 months in the BCMA naive, with durable responses maintained after the completion of treatment. Cytokine release syndrome was grade 1 or 2 in the 0.3/1.2/3.6/160 mg triple step-up cohort (RP2D). Cevostamab had manageable safety and induced durable remissions in late-line relapsed or refractory multiple myeloma. ClinicalTrials.gov registration: NCT03275103 .","[""Journal Article""]","[""Cohen AD"", ""Richter J"", ""Trudel S"", ""Lesokhin A"", ""Laubach JP"", ""Thomas SK"", ""Harrison SJ"", ""Costa LJ"", ""Spencer A"", ""Fonseca R"", ""Forsberg PA"", ""Berdeja JG"", ""Kaedbey R"", ""Bahlis NJ"", ""Rodriguez-Otero P"", ""Mateos MV"", ""Tyagi T"", ""Samineni D"", ""Liu W"", ""Nakamura R"", ""Choeurng V"", ""Wong C"", ""Cooper J"", ""Krishnan A""]",10.1038/s41591-026-04522-3,Cohen AD,Nature medicine,1078-8956,,Nat Med,eng,Krishnan A,[],,42487061,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42487061/,FcRH5×CD3 bispecific antibody cevostamab in relapsed or refractory multiple myeloma: a phase 1 trial,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""Journal Article""]","[""Occhipinti JA"", ""Prodan A"", ""Buchanan J"", ""Martin M"", ""Khalatbari-Soltani S"", ""Swieboda P"", ""Eyre H"", ""Crosland P"", ""Hosseini SH"", ""van Zwieten A"", ""Samtani S"", ""Sawan M"", ""Cobos Muñoz D"", ""Okamoto S"", ""Robinson J"", ""Norris D"", ""Jeste DV"", ""Destrebecq F"", ""Heffernan M"", ""Tanner M"", ""Miranda JJ""]",10.1038/s41591-026-04535-y,Occhipinti JA,Nature medicine,1078-8956,,Nat Med,eng,Miranda JJ,[],,42487060,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42487060/,Governing the social production of care: the hidden foundation of health systems,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""Journal Article""]","[""Araújo de França GV"", ""Lupatini EO"", ""Rocha RT"", ""Toledo RCP"", ""Figueiredo GSF"", ""Gonçalves CEI"", ""Machado ILO"", ""Anzolin AP"", ""Gontijo CC"", ""Vidal JFD"", ""Ramos PIP"", ""Carreiro RP"", ""Freitas MS"", ""De Negri F""]",10.1038/s41591-026-04523-2,Araújo de França GV,Nature medicine,1078-8956,,Nat Med,eng,De Negri F,[],,42481853,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42481853/,Genomas Brasil program: building precision public health within Brazil's Unified Health System,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""Letter""]","[""Borelli C""]",10.1038/s41591-026-04536-x,Borelli C,Nature medicine,1078-8956,,Nat Med,eng,Borelli C,[],,42481852,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42481852/,A new additive in the opioid supply is causing disastrous complications,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"SCN2A variants are among the most common genetic causes of developmental and epileptic encephalopathies (DEEs), which can present with uncontrolled seizures at birth and account for 1-2% of all epileptic encephalopathies. A substantial fraction of causal variants are gain-of-function or mixed-function variants associated with increased channel open probability or greater sodium current flux. Here two parallel n = 1 clinical studies were conducted in two patients (9-year-old and 14-year-old boys) with SCN2A-related DEE. Individualized allele-selective antisense oligonucleotides (ASOs) were designed to target heterozygous intronic single-nucleotide polymorphisms (SNPs) for decreased expression of mutant SCN2A transcript while preserving the wild-type copy. Primary endpoints included quantitative change from baseline in seizure frequency and neurodevelopment, including motor scores. Efficacy measures were also individualized to each patient's phenotype, including refractory seizures, developmental delay, autism spectrum disorder, choreoathetosis and gastrointestinal dysfunction. Patients experienced a reduction in seizure frequency (26% and 90% in the two patients, respectively), decreased use of concomitant medications and improvement in neurodevelopmental skills. Both ASOs were well tolerated, with no ASO-related serious adverse events. Continued long-term follow-up of these preliminary positive safety and efficacy findings is needed to confirm the disease-modifying potential of these ASOs. Haplotype phasing in a separate cohort of infants with SCN2A-related disorder (SCN2A-RD), diagnosed by rapid whole-genome sequencing, identified 16% of patients with compatible SNPs. These data provide a pathway from n = 1 to n of more patients with SCN2A-RD and other monogenic disorders. ClinicalTrials.gov registration: NCT06314490 .","[""Journal Article""]","[""Kim-McManus O"", ""Mignon L"", ""Douville J"", ""Pu H"", ""Parisien C"", ""Glass S"", ""Bennett CF"", ""Celso J"", ""Robbins K"", ""Ung H"", ""Olson H"", ""Kingsmore SF"", ""Petrou S"", ""Crooke ST"", ""Gleeson JG"", ""Berry-Kravis E""]",10.1038/s41591-026-04527-y,Kim-McManus O,Nature medicine,1078-8956,,Nat Med,eng,Berry-Kravis E,[],,42481851,,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42481851/,Individualized antisense oligonucleotides for SCN2A-related developmental epileptic encephalopathy,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""News""]","[""O'Leary K""]",10.1038/d41591-026-00037-z,O'Leary K,Nature medicine,1078-8956,,Nat Med,eng,O'Leary K,[],,42469479,,2026 Jul 17,2026,https://pubmed.ncbi.nlm.nih.gov/42469479/,An AI co-scientist to accelerate biomedical research,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"Millions of people worldwide are living with movement and sensory impairments owing to spinal cord injury, stroke and other neurological conditions. Here we report a double neural bypass (DNB), a hybrid neuroprosthetic system designed to restore both immediate and lasting gains in movement and sensation after a severe, complete spinal cord injury. The DNB links an intracortical brain-computer interface with targeted and patterned neuromodulation of the spinal cord and cortex. This allows brain signals associated with movement intention to directly control the movement of the user's own hand in real time while also promoting long-term sensorimotor recovery-even after the system is turned off. The DNB system uses recurrent artificial neural networks and reinforcement learning for fine grasp control, together with patterned spinal cord stimulation and activity-informed intracortical microstimulation ('cortical mirroring') to promote neuroplasticity and durable recovery of function. In a participant with chronic C4 sensory/C5 motor complete tetraplegia, this hybrid approach enabled recovery of functional abilities including self-feeding and manipulation of delicate objects, while also producing significant and persistent improvements in elbow flexion and wrist tactile sensation. These findings demonstrate the potential of combining a sensorimotor neuroprosthesis with targeted brain and spinal neuromodulation to restore clinically relevant function in severe paralysis.","[""Journal Article"", ""Case Reports""]","[""Chandrasekaran S"", ""Wandelt SK"", ""Jangam A"", ""Elias Z"", ""Ibroci E"", ""Maffei C"", ""Rosenthal IA"", ""Ramdeo R"", ""Kim JW"", ""Xu J"", ""Glasser MF"", ""Neuwirth A"", ""Goldstein TA"", ""Crone NE"", ""Fifer MS"", ""Tostaeva G"", ""Bickel S"", ""Griffin D"", ""Funaro M"", ""Carras NG"", ""Pruitt R"", ""Ben-Shalom N"", ""Stein AB"", ""Mehta AD"", ""Bouton CE""]",10.1038/s41591-026-04498-0,Chandrasekaran S,Nature medicine,1078-8956,7,Nat Med,eng,Bouton CE,"[""Humans"", ""Quadriplegia"", ""Hand"", ""Movement"", ""Spinal Cord Injuries"", ""Brain-Computer Interfaces"", ""Recovery of Function"", ""Neural Prostheses"", ""Sensation"", ""Male"", ""Adult""]",2591-2601,42463883,pmc-id: PMC13375563;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42463883/,A neuroprosthesis for restoring hand movement and sensation in a person with complete tetraplegia,32,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""Published Erratum""]","[""Ferrand RA"", ""Dauya E"", ""Chikwari CD"", ""Bandason T"", ""Bernays S"", ""Mackworth-Young C"", ""Doyle AM"", ""Grundy C"", ""Indravudh P"", ""Terris-Prestholt F"", ""Mavodza CV"", ""Mugurungi O"", ""Apollo T"", ""Ncube G"", ""Larsson L"", ""McCarthy O"", ""Simms V"", ""Tembo M"", ""Kranzer K"", ""Hayes RJ""]",10.1038/s41591-026-04581-6,Ferrand RA,Nature medicine,1078-8956,,Nat Med,eng,Hayes RJ,[],,42463854,,2026 Jul 16,2026,https://pubmed.ncbi.nlm.nih.gov/42463854/,Author Correction: Integrated community-based HIV and sexual and reproductive health services for youth: a cluster-randomized trial,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""Published Erratum""]","[""Klempner SJ"", ""Sundar R""]",10.1038/s41591-026-04569-2,Klempner SJ,Nature medicine,1078-8956,,Nat Med,eng,Sundar R,[],,42463853,,2026 Jul 16,2026,https://pubmed.ncbi.nlm.nih.gov/42463853/,Author Correction: Evolution of claudin18.2 therapies in gastroesophageal cancers,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"There is an unmet need for effective, off-the-shelf therapies for relapsed or refractory aggressive B cell non-Hodgkin lymphoma (B-NHL). Part 2 of the current study was an open-label, nonrandomized, phase 1 study of escalating doses of the CD19-4-1BBL co-stimulatory molecule, englumafusp alfa, in combination with glofitamab in patients with relapsed or refractory B-NHL. Obinutuzumab pretreatment was administered 7 days before the first glofitamab dose. Glofitamab step-up dosing in cycle 1 was followed by 11 cycles of glofitamab plus englumafusp alfa. Englumafusp alfa was administered at escalating doses, with the initial dose on cycle 2 day 8 (C2D8) or cycle 1 day 10 (C1D10). Primary objectives were to establish the maximum tolerated dose, and safety and tolerability. A total of 134 patients were enrolled, including 109 with aggressive B-NHL and 25 with indolent B-NHL. The maximum tolerated dose of englumafusp alfa was not reached; one dose-limiting toxicity occurred (grade 5 Pneumocystis jirovecii pneumonia). Adverse events were reported in 98.5% of all patients, with grade 3/4 adverse events in 59.0%. Grade 5 adverse events occurred in ten patients. In the subgroup of C2D8 patients with aggressive B-NHL (n = 83), overall response and complete metabolic response rates were 68.7% and 56.6%, respectively; among those without previous exposure to chimeric antigen receptor T cell therapy (n = 41), the corresponding rates were 73.2% and 65.9%. Pharmacodynamic changes following englumafusp alfa administration supported its co-stimulatory mode of action. These data demonstrate that the addition of englumafusp alfa to glofitamab is associated with encouraging efficacy and robust pharmacodynamic modulation, as well as a safety profile consistent with glofitamab monotherapy, in patients with relapsed or refractory B-NHL. CTIS identifier: 2022-502616-37-00 ; ClinicalTrials.gov identifier: NCT04077723 .","[""Journal Article""]","[""Hutchings M"", ""Dickinson M"", ""Gritti G"", ""Carlo-Stella C"", ""Townsend W"", ""Bosch F"", ""Bartlett NL"", ""Cartron G"", ""Ghesquieres H"", ""Houot R"", ""Walter H"", ""Offner F"", ""Dimier N"", ""Jamois C"", ""Herter S"", ""Keelara A"", ""Wilson S"", ""Gallien J"", ""Hinton H"", ""Gonzalez-Albo IP"", ""Korfi K"", ""Kazantzidis G"", ""Wasmer MH"", ""Lechner K"", ""Morschhauser F""]",10.1038/s41591-026-04533-0,Hutchings M,Nature medicine,1078-8956,,Nat Med,eng,Morschhauser F,[],,42463852,,2026 Jul 16,2026,https://pubmed.ncbi.nlm.nih.gov/42463852/,Englumafusp alfa plus glofitamab in B cell non-Hodgkin lymphoma: a phase 1 trial,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""News""]","[""O'Leary K""]",10.1038/d41591-026-00036-0,O'Leary K,Nature medicine,1078-8956,,Nat Med,eng,O'Leary K,[],,42463498,,2026 Jul 16,2026,https://pubmed.ncbi.nlm.nih.gov/42463498/,Mining antigens for a universal malaria vaccine,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""News""]","[""Arnold C""]",10.1038/d41591-026-00035-1,Arnold C,Nature medicine,1078-8956,,Nat Med,eng,Arnold C,[],,42458038,,2026 Jul 15,2026,https://pubmed.ncbi.nlm.nih.gov/42458038/,A turning point for gene editing in severe blood disorders,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"While Alzheimer's disease (AD) is initiated by amyloid plaque accumulation, its progression involves local neuroinflammation that the brain cannot resolve when age-related dysfunction of the systemic immune system limits peripheral immune support. Preclinical studies using rodent models showed that transient systemic blockade of programmed death-ligand 1 is associated with reduced neuroinflammation, neuroprotection and attenuation of disease progression. Based on the underlying mechanism, a new short-lived anti-programmed death-ligand 1 antibody with Fc-effector silencing and reduced FcRn binding (IBC-Ab002) was engineered. Here, we report a randomized, double-blind, phase 1b first-in-human trial in early AD, with safety and tolerability as the primary endpoint. Forty participants were enrolled across five ascending dose cohorts (1-30 mg kg-1), with dosing administered four times at 3-month intervals. Treatment was well tolerated, with no treatment-related serious adverse events or evidence of amyloid-related imaging abnormalities. Exploratory analyses at week 48 showed directional changes in cerebrospinal fluid biomarkers of neuronal and synaptic damage favoring the 30 mg kg-1 dose, although no doses reached statistical significance given the limited sample size. The safety and tolerability profile supports further clinical development of systemic, intermittently administered IBC-Ab002 in early AD. ClinicalTrials.gov registration: NCT05551741 .","[""Journal Article""]","[""Croese T"", ""Mummery CJ"", ""Bregman N"", ""Bracha D"", ""Baruch K"", ""Kertser A"", ""Raveh S"", ""Shochat E"", ""Schwartz M""]",10.1038/s41591-026-04547-8,Croese T,Nature medicine,1078-8956,,Nat Med,eng,Schwartz M,[],,42458012,,2026 Jul 15,2026,https://pubmed.ncbi.nlm.nih.gov/42458012/,"Immunotherapy with a short-lived anti-PD-L1 antibody in Alzheimer's disease: a phase 1b, randomized, double-blind trial",,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""Journal Article""]",[],10.1038/s41591-026-04515-2,,Nature medicine,1078-8956,,Nat Med,eng,,[],,42458011,,2026 Jul 15,2026,https://pubmed.ncbi.nlm.nih.gov/42458011/,Multi-omics maps human-pig interactions in extracorporeal liver cross-circulation,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""Letter""]","[""Nasari A"", ""Nasari A"", ""Marzouk S"", ""Prasad T"", ""Fanzo J""]",10.1038/s41591-026-04507-2,Nasari A,Nature medicine,1078-8956,,Nat Med,eng,Fanzo J,[],,42458010,,2026 Jul 15,2026,https://pubmed.ncbi.nlm.nih.gov/42458010/,Fertilizer scarcity as a failure of global health governance,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""Journal Article""]","[""de Mast Q"", ""Brown CV"", ""Mwakasungura F"", ""Nakanjako D"", ""Temba GS"", ""Kumar V"", ""Pramono A"", ""Crișan TO"", ""Riza A"", ""de Jonge MI"", ""Wagner N"", ""Hoentjen F"", ""Ferreira AVM"", ""Chakraborty A"", ""Teixeira M"", ""Fekadu A"", ""Xavier RJ"", ""Sunguya B"", ""Netea MG""]",10.1038/s41591-026-04520-5,de Mast Q,Nature medicine,1078-8956,,Nat Med,eng,Netea MG,[],,42458009,,2026 Jul 15,2026,https://pubmed.ncbi.nlm.nih.gov/42458009/,Studying vanishing dietary diversity before it is lost: the World Diet Initiative,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""Journal Article""]","[""Vigod SN""]",10.1038/s41591-026-04526-z,Vigod SN,Nature medicine,1078-8956,,Nat Med,eng,Vigod SN,[],,42458008,,2026 Jul 15,2026,https://pubmed.ncbi.nlm.nih.gov/42458008/,When caution becomes harm,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease partly caused by gain-of-function mutations in superoxide dismutase 1 (SOD1). Here we developed RAG-17, an siRNA-targeting SOD1, using an accessory oligonucleotide conjugate platform for enhanced central nervous system (CNS) delivery. Preclinically, RAG-17 rescued motor neuron degeneration, delayed disease progression, preserved motor function and extended survival in SOD1G93A ALS rodents, even with advanced-stage treatment. In cynomolgus monkeys, intrathecal RAG-17 led to dose-dependent, durable reductions in SOD1 mRNA (CNS) and protein (cerebrospinal fluid (CSF)). In a first-in-human trial in patients with SOD1-ALS (n = 6), participants were assigned to two cohorts-cohort 1 (n = 3) received an initial 60 mg dose (seven doses total) and cohort 2 (n = 3) received an initial 90 mg dose (six doses total). The dose was escalated in 30 mg steps to maintenance doses of 150 mg (n = 5) or 180 mg (n = 1). Thus, the primary safety endpoint was met, showing acceptable safety and tolerability. Treatment-emergent adverse events (TEAEs) occurred in 33% of participants (two of six). All TEAEs were mild to moderate, including muscle tremor (two patients) and elevated alanine aminotransferase (one patient), all of which resolved. No serious adverse events were reported. Furthermore, no other clinically meaningful changes were observed in laboratory parameters, vital signs, the ALS Functional Rating Scale-Revised score, physical or neurological examinations or ECG. The key secondary endpoints showed CSF SOD1 reductions of 69% (cohort 1, day 240) and 56% (cohort 2, day 210), and plasma neurofilament light chain reductions of 62% (cohort 1) and 52% (cohort 2), from baseline; no patient required invasive mechanical ventilation or died by the end of the study. These results demonstrate a favorable safety outcome, supporting the continued clinical evaluation of RAG-17 for SOD1-ALS. ClinicalTrials.gov registration: NCT05903690 .","[""Journal Article"", ""Clinical Trial, Phase I""]","[""Chen W"", ""Jiang L"", ""Duan C"", ""Kang M"", ""Ye J"", ""Wang L"", ""Pan Y"", ""Qu H"", ""Liao X"", ""Zhou X"", ""Li Y"", ""Gan Z"", ""Chen J"", ""Schacht I"", ""Place RF"", ""Li LC"", ""Wang Y""]",10.1038/s41591-026-04491-7,Chen W,Nature medicine,1078-8956,7,Nat Med,eng,Wang Y,"[""Amyotrophic Lateral Sclerosis"", ""Humans"", ""Animals"", ""Superoxide Dismutase-1"", ""Female"", ""Male"", ""RNA, Small Interfering"", ""Oligonucleotides"", ""Macaca fascicularis"", ""Middle Aged"", ""Aged"", ""Adult"", ""Motor Neurons""]",2619-2628,42458007,pmc-id: PMC13375534;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42458007/,Oligonucleotide-siRNA conjugate for SOD1 amyotrophic lateral sclerosis: a phase 1 trial,32,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""Published Erratum""]","[""Sounderajah V"", ""Guni A"", ""Liu X"", ""Collins GS"", ""Karthikesalingam A"", ""Markar SR"", ""Golub RM"", ""Denniston AK"", ""Shetty S"", ""Moher D"", ""Bossuyt PM"", ""Darzi A"", ""Ashrafian H"", ""STARD-AI Steering Committee""]",10.1038/s41591-026-04570-9,Sounderajah V,Nature medicine,1078-8956,,Nat Med,eng,Ashrafian H,[],,42443516,,2026 Jul 13,2026,https://pubmed.ncbi.nlm.nih.gov/42443516/,Author Correction: The STARD-AI reporting guideline for diagnostic accuracy studies using artificial intelligence,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"Metastatic uveal melanoma (mUM) is an aggressive cancer with limited treatment options; 85-90% of tumors harbor activating GNAQ and GNA11 mutations. Uveal melanoma cells also express PMEL (also known as PMEL17 or gp100), a melanocyte lineage antigen. DYP688, a novel biology-matched antibody-drug conjugate, binds surface PMEL and delivers the potent Gαq/Gα11 (Gq/11) inhibitor SDZ475 as payload by internalization. This dose-escalating first-in-human phase 1 study of DYP688 in patients with metastatic uveal melanoma and other GNAQ/GNA11-mutant melanomas assessed safety as the primary endpoint and pharmacokinetics and preliminary antitumor activity as secondary endpoints. Sixty-six patients received varying DYP688 doses and schedules. Grade 3 treatment-related adverse events occurred in five patients (7.6%), including one dose-limiting toxicity of grade 3 hypotension. Objective responses were seen in 13 out of 66 patients (19.7%) and tumor reduction in 47 out of 66 patients (71.2%). Median progression-free survival was 7.2 (95% CI: 5.3-7.8) months. In summary, DYP688 was well tolerated and showed preliminary efficacy, supporting this novel therapeutic approach. ClinicalTrials.gov identifier: NCT05415072 .","[""Journal Article""]","[""Carlino MS"", ""Kapiteijn E"", ""Piperno-Neumann S"", ""Sullivan RJ"", ""Carvajal R"", ""Dummer R"", ""Gromke T"", ""Hassel JC"", ""Kee D"", ""Ramelyte E"", ""Shoushtari AN"", ""Wei AZ"", ""Enk A"", ""Handel EE"", ""Montazeri K"", ""Ramon-Patino J"", ""Richly H"", ""Rodrigues M"", ""Sandhu S"", ""Smithy J"", ""Speetjens FM"", ""Milanez-Almeida P"", ""Chaudhury A"", ""Hoffmaster K"", ""Ising M"", ""Otero JA"", ""RamKumar T"", ""Reynolds A"", ""Sharaby S"", ""Werner L"", ""Yerramilli-Rao P"", ""Calvo E""]",10.1038/s41591-026-04518-z,Carlino MS,Nature medicine,1078-8956,,Nat Med,eng,Calvo E,[],,42443515,,2026 Jul 13,2026,https://pubmed.ncbi.nlm.nih.gov/42443515/,An anti-PMEL antibody-drug conjugate with a G(q/1)(1) inhibitor payload in GNAQ/GNA11-mutant melanomas: a phase 1 trial,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"Lymphocyte activation gene 3 (LAG-3) is an immune checkpoint implicated in T cell exhaustion and a potential therapeutic target in glioblastoma (GBM). We conducted a multicenter, open-label, phase 1 study with sequential allocation to evaluate the safety and preliminary activity of the anti-LAG-3 antibody relatlimab, administered alone or with the anti-programmed cell death protein 1 (PD-1) antibody nivolumab, in patients with recurrent GBM. Forty-six patients were treated (23 per cohort). The primary endpoint of safety was met, with maximum tolerated doses of 800 mg relatlimab for monotherapy and 160 mg relatlimab/240 mg nivolumab for combination therapy. Treatment-related grade 3-4 adverse events occurred in 6 of 23 patients receiving combination therapy and were not observed with monotherapy. Neoadjuvant administration was associated with increased intratumoral CD8+ T cell infiltration for both monotherapy and combination therapy. Exploratory analyses suggested that tumors with elevated baseline interferon signaling and increased T cell clonality were enriched among patients with durable responses to combination therapy. Twelve-month overall survival was 34.8% with relatlimab alone and 52.2% with combination therapy; however, this study was not designed to assess efficacy. These findings demonstrate an acceptable safety profile and provide preliminary immunologic and clinical signals supporting further evaluation of LAG-3 blockade in GBM. ClinicalTrials.gov identifier: NCT02658981 .","[""Journal Article"", ""Clinical Trial, Phase I"", ""Multicenter Study""]","[""Lim M"", ""Ye X"", ""Piotrowski AF"", ""Desai A"", ""Ahluwalia MS"", ""Walbert T"", ""Lesser G"", ""Ellingson BM"", ""Peereboom DM"", ""Fisher JD"", ""Desideri S"", ""Jackson C"", ""Pant A"", ""Jain A"", ""Verma R"", ""Oberlton B"", ""Piyadasa H"", ""Bettegowda C"", ""Engle L"", ""Taube J"", ""Bendall SC"", ""Choi J"", ""Drappatz J"", ""Lieberman FS"", ""Kleinberg LR"", ""Pardoll DM"", ""Nabors LB"", ""Wen PY"", ""Grossman SA""]",10.1038/s41591-026-04475-7,Lim M,Nature medicine,1078-8956,7,Nat Med,eng,Grossman SA,"[""Humans"", ""Glioblastoma"", ""Female"", ""Lymphocyte Activation Gene 3 Protein"", ""Male"", ""Middle Aged"", ""Programmed Cell Death 1 Receptor"", ""Aged"", ""Adult"", ""Antigens, CD"", ""Neoplasm Recurrence, Local"", ""Nivolumab"", ""Brain Neoplasms"", ""CD8-Positive T-Lymphocytes"", ""Antibodies, Monoclonal, Humanized"", ""Antineoplastic Combined Chemotherapy Protocols""]",2449-2460,42432293,pmc-id: PMC13375532;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42432293/,Anti-LAG-3 with or without anti-PD-1 in recurrent glioblastoma: a phase 1 trial,32,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"Frontier artificial intelligence (AI) models have advanced rapidly through training on internet-scale public data, yet such systems lack access to private clinical data. Neuroimaging is underrepresented in the public domain due to identifiable facial features within magnetic resonance imaging (MRI) and computed tomography (CT) scans, restricting model performance in clinical medicine. Here we show that frontier models underperform on neuroimaging tasks and that learning directly from uncurated data generated during routine clinical care at health systems, a paradigm we call 'health system learning', yields high-performance, generalist neuroimaging models. We introduce NeuroVFM, a visual foundation model trained on 5.24 million clinical MRI and CT volumes using a scalable volumetric predictive architecture. NeuroVFM learns comprehensive representations of brain anatomy and pathology, achieving state-of-the-art performance across multiple clinical tasks, including radiologic diagnosis and report generation. The model embeds MRI and CT scans into a shared neuroanatomic latent space and grounds diagnostic findings. When paired with open-source language models, NeuroVFM generates radiology reports that surpass frontier models in accuracy, clinical triage and expert preference. NeuroVFM reduces hallucinated findings and critical errors, offering safer clinical decision support. These results establish health system learning as a paradigm for building generalist medical AI and provide a scalable framework for clinical foundation models.","[""Journal Article""]","[""Kondepudi A"", ""Rao A"", ""Zhao C"", ""Lyu Y"", ""Harake S"", ""Banerjee S"", ""Ogle J"", ""Joshi R"", ""Meissner AK"", ""Hou X"", ""Jiang C"", ""Chowdury A"", ""Srinivasan A"", ""Athey B"", ""Gulani V"", ""Pandey A"", ""Lee H"", ""Hollon T""]",10.1038/s41591-026-04497-1,Kondepudi A,Nature medicine,1078-8956,,Nat Med,eng,Hollon T,[],,42432292,,2026 Jul 10,2026,https://pubmed.ncbi.nlm.nih.gov/42432292/,Health system learning enables generalist neuroimaging models,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"KRASG12D is the predominant oncogenic driver in pancreatic ductal adenocarcinoma (PDAC). While most investigational KRAS-G12D inhibitors are oral small molecules limited by gastrointestinal toxicities and suboptimal tumor exposure, HRS-4642 is a new, high‑affinity, noncovalent KRAS-G12D inhibitor. Formulated as a liposomal nanoparticle for intravenous administration, it is designed to enhance tumor accumulation and prolong the duration of target inhibition. This phase 1b/2 study evaluated HRS-4642 in combination with nab-paclitaxel and gemcitabine (AG) in patients with advanced KRASG12D-mutant PDAC. As of 5 December 2025, 68 patients were screened and 31 (1 previously treated patient and 30 treatment-naive patients) were enrolled and treated. In the phase 1b portion, no dose-limiting toxicities were observed, and the starting dose (500 mg on day 1 and 1,200 mg on day 8, every 3 weeks) was selected as the recommended phase 2 dose. In the phase 2 portion, with a median follow-up of 12.3 months (95% confidence interval (CI) = 12.2-13.0), the primary endpoint was met-the confirmed objective response rate in 30 treatment-naive patients was 63.3% (95% CI = 43.9-80.1). Grade ≥3 treatment-related adverse events (TRAEs) occurred in 90.3% patients, primarily hematologic toxicities consistent with AG chemotherapy. No TRAEs led to treatment discontinuation or death. In conclusion, HRS-4642 combined with AG demonstrates promising antitumor activity and a manageable safety profile in advanced KRASG12D-mutant PDAC, supporting further investigation. Clinicaltrials.gov registration: NCT06520488 .","[""Journal Article""]","[""Cui J"", ""Jiang K"", ""Li W"", ""Ni S"", ""Zong H"", ""Du J"", ""He Y"", ""Liu Z"", ""Kong G"", ""Zhang Y"", ""Li X"", ""Han H"", ""Yao F"", ""Chen Y"", ""Zhou M"", ""Wang L""]",10.1038/s41591-026-04538-9,Cui J,Nature medicine,1078-8956,,Nat Med,eng,Wang L,[],,42426224,,2026 Jul 9,2026,https://pubmed.ncbi.nlm.nih.gov/42426224/,KRAS-G12D inhibitor HRS-4642 plus chemotherapy in advanced KRAS(G12D)-mutant pancreatic cancer: a phase 1b/2 trial,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"Parkinson's disease (PD) is characterized by progressive loss of nigral dopaminergic neurons, resulting in disabling motor symptoms. Intracerebral transplantation of stem cell-derived dopaminergic progenitors to replace lost endogenous dopaminergic neurons offers a new potentially restorative therapeutic approach for PD. Here we report the 12-month primary safety end point and interim efficacy outcomes from a phase 1/2, open-label, multicenter trial evaluating STEM-PD, a cryopreserved, off-the-shelf dopaminergic progenitor product derived from human pluripotent stem cells. Eight individuals with moderate PD underwent bilateral intraputaminal transplantation at two escalating doses (n = 4 per cohort), followed by 12 months of immunosuppression. Seven participants completed 12-month follow-up; one participant died from a pulmonary infection. No serious adverse events were attributed to the cell product, no graft-induced dyskinesias were observed and serial magnetic resonance imaging showed no evidence of tumor formation. These findings support the feasibility and favorable safety profile of human pluripotent stem cell-derived dopaminergic progenitor transplantation in this early-phase study, with risks primarily associated with the immunosuppression regimen. Ongoing follow-up to 36 months will further evaluate durability, clinical outcomes and graft function. ClinicalTrials.gov identifier: NCT05635409 .","[""Journal Article""]","[""Paul G"", ""Bjartmarz H"", ""Kirkeby A"", ""Nelander J"", ""Smith R"", ""Kayhanian S"", ""Evans A"", ""Harry B"", ""Cutting E"", ""Fazal S"", ""Lao-Kaim NP"", ""van Vliet T"", ""Ullén S"", ""Grubor I"", ""Hansson O"", ""Piccini P"", ""Lindvall O"", ""Björklund A"", ""Widner H"", ""Parmar M"", ""Barker RA""]",10.1038/s41591-026-04525-0,Paul G,Nature medicine,1078-8956,,Nat Med,eng,Barker RA,[],,42426223,,2026 Jul 9,2026,https://pubmed.ncbi.nlm.nih.gov/42426223/,Human embryonic stem cell-derived dopaminergic cells for Parkinson's disease: a phase 1/2 open-label trial,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""Journal Article""]","[""Oh J"", ""Barkhof F"", ""Bar-Or A"", ""Ciccarrelli O"", ""Coetzee T"", ""Filippi M"", ""Granziera C"", ""Hacohen Y"", ""Hemmer B"", ""Kantarci OH"", ""Kim HJ"", ""Lebrun-Frenay C"", ""Montalban X"", ""Mowry E"", ""Ontaneda D"", ""Prat A"", ""Reich DS"", ""Rovira À"", ""Sati P"", ""Siva A"", ""Solomon AJ"", ""Sormani MP"", ""Stankoff B"", ""Thompson A"", ""Tintore M"", ""Traboulsee A"", ""van der Walt A"", ""Wiendl H"", ""Calabresi PA""]",10.1038/s41591-026-04490-8,Oh J,Nature medicine,1078-8956,,Nat Med,eng,Calabresi PA,[],,42426222,,2026 Jul 9,2026,https://pubmed.ncbi.nlm.nih.gov/42426222/,Challenges and future directions for multiple sclerosis after the 2024 McDonald diagnostic criteria,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""News""]","[""Guenot M""]",10.1038/s41591-026-04484-6,Guenot M,Nature medicine,1078-8956,7,Nat Med,eng,Guenot M,[],2324-2327,42426221,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42426221/,When the real world becomes the trial,32,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""Journal Article""]","[""Strenzke N""]",10.1038/s41591-026-04512-5,Strenzke N,Nature medicine,1078-8956,,Nat Med,eng,Strenzke N,[],,42426220,,2026 Jul 9,2026,https://pubmed.ncbi.nlm.nih.gov/42426220/,A second chance for gene therapy to restore natural hearing,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"There are extensive ongoing efforts to slow or even reverse human aging, such as with epigenetic cellular reprogramming, thymus rejuvenation or senolytics. In parallel, new and diverse metrics-known as biological clocks-have been discovered and shown to track the pace of aging in an individual and their organs, tissues and cells. These clocks have multiple potential use cases, including identifying people at high risk of disease, serving as a foundation for prevention or early detection, and determining whether lifestyle factors or an intervention can modulate the aging process. This review provides a critical appraisal of the progress that is being made with biological clocks and how they might ultimately help understand pathobiology, reduce the burden of disease and extend healthspan.","[""Journal Article"", ""Review""]","[""Wyss-Coray T"", ""Topol EJ""]",10.1038/s41591-026-04495-3,Wyss-Coray T,Nature medicine,1078-8956,7,Nat Med,eng,Topol EJ,"[""Humans"", ""Aging"", ""Biological Clocks"", ""Animals"", ""Epigenesis, Genetic""]",2383-2394,42426219,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42426219/,Biological aging clocks in health and disease,32,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"The World Health Organization (WHO) Global Breast Cancer Initiative aims to attain meaningful global breast cancer mortality reductions by 2040-a target that hinges on improvements in patient outcomes and survival. So far, however, data on cancer survival remain limited in low- and middle-income countries. The WHO estimated population-based age-standardized 5-year net survival for women diagnosed with breast cancer between 2017 and 2021 across all 194 Member States, providing a global benchmark for monitoring breast cancer outcomes. Here we found that median 5-year net survival varied widely across WHO regions during 2017-2021: 39.1% (95% uncertainty interval 34.1-44.7%) in the African Region, 61.0% (51.4-69.8%) in the Eastern Mediterranean Region, 66.3% (57.7-73.7%) in the South-East Asia Region, 81.1% (78.6-83.5%) in the Western Pacific Region, 84.0% (82.8-85.1%) in the European Region and 88.5% (86.7-90.1%) in the Region of the Americas. Persisting disparities in survival reflect profound global inequities; sustained initiatives to narrow gaps in access to diagnosis and treatment for breast cancer are crucial to strengthening health systems. This will enable all countries to ensure optimal outcomes for their patients with breast cancer and achieve Global Breast Cancer Initiative and Sustainable Development Goals targets.","[""Journal Article""]","[""Girardi F"", ""Nyangasi M"", ""Callender C"", ""Ng M"", ""Narita S"", ""Torode J"", ""AlSawahli H"", ""Ong SK"", ""Gnangnon F"", ""McCormack V"", ""Shelpai W"", ""Rizu"", ""Mahmoud L"", ""Wang H"", ""Ilbawi AM""]",10.1038/s41591-026-04531-2,Girardi F,Nature medicine,1078-8956,,Nat Med,eng,Ilbawi AM,[],,42420542,,2026 Jul 8,2026,https://pubmed.ncbi.nlm.nih.gov/42420542/,Global breast cancer survival estimates in 2017-2021 to advance the WHO Global Breast Cancer Initiative,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
,"[""Editorial""]",[],10.1038/s41591-026-04554-9,,Nature medicine,1078-8956,7,Nat Med,eng,,[],2321,42420541,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42420541/,Oncology must confront hidden side effects,32,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"Extracorporeal liver cross-circulation (ELC) using gene-edited porcine liver xenografts offers a potential bridge therapy for liver failure. We previously performed five ELC procedures in four brain-dead human decedents, during which the recipients developed severe thrombocytopenia. The porcine liver xenografts maintained their parenchymal structure, with immune cell infiltration and detectable IgM deposition on endothelial cells. Here, to investigate the underlying host-xenograft interactions, we performed longitudinal proteomic, lipidomic and metabolomic profiling of 64 blood samples, alongside spatial transcriptomics and histology of 25 porcine liver xenograft and 3 native human liver biopsies. Spatial transcriptomic analysis revealed progressive infiltration of human immune cells (predominantly inflammatory macrophages and neutrophils) in the xenografts, concurrent with the loss of porcine Kupffer-like macrophages and T cells. Distinct human and porcine complement dynamics were observed, with suppressed human but elevated porcine complement levels, accompanied by increased levels of porcine acute-phase proteins and coagulation factors. Moreover, multiomics analyses identified candidate cellular and molecular factors associated with thrombocytopenia. Human platelets colocalized with activated porcine endothelial cells, which showed increasing porcine vWF expression over time, as well as with immune cells (primarily macrophages and neutrophils) and hepatocytes in the xenografts. Integrative analyses indicated that ELC procedures provided hepatic support for apolipoprotein synthesis, bilirubin clearance, energy metabolism and detoxification, although circulating lipid levels remained low under anhepatic conditions. Collectively, these findings yield insights into the complex interplay between human and xenograft systems during ELC and inform strategies to improve liver xenograft biocompatibility for clinical translation.","[""Journal Article""]","[""Guo Q"", ""Wang C"", ""Mauduit V"", ""Stukalov A"", ""Mohebnasab M"", ""Sagar A"", ""Vikman S"", ""Williams SH"", ""Maden B"", ""Eitan T"", ""Barone K"", ""Motter JD"", ""Dowdell AK"", ""Robinson FL"", ""Guillot-Tantay C"", ""Zayas Z"", ""Little JP"", ""Verrou KM"", ""Gálvez-Merchán Á"", ""Guo P"", ""Moi K"", ""Stimson E"", ""Gao H"", ""Argibay D"", ""Wu L"", ""Holmes AG"", ""Bartlett AQ"", ""Xin D"", ""Futeran H"", ""Batzoglou S"", ""Joshi S"", ""Rophina M"", ""Zanoni F"", ""Elzawahry MA"", ""Fallon JI"", ""Abbas SH"", ""Olthoff KM"", ""Abrams CS"", ""Chhangawala S"", ""Griesemer A"", ""Friend P"", ""Siddiqui A"", ""Schmauch E"", ""Piening BD"", ""Shaked A"", ""Keating BJ""]",10.1038/s41591-026-04511-6,Guo Q,Nature medicine,1078-8956,,Nat Med,eng,Keating BJ,[],,42414621,,2026 Jul 7,2026,https://pubmed.ncbi.nlm.nih.gov/42414621/,Longitudinal multiomics profiling of extracorporeal cross-circulation with pig liver xenografts in human decedents,,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"Oropouche virus (OROV) was reported in Cuba in May 2024 and rapidly spread throughout the country. Here, among 147 reverse-transcription polymerase chain reaction-positive cases identified from May to July 2024, we sequenced 39 whole genomes of OROV. Phylogenetic analysis revealed that all sequences formed a monophyletic cluster nested within the reassortant lineage, named OROVBR-2015-2025, which has been circulating extensively in Brazil since 2023. Additional phylogeographic analyses demonstrated that the Cuban subclade probably originated from a single viral introduction from the Brazilian state of Acre in early February 2024, followed by cryptic circulation until its identification in May. The introduction probably occurred in the central region of the country, from which the virus spread and established secondary transmission hubs in the western and eastern regions. These findings underscore the capacity of OROV to spread well beyond South America, which was considered its endemic area of circulation.","[""Journal Article""]","[""Gravier R"", ""Perez MM"", ""Álvarez M"", ""Pérez L"", ""Benítez AJ"", ""Hernández D"", ""Serrano S"", ""de Armas JR"", ""Peña C"", ""Rivera M"", ""Franco L"", ""Leite J"", ""Gresh L"", ""Méndez J"", ""Souza V"", ""Mejía M"", ""Bello G"", ""Arantes I"", ""Resik S"", ""Kouri V"", ""Naveca FG"", ""Guzman MG""]",10.1038/s41591-026-04411-9,Gravier R,Nature medicine,1078-8956,7,Nat Med,eng,Guzman MG,"[""Cuba"", ""Phylogeny"", ""Humans"", ""Disease Outbreaks"", ""Orthobunyavirus"", ""Bunyaviridae Infections"", ""Genome, Viral"", ""Phylogeography"", ""Brazil""]",2401-2404,42414620,pmc-id: PMC13375556;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42414620/,Spatiotemporal diffusion of the 2024 Oropouche outbreak in Cuba,32,r9GDF8oUQxUgnesSn,XPdoULSRbkZbN0WmB
"Coronary artery bypass grafting (CABG) is a common but invasive operation traditionally performed through a median sternotomy. Minimally invasive cardiac surgery (MICS) CABG via small thoracotomy might improve postoperative recovery, but randomised evidence has been scarce. We aimed to compare patient-reported recovery after MICS CABG versus sternotomy CABG in patients with multivessel coronary artery disease and to describe clinical and safety outcomes. MIST was an investigator-initiated, international, open-label, randomised controlled trial done at seven centres (four academic hospitals and three community hospitals) in Canada, India, China, Germany, the USA, and Japan. Patients referred to participating surgeons for CABG were eligible if they were aged 18 years or older; had angiographically confirmed multivessel coronary artery disease, defined as lesions of at least 70% stenosis in at least two major epicardial vessels and at least two separate coronary artery territories (left anterior descending artery, left circumflex artery, or right coronary artery) or left main coronary stenosis of 50% or more; and were suitable for coronary surgery both with sternotomy CABG and MICS CABG. Patients who were haemodynamically compromised, had contraindications to either approach, had had previous cardiac surgery, or required concomitant procedures were excluded. Eligible patients were randomly assigned (1:1) to MICS CABG or sternotomy CABG by a central, web-based system, stratified by centre, with block sizes of four and six. The primary endpoint was patient-reported physical recovery at 1 month, assessed by the 36-item Short Form Health Survey Physical Component Summary (SF-36 PCS) score. The primary analysis was by intention to treat; safety analyses were done according to treatment received. Missing 1-month questionnaire data were handled by multiple imputation. The trial was registered with ClinicalTrials.gov (NCT03447938), and is closed to recruitment. Between Aug 24, 2018, and Nov 26, 2024, 176 patients were enrolled, 170 of whom were randomly assigned to MICS CABG (n=86) or sternotomy CABG (n=84). The median age of patients was 67·0 years (IQR 61·0-72·0), 154 (91%) patients were male, and 16 (9%) were female. At 1 month after surgery, SF-36 PCS scores were significantly higher in the MICS CABG group than in the sternotomy CABG group (mean 45·1 [SD 8·0] vs 42·2 [9·1]; mean difference 2·9 [95% CI 0·3-5·5]; p=0·031). Clinical and safety follow-up at 1 month was complete in all patients; 12-month clinical and safety follow-up was complete in all except three patients in the sternotomy CABG group. Up to 12 months after surgery, there were no deaths or strokes in either group; one major adverse cardiac or cerebrovascular event occurred in the MICS CABG group before 1 month and none in the sternotomy CABG group. For selected patients with multivessel coronary artery disease, MICS CABG performed by experienced teams improved patient-reported physical recovery at 1 month compared with sternotomy CABG, with no apparent safety penalty through to 12 months. These findings support consideration of MICS CABG in appropriately selected patients treated by experienced teams, and further studies of implementation, recovery pathways, and long-term outcomes. Medtronic.","[""Journal Article""]","[""Ruel M"", ""Nambala S"", ""Guo MH"", ""Verevkin A"", ""Rabindranauth P"", ""Kikuchi K"", ""Davierwala PM"", ""Lemma M"", ""Ponnambalam M"", ""Sheikh A"", ""Black A"", ""Borger MA"", ""Whitlock RP"", ""Zhang Y"", ""Wells GA""]",10.1016/S0140-6736(26)01288-2,Ruel M,"Lancet (London, England)",0140-6736,,Lancet,eng,Wells GA,[],,42537680,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42537680/,"Multivessel coronary artery bypass grafting via small thoracotomy versus sternotomy (MIST): an investigator-initiated, international, open-label, randomised controlled trial",,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Sondos HA""]",10.1016/S0140-6736(26)01415-7,Sondos HA,"Lancet (London, England)",0140-6736,,Lancet,eng,Sondos HA,[],,42537679,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42537679/,Oncology and emergency care collapse in the West Bank,,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Hossain MS""]",10.1016/S0140-6736(26)01477-7,Hossain MS,"Lancet (London, England)",0140-6736,,Lancet,eng,Hossain MS,[],,42532082,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42532082/,"July 2026 floods in Chattogram, Bangladesh: an escalating emergency",,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Journal Article""]","[""Chow E"", ""Bai Z""]",10.1016/S0140-6736(26)01487-X,Chow E,"Lancet (London, England)",0140-6736,,Lancet,eng,Bai Z,[],,42532081,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42532081/,A novel unimolecular GLP1 and amylin receptor agonist for glucose and weight control,,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
"Zenagamtide (formerly amycretin) is a unimolecular agonist of GLP-1, amylin, and calcitonin receptors. We aimed to investigate the dose-response relationship with respect to the efficacy and safety of once-weekly subcutaneous zenagamtide compared with placebo in adults with type 2 diabetes. This 36-week, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial was conducted at 83 hospital and clinic sites across 11 countries. The trial consisted of a 3-week screening period, a 36-week intervention period, and a 4-week follow-up period. Adults (aged 18-75 years) with type 2 diabetes (glycated haemoglobin [HbA1c] 7·0-10·0% [53-86 mmol/mol]), treated with stable doses of metformin with or without a SGLT2 inhibitor, and with a BMI of 23·0 to <50·0 kg/m2 were randomly assigned (6:1) to once-weekly subcutaneous zenagamtide or placebo using a randomisation and trial supplies management system, before being further randomly assigned to one of six dose groups (1:1:1:1:1:1; 0·4, 1·5, 5, 10, 20, or 40 mg). Participants assigned to placebo were similarly allocated to matched placebo regimens corresponding to each dosing schedule. Randomisation was stratified by HbA1c (<8·5% or ≥8·5%) at screening and country of residence (Japan or other countries). The starting dose of subcutaneous zenagamtide was 0·2 mg, with dose escalations every 4 weeks until the maintenance dose was reached (0·4-40 mg). Participants and staff were masked within each dose level to placebo or zenagamtide. The primary outcome was change in HbA1c from baseline to week 36. The primary outcome was assessed in all randomly assigned participants using the efficacy estimand based on on-treatment data without rescue medication. Safety outcomes were assessed in all randomly assigned participants exposed to treatment. The trial is registered with ClinicalTrials.gov, NCT06542874, and is completed. Between Aug 7 and Dec 27, 2024, 262 (29%) of 915 screened individuals were randomly assigned to subcutaneous zenagamtide (n=225) or placebo (n=37). Participants were further randomly assigned (1:1:1:1:1:1) to one of six doses (38 participants to 0·4 mg, 36 participants to 1·5 mg, 37 participants to 5 mg, 38 participants to 10 mg, 38 participants to 20 mg, and 38 participants to 40 mg) or placebo (37 participants). 261 participants were exposed to treatment. At week 36, estimated change in HbA1c (mean across all groups at baseline 7·8% [SD 0·8]) ranged from -0·9% with zenagamtide 0·4 mg (estimated treatment difference vs placebo: -0·77% [95% CI -1·26 to -0·28]; p=0·0021) to -1·7% with zenagamtide 40 mg (-1·56% [-2·05 to -1·07]; p<0·0001). Most adverse events were gastrointestinal and mild to moderate in severity. 21 (8%) of 261 participants reported serious adverse events (four with zenagamtide 0·4 mg, three with 1·5 mg, two with 5 mg, five with 10 mg, three with 20 mg, one with 40 mg, and three with placebo). No deaths occurred. In people with type 2 diabetes, once-weekly subcutaneous zenagamtide 0·4-40 mg demonstrated clinically meaningful and significant improvements in change in HbA1c from baseline to week 36 compared with placebo, with a safety and tolerability profile consistent with that of other GLP-1-based and amylin-based therapies. Novo Nordisk.","[""Journal Article""]","[""Mora P"", ""Aroda VR"", ""Asong M"", ""Blüher M"", ""Heftdal LD"", ""Carlander AF"", ""Vilsen LN"", ""Rosenstock J""]",10.1016/S0140-6736(26)01248-1,Mora P,"Lancet (London, England)",0140-6736,,Lancet,eng,Rosenstock J,[],,42532080,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42532080/,"Efficacy and safety of once-weekly subcutaneous zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial",,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
"Zenagamtide (formerly amycretin) is a unimolecular peptide agonist of GLP-1, amylin, and calcitonin receptors. We aimed to investigate the dose-response relationship with respect to the efficacy and safety of once-daily oral zenagamtide compared with placebo in adults with type 2 diabetes. This 36-week, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial was conducted at 83 hospital and clinic sites across 11 countries. The trial consisted of a 3-week screening period, a 36-week intervention period, and a 4-week follow-up period. Adults (aged 18-75 years) with type 2 diabetes (glycated haemoglobin [HbA1c] 7·0-10·0% [53-86 mmol/mol]), treated with stable doses of metformin with or without a SGLT2 inhibitor, and with a BMI of 23·0 to <50·0 kg/m2 were randomly assigned (5:1) to oral zenagamtide or placebo using a randomisation and trial supplies management system, then further randomly assigned (1:1:1) to one of three dose groups (6, 25, or 50 mg). Participants assigned to placebo were similarly assigned to matched placebo regimens corresponding to each dosing schedule. Randomisation was stratified by HbA1c (<8·5% or ≥8·5%) at screening and country of residence (Japan or other countries). The starting dose of oral zenagamtide was 1·5 mg, with dose escalations every 4 weeks until the maintenance dose was reached (6, 25, or 50 mg). Participants and staff were masked within each dose level to placebo or zenagamtide. The primary outcome was change in HbA1c from baseline to week 36. The primary outcome was assessed in all randomly assigned participants using the efficacy estimand based on on-treatment data without rescue medication. Safety outcomes were assessed in all randomly assigned participants exposed to treatment. This trial is registered with ClinicalTrials.gov, NCT06542874, and is completed. Between Aug 7 and Dec 27, 2024, 186 (20%) of 915 screened participants were randomly assigned to oral zenagamtide (54 participants to 6 mg, 51 participants to 25 mg, and 51 participants to 50 mg) or placebo (30 participants) and were included in the full analysis set. At week 36, from baseline (mean range 7·9-8·1%), estimated mean change in HbA1c was -0·9% with zenagamtide 6 mg (estimated treatment difference [ETD] vs placebo -0·5% [95% CI -1·04 to -0·04]; p=0·033), -1·3% with zenagamtide 25 mg (-0·99% [-1·49 to -0·49]; p=0·0001), and -1·4% with zenagamtide 50 mg (-1·09% [-1·59 to -0·59]; p<0·0001). The most common adverse events were gastrointestinal, occurring in 14 (26%) of 54 participants in the zenagamtide 6 mg group, 21 (41%) of 51 participants in the zenagamtide 25 mg group, 24 (47%) of 51 participants in the zenagamtide 50 mg group, and seven (23%) of 30 participants in the placebo group. Serious adverse events were reported in seven (4%) of 186 participants receiving zenagamtide: two in the 6 mg group, two in the 25 mg group, and three in 50 mg group. No serious adverse events were reported in the placebo group. No deaths occurred during the trial. In people with type 2 diabetes, once-daily oral zenagamtide showed clinically meaningful and significant improvements in HbA1c from baseline to week 36 compared with placebo at all three dose levels (6, 25, and 50 mg). The safety and tolerability of oral zenagamtide was consistent with other GLP-1 and amylin receptor agonists. Novo Nordisk.","[""Journal Article""]","[""Mora P"", ""Aroda VR"", ""Asong M"", ""Blüher M"", ""Carlander AF"", ""Kaltoft M"", ""Vilsen LN"", ""Rosenstock J""]",10.1016/S0140-6736(26)01247-X,Mora P,"Lancet (London, England)",0140-6736,,Lancet,eng,Rosenstock J,[],,42532079,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42532079/,"Efficacy and safety of once-daily oral zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in adults with type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial",,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Nyberg ST"", ""Frank P"", ""Kivimäki M""]",10.1016/S0140-6736(26)01133-5,Nyberg ST,"Lancet (London, England)",0140-6736,10553,Lancet,eng,Kivimäki M,[],416,42532065,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42532065/,How definitions shape obesity-attributable death estimates - Authors' reply,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Boulares A"", ""Bragazzi NL""]",10.1016/S0140-6736(26)01029-9,Boulares A,"Lancet (London, England)",0140-6736,10553,Lancet,eng,Bragazzi NL,[],415-416,42532064,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42532064/,How definitions shape obesity-attributable death estimates,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Renzullo AM"", ""Benvenuto S""]",10.1016/S0140-6736(26)01030-5,Renzullo AM,"Lancet (London, England)",0140-6736,10553,Lancet,eng,Benvenuto S,[],414,42532063,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42532063/,PUSH trial limits: why fluids still matter,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Scales CD Jr"", ""Desai AC"", ""Reese PP"", ""Lieske JC"", ""Tasian GE""]",10.1016/S0140-6736(26)01282-1,Scales CD Jr,"Lancet (London, England)",0140-6736,10553,Lancet,eng,Tasian GE,[],414-415,42532062,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42532062/,PUSH trial limits: why fluids still matter - Authors' reply,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Thomson DJ"", ""Price JM"", ""Tyler M"", ""Hall E""]",10.1016/S0140-6736(26)01182-7,Thomson DJ,"Lancet (London, England)",0140-6736,10553,Lancet,eng,Hall E,[],413-414,42532061,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42532061/,Perspective on proton beam therapy for oropharyngeal cancer - Authors' reply,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Allemani C"", ""Di Carlo V"", ""Ssenyonga N"", ""Arias-Ortiz NE"", ""Coleman MP""]",10.1016/S0140-6736(26)01284-5,Allemani C,"Lancet (London, England)",0140-6736,10553,Lancet,eng,Coleman MP,[],412,42532060,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42532060/,Representativeness of the Cancer Survival Index in Colombia - Authors' reply,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""De Luca P"", ""Bussu F"", ""Camaioni A""]",10.1016/S0140-6736(26)01070-6,De Luca P,"Lancet (London, England)",0140-6736,10553,Lancet,eng,Camaioni A,[],412-413,42532059,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42532059/,Perspective on proton beam therapy for oropharyngeal cancer,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Ramirez O"", ""Quijano-Lievano ML"", ""Lauzardo M"", ""Bravo LE"", ""Aristizabal P"", ""VIGICANCER Working Group""]",10.1016/S0140-6736(26)01063-9,Ramirez O,"Lancet (London, England)",0140-6736,10553,Lancet,eng,Aristizabal P,[],411-412,42532058,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42532058/,Representativeness of the Cancer Survival Index in Colombia,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Evison M"", ""Mullen KA"", ""Mir H""]",10.1016/S0140-6736(26)01365-6,Evison M,"Lancet (London, England)",0140-6736,10553,Lancet,eng,Mir H,[],410-411,42532057,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42532057/,Global tobacco control in 2026: progress yet deepening inequity,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Cloete K"", ""Chopra M""]",10.1016/S0140-6736(26)01364-4,Cloete K,"Lancet (London, England)",0140-6736,10553,Lancet,eng,Chopra M,[],410,42532056,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42532056/,An eleventh lesson: escaping the scarcity equilibrium,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Wakefield D""]",10.1016/S0140-6736(26)01197-9,Wakefield D,"Lancet (London, England)",0140-6736,10553,Lancet,eng,Wakefield D,[],409-410,42532055,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42532055/,Pandora's box: why context is key in inequalities research,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Editorial""]","[""The Lancet""]",10.1016/S0140-6736(26)01548-5,The Lancet,"Lancet (London, England)",0140-6736,10553,Lancet,eng,The Lancet,[],381,42532054,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42532054/,Learning from a decade of progress in amyloidosis,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
"Psoriasis is a common, chronic, immune-mediated skin disease affecting more than 40 million individuals worldwide. Psoriasis, along with psoriatic arthritis, are part of a broader psoriatic disease spectrum, and present with inflammatory skin and musculoskeletal manifestations driven by shared genetic, environmental, and immunological mechanisms. Skin psoriasis presents with diverse clinical phenotypes, including chronic plaque psoriasis, guttate, palmoplantar, erythrodermic, and pustular forms. Beyond cutaneous manifestations, psoriasis is associated with a substantial psychosocial burden and a wide range of comorbidities, including mental health disorders and cardio-metabolic diseases. Key psoriasis risk factors include genetic polymorphisms (most notably HLA-C*06:02), obesity, and environmental factors such as trauma, infections, and specific medications. Advances in understanding the key role of the IL-23-IL-17 inflammatory axis and related immunogenetic pathways have redefined psoriasis as a complex immune disorder, leading to the development of highly effective targeted biologic and small-molecule therapies that modulate cytokine signalling and intracellular pathways, offering improved disease control across cutaneous and musculoskeletal domains.","[""Journal Article"", ""Review""]","[""Eder L"", ""Perez-Chada L"", ""Liao W"", ""Merola JF""]",10.1016/S0140-6736(26)00349-1,Eder L,"Lancet (London, England)",0140-6736,,Lancet,eng,Merola JF,[],,42526473,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42526473/,Psoriasis,,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
"Duchenne muscular dystrophy (DMD) is an X-linked genetic disease of skeletal and cardiac muscle that leads to loss of ambulation and premature death due to progressive myopathy and cardiomyopathy. Deramiocel, a heart-derived cellular therapy consisting of human allogeneic cardiosphere-derived cells, improved cardiac and skeletal muscle function in phase 1-2 studies of DMD. Our aim was to assess the efficacy and safety of deramiocel in advanced DMD and support the findings of HOPE-2. HOPE-3, a phase 3, multicentre, randomised (1:1), double-blind, placebo-controlled study, included participants aged 10 years or older with DMD. Investigational product was infused intravenously every 3 months in outpatient settings. Skeletal and cardiac function was evaluated at 12 months. The primary endpoint was total Performance of the Upper Limb 2.0 (PUL2.0) percentage change from baseline. The trial is registered with ClinicalTrials.gov (NCT05126758). Between June 22, 2022, and May 28, 2024, 139 participants were screened, of whom 106 were randomly assigned to deramiocel (n=54) or placebo (n=52), and included in the intention-to-treat population. The primary endpoint showed significant improvements in the deramiocel group versus placebo. For total PUL2.0, least-squares mean percentage change at 12 months favoured deramiocel by 4·55% (95% CI 0·47-8·63; p=0·029). The safety profile of deramiocel was similar to that of placebo. Deramiocel safely slows disease progression in advanced DMD, preserving skeletal muscle function. Administered quarterly in a simple outpatient regimen, deramiocel is a promising treatment for DMD, agnostic to the precise underlying genetic lesion. Capricor Therapeutics.","[""Journal Article""]","[""McDonald CM"", ""Villa C"", ""Soslow JH"", ""Maharry K"", ""Hogan N"", ""Binks M"", ""Berth KC"", ""Elliott KA"", ""Taylor M"", ""Hor KN"", ""Signorovich J"", ""Henricson EK"", ""Phan HC"", ""Apkon S"", ""Ghosh PS"", ""Tian C"", ""Veerapandiyan A"", ""Ramos-Platt L"", ""Gambetta K"", ""Bernes SM"", ""Varadhachary AS"", ""Iannaccone ST"", ""Laverty CG"", ""Perlman SJ"", ""Bass NE"", ""Mosher K"", ""Butterfield RJ"", ""Mathews KD"", ""Scharf RJ"", ""Smith EC"", ""Emerson JA"", ""Mercuri E"", ""Awadalla MS"", ""Marbán L"", ""Marbán E"", ""HOPE-3 Investigators""]",10.1016/S0140-6736(26)01385-1,McDonald CM,"Lancet (London, England)",0140-6736,,Lancet,eng,Marbán E,[],,42526472,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42526472/,"Deramiocel heart-derived cellular therapy in advanced Duchenne muscular dystrophy (HOPE-3): a phase 3, randomised, double-blind, placebo-controlled trial",,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
"Pulmonary arterial hypertension (PAH) is a rare, progressive disease characterised by elevated pulmonary vascular resistance that can lead to right ventricular failure and premature death. Ralinepag is an oral, once-daily, selective prostacyclin IP receptor agonist developed to treat PAH. We aimed to evaluate the efficacy and safety of ralinepag in patients with PAH. ADVANCE OUTCOMES was a randomised, double-blind, placebo-controlled, event-driven, phase 3 trial of ralinepag in patients with PAH. Eligible patients were aged 18 years or older and PAH was diagnosed on the basis of the 2022 European Society of Cardiology and European Respiratory Society guidelines (mean pulmonary artery pressure >20 mm Hg, pulmonary artery wedge pressure ≤15 mm Hg, and pulmonary vascular resistance of >2 Wood units). Patients were randomly assigned (1:1) to ralinepag or placebo, initiated at a dose of 50 μg once daily and titrated weekly until the highest tolerated individualised dose was reached. Randomisation was stratified by baseline 6-minute walk distance (6MWD), PAH aetiology, and oral background therapy. A block size of four was used within each combination of stratification factors. The sponsor, patients, and all personnel directly involved with the conduct of the study were masked to study drug identity and randomisation assignments. The primary outcome was time to first clinical worsening event, a composite of death from any cause, admission to hospital due to worsening PAH or right heart failure, initiation of parenteral or inhaled prostacyclin-pathway therapy, disease progression, or unsatisfactory long-term clinical response. Efficacy analyses were done in the full analysis set and safety analyses in the safety set; both sets comprised 687 patients after exclusion of 41 randomly assigned and treated patients from sites in China (exclusions due to regulatory challenges and data integrity concerns). This study is registered with ClinicalTrials.gov (NCT03626688) and euclinicaltrials.eu (2023-509304-16-00) and is complete. Patients were enrolled between Jan 24, 2019, and June 20, 2025. Of 1037 patients screened for eligibility, 728 were randomly assigned and received at least one dose of ralinepag or placebo; 687 were included in the full analysis and safety sets, of whom 350 received ralinepag and 337 received placebo. Median follow-up from randomisation to clinical worsening event, censoring, or study closure was 85·0 weeks (IQR 27·6-160·9) in the ralinepag group and 78·4 weeks (34·6-137) in the placebo group. At baseline, patients had a mean 6MWD of 438·9 m (SD 104·8) and 548 (80%) of 687 patients were receiving dual background PAH therapy. Overall, 64 (18%) of 350 patients in the ralinepag group and 121 (36%) of 337 patients in the placebo group had a first clinical worsening event (hazard ratio 0·45 [95% CI 0·33-0·62]; p<0·0001). The largest numerical between-group differences in components of the composite outcome were observed for disease progression, initiation of parenteral or inhaled prostacyclin-pathway therapy, and unsatisfactory long-term clinical response. Adverse event was the primary reason for treatment discontinuation in 65 (19%) of 350 patients in the ralinepag group and ten (3%) of 337 patients in the placebo group. Serious adverse events occurred in 98 (28%) patients in the ralinepag group and 104 (31%) patients in the placebo group. Adverse events leading to death occurred in 15 (4%) and 14 (4%) patients, respectively. In patients with PAH receiving contemporary background therapy, ralinepag significantly reduced the risk of first clinical worsening compared with placebo, but was associated with more adverse-event-related treatment discontinuations. These results support the use of ralinepag as an oral, once-daily prostacyclin-pathway treatment option for PAH. United Therapeutics Corporation.","[""Journal Article""]","[""McLaughlin VV"", ""Solum D"", ""Lachant D"", ""Ataya A"", ""Barberà JA"", ""Meyer GB"", ""Chang SA"", ""Channick R"", ""Church C"", ""Feenstra J"", ""Gaine S"", ""Giannakoulas G"", ""Jerjes-Sanchez C"", ""Khanna D"", ""Kim NH"", ""Oudiz R"", ""Preston IR"", ""Sood N"", ""Torres F"", ""Vachiery JL"", ""Pulido T"", ""Cella D"", ""Deng C"", ""Escudero M"", ""Lacasse V"", ""Peterson L"", ""Benza R"", ""Humbert M"", ""ADVANCE OUTCOMES Investigators""]",10.1016/S0140-6736(26)01011-1,McLaughlin VV,"Lancet (London, England)",0140-6736,,Lancet,eng,Humbert M,[],,42520828,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42520828/,"Ralinepag for the treatment of pulmonary arterial hypertension (ADVANCE OUTCOMES): a randomised, double-blind, placebo-controlled phase 3 study",,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Khan M"", ""Mahroof-Shaffi S"", ""Wiley E"", ""Mohiud-Din S""]",10.1016/S0140-6736(26)01414-5,Khan M,"Lancet (London, England)",0140-6736,10553,Lancet,eng,Mohiud-Din S,[],409,42508444,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42508444/,Medical emergency: urgent medical care for Dr Hussam Abu Safiya,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Journal Article""]","[""Koay A"", ""Kaur G"", ""Khepla M"", ""Guinto RR""]",10.1016/S0140-6736(26)01417-0,Koay A,"Lancet (London, England)",0140-6736,,Lancet,eng,Guinto RR,[],,42497874,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42497874/,Intersectionality in climate and health equity research,,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
"WHO recommends 5 days of intravenous antibiotics for children hospitalised with severe community-acquired pneumonia (CAP). We aimed to investigate the safety of a step-down to different oral antibiotics and the shortest effective duration. PediCAP was an open-label, parallel group, 2 × 5 factorial randomised controlled trial of children aged 2 months to 6 years hospitalised with severe CAP without complicating factors in 13 hospitals across five sub-Saharan African countries. Children weighing 3-30 kg and with point-of-care C-reactive protein of more than 10 mg/L were randomly assigned (5:5:1) to either a step-down from intravenous antibiotics to oral amoxicillin (250 mg) or amoxicillin-clavulanate (co-amoxiclav; 200 mg amoxicillin to 28·5 mg clavulanate) via dispersible tablets twice daily (superiority comparison) for five total (intravenous plus oral) durations (4-8 days; non-inferiority comparison), or a 5-day, fixed-duration, intravenous-only treatment (non-inferiority comparison). Children were stepped down when clinically improved and able to take oral antibiotics. Clinicians could change antibiotics if clinically indicated. The primary outcome was the proportion of readmission or death at day 28 (non-inferiority margin vs intravenous only: +10%). The study was registered with the ISRCTN registry (ISRCTN63115131) and is complete. Between Dec 7, 2020, and Aug 14, 2023, 2248 children were screened for eligibility and 1101 were randomly allocated (480 [43·6%] girls and 621 [56·4%] boys). The primary outcome was available in 1055 (95·8%) children. For children in the step-down groups, the mean total antibiotic exposure was 6·0 days (SD 3·5) in the 4-day group, 6·8 days (4·2) in the 5-day group, 7·4 (3·6) in the 6-day group, 8·3 days (3·4) in the 7-day group, and 9·2 days (2·9) in the 8-day group (p<0·0001), with 140 (68·6%) of 204, 151 (76·3%) of 198, 167 (85·2%) of 196, 179 (89·5%) of 200, and 186 (91·6%) of 203, respectively, stepping down within their randomised duration (p<0·0001). Primary outcomes occurred in 33 (6·9%) of 475 in the co-amoxiclav group, 27 (5·6%) of 484 in the amoxicillin group, and six (6·3%) of 96 in the intravenous-only group, with both oral step-down strategies non-inferior to the intravenous-only strategy (upper 95% CIs of 6·0 for co-amoxiclav and 5·7 for amoxicillin) and no evidence of superiority for co-amoxiclav over amoxicillin (adjusted risk difference 1·3% [95% CI -1·8 to 4·4]; p=0·40). Primary outcomes occurred in eight (4·1%) of 194 in the 4-day group, ten (5·3%) of 190 in the 5-day group, 16 (8·5%) of 188 in the 6-day group, 16 (8·3%) of 193 in the 7-day group, and ten (5·2%) of 194 in the 8-day group; all durations were non-inferior to the 8-day group (all upper 95% CIs ≤6·0%). There was no evidence of consistent differences in adverse events for oral antibiotic or duration comparisons. For antibiotic-related or serious adverse events, there was one (1·0%) in the intravenous-only group and 12 (2·5%) in the amoxicillin group (adjusted risk difference -2·3% [95% CI -4·2 to -0·3]; p=0·025), and 16 (3·4%) in the co-amoxiclav group (+0·8% [-1·2 to 2·8]; p=0·42); rates increased with randomised duration (slope estimate +0·9% [0·1 to 1·7]; p=0·032). For sub-Saharan African children hospitalised with severe CAP without complicating factors, a strategy of stepping down upon clinical improvement to oral amoxicillin after initial intravenous antibiotics, with a total treatment duration of 4-5 days, is non-inferior to WHO-recommended 5-day intravenous treatment. The Second European and Developing Countries Clinical Trials Partnership (EDCTP2).","[""Journal Article""]","[""Bielicki JA"", ""Clements M"", ""Musiime V"", ""Moore DP"", ""Sidat M"", ""Mulenga V"", ""Mutata C"", ""Nalwanga D"", ""Waggie Z"", ""Chilundo J"", ""Chabala C"", ""Bwakura-Dangarembizi M"", ""Archary M"", ""Kiggwe A"", ""Dangor Z"", ""Spittle B"", ""Kapasa M"", ""Tagoola A"", ""Jeki C"", ""Sacarlal J"", ""Buck WC"", ""Chanda S"", ""Mujuru HA"", ""Giaquinto C"", ""Madhi SA"", ""Walker AS"", ""Sharland M"", ""PediCAP trial team""]",10.1016/S0140-6736(26)00879-2,Bielicki JA,"Lancet (London, England)",0140-6736,,Lancet,eng,Sharland M,[],,42492562,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42492562/,"Oral step-down, optimal drug, and total duration of antibiotic treatment in African children hospitalised with severe community-acquired pneumonia (PediCAP): a factorial randomised controlled trial",,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Journal Article""]","[""Gallagher JC""]",10.1016/S0140-6736(26)01289-4,Gallagher JC,"Lancet (London, England)",0140-6736,,Lancet,eng,Gallagher JC,[],,42492561,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42492561/,How long must we treat? A question as old as penicillin,,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Published Erratum""]",[],10.1016/S0140-6736(26)01491-1,,"Lancet (London, England)",0140-6736,10552,Lancet,eng,,[],324,42492554,,2026 Jul 25,2026,https://pubmed.ncbi.nlm.nih.gov/42492554/,Department of Error,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Published Erratum""]",[],10.1016/S0140-6736(26)01492-3,,"Lancet (London, England)",0140-6736,10552,Lancet,eng,,[],324,42492553,,2026 Jul 25,2026,https://pubmed.ncbi.nlm.nih.gov/42492553/,Department of Error,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Published Erratum""]",[],10.1016/S0140-6736(26)01493-5,,"Lancet (London, England)",0140-6736,10552,Lancet,eng,,[],324,42492552,,2026 Jul 25,2026,https://pubmed.ncbi.nlm.nih.gov/42492552/,Department of Error,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Azzopardi P"", ""Baird S"", ""Biermann O"", ""Ezeh A"", ""Kennedy E"", ""Viner R"", ""Sawyer S""]",10.1016/S0140-6736(25)01903-8,Azzopardi P,"Lancet (London, England)",0140-6736,10552,Lancet,eng,Sawyer S,[],323-324,42492551,,2026 Jul 25,2026,https://pubmed.ncbi.nlm.nih.gov/42492551/,Firearm violence exposure as an adverse childhood experience - Authors' reply,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Díaz-Faes DA"", ""Branas CC"", ""Rajan S""]",10.1016/S0140-6736(25)01738-6,Díaz-Faes DA,"Lancet (London, England)",0140-6736,10552,Lancet,eng,Rajan S,[],323,42492550,,2026 Jul 25,2026,https://pubmed.ncbi.nlm.nih.gov/42492550/,Firearm violence exposure as an adverse childhood experience,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Degeling C"", ""Johnson J"", ""Shanahan EA"", ""Peel AJ""]",10.1016/S0140-6736(26)00861-5,Degeling C,"Lancet (London, England)",0140-6736,10552,Lancet,eng,Peel AJ,[],321-322,42492549,,2026 Jul 25,2026,https://pubmed.ncbi.nlm.nih.gov/42492549/,Ecological integration for a legitimate and authentic One Health: a Hendra virus case study,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Costa A""]",10.1016/S0140-6736(26)01228-6,Costa A,"Lancet (London, England)",0140-6736,10552,Lancet,eng,Costa A,[],320-321,42492548,,2026 Jul 25,2026,https://pubmed.ncbi.nlm.nih.gov/42492548/,Newborn screening for birth defects in LMICs cannot wait,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Journal Article""]","[""Thornton J""]",10.1016/S0140-6736(26)01439-X,Thornton J,"Lancet (London, England)",0140-6736,10552,Lancet,eng,Thornton J,[],316,42492547,,2026 Jul 25,2026,https://pubmed.ncbi.nlm.nih.gov/42492547/,Bernard Roizman,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Journal Article""]","[""Shuttleworth S""]",10.1016/S0140-6736(26)01438-8,Shuttleworth S,"Lancet (London, England)",0140-6736,10552,Lancet,eng,Shuttleworth S,[],314-315,42492546,,2026 Jul 25,2026,https://pubmed.ncbi.nlm.nih.gov/42492546/,Wintering in Davos,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Journal Article""]","[""Weston G""]",10.1016/S0140-6736(26)01436-4,Weston G,"Lancet (London, England)",0140-6736,10552,Lancet,eng,Weston G,[],311,42492545,,2026 Jul 25,2026,https://pubmed.ncbi.nlm.nih.gov/42492545/,Tamzin Cuming: supporting inclusivity in surgery,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Editorial""]","[""The Lancet""]",10.1016/S0140-6736(26)01497-2,The Lancet,"Lancet (London, England)",0140-6736,10552,Lancet,eng,The Lancet,[],293,42492544,,2026 Jul 25,2026,https://pubmed.ncbi.nlm.nih.gov/42492544/,Who owns cardiometabolic disease?,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
"Consolidation therapy for primary CNS lymphoma (PCNSL) includes high-dose chemotherapy with autologous stem-cell transplantation (HCT-ASCT), yet its efficacy compared with non-myeloablative chemoimmunotherapy remains uncertain. This study aimed to provide randomised comparative evidence on the efficacy and safety of thiotepa-based HCT-ASCT versus non-myeloablative R-DeVIC consolidation after uniform MATRix induction in newly diagnosed PCNSL. This open-label, randomised, phase 3 trial was conducted across 56 university and academic non-university hospitals with established transplantation facilities in five European countries. Eligible for inclusion were untreated, immunocompetent patients with B-cell PCNSL, aged 18-65 years regardless of Eastern Cooperative Oncology Group (ECOG) performance status, or 66-70 years with ECOG performance status 0-2. Pretreatment corticosteroids were permitted. Exclusion criteria included lymphoma manifestation outside the CNS, and congenital or acquired immunodeficiency. Patients received four cycles of MATRix induction (comprising rituximab, high-dose cytarabine, and thiotepa, in addition to high-dose methotrexate). Patients reaching at least partial response were randomly assigned (1:1) to two cycles of R-DeVIC (rituximab plus dexamethasone, etoposide, ifosfamide, and carboplatin) or HCT-ASCT with carmustine and thiotepa. The primary endpoint was progression-free survival, assessed in the full analysis set (excluding patients with major violations of entry criteria). The safety analysis set contained all randomised patients who initiated therapy. This study is registered with ClinicalTrials.gov (NCT02531841) and the EU Clinical Trials Register (EudraCT number 2012-000620-17). The study is completed. Between July 16, 2014, and Aug 31, 2019, 368 patients were enrolled. 346 (94%) patients started induction treatment, and 230 were randomly assigned; 229 patients were analysed (R-DeVIC group, n=115; HCT-ASCT group, n=114). After a median follow-up of 45·3 months, 3-year progression-free survival was significantly superior in the HCT-ASCT group (hazard ratio 0·43 [95% CI 0·27-0·68]; p=0·0003). The 3-year progression-free survival was 78% (95% CI 69-85) in the HCT-ASCT group compared with 51% (41-60) in the R-DeVIC group. The mean number of adverse events per patient was 9·3 (SD 4·4) in the R-DeVIC group and 14·6 (5·8) in the HCT-ASCT group. Fatal serious adverse events following consolidation treatment occurred in two patients in the R-DeVIC group (both acute myeloid leukaemia) and in five patients in the HCT-ASCT group (infections and infestations [n=4], pulmonary embolism [n=1]); all of these events apart from the pulmonary embolism were judged to be possibly related to treatment. In the largest randomised trial in untreated PCNSL to date, HCT-ASCT significantly improved progression-free and overall survival compared with non-myeloablative consolidation in patients who had completed induction treatment, establishing it as the preferred consolidation strategy in fit patients. German Federal Ministry of Research, Technology and Space; Swiss Cancer Research Foundation; and Riemser Pharma.","[""Journal Article""]","[""Illerhaus G"", ""Ferreri AJM"", ""Wendler J"", ""Binder M"", ""Borchmann P"", ""Hasenkamp J"", ""Stilgenbauer S"", ""Röth A"", ""Egerer G"", ""Ernst T"", ""Weber T"", ""Hertenstein B"", ""Lenz G"", ""Dreyling M"", ""Möhle R"", ""Kobbe G"", ""Schmidt CA"", ""Brunnberg U"", ""Panse J"", ""Kneba M"", ""Heinicke T"", ""Schroll S"", ""Larsen TS"", ""Thurner L"", ""Pukrop T"", ""Salwender H"", ""Naumann R"", ""Hess G"", ""Kroschinsky FP"", ""Blystad AK"", ""Keller U"", ""Pulczynski EJ"", ""Pedersen MB"", ""Re F"", ""Orsucci L"", ""Pospiech L"", ""La Rosée P"", ""Deckert M"", ""Ponzoni M"", ""Gmehlin D"", ""Backenstrass M"", ""Jensch A"", ""Valk E"", ""Calimeri T"", ""Kasenda B"", ""Trepel M"", ""Fricker H"", ""Semenova I"", ""Scherer F"", ""von Gottberg P"", ""Burger E"", ""Grishina O"", ""Hader C"", ""Ihorst G"", ""Finke J"", ""Zucca E"", ""Schorb E""]",10.1016/S0140-6736(26)00917-7,Illerhaus G,"Lancet (London, England)",0140-6736,,Lancet,eng,Schorb E,[],,42486133,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42486133/,High-dose chemotherapy followed by autologous stem-cell transplantation versus non-myeloablative consolidation in primary CNS lymphoma (MATRix/IELSG43): a randomised phase 3 trial,,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Journal Article""]","[""Schaff LR"", ""Scordo M"", ""Grommes C""]",10.1016/S0140-6736(26)00973-6,Schaff LR,"Lancet (London, England)",0140-6736,,Lancet,eng,Grommes C,[],,42486132,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42486132/,Redefining consolidation in primary CNS lymphoma: autologous stem-cell transplantation as the standard,,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Published Erratum""]",[],10.1016/S0140-6736(26)01486-8,,"Lancet (London, England)",0140-6736,10553,Lancet,eng,,[],416,42480575,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42480575/,Department of Error,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Schwartz L"", ""Ahmed E"", ""Palmero A"", ""Ho CWL"", ""Ravinetto R""]",10.1016/S0140-6736(26)01367-X,Schwartz L,"Lancet (London, England)",0140-6736,10552,Lancet,eng,Ravinetto R,[],319-320,42468542,,2026 Jul 25,2026,https://pubmed.ncbi.nlm.nih.gov/42468542/,Pregnancy as exclusion criterion in Ebola research: not again,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
"Mortality among infants with severe HIV-associated pneumonia remains high. This trial (EMPIRICAL) tested whether empirical valganciclovir treatment for cytomegalovirus improves survival in infants in Africa. This multicentre, open-label, group-sequential designed, 2 × 2 factorial, randomised, controlled, superiority trial was conducted in 19 hospitals across Côte d'Ivoire, Malawi, Mozambique, Uganda, Zambia, and Zimbabwe. Infants aged 28-365 days admitted with severe HIV-associated pneumonia were centrally and individually randomly assigned (1:1:1:1) using a secure web-based system stratified by site and severity to receive standard of care (SOC) comprising treatment for bacterial (WHO-recommended antibiotics) and Pneumocystis jirovecii (cotrimoxazole and steroids) pneumonia, SOC plus 15 days of oral valganciclovir (16 mg/kg per 12 h), or SOC plus 6 months of tuberculosis treatment (isoniazid, rifampicin, pyrazinamide, and ethambutol for 2 months, plus isoniazid and rifampicin for 4 subsequent months), or both interventions combined. The primary endpoint was all-cause mortality, assessed at day 15 and over 1-year follow-up in the intention-to-treat population. In this Article, we report results for the valganciclovir comparison groups. The trial is registered with ClinicalTrials.gov, NCT03915366 and is complete. From March 15, 2020, to Jan 31, 2024, 563 participants were enrolled; 558 were included in the analyses, with 276 allocated to valganciclovir groups (140 valganciclovir; 136 valganciclovir plus tuberculosis treatment) and 282 to groups without valganciclovir (142 SOC; 140 tuberculosis treatment). The median patient age was 4·4 months (IQR 3·2-7·4), and 274 (49%) were female. There was no evidence of interaction between valganciclovir and tuberculosis treatment (adjusted hazard ratio 1·19 [95% CI 0·73-1·95], heterogeneity p=0·48). At day 15, 64 (23%) of 276 participants in the valganciclovir group and 76 (27%) of 282 in groups without valganciclovir died (rate ratio 0·81 [95% CI 0·61-1·08], p=0·15). 24 (9%) of 276 participants and 13 (5%) of 282, respectively, were lost to follow-up. After 12 months, 119 (43%) of 276 participants in the valganciclovir groups and 134 (48%) of 282 in the groups without valganciclovir died (0·88 [95% CI 0·74-1·05] p=0·15). In a time-varying effects model, at day 15, the adjusted hazard ratio of death was 0·60 (95% CI 0·41-0·87, p=0·0063), and their hazard of death over 1 year was 0·79 (0·62-1·01; p=0·068), or 0·76 (0·58-1·00; p=0·0500) when excluding deaths within 48 h of treatment. Severe adverse events during follow-up were not more common in the valganciclovir treatment groups (odds ratio 0·64 [95% CI 0·35-1·16]). Empirical valganciclovir treatment appeared to be associated with a lower hazard of death in infants with severe HIV-associated pneumonia than SOC alone or SOC plus empirical tuberculosis treatment, and there was little evidence of associated harms. European and Developing Countries Clinical Trials Partnership.","[""Journal Article""]","[""Moraleda C"", ""Tagarro A"", ""Domínguez-Rodríguez S"", ""Musiime V"", ""Mujuru H"", ""Chabala C"", ""Mvalo T"", ""Iroh-Tam PY"", ""Bramugy J"", ""Madrid L"", ""Sacarlal J"", ""Passanduca A"", ""Sidat M"", ""Cassia U"", ""Aanyu HT"", ""Tagoola A"", ""Mutata C"", ""Nduna B"", ""Chawinga C"", ""Ghambi L"", ""Bates M"", ""Fernández-Luis S"", ""Seni A"", ""Gafur M"", ""Nalwanga D"", ""Nansera D"", ""Bwakura-Dangarembizi M"", ""Namuziya N"", ""Egbe FN"", ""Tembo J"", ""Ballesteros Á"", ""Moh R"", ""Manukyan L"", ""Lora D"", ""Marcy O"", ""Jacobs TG"", ""Burger D"", ""Bassat Q"", ""Leroy V"", ""Nardone A"", ""Buck WC"", ""Rojo P"", ""Empirical Clinical Trial Group""]",10.1016/S0140-6736(26)00754-3,Moraleda C,"Lancet (London, England)",0140-6736,,Lancet,eng,Rojo P,[],,42468541,,2026 Jul 17,2026,https://pubmed.ncbi.nlm.nih.gov/42468541/,"Empirical treatment with valganciclovir in infants living with HIV and hospitalised with severe pneumonia in Africa: a multicentre, open-label, factorial, randomised, controlled, superiority trial",,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Zhu Y"", ""Gaudino M"", ""Zhao Q""]",10.1016/S0140-6736(26)01132-3,Zhu Y,"Lancet (London, England)",0140-6736,10551,Lancet,eng,Zhao Q,[],218,42462740,,2026 Jul 18,2026,https://pubmed.ncbi.nlm.nih.gov/42462740/,Physiology-guided coronary artery bypass grafting in valve surgery - Authors' reply,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Published Erratum""]",[],10.1016/S0140-6736(26)01339-5,,"Lancet (London, England)",0140-6736,10551,Lancet,eng,,[],218,42462739,,2026 Jul 18,2026,https://pubmed.ncbi.nlm.nih.gov/42462739/,Department of Error,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Published Erratum""]",[],10.1016/S0140-6736(26)01383-8,,"Lancet (London, England)",0140-6736,10551,Lancet,eng,,[],218,42462738,,2026 Jul 18,2026,https://pubmed.ncbi.nlm.nih.gov/42462738/,Department of Error,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Magouliotis DE"", ""Sicouri S"", ""Ramlawi B""]",10.1016/S0140-6736(26)01028-7,Magouliotis DE,"Lancet (London, England)",0140-6736,10551,Lancet,eng,Ramlawi B,[],217-218,42462737,,2026 Jul 18,2026,https://pubmed.ncbi.nlm.nih.gov/42462737/,Physiology-guided coronary artery bypass grafting in valve surgery,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Jing S"", ""Song J""]",10.1016/S0140-6736(26)00858-5,Jing S,"Lancet (London, England)",0140-6736,10551,Lancet,eng,Song J,[],216,42462736,,2026 Jul 18,2026,https://pubmed.ncbi.nlm.nih.gov/42462736/,From targets to minutes: making movement advice actionable,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Ekelund U"", ""Tarp J"", ""Ding D"", ""Dalene KE"", ""Fagerland MW""]",10.1016/S0140-6736(26)01130-X,Ekelund U,"Lancet (London, England)",0140-6736,10551,Lancet,eng,Fagerland MW,[],216-217,42462735,,2026 Jul 18,2026,https://pubmed.ncbi.nlm.nih.gov/42462735/,From targets to minutes: making movement advice actionable - Authors' reply,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Frieden TR"", ""Garg R"", ""Moran AE"", ""Whelton PK""]",10.1016/S0140-6736(26)01230-4,Frieden TR,"Lancet (London, England)",0140-6736,10551,Lancet,eng,Whelton PK,[],215-216,42462734,,2026 Jul 18,2026,https://pubmed.ncbi.nlm.nih.gov/42462734/,Facility-based blood pressure measurement and treatment,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Landrigan PJ"", ""Lundberg BE""]",10.1016/S0140-6736(26)01304-8,Landrigan PJ,"Lancet (London, England)",0140-6736,10551,Lancet,eng,Lundberg BE,[],214-215,42462733,,2026 Jul 18,2026,https://pubmed.ncbi.nlm.nih.gov/42462733/,The false promise of nuclear power,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Letter""]","[""Mehta P"", ""Vinuesa CG""]",10.1016/S0140-6736(26)01155-4,Mehta P,"Lancet (London, England)",0140-6736,10551,Lancet,eng,Vinuesa CG,[],213-214,42462732,,2026 Jul 18,2026,https://pubmed.ncbi.nlm.nih.gov/42462732/,Protecting early-career researchers through fair authorship governance,408,ppdsgaWlJ1TdzOe73,lLQ16vE7MEKZqQyzP
,"[""Journal Article""]","[""Khan T""]",10.1056/NEJMp2515506,Khan T,The New England journal of medicine,0028-4793,,N Engl J Med,eng,Khan T,[],,42545006,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42545006/,Doctor's Dirty Little Secret - The Cost of Silence,,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Journal Article""]","[""Kavanagh MM"", ""Stiglitz JE"", ""Geingos M"", ""Byanyima W"", ""Marmot MG"", ""Global Council on Inequality, AIDS, and Pandemics""]",10.1056/NEJMp2607839,Kavanagh MM,The New England journal of medicine,0028-4793,,N Engl J Med,eng,Marmot MG,[],,42526045,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42526045/,The Inequality-Pandemic Cycle - Rethinking Preparedness,,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter""]","[""Watanabe T"", ""Koga M"", ""Nojima M"", ""Kono M"", ""Tomita Y"", ""Maemura T"", ""Anzai I"", ""Furusawa Y"", ""Duong C"", ""Kino Y"", ""Halfmann PJ"", ""Nagamura F"", ""Yotsuyanagi H"", ""Kawaoka Y""]",10.1056/NEJMc2518666,Watanabe T,The New England journal of medicine,0028-4793,,N Engl J Med,eng,Kawaoka Y,[],,42526044,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42526044/,"iEvac-Z, an Inactivated Ebola Vaccine - Phase 1 Study in Japan",,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter""]","[""Schett G"", ""Wirsching A"", ""Rothe T"", ""Visconti V"", ""Kramer N"", ""Metzler M"", ""Krickau T"", ""Kirschen GW"", ""Landau D"", ""Elgarten C"", ""Majithia V"", ""De Langhe E"", ""Vandenberghe P"", ""Maurer B"", ""Amoura Z"", ""Simon D"", ""Krönke G"", ""Gergely P"", ""Fernandes M"", ""Shisha T"", ""Law BM"", ""Koegel A"", ""Chang DJ"", ""Mackensen A"", ""Müller F"", ""Hagen M""]",10.1056/NEJMc2607737,Schett G,The New England journal of medicine,0028-4793,,N Engl J Med,eng,Hagen M,[],,42526043,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42526043/,Pregnancies in Patients with Autoimmune Disease Receiving CAR T-Cell Therapy,,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter"", ""Comment""]","[""Skeith L"", ""Bates SM""]",10.1056/NEJMc2606372,Skeith L,The New England journal of medicine,0028-4793,5,N Engl J Med,eng,Bates SM,[],,42526042,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42526042/,Sex Hormone Influences on Cardiovascular Risk. Reply,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter"", ""Comment""]","[""Bonnet F"", ""Vaduva P""]",10.1056/NEJMc2606372,Bonnet F,The New England journal of medicine,0028-4793,5,N Engl J Med,eng,Vaduva P,[],519-520,42526041,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42526041/,Sex Hormone Influences on Cardiovascular Risk,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter"", ""Comment""]","[""Douxfils J"", ""Creinin MD"", ""Foidart JM""]",10.1056/NEJMc2606372,Douxfils J,The New England journal of medicine,0028-4793,5,N Engl J Med,eng,Foidart JM,[],518-519,42526040,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42526040/,Sex Hormone Influences on Cardiovascular Risk,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter"", ""Comment""]","[""Langley RE"", ""Gilbert DC"", ""Nankivell M""]",10.1056/NEJMc2607173,Langley RE,The New England journal of medicine,0028-4793,5,N Engl J Med,eng,Nankivell M,[],517-518,42526039,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42526039/,Transdermal Estradiol Patches in Prostate Cancer. Reply,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter"", ""Comment""]","[""Grossmann M"", ""Russell N""]",10.1056/NEJMc2607173,Grossmann M,The New England journal of medicine,0028-4793,5,N Engl J Med,eng,Russell N,[],517,42526038,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42526038/,Transdermal Estradiol Patches in Prostate Cancer,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter"", ""Comment""]","[""Sears C"", ""Schuller L""]",10.1056/NEJMc2607173,Sears C,The New England journal of medicine,0028-4793,5,N Engl J Med,eng,Schuller L,[],517,42526037,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42526037/,Transdermal Estradiol Patches in Prostate Cancer,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter"", ""Comment""]","[""Lee YJ"", ""Kim BK""]",10.1056/NEJMc2606270,Lee YJ,The New England journal of medicine,0028-4793,5,N Engl J Med,eng,Kim BK,[],516,42526036,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42526036/,LDL Cholesterol Targeting in Cardiovascular Disease. Reply,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter"", ""Comment""]","[""Cravedi P"", ""Ruggenenti PL"", ""Remuzzi G""]",10.1056/NEJMc2606270,Cravedi P,The New England journal of medicine,0028-4793,5,N Engl J Med,eng,Remuzzi G,[],515-516,42526035,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42526035/,LDL Cholesterol Targeting in Cardiovascular Disease,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter"", ""Comment""]","[""Zhu Q"", ""Wang S""]",10.1056/NEJMc2606270,Zhu Q,The New England journal of medicine,0028-4793,5,N Engl J Med,eng,Wang S,[],515,42526034,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42526034/,LDL Cholesterol Targeting in Cardiovascular Disease,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter"", ""Comment""]","[""van Twist DJL"", ""Beeren J""]",10.1056/NEJMc2606270,van Twist DJL,The New England journal of medicine,0028-4793,5,N Engl J Med,eng,Beeren J,[],514-515,42526033,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42526033/,LDL Cholesterol Targeting in Cardiovascular Disease,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter"", ""Comment""]","[""Howell RR"", ""Jones KW""]",10.1056/NEJMc2606270,Howell RR,The New England journal of medicine,0028-4793,5,N Engl J Med,eng,Jones KW,[],514,42526032,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42526032/,LDL Cholesterol Targeting in Cardiovascular Disease,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter"", ""Comment""]","[""Mallidi J"", ""Lotif A""]",10.1056/NEJMc2606270,Mallidi J,The New England journal of medicine,0028-4793,5,N Engl J Med,eng,Lotif A,[],513-514,42526031,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42526031/,LDL Cholesterol Targeting in Cardiovascular Disease,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter""]","[""Schatzl M"", ""Mayer KA"", ""Agis H"", ""Haindl S"", ""Kriks D"", ""Fischer G"", ""Exner M"", ""Hönger G"", ""Veljancic N"", ""Allmer DM"", ""Graf I"", ""Diebold M"", ""Halloran PF"", ""Halpin A"", ""Li C"", ""West L"", ""Kozakowski N"", ""Böhmig GA""]",10.1056/NEJMc2603853,Schatzl M,The New England journal of medicine,0028-4793,5,N Engl J Med,eng,Böhmig GA,[],511-513,42526030,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42526030/,T-Cell Engager-Mediated HLA Antibody Depletion before Kidney Transplantation,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter""]","[""Meneghini V"", ""Calbi V"", ""Casalini F"", ""Mangiameli E"", ""Morena F"", ""Piccoli M"", ""Laface I"", ""Rossomanno I"", ""Ornaghi F"", ""Ghiroldi A"", ""Rancoita PMV"", ""Fumagalli F"", ""Martino S"", ""Anastasia L"", ""Naldini L"", ""Aiuti A"", ""Gritti A""]",10.1056/NEJMc2505002,Meneghini V,The New England journal of medicine,0028-4793,5,N Engl J Med,eng,Gritti A,[],508-511,42526029,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42526029/,Cross-Correction in HSC Gene Therapy for Metachromatic Leukodystrophy,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Case Reports"", ""Journal Article""]","[""Gray ST"", ""Geadas CD"", ""Sadow PM""]",10.1056/NEJMcpc2603178,Gray ST,The New England journal of medicine,0028-4793,5,N Engl J Med,eng,Sadow PM,[],493-501,42526028,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42526028/,Case 22-2026: A 37-Year-Old Woman with Persistent Nasal Ulceration,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Case Reports"", ""Journal Article""]","[""Woller J"", ""Ulger AZ""]",10.1056/NEJMicm2601847,Woller J,The New England journal of medicine,0028-4793,5,N Engl J Med,eng,Ulger AZ,[],492,42526027,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42526027/,Milwaukee Shoulder Syndrome,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
"Nav1.8, a voltage-gated sodium channel expressed in the peripheral nervous system, has a critical role in pain signaling. Previous trials of NaV1.8 inhibitors have shown effectiveness in reducing postoperative pain. We conducted a phase 2b, double-blind, randomized, placebo-controlled trial to evaluate LTG-001, a selective Nav1.8 inhibitor, in patients with moderate-to-severe pain after abdominoplasty. Patients were randomly assigned in a 1:1:1:1 ratio to receive a 300-mg loading dose of LTG-001, followed by 150 mg every 12 hours (low-dose group); a 450-mg loading dose of LTG-001, followed by 300 mg every 12 hours (high-dose group); hydrocodone bitartrate-acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen) every 6 hours; or placebo every 6 hours. All doses were administered orally over a 48-hour period. The primary end point was the time-weighted sum of the pain-intensity difference (SPID) over the 48-hour treatment period (SPID48), based on scores on the Numeric Pain Rating Scale (range, 0 to 10, with higher values indicating more severe pain; higher SPID48 values indicate greater pain reduction). Secondary end points included the amount of opioid rescue medication consumed in morphine milligram equivalents (MME) and no receipt of opioid rescue medication. A total of 343 patients underwent randomization. The least-squares mean SPID48 was 161.05 (95% confidence interval [CI], 142.93 to 179.16) in the low-dose group, 185.30 (95% CI, 167.26 to 203.34) in the high-dose group, 164.08 (95% CI, 146.02 to 182.14) in the hydrocodone bitartrate-acetaminophen group, and 123.22 (95% CI, 105.23 to 141.21) in the placebo group. The least-squares mean difference in the SPID48 between LTG-001 and placebo was significant for each dose (low dose: 37.82 [P = 0.003]; high dose: 62.08 [P<0.001]), and that between hydrocodone bitartrate-acetaminophen and placebo was 40.86. High-dose LTG-001, but not low-dose LTG-001, was associated with significantly lower opioid use than placebo (11.00 MME vs. 18.35 MME, P = 0.01), as well as a significantly higher percentage of patients who received no opioid rescue medication (52% vs. 22%, P<0.001). High-dose LTG-001 was associated with a higher incidence of pyrexia than placebo (7% vs. 2%) and a higher incidence of presyncope (6% vs. 1%). LTG-001 led to significantly greater reductions in pain scores than placebo over the course of 48 hours after abdominoplasty. (Funded by Latigo Biotherapeutics; LTG-001-010 ClinicalTrials.gov number, NCT07102459.).","[""Journal Article"", ""Randomized Controlled Trial"", ""Clinical Trial, Phase II"", ""Multicenter Study""]","[""Singla N"", ""Katz NP"", ""Vaughn B"", ""Rogier T"", ""Bertoch T"", ""Minkowitz H"", ""Loflin M""]",10.1056/NEJMoa2602910,Singla N,The New England journal of medicine,0028-4793,5,N Engl J Med,eng,Loflin M,"[""Adult"", ""Female"", ""Humans"", ""Male"", ""Middle Aged"", ""Acetaminophen"", ""Acute Pain"", ""Analgesics, Opioid"", ""Double-Blind Method"", ""Drug Combinations"", ""Hydrocodone"", ""NAV1.8 Voltage-Gated Sodium Channel"", ""Pain Measurement"", ""Postoperative Pain"", ""Voltage-Gated Sodium Channel Blockers"", ""Abdominoplasty"", ""Anti-Inflammatory Agents, Non-Steroidal"", ""Incidence"", ""Dose-Response Relationship, Drug"", ""Fever"", ""Syncope"", ""Young Adult"", ""Treatment Outcome""]",454-464,42526026,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42526026/,Phase 2b Trial of a Na(V)1.8 Inhibitor for Acute Pain,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
"Once-daily, single-tablet regimens have transformed care for persons living with human immunodeficiency virus type 1 (HIV-1); however, challenges to adherence continue to limit effective treatment. Long-acting oral-drug combinations could offer new options with less frequent dose administration. We conducted a phase 3, double-blind, randomized, active-controlled, noninferiority trial in 12 countries to evaluate the efficacy and safety of a switch to once-weekly oral islatravir-lenacapavir (ISL/LEN) from once-daily oral bictegravir-emtricitabine-tenofovir alafenamide (B/F/TAF) in adults in whom HIV-1 had been virologically suppressed for at least 6 months while they were receiving B/F/TAF. Participants were assigned in a 1:1 ratio to receive once-weekly ISL/LEN (2 mg/300 mg) or to continue once-daily B/F/TAF for 96 weeks; all received matched placebo for the alternative regimen. The primary end point was the percentage of participants with an HIV-1 RNA level of 50 copies per milliliter or higher at week 48, as determined by the Food and Drug Administration-defined snapshot algorithm. Noninferiority was determined at a margin of 4 percentage points. A total of 607 participants underwent randomization; 304 were assigned to the ISL/LEN group and 303 to the B/F/TAF group. A total of 21% of the participants were women, 31% were Black, 26% were Hispanic or Latine, and 15% were 65 years of age or older. At week 48, an HIV-1 RNA level of 50 copies per milliliter or higher was reported in no participants in the ISL/LEN group and 1 (0.3%) in the B/F/TAF group (difference, -0.3 percentage points; 95.002% confidence interval [CI], -1.4 to 0.8); an HIV-1 RNA level of less than 50 copies per milliliter was reported in 284 (93.4%) and 280 (92.4%), respectively (difference, 1.0 percentage point, 95% CI, -3.2 to 5.2). The mean change in the CD4+ T-cell count at week 48 was -10 cells per microliter with ISL/LEN and -18 cells per microliter with B/F/TAF (least-squares mean difference, 12 cells per microliter; 95% CI, -16 to 39). The trial regimen was discontinued owing to adverse events in 6 participants (2.0%) in the ISL/LEN group and 5 (1.7%) in the B/F/TAF group; serious adverse events occurred in 16 (5.3%) and 14 (4.6%), respectively. Among persons with virologically suppressed HIV-1, once-weekly oral ISL/LEN was noninferior to once-daily B/F/TAF in maintaining HIV viral load suppression. (Funded by Gilead Sciences and Merck Sharp and Dohme; ISLEND-1 ClinicalTrials.gov number, NCT06630286.).","[""Journal Article""]","[""Rockstroh JK"", ""Ramgopal MN"", ""Curran Fàbregas A"", ""Hedgcock M"", ""Workowski KA"", ""Ronot-Bregigeon S"", ""Cassetti I"", ""Brinson C"", ""Gupta SK"", ""Hung CC"", ""O'Reilly M"", ""Slim J"", ""Gatanaga H"", ""Shalit P"", ""Liu SY"", ""Klopfer SO"", ""Shihadeh F"", ""Patel N"", ""Mercier RC"", ""Shaughnessy M"", ""Dvory-Sobol H"", ""SenGupta D"", ""Llamoso C"", ""Rhee MS"", ""Orkin C"", ""ISLEND-1 Study Team""]",10.1056/NEJMoa2607973,Rockstroh JK,The New England journal of medicine,0028-4793,,N Engl J Med,eng,Orkin C,[],,42525925,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42525925/,Phase 3 Trial of Weekly Oral Islatravir-Lenacapavir for HIV-1 Treatment,,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Journal Article""]","[""Reilly BM""]",10.1056/NEJMp2517208,Reilly BM,The New England journal of medicine,0028-4793,5,N Engl J Med,eng,Reilly BM,[],423-425,42504838,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42504838/,Braking Bad News,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Journal Article""]","[""Buchbinder M""]",10.1056/NEJMp2606019,Buchbinder M,The New England journal of medicine,0028-4793,5,N Engl J Med,eng,Buchbinder M,[],417-419,42504828,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42504828/,The Paradox of Medical Aid in Dying,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Journal Article""]","[""Barsky BA"", ""Reid B"", ""Robertson C""]",10.1056/NEJMp2605975,Barsky BA,The New England journal of medicine,0028-4793,5,N Engl J Med,eng,Robertson C,[],419-421,42504821,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42504821/,Medical Standards by Federal Fiat,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Case Reports"", ""Journal Article""]","[""Vaz A"", ""Araújo L""]",10.1056/NEJMicm2601392,Vaz A,The New England journal of medicine,0028-4793,5,N Engl J Med,eng,Araújo L,[],e6,42504820,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42504820/,Pulsatile Liver in Severe Tricuspid Regurgitation,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter""]","[""Lhomme E"", ""Wiedemann A"", ""Ayouba A"", ""Ben-Farhat S"", ""Thaurignac G"", ""Roy C"", ""Beavogui AH"", ""Doumbia S"", ""Kieh M"", ""Leigh B"", ""Sow S"", ""Migueles SA"", ""Watson-Jones D"", ""Yazdanpanah Y"", ""Thiébaut R"", ""Peeters M"", ""Richert L"", ""Levy Y"", ""PREVAC Study Team""]",10.1056/NEJMc2608018,Lhomme E,The New England journal of medicine,0028-4793,,N Engl J Med,eng,Levy Y,[],,42485649,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42485649/,Cross-Reactive Bundibugyo Antibody Responses after Receipt of Licensed Ebola Vaccines,,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Journal Article""]","[""Abdulnour RE"", ""Akbarialiabad H"", ""Haghighi A"", ""Leachman SA""]",10.1056/NEJMp2600938,Abdulnour RE,The New England journal of medicine,0028-4793,,N Engl J Med,eng,Leachman SA,[],,42485645,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42485645/,Crew Resource Management - Navigating AI's Automation Paradox,,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter""]","[""Samelson-Jones BJ"", ""Martos-Rus C"", ""Yrigollen CM"", ""Tecedor L"", ""Small JC"", ""Matesanz SE"", ""Watson CT"", ""Vanden Heuvel AR"", ""Carrig S"", ""Yum SW"", ""Brandsema JF"", ""Lin K"", ""Wittlieb-Weber C"", ""Viaene AN"", ""Russo PP"", ""Partington S"", ""Huynh K"", ""Seneviratne T"", ""Juarez Rojas S"", ""Doshi BS"", ""Shieh P"", ""Flanigan KM"", ""Frair E"", ""Nicolau S"", ""Lawlor MW"", ""Crudele JM"", ""Davidson BL"", ""George LA""]",10.1056/NEJMc2518477,Samelson-Jones BJ,The New England journal of medicine,0028-4793,,N Engl J Med,eng,George LA,[],,42485644,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42485644/,Cardiotoxic Effects and Microdystrophin Expression after Gene Therapy for DMD,,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter"", ""Comment""]","[""Chrispin J"", ""Prakosa A"", ""Trayanova N""]",10.1056/NEJMc2605923,Chrispin J,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Trayanova N,[],415,42485642,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42485642/,More on Digital Twin-Guided Ablation for Ventricular Tachycardia. Reply,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter"", ""Comment""]","[""Bhagirath P"", ""Porta-Sanchez A"", ""Roca-Luque I""]",10.1056/NEJMc2605923,Bhagirath P,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Roca-Luque I,[],415,42485641,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42485641/,More on Digital Twin-Guided Ablation for Ventricular Tachycardia,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter"", ""Comment""]","[""Wolpin BM"", ""Hong DS""]",10.1056/NEJMc2607459,Wolpin BM,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Hong DS,[],414,42485640,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42485640/,Daraxonrasib in Advanced RAS-Mutated Pancreatic Cancer. Reply,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter"", ""Comment""]","[""Sun X"", ""Chen B"", ""Wang S""]",10.1056/NEJMc2607459,Sun X,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Wang S,[],414,42485639,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42485639/,Daraxonrasib in Advanced RAS-Mutated Pancreatic Cancer,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter"", ""Comment""]","[""Landmesser U"", ""Skurk C"", ""Eitel I""]",10.1056/NEJMc2606055,Landmesser U,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Eitel I,[],413,42485638,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42485638/,Left Atrial Appendage Closure in Atrial Fibrillation. Reply,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter"", ""Comment""]","[""Garg J"", ""Lakkireddy D""]",10.1056/NEJMc2606055,Garg J,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Lakkireddy D,[],412-413,42485637,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42485637/,Left Atrial Appendage Closure in Atrial Fibrillation,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter"", ""Comment""]","[""Llamoza-Torres CJ"", ""Fuentes-Pardo M""]",10.1056/NEJMc2606055,Llamoza-Torres CJ,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Fuentes-Pardo M,[],412,42485636,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42485636/,Left Atrial Appendage Closure in Atrial Fibrillation,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter"", ""Comment""]","[""Galea R"", ""Räber L""]",10.1056/NEJMc2606055,Galea R,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Räber L,[],411-412,42485635,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42485635/,Left Atrial Appendage Closure in Atrial Fibrillation,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter"", ""Comment""]","[""Frazzetto M"", ""Valgimigli M""]",10.1056/NEJMc2606055,Frazzetto M,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Valgimigli M,[],411,42485634,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42485634/,Left Atrial Appendage Closure in Atrial Fibrillation,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Letter""]","[""Ernst CM"", ""Fischer LKS"", ""Manson AL"", ""Li L"", ""Ma P"", ""Anahtar MN"", ""Bhattacharyya RP"", ""Earl AM"", ""Clatworthy AE"", ""Hung DT""]",10.1056/NEJMc2108952,Ernst CM,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Hung DT,[],408-410,42485633,pmc-id: PMC13403934;manuscript-id: NIHMS2166843;,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42485633/,Klebsiella Brain Abscess and Evolution of Heterovirulence in the Urinary Tract,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Editorial""]","[""Sridhar SS""]",10.1056/NEJMe2605872,Sridhar SS,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Sridhar SS,[],402-404,42485632,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42485632/,A New Standard in Muscle-Invasive Bladder Cancer - The End of the Cisplatin Era?,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Editorial""]","[""Sivakumar S""]",10.1056/NEJMe2606948,Sivakumar S,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Sivakumar S,[],400-401,42485631,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42485631/,Breaking the RAS Barrier in Pancreatic Cancer,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Case Reports"", ""Journal Article""]","[""Gilbert AL"", ""Chwalisz BK"", ""Gue RS"", ""Bebell LM""]",10.1056/NEJMcpc2518086,Gilbert AL,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Bebell LM,[],389-398,42485630,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42485630/,Case 21-2026: A 28-Year-Old Man with Headache and Vision Loss in the Right Eye,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Case Reports"", ""Journal Article""]","[""Demir Y"", ""Kutlubay Z""]",10.1056/NEJMicm2603647,Demir Y,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Kutlubay Z,[],e5,42485629,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42485629/,Koebner Phenomenon from Wet Cupping,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
"The development of effective treatment strategies for human immunodeficiency virus (HIV) infection is a major achievement. Antiretroviral drugs inhibit key steps in the viral replication cycle and consist of six mechanistic classes: HIV entry inhibitors, reverse-transcriptase inhibitors (both nucleosides and nonnucleosides), capsid inhibitors, integrase inhibitors, and protease inhibitors. Antiretroviral therapy (ART) suppresses viral replication, thereby enhancing immune function, decreasing morbidity and mortality, and preventing viral transmission. Consequently, ART is recommended for all persons with HIV infection. On the basis of randomized clinical trials, the Food and Drug Administration has approved 36 antiretroviral drugs for the treatment of HIV infection since 1987; of these, 28 are currently available in the United States, and combination ART regimens are used. Initial preferred ART regimens are potent, convenient, and unlikely to cause side effects and consist of an HIV integrase inhibitor with a high barrier to resistance combined with one or two nucleoside reverse-transcriptase inhibitors. In the majority of patients using current ART regimens, viral replication is durably suppressed below detectable levels. Patients receiving ART are monitored for virologic response over time, and if virologic failure occurs, the next regimen is selected on the basis of treatment history and the results of drug-resistance testing; often, antiretroviral drugs from new classes are administered. Today, the life expectancy of someone with HIV infection who consistently takes ART approaches that of the general population.","[""Journal Article"", ""Review""]","[""Gulick RM""]",10.1056/NEJMra2511692,Gulick RM,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Gulick RM,"[""Humans"", ""Anti-HIV Agents"", ""Drug Resistance, Viral"", ""Drug Therapy, Combination"", ""HIV Infections"", ""HIV Integrase Inhibitors"", ""HIV-1"", ""Reverse Transcriptase Inhibitors"", ""Virus Replication"", ""Virus Internalization"", ""HIV Protease Inhibitors"", ""Randomized Controlled Trials as Topic"", ""United States"", ""Drug Approval"", ""United States Food and Drug Administration"", ""Life Expectancy""]",374-387,42485628,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42485628/,Antiretroviral Therapy,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
"Neoadjuvant cisplatin-based chemotherapy is a standard therapy for muscle-invasive bladder cancer. The efficacy and safety of neoadjuvant and adjuvant (perioperative) enfortumab vedotin-pembrolizumab as compared with neoadjuvant cisplatin-based chemotherapy in persons with this cancer are unclear. We conducted a phase 3, open-label, randomized trial involving adults with muscle-invasive bladder cancer eligible for cisplatin-based chemotherapy and radical cystectomy with pelvic lymph-node dissection (cystectomy). Participants were assigned to receive neoadjuvant enfortumab vedotin-pembrolizumab (4 cycles; enfortumab vedotin [1.25 mg per kilogram of body weight on days 1 and 8] and pembrolizumab [200 mg on day 1] every 3 weeks), cystectomy, and 5 cycles of enfortumab vedotin and 13 cycles of pembrolizumab as adjuvant therapy or to receive neoadjuvant cisplatin-gemcitabine (4 cycles; cisplatin [70 mg per square meter of body-surface area on day 1] plus gemcitabine [1000 mg per square meter on days 1 and 8] every 3 weeks) and cystectomy. The primary end point was event-free survival; key secondary end points were overall survival and pathological complete response. Safety was assessed. A total of 405 participants were assigned to receive enfortumab vedotin-pembrolizumab and 403 to receive cisplatin-gemcitabine. The median time from randomization to the data-cutoff date was 33.6 months (range, 22.5 to 53.6). A total of 86.7% of the participants in the enfortumab vedotin-pembrolizumab group and 89.6% of those in the cisplatin-gemcitabine group underwent cystectomy. At 2 years, estimated event-free survival was 79.4% with enfortumab vedotin-pembrolizumab and 66.2% with cisplatin-gemcitabine (hazard ratio for an event or death, 0.53; 95% confidence interval [CI], 0.41 to 0.70; P<0.001); estimated overall survival was 86.9% and 81.3%, respectively (hazard ratio for death, 0.65; 95% CI, 0.48 to 0.89; two-sided P = 0.006). A pathological complete response occurred in 55.8% and 32.5% of the participants (P<0.001). The incidence of grade 3 or higher adverse events of any cause was 75.7% with enfortumab vedotin-pembrolizumab and 67.2% with cisplatin-gemcitabine. Among participants with muscle-invasive bladder cancer eligible for cisplatin-based chemotherapy, perioperative enfortumab vedotin-pembrolizumab led to significantly better event-free and overall survival outcomes and a significantly higher incidence of pathological complete response than neoadjuvant cisplatin-gemcitabine, but with more adverse events of grade 3 or higher. (Funded by Merck Sharp and Dohme and others; KEYNOTE-B15/EV-304 ClinicalTrials.gov number, NCT04700124.).","[""Clinical Trial, Phase III"", ""Comparative Study"", ""Journal Article"", ""Multicenter Study"", ""Randomized Controlled Trial"", ""Video-Audio Media""]","[""Galsky MD"", ""Valderrama BP"", ""Maruzzo M"", ""Font A"", ""Ciuleanu T"", ""Chatzkel J"", ""Koie T"", ""Hoimes CJ"", ""Puente J"", ""Zakharia Y"", ""Rosenbaum E"", ""Boehm K"", ""Loriot Y"", ""Bedke J"", ""Powles TB"", ""Necchi A"", ""Wiechno P"", ""Álvarez-Fernández C"", ""Kim TH"", ""Oliveira N"", ""Flaig TW"", ""Wirtz HS"", ""Mihm M"", ""Huang Q"", ""Rogiers A"", ""Homet Moreno B"", ""Gómez de Liaño A"", ""KEYNOTE-B15/EV-304 Investigators""]",10.1056/NEJMoa2601486,Galsky MD,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Gómez de Liaño A,"[""Adult"", ""Aged"", ""Female"", ""Humans"", ""Male"", ""Middle Aged"", ""Antibodies, Monoclonal"", ""Antibodies, Monoclonal, Humanized"", ""Antineoplastic Combined Chemotherapy Protocols"", ""Chemotherapy, Adjuvant"", ""Cisplatin"", ""Cystectomy"", ""Gemcitabine"", ""Kaplan-Meier Estimate"", ""Neoadjuvant Therapy"", ""Urinary Bladder Neoplasms"", ""Neoplasm Invasiveness"", ""Urinary Bladder"", ""Lymph Node Excision"", ""Progression-Free Survival"", ""Pathologic Complete Response"", ""Aged, 80 and over""]",338-348,42485627,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42485627/,Enfortumab Vedotin and Pembrolizumab in Cisplatin-Eligible Bladder Cancer,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Journal Article""]","[""Rich JD"", ""Thornton K"", ""Akiyama MJ""]",10.1056/NEJMp2602773,Rich JD,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Akiyama MJ,[],316-318,42474118,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42474118/,National Elimination of Hepatitis C - The Case for Starting in Prisons and Jails,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Journal Article""]","[""Krüger N"", ""Kong Y"", ""Bachinger M"", ""Kesselheim AS""]",10.1056/NEJMp2602486,Krüger N,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Kesselheim AS,[],319-321,42474117,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42474117/,When Celebrities Prescribe - Regulating Drug Promotion on the Internet,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Journal Article""]","[""Jones T""]",10.1056/NEJMp2516818,Jones T,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Jones T,[],321-323,42474111,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42474111/,Love and Death,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Case Reports"", ""Journal Article""]","[""Lee RLM"", ""Pedregosa BC 2nd""]",10.1056/NEJMicm2603020,Lee RLM,The New England journal of medicine,0028-4793,4,N Engl J Med,eng,Pedregosa BC 2nd,[],388,42474108,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42474108/,Neurocysticercosis,395,6Kb9UQIDVXcK3fnqP,m6u8rms2aWVYUKhVZ
,"[""Journal Article""]","[""Ravensberg J"", ""Gussekloo J"", ""Poortvliet RKE""]",10.1001/jama.2026.11178,Ravensberg J,JAMA,0098-7484,,JAMA,eng,Poortvliet RKE,[],,42545717,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545717/,Discontinuation of Levothyroxine-Reply,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Curfman G""]",10.1001/jama.2026.15043,Curfman G,JAMA,0098-7484,,JAMA,eng,Curfman G,[],,42545714,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545714/,Regulation of General Wellness Devices,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Zaidat OO"", ""Al Kasab S"", ""Sheth SA"", ""Rai AT"", ""Ortega-Gutierrez S"", ""Given CA 2nd"", ""Zaidi SF"", ""Grandhi R"", ""Cuellar-Saenz H"", ""Mokin M"", ""Katz JM"", ""Alshekhlee A"", ""Taqi MA"", ""Ansari SA"", ""Siddiqui AH"", ""Barazangi N"", ""Maud A"", ""Kirmani J"", ""Gupta R"", ""Yavagal DR"", ""Tarpley J"", ""Pandya DJ"", ""Cress MC"", ""Dharmadhikari S"", ""Asif KS"", ""Kass-Hout T"", ""Puri AS"", ""Janjua N"", ""Majjhoo AQ"", ""Badruddin A"", ""Spiotta AM"", ""Bhuva P"", ""Salazar-Marioni S"", ""Lin E"", ""Samaniego EA"", ""Kolikonda MK"", ""Jumaa MA"", ""Majoie CBLM"", ""Elijovich L"", ""Jadhav A"", ""Olvany JM"", ""Tariq Z"", ""Brown S"", ""Nguyen TN"", ""Gress D"", ""Dippel DWJ"", ""Smith WS"", ""Yoo AJ"", ""TESLA Investigators""]",10.1001/jama.2026.12814,Zaidat OO,JAMA,0098-7484,,JAMA,eng,Yoo AJ,[],,42545711,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545711/,One-Year Outcomes After Endovascular Treatment for Large Acute Ischemic Stroke: The TESLA Randomized Clinical Trial,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Kaneda Y""]",10.1001/jama.2026.11175,Kaneda Y,JAMA,0098-7484,,JAMA,eng,Kaneda Y,[],,42545710,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545710/,Discontinuation of Levothyroxine,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]",[],10.1001/jama.2026.9499,,JAMA,0098-7484,,JAMA,eng,,[],e269499,42545706,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545706/,Addition of High-Dose Vitamin D3 to Standard Treatment in Patients With Metastatic Colorectal Cancer: Research Summary,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Kishore SP"", ""Narang P"", ""Auerbach A""]",10.1001/jama.2026.13895,Kishore SP,JAMA,0098-7484,,JAMA,eng,Auerbach A,[],,42545692,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545692/,Sorting Results of Unknown Significance-A Framework for Clinicians Navigating Wearable Data in the AI Era,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Whyte JJ""]",10.1001/jama.2026.14789,Whyte JJ,JAMA,0098-7484,,JAMA,eng,Whyte JJ,[],,42545688,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545688/,The Need to Avoid a Regulatory Gray Zone in Digital Wellness,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
"In a phase 2 randomized clinical trial, high-dose vitamin D3 added to standard treatment improved progression-free survival (PFS) compared with standard-dose vitamin D3 in patients with metastatic colorectal cancer (mCRC). To determine if high-dose vitamin D3 added to standard chemotherapy improves outcomes in patients with previously untreated mCRC. Double-blind phase 3 randomized clinical trial enrolling 455 patients with previously untreated mCRC, conducted in the US through the National Clinical Trials Network from October 2019 to December 2022 (database freeze: July 15, 2024). mFOLFOX6 (modified FOLFOX6 [5-fluorouracil, leucovorin, oxaliplatin]) or FOLFIRI (5-fluorouracil, leucovorin, irinotecan) plus bevacizumab every 2 weeks with either high-dose vitamin D3 (8000 IU daily × 14 days as loading dose followed by 4000 IU daily) or standard-dose vitamin D3 (400 IU daily) until disease progression, intolerable toxicity, or withdrawal of consent. The primary end point was PFS assessed by the unstratified log-rank test. Secondary end points included objective response rate, overall survival, and toxicity. Prespecified subgroup analyses of PFS were performed according to known prognostic factors. Among 455 randomized patients (median age, 59 years; 181 [40%] female) with median follow-up 20 months, the median PFS for high-dose vitamin D3 (n = 228) was 11.8 months (95% CI, 10.3-13.3) vs 10.3 months (95% CI, 9.4-12.2) for standard-dose vitamin D3 (n = 227) (1-sided log-rank P = .25). There were no significant differences in objective response rate between high-dose and standard-dose vitamin D3 (51% [95% CI, 44%-58%] vs 44% [95% CI, 37%-50%], respectively; P = .12), or in overall survival (median, 25.6 vs 27.0 months; 1-sided log-rank P = .66). There were no clinically meaningful differences in the most common grade 3 or greater adverse events between the high- and standard-dose groups, including neutropenia (n = 67 [32%] vs n = 62 [30%]) and hypertension (n = 42 [20%] vs n = 49 [23%]) or in incidence of vitamin D-associated toxicities. Among patients with previously untreated mCRC, addition of high-dose vitamin D3, vs standard-dose vitamin D3, to standard chemotherapy plus bevacizumab did not improve PFS. ClinicalTrials.gov Identifier: NCT04094688.","[""Journal Article""]","[""Ng K"", ""Ou FS"", ""Zemla T"", ""Jackson NA"", ""Kalyan A"", ""Devoe C"", ""Shusterman M"", ""Vijayvergia N"", ""Wu CS"", ""Cohen SA"", ""Pulsipher S"", ""Shergill A"", ""Watson Y"", ""Kleiber B"", ""Lee M"", ""Kohn CG"", ""Thalappillil JS"", ""Schwartz LH"", ""Zuckerman D"", ""Hollis BW"", ""O'Reilly EM"", ""Meyerhardt JA""]",10.1001/jama.2026.9350,Ng K,JAMA,0098-7484,,JAMA,eng,Meyerhardt JA,[],,42545685,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545685/,Addition of High-Dose Vitamin D3 to Standard Treatment in Patients With Metastatic Colorectal Cancer: The SOLARIS Randomized Clinical Trial (Alliance A021703),,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article"", ""Published Erratum""]",[],10.1001/jama.2026.15000,,JAMA,0098-7484,,JAMA,eng,,[],,42545683,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545683/,Incorrect Author Affiliations,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Anderer S""]",10.1001/jama.2026.9497,Anderer S,JAMA,0098-7484,,JAMA,eng,Anderer S,[],,42536388,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536388/,"Ischemic Heart Disease Deaths Increasingly Tied to BMI, Hyperglycemia",,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Anderer S""]",10.1001/jama.2026.9491,Anderer S,JAMA,0098-7484,,JAMA,eng,Anderer S,[],,42536382,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536382/,FDA Approves First Oral PCSK9 Inhibitor to Lower LDL Cholesterol,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Anderer S""]",10.1001/jama.2026.9495,Anderer S,JAMA,0098-7484,,JAMA,eng,Anderer S,[],,42536380,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536380/,FDA Approves At-Home Starting Dose for Anti-Amyloid Therapy,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Rubin R""]",10.1001/jama.2026.14334,Rubin R,JAMA,0098-7484,,JAMA,eng,Rubin R,[],,42536379,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536379/,"Soccer Players' Brains, P-Tau217 Blood Tests, Lifestyle and Dementia Risk, and More From AAIC 2026",,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Anderer S""]",10.1001/jama.2026.9494,Anderer S,JAMA,0098-7484,,JAMA,eng,Anderer S,[],,42536367,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536367/,ACOG Releases New HIV Screening and Prevention Guidelines,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Anderer S""]",10.1001/jama.2026.9496,Anderer S,JAMA,0098-7484,,JAMA,eng,Anderer S,[],,42536365,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536365/,HHS Launches Voluntary Pledge for More Nutritious Hospital Food,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Anderer S""]",10.1001/jama.2026.9493,Anderer S,JAMA,0098-7484,,JAMA,eng,Anderer S,[],,42536359,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536359/,Infections Linked to Increased Risk of Psychiatric and Neurological Disorders,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]",[],10.1001/jama.2026.14955,,JAMA,0098-7484,,JAMA,eng,,[],e2614955,42536021,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536021/,Initial HIV Therapy for Adults and Treatment-Associated Weight Gain: Research Summary,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
"Antiretroviral therapy (ART), particularly regimens containing tenofovir alafenamide with dolutegravir or bictegravir, is associated with substantial weight gain, potentially exacerbating cardiometabolic risk in people with HIV. To determine whether a regimen with doravirine, lamivudine, and tenofovir disoproxil fumarate results in less weight gain than a regimen with dolutegravir, emtricitabine, and tenofovir alafenamide while maintaining noninferior viral suppression. Open-label, noninferiority randomized clinical trial including ART-naive adults (≥18 years of age) with an HIV RNA level greater than 500 copies/mL and no detectable baseline, high-level doravirine resistance. The study was conducted at 2 South African sites and individuals were recruited between October 2023 and March 2025. The final participant visit occurred in February 2026. A once-daily regimen with 100 mg of doravirine, 300 mg of lamivudine, and 300 mg of tenofovir disoproxil fumarate (n = 299) or 50 mg of dolutegravir, 200 mg of emtricitabine, and 25 mg of tenofovir alafenamide (n = 301). The primary outcome was viral suppression (HIV RNA level <50 copies/mL) at week 48 (prespecified noninferiority margin of -10 percentage points). The key secondary outcomes included changes in body weight, treatment-associated effects on body composition, and safety and adverse events. Among 600 participants, 597 (99.5%) were Black African, 413 (68.8%) were assigned female at birth, and the median age was 34 years (IQR, 28-41). At week 48, 266 participants (89.0%) in the doravirine, lamivudine, and tenofovir disoproxil fumarate group achieved viral suppression (HIV RNA level <50 copies/mL) vs 273 participants (90.7%) in the dolutegravir, emtricitabine, and tenofovir alafenamide group (between-group difference, -1.7 percentage points [95% CI, -6.6 to 3.1], meeting the prespecified noninferiority margin of -10 percentage points). The median weight gain was 3.0 kg in the doravirine, lamivudine, and tenofovir disoproxil fumarate group vs 5.0 kg in the dolutegravir, emtricitabine, and tenofovir alafenamide group (between-group difference, -2.0 kg [95% CI, -3.0 to -1.0 kg]; P < .001). Among participants in the doravirine, lamivudine, and tenofovir disoproxil fumarate group, the median change in hip bone mineral density (BMD) was -2.1% (IQR, -4.1% to -0.5%) and was -3.2% (IQR, -5.4% to -0.8%) for spine BMD vs -0.5% (IQR, -1.9% to 1.2%) for hip BMD and -1.3% (IQR, -3.2% to 0.8%) for spine BMD with dolutegravir, emtricitabine, and tenofovir alafenamide (P < .001 for each between-group comparison). Resistance to doravirine emerged among 7 of 9 participants experiencing virologic failure in the doravirine, lamivudine, and tenofovir disoproxil fumarate group. Of these 7 participants, 5 of 6 achieved viral suppression after switching to dolutegravir-based therapy and 1 was lost to follow-up. Serious adverse events and deaths (n = 2) were infrequent and not considered treatment-related. Among predominantly Black African adults initiating ART, a regimen with doravirine, lamivudine, and tenofovir disoproxil fumarate was noninferior to a regimen with dolutegravir, emtricitabine, and tenofovir alafenamide for 48-week viral suppression and was associated with less weight gain. ClinicalTrials.gov Identifier: NCT05924438.","[""Journal Article""]","[""Woods J"", ""Lebina L"", ""Möller K"", ""Venter WDF"", ""Akpomiemie G"", ""Manentsa N"", ""Taukobong I"", ""Macholo P"", ""Behuhuma NO"", ""Lalla-Edward ST"", ""Manne-Goehler J"", ""Siedner MJ"", ""Collings T"", ""Mashabane N"", ""Hill A"", ""Sokhela SM""]",10.1001/jama.2026.14762,Woods J,JAMA,0098-7484,,JAMA,eng,Sokhela SM,[],,42536019,pmc-id: PMC13428290;embargo-date: 2027/01/31;,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536019/,Initial HIV Therapy for Adults and Treatment-Associated Weight Gain: The Opti-DOR Randomized Clinical Trial,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Winkelmayer WC"", ""Chertow GM""]",10.1001/jama.2026.7477,Winkelmayer WC,JAMA,0098-7484,,JAMA,eng,Chertow GM,[],,42530951,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42530951/,Dapagliflozin to Reduce the Risk of Perioperative Acute Kidney Injury in Elective Cardiac Surgery,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Walter KL""]",10.1001/jama.2026.12580,Walter KL,JAMA,0098-7484,,JAMA,eng,Walter KL,[],,42530946,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42530946/,What Are Nicotine Pouches?,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Park KU"", ""Brindle M""]",10.1001/jama.2026.10778,Park KU,JAMA,0098-7484,,JAMA,eng,Brindle M,[],,42530923,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42530923/,Changes in Clinician Time Expenditure and Visit Quantity With Artificial Intelligence-Powered Scribes,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]",[],10.1001/jama.2026.9483,,JAMA,0098-7484,,JAMA,eng,,[],e269483,42530922,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42530922/,Dapagliflozin and Acute Kidney Injury Following Cardiac Surgery: Research Summary,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Shirani A""]",10.1001/jama.2026.10775,Shirani A,JAMA,0098-7484,,JAMA,eng,Shirani A,[],,42530917,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42530917/,Changes in Clinician Time Expenditure and Visit Quantity With Artificial Intelligence-Powered Scribes,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Hartmann-Boyce J""]",10.1001/jama.2026.14359,Hartmann-Boyce J,JAMA,0098-7484,,JAMA,eng,Hartmann-Boyce J,[],,42530911,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42530911/,Physician Advice on E-Cigarettes for Smoking Cessation: Differentiating Evidence From Values,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
"Two percent to 50% of patients undergoing elective cardiac surgery experience acute kidney injury (AKI) postoperatively. Medications to prevent AKI after elective cardiac surgery have not been identified. In patients undergoing elective cardiac surgery, to evaluate whether initiating dapagliflozin 1 day prior to surgery reduces the incidence of AKI at 7 days after cardiac surgery, compared with placebo. Multicenter, double-blind, placebo-controlled randomized clinical trial conducted at 2 academic medical centers and 5 nonacademic hospitals in the Netherlands. Eligible participants were adults undergoing elective cardiac surgery. Enrollment occurred between June 8, 2023, and January 27, 2025. Final follow-up occurred May 16, 2025. Patients were randomized 1:1 to receive either dapagliflozin (10 mg orally; n = 392) or placebo once daily (n = 392), beginning on the day before surgery and continuing through the second postoperative day (total of 4 doses). The primary outcome was the between-group difference in AKI (defined as an increase in serum creatinine level by at least 0.3 mg/dL [26.5 µmol/L] within 48 hours after surgery, a 1.5-fold creatinine increase within 7 days of surgery, or urine output less than 0.5 mL/kg/h for 6 to 12 hours according to Kidney Disease: Improving Global Outcomes criteria) during the first 7 postoperative days. Of 784 participants enrolled, 778 (99%) completed follow-up testing (median age, 68 [61-74] years; 76% male; 97% White; median body mass index, 27 [IQR, 25-30]; and median estimated glomerular filtration rate, 80 [IQR, 67-89] mL/min/1.73 m2). Compared with placebo, dapagliflozin reduced the incidence of AKI (28% vs 52%; relative risk, 0.54 [95% CI, 0.45-0.65]; P < .001) over 7-day follow-up after surgery. Atrial fibrillation and reoperation were the most frequent adverse events. The incidence of atrial fibrillation was 45% (176/392) in the dapagliflozin group vs 45% (176/392) in the placebo group, and the incidence of reoperation was 11% (43/392) vs 10% (39/392), respectively. In patients undergoing elective cardiac surgery, 4 doses of dapagliflozin, beginning the day before surgery, reduced the incidence of AKI during the 7-day postoperative period. ClinicalTrials.gov Identifier: NCT05590143.","[""Journal Article""]","[""Oosterom-Eijmael MJP"", ""Hulst AH"", ""de Oliveira NPM"", ""Niesten ED"", ""Wietsma NE"", ""Gerritse BM"", ""Scohy TV"", ""Rettig TCD"", ""Snellen FTF"", ""Voogd MF"", ""Godfried MB"", ""de Boer RN"", ""Wink J"", ""van der Werff LMM"", ""Cobbaert CM"", ""Ruhaak LR"", ""Eberl S"", ""Preckel B"", ""Hollmann MW"", ""Schenk J"", ""Hermanides J"", ""van Raalte DH"", ""MERCURI-2 Study Group""]",10.1001/jama.2026.9268,Oosterom-Eijmael MJP,JAMA,0098-7484,,JAMA,eng,van Raalte DH,[],,42530910,pmc-id: PMC13425237;embargo-date: 2027/01/30;,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42530910/,Dapagliflozin and Acute Kidney Injury Following Cardiac Surgery: A Randomized Clinical Trial,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Shkabari B"", ""Vorko NI"", ""Geerlinks WM"", ""Purh E"", ""Diana-Gonsalves CM"", ""Sutaria S"", ""Gyawali B""]",10.1001/jama.2026.12089,Shkabari B,JAMA,0098-7484,,JAMA,eng,Gyawali B,[],,42530909,pmc-id: PMC13425235;embargo-date: 2027/01/30;,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42530909/,Cancer Medicine Approvals in the US,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Piasecki TM"", ""Piper ME"", ""Kathuria H""]",10.1001/jama.2026.11806,Piasecki TM,JAMA,0098-7484,,JAMA,eng,Kathuria H,[],,42530908,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42530908/,Nicotine Pouches,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
"Cigarette smoking, maintained predominantly by nicotine dependence, is a long-term and relapsing behavior that continues to be a leading cause of preventable death and disease worldwide. E-cigarettes with nicotine are less harmful than cigarettes and have been shown to be more effective for smoking cessation than US Food and Drug Administration-approved nicotine replacement therapies. However, misperceptions of the harms of e-cigarettes are common, even among clinicians. This Special Communication is a position manuscript developed by a working group within the Treatment Research Network of the international Society for Research on Nicotine and Tobacco. The aims of the manuscript were to summarize the evidence on the use of e-cigarettes for smoking cessation and to provide recommendations for clinicians on how to engage in conversations with adult patients who currently smoke cigarettes. Specifically, advice is provided on (1) integration of e-cigarettes into patient-centered shared decision-making conversations on the risks and benefits of various pharmacologic smoking cessation treatments; and (2) practical guidance on the use of e-cigarettes for smoking cessation. This Special Communication includes one overarching recommendation: integrate e-cigarettes into conversations on the risks and benefits of all evidence-based pharmacologic treatments for smoking cessation. In support of this recommendation, specific guidance is provided regarding how to discuss potential misperceptions and suggests questions to guide patient conversations. Finally, evidence-based best practices are provided for using e-cigarettes to quit smoking, which can be shared with patients. The significant burden of cigarette smoking, coupled with scientific evidence supporting e-cigarettes for smoking cessation, clearly indicates that it is appropriate to include e-cigarettes in discussions of evidence-based pharmacologic treatment for smoking cessation to reduce the harms of cigarette smoking. These recommendations are intended to provide evidence-informed guidance to clinicians regarding use of e-cigarettes for smoking cessation.","[""Journal Article""]","[""Leavens ELS"", ""Pebley K"", ""Smith TT"", ""Ahluwalia JS"", ""Bello MS"", ""Bold KW"", ""Cantrell J"", ""Carpenter MJ"", ""Cioe PA"", ""Felicione NJ"", ""Havard A"", ""Hawk LW Jr"", ""Kaye JT"", ""Klemperer EM"", ""Kleykamp BA"", ""Lindson N"", ""McClure EA"", ""McRobbie H"", ""Murphy CM"", ""Rigotti NA"", ""Walker NK"", ""Yang MJ"", ""Rojewski AM"", ""Johnson AL"", ""Members of the Society for Research on Nicotine and Tobacco, Treatment Research Network, Harm Reduction Workgroup""]",10.1001/jama.2026.13087,Leavens ELS,JAMA,0098-7484,,JAMA,eng,Johnson AL,[],,42530900,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42530900/,Nicotine E-Cigarettes for Cigarette Smoking Cessation: Recommendations to US-Based Clinicians,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Rotenstein LS"", ""Mishuris R"", ""Holmgren AJ""]",10.1001/jama.2026.10781,Rotenstein LS,JAMA,0098-7484,,JAMA,eng,Holmgren AJ,[],,42530899,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42530899/,Changes in Clinician Time Expenditure and Visit Quantity With Artificial Intelligence-Powered Scribes-Reply,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Basu S"", ""Huynh BQ"", ""Andrews JR""]",10.1001/jama.2026.10772,Basu S,JAMA,0098-7484,,JAMA,eng,Andrews JR,[],,42525428,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42525428/,Immigration and Customs Enforcement Detention-Reply,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Ohaghuenyi S"", ""Schwabowski S"", ""Soyemi K""]",10.1001/jama.2026.10769,Ohaghuenyi S,JAMA,0098-7484,,JAMA,eng,Soyemi K,[],,42525425,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42525425/,Immigration and Customs Enforcement Detention,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Huffman MD"", ""Dávila-Román VG"", ""Agarwal A""]",10.1001/jama.2026.10083,Huffman MD,JAMA,0098-7484,,JAMA,eng,Agarwal A,[],,42525406,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42525406/,Global Low-Density Lipoprotein Cholesterol-Leveraging Estimation for Action,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
"Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C-related burden is critical for guiding prevention and treatment strategies. To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Population-level LDL-C concentrations. Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C-attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C-attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.","[""Journal Article""]","[""GBD 2023 LDL Cholesterol Collaborators"", ""Razo C"", ""DeCleene NK"", ""Johnson CO"", ""Stark BA"", ""LeGrand K"", ""Aalruz H"", ""Abaraogu UO"", ""Abd ElHafeez S"", ""Abdelmasseh M"", ""Abdelnabi M"", ""Abd-Elsalam S"", ""Abdelsalam Elshenawy R"", ""Abdelwahab SI"", ""Abdolizadeh A"", ""Abdollahi A"", ""Abdoun M"", ""Abdrabou MM"", ""Abdulah DM"", ""Abdullahi A"", ""Abdul-Rahman T"", ""Abebe MS"", ""Abebe Getahun H"", ""Abiodun OO"", ""Abiodun O"", ""Abohashem S"", ""Abonie US"", ""Abourashed NM"", ""Abramov D"", ""Abrar MM"", ""Abtahi D"", ""Abu Farha RK"", ""Abubakar B"", ""Abuhelwa AY"", ""Abukhadijah HJ"", ""Aburuz S"", ""Abushanab D"", ""Adams LC"", ""Adamu NLL"", ""Adane MM"", ""Addo IY"", ""Adedokun KA"", ""Adegbile OE"", ""Adegoke NA"", ""Adekola SA"", ""Adeleke OT"", ""Adesina MA"", ""Adisu MA"", ""Adnan M"", ""Afoakwah C"", ""Afolabi AA"", ""Afrashteh F"", ""Afrifa-Yamoah E"", ""Afzal S"", ""Agordoh PD"", ""Agyemang-Duah W"", ""Ahmad A"", ""Ahmad K"", ""Ahmad S"", ""Ahmad S"", ""Ahmed A"", ""Ahmed GS"", ""Ahmed LA"", ""Ahmed MS"", ""Ahmed MS"", ""Ahmed MSA"", ""Ahmed M"", ""Ahmed N"", ""Ahmed SA"", ""Ahmed Z"", ""Aiyer A"", ""Ajami M"", ""Akalanka KHM"", ""Akhtar MN"", ""Akindele MO"", ""Akkaif MA"", ""Akrami AE"", ""Akyea RK"", ""Al Hasan SM"", ""Al Zoubi MAM"", ""Alahdab F"", ""Al-Ahmad MM"", ""Alajajian S"", ""Alajlani MM"", ""Alalwan TA"", ""Al-Aly Z"", ""Al-Amri IS"", ""Alanzi TM"", ""Alarifi A"", ""Al-Ashwal FY"", ""Al-Azayzih A"", ""Al-Azzam S"", ""Al-Bashaireh AM"", ""Albashtawy M"", ""Al-Dewik N"", ""Aleidi SM"", ""Algahtani FD"", ""Algammal AM"", ""Alhabib KF"", ""Alhalaiqa FN"", ""Ali A"", ""Ali A"", ""Ali BR"", ""Ali MD"", ""Ali MU"", ""Ali R"", ""Ali SS"", ""Al-Iede M"", ""Alif SM"", ""Alipour M"", ""Al-Jabi SW"", ""Aljunid SM"", ""Alkhatib MH"", ""Alkubati SA"", ""Allawi RH"", ""Allemailem KS"", ""Allouh MZ"", ""Almagharbeh WT"", ""Almahmeed W"", ""Al-Marwani S"", ""Almazan JU"", ""Alnaeem MM"", ""Alniss HY"", ""Alomari MA"", ""Alotaibi HFF"", ""Alqahtani SA"", ""AlQudah M"", ""Alqudimat MR"", ""Al-Qudimat AR"", ""Al-Raddadi RM"", ""Alrimawi I"", ""Alrousan SM"", ""Alsbou M"", ""Alshahrani NZ"", ""Al-Shami AS"", ""Altaany Z"", ""Altaf A"", ""Althobiani MA"", ""Altwalbeh D"", ""Alwafi H"", ""Al-Worafi YM"", ""Aly H"", ""Al-Zalabani AH"", ""Alzoubi A"", ""Alzoubi KH"", ""Al-Zubairi AS"", ""Amafah J"", ""Mohammadi MA"", ""Amin A"", ""Amini S"", ""Amini-Salehi E"", ""Amusa GA"", ""Ananda RA"", ""Ancuceanu R"", ""Ang SP"", ""Anieto EM"", ""Anil A"", ""Anjana P"", ""Anuoluwa BS"", ""Anvari S"", ""Anwar SL"", ""Anyasodor AE"", ""Appati W"", ""Arabloo J"", ""Arafa EA"", ""Arafat M"", ""Aravkin AY"", ""Areda D"", ""Arefnezhad R"", ""Aregawi BB"", ""Arias de la Torre J"", ""Aripov T"", ""Arockiaraj J"", ""de Arruda GA"", ""Asdaq SMB"", ""Asghari-Jafarabadi M"", ""Ashraf S"", ""Ashraf SA"", ""Ashraf T"", ""Asiamah-Asare BKY"", ""Atac O"", ""Athar M"", ""Athari SS"", ""Atorkey P"", ""Aurangzeb K"", ""Awan SJ"", ""Awan UA"", ""Awol KLL"", ""Awotidebe AW"", ""Ayala CO"", ""Ayli BI"", ""Azad AKM"", ""Azarboo A"", ""Aziz SA"", ""Azzam AY"", ""Azzolino D"", ""Babiker R"", ""Babu AS"", ""Babu GR"", ""Badar M"", ""Badiye AD"", ""Badran AA"", ""Baghlaf KK"", ""Baig AA"", ""Bakhshali MA"", ""Balabekova M"", ""Balakrishnan S"", ""Baltatu OC"", ""Banach M"", ""Banik PC"", ""Barqawi HJ"", ""Barrow A"", ""Barua L"", ""Bashir MI"", ""Bashir S"", ""Bashiri A"", ""Bastan MM"", ""Bayat M"", ""Bayih MT"", ""Beeraka NM"", ""Begum T"", ""Behera P"", ""Behera SM"", ""Behnam B"", ""Bejarano Ramirez DF"", ""Belayneh M"", ""Bello AB"", ""Belo L"", ""Berihun AA"", ""Bhaskar S"", ""Bhattacharjee P"", ""Bhatti GK"", ""Bhatti JS"", ""Biswas A"", ""Biswas B"", ""Bizzozero-Peroni B"", ""Bodur M"", ""Bogale SK"", ""Bohn L"", ""Boloor A"", ""Bolourinejad P"", ""Bonny A"", ""Botero Carvajal A"", ""Bouaoud S"", ""Boudalia S"", ""Britton G"", ""Bugiardini R"", ""Busch F"", ""Bustanji Y"", ""Butt ZA"", ""Campos LA"", ""Cao Y"", ""Catapano AL"", ""Cegolon L"", ""Cembranel F"", ""Cenko E"", ""Cerin E"", ""Chadwick J"", ""Chakraborty C"", ""Chandika RM"", ""Chandrasekar EK"", ""Chandrasekaran B"", ""Chattu VK"", ""Chau LD"", ""Chaudhary AA"", ""Chaudhuri S"", ""Cheema AAA"", ""Chen AT"", ""Chen H"", ""Chen H"", ""Cheng H"", ""Cheung KC"", ""Chew NWS"", ""Chi G"", ""Chichagi F"", ""Ching PR"", ""Cho WCS"", ""Choi DW"", ""Chong B"", ""Chopra D"", ""Chopra H"", ""Chopra S"", ""Choudhari SG"", ""Chu DT"", ""Chukwu CW"", ""Chung SC"", ""Chung S"", ""Cicero AFG"", ""Cosma C"", ""Criqui MH"", ""Cruz-Martins N"", ""Dadras O"", ""Dahabiyeh L"", ""Dahal Khatri B"", ""Dai X"", ""Dai Z"", ""Dalakoti M"", ""D'Amico E"", ""Damtie ET"", ""Dandona L"", ""Dandona R"", ""D'Anna L"", ""Danpanichkul P"", ""Darcho SD"", ""Dardas LA"", ""Das SK"", ""Davletov D"", ""Davletov K"", ""Dejenie TA"", ""Del Bo' C"", ""Delgado-Enciso I"", ""Denova-Gutiérrez E"", ""Dergaa I"", ""Derseh HA"", ""Derviševic E"", ""Desale AT"", ""Devanbu VGC"", ""Devegowda D"", ""Dewan SMR"", ""Dhali A"", ""Dhimal M"", ""Dhungel B"", ""Dias da Silva D"", ""Didehvar K"", ""Ding X"", ""Do TC"", ""Do THP"", ""Dohare S"", ""Dong D"", ""D'Oria M"", ""Dorostkar F"", ""Doshi OP"", ""Doshi RP"", ""Dourado PMM"", ""Dowou RK"", ""Dresse MT"", ""Du M"", ""Duncan BB"", ""Duraes AR"", ""Ebohon O"", ""Ebraheim LLM"", ""Edeh C"", ""Eftekhari B"", ""Sedeh AE"", ""Ekholuenetale M"", ""El Arab RA"", ""Eladl MA"", ""Eldaboush A"", ""El-Dahiyat F"", ""Elgendy IY"", ""Elhadi M"", ""Elhoumed M"", ""El-Huneidi W"", ""Elmeligy OAA"", ""Elmonem MA"", ""Elmoselhi AB"", ""Elnaem MH"", ""Eltahawy AS"", ""Etaee F"", ""Fabin N"", ""Fadaka AO"", ""Fagbamigbe AF"", ""Fakhradiyev IR"", ""Fakorede S"", ""Farasani A"", ""Fareed M"", ""Farhana A"", ""Faris MEM"", ""Farsi F"", ""Fatima Z"", ""Fayaz M"", ""Fazylov T"", ""Fekadu G"", ""Fernandez-Jimenez R"", ""Ferreira N"", ""Fischer F"", ""Fogacci F"", ""Fonzo M"", ""Foschi M"", ""Gadanya MA"", ""Gajdács M"", ""Galali Y"", ""Ganesan B"", ""Ganesh B"", ""Gangachannaiah S"", ""Gao D"", ""Garcia-Azorin D"", ""Garg P"", ""Gasevic D"", ""Gautam RK"", ""Gaye B"", ""Gebresilassie MH"", ""Getacher L"", ""Gete KY"", ""Ghadirian F"", ""Ghaffari K"", ""Ghaffari Jolfayi A"", ""Ghamkhar A"", ""Gharaibeh L"", ""Ghasemi M"", ""Ghazy RM"", ""Ghimire S"", ""Ghith N"", ""Gil AU"", ""Gilani SA"", ""Gill PS"", ""Gnedovskaya EV"", ""Goh LH"", ""Gohari K"", ""Gohil MN"", ""Golechha M"", ""Goleij P"", ""Golmohammadi M"", ""Goulart AC"", ""Goyal A"", ""Grada A"", ""Grover A"", ""Gu L"", ""Gubari MIM"", ""Gufue ZH"", ""Guha A"", ""Gunawardane DA"", ""Guo Z"", ""Gupta R"", ""Gupta S"", ""Gurgoglione FL"", ""Guzman-Esquivel J"", ""Guzmán-Muñoz E"", ""Haghtalab A"", ""Nam NH"", ""Hailu KT"", ""Halder P"", ""Hamdy NM"", ""Hamidi H"", ""Hamidi S"", ""Hammad EA"", ""Hamoudi R"", ""Hanif A"", ""Hanifi N"", ""Hankey GJ"", ""Harsini S"", ""Hartmann P"", ""Hasan I"", ""Hashempur MH"", ""Hasnain MS"", ""Hassan A"", ""Hassan IN"", ""Hassan I"", ""Hassan N"", ""Hassan TS"", ""Hassan Ahmed O"", ""Hayat K"", ""Hebert JJ"", ""Helmy YA"", ""Hezam K"", ""Hiraike Y"", ""Holla R"", ""Hoseinzadeh M"", ""Hostiuc M"", ""Hostiuc S"", ""Hotwani P"", ""Htay MNN"", ""Hu Y"", ""Huang J"", ""Huang YS"", ""Hushmandi K"", ""Hussein D"", ""Hussein MA"", ""Hwang BF"", ""Ibitoye SE"", ""Ibrahim IA"", ""Ibrahim KS"", ""Ibrayeva A"", ""Ikiroma A"", ""Ikram J"", ""Ilesanmi OS"", ""Ilic IM"", ""Ilic MD"", ""Imam MT"", ""Imani M"", ""Imodoye SO"", ""Imoh LC"", ""Inbaraj LR"", ""Ionescu AI"", ""Ionescu RT"", ""Iqhrammullah M"", ""Irham LM"", ""Ishaqui AA"", ""Islek D"", ""Ismail NE"", ""Ismoldayev Y"", ""Isola G"", ""Iwagami M"", ""Iyer M"", ""Izquierdo-Condoy JSS"", ""Jacob J"", ""Jafari-Khounigh A"", ""Jahanshahi A"", ""Jahrami H"", ""Jakovljevic M"", ""Jamal A"", ""Jamali N"", ""Jamaluddin J"", ""James J"", ""Jamshidi M"", ""Jansen R"", ""Jarrahi E"", ""Javaid SS"", ""Jawaid T"", ""Jayasinghe YA"", ""Jebasingh FK"", ""Jemal M"", ""Jeong S"", ""Jeswani BM"", ""Ji Z"", ""Jibat NT"", ""Jin W"", ""Jokar M"", ""Joo T"", ""Joseph AP"", ""Joseph MA"", ""Joseph N"", ""Raj JVSJM"", ""Joshi K"", ""Joshua CE"", ""Jung SH"", ""Jürisson M"", ""K V"", ""Kadir DHH"", ""Kahe F"", ""Kakkar AK"", ""Kalani R"", ""Kalavani K"", ""Kalra S"", ""Kamenova S"", ""Kamorudeen RT"", ""Kamyshnyi O"", ""Kanaan SF"", ""Kanmodi KK"", ""Kansal S"", ""Kantar RS"", ""Kapoor N"", ""Kar D"", ""Karajizadeh M"", ""Karakasis P"", ""Karasneh RA"", ""Karimi A"", ""Karimi Behnagh A"", ""Karun S"", ""Kashoo FZ"", ""Kashyap MK"", ""Kausar MA"", ""Kazemian S"", ""Kebede YT"", ""Kesse-Guyot E"", ""Khademi R"", ""Khader YS"", ""Khajuria H"", ""Khaleel A"", ""Khalid N"", ""Khalid S"", ""Khalil AA"", ""Khalili A"", ""Khalili P"", ""Khan A"", ""Khan M"", ""Khan MAS"", ""Khan MI"", ""Khan MAB"", ""Khan MH"", ""Khan S"", ""Khan S"", ""Khan YS"", ""Khasbage SU"", ""Khatatbeh MM"", ""Kheirallah KA"", ""Khoshvaght S"", ""Khosla P"", ""Khosravi S"", ""Kim HJ"", ""Kim K"", ""Kimokoti RW"", ""Kisa A"", ""Kishore L"", ""Kivimäki M"", ""Kokkorakis M"", ""Kolahi AA"", ""Kompani F"", ""Kondybayeva A"", ""Korzh O"", ""Kostev K"", ""Koulmane Laxminarayana SL"", ""Krishan K"", ""Kua CH"", ""Kuddus M"", ""Kulimbet M"", ""Kulkarni V"", ""Kumar C"", ""Kumar D"", ""Kumar GA"", ""Kumar J"", ""Kumar L"", ""Kumar N"", ""Kumar SK"", ""Kundu A"", ""Kundu S"", ""Kunutsor SK"", ""Kurniasari MD"", ""Kurpad KP"", ""Kusuma D"", ""Kytö V"", ""Lahariya C"", ""Lai DTC"", ""Lai H"", ""Lajunen T"", ""Lakanova B"", ""Lallukka T"", ""Lantos T"", ""Larebo YM"", ""Larsson AO"", ""Lasrado S"", ""Le DT"", ""Le TTT"", ""Le T"", ""Le TTB"", ""Ledda C"", ""Lee H"", ""Lee H"", ""Lee SW"", ""Lee SV"", ""Lee SW"", ""Lee WC"", ""Leivaditis V"", ""Lema GK"", ""Lemma DA"", ""Lenjisa J"", ""Lewis MS"", ""Li C"", ""Li MC"", ""Li Q"", ""Li S"", ""Li X"", ""Li Y"", ""Lim LL"", ""Lindholm D"", ""Liu H"", ""Liu X"", ""Liu X"", ""Liu Y"", ""Livingstone KM"", ""Llanaj E"", ""Lodhi MS"", ""Lokunarangoda NC"", ""López-Gil JF"", ""Lorkowski S"", ""Lucchetti G"", ""Lui PPY"", ""Luo P"", ""Lv L"", ""Lytvyak E"", ""M Amin HI"", ""Ma KS"", ""Mabrok M"", ""Machoy-Rakoczy M"", ""Madinehzad SA"", ""Maffia P"", ""Magaña Gómez JA"", ""Mahalleh M"", ""Mahmood NH"", ""Malik AA"", ""Malik MZ"", ""Malik T"", ""Malta DC"", ""Mamand DR"", ""Maniya MT"", ""Mannethodi K"", ""Mansoor F"", ""Mansourian M"", ""Manzoor S"", ""Maqsood K"", ""Marateb HR"", ""Marghani BH"", ""Marino M"", ""Martinez-Piedra R"", ""Martini D"", ""Martini S"", ""Martorell M"", ""März W"", ""Marzouk S"", ""Masi S"", ""Masrouri S"", ""Mathur N"", ""Matozinhos FP"", ""Mattiello R"", ""Maude RJ"", ""Mavrovounis G"", ""McPhail SM"", ""Mehto S"", ""Meles HN"", ""Mendoza W"", ""Menezes GA"", ""Menezes RG"", ""Mengistie EA"", ""Menon TP"", ""Mensah GA"", ""Merlino G"", ""Mestrovic T"", ""Mettananda CDK"", ""Mettananda S"", ""Metwally MMM"", ""Miao Jonasson J"", ""Mikrajab MAN"", ""Minhas AMK"", ""Mirrakhimov EM"", ""Mitra S"", ""Mitra T"", ""Mittal M"", ""Modi D"", ""Mohamed MG"", ""Mohamed NS"", ""Mohamed Ahmed KAH"", ""Mohammad AM"", ""Mohammad T"", ""Mohammadi A"", ""Mohammadi M"", ""Mohammadi S"", ""Mohammadian-Hafshejani A"", ""Mohammed O"", ""Mohan S"", ""Mohsen Y"", ""Molla TS"", ""Molokhia M"", ""Monazzami A"", ""Moni MA"", ""Montazeri Namin S"", ""Moodi Ghalibaf A"", ""Morovvati M"", ""Mosaddeghi Heris R"", ""Motappa R"", ""Mousavi SA"", ""Mousavi Kiasary SMS"", ""Mozafar M"", ""Mozahheb Yousefi K"", ""Mubarik S"", ""Muhammad JS"", ""Munkhsaikhan Y"", ""Munshi A"", ""Musa S"", ""Muthu S"", ""Mwita JC"", ""Myung W"", ""Nabipoorashrafi S"", ""Nagarajan AJ"", ""Naik GR"", ""Naik H"", ""Nainu F"", ""Nargus S"", ""Nartey Y"", ""Nasrollahizadeh A"", ""Nassar M"", ""Natto ZS"", ""Nauman J"", ""Naureen Z"", ""Navaratna SNK"", ""Nawaiseh HK"", ""Nayak BP"", ""Nayak VC"", ""Nazari M"", ""Ndakotsu AK"", ""Nega AT"", ""Nega MH"", ""Negash AA"", ""Negoi I"", ""Nejad Shahrokh Abadi R"", ""Nematollahi MH"", ""Nguyen CD"", ""Nguyen CT"", ""Nguyen HTH"", ""Nguyen NP"", ""Nguyen PT"", ""Nguyen VT"", ""Niazi RK"", ""Nieddu L"", ""Nketia R"", ""Nomura S"", ""Noreen M"", ""Nawsherwan"", ""Noubiap JJ"", ""Nri-Ezedi CA"", ""Ntsekhe M"", ""Nugen F"", ""Nur A"", ""Oancea B"", ""Odat RM"", ""Oddi FM"", ""Odediji SA"", ""Ogunmodede OS"", ""Oh IH"", ""Ojedoyin OO"", ""Ojo OA"", ""Okati-Aliabad H"", ""Okekunle AP"", ""Okonji OC"", ""Oliveira GMM"", ""Olorukooba AA"", ""Ong QC"", ""Ordak M"", ""Orru H"", ""Orscelik A"", ""Ortiz A"", ""Ortiz-Prado E"", ""Osborne A"", ""Osei GN"", ""Ostrominski JW"", ""Osuagwu UL"", ""Oumer A"", ""Ouyahia A"", ""Owolabi MO"", ""Oyebola K"", ""Ozsahin I"", ""Padukudru Anand M"", ""Padron-Monedero A"", ""Padubidri JR"", ""Palicz T"", ""Panda SK"", ""Pandi-Perumal SR"", ""Panos GD"", ""Papa MV"", ""Papadimopoulos I"", ""Pardhan S"", ""Parija PP"", ""Parikh RR"", ""Pascucci E"", ""Pasovic M"", ""Passera R"", ""Patel KN"", ""Patel M"", ""Patel NN"", ""Patel NR"", ""Patel S"", ""Patil A"", ""Patil S"", ""Patoulias D"", ""Pattnaik S"", ""Pazoki Toroudi H"", ""Pekarcikova J"", ""Peprah P"", ""Pereira G"", ""Perico N"", ""Perna S"", ""Petermann-Rocha F"", ""Pirera E"", ""Pirnejad H"", ""Plotnikov E"", ""Poddighe D"", ""Poluru R"", ""Porntaveetus T"", ""Pradhan PMS"", ""Prasad M"", ""Prashant A"", ""Prates EJS"", ""Pugliese NR"", ""Puvvula J"", ""Qi X"", ""Qiu JY"", ""Qureshi A"", ""Radhakrishnan V"", ""Raghav P"", ""Raghav YSR"", ""Raghuveer P"", ""Rahamon SK"", ""Rahim F"", ""Rahim HM"", ""Rahimi S"", ""Rahman FM"", ""Rahman MM"", ""Rahman MHU"", ""Rahman M"", ""Rahman MA"", ""Raj JP"", ""Raja A"", ""Rajendran J"", ""Rajput P"", ""Ramadan MM"", ""Ramasamy C"", ""Ramasamy SK"", ""Rao AG"", ""Rao M"", ""Rao SJ"", ""Rashedi V"", ""Rasouli-Saravani A"", ""Rath S"", ""Rathi I"", ""Rathish D"", ""Rauniyar SK"", ""Rawaf DL"", ""Rawaf S"", ""Rawassizadeh R"", ""Ray A"", ""Reddy MMRK"", ""Redwan EM"", ""Rehman NU"", ""Remuzzi G"", ""Rezaei M"", ""Rezaei N"", ""Rezaeian M"", ""Rodriguez JAB"", ""Roever L"", ""Romadlon DS"", ""Romoli M"", ""Rony MKK"", ""Ross AGP"", ""Roy S"", ""Roy S"", ""Rubeshkumar P"", ""Russo M"", ""Rwegerera GM"", ""Saad AMA"", ""Saber-Ayad MM"", ""Sabet CJ"", ""Sadarangani KP"", ""Sadat Rafiei SK"", ""Saddique MN"", ""Sadee BA"", ""Sadeghi E"", ""Sadeghi E"", ""Sadeghi M"", ""Sadek B"", ""Sadek M"", ""Sadr H"", ""Saeb MR"", ""Saeed M"", ""Saeed U"", ""Saeedi M"", ""Safiullah M"", ""Saghazadeh A"", ""Sagoe D"", ""Sah AK"", ""Sharif-Askari FS"", ""Sahebkar A"", ""Sajadi SM"", ""Sajid MR"", ""Saki M"", ""Sakshaug JW"", ""Salami AA"", ""Saleem RSZ"", ""Saleh MA"", ""Salehi M"", ""Salihu AT"", ""Salimi S"", ""Samargandy S"", ""Samodra YL"", ""Samy AM"", ""Saravanan A"", ""Sarfo JO"", ""Sarmadi M"", ""Sarode GS"", ""Sarode SC"", ""Sarrafzadegan N"", ""Sassano M"", ""Sathian B"", ""Sathya Narayanan MK"", ""Savabi Far M"", ""Schlaich MP"", ""Schuermans A"", ""Schwarz G"", ""Sejben A"", ""Selvaraj S"", ""Semreen MH"", ""Senol YC"", ""Serban D"", ""Sessa F"", ""Sethi Y"", ""Setiawan CH"", ""Sewor C"", ""Seylani A"", ""Shahid S"", ""Shahini E"", ""Shahrahmani F"", ""Shahwan MJ"", ""Sham S"", ""Shamim MA"", ""Shamsi A"", ""Shan D"", ""Shanawaz M"", ""Shannawaz M"", ""Sharif N"", ""Sharifan A"", ""Sharma BK"", ""Sharma B"", ""Sharma K"", ""Sharma M"", ""Sharma RK"", ""Sharma U"", ""Sharma V"", ""Shastry S"", ""Shehzadi S"", ""Sheidaei A"", ""Shenoy RR"", ""Shetty M"", ""Shetty PH"", ""Shi F"", ""Shi HZ"", ""Shi Y"", ""Shimels T"", ""Shiri R"", ""Shittu A"", ""Shiue I"", ""Shoaib A"", ""Shool S"", ""Shorofi SA"", ""Shrestha S"", ""Shuval K"", ""Sia CH"", ""Siddig EE"", ""Siddiqi AK"", ""Siddiqua A"", ""Silva DAS"", ""Silva LMLR"", ""Simkhada PP"", ""Singh A"", ""Singh B"", ""Singh H"", ""Singh H"", ""Singh JA"", ""Singh L"", ""Singh P"", ""Singh PS"", ""Singh P"", ""Singh S"", ""Singh SK"", ""Singh S"", ""Singh V"", ""Sinha MK"", ""Sinha R"", ""Skryabin VY"", ""Sokhal BS"", ""Sood P"", ""Soraneh S"", ""Sorensen RJD"", ""Sorrentino M"", ""Spartalis M"", ""Srivastav P"", ""Stachteas P"", ""Stanikzai MH"", ""Starodubova AV"", ""Straube S"", ""Stubbs P"", ""Su CY"", ""Subramaniyan V"", ""Suhag A"", ""Sulaieva O"", ""Sulaiman SK"", ""Suleiman Odidi M"", ""Sulistiyorini D"", ""Sun J"", ""Sun Z"", ""Swain CK"", ""Szarpak L"", ""Ty SS"", ""Tabaee Damavandi P"", ""Tabarés-Seisdedos R"", ""Tabatabaei SM"", ""Tabatabaeizadeh SA"", ""Tabatabai S"", ""Tabche C"", ""Tadele A"", ""Tagiisuran B"", ""Taha Osman Ali E"", ""Taheri Soodejani M"", ""Taiba J"", ""Tajabadi S"", ""Talic S"", ""Talukder A"", ""Tamehri Zadeh SS"", ""Tamiru Adugna D"", ""Tampa M"", ""Tan J"", ""Tanabayeva D"", ""Tanashat M"", ""Tang J"", ""Tantisattamo E"", ""Tariku MK"", ""Tariq S"", ""Tavangar SM"", ""Tedla MG"", ""Temsah R"", ""Teramoto M"", ""Tesfamariam WB"", ""Tesfu AA"", ""Tewari J"", ""Thakar V"", ""Thangavelu L"", ""Tharwat I"", ""Tharwat S"", ""Thienemann F"", ""Thiruvengadam M"", ""Thomas NK"", ""Ticoalu JHV"", ""Tiruye TY"", ""Tiwari K"", ""Tleshev M"", ""Tomo S"", ""Tonelli M"", ""Topor-Madry R"", ""Touvier M"", ""Tovani-Palone MR"", ""Tran AT"", ""Tran TH"", ""Tran Minh Duc N"", ""Trico D"", ""Tristan CD"", ""Tse G"", ""Tseriotis VS"", ""Tualeka AR"", ""Tye SC"", ""Udoakang AJ"", ""Ullah A"", ""Ullah R"", ""Ullah S"", ""Umair M"", ""Umar L"", ""Upadhya D"", ""Upadhyay E"", ""Usman JS"", ""Uzun Ozsahin D"", ""Uzunçibuk H"", ""Vaithinathan AG"", ""Vakili O"", ""Van den Eynde J"", ""Varghese J"", ""Vasankari TJ"", ""Vellingiri B"", ""Venketasubramanian N"", ""Verma AK"", ""Verma P"", ""Villalobos-Daniel VE"", ""Vlassov V"", ""Wan JY"", ""Wang C"", ""Wang N"", ""Wang Q"", ""Wang S"", ""Wang S"", ""Wang W"", ""Wang W"", ""Wang W"", ""Wang Y"", ""Wang Y"", ""Wang Z"", ""Wani TAA"", ""Waqar AB"", ""Wei MY"", ""Weintraub RG"", ""Wibowo YC"", ""Wicaksana AL"", ""Wickramasinghe DP"", ""Wickramasinghe ND"", ""Wilandika A"", ""Witts WK"", ""Wonde TE"", ""Wongsin U"", ""Wu P"", ""Xiao G"", ""Xie W"", ""Xu S"", ""Xu S"", ""Xu W"", ""Xu X"", ""Yadav V"", ""Yadegar A"", ""Yahoo S"", ""Yamagishi K"", ""Yang H"", ""Yano Y"", ""Yao H"", ""Yarahmadi A"", ""Yaribeygi H"", ""Yesuf SA"", ""Yin D"", ""Yismaw YE"", ""Yon DK"", ""Yonemoto N"", ""Yu C"", ""Yu EA"", ""Yu H"", ""Yu Y"", ""Yuan Q"", ""Yuzbashian E"", ""Zafar M"", ""Zaghampour M"", ""Zamagni G"", ""Zamora N"", ""Zanghì A"", ""Zargar S"", ""Zawiah M"", ""Zeariya MGM"", ""Zeru EM"", ""Zhang B"", ""Zhang CJP"", ""Zhang H"", ""Zhang JMF"", ""Zhang Y"", ""Zhang Z"", ""Zhanuzakov M"", ""Zhao Z"", ""Zheng MH"", ""Zhong A"", ""Zhong CC"", ""Zhou H"", ""Zhou J"", ""Zhou XD"", ""Zhu Z"", ""Zhumagaliuly A"", ""Zitoun OA"", ""Zoghi G"", ""Zoromba MA"", ""Zumla A"", ""Zyoud AH"", ""Zyoud SH"", ""Zyoud SH"", ""Hay SI"", ""Mokdad AH"", ""Murray CJL"", ""Roth GA""]",10.1001/jama.2026.8628,Razo C,JAMA,0098-7484,,JAMA,eng,Roth GA,[],,42525403,pmc-id: PMC13420188;embargo-date: 2027/01/29;,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42525403/,Global Burden of Elevated LDL-C: Findings From the Global Burden of Disease Study 2023,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Malhotra A"", ""Kumar AJ"", ""Mesarwi OA""]",10.1001/jama.2026.9551,Malhotra A,JAMA,0098-7484,,JAMA,eng,Mesarwi OA,[],,42525392,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42525392/,Sleep Health and Obesity,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]",[],10.1001/jama.2026.12150,,JAMA,0098-7484,,JAMA,eng,,[],e2612150,42507466,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42507466/,Multidomain Intervention for Growth in Term Small-for-Gestational-Age Infants: Research Summary,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Bruzelius E"", ""Bandoli G"", ""Martins SS""]",10.1001/jama.2026.11864,Bruzelius E,JAMA,0098-7484,,JAMA,eng,Martins SS,[],,42507429,pmc-id: PMC13409117;embargo-date: 2027/01/27;,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42507429/,Trends in Alcohol Consumption During Pregnancy in the US,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Yousafzai AK""]",10.1001/jama.2026.13846,Yousafzai AK,JAMA,0098-7484,,JAMA,eng,Yousafzai AK,[],,42507426,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42507426/,Nurturing Care for Term Small-for-Gestational-Age Infants,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Tejpal A"", ""Sklar MC""]",10.1001/jama.2026.10581,Tejpal A,JAMA,0098-7484,,JAMA,eng,Sklar MC,[],,42507396,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42507396/,Restrictive vs Liberal Physical Restraint Use,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Sonneville R"", ""Cornic R"", ""Bouadma L""]",10.1001/jama.2026.10587,Sonneville R,JAMA,0098-7484,,JAMA,eng,Bouadma L,[],,42507395,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42507395/,Restrictive vs Liberal Physical Restraint Use-Reply,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
"Small-for-gestational-age (SGA) infants face elevated risk of undernutrition and developmental delays. Multidomain interventions may be needed to promote growth and neurodevelopment. To evaluate the effect of an integrated intervention package on growth and neurodevelopment in term SGA infants. Individually randomized clinical trial conducted in low-resource neighborhoods of South Delhi, India. Term SGA infants were enrolled within 14 days of birth; 1300 infants were randomized and followed up to 12 months of age. Recruitment occurred from January 14, 2023, until July 31, 2024, with follow-up completed on August 6, 2025. Outcome assessors were blinded to participant allocation. Infants were randomized in a 1:1 ratio to receive either an integrated intervention package including health, nutrition, early child stimulation, and psychosocial support (n = 647) or usual care through government programs (n = 653). The primary outcomes were weight and weight-for-age z score at 12 months. Secondary outcomes included linear growth, neurodevelopment (assessed using the Bayley Scales of Infant and Toddler Development, Third Edition), anemia, and mortality. At 12 months, 1261 infants (97%) (mean age, 6 days; 48.1% male) had completed follow-up. The mean weight was 8.0 kg (SD, 0.9 kg) in the intervention group vs 7.8 kg (SD, 0.9 kg) in the usual care group (mean difference, 0.22 kg [95% CI, 0.11-0.32 kg]). The mean weight-for-age z score was -1.3 (SD, 0.9) vs -1.6 (SD, 1.0), respectively (mean difference, 0.24 [95% CI, 0.14-0.35]). The intervention group had a lower prevalence of underweight (23.9% vs 32.6%; risk difference, -8.75 [95% CI, -13.70 to -3.80] percentage points), stunting (20.1% vs 27.2%; risk difference, -7.17 [95% CI, -11.85 to -2.49] percentage points), wasting (13.9% vs 19.4%; risk difference, -5.52 [95% CI, -9.63 to -1.41] percentage points), and anemia (34.0% vs 72.5%; risk difference, -38.49 [95% CI, -44.36 to -32.61] percentage points) and higher cognitive scores (mean difference, 1.73 [95% CI, 0.32-3.14]), language scores (mean difference, 2.74 [95% CI, 1.51-3.98]), and motor composite scores (mean difference, 2.32 [95% CI, 1.25-3.38]). Nine children in the usual care group and 5 in the intervention group died. Among term SGA infants, an integrated intervention improved weight and weight-for-age z scores at 12 months. Clinical Trials Registry-India Identifier: CTRI/2021/11/037881.","[""Journal Article""]","[""Chowdhury R"", ""Manapurath R"", ""Upadhyay RP"", ""Sandøy IF"", ""Shaikh S"", ""Chellani H"", ""Jain A"", ""Dhabhai N"", ""Sapra S"", ""Khan A"", ""Choudhary TS"", ""Bhatia K"", ""Martines J"", ""Bhandari N"", ""Strand TA"", ""Taneja S"", ""Small Babies Trial Study Group""]",10.1001/jama.2026.12117,Chowdhury R,JAMA,0098-7484,,JAMA,eng,Taneja S,[],,42507387,pmc-id: PMC13409123;embargo-date: 2027/01/27;,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42507387/,Multidomain Intervention for Growth in Term Small-for-Gestational-Age Infants: A Randomized Clinical Trial,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Chen S"", ""Liu J"", ""Ma Y""]",10.1001/jama.2026.10584,Chen S,JAMA,0098-7484,,JAMA,eng,Ma Y,[],,42507385,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42507385/,Restrictive vs Liberal Physical Restraint Use,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Rosenthal DI"", ""Verghese A""]",10.1001/jama.2026.13582,Rosenthal DI,JAMA,0098-7484,,JAMA,eng,Verghese A,[],,42507375,,2026 Jul 27,2026,https://pubmed.ncbi.nlm.nih.gov/42507375/,The iPatient Meets the iDoctor,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Anderer S""]",10.1001/jama.2026.9488,Anderer S,JAMA,0098-7484,,JAMA,eng,Anderer S,[],,42496997,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42496997/,FDA Approves Gene Therapy for Younger Children With Sickle Cell Disease,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Anderer S""]",10.1001/jama.2026.9490,Anderer S,JAMA,0098-7484,,JAMA,eng,Anderer S,[],,42496996,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42496996/,WHO Releases Global Status Report on Cancer,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Anderer S""]",10.1001/jama.2026.9486,Anderer S,JAMA,0098-7484,,JAMA,eng,Anderer S,[],,42496990,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42496990/,Flu Vaccine Remains Highly Effective Against Pediatric Mortality,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Anderer S""]",10.1001/jama.2026.14333,Anderer S,JAMA,0098-7484,,JAMA,eng,Anderer S,[],,42496988,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42496988/,"A Decade After the CDC's Opioid Prescribing Guidelines, Have Clinicians Struck the Right Balance?",,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Schweitzer K""]",10.1001/jama.2026.13202,Schweitzer K,JAMA,0098-7484,,JAMA,eng,Schweitzer K,[],,42496987,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42496987/,Wild West or Gold Rush: How Long-Neglected Menopause Care Has Spawned a Booming Marketplace,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Anderer S""]",10.1001/jama.2026.9485,Anderer S,JAMA,0098-7484,,JAMA,eng,Anderer S,[],,42496984,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42496984/,US Death Rates Reach All-Time Low in 2025,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Anderer S""]",10.1001/jama.2026.9489,Anderer S,JAMA,0098-7484,,JAMA,eng,Anderer S,[],,42496982,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42496982/,"Metals Found in Tampons Within Margin of Safety, FDA Study Finds",,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
,"[""Journal Article""]","[""Anderer S""]",10.1001/jama.2026.9487,Anderer S,JAMA,0098-7484,,JAMA,eng,Anderer S,[],,42496971,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42496971/,GLP-1 Medications May Improve Health in People With PAD and Diabetes,,OBhgaBZChJvelMzWc,ffyRJJckpz4BLZfY5
"Over recent decades, non-pharmacological pain management approaches have gained increasing importance in pediatric care, as they can be applied with low cost and minimal time investment while significantly contributing to the improvement of care quality. The aim of this review article is to provide an overview of non-pharmacological options for procedural pain management based on the literature, and to present the dissemination of this approach in Hungary through the support of a child-centered, trust-based healthcare model. This paper presents a narrative review of the key findings of international literature on non-pharmacological management of procedural pain. In addition, it describes the practical implementation of an interdisciplinary non-pharmacological pain management program based on the principles of the Comfort Promise, which has been operating since 2021 at the Bethesda Children's Hospital of the Hungarian Reformed Church. The article outlines the steps of implementation, the tools and techniques applied, and summarizes clinical experiences. Methods shown to be effective in the literature - such as distraction, breathing exercises, comfort positioning, breastfeeding, and the use of various sensory tools - are, in line with international evidence, also supported by clinical experience as contributing to the reduction of children's anxiety, increasing parental satisfaction, and improving the quality of care. Experience suggests that integrating non-pharmacological methods into everyday clinical practice does not require significant additional resources; however, it does necessitate a shift in mindset and a structured implementation process. Interdisciplinary collaboration, staff training, the establishment of a volunteer network, and the active involvement of parents and children are key factors for sustainable implementation. Based on current experience, the combined application of this approach and its methods has proven to be effective. According to international literature, anxiety-reducing interventions - including parental presence, appropriate information provision, distraction, and relaxation techniques - contribute to the alleviation of procedural pain through neural mechanisms influencing pain perception, which is also supported by the institutional experience presented. Orv Hetil. 2026; 167(31): 1215-1223.","[""Journal Article"", ""Review"", ""English Abstract""]","[""Vargay A"", ""Bencsik AS"", ""Szabó V"", ""Székely IZ"", ""Károlyi L"", ""Forgács-Kristóf K"", ""Perczel K"", ""Gyimesi-Szikszai A"", ""Major J""]",10.1556/650.2026.33576,Vargay A,Orvosi hetilap,0030-6002,31,Orv Hetil,hun,Major J,"[""Humans"", ""Hungary"", ""Pain Management"", ""Child"", ""Hospitals, Pediatric"", ""Procedural Pain"", ""Pediatrics"", ""Anxiety""]",1215-1223,42543014,,2026 Aug 2,2026,https://pubmed.ncbi.nlm.nih.gov/42543014/,[Non-pharmacological pain management methods in pediatrics and their application at the Bethesda Children's Hospital of the Hungarian Reformed Church],167,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"The aim of this study was to develop a conceptual framework for understanding surgeon grief in pediatric neurosurgery, examine its intersection with moral distress and professional burnout, and review evidence for institutional interventions supporting physician well-being after patient death. The author conducted a narrative review of English-language literature on physician grief, moral distress, and burnout in surgical specialties, with attention to pediatric practice. PubMed, PsycINFO, and CINAHL were searched for publications from January 2000 to December 2024. The initial search yielded 847 articles; after screening, 67 met inclusion criteria for narrative synthesis. An illustrative case of a neonate with an unresectable brain tumor contextualizes the framework. Five dimensions of surgeon grief specific to therapeutic futility were identified: grief of unexpressed mastery (inability to deploy technical expertise), grief of identity disruption (challenge to action-oriented surgical identity), grief of anticipatory knowledge (burden of prognostic awareness), grief of perceived failure (internalization of patient death as personal defeat), and disenfranchised grief (grief not socially recognized within surgical culture). These dimensions interact bidirectionally with moral distress to produce cumulative emotional burden contributing to burnout and career attrition. Evidence supports institutional interventions that include structured debriefing, peer support programs, Schwartz Rounds, and early palliative care integration. Surgeon grief represents a significant but understudied occupational hazard in pediatric neurosurgery. The proposed 5-dimension framework provides a conceptual foundation for research, instrument development, and targeted interventions. Recognizing that providing a good death is a form of surgical success and that surgeon grief reflects preserved humanity is essential for workforce sustainability.","[""Journal Article"", ""Review""]","[""Udayakumaran S""]",10.3171/2026.5.FOCUS26127,Udayakumaran S,Neurosurgical focus,1092-0684,2,Neurosurg Focus,eng,Udayakumaran S,"[""Humans"", ""Grief"", ""Infant, Newborn"", ""Neurosurgeons"", ""Burnout, Professional"", ""Neurosurgery"", ""Pediatrics""]",E15,42541803,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42541803/,When newborns die: walking the extra mile. Surgeon grief in pediatric neurosurgery: qualitative synthesis and framework development,61,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Pediatric neuro-oncology exposes healthcare professionals to high technical complexity, ethical uncertainty, and sustained emotional stress. Professional grief, moral distress, and second victim experiences are increasingly recognized in pediatric oncology, yet they remain insufficiently characterized in pediatric neuro-oncological neurosurgery. The authors conducted a cross-sectional, anonymous survey among healthcare professionals involved in pediatric neuro-oncology at a tertiary children's hospital. A 27-item questionnaire assessed 5 domains: professional grief, moral distress, second victim/emotional impact, neuro-oncology-specific emotional burden, and organizational support. The Pediatric Neuro-Oncology Professional Grief Score (PNOP-GS; range 27-135) was calculated as the sum of all items. Descriptive statistics, internal consistency analyses, and exploratory comparisons by training and exposure were performed. Forty-one complete responses were analyzed. Participants included nurses (46.3%), physicians (41.5%), and psychologists (9.8%), with 87.8% reporting exposure to children with advanced or terminal brain tumors in the preceding 12 months. The mean PNOP-GS was 91.2 ± 18.2, corresponding to a mean item score of 3.38 ± 0.67. Neuro-oncology-specific emotional burden (3.57 ± 0.96) and professional grief (3.42 ± 0.88) were the highest-scoring domains, while perceived organizational support was low (1.83 ± 0.78). Prior training in pediatric palliative care, communication of poor prognosis, or grief management was associated with significantly lower emotional burden (p = 0.002). Greater exposure to terminal cases correlated with higher PNOP-GSs (p = 0.049). Emotional burden did not differ significantly across professional roles. Internal consistency of the overall instrument was good (Cronbach's α = 0.82). Healthcare professionals in pediatric neuro-oncology experience substantial professional grief and emotional burden extending beyond patient death to ethical complexity and neurological morbidity. Training and organizational support represent modifiable protective factors and should be systematically integrated into pediatric neuro-oncological practice.","[""Journal Article""]","[""Vitulli F"", ""Micucci M"", ""Spennato P"", ""Ferrara R"", ""Dolcini A"", ""Monorchio P"", ""Cinalli G"", ""Quaglietta L""]",10.3171/2026.5.FOCUS26162,Vitulli F,Neurosurgical focus,1092-0684,2,Neurosurg Focus,eng,Quaglietta L,"[""Humans"", ""Grief"", ""Cross-Sectional Studies"", ""Male"", ""Ethical Dilemmas"", ""Female"", ""Burnout, Professional"", ""Surveys and Questionnaires"", ""Adult"", ""Neurosurgery"", ""Child"", ""Psychologists"", ""Brain Neoplasms"", ""Pediatrics""]",E14,42541797,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42541797/,Beyond burnout: professional grief and moral distress in pediatric neuro-oncological neurosurgery,61,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"This narrative review synthesizes recent technological and organizational developments in pediatric telemedicine, maps their principal clinical applications, and critically discusses implementation, safety, equity, and future priorities. This narrative review used a transparent, non-systematic literature-search approach in PubMed/MEDLINE, Scopus, and Google Scholar, considering publications available through April 2026. Searches were intended to identify and contextualize relevant literature across pediatric settings rather than to provide an exhaustive, reproducible systematic evidence synthesis. No formal risk-of-bias assessment, meta-analysis, or certainty-of-evidence grading was undertaken; therefore, findings are interpreted cautiously and according to the maturity and consistency of the available evidence. Evidence suggests that telemedicine can support follow-up, access to specialist care, and family engagement in several pediatric chronic-care pathways, particularly diabetes and asthma. However, the evidence base is heterogeneous across specialties, frequently relies on observational or implementation studies, and is less mature for acute assessment, neonatal and rehabilitation uses, wearables, and AI-enabled tools. Telemedicine should be considered a complementary component of pediatric healthcare rather than a replacement for in-person assessment. Hybrid models may support accessibility, continuity, and sustainability when embedded in structured, patient-centered, equitable, and clinically appropriate pathways. • Telemedicine expanded rapidly in pediatrics during the COVID-19 pandemic and is now used across many specialties. • It can improve access, continuity of care, remote monitoring, and family engagement, especially in chronic and complex conditions. • This review summarizes recent technological and organizational innovations, including wearables, mHealth, EHR integration, AI, and hybrid care models. • It highlights current limits and future requirements for safe, equitable, and sustainable integration into routine pediatric care.","[""Journal Article"", ""Review""]","[""Zuccotti G"", ""Scavone IAM"", ""Cordaro E"", ""Rossi V"", ""Calcaterra V""]",10.1007/s00431-026-07262-1,Zuccotti G,European journal of pediatrics,0340-6199,8,Eur J Pediatr,eng,Calcaterra V,"[""Humans"", ""Telemedicine"", ""Pediatrics"", ""Child"", ""Digital Health""]",,42541600,pmc-id: PMC13428713;,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42541600/,"Telemedicine in pediatrics: a critical narrative review of innovations, limitations, and future priorities",185,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Background: Children with cancer in low- and middle-income countries (LMICs) experience disproportionately high mortality. Nutritional care improves treatment tolerance and survival, yet access to trained nutrition professionals remains limited. The International Initiative for Pediatrics and Nutrition (IIPAN) was established to strengthen hospital-based clinical nutrition services through capacity-building, education, and mentorship. Objectives: To evaluate the IIPAN global clinical nutrition capacity-building program across hospitals in LMICs. Methods: A monitoring and evaluation framework was implemented across 16 hospitals in 11 countries (February 2024-June 2025). Monthly indicators captured patient characteristics, nutritional status, delivery of nutrition interventions, and dietary diversity. Nutritional status was classified using body mass index (BMI)-for-age, mid-upper arm circumference (MUAC), and height-for-age z-scores based on World Health Organization standards. Findings: Across all sites, 29,295 clinical visits were reported. Most consultations occurred in inpatient settings (79.9%) and were follow-up assessments (85.1%). Among patients, 52.5% had solid tumors and 39.6% had hematologic malignancies. Based on BMI-for-age, 10.3% were classified with severe acute malnutrition (SAM) and 13.5% with moderate acute malnutrition (MAM). Height-for-age analysis indicated that 27.2% were stunted. Nearly all hospitalized patients (95.8%) received a nutrition assessment within 24 hours of admission, and 96.0% received individualized or group nutrition education. Therapeutic foods or formulas were provided in 42.8% of consultations, while advanced nutrition therapy was administered in 3.5%. The prevalence of acute malnutrition decreased significantly between initial and follow-up assessments (38.9% to 25.2%; P < 0.001). In sites with food kitchens, provision of therapeutic nutrition was substantially higher than program-wide for both children consuming ≤50% of estimated needs (87.4% vs 55%) and for children with SAM (99.1% vs 86%). Conclusions: The IIPAN model demonstrates that integrated, hospital-based nutrition care led by trained nutritionists can reduce acute malnutrition and improve access to essential nutrition services in LMICs.","[""Journal Article""]","[""Leonardo S"", ""Antillón F"", ""Ayalew M"", ""de Los Angeles Carrillo M"", ""Espinoza DM"", ""Chapagain RH"", ""Damasco-Avila E"", ""Dawit T"", ""Domínguez TA"", ""Dhungana J"", ""Ecleo SY"", ""Ferman S"", ""Fu L"", ""Gassant P"", ""Hailu D"", ""Hailu T"", ""Henry A"", ""Kambugu J"", ""Kouya F"", ""Majaliwa E"", ""Muliro B"", ""Murra M"", ""Nkya E"", ""Nzamu I"", ""Oliveira W"", ""Pedro M"", ""Sapkota S"", ""Scanlan T"", ""Semujju JM"", ""de Macedo Soares CF"", ""Sui TH"", ""Viani K"", ""Walters M"", ""Yemane E"", ""Yitbarek T"", ""Sagastizado SZ"", ""Ladas EJ""]",10.5334/aogh.5194,Leonardo S,Annals of global health,2214-9996,1,Ann Glob Health,eng,Ladas EJ,"[""Humans"", ""Neoplasms"", ""Resource-Limited Settings"", ""Child"", ""Child, Preschool"", ""Nutritional Status"", ""Developing Countries"", ""Female"", ""Infant"", ""Male"", ""Malnutrition"", ""Program Evaluation"", ""Capacity Building"", ""Adolescent"", ""Pediatrics"", ""Child Nutrition Disorders""]",72,42540666,pmc-id: PMC13426452;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540666/,Evaluating a Global Clinical Nutrition Program for Pediatric Oncology in Resource-Limited Settings,92,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"In recent years, the Association of Pediatric Program Directors and American College of Graduate Medical Education surveys have highlighted challenges in pediatric residency, including burnout and suboptimal faculty-trainee relationships. Coaching has emerged as a promising strategy to support learner-centered professional development, but most medical faculty lack formal training in coaching. We developed a faculty coaching retreat to train a select set of faculty members who would then participate in a longitudinal pediatric residency coaching program. The retreat consisted of a 1-day (7.5-hour) training event including introductions to program structure, a keynote presentation on coaching mindset, and interactive small-group role-plays. We collected qualitative and quantitative data from faculty coaches before and after the retreat, measuring their ability to differentiate coaching versus advising interactions and to describe attributes of an effective coach. Quantitative data were compared using a Wilcoxon rank-sum test, and qualitative data were organized into themes. Eighteen faculty coaches participated in the coaching retreat. Faculty demonstrated improvements in their ability to distinguish between coaching and advising, with a median score of 90% (interquartile range 70-92.5) to 100% (interquartile range 90-100) (P = .003) on the knowledge assessment. Comparing pre- to postretreat qualitative data, new themes emerged, including curiosity and a resident-driven approach, both key concepts emphasized during the retreat. This faculty coaching retreat increased participants' knowledge and understanding about what it means to be an effective pediatric residency coach, effectively setting the stage for initiation of a longitudinal residency coaching program.","[""Journal Article""]","[""Fashina O"", ""Thorvilson M"", ""Mavis S"", ""Thorn PM"", ""Pittock S"", ""Munger K"", ""McKone J"", ""Raevsky E"", ""Johnson KL""]",10.15766/mep_2374-8265.11624,Fashina O,MedEdPORTAL : the journal of teaching and learning resources,2374-8265,,MedEdPORTAL,eng,Johnson KL,"[""Mentoring"", ""Humans"", ""Internship and Residency"", ""Faculty, Medical"", ""Pediatrics"", ""Surveys and Questionnaires"", ""Education, Medical, Graduate""]",11624,42539593,pmc-id: PMC13423840;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42539593/,A Pediatric Resident Physician Coaching Program With Faculty Retreat Developed in Partnership With a Master Certified Coach,22,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Specialized outpatient palliative care (SOPC) provides home-based care for terminally ill patients and is associated with improved quality of life and prolonged survival. Due to its decentralized structure and growing demand, SOPC is a key target for digital transformation. Telehealth, mobile health, and AI offer considerable potential benefits but also present challenges, particularly with regard to user acceptance. Although both children and adults receive SOPC under the German statutory health insurance system, services differ in terms of patient characteristics, duration of care, and geographic coverage. Moreover, there is limited knowledge regarding the extent to which digital health applications are transferable across different areas of palliative care. This study assesses the extent to which needs and concerns regarding digitalization in SOPC for children are transferable to adult SOPC, using the PalliDoc Mobile app as a case example. Two adult SOPC teams using the PalliDoc Mobile app (a pediatric-origin mobile app) were surveyed between March 2022 and March 2025 using an embedded mixed methods design to assess digitalization needs and concerns. Therefore, a focus group study took place in the respective offices of the included teams. Twenty-five members from both teams, who were recruited via the personal network of the authors, participated, representing urban and rural care areas in Germany. Using an open-ended interview guide, the needs and concerns were first discussed with all participating members of each team. In a second step, the participants were allocated to profession-specific subgroups to further explore and prioritize the identified needs using a quantitative voting format. The focus group discussions were analyzed using qualitative content analysis, while the analysis of the prioritization votes was performed using descriptive statistics. The triangulation of qualitative and quantitative findings revealed a total of 13 needs within the examined care teams for adults, with functions focusing on voice control being the highest priority (n=8 positive votes and no negative votes for voice input; n=6 positive votes and no negative votes for voice output). Additionally, functions relating to digitization and organizational tasks were viewed as predominantly helpful. Unlike in pediatrics, telehealth functions like video contacts, telemetry, and electronic patient-reported outcome measures are neither used here now nor intended to be used in the future. The identified concerns predominantly addressed the potential risk of AI-assisted documentation (n=2 positive votes and n=7 negative votes) altering or distorting health care professionals' perception of information related to patients. Cross-setting telehealth applications may work, but they are no ""plug-and-play solution."" Needs and concerns in each setting should be addressed to guarantee customized services.","[""Journal Article""]","[""Hocher R"", ""Weyandt S"", ""Zimmermann J"", ""Fischer S"", ""Seibel K"", ""Becker G"", ""Nathrath M"", ""Voelker T"", ""Deckers M""]",10.2196/92048,Hocher R,JMIR formative research,2561-326X,,JMIR Form Res,eng,Deckers M,"[""Humans"", ""Germany"", ""Palliative Care"", ""Telemedicine"", ""Home Care Services"", ""Adult"", ""Male"", ""Focus Groups"", ""Female"", ""Mobile Applications"", ""Pediatrics"", ""Middle Aged"", ""Child"", ""Qualitative Research"", ""Health Personnel"", ""Digital Health"", ""Needs Assessment"", ""Surveys and Questionnaires""]",e92048,42536989,pmc-id: PMC13427069;,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536989/,Needs and Concerns Regarding a Pediatric Palliative Telehealth App for Use in Palliative Home Care for Adults Among Providers in Germany: Embedded Mixed Methods Study,10,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Aim: To analyze key aspects of the application of AI as a clinical mentor in telemedicine-based medical education, and to assess the related opportunities, challenges, and attitudes of pediatric students. Materials and Methods: A cross-sectional study was conducted to assess the level of digital competence of future pediatricians regarding telemedicine and AI. A total of 251 students from the Faculty of Pediatrics at Bogomolets National Medical University (BNMU) participated in the survey. Participants were aged 17 to 26 years, of whom 17.9% were male and 82.1% were female. The questionnaire included items on demographic characteristics, knowledge and use of telemedicine and AI tools, self-assessment of digital competence, and attitudes toward the integration of AI in healthcare. Data were analyzed using descriptive statistics and presented as relative frequencies (%). Results: The study assessed digital competence and the use of AI among 251 future pediatricians regarding telemedicine-based medical education. Survey results indicated active engagement with AI tools in educational and professional tasks (63.7% positive responses), moderate confidence in integrated digital devices (55.0%), and cautious self-assessment of clinical decision support systems (53.4%). These findings informed the development and revision of courses at BNMU, enhancing students' practical skills and digital competence. Conclusions: Future pediatricians actively engage with digital tools and AI, although confidence is higher in AI tasks than in integrated devices or clinical decision systems. The findings guided the development of updated courses to strengthen digital competence, practical skills, and critical evaluation of AI. Successful telemedicine implementation requires addressing data security, regulation, human-centred care, and digital inclusion to ensure safe, effective, and equitable healthcare.","[""Journal Article""]","[""Kucherenko II"", ""Vygovska OV"", ""Terentyuk VG"", ""Nataliia KS"", ""Shadrin VO"", ""Nizhehorodtsev VO"", ""Matukova DG""]",10.36740/WLek/222585,Kucherenko II,"Wiadomosci lekarskie (Warsaw, Poland : 1960)",0043-5147,6,Wiad Lek,eng,Matukova DG,"[""Humans"", ""Male"", ""Female"", ""Cross-Sectional Studies"", ""Telemedicine"", ""Adult"", ""Adolescent"", ""Young Adult"", ""Artificial Intelligence"", ""Education, Medical"", ""Surveys and Questionnaires"", ""Students, Medical"", ""Pediatrics"", ""Clinical Competence"", ""Digital Health""]",1292-1299,42536946,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536946/,Artificial intelligence as a clinical tutor in telemedicine: Opportunities and challenges in medical education,79,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Resident scheduling is a high-dimensional optimization problem with implications for workload, fatigue risk, and equity. Real-world evaluations of AI-based constraint-optimization in health care are limited. This study aimed to evaluate an AI-based constraint-optimization scheduler versus a legacy rule-based scheduler for pediatric residency night calls. This is a single-center retrospective before-after study at a 235-bed tertiary pediatric center. Twenty-four consecutive months of night-call rosters were analyzed: preimplementation (January to December 2024, legacy rule-based autoscheduler) and postimplementation (January to December 2025, AI-based constraint-programming scheduler combining a local-search metaheuristic solver with human-in-the-loop review). The analytic unit was the resident-month. Outcomes were workload distribution, threshold exceedances (>6 total and >2 weekend calls/month), undesirable sequences (consecutive weekend calls; call-rest-call; call-rest-call-rest-call), equity (mean absolute error from equal share [MAE-ES], root mean square error from equal share), publication lead time, as well as pre- and postsurvey experience. We analyzed 6519 shifts across 1530 resident-months (legacy: 803 resident-months/107 physicians; AI: 727/87; weekend share 28.8% [934/3246] vs 28.6% [935/3273]; service mix P=.99). Mean calls/resident-month did not decline (4.04 vs 4.50; P<.001), but within-period SD was approximately halved. Threshold exceedances fell from 133/803 (16.6%) to 28/727 (3.9%) for >6 calls per month (risk ratio [RR] 0.24, 95% CI 0.15-0.34) and 89/803 (11.1%) to 21/727 (2.9%) for >2 weekend calls (RR 0.27, 95% CI 0.16-0.40; both P<.001). Undesirable sequences declined: consecutive weekends 24.4→18.7/100 resident-months (RR 0.77; P=.02); call-rest-call 51.2→23.4 (RR 0.46); call-rest-call-rest-call 5.6→1.0 (RR 0.18; both P<.001). Equity improved overall and within every qualification stratum: MAE-ES -0.26 shifts (95% CI -0.28 to -0.23) and RMSE-ES -0.29 (95% CI -0.32 to -0.26); Senior, Advanced, and Novice strata were all P<.001 after Holm correction. Publication lead time more than doubled (10.7→21.2 d; Δ+10.5, Cohen d=4.78; Cliff δ=1.00; P<.001). Interrupted time-series confirmed immediate level shifts for >6-call exceedances (β=-8.88; P=.004), MAE-ES (β=-0.18; P<.001), call-rest-call (β=-13.17; P=.002), call-rest-call-rest-call (β=-2.35; P=.03), and >2 weekend exceedances (β=-7.32; P<.001), with stable postimplementation fairness slopes. Among survey respondents (n=47 pre; n=38 post), software satisfaction rose 6.77→8.71/10, perceived timeliness 3.28→4.61/5, perceived consecutive-night frequency 3.15→4.24, and perceived equity 2.98→3.61 (all P≤.006). An AI-based constraint-optimization scheduler was associated with significantly more equitable on-call workload across all qualification strata, large reductions in high-risk shift sequences and threshold exceedances, and a doubling of publication lead time, despite no reduction in mean per-physician burden once all physicians were retained. Multisite prospective replication is warranted before generalization.","[""Journal Article"", ""Comparative Study""]","[""Gilad D"", ""Farbstein-Aljanati T"", ""Kassif Lerner R"", ""Ashkenazi M"", ""Pessach IM""]",10.2196/88340,Gilad D,Journal of medical Internet research,1439-4456,,J Med Internet Res,eng,Pessach IM,"[""Retrospective Studies"", ""Internship and Residency"", ""Humans"", ""Pediatrics"", ""Workload"", ""Personnel Staffing and Scheduling"", ""Artificial Intelligence""]",e88340,42536508,pmc-id: PMC13426424;,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536508/,Evaluation of an AI-Based Constraint-Optimization Scheduler to Optimize On-Call Schedule Equity and Reduce Administrative Burden in a Pediatric Residency: Retrospective Comparative Study,28,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Perspectives of families from historically marginalized groups regarding pediatric oncology clinical trial participation are not well-represented in the literature. To describe clinician- and parent-perceived facilitators and barriers to clinical trial participation. This single-center cross-sectional study with an explanatory sequential mixed-methods design enrolled parents of Black and Hispanic children with cancer as well as pediatric oncology clinicians from a large pediatric cancer center in Boston, Massachusetts. Parent participants completed single-time point surveys, and a subset, purposively sampled based on self-identified race and ethnicity, language, and household material hardship (HMH; ie, food, housing, transportation, or utility insecurity), completed semistructured interviews from September to December 2021. Clinicians completed semistructured interviews from February to March 2022. Data were analyzed from April 2022 to October 2025. Key factors influencing clinical trial participation in pediatric oncology among parents from historically marginalized groups. Quantitative data were summarized descriptively. Interview transcripts were analyzed using thematic analysis and integrated along key domains. A total of 60 parents completed the questionnaire; self-identified race and ethnicity included 5 Hispanic Black (8%), 10 Hispanic White (17%), 21 Hispanic other (35%), 21 non-Hispanic Black (35%), and 3 non-Hispanic White (5%) parents; most were mothers (51 [85%]). Twenty parents participated in interviews. Fifteen clinicians (10 [67%] female participants; 10 [67%] with ≥10 years caring for children with cancer) were interviewed, including 12 (80%) attendings and 3 (20%) advanced practice practitioners; most identified as non-Hispanic White (14 [93%]). Most families experienced HMH (44 [73%]) and reported high trust in their oncology team (mean [SD] score, 4.63 [0.65] of 5.00). Qualitatively, parents and clinicians aligned in identifying altruism and trustworthiness as facilitators to trial participation, while the informed consent discussion, non-English language preference, trial materials, and study requirements were participation barriers. Unlike clinicians, parents did not identify HMH or the experimental nature of trials as significant barriers to participation. Parents identified the desire for representation as a facilitator to participation, and clinicians identified gatekeeping as a barrier. In this cross-sectional study of pediatric oncology families from historically marginalized groups and clinicians, clinician- and parent-perceived barriers identified opportunities to increase equitable trial participation. Next steps include standardization of trial eligibility screening and systematic HMH screening and support to reduce gatekeeping.","[""Journal Article""]","[""Umaretiya PJ"", ""Paul MA"", ""Valenzuela A"", ""Hawkins A"", ""Revette AC"", ""Nava-Coulter B"", ""Eche-Ugwu IJ"", ""Snaman JM"", ""Aziz-Bose R"", ""Kelly CA"", ""Nguyen G"", ""Pruitt SL"", ""Wolfe J"", ""Bona K""]",10.1001/jamanetworkopen.2026.26538,Umaretiya PJ,JAMA network open,2574-3805,7,JAMA Netw Open,eng,Bona K,"[""Humans"", ""Cross-Sectional Studies"", ""Female"", ""Male"", ""Child"", ""Clinical Trials as Topic"", ""Hispanic or Latino"", ""Neoplasms"", ""Parents"", ""Black or African American"", ""Boston"", ""Medical Oncology"", ""Adult"", ""Surveys and Questionnaires"", ""Pediatrics"", ""Patient Participation"", ""Adolescent"", ""Child, Preschool""]",e2626538,42536371,pmc-id: PMC13428278;,2026 Jul 1,2026,https://pubmed.ncbi.nlm.nih.gov/42536371/,Pediatric Oncology Clinical Trial Participation Among Families From Historically Marginalized Groups,9,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"To systematically review educational interventions for staff working on acute paediatric wards aimed at improving the care of children and young people (CYP) admitted for mental health support. We conducted a systematic search of PubMed, The Education Resources Information Centre, PsychInfo and Web of Science from 2000 to March 2026 using terms related to healthcare professionals, training/education, mental health and children/young people. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Interventions were classified using the Kirkpatrick model and the Behavioural Change Technique Taxonomy (BCT V.1) to identify mechanisms underpinning effective change. We found nine studies meeting inclusion criteria, across a range of teaching methodologies and settings. Most interventions were designed and applied for nurses. Overall quality of evidence was poor. Although no single intervention could be recommended, analysis identified potentially useful components tailored to different learner needs, mapped through the Kirkpatrick and BCT frameworks. A notable gap was a lack of codesign with CYP and carers with lived experience and the absence of strategies to engage ambivalent or reluctant learners who might not attend educational interventions voluntarily. Existing educational interventions contain elements that may support behavioural and practice change among staff caring for CYP with mental health needs. However, future research should prioritise high-quality, framework-based evaluations developed through codesign with CYP and carers. Interventions should also address how to engage learners who may be reluctant to participate in training for this area of clinical practice.","[""Journal Article"", ""Systematic Review""]","[""Sanwo O"", ""Rich A"", ""Pomfret I"", ""Downs J"", ""Davis S"", ""Dearden J"", ""Buchanan M"", ""Omer L"", ""Griffin A"", ""Hudson LD""]",10.1136/bmjpo-2026-004809,Sanwo O,BMJ paediatrics open,2399-9772,1,BMJ Paediatr Open,eng,Hudson LD,"[""Humans"", ""Child"", ""Adolescent"", ""Patient Care Team"", ""Health Personnel"", ""Mental Health"", ""Mental Disorders"", ""Pediatrics""]",,42532654,pmc-id: PMC13422820;,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42532654/,What works in educational interventions for teams caring for children and young people admitted to general acute paediatric wards for mental health? A systematic review,10,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Pediatric vascular surgical problems are rare and variable in presentation, thus making them challenging to characterize and treat. The diversity of patient conditions and size combined with variability in pediatric vascular surgical training leads to an ad hoc approach to these patients. With few published guidelines as well as a lack of robust research to support evidence-based assertions, pediatric vascular practices have been largely driven by anecdotal evidence and limited retrospective single-institution reviews. Collaborative data collection in vascular surgery is necessary to generate more robust data, improve understanding of nuances in pediatric vascular surgery, and establish standardized practices in the pediatric patient population. The aim of this review is to assess multicenter surgical registries and identify opportunities for similar entities in pediatric vascular surgery. LEVEL OF EVIDENCE: n/a.","[""Journal Article"", ""Review""]","[""Koh EY"", ""Wang SK"", ""DuBose JJ"", ""Lally P"", ""Harting MT"", ""Cox CS Jr"", ""Drucker NA""]",10.1016/j.jpedsurg.2025.162239,Koh EY,Journal of pediatric surgery,0022-3468,8,J Pediatr Surg,eng,Drucker NA,"[""Humans"", ""Vascular Surgical Procedures"", ""Registries"", ""Pediatrics"", ""Quality Improvement"", ""Databases, Factual"", ""Child""]",162239,42532610,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42532610/,Leveraging multicenter databases to improve care in pediatric vascular surgery,61,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"To analyse the association between organisational patient safety practices, including training in patient safety and clinical simulation, and safety culture and adverse event (AE) reporting in paediatric emergency departments. Observational analytical multicentre cross-sectional study. 19 paediatric emergency departments at different levels of healthcare. Healthcare professionals working in paediatric emergency departments. Not applicable PRIMARY AND SECONDARY OUTCOMES: Safety culture was analysed using the Hospital Survey on Patient Safety Culture, following the Agency for Healthcare Research and Quality methodology. Logistic regression analyses were performed. Organisational patient safety practices included the presence of patient safety specialists, leadership walkarounds, additional reporting systems and training in patient safety and clinical simulation. A total of 1176 professionals participated (response rate 63.8%). The presence of patient safety specialists was associated with more favourable scores in 'supervisor/manager expectations and actions', 'organisational learning' and 'teamwork' (p<0.001). Additional reporting systems were associated with higher scores in 'frequency of events reported' and 'feedback' (p<0.001). Leadership walkarounds were associated with higher response rates in 'supervisor/manager expectations and actions' (p=0.013) and 'organisational learning' (p=0.048). Training in patient safety and clinical simulation were associated with higher positive response rates across most questionnaire dimensions. Higher AE reporting was observed in centres with clinical simulation training, presence of patient safety specialists, leadership walkarounds and additional reporting systems in bivariate analyses. However, in the multivariable model, only other reporting systems (OR 2.690; 95% CI 1.565 to 4.662) and annual emergency department visit volume (OR 1.023; 95% CI 1.1013 to 1.033) were independently associated with AE reporting. The presence of more than two patient safety specialists was associated with lower reporting (OR 0.553; 95% CI 0.306 to 0.998). Paediatricians were more likely to report AEs. Organisational patient safety practices were associated with favourable safety culture dimensions. However, after the adjustment, AE reporting was primarily associated with reporting infrastructure and organisational characteristics. The implementation of these practices varied across centres, highlighting differences in the availability of organisational safety practices. Further research is needed to better understand these associations in paediatric emergency departments.","[""Journal Article"", ""Multicenter Study"", ""Observational Study""]","[""Collado-González B"", ""Navarta-Sánchez MV"", ""Sanz-Garcia A"", ""Palmar-Santos AM"", ""Emergency Safety Culture Group"", ""Paediatric Emergency Safety Culture Group""]",10.1136/bmjopen-2026-118551,Collado-González B,BMJ open,2044-6055,7,BMJ Open,eng,Palmar-Santos AM,"[""Humans"", ""Cross-Sectional Studies"", ""Emergency Service, Hospital"", ""Patient Safety"", ""Spain"", ""Organizational Culture"", ""Safety Management"", ""Logistic Models"", ""Surveys and Questionnaires"", ""Pediatrics"", ""Female"", ""Male""]",e118551,42532562,pmc-id: PMC13422817;,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42532562/,"Association between organisational patient safety practices, safety culture and adverse event reporting in paediatric emergency departments in Spain: a multicentre cross-sectional survey study",16,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"The purpose of this study was to develop best practices for conducting cognitive debriefing interviews with pediatric populations by drawing on the currently available literature and insights from experts in the health-related quality of life research community. A scoping review of the literature was conducted to identify existing recommendations, considerations, and methods for conducting cognitive debriefing interviews with pediatric populations. Findings from the review informed the development of a draft set of best practices, which were subsequently reviewed and refined through a two‑round modified Delphi process. The Delphi panel was composed of experts (i.e., researchers) in patient-reported outcome instrument development and evaluation with experience conducting interviews with pediatric populations. Thirty-five articles or guidance documents were included in the final scoping review, contributing insights that were used to develop a draft set of 17 best practices. Following the two rounds of review by the Delphi panel, the final set of 17 best practices, which reflects panel consensus, addresses: developing the interview guide, evaluating the characteristics of the instrument to be debriefed, and interview conduct. The best practices described in this article provide evidence‑based guidance that can help to standardize and strengthen the rigor of cognitive debriefing interviews with pediatric populations while potentially also improving the experience for participants. Broader implementation across drug development programs may enhance the reliability of measurement, improve the quality of pediatric participant input, and promote more patient‑centered decision‑making.","[""Journal Article"", ""Review""]","[""Broderick L"", ""O'Connor M"", ""Brennan E"", ""Bayliss M""]",10.1007/s11136-026-04352-3,Broderick L,"Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation",0962-9343,9,Qual Life Res,eng,Bayliss M,"[""Humans"", ""Patient Reported Outcome Measures"", ""Delphi Technique"", ""Child"", ""Quality of Life"", ""Pediatrics"", ""Cognition"", ""Interviews as Topic"", ""Psychometrics"", ""Surveys and Questionnaires""]",,42530707,pmc-id: PMC13423988;,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42530707/,"""Reading level is just one component"": best practices for cognitive debriefing patient-reported outcome instruments with pediatric populations",35,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Pediatric patients require age-appropriate dosage forms because developmental differences in physiology, pharmacokinetics and swallowing ability can significantly affect therapeutic outcomes. Conventional dosage forms are often unsuitable for children and practices such as tablet splitting, crushing or extemporaneous preparation may lead to dose inaccuracy, altered stability, poor palatability and reduced adherence. These limitations highlight the need for innovative formulation strategies that provide precise dosing while improving acceptability and therapeutic effectiveness. In this context, three-dimensional (3D) printing has emerged as a promising platform for personalized pediatric drug delivery. This review critically examines recent advances in 3D printing technologies for pediatric drug delivery and provides a formulation-focused and translational perspective by integrating pediatric therapeutic needs with technology selection, polymer considerations and dosage form design flexibility. A comprehensive literature review was conducted to evaluate recent developments in pediatric pharmaceutical applications of 3D printing. Major technologies including fused deposition modeling, semi-solid extrusion, binder jet printing and inkjet printing were assessed with respect to formulation design, polymer selection, drug-polymer compatibility and pediatric suitability. Particular emphasis was placed on taste-masking approaches, personalized dosing capability and dosage adaptability for different pediatric age groups. Three-dimensional printing enables fabrication of diverse pediatric-friendly dosage forms including chewable gummies, mini-tablets, orodispersible films and confectionery-like formulations. Published studies demonstrated improved dose precision, effective taste masking, customizable drug release profiles and enhanced patient acceptability. Regulatory approval of Spritam further supports the clinical feasibility of this technology. However, challenges remain regarding printer calibration, reproducibility, limited pharmaceutical-grade printable materials, long-term stability and regulatory harmonization. Three-dimensional printing represents an important advancement in patient-centric pediatric pharmacotherapy by enabling precise control over dose, geometry, release kinetics and sensory attributes. This review highlights its practical potential and translational readiness for pediatric healthcare.","[""Journal Article"", ""Review""]","[""Phadte P"", ""Jeedigunta MK"", ""Rao G"", ""Chellampillai B""]",10.1007/s40199-026-00630-0,Phadte P,"Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences",1560-8115,2,Daru,eng,Chellampillai B,"[""Printing, Three-Dimensional"", ""Humans"", ""Drug Delivery Systems"", ""Child"", ""Chemistry, Pharmaceutical"", ""Polymers"", ""Pediatrics"", ""Pharmaceutical Preparations"", ""Technology, Pharmaceutical"", ""Taste"", ""Dosage Forms""]",,42530696,pmc-id: PMC13424067;embargo-date: 2027/07/30;,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42530696/,"Three-dimensional printing as a transformative platform for patient-centric pediatric drug delivery: technologies, formulation strategies and clinical translation",34,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Children are disproportionately affected by disasters and represent a vulnerable population in such settings. However, no internationally recognized core competencies exist to guide health care providers in caring for children impacted by disasters (particularly non-pediatricians). This study aimed to establish consensus-based core competencies for pediatric disaster response through international expert agreement across disciplines. A three-round modified Delphi study was conducted following CREDES criteria, using competency statements generated via a comprehensive scoping review of pediatric disaster literature. International disaster medicine experts rated competency statements on a 7-point linear scale (1 = disagree, 7 = agree). Consensus was defined a priori as standard deviation (SD) ≤ 1.0. Data were collected and analyzed using the STAT59 online platform. 57 competencies met consensus criteria across three Delphi rounds, with mean scores ranging from 5.4 to 6.6. The highest-ranked competencies (mean = 6.6) were pediatric vulnerabilities recognition, pediatric transport management, child identification and tracking, and child-parent reunification. Decontamination initiation was also highly ranked (mean = 6.5). The 57 consensus-based core competencies for pediatric disaster medicine response, spanning 16 practice domains, provide a foundation to further develop standardized curricula, guide preparedness and response efforts, and define minimum training expectations for health care providers caring for children impacted by disasters.","[""Journal Article""]","[""Grodman SZ"", ""Hertelendy AJ"", ""Issa F"", ""Hart A"", ""Woodward CA"", ""Sarin R"", ""Franc JM"", ""Voskanyan A"", ""Issa Y"", ""Hertelendy A"", ""Weiner D"", ""Ciottone G""]",10.1017/dmp.2026.10414,Grodman SZ,Disaster medicine and public health preparedness,1935-7893,,Disaster Med Public Health Prep,eng,Ciottone G,"[""Humans"", ""Delphi Technique"", ""Pediatrics"", ""Disaster Medicine"", ""Clinical Competence"", ""Child"", ""Consensus"", ""Female""]",e138,42529878,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42529878/,Core Competencies for Pediatric Disaster Medicine: An International Modified Delphi Study,20,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Educational interventions addressing counseling at extreme prematurity to date have focused on single-specialty clinicians, overlooking the important communication and collaboration required by maternal-fetal medicine and neonatology for optimal counseling. This simulation-based workshop aimed to unite maternal-fetal and neonatology clinicians to enhance interspecialty-personalized and family-focused counseling at extreme prematurity. We developed and conducted 3 half-day virtual workshops with neonatology and maternal-fetal medicine attendings and fellows utilizing a combination of didactics, scenarios with simulated participants, and facilitated debriefs, including a cofacilitator with lived patient-family neonatal intensive care unit experience. A total of 26 clinicians participated in the 3 workshops. After the workshop, 92% of participants felt ""more prepared"" or ""much more prepared"" to have difficult conversations with families. Qualitative analysis of open-ended responses found key themes among participants, including increased adoption of parent-driven and personalized counseling approaches, enhanced interspecialty collaboration between maternal-fetal medicine and neonatology, and greater awareness of and efforts to mitigate bias in antenatal counseling. This novel workshop facilitated interspecialty collaboration between maternal-fetal medicine and neonatology when counseling at extreme prematurity and emphasized relational skills, personalized counseling, and bias mitigation techniques.","[""Journal Article""]","[""Sullivan A"", ""Brown SD"", ""Ward E"", ""Williams D"", ""Luff D"", ""Duffy CR"", ""Sage YH"", ""Spiel M"", ""Cummings C""]",10.15766/mep_2374-8265.11623,Sullivan A,MedEdPORTAL : the journal of teaching and learning resources,2374-8265,,MedEdPORTAL,eng,Cummings C,"[""Humans"", ""Infant, Newborn"", ""Neonatology"", ""Counseling"", ""Female"", ""Education"", ""Simulation Training"", ""Infant, Extremely Premature"", ""Qualitative Research""]",11623,42528897,pmc-id: PMC13415433;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42528897/,Development of a Joint-Specialty Simulation-Based Workshop to Optimize Counseling at Extreme Prematurity,22,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
,"[""Journal Article"", ""Consensus Statement""]","[""Subspecialty Group of Infectious Diseases, the Society of Pediatrics, Chinese Medical Association"", ""Gut Microbiota Collaborative Group of the Chinese Society for Parenteral and Enteral Nutrition"", ""Collaborative Group for Pediatric Gut Microbiota and Fecal Microbiota Transplantation of the Precision Medicine Committee, China Maternal and Child Health Association""]",10.3760/cma.j.cn112140-20260120-00064,"Subspecialty Group of Infectious Diseases, the Society of Pediatrics, Chinese Medical Association",Zhonghua er ke za zhi = Chinese journal of pediatrics,0578-1310,8,Zhonghua Er Ke Za Zhi,chi,"Collaborative Group for Pediatric Gut Microbiota and Fecal Microbiota Transplantation of the Precision Medicine Committee, China Maternal and Child Health Association","[""Humans"", ""Fecal Microbiota Transplantation"", ""Child"", ""Gastrointestinal Microbiome"", ""China"", ""Pediatrics""]",863-872,42527128,,2026 Aug 2,2026,https://pubmed.ncbi.nlm.nih.gov/42527128/,[Expert consensus on the clinical application and management of pediatric fecal microbiota transplantation (2026)],64,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"The global need for training in clinical research is substantial, particularly in resource-limited settings. We describe an international collaboration to build capacity in clinical research skills through a semi-personalized curriculum. Five sequential workshops (2020-2025) combined online modules with on-site, project-based learning. The curriculum across workshops included research project planning, proposal writing, and manuscript publishing. Topics included fundamentals of clinical study design, data registries, statistical considerations, research ethics, and scientific writing. At registration, applicants submitted an abstract for further development. An average of 35 applicants per workshop were selected. Participants' experiences were evaluated through postworkshop surveys. Participants across the workshops presented from 17 countries and seven disciplines, with the majority being physicians (66%) and nurses (16%). During each 2.5-day workshop, participants refined their abstracts with structured guidance and shared their work in a 10-minute presentation. Workshop 1 used a group-based model where each group developed one common abstract. Workshop 2 focused on quality improvement research; each group worked on preselected mock concepts through a structured learning exercise. Workshops 3 and 4 involved individualized learning, with each participant developing their own abstract into a study proposal. Workshop 5 focused on scientific writing, guiding participants to develop their abstracts into a manuscript outline. Surveys after each workshop consistently demonstrated a high level of satisfaction and perceived gain in knowledge and skill. These workshops effectively engaged trainees with various levels of clinical research training and imparted skills for research planning and manuscript writing. Future iterations will include thematic workshops including advanced statistical methods. Combining asynchronous learning modules with on-site, project-based training can be implemented across other regions and specialties in context-relevant settings.","[""Journal Article""]","[""Saab R"", ""Nasr R"", ""Sidhom I"", ""Belgaumi A"", ""Devidas M"", ""Naidu P"", ""Saha V"", ""Sultan I"", ""Friedrich P"", ""Fanous M"", ""Ghamloush F"", ""Gulten G"", ""Rodriguez-Galindo C"", ""Jeha S"", ""Santana VM""]",10.1200/GO-26-00157,Saab R,JCO global oncology,2687-8941,7,JCO Glob Oncol,eng,Santana VM,"[""Humans"", ""Capacity Building"", ""Resource-Limited Settings"", ""Biomedical Research"", ""Medical Oncology"", ""Pediatrics"", ""Education"", ""Curriculum""]",e2600157,42525911,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42525911/,Clinical Research Capacity Building in Pediatric Oncology in Resource-Limited Settings: Application and Early Results of Regional Educational Workshops,12,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Pediatric migrant health has been identified by the World Health Organization as a critical area for interdisciplinary research to improve care for children and adolescents with migration experience. Nevertheless, research agendas have rarely been shaped systematically by individuals with lived and professional experience, limiting relevance and impact. To identify and prioritize the most important unanswered research questions in pediatric migrant health in Europe through a structured, participatory priority-setting process. This multiphase survey study (April 2024 to June 2025), led by migrants and clinicians using the James Lind Alliance participatory priority-setting methodology, comprised 2 online consultations informed by Delphi procedures and a final in-person consensus workshop using a modified nominal group technique. Participants residing in multiple European countries included migrant caregivers, former migrant children and adolescents, health care workers in pediatric migrant health, and double experts with combined lived and professional experience. They were recruited via professional networks, community organizations, and open calls. The final in-person consensus workshop convened in Basel, Switzerland, in June 2025. The primary outcome was a ranked list of the top 10 unanswered research priorities in pediatric migrant health based on participant-generated questions and consensus methods. In consultation 1, 256 participants (156 [61.0%] with lived migration experience; 25 countries of residence, 41 countries of origin; 115 aged <35 years [44.9%], 138 aged ≥35 years [53.9%]; 158 female [61.7%]) submitted 1589 questions and comments, which were consolidated into 53 unanswered summary questions after qualitative content analysis and evidence checking. In consultation 2, rankings from 576 participants (214 [37.2%] with lived migration experience; 31 countries of residence, 50 countries of origin; 193 aged ≤35 years [33.5%], 364 aged ≥35 years [63.2%]; 412 female [71.5%]) yielded a short list of 25 questions. During the final consensus workshop, participants selected the top 10 research priorities. The 3 highest ranked priorities focused on universal access to health care, the health impact of racism and discrimination, and barriers to accessing care. Remaining priorities addressed health effects of migration, social determinants of health, needs of at-risk groups (including unaccompanied or undocumented minors and children with medical complexities), professional language support, training of health care workers, and family involvement in care. The research priorities identified in this survey study could provide a roadmap for future multidisciplinary and participatory research to improve health equity for pediatric migrants in Europe.","[""Journal Article""]","[""Wiemker V"", ""Kazi F"", ""Marcolin M"", ""Alothman I"", ""Ara F"", ""Asonganyi M"", ""Bianchi L"", ""Burzio V"", ""Chernet A"", ""Khrosh Z"", ""Matmuja S"", ""Sima B"", ""Teslenko M"", ""Haag J"", ""de Guchtenaere A"", ""Gronlund T"", ""Wanigaratne S"", ""Guttmann A"", ""Severoni S"", ""Nyankovska O"", ""Kruse A"", ""Neville S"", ""Weydmann N"", ""Brandenberger J"", ""Refugees and Migrants in Europe–Adolescent and Child Health (REACH) Network""]",10.1001/jamanetworkopen.2026.26087,Wiemker V,JAMA network open,2574-3805,7,JAMA Netw Open,eng,Brandenberger J,"[""Humans"", ""Transients and Migrants"", ""Female"", ""Child"", ""Male"", ""Adolescent"", ""Europe"", ""Caregivers"", ""Health Priorities"", ""Adult"", ""Research"", ""Surveys and Questionnaires"", ""Pediatrics""]",e2626087,42525410,pmc-id: PMC13421195;,2026 Jul 1,2026,https://pubmed.ncbi.nlm.nih.gov/42525410/,Partnering With Caregivers and Clinicians to Determine Research Priorities in Pediatric Migrant Health,9,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"to validate the content of a digital serious game on pediatric sepsis. methodological content validation study conducted in two rounds with expert judges (nurses and physicians). In the first round, the expert panel evaluated all screens of the initial prototype. After adjustments, the second version of the game underwent content validation using the Health Educational Content Validation Instrument (IVCES), and the agreement rate and Content Validity Index (CVI) were calculated. in the first round, 11 judges evaluated the game and made suggestions, all of which were incorporated. The second round involved nine judges. The overall agreement rate for the prototype items was 100%, and the overall CVI was 0.99. the game was modified according to the judges' feedback, and its content was validated for use as a tool for teaching and learning about pediatric sepsis.","[""Journal Article""]","[""Alves JB"", ""Pimenta RA""]",10.1590/0034-7167-2025-0099,Alves JB,Revista brasileira de enfermagem,0034-7167,,Rev Bras Enferm,eng,Pimenta RA,"[""Humans"", ""Sepsis"", ""Pediatrics"", ""Video Games"", ""Child"", ""Reproducibility of Results""]",e20250099,42524967,pmc-id: PMC13403641;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42524967/,Prev-Sepse Pediátrica: content validation of a digital serious game on pediatric sepsis,79,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Inequitable assessments in medical education disproportionately affect historically marginalized trainees and undermine development of a diverse physician workforce. With programs around the world incorporating competency-based medical education (CBME), understanding whether assessment disparities exist in specialty-specific competency frameworks is critical. This study examined disparities in program-reported performance assessments of pediatric residents across demographic groups in two pediatric-specific competency frameworks: the General Pediatrics Entrustable Professional Activities (EPAs) and Accreditation Council for Graduate Medical Education (ACGME) pediatric milestones. This prospective cohort study was conducted at 15 pediatric residency programs in the U.S. across the 2021-22, 2022-23, and 2023-24 academic years. Clinical Competency Committee-assigned entrustment-supervision levels for 5 EPAs and all milestone levels were collected twice yearly. Residents self-reported ethnoracial group and sex, analyzed as exposure to systems of racism and sexism. Time-to-event analysis and growth curve modeling with intersectional analytic approaches examined disparities across demographic groups. 475 of 803 (59%) residents completed demographic surveys, including 17.3% underrepresented in medicine (URiM), 22.9% Asian, 56.4% white, 70.7% female, and 27.8% male. Time-to-event analyses revealed significant differences for Asian and Asian female residents in reaching the highest EPA supervision level across all EPAs. Growth curve analyses showed Asian males had significantly flatter growth trajectories for EPA 15 (Lead an Interprofessional Team), resulting in lower estimated scores at graduation. URiM female residents had significantly lower scores on EPA 16 (Facilitate Handovers) at graduation. URiM residents showed lower Milestone growth curves for interpersonal communication, and Asian residents for systems-based practice. Subtle but meaningful disparities exist in program-reported assessments of pediatric residents, with distinct patterns affecting Asian and URiM residents across both frameworks. These findings highlight the need for proactive attention to equity in competency-based medical education assessment systems.","[""Journal Article""]","[""Anderson HLK"", ""West DC"", ""Schwartz AJ"", ""Lockwood L"", ""Rassbach CE"", ""Winn AS"", ""Michelson CD"", ""Kinnear B"", ""Chen JG"", ""Martini A"", ""Turner DA"", ""Schumacher DJ""]",10.5334/pme.2862,Anderson HLK,Perspectives on medical education,2212-2761,1,Perspect Med Educ,eng,Schumacher DJ,"[""Humans"", ""Internship and Residency"", ""United States"", ""Pediatrics"", ""Prospective Studies"", ""Female"", ""Male"", ""Clinical Competence"", ""Educational Measurement"", ""Sex Factors"", ""Surveys and Questionnaires"", ""Adult""]",621-632,42499955,pmc-id: PMC13398601;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42499955/,"Assessment of Pediatric Residents in the United States by Sex, Ethnoracial and Intersectional Group",15,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Disparities in early childhood development due to poverty are linked to lifelong gaps in health and well-being. To address such disparities, interventions must not only include the prevention of toxic stress, but also the promotion of early relational health-that is the presence of safe, stable, nurturing relationships between young children and their caregivers. Moreover, a public health approach that integrates multiple programs in order to meet the unique needs and build on the varied resources of individual families is needed to effect population-level change. This randomized controlled trial seeks to examine the implementation and effectiveness of combining two evidence-based interventions, HealthySteps and PlayReadVIP. A total of 355 parent-child dyads, 35 in the implementation phase and 320 in the effectiveness phase, will be randomly assigned to receive HealthySteps+PlayReadVIP or traditional HealthySteps, as an active Control. Families will receive the intervention at each pediatric well-child visit from birth to age 2 and will complete assessments at enrollment and child age 12 and 24 months. In addition, up to ten HealthySteps Specialists and other care providers will be enrolled and will complete surveys at each assessment point. The primary outcomes include positive parent-child relationship, parent cognitive stimulation, and child socioemotional development.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Canfield CF"", ""Miller EB""]",10.1371/journal.pone.0354239,Canfield CF,PloS one,1932-6203,7,PLoS One,eng,Miller EB,"[""Humans"", ""Poverty"", ""Infant"", ""Child, Preschool"", ""Single-Blind Method"", ""Female"", ""Child Development"", ""Male"", ""Infant, Newborn"", ""Parent-Child Relations"", ""Pediatrics""]",e0354239,42497181,pmc-id: PMC13399281;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42497181/,Randomized single-blind study to examine the implementation and effectiveness of integrating evidence-based early relational health programs in pediatrics for families with low incomes: A clinical trial protocol,21,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"It is critical to identify factors in the work environment that contribute to physician burnout to foster a professional culture that nurtures wellness. This study examined the prevalence of burnout symptoms among a group of Canadian pediatric undergraduate education leaders and explored how membership in a national community (Paediatric Undergraduate Program Directors of Canada, PUPDOC) may serve as a potential mitigating factor. This mixed-methods study involved a survey and subsequent focus groups of PUPDOC members. Survey comprised questions from the Maslach burnout index (MBI) adapted for the educational context. Data were analyzed using descriptive statistics. A qualitative descriptive approach was selected and focus group transcripts were analyzed using content analysis. Themes were generated that relate to PUPDOC's role in shaping members' educational and academic work. Sixteen members completed the survey (16/23, 70%). On the traditional MBI screen, three of 16 participants scored high-risk for burnout, but none reported high levels of symptoms on the adapted questions. Eighteen members participated in focus groups. Themes were interrelated, and included the significance of a sense of community, strengths and stressors of the job, finding meaning in one's work, opportunities, and legitimacy associated with belonging to a group. Our small group of pediatric undergraduate education leaders demonstrated a relatively low burnout rate compared to published rates in physician colleagues. We propose a sense of community that transcends institutions may help to mitigate burnout. By encouraging membership in such organizations, academic institutional leadership can support resilience and invest in the wellbeing of their education leaders.","[""Journal Article""]","[""Punnett AS"", ""Forbes KL"", ""Bannister SL"", ""Weiler G"", ""Mickleborough T""]",10.1080/10872981.2026.2706897,Punnett AS,Medical education online,1087-2981,1,Med Educ Online,eng,Mickleborough T,"[""Humans"", ""Burnout, Professional"", ""Resilience, Psychological"", ""Focus Groups"", ""Leadership"", ""Canada"", ""Pediatrics"", ""Female"", ""Male"", ""Academia"", ""Surveys and Questionnaires"", ""Education, Medical, Undergraduate""]",2706897,42496688,pmc-id: PMC13403545;,2026 Dec 31,2026,https://pubmed.ncbi.nlm.nih.gov/42496688/,"""From Exhaustion to Invigoration"": a mixed-methods study exploring the role of a community in supporting resilience of pediatric education leaders",31,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Pediatric oncology drug development remains uniquely challenging due to the rarity and biological heterogeneity of childhood cancers, ethical considerations in trial conduct, and the limited feasibility of large, randomized studies. Despite these barriers, recent years have seen a notable acceleration in the approval of oncology therapies for pediatric populations, driven by advances in molecularly targeted treatments, evolving regulatory requirements, and innovation in trial design. Reducing nonclinical data requirements and increasing the adaptation of model‑informed drug development approaches are also contributing to advances in pediatric oncology treatment by supporting dose selection, optimizing study design, and reducing unnecessary patient burden. In this review, recent regulatory requirements from the United States, the EU, and other key regions on pediatric oncology drug development are discussed. Thirty-three drugs with oncology indications in pediatric populations approved by the US FDA between 2018 and 2025 are reviewed. These approvals provide examples of how nonclinical and clinical data were generated with a focus on strategies for dose-finding and justification. Common challenges and considerations related to clinical operations and formulation development in pediatric populations and the emerging use of real-world data, external controls, and artificial intelligence/machine learning are also discussed.","[""Journal Article"", ""Review""]","[""Wen YF"", ""Wang X"", ""Boyanapalli S"", ""Anderson L"", ""Dang T"", ""Xing G"", ""Calvet M"", ""Hart T"", ""Kasichayanula S"", ""Zhao X""]",10.1002/jcph.70242,Wen YF,Journal of clinical pharmacology,0091-2700,7,J Clin Pharmacol,eng,Zhao X,"[""Humans"", ""Drug Development"", ""Antineoplastic Agents"", ""Child"", ""United States"", ""Clinical Trials as Topic"", ""Neoplasms"", ""Drug Approval"", ""United States Food and Drug Administration"", ""Pharmacology, Clinical"", ""Pediatrics"", ""Research Design""]",e70242,42496364,pmc-id: PMC13398400;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42496364/,"Accelerating Pediatric Oncology Drug Development: Advances in Clinical Pharmacology, Trial Design, Non-Clinical Evidence, and Regulatory Science",66,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"The paediatric workforce plays a central role in health systems worldwide. National reports and studies have described its size and structure, as well as the retention of staff within the paediatric workforce. However, there have been few syntheses of empirical evidence examining workforce trends across career stages, and none have focused specifically on paediatric staff. We aimed to systematically synthesise evidence on the global trends of the availability, distribution, career progression, and differences across career stages among the paediatric workforce. We searched CENTRAL, Embase, MEDLINE, and Scopus between 1 and 20 November 2025 for primary studies reporting on the above-mentioned trends within the paediatric workforce. We extracted and narratively synthesised the related data, and assessed the risk of bias of included studies using Joanna Briggs Institute tools. We included 35 studies from high-income and upper-middle-income countries, with no low- or lower-middle-income countries being eligible. Workforce supply increased steadily over time in high-income countries, driven largely by subspecialty growth. However, geographic imbalances persisted, with low representation of paediatric staff in rural areas. In terms of career stage, early-career paediatricians reported higher workload burden, dissatisfaction, and career uncertainty compared with their senior counterparts. Women progressively came to account for most of the workforce, although men continued to predominate in leadership positions. Evidence from upper-middle-income countries focused primarily on training preparedness and early-career experiences. Despite growth in the size of the paediatric workforce in high-income countries, challenges related to distribution, retention, and equity persist, particularly during early career stages. Importantly, the evidence base on this topic heavily underrepresents low- and lower-income countries. Future research should prioritise career-stage specific data to support equitable global workforce planning. PROSPERO: CRD420261283831.","[""Journal Article"", ""Systematic Review""]","[""Yao X"", ""Wang Z"", ""Xiong T"", ""Tao M"", ""Hu X""]",10.7189/jogh.16.04186,Yao X,Journal of global health,2047-2978,,J Glob Health,eng,Hu X,"[""Humans"", ""Pediatrics"", ""Health Workforce"", ""Career Mobility"", ""Developing Countries"", ""Developed Countries"", ""Global Health"", ""Staff Development""]",04186,42495734,pmc-id: PMC13411957;,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42495734/,Global trends and career development of human resources for paediatrics: a systematic review,16,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Organizational health literacy (OHL) remains a critical yet underexplored dimension of health equity, particularly at the interface between clinical training and patient care. This article proposes a conceptual reframing of the Mini-Clinical Evaluation Exercise (Mini-CEX) as an OHL-oriented formative assessment tool within case-based learning for pediatric pneumonia. The OHL-Mini-CEX model integrates three assessment domains-teach-back evaluation, de-jargonization capacity, and empowering guidance-to systematically evaluate residents' communicative competence in addressing health literacy barriers. We delineate the mechanisms through which this instrument operates: embedding equity-conflict scenarios into teaching cases, generating bidirectional formative feedback for both clinicians and organizations, and constructing a closed loop from micro-level training to macro-level health equity outcomes. Implementation challenges, including faculty preparedness gaps and psychometric rigor, are examined alongside integrated strategies drawing on public health collaboration. This perspective advances a theoretically grounded and practically actionable pathway for transforming clinical education into an institutional driver of health equity.","[""Journal Article""]","[""Ge SN"", ""Li B"", ""Mu BY"", ""Wan LS""]",10.3389/fpubh.2026.1880936,Ge SN,Frontiers in public health,2296-2565,,Front Public Health,eng,Wan LS,"[""Humans"", ""Health Literacy"", ""Pneumonia"", ""Pediatrics"", ""Problem-Based Learning"", ""Educational Measurement"", ""Child""]",1880936,42487800,pmc-id: PMC13388563;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42487800/,Enhancing organizational health literacy through pediatric clinical training: Mini-CEX-based formative assessment in case-based learning for pediatric pneumonia-a perspective,14,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"To evaluate the perception of autonomy and the main formative strengths and weaknesses of fourth-year (R4) and fifth-year (R5) Pediatric Surgery residents (MIR) in Spain, in order to identify areas for improvement in their surgical and clinical training. A descriptive cross-sectional study was conducted using an anonymous survey distributed via Google Forms during the last quarter of 2023. The questionnaire included 8 questions on demographic data, surgical activity, outpatient clinics, and training suggestions. The results underwent a descriptive statistical analysis. Eighteen residents participated (11 women and 7 men), with a mean age of 29.6 years; 61% were MIR-5 and 39% MIR-4. R4s perceived greater autonomy in frequent procedures (open orchidopexy, inguinal herniorrhaphy, appendectomy, and upper gastrointestinal endoscopy) and less in neonatal surgery and urological pathology. R5s reported greater independence in common general surgery and less in esophageal atresia, diaphragmatic hernia, pyeloplasty, and nephrectomy. In outpatient clinics, autonomy was greater in abdominal and skin pathology, and lower in urology and head and neck pathology. Among the main limitations noted were the low volume of neonatal surgery, the high number of residents, and the scarce offer of structured training activities. The lower perceived autonomy is concentrated in neonatal surgery and complex urological pathology. Coordinated training strategies are required at the national level, including surgical simulation, structured online training, and rotations in reference centers, to optimize the acquisition of competencies and ensure that training is as complete as possible.","[""Journal Article""]","[""Comajuncosas Pérez E"", ""Moreno-Alfonso JC"", ""Molina Caballero AY"", ""Pérez Martínez A""]",10.54847/cp.2026.03.14,Comajuncosas Pérez E,Cirugia pediatrica : organo oficial de la Sociedad Espanola de Cirugia Pediatrica,0214-1221,3,Cir Pediatr,eng,Pérez Martínez A,"[""Humans"", ""Cross-Sectional Studies"", ""Spain"", ""Female"", ""Internship and Residency"", ""Male"", ""Pediatrics"", ""Surveys and Questionnaires"", ""Adult"", ""Clinical Competence"", ""Professional Autonomy""]",102-107,42487422,,2026 Jul 20,2026,https://pubmed.ncbi.nlm.nih.gov/42487422/,Formative perception of 4th and 5th year Pediatric Surgery residents in Spain,39,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"In recent decades, initiatives have been developed to promote the de-implementation of low-value practices through ""do not do"" recommendations (RNH). This study aimed to estimate the level of awareness and the state of implementation of representative RNH in Pediatric Surgery Departments within the Spanish National Health System (SNS), as the initial phase of the NOCIPE project, endorsed by the Spanish Society of Pediatric Surgery (SECP). Observational, descriptive, cross-sectional study using a self-administered survey addressed to the heads of Pediatric Surgery departments within the SNS. Descriptive analysis and non-parametric comparisons for independent samples were performed. A total of 16/37 (43%) responses were obtained. Among respondent centers, 9 (56.2%) reported having a clinical practice appropriateness entity, and 5 (31.2%) included RNH in management agreements. The median number of RNH assessed per center was 6.5/8 known (81%; IQR 3), 5/8 implemented (62%; IQR 4), and 1/8 measured (12%; IQR 1). No significant differences were observed in the number of implemented RNH according to the presence of an appropriateness entity or inclusion in management agreements. Nine additional RNH were collected and used as a complementary source in subsequent phases of the project. The findings reveal a significant gap between awareness, implementation, and particularly the measurement of RNH, highlighting the need to strengthen dissemination strategies, facilitate implementation, and standardize indicators and tools to assess their impact and guide comparable improvements across centers.","[""Journal Article"", ""Observational Study""]","[""Hernández AE"", ""Soto C"", ""Girón Ó"", ""de Diego M""]",10.54847/cp.2026.03.13,Hernández AE,Cirugia pediatrica : organo oficial de la Sociedad Espanola de Cirugia Pediatrica,0214-1221,3,Cir Pediatr,eng,de Diego M,"[""Cross-Sectional Studies"", ""Spain"", ""Humans"", ""Pediatrics"", ""Surgery Department, Hospital"", ""Guideline Adherence"", ""Low-Value Care"", ""Surveys and Questionnaires"", ""Health Knowledge, Attitudes, Practice""]",97-101,42487421,,2026 Jul 20,2026,https://pubmed.ncbi.nlm.nih.gov/42487421/,"Knowledge and level of implementation of ""Do Not Do"" recommendations in Spanish pediatric surgery departments",39,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Metabolomics studies small-molecule metabolites to provide insights into health and disease, supporting early diagnosis and personalized medicine. Advances in mass spectrometry and nuclear magnetic resonance (NMR) have expanded its use in metabolic, cancer, and cardiovascular diseases. In pediatrics, high-resolution NMR metabolomics has been instrumental in identifying age-related metabolic changes during early childhood and their associations with growth, nutrition, and disease risk. However, a comprehensive review of its clinical applications and future potential remains limited. This review highlights how utilizing specific NMR pulse sequences, such as CPMG and NOESY, allows for precise and non-destructive metabolic profiling of diverse biofluids, supported by minimal sample preparation and high-throughput automated analysis. Data processing tools like NMRProcFlow and MetaboAnalyst facilitate spectral preprocessing, statistical analysis, and biological interpretation, streamlining metabolomics workflows. Clinically, NMR-based metabolomics has elucidated metabolic alterations in pediatric growth, prematurity, nutrition-related sensitizations, allergic diseases, lipid metabolism, infectious conditions, and neurobehavioral disorders. In particular, metabolomics has been applied to identify specific metabolic signatures underlying the molecular mechanisms of childhood allergic asthma. Despite limitations in detecting low-abundance metabolites, NMR's ability to preserve sample integrity and integrate multi-omics data, especially gut microbiota-derived metabolites, shows great promise in advancing precision pediatric medicine, early disease screening, and personalized therapeutic strategies.","[""Journal Article"", ""Review""]","[""Kuo CN"", ""Chiang MH"", ""Lee HJ"", ""Yu YY"", ""Shen EY"", ""Chiu CY""]",10.38212/2224-6614.3574,Kuo CN,Journal of food and drug analysis,1021-9498,1,J Food Drug Anal,eng,Chiu CY,"[""Humans"", ""Metabolomics"", ""Magnetic Resonance Spectroscopy"", ""Child"", ""Pediatrics""]",68-77,42485526,pmc-id: PMC13391010;,2026 Jun 1,2026,https://pubmed.ncbi.nlm.nih.gov/42485526/,Applications of nuclear magnetic resonance spectroscopy in pediatric clinical metabolomics: From research to future perspectives,34,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Pediatric clinicians have the potential to exert a large influence on health care sustainability for children and families as part of broader system transformation to promote sustainable practices. As a significant contributor to global greenhouse gas emissions, health care systems and providers have a responsibility to reduce emissions that negatively affect children's health. All pediatric clinicians should understand ways that we can mitigate health care impacts on our environment and should actively contribute to solutions in everyday practice through conversations with patients, trainees, and colleagues; and advocacy for institution-level, system-level, community-level, and global-level change.","[""Journal Article"", ""Review""]","[""Parnes MF"", ""Weiss EM"", ""Grow HM""]",10.1016/j.yapd.2026.02.003,Parnes MF,Advances in pediatrics,0065-3101,1,Adv Pediatr,eng,Grow HM,"[""Humans"", ""Climate Change"", ""Child"", ""Environmental Health"", ""Pediatrics""]",353-370,42481102,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42481102/,Climate Stewardship in the Clinical Setting,73,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Influenza vaccination coverage is suboptimal nationwide. To evaluate the effectiveness of centralized text message recall for influenza vaccination among children conducted by the New York City Department of Health and Mental Hygiene. A randomized assignment of 149 860 children, split between the intervention and control groups. Pediatric patients drawn from the Citywide Immunization Registry in New York City. Children aged 15 months to 18 years who did not receive an influenza vaccine in the 2016-2017 season and as of the study date in the 2017-2018 season. The Citywide Immunization Registry sent a generic Short Message Service (SMS) text message to the parents or guardians of the children: ""The Health Department recommends that your child/children receive an annual flu shot. Call your doctor today!"" Risk ratios of the proportions of children who received an influenza vaccine in the intervention and control groups within 28 days after the text message was sent. On October 25-26, 2017, 74 553 parents or guardians were sent a text message and 74 526 served as the control group. Of text messages sent, 73% were delivered successfully. Within 28 days of the intervention, 4.7% of children aged 15 months to 4 years in the text message group received an influenza vaccine compared with 4.3% in the control group, a statistically significant 9.5% relative increase in vaccination uptake (RR: 1.095, 95% CI: 1.001-1.199). Centralized text messages had a small positive effect on influenza vaccination among younger children. This approach may contribute to improving influenza vaccination in the pediatric population.","[""Journal Article""]","[""Cheng I"", ""Papadouka V"", ""Ternier A"", ""Langdon-Embry M"", ""Daskalakis DC"", ""Zucker JR""]",10.1097/PHH.0000000000002380,Cheng I,Journal of public health management and practice : JPHMP,1078-4659,5,J Public Health Manag Pract,eng,Zucker JR,"[""Humans"", ""Text Messaging"", ""New York City"", ""Child, Preschool"", ""Influenza Vaccines"", ""Infant"", ""Child"", ""Influenza, Human"", ""Female"", ""Reminder Systems"", ""Vaccination"", ""Male"", ""Adolescent"", ""Pediatrics""]",E211-E218,42479583,,2026 Sep-Oct 01,2026,https://pubmed.ncbi.nlm.nih.gov/42479583/,"A Centralized Text Message Recall for Pediatric Influenza Vaccination, New York City, 2017",32,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Residents in pediatric endocrinology subspecialty units encounter diverse educational scenarios spanning theory, skills, and attitudes; yet, brief residencies frequently limit their exposure to certain clinical cases. Research in medical education demonstrates that e-learning can address such challenges efficiently. We implemented a blended learning model grounded in the Kolb learning cycle that uses structured, case-based e-learning. We aimed to evaluate the utility and usability of blended learning using a novel e-learning tool. We used a problem-solving approach and used the physical separation of case-based e-learning (interactive, patient scenario-based online modules) and theoretical content delivery as the educational model for residents in a pediatric endocrinology and diabetology unit. Residents worked asynchronously (on their own time, not simultaneously with others) on clinical scenarios and completed formative assessments (practice tests designed to provide feedback for learning rather than grades) with immediate feedback using a flipped classroom teaching method, in which students review material before group instruction. In addition, all cases could be discussed with specialists during face-to-face learning opportunities through a blended learning approach that combines online and in-person elements. We evaluated Kirkpatrick level 1 (reaction, how participants respond to training) and level 2 (learning, measured as an increase in knowledge or capability) outcomes using the postgraduate Medical E-learning Evaluation Survey (MEES) and the User Experience Questionnaire (UEQ), which assesses users' perceptions of e-learning platforms. Questionnaires from 12 pediatric residents and 1 questionnaire from a fourth-year medical student were evaluated. The main strengths identified were the tool's support for applying content to daily clinical work (12/13, 92% users), provision of timely summaries (n=9, 69% users), access to reliable information sources (n=9, 69% users), and immediate feedback on responses (n=8, 62% users). Key weaknesses included device compatibility for e-learning (n=5, 38% users), limited content personalization (n=4, 31% users), and a lack of a navigation aid (n=4, 31% users). No significant functional issues were reported. The UEQ evaluation showed that dependability received the lowest rating, while attractiveness and stimulation received the highest rating. Our e-learning proposal provides a practical way to apply theoretical knowledge through interactive clinical cases. Evaluations show that users are highly motivated to engage with e-learning, highlighting our tool's adaptability and effectiveness for postgraduate medical education in pediatric endocrinology. Identifying strengths and weaknesses will guide future improvements. Evaluating various aspects of e-learning remains crucial, as these aspects can affect learning outcomes. However, more longitudinal evaluations of e-learning are necessary to achieve a comprehensive understanding of its effectiveness.","[""Case Reports"", ""Journal Article""]","[""Hrasnica F"", ""Pitteloud S"", ""Jacot J"", ""Antoniou MC"", ""Ruiz-Arana IL"", ""Bouthors T"", ""Busiah K"", ""Stoppa-Vaucher S"", ""Hauschild M""]",10.2196/89064,Hrasnica F,JMIR formative research,2561-326X,,JMIR Form Res,eng,Hauschild M,"[""Humans"", ""Pilot Projects"", ""Endocrinology"", ""Pediatrics"", ""Internship and Residency"", ""Computer-Assisted Instruction"", ""Education, Distance"", ""Male"", ""Educational Measurement"", ""Female""]",e89064,42478930,pmc-id: PMC13386660;,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42478930/,Development and Usability Evaluation of an E-Learning Tool for Blended Learning in Pediatric Endocrinology: Formative Pilot Study,10,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Artificial intelligence (AI) adoption in health care is rapidly accelerating, with pediatrics positioned to benefit from improvements in quality, efficiency, and access to care. Recent frameworks have articulated ethical commitments for trustworthy AI in pediatrics, but less attention has been paid to the foundational infrastructure required to achieve them. In this article, we examine the challenges that emerge at the intersection of AI and pediatrics: unique challenges that AI poses for pediatric care, including nonintuitive errors, impacts on clinician cognition, and new infrastructure requirements; and unique challenges that pediatrics poses for AI, including adequate training data, accommodation of developmental heterogeneity, and navigation of evolving patient autonomy. We then outline the data systems, governance structures, validation frameworks, and public trust infrastructure that must be established before the field can meet these challenges. We conclude with concrete recommendations for clinicians, caregivers, health care systems, government, technologists, and academic institutions seeking to lay the foundation for trustworthy and beneficial AI in pediatrics.","[""Journal Article"", ""Review""]","[""Finlayson SG"", ""Wightman A"", ""Weiss EM"", ""Gallo V"", ""Rabbani N"", ""Diekema DS"", ""Sarabu C"", ""Võ HH"", ""MacDuffie KE"", ""Mazwi ML"", ""Lin YC"", ""Opel DJ""]",10.1542/peds.2026-076194,Finlayson SG,Pediatrics,0031-4005,2,Pediatrics,eng,Opel DJ,"[""Humans"", ""Pediatrics"", ""Artificial Intelligence"", ""Child"", ""Trust""]",,42476575,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42476575/,Building the Foundations for Trustworthy AI in Pediatrics,158,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Medical child abuse is an underrecognized and undertaught condition with potentially fatal consequences. Clinicians must learn to recognize and manage harmful overmedicalization of children. We developed a 2-part interactive workshop on medical child abuse for pediatric clinicians. We evaluated part 1, an interactive high-yield lecture, using a pre- and postmodule assessment of self-rated confidence and knowledge in 1 resident conference and 3 multidisciplinary grand rounds settings across 2 institutions. We evaluated part 2, a popcorn-style role-play, with an additional postmodule confidence assessment at 2 resident conferences. We excluded duplicate participants. Part 1 duration was 45 minutes and part 2 was 60 minutes. We summarized results using descriptive statistics and analyzed paired data using paired t tests for knowledge (mean ± SD), and Wilcoxon signed-rank tests for confidence (median and interquartile range [IQR]). A total of 203 and 36 unique participants participated in part 1 and part 2, respectively. Participant confidence in recognizing and managing medical child abuse increased from a median of 5 (IQR 4-6; n = 124) to 7 (IQR 6-8) after part 1 (P < .001). Among participants completing part 2 (n = 20), confidence increased further to 8 (IQR 8-9; P <.001). Knowledge scores increased from 66% (SD = 29%) premodule to 88% (SD = 20%) postmodule (n = 119; P < .001). This interactive 2-part workshop was adaptable across clinical audiences and settings and improved confidence and knowledge in recognition and management of medical child abuse.","[""Journal Article""]","[""Harvey SL"", ""Crumm CE"", ""Brown ECB"", ""Johnson KL""]",10.15766/mep_2374-8265.11620,Harvey SL,MedEdPORTAL : the journal of teaching and learning resources,2374-8265,,MedEdPORTAL,eng,Johnson KL,"[""Humans"", ""Child Abuse"", ""Curriculum"", ""Pediatrics"", ""Child"", ""Clinical Competence"", ""Physicians"", ""Internship and Residency""]",11620,42465685,pmc-id: PMC13372927;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42465685/,Medical Child Abuse Module in the Child Abuse Pediatrics Curriculum for Physicians (CAP-CuP),22,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"The healthcare disparity focus group within the Western Regional Alliance for Pediatric Emergency Management aimed to identify barriers to optimal care for children affected by disasters and potential opportunities for improvement. The study was conducted in six focus groups during the summer of 2023. A survey was distributed to individuals in emergency management and disaster medicine to collect demographic data. The survey also assessed the total number of trainings that participants attended. The focus group discussions were led by experienced qualitative researchers. Participants could also respond to the questions during the meetings on a digital note-taking platform. These discussions were then transcribed and analyzed using ATLAS.ti. The data from the survey were analyzed using SPSS, Windows Version 29.0. The survey included 49 people. The focus group meetings revealed multiple themes and subthemes that reflected the challenges that emergency management and disaster medicine professionals face when combating health disparities and raising awareness for pediatric populations. The challenges that these professionals face include funding, communication, gaps in knowledge, gaps in technology, and a lack of emergency preparedness plans. The focus groups also highlighted facilitators to preparedness, team cohesion, engagement, and the presence of certain grants to help with funding as ways to combat health disparities and raise awareness for pediatric populations during emergencies. The results of the focus groups can effectively be utilized to assess the challenges emergency management and disaster medicine professionals experience. The results highlight the need to prioritize funding, communication, and addressing gaps in knowledge, gaps in technology, and a lack of emergency preparedness plans. The results can be used to explore different approaches to improve health disparities through awareness initiatives as a forefront priority for pediatric populations.","[""Journal Article""]","[""Hicks CD"", ""Hasson C"", ""Bhatt S"", ""Chiari-Keith L"", ""Newton C"", ""Burke RV""]",10.5055/ajdm.0533,Hicks CD,American journal of disaster medicine,1932-149X,2,Am J Disaster Med,eng,Burke RV,"[""Humans"", ""Focus Groups"", ""Disaster Planning"", ""Pediatrics"", ""Healthcare Disparities"", ""Child"", ""Female"", ""Surveys and Questionnaires"", ""Male""]",189-199,42461682,,2026 Spring,2026,https://pubmed.ncbi.nlm.nih.gov/42461682/,"Pediatric disaster preparedness and health disparities: Gaps, future goals, and recommendations",21,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"An interruptive alert as a clinical decision support tool has been implemented to reduce the ordering of unnecessary urine cultures in a tertiary paediatric emergency department. Following its introduction, there was an immediate and sustained reduction in urine culture ordering rates of 25%, with a small increase in cultures with pure growth over a twelve-month period.","[""Journal Article""]","[""Fondum T"", ""Cheek J""]",10.3233/SHTI260959,Fondum T,Studies in health technology and informatics,0926-9630,,Stud Health Technol Inform,eng,Cheek J,"[""Decision Support Systems, Clinical"", ""Humans"", ""Emergency Service, Hospital"", ""Urinalysis"", ""Unnecessary Procedures"", ""Child"", ""Pediatrics""]",26-28,42460587,,2026 Jul 15,2026,https://pubmed.ncbi.nlm.nih.gov/42460587/,Reducing Low Value Care Through Implementation of a Clinical Decision Support Tool Addressing Urine Culture in a Paediatric Emergency Department,339,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Malawi's paediatric and child health workforce faces a critical shortage. In response, the Kamuzu University of Health Sciences has been training clinical officers (29 to date) in a Bachelor of Science in Paediatric and Child Health (BSc PCH) program since 2012 to serve as paediatric and child health district leaders in mostly rural areas. However, little is known about their workplace reality, and how it affects their fulfilment professionally, and such information may have policy implications. Therefore, we aimed to investigate Malawian BSc PCH clinical officers' workplace satisfaction, retention and influencing factors. In a mixed-methods, sequential, explanatory design study, we used a quantitative workplace satisfaction survey (five-point Likert scale) covering 11 dimensions, and qualitative in-depth interviews. Analysis included paired t-tests applied to Herzberg's two-factor theory of individual needs dimensions contributing to workplace satisfaction. During data collection in 2022, a total of 27 (93%) clinical officers participated in the survey, and 15 clinical officers and 14 key informants participated in in-depth interviews. BSc PCH clinical officers worked at public district hospitals (n=13), public central hospitals (n=8), and at non-governmental organisations (NGOs) (n=6). Moral satisfaction and workplace/team harmony dimensions scored highest with means of 3.94&plusmn;0.50 and 3.85&plusmn;0.69, respectively. In contrast, career advancement and salary and benefits scored lowest with 2.01&plusmn;0.99 and 2.46&plusmn;0.80, respectively. Differences existed between clinical officers at public district hospitals compared to public central hospitals for the dimensions of tasks (eg variety, job description clarity) (p=0.034), work environment (p=0.006), and salary and benefits (p=0.032). Similarly, clinical officers at public district hospitals vs NGOs differed for the work environment (p=0.016), management style (p=0.003), and salary and benefits (p=0.002). Seventeen clinical officers considered leaving their current position, with salary being a significant reason (p=0.048). Moreover, delayed recognition and promotion, non-specific job descriptions, limited professional development opportunities, a lack of supervision, and career advancement barriers obstructed workplace satisfaction, according to the in-depth interviews. BSc PCH clinical officers program graduates' workplace satisfaction differs according to the workplace. Graduates working in public hospitals at district level, located mostly in rural areas, appear to be most critically affected and may leave government services. Changes in their specific work environment, career and professional development and remuneration may offer stakeholders opportunities to improve BSc PCH clinical officers' workplace satisfaction and retain them where they are needed most.","[""Journal Article""]","[""Yasmin F"", ""Moons P"", ""Phiri A"", ""Appelbaum S"", ""Nserebo-Banda L"", ""Krüger C"", ""Weigel R"", ""Chimalizeni YF""]",10.22605/RRH9644,Yasmin F,Rural and remote health,1445-6354,3,Rural Remote Health,eng,Chimalizeni YF,"[""Humans"", ""Job Satisfaction"", ""Malawi"", ""Male"", ""Female"", ""Workplace"", ""Adult"", ""Personnel Turnover"", ""Working Conditions"", ""Pediatrics"", ""Attitude of Health Personnel"", ""Salaries and Fringe Benefits"", ""Surveys and Questionnaires""]",9644,42458697,,2025 Jul,2025,https://pubmed.ncbi.nlm.nih.gov/42458697/,Factors influencing workplace satisfaction and retention of paediatric and child health clinical officers in Malawi's public health sector: a mixed-methods study,25,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"IntroductionNon-profit organizations play a key role in supporting knowledge dissemination activities. However, their contribution to these activities in-person and online in the pediatric oncology field remains unclear. Our study aims to provide an overview of the pediatric oncology charitable organizational landscape and describe their knowledge mobilization efforts related to dissemination, highlighting existing strengths, gaps, and opportunities to strengthen and unite efforts.MethodsA bilingual environmental scan was conducted using an internet-based search strategy to identify Canadian pediatric oncology non-profit organizations. Eligible organizations were screened, and data on their characteristics and knowledge dissemination strategies were extracted. Extracted data were analyzed descriptively and presented in tables, spatially, and narratively with figures.ResultsThe scan identified 906 results, and 25 organizations were eligible for inclusion in the study. Eleven organizations (44%) are based in Ontario. The decade where the highest number of organizations were founded is 2000-2009 (n = 9, 36%), offering primarily English-only content (n = 18, 72%). Only six (26.1%) provided bilingual resources. Among the knowledge dissemination strategies, digital knowledge dissemination activities were utilized often, with all organizations using websites and social media (particularly Facebook, n=25 (100%), and Instagram, n =24 (96%)).ConclusionThis study identified the current list and knowledge dissemination efforts of non-profit organizations in the pediatric oncology community in Canada but reveals gaps in bilingual content and in other major languages spoken in the country, geographic physical location, and centralized resources.","[""Journal Article""]","[""Foulem C"", ""Drake EK"", ""Lui A"", ""Dias S"", ""Damoulianos E"", ""Reid S"", ""Cossette P"", ""Duval M"", ""Efremov K"", ""Foster J"", ""Haas K"", ""Tsimicalis A""]",10.1177/00469580261468769,Foulem C,"Inquiry : a journal of medical care organization, provision and financing",0046-9580,,Inquiry,eng,Tsimicalis A,"[""Humans"", ""Canada"", ""Organizations, Nonprofit"", ""Information Dissemination"", ""Pediatrics"", ""Medical Oncology"", ""Child"", ""Internet""]",469580261468769,42454748,pmc-id: PMC13373428;,2026 Jan-Dec,2026,https://pubmed.ncbi.nlm.nih.gov/42454748/,Pediatric Oncology Knowledge Mobilization in Canada: A Environmental Scan,63,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Artificial intelligence (AI) medical scribes are an emerging technology intended to reduce the documentation burden. In pediatrics, evidence on implementation in the Spanish context is very limited. To evaluate the implementation of an AI medical scribe in pediatric outpatient clinics, examining its effects on clinician-patient interaction, documentation quality, and barriers to adoption. Prospective observational proof-of-concept study (February-October 2025) conducted at a tertiary pediatric hospital. Forty physicians from three subspecialties participated, and 197 visits were documented. The evaluation combined direct observations (n = 30), surveys of clinicians (n = 18) and patients (n = 20), and a quality assessment using a rubric based on the mPDQI-9. With the AI scribe, eye contact increased (median 95.7% vs. 78.6%; p < 0.001), with no significant change in visit duration (25.7 vs. 21.9 min; p = 0.262). Documentation quality improved in accuracy/completeness (p = 0.008), organization/structure (p < 0.001), and overall score (median 23 vs. 17; p = 0.008). Documentation of information provided to the patient was more frequent (80% vs. 20%; p = 0.003). Post-visit review time accounted for 33%-38% of total time. Fifty-five percent of users reported being satisfied or very satisfied, although 67% reported technical issues and 33% reported requiring extensive corrections. Adoption was concentrated in fewer than one-third of trained clinicians. The AI medical scribe was associated with improvements in interaction and selected domains of documentation quality. However, technical barriers and limited adoption persisted and should be addressed before wider deployment.","[""Journal Article"", ""Observational Study""]","[""Vallejo V"", ""Farreras J"", ""Valero L"", ""González-Grado C"", ""Peral I"", ""Cano I"", ""Launes C"", ""Grupo de estudio LAIA-DOC""]",10.1016/j.medcli.2026.107541,Vallejo V,Medicina clinica,0025-7753,8,Med Clin (Barc),eng,Launes C,"[""Humans"", ""Prospective Studies"", ""Documentation"", ""Artificial Intelligence"", ""Child"", ""Pediatrics"", ""Physician-Patient Relations"", ""Male"", ""Female"", ""Electronic Health Records"", ""Spain"", ""Ambulatory Care""]",107541,42447762,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42447762/,"Ambient AI scribe in pediatric outpatient visits: documentation burden, quality, and scale-up limits",166,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"To explore care recipients (patients' and their caregivers) and care providers (healthcare providers' and law enforcement officers') perspectives on paediatric mental health presentations to emergency departments, to identify challenges to care. Secondary qualitative analysis of free-text responses from a Delphi study conducted within the Paediatric Research in Emergency Departments International Collaborative (PREDICT) network in 2022. The original Delphi process aimed to identify research themes and key data points for child and adolescent mental health ED presentations; however, a large number of additional free-text responses were received. The primary aim of this specific study was to identify major categories using the General Inductive Approach (GIA) of these free-text responses to explore the experiences, service delivery and perceived challenges of care recipients and care providers. Patients were recruited from 12 EDs across three Australian states, and pre-hospital services (two police and three ambulance departments) across four Australian states. A total of 184 participants provided responses (36 care recipients and 148 care providers). Three main categories are described: (1) care continuity and communication gaps, (2) challenges in the ED environment and (3) need for improved training and education and behavioural support. Care recipients and care providers identified challenges in service coordination, clinician readiness and the ED environment. Strengthening communication, expanding training, reducing sensory overload and improving privacy in physical EDs and improving links to community care could enhance patient experiences and outcomes.","[""Journal Article""]","[""Sufian M"", ""Xu Y"", ""John-White M"", ""Muscara F"", ""Babl FE"", ""Anderson V"", ""Wilson CL"", ""Borland ML"", ""Tonge BJ"", ""Gray KM"", ""Melvin GA"", ""Kochar A"", ""Borschmann R"", ""Haslam R"", ""Tavender E"", ""Gordon MS"", ""Dalziel S"", ""Smith K"", ""Craig S""]",10.1111/1742-6723.70309,Sufian M,Emergency medicine Australasia : EMA,1742-6731,4,Emerg Med Australas,eng,Craig S,"[""Humans"", ""Female"", ""Qualitative Research"", ""Caregivers"", ""Child"", ""Emergency Service, Hospital"", ""Male"", ""Australia"", ""Adolescent"", ""Delphi Technique"", ""Mental Disorders"", ""Pediatrics"", ""Adult"", ""Perception""]",e70309,42442415,pmc-id: PMC13364286;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42442415/,Caregiver and Care Recipient Perspectives on Paediatric ED Mental Health Presentations: A Qualitative Study,38,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Children, neonates, and pregnant women are particularly vulnerable during disasters. Fragmentation between specialized pediatric-perinatal systems and general disaster response frameworks can hinder coordinated care. Following lessons from the 2011 Great East Japan Earthquake, Japan established the Disaster Liaison for Pediatric and Perinatal Medicine (DLPPM) to embed specialists within disaster command structures. However, large-scale activation under prolonged infrastructure disruption has not been systematically evaluated. We conducted a structured retrospective descriptive analysis of DLPPM operational records during the first month after the 2024 Noto Peninsula Earthquake. Activities were reviewed across five pre-specified domains to examine how the liaison framework functioned during the acute and subacute phases. DLPPM was integrated into the prefectural disaster headquarters and consolidated maternal-child health information, enabling centralized identification of 83 pregnant women, estimated to represent most pregnant women in the severely affected region. Twenty-one obstetric transfers were coordinated. Pediatric transfers and evacuation of medically dependent children were facilitated through established networks. During the subacute phase, DLPPM initiated maternal-child support measures, including a ""Children's Conference"" and a support website. These findings suggest that DLPPM functioned as a centralized coordination hub linking specialized clinical networks with disaster governance, although real-time identification of vulnerable families in shelters remained limited. Embedding pediatric and perinatal specialists within disaster headquarters can support structured medical coordination for vulnerable populations. Earlier and more systematic integration with public health and welfare systems is essential to extend this hub function beyond hospital-centered care.","[""Journal Article""]","[""Kagami K"", ""Imai K"", ""Ueno Y"", ""Kitano H"", ""Hirabuki S"", ""Sasaki H"", ""Sato H"", ""Mitani Y"", ""Iwasaki H"", ""Wada T"", ""Fujiwara H"", ""Unno N""]",10.1111/ped.70488,Kagami K,Pediatrics international : official journal of the Japan Pediatric Society,1328-8067,1,Pediatr Int,eng,Unno N,"[""Humans"", ""Earthquakes"", ""Japan"", ""Female"", ""Retrospective Studies"", ""Pregnancy"", ""Infant, Newborn"", ""Disaster Planning"", ""Pediatrics"", ""Perinatal Care"", ""Child"", ""Infant"", ""Disasters""]",e70488,42438887,pmc-id: PMC13358397;,2026 Jan-Dec,2026,https://pubmed.ncbi.nlm.nih.gov/42438887/,System-Level Analysis of Japan's Pediatric-Perinatal Disaster Liaison Operations During the 2024 Noto Earthquake,68,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Identifying factors related to physicians' specialty choice is crucial to ensure a sustainable healthcare workforce. However, knowledge regarding the factors influencing the choice of pediatrics remains inadequate. This study aimed to clarify physicians' background characteristics associated with choosing pediatrics and factors associated with hospital-based practice among pediatricians in Japan. This cross-sectional study, comprising an online survey of eligible physicians (N = 6415), was conducted in June 2022 via the Nikkei Medical Online website. The primary outcome was the choice of pediatrics, whereas factors associated with hospital-based pediatricians were examined in a secondary analysis. Multivariate logistic regression analyses were used to assess the association between physician background characteristics and outcomes. Among 6415 physicians, 340 (5.3%) were pediatricians. Factors associated with choosing pediatrics included being female (adjusted odds ratio [aOR] 1.84, 95% CI 1.39-2.44), having children (aOR 1.71, 95% CI 1.27-2.29), and graduating from a public university (aOR 1.67, 95% CI 1.24-2.26). Analyses restricted to pediatricians demonstrated that willingness to work in rural areas (aOR 3.24, 95% CI 1.05-10.04) was positively associated with hospital-based practice, whereas age (per 1-year increase; aOR 0.93, 95% CI 0.90-0.95), an urban hometown (aOR 0.54, 95% CI 0.29-0.98), and having a physician father (aOR 0.40, 95% CI 0.19-0.83) were negatively associated. These findings indicate that pediatric healthcare workforces may be shaped by structural factors, such as educational environment, regional background, and family background, in addition to individual preferences.","[""Journal Article""]","[""Otsuka T"", ""Sakaguchi K"", ""Ueno N"", ""Watari T""]",10.1111/ped.70475,Otsuka T,Pediatrics international : official journal of the Japan Pediatric Society,1328-8067,1,Pediatr Int,eng,Watari T,"[""Humans"", ""Japan"", ""Female"", ""Cross-Sectional Studies"", ""Career Choice"", ""Pediatricians"", ""Male"", ""Pediatrics"", ""Surveys and Questionnaires"", ""Adult"", ""Middle Aged""]",e70475,42438863,pmc-id: PMC13358644;,2026 Jan-Dec,2026,https://pubmed.ncbi.nlm.nih.gov/42438863/,Physician Characteristics Associated With Choosing Pediatrics in Japan: A Nationwide Survey,68,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Caregivers who use languages other than English (LOEs) experience health disparities. However, little is known about how spoken and written language services are experienced in pediatric primary care. The goal of this exploratory, cross-sectional study was to ask caregivers who use LOEs in health care about language services received during pediatric primary care visits. We conducted the study in 3 pediatric primary care clinics in Southwestern Pennsylvania. Caregivers labeled in the electronic health record as using an LOE were called within 2 weeks after a visit and completed an interpreter-assisted structured interview. Questions included receipt of spoken and written services during their most recent visit, satisfaction with language services, and recommendations to improve care. Interviews lasted 45 minutes, and interviewers captured answers via Qualtrics. Descriptive statistics and qualitative thematic analysis were used. One hundred twenty-four participants were interviewed; 13 who reported preferring English were excluded. The remaining 111 participants used 21 different languages for health care. Most participants reported receiving spoken language-concordant services (professional interpreter or bilingual clinicians) with the health care clinician (94/111, 85%), but fewer when scheduling (62/111, 56%), rooming (43/109, 39%), or with nursing needs (26/58, 45%). Less than one-fourth reported receiving language-concordant written materials such as questionnaires or pre-appointment reminders. Most reported ""Excellent""-quality interpreters and bilingual health care clinicians. Participants reported high-quality communication with the health care clinician; however, fewer received language-concordant written materials or spoken services during other visit touchpoints. Future work should implement processes to ensure receipt of language services before, during, and after a visit.","[""Journal Article""]","[""Yu L"", ""Migliori O"", ""Schweiberger K"", ""Kurs-Lasky M"", ""Schoemer P"", ""Heidenerich K"", ""Lion KC"", ""DeCamp LR"", ""Ray K"", ""Chaves-Gnecco D"", ""Saladino J"", ""Ragavan MI""]",10.1542/peds.2025-075312,Yu L,Pediatrics,0031-4005,2,Pediatrics,eng,Ragavan MI,"[""Humans"", ""Cross-Sectional Studies"", ""Primary Health Care"", ""Female"", ""Male"", ""Caregivers"", ""Medical Interpreting"", ""Communication Barriers"", ""Child, Preschool"", ""Child"", ""Quality of Health Care"", ""Pennsylvania"", ""Pediatrics"", ""Language"", ""Infant""]",,42437677,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42437677/,Caregiver-Reported Quality of Pediatric Primary Care Language Services,158,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"To identify factors influencing implementation and integration of the paediatric ESCALATION system in country Western Australia. Health professionals (nurses and doctors) working in country Western Australia. A multi-methods study using an interpretive descriptive approach guided by the Practical Robust Implementation and Sustainability Model (PRISM) and Normalisation Process Theory (NPT). Data collection across six sites included patient chart audit, health professional survey and focus groups/interviews. Data were analysed descriptively (audit and survey) and thematically (focus groups/interviews). An audit of 94 patient charts showed 61.7% met escalation of care criteria, while 69.0% of cases were escalated per policy. Among 114 survey responses, findings indicated system integration, with 95.6% reporting ESCALATION was part of their role, 93.5% agreeing it supported early detection of clinical deterioration and 93.8% reporting ease of use. Fewer identified local champions (66.7%), had confidence in others' use of the system (61.1%), reported sufficient training (69.0%), or were aware of reports demonstrating system effectiveness (55.0%). Seventy-eight health professionals participated in focus groups/interviews. Three themes were interpreted through the PRISM and NPT frameworks: (i) Enhanced patient safety (intervention characteristics and participants' perspectives; coherence; cognitive participation), (ii) Strengthening clinical decision-making (implementation and sustainability infrastructure; cognitive participation; collective action), (iii) Monitoring and fidelity (implementation and sustainability infrastructure, external; collective action; reflexive monitoring). The paediatric ESCALATION system is embedded and valued, but sustaining fidelity through scale-up requires ongoing training, teamwork, confident communication and organisational support across regional, rural and remote WA health services.","[""Journal Article""]","[""Boyle E"", ""Laird P"", ""Leslie GD"", ""Stokes S"", ""Andrew J"", ""Howard J"", ""Robinson M"", ""Harris T"", ""Gill FJ""]",10.1111/ajr.70229,Boyle E,The Australian journal of rural health,1038-5282,4,Aust J Rural Health,eng,Gill FJ,"[""Humans"", ""Western Australia"", ""Focus Groups"", ""Child"", ""Pediatrics"", ""Program Evaluation"", ""Rural Health Services"", ""Child Health Services""]",e70229,42423302,pmc-id: PMC13348011;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42423302/,Evaluating the Scale-Up and Sustainability of the Paediatric ESCALATION System in Country Western Australia: A Multi-Methods Study,34,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Over 80% of all pediatric emergency visits occur in non-pediatric emergency departments (EDs). Continuous quality improvement (QI) is linked to higher pediatric readiness and improved patient outcomes, and, consequently, can lead to a 76% decreased mortality risk for critically ill and injured children. However, fewer than one third of EDs use quality indicators to evaluate and improve pediatric care delivery. Major barriers to QI in non-pediatric EDs include the absence of performance standards; challenges with standardized data collection, analysis, and benchmarking; and limited institutional resources to enhance pediatric emergency care. The authors describe the National Pediatric Readiness Quality Initiative (NPRQI), a free and secure platform that provides ED-based health care teams with real-time, crucial insights into the quality of pediatric emergency care delivery to empower providers to engage in pediatric QI. The NPRQI overcomes the aforementioned barriers to QI by providing (1) the first nationally vetted pediatric quality measures that apply to all types of EDs, including resource-restricted, low-volume EDs; (2) standardized data collection, performance visualization, and benchmarking for participating EDs; and (3) a free, secure web-based direct-to-provider interface for rapid interpretation and action by health care teams. Since its launch in 2023, the NPRQI has engaged more than 100 diverse EDs across 26 states. The NPRQI seeks to transform pediatric emergency care by shortening the time to adoption of and adherence to evidence-derived clinical processes through data transparency and benchmarking. Furthermore, by capturing pediatric care delivery nationally across all types of EDs, the NPRQI is poised to establish the first set of national standards for pediatric emergency care following the model of standards established for stroke and cardiac centers.","[""Journal Article""]","[""Desai S"", ""Edgerton E"", ""Jensen AR"", ""Remick K""]",10.1056/CAT.25.0185,Desai S,NEJM catalyst innovations in care delivery,2642-0007,7,NEJM Catal Innov Care Deliv,eng,Remick K,"[""Humans"", ""Emergency Service, Hospital"", ""Quality Improvement"", ""Child"", ""Pediatrics"", ""Quality Indicators, Health Care"", ""United States"", ""Benchmarking""]",CAT250185,42418619,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42418619/,The National Pediatric Readiness Quality Initiative: Empowering Emergency Departments to Improve Pediatric Care,7,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Laparoscopic training is an established component of minimally invasive surgery education, and involves different tools: virtual reality, training box and in vivo models. The use of porcine models is the most similar to human anatomy. Its role is well known during the residency program, but its specific impact on paediatric surgery consultants performance is poorly explored. Six consultant surgeons attempted a consecutive 4-h a week laparoscopic training on porcine models for a total of 12 weeks, focusing on refinement of fine dissection, intracorporeal suturing, and management of intraoperative complications. Participants underwent pre- and post-training (respectively Period A and B) assessment of surgical effectiveness by assessment of mean operative time, intraoperative and postoperative complications on three commonly performed procedures: inguinal hernia repair, varicocelectomy and laparoscopic orchiopexy. 210 procedures were analysed, 109 before and 101 after the training. We observed a significant overall reduction in operative time for all procedures (p = 0.007); more precisely, inguinal hernia repair and varicocelectomy showed a significant reduction in operative time (p = 0.028 and p = 0.04 respectively), while no significant reduction in operative time for laparoscopic orchidopexy was observed (p = 0.2668). Mean age at surgical intervention was significantly reduced in period B for herniorrhaphy. Laparoscopic training in porcine models could be considered an effective tool to improve skills of paediatric surgery consultants. Its use could allow the improvement of laparoscopic confidence and effectiveness also in surgeons with an already acquired learning curve, supporting the systematic and continuous integration of such programmes into the professional development.","[""Journal Article""]","[""Pensabene M"", ""Patti M"", ""Baldanza F"", ""Grasso F"", ""Cicero L"", ""Sergio M"", ""Di Pace MR""]",10.1007/s00383-026-06510-7,Pensabene M,Pediatric surgery international,0179-0358,1,Pediatr Surg Int,eng,Di Pace MR,"[""Animals"", ""Laparoscopy"", ""Swine"", ""Clinical Competence"", ""Pediatrics"", ""Male"", ""Hernia, Inguinal"", ""Humans"", ""Models, Animal"", ""Orchiopexy"", ""Herniorrhaphy"", ""Varicocele"", ""Operative Time""]",,42417972,pmc-id: PMC13346154;,2026 Jul 8,2026,https://pubmed.ncbi.nlm.nih.gov/42417972/,Laparoscopic training in porcine models: a tool for continuous professional skill enhancement for paediatric surgeons,42,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"To identify and analyze the most influential articles within the field of pediatric neurology through a bibliometric lens. As pediatric neurology continues to expand across subspecialties, identifying landmark studies is critical for understanding clinical and research priorities. Bibliometric analysis enables the evaluation of citation trends to highlight impactful contributions that have shaped the field. A bibliometric analysis of the 50 most-cited pediatric neurology articles was conducted. Articles were assessed by citation metrics, study design, subspecialty, journal impact factor (JIF), and funding status. Correlation and regression analyses evaluated associations between variables. Citation counts ranged from 185 to 1,440 (median: 332). Epilepsy accounted for the largest proportion of studies (26%) but showed lower citation density (31.5 cites/year) compared with subspecialties such as neuroimmunology (45 cites/year). International collaboration was the strongest predictor of citation impact; each additional collaborating country increased total citations (β = 48.9, p = 0.002) and citation density (β = 5.3, p < 0.001), resulting in a 42% higher citation density than single-nation studies. While publication year negatively affected total citations (β = -22.4, p < 0.001), newer studies demonstrated faster citation accrual. Funding modestly increased citation count (β = 135.3, p = 0.026), whereas JIF showed no significant effect (p = 0.846). Neurodevelopmental topics had the highest mean citations, and open-access articles exhibited 38% greater citation density than paywalled publications. The most influential studies were collaborative, funded, and open access. Recent works, especially in neurogenetics and neurocritical care, are gaining rapid traction. International collaboration and topic selection drive scholarly impact. Future research should focus on high-impact and underrepresented specialties.","[""Journal Article""]","[""Alyazidi A"", ""Muthaffar O"", ""Bamaga A"", ""Qashqari H"", ""Alhithlool A"", ""Alanezi A"", ""Almehmadi S"", ""Babiker M"", ""Bashiri F""]",10.17712/1658-3183.2810,Alyazidi A,"Neurosciences (Riyadh, Saudi Arabia)",1319-6138,3,Neurosciences (Riyadh),eng,Bashiri F,"[""Bibliometrics"", ""Neurology"", ""Humans"", ""Pediatrics"", ""Journal Impact Factor"", ""Periodicals as Topic""]",315-323,42415970,pmc-id: PMC13340610;,2026 Mar,2026,https://pubmed.ncbi.nlm.nih.gov/42415970/,The Top 50 Cited Articles in Pediatric Neurology: A Bibliometric Analysis,31,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Effective communication of adverse events is a critical skill for health care practitioners, particularly those in anesthesiology. Despite the importance of delivering bad news to guardians after complications, many anesthesia practitioners receive little to no formal training in this area. This curriculum aims to address this by introducing a learning activity that integrates the SPIKES and NURSE frameworks with simulated parent (SP) encounters. A randomized waitlist control design was used to evaluate this 3-hour simulation curriculum. Learners were randomly assigned to receive either immediate training in communication skills (a 1-hour didactic session on the SPIKES and NURSE framework, followed by SP deliberate practice) or delayed training after 1 month. Both groups completed a pretest, posttest, and delayed posttest. Communication skills were evaluated using a published checklist based on the SPIKES and NURSE frameworks. Course surveys were also administered to assess changes in learners' self-reported confidence and overall course satisfaction with the training. Twenty-one learners (15 attending anesthesiologists and 6 certified registered nurse anesthetists) participated in this educational activity. Both groups demonstrated significant improvements in checklist-scored communication skills and self-reported confidence following the simulation curriculum (P < .001). In the Early Intervention group, these improvements in simulated communication skills were sustained after a 1-month delay. Overall, course satisfaction was high, with a median score of 5 (IQR 5-5). Our findings demonstrate that a structured curriculum incorporating the SPIKES and NURSE frameworks, combined with SP deliberate practice, enhances communication skills for difficult perioperative conversations with pediatric guardians.","[""Journal Article""]","[""Phillips ML"", ""Yanko F"", ""Vermylen JH"", ""Ballard HA""]",10.15766/mep_2374-8265.11616,Phillips ML,MedEdPORTAL : the journal of teaching and learning resources,2374-8265,,MedEdPORTAL,eng,Ballard HA,"[""Humans"", ""Anesthesiology"", ""Communication"", ""Simulation Training"", ""Curriculum"", ""Female"", ""Male"", ""Surveys and Questionnaires"", ""Pediatrics"", ""Parents"", ""Child""]",11616,42415715,pmc-id: PMC13337673;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42415715/,Perioperative Difficult Conversations With Guardians of Pediatric Patients: A Simulation-Based Workshop for Anesthesiology Practitioners Using the VitalTalk Framework,22,eOiN7RKT0bvVpVvB8,d0GtUFdx7zKeUHgLi
"Lattice radiotherapy (LRT) is a spatially fractionated technique that delivers three-dimensional high-dose vertices within tumors. However, conventional LRT is constrained by geometric limitations when applied to small and medium-sized tumor volumes, primarily due to the large beam sizes that restrict optimal lattice pattern formation. This study aims to investigate a photon minibeam-based LATTICE radiotherapy (mini-LRT) approach designed to overcome the geometric limitations of conventional LRT and enable effective spatially fractionated treatment for small and medium-sized tumors adjacent to critical organs. Three brain cases and three lung cases, with clinical target volumes ranging from 12.34 cc to 40.88 cc, were presented for treatment planning comparison between conventional LRT and mini-LRT. A multi-collimator delivery strategy employing shifted slit patterns was implemented to achieve complementary spatial coverage. Dose calculation and optimization were performed using Monte Carlo simulations and solved via an iterative convex relaxation algorithm. Reference stereotactic body radiation therapy (SBRT) plans were generated for all six cases, and setup-error robustness analysis was performed for two representative cases using nominal and shifted dose-influence matrix scenarios. Mini-LRT produced denser lattice structures in all cases, generating 5-11 vertices compared to only 1-3 vertices achievable with conventional LRT. Vertex diameters were reduced from 15.0 mm to 3.0-4.0 mm, and vertex-to-vertex distances decreased from 25.0 mm to 12.5 mm. The lattice volume ratio ranged from 0.68% to 1.07% with mini-LRT. Organs at risk (OARs) dose reductions were observed in the evaluated cases, including reduced mean dose to brainstem, heart, and esophageal. Furthermore, mini-LRT achieved a higher peak-to-valley dose ratio (PVDR) ranging from 2.19 to 2.94, compared to 1.75-2.34 for conventional LRT. Reference SBRT plans achieved clinical target volume (CTV) D95 = 50 Gy in all cases but showed elevated D0.03cc to adjacent OARs in selected anatomically constrained cases. In the representative robustness analysis, worst-case setup-error scenarios showed modest PVDR degradation. This proof-of-concept dosimetric planning study suggests that photon minibeam-based LATTICE radiotherapy can generate compact spatially fractionated dose distributions in selected small and medium-sized tumors. Compared with conventional LRT, mini-LRT increased vertex density, reduced lattice volume ratio, and improved OAR sparing in the evaluated cases. Additional experimental validation, motion assessment, and larger patient studies are required before clinical translation.","[""Journal Article""]","[""Wu W"", ""Shinde N"", ""Li J"", ""Vanhaezebrouck I"", ""Jiang K"", ""Lin Y"", ""Li Q"", ""Gao H""]",10.1002/mp.70596,Wu W,Medical physics,0094-2405,8,Med Phys,eng,Gao H,"[""Photons"", ""Humans"", ""Radiotherapy Planning, Computer-Assisted"", ""Monte Carlo Method"", ""Brain Neoplasms"", ""Radiometry"", ""Tumor Burden"", ""Lung Neoplasms"", ""Radiotherapy Dosage""]",e70596,42545080,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42545080/,Photon minibeam-based LATTICE radiotherapy for small and medium-sized tumors: A dosimetric planning study,53,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"The Global Positioning System (GPS)-based metabolic power model for soccer, proposed by di Prampero and applied by Osgnach, rests on a fixed energy cost (EC) of running of 4.6 J·kg-1·m-1 and a biomechanical equivalence between accelerated level and constant-speed uphill running. A narrative review was conducted via PubMed, Scopus, and Web of Science using terms like metabolic power, EC of running, GPS soccer, sprint biomechanics, equivalent slope, and running economy (2005-2025). Running EC is relatively speed-independent across submaximal velocities typical of football (~6-18 km·h-1). The geometric principle underlying the accelerated-to-inclined running equivalence is accepted, and GPS metabolic power provides a useful metric for relative load comparisons. A universal fixed EC ignores interindividual variability (~20%), fatigue, surfaces, and drag. The equivalence model has vector orientation inconsistencies, employs the imprecise term 'equivalent mass', and derives its postural reference from sprint-start conditions unrepresentative of match-play accelerations (~2-4 m·s-2). Validation studies show systematic underestimations of 29%-85% relative to indirect calorimetry. Refinements exist but remain unimplemented in most commercial platforms. Individually calibrated EC values, inertial measurement unit integration, and hybrid models combining GPS kinematics with cardiorespiratory data are promising. Force-velocity profiling offers a biomechanically grounded alternative for individual sprint characterization. Priorities include calorimetric validation under match conditions; player-specific EC models incorporating fatigue, surface, and role; implementing model updates in commercial software; and comparing alternative load metrics for injury-risk prediction.","[""Journal Article"", ""Review""]","[""Barba F"", ""Padulo J"", ""Maffulli N""]",10.1093/bmb/ldag022,Barba F,British medical bulletin,0007-1420,1,Br Med Bull,eng,Maffulli N,"[""Humans"", ""Soccer"", ""Energy Metabolism"", ""Running"", ""Biomechanical Phenomena"", ""Geographic Information Systems"", ""Athletic Performance"", ""Models, Biological""]",,42544508,,2026 Jul 3,2026,https://pubmed.ncbi.nlm.nih.gov/42544508/,Indirect calculation of metabolic power in soccer: a critical analysis of a popular model,159,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Health services increasingly face decisions about how to integrate immersive technologies into routine practice. International guidance highlights the need for structured governance in digital health, yet extended reality (XR) initiatives are often launched through isolated pilots without a clear assessment of organizational readiness or implementation risk. Although factors influencing XR adoption are well documented, health care organizations and system-level decision-makers still lack practical, governance-oriented tools to translate these determinants into structured strategic decisions made before implementation. This study aims to develop multicriteria decision analysis for extended reality (MCDA-XR), a strategic governance framework that translates behavioral, organizational, and technical implementation determinants into a structured decision-support process for health care organizations. The study followed a sequential mixed methods design covering the first 2 phases of a 3-stage framework development and validation project. Phase 1 (identification) defined strategic criteria by integrating theoretical perspectives on organizational complexity, behavior change, technology acceptance, and immersive safety, together with a targeted review of XR implementation evidence. Phase 2 (construction) refined the framework through participatory sessions. A multidisciplinary group of 33 stakeholders, including professionals and managers from hospital and primary care settings, and postgraduate students, evaluated the proposed criteria for strategic relevance and operational clarity. This process resulted in a refined 10-criterion structure and the establishment of a dual-score assessment logic. Phase 3 (validation), planned as a subsequent step, will examine how the framework performs when applied prospectively in clinical settings. The development process yielded a framework comprising 10 operational criteria grouped into 3 conceptual domains (human, organizational, and technical). Stakeholder ratings indicated high strategic relevance across all criteria, with mean scores ranging from 4.03 (SD 0.95) for workflow integration to 4.61 (SD 0.56) for safety and comfort. The final instrument applies a dual-assessment approach in which each criterion is rated separately for strategic importance and organizational readiness. Mapping these dimensions enables organizations to identify priority gaps, particularly areas of high importance and low readiness, and to distinguish between manageable constraints and critical barriers requiring targeted preparatory action prior to implementation. MCDA-XR addresses a key governance gap in XR implementation by providing a structured way to align adoption decisions with institutional priorities and operational constraints. Rather than relying on descriptive feasibility assessments, the framework is intended to support explicit prioritization and action-oriented decision-making at the organizational level. MCDA-XR is positioned for Phase 3 evaluation, which will examine the practical utility, interpretability, and implementation relevance of the framework when applied prospectively in real-world clinical deployments.","[""Journal Article""]","[""Ferrer Costa J"", ""Armayones Ruiz M"", ""Bourdin-Kreitz P""]",10.2196/89801,Ferrer Costa J,Journal of medical Internet research,1438-8871,,J Med Internet Res,eng,Bourdin-Kreitz P,"[""Humans"", ""Decision Support Techniques"", ""Delivery of Health Care"", ""Digital Health""]",e89801,42544118,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42544118/,The Multicriteria Decision Analysis for Extended Reality (MCDA-XR) Governance Framework for Health Care Adoption: Mixed Methods Development Study,28,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Synthetic MRI can generate multiple contrasts from a single acquisition, yet synthetic fluid-attenuated inversion recovery (FLAIR) generally shows lower quality than conventional FLAIR. We aimed to improve 3D synthetic FLAIR image quality using deep learning, without losing the scan-time advantage of synthetic MRI. We studied 55 adults with inflammatory demyelinating diseases who underwent 3T MRI. For each participant, five 3D quantification using an interleaved Look-Locker acquisition sequence with T2 preparation (3D-QALAS) source images and a conventional 3D-FLAIR image were acquired, and a synthetic FLAIR image was generated from the 3D-QALAS data. We trained a deep learning model in which a 3D U-shaped convolutional network (U-Net)-based attention network predicted voxel-wise weights for generating FLAIR images from the five 3D-QALAS source images, using conventional 3D-FLAIR images as the reference. The model was trained with a combined loss function of mean squared error, content loss, and style loss. Agreement with the reference was assessed using image similarity and error metrics, lesion overlap using the Dice similarity coefficient, and overall image quality and focal lesion visibility using blinded radiologist ratings. Synthetic FLAIR and the deep learning-generated FLAIR images were compared using 2-sided Wilcoxon signed-rank tests; P < 0.05 was considered statistically significant. The deep learning-generated FLAIR images showed significantly higher agreement with the reference image than synthetic FLAIR images (all P < 0.001). Lesion overlap was higher with the deep learning-generated FLAIR images (median [interquartile range]: 0.642 [0.528-0.711] versus 0.487 [0.344-0.641]). Qualitatively, the deep learning-generated FLAIR images improved overall image quality and focal lesion visibility, but reader scores remained lower than those for the reference conventional 3D-FLAIR images (all P < 0.001). A deep learning-based approach applied to five 3D-QALAS source images improved the image quality of 3D synthetic FLAIR. These improvements may increase the clinical utility of 3D synthetic MRI for neuroradiologic assessment.","[""Journal Article""]","[""Kamio S"", ""Hagiwara A"", ""Otsuka Y"", ""Nakaya M"", ""Hosoi R"", ""Hoshino Y"", ""Tomizawa Y"", ""Tsukamoto Y"", ""Hara N"", ""Kikuta J"", ""Andica C"", ""Akashi T"", ""Wada A"", ""Kusahara H"", ""Yano R"", ""Hatano T"", ""Abe O"", ""Kamagata K""]",10.2463/mrms.mp.2026-0101,Kamio S,Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine,1347-3182,4,Magn Reson Med Sci,eng,Kamagata K,"[""Humans"", ""Imaging, Three-Dimensional"", ""Magnetic Resonance Imaging"", ""Image Enhancement"", ""Deep Learning"", ""Adult"", ""Female"", ""Male"", ""Middle Aged"", ""Demyelinating Diseases"", ""Image Interpretation, Computer-Assisted"", ""Aged""]",,42543682,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42543682/,Structure-preserving Image-quality Enhancement for 3D Synthetic FLAIR Using a 3D U-Net with Content and Style Losses,25,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Dengue fever remains a major mosquito-borne disease in Southeast Asia, with increasing incidence in rapidly urbanizing settings. In Vietnam, Hanoi has experienced recurrent outbreaks; however, comprehensive analyses of recent dengue epidemiology in northern regions remain limited. This study aimed to characterize the spatiotemporal dynamics of dengue in Hanoi from 2018 to 2022. A retrospective descriptive study was conducted using routine dengue surveillance data collected by the Hanoi Center for Disease Control. All clinically diagnosed and laboratory-confirmed dengue cases reported between January 2018 and December 2022 were included. Temporal trends were examined using descriptive analysis of monthly and annual incidence rates. District-level incidence rates were calculated and visualized using a geographic information system (GIS) mapping. Serotype distribution was examined using available virological data. A total of 46,650 dengue cases were reported during the study period. Dengue transmission occurred annually, with substantial inter-annual variability; the highest incidence was recorded in 2022 (236 per 100,000 population), while the lowest occurred in 2021 (41 per 100,000 population). A clear seasonal pattern was observed, with cases increasing from June and peaking between September and November. Spatial analysis revealed marked heterogeneity, with higher incidence consistently observed in peri-urban districts. All four dengue virus serotypes co-circulated, with DENV-1 and DENV-2 predominating and a shift toward DENV-2 dominance in later years. Dengue transmission in Hanoi exhibits pronounced seasonal and spatial patterns influenced by urbanization and ecological factors. Strengthening pre-season vector control activities and district-level surveillance may help reduce outbreak risk and maintaining integrated epidemiological and virological surveillance is essential to mitigate future outbreaks.","[""Journal Article""]","[""Bau VH"", ""Nguyen HN"", ""Le MD"", ""Hoang NS"", ""Nguyen VK"", ""Vu KT"", ""Nguyen VA""]",10.47665/tb.43.2.011,Bau VH,Tropical biomedicine,0127-5720,2,Trop Biomed,eng,Nguyen VA,"[""Vietnam"", ""Humans"", ""Dengue"", ""Incidence"", ""Retrospective Studies"", ""Seasons"", ""Dengue Virus"", ""Spatio-Temporal Analysis"", ""Urban Population"", ""Serogroup"", ""Disease Outbreaks"", ""Geographic Information Systems""]",211-218,42543556,,2026 Jun 1,2026,https://pubmed.ncbi.nlm.nih.gov/42543556/,"Temporal and spatial distribution of dengue in an urban setting: evidence from Hanoi, Vietnam (2018-2022)",43,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Based on a data science perspective, this study systematically elucidated the prescription patterns and core compatibility mechanisms of Carthami Flos-containing formulas in the treatment of diabetic peripheral neuropathy(DPN), aiming to provide scientific evidence for optimizing evidence-based TCM therapeutic strategies. A comprehensive literature search was conducted across CNKI, Wanfang, VIP, and PubMed databases, covering publications from database inception to September 18, 2025. Following rigorous screening, 297 clinical studies were included, all focusing on DPN as the primary condition, employing orally administered Chinese herbal medicines, and reporting effective clinical outcomes, encompassing a total of 12 783 cases. Frequency analysis was performed using R software, combined with association rule mining, network topology analysis, prescription similarity assessment, and cluster analysis, to clarify the structural composition and dosage distribution patterns of Carthami Flos-containing formulas. Data analysis showed that decoctions were the predominant dosage form in the clinical treatment of DPN. The core syndrome patterns were highly concentrated in Qi deficiency with blood stasis and combined Qi-Yin deficiency. Major outcome measures included nerve conduction velocity, blood glucose levels, and hemorheological parameters. Within the high-frequency herbal spectrum, Carthami Flos, Astragali Radix, Angelicae Sinensis Radix, Chuanxiong Rhizoma, and Paeoniae Radix Rubra occupied dominant positions. The core prescription network exhibited a compatibility structure centered on Astragali Radix, Chuanxiong Rhizoma, and Angelicae Sinensis Radix, with the &quot;Astragali Radix-Angelicae Sinensis Radix&quot; combination demonstrating the highest support in association rule analysis. The core network-derived combination of &quot;Carthami Flos-Chuanxiong Rhizoma-Paeoniae Radix Rubra-Pheretima-Angelicae Sinensis Radix-Persicae Semen&quot; closely corresponded to the classical formula Buyang Huanwu Decoction. Dosage analysis further revealed that the most common compatibility ratio of Astragali Radix to Carthami Flos was 3∶1, and that the dosages of Astragali Radix(mean 36 g) and Angelicae Sinensis Radix(mean 12 g) frequently exceeded standard pharmacopeial recommendations, reflecting a therapeutic strategy characterized by high-dose Qi supplementation to promote blood circulation. The findings suggest that, despite the complex and mixed deficiency-excess pathogenesis of DPN, blood stasis persists throughout the disease course. Carthami Flos-containing formulas primarily act through tonifying Qi, activating blood circulation, resolving stasis, and unblocking the collaterals, embodying a modern clinical strategy of simultaneous regulation of Qi and blood. This study not only quantitatively validates the guiding significance of classical TCM theories in modern DPN management and elucidates the dose-effect relationships of core prescriptions, but also provides a reproducible methodological framework for mining prescription patterns in complex diseases, offering substantial academic value for the modernization and internationalization of TCM.","[""Journal Article"", ""Review"", ""English Abstract""]","[""Zhang X"", ""Wang H"", ""Zhang XW"", ""Gao G"", ""Dan WC""]",10.19540/j.cnki.cjcmm.20260119.501,Zhang X,Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica,1001-5302,12,Zhongguo Zhong Yao Za Zhi,chi,Dan WC,"[""Drugs, Chinese Herbal"", ""Data Mining"", ""Humans"", ""Diabetic Neuropathies"", ""Carthamus"", ""Drug Prescriptions"", ""Flowers""]",3590-3600,42543318,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543318/,[Prescription patterns of Carthami Flos-containing compound formulas in intervention of diabetic peripheral neuropathy based on data mining],51,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Reverificate the taxonomic information of Lacticaseibacillus casei in the genome database of National Center for Biotechnology Information (NCBI) to afford accurate genomic information for L. casei species-specific sequence analysis. Based on the whole genome sequence downloaded from NCBI database, the taxonomic information of 45 L. casei was reverificated by average nucleotide identity (ANI) analysis and phylogenetic analysis based on 16S rRNA gene and 49 core genes. No 16S rRNA gene sequence was extracted from 4 genomes. Of the remaining 41 genomes, the analysis results of ANI were highly in accordance with that of core gene phylogenetic analysis. The results were 21 genomes identified as L. casei and 20 genomes as L. casei related species. Using 16S rRNA gene alone could not accurately identify L. casei and its related species. It is necessary to reverificate the taxonomic information of L. casei in NCBI genome database before using its genome information for further analysis.","[""English Abstract"", ""Journal Article""]","[""Wang Q"", ""Yang L"", ""Wang W"", ""Wei H"", ""Wei Y"", ""Li D"", ""Zhang H""]",10.19813/j.cnki.weishengyanjiu.2026.04.005,Wang Q,Wei sheng yan jiu = Journal of hygiene research,1000-8020,4,Wei Sheng Yan Jiu,chi,Zhang H,"[""Phylogeny"", ""Genome, Bacterial"", ""Lacticaseibacillus casei"", ""RNA, Ribosomal, 16S"", ""Databases, Genetic"", ""Whole Genome Sequencing"", ""Sequence Analysis, DNA""]",558-566,42543226,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543226/,[Evaluating the taxonomy of Lacticaseibacillus casei in National Center for Biotechnology Information genome database based on whole-genome sequence analysis],55,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"To assess the risk of major congenital anomalies (MCAs) and other adverse outcomes following prenatal exposure to modafinil. This retrospective cohort study used the French national healthcare database (SNDS) to include singleton children born between January 2009 and September 2024 of women aged 15-55 years. Prenatal exposure to psychostimulants was defined as maternal dispensation during pregnancy. Children prenatally exposed to modafinil were compared with two control groups: children prenatally exposed to methylphenidate and children prenatally unexposed to any psychostimulant matched to the exposed group using propensity-score matching (PSM). Outcomes included MCAs, neurodevelopmental disorders (NDs), and specialized consultations. Analyses included descriptive statistics, survival analysis, regression models, and dose-response analyses. Of 10 955 766 included children, 865 were prenatally exposed to modafinil and 950 to methylphenidate. Exposure to modafinil during the first trimester of pregnancy was statistically associated with increased risk of MCA compared to methylphenidate, although the confidence interval was wide and close to the null (aRR = 1.77 [1.01-3.07]). Comparison with PS-matched unexposed population indicated a possible modest increase in risk, albeit with a wide confidence interval crossing the null (aRR = 1.23 [0.76-1.99]), showing no clear association. Occurrence of NDs (aHR = 0.96 [0.56-1.65]), and specialized consultations (aHR = 1.08 [0.91-1.28]) were similar in the modafinil and PSM unexposed groups but were higher in the methylphenidate group (NDs: aHR = 0.48 [0.29-0.80]; specialized consultations: aHR = 0.71 [0.59-0.85]). This study shows no increase in neurodevelopmental risk, while a moderate MCA risk cannot be excluded.","[""Journal Article""]","[""Kanoun M"", ""Bouazza N"", ""Treluyer JM"", ""Collier M""]",10.1002/pds.70448,Kanoun M,Pharmacoepidemiology and drug safety,1053-8569,8,Pharmacoepidemiol Drug Saf,eng,Collier M,"[""Humans"", ""Female"", ""Modafinil"", ""Pregnancy"", ""Retrospective Studies"", ""Prenatal Exposure Delayed Effects"", ""Methylphenidate"", ""Adolescent"", ""Adult"", ""Abnormalities, Drug-Induced"", ""Central Nervous System Stimulants"", ""Databases, Factual"", ""Infant, Newborn"", ""Young Adult"", ""France"", ""Middle Aged"", ""Cohort Studies"", ""Neurodevelopmental Disorders"", ""Child"", ""Dose-Response Relationship, Drug""]",e70448,42543074,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42543074/,Prenatal Exposure to Modafinil and the Risk of Major Congenital Anomalies and Other Adverse Neonatal and Pediatric Outcomes,35,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Oral cancer is among the ten most common malignancies worldwide and can be highly lethal if not diagnosed and treated promptly. Mapping the spatial and geographic distribution of this cancer can assist health authorities in planning effective prevention, control, and treatment strategies by identifying its geographic and demographic patterns. This study aimed to investigate the demographic characteristics and geographic distribution of oral cancer in Golestan Province, Iran, during the period 2014-2021. This trend study used data from the National Cancer Registry System of Golestan Province, Iran, covering the period from 2014 to 2021. Geographic mapping of the cities in Golestan Province was performed using ArcGIS software. The annual incidence of oral cancer was calculated for each city and expressed as the number of cases per 100,000 population per year. A total of 390 patients with oral cancer were identified in Golestan Province between 2014 and 2021. Of these, 200 (51.3%) were male and 190 (48.7%) were female. The mean age of the patients was 56.18 ± 17.37 years, ranging from 2 to 96 years. The standardized annual incidence rate of oral cancer in Golestan Province ranged from 4.25 to 6.75 cases per 100,000 population during the study period. Among the cities of the Province, Maraveh Tappeh showed the highest incidence rate, with an average incidence of 12.35 cases per 100,000 population. The incidence of oral cancer in Golestan Province demonstrated temporal fluctuations during the study period, with higher rates observed in several northern cities. Geographic mapping of the disease may provide valuable insights into the potential influence of environmental, cultural, and lifestyle factors on the distribution of oral cancer and can support more targeted prevention and control strategies.","[""Journal Article""]","[""Ghelichli M"", ""Roshandel G"", ""Sohrabi S""]",10.1186/s12903-026-09308-0,Ghelichli M,BMC oral health,1472-6831,1,BMC Oral Health,eng,Sohrabi S,"[""Humans"", ""Iran"", ""Female"", ""Mouth Neoplasms"", ""Male"", ""Adolescent"", ""Middle Aged"", ""Aged"", ""Child"", ""Child, Preschool"", ""Adult"", ""Incidence"", ""Aged, 80 and over"", ""Geographic Mapping"", ""Young Adult"", ""Geographic Information Systems"", ""Registries""]",,42542542,pmc-id: PMC13429022;,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42542542/,"Investigating demographic factors and geographical information mapping (GIS) of oral cancer in Golestan Province, Iran in 2014 to 2021",26,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Protein posttranslational modifications (PTMs) are crucial and dynamic modulators of protein functions, interactions, and localizations, as well as biological pathways and cellular signaling. Lysine succinylation analysis remains challenging, but sophisticated workflows combining succinylated peptide enrichments and quantitative mass spectrometry approaches have revolutionized proteome-wide succinylome analysis. The implementation of data-independent acquisition (DIA)-mass spectrometry has greatly advanced the detection of low-abundance succinylated peptides, succinylome coverage, identification reproducibility, and quantification accuracy. However, the complexity of DIA data requires dedicated data processing algorithms and tools, which typically rely on spectral libraries. These reference libraries can be generated from experimental data-dependent acquisition (DDA) acquisitions of representative study samples submitted to DDA database search engines for confident succinylated peptide identification and precise PTM site localization. Here, we describe how to build DDA PTM spectral libraries using various software tools, specifically Spectronaut, SpectroMine, and MSFragger. The generated libraries were imported into Skyline for the analysis of previously published DIA succinylome data of Sirtuin-5 knocked-out vs wild-type mouse brains in order to accurately quantify and visualize PTM-containing peptides.","[""Journal Article""]","[""Zhang A"", ""Schilling B"", ""Bons J""]",10.1007/978-1-0716-5166-7_11,Zhang A,"Methods in molecular biology (Clifton, N.J.)",1064-3745,,Methods Mol Biol,eng,Bons J,"[""Protein Processing, Post-Translational"", ""Proteome"", ""Proteomics"", ""Software"", ""Animals"", ""Succinic Acid"", ""Mice"", ""Peptide Library"", ""Tandem Mass Spectrometry"", ""Databases, Protein"", ""Peptides""]",169-181,42542529,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42542529/,Generation of High-Quality Succinyl Spectral Libraries for Improved Proteome-Wide Succinylome Analysis Using Data-Independent Acquisition,3018,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Post-translational modifications (PTM) are the covalent modifications of proteins after their biosynthesis. PTMs change the structure and functions of proteins, which eventually regulate various biological processes that are closely related to the onset and development of diseases. Hundreds of different forms of PTMs have been discovered so far and mass spectrometry (MS) has become one of the most important tools to analyze PTMs. With the development of new methods in sample preparation, advances in MS instrumentation, and inventions of new bioinformatic tools, MS-based methods can identify most forms of PTMs, precisely locate the site of modification, sensitively and accurately quantify the changes of modification levels from various of biological samples. This chapter will summarize generic procedures to analyze PTMs with MS methods and provide an update with the latest development in sample preparation, MS analysis, and database search that advanced the way for PTM analysis, improving our knowledge of PTMs and understanding of their roles in various diseases.","[""Journal Article"", ""Review""]","[""Chen R"", ""Zhang X"", ""Li J""]",10.1007/978-1-0716-5166-7_1,Chen R,"Methods in molecular biology (Clifton, N.J.)",1064-3745,,Methods Mol Biol,eng,Li J,"[""Protein Processing, Post-Translational"", ""Mass Spectrometry"", ""Humans"", ""Proteomics"", ""Computational Biology"", ""Proteins"", ""Animals"", ""Databases, Protein""]",3-21,42542519,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42542519/,An Overview of Mass Spectrometry-Based Methods to Analyze Post-Translational Modifications,3018,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"ObjectiveChildren with congenital heart disease are highly vulnerable to drug-related adverse effects due to the use of complex polypharmacy. This study aimed to develop and retrospectively evaluate a hybrid clinical decision support system for predicting drug-related adverse effects in this population.MethodsThis two-phase study combined machine-learning techniques and expert clinical rules. Phase 1 included a retrospective analysis of 4651 pediatric congenital heart disease reports from the Food and Drug Administration Adverse Event Reporting System to train and compare five machine-learning models. The best-performing model, Random Forest, was selected. In Phase 2, a hybrid clinical decision support system integrating the Random Forest model with an expert-validated rule-based engine was developed and retrospectively evaluated using 330 inpatient records of pediatric patients with congenital heart disease.ResultsThe Random Forest model achieved a mean area under the receiver operating characteristic curve of 0.902. During clinical validation, the hybrid clinical decision support system demonstrated a mean accuracy of 0.85 across 11 common drug-adverse effect pairs, outperforming standalone machine-learning- and rule-based approaches. This study demonstrated the feasibility and clinical fidelity of using a hybrid clinical decision support system for predicting drug-related adverse effects in pediatric patients with congenital heart disease, supporting safer and more personalized pharmacotherapy.ConclusionsThis study demonstrated the feasibility and clinical fidelity of using a hybrid clinical decision support system for predicting drug-related adverse effects in pediatric patients with congenital heart disease, supporting safer and more personalized pharmacotherapy.","[""Journal Article""]","[""Toni E"", ""Ayatollahi H"", ""Abbaszadeh R"", ""Fotuhi Siahpirani A""]",10.1177/03000605261472034,Toni E,The Journal of international medical research,0300-0605,7,J Int Med Res,eng,Fotuhi Siahpirani A,"[""Humans"", ""Heart Defects, Congenital"", ""Decision Support Systems, Clinical"", ""Retrospective Studies"", ""Child"", ""Drug-Related Side Effects and Adverse Reactions"", ""Female"", ""Random Forest"", ""Child, Preschool"", ""Male"", ""Machine Learning"", ""Infant"", ""ROC Curve"", ""Predictive Learning Models"", ""Adverse Drug Reaction Reporting Systems"", ""Prediction Algorithms""]",3000605261472034,42541705,pmc-id: PMC13428899;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42541705/,A clinical decision support system for predicting drug-related adverse effects in pediatric patients with congenital heart disease: Development and retrospective evaluation,54,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Diabetes mellitus (DM) approximately doubles the risk of atherosclerotic cardiovascular disease (ASCVD) events, but the molecular basis is poorly understood. Using RNA-sequencing data from two arterial sites in >90 people with DM and >330 controls, we defined differentially expressed genes (DEGs) associated with DM. UK Biobank (UKB) was then used to corroborate that DEGs in their plasma protein form were differentially abundant in people with DM and associated with ASCVD events. 619 and 356 DEGs were associated with DM in the thoracic aorta and tibial artery, respectively. Of these, 22 were common to both arteries, all of which were directionally concordant. Of these, 5 were included in the UKB plasma proteomics dataset and we corroborated 4 (ACP5, LEFTY2, LILRA5 and PSME2) as showing concordant differential abundance in people with DM; all were associated with a range of incident ASCVD events. Addition of the 4 proteins to the SCORE2 and SCORE2-Diabetes risk models (for people without and with DM, respectively) improved the population-level discrimination, classification and calibration of these models. These data show that DM is associated with a distinct arterial gene expression profile, hits from which are associated with ASCVD events and add value to risk prediction.","[""Journal Article""]","[""Shouma A"", ""Giannoudi M"", ""Conning-Rowland M"", ""Drozd M"", ""Brown OI"", ""Cheng C"", ""Sukumar P"", ""Bridge KI"", ""Levelt E"", ""Bailey MA"", ""Griffin KJ"", ""Kearney MT"", ""Cubbon RM""]",10.1177/14791641261474099,Shouma A,Diabetes & vascular disease research,1479-1641,4,Diab Vasc Dis Res,eng,Cubbon RM,"[""Humans"", ""Transcriptome"", ""Diabetic Angiopathies"", ""Gene Expression Profiling"", ""Case-Control Studies"", ""Proteomics"", ""UK Biobank"", ""Risk Assessment"", ""Biomarkers"", ""Genetic Markers"", ""Predictive Value of Tests"", ""Male"", ""Atherosclerosis"", ""Female"", ""Prognosis"", ""Risk Factors"", ""Middle Aged""]",14791641261474099,42541450,pmc-id: PMC13428926;,2026 Jul-Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42541450/,Analysis of the diabetic arterial transcriptome to define novel biomarkers of macrovascular disease,23,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"In renal transplant recipients, infections can have atypical outcomes due to immunosuppression therapy, and delayed diagnosis causes high mortality. We developed an infection risk score in renal transplant recipients to rapidly predict infection risk in emergency departments. Of 870 renal transplant recipients admitted to the emergency department, we included 608 patients and 262 control cases. Hospital record system data for renal transplant recipients were retrospectively investigated for the period January 2021 through December 2025. Laboratory and vital signs of patients suspected of infection were compared versus asymptomatic control cases admitted for routine check -ups. All of our patients metethical standards and were selected as related donors and recipients. Demographic characteristics and findings of 608 patients and 262 control cases were compared, and no significant difference was found between the 2 groups in terms of comorbidities (P > .05 ). The most frequent presenting symptom was diarrhea (20.1 % ); the least frequent symptom was sore throat (6.6 % ). Leukocytes, neutrophils, neutrophil -lymphocyte ratio, plasma -lymphocyte ratio, C -reactive protein, and sodium and potassium levels, as well as vital signs including fever, pulse, blood pressure, and peripheral oxygen saturation, were associated with infection. This novel infection risk score comprised 6 parameters, including C-reactive protein, neutrophil -lymphocyte ratio, sodium, fever, pulse, and systolic blood pressure, predicted infections with 89.1 % (area under the curve ) accuracy. Sensitivity, specificity, positive predictive value, and negative predictive value of the score were 0.734, 0.905, 0.947, and 0.594, respectively. The novel infection risk score developed in our study predicts infections in renal transplant recipients with high accuracy using only routine biochemical and vital parameters. This practical, rapid, and reliable system can contribute to early diagnosis processes in emergency departments. Future external validation through multicenter studies is needed to support its integration into clinical guidelines.","[""Journal Article""]","[""Muratoglu M"", ""Bulut B"", ""Manevi AR"", ""Yıldırım HS"", ""Kilicoglu Tanir S"", ""Cheraqi MS"", ""Safak A"", ""Yildirim S"", ""Haberal M""]",10.6002/ect.2026.0152,Muratoglu M,Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation,1304-0855,6,Exp Clin Transplant,eng,Haberal M,"[""Humans"", ""Kidney Transplantation"", ""Female"", ""Risk Factors"", ""Risk Assessment"", ""Predictive Value of Tests"", ""Retrospective Studies"", ""Male"", ""Adult"", ""Middle Aged"", ""Immunosuppressive Agents"", ""Decision Support Techniques"", ""Immunocompromised Host"", ""Treatment Outcome"", ""Emergency Service, Hospital"", ""Emergency Room Visits"", ""Opportunistic Infections"", ""Time Factors"", ""Communicable Diseases""]",450-459,42541323,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42541323/,Development of A Novel Infection Risk Score for Prediction of Infections in Renal Transplant Recipients,24,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"CBS microdata is a valuable resource that provides researchers secure access to nearly all individual-level data available within Statistics Netherlands (CBS). The data is originated from administrative registers (e.g., Dutch Tax Authority, Personal records database (BRP)) and statistical surveys conducted by CBS. As such, CBS microdata includes information on individuals, households, businesses, and more, making it highly relevant for demographic, sociological and economic research. One of the key strengths of CBS microdata is its ability to link diverse datasets, enabling researchers to connect individuals to households, jobs to individuals, companies to jobs, and many other relationships. Furthermore, data can be linked across time, allowing for in-depth longitudinal studies. Researchers can also upload their own datasets, which can be pseudonymized and linked with CBS microdata to create even richer data analyses. CBS places a high priority on data security. Access to CBS microdata is strictly controlled and granted only to authorized institutions. Universities, scientific organizations, and public policy institutes in EEA countries can request authorization. All research is carried out within a secure CBS microdata environment, with privacy safeguards in place to ensure no individual-level data leaves this environment. Thanks to the vast amount of data, it's detailed level, the ability to link datasets, and robust data security, CBS microdata provides valuable insights into complex societal trends and relationships and therefore plays a vital role in supporting scientific or statistical research. More information can be found here: https://www.cbs.nl/en-gb/our-services/customised-services-microdata/microdata-conducting-your-own-research.","[""Journal Article""]","[""Slager T""]",10.23889/ijpds.v11i5.3712,Slager T,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Slager T,"[""Netherlands"", ""Humans"", ""Databases, Factual"", ""Computer Security"", ""Registries""]",3712,42541140,pmc-id: PMC13426809;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42541140/,CBS Microdata,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"My presentation uses data linkage to build data on Taiwan indigenous peoples (TIPs) as an example. TIPs used to be invisible and marginalized in Taiwan. In recent years, TIPs not only become very visible in Taiwan, but are also known globally. The most important contribution that helps TIPs become visible and are empowered in the real world is successfully building a number of big open data sets (see TIPD at https://osf.io/e4rvz/), based on open science, open data, data science, and scientific computing. Central to the processes of building open data are data linkage, including deterministic and probabilistic, that integrate Taiwan household registers and other administrative data from 2007 to 2024. Using data linkage, I have successfully built longitudinally linked register big data of population dynamics, with individual-level spatial information (point) and temporal information (monthly) being integrated in the linked data. In my presentation, I will demonstrate data linkage in building big complexed liked data (e.g., longitudinal and genealogy data), with a particular emphasis on the role of fine-tuning computing infrastructure (e.g., accelerating CPUs, DRAM, data transfer buses between CPUs-DRAM and between CPUs-PCIe lanes) to accelerate computing speed while conducting massive data linkage. In addition, I will demonstrate an automated geocoding method that allows us to parse spatial information from Google Map quickly and how legal and ethical issues are resolved. For reference, see https://link.springer.com/article/10.1007/s43545-025-01049-1.","[""Journal Article""]","[""Lin J""]",10.23889/ijpds.v11i5.3617,Lin J,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Lin J,"[""Taiwan"", ""Humans"", ""Registries"", ""Big Data"", ""Longitudinal Studies"", ""Information Storage and Retrieval""]",3617,42541097,pmc-id: PMC13426832;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42541097/,How Data Linkage Is Applied to Build Longitudinally Linked Data and Genealogy Data Based on Massive Sources of Administrative Data: A Two-decade Research on Linking Taiwan Household Registers,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"While data linkage has traditionally used bespoke, customer led methods, an increased demand for linked data has led to the development of indexes representing people, businesses and locations. Data are linked to indexes through generalised methods, and an index ID is appended to each statistical entity in the dataset. Users request relevant data and join them on index IDs. This process is called indexing. This approach has clear benefits, but there is still uncertainly about the quality of indexing and the quality of datasets linked through index IDs. The Indexing First Research programme provides evidence to better understand the quality outputs of these processes and give clear precedents to direct the future application of indexing. It takes existing bespoke linkages and compares them to an indexing approach on the same project. This provides evidence on the coverage of the indexes, precision and recall of different methods and bias in each linkage method. This paper will set out the aims of the research programme and the progress to date. It will discuss the outcomes of indexing hard to link populations (ie. homeless people and prisoners), of comparing bespoke linkages and linkages via the indexes (ie. births-deaths linkages), and the accuracy of indexing data through generalised methods (ie. nursing data linked to the persons index). This research has implications for the approach taken to data linkage and gives direction for when indexing is appropriate and when bespoke linkage is required.","[""Journal Article""]","[""Lewis E"", ""Cummins S"", ""O'Connor N"", ""Allen B""]",10.23889/ijpds.v11i5.3693,Lewis E,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Allen B,"[""Humans"", ""Information Storage and Retrieval"", ""Abstracting and Indexing"", ""Data Accuracy""]",3693,42541071,pmc-id: PMC13426769;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42541071/,Indexing First Research: understanding the quality of generalised data linkage processes,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Scalelink is an innovative probabilistic data linkage method based on multiple correspondence analysis. Unlike the current gold-standard probabilistic algorithm, Fellegi-Sunter, it does not assume linkage variable independence. All real-world linkage contains dependent linkage variables. Thus, avoiding this assumption has potential to improve data linkage quality. However, to date there are no recommendations regarding handling missing data values when using Scalelink. As all real-world data contains missingness, this means Scalelink cannot currently be used for real-world linkage. Seven candidate methods were identified from the literature as being used in multiple correspondence analysis. They were iteratively tested, first using tiny artificial datasets and subsequently using random samples of real-world census data. These tests were performed using a novel Python/PySpark implementation of Scalelink. Initial testing resulted in a three-method short-list: the Missing Single method (which treats missingness as an agreement state) and two variants of the Missing Insertion method (which removes missingness by imputing donor values). Following testing, results were analysed by comparing precision, recall and the F1 metric. From this, the Missing Single method was clearly unsuitable for use with Scalelink. However, both of the other methods worked well, although they should be used for different types of missingness. Despite imputation being highly counter-intuitive for linkage, this work demonstrates that it is the best way to handle missingness when using Scalelink. This finding supports further testing of Scalelink in more realistic scenarios, increasing its potential to improve probabilistic data linkage and facilitate more reliable decision-making based on linked datasets.","[""Journal Article""]","[""Cleaton M"", ""Thomson G"", ""Plachta J"", ""Shipsey R""]",10.23889/ijpds.v11i5.3533,Cleaton M,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Shipsey R,"[""Algorithms"", ""Humans"", ""Information Storage and Retrieval"", ""Models, Statistical""]",3533,42541040,pmc-id: PMC13426765;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42541040/,Handling missing data when using Goldstein et al.'s Scalelink method of data linkage,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Across the United States, linking electronic health record (EHR) data with public health and other publicly available datasets remains a significant challenge due to the lack of a universal patient ID and limited interoperability. While technology exists to overcome these barriers, silos between primary care, tertiary care, and public health (PH) entities continue. AllianceChicago (AC), a network of Federally Qualified Health Centers (FQHCs), participates in two key initiatives, Multi-State EHR-based Network for Disease Surveillance (MENDS) and CAPriCORN, a Federated Data Network, to connect clinical data for public health surveillance, research, and care continuity. AC is working to bridge these efforts to strengthen integration between healthcare delivery and public health systems. A recent project completed using CAPriCORN related to Youth Suicide Prevention analyzed care utilization patterns linking a primary care cohort of youth (age ≤24) hospitalized for suicide attempt or ideation to tertiary care data. Findings revealed gaps in timely follow-up care, with only 16% receiving a primary care visit and 41% a psychiatric visit within 30 days of discharge. These insights informed the development of solutions to improve referral pathways between social and behavioral services and healthcare for care continuity. Similarly, MENDS, leverages standardized EHR data for chronic disease surveillance. AC contributes de-identified data from 17 FQHCs and collaborates with PH agencies using vetted tools to identify geographic risk hotspots and inform program planning. Emerging use cases demonstrate that improved data linkage and infrastructure can enhance PH surveillance and care coordination, paving the way for more effective health systems.","[""Journal Article""]","[""Hamilton A"", ""Sital S"", ""VanDoren K""]",10.23889/ijpds.v11i5.3715,Hamilton A,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,VanDoren K,"[""Electronic Health Records"", ""Humans"", ""United States"", ""Population Surveillance"", ""Public Health"", ""Population Health"", ""Digital Health"", ""Primary Health Care"", ""Datasets as Topic""]",3715,42541036,pmc-id: PMC13426787;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42541036/,Real World Use of EHR data and Public Data Sets to Inform Public Health and Population Health Research and Surveillance,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Adolescents with neurodisability (neurological conditions causing functional limitations) have more complex needs than their peers, yet population-level evidence on secondary school outcomes remains limited. Using linked health and education records from the ECHILD database, we developed a national cohort of Year 6 pupils (final year of primary school, ages 10-11) in state schools between 2007/08-2016/17. Neurodisability was identified from hospital and school records before Year 6. We described the proportion of pupils with Special Educational Needs and Disabilities (SEND) provision in Year 6, and examined planned and unplanned hospital admission rates and school absence rates (% of school sessions missed) from Year 6 through secondary school (Years 6-11, ages 10-16). Of 5,291,458 adolescents in Year 6, 226,689 (4.3%) had recorded neurodisability, 78% of whom had any SEND provision (versus 20% without neurodisability). One-quarter had intensive local government-funded provision. Between Years 6-11, adolescents with neurodisability had 5 times higher planned admission rates (19.8 vs 3.7 per 100 person-years), 3 times higher unplanned rates (9.7 vs 3.8 per 100 person-years), and 2 times higher stress-related rates (2.5 vs 1.3 per 100 person-years) compared with peers. Overall absence rates were 7.2% versus 5.4% for peers, increasing over time and driven by authorised absences (5.8%, mostly health-related). Unauthorised rates were comparable (1.2-1.4%). Girls had consistently higher admission and absence rates than boys. Adolescents with neurodisability experience substantially greater health and educational challenges. Linked administrative datasets can inform targeted and integrated support from secondary school transition onward.","[""Journal Article""]","[""Macaulay L"", ""Saxton J"", ""Ford T"", ""Logan S"", ""Harron K"", ""Gilbert R"", ""Shumway J"", ""Nguyen V"", ""De Stavola B"", ""Totsika V""]",10.23889/ijpds.v11i5.3593,Macaulay L,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Totsika V,"[""Humans"", ""Adolescent"", ""Female"", ""Male"", ""England"", ""Child"", ""Education, Special"", ""Educational Status"", ""Databases, Factual"", ""Nervous System Diseases"", ""Health Status""]",3593,42541006,pmc-id: PMC13426650;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42541006/,Health and educational outcomes among adolescents with neurodisability in England: a population-based linked data study using ECHILD,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Comparing names is at the core of many data linkage applications. Names can be recorded with variations and errors (typographical, phonetic, or scanning, depending on how names have been captured). Furthermore, names can change over time. Therefore, approximate string comparison functions are commonly employed to calculate similarities between names. There are many such comparison functions, with popular ones including Jaro-Winkler, edit distance, and q-gram based techniques. Which ones are suitable for a given data linkage application is a topic that has not been explored in much detail. Selecting a suitable string comparison function is, however, crucial in the context of bias and fairness when linking population databases that can contain ethnically diverse names, as recent research has shown (for example, see Lam et al,. IPDLN 2024).In this work, we investigate the following question: Do different string comparison functions result in different levels of bias when names from different ethnic groups are being compared? We conducted extensive experiments on a large public population database where the ethnicity of each record is available. By comparing name variations of the same person using multiple string comparison functions, we show that some of these functions exhibit larger similarity ranges than others, while very different similarities are obtained for the same name pair depending upon which comparison function is employed. Our results provide important insights into how practical data linkage of large population-level databases should be conducted in order to limit linkage bias with regard to ethnic groups by employing suitable string comparison functions.","[""Journal Article""]","[""Dharmawimala Y"", ""Christen P"", ""Ziyad S"", ""Vidanage A"", ""Lam J"", ""Schnell R""]",10.23889/ijpds.v11i5.3756,Dharmawimala Y,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Schnell R,"[""Names"", ""Humans"", ""Ethnicity"", ""Databases, Factual""]",3756,42541000,pmc-id: PMC13426649;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42541000/,The influence of ethnic name characteristics on string similarities when linking large heterogeneous population databases,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Cross-agency data-sharing collaborations have proven crucial to ensure effective usage of often limited funds. Through, delivering these resources to the right people in the right circumstances at the right time. Despite the cumbersome and often time-consuming process of setting those collaborations up. The data linkage part of those collaborations does not need to be time consuming. If it is well planned. Here we present two vastly different data linkage experiences and lessons learned, from our Scottish Safe Haven, supporting cross-agency social-housing and health projects. Collaborations between health board, local authorities, universities and charities, that set out to improve the health and well-being of vulnerable groups while simultaneously reducing the pressure on the local health system. Both projects required data linkage between the partners datasets; an NHS identified group of vulnerable people and a variety of property details and metrics, to identify those most in need. These datasets are inherently not homogenised nor set up for cross-sector data linkage. One project required a time-intensive multi-stage mixed-method linkage approach combining direct matching across multiple variable fields with fuzzy-matching techniques and manual verification. Where a year later, the other project was able to utilise a unique property identifier, that only had recently been introduced into the data of the national health care provider. Whilst we recognise, that a single unifying unique identifier is not always available for data linkage across different agencies. We propose a framework of recommendations to consider before the data sharing that can facilitate a smooth data linkage process.","[""Journal Article""]","[""Scheliga B"", ""Wilde K"", ""Evans J"", ""E Butler J"", ""Berrocal-Martin R""]",10.23889/ijpds.v11i5.3680,Scheliga B,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Berrocal-Martin R,"[""Humans"", ""Information Dissemination"", ""Scotland"", ""Information Storage and Retrieval"", ""Cooperative Behavior""]",3680,42540995,pmc-id: PMC13426659;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540995/,An Experience-Driven Framework for Overcoming Challenges in Cross-Agency Data Linkage,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Established in 2020, the National Centre for Healthy Ageing (NCHA) Data Platform is Australia's first linked hospital-based electronic health record (EHR) research database covering all residents within a geographic region. Recent activities have expanded its scope, reach, and innovation. The platform houses internally linked data for >1 million people, 4 million clinical encounters (2015 onwards) from two acute hospitals, two sub-acute hospitals, and >10 community health services serving 300,000 residents. Automated weekly updates and data improvement processes enhance reliability. Semi-automated extraction and streamlined ethics/governance enable rapid data access within a Trusted Research Environment. Expansion efforts include an AI pipeline to extract concepts from clinical notes and linkage to local, state, and national datasets (e.g., primary care, medication, aged care, Medicare, cohort studies). National collaborations are exploring expansion to other Australian regions. The platform has overcome barriers to optimising EHR data for research, providing a test-bed for national and international priorities. Researchers have leveraged the platform for >60 projects, securing >$20M in grants on topics including dementia, aged care, medication use, homelessness, environmental health, and healthcare redesign. NLP models have been trained to detect dementia and opioid harms. Linked state and commonwealth data for 179,089 residents aged over 60 years (2010-2021) achieved 98.4% accuracy. Expansion feasibility is being explored through a national working group, and future inclusion in the National Person Level Integrated Data Asset. The NCHA Data Platform exemplifies how linked EHR data can advance population health research and underpin data-driven innovation across domains.","[""Journal Article""]","[""Andrew N"", ""Beare R"", ""Mann E"", ""Parikh S"", ""Carver A"", ""Collyer T"", ""Ung D"", ""Dhillon R"", ""Srikanth V""]",10.23889/ijpds.v11i5.3648,Andrew N,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Srikanth V,"[""Electronic Health Records"", ""Humans"", ""Australia"", ""Medical Record Linkage"", ""Databases, Factual"", ""Healthy Aging"", ""Hospitals"", ""Digital Health""]",3648,42540987,pmc-id: PMC13426665;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540987/,"Hospital Electronic Health Records as a research resource: data linkage, national scale-up, and five-year Impact of the National Centre for Healthy Ageing Data Platform",11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Administrative Data Research (ADR) is transforming evaluation practice by improving robustness, complementing more traditional methods, and enabling evidence-based decision-making. In Wales, ADR Wales has embedded administrative data linkage into all Welsh Government evaluability assessments as standard practice, ensuring evaluations consider these rich data sources. Through the Secure Anonymised Information Linkage (SAIL) Databank, more Welsh population-level administrative data is available in Trusted Research Environments (TREs) that can be linked together, creating opportunities for evaluators to innovate. ADR Wales-a partnership between Welsh Government, Swansea University Medical School, and WISERD at Cardiff University-has demonstrated the value of linked data to Ministers and policy colleagues by informing evaluations of major initiatives, including early years interventions, the 20mph speed limit legislation, the basic income pilot for care leavers, tertiary education reform, and much more. Working alongside the UK Evaluation Society and the UK Evaluation Taskforce, ADR Wales is helping to mainstream administrative data use across the ADR UK network. This work improves evaluation quality, delivers value for money, and has a direct impact on citizens' lives. Supported by UK Research and Innovation and the ESRC, our renewed five-year funding will strengthen collaboration and expand data linkage opportunities. This session will showcase Welsh innovations in linked ADR, highlight practical strategies for integrating administrative data into evaluation design, using administrative data to complement other evaluation methods, and share lessons on how to encourage data owners (e.g. police, local authorities, and the third sector) to share data in TREs to unlock future evaluation potential.","[""Journal Article""]","[""Gracey F"", ""Davies H""]",10.23889/ijpds.v11i5.3748,Gracey F,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Davies H,"[""Databases, Factual"", ""United Kingdom"", ""Wales"", ""Routinely Collected Health Data""]",3748,42540986,pmc-id: PMC13426666;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540986/,Capitalising on administrative data to innovate and drive evaluation excellence,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Parental substance misuse is a known risk factor for adverse child outcomes, yet large-scale UK evidence linking household misuse across health and justice systems to education remains limited. This study leverages whole-population linked administrative data in Wales to address this gap, operationalising policy commitments for earlier intervention. This retrospective electronic cohort study utilised the Secure Anonymised Information Linkage (SAIL) Databank. The cohort included children aged 11-15. A novel linkage combined Magistrates Court data with health records to define household substance misuse (SMHH). Children were categorised by the adult's misuse source: health only (SMHH-H), justice only (SMHH-J), or both (SMHH-HJ). Multilevel models analysed associations with school attendance and exclusions, adjusting for deprivation and Special Educational Needs (SEN). Exposure to household substance misuse was significantly associated with reduced attendance and increased exclusion odds. A clear risk gradient emerged: children in the SMHH-HJ group (misuse identified in both health and justice systems) experienced the poorest educational outcomes: highest likelihood of exclusion, lower attendance rates. These associations remained significant after adjusting for SEN and mental health, with effects compounded by socioeconomic deprivation. Household substance misuse, particularly when interacting with the justice system, is a critical marker for educational disengagement. By linking cross-sectoral data at a population scale, this study highlights the necessity of integrated preventative strategies across health, justice, and education to break cycles of disadvantage.","[""Journal Article""]","[""Farr I"", ""Turner Evans H"", ""Bailey G"", ""Davies G"", ""James D"", ""Smith J""]",10.23889/ijpds.v11i5.3628,Farr I,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Smith J,"[""Humans"", ""Wales"", ""Substance-Related Disorders"", ""Retrospective Studies"", ""Child"", ""Adolescent"", ""Female"", ""Male"", ""Educational Status"", ""Family Characteristics"", ""Risk Factors"", ""Socioeconomic Factors"", ""Information Storage and Retrieval""]",3628,42540976,pmc-id: PMC13426804;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540976/,"Educational Outcomes for Children in Intergenerational Households with Substance Misuse: A National Data Linkage Study in Wales, UK",11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Linkage of National Pupil Database (NPD) to national hospital data has the potential to provide almost universal population coverage of children and young people in England. However, quantifying who is missed is a key requirement for producing unbiased population estimates. Deterministic linkage was conducted between longitudinal data from the NPD and secondary healthcare services via the NHS Personal Demographic Service. National Data OptOuts were applied to the linked data. We assessed the proportion of individuals who linked and used modified Poisson regression with robust standard errors to evaluate the risk of non-linkage when accounting for a variety of social determinants. Of 25,286,870 individuals born between 1984-2020 included in NPD, 84% (21,287,176/25,286,870) linked to a secondary care dataset. Linkage rates improved from 66% (507,820/765,642) for those born in 1985/86 to 98% (306,165/311,121) in 2019/20 and ranged from 89% (908,998/1,026,575) for those with Black ethnicity to 95% (13,644,182/14,401,835) in White groups. Females (IRR: 1.08, 95%CI: 1.08- 1.09) and those living in more deprived areas or in London were more likely to be unlinked. Individuals with recorded Special Educational Needs provision (IRR: 0.81, 95%CI: 0.81-0.82) or Free School Meals (IRR: 0.67, 95%CI: 0.67-0.68) were less likely to be unlinked. Whilst linkage rates have improved over time, there remain important differences in sex, ethnicity, deprivation and geography, between those who are and are not included in the linked dataset. Given high overall linkage rates reported by data providers, these differences are primarily driven by the application of Opt-Outs.","[""Journal Article""]","[""Nguyen V"", ""Ramzan F"", ""Ruiz Nishiki M"", ""Blackburn R"", ""Gilbert R"", ""Harron K""]",10.23889/ijpds.v11i5.3520,Nguyen V,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Harron K,"[""Humans"", ""England"", ""Female"", ""Male"", ""Child"", ""Adolescent"", ""Educational Status"", ""Databases, Factual"", ""Hospitals"", ""Child, Preschool""]",3520,42540975,pmc-id: PMC13426679;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540975/,Linking population-level education and hospital data in England: who are we missing in ECHILD?,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"This paper introduces the Longitudinal Education Outcomes Northern Ireland (LEO NI) dataset-an anonymised, research-ready resource that exemplifies the transformative potential of administrative data linkage. LEO NI integrates school-level records for individuals aged 14+ across eight academic years with seven years of post-16 data from Apprenticeships, Training Programmes, Further Education (FE), and Higher Education (HE). The dataset is designed to advance population data science by enabling empirical studies on educational attainment and post-16 trajectories, with direct implications for policy and practice. We detail methodological innovations in linking diverse administrative sources from the Department of Education and Department for the Economy, including School Census (with attendance), School Leavers Survey, and training/apprenticeship records. Linkage was achieved using anonymised identifiers under robust governance frameworks, ensuring privacy and compliance with legal standards. Additional variables capture Special Educational Needs (SEN) and health conditions, supporting complex, multi-dimensional analyses. The resulting dataset comprises circa 0.5 million unique individuals and includes comprehensive metadata and a researcher guide. We outline quality assurance processes, linkage accuracy, and strategies for managing high-volume, heterogeneous data. These methodological insights contribute to best practices in large-scale data infrastructures. We highlight policy areas where this dataset can be used. Scheduled for release in Spring 2026 via secure research environments, LEO NI offers unprecedented opportunities for longitudinal analysis of education and employment outcomes. By translating methodological advances into actionable evidence, LEO NI demonstrates how linked administrative data can inform policy across sectors and jurisdictions, while addressing ethical and governance challenges.","[""Journal Article""]","[""Wilgar P"", ""McCullough N"", ""Norris E"", ""Foley B"", ""Ross J""]",10.23889/ijpds.v11i5.3547,Wilgar P,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Ross J,"[""Northern Ireland"", ""Humans"", ""Longitudinal Studies"", ""Educational Status"", ""Datasets as Topic""]",3547,42540955,pmc-id: PMC13426728;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540955/,Building the Longitudinal Education Outcomes Northern Ireland (LEO NI) Dataset: Linking Administrative Data for Policy Impact,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Millions of children in the UK experience early adversity, with many requiring children's social care (CSC) support. National longitudinal data on these children is essential to understand lifelong impacts on health and development, yet they are often excluded from the UK's leading child development studies. This study explored the feasibility of using linked administrative records for sampling, supported by discussions with data owners. We analysed populationlevel administrative data from the SAIL Databank (Wales) and the ECHILD database (England) to identify maternal psychosocial risk factors (such as mental health conditions, substance misuse and domestic violence) and CSC involvement before age six. A cohort was created of mothers with live births between April 2009 and March 2016, linked to secondary healthcare and CSC records. In parallel, we engaged with data providers across the UK to assess practical and governance considerations. In Wales, 15% of mothers whose child was involved in CSC had psychosocial risk factors. By contrast, only 4% of mothers without these risk factors had a child with CSC involvement. Further analyses are ongoing. Data providers confirmed that while administrative records have precedent for recruitment, ethical and sensitivity concerns pose barriers. Findings highlight links between maternal vulnerability and CSC involvement, alongside rising psychosocial adversities. Administrative data offers valuable insights but using it to identify children at risk remains complex. Differences in legislation, governance, and data access across UK nations hinder a unified sampling frame, especially given the sensitivity of maternal and social care records.","[""Journal Article""]","[""Jane Griffiths L"", ""Raybould A"", ""Dennison K"", ""Harron K"", ""Bailey G""]",10.23889/ijpds.v11i5.3588,Jane Griffiths L,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Bailey G,"[""Humans"", ""Female"", ""Risk Factors"", ""Mothers"", ""Child"", ""Wales"", ""Child, Preschool"", ""Infant"", ""Databases, Factual"", ""United Kingdom"", ""Substance-Related Disorders"", ""England""]",3588,42540932,pmc-id: PMC13426604;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540932/,Can and should we? Use of maternal administrative data to identify children at risk of poor outcomes,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"This work aims to construct a dataset of unique addresses from Brazilian administrative, socioeconomic, and health databases. We assess the potential of iterative deduplication to generate a parent-duplicate data structure that supports address management and downstream information retrieval tasks. Our approach followed three steps: local deduplication within each database to establish parent-duplicate relationships; cross-database deduplication to identify global parent records and propagate their identifiers; and iterative deduplication of global parent records, updating assignments across databases. Graph-based modeling was used to identify shared connected components, enhancing geocoding coverage. Deduplication accuracy was evaluated through manual review of state-stratified samples (N = 2,000), with independent assessment by at least two reviewers and disagreements resolved by a third. Five data sources from Northeastern Brazil were used: the National Register of Addresses from 2010 (CNEFE 2010; N = 17,839,562), CNEFE 2022 (N = 30,545,117), the 100 Million Brazilian Cohort baseline (CadÚnico; N = 54,985,455), Mortality (SIM; N = 6,431,199), and Live Birth (SINASC; N = 17,199,287). Local deduplication substantially reduced data volume, identifying 8.25M, 531 thousand, and 583 thousand parent records for the CadÚnico, SIM, and SINASC, corresponding to reductions of 77.84%, 91.74%, and 96.61%. After iterative cross-database deduplication. The resulting database comprised 28.6M records, including 24.8M unique parent addresses and 5.9M duplicates. Average deduplication precision across all steps exceeded 0.9. Iterative deduplication is an effective strategy for enhancing data management and quality across heterogeneous datasets, facilitating large-scale spatial analysis for public health and climate change research.","[""Journal Article""]","[""Pita R"", ""Ichihara M"", ""Rocha G"", ""Santos C"", ""Ribeiro L"", ""Pita P"", ""Sena S"", ""Eustáquio F"", ""Gomes J"", ""Silva R""]",10.23889/ijpds.v11i5.3727,Pita R,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Silva R,"[""Brazil"", ""Humans"", ""Databases, Factual"", ""Geographic Information Systems"", ""Geographic Mapping""]",3727,42540920,pmc-id: PMC13426779;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540920/,Large-scale geocoding via iterative deduplication: Building a unified address database in Brazil with CIDACS-RL,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Leveraging routinely collected health services data to conduct scientifically robust research requires a clear understanding and standardization of data from disparate clinical information systems which often change over time. Within Alberta Provincial Research Data Services (PRDS) a large team of analysts utilize a vast Enterprise Data Warehouse containing dozens of datasets with various update cycles and availability, generally spanning more than 20 years of data for a Canadian province of over 4 million people. We examine two recently developed standardized data marts for mortality and medical lab tests. These data marts are now updated daily using Snowflake Tasks to ensure timely data can be accessed as needed to support research studies. The mortality data are linked from three sources to ensure comprehensive coverage: Vital Statistics, Provincial Registry, and Connect Care (the provincial Epic based electronic medical record) and resolves inconsistencies in personal health numbers and discrepancies in dates of death. The Lab data mart uses test level data from several different historical lab systems and the current Connect Care system and consolidates coding and definitions over time to create a clean, easy to use data mart. Both use cases create a single, validated and linkable source of truth that is easy to use for research studies, negating the need for each analyst to re-engineer from several different source tables each time. The process used here will be applied to other subject matters internally and could be similarly applied data warehouse environments in other jurisdictions.","[""Journal Article""]","[""Youngson E"", ""Armani N"", ""Whitten T"", ""Quan H"", ""Li B"", ""Wang T"", ""Bakal J""]",10.23889/ijpds.v11i5.3678,Youngson E,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Bakal J,"[""Humans"", ""Alberta"", ""Data Warehousing"", ""Electronic Health Records"", ""Registries""]",3678,42540915,pmc-id: PMC13426613;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540915/,"Clean Data, Breakthrough Insights: The Importance of Standardizing Your Research Warehouse",11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Many jurisdictions have linked education and health data throughout childhood to address policy questions relating to equity and effectiveness of services. We use the example of special educational needs and disability (SEND) policy to show that causal evidence of effectiveness, based on administrative data, can be limited and potentially misleading. We discuss what needs to change. We derived health phenotypes to group children likely to benefit from SEND provision and used the target trial emulation framework to define causal contrasts, reduce design biases and guide analytic methods. We estimated the effectiveness of SEND provision at age 5/6 on outcomes recorded in health and education data for two phenotypes (cerebral palsy and cleft lip/palate). SEND provision did not improve rates of unplanned hospital admissions or educational attainment but did reduce rates of unauthorised school absences for both phenotypes. These results are likely biased due to unmeasured confounding and imprecise measures of SEND provision and relevant outcomes. We failed to find instrumental variables to account for unmeasured confounding. Despite the detailed information on health and school characteristics in ECHILD, there is insufficient information on which children are selected for which SEND interventions or comparators. Causal evaluations of SEND provision using observational analyses of ECHILD need linkage to additional measures of need, interventions and outcomes. Adding similar measures to linked health-education data across jurisdictions, and wider use of experimental designs, would help to quantify effective and generalisable SEND practices. These lessons are likely relevant to other practitioner-based interventions.","[""Journal Article""]","[""Gilbert R"", ""De Stavola B"", ""Nguyen V"", ""Harron K""]",10.23889/ijpds.v11i5.3684,Gilbert R,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Harron K,"[""Humans"", ""England"", ""Education, Special"", ""Child Health"", ""Child"", ""Child, Preschool"", ""Databases, Factual"", ""Cerebral Palsy"", ""Causality"", ""Cleft Lip"", ""Cleft Palate"", ""Female"", ""Educational Status"", ""Male"", ""Secondary Data Analysis""]",3684,42540912,pmc-id: PMC13426612;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540912/,What is needed to make administrative data 'research ready' for causal inference? A case study of the Education and Child Health Insights from Linked Data (ECHILD) database of 15 million children in England,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"This presentation demonstrates how the ODISSEI research infrastructure enables interoperable, population-scale social science through the integration of data, compute, and services. At the core of the architecture is access to high-quality administrative microdata via Statistics Netherlands (CBS), combined with secure storage and linkage through the CBS Data Storage environment. Discovery and contextualisation of these data are facilitated through the ODISSEI Data Access Broker (DAB) and the ODISSEI Portal, which together streamline dataset findability, access requests, and metadata harmonisation across providers. The analysis leverages population-scale networks constructed within the Secure Analytics Environment (SANE), enabling computationally intensive network operations while complying with legal and ethical constraints. Interoperability across services is achieved through shared standards, coordinated identifiers, and integrated workflows across ODISSEI's service stack, including the ODISSEI Secure Supercomputer (OSSC) for scalable analysis and the ODISSEI Code Library for transparent documentation, versioning, and reuse of analytical pipelines. By linking administrative registers, derived network layers, and reproducible code within a single federated infrastructure, ODISSEI lowers barriers to complex, multi-source research while increasing robustness and replicability. The presentation focuses on the architectural design rather than the empirical results, showing how ODISSEI functions as an integrated ecosystem rather than a collection of standalone tools and illustrates how national research infrastructures can operationalize FAIR principles, support population-scale analytics, and provide a blueprint for interoperable social science infrastructures in Europe.","[""Journal Article""]","[""Emery T""]",10.23889/ijpds.v11i5.3581,Emery T,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Emery T,"[""Netherlands"", ""Social Sciences"", ""Humans"", ""Information Storage and Retrieval""]",3581,42540888,pmc-id: PMC13426633;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540888/,ODISSEI: the Dutch National Infrastructure for Social Science,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"The Provincial Health Data Centre (PHDC) integrates person-level clinical and administrative data in the public health systems, using clinically-informed phenotypic algorithms to infer health conditions (episodes), from laboratory, medication and service-use data. Identifying patients living with CKD and requiring palliative care is essential for effective health service delivery, as existing data sources, such as the national kidney replacement therapy registry and morphine monitoring, underestimate true prevalence. To develop and apply a phenotypic algorithm (ascertainment) to define CKD and palliative care episodes, and to integrate end-stage renal disease (ESRD) patients into the palliative care episode. Ascertainment used a rules-based inference engine processing data via phenotype algorithms. CKD clinical data points (evidences) included longitudinal laboratory data defining CKD by KDIGO eGFR criteria, the South African Renal Registry, triangulated clinical data, and associated medications. Palliative care episodes were inferred using ICD-10 codes, morphine dispensing, referrals, and an ESRD disease-specific layer. Descriptive statistics characterised the epidemiology for both conditions in the public sector of the Western Cape. The PHDC enumerated 224 469 CKD patients (170 977 alive and 145 719 visited health facilities within the last 5 years) and 56 931 palliative care patients identified(26 397 alive and 18 561 last visited a facility within the last 5 years) from 2000 to 2024. The ascertainment algorithm and ESRD integration more effectively identified patients requiring palliative care than previously possible. These findings demonstrate effective use of routine, linked health data to identify CKD patients with palliative care requirements, supporting health service delivery and planning.","[""Journal Article""]","[""Phelanyane F"", ""Tiffin N"", ""Boulle A""]",10.23889/ijpds.v11i5.3739,Phelanyane F,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Boulle A,"[""Humans"", ""Palliative Care"", ""South Africa"", ""Renal Insufficiency, Chronic"", ""Female"", ""Algorithms"", ""Male"", ""Health Information Exchange"", ""Middle Aged"", ""Registries"", ""Aged"", ""Adult"", ""Kidney Failure, Chronic""]",3739,42540877,pmc-id: PMC13426638;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540877/,"Ascertainment of Chronic Kidney Disease and Palliative Care using routine health administrative data consolidated in a Health Information Exchange, Western Cape South Africa",11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"The linkage evaluation toolkit project aims to develop tools and criteria that can be used to evaluate data linkage pipelines and methods. This toolkit will not only allow assessment of a single pipeline, but will also facilitate the comparison between pipelines; enabling analysts to identify their strengths and weaknesses. There are currently limited standardised evaluation metrics for linkage pipelines, except for the precision, recall, and bias of the linked datasets. Eight key evaluation areas were identified; accuracy, bias in linkage error, flexibility in input datasets, scalability, efficiency, platform suitability, ease of use, and the ease and transparency of quality assurance. Evaluation criteria for each area were identified and quantified. Tools are being developed to enable users to assess pipelines across these criteria. These include tools for stress-testing, testing the pipelines under different parameters, assessing bias, and capturing and quantifying qualitative feedback. We are liaising with quality teams for standardised tools to assess precision and recall. Once finalised, the toolkit will be used to compare linkage pipelines when linking the same administrative datasets, to identify which pipeline performs best across each criterion. Future use will include identifying suitable linkage methods to support the UK's 2031 Census. The evaluation toolkit will allow analysts to evaluate the strengths and weaknesses of linkage pipelines, in both their use and impact on linked outputs. The methods can be used to improve existing pipelines, and to support the development and evaluation of new methodologies in future.","[""Journal Article""]","[""Quinn L"", ""Seguin M"", ""Hanif S"", ""White Z""]",10.23889/ijpds.v11i5.3683,Quinn L,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,White Z,"[""Humans"", ""Information Storage and Retrieval"", ""Software""]",3683,42540872,pmc-id: PMC13426733;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540872/,Developing an Evaluation Toolkit for Data Linkage Pipelines,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"While no province in Canada covers the cost of prescriptions for all of its residents, all have some form of provincial supplementary coverage (PSC) to cover some costs for particular subgroups (based on age, economics, and/or diagnosis). This PSC data can provide insights into the drug dispensation patterns of the population, but they often have significant biases that are often ignored in the literature. The objective of this research is to explore the differences between Drug Information System (DIS) and PSC data in the province of Nova Scotia (NS). METHODS: Demographic data on all eligible Nova Scotians, and their prescriptions in both the DIS and NSSPP, were extracted from August 2016-December 2024. Residents were classified as recipients, non-recipients, and non-consumers, and their demographics and prescription patterns were explored. There were over 342 000 residents eligible for NSSPP during the study window. Over 61 million prescriptions for these individuals were dispensed across the two databases, 38 million of which were paid for by NSSPP (63%). NSSPP paid for prescriptions for 58% of the population, though very few citizens had their prescriptions exclusively paid for by NSSPP (8.2%). Those that didn't receive prescriptions through NSSPP tended to be younger and more female. The data from NS show a clear potential for biases in using PSC data as a representative sample of seniors, with biases based on both age and gender. Future research will explore how potential patient disease patterns may influence coverage within the system.","[""Journal Article""]","[""A Stewart S"", ""Park J"", ""von Maltzahn M"", ""Black E"", ""E Isenor J"", ""Sketris I"", ""Trenaman S""]",10.23889/ijpds.v11i5.3631,A Stewart S,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Trenaman S,"[""Humans"", ""Nova Scotia"", ""Female"", ""Aged"", ""Male"", ""Bias"", ""Drug Prescriptions"", ""Databases, Factual"", ""Drug Information Services"", ""Aged, 80 and over""]",3631,42540860,pmc-id: PMC13426606;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540860/,Investigating Biases in Seniors' Drug Data Coverage in Canada,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Data linkage is often used to make inferences from distinct data sources. The data may be linked by a set of variables with high discrimination, for example, a social security number or some personal information. A good linking variable often implies a high disclosure risk in identifying the corresponding person. To prevent the disclosure risk, the data linker may choose to remove the linking variables before publishing the linked datasets. The design of the original data sources, the response pattern, and the unlinked part of the original data are often also unknown to the secondary user. However, the quality of the linked data is constrained by the original data sources and the linking process. Without considering the potential error or bias in linked datasets, naïvely treating them as error-free in secondary analysis may result in biased inference. To indicate the quality of the linked dataset without sacrificing privacy, we propose publishing correction weights alongside the linked datasets. The weights are generated given the information in the original data sources and the quality of the linkage. Both selection issues of the sample and measurement issues of the linking variables are addressed in the constructed weights, and we allow the possibility of having multiple potential links for a record. Secondary users may apply design-based estimators for subsequent analyses based on the correction weights, or apply sensitivity analysis given different sample inclusion criteria. An example is presented, and the option of secondary analysis given the constructed weights is discussed.","[""Journal Article""]","[""Liu A"", ""Lugtig P"", ""Scholtus S"", ""de Waal T""]",10.23889/ijpds.v11i5.3531,Liu A,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,de Waal T,"[""Humans"", ""Information Storage and Retrieval"", ""Publishing"", ""Bias""]",3531,42540857,pmc-id: PMC13426566;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540857/,Publishing Linked Data with Correction Weights,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Efficient estimation of linkage error in large linked datasets requires careful allocation of limited clerical review resources. We investigate the use of small stratified ""pilot"" samples as an initial, low-cost strategy for informing sample size calculation and allocation across strata when estimating binomial error proportions. Stratified candidate links and unlinked pairs exhibit heterogeneous error rates and variances; however, without prior variance information, optimal allocation - such as Neyman allocation - cannot be applied. We show that pilot samples of approximately nh = 30 per stratum provide sufficiently informative variance estimates at minimal cost, enabling efficient allocation of subsequent sampling effort. Using binomial absolute margin-of-error behaviour as a rough guide we calculate uncertainty for error proportions up to a maximum of p = 0.5, and use simulations to show that beyond nh ≈ 30 the marginal reduction in uncertainty grows negligible. Simulations illustrate also that these small pilots successfully differentiate high- and low-variance strata, supporting targeted sampling in the final round. When pilots are combined with Neyman allocation, the resulting stratum-level confidence intervals were shown to become more homogeneous, reducing overall population-level variance relative to proportional allocation. Empirical comparisons therefore show that, for equal total clerical review effort, Neyman allocation informed by pilots consistently yields narrower population-level confidence intervals than proportional allocation (0.85% vs 0.93% MoE). This confirms that even very small pilot samples can materially improve efficiency by enabling variance-driven sample size calculation and allocation. The method offers a practical, scalable approach for organisations conducting clerical review of linkage errors in large datasets.","[""Journal Article""]","[""Thomson G"", ""Wray M""]",10.23889/ijpds.v11i5.3629,Thomson G,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Wray M,"[""Computer Simulation"", ""Pilot Projects"", ""Sample Size"", ""Datasets as Topic""]",3629,42540820,pmc-id: PMC13426563;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540820/,Pilot Samples for Estimation of Linkage Error,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Australia's administrative data linkage environment has evolved from state-based repositories used for internal reporting, to an ecosystem of national linked data assets alongside bespoke linkage services. This has increased complexity for researchers seeking linked data access. A 2024 national consultation identified a need for tools to support transparent exploration of researcher-appropriate access pathways. The Population Health Research Network led a researcher-centred, co-design process with data linkage units, Commonwealth organisations, and research end-users to develop the Data Access Pathways tool, an online decision-support tool that enables researchers to input their project parameters and discover access pathway options. Tool development involved specification of pathway logic, business rules, wireframes, and iterative user testing. Access pathways present different ethics, governance and operational requirements, and importantly variations in data breadth and granularity. Such complex challenges also exist in federated or multi-agency linkage systems internationally (e.g., Canada, UK). The Data Access Pathways tool demonstrates that structured decision logic embedded in a user-friendly tool can simplify the complexity by supplying pathway options, guidance and contact points - building researcher capacity, reducing planning overhead, and promoting equitable access. The Data Access Pathways tool translates national-level consultation and stakeholder collaboration into practical, scalable infrastructure. Although developed for Australia, the underlying principles - neutrality, transparency, co-design, and flexible decision logic - are broadly applicable to other systems with fragmented or evolving linkage landscapes. This work offers a model for strengthening national data infrastructure and facilitating population data research globally.","[""Journal Article""]","[""Dombrovskaya M"", ""Hagemann E"", ""Flack F""]",10.23889/ijpds.v11i5.3516,Dombrovskaya M,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Flack F,"[""Australia"", ""Access to Information"", ""Humans"", ""Information Storage and Retrieval""]",3516,42540817,pmc-id: PMC13426724;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540817/,From Consultation to Innovation: A Data Access Pathways Tool to Navigate Australia's Linked Data Landscape,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"In collaboration with the Schools Health Research Network in Scotland (SHINE), Generation Scotland (GS) developed a free schools resource to educate students about health data and the value of taking part in research, supporting the recruitment of young people to the GS cohort. A scoping exercise with SHINE helped identify needs, and teachers and young people were engaged through their national conference and online focus groups to shape core content. In April 2025, funding from Research Data Scotland enabled revision and expansion of the resource based on teacher feedback. The resulting pack comprises three 45-minute lessons focused on ""What is Big Data?"" and introduces key concepts in health research, including big data, data linkage and data ethics. The resource was distributed to more than 50 interested schools via various newsletters and partner organisations, reaching schools in 22 of Scotland's 32 local authorities. Three schools have provided detailed feedback after delivering the lessons to approximately 150-250 pupils each. Offering these lesson plans created a reciprocal relationship that enabled recruitment of young people through schools. Teachers reported that the resource filled a gap in the curriculum, and delivering the lessons alongside GS recruitment materials provided a scalable, sustainable approach by leveraging existing school infrastructure. This not only supported recruitment but also contributed to lasting improvements in students' health research literacy and understanding of the value of data in research. The resource was developed with input from the SHINE network, extensive teacher feedback and contributions from the GS Young Persons Advisory Group.","[""Journal Article""]","[""Robertson S"", ""Milbourn H"", ""Campbell A"", ""Clark F"", ""Flaig R"", ""Kirby L"", ""Xiao X"", ""Whalley H"", ""Sudlow C""]",10.23889/ijpds.v11i5.3732,Robertson S,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Sudlow C,"[""Humans"", ""Scotland"", ""Big Data"", ""Adolescent"", ""Schools"", ""Focus Groups""]",3732,42540800,pmc-id: PMC13426653;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540800/,Why Big Data Matters - Free schools resource to engage young people in health research,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Trusted Research Environments (TREs) increasingly underpin cross-sectoral and population-scale data linkage research, yet no single product currently provides a flexible, interoperable way to store and expose the breadth of a TRE's data assets, let alone in a useful way. Existing systems often lack the adaptability needed to incorporate diverse TRE outputs or support an organisation's workflow requirements. We sought to develop a system that enhances interoperability, integration, and usability of diverse data sources to drive core TRE functions. SeRP created the Data Portal platform to address this gap, using an in-house development approach to ensure tight integration with its own TRE operations. The platform enables the capture, management, and dissemination of metadata through three core components: a configurable form builder to capture data first-hand within the system and import tool for data capture from external sources; a high-performance database to store and serve metadata at scale; and a template engine for a flexible user interface presentation. This architecture supports a wide array of TRE-relevant asset types-including dataset definitions, data linkage releases, data quality assessments, provisioning specifications, project and governance metadata, and project outputs and is designed to interoperate with SeRP's own TRE management tools and third party infrastructures. Harnessing this data from one central repository allows it to be used to drive essential TRE services such as project applications, dataset and variable selections for provisioning, governance management, project impact tracking, data cataloguing etc. which will ultimately improve research with linked population data.","[""Journal Article""]","[""Bale M"", ""Thompson S""]",10.23889/ijpds.v11i5.3711,Bale M,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Thompson S,"[""Metadata"", ""Humans"", ""Information Storage and Retrieval"", ""Databases, Factual"", ""Systems Integration""]",3711,42540798,pmc-id: PMC13426595;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540798/,Strengthening Trusted Research Environment Interoperability: A Metadata Platform Enabling Population-Scale Data Linkage Research,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Similarity-based geocoding pipelines are highly sensitive to lexical noise in address data. This work evaluates the potential of language models to enhance and standardize address inputs during preprocessing, thereby improving geocoding accuracy in CIDACS-RL, which relies on Jaro-Winkler similarity and is sensitive to string length and prefix agreement. We extended CIDACS-RL with a preprocessing step that removes street types (e.g., street, avenue, lane) and stop words and expands numeric and abbreviated address components. Two pre-trained language models were included in the experiments. Records from nine Northeastern Brazilian states in the cohort baseline (N = 54,985,455) were geocoded by linking addresses to census tracts or coordinates from the Brazilian National Register of Addresses (CNEFE; N = 30,545,117). After linkage, we manually assessed the accuracy of our extension against previous CIDACS-RL version using stratified samples (N = 2,000) from each run to determine the cutoff points. The geocoding was evaluated using accuracy and precision. Overall, the proposed extension achieved competitive performance, with higher mean precision (0.86, SD = 0.01) and accuracy (0.94, SD = 0.024) compared to the original CIDACS-RL, which achieved a mean precision of 0.84 (SD = 0.02) and a mean accuracy of 0.93 (SD = 0.024). The largest gains were observed in states with shorter average street name lengths, such as Alagoas and Pernambuco, where precision increased by approximately 3% to 10%. Our findings support that geocoding tasks may benefit from pre-trained language models for preprocessing steps, addressing the limitation of well-posed similarity measures.","[""Journal Article""]","[""Pita R"", ""Rocha G"", ""Ichihara M"", ""Harron K"", ""Brito P"", ""Carreiro R"", ""Almeida B"", ""Ramos P"", ""Barreto M"", ""Barreto M""]",10.23889/ijpds.v11i5.3757,Pita R,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Barreto M,"[""Brazil"", ""Geographic Mapping"", ""Humans"", ""Geographic Information Systems"", ""Large Language Models""]",3757,42540796,pmc-id: PMC13426686;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540796/,Enhancing geocoding in Brazil through language model-based preprocessing,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Using the correct linkage keys to join tables is essential when combining data from multiple sources. Although Trusted Research Environments (TREs) provide metadata to support data linkage, to the best of our knowledge, none currently automate the creation of detailed table-level linkage information. Researchers often conduct linkages, and complex linkages exist at many levels. However, this manual approach may misuse available linkages. As the number of data sources and datasets increases in complexity, ensuring correct linkages within and across data sources becomes difficult, reducing efficiency and reproducibility. The framework provides an end-to-end solution for data in the Secure Anonymised Information Linkage (SAIL) Databank by generating a full linkage matrix and documentation directly from common metadata fields (e.g., table_name, column_name, datatype) using configurable pattern-matching rules (e.g., column_name ending in '_E' denotes an encrypted ID field). The algorithm then compares shared keys across all tables to identify every combination of internal and external linkages, producing linkage matrix with structured natural-language statements for users, which can subsequently be used to generate linkage diagrams. The framework has been validated to ensure accuracy, including verifying that all linkage keys and information are detected. To assess performance, the framework calculates accuracy, precision, and recall by comparing results against a manually generated standard reference, which is validated by the SAIL User-and-Data-Support-Services (UDSS) team. Our approach offers major benefits for TREs and researchers by standardising scalable and reusable linkage documentation. We improved the consistency of linkage metadata production for complex, multi-table datasets within SAIL.","[""Journal Article""]","[""Mhereeg M"", ""Rawlings A"", ""Davies G"", ""Howell-Wright O"", ""Hughes L"", ""Akbari A"", ""Evans H""]",10.23889/ijpds.v11i5.3517,Mhereeg M,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Evans H,"[""Metadata"", ""Information Storage and Retrieval"", ""Algorithms"", ""Databases, Factual"", ""Humans""]",3517,42540782,pmc-id: PMC13426578;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540782/,"The automated generation of data linkage Information: A reusable, scalable metadata framework for Trusted Research Environments",11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Splink is the award-winning open-source data-linkage software developed by the UK's Ministry of Justice (MoJ). It implements the probabilistic Fellegi-Sunter model in SQL, allowing users to employ their execution backend of choice, whether that be with DuckDB, Spark, or another engine of preference. Splink's focus on performance, accuracy, scalability, and rich feature set have enabled it to accrue a wide user base across the public sector, academia, and beyond. Splink is in continuous development, motivated by the ever-developing needs for record linkage within the MoJ, as well as the challenges faced by our wide range of users across the globe. We will discuss some of the latest developments within Splink, as well as a look at features that are on the near horizon. Recent focus includes work to allow scaling of linkages to ever-larger datasets, and to provide much greater flexibility for users to control the individual portions of their data-linking workflow. A particular focus has been our work on near-realtime record linkage. We have developed a system for operational record-linkage that keeps in sync with continuous updates to source data using incremental linkage, which brings unique challenges for performance and scaling compared to batch-processed linkage. We will discuss some of the issues around this, how it informed the design of our system in order to make its operation a reality, and how we have then folded these ideas back into Splink to make it more straightforward for other users to do likewise.","[""Journal Article""]","[""Bond A""]",10.23889/ijpds.v11i5.3598,Bond A,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Bond A,"[""Software"", ""Humans"", ""United Kingdom"", ""Information Storage and Retrieval""]",3598,42540781,pmc-id: PMC13426631;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540781/,Splink: recent developments and realtime linkage,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"We have created an unprecedented interdisciplinary infrastructure integrating data from UK-wide LPS linked to participants' health (NHS), administrative (DWP, HMRC) and place-based records (e.g. environmental pollutants, proximity to healthy assets). Researchers can apply to access all these data via a single application. This organisation is a collaboration of over 25 of the UK's most established LPS with over 425,000 participant records. With new LPS joining, the resource will comprise more than 2 million linked participant's records by 2027. The UK LLC enables integrated and curated data for pooled analysis within a functionally anonymous Digital Economy Act and ISO 27001 accredited TRE. Initially this resource was only available to UK researchers, will be open to international researchers in 2026. This data flow is enabled by: (1) a model where a Trusted Third Party processes participant identifiers for many different data owners; (2) creation of a novel longitudinal data pipeline, enabling linkage, data extraction and update of records over time; (3) an access framework where a Linked Data Access Panel considers applications on behalf of data owners (e.g., the NHS), with review by a public panel and distributing applications to LPS for approval. UK LLC provides a simple-to-access strategic research-ready platform for longitudinal research to investigate cross-cutting themes such as understanding health and social inequalities, health-social-environmental interactions. The greater availability of large scale, diverse linked data will help provide the numbers for researchers to study rarer outcomes and seldom-reached populations.","[""Journal Article""]","[""Boyd A"", ""Flaig R"", ""Oakley J"", ""Campbell K"", ""Evans Stela McLachlan K"", ""Thomas Emma Turner R""]",10.23889/ijpds.v11i5.3550,Boyd A,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Thomas Emma Turner R,"[""United Kingdom"", ""Longitudinal Studies"", ""Humans"", ""Information Storage and Retrieval"", ""Cooperative Behavior""]",3550,42540777,pmc-id: PMC13426597;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540777/,The UK Longitudinal Linkage Collaboration: the Trusted Research Environment for data linkage in longitudinal population research,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"The presentation will outline the data linkage methodology underpinning the evaluation of Wales' Basic Income Pilot (BIP), with a particular focus on connecting BIP participant data to the Longitudinal Education Outcomes (LEO) datasets. The BIP is a landmark pilot providing care-leavers with a monthly income for two years. The evaluation aims to assess the education and labour market outcomes of BIP recipients compared to their non-recipient peers. The LEO dataset integrates multiple educational datasets, as well as employment and benefits data from the Department for Work and Pensions (DWP) and His Majesty's Revenue and Customs (HMRC) providing a comprehensive view of education and employment outcomes. To facilitate this analysis, a secure and privacy-conscious linkage process has been designed. The BIP monitoring database, containing personal identifiers for pilot recipients, will be matched to the constituent education datasets held within LEO, using select data points. The linkage will take place within the Welsh Government, which already holds all the relevant datasets. This internal linkage avoids the need to transfer any personal data externally, minimising privacy risks and ensuring compliance with data governance protocols. Following linkage, the evaluation contractors will receive an anonymised, flagged dataset via the Welsh Government Secure e-Research Platform, containing the LEO data relevant to the BIP recipients. Contractors will not be able to identify individuals, preserving participant confidentiality. Access to the data is further restricted to accredited researchers. This approach demonstrates a robust, ethical model for linking administrative data in policy evaluation, balancing analytical needs with stringent privacy protections.","[""Journal Article""]","[""Fallick S"", ""Helliwell K""]",10.23889/ijpds.v11i5.3658,Fallick S,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Helliwell K,"[""Wales"", ""Humans"", ""Pilot Projects"", ""Income"", ""Information Storage and Retrieval"", ""Employment"", ""Longitudinal Studies""]",3658,42540774,pmc-id: PMC13426625;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540774/,Use of data linkage and LEO data in the evaluation of the Basic Income Pilot in Wales,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Clerical review is an integral step of many data linkage systems. It employs human expertise to assess record pairs for which a decision model, such as probabilistic record linkage, has not been able to make a match (two records refer to the same individual) or non-match (two records refer to different individuals) decision. While clerical review is used in many practical applications, there is surprising little research that systematically investigates how to best conduct this important step in the data linkage process.In this work, we explore one aspect of clerical review: How does the diversity of the record pairs selected for manual review affect the final linkage quality? To investigate this question, we generated diverse samples of difficult to classify record pairs from a large public population database, where each sample contained 100 pairs of true matches and 100 pairs of true non-matches. The samples differed in (1) the number of unique similarity patterns they had (calculated over a set of compared quasi-identifiers such as names and addresses), and (2) the actual set of quasi-identifiers available for manual review. All authors conducted a blinded manual assessment of all samples.Our results indicate that the diversity of the agreement patterns is less important for making informed decisions compared to the set of quasi-identifiers available for review. Furthermore, reviewers seem to make decisions based on mental models of how they think a match or non-match looks like. Our results will help design improved approaches for clerical review in practical linkage applications.","[""Journal Article""]","[""Dharmawimala Y"", ""Christen P"", ""Ziyad S"", ""Lam J"", ""Vidanage A"", ""Schnell R""]",10.23889/ijpds.v11i5.3620,Dharmawimala Y,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Schnell R,"[""Humans"", ""Information Storage and Retrieval""]",3620,42540771,pmc-id: PMC13426657;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540771/,Diversity of record pairs and mental models in clerical review: What reviewers use to decide matches,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Since 2015, South London and Maudsley NHS Foundation Trust (London, United Kingdom) has maintained a data linkage between its de-identified Child and Adolescent Mental Health Services records and the Department for Education's National Pupil Database. Most recently refreshed up to the 2023/24 academic year, this linkage is used to conduct population and clinical research spanning mental health and education. In this presentation, we will outline the linkage's evolution, including governance and data-sharing frameworks that we have navigated, changes encountered in the decade since its original formation, and key learnings. We will discuss public engagement activities we have undertaken around the linkage, including novel approaches to directly involve children and young people in complex analytical decisions. Finally, we will showcase the wide array of research that has arisen from this linkage, spanning depression, Attention-Deficit/Hyperactivity Disorder (ADHD), educational attainment, special educational needs support, and more. Many of our findings have informed policymakers. Our most recent study replicates a longitudinal analysis first conducted in Norway, showing diminishing associations between ADHD and end-of-school exam performance. This demonstrates how the growing availability of data linkages permits international research replication. By identifying overlapping trends, countries can work jointly on policy solutions in full confidence that many of us are grappling with the same challenges, despite having mental health and education systems that diverge operationally. In the decade since its inception, this linkage has exemplified how administrative data drives research and policy, and there is greater opportunity than ever before for global collaboration.","[""Journal Article""]","[""Wickersham A"", ""Downs J""]",10.23889/ijpds.v11i5.3591,Wickersham A,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Downs J,"[""Humans"", ""London"", ""Mental Health"", ""Retrospective Studies"", ""Adolescent"", ""Child"", ""Mental Health Services"", ""Health Policy"", ""Information Storage and Retrieval""]",3591,42540750,pmc-id: PMC13426584;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540750/,Using mental health and education data for research and policy insights: A ten-year retrospective of a South London data linkage,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"To develop a resource that maps health outcomes across coding schemas in linked administrative data in UK Biobank, addressing the challenge of identifying equivalent outcomes from multiple sources. UK Biobank is a prospective cohort study of ∼500,000 adults, recruited between 2006-2010, with follow up for health outcomes through linkage with administrative data. Clinical codes include Read Version 2 (Read2) and Clinical Terms Version 3 (CTV3) from primary care, and International Classification of Diseases (ICD) 9th and 10th editions (ICD-9 and ICD-10) from hospitals, cancer registries, and death records; self-reported conditions were also reported at recruitment. We reviewed existing mapping resources and mapped clinical codes in different schemas to 4-digit ICD-10 codes. We successfully mapped 81% of Read2 (N = 12,448), 93% of CTV3 (24,188), 92% of ICD-9 (3,060), and 100% of self-reported codes (509) to ICD-10 codes. Although existing resources frequently allowed one-to-one mapping of ICD-10 codes (94% of the mapped codes for Read2, 58% of CTV3, and 79% of ICD-9), the remaining codes required extensive clinical review, which is ongoing. The conversion increased the granularity of health outcomes by 3.8 times from 2,000 3-digit to 7,500 4-digit ICD-10 codes. The mapping quality will be evaluated using phecodes, and by assessing consistency across data sources. Our approach preserves clinical detail, increases coding granularity, uncovers nuanced outcomes, and enables precise, internationally comparable research using enriched UK Biobank data. Although harmonisation supports cross-cohort research, validation of outcomes across data sources remains essential to avoid misclassification and minimise bias.","[""Journal Article""]","[""Domzaridou E"", ""Lacey B"", ""Conroy M"", ""Allen N"", ""Li Nuffield Y""]",10.23889/ijpds.v11i5.3675,Domzaridou E,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Li Nuffield Y,"[""Humans"", ""United Kingdom"", ""International Classification of Diseases"", ""UK Biobank"", ""Prospective Studies"", ""Clinical Coding"", ""Biological Specimen Banks"", ""Outcome Assessment, Health Care""]",3675,42540745,pmc-id: PMC13426564;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540745/,"Harmonised Health Outcomes Across Administrative Data: Lessons, Opportunities, and Challenges from UK Biobank",11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"Multiple Sclerosis (MS) is the commonest non-traumatic cause of disability in younger people. Prevalence of MS by deprivation and ethnicity is rarely reported, as ethnicity is not accurately or consistently recorded in national datasets. Ethnicity data within the Secure Anonymised Information Linkage (SAIL) Databank is stored in clinical datasets that are linkable to the Welsh Demographic Service (WDS) but data collection is variable. We linked WDS to data from the Office of National Statistics (ONS) which has complete ethnicity and birthplace data from the most recent 2021 census. WDS and ONS data were merged to determine census age, sex, birthplace, ethnicity and Welsh Index of Multiple Deprivation (WIMD). An algorithm (Nicholas, 2024) identified people with MS (pwMS) in Wales. 3.1M ONS and 3.2M WDS were linked producing 2.5M unique records of whom 5934 had MS. MS prevalence (per 100,000) was highest aged 51-60 (445.9 [424.6-467.9]); higher in females than males (325.2 [315.6-335] versus 131.7 [125.3-138.3]) and significantly lower in Asian (58.2 [41-80.3]) or Black (126.8 [80.3-190.2]) ethnicity versus white (240 [233.9-246.3]). PwMS in Wales were less likely to be born outside of the UK (96.4%) versus the Welsh population (93.9%). 853 pwMS (14.9%) were in the most deprived WIMD quintile, compared to 18.8% of the Welsh population (p<0.001). Linkage of population-wide datasets enables an overview of MS prevalence by age, sex, ethnicity and social deprivation. Further work is needed to improve linkage between datasets.","[""Journal Article""]","[""Witts J"", ""Tallantyre E"", ""Rodgers J"", ""Nicholas R"", ""Middleton R""]",10.23889/ijpds.v11i5.3642,Witts J,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Middleton R,"[""Adolescent"", ""Adult"", ""Aged"", ""Female"", ""Humans"", ""Male"", ""Middle Aged"", ""Young Adult"", ""Databases, Factual"", ""Ethnicity"", ""Multiple Sclerosis"", ""Prevalence"", ""Wales"", ""Black People"", ""Asian People"", ""White People""]",3642,42540729,pmc-id: PMC13426553;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540729/,Multiple Sclerosis and ethnicity in Wales: a SAIL Databank study,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"The global rise in older populations has profound implications for health and social systems. Governments are investing in policies to support ageing in the community, yet robust evidence of effectiveness is limited. We are conducting population-level comparative effectiveness studies of Australian government policies in delaying transition to residential aged care (RAC). A comprehensive regional Electronic Health Record dataset will be established within the National Centre for Healthy Ageing (NCHA) and linked to national aged care, health and social data, the first linkage of this kind in Australia. A policy-specific framework for target trial emulation, according to the TARGET Statement, will be developed. Patient journey mapping and expert consensus will identify high-value covariates for statistical models. Uncoded covariates will be AI-derived from unstructured clinical notes using Natural Language Processing. The trial emulation framework and enriched linked dataset will underpin agent-based modelling to simulate diverse future policy scenarios. >200,000 older residents (2015-2026) have been identified for linkage (median age 70, 55% female) providing 80% power to detect a 5.5% reduction in RAC transitions. A reference committee of government, consumer, provider, and clinical representatives meets quarterly to guide data strategy and policy relevance. Journey mapping with ∼50 older people and carers in receipt of relevant policies is underway and a preliminary framework of simulation modelling established. This project harnesses advances in data linkage, simulation modelling, AI, and research infrastructure at the NCHA to deliver rapid, robust evaluation and simulation of aged care policies, while pioneering innovative data-enhancement techniques.","[""Journal Article""]","[""Andrew N"", ""Collyer T"", ""Beare R"", ""Carver A"", ""Long K"", ""Churilov L"", ""Ilomäki J"", ""Sq Tan G"", ""Ung D"", ""Kilkenny M"", ""Lannin N""]",10.23889/ijpds.v11i5.3738,Andrew N,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Lannin N,"[""Humans"", ""Australia"", ""Female"", ""Health Policy"", ""Aged"", ""Male"", ""Electronic Health Records"", ""Computer Simulation"", ""Information Storage and Retrieval"", ""Health Services for the Aged""]",3738,42540721,pmc-id: PMC13426582;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540721/,From Data Linkage to Simulation: A New Framework for Evaluating Aged Care Policies,11,rjxlJyWyVQdbk42ae,eECllsEMa92f7cpQM
"To address the problem that conventional evaluation methods struggle to comprehensively characterize the complex flow behavior of TCM powders, this study utilized an FT4 powder rheometer to perform a multidimensional characterization of 24 representative samples, including decoction pieces, extracts, excipients, and granules. In addition to traditional static parameters like angle of repose(α) and Carr index(IC), the study focused on dynamic rheological characteristics, specifically basic flow energy(BFE) and flow rate index(FRI),alongside shear and bulk property indicators such as cohesion(C_o) and flow function coefficient(FFc). Data analysis revealed that individual indicators frequently yield conflicting assessments for the same sample, underscoring the dimensional limitations of isolated metrics. By leveraging correlation analysis and principal component analysis(PCA), the study extracted core contributing factors to construct a weighted flowability comprehensive index(FCI). The results indicated that the FCI successfully integrated multi-source heterogeneous data, showing strong alignment with core flowability parameters and enabling precise classification of powder flow grades. This index offers a robust quantitative framework for enhancing stability assessment and quality control in TCM powder preparation processes.","[""English Abstract"", ""Journal Article""]","[""Hu HQ"", ""Wan XH"", ""Liu Y"", ""Hu H"", ""Liu YH"", ""Li YH"", ""Peng CC"", ""Wu ZF""]",10.19540/j.cnki.cjcmm.20260416.302,Hu HQ,Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica,1001-5302,13,Zhongguo Zhong Yao Za Zhi,chi,Wu ZF,"[""Powders"", ""Drugs, Chinese Herbal"", ""Principal Component Analysis"", ""Rheology"", ""Quality Control"", ""Chemistry, Pharmaceutical""]",3687-3696,42543358,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543358/,[Development and application of multidimensional comprehensive evaluation system for flowability of TCM powders based on principal component analysis],51,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"As the dominant dosage form in clinical practice of TCM, solid preparations face core challenges concerning quality stability and consistent therapeutic efficacy. Clinical observations have revealed efficacy variations among different preparation forms of the same TCM or even among products of the same preparation from different manufacturers. Such variations are attributed not only to the complexity of the production process but also to the physicochemical states of the drug substances, among which crystal forms likely serve as a critical factor influencing the drug state and subsequent efficacy divergence. TCM crystal forms, as a fundamental microscopic attribute of active ingredients in TCM, directly determine physicochemical properties and biological activities of drugs, representing a root cause of quality fluctuation and efficacy variation. Currently, significant progress has been made in the study of TCM crystal forms based on TCM active ingredients and compound preparations. A comprehensive technical framework encompassing preparation, characterization, and property analysis has been established. Its core value lies in revealing the scientific essence of &quot;identical composition but heterogeneous activity&quot;, and it is expected to provide quantitative and precise technical support for quality control across the entire TCM industry chain. However, research on the crystal forms of TCM solid preparations remains a major challenge. Whether it concerns the discovery, characterization, and identification of preferred crystal forms in Chinese patent medicines, or the quality control of crystal forms of Chinese patent medicines and their impact on clinical efficacy, these areas remain largely unexplored territory awaiting further investigation. This article proposed the crystal form issues in TCM solid preparations. It comprehensively reviewed the research landscape of TCM crystal forms, spanning from single components to compound preparations, systematically elucidated the associated technical systems and category characteristics of TCM crystal forms, and innovatively proposed a crystal form-based strategy for quality control. This perspective provides a novel research framework for enhancing the quality control of TCM solid preparations and discovering new formula-derived nanoparticle drugs, holding significant importance for enhancing the standardization of TCM solid preparations, ensuring clinical efficacy, and advancing the development of TCM nanoscience.","[""Journal Article"", ""Review"", ""English Abstract""]","[""Hua H"", ""Ji YL"", ""Ao Z"", ""Zhao JN""]",10.19540/j.cnki.cjcmm.20260413.301,Hua H,Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica,1001-5302,13,Zhongguo Zhong Yao Za Zhi,chi,Zhao JN,"[""Drugs, Chinese Herbal"", ""Crystallization"", ""Quality Control"", ""Humans"", ""Medicine, Chinese Traditional"", ""Chemistry, Pharmaceutical"", ""Drug Compounding""]",3617-3630,42543351,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543351/,[Crystal form issues and development prospects of TCM solid preparations],51,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Lumbrokinase, a serine protease complex extracted from Pheretima, possesses specific fibrinolytic activity and is clinically used for thrombolytic therapy in cardiovascular and cerebrovascular diseases. Due to its low bleeding risk profile, novel formulation technologies have significantly enhanced its therapeutic efficacy in acute thrombotic diseases. This study discussed the physicochemical properties, absorption properties, pharmacological effects, formulation strategies, and existing challenges of lumbrokinase, providing a comprehensive analysis for its future application and development.","[""Journal Article"", ""Review"", ""English Abstract""]","[""Luo WY"", ""Zhao FY"", ""Huang JF"", ""Zhang XW"", ""Huang XY"", ""Fu Y"", ""Jiang W"", ""Li WS"", ""Yue PF""]",10.19540/j.cnki.cjcmm.20260408.302,Luo WY,Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica,1001-5302,14,Zhongguo Zhong Yao Za Zhi,chi,Yue PF,"[""Animals"", ""Humans"", ""Fibrinolytic Agents"", ""Serine Endopeptidases"", ""Drug Compounding"", ""Chemistry, Pharmaceutical"", ""Endopeptidases""]",3929-3938,42543323,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543323/,[Analysis and reflection on pharmacological effects and novel formulation technologies of lumbrokinase from Pheretima],51,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Individualized immunosuppression represents a paradigm shift in kidney transplant from traditional ""trial-and-error"" dosing strategies toward individualized regimens. Precision immunosuppression is informed by pharmacogenetics, biomarkers, therapeutic drug monitoring, and recently artificial intelligence-based prediction models, although stratified risk assessment of patients is still mandatory. This review investigated the current evidence on individualized induction and maintenance immunosuppression. In addition, the roles of pharmacokinetics, pharmacogenomics, and emerging biomarker platforms were reviewed and future pathways for tailored posttransplant care were outlined. In summary, the data indicate that optimized immunosuppressive therapy improves graft outcomes, reduces toxicity, and enables targeted minimization strategies in selected recipients.","[""Journal Article"", ""Review""]","[""Argani H""]",10.6002/ect.MESOT2025.L35,Argani H,Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation,1304-0855,Suppl 2,Exp Clin Transplant,eng,Argani H,"[""Humans"", ""Kidney Transplantation"", ""Immunosuppressive Agents"", ""Graft Rejection"", ""Graft Survival"", ""Treatment Outcome"", ""Risk Factors"", ""Precision Medicine"", ""Predictive Value of Tests"", ""Risk Assessment"", ""Drug Monitoring"", ""Pharmacogenetics"", ""Drug Dosage Calculations"", ""Biomarkers""]",20-25,42538652,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42538652/,Precision Immunosuppression in Kidney Transplantation: A Comprehensive Review,24,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Rare‑disease drug development is constrained by small and heterogeneous patient populations, limited natural‑history data, and the impracticality of large, randomized trials. Despite increasing regulatory acceptance of totality-of-evidence and mechanism-based development pathways, generating reliable, decision-ready evidence under these constraints remains challenging. This review describes how clinical pharmacology contributes within an evidence‑integration and decision‑support framework through quantitative, model‑informed approaches to address this gap. By integrating nonclinical data, pharmacokinetics, pharmacodynamics, biomarkers, natural‑history information, and clinical efficacy and safety outcomes, and through close collaboration with clinical, statistical, and translational experts, clinical pharmacology supports interpretation of treatment effects and quantitative characterization of uncertainty when conventional evidence is limited. In practice, these approaches inform key development decisions, including dose selection, innovative trial designs, extrapolation and bridging across populations, use of external controls, and evaluation of biomarkers and surrogate endpoints. Importantly, such practices help align regulatory expectations with patient needs, particularly in pediatric and ultra‑rare settings, by enabling appropriate dosing, reduced trial and patient burden, and quantitative assessment of benefit/risk. Examples from rare‑disease programs illustrate how integrated quantitative evidence has supported regulatory decisions, including label expansion and accelerated approval when data may be sparse, heterogeneous, or evolving. Looking ahead, emerging technologies such as artificial intelligence, digital biomarkers, and individualized approaches are expected to further advance rare‑disease drug development. With this evolving landscape, clinical pharmacology is expected to continue playing an important role in evaluating mechanistic plausibility, ensuring analytic rigor, and translating small datasets into meaningful evidence to inform development and regulatory decisions in rare diseases.","[""Journal Article"", ""Review""]","[""Xu Y"", ""Verone-Boyle A"", ""Schmitz N"", ""Zahir H"", ""Willis BA""]",10.1002/jcph.70250,Xu Y,Journal of clinical pharmacology,0091-2700,8,J Clin Pharmacol,eng,Willis BA,"[""Humans"", ""Rare Diseases"", ""Pharmacology, Clinical"", ""Drug Development"", ""Big Data""]",e70250,42535720,pmc-id: PMC13426045;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42535720/,From Small Data to Big Decisions: How Clinical Pharmacology Shapes Rare Disease Development,66,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Clinical drug development for rare diseases continues to face significant challenges due to disease heterogeneity, fewer available patients, and incomplete understanding of pathogenesis, resulting in trials with limited clinical data, thus constraining traditional development pathways. Clinical pharmacology, modeling, and simulation-based approaches can help address these challenges by informing decision-making, mitigating uncertainty, and guiding optimal dose and regimen selection for the appropriate patient population. These approaches help streamline trial designs by reducing the scope and number of clinical trial evaluations, using exposure-response analyses to optimize dosing, the use of mechanistic-physiologically based pharmacokinetics (M-PBPK)-based approaches for biopharmaceutical and formulation optimization, evaluations of drug-drug interactions, and organ impairment. These strategies increase development efficiency across all stages of drug development, thereby improving the probability of success. This review highlights case studies that applied innovative clinical and quantitative pharmacology approaches across early and late stages of drug development and regulatory decision-making in rare diseases. The specific examples illustrate the application of pharmacokinetics/pharmacodynamics (PK/PD) and model-informed drug development (MIDD) strategies to support dose and regimen selection, enabling efficient use of direct or adaptive trial designs, facilitating bridging across populations and indications, biopharmaceutics-based transitions, and generating integrated PK/PD evidence to support labeling. Examples include drug repurposing, characterizing PK/PD in early phase to inform late-phase development, population PK analysis to guide trial dosing and label recommendations, using phenotype-targeted study design to address disease heterogeneity, expanding dosing regimen across indications using MIDD, quantitatively evaluating immunogenicity to support mitigation strategies, biomarker bridging, and applying M-PBPK to predict clinical PK in organ impairment populations.","[""Journal Article"", ""Review""]","[""Oberoi RK"", ""Peer CJ"", ""Tripathi A"", ""Mohammad AS"", ""Sun Y"", ""Der K"", ""Song Y"", ""Huang J"", ""Upreti VV""]",10.1002/jcph.70246,Oberoi RK,Journal of clinical pharmacology,0091-2700,8,J Clin Pharmacol,eng,Upreti VV,"[""Humans"", ""Rare Diseases"", ""Drug Development"", ""Pharmacology, Clinical"", ""Models, Biological"", ""Computer Simulation""]",e70246,42530141,pmc-id: PMC13422008;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42530141/,"Innovative Clinical Pharmacology, Modeling, and Simulation Strategies for Accelerating Rare Disease Drug Development",66,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Physiologically based pharmacokinetic (PBPK) and physiologically-based biopharmaceutics (PBBM) modeling are valuable tools in drug development, allowing mechanistic predictions of drug absorption and disposition. However, sex-related differences in gastrointestinal physiology are often underrepresented in virtual populations, potentially limiting prediction accuracy. This study aimed to evaluate how sex-related physiological differences are incorporated into commonly used PBPK platforms and to illustrate their impact on pharmacokinetic predictions using ketoprofen as a case study. Three PBPK platforms were systematically reviewed to assess predefined sex-specific gastrointestinal parameters. All three platforms incorporated sex-related differences in general anatomy and physiology but overlooked sex-specific variability in gastrointestinal tract parameters. In addition, three PBBM models of ketoprofen were developed and verified in males and subsequently extrapolated to females using default and refined sex-specific parameters. Under default female settings, the models overpredicted Cmax and underestimated Tmax, resulting in concentration-time profiles that were nearly indistinguishable from those of males. Refining gastrointestinal tract parameters for females population improved prediction performance and better reflected observed sex differences. These findings indicate that current PBPK platforms may require user-defined adjustments to adequately represent sex-specific gastrointestinal physiology and that incorporating such parameters could lead to more representative PBBM applications.","[""Journal Article""]","[""Chavarría-Rojas M"", ""Murshed M"", ""Lorier M"", ""Fotaki N"", ""Ibarra M""]",10.1002/psp4.70310,Chavarría-Rojas M,CPT: pharmacometrics & systems pharmacology,2163-8306,8,CPT Pharmacometrics Syst Pharmacol,eng,Ibarra M,"[""Female"", ""Humans"", ""Models, Biological"", ""Ketoprofen"", ""Male"", ""Biopharmaceutics"", ""Gastrointestinal Tract"", ""Sex Factors"", ""Sex Characteristics""]",e70310,42528013,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42528013/,Sex-Related Differences in Physiologically-Based Biopharmaceutics Modeling,15,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Herbal medicine has emerged as an important area of investigation in gastrointestinal cancers owing to its multitarget therapeutic potential and growing integration with modern oncology. However, the rapid expansion of the literature has resulted in a fragmented understanding of the field's knowledge structure, research evolution, and emerging directions. A bibliometric analysis was performed using publications retrieved from the Web of Science Core Collection between 2016 and 2025. Bibliometrix, VOSviewer, and CiteSpace were employed to evaluate publication trends, collaboration networks, thematic evolution, and knowledge foundations. To further assess the biological relevance of major research themes, representative molecular markers associated with apoptosis, cell-cycle regulation, and epithelial biology were examined using transcriptomic data integrated from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project through the Gene Expression Profiling Interactive Analysis (GEPIA) platform. A total of 1,985 publications were included. Research activity increased substantially over the study period, particularly after 2020. Bibliometric analyses revealed a progressive transition from traditional investigations of apoptosis, proliferation, and metastasis toward emerging themes involving tumor microenvironment regulation, ferroptosis, gut microbiota interactions, network pharmacology, and molecular docking. Knowledge structure analyses demonstrated increasing integration of experimental oncology, bioinformatics, and traditional Chinese medicine research. China dominated global publication output, while the United States exhibited the strongest international collaborative profile. Exploratory transcriptomic validation showed that representative molecular markers (BCL2, CCND1, and CDH1) exhibited differential expression patterns across multiple gastrointestinal malignancies, supporting the biological relevance of the dominant research themes identified through bibliometric analyses. Research on herbal medicine for gastrointestinal cancers is transitioning from descriptive pharmacological investigations toward mechanism-oriented, data-driven, and translational research. By integrating bibliometric visualization with exploratory pan-gastrointestinal-cancer transcriptomic validation, this study provides a comprehensive overview of the field's evolution and offers a complementary framework linking knowledge mapping with molecular-level evidence. These findings provide biological context for emerging research priorities and may facilitate future biomarker discovery and precision-oriented herbal medicine research for gastrointestinal cancers.","[""Journal Article"", ""Review""]","[""Zhao L"", ""Wang H"", ""Jiang Y"", ""Zhao Z"", ""Liang Q"", ""Li Y"", ""Wang J"", ""Zhong W"", ""Xu Y"", ""Zeng X"", ""Liu T"", ""Yang Y"", ""Wu Q"", ""Xu K""]",10.1007/s11912-026-01811-5,Zhao L,Current oncology reports,1523-3790,1,Curr Oncol Rep,eng,Xu K,"[""Humans"", ""Gastrointestinal Neoplasms"", ""Bibliometrics"", ""Herbal Medicine""]",,42527723,,2026 Jul 30,2026,https://pubmed.ncbi.nlm.nih.gov/42527723/,The Application and Advancement of Herbal Medicine in Gastrointestinal Cancers: A Bibliometrix Visualization and Pan-cancer Analysis,28,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Wireless in vivo neuropharmacology and optogenetics offer a powerful way to link molecular signaling, defined neural populations, and behavior in freely moving animals. However, existing implantable wireless systems developed for this purpose often suffer from imprecise dosing, backflow contamination, and nonrefillable reservoirs, and their reliance on experimenter presence can itself alter neural activity and behavior. Here, we introduce a remotely actuated and programmable implant for drug delivery and optical stimulation (RAPIDO), which integrates a refillable, replaceable, and backflow-free fluidic module with a microscale inorganic light-emitting diode probe in a single miniaturized implant. A replaceable cartridge with an integrated unidirectional valve enables rapid refilling with contamination-free dosing, while a programmable electrochemical pump provides multilevel flow-rate control and linear dose modulation. Dual wireless modes combine smartphone control for on-site interactive experiments with internet connectivity for remotely scheduled, observer-free operation. In freely behaving rodents, RAPIDO enabled repeated wireless pharmacological modulation of locomotor behavior and independent optogenetic manipulation of intracellular signaling during cocaine conditioning. This platform establishes a foundation for chronic multimodal neuromodulation, supporting long-term circuit studies across distributed laboratories.","[""Journal Article""]","[""Jeong EY"", ""Park JW"", ""Cho S"", ""Han D"", ""Kim CY"", ""Kim SW"", ""Lee W"", ""Kim WY"", ""Kim JH"", ""Jeong JW""]",10.1126/sciadv.aee8648,Jeong EY,Science advances,2375-2548,31,Sci Adv,eng,Jeong JW,"[""Optogenetics"", ""Animals"", ""Wireless Technology"", ""Neuropharmacology"", ""Rats"", ""Cocaine"", ""Drug Delivery Systems"", ""Mice""]",eaee8648,42525762,pmc-id: PMC13418541;,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42525762/,"IoT-enabled wireless neural implant for chronic, programmable neuropharmacology and optogenetics",12,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Ketorolac tromethamine (KT) is a potent nonsteroidal anti-inflammatory drug (NSAID) used for moderate to severe pain management. Its short elimination half-life necessitates frequent dosing, which can reduce patient compliance. The objective of this study was to formulate, develop, and optimize a novel biphasic-release tablet-in-tablet (TIT) system for KT to provide immediate pain relief followed by extended drug release. A TIT system was designed, comprising an immediate-release (IR) outer layer and an extended-release (ER) core matrix. The ER core was optimized using a 32 full factorial design, with the amounts of HPMC K100M and HPMC K4M as independent variables. Formulations were evaluated for pre- and post-compression parameters, drug-excipient compatibility, and in vitro drug release. The drug release kinetics and mechanism were analyzed using various mathematical models. The optimal ER core formulation (F1) exhibited a drug release of 4.6% at 0.5 h and 66.1% at 12 h, closely matching the theoretical profile (similarity factor f2 = 51). Release kinetics followed the first-order model and the Korsmeyer-Peppas model indicated an anomalous (non-Fickian) release mechanism (n = 0.831). The corresponding TIT formulation (F11) demonstrated desired physicochemical properties: hardness of 75 N, friability of 0.59%, and rapid outer layer disintegration (<50 s). The TIT provided an initial burst release (~30%) within 30 minutes, followed by sustained release exceeding 90% over 24 hours. This TIT system represents a promising alternative to conventional KT tablets for effective pain management.","[""Journal Article""]","[""Zou P"", ""Zeng Y"", ""Liao XR"", ""Xie XY"", ""Li YK"", ""Ma YH"", ""Liu H""]",10.1371/journal.pone.0354689,Zou P,PloS one,1932-6203,7,PLoS One,eng,Liu H,"[""Ketorolac Tromethamine"", ""Tablets"", ""Delayed-Action Preparations"", ""Drug Liberation"", ""Chemistry, Pharmaceutical"", ""Anti-Inflammatory Agents, Non-Steroidal"", ""Kinetics"", ""Excipients""]",e0354689,42525646,pmc-id: PMC13421754;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42525646/,Formulation development of a biphasic release tablet-in-tablet system containing ketorolac tromethamine,21,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Sorbitol is a commonly used excipient in pediatric oral liquid formulations. Previous research revealed that sorbitol as an excipient can diminish the bioavailability of concomitant drugs. The reported cases and amount of sorbitol in pediatric formulations has not been explored, thus the aims of this study were to (1) examine the number of reports of sorbitol as an excipient in orally administered drugs with liquid formulations used in pediatrics, and (2) estimate the maximum amount of sorbitol that may be consumed per day for each drug. A compilation of drug products containing sorbitol as an excipient was retrieved from the Interagency Agreement between the National Institute of Child Health and Human Development (NICHD) and the Food and Drug Administration (FDA), and products with oral liquid formulations were selected. Maximum daily sorbitol amount was categorized into level 0 (< 3,200 mg), level 1 (3,200 mg to < 10,200 mg), level 2 (10,200 mg to < 13,400 mg), and level 3 (≥ 13,400 mg). Results indicated that sorbitol amount ranged between 0.06% and 45.7% weight to volume (w/v) across several therapeutic areas with the most prevalent being drugs intended for nervous system disorders. Corticosteroid drug products had the highest daily exposures to sorbitol, with amounts surpassing 45 grams. Percentages of products at levels 3, 2, 1 and 0 were 11.5%, 7.1%, 39.3%, and 42%, respectively. The potential impact of sorbitol content in pediatric formulations and the best practices for its use in pediatric polypharmacy needs to be further investigated.","[""Journal Article""]","[""Abulwerdi GA"", ""Cote B"", ""Abdel-Rahman S"", ""Fletcher EP"", ""Burckart GJ""]",10.1208/s12248-026-01265-4,Abulwerdi GA,The AAPS journal,1550-7416,5,AAPS J,eng,Burckart GJ,"[""Sorbitol"", ""Excipients"", ""United States"", ""Humans"", ""United States Food and Drug Administration"", ""Administration, Oral"", ""Chemistry, Pharmaceutical"", ""Child"", ""Biological Availability""]",,42521898,,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42521898/,Assessment of Sorbitol as a Pharmaceutical Excipient in Oral Liquid Pediatric Formulations Submitted to the U.S. FDA,28,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Antioxidants protect the skin from free radicals, which are associated with signs of aging, pigmentation, and loss of elasticity. Combining antioxidants in cosmetic formulations may provide broader antioxidant potential. This study focuses on the formulation and optimization of a polyherbal antioxidant peel-off mask using extracts of Ocimum sanctum (Tulsi), Moringa oleifera (Moringa), and Trigonella foenum-graecum (Fenugreek), which are reported to possess antioxidant and skin-beneficial properties. The formulation and optimization of the polyherbal peel-off mask were carried out using Central Composite Design (CCD). Polyvinyl alcohol (PVA) and carbomer 940 served as film-forming agents, while triethanolamine was used to adjust viscosity. The optimized formulation was evaluated for physicochemical characteristics, in vitro antioxidant activity, and irritation potential using the HET-CAM assay. The optimized formulation exhibited a drying time of 25.3 minutes and an applicability score of 18.82. Physicochemical evaluation showed acceptable homogeneity, smooth texture, and pH suitable for topical application. In vitro antioxidant assays demonstrated a lower IC50 value for the polyherbal mask compared to the standard vitamin C formulation, indicating notable antioxidant activity. Furthermore, the CAM (chorio-allantoic membrane) irritation test showed no observable signs of irritation such as hemorrhage, lysis, or coagulation under the study conditions. This study successfully formulated and optimized a polyherbal peel-off mask with promising in vitro antioxidant activity and acceptable physicochemical characteristics. The use of Central Composite Design (CCD) enabled systematic optimization of the formulation variables. The findings suggest the potential applicability of the developed herbal formulation for cosmetic skincare applications; however, further stability studies and in vivo safety and efficacy evaluations are required.","[""Journal Article""]","[""Ramakrishnan D"", ""Mr J"", ""Joy J"", ""Jojo GM"", ""Abbas FS""]",,Ramakrishnan D,International journal of pharmaceutical compounding,1092-4221,3,Int J Pharm Compd,eng,Abbas FS,"[""Antioxidants"", ""Plant Extracts"", ""Animals"", ""Drug Compounding"", ""Cosmetics"", ""Chemistry, Pharmaceutical"", ""Skin""]",237-252,42520812,,2026 May-Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42520812/,Development and Optimization of Antioxidant Poly Herbal Peel-off Mask using Doe Based Approach,30,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Processing herbal medicine generates substantial quantities of by-products that are discarded as waste. These residues may retain polysaccharides, flavonoids, saponins, terpenoids, and other constituents with pharmacological relevance. This review discusses the bioactive potential of by-products derived from single traditional Chinese and Korean herbal medicines, with emphasis on antioxidant, anti-inflammatory, and immunomodulatory mechanisms documented in preclinical in vivo studies. Representative in vivo evidence suggests that selected residues, marc fractions, fermentation products, and re-extracted by-products were reported to modulate oxidative stress markers, inflammatory cytokines, immune responses, and tissue-protective pathways across diverse experimental models. Processing method appears to be a key determinant of activity, as fermentation, high-temperature/high-pressure treatment, re-extraction, and targeted purification may enhance or diversify residual bioactivity. Current evidence remains limited by inconsistent chemical characterization, heterogeneous animal models, and incomplete reporting of experimental design. Re-evaluating herbal medicine processing by-products as bioactive resources may support sustainable herbal medicine manufacturing and circular bioeconomy frameworks.","[""Journal Article"", ""Review""]","[""Hwang JH"", ""Jung JH""]",10.3390/molecules31142516,Hwang JH,"Molecules (Basel, Switzerland)",1420-3049,14,Molecules,eng,Jung JH,"[""Antioxidants"", ""Anti-Inflammatory Agents"", ""Humans"", ""Animals"", ""Immunologic Factors"", ""Herbal Medicine"", ""Immunomodulating Agents"", ""Plants, Medicinal""]",,42513194,pmc-id: PMC13416048;,2026 Jul 18,2026,https://pubmed.ncbi.nlm.nih.gov/42513194/,"Herbal Medicine Processing By-Products as Bioactive Resources: In Vivo Evidence for Antioxidant, Anti-Inflammatory, and Immunomodulatory Effects",31,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"The collection of manuscripts presented in this issue exemplifies the breadth and vitality of contemporary medicinal chemistry, demonstrating how innovative molecular design, sophisticated synthetic methodologies, and biologically driven investigations continue to expand the frontiers of chemical and pharmaceutical sciences [...].","[""Editorial"", ""Introductory Journal Article""]","[""Christodoulou MS"", ""Athanassopoulos CM""]",10.3390/molecules31142454,Christodoulou MS,"Molecules (Basel, Switzerland)",1420-3049,14,Molecules,eng,Athanassopoulos CM,"[""Chemistry, Pharmaceutical"", ""Chemistry Techniques, Synthetic"", ""Humans"", ""Drug Design""]",,42513138,pmc-id: PMC13414069;,2026 Jul 14,2026,https://pubmed.ncbi.nlm.nih.gov/42513138/,Exclusive Feature Papers in Synthetic Medicinal Chemistry,31,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Rapid and non-destructive authentication of herbal medicines is important for quality control and market supervision. This study established an interpretable spectral evidence learning framework for visible and near-infrared (Vis/NIR) imaging-based authentication of Codonopsis Radix (CR) and Aurantii Fructus (AF). Compact 31-band mean gray-value spectra were analyzed at ROI and sample levels. CR sample-level spectra were obtained by ROI-group averaging, whereas AF records were retained as individual sample spectra with image-group information used for leakage-controlled validation. Raw spectra, Savitzky-Golay smoothing, multiplicative scatter correction, and standard normal variate correction were compared with machine-learning and deep-learning classifiers. A fold-contained lightweight diffusion (LD) module was further introduced to provide class-conditioned spectral augmentation and denoising-error evidence. Under grouped cross-validation, the strongest non-LD Linear SVM models achieved accuracy/macro-F1 values of 0.9231/0.9238 for CR and 0.9025/0.9018 for AF. After LD augmentation, the best LD-augmented SVM models reached macro-F1 values of 0.9427 and 0.9197, respectively. Across all evaluated model-dataset combinations, LD increased the overall mean macro-F1 from 0.7302 to 0.8189. Model-aligned wavelength evidence and top-wavelength subset tests further showed that selected LED-band subsets retained useful discriminative information within the present imaging configuration. These results support the feasibility of compact Vis/NIR image-based authentication of herbal materials under grouped validation.","[""Journal Article""]","[""Fan Z"", ""Ma C"", ""Jing S"", ""Huang J"", ""Zhang M""]",10.3390/molecules31142444,Fan Z,"Molecules (Basel, Switzerland)",1420-3049,14,Molecules,eng,Zhang M,"[""Spectroscopy, Near-Infrared"", ""Herbal Medicine"", ""Drugs, Chinese Herbal"", ""Support Vector Machine"", ""Machine Learning"", ""Plants, Medicinal""]",,42513128,pmc-id: PMC13415804;,2026 Jul 12,2026,https://pubmed.ncbi.nlm.nih.gov/42513128/,Interpretable Spectral Evidence Learning from Vis/NIR Imaging for Non-Destructive Authentication of Herbal Medicines,31,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"The NAT2 gene encodes N-acetyltransferase 2, an enzyme critically involved in the biotransformation of numerous xenobiotics and aromatic amines, including isoniazid, a cornerstone drug in tuberculosis therapy. Genetic polymorphisms in NAT2 lead to variable acetylation rates, clinically categorized as poor, intermediate, or rapid metabolizer phenotypes influencing drug efficacy and toxicity. This study aims to characterize the NAT2 polymorphisms in 240 Moroccan individuals using pre-existing clinical exome sequencing data. A total of fourteen variants were identified in the NAT2 coding region, with the most frequent being c.341 T>C (50%), c.803G>A (48.95%), c.481C>T (48.33%), and c.282C>T (29.16%). Diplotype-based phenotype prediction showed that 148 individuals (61.67%) were poor metabolizers, 71 (29.58%) intermediate metabolizers, and 14 (5.83%) rapid metabolizers. Seven individuals could not be classified due to the presence of variants with unreported diplotype-phenotype correlations. These findings provide a comprehensive pharmacogenetic profile of NAT2 in the Moroccan population and support the implementation of diplotype-guided isoniazid dosing strategies in tuberculosis-endemic settings.","[""Journal Article""]","[""Benyahya N"", ""El-Hamri MA"", ""Lyahyai J"", ""Ratbi I"", ""Cherkaoui I"", ""Rchiad Z"", ""Sefiani A""]",10.1111/cts.70670,Benyahya N,Clinical and translational science,1752-8054,8,Clin Transl Sci,eng,Sefiani A,"[""Humans"", ""Arylamine N-Acetyltransferase"", ""Isoniazid"", ""Morocco"", ""Antitubercular Agents"", ""Tuberculosis"", ""Female"", ""Pharmacogenetics"", ""Male"", ""Exome Sequencing"", ""Phenotype"", ""Adult"", ""Polymorphism, Single Nucleotide"", ""Pharmacogenomic Variants""]",e70670,42504089,pmc-id: PMC13402876;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42504089/,Genetic Landscape of NAT2 in the Moroccan Population: Implications for Isoniazid Pharmacogenetics in Tuberculosis,19,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Direct-to-consumer (DTC) pharmacogenomic (PGx) testing is expanding rapidly in the UK, yet no dedicated regulatory framework currently governs these services. Although a 2021 parliamentary inquiry recommended stronger safeguards and clearer technical standards for genomic testing, these proposals have not been applied to PGx. This study explores public attitudes toward DTC PGx testing, focusing on expectations for pre-test information, quality standards, and NHS data use. We conducted focus groups with members of the public, both with and without prior experience of purchasing DTC PGx tests, or other online health tests. Focus groups were audio-recorded with consent, transcribed, and analysed thematically. We identified three themes: (mis)understanding towards and awareness of DTC PGx testing; altruistic motivation and equity concerns; and (mis)trust. Participants were generally enthusiastic about PGx testing, as long as issues of equity, data protection, and regulation were addressed, with data sharing concerns being particularly prominent.","[""Journal Article""]","[""Mathieson A"", ""Brunton L"", ""Gillibrand S"", ""Moldovan R"", ""McDermott JH""]",10.1038/s41397-026-00425-1,Mathieson A,The pharmacogenomics journal,1470-269X,4,Pharmacogenomics J,eng,McDermott JH,"[""Humans"", ""United Kingdom"", ""Direct-To-Consumer Screening and Testing"", ""Pharmacogenomic Testing"", ""Public Opinion"", ""Focus Groups"", ""Female"", ""Male"", ""Qualitative Research"", ""Adult"", ""Pharmacogenetics"", ""Middle Aged"", ""Genetic Testing""]",,42502143,pmc-id: PMC13401518;,2026 Jul 25,2026,https://pubmed.ncbi.nlm.nih.gov/42502143/,Understanding public perspectives on direct-to-consumer pharmacogenomic testing in the UK: a qualitative study,26,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Thiopurines remain an effective treatment for maintaining remission in inflammatory bowel disease (IBD), yet their use is often limited by thiopurine-induced leukopenia (TIL), a potentially life-threatening adverse effect. We aimed to investigate pharmacogenetic associations with TIL in patients with IBD. We retrospectively analyzed 218 thiopurine-treated patients from two independent IBD cohorts with whole-exome sequencing. Pharmacogenetic subgroups were defined using Clinical Pharmacogenetics Implementation Consortium star allele-based molecular phenotypes or genotype-based classifications. Genetic associations with TIL, defined as white blood cell count ≤3000/µL, were analyzed using Andersen-Gill models adjusted for clinical covariates. NUDT15 intermediate metabolizers [hazard ratio (HR) 5.21, p<0.001], poor metabolizers (HR 6.42, p<0.001), and IL6 heterozygotes (HR 4.35, p<0.001) showed reproducible, independent associations with increased TIL risk. Incorporating IL6 into the traditional TPMT/NUDT15 model significantly improved sensitivity (p=0.0156) and negative predictive value (p=0.046). Our findings confirm the central role of NUDT15 in TIL susceptibility and identify IL6 as a novel, independent contributor in Korean patients with IBD. Incorporating IL6 into existing pre-emptive pharmacogenetic testing may support safer thiopurine therapy.","[""Journal Article""]","[""Boo EK"", ""Yu J"", ""Oh S"", ""Cheon JH"", ""Kim JH""]",10.3349/ymj.2025.0364,Boo EK,Yonsei medical journal,0513-5796,8,Yonsei Med J,eng,Kim JH,"[""Humans"", ""Leukopenia"", ""Inflammatory Bowel Diseases"", ""Female"", ""Male"", ""Risk Factors"", ""Pyrophosphatases"", ""Retrospective Studies"", ""Nudix Hydrolases"", ""Adult"", ""Pharmacogenetics"", ""Interleukin-6"", ""Mercaptopurine"", ""Middle Aged"", ""Azathioprine"", ""Genotype"", ""Methyltransferases""]",603-615,42494268,pmc-id: PMC13407061;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42494268/,Pharmacogenetic Risk Factors for Thiopurine-Induced Leukopenia in Patients with Inflammatory Bowel Disease,67,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"The pharmaco-epidemiological research program in kidney transplantation (PERP-KT) aims to evaluate, for the principal maintenance immunosuppressive drugs (MISDs): the influence of model-informed precision dosing on graft and patient survival; long-term exposure-effects relationships; and the benefit-harm balance of their combinations and time sequences in patient groups or clinical settings not adequately evaluated in comparative randomized clinical trials. It also aims to develop a hybrid, dynamic, deep learning model capable of predicting the rate of renal graft function decline, thereby providing a platform for individualized prediction of the benefits and risks associated with MISDs. After obtaining all regulatory andd ethical approvals, de-identified extracts of three national databases were linked to create the nationwide PERP-KT dataset, which is hosted within the highly secure environment of the French Health Data Hub. CRISTAL (the exhaustive registry of the French Agence de la Biomédecine) comprises data from 49 886 kidney donors and the corresponding 47 842 transplant recipients between 2005 and 2020. Following iterative deterministic matching and extensive quality control procedures, CRISTAL data were successfully linked to: the French national Health Data System (SNDS), which records reimbursed healthcare utilization, for 30 782 kidney transplant recipients; and to ISBA, a web-based platform for Bayesian dose adjustment of MISDs that contains pharmacological data, for 17 700 kidney grafts and 17 576 recipients. More than 20 pharmaco-epidemiological studies will leverage the database's extensive follow-up, large population size and richness of clinical, healtcare-utilization, and pharmacological data.","[""Journal Article""]","[""Marquet P"", ""Humeau A"", ""Crépin S"", ""Benoist C"", ""Couderc S"", ""Monchaud C"", ""Labriffe M"", ""Saint-Marcoux F""]",10.1002/pds.70442,Marquet P,Pharmacoepidemiology and drug safety,1053-8569,8,Pharmacoepidemiol Drug Saf,eng,Saint-Marcoux F,"[""Kidney Transplantation"", ""Humans"", ""Databases, Factual"", ""Immunosuppressive Agents"", ""Pharmacoepidemiology"", ""France"", ""Graft Survival"", ""Female"", ""Male"", ""Graft Rejection"", ""Registries"", ""Middle Aged"", ""Adult""]",e70442,42494189,pmc-id: PMC13396964;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42494189/,A Pharmaco-Epidemiological Research Program Leveraging a Nationwide Database of Kidney Transplantation,35,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Covalent inhibition continues to gain momentum as a strategy for selective protein modulation in both therapeutic and chemical biology contexts. Covalent reactive groups (CRGs) typically engage nucleophilic residues such as cysteine, resulting in targeted protein inactivation. However, common electrophiles such as acrylamides often suffer from nonselective reactivity, leading to off-target effects and toxicity. To overcome these limitations, we developed a modular sulfur(IV) reagent platform for the mild, late-stage installation of sulfonyl- and sulfonimidoyl-bicyclobutane motifs with complete cysteine selectivity. This methodology enables access to diverse sulfur(VI) CRGs with tunable strain-release reactivity. Incorporation into US Food and Drug Administration-approved covalent inhibitors demonstrated effective bioisosteric replacement of acrylamides and the potential of strain-release CRGs for selective protein targeting. Preclinical studies in mice have validated this approach, highlighting its promise for next-generation covalent drug design.","[""Journal Article""]","[""Shultz ZP"", ""Lee-Sam A"", ""Chang YP"", ""Sun L"", ""Grassie D"", ""Gabellini A"", ""Pedretty K"", ""Scattolin T"", ""Izumi V"", ""Fang B"", ""Sansil S"", ""Kakumanu R"", ""Wojtas L"", ""Koomen J"", ""Schönbrunn E"", ""Monastyrskyi A"", ""Duckett D"", ""Lopchuk JM""]",10.1126/science.adx7219,Shultz ZP,"Science (New York, N.Y.)",0036-8075,6809,Science,eng,Lopchuk JM,"[""Animals"", ""Mice"", ""Acrylamides"", ""Bioisosterism"", ""Cysteine"", ""Drug Design"", ""Proteins"", ""Sulfur""]",408-416,42490492,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42490492/,Late-stage functionalization with strain-release warheads enables tunable covalent inhibition,393,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Pitavastatin (PVN), a BCS class-II drug, exhibits poor aqueous solubility leading to limited oral bioavailability and therapeutic efficacy. This study aimed to enhance the solubility and anti-hyperlipidemic efficacy of Pitavastatin (PVN) by encapsulating it in chitosan-based polymeric nanoparticles. Pitavastatin-loaded chitosan nanoparticles (NPs) were prepared using the ionic gelation method. Formulations were characterized by particle size, zeta potential, drug loading, In-vitro drug release and surface morphology. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermal analysis (TGA and DSC), ex-vivo intestinal permeability and in-vivo pharmacodynamic analysis were also performed. The size of PVN-loaded NP ranged from 219.9±1.11 to 292.7±2.29 nm with PDI 0.2-0.4, surface charge of +28.4 ± 0.43 to 32.5 ± 1.02 mV and entrapment efficiency 65±1.12-93±1.23%. Solubility in different media (PBS (pH 6.8), 0.1N HCl (pH 1.2) and distilled water showed a 56-102-fold increase compared to PVN. SEM analysis revealed a smooth surface and spherical geometry of the NP. FTIR analysis confirmed that there was no physicochemical interaction between PVN and chitosan in NP formulations (NP1-NP5). XRD and thermal analysis indicated the amorphous nature of PVN-loaded NP. In-vitro drug release from NP formulations (NPI-NP5) ranged from 80.97±4.80 to 81±3.90% indicating sustained release, while ex-vivo intestinal permeability was 1.5-fold higher than PVN. The optimized formulation (NP1) followed Higuchi release model, indicating Fickian diffusion. Pharmacodynamic analysis of lipid profiles in hyperlipidemic albino rats suggested that NP1 reduced low-density lipoprotein (LDL) by 33±1.24 %, total cholesterol by 29±2.13% and triglycerides by 23±1.21%, showing better results than PVN. Chitosan-based Pitavastatin nanoparticles successfully enhanced drug solubility and provided sustained release, leading to improved ex-vivo permeability and greater in-vivo anti-hyperlipidemic activity in albino rats. This approach represents a promising strategy for enhancing therapeutic potential of Pitavastatin.","[""Journal Article""]","[""Arshad A"", ""Zaman M"", ""Riaz H"", ""Haider MS"", ""Ishaq W"", ""Adnan S"", ""Masood Z"", ""Ahmed H"", ""Ameer N"", ""Rahman HMA"", ""Waqas M"", ""Farooq M""]",10.36721/PJPS.2026.39.10.295.1,Arshad A,Pakistan journal of pharmaceutical sciences,1011-601X,10,Pak J Pharm Sci,eng,Farooq M,"[""Chitosan"", ""Animals"", ""Quinolines"", ""Nanoparticles"", ""Solubility"", ""Male"", ""Particle Size"", ""Delayed-Action Preparations"", ""Rats"", ""Drug Liberation"", ""Drug Carriers"", ""Hypolipidemic Agents"", ""Hyperlipidemias"", ""Intestinal Absorption"", ""Chemistry, Pharmaceutical"", ""Rats, Wistar"", ""Spectroscopy, Fourier Transform Infrared"", ""Drug Compounding""]",3186-3196,42489300,,2026 Oct 1,2026,https://pubmed.ncbi.nlm.nih.gov/42489300/,Formulation and evaluation of sustained-release pitavastatin-loaded chitosan nanoparticles for enhanced anti-hyperlipidemic activity,39,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Pharmaceutical salts are commonly used to enhance the bioavailability of poorly water-soluble drugs. The maximum solubility in water and the physical stability of a salt are closely linked to its pHmax, the pH at which both the free form (acid or base) and the salt can coexist. However, several aspects related to pHmax are only partially addressed or unexplored: (1) before salt screening, which usually consumes significant materials and efforts, whether pHmax can be predicted based on molecular properties; (2) whether salt disproportionation proceeds via a solid-state or water-mediated mechanism; and (3) whether disproportionation risk can be graded systematically and predicted. In this work, the relationship between pHmax and the physical properties of the basic compounds was examined, and a regression model was constructed based on their correlations. The pHmax values of 106 monosalts for 35 basic drugs were compiled from the literature. In the data set examined, the pHmax is strongly correlated with the pKa of the drug (2-10), but not significantly with the pKa of the counter-acid (-8 to 5), and is slightly influenced by the molecular weights of the drug and counter-acid. Accordingly, before salt screening, pHmax of a monosalt can be predicted as a function of the drug pKa and the relevant molecular weights. Across a pH range of 1-11, for the 106 monosalts studied, 74% of the predicted pHmax values were found to be within experimental errors. To determine whether disproportionation between pharmaceutical salts of basic drugs and basic excipients is a solid-state reaction or not, differential scanning calorimetry (DSC) is performed. The results showed that a solid-state reaction did not occur even at high temperatures where the excipient either melted or was liquefied above its glass transition temperature. Disproportionation risk levels were systematically defined based on development requirements and were exemplified using model HCl salts (sertraline, prazosin, phenazopyridine, and pioglitazone) across a wide pHmax range. The risk level shows a strong correlation with the pH difference between the equilibrium pH of the excipient (pHee) and the pHmax of the salt. Notably, the risk level increases more sharply with the pH difference (pHee - pHmax) for highly hygroscopic excipients. A prediction workflow for disproportionation risk level is proposed based on the above correlation and the self-disproportionation type of pharmaceutical salts.","[""Journal Article""]","[""Yao X"", ""Yu M"", ""Chen F"", ""Du S"", ""Kallemeyn LC"", ""Bergman J"", ""Lesslie MW"", ""Chen S"", ""Sheikh AY""]",10.1021/acs.molpharmaceut.6c00644,Yao X,Molecular pharmaceutics,1543-8384,8,Mol Pharm,eng,Sheikh AY,"[""Hydrogen-Ion Concentration"", ""Salts"", ""Solubility"", ""Pharmaceutical Preparations"", ""Drug Stability"", ""Bulk Drugs"", ""Water"", ""Chemistry, Pharmaceutical""]",4298-4310,42487463,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42487463/,Predicting pHmax and Salt Disproportionation Risk for Basic Drugs,23,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Plasmode simulation has become an important tool for evaluating operating characteristics of different statistical methods in complex settings, such as pharmacoepidemiological studies of treatment effectiveness using electronic health records (EHR) data. These studies provide insight into how estimator performance is impacted by challenges including rare events, small sample size and so forth that can indicate which among a set of methods performs best in a real-world dataset. Plasmode simulation combines data resampled from a real-world dataset with data from a probabilistic model to generate a known truth for an estimand in realistic data. There are different potential plasmode strategies currently in use. We compare two popular plasmode simulation frameworks for the evaluation of methods estimating a point treatment estimand. We provide numerical evidence and a theoretical result that shows one of these frameworks can cause certain estimators to incorrectly appear overly biased. Detailed simulation studies using both model-generated and real-world EHR data demonstrate these pitfalls remain at large sample sizes and when analyzing data from a randomized controlled trial. We conclude with guidance for the choice of a plasmode framework that maintains good theoretical properties to allow a fair evaluation of statistical methods while also maintaining the desired similarity to real data.","[""Journal Article""]","[""Shaw PA"", ""Gruber S"", ""Williamson BD"", ""Desai R"", ""Shortreed SM"", ""Krakauer C"", ""Nelson JC"", ""van der Laan MJ""]",10.1002/sim.70676,Shaw PA,Statistics in medicine,0277-6715,18-19,Stat Med,eng,van der Laan MJ,"[""Computer Simulation"", ""Humans"", ""Models, Statistical"", ""Electronic Health Records"", ""Randomized Controlled Trials as Topic"", ""Causality"", ""Pharmacoepidemiology"", ""Data Interpretation, Statistical"", ""Bias"", ""Sample Size""]",e70676,42487285,pmc-id: PMC13392349;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42487285/,A Cautionary Note for Plasmode Simulation Studies in the Setting of Causal Inference,45,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Cannabidiol (CBD) exhibits poor oral bioavailability (approximately 6%) due to low solubility and excessive first-pass metabolism, limiting its therapeutic potential. This study introduces a novel phospholipid complex self-nanoemulsifying drug delivery system (CBD-PLC-SNEDDS) to enhance CBD delivery. CBD-PLC was integrated into an optimized SNEDDS via Design of Experiments (DoE), yielding nanoemulsions with 118.9 ± 0.77 nm particle size, 0.258 PDI, and -21.9 mV zeta potential. Physicochemical characterization (DSC, FTIR) confirmed amorphization and physical encapsulation without chemical alteration. In vitro dissolution showed 100% CBD release within 1 h for CBD-PLC-SNEDDS vs. 8 h for CBD-SNEDDS. Stability studies (ICH guidelines) retained 94.73% ± 0.62% CBD at 25 °C/60% RH and 80.21% ± 0.61% at 40 °C/75% RH after 4 months with preservatives. In vivo pharmacokinetics in Sprague-Dawley rats (n = 9, 20 mg/kg oral; 4 mg/kg IV) demonstrated that CBD-PLC-SNEDDS significantly enhanced systemic exposure, achieving a calculated absolute bioavailability (F) of 92%, compared to 47% for the oleic acid control. The formulation yielded a 5-fold higher C max (593 ± 246 vs 118 ± 63 ng/mL) doubled AUC0-∞ (88 vs. 45 h·kg·ng/mL/mg), faster T max (2 ± 0.3 vs. 7.4 ± 2.3 h), and extended T 1/2 (3.7 ± 0.9 vs. 1.9 ± 0.6 h) versus control. CBD-PLC alone yielded only 39%. IVIVC modelling via Wagner-Nelson deconvolution established a strong correlation (R2 > 0.7) between in vitro dissolution and in vivo absorption, validating the system's predictive performance. This synergistic PLC-SNEDDS platform outperforms prior systems, offering a scalable template for lipophilic drugs and paving the way for clinical CBD therapeutics.","[""Journal Article""]","[""Muta T"", ""Mukhopadhyay S"", ""Noll B"", ""Song Y"", ""Garg S""]",10.1080/10717544.2026.2702143,Muta T,Drug delivery,1071-7544,1,Drug Deliv,eng,Garg S,"[""Cannabidiol"", ""Animals"", ""Biological Availability"", ""Phospholipids"", ""Administration, Oral"", ""Emulsions"", ""Rats, Sprague-Dawley"", ""Rats"", ""Particle Size"", ""Male"", ""Drug Delivery Systems"", ""Solubility"", ""Nanoparticles"", ""Nanoparticle Drug Delivery System"", ""Drug Stability"", ""Chemistry, Pharmaceutical"", ""Drug Liberation""]",2702143,42487275,pmc-id: PMC13398106;,2026 Dec 31,2026,https://pubmed.ncbi.nlm.nih.gov/42487275/,Development and in vivo pharmacokinetic evaluation of a phospholipid complex self-nanoemulsifying drug delivery system (PLC-SNEDDS) for enhanced oral bioavailability of cannabidiol,33,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"The first column in this 2-part series covered the history of clinical psychopharmacology from the author's perspective from 1975 to 2000. This column covers the last 26 years of clinical psychopharmacology as experienced by the author from 2000 to 2026. It focuses on the following major areas: (1) system-level neurobiology of neuropsychiatric drugs with an early focus on antidepressants; (2) circuit-based drug discovery; (3) pharmacokinetic, pharmacodynamic, and metabolic determination of psychotropic drug response as encompassed by Preskorn's Organizing Equation; (4) therapeutic drug monitoring (TDM) and pharmacology safety based on the use of TDM's ability to measure the functional as opposed to just the genetic capability of a patient to metabolize a medication; (5) enzyme-mediated drug-drug interactions; (6) multiple medication use in everyday clinical practice; (7) the results and implications of the results of the NIMH-funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study; and (8) early phase clinical investigation of novel central nervous system mechanisms. The column illustrates the author's goal to bring science to the practice of psychiatry, beginning in the mid-1970s, when psychoanalysis dominated psychiatric thinking, up through 2026, within our current limits of understanding. It also illustrates how, at least for one psychiatrist, knowledge in our field has evolved and his reason for having this goal.","[""Journal Article"", ""Historical Article"", ""Review""]","[""Preskorn SH""]",10.1097/PRA.0000000000000936,Preskorn SH,Journal of psychiatric practice,1527-4160,4,J Psychiatr Pract,eng,Preskorn SH,"[""Humans"", ""Psychopharmacology"", ""History, 20th Century"", ""History, 21st Century"", ""Psychotropic Drugs"", ""Antidepressive Agents"", ""Drug Monitoring"", ""Drug Discovery"", ""Mental Disorders""]",196-202,42475378,,2026 Jul 1,2026,https://pubmed.ncbi.nlm.nih.gov/42475378/,Developments in Clinical Psychopharmacology From 2000 Through 2026: A Personal Perspective,32,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Poor aqueous solubility remains a major barrier to small-molecule drug development. Pharmaceutical nanosuspensions, composed mainly of drug nanocrystals stabilized by small amounts of excipients, can improve dissolution and have been translated into several oral products and long-acting injectables. However, their simple compositions do not make them biologically inert. Nanosizing changes the surface area, dissolution, interfacial properties, aggregation, and interactions with biological fluids, thereby affecting local and systemic safety. This review examines nanosuspension safety from a product-level perspective. It focuses on formulation states generated during storage, handling, administration, and biological exposure, with attention to particle-size distribution, large-particle tails, stabilizer coverage and free excipient, crystal form, dissolution behavior, redispersibility, and in-use stability. These attributes are linked to blood compatibility, complement activation, immune responses, route-specific toxicity, biodistribution, macrophage-associated retention, depot persistence, clinical experience, and regulatory translation. Current evidence supports nanosuspensions under well-controlled conditions, especially for oral nanocrystal products and selected long-acting injectables. Key uncertainties remain for repeated intravenous use, chronic pulmonary exposure, particle-specific biodistribution, depot reversibility, long-term tissue exposure, and vulnerable populations. Safety assessment should, therefore, connect critical quality attributes with route-relevant exposure and biological responses, providing a basis for safety by design.","[""Journal Article"", ""Review""]","[""Ma Y"", ""Wang L"", ""Wang Y""]",10.1021/acs.molpharmaceut.6c00558,Ma Y,Molecular pharmaceutics,1543-8384,8,Mol Pharm,eng,Wang Y,"[""Humans"", ""Nanoparticles"", ""Suspensions"", ""Animals"", ""Solubility"", ""Drug Delivery Systems"", ""Particle Size"", ""Excipients"", ""Administration, Oral"", ""Chemistry, Pharmaceutical"", ""Drug Compounding"", ""Tissue Distribution"", ""Drug Stability""]",4003-4024,42470382,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42470382/,"Safety of Pharmaceutical Nanosuspensions in Drug Delivery: Evidence, Knowledge Gaps, and Safety-By-Design Strategies",23,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Clinical pharmacology plays a crucial role in the successful treatment and prevention of HIV and other viral infections. Information from the field of clinical pharmacology leads to the development of novel antiviral treatments, supports the evaluation of efficacy and safety of antiviral therapies, informs the management of drug-drug interactions, and defines the optimal dosing and drug selection for special populations. The International Workshop on Clinical Pharmacology of HIV, Hepatitis, and Other Antiviral Drugs recently held its 26th meeting. This review focuses on selected abstracts presented at the 2025 workshop and provides insights to assist clinicians in applying this new knowledge to clinical practice.","[""Review"", ""Journal Article""]","[""Scarsi KK"", ""Marzolini C"", ""Marra F"", ""Tseng AL""]",,Scarsi KK,Topics in antiviral medicine,2161-5861,3,Top Antivir Med,eng,Tseng AL,"[""Humans"", ""Antiviral Agents"", ""HIV Infections"", ""Pharmacology, Clinical"", ""Drug Interactions"", ""Hepatitis, Viral, Human""]",545-553,42467807,pmc-id: PMC13422888;,2026 Jul 16,2026,https://pubmed.ncbi.nlm.nih.gov/42467807/,"Selected highlights from the 26th International Workshop on Clinical Pharmacology of HIV, Hepatitis, and Other Antiviral Drugs",34,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Self-microemulsifying drug delivery systems (SMEDDS) containing volatile phytotherapeutics such as thymol (T), carvacrol (C), and eugenol (E) present significant formulation challenges, even when solidified. Their instability and interactions with coatings often hinder intestinal delivery. To address these limitations, we developed solid SMEDDS consisting of pellets (microcrystalline cellulose/magnesium aluminometasilicate/chitosan) and enteric capsules (CEC) for enhanced intestinal delivery. Based on solubility and pseudo-ternary phase diagrams, SMEDDS formulations (SES1-3) differing in component ratios (glycerol monooleate/caprylocaproyl macrogol-8 glycerides/diethylene glycol monoethyl ether) with 5% w/w of each drug were identified, demonstrating nano-scale droplet sizes (PDI <0.4) and showing no phase separation over 6 months. Thermodynamic stability and liquid-state NMR revealed particle size variations with preserved structural integrity. The lead formulation SES1 exhibited superior ex-vivo intestinal permeation (T-SES1). CECs filled with T-, C-, and E-loaded SES1 pellets, respectively, prepared via extrusion/spheronization, exhibited in-vitro gastro-resistant release, and achieved > 85% drug release within 120  min after a pH change to 6.8 during a one-year stability study (25 °C; 60% RH). FTIR-ATR analysis of the CEC internal surface confirmed the temperature-dependent restructuring of hypromellose and E sorption, a phenomenon not observed with C or T, which is likely attributable to physicochemical distinctions. Oral administration of CEC with T-SES1-pellets (0.5  mg/kg) in piglets demonstrated a delayed peak plasma concentration (Cmax 11.67  ng/mL at 9 h) and sustained systemic exposure (AUC 119.8 ng·h/mL). These in-vivo findings substantiate the gastro-protective effect and enhanced intestinal absorption, positioning the pellet/CEC system as a promising strategy for the application of volatile phytotherapeutics in current pharmacotherapy.","[""Journal Article""]","[""Koutná G"", ""Kotouček J"", ""Macků J"", ""Kubová K"", ""Urbanová M"", ""Janisová L"", ""Šeděnková I"", ""Muselík J"", ""Vysloužil J"", ""Mašek J"", ""Mašková E"", ""Pavelková M"", ""Vetchý D"", ""Brus J""]",10.1080/10717544.2026.2702133,Koutná G,Drug delivery,1071-7544,1,Drug Deliv,eng,Brus J,"[""Animals"", ""Drug Delivery Systems"", ""Emulsions"", ""Solubility"", ""Intestinal Absorption"", ""Particle Size"", ""Drug Stability"", ""Chemistry, Pharmaceutical"", ""Excipients"", ""Swine"", ""Administration, Oral""]",2702133,42454740,pmc-id: PMC13374766;,2026 Dec 31,2026,https://pubmed.ncbi.nlm.nih.gov/42454740/,"Phytotherapeutics self-microemulsifying systems in pellet dosage form for enhanced intestinal drug delivery: formulation, stability, and in-vivo performance",33,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"The objective of this study was to develop and optimize a dry powder inhalation formulation of Posaconazole-loaded Chitosan Nanoparticles (POS-CSNPs) using a Quality by Design (QbD) approach. The aim was to enhance pulmonary drug delivery and antifungal efficacy, particularly against Rhizopus oryzae, by improving drug encapsulation, particle dispersion, and lung deposition using leucine as a performance enhancer. A Box-Behnken Design (BBD) was employed to evaluate the effects of Chitosan-to- Tripolyphosphate (CS:TPP) ratio, stirring speed, and polymer concentration on particle size, Polydispersity Index (PDI), and Entrapment Efficiency (EE). Nanoparticles were prepared via ionic gelation and spray-dried with varying concentrations of lactose and leucine. Characterization techniques included FTIR for drug-excipient compatibility, Dynamic Light Scattering (DLS) for size and zeta potential, TEM for morphology, and XRD for crystallinity. In vitro drug release, pulmonary deposition using a twin-stage impinger, antifungal activity, and stability under ICH conditions were assessed. The optimized formulation had a particle size of 248.20 ± 6.82 nm, PDI of 0.225 ± 0.010, zeta potential of 21.92 ± 0.84 mV, and EE of 68.17 ± 1.73%. In vitro release showed sustained drug delivery over 48 hours. The Fine Particle Fraction (FPF) reached 68.9% in leucine-based formulations, and antifungal activity was significantly higher compared to the pure drug, with a zone of inhibition of 21 ± 0.5 mm. The results demonstrated improved particle characteristics, drug release, and antifungal efficacy. Leucine significantly enhanced dispersibility and deposition. However, scale-up and batch consistency remain challenges. Further in vivo studies are needed to confirm clinical applicability. The study successfully developed a stable, effective dry powder POS-CSNP formulation with enhanced pulmonary delivery and antifungal activity, offering potential for improved treatment of pulmonary fungal infections.","[""Journal Article""]","[""Singh SK"", ""Pancholi SS""]",10.2174/0118715265376840250717072610,Singh SK,Infectious disorders drug targets,1871-5265,3,Infect Disord Drug Targets,eng,Pancholi SS,"[""Chitosan"", ""Antifungal Agents"", ""Triazoles"", ""Leucine"", ""Particle Size"", ""Nanoparticles"", ""Drug Compounding"", ""Rhizopus oryzae"", ""Administration, Inhalation"", ""Drug Liberation"", ""Powders"", ""Chemistry, Pharmaceutical"", ""Excipients"", ""Dry Powder Inhalers"", ""Drug Carriers""]",33,42453019,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42453019/,Optimizing Chitosan-based Posaconazole Dry Powder Formulation Using Box-Behnken Design: The Role of Leucine in Enhancing Performance,26,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Artificial intelligence-driven molecular generation has become an increasingly used computational approach for proposing candidate chemical structures in early-stage drug discovery, yet the practical value of the molecules produced is often difficult to judge. Many studies still rely mainly on model-level metrics such as validity, uniqueness, novelty, and diversity. These metrics describe whether a generator produces parsable, non-redundant structures that extend beyond a reference set, but they do not show whether the molecules are chemically credible, biologically relevant, or experimentally actionable. AI-generated molecules are best treated as testable hypotheses requiring staged, complementary evidence rather than judgments based on generic generative statistics. We discuss the interpretive limits of common metrics, examine complementary levels of evaluation including medicinal chemistry feasibility, target relevance and prediction reliability, structure-based plausibility, and translational readiness, and identify recurring failure modes such as false novelty, reward exploitation, predictor bias, docking overinterpretation, and selective reporting. We propose a six-stage, failure-aware evaluation framework spanning molecular correctness, medicinal chemistry feasibility, novelty and diversity in context, target relevance and prediction reliability, structure-based plausibility, and translational readiness. This framework does not replace experimental validation; instead, it helps align computational claims with the strength of supporting evidence and promotes more transparent and reproducible evaluation of AI-generated molecules in drug discovery.","[""Journal Article"", ""Review""]","[""Liu X"", ""Liu H""]",10.3390/ijms27135916,Liu X,International journal of molecular sciences,1422-0067,13,Int J Mol Sci,eng,Liu H,"[""Drug Discovery"", ""Artificial Intelligence"", ""Generative Artificial Intelligence"", ""Humans"", ""Chemistry, Pharmaceutical""]",,42450185,pmc-id: PMC13362286;,2026 Jun 30,2026,https://pubmed.ncbi.nlm.nih.gov/42450185/,Evaluating AI-Generated Molecules for Drug Discovery: From Generic Metrics to Translational Readiness,27,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Glucose transporter 1 (GLUT1), the most extensively distributed member of the glucose transporter protein family, plays a pivotal role in regulating glucose metabolism and is indispensable for cellular growth, proliferation, and differentiation. Various metabolic disorders arise from the dysregulation of GLUT1 expression, which disrupts glucose homeostasis. The upregulation of GLUT1 has been identified in multiple cancer cells, facilitating tumor progression, metastasis, and resistance to treatment. Recent years have seen a surge in the discovery of GLUT1 inhibitors exhibiting improved selectivity and efficacy. Herein, we introduce the structure and biological function of GLUT1, GLUT1 related oncogenesis, and primarily focuses on recent advancements in the study of GLUT1 inhibitors over the last decade. Notably, this review is restricted to inhibitors that act through direct interaction with the GLUT1 protein, excluding agents that exert indirect effects via upstream signaling or metabolic regulation.","[""Journal Article"", ""Review""]","[""Meng Z"", ""Tian E"", ""Hu W"", ""Ren C"", ""Li J""]",10.1007/s00044-025-03514-1,Meng Z,Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents,1054-2523,2,Med Chem Res,eng,Li J,"[""Humans"", ""Glucose Transporter Type 1"", ""Neoplasms"", ""Antineoplastic Agents"", ""Drug Discovery"", ""Animals"", ""Chemistry, Pharmaceutical""]",316-339,42446694,,2026 Feb,2026,https://pubmed.ncbi.nlm.nih.gov/42446694/,Direct targeting of GLUT1 in cancer: A decade of inhibitor discovery and medicinal chemistry insights,35,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Piperazine has become essential for designing anticancer drugs because of its basicity, conformational flexibility, and capacity to serve as a solubilizing agent and molecular linker between hybrid pharmacophores. Researchers have found piperazine to function as a medicinal chemistry component that helps develop bioactive scaffolds through its capacity to control solubility, linker design, and target binding properties. The review presents a comprehensive assessment of piperazine-based anticancer drug research published between 2015 and 2025 through its evaluation of clinically relevant medicinal chemistry findings. The literature is organized based on piperazine's three main functional roles, which include its use as a linker and solubilizing/basic motif and direct target-recognition element. The study examines major cancer types through scaffold-based structure-activity relationship (SAR) analysis, which includes breast cancer, liver cancer, colon cancer, cervical cancer, prostate cancer, brain cancer, and leukemia models. The research demonstrated that various derivatives achieved IC₅₀ values in the low-nanomolar to low-micromolar range in MCF-7, HepG2, and HCT-116, HeLa, PC-3, and K562 cell lines. Researchers have demonstrated how protonatable piperazine nitrogens improve aqueous solubility and formulation development, and interactions of enzyme and kinase active sites with acidic residues, which results in better binding strength and selectivity. The review presents major translational obstacles, which include excessive dependence on 2D in vitro studies, insufficient in vivo and ADME/PK information, and limited progress in clinical applications. The research studies the development of clinically usable piperazine-based anticancer drugs through novel methods, which include green chemistry, click chemistry, molecular docking, and QSAR-focused design.","[""Journal Article"", ""Review""]","[""Porwal T"", ""Kumar R"", ""Tripathi S"", ""Salahuddin""]",10.1007/s00044-026-03567-w,Porwal T,Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents,1054-2523,6,Med Chem Res,eng,Salahuddin,"[""Humans"", ""Antineoplastic Agents"", ""Structure-Activity Relationship"", ""Piperazines"", ""Neoplasms"", ""Chemistry, Pharmaceutical"", ""Piperazine""]",1031-1063,42446683,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42446683/,"Piperazine derivatives as anticancer agents: a medicinal chemistry review of structure, mechanism, and clinical translation",35,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Pyridine is a common nitrogen-containing heteroaromatic motif in antitumor medicinal chemistry, but its design value is highly context dependent. Here, we synthesize structure-oriented medicinal chemistry principles that govern the use of pyridine-related motifs in antitumor drug design. We discuss pyridine-containing antitumor agents with emphasis on target recognition, scaffold organization, structure-activity relationship (SAR), drug metabolism and pharmacokinetics (DMPK), and absorption, distribution, metabolism, excretion, and toxicity (ADMET) liabilities. Representative approved drugs, antibody-drug conjugate (ADC) payloads, targeted degraders, and polypyridyl metal complexes are used to illustrate how pyridine-related motifs can support binding, property tuning, and modality adaptation. By grouping representative compounds according to the medicinal chemistry function of their pyridine-related motifs, this review provides a practical framework for future scaffold design. Overall, pyridine should not be viewed as a universally beneficial privileged scaffold; it is better treated as a context-dependent design module that requires validation through integrated structural, SAR, ADMET, and translational evidence.","[""Journal Article"", ""Review""]","[""Zhao W"", ""Bie B"", ""Wang J"", ""Liu X"", ""Fang H"", ""Niu R""]",10.1007/s00044-026-03588-5,Zhao W,Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents,1054-2523,7,Med Chem Res,eng,Niu R,"[""Pyridines"", ""Humans"", ""Structure-Activity Relationship"", ""Antineoplastic Agents"", ""Chemistry, Pharmaceutical"", ""Animals"", ""Drug Design""]",1316-1329,42446547,pmc-id: PMC13385078;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42446547/,"Pyridine-containing antitumor agents: structure-oriented medicinal chemistry, structure-activity relationships, and ADMET liabilities",35,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Traditional medicine is now moving from the ""one-size-fits-all"" model toward personalized medicine, where diagnostic and therapeutic decisions are guided by the patient's unique genetic profile. Recent advances in genomics and pharmacogenomics have facilitated the identification of genetic variants linked to disease susceptibility and progression, as well as variability in drug response. However, translating these findings into clinical practice remains challenging, primarily due to the high cost and sophisticated genetic analysis infrastructure, which is only available in centralized genetic laboratories. A newly developed Portable Genetic Analyzer (PortaGen) was designed for point-of-care molecular genetics and pharmacogenomics analysis and evaluated in this study. PortaGen integrates 3D-printed parts and laptop-based centralized software control, along with digital recording and storage of results to support decentralized genetic testing. The prototype portable device was validated in comparison with an established portable polymerase chain reaction (PCR) workstation that complies with current operational standards and a reference laboratory-based method. Genotyping analysis was performed using ARMS-PCR (Amplification Refractory Mutation System Polymerase Chain Reaction) to detect and analyze CYP2C19 genetic variants (CYP2C19 ∗ 2; rs4244285, and CYP2C19 ∗ 17; rs12248560), relevant to pharmacogenomics, as well as the HBB: c.93-21(G>A) genetic variant, the most common variant leading to β-thalassemia. Concordance in genotyping calls between the new device, the established portable workstation, and the reference method was assessed using percentage agreement and Cohen's kappa coefficient, demonstrating consistently high concordance with statistically significant results (p < 0.05). These findings demonstrate that the new portable genotyping analyzer has improved throughput, visualization, and workflow efficiency into a suitcase-sized, portable point-of-care molecular genetic analysis device, which holds promise to advance personalized medicine interventions in a scalable and affordable fashion.","[""Journal Article""]","[""Poulida I"", ""Karamperis K"", ""Routsi IK"", ""Sarris I"", ""Mantzouranis G"", ""Kostopoulos V"", ""Mitropoulou C"", ""Patrinos GP""]",10.1155/humu/9614566,Poulida I,Human mutation,1059-7794,,Hum Mutat,eng,Patrinos GP,"[""Humans"", ""Point-of-Care Systems"", ""Cytochrome P-450 CYP2C19"", ""Pharmacogenetics"", ""Precision Medicine"", ""Genotype"", ""Genetic Testing"", ""Rapid Diagnostic Tests""]",9614566,42444709,pmc-id: PMC13357681;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42444709/,Development of a New Portable Genetic Analyzer for Point-of-Care Molecular Genetics and Pharmacogenomics Analysis,2026,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"the use of real-world (RW) data has become an integral part of pharmacoepidemiological research and regulatory assessment. However, access to individual-level data, especially for purposes other than the original ones (secondary use), is often restricted by legal and ethical constraints related to privacy protection. In this context, generating synthetic data, defined as artificially generated data that reproduce the statistical properties and relationships of real data without containing information traceable to real individuals, offers an innovative opportunity to balance privacy protection with the need to generate RW evidence to support regulatory decision-making. to compare two methods of generating tabular synthetic data: synthpop, based on transparent and interpretable inferential methodologies, and Conditional Tabular-Generative Adversarial Networks (CT-GANs), which leverage deep learning approaches to reproduce complex multivariate distributions. The focus is on evaluating the ability of both approaches to preserve the statistical structure of real data and reduce the risk of disclosure/re-identification. comparative study of two synthetic data generation methods. a large anonymized RW dataset including 42,926 patients hospitalized for COVID-19 in Italy during the early phase of the pandemic. The dataset was obtained through record linkage of administrative databases and the COVID-19 registry using the TheShinISS tool. synthetic versions of the original dataset were generated using both synthpop and CT-GAN methods. Real and synthetic data were compared using three type of measures: 1. general utility measures (univariate, bivariate, and global), including comparison of variable distributions using plots, descriptive statistics, standardized mean differences (SMD), and Propensity Score Mean Squared Error; 2. specific utility measures, assessing the similarity of associations estimates from univariate and multivariable Cox models by evaluating the overlap of 95% confidence intervals (CI) of hazard ratios (HR), and comparison of Kaplan-Meier curves using the log-rank test; 3. disclosure (re-identification) measures, estimating the risk of identity and attribute disclosure using dedicated metrics (Unique in Original - UiO, replicated Uniques - repU, Disclosive in Original - Dorig, Disclosive in Synthetic Correct Original - DiSCO). in terms of general utility, results confirmed the superiority of synthpop over CT-GAN, with more than half of the variables exceeding the acceptable SMD threshold. Moreover, synthpop showed higher specific utility than CT-GAN, with a median overlap of 95%CI of HR of 75% (interquartile range, IQR: 66%-95%) compared with 0% (IQR: 0%-6%) for CT-GAN. Concerning disclosure measures, although the original dataset already presented a negligible risk of identity disclosure (UiO=0.23%), making synthesis largely redundant, both methods further reduced this risk (synthpop: repU=0.06%; GAN: repU=0.05%). in this study, considering the three evaluated aspects, synthpop performed better in balancing statistical accuracy and privacy protection. It also offered greater methodological transparency based on explicit statistical models and required lower computational time. These findings contribute to the ongoing debate on the potential use of synthetic data in research and regulatory assessments supporting their integration into RW data analysis workflows. The disclosure measures adopted may serve as a practical starting point, however, the definition of shared standards for these measures, as well as acceptable disclosure risk thresholds, would be desirable and should be developed collaboratively by the scientific community and data protection authorities. Future studies should focus on generating synthetic data where non-explicit relationships exist in real data (i.e., relationships that are not directly attributable to additive or multiplicative structures).","[""Journal Article"", ""Comparative Study"", ""English Abstract""]","[""Mayer F"", ""Fazio ML"", ""Cutillo M"", ""Stendardo G"", ""Spila Alegiani S"", ""Trifirò G"", ""Massari M""]",10.19191/EP26.3.A992.059,Mayer F,Epidemiologia e prevenzione,1120-9763,3,Epidemiol Prev,ita,Massari M,"[""Humans"", ""Generative Adversarial Networks"", ""Pharmacoepidemiology"", ""Reproducibility of Results"", ""Privacy"", ""Confidentiality"", ""Italy""]",279-289,42444462,,2026 May-Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42444462/,[Comparing synthetic data generation methods in pharmacoepidemiology: reconciling reproducibility with privacy protection],50,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Cassava (Manihot esculenta) is a significant source of starch in Ethiopia, with potential pharmaceutical applications. However, native starches often require modifications to enhance their utility, particularly as disintegrants. Carboxymethylation is a well-known modification that improves swelling and disintegration capacity. Therefore, this study is aimed at evaluating carboxymethylated cassava starch (CMCS) as a tablet disintegrant. CMCSs were produced using monochloroacetic acid under varying reaction conditions. Structural modification was confirmed with FTIR spectroscopy. Physicochemical and powder properties, including degree of substitution (DS), swelling power, viscosity, and flow behavior, were characterized using standard methods. Tablets were prepared using the direct compression method. The tablets were assessed for physical characteristics, disintegration, and dissolution to compare the disintegrant performance of CMCS, native cassava starch (NCS), and sodium starch glycolate (SSG). Nine CMCS batches were obtained from the modification process and confirmed by FTIR analysis. CMCSs showed improved characteristics such as hydration capacity, swelling power, and solubility compared to NCS. Specifically, CMCS7 (DS = 0.227) exhibited comparable flow, swelling, hydration, and viscosity to SSG. Thus, it was selected as an optimal batch to be used as a disintegrant. Tablets formulated with CMCS7 exhibited superior mechanical strength, low friability, and higher disintegration efficiency ratios compared to NCS while performing comparably to SSG. Tablets containing CMCS showed comparable disintegration to SSG and enhanced initial dissolution. CMCS demonstrated promising disintegrant properties and could serve as a potential alternative local super-disintegrant in pharmaceutical tablet formulations.","[""Journal Article""]","[""Abraha T"", ""Molla F"", ""Teklebrhan A"", ""Hussen H"", ""Getachew A""]",10.1155/bmri/4575160,Abraha T,BioMed research international,2314-6133,1,Biomed Res Int,eng,Getachew A,"[""Starch"", ""Manihot"", ""Tablets"", ""Solubility"", ""Viscosity"", ""Spectroscopy, Fourier Transform Infrared"", ""Drug Compounding"", ""Excipients"", ""Chemistry, Pharmaceutical""]",e4575160,42434809,pmc-id: PMC13355292;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42434809/,Carboxymethylation and Evaluation of Cassava (Manihot esculenta) Starch as a Potential Super-Disintegrant in Tablet Formulations,2026,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Negative controls (NCs) are increasingly used in real-world observational studies to detect residual confounding and systematic bias, but their implementation and reporting remain heterogeneous in applied pharmacoepidemiology. We conducted a methodological scoping review to characterize how NCs were selected, implemented, reported, and interpreted in real-world studies evaluating glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for non-indicated clinical outcomes. We systematically searched PubMed and Embase from database inception through November 2025 and additionally screened reference lists of included studies. Eligible studies used real-world data, applied an observational analytic framework to evaluate GLP-1 RAs, focused on non-indicated outcomes, and explicitly incorporated NCs for bias detection, falsification, validation, or empirical calibration. Among 489 records identified, 42 studies met the inclusion criteria. Most studies were cohort-based and were conducted in diabetes-related populations using electronic health records or administrative claims. Negative control outcomes (NCOs) were the dominant approach, whereas negative control exposures (NCEs), positive controls, and empirical calibration were less common. An explicit rationale for NC selection was reported in most studies, but none of the included studies explicitly discussed the assumptions underlying NC analysis. Most NC findings were reported as null or consistent with expectations, and were primarily used to support validity or robustness rather than to materially alter interpretation. Overall, our findings suggest that the current use of NCs in GLP-1 RA observational research has increased, while standardized implementation and reporting have lagged. Greater transparency regarding why NCs were selected, what source of bias they were intended to probe, how results were interpreted, and whether they changed analytic conclusions may improve the credibility and interpretability of real-world evidence in this rapidly evolving therapeutic area.","[""Journal Article"", ""Scoping Review""]","[""Li Z"", ""Huang Y"", ""Chen H"", ""Li J""]",10.1002/pds.70420,Li Z,Pharmacoepidemiology and drug safety,1053-8569,7,Pharmacoepidemiol Drug Saf,eng,Li J,"[""Glucagon-Like Peptide-1 Receptor Agonists"", ""Pharmacoepidemiology"", ""Humans"", ""Observational Studies as Topic"", ""Hypoglycemic Agents"", ""Bias"", ""Confounding Factors, Epidemiologic"", ""Research Design""]",e70420,42432825,pmc-id: PMC13354716;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42432825/,How Negative Controls Are Used in Pharmacoepidemiology: A Methodological Scoping Review of Real-World Observational Studies of Glucagon-Like Peptide-1 Receptor Agonists,35,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"This review summarizes the evolution of our research on anticancer agents, from early efforts on hypoxia-selective cytotoxins to more recent developments in chemoprevention, molecular targeting, and radiopharmacy. Initial studies focused on the design of N-oxide-containing heterocycles as bioreductive-prodrugs activated under tumor hypoxia. While early triazine N-oxides and furoxans showed limited selectivity, these studies underscored the importance of redox-properties in biological activities. This led to the identification of phenazine 5,10-dioxides as a more suitable pharmacophore, affording compounds with improved potency- and hypoxia-selectivity, supported by mechanistic-, physicochemical-, and in vivo studies. Parallel efforts explored metal-based complexes and formulation strategies enhancing bioavailability and therapeutic performance. Alongside these efforts, cancer chemopreventive-agents were investigated, particularly chalcone-derived scaffolds and related hybrids capable of modulating phase I/II enzymes through Nrf2 activation. Additionally, attention has shifted toward targeted- and diagnostic-approaches, including radiopharmaceuticals for hypoxia-imaging and the use of biomolecular recognition systems, such as aptamers, polypeptides, and antibodies, to selectively address tumor-associated biomarkers. These strategies include aptamer-based biotherapeutics for drug delivery and imaging, as well as approaches combining tyrosine kinase receptor targeting with BNCT. Furthermore, bioorthogonal-methodologies have been explored enabling selective in situ activation and targeting. Together, these studies illustrate a multidisciplinary approach integrating chemistry, biology, and pharmacology toward more selective anticancer strategies.","[""Journal Article"", ""Review""]","[""Lavaggi ML"", ""García MF"", ""Cabrera M"", ""Couto M"", ""Cerecetto H""]",10.1002/cmdc.70361,Lavaggi ML,ChemMedChem,1860-7179,13,ChemMedChem,eng,Cerecetto H,"[""Humans"", ""Antineoplastic Agents"", ""Neoplasms"", ""Animals"", ""Chemistry, Pharmaceutical""]",e70361,42432465,pmc-id: PMC13354720;,2026 Jul 14,2026,https://pubmed.ncbi.nlm.nih.gov/42432465/,Medicinal Chemistry of Agents for Cancer Therapy and Diagnosis From Uruguay,21,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Since its introduction in 1951, bioisosterism has become a cornerstone strategy in drug design and development, enabling chemists to rationally modify molecular structures to optimize biological and physicochemical properties. In this perspective, we examine 57 FDA-approved drugs and 18 advanced drug candidates wherein bioisosteric replacements were successfully employed to address a range of developability challenges encountered during lead optimization. These strategic substitutions have led to significant improvements in potency, selectivity, solubility, and metabolic stability, while simultaneously mitigating issues related to lipophilicity, plasma protein binding, and the formation of reactive metabolites. Together, these examples highlight the enduring impact of bioisosterism as a versatile tool for fine-tuning drug candidates and overcoming the multifaceted challenges of modern medicinal chemistry.","[""Journal Article"", ""Review""]","[""Wu YJ"", ""Chmiel AF"", ""Bronson JJ""]",10.1021/acs.jmedchem.5c03492,Wu YJ,Journal of medicinal chemistry,0022-2623,14,J Med Chem,eng,Bronson JJ,"[""Bioisosterism"", ""Humans"", ""Drug Design"", ""United States Food and Drug Administration"", ""Drug Discovery"", ""Drug Approval"", ""United States"", ""Animals"", ""Pharmaceutical Preparations""]",16143-16208,42431828,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42431828/,Application of Bioisosteres in the Design and Discovery of FDA-Approved Drugs and Advanced Clinical Candidates,69,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Sixteen years ago, the fraction of sp3 centers (Fsp3) in a molecule was correlated with clinical progression, solubility, and promiscuity in Lovering's ""Escape from Flatland"" papers. These trends captivated academia and industry alike, motivating a flurry of strategies to incorporate sp3 carbons into targets for medicinal chemistry. Given this widespread impact, we performed a retrospective analysis on the small molecule portfolio of Merck & Co., Inc., Rahway, New Jersey, USA (hereinafter ""MSD""). We probe how Fsp3 changed with year of synthesis and target class from 2000 to 2024, and whether Fsp3 impacted compound progression. To investigate explanations for these trends, we analyze Fsp3's influence on lipophilicity, permeability, solubility, and off-target potency and compare these findings with previous studies. Leveraging MSD's compound collection (millions of small molecules), we provide further context for the originally reported correlations and novel insights into incorporating Fsp3 effectively in future drug designs.","[""Journal Article"", ""Review""]","[""Garry OL"", ""Cheng AC"", ""Northrup AB"", ""Merchant RR"", ""Yeung CS""]",10.1021/acs.jmedchem.6c01038,Garry OL,Journal of medicinal chemistry,0022-2623,14,J Med Chem,eng,Yeung CS,"[""Humans"", ""Small Molecule Libraries"", ""Solubility"", ""Drug Industry"", ""Drug Discovery"", ""Chemistry, Pharmaceutical""]",16279-16287,42425067,,2026 Jul 23,2026,https://pubmed.ncbi.nlm.nih.gov/42425067/,"Retrospective Analysis of the Impact of the ""Escape from Flatland"" Publication on the Merck & Co., Inc., Small Molecule Portfolio",69,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"BACKGROUND Hypertension management is often suboptimal due to interindividual variability in drug response. Pharmacogenomics testing may guide personalized therapy by identifying genetic polymorphisms affecting drug efficacy and safety. This study aimed to evaluate whether pharmacogenomics-guided therapy improves blood pressure control and treatment compliance and reduces rehospitalization in patients with hypertension. MATERIAL AND METHODS In this prospective randomized controlled trial, 900 patients with hypertension were assigned to a control group (CG, n=450) receiving conventional care or a study group (SG, n=450) receiving pharmacogenomic-guided therapy. Six gene loci (CYP2D6, CYP2C9, AGTR1, ACE, NPPA, CYP3A5) related to 5 antihypertensive drug classes were tested. Outcomes included blood pressure control rate, compliance, adverse reactions, drug adjustments, and 6-month readmission rate. RESULTS The SG achieved significantly higher blood pressure control rates at 3 months (80.7% vs 70.2%, P<0.001) and 6 months (78.4% vs 65.1%, P<0.001) compared with the CG. Treatment compliance was also higher in the SG (98.0% vs 74.0%, P<0.001). angiotensin-converting enzyme inhibitor-related dry cough incidence was lower in the SG (1.6% vs 8.3%, P<0.001). The SG required fewer drug adjustments during hospitalization and had a lower 6-month readmission rate (2.4% vs 8.9%, P<0.001). CONCLUSIONS Pharmacogenomic-guided individualized therapy improves blood pressure control, enhances treatment adherence, reduces specific adverse reactions, and decreases rehospitalization. These findings support integrating pharmacogenomic testing into personalized hypertension management.","[""Journal Article"", ""Randomized Controlled Trial""]","[""Xie D"", ""Deng M"", ""Yang X"", ""Huang J"", ""Hong X"", ""Xu N""]",10.12659/MSM.952296,Xie D,Medical science monitor : international medical journal of experimental and clinical research,1234-1010,,Med Sci Monit,eng,Xu N,"[""Humans"", ""Hypertension"", ""Antihypertensive Agents"", ""Female"", ""Blood Pressure"", ""Male"", ""Middle Aged"", ""Prospective Studies"", ""Pharmacogenetics"", ""Pharmacogenomic Testing"", ""Treatment Outcome"", ""Aged"", ""Precision Medicine""]",e952296,42421289,pmc-id: PMC13367096;,2026 Jul 9,2026,https://pubmed.ncbi.nlm.nih.gov/42421289/,Preliminary Application of Antihypertensive Gene Detection in the Treatment of Hypertension,32,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Targeted drug delivery systems play a crucial role in improving the effectiveness and precision of cancer treatments. Liposomes have been widely investigated as drug carriers due to their versatility. Traditional methods for functionalizing liposomes involve covalent bonding of targeting ligands, which, while effective, can be complex and may affect the activity of the ligands. In contrast, non-covalent peptide insertion offers a simpler, more adaptable approach for incorporating targeting peptides into liposomal membranes using mechanisms such as hydrophobic interactions and electrostatic forces. This review examines non-covalent peptide-liposome interactions as the primary focus. We analyze mechanisms, incorporation techniques, and therapeutic applications with emphasis on formulation-relevant criteria including stability, manufacturability, and clinical translation. Critical evaluation of comparative advantages and limitations of each strategy provides decision frameworks for formulation scientists. We also address manufacturing challenges, quality control strategies, and regulatory considerations that influence clinical translation.","[""Journal Article"", ""Review""]","[""Maikifi AS"", ""Boonkanokwong V""]",10.1208/s12249-026-03488-2,Maikifi AS,AAPS PharmSciTech,1530-9932,5,AAPS PharmSciTech,eng,Boonkanokwong V,"[""Liposomes"", ""Humans"", ""Peptides"", ""Neoplasms"", ""Drug Carriers"", ""Nanoparticles"", ""Drug Delivery Systems"", ""Antineoplastic Agents"", ""Hydrophobic and Hydrophilic Interactions"", ""Animals"", ""Chemistry, Pharmaceutical""]",,42414738,,2026 Jul 7,2026,https://pubmed.ncbi.nlm.nih.gov/42414738/,A Review on Modular Peptide Anchoring Strategies for Functionalizing Liposomal Nanocarriers: Advancing Non-covalent Design Toward Targeted Cancer Therapy,27,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"The imidazoline receptor (IR) system, comprising the I1R, I2R, and I3R subtypes, consists of binding sites involved in cardiovascular, metabolic, and neurological disorders. This review updates the 2004 compilation by Dardonville and Rozas on IR ligands, emphasizing promising ligands, subtype selectivity, and pharmacological profiling. Representative ligands for each subtype are analyzed to highlight key pharmacological aspects, including affinity, selectivity, and functional activity, integrating findings from preclinical and clinical studies. Critical molecular targets such as Nischarin/IRAS for I1R and MAO-B-associated sites for I2R are discussed in the context of ligand design and CNS penetration. I1R-selective ligands, exemplified by rilmenidine, show improved selectivity over α2-adrenoceptors and exhibit antihypertensive, metabolic, and neuroprotective effects. I2R ligands display neuroprotective, anti-inflammatory, and analgesic activities, with CR4056 progressing to Phase II trials. PET imaging with [11C]BU99008 has validated I2R upregulation as a biomarker for neurodegeneration. Overall, the IR system presents therapeutic opportunities: I1R for cardiovascular and metabolic disorders, I2R for pain and neurodegeneration, and I3R for diabetes. Continued ligand optimization and receptor characterization are essential for clinical translation.","[""Journal Article"", ""Review""]","[""Kouridaki ME"", ""Pallàs M"", ""Escolano C""]",10.1002/cmdc.70350,Kouridaki ME,ChemMedChem,1860-7179,13,ChemMedChem,eng,Escolano C,"[""Imidazoline Receptors"", ""Humans"", ""Ligands"", ""Animals"", ""Neuroprotective Agents"", ""Chemistry, Pharmaceutical"", ""Analgesics""]",e70350,42414242,pmc-id: PMC13342470;,2026 Jul 14,2026,https://pubmed.ncbi.nlm.nih.gov/42414242/,"Pharmacology, Medicinal Chemistry, and Therapeutic Potential of Imidazoline Receptor Ligands",21,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Parkinson's disease is a distinctly age-associated neurodegenerative disorder in which oral levodopa remains the therapeutic foundation, particularly in older adults. Yet with advancing age, the reliability of oral therapy progressively declines not simply due to inadequate dosing, but because ageing reshapes the gastrointestinal environment on which drug absorption depends. This review integrates evidence spanning neuromuscular decline, epithelial barrier fragility, altered luminal chemistry, immune dysregulation, microbiome remodelling, and enteric neurodegeneration to explain how the ageing gut generates exposure instability. Delayed gastric emptying, inconsistent proximal intestinal delivery, microbial drug metabolism, and real-world administration constraints collectively amplify pharmacokinetic variability, producing erratic onset, fluctuating plasma profiles, and reduced therapeutic predictability. Using levodopa as a clinically established model system, we extend these insights to the broader challenge of ensuring reliable performance of oral therapies in ageing populations. We argue that therapeutic success in older adults depends less on maximizing mean bioavailability and more on stabilising exposure under heterogeneous physiological and practical conditions. Accordingly, the review integrates ageing-associated gastrointestinal decline, altered luminal and epithelial determinants of drug absorption, pharmacokinetic instability, and formulation design responses into a unified translational framework for ageing-aware oral therapy. By reframing levodopa failure as a consequence of ageing-driven gut-drug instability, this review proposes an ageing-aware formulation framework and identifies exposure-stability endpoints to guide the development and evaluation of physiologically resilient oral therapies for older adults.","[""Journal Article"", ""Review""]","[""Madny MA"", ""Yadav KS""]",10.1016/j.ejpb.2026.115179,Madny MA,European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V,0939-6411,,Eur J Pharm Biopharm,eng,Yadav KS,"[""Humans"", ""Levodopa"", ""Parkinson Disease"", ""Aging"", ""Administration, Oral"", ""Antiparkinson Agents"", ""Gastrointestinal Tract"", ""Animals"", ""Intestinal Absorption"", ""Biological Availability"", ""Chemistry, Pharmaceutical"", ""Drug Compounding""]",115179,42413884,,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42413884/,Ageing-driven gastrointestinal variability in Parkinson's disease: implications for oral levodopa pharmacokinetics and formulation design,226,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"The growing demand for subcutaneous (SC) self-administration of biotherapeutics, driven by the rising prevalence of chronic diseases and healthcare cost-containment pressures, has accelerated the development of high-concentration formulations (HCFs). However, protein concentrations exceeding 100 mg/mL introduce significant challenges, including solubility limitations, high viscosity, aggregation propensity, injectability constraints, and manufacturing complexities. This review systematically examines the primary obstacles in HCF development and highlights recent advances in formulation and process technologies. Key strategies include: (i) excipient-based viscosity reducers; (ii) hyaluronidase-enabled large-volume SC delivery; (iii) lyophilization for decoupling manufacturing from final concentration; (iv) spray drying platforms including SnapShot™ and XeriJect®; (v) electrostatic spray drying (Elektroject™ Hypercon™); (vi) Microglassification™ dehydration technology; and (vii) protein crystallization (Crystalomics®). Collectively, these innovations are reshaping the landscape of high-concentration biologic drug products, enabling the transition from intravenous to subcutaneous administration for a broader range of therapeutics. This review serves as a strategic guide for formulation scientists and drug developers engaged in next-generation subcutaneous biologics.","[""Journal Article"", ""Review""]","[""Ma J""]",10.1016/j.ejpb.2026.115178,Ma J,European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V,0939-6411,,Eur J Pharm Biopharm,eng,Ma J,"[""Humans"", ""Excipients"", ""Injections, Subcutaneous"", ""Biological Products"", ""Chemistry, Pharmaceutical"", ""Drug Delivery Systems"", ""Animals"", ""Solubility"", ""Drug Compounding"", ""Freeze Drying"", ""Viscosity"", ""Hyaluronoglucosaminidase"", ""Crystallization"", ""Technology, Pharmaceutical"", ""Proteins""]",115178,42413883,,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42413883/,"High-concentration biologic formulations: challenges, strategies, and emerging technologies for subcutaneous delivery",226,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"The aim of this study was to evaluate scanning electron microscopy (SEM) combined with energy-dispersive X-ray spectroscopy (EDS) as complementary analytical tools for supporting continuous improvement in pharmaceutical granule manufacturing. Pilot-scale cefixime granules for oral suspension were prepared as defined process scenarios, including placebo, reference, intermediate, stress-exposed, and optimised batches. SEM was used to compare granule morphology, surface integrity, and agglomeration behaviour, whereas EDS provided qualitative and semi-quantitative information on localised elemental composition, with emphasis on sulfur as an API-related marker and oxygen-to--sulfur trends as surface-sensitive indicators of process- or stress-related variability. Intermediate and stress-exposed batches showed increased surface roughness, microstructural deterioration, and higher oxygen-to-sulfur ratios, whereas reference and optimised batches showed more uniform morphology and comparable elemental profiles. The findings indicate that SEM/EDS can provide useful material-level insight into process-related variability and may support root--cause investigation and process refinement. Overall, SEM/EDS is proposed as a complementary, localised, and semi-quantitative approach for supporting continuous improvement in pharmaceutical granule manufacturing.","[""Journal Article""]","[""Mitrevska I"", ""Karpicarov D"", ""Mihailovska A"", ""Mirakovski D"", ""Paneva O"", ""Petrushevski G""]",10.2478/acph-2026-0018,Mitrevska I,"Acta pharmaceutica (Zagreb, Croatia)",1330-0075,2,Acta Pharm,eng,Petrushevski G,"[""Cefixime"", ""Microscopy, Electron, Scanning"", ""Spectrometry, X-Ray Emission"", ""Anti-Bacterial Agents"", ""Suspensions"", ""Administration, Oral"", ""Chemistry, Pharmaceutical"", ""Drug Compounding"", ""Surface Properties"", ""Bulk Drugs""]",1-11,42412954,,2026 Jun 1,2026,https://pubmed.ncbi.nlm.nih.gov/42412954/,SEM/EDS analysis as a complementary tool for continuous improvement of cefixime granules for oral suspension,76,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"3D printing has emerged as a novel technology for producing personalized dosage forms tailored to patients' therapeutic needs. Hot-melt extrusion (HME) is commonly used to produce filaments for most extrusion-based 3D printers. This study aimed to investigate the effect of three different ethylcellulose (EC) grades (7N, 10N, and 20N) on the physicochemical properties, matrix restructuring, and sustained-release behavior of bupropion hydrochloride (BUP·HCl)-loaded tablets. The extrudates were fabricated using HME, pelletized, and used as feedstock for screw-based 3D printing, thereby overcoming the limitations of filament-based systems. The formulations were evaluated for drug release, hardness, swelling, and porosity before and after dissolution using micro-computed tomography (microCT). The influence of tablet geometry on drug release was also investigated. Morphology, crystallinity, and thermal properties were characterized using scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). All formulations exhibited sustained BUP·HCl release, with drug release decreasing as EC viscosity grade increased. Tablets prepared with higher-viscosity EC showed greater hardness, reduced swelling, and lower post-dissolution porosity. MicroCT analysis revealed raster-related internal pores in all tablets before dissolution. However, initial porosity did not correlate with release behavior; tablets containing EC 20N exhibited the highest initial porosity but the lowest post-dissolution porosity and slowest drug release, whereas EC 7N tablets showed the opposite trend. Larger, thinner tablets released drug faster due to higher surface-area-to-volume ratio. The findings demonstrate that EC molecular weight plays a critical role in governing hydration-driven matrix restructuring and controlling sustained-release behavior of the 3D-printed tablets.","[""Journal Article""]","[""Protopapa C"", ""Junqueira LA"", ""Kolipaka SS"", ""Economidou S"", ""Pappas D"", ""Douroumis D"", ""Vlachou M""]",10.1208/s12249-026-03494-4,Protopapa C,AAPS PharmSciTech,1530-9932,5,AAPS PharmSciTech,eng,Vlachou M,"[""Printing, Three-Dimensional"", ""Delayed-Action Preparations"", ""Cellulose"", ""Tablets"", ""Bupropion"", ""Drug Liberation"", ""Porosity"", ""Drug Compounding"", ""Solubility"", ""Chemistry, Pharmaceutical"", ""Hot Melt Extrusion Technology"", ""Calorimetry, Differential Scanning"", ""Viscosity"", ""Excipients"", ""X-Ray Microtomography"", ""Hardness"", ""X-Ray Diffraction""]",,42410104,,2026 Jul 6,2026,https://pubmed.ncbi.nlm.nih.gov/42410104/,Hot-Melt Extrusion of Bupropion with Three Ethylcellulose Grades for Pellet Feedstock Preparation and Screw-Based 3D Printing of Sustained-Release Tablets,27,UjoTgZKqkiah7PEEk,sMHJETYjjnZkPtPfs
"Predicted deleterious mutations (SNPs) have different distributions of effects compared to random SNPs based on population composition. Variant prioritization of markers based on deleterious scores can improve the prediction of yield. Favoring mating schemes between parents with fewer highly deleterious mutations can increase the rate of genetic gain. The study of mutations is fundamental to understanding evolution, domestication, and genetics. Characterizing mutations has potential to accelerate breeding programs through selection and purging deleterious mutations (DelMut). We investigated how predicting DelMut in breeding populations informs genomic prediction (GP) increasing the rate of genetic gain. DelMut were annotated in three independent common bean populations using a previously developed random forest (RF) model for common bean incorporating phylogenetic and protein information. Deleterious scores from the RF model were around 0.25, with the top 1% (highly DelMut) of variants scoring between 0.78 and 0.82 among populations. All populations showed variation in the number of highly DelMut per line (max. 13-197) and in genetic load. We assessed the impact of incorporating a priori information on DelMut for variant prioritization and weighting in GP models for yield and flowering time. Stochastic simulations were conducted to evaluate how designing mating schemes based on variable numbers of DelMut per parent can affect genetic gain. Variants with higher predicted scores had significantly different effect distributions compared to random or lower-scored markers. Simulated breeding cycles showed that selecting parents with fewer highly DelMut consistently increases the rate of genetic gain, and depending on the population, can be superior to phenotypic selection. These results highlight the potential of DelMut information for variant prioritization and the optimization of common bean breeding programs. The approaches we developed can be applied to other species to improve the efficacy of crop improvement.","[""Journal Article""]","[""Cordoba-Novoa H"", ""Hoyos-Villegas V""]",10.1007/s00122-026-05329-z,Cordoba-Novoa H,TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik,0040-5752,8,Theor Appl Genet,eng,Hoyos-Villegas V,"[""Phaseolus"", ""Mutation"", ""Models, Genetic"", ""Genome, Plant"", ""Plant Breeding"", ""Computer Simulation"", ""Polymorphism, Single Nucleotide"", ""Genomics"", ""Phenotype"", ""Genotype"", ""Random Forest"", ""Genetic Markers""]",,42545427,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545427/,"Prioritization of deleterious mutations informs genomic prediction and increases the rate of gain in common bean (Phaseolus vulgaris L.), a simulation study",139,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Six bacterial strains (BT523T, BT559T, 15J16-1T3BT, BT730T, DG25AT, and DG25BT) were isolated from soil samples in Korea and assigned to the family Hymenobacteraceae (order Cytophagales, class Cytophagia). Phylogenetic analysis based on 16S rRNA gene sequences showed that the strains formed distinct lineages within the genus Hymenobacter. Strains BT523T, BT559T, and 15J16-1T3BT exhibited highest sequence similarities to Hymenobacter armeniacus BT189T (97.6%), Hymenobacter polaris RP-2-7 T (97.8%), and Hymenobacter paludis KBP-30 T (98.3%), respectively, while strains BT730T, DG25AT, and DG25BT were most closely related to Hymenobacter tibetensis XTM003T, with similarities of 96.3-96.6%. All strains were Gram-negative, aerobic, rod-shaped, and formed red to pink pigmented colonies. Whole-genome analysis revealed genome sizes ranging from 3.78 to 6.33 Mb with G + C contents of 55.5-65.0%. Average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between the strains and their closest relatives were below the accepted thresholds for species delineation, supporting their classification as novel species. Functional annotation indicated the presence of genes associated with core metabolism, stress response, and pigment biosynthesis, reflecting adaptation to soil environments. Secondary metabolite analysis further revealed the presence of biosynthetic gene clusters, including terpene and siderophore pathways. Based on polyphasic taxonomic evidence, the six strains are proposed to represent six novel species of the genus Hymenobacter, for which the names Hymenobacter miniatus sp. nov., Hymenobacter madidus sp. nov., Hymenobacter convexus sp. nov., Hymenobacter rubellus sp. nov., Hymenobacter erythromyxa sp. nov., and Hymenobacter radioresistens sp. nov. are proposed. The type strains are BT523T (= KCTC 72341 T = NBRC 114851 T), BT559T (= KACC 21821 T = NBRC 114852 T), 15J16-1T3BT (= KCTC 42995 T = NBRC 112818 T), BT730T (= KACC 22457 T = NBRC 116482 T), DG25AT (= KCTC 32451 T = TBRC 19856 T), and DG25BT (= KCTC 32452 T = JCM 19444 T).","[""Journal Article""]","[""Park Y"", ""Park S"", ""Maeng S"", ""Kim MK""]",10.1007/s10482-026-02392-w,Park Y,Antonie van Leeuwenhoek,0003-6072,9,Antonie Van Leeuwenhoek,eng,Kim MK,"[""Soil Microbiology"", ""Phylogeny"", ""Republic of Korea"", ""RNA, Ribosomal, 16S"", ""Cytophagaceae"", ""DNA, Bacterial"", ""Genome, Bacterial"", ""Sequence Analysis, DNA"", ""Bacterial Typing Techniques"", ""Base Composition"", ""Genomics"", ""Fatty Acids""]",,42545405,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545405/,Genomic and polyphasic characterization of six novel Hymenobacter species isolated from soil in Korea,119,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Arsenic occurs extensively in the environment and is classified as a potent carcinogenic substance in humans. Prolonged intake of water contaminated with arsenic results in the development of arsenicosis. In the present study, a toxicoproteomic approach was employed to elucidate arsenic-induced alterations in lens proteins using a fish model. Juveniles of Labeo rohita were exposed to sodium meta-arsenite (NaAsO2) at concentrations of 5, 10, 15, and 20 ppm for a period of 10 days in triplicate experimental groups. Soluble lens proteins were analyzed using one- and two-dimensional gel electrophoresis, immunoblotting of αA-crystallin and MALDI-TOF mass spectrometry. Cataract development was observed at arsenic concentrations ≥ 15 ppm. Proteomic analyses revealed concentration-dependent alterations in lens protein abundance, including significant reductions in βB1, βB2, and βA2b-crystallin, small heat shock protein and skeletal α-actin (p < 0.05). In addition, αA, βA2, and βA2a-crystallin exhibited reduced abundance trends, although these changes were not statistically significant. Two-dimensional immunoblotting revealed 15 distinct αA-crystallin isoforms in control lenses, several of which showed a progressive decrease with increasing arsenic exposure, culminating in complete degradation at 20 ppm. These findings demonstrate that arsenic exposure is associated with substantial alterations in lens crystallins and other proteins involved in structural organization and protein homeostasis, coinciding with cataract development at higher exposure concentrations. The identified proteins may serve as potential toxicoproteomic biomarkers of lens damage in aquatic organisms and provide a foundation for future studies investigating the molecular mechanisms of arsenic-induced lens toxicity.","[""Journal Article""]","[""Bhattacharjee S"", ""Pati MK"", ""Bisai K"", ""Mohanty BP""]",10.1007/s10695-026-01762-5,Bhattacharjee S,Fish physiology and biochemistry,0920-1742,4,Fish Physiol Biochem,eng,Mohanty BP,"[""Animals"", ""Lens, Crystalline"", ""Water Pollutants, Chemical"", ""Proteomics"", ""Crystallins"", ""Cyprinidae"", ""Arsenic"", ""Fish Proteins"", ""Arsenites"", ""Sodium Compounds"", ""Electrophoresis, Gel, Two-Dimensional"", ""Cataract"", ""Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization""]",,42545397,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545397/,Toxicoproteomic analysis reveals arsenic-induced alterations in eye lens proteins of Labeo rohita,52,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Transposable elements (TEs) are dynamic components of eukaryotic genomes and a major source of structural and regulatory variation, yet their contribution to ecological adaptation over evolutionary time remains unresolved. This uncertainty is particularly acute in species that occupy broad environmental niches despite chronically low nucleotide diversity, where conventional models predict limited adaptive potential. Here we show that ancient TE polymorphisms underpin global ecological adaptation in Spirodela polyrhiza, one of the smallest flowering plants with low genome-wide nucleotide diversity. Most TE polymorphisms predate continental population divergence. Cold-season temperature emerges as the dominant selective axis, with adaptive signals overwhelmingly associated with TE polymorphisms rather than SNPs. These adaptive TEs bear signatures of selection on standing variation and are embedded in genomic regions shaped by relaxed selective constraint rather than recent hard sweeps. Our results reveal how ancient TE variation sustains ecological adaptation despite chronically depleted nucleotide diversity, resolving a longstanding evolutionary paradox.","[""Journal Article""]","[""Zhang A"", ""Bemmels JB"", ""Wei N""]",10.1111/mec.70497,Zhang A,Molecular ecology,0962-1083,15,Mol Ecol,eng,Wei N,"[""DNA Transposable Elements"", ""Adaptation, Physiological"", ""Araceae"", ""Selection, Genetic"", ""Evolution, Molecular"", ""Genetics, Population"", ""Polymorphism, Genetic"", ""Sequence Analysis, DNA"", ""Genetic Variation"", ""DNA, Plant"", ""Polymorphism, Single Nucleotide"", ""Genome, Plant"", ""Adaptation, Biological""]",e70497,42544692,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544692/,Ancient Transposable Elements Sustain Global Ecological Adaptation Despite Chronically Low Nucleotide Diversity,35,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Brady and colleagues investigated the mutational consequences of cancer treatment on the genomes of 160 childhood cancer survivors who developed a subsequent neoplasm (SN). Their research aids in directing the next steps toward the prevention of SNs. See related article by Brady et al., p. 1590.","[""Journal Article""]","[""Bertrums EJM"", ""van Boxtel R""]",10.1158/2159-8290.CD-26-1036,Bertrums EJM,Cancer discovery,2159-8274,8,Cancer Discov,eng,van Boxtel R,"[""Humans"", ""Neoplasms"", ""Genomics"", ""Cancer Survivors"", ""Child"", ""Mutation""]",1483-1485,42544045,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42544045/,Genomics of Subsequent Neoplasms in Childhood Cancer Survivors,16,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Objective To assess the forensic application value of 59 InDel loci and two miniSTR loci in Chinese Kyrgyz group,and to explore the genetic structure and genetic background of this group. Methods A total of 99 Kyrgyz individuals were genotyped through the 64-plex panel,which was developed independently by our lab.Allele frequencies and forensic parameters were calculated for the InDel loci and miniSTR loci included in the 64-plex panel.The application potential of these loci for full sibling identification was assessed by simulating 5 000 pairs of full siblings and unrelated individuals,respectively,via Familias v3 software.Additionally,various population analysis methods were employed to systematically explore the genetic relationships among the Kyrgyz group and 35 reference populations from five continents. Results The average polymorphism information content of the 59 InDel loci and two miniSTR loci in the Kyrgyz group were 0.365 1 and 0.753 6,respectively.The cumulative discrimination power and cumulative probability of exclusion of the 61 loci mentioned above were 1-1.928 4×10-27 and 0.999 996 539 2,respectively.When the likelihood threshold was set at 100,the accuracy of this panel in distinguishing full siblings from unrelated individuals reached 93.93%.The results of population genetic analyses indicated that the Kyrgyz group had the mixed genetic components of East Asian and European populations,and was genetically closer to the East Asian populations,particularly the Mongolian group. Conclusions The 59 InDel loci and two miniSTR loci show high forensic application value in individual identification and parentage testing and demonstrate certain application potential in full sibling relationship identification.Meanwhile,the results further reveal the mixed East Asian-European genetic background of the Kyrgyz group.This study enriches the genetic resource information on Chinese ethnic minorities and provides basic data to support forensic practice.","[""Journal Article""]","[""Wu XL"", ""Liu QL"", ""Cai MM"", ""Lan Q"", ""Liu YF"", ""Zhu BF""]",10.3881/j.issn.1000-503X.16943,Wu XL,Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae,1000-503X,3,Zhongguo Yi Xue Ke Xue Yuan Xue Bao,eng,Zhu BF,"[""Humans"", ""Polymorphism, Genetic"", ""Genetics, Population"", ""Gene Frequency"", ""Asian People"", ""Microsatellite Repeats"", ""Genotype"", ""INDEL Mutation"", ""Kyrgyzstan""]",422-431,42543827,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543827/,Application of a 64-plex Panel in the Study of Genetic Polymorphism and Population Structure of Kyrgyz Group,48,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"With the widespread adoption of genomic testing, germline predisposition syndromes such as RUNX1-familial platelet disorder with associated myeloid malignancy (FPD-MM) are increasingly encountered in routine hematological practice. FPD-MM is driven by RUNX1 haploinsufficiency, which initially manifests as quantitative and qualitative platelet abnormalities. Over time, this constitutional defect promotes the formation of an inflammation-dominant bone marrow microenvironment, facilitating clonal hematopoiesis, clonal expansion, and the stepwise accumulation of secondary somatic alterations, ultimately leading to myeloid or lymphoid malignancies. Accurate diagnosis requires careful interpretation of tumor-based sequencing results, followed by confirmatory testing using appropriate germline specimens in conjunction with standardized variant classification frameworks. Clinical management encompasses bleeding risk mitigation and disease-specific therapy for overt hematologic neoplasms, including allogeneic hematopoietic stem cell transplantation. Genetic counseling is an essential component of donor coordination in FPD-MM, given the documented risk of donor-derived leukemia when related donors harbor the same pathogenic germline variant as the proband. Beyond the management of affected individuals, surveillance for asymptomatic variant carriers is also essential for early intervention before disease progression. This review summarizes the pathobiology, diagnostic strategy, and practical clinical management of FPD-MM, emphasizing family management as a central medical and ethical challenge at the intersection of hematology and clinical genetics.","[""Journal Article"", ""Review"", ""English Abstract""]","[""Watanabe M""]",10.11406/rinketsu.67.846,Watanabe M,[Rinsho ketsueki] The Japanese journal of clinical hematology,0485-1439,7,Rinsho Ketsueki,jpn,Watanabe M,"[""Humans"", ""Blood Platelet Disorders"", ""Myeloproliferative Disorders"", ""Hematologic Neoplasms"", ""Genetic Predisposition to Disease"", ""Genetic Counseling"", ""Germ-Line Mutation"", ""Core Binding Factor Alpha 2 Subunit"", ""Genetic Testing"", ""Hematopoietic Stem Cell Transplantation"", ""Leukemia, Myeloid, Acute"", ""Blood Coagulation Disorders, Inherited""]",846-853,42543658,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42543658/,[Clinical management of familial platelet disorder with associated myeloid malignancies: at the crossroads of hematology and clinical genetics],67,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Genomic information for hematologic malignancies is now routinely available in clinical practice, supporting the adaptation of hematopoietic cell transplantation, selection of conditioning intensity, and implementation of post-transplant maintenance therapy through refinement of disease risk assessment and minimal residual disease (MRD) measurement. This review presents the current evidence on the effective utilization of genomic information for acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPN). It also presents an up-to-date framework for optimal donor selection based on donor genome information, addressing both donor clonal hematopoiesis of indetermined significance and the risk that related donor candidates may carry the same hereditary predisposition. Finally, it discusses research showing that patient and donor genetic polymorphisms (SNPs) can predict transplant complications such as GVHD, and that reduced gut microbiota diversity, as detected by metagenomic analysis, impacts GVHD severity and survival. These examples illustrate the multifaceted role of genomic information in research efforts to improve hematopoietic cell transplantation outcomes.","[""Journal Article"", ""Review"", ""English Abstract""]","[""Nannya Y""]",10.11406/rinketsu.67.794,Nannya Y,[Rinsho ketsueki] The Japanese journal of clinical hematology,0485-1439,7,Rinsho Ketsueki,jpn,Nannya Y,"[""Humans"", ""Hematopoietic Stem Cell Transplantation"", ""Myelodysplastic Syndromes"", ""Genomics"", ""Neoplasm, Residual"", ""Polymorphism, Single Nucleotide"", ""Hematologic Neoplasms"", ""Leukemia, Myeloid, Acute"", ""Graft vs Host Disease""]",794-801,42543651,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42543651/,[Hematopoietic cell transplantation in the era of genome analysis],67,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are driven by recurrent driver mutations and evolve through the stepwise accumulation of additional genetic alterations and clonal evolution. Some large cohort studies have demonstrated that individual additional mutations significantly influence prognosis, leukemic transformation, and progression to myelofibrosis. Furthermore, certain mutations frequently co-occur with other adverse mutations and may act as molecular hubs that amplify clinical impact. Based on these findings, mutation-integrated scoring systems have been developed to improve risk stratification and refine therapeutic decision-making. However, despite the recent adoption of comprehensive genomic testing in clinical practice, there is still limited evidence to guide treatment selection or determine the optimal timing of therapeutic intervention based on mutational profiles or molecular monitoring results. A deeper understanding of clonal evolution, grounded in genomic abnormality data, will be essential for establishing more rational and biology-driven therapeutic strategies.","[""Journal Article"", ""Review"", ""English Abstract""]","[""Ogata H"", ""Minami Y""]",10.11406/rinketsu.67.716,Ogata H,[Rinsho ketsueki] The Japanese journal of clinical hematology,0485-1439,7,Rinsho Ketsueki,jpn,Minami Y,"[""Humans"", ""Myeloproliferative Disorders"", ""Mutation"", ""Genomics"", ""Prognosis""]",716-724,42543640,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42543640/,[Genomic abnormalities in myeloproliferative neoplasms],67,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"The field of epitranscriptomics, an area of genetics concerning the regulation of gene expression via post-transcriptional RNA modification, is currently attracting substantial research attention. In epitranscriptomics, proteins, collectively termed writers, erasers, and readers, enter into complex interactions that contribute to modifying RNA, thereby maintaining biological homeostasis. However, abnormalities in the expression or function of these proteins can lead to the onset and progression of cancers and neuropsychiatric disorders. Using prostate cancer clinical specimens, I cloned a novel gene, prostate cancer antigen-1 (PCA-1), containing a domain similar to the 2-oxoglutarate, iron(II) [Fe(II)]-dependent oxygenase domain of the Escherichia coli AlkB protein and characterized by enzymatic activity associated with the demethylation of methylated RNA. This was accordingly designated AlkB homolog 3 (ALKBH3). I demonstrate that ALKBH3 is highly expressed in tumor cells in prostate, pancreatic, lung, and other cancers, and its activity is correlated with a poor prognosis. In addition, I developed novel compounds that inhibit the RNA demethylase activity of ALKBH3, thereby providing a basis for developing a first-in-class cancer therapeutic. I also succeeded in cloning the ALKBH8 gene. High ALKBH8 expression was also observed in bladder cancer cells. Furthermore, abnormalities in development and behavior were noted in the generated Alkbh8 knockout mice. On the basis of the experience gained from ALKBH3 drug discovery research, I have established a foundation system for supporting academic drug discovery research. In this review, I describe the pathway followed in integrating the findings of basic pharmaceutical and drug discovery research and further developments.","[""Journal Article"", ""Review"", ""English Abstract""]","[""Tsujikawa K""]",10.1248/yakushi.26-00016,Tsujikawa K,Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan,0031-6903,8,Yakugaku Zasshi,jpn,Tsujikawa K,"[""Drug Discovery"", ""Humans"", ""Animals"", ""AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase"", ""Epitranscriptomics"", ""Neoplasms"", ""Epitranscriptome"", ""Drug Development"", ""Mice""]",683-696,42543607,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42543607/,[Development of Drug Discovery Research Based on the Discovery of AlkB Homolog 3 and Establishment of an Academic Drug Discovery Platform],146,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"This study aimed to evaluate the antidepressant activity of Piper laetispicum extract and preliminarily explore its underlying mechanism using a zebrafish model of depression combined with quantitative proteomics. A chronic unpredictable mild stress(CUMS) paradigm was employed to establish the depression model. AB strain zebrafish were randomly assigned into four groups: control, model, P. laetispicum, and fluoxetine, with 15 fish in each group. Except the control group, all groups were subjected to CUMS for 2 weeks. Intervention of P. laetispicum extract or fluoxetine lasted for 3 consecutive weeks. Upon completion of the experiment, the pathological morphology of zebrafish brain tissue was observed, and the expression levels of tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1β), brain-derived neurotrophic factor(BDNF), and 5-hydroxytryptamine receptor 2A(5-HT2A) were measured in each group. Brain tissue proteins were extracted and subjected to quantitative proteomic analysis to identify differentially expressed proteins(DEPs), which was followed by bioinformatics analysis. Key DEPs were validated using Western blot and RT-qPCR. The results demonstrated that P. laetispicum extract significantly ameliorated CUMS-induced brain histopathological damage, reduced the levels of the inflammatory cytokines TNF-α and IL-1β, and reversed the aberrant expression of BDNF and 5-HT2A. Proteomic profiling identified a total of 11 633 proteins, among which the expression levels of 81 proteins were markedly reversed following P. laetispicum extract treatment. Subsequent validation by Western blot and RT-qPCR confirmed that P. laetispicum significantly modulated the expression of annexin A1(Anxa1) and transcription factor JunB(JunB). Collectively, these findings suggest that P. laetispicum exerts antidepressant effects potentially through the regulation of Anxa1 and JunB expression.","[""English Abstract"", ""Journal Article""]","[""Duan YA"", ""Wang YJ"", ""Bian XF"", ""Dai GL"", ""Ju WZ""]",10.19540/j.cnki.cjcmm.20260414.701,Duan YA,Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica,1001-5302,13,Zhongguo Zhong Yao Za Zhi,chi,Ju WZ,"[""Animals"", ""Zebrafish"", ""Proteomics"", ""Antidepressive Agents"", ""Depression"", ""Piper"", ""Disease Models, Animal"", ""Male"", ""Tumor Necrosis Factor-alpha"", ""Interleukin-1beta"", ""Brain-Derived Neurotrophic Factor"", ""Humans"", ""Stress, Psychological"", ""Drugs, Chinese Herbal"", ""Brain"", ""Plant Extracts""]",3742-3750,42543364,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543364/,[Investigation on antidepressant mechanism of Piper laetispicum extract based on quantitative proteomics and zebrafish model of depression induced by chronic unpredictable mild stress],51,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Medicinal plants represent a critical resource for both traditional medicine and contemporary natural product research. Studies on their genetic breeding are of paramount significance in ensuring the quality of medicinal materials, enhancing the content of bioactive constituents, and cultivating elite varieties. With the rapid advancement of sequencing technologies, omics approaches have evolved from reliance on single molecular markers to multidimensional research paradigms encompassing genomics, transcriptomics, proteomics, metabolomics, epigenomics, and single-cell omics. This article systematically reviews the concepts of various omics sequencing technologies and their applications in the identification of germplasm resources, analysis of genetic diversity, elucidation of geo-authenticity mechanisms, biosynthesis of active compounds, and molecular breeding in medicinal plants. Furthermore, it prospects the potential of multi-omics integration in future precision breeding of medicinal plants, aiming to provide a theoretical reference for systematic, precision, and efficient genetic breeding research for medicinal plants.","[""Journal Article"", ""Review"", ""English Abstract""]","[""Liu Y"", ""Qi YJ"", ""Quan WY"", ""Jia XW"", ""Zeng CY"", ""Wang HZ"", ""Gao SF"", ""Guo DQ"", ""Guo WC"", ""Zhang XJ"", ""Chen HG"", ""DU T""]",10.19540/j.cnki.cjcmm.20260223.401,Liu Y,Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica,1001-5302,12,Zhongguo Zhong Yao Za Zhi,chi,DU T,"[""Plants, Medicinal"", ""Plant Breeding"", ""Genomics"", ""Multiomics"", ""Proteomics"", ""Metabolomics""]",3387-3395,42543297,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543297/,[Research and application of omics technologies in genetic breeding of medicinal plants],51,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"O-acetylation of sialoglycans plays a critical role in modulating the structural and functional properties of glycoproteins, with implications in immune response, cell signaling, and disease pathology. Among sialic acids, N-acetylneuraminic acid (Neu5Ac) and its derivatives have garnered attention as biomarkers for various cancers and inflammatory conditions due to their terminal positioning on glycan chains and their susceptibility to biochemical modification. Despite their biological relevance, comprehensive analysis of O-acetylation patterns remains challenging due to their chemical lability and loss during conventional glycomic workflows, such as permethylation. This protocol outlines a robust workflow combining methylamidation and permethylation with porous graphitic carbon (PGC)-based purification and high-resolution MALDI-MS and LC-MS/MS to analyze O-acetylation in serum/plasma-derived N-sialoglycans. We demonstrate sensitive and reproducible profiling of sialylated glycan structures. This method enables deeper insight into glycan modification dynamics and can be broadly applied to biomarker discovery and comparative glycomics.","[""Journal Article""]","[""Wu Z"", ""Sirois I""]",10.1007/978-1-0716-5166-7_14,Wu Z,"Methods in molecular biology (Clifton, N.J.)",1064-3745,,Methods Mol Biol,eng,Sirois I,"[""Acetylation"", ""Tandem Mass Spectrometry"", ""Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization"", ""Methylation"", ""Liquid Chromatography-Mass Spectrometry"", ""Polysaccharides"", ""Humans"", ""Glycomics"", ""Chromatography, Liquid"", ""Sialic Acids""]",211-225,42542532,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42542532/,Profiling O-Acetylation in Sialoglycans Using MALDI-TOF and LC-MS/MS with Methylamidation and Permethylation Derivatization,3018,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Top-down proteomics enables large-scale identification of proteoforms by analyzing intact proteins extracted from biological samples using mass spectrometry systems coupled with liquid chromatography or capillary electrophoresis. In this chapter, we present the PEPPI-SP3 workflow, a high-resolution sample prefractionation method that significantly enhances the analytical depth of top-down proteomics by combining highly efficient passive extraction of in-gel proteins separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis with SP3 bead-based purification of intact proteins.","[""Journal Article""]","[""Takemori A"", ""Kline JT"", ""Fornelli L"", ""Takemori N""]",10.1007/978-1-0716-5166-7_13,Takemori A,"Methods in molecular biology (Clifton, N.J.)",1064-3745,,Methods Mol Biol,eng,Takemori N,"[""Proteomics"", ""Mass Spectrometry"", ""Electrophoresis, Polyacrylamide Gel"", ""Workflow"", ""Proteins"", ""Chromatography, Liquid"", ""Proteome""]",199-209,42542531,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42542531/,PEPPI-SP3: A Gel-Based High-Resolution Sample Preparation Workflow for In-Depth Top-Down Analysis of Intact Proteoforms by Mass Spectrometry,3018,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Mass spectrometry (MS)-based top-down proteomics (TDP) analysis of histone proteoforms provides critical information about combinatorial posttranslational modifications (PTMs), which is vital for pursuing a better understanding of epigenetic regulation of gene expression. Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) separates histone proteins (H1, H2, H3, and H4) based on their molecular weight, while capillary zone electrophoresis (CZE) provides additional separation of proteoforms of each histone protein based on their electrophoretic mobility, which is affected by PTMs, e.g., acetylation and phosphorylation. Here, we describe the combination of SDS-PAGE-based protein fractionation with CZE-tandem MS (MS/MS) for high-resolution characterization of histone proteoforms. Over 200 histone proteoforms from a commercial calf thymus histone sample were identified with good reproducibility.","[""Journal Article""]","[""Fang F"", ""Sun L""]",10.1007/978-1-0716-5166-7_12,Fang F,"Methods in molecular biology (Clifton, N.J.)",1064-3745,,Methods Mol Biol,eng,Sun L,"[""Histones"", ""Proteomics"", ""Tandem Mass Spectrometry"", ""Electrophoresis, Capillary"", ""Electrophoresis, Polyacrylamide Gel"", ""Protein Processing, Post-Translational"", ""Animals"", ""Cattle""]",185-198,42542530,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42542530/,Combining SDS-PAGE with Capillary Zone Electrophoresis-Tandem Mass Spectrometry for Top-Down Proteomics Analysis of Intact Histone Proteoforms,3018,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Among the various posttranslational modifications (PTMs) found in microbiome samples, lysine acetylation is known to be abundant and plays an important role in regulating microbial short-chain fatty acid (SCFA) metabolism. The latter is a crucial microbiome function that significantly impacts human intestinal health. This chapter describes a detailed protocol for lysine acetylomic profiling of microbial proteins in human fecal microbiome samples. The protocol consists of stool sample preprocessing, microbiome protein extraction and digestion, immunoaffinity enrichment of lysine acetylated peptides, and high-resolution mass spectrometry analysis for the identification and quantification of lysine-acetylated proteins.","[""Journal Article""]","[""Zhang X"", ""Ning Z"", ""Figeys D""]",10.1007/978-1-0716-5166-7_10,Zhang X,"Methods in molecular biology (Clifton, N.J.)",1064-3745,,Methods Mol Biol,eng,Figeys D,"[""Acetylation"", ""Humans"", ""Lysine"", ""Proteomics"", ""Feces"", ""Protein Processing, Post-Translational"", ""Proteome"", ""Microbiota"", ""Gastrointestinal Microbiome""]",155-168,42542528,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42542528/,Enrichment and Metaproteomic Analysis of Lysine Acetylation in Fecal Microbiome Samples,3018,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Lysine methylation is a dynamic posttranslation modification (PTM) involved in the regulation of numerous biological processes. Depending on the context, site- and state-specific lysine methylation has been shown to regulate key features of proteins, such as stability, activity, and interactions. Assessing site- and state-specific lysine methylation within the proteome is difficult without access to antibodies that are able to detect the modification site. As the commercially available options for reliable antibodies that are specific to a methylation site and state are limited, mass spectrometry (MS)-based methods are more appealing as they enable detection of site- and state-specific methylation events with broad applicability. Here, we describe the use of immunoprecipitation and targeted-MS to detect and perform relative quantification of site-specific lysine methylation events occurring on endogenous proteins of interest. As an example, detection and relative quantification of hypoxia-responsive PGC1α-K224me2 and RNF20-K610me3/K614me3 lysine methylation, occurring in hypoxia-treated human colorectal cancer cells, are described.","[""Journal Article""]","[""Chopra A"", ""Hoekstra M"", ""Willmore WG"", ""Biggar KK""]",10.1007/978-1-0716-5166-7_9,Chopra A,"Methods in molecular biology (Clifton, N.J.)",1064-3745,,Methods Mol Biol,eng,Biggar KK,"[""Lysine"", ""Humans"", ""Methylation"", ""Protein Processing, Post-Translational"", ""Mass Spectrometry"", ""Immunoprecipitation"", ""Proteomics""]",139-153,42542527,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42542527/,Mapping Cellular Protein Lysine Methylation Using Targeted-Mass Spectrometry,3018,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"In this chapter, we describe a general sample preparation workflow for small extracellular vesicles (sEVs) from breast cancer cell lines using techniques such as protein solubilization, enzymatic digestion, and Fe3+-immobilized metal affinity chromatography (IMAC) and titanium dioxide (TiO2) enrichment prior to mass spectrometry-based proteomic analysis. This workflow can be used to perform global phosphoproteomics of sEVs enabling the study of tumor biology and the discovery of biomarkers for cancer diagnosis and treatment.","[""Journal Article""]","[""Minic Z"", ""Poolsup S"", ""Li Y"", ""D'Mello R"", ""Berezovski MV""]",10.1007/978-1-0716-5166-7_8,Minic Z,"Methods in molecular biology (Clifton, N.J.)",1064-3745,,Methods Mol Biol,eng,Berezovski MV,"[""Humans"", ""Proteomics"", ""Extracellular Vesicles"", ""Biomarkers, Tumor"", ""Chromatography, Affinity"", ""Titanium"", ""Phosphopeptides"", ""Phosphoproteins"", ""Cell Line, Tumor"", ""Breast Neoplasms"", ""Mass Spectrometry"", ""Female""]",123-137,42542526,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42542526/,Phosphoproteomics Protocol for the Identification of Novel Biomarkers from Extracellular Vesicles of Cancerous Cells,3018,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Protein phosphorylation (O-linked and N-linked) is associated with a wide range of biological processes and cell signaling pathways. Aberrant phosphorylation is often observed as a hallmark of diseases, including cancer, neurodegenerative disorders, and metabolic syndromes. Mass spectrometry (MS) is an indispensable tool for studying protein phosphorylation. This is primarily due to its high sensitivity and throughput, which allows for comprehensive identification and quantification of phosphorylation events in complex biological samples. In this chapter, we describe a detailed protocol for phosphoproteomic analysis using one-dimensional online alkaline-pH reversed-phase nanoelectrospray-tandem MS (alkaline-pH-MS/MS). It complements traditional online low-pH reversed-phase nanoelectrospray-tandem MS (low-pH-MS/MS) by modulating the charge state distribution of phosphopeptides, which may facilitate the characterization of phosphoproteins with significant biological functions.","[""Journal Article""]","[""Wang Y"", ""Tang M"", ""Xie W""]",10.1007/978-1-0716-5166-7_7,Wang Y,"Methods in molecular biology (Clifton, N.J.)",1064-3745,,Methods Mol Biol,eng,Xie W,"[""Tandem Mass Spectrometry"", ""Proteomics"", ""Phosphoproteins"", ""Phosphorylation"", ""Spectrometry, Mass, Electrospray Ionization"", ""Chromatography, Reverse-Phase"", ""Hydrogen-Ion Concentration"", ""Phosphopeptides"", ""Humans"", ""Nanotechnology""]",111-122,42542525,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42542525/,O- and N-Phosphoproteomic Analysis Using Online Alkaline-pH Reversed-Phase Nanoelectrospray-Tandem Mass Spectrometry,3018,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"The analysis of endogenous phosphopeptides is crucial for identifying biomarkers of cellular signaling alterations and monitoring disease-related pathophysiological changes in vivo. While phosphoproteomics has seen remarkable progress in recent years, the field of endogenous phosphopeptidomics has lagged behind. A major challenge in endogenous phosphopeptidomics analysis lies in the presence of highly abundant nonmodified peptides and proteins within complex biological matrices, such as biofluids, which can obscure the detection of low-abundance phosphopeptides. In this chapter, we describe a protocol of a recently developed approach by utilizing Zirconium (IV)-grafted mesoporous beads for selective phosphopeptide enrichment, followed by high-resolution nanoRPLC-MS/MS analysis, enabling enhanced sensitivity and specificity in the detection of endogenous phosphopeptides from serum samples.","[""Journal Article""]","[""Wu C"", ""Liu B"", ""Ma J""]",10.1007/978-1-0716-5166-7_6,Wu C,"Methods in molecular biology (Clifton, N.J.)",1064-3745,,Methods Mol Biol,eng,Ma J,"[""Phosphopeptides"", ""Proteomics"", ""Tandem Mass Spectrometry"", ""Humans"", ""Zirconium"", ""Porosity"", ""Chromatography, High Pressure Liquid""]",99-109,42542524,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42542524/,Endogenous Phosphopeptidomics Analysis by Using Mesoporous IMAC Materials,3018,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Protein SUMOylation is a dynamic post-translational modification that regulates numerous cellular processes, including DNA repair, transcription, and proteostasis. SUMO modifiers are conjugated to lysine residues on substrate proteins via a conserved enzymatic cascade and can form diverse chain architectures that encode specific cellular outcomes. The identification of SUMOylated proteins and their modification sites has historically been challenging due to the low abundance of SUMOylation and the complexity of SUMO remnants after proteolysis. Recent advances in proteomics have led to the development of enrichment strategies and mass spectrometry (MS)-based methods that now enable the site-specific mapping of SUMO modifications. This chapter provides an overview of the biological roles and structural diversity of SUMOylation, and presents an MS-based workflow designed to identify SUMOylation sites with high specificity and depth. These tools offer new opportunities to dissect the SUMO-modified proteome in health and disease.","[""Journal Article""]","[""Li C"", ""Thibault P""]",10.1007/978-1-0716-5166-7_3,Li C,"Methods in molecular biology (Clifton, N.J.)",1064-3745,,Methods Mol Biol,eng,Thibault P,"[""Sumoylation"", ""Proteome"", ""Protein Processing, Post-Translational"", ""Proteomics"", ""Mass Spectrometry"", ""Humans"", ""Small Ubiquitin-Related Modifier Proteins"", ""Workflow"", ""Animals""]",41-56,42542521,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42542521/,Decoding the SUMO Proteome: A Mass Spectrometry Workflow for Site-Specific Identification,3018,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Alzheimer's disease (AD) is characterised by the intraneuronal aggregation of phosphorylated Tau (pTau) into neurofibrillary tangles and by the extracellular deposition of β-amyloid (Aβ). Tau pathology restricted to the hippocampal formation is frequently observed in the elderly brain in the absence of any Aβ deposition and considered as ""primary age-related tauopathy"" (PART). Here, we applied an unbiased proteomic approach to determine how concomitant Aβ pathology modifies the neurofibrillary tangle proteome. Neurofibrillary tangles were isolated by dissecting Tau pSer202/pThr205 ""AT8"" immunopositive neuronal profiles, combining chromogenic immunohistochemistry with laser capture microdissection, from hippocampal sections of 17 post-mortem brains spanning three groups: PART (n = 5; A0, B1-2, C0 scores), intermediate AD (n = 6; A1-2, B2-3, C1-2 scores) and advanced AD (n = 6; A3, B3, C3 scores). A label-free quantitative liquid chromatography-mass spectrometry based proteomic analysis, using data independent acquisition (DIA) on a Bruker timsTOF, was performed. A conserved core of 63 proteins was identified as enriched in tangles across all groups, mostly associated with ""RNA binding"" and ""regulation of mRNA metabolic process"", based on the Gene Ontology database. Group-specific signatures were also observed: 33 proteins were significantly enriched only in tangles collected from PART cases and were predominantly linked to ""structural molecule activity"", whereas Aβ-positive cases showed specific enrichment of ""RNA binding"" and ""cytoplasmic translation"" pathways-with intermediate AD cases displaying a transitional profile. Our findings are consistent with PART having distinct tangle proteomic features; however, the majority of its proteomic signature is in common with tangles within the AD continuum. By addressing how Aβ accumulation alters the tangle proteome, this study provides mechanistic insights into the expansion of Tau pathology, paving the way towards the identification of biomarkers and therapeutic strategies that would allow for stabilisation of Tau pathology in the elderly.","[""Journal Article"", ""Comparative Study""]","[""Thierry M"", ""Leitner D"", ""Balcomb K"", ""Kavanagh T"", ""Tang L"", ""Kanshin E"", ""William C"", ""Oakley D"", ""Hyman B"", ""Ueberheide B"", ""Drummond E"", ""Wisniewski T""]",10.1007/s00401-026-03064-9,Thierry M,Acta neuropathologica,0001-6322,1,Acta Neuropathol,eng,Wisniewski T,"[""Humans"", ""Neurofibrillary Tangles"", ""Alzheimer Disease"", ""Hippocampus"", ""Proteomics"", ""Aged, 80 and over"", ""Female"", ""tau Proteins"", ""Male"", ""Aged"", ""Amyloid beta-Peptides"", ""Laser Capture Microdissection""]",,42542447,pmc-id: PMC13428778;,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42542447/,"Proteomic comparison of hippocampal neurofibrillary tangles in PART, intermediate Alzheimer's disease and advanced Alzheimer's disease",152,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Immunocompromised patients, especially hematopoietic stem cell transplants (HSCT) / bone marrow transplant recipients, are at risk for colonization and infection with carbapenem-resistant Klebsiella pneumoniae (CR-KP) which is associated with increased bloodstream infections and mortality in this population. In this susceptible population, we investigated the molecular epidemiology of CR-KP. The strains isolated over a five-year period (2017-2021) were then characterized by PCR and sequencing targeting carbapenemase genes. ERIC-PCR was utilized to examine clonal relations, while multilocus sequence typing was carried out on representative isolates. Analysis of 142 CR-KP uncovered remarkable genetic heterogeneity with six predominant clusters making up for 83,8% of strains and one major cluster. Novel findings in K. pneumoniae included: undescribed MLST profile ST5187, emergence of blaVIM-1 in ST397, emergence of blaOXA-48-like in ST219, co-carriage of either blaNDM-1 + blaOXA-48-like in ST15 or blaVIM-like + blaNDM-1 in ST405. CR-KP, brought to light new carbapenemase gene associations and undescribed MLST profiles. To prevent transmission of high-risk clones in immunocompromised populations, enhanced molecular surveillance and robust infection control are of high importance.","[""Journal Article""]","[""Ben Hamza A"", ""Raddaoui A"", ""Frigui S"", ""Chebbi Y"", ""Achour W""]",10.1007/s00203-026-05101-3,Ben Hamza A,Archives of microbiology,0302-8933,10,Arch Microbiol,eng,Achour W,"[""beta-Lactamases"", ""Klebsiella pneumoniae"", ""Humans"", ""Multilocus Sequence Typing"", ""Klebsiella Infections"", ""Bacterial Proteins"", ""Anti-Bacterial Agents"", ""Carbapenems"", ""Molecular Epidemiology"", ""Microbial Sensitivity Tests""]",,42541569,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42541569/,Emergence of gene associations in high-risk K. pneumoniae clones: bla(NDM-1) + bla(OXA-48-like) in ST15 and bla(VIM) + bla(NDM-1) in ST405,208,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"We started a family-based genetic epidemiology study in 2006-11 which recruited 24,000 adult volunteers from 7000 families across Scotland with consent for follow-up through medical record linkage and re-contact. In 2022-25 we have recruited a further 16,000 volunteers, with consent extended to administrative records, and age range now 12+. Original volunteers completed demographic, health and lifestyle questionnaires, provided biological samples, and underwent detailed clinical assessment. The samples, phenotype and genotype data form a resource for research on the genetics of conditions of public health importance. This has become a longitudinal dataset by linkage to routine NHS records: hospital, maternity, lab test, prescriptions, dentistry, mortality, imaging, cancer screening, GP data, Covid-19 testing and vaccinations, as well as follow-up questionnaires. The new wave of recruitment is all online with DNA from saliva collected by post. Teenagers aged 12-15 can join with parental consent. Researchers can find prevalent and incident disease cases and controls to test research hypotheses on a stratified population. They can also do targeted recruitment of participants to new studies, including recall by genotype. We have established and validated E-HR linkage with the NHS Scotland CHI Register, overcoming technical and governance issues in the process. We contribute to major international consortia, with collaborators from institutions worldwide, both academic and commercial. The Research Tissue Bank resources are available to academic and commercial researchers through a managed access process.","[""Journal Article""]","[""Buchanan D""]",10.23889/ijpds.v11i5.3579,Buchanan D,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Buchanan D,"[""Humans"", ""Scotland"", ""Female"", ""Adolescent"", ""Adult"", ""Child"", ""Medical Record Linkage"", ""Male"", ""Young Adult"", ""Middle Aged"", ""Surveys and Questionnaires"", ""Molecular Epidemiology""]",3579,42541045,pmc-id: PMC13426767;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42541045/,Generation Scotland - Linking all the records we can,11,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"The integration of genomics data into dementia research offers transformative potential for understanding disease mechanisms and enabling precision medicine. However, its utility is constrained by significant challenges in data sharing, privacy, standardization, and computational scale. To address these barriers, we designed and implemented a secure, novel and scalable genomics ingest and processing pipeline within the Dementias Platform UK (DPUK) Trusted Research Environment. Our comprehensive, end-to-end framework encompasses a seven-stage process, including cohort discovery via an interactive metadata matrix, rigorous quality and privacy controls using bioinformatic tools (e.g. PLINK, VCFtools, etc.), a genomic data organization standard for scalability and balance between interoperability and flexibility, as well as secure provisioning within a Five Safes governance model. A key innovation is the use of a MinIO-based object storage architecture with custom metadata tagging, enabling efficient, privacy-preserving data access at large scale. We also operationalized a standardized polygenic risk score (PRS) pipeline to generate validated, derived datasets. This integrated system now facilitates secure research access to harmonized genomic data across 15 diverse cohorts, including population-based, clinical, and family studies, significantly expanding the resources available for dementia research. This work presents a replicable and governance-first model for the responsible management of complex, high-volume linked data. Looking ahead, we plan to migrate key computational modules, particularly the PRS generation and quality control workflows, to Nextflow. This migration will enhance computational reproducibility, enable portable and parallelized execution across high-performance environments, and further standardize analytical processes, directly advancing the methodological innovation and scalability goals of population data science.","[""Journal Article""]","[""Saraband Moghaddam A"", ""Hotchkiss L"", ""Squires E"", ""Thompson S""]",10.23889/ijpds.v11i5.3709,Saraband Moghaddam A,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Thompson S,"[""Dementia"", ""Genomics"", ""Humans"", ""Computer Security"", ""Metadata"", ""Information Dissemination"", ""Genetic Risk Score"", ""Computational Biology""]",3709,42540726,pmc-id: PMC13426568;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540726/,"Implementing a Scalable, Secure Genomics Ingest and Processing Pipeline in a Trusted Research Environment for Dementia Research",11,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Kidney transplant recipients are highly susceptible to opportunistic and nosocomial infections that demand rapid and accurate diagnosis due to the broad and complex spectrum of pathogens. Conventional microbiological testing (CMT) is often limited, particularly when patients are already receiving antimicrobial therapy at the time of sampling. This study aimed to evaluate the clinical value of metagenomic next-generation sequencing (mNGS) as a complementary diagnostic approach to CMT, with a focus on concordance and discrepancies between the two methods across peripheral blood, sputum, bronchoalveolar lavage fluid (BALF), and urine samples. We conducted a retrospective study of kidney transplant recipients with suspected infections who underwent simultaneous mNGS and CMT testing between March 2022 and May 2024. The impact of prior antibiotic exposure on diagnostic yield was assessed. Detection of antimicrobial resistance (AMR) genes by mNGS and subsequent modifications in anti-infective management were also analyzed. A total of 243 samples (57 blood, 96 sputum, 71 BALF, 19 urine) were included. Across all sample types, mNGS demonstrated significantly higher positive rates than CMT (blood: 78.95% vs 21.05%; BALF: 90.14% vs 19.72%; sputum: 92.71% vs 20.83%; urine: 89.47% vs 36.84%; all P<0.001). Prior antibiotic exposure markedly reduced CMT positivity but had minimal impact on mNGS detection. Concordance analysis showed 40.35% of samples were positive by both methods, while 60.1% were negative by CMT but positive by mNGS. In addition to pathogens identified by CMT, mNGS detected a broader range of microorganisms, including viruses (e.g., cytomegalovirus, Epstein-Barr virus, SARS-CoV-2), fungi (Pneumocystis jirovecii), and parasites (Strongyloides stercoralis, Toxoplasma gondii). Overall, mNGS-guided results refined antibiotic treatment strategies in 110 cases (60.11%). mNGS serves as a valuable adjunct to CMT in kidney transplant recipients, providing rapid and comprehensive pathogen identification. However, from a health economics perspective, mNGS should be applied selectively according to clinical needs, rather than as a universal first-line diagnostic method.","[""Journal Article""]","[""Vuth H"", ""Wang W"", ""Qin W"", ""Yang M"", ""Li Y"", ""Zhou Q"", ""Xu X"", ""Zhang J"", ""Zhao H""]",10.3389/fcimb.2026.1713707,Vuth H,Frontiers in cellular and infection microbiology,2235-2988,,Front Cell Infect Microbiol,eng,Zhao H,"[""Humans"", ""Kidney Transplantation"", ""High-Throughput Nucleotide Sequencing"", ""Metagenomics"", ""Retrospective Studies"", ""Female"", ""Male"", ""Transplant Recipients"", ""Bronchoalveolar Lavage Fluid"", ""Middle Aged"", ""Adult"", ""Sputum"", ""Bacteria"", ""Microbiological Techniques"", ""Aged""]",1713707,42539859,pmc-id: PMC13424443;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42539859/,Application of metagenomic next-generation sequencing as an adjunct to conventional microbiological testing for the diagnosis of infection in kidney transplant recipients,16,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovitis, invasive pannus formation, cartilage degradation, and bone erosion. Although metabolic reprogramming and epigenetic dysregulation are increasingly recognized as central features of rheumatoid arthritis, the mechanisms by which local metabolic stress is converted into durable pathogenic cellular states remain incompletely understood. Recent advances in epitranscriptomics suggest that dynamic RNA modifications, particularly RNA methylation, act as critical post-transcriptional regulators of immune and stromal cell adaptation. Local hypoxia, enhanced glycolytic flux, lactate accumulation, mitochondrial dysfunction, oxidative stress, and lipid metabolic imbalance collectively influence the expression, activity, substrate availability, and transcript selectivity of RNA methylation regulators. These metabolically conditioned RNA modification programs, including canonical N6-methyladenosine (m6A) and emerging non-m6A marks such as internal N7-methylguanosine (m7G), may help stabilize pathogenic phenotypes across multiple cell types. In fibroblast-like synoviocytes (FLS), RNA methylation sustains glycolytic fitness, invasive behavior, and resistance to apoptosis and ferroptosis. In macrophages, it reinforces inflammatory polarization and extracellular vesicle-mediated communication. In T cells and neutrophils, it contributes to Th17 skewing, defective autophagy, oxidative stress responses, and excessive neutrophil extracellular trap (NET) formation. We further discuss how RNA methylation integrates non-coding RNA networks, extracellular vesicle signaling, and regulated cell death pathways to maintain chronic synovial inflammation and tissue destruction. Finally, we highlight the translational implications of this metabolic-epitranscriptomic interface, including biomarker discovery, patient stratification, and microenvironment-informed therapeutic strategies. Targeting both metabolic stress and RNA methylation-dependent adaptation may provide new opportunities for precision-oriented intervention in rheumatoid arthritis.","[""Journal Article"", ""Review""]","[""Li S"", ""Wan L"", ""Yang J"", ""Wang K"", ""Zhang X"", ""Liu X""]",10.3389/fimmu.2026.1865927,Li S,Frontiers in immunology,1664-3224,,Front Immunol,eng,Liu X,"[""Humans"", ""Arthritis, Rheumatoid"", ""RNA Methylation"", ""Animals"", ""Epitranscriptome"", ""Metabolic Reprogramming"", ""Epitranscriptomics"", ""Synoviocytes"", ""Epigenesis, Genetic"", ""Stress, Physiological"", ""Synovial Membrane""]",1865927,42539559,pmc-id: PMC13423929;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42539559/,Metabolic control of RNA methylation in rheumatoid arthritis: from synovial stress to pathogenic cellular adaptation,17,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"The intensification of climate change has led to frequent extreme flooding events, which threaten plant growth and food security. Studying the molecular mechanisms underlying plant flooding resistance is crucial for germplasm improvement. Distylium chinense, a perennial shrub found in the water-level fluctuation zone of the Three Gorges Reservoir, has both strong flooding tolerance and high ornamental value, making it an ideal material for studying plant flooding resistance mechanisms. By integrating multiple sequencing technologies, we assembled a high-quality 917 Mb near telomere-to-telomere genome of D. chinense with a contig N50 size of 73 Mb, representing the first high-quality genome of the Hamamelidaceae family. Whole-genome duplication analysis revealed that D. chinense experienced gamma events that are common to those of core eudicots. In addition, this study revealed three different flooding stress response stages in D. chinense, namely, the acute stress period, the outbreak period, and the long-term adaptation period. Among these, the outbreak period could be an important turning point, during which D. chinense switches from survival mode to adaptation mode. This study also revealed that the expression of the group VII ethylene-responsive factor (ERF-VII) gene g3958 was significantly upregulated under flooding stress and that this gene can be directly activated by the AtWRKY33-homologous gene g19705. On the basis of a comprehensive analysis, a potential dual pathway regulatory model between MKK9 and ERF-VII was further proposed. This study provides important genetic resources for improving flood-resistant germplasms and further contributes to the protection and restoration of the ecosystem in the water-level fluctuation zone of the Three Gorges Reservoir.","[""Journal Article""]","[""Xia C"", ""Ding B"", ""Zhang X"", ""Zhang X"", ""Li W"", ""Zeng J"", ""Zhao F"", ""Jiang S"", ""Deng H"", ""Huang M""]",10.1111/tpj.71066,Xia C,The Plant journal : for cell and molecular biology,0960-7412,3,Plant J,eng,Huang M,"[""Floods"", ""Plant Proteins"", ""Genome, Plant"", ""Gene Expression Regulation, Plant"", ""Adaptation, Physiological"", ""Water"", ""Genomics"", ""Stress, Physiological""]",e71066,42537048,pmc-id: PMC13427377;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42537048/,Genomic insights into flooding tolerance of Distylium chinense in the water-level fluctuation zone of the Three Gorges Reservoir,127,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Modern sequencing technologies can now capture multiple omic layers from the same biological system, but integrating these views into a coherent model is far from trivial. Graph-based deep learning has become an attractive strategy because it can represent complex molecular interactions and sample relationships in a flexible way. In this review, we survey how graphs are constructed and used in multi-omics deep learning models, organizing methods by node schema, edge semantics, interaction type, integration strategy, graph context, and model architecture across bulk, single-cell, and spatial settings. We summarize the strengths and weaknesses of different design choices in terms of interpretability, data requirements, robustness to noise and missing modalities, and suitability for tasks ranging from prediction to mechanism-oriented discovery. Based on these insights, we outline a general, practical pipeline for constructing, curating, and evaluating graphs that can serve as a starting point for new multi-omics studies.","[""Journal Article"", ""Review""]","[""Alif MN"", ""Tanvir Ahmed K"", ""Baul S"", ""Zhang W""]",10.1093/bib/bbag410,Alif MN,Briefings in bioinformatics,1467-5463,4,Brief Bioinform,eng,Zhang W,"[""Multiomics"", ""Deep Learning"", ""Humans"", ""Computational Biology"", ""Genomics""]",,42537003,,2026 May 4,2026,https://pubmed.ncbi.nlm.nih.gov/42537003/,Graph designs for deep learning-based multi-omics integration,27,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"The European Union (EU) enforces strict regulations on the traceability and labeling of genetically modified organisms (GMOs), including genome-edited (GE) lines produced through new genomic techniques (NGTs). Identifying GE organisms created by single nucleotide variations (SNVs) is however challenging, as a single SNV alone cannot unambiguously define a GE line. Recently, we introduced the concept of generating a genetic fingerprint to distinguish a specific GE rice line. This proof-of-concept approach integrated whole-genome sequencing (WGS)-based characterization with the Illumina technology, the public 3 K Rice Genomes (3KRG) database, and statistical feature-selection tools, to select and combine key genetic elements, including GE on-target site(s) and cultivar-specific 2-SNV barcodes, into a unique genetic fingerprint. In the present study, we expand this concept into a generalized data-driven framework allowing identification of multiple rice lines. Supported by newly developed bioinformatics and statistical feature-selection-based pipelines, this optimized strategy enables the generation of genetic fingerprints irrespective of a rice cultivar's inclusion in publicly available databases like 3KRG. In addition, this refined strategy can leverage WGS data generated from both Illumina and Oxford Nanopore Technologies (ONT) platforms for fingerprint generation and GE line identification. Using two distinct in-house GE rice lines from different cultivars, along with various publicly available WGS datasets, we demonstrated the robustness, scalability, and specificity of this approach for reliable GE rice line identification. Our findings provide a methodological foundation for data-driven traceability of GE rice lines, reinforcing regulatory compliance, supporting intellectual property (IP) protection, and contributing to the responsible implementation of EU GMO/NGT legislation.","[""Journal Article""]","[""Zolfaghari A"", ""Fraiture MA"", ""Vanneste K"", ""Stuyts A"", ""Frouin J"", ""Meunier AC"", ""Deforce D"", ""Roosens NHC"", ""D'aes J""]",10.1093/bib/bbag406,Zolfaghari A,Briefings in bioinformatics,1467-5463,4,Brief Bioinform,eng,D'aes J,"[""Oryza"", ""Genome, Plant"", ""Plants, Genetically Modified"", ""Gene Editing"", ""Software"", ""Computational Biology"", ""Polymorphism, Single Nucleotide"", ""Whole Genome Sequencing"", ""Genomics"", ""DNA Fingerprinting""]",,42537001,,2026 May 4,2026,https://pubmed.ncbi.nlm.nih.gov/42537001/,RiSpy: a feature selection-based fingerprinting framework for accurate identification of genome-edited rice lines,27,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Helicobacter pylori (H. pylori) infection is the principal etiological factor for gastric cancer (GC), which ranks as the fourth leading cause of cancer-related mortality globally. Although the Correa cascade describes the stepwise progression from chronic gastritis to intestinal-type GC, the molecular events underlying this ""inflammation-to-cancer"" transition remain incompletely characterized. This study aimed to delineate stage-specific proteomic alterations across H. pylori-associated gastric mucosal lesions and to identify candidate progression-associated biomarkers in GC. Label-free quantitative proteomic analysis (LC-MS/MS) was performed on gastric tissue specimens from 22 patients stratified into four histopathological stages: H. pylori-negative chronic non-atrophic gastritis (HpN-CG), H. pylori-positive chronic non-atrophic gastritis (HpC-CG), H. pylori-positive chronic atrophic gastritis (HpC-CAG), and intestinal-type GC. Functional enrichment (GO, KEGG), temporal clustering (Mfuzz), and protein-protein interaction (PPI) network analyses were conducted. Key hub genes were externally assessed using GEPIA RNA-seq data from TCGA and GTEx. A total of 6,019 proteins were quantified. Differential expression analysis identified 771 DEPs between HpC-CG and HpN-CG, 101 DEPs between HpC-CAG and HpC-CG, and 535 DEPs between GC and HpC-CAG. Immune response pathways were up-regulated upon H. pylori infection, whereas oxidative phosphorylation was progressively suppressed throughout disease progression. Mfuzz clustering revealed that Cluster 4 ribosome-biogenesis proteins, including NIP7 and PDCD11 identified in the proteomic/PPI analysis, exhibited continuous up-regulation from precancerous stages to GC. External RNA-expression validation supported significant up-regulation of seven Cluster 4 hub genes, whereas Cluster 6 proteins did not show concordant transcript-level down-regulation. This study provides a comprehensive proteomic landscape of H. pylori-driven gastric carcinogenesis. Cluster 4 ribosome-biogenesis proteins represent candidate progression-associated protein markers requiring further protein-level validation, while the progressive decline in oxidative phosphorylation underscores mitochondrial dysfunction as a hallmark of disease progression.","[""Journal Article""]","[""Huang X"", ""Ma J"", ""Xiao Y"", ""Pan J"", ""Xu Q"", ""Cao X"", ""Liu Y"", ""Yi X"", ""Tian F""]",10.1371/journal.pone.0353347,Huang X,PloS one,1932-6203,7,PLoS One,eng,Tian F,"[""Humans"", ""Helicobacter Infections"", ""Proteomics"", ""Helicobacter pylori"", ""Gastric Mucosa"", ""Stomach Neoplasms"", ""Female"", ""Gastritis, Atrophic"", ""Male"", ""Middle Aged"", ""Tandem Mass Spectrometry"", ""Protein Interaction Maps"", ""Proteome"", ""Disease Progression"", ""Gastritis""]",e0353347,42536619,pmc-id: PMC13426948;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42536619/,The quantitative proteomics analysis of multi-stage gastric mucosal lesions associated with Helicobacter pylori infection,21,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Cleaner wrasse (Labroides dimidiatus) undergoes sex reversal to male, and the two sexes exhibit distinctive cleaning behavior mediated by vision. As a keystone cleaner species in coral reef ecosystems, this fish plays an indispensable ecological role. Yet, the visual regulatory mechanisms underlying its sex-specific cleaning behaviors remain unknown. Through genome annotation and phylogenetic analysis, visual opsin genes were identified in the cleaner wrasse genome. Gene expression levels were quantified by RT-qPCR to examine sexual dimorphism. Additionally, 4 C-seq coupled with dual-luciferase reporter assays was employed to identify and validate putative enhancers regulating opsin gene expression. Eight visual opsin genes in five families were identified: rhodopsin (RH1), green-sensitive (RH2), ultraviolet-sensitive (SWS1), blue-sensitive (SWS2), and red-sensitive (LWS). Notably, RH2 has undergone diversification into four genes, indicating a high degree of functional specialization in hue resolution. All opsins maintain high homology in conserved motifs and functional domains, while also possessing distinct regions that may facilitate adaptation to complex photic environments. RT-qPCR revealed significant sexual dimorphism in opsin expression. Females exhibited higher expression of SWS1, SWS2B and RH2 family genes, consistent with their primary role as cleaners, which requires precise visual discrimination of client fish coloration and ectoparasites. In contrast, males showed significantly higher expression of RH1 and LWS, likely reflecting adaptation for territorial patrol and social competition following sex change. Furthermore, using 4 C-seq coupled with dual-luciferase reporter assays, we identified and validated active enhancers upstream of RH1 and RH2-1 genes. RH1 was found to be regulated by multiple enhancers acting in concert, suggesting a capacity for robust environmental responsiveness and developmental stage-specific modulation. In contrast, RH2-1 appears to be under the control of a single enhancer binding to transcription factors. These findings help elucidate the molecular basis of visual system adaptation in cleaner wrasse and provide preliminary insights into the potential links between visual opsin gene regulation, cleaning behavior, and ecological adaptation.","[""Journal Article""]","[""Zhao SY"", ""Luo KW"", ""Guo HY"", ""Liu D""]",10.1007/s11033-026-12517-z,Zhao SY,Molecular biology reports,0301-4851,1,Mol Biol Rep,eng,Liu D,"[""Animals"", ""Male"", ""Female"", ""Phylogeny"", ""Opsins"", ""Gene Expression Regulation"", ""Perciformes"", ""Fish Proteins"", ""Sex Characteristics"", ""Enhancer Elements, Genetic"", ""Behavior, Animal"", ""Rod Opsins"", ""Genomics""]",,42536208,,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536208/,"Genomic and regulatory basis of visual opsin genes in the cleaner wrasse behavior: features, expression, and enhancer mechanisms",53,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Safer and more efficient products and processes are current global demands that drive the field of bioprospective research. Microbial sources are the main natural alternative solutions that have contributed to this biotechnological line, with environmental fungi representing important promising forces. Particularly, those inhabiting the most unexplored extreme geographical areas of the planet, marked by severe aridity, with hot and/or cold thermal profiles, e.g., the Atacama Desert, Saudi Arabia, Taklamakan Desert, semi-arid regions (Caatinga and Mexico), and polar and alpine ecosystems. In these habitats, many abiotic stressors are present, and fungi thrive through a combination of adaptations, including the production of pigmented secondary metabolites with diverse active biological functions that have high potential for innovative industrial applications, which is being explored in greater depth at the present time. In this sense, this article has aimed to review pigmented fungi from extreme arid environments from a taxonomic, genomic and biotechnological perspective. An attempt has been made to compile information on pigmented fungi in pure culture, their chromatic aspects, chemical classes, genomic data and application across diverse domains. There were more ascomycete and basidiomycete representatives producing a wide spectrum of endo- and extracellular colors categorized as melanins, carotenoids, and polyketides. Furthermore, they prove useful across multiple biotechnological sectors, ranging from agriculture, food, cosmetics, and medicine to astrobiology. Those with investigated genomes showed genes linked to the biosynthesis of these pigments and to environmental adaptation. Thus, with this initiative, we accessed the bioprospective importance of extremophilic colored fungi from arid habitats.","[""Journal Article"", ""Review""]","[""da Silva MK"", ""da Silva RC"", ""de Souza Melo BM"", ""Cavalcante TJC"", ""da Silva Santos L"", ""E Silva JGP"", ""Maia VRT"", ""da Silva Bernardo M"", ""da Silva Sousa K"", ""da Silva AV"", ""de Oliveira AJ"", ""de Queiroz AC"", ""Rosa LH"", ""Duarte AWF""]",10.1007/s11274-026-05160-0,da Silva MK,World journal of microbiology & biotechnology,0959-3993,8,World J Microbiol Biotechnol,eng,Duarte AWF,"[""Desert Climate"", ""Fungi"", ""Biotechnology"", ""Genomics"", ""Ecosystem"", ""Pigments, Biological"", ""Cold Temperature"", ""Genome, Fungal"", ""Ascomycota"", ""Melanins"", ""Phylogeny"", ""Basidiomycota""]",,42536097,pmc-id: PMC13427916;,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536097/,"Pigmented fungi derived from hot and cold deserts ecosystems: taxonomy, genomic and biotechnological approach",42,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Following the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7), serotype 19A Streptococcus pneumoniae emerged as a major cause of paediatric pneumococcal disease in Japan. Unlike global trends, in which multidrug-resistant serotype 19A-sequence type (ST)320 predominated, serotype 19A-ST2331 became one of the dominant lineages in Japan. The evolutionary origins of serotype 19A-ST2331 and the reasons for its domestic success remain unclear. To investigate the evolutionary origin and dissemination of the serotype 19A-ST2331 lineage, we analysed whole-genome sequences of 42 clonal complex (CC)2331 isolates collected in Japan between 2004 and 2017 and compared them with 825 genetically related global isolates. Phylogenetic analysis showed that Japanese serotype 19A-ST2331 isolates formed a distinct Japan-associated cluster within Global Pneumococcal Sequence Cluster 32 that was closely related to the globally disseminated Pneumococcal Molecular Epidemiology Network (PMEN)34 clone, typically represented by serotype 12F-ST218. Among the 42 Japanese CC2331 isolates, 40 were serotype 19A, whereas only two non-19A isolates were identified. Serotype 19A was absent from the 825 non-Japanese isolates, indicating that serotype 19A-ST2331 represents a globally rare, Japan-specific lineage. Most Japanese isolates remained susceptible to β-lactams, whereas 83.3% were erythromycin-resistant and carried either mefA/E or ermB. A highly clonal mefA/E-positive subclade was dated to a most recent common ancestor at ∼1998.5. These findings indicate that serotype 19A-ST2331 emerged before 2000 from an ST218-related ancestor through serotype switching and subsequently underwent local expansion in Japan. Although the ancestral intermediate was not represented in the present collection, the successful establishment of this clone may have been facilitated by the combined selective advantages conferred by the serotype 19A capsule and macrolide resistance in the post-PCV7 setting in Japan.","[""Journal Article""]","[""Koide S"", ""Nakano S"", ""Fujisawa T"", ""Ito Y"", ""Chang B"", ""Suga S"", ""Sugawara Y"", ""Akeda Y"", ""Sugai M""]",10.1099/mgen.0.001808,Koide S,Microbial genomics,2057-5858,7,Microb Genom,eng,Sugai M,"[""Streptococcus pneumoniae"", ""Japan"", ""Phylogeny"", ""Serogroup"", ""Humans"", ""Pneumococcal Infections"", ""Molecular Epidemiology"", ""Heptavalent Pneumococcal Conjugate Vaccine"", ""Whole Genome Sequencing"", ""Anti-Bacterial Agents"", ""Genome, Bacterial"", ""Drug Resistance, Multiple, Bacterial"", ""Pneumococcal Vaccines""]",,42536061,pmc-id: PMC13426510;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42536061/,Phylogenetic analysis of serotype 19A-sequence type (ST)2331 Streptococcus pneumoniae associated with the Pneumococcal Molecular Epidemiology Network (PMEN)34 clone predominant in Japan after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7),12,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"High-throughput sequencing has revolutionised conservation genomics by enabling genome-wide information even in non-model species. However, obtaining non-invasive samples for genomics remains challenging in species like sea turtles, which spend most of their lives in the open ocean. In addition, traditional sampling methods are often impractical or unsafe for hatchlings, highlighting the need for alternative approaches. We investigated the potential of umbilical cords (UCs), both from the proximal and distal regions, as a non-invasive sampling method. We assessed the suitability of UC sampling by evaluating prevalence under different incubation conditions, and whether the UC reflected a genetic origin from the mother or offspring. We analysed 76 samples with 2bRAD from five Spanish loggerhead turtle (Caretta caretta) emerging nests, including UCs from 13 hatchlings (both proximal and distal region), 48 hatchling blood samples (four with genotyped UCs) and blood from two breeding females. Using the Percentage of Shared Genotypes (PSG) analysis, we determined that the UC genotype from both sides matched the hatchling blood genotype (97.7%), while PSG were lower between related individuals (73.5%) and even lower between unrelated individuals (56.5%). UC prevalence varied by incubation type, appearing in 100% of artificially incubated nests in Spain, in 25% of Spain's naturally incubated nests, an emergent nesting population, and in only 4.5% of nests naturally incubated in Cape Verde, an established nesting population. Our findings establish UCs as a reliable non-invasive DNA source for hatchlings, particularly in incubator-hatched eggs. This approach advances genomic analysis while minimising disturbance, offering insights into population genetics and conservation strategies.","[""Journal Article""]","[""Marín-Capuz G"", ""Abella E"", ""Pascual M"", ""Pegueroles C"", ""Carreras C""]",10.1111/1755-0998.70184,Marín-Capuz G,Molecular ecology resources,1755-098X,6,Mol Ecol Resour,eng,Carreras C,"[""Animals"", ""Turtles"", ""DNA"", ""Female"", ""Genomics"", ""Umbilical Cord"", ""Spain"", ""Genotype""]",e70184,42535825,pmc-id: PMC13426248;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42535825/,Umbilical Cord: A Non-Invasive DNA Source for Sea Turtle Genomics,26,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Immunoglobulin A nephropathy (IgAN), the most common primary glomerular disease and a leading cause of end-stage kidney disease (ESKD), is associated with cardiovascular and metabolic abnormalities. To explore these genetic overlaps, we integrated large-scale GWAS data from IgAN, 21 pan-vascular diseases (PVDs), 13 metabolic traits, 11 immune cell phenotypes, and established IgAN risk factors. Cross-trait analyses (LDSC, GNOVA, SUPERGNOVA) revealed significant genetic correlations between IgAN and multiple PVDs, including coronary artery disease, heart failure, stroke, aortic aneurysm, and varicose veins. Multi-omics prioritization (TWAS, SMR, MAGMA, and fastBAT) identified shared variants and candidate genes associated with immune regulation, lipid transport, and cardiovascular function. Gene expression profiling demonstrated enrichment of these genes in endothelial cells, macrophages, spleen, lung, and blood. Drug repurposing analysis based on gene-drug matching scores (>0.5) identified promising therapeutic candidates, including immunosuppressants (prednisolone, cyclosporine, azathioprine), lipid-lowering agents (pitavastatin, fenofibrate), and the antiplatelet drug aspirin. These findings offer novel opportunities for precision medicine and drug repurposing in IgAN patients with cardiometabolic disorders.","[""Journal Article""]","[""Dai L"", ""Chen G"", ""Yang Y"", ""Yan Y"", ""Zhao Q"", ""He N"", ""Xiang Y"", ""Li Z"", ""Chen Y""]",10.1080/0886022X.2026.2706884,Dai L,Renal failure,0886-022X,1,Ren Fail,eng,Chen Y,"[""Humans"", ""Glomerulonephritis, IGA"", ""Genome-Wide Association Study"", ""Cardiovascular Diseases"", ""Genomics"", ""Genetic Predisposition to Disease"", ""Immunosuppressive Agents"", ""Gene Expression Profiling"", ""Multiomics"", ""Metabolic Diseases""]",2706884,42535737,,2026 Dec,2026,https://pubmed.ncbi.nlm.nih.gov/42535737/,Shared genetics of IgA nephropathy and cardiometabolic diseases revealed by integrative genomic analysis,48,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Animal biomineralization has evolved repeatedly, yielding diverse skeletal structures. A key question is whether this diversity stems from molecular convergence or a shared ancestral toolkit. Studying lophotrochozoans-a group with carbonate, phosphate, iron, and mixed mineralization systems-provides an ideal framework for addressing this issue but remains underrepresented in comparative omics studies. Here, we present a genome assembly and shell matrix proteome of the phosphate-biomineralizing brachiopod Lingula anatina CN, derived from a geographically distinct population. By integrating these data with comparative proteomic analysis across seven lophotrochozoan lineages representing diverse mineralization chemistries, we provide novel insights into the molecular basis of biomineralization. Sequence-based comparisons reveal extensive lineage specificity of shell matrix proteins, with little conservation across distant taxa. In contrast, domain-level analyses uncover a broadly conserved repertoire of functional modules-including EF-hand, von Willebrand factor type A, collagen-related, chitin-binding, and ferritin-like domains-recurrently recruited into shell matrix proteins across lineages. Importantly, similarity in shell matrix protein composition correlates more strongly with mineralization chemistry than with phylogenetic distance. Specifically, phosphate-mineralizing systems share a higher proportion of conserved shell matrix proteins and domains across deep evolutionary distances than do carbonate-based systems, indicating that mineral chemistry exerts a dominant selective pressure on the evolution of biomineralization-associated proteins. Lineage-specific innovations appear to arise primarily through domain shuffling, expansion of low-complexity regions, and gene family diversification. These findings support a model wherein lophotrochozoan biomineralization is underpinned by a shared ancestral molecular toolkit, differentially filtered and elaborated according to mineral chemistry, providing new insights into the early evolution of animal skeletal systems.","[""Journal Article"", ""Comparative Study""]","[""Chen Y"", ""Li J"", ""Peng Z"", ""Lv F"", ""Wang Y"", ""Teng W"", ""Li C"", ""Zhang L""]",10.1093/gbe/evag146,Chen Y,Genome biology and evolution,1759-6653,7,Genome Biol Evol,eng,Zhang L,"[""Animals"", ""Biomineralization"", ""Proteomics"", ""Phylogeny"", ""Invertebrates"", ""Proteome"", ""Evolution, Molecular"", ""Calcification, Physiologic"", ""Animal Shells""]",,42535640,pmc-id: PMC13425148;,2026 Jul 1,2026,https://pubmed.ncbi.nlm.nih.gov/42535640/,Comparative Proteomics Reveals Conserved and Lineage-Specific Molecular Toolkits in Lophotrochozoan Biomineralization,18,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"The gut microbiota comprises a diverse and dynamic community of microorganisms that collectively enhance host metabolism, physiology, and overall functionality. In this context, the swine archaeome remains largely underexplored despite growing evidence that archaea may greatly influence host health. Advances in high-throughput approaches provide new opportunities to reveal the dynamics and composition of archaea. Herein, we uncover the taxonomic and functional landscape of the piglet archaeome during the weaning transition under multiple experimental conditions, integrating shotgun metagenomic and metatranscriptomic analyses to elucidate its contribution to gut microbial ecology. The seven experimental conditions included four antibiotic treatments for post-weaning diarrhoea (trimethoprim/sulfamethoxazole, colistin, gentamicin, amoxicillin), an oral vaccine, acidifiers in drinking water, and a no-intervention group. A total of 280 faecal samples were collected longitudinally one day before weaning (ST1), three days (ST2), two weeks (ST3), and four weeks (ST4) after the start of the treatment. Treatment was initiated eleven days after arrival at the experimental farm following the onset of clinical signs. Shotgun metagenomics was used to assess archaeal taxonomic diversity and recover archaeal metagenome-assembled genomes (aMAGs), while metatranscriptomics was integrated to assess differentially expressed genes at ST1, ST2, and ST4. The results revealed archaea as the second most abundant microorganism, exhibiting a longitudinal increase in diversity over the experimental time. The most predominant genus was Methanobrevibacter, including Methanobrevibacter smithii. Eleven high-quality aMAGs were recovered, belonging to the Methanobacteriota and Thermoplasmatota phyla. Genome-inferred functional analyses revealed that the predominant metabolic processes included the biosynthesis of nucleic acids, amino acids, organic anions, and vitamins. Additional functional traits suggested potential roles in the degradation of sugars, amino acids, and antibiotics were also observed. Moreover, significant differences were detected on the archaeal metatranscriptome between the experimental groups treated with antibiotics and the rest of the groups, underscoring their response to changes in microbial interactions, substrate availability and, in some cases, direct effect of the antimicrobials on metabolic pathways. Altogether, this study highlights the biological significance of archaeal dynamics during initial life stages and demonstrates how combining metagenomics and metatranscriptomics uncovers their functional potential and the pathways actively expressed in the piglets' gut.","[""Journal Article""]","[""Guitart-Matas J"", ""Bravo M"", ""Tort-Miró C"", ""Giler-Baquerizo N"", ""Fraile L"", ""Caldas-Ramayo Y"", ""Ballester M"", ""Migura-Garcia L""]",10.3389/fcimb.2026.1833734,Guitart-Matas J,Frontiers in cellular and infection microbiology,2235-2988,,Front Cell Infect Microbiol,eng,Migura-Garcia L,"[""Animals"", ""Archaea"", ""Swine"", ""Metagenomics"", ""Gastrointestinal Microbiome"", ""Feces"", ""Metagenome"", ""Weaning"", ""Biodiversity"", ""Anti-Infective Agents"", ""Gene Expression Profiling"", ""Phylogeny"", ""Diarrhea"", ""Anti-Bacterial Agents""]",1833734,42534899,pmc-id: PMC13422161;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42534899/,Dynamics of archaeal diversity and functionality in the piglet gut microbiome under common antimicrobial treatments,16,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"The antler primary growth center, located at the distal tip of the growing antler, comprises five consecutive tissue zones beneath the velvet skin. Because the outermost reserve mesenchyme contains blastema progenitor cells with multipotent differentiation capacity, antler regeneration recapitulates embryonic skeletal development through endochondral ossification (ECO). The molecular mechanisms governing cell fate decisions and tissue morphogenesis across these zones remain poorly understood. We profiled the proteome of the sika deer (Cervus nippon) antler growth center across all five tissue zones using the Orbitrap Astral platform in data-independent acquisition (DIA) mode. Protein identification and quantification were performed with DIA-NN. Proteome dynamics were analyzed by integrating three complementary clustering approaches including weighted gene co-expression network analysis (WGCNA), Fuzzy C-means clustering, and monotonic feature selection. Differentially expressed proteins were annotated by gene ontology (GO) enrichment analysis. Transcriptomic data from the same tissue zones were reanalyzed to assess mRNA-protein concordance. A total of 8,173 proteins were identified across the five tissue zones, representing the most comprehensive proteomic coverage of the antler growth center. Clustering analyses resolved distinct protein expression modules corresponding to sequential ECO stages from mesenchymal proliferation in the reserve mesenchyme to cartilage mineralization in the innermost zone. Deep proteome coverage enabled detection of low-abundance chondrogenic transcription factors SOX9, SOX6, and RUNX3, whose spatial expression matched their known roles in chondrogenesis. At the protein level, the reserve mesenchyme co-expressed 11 embryonic and 23 mesenchymal stem cell markers, indicating that antler stem cells represented a unique mesenchymal stem cell (MSC) population possessing partial embryonic stem cell (ESC)-like features. This study provides a spatially resolved proteomic atlas of the complete antler growth center and identifies key regulatory proteins at each stage of endochondral ossification. The findings offer new insights into progenitor cell characteristics, transcription factor activity, and protein dynamics during bone development, with potential relevance to bone repair and regenerative medicine.","[""Journal Article""]","[""Xi X"", ""Cao X"", ""Zhou Y"", ""Tian Z"", ""Hou N"", ""Li Z"", ""Zhou Z"", ""Li X"", ""Su H""]",10.7717/peerj.21568,Xi X,PeerJ,2167-8359,,PeerJ,eng,Su H,"[""Animals"", ""Antlers"", ""Osteogenesis"", ""Deer"", ""Proteomics"", ""Proteome"", ""Chondrogenesis""]",e21568,42534826,pmc-id: PMC13421809;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42534826/,Proteomic dynamics in endochondral ossification: insights from antler tip analysis,14,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"The ring distribution pattern offers a unique perspective for analysing the mechanisms of species or population differentiation. The semi-closed South China Sea (SCS) region, with its islands, peninsulas, and continental margins, is ideal for studying the formation of ring distribution patterns and the evolutionary dynamics of island populations. This study focused on Malcus flavidipes, a species distributed in the SCS region. Based on double-digest restriction-associated DNA data and geographic distribution data, population genetic approaches and species distribution modeling were employed to investigate its distribution pattern formation and the evolutionary characteristics of island populations. The results revealed five geographic clades around the SCS, located on the Yunnan-Indochina Peninsula, southern China, Hainan Island, Kalimantan and the Philippines. Genetic diversity evidence supported that the ring distribution pattern originated in the Yunnan-Indochina Peninsula and diffused through the land bridges exposed during the Pleistocene glaciation along two routes: the northern route extended from southern China to Hainan Island, whereas the southern route stretched from Kalimantan to the Philippines. Island populations show significantly lower genetic diversity and higher within-population inbreeding coefficients than mainland ones. The genetic structural differences among different island populations are closely related to their geographic distance from mainland, responses to historical climatic fluctuations, and selective pressures from island environments. This study provides important empirical evidence for the ring differentiation of species in the SCS region, and offers a new perspective for understanding the evolutionary mechanisms of island populations under the combined effects of geographical isolation, genetic drift, and environmental selection.","[""Journal Article""]","[""Li YF"", ""Guo MQ"", ""Chen JH"", ""Ai DQ"", ""Li ZH"", ""Zhang JY"", ""Ye Z"", ""Xue HJ"", ""Wang SJ"", ""Bu WJ""]",10.24272/j.issn.2095-8137.2025.400,Li YF,Zoological research,2095-8137,4,Zool Res,eng,Bu WJ,"[""Animals"", ""China"", ""Phylogeography"", ""Heteroptera"", ""Genetic Variation"", ""Islands"", ""Animal Distribution"", ""Adaptation, Physiological""]",1253-1264,42533578,,2026 Jul 18,2026,https://pubmed.ncbi.nlm.nih.gov/42533578/,Phylogeographic history of the ring distribution in Malcus flavidipes (Heteroptera: Malcidae) shaped by directional dispersal and island adaptation in the South China Sea region,47,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Long-term spaceflight poses substantial challenges to human physiology, with the liver being highly susceptible due to its central metabolic role. To determine whether hepatic alterations represent transient stress or sustained remodeling, we performed an integrated multi-omics analysis in a rat model simulating chronic space radiation and microgravity. Herein, we applied an integrated multi-omics and AI-driven analytical framework combining histopathology, cytokine and miRNA profiling, proteomics, metabolomics and Western blot validation. After 21 days of simulated space conditions, rats exhibited significant hepatic atrophy, histopathological injury, and metabolic dysfunction resembling a NAFLD-like phenotype, accompanied by multi-omics signatures of impaired oxidative phosphorylation, disrupted TCA cycle activity, altered lipid-metabolic regulation, and inflammatory remodeling. During a 14-day recovery phase, hepatic atrophy and histological lesions were incompletely improved, with omics changes suggesting partial restoration of mitochondrial related energy metabolism, PPAR associated lipid regulation, and fatty acid β-oxidation. Machine learning-based proteomics identified a panel of energy-related and lipid-metabolic proteins that robustly distinguished injury from recovery states. External validation with NASA GeneLab transcriptomic datasets supported the suppression of extracellular matrix programs and structural repair during injury. Together, these findings organize the hepatic response to simulated spaceflight into (1) AMPK/PPAR-γ/PGC-1α-centered energy-related lipid/mitochondrial regulation, (2) ACSM5/CRAT-associated fatty-acid utilization and carnitine-shuttle remodeling, and (3) TGF-β/IGF1-related structural repair and anabolic signaling. This study provides a comprehensive organ-level overview for understanding hepatic adaptation to extreme spaceflight environments and identifies potential targets for mitigating astronaut health risks during long-duration missions.","[""Journal Article""]","[""Zhang H"", ""Li B"", ""Zou Y"", ""Yao F"", ""Su W"", ""Li B""]",10.1096/fj.202504206RR,Zhang H,FASEB journal : official publication of the Federation of American Societies for Experimental Biology,0892-6638,15,FASEB J,eng,Li B,"[""Animals"", ""Space Flight"", ""Rats"", ""Liver"", ""Multiomics"", ""Machine Learning"", ""Male"", ""Weightlessness Simulation"", ""Adaptation, Physiological"", ""Proteomics"", ""Metabolomics"", ""Stress, Physiological"", ""Energy Metabolism"", ""Lipid Metabolism"", ""Rats, Sprague-Dawley""]",e72165,42533568,pmc-id: PMC13424968;,2026 Aug 15,2026,https://pubmed.ncbi.nlm.nih.gov/42533568/,From Collapse to Active Self-Repair: Integrative Multi-Omics and Machine Learning Analysis Map the Hepatic Metabolic Adaption in Response to Simulated Spaceflight Stress,40,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Korean individuals with BRCA pathogenic/likely pathogenic (P/LP) variants have limited access to genetic counseling due to shortages of genetic professionals and lack of reimbursement. Despite the growing interest in digital health interventions, few digital counseling support tools have been designed to address the diverse information needs of this population. This study aimed to develop a user information needs-based chatbot for providing individualized information for individuals with BRCA pathogenic variants and to evaluate its usability. The chatbot, All about BRCA, was developed using a commercial chatbot platform through three stages from October 2021 to September 2022: identifying information needs via a systematic review and web-crawling analysis of patient-generative questions from online communities; developing a prototype chatbot validated by seven healthcare professionals and implementing it as rule-based system; conducting usability testing with individuals with P/LP variants in BRCA genes, using the modified mHealth App Usability Questionnaire and daily usage diaries. The modified mHealth App Usability Questionnaire scores were analyzed using descriptive statistics, and narrative diary data were analyzed using content analysis. Following iterative rounds of reviews and usability testing, the final chatbot comprised 10 information categories with 62 predefined question-scenario-responses. Nineteen participants evaluated the chatbot, yielding a mean modified mHealth App Usability Questionnaire score of 5.7 ± 0.8 out of 7. Scoring on all subscales, that is, ease of use, interface/satisfaction, and usefulness, exceeded 5.5. Responses on narrative diary data were predominantly positive, with users valuing systematic, detailed, and practical information. Key limitations of the chatbot included restricted question recognition and limited information depth. Despite limitations in question recognition, the chatbot demonstrated acceptable usability as a complementary tool to support individuals with BRCA pathogenic variants. It may help address constraints of limited consultation time and genetic expert shortages. Future development should strengthen conversational capabilities.","[""Journal Article""]","[""Park SY"", ""Kim Y"", ""Katapodi MC"", ""Kim S""]",10.1002/jgc4.70268,Park SY,Journal of genetic counseling,1059-7700,4,J Genet Couns,eng,Kim S,"[""Humans"", ""Female"", ""Republic of Korea"", ""Genetic Counseling"", ""Genes, BRCA1"", ""Genes, BRCA2"", ""Adult"", ""Surveys and Questionnaires"", ""BRCA1 Protein""]",e70268,42533411,pmc-id: PMC13424905;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42533411/,Development and Usability Testing of an Information Needs-Based Chatbot for Individuals With Pathogenic Variants in BRCA Genes in Korea: A Methodological Study,35,5hnMr6g7NIBaUo2Qv,kQ3aWxbeD7LUORfBe
"Time in Tight Range (TITR) is physiologically closer to normoglycemia than time in range (TIR) and has been linked to microvascular risk. We aimed to evaluate associations of TITR with diabetic retinopathy (DR) and optical coherence tomography angiography (OCTA)-derived retinal parameters in adults with type 1 diabetes (T1D) and to compare its performance with TIR. We retrospectively included adults with T1D who underwent continuous glucose monitoring (CGM) and OCTA. TITR-DR associations were tested using multivariable logistic regression with restricted cubic splines. Linear mixed-effects models assessed TITR/TIR associations with OCTA-derived parameters, followed by exploratory threshold-based comparisons. DR discrimination of TITR versus TIR was assessed using ROC analysis. We analyzed 259,568 glucose readings from 153 participants. Each 10-percentage-point increase in TITR was associated with 29.5% lower odds of DR (adjusted OR 0.705; p = 0.004), without evidence of nonlinearity. In continuous analyses, both TITR and TIR were positively associated with deep vascular complex (DVC) vessel density and perfusion area; in exploratory threshold-based analyses, the TITR 50% cutoff showed significant DVC differences, whereas the TIR 70% cutoff showed no consistent differences. DR discrimination was similar for TITR and TIR (p = 0.635), whereas TITR was more closely related to hypoglycemia exposure (p < 0.01). Higher TITR was associated with lower odds of DR and more favorable DVC vessel density and perfusion area in hospitalized adults with T1D. TITR showed DR discrimination comparable to TIR but may provide complementary information on hypoglycemia exposure and DVC differences in threshold-based analyses.","[""Journal Article""]","[""Zheng R"", ""Zhang C"", ""Sun X"", ""Li J"", ""Wang L"", ""Huang S"", ""Hou R"", ""Dong S"", ""Wu S"", ""Li H"", ""Zhang L"", ""Kuang B"", ""Zheng L"", ""Zhang B"", ""Yang C"", ""Kuang H""]",10.1007/s12020-026-04735-z,Zheng R,Endocrine,1355-008X,1,Endocrine,eng,Kuang H,"[""Humans"", ""Diabetes Mellitus, Type 1"", ""Diabetic Retinopathy"", ""Female"", ""Male"", ""Adult"", ""Continuous Glucose Monitoring"", ""Retrospective Studies"", ""Tomography, Optical Coherence"", ""Middle Aged"", ""Retinal Vessels"", ""Blood Glucose"", ""Microvessels"", ""Hospitalization"", ""Time Factors""]",,42545593,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545593/,Time in tight range and time in range in relation to diabetic retinopathy and OCTA-derived retinal microvascular parameters in hospitalized adults with type 1 diabetes,91,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Hepatic involvement in Type 1 Diabetes Mellitus (T1DM) is increasingly recognized, with hepatopathy emerging as an important but underexplored comorbidity. Data on its prevalence and associated factors, particularly in Indian children and adolescents, remain limited. To estimate the prevalence of ultrasound-diagnosed hepatopathy and identify its associated risk factors among Indian children and adolescents with T1DM. This cross-sectional study included 510 children and adolescents with T1DM from a tertiary care center in western India. Clinical, anthropometric, biochemical, dietary, physical activity, and resting metabolic rate (RMR) data were collected. Hepatopathy was assessed using ultrasonography. Logistic regression analysis was performed to identify independent associated factors. The prevalence of hepatopathy was 10.4%. Children with hepatopathy had significantly higher waist circumference, blood pressure, insulin requirements, and lower moderate-to-vigorous physical activity (p < 0.05). They also exhibited poorer glycemic control, dyslipidemia, elevated liver enzymes, and reduced insulin sensitivity. RMR adjusted for insulin was significantly lower in those with hepatopathy. Multivariable analysis identified that higher waist circumference, higher insulin dose, elevated triglycerides, poor glycemic control, lower physical activity, and lower RMR were associated with hepatopathy (p < 0.05). Hepatopathy is a clinically relevant comorbidity among Indian children and adolescents with T1DM, associated with metabolic dysfunction, lifestyle factors, and altered energy metabolism. Early identification through ultrasound-based screening and targeted interventions focusing on glycemic control, adiposity, and physical activity may be critical in preventing long-term hepatic and cardiometabolic complications.","[""Journal Article""]","[""Mondkar S"", ""Deshpande M"", ""Wagle S"", ""Khadilkar A"", ""Khadilkar V""]",10.1007/s12020-026-04733-1,Mondkar S,Endocrine,1355-008X,1,Endocrine,eng,Khadilkar V,"[""Humans"", ""Adolescent"", ""Diabetes Mellitus, Type 1"", ""India"", ""Male"", ""Female"", ""Ultrasonography"", ""Cross-Sectional Studies"", ""Prevalence"", ""Child"", ""Risk Factors"", ""Liver Diseases"", ""Comorbidity"", ""Insulin Resistance""]",,42545581,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545581/,Prevalence and factors associated with ultrasound-detected hepatopathy in Indian adolescents with type 1 Diabetes Mellitus,91,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Longitudinal association of triglyceride glucose-Chinese visceral adiposity index (TyG-CVAI) with the risk of new-onset sarcopenia in middle-aged and older adults with diabetes remains unclear. This study aimed to investigate whether baseline and cumulative TyG-CVAI is associated with incident sarcopenia risk in middle-aged and older adults with diabetes. We included participants aged ≥ 50 years with diabetes from the China Health and Retirement Longitudinal Study (CHARLS) 2011-2012. TyG-CVAI was calculated as TyG index multiplied by CVAI. Multivariable Cox regression and logistic regression were used to examine the associations of baseline and cumulative TyG-CVAI with new-onset sarcopenia. Receiver operating characteristic (ROC) curves were employed to compare the predictive capability of TyG-CVAI with its individual components. A total of 763 participants with diabetes were included in the baseline analysis. During the 4-year follow-up, 62 (8.1%) participants developed new-onset sarcopenia. Compared with the lowest quartile (Q1) of baseline TyG-CVAI, the highest quartile (Q4) was significantly associated with an increased risk of sarcopenia (HR = 2.368, 95% CI: 1.014-5.532) in the fully adjusted model, with a significant trend across quartiles (P for trend = 0.017). Compared with the low-stable group (Cluster 1, n = 198), the high-stable group (Cluster 2, n = 276) had a significantly higher risk of new-onset sarcopenia (OR = 1.100, 95% CI: 1.020-1.321). The predictive performance of baseline TyG-CVAI (AUC = 0.685, 95% CI: 0.611-0.747) and cumulative TyG-CVAI (AUC = 0.917, 95% CI: 0.845-0.962) was higher than that of baseline and cumulative TyG and CVAI. Elevated baseline and cumulative TyG-CVAI are associated with new-onset sarcopenia in middle-aged and older Chinese adults with diabetes.","[""Journal Article""]","[""Chen Y"", ""Gao T"", ""Gao J"", ""Feng X""]",10.1007/s12020-026-04734-0,Chen Y,Endocrine,1355-008X,1,Endocrine,eng,Feng X,"[""Humans"", ""Sarcopenia"", ""Female"", ""Middle Aged"", ""Male"", ""Aged"", ""China"", ""Prospective Studies"", ""Triglycerides"", ""Blood Glucose"", ""Adiposity"", ""Intra-Abdominal Fat"", ""Incidence"", ""Diabetes Mellitus"", ""Risk Factors"", ""Longitudinal Studies"", ""East Asian People""]",,42545547,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545547/,Association of the triglyceride glucose-Chinese visceral adiposity index with incident sarcopenia among middle-aged and older adults with diabetes: a prospective cohort study,91,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Adolescence is a critical phase characterized by temporary insulin resistance and a tendency for a later chronotype, potentially influencing the risk of developing type 2 diabetes (T2D) later in life. This study explores how morning and evening carbohydrate (CHO) intake during adolescence are prospectively related to T2D risk factors-such as insulin resistance (HOMA2-IR), liver fat indices, and subclinical inflammation- in adulthood while considering the role of chronotype. This analysis utilizes data from 224 DONALD study participants (58% female) who provided 3-day weighed dietary records during adolescence (median age = 12 years) and a blood sample in adulthood (median age = 22 years). Owing to detected interactions between the timing of CHO intake i.e. CHOevening(E%)-CHOmorning(E%), (eveningness in CHO intake) and chronotype, analyses were stratified accordingly. An inverse relationship was found between morning CHO intake (before 11 a.m.) and adult HOMA2-IR levels (beta and 95% CI for high (T3) vs. low (T1): -0.12 (-0.21; -0.04), ptrend = 0.01). For individuals with an earlier chronotype, a higher ""eveningness in CHO intake"" was linked to higher HOMA2-IR (ptrend = 0.03). Conversely, those with a later chronotype exhibited the lowest HOMA2-IR in the median ""eveningness in CHO intake"" category (T2). No significant associations were observed between evening CHO intake and other risk markers. Consuming CHOs in the morning during adolescence is associated with lower HOMA2-IR in adulthood, irrespective of chronotype. However, the favorable morning CHO intake amount appears to vary by chronotype, indicating a personalized approach may be beneficial.","[""Journal Article""]","[""Jankovic N"", ""Schmitting S"", ""Perrar I"", ""Hohoff E"", ""Lesani A"", ""Goletzke J"", ""Stutz B"", ""Herder C"", ""Wudy SA"", ""Nöthlings U"", ""Alexy U""]",10.1007/s00394-026-04056-x,Jankovic N,European journal of nutrition,1436-6207,5,Eur J Nutr,eng,Alexy U,"[""Humans"", ""Chronotype"", ""Diabetes Mellitus, Type 2"", ""Female"", ""Dietary Carbohydrates"", ""Adolescent"", ""Risk Factors"", ""Male"", ""Young Adult"", ""Biomarkers"", ""Circadian Rhythm"", ""Child"", ""Insulin Resistance"", ""Adult"", ""Prospective Studies""]",,42545501,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545501/,Circadian distribution of carbohydrate intake during adolescence and association with risk markers of type 2 diabetes in adulthood-the role of chronotype,65,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Vitamin D deficiency is one of the most common endocrine disorders and plays a significant role in the pathogenesis of carbohydrate metabolism disturbances. Low serum 25(OH)D levels are associated with the development of insulin resistance, metabolic syndrome, prediabetes, and type 2 diabetes mellitus (T2DM). However, data on the prevalence of vitamin D deficiency and its age-related characteristics in the population of Uzbekistan remain limited. To investigate the prevalence of vitamin D deficiency in individuals with prediabetes and newly diagnosed T2DM based on screening data from the city of Andijan and the Markhamat district of the Andijan region, Uzbekistan. A total of 3,400 individuals over 40 years of age were screened (1,800 in Markhamat district, 1,600 in Andijan city) using the FINDRISC questionnaire. Serum 25(OH)D levels, carbohydrate and lipid metabolism parameters, and HOMA-IR index were assessed in 205 subjects with prediabetes, 102 patients with newly diagnosed T2DM, and 60 controls. Prediabetes and T2DM were diagnosed according to WHO criteria. Mean vitamin D levels were significantly lower in patients with prediabetes and T2DM compared to the control group (p&lt;0.05). The most severe deficiency was observed in patients with T2DM, especially among women and individuals aged 45-59 and 60-74 years. In Andijan city, vitamin D deficiency was detected in 100% of T2DM patients, while in Markhamat district the prevalence reached 40.3%. Vitamin D deficiency is highly prevalent among patients with prediabetes and T2DM, with severity increasing with age and more pronounced in women. These findings highlight the need for routine monitoring of serum 25(OH)D and preventive strategies in high-risk groups.","[""English Abstract"", ""Journal Article""]","[""Yusupova SK"", ""Nishanova MS"", ""Yusupov KA"", ""Abdurazakova DS"", ""Mukhamedova VM"", ""Abdulazizhojiyeva RB"", ""Chartakova KK"", ""Juliyeva YG"", ""Khamidova MI"", ""Ismoilova SK"", ""Khalilova SR"", ""Supichakov KK""]",10.14341/probl13659,Yusupova SK,Problemy endokrinologii,0375-9660,3,Probl Endokrinol (Mosk),rus,Supichakov KK,"[""Humans"", ""Female"", ""Vitamin D Deficiency"", ""Diabetes Mellitus, Type 2"", ""Carbohydrate Metabolism"", ""Prediabetic State"", ""Middle Aged"", ""Adult"", ""Male"", ""Uzbekistan"", ""Insulin Resistance"", ""Vitamin D"", ""Prevalence"", ""Climate""]",53-59,42545323,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42545323/,[Regional features of the main indicators of carbohydrate metabolism in young residents of various climatic and geographical zones of residence],72,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Gluconeogenesis, a dual-purpose pathway in type 2 diabetes mellitus (T2DM), not only synthesizes glucose but also clears metabolic waste via the Cori cycle (lactate recycling through LDH, PC, PEPCK) and Alanine cycle (nitrogen disposal via ALT, GDH, urea cycle), preventing acidosis, ROS accumulation, and ammonia toxicity. Metformin, the cornerstone T2DM therapy, inhibits gluconeogenesis by targeting mitochondrial complex I, elevating AMP/ATP ratios, and activating AMPK-PKCι/λ signaling to repress CREB-CRTC2-driven PEPCK/G6Pase expression, disrupting these cycles. This leads to lactate, pyruvate, and ammonia buildup, triggering pro-inflammatory cascades: HIF-1α stabilization induces IL-6/VEGF, ROS from pyruvate excess activates NF-κB for TNF-α, and ammonia primes NLRP3 inflammasome for IL-1β/IL-18 release, fostering chronic inflammation. Multisystem consequences include musculoskeletal fatigue from ATP deficits, cognitive fog via neuroinflammation, atherosclerosis from endothelial dysfunction, hepatic fibrosis from urea cycle stress, and immune inflammaging impairing macrophage function. Clinical evidence reveals short-term anti-inflammatory benefits (reduced IL-6, CRP) via AMPK and microbiota effects, contrasted by long-term risks like lactic acidosis and neurodegeneration in renal-impaired or elderly patients. This review integrates physiological roles, molecular mechanisms, inflammatory pathways, systemic impacts, and clinical findings, highlighting metformin's dual-edged profile glycemic efficacy versus ""inflammatory debt."" Researchers are urged to explore precision interventions, such as antioxidants or biomarker-guided dosing, to optimize metformin's pleiotropic potential in T2DM and inflammaging-related disorders, redefining therapeutic paradigms.","[""Journal Article"", ""Review""]","[""Akl M"", ""Ahmed A""]",10.14341/probl13618,Akl M,Problemy endokrinologii,0375-9660,3,Probl Endokrinol (Mosk),eng,Ahmed A,"[""Metformin"", ""Humans"", ""Diabetes Mellitus, Type 2"", ""Inflammation"", ""Gluconeogenesis"", ""Hypoglycemic Agents"", ""NF-kappa B"", ""Animals"", ""Alanine"", ""Signal Transduction""]",44-52,42545322,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42545322/,"Metformin's disruption of gluconeogenesis in type 2 diabetes impairments of the cori and alanine cycles as hidden drivers of metabolic waste accumulation, NF-κBHIF-1α-mediated low-grade inflammation, and multisystem dysfunction",72,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Functional health literacy (FHL) plays a dynamic role in diabetes care, yet research on its implications is erratic in Bangladesh. The aim of this study was to ascertain the level of FHL among patients with type 2 diabetes (T2D) in Dhaka and its correlation with their glycemic level, lifestyle, sleep quality, and sociodemographic characteristics. A total of 401 patients with T2D were included by simple random sampling method in this cross-sectional study from three diabetes centers in Dhaka. A Bengali adaptation of the S-TOFHLA (Short Test of Functional Health Literacy) and a semi-structured questionnaire was used to collect data on FHL and other study information. Bivariate analysis, multi-nominal regression, Pearson's χ2 test, and Cramér's V coefficient was used to assess the correlations between variables, with a significance threshold of p < .05. Among the 401 participants, 59% were female and 34.9% lived in rural areas; among whom only 27.3% had adequate FHL. Sex, occupation, education, income, physical activity regularity, diabetes treatment regimen, family history, current fasting blood sugar (FBS), 3-month average FBS, 3-month average 2-hour after breakfast blood glucose, and hemoglobin A1c showed significant associations (p < .0001) with the level of FHL. Higher education level significantly increased the odds for adequate FHL (adjusted odds ratios (AOR) = 5.70 to 78.81). Adequate FHL was significantly associated with higher sleep metrics (AOR = 5.67 and 9.17). Longer sleep duration and higher quality sleep increased the likelihood of having adequate FHL (AOR = 9.17 and 5.67, respectively; p < .05) and higher glucose levels were linked to reduced FHL odds (AOR <1). Higher FHL was associated with better diabetes management. FHL interventions should be evaluated to determine if increasing a patient's health literacy will improve their diabetes management.","[""Journal Article""]","[""Islam MM"", ""Hossain SB"", ""Rahman KM"", ""Sinthia MK"", ""Chowdhury ABMA"", ""Khan S""]",10.3928/24748307-20260409-02,Islam MM,Health literacy research and practice,2474-8307,3,Health Lit Res Pract,eng,Khan S,"[""Humans"", ""Female"", ""Cross-Sectional Studies"", ""Diabetes Mellitus, Type 2"", ""Male"", ""Bangladesh"", ""Health Literacy"", ""Middle Aged"", ""Surveys and Questionnaires"", ""Adult"", ""Aged""]",e92-e102,42545221,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42545221/,Association of Functional Health Literacy Among Patients With Type-2 Diabetes in Bangladesh: A Cross-sectional Study,10,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Human Serum Albumin (HSA) is abundant plasma protein in human blood. It plays a critical role in the transport and distribution of endogenous and exogenous compounds. Protein binding affects free fraction of a drug thus affecting pharmacokinetics and therapeutic efficacy. Glycation of HSA under diabetic conditions and the accumulation of uremic toxins in uraemia may alter drug-protein interactions. Therefore, the present study aimed to investigate the binding interactions of ribavirin and selected uremic toxins with binding interactions involving glycation-sensitive HSA residues using molecular docking analysis. Molecular docking results demonstrated that ribavirin bind to HSA with hydrogen bonding and hydrophobic interactions. Key glycation-prone residues, including ARG222, ARG218, and LYS195, were identified at the ribavirin binding site. Several of these residues were also involved in the binding of uremic toxins, indicating potential competition for ligand binding in diabetic and uremic conditions. The overlap of interaction sites suggests that glycation and toxin accumulation may influence the structural and biochemical properties of HSA, thereby affecting ribavirin binding affinity and distribution. In conclusion, this study highlights the important role of glycation-sensitive HSA residues in mediating ribavirin and uremic toxin interactions. These insights may support the future design and optimization of ribavirin-based therapeutics.","[""Journal Article""]","[""Almutairi FM"", ""Ajmal MR""]",10.14715/cmb/2026.72.4.4,Almutairi FM,"Cellular and molecular biology (Noisy-le-Grand, France)",0145-5680,4,Cell Mol Biol (Noisy-le-grand),eng,Ajmal MR,"[""Humans"", ""Molecular Docking Simulation"", ""Ribavirin"", ""Antiviral Agents"", ""Protein Binding"", ""Binding Sites"", ""Serum Albumin"", ""Uremia"", ""Hydrogen Bonding"", ""Diabetes Mellitus"", ""Glycosylation"", ""Hydrophobic and Hydrophilic Interactions""]",22-28,42545141,,2026 Apr 30,2026,https://pubmed.ncbi.nlm.nih.gov/42545141/,Antiviral ribavirin binding to human serum albumin in diabetes and uraemia: A molecular docking study,72,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Pancreatic β cells regulate glucose homeostasis through insulin secretion, but nutrient overload and genetic defects can trigger ER stress and apoptosis, contributing to type 2 diabetes. Within β cells, the kinases PERK, IRE1α, and ATF6 initiate the unfolded protein response (UPR) as a result of ER stress, a process that is constitutively suppressed under nonstress conditions by GRP78 binding to these proteins. To gain insight into the mechanisms of β cell death upon dysregulated ER stress, Sharma et al. used β cell-specific GRP78 knockout models, revealing that hyperactivation of the UPR promoted β cell death primarily through the IRE1α/JNK/p53 signaling pathway. Pharmacological inhibition of JNK improved β cell survival, increased insulin levels, and lowered blood glucose in multiple diabetic mouse models. These findings highlight JNK signaling as a promising therapeutic target for preserving β cell function.","[""Journal Article""]","[""Palozzi JM"", ""Puigserver P""]",10.1172/JCI209808,Palozzi JM,The Journal of clinical investigation,0021-9738,15,J Clin Invest,eng,Puigserver P,"[""Animals"", ""Insulin-Secreting Cells"", ""Endoplasmic Reticulum Chaperone BiP"", ""Humans"", ""Mice"", ""Diabetes Mellitus, Type 2"", ""Unfolded Protein Response"", ""Protein Serine-Threonine Kinases"", ""Endoplasmic Reticulum Stress"", ""Heat-Shock Proteins"", ""JNK Mitogen-Activated Protein Kinases"", ""Apoptosis"", ""Endoribonucleases"", ""eIF-2 Kinase"", ""MAP Kinase Signaling System"", ""Activating Transcription Factor 6"", ""Endoplasmic Reticulum"", ""Signal Transduction"", ""Mice, Knockout"", ""Insulin""]",,42544576,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42544576/,Diabetic and ER-stressed pancreatic islet β cells are in need of some JNK removal,136,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Endoplasmic reticulum (ER) stress contributes to β cell death in both Type 1 and Type 2 diabetes (T1D and T2D). However, the molecular mechanisms driving β cell death during ER stress remain insufficiently defined, limiting development of protective therapies. GRP78, an ER chaperone, is the master regulator of unfolded protein response (UPR), suppressing UPR initiators during the unstressed state and releasing them to allow UPR activation during stress. To dissect the pathways leading to ER-stress response related β cell decompensation, we engineered mice genetically lacking GRP78 in pancreatic β cells. GRP78 deletion caused acute insulin-deficient diabetes in pups before weaning, with reduced β cell mass due to increased apoptosis. Molecular studies identified deregulated UPR, specifically IRE1 activity, as driving cell death. Unbiased and targeted analyses identified a JNK-p53 axis downstream of IRE1 kinase as a key mediator of β cell death during UPR activation. In vivo JNK inhibition protected against β cell death in 2 distinct ER stress diabetes models. In human β cells, pharmacological inhibition of both JNK and p53 improved β cell survival during GRP78 knockdown-induced UPR. These findings provide insight into mechanisms causing β cell death during ER stress and outline possible therapeutic targets to preserve insulin secretory capacity in diabetes.","[""Journal Article""]","[""Sharma RB"", ""Darko C"", ""Wang Y"", ""Castro TA"", ""Lama TD"", ""Gablaski B"", ""Rappa A"", ""Redmond D"", ""Kim JK"", ""Lee AS"", ""Alonso LC""]",10.1172/JCI193035,Sharma RB,The Journal of clinical investigation,0021-9738,15,J Clin Invest,eng,Alonso LC,"[""Animals"", ""Endoplasmic Reticulum Chaperone BiP"", ""Unfolded Protein Response"", ""Insulin-Secreting Cells"", ""Humans"", ""Tumor Suppressor Protein p53"", ""Mice"", ""Heat-Shock Proteins"", ""Protein Serine-Threonine Kinases"", ""Endoplasmic Reticulum Stress"", ""Mice, Knockout"", ""Endoribonucleases"", ""Apoptosis"", ""JNK Mitogen-Activated Protein Kinases"", ""Diabetes Mellitus, Type 2"", ""MAP Kinase Signaling System""]",,42544575,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42544575/,JNK and p53 cause human and mouse β cell death during excessive unfolded protein response,136,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), are established therapies for obesity and type 2 diabetes mellitus, providing sustained weight reduction, improved glycaemic control, cardiovascular and renal benefits. Despite these established benefits, safety concerns remain an important clinical issue because adverse events may affect treatment persistence, patient acceptability, and clinical decision-making. This review evaluates a number of safety profiles of GLP-1RAs using clinical, mechanistic, and pharmacovigilance evidence, with attention to both common adverse events and emerging safety signals. A narrative review was conducted to evaluate the safety profile of GLP-1RAs in obesity and type 2 diabetes mellitus. PubMed/MEDLINE, Embase, and Web of Science were searched for studies published between January 2005 and April 2026. Evidence from randomised controlled trials, observational studies, meta-analyses, pharmacovigilance investigations, and regulatory safety reports was synthesised qualitatively. Findings from 60 studies and safety reports were included. Common adverse events were predominantly gastrointestinal, particularly nausea, vomiting, diarrhoea, and constipation, and represented the most consistently reported adverse effects and the principal cause of treatment discontinuation. Uncommon safety concerns included renal adverse events, which were reported infrequently and often occurred in clinical contexts involving gastrointestinal intolerance, volume depletion, or other predisposing factors. Gallbladder and biliary complications were also infrequent and appeared to be influenced by rapid weight loss and baseline patient risk factors. Acute pancreatitis remained rare in clinical trials, although severe cases have been reported in postmarketing settings. Human evidence did not demonstrate an increased risk of thyroid malignancy. Emerging safety signals, including early worsening of diabetic retinopathy, muscle mass reduction, psychiatric symptoms, and alopecia, were identified mainly through observational and pharmacovigilance evidence. GLP-1RA adverse events predominantly reflect predictable pharmacological and physiological effects rather than off-target toxicity. Safety profiles appear agent-specific, dose-dependent, and influenced by underlying mechanisms and patient characteristics. Risk-stratified prescribing should therefore align agent selection, dose escalation, and monitoring intensity with patient-specific vulnerabilities, particularly gastrointestinal tolerability, risk of renal dehydration, gallbladder history, retinopathy risk during rapid glycaemic improvement, and frailty or sarcopenia risk. Continued long-term surveillance and further evidence generation are needed to better define rare, delayed, and emerging safety signals and to optimise safe use across diverse clinical populations.","[""Journal Article"", ""Review""]","[""Tobaiqy M"", ""Alqutub ST""]",10.2147/DDDT.S622972,Tobaiqy M,"Drug design, development and therapy",1177-8881,,Drug Des Devel Ther,eng,Alqutub ST,"[""Humans"", ""Incretins"", ""Diabetes Mellitus, Type 2"", ""Glucagon-Like Peptide-1 Receptor Agonists"", ""Obesity"", ""Hypoglycemic Agents""]",622972,42544311,pmc-id: PMC13429114;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42544311/,"Adverse Events Associated with Incretin-Based Therapies: A Narrative Review on Mechanisms, Clinical Management, and Risk Mitigation",20,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Dear Editor, We read with interest the expert consensus by Seshadri et al. on imeglimin for the management of type 2 diabetes mellitus (T2DM). The article is timely and informative, particularly in view of the increasing complexity of diabetes management in India. The debate around the novel mechanism of imeglimin, which addresses both insulin resistance and mitochondrial dysfunction through mitochondrial routes, is well summarized and is in line with the increasing emphasis on preserving the function of the beta cell.1.","[""Journal Article"", ""Consensus Statement""]","[""Duraiswamy J"", ""Gawari NC"", ""Naik T"", ""Deshpande TA""]",10.59556/japi.74.1567,Duraiswamy J,The Journal of the Association of Physicians of India,0004-5772,7,J Assoc Physicians India,eng,Deshpande TA,"[""Humans"", ""Diabetes Mellitus, Type 2"", ""India"", ""Hypoglycemic Agents"", ""Insulin Resistance"", ""Consensus""]",94,42544002,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42544002/,Imeglimin in Type 2 Diabetes Mellitus: Expert Opinions and Consensus in Indian Context,74,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"One of the global epicenters of the diabetes mellitus pandemic is India. Over the past 40 years, there has been a sharp rise in the prevalence of diabetes mellitus in India due to rapid socioeconomic development, demographic shifts, and increasing susceptibility in the Indian population. Diabetes affects 74.2 million individuals in India, which places a significant strain on the country's economy and healthcare system. A patient's diet, lifestyle, medication, and glucose monitoring must all be customized for optimal diabetes control. The rates of glucose monitoring in India are abysmal. Most of the monitoring methods currently in use are based on single-point-in-time readings, which may not be totally indicative of the state of diabetes control. This presents problems. With advancements in technology, the new monitoring tool-continuous glucose monitoring (CGM)-provides visibility into the glycemic profile 24 × 7 with user-friendly reports that provide information much beyond glycated hemoglobin (HbA1c) and self-monitoring of blood glucose. This device also detects the time spent in range by the individual with diabetes. This review article discusses CGM in terms of its purposes, technologies, accuracy, clinical indications, benefits, and problems associated with it.","[""Journal Article"", ""Review""]","[""Kushwaha A"", ""Kodirekkala AN"", ""Saharawat A"", ""Jaiswal R""]",10.59556/japi.74.1615,Kushwaha A,The Journal of the Association of Physicians of India,0004-5772,7,J Assoc Physicians India,eng,Jaiswal R,"[""Humans"", ""Continuous Glucose Monitoring"", ""India"", ""Blood Glucose Self-Monitoring"", ""Diabetes Mellitus"", ""Blood Glucose"", ""Glycated Hemoglobin""]",70-72,42543995,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543995/,"Continuous Glucose Monitoring-Purposes, Benefits, and Problems: A Review of the Indian Scenario",74,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"India is witnessing a rapid rise in metabolic dysfunction-associated steatotic liver disease (MASLD), driven by the country's expanding population with obesity, type 2 diabetes (T2D), and other metabolic comorbidities. Despite this growing burden, structured liver disease screening is absent from routine noncommunicable disease (NCD) services at the primary care level. A majority of MASLD diagnoses in India occur only after progression to advanced fibrosis or cirrhosis, even among individuals regularly engaged with healthcare systems for diabetes or hypertension. Primary health centers (PHCs) and community health centers (CHCs) currently lack standardized protocols for liver risk stratification, leading to critical missed opportunities for early intervention. This article outlines a scalable, systems-integrated model for community-based liver care, piloted at the All India Institute of Medical Sciences (AIIMS), Rishikesh. The model incorporates noninvasive fibrosis scoring tools (FIB-4, APRI), selective deployment of nurse-led FibroScan services, maternal hepatitis B virus screening, lifestyle modification strategies, and digital follow-up systems-seamlessly embedded within existing maternal health and NCD platforms. Insights: A real-world vignette from an urban diabetes outreach program in Kolkata illustrates the diagnostic gap: a high-risk patient remained undiagnosed for MASLD despite multiple healthcare encounters. International experiences, such as the Gwent model in Wales, further reinforce the feasibility of decentralized hepatology through community triage, nurse-led services, and simplified biochemical tools. India stands at a pivotal moment in redefining hepatology as a preventive, public health-oriented discipline. By embedding liver screening within existing NCD frameworks, leveraging task-sharing, and mobilizing digital infrastructure and public-private partnerships, India can develop a replicable model for early MASLD detection and intervention. This community hepatology framework-if scaled nationally-has the potential to position India as a global leader in MASLD prevention for low- and middle-income countries.","[""Journal Article""]","[""Samajdar SS"", ""Bandyopadhyay S"", ""Joshi SR""]",10.59556/japi.74.1511,Samajdar SS,The Journal of the Association of Physicians of India,0004-5772,7,J Assoc Physicians India,eng,Joshi SR,"[""Humans"", ""India"", ""Fatty Liver"", ""Public Health"", ""Primary Health Care"", ""Community Health Services"", ""Diabetes Mellitus, Type 2"", ""Non-alcoholic Fatty Liver Disease""]",67-69,42543994,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543994/,From Clinic to Community: A Public Health Framework for Metabolic Dysfunction-associated Steatotic Liver Disease Prevention in India,74,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Diabetic retinopathy (DR) represents a frequent microvascular consequence of type 2 diabetes mellitus (T2DM). Both inflammatory activity and nutritional status influence its development. The hemoglobin-albumin-lymphocyte-platelet (HALP) index is a composite marker that reflects these factors and has been explored in several diseases. This study assessed its association with the occurrence and severity of DR. We carried out a cross-sectional analysis of 150 individuals with T2DM (equal male-female distribution, mean age 58.9 ± 10.9 years). Retinal changes were graded through fundus examination. Laboratory values for calculating the HALP index were obtained. Statistical analysis included t-tests, Mann-Whitney U tests, and receiver operating characteristic (ROC) curves. DR was found in 43.4% of patients, predominantly in the moderate stage. The mean HALP index was 34.3 ± 36.6. Differences in HALP values between the DR and non-DR groups were not statistically significant (p = 0.249), although lower scores tended to appear in DR. ROC analysis showed modest discriminatory power (AUC 0.555 for DR; 0.599 for moderate-severe DR). Hemoglobin was significantly higher among those with moderate-severe DR (p = 0.006). Although the HALP index did not independently predict DR, its downward trend in advanced stages suggests potential as part of a multifactorial risk assessment. Owing to its affordability and simplicity, the HALP index may complement existing tools for identifying patients at higher risk of vision-threatening DR.","[""Journal Article""]","[""Kumar V"", ""Gururaj K"", ""Modi P"", ""Kumar S"", ""Balivada A"", ""Raj A""]",10.59556/japi.74.1605,Kumar V,The Journal of the Association of Physicians of India,0004-5772,7,J Assoc Physicians India,eng,Raj A,"[""Humans"", ""Diabetic Retinopathy"", ""Female"", ""Male"", ""Diabetes Mellitus, Type 2"", ""Middle Aged"", ""Cross-Sectional Studies"", ""Platelet Count"", ""Hemoglobins"", ""Severity of Illness Index"", ""ROC Curve"", ""Aged"", ""Lymphocyte Count"", ""Biomarkers"", ""Serum Albumin""]",42-48,42543991,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543991/,Association of Hemoglobin-Albumin-Lymphocyte-Platelet Count (HALP) Score and Type 2 Diabetes Retinopathy,74,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Diabetes is a dynamic disease, an ever-evolving entity. In existence for centuries, the prevalence of diabetes has increased manifold over the past few decades.1 This evolution is associated with a change in classification, clinical features, comorbidities, complications, and clinical management strategies. These changes are what we describe as the Darwinization of diabetes. Charles Darwin was one of the most important scientists in human history. His research forms the basis of evolutionary biology. His hypothesis on natural selection, created along with Alfred Wallace, is accepted as the most important mechanism of evolution.2 A similar situation occurs with diabetes.","[""Journal Article"", ""Historical Article""]","[""Kalra S"", ""Vora A"", ""Tiwaskar M"", ""Raizada N"", ""Verma M"", ""Kapoor N""]",10.59556/japi.74.1562,Kalra S,The Journal of the Association of Physicians of India,0004-5772,7,J Assoc Physicians India,eng,Kapoor N,"[""Humans"", ""Diabetes Mellitus"", ""History, 19th Century"", ""Biological Evolution"", ""Selection, Genetic"", ""History, 20th Century""]",11-12,42543983,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543983/,The Darwinization of Diabetes,74,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Often referred to as the diabetes capital of the world, new-wave urbanization and westernization of lifestyle have rendered India vulnerable to the so-called lifestyle diseases, especially diabetes mellitus. Arguably the most characterized of diseases, diabetes somehow still has a few tricks up its sleeve. Diabetic striatopathy (DS), also known as hyperglycemic nonketotic hemichorea/hemiballism, chorea/hemichorea associated with nonketotic hyperglycemia, diabetic hemiballism/hemichorea, or chorea-hyperglycemia-basal ganglia syndrome, is a long-known disease of many names but sparse characterization. With an estimated prevalence of 1 in 100,000 (Ondo, 2011), DS is, in our opinion, greatly underestimated and is often misdiagnosed as intracerebral hemorrhage (ICH), which is a travesty given the excellent prognosis DS carries, even with just the control of blood sugar levels. Here, we describe the case of a 73-year-old male, previously undiagnosed diabetic, who presented with an acute-onset movement disorder, initially thought to have had a stroke, but was later diagnosed as DS. We also discuss in brief the pathophysiology and treatment options.","[""Journal Article"", ""Case Reports""]","[""Agrawal BK"", ""Singhal K"", ""Sharma NK"", ""Sharma AA""]",10.59556/japi.74.1392,Agrawal BK,The Journal of the Association of Physicians of India,0004-5772,6S,J Assoc Physicians India,eng,Sharma AA,"[""Humans"", ""Male"", ""Aged"", ""Hyperkinesis"", ""Diabetes Mellitus, Type 2"", ""Diagnosis, Differential"", ""Chorea"", ""Diabetes Complications"", ""Movement Disorders""]",32-33,42543967,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543967/,Index Presentation of Diabetes Mellitus as a Hyperkinetic Movement Disorder: A Thin-veiled Entity Colloquially called Diabetic Striatopathy,74,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Diabetic kidney disease (DKD) is becoming an increasingly common consequence of diabetes in India, where the number of affected individuals is rising at an alarming pace. The illness is often silent in its early stages, and many patients are diagnosed only when kidney damage is advanced, leading to high rates of kidney failure and cardiovascular complications. This consensus document was developed by a broad group of experts to provide practical, evidence-based recommendations tailored for Indian healthcare settings. It stresses the importance of timely screening using the urine albumin-to-creatinine ratio and estimated glomerular filtration rate, along with routine evaluation of cardiovascular risks. The guidance covers key management areas such as blood pressure and glycemic control, the use of renin-angiotensin system blockers, newer agents such as sodium-glucose cotransporter 2 inhibitors (SGLT2) inhibitors and finerenone, as well as lifestyle and dietary measures. Equal attention is given to affordability, patient education, and integrating care into national health programs. By adapting international standards to local realities, this document aims to improve early detection, reduce inequalities in treatment, and support better long-term outcomes for people living with DKD in India.","[""Journal Article"", ""Consensus Statement""]","[""Yadav K"", ""Jha V"", ""Abraham G"", ""Almeida AF"", ""Bansal S"", ""Bansal SB"", ""Bhowmik D"", ""Ghosh S"", ""Gopalakrishnan N"", ""Gulati S"", ""Joshi SR"", ""Kalra S"", ""Kesavadev J"", ""Kher V"", ""Khullar D"", ""Mahajan AU"", ""Mohan V"", ""Oomman A"", ""Parameswaran S"", ""Phadke U"", ""Ponde CK"", ""Prakash SR"", ""Prasad N"", ""Raju SB"", ""Ramachandran A"", ""Sahay M"", ""Sahay RK"", ""Sawhney J"", ""Sethi BK"", ""Sethi DS"", ""Shah P"", ""Sharma RK"", ""Singh S"", ""Sreedhara R"", ""Tiwaskar M"", ""Wangnoo SK""]",10.59556/japi.74.1537,Yadav K,The Journal of the Association of Physicians of India,0004-5772,7E,J Assoc Physicians India,eng,Wangnoo SK,"[""Humans"", ""Diabetic Nephropathies"", ""India"", ""Sodium-Glucose Transporter 2 Inhibitors""]",e24-e29,42543958,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543958/,Consensus Guidance for the Diagnosis and Management of Diabetic Kidney Disease: Executive Summary,74,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Fixed-dose combinations (FDCs), particularly sulfonylurea-based triple therapies, play a central role in managing type 2 diabetes in India. With growing focus on safety and personalization, lower-dose alternatives are gaining attention, especially for early-stage and vulnerable patients. To obtain expert consensus from Indian physicians on the clinical relevance, preferred patient profiles, and prescribing intent for a low-dose triple FDC comprising glimepiride 0.5 mg, metformin 500 mg sustained-release (SR), and voglibose 0.2 mg. A structured cross-sectional survey was conducted among 112 physicians from metro and nonmetro regions of India. The survey used close- and open-ended questions to explore the need, clinical positioning, and use scenarios for this low-dose triple combination. Responses were analyzed and synthesized into expert consensus per the Oxford Centre for Evidence-Based Medicine (OCEBM) framework (Level V evidence). Most physicians (86.6%) supported the need for this combination. Common use cases included early-stage diabetes, elderly patients, and those with postprandial hyperglycemia or hypoglycemia risk. It was also preferred for step-up therapy and deintensification with agents, such as SGLT2 inhibitors or insulin (77.7%). Advantages cited included improved safety, simplified dosing, and affordability. Expert consensus affirms this FDC's clinical relevance across multiple diabetes stages. Further real-world evidence and outcome-driven studies are warranted to support broader clinical integration and guideline inclusion.","[""Journal Article"", ""Consensus Statement""]","[""Kesavadev J"", ""Unnikrishnan AG"", ""Saboo B"", ""George J"", ""Kalra S"", ""Sen SS"", ""Gadia S"", ""Anthuvan T""]",10.59556/japi.74.1363,Kesavadev J,The Journal of the Association of Physicians of India,0004-5772,6E,J Assoc Physicians India,eng,Anthuvan T,"[""Humans"", ""Diabetes Mellitus, Type 2"", ""India"", ""Hypoglycemic Agents"", ""Sulfonylurea Compounds"", ""Cross-Sectional Studies"", ""Metformin"", ""Drug Combinations"", ""Consensus"", ""Practice Patterns, Physicians'"", ""Male""]",e42-e47,42543954,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543954/,Expert Consensus and Physician Perspectives on a Low-dose Triple Fixed-dose Combination for Type 2 Diabetes in India,74,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Time in range (TIR) is now widely adopted as a metric in diabetes management, offering a dynamic improvement over HbA1c alone. However, TIR does not capture the clinically relevant burden of glucose oscillations-rhythmic, intrarange fluctuations that independently drive oxidative stress, endothelial dysfunction, and inflammation, even when mean glucose remains well-controlled. We propose oscillatory burden as a measurable, actionable dimension of glycemic risk. This review synthesizes mechanistic and clinical evidence linking oscillations to vascular complications and outlines a conceptual oscillatory burden index (OBI) that combines amplitude and frequency metrics using continuous glucose monitoring (CGM) data. We reviewed studies published from 2002 to 2024 examining postprandial and intraday glucose dynamics, oxidative and inflammatory biomarkers, endothelial dysfunction, and real-world CGM applications. Intermittent glucose swings increase mitochondrial ROS generation, activate NF-κB, and impair nitric oxide availability-mechanisms confirmed by translational studies. Patients with comparable TIR (70-80%) but high oscillatory burden showed 2-3 times higher CRP and ICAM-1 levels compared to low-burden peers (p < 0.05). Practical strategies-precision meal timing, low-GI diets, gut microbiota modulation, and advanced CGM-driven insulin titration-can reduce oscillatory burden by up to 30%. Achieving TIR must not mask hidden glucose instability. Integrating oscillatory metrics into routine practice, supported by modern CGM analytics and patient-specific coaching, offers a new frontier for protecting vascular health in diabetes.","[""Journal Article"", ""Review""]","[""Patankar NM"", ""Sanghvi SJ""]",10.59556/japi.74.1501,Patankar NM,The Journal of the Association of Physicians of India,0004-5772,6E,J Assoc Physicians India,eng,Sanghvi SJ,"[""Humans"", ""Continuous Glucose Monitoring"", ""Blood Glucose"", ""Oxidative Stress"", ""Diabetes Mellitus"", ""Diabetic Angiopathies"", ""Postprandial Period""]",e39-e41,42543953,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543953/,Beyond Time in Range: Targeting Glucose Oscillations to Transform Vascular Outcomes in Diabetes,74,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Type 2 diabetes mellitus (T2DM) poses a significant health burden globally, with India accounting for a large proportion of cases. Beyond physical complications, diabetes distress (DD)-the emotional and psychological strain associated with diabetes management-is increasingly recognized as a critical factor affecting patient outcomes. However, data on the prevalence and determinants of DD in Western India remain limited. A cross-sectional study was conducted among 158 adult T2DM patients attending an outpatient clinic in Vadodara, Gujarat. DD was assessed using the validated Diabetes Distress Scale-17 (DDS-17). Demographic, clinical, and psychosocial variables were collected and analyzed using descriptive statistics, Chi-squared tests, t-tests, and logistic regression to identify factors associated with DD. The prevalence of DD was 70.2%, with 31.6% experiencing moderate distress and 38.6% experiencing high distress. Emotional burden was the most prevalent distress domain, followed by regimen-related, interpersonal, and physician-related distress. Factors significantly associated with lower DD included higher education, good family support, regular physical activity, and diabetes duration over 10 years. Conversely, poor glycemic control, insulin therapy, hypoglycemic episodes, and the presence of diabetic complications were linked to higher DD. DD is highly prevalent among T2DM patients in Western India and is influenced by both clinical and psychosocial factors. Incorporating routine psychosocial screening and patient-centered interventions into diabetes care is essential to address this underrecognized burden and improve overall disease management.","[""Journal Article""]","[""Mitra S"", ""Patel P"", ""Muley A"", ""Patel R"", ""Kella M"", ""Patel K""]",10.59556/japi.74.1506,Mitra S,The Journal of the Association of Physicians of India,0004-5772,6E,J Assoc Physicians India,eng,Patel K,"[""Humans"", ""Diabetes Mellitus, Type 2"", ""India"", ""Female"", ""Male"", ""Cross-Sectional Studies"", ""Prevalence"", ""Middle Aged"", ""Adult"", ""Stress, Psychological"", ""Aged"", ""Risk Factors""]",e25-e29,42543950,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543950/,Diabetes Distress: Identifying Prevalence and Associated Factors in Type 2 Diabetes Mellitus Patients in Western India,74,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual incretin therapies such as tirzepatide have transformed the management of type 2 diabetes mellitus and obesity, with expanding cardiometabolic indications and rapid market growth globally and in India. However, emerging postmarketing evidence has raised concerns regarding ocular safety. Pharmacovigilance analyses, cohort studies, and case reports suggest an association between GLP-1-based therapies and ophthalmic adverse events, including early worsening of diabetic retinopathy and, more concerningly, nonarteritic anterior ischemic optic neuropathy (NAION)-a potentially irreversible cause of sudden vision loss in adults over 50 years. Although the absolute risk appears very low, regulatory agencies, including the WHO and European Medicines Agency, now recognize NAION as a very rare adverse effect of semaglutide, and similar signals are being explored for other agents, suggesting a possible class effect. Proposed mechanisms include altered optic nerve head perfusion, sympathetic-mediated vasoconstriction, and rapid glycemic shifts affecting vascular autoregulation; however, causality remains unproven. In India, where over 100 million adults live with diabetes and obesity rates are rising, even rare adverse events may translate into substantial public health impact, particularly given limited access to ophthalmic care and increasing unsupervised drug use. We advocate a balanced approach: baseline ophthalmic evaluation in high-risk individuals, informed consent regarding visual symptoms, early referral for visual complaints, strengthened pharmacovigilance, and coordinated endocrinology-ophthalmology surveillance systems. As newer triple agonists approach clinical use, integrating ocular safety into prescribing frameworks is imperative. Metabolic gains must not come at the cost of preventable vision loss.","[""Journal Article"", ""Review""]","[""Saxena A"", ""Prakash A""]",10.59556/japi.74.1507,Saxena A,The Journal of the Association of Physicians of India,0004-5772,6,J Assoc Physicians India,eng,Prakash A,"[""Humans"", ""India"", ""Diabetes Mellitus, Type 2"", ""Hypoglycemic Agents"", ""Semaglutide"", ""Glucagon-Like Peptide-1 Receptor Agonists"", ""Glucagon-Like Peptides"", ""Optic Neuropathy, Ischemic"", ""Blindness"", ""Diabetic Retinopathy""]",94-96,42543940,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543940/,Glucagon Agonist Therapies and Vision Loss: Balancing Promise with Prudence in India,74,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Diabetes is associated with an increased risk of cognitive dysfunction. We are aimed at examining cognitive performance in people with Type 2 diabetes mellitus (T2DM) and their correlation with physical activity (PA)/fitness level and mood. A cross-sectional study involving 47 individuals with T2DM, 30 diabetes-free individuals (controls): ages of 40-65 years and without dementia. Subjects were evaluated using a neuropsychological test battery that included Stroop, VLMT, CORSI, TMT and neuropsychiatric scales. The Global Physical Activity Questionnaire (GPAQ) was assessed. Physical fitness was evaluated using a maximal cardiopulmonary exercise testing (CPX). Compared with controls, people with T2DM had lower cardiorespiratory fitness (CRF) and more frequent cognitive performance below 1 SD of the normative value. Those individuals with T2DM, who displayed low fitness, showed significantly poorer cognitive inhibition (Stroop, p < 0.001), processing speed (TMT-A, p < 0.001), cognitive flexibility (TMT-B, p < 0.001), visuospatial memory (CORSI, p < 0.001) and memory consolidation (VLMT, p < 0.001). Higher ventilatory and metabolic CRF markers and higher PA levels correlated significantly with higher cognitive performance. None of the neuropsychological or psychiatric background variables correlated significantly with any of the cognitive scales. Individual CRF markers and PA levels correlated positively with cognitive performance in people with T2DM and in nondiabetic individuals. However, individuals with T2DM showed at least two to three times more frequent cognitive performances more than 1 SD below norm as compared with controls. Among people with T2DM, those with low aerobic fitness/PA levels showed significantly lower cognitive performance, especially in the attention-concentration, executive functioning, episodic memory and visuospatial processing domains.","[""Journal Article""]","[""Rojas Vega S"", ""Solera-Herrera A"", ""Vafa R"", ""Acero-Moreno D"", ""Wahrmann V"", ""Scheef L""]",10.1155/jdr/1311227,Rojas Vega S,Journal of diabetes research,2314-6753,1,J Diabetes Res,eng,Scheef L,"[""Humans"", ""Diabetes Mellitus, Type 2"", ""Cardiorespiratory Fitness"", ""Middle Aged"", ""Cross-Sectional Studies"", ""Male"", ""Female"", ""Exercise"", ""Neuropsychological Tests"", ""Adult"", ""Aged"", ""Cognitive Dysfunction"", ""Cognition"", ""Exercise Test"", ""Processing Speed""]",e1311227,42543851,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42543851/,Type 2 Diabetes and Cognitive Dysfunction: Cardiorespiratory Fitness and Physical Activity Matters,2026,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Numerous clinical trials (CTs) and population pharmacokinetic (PK) models have been published on dapagliflozin, an approved SGLT2 inhibitor used to treat type 2 diabetes, heart failure, and chronic kidney disease. This study proposes a Bayesian workflow for the development of minimal physiologically-based PK models (mPBPK) that integrates all available PK information, to support uncertainty quantification and informed drug development. First, a systematic collection of published dapagliflozin PK data and models was performed. A mPBPK model was then developed, and posterior parameter distributions were obtained based on data from parallel-design CTs. Three Bayesian modeling packages: NIMBLE (v1.1.0), MCSim (v6.2.0), and Torsten (v0.89.0), and three alternative prior specifications were evaluated. Model validation was performed using PK data from crossover CTs and urinary recovery data, followed by sensitivity analysis. 18 studies reporting PK data and 10 reporting PK models were identified. Posterior distributions were comparable across programs: 95% credible intervals overlapped. Torsten showed superior sampling efficiency, as compared to NIMBLE and MCSim (5.7 and 10.0 times higher in tails and central posterior regions, respectively); however, the average effective sample size per hour was comparable for Torsten and MCSim. The predicted urinary recovery was 2.2%-4.4% (mean 3.2%), while the observed values were in the 0.8%-4.0% range (mean 2.0%). Glomerular filtration rate and fraction unbound were the main contributors to inter-trial variability in urinary recovery, while volume of distribution and clearance had the highest influence on maximum concentration and area-under-the-concentration curve, respectively. The proposed Bayesian workflow is flexible and transferable to other mechanistic model types.","[""Journal Article""]","[""Mikhailova A"", ""Peskov K"", ""Helmlinger G"", ""Sokolov V""]",10.1002/psp4.70307,Mikhailova A,CPT: pharmacometrics & systems pharmacology,2163-8306,8,CPT Pharmacometrics Syst Pharmacol,eng,Sokolov V,"[""Benzhydryl Compounds"", ""Bayes Theorem"", ""Glucosides"", ""Humans"", ""Models, Biological"", ""Sodium-Glucose Transporter 2 Inhibitors"", ""Workflow"", ""Diabetes Mellitus, Type 2""]",e70307,42543489,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42543489/,Bayesian Workflow for Minimal PBPK Models: Case Study of Dapagliflozin,15,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Using multiple statistical methods, this study investigated the core diagnostic information from the four diagnostic methods, the distribution patterns of syndrome elements, and their relationship with laboratory biochemical indicators in diabetic peripheral neuropathy(DPN). The aim is to deepen the understanding of the disease-symptom-syndrome relationship in DPN. A retrospective study was conducted on 1 420 inpatients diagnosed with DPN patients at the Department of Endocrinology, the First Affiliated Hospital of Anhui University of Chinese Medicine, from June 2014 and June 2023. Data mining techniques, including frequency statistics, association rule analysis, factor analysis, cluster analysis, and Bayesian network analysis, were applied to examine general patient information, TCM diagnostic data from the four diagnostic methods, and laboratory biochemical indicators. The core clinical manifestations in DPN patients were dry mouth, limb numbness, blurred vision, fatigue, thirst, and a thready pulse. Association rule analysis indicated Yin deficiency leading to blood stasis is the core pathogenesis. Factor analysis indicated that the disease location primarily involved the spleen, kidney, and liver, while main disease nature elements were Yin deficiency, Qi deficiency, and blood stasis, often complicated by concomitant phlegm turbidity, Yang deficiency, and essence depletion. Cluster analysis identified five syndrome patterns: Yin deficiency with blood stasis syndrome, Qi deficiency with blood stasis syndrome, Yang deficiency with cold aggregation syndrome, phlegm stasis obstructing collateral syndrome, and liver-kidney deficiency syndrome. Among these, Yin deficiency with blood stasis syndrome and Qi deficiency with blood stasis syndrome were the most prevalent. Bayesian network analysis revealed associations between abnormal fasting blood glucose(FBG) and symptoms such as chest tightness, palpitations, dizziness, insomnia, and constipation. Abnormal glycosylated hemoglobin(HbA1c) was associated with frequent urination, polyphagia, polydipsia, thirst and dry mouth. Abnormal total cholesterol(TC) was linked to emaciation, fear of cold and cold limbs, and a weak pulse. Abnormal serum creatinine(SCr) was associated with slow reaction, a wiry pulse, and limb pain. The distribution of TCM syndromes in DPN primarily involves Yin deficiency with blood stasis syndrome and Qi deficiency with blood stasis syndrome. The core pathogenesis is Yin deficiency leading to blood stasis, with the disease location in the spleen, kidney, and liver. The identified associations between FBG, HbA1c, TC, SCr and specific TCM syndromes provide an objective basis for the microscopic syndrome differentiation of DPN and its integrated diagnosis and treatment combining Chinese and western medicine.","[""English Abstract"", ""Journal Article""]","[""Li JJ"", ""Liu JX"", ""Guo JC"", ""Jiang AJ"", ""Fang ZH"", ""Shen GM"", ""Wen WB""]",10.19540/j.cnki.cjcmm.20260401.501,Li JJ,Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica,1001-5302,13,Zhongguo Zhong Yao Za Zhi,chi,Wen WB,"[""Humans"", ""Female"", ""Diabetic Neuropathies"", ""Male"", ""Medicine, Chinese Traditional"", ""Middle Aged"", ""Retrospective Studies"", ""Aged"", ""Adult"", ""Yin Deficiency"", ""Diagnosis, Differential"", ""Bayes Theorem"", ""Cluster Analysis""]",3899-3910,42543379,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543379/,[Distribution patterns and clinical characteristics of traditional Chinese medicine syndromes in diabetic peripheral neuropathy],51,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Diabetic macroangiopathy, a major chronic complication of diabetes, is characterized by atherosclerosis. Its pathological core involves the phenotype transformation of vascular smooth muscle cells(VSMCs) towards synthesis, aging, calcification, macrophage-like and fibroblast-like phenotypes. These phenotypic transformations jointly drive atherosclerotic plaque formation, vascular remodeling and calcification, leading to high-risk events such as myocardial infarction and stroke, which are important causes of disability and mortality in diabetic patients. Current conventional treatment provides insufficient long-term protection against macroangiopathy. In contrast, traditional Chinese medicine(TCM), through its holistic regulation via multi-component and multi-target mechanisms, has shown unique advantages in regulating VSMCs phenotype transformation. The progression of diabetic macroangiopathy mediated by VSMCs phenotypic transformation is characterized by deficiency in origin and excess in superficiality in TCM theory. Conceptualizing this phenotypic switching as &quot;phlegm turbidity and blood stasis obstructing the collaterals&quot;, therapeutic strategies should focus on resolving phlegm and turbidity, transforming stasis and unblocking collaterals, while simultaneously reinforcing healthy Qi and tonifying deficiencies. A growing body of research indicates that monomers such as matrine, baicalein, and tanshinone Ⅱ_A, as well as sour Chinese herbal medicines and compound formulas such as Huoluo Xiaoling Dan, can inhibit pathological VSMCs phenotype transformations, including abnormal proliferation, migration, aging, and calcification. These interventions align with the pathogenesis and therapeutic principles, thereby delaying the progression of vascular lesions. This review briefly outlined the pathological progression of diabetic macroangiopathy, elaborated on how VSMCs phenotype transformation mediated diabetic macroangiopathy, and summarized key studies on the intervention of TCM active compounds, monomers and formulas in diabetic macroangiopathy by regulating VSMCs phenotype transformation. It aims to provide new strategies for the prevention and treatment of diabetic macroangiopathy and ultimately enhance clinical diagnosis and treatment.","[""Journal Article"", ""Review"", ""English Abstract""]","[""Liu HY"", ""Zhang ZH"", ""Zhu YJ"", ""Li XL"", ""Wang XR"", ""Yang C"", ""Xie CG""]",10.19540/j.cnki.cjcmm.20260305.702,Liu HY,Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica,1001-5302,13,Zhongguo Zhong Yao Za Zhi,chi,Xie CG,"[""Humans"", ""Muscle, Smooth, Vascular"", ""Animals"", ""Drugs, Chinese Herbal"", ""Phenotype"", ""Diabetic Angiopathies"", ""Medicine, Chinese Traditional"", ""Myocytes, Smooth Muscle"", ""Disease Progression""]",3657-3665,42543355,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543355/,[Roles of vascular smooth muscle cells phenotype transformation in mediating progression of diabetic macroangiopathy and current status of traditional Chinese medicine treatment],51,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Renal metabolomics and molecular biology techniques were employed to investigate the interventional effect and underlying mechanism of Qingxin Lianzi Decoction(QXLZ) in rats with diabetic kidney disease(DKD). Sprague-Dawley rats were randomly assigned to the following groups: a blank group, a model group, a metformin(0.2 g·kg~(-1)) group, and QXLZ low-, medium-, and high-dose groups(10, 20, and 40 g·kg~(-1), respectively). The DKD model was established in all groups except the blank group by feeding with a high-fat diet combined with intraperitoneal injection of streptozotocin(STZ, 30 mg·kg~(-1)). After successful modeling, the rats received the corresponding treatments by oral gavage for six consecutive weeks. Upon completion of the intervention, random blood glucose levels were measured to assess the glucose-regulating capacity of QXLZ in DKD rats. Renal histopathological changes and fibrosis degree were evaluated by hematoxylin-eosin, Masson's trichrome, and periodic acid-Schiff staining. Renal function indicators(24-hour urinary total protein [24h-UTP], blood urea nitrogen [BUN], creatinine [Cr]) were measured by biochemical assays. The levels of blood glucose(glycated hemoglobin [GHb]), inflammatory markers(tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β]), and fibrosis markers(collagen type Ⅳ [Col Ⅳ], α-smooth muscle actin [α-SMA]) were detected by enzyme-linked immunosorbent assay. Immunofluorescence was used to determine the expression of TNF-α, IL-1β, α-SMA, and Col Ⅳ in renal tissues. Metabolomics was applied to identify differentially expressed metabolites in renal tissues. The results showed that compared with the blank group, the model group showed significant increases in several key indicators, including random blood glucose and GHb reflecting glucose metabolism, 24h-UTP, BUN, and Cr assessing renal function, as well as the inflammatory cytokines TNF-α and IL-1β and the fibrosis markers Col Ⅳ and α-SMA(P&lt;0.05). The renal histology also exhibited typical features of DKD. Compared with the model group, all intervention groups showed significant reductions in these indicators, along with decreased collagen deposition and inflammatory resolution. Metabolomic analysis revealed that the intervention of QXLZ in DKD was closely associated with the arachidonic acid metabolism pathway. In conclusion, QXLZ effectively regulates blood glucose, improves renal function, and ameliorates renal inflammation and fibrotic injury in DKD rats, and its mechanism may be related to the arachidonic acid metabolic pathway.","[""English Abstract"", ""Journal Article""]","[""Chen J"", ""Bai M"", ""Yu RS"", ""Liu Y"", ""Su X"", ""Zhu XD""]",10.19540/j.cnki.cjcmm.20260428.401,Chen J,Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica,1001-5302,12,Zhongguo Zhong Yao Za Zhi,chi,Zhu XD,"[""Animals"", ""Drugs, Chinese Herbal"", ""Diabetic Nephropathies"", ""Rats"", ""Rats, Sprague-Dawley"", ""Male"", ""Kidney"", ""Metabolomics"", ""Humans"", ""Tumor Necrosis Factor-alpha"", ""Blood Glucose""]",3581-3589,42543317,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543317/,[Therapeutic effect and mechanism of Qingxin Lianzi Decoction in ameliorating diabetic kidney disease based on renal metabolomics],51,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"This study aims to investigate the action mechanism and target molecules of the ultrafiltration membrane extract of Angelicae Sinensis Radix and Hedysari Radix in improving renal tissue injury in rats with diabetic kidney disease(DKD) from the perspective of mitochondrial function. Ten SPF-grade male Wistar rats were selected as the control group, while 40 rats were fed a high-fat and high-sugar diet for four weeks followed by a single intraperitoneal injection of streptozotocin(STZ) 35 mg·kg~(-1) to establish the DKD model. The successfully modeled rats were then randomly divided into four groups: the model group, the canagliflozin group, the Angelicae Sinensis Radix and Hedysari Radix aqueous decoction group, and the ultrafiltration membrane extract of Angelicae Sinensis Radix and Hedysari Radix group, with ten rats per group. All groups were administered via gavage for eight weeks. Renal function was assessed through 24 h urinary total protein(24-UTP) and biochemical parameters. HE staining, TUNEL staining, and transmission electron microscope were used to observe pathological morphological changes, apoptosis, and the status of intracellular organelles in cells. ELISA and Western blot were employed to measure adenosine triphosphate(ATP) content and the expression of mitochondrial function-related proteins, including optic atrophy 1(OPA1), mitofusin 2(Mfn2), dynamin-related protein 1(Drp1), ubiquitin-binding protein P62(P62), B-cell lymphoma/leukemia-2(Bcl-2), Bcl-2 interacting protein1(Beclin-1), and Bcl-2-associated X protein(Bax) in renal tissue. The results show that, compared to those in the control group, the rats in the model group exhibit a significant decrease in body weight(P&lt;0.01), along with elevated levels of blood glucose, 24-UTP, blood urea nitrogen(BUN), and serum creatinine(Scr)(P&lt;0.01). Renal tubular dilation, vacuolar changes in renal tissue cells, and a significant increase in apoptosis rate(P&lt;0.01) are observed, accompanied by mitochondrial swelling, cristae disappearance, and rupture. ATP levels in renal tissue are significantly reduced(P&lt;0.01), while the protein expressions of OPA1, Mfn2, Drp1, Beclin-1, and Bax are significantly increased(P&lt;0.05, P&lt;0.01). The expression levels of P62 and Bcl-2 are significantly decreased(P&lt;0.01). Compared to those in the model group, the rats in the ultrafiltration membrane extract group show an upward trend in body weight, with reductions in 24-UTP, BUN, and Scr levels(P&lt;0.01). Renal tubular dilation and glomerular cell vacuolation are alleviated, and the apoptosis rate of renal tissue cells is significantly reduced(P&lt;0.01). Mitochondria exhibit mild swelling but remain largely intact. ATP levels in renal tissue are significantly increased(P&lt;0.01), while the expressions of OPA1, Mfn2, Drp1, Beclin-1, and Bax are significantly decreased(P&lt;0.01). The expression of Bcl-2 is significantly increased(P&lt;0.01). In conclusion, ultrafiltration membrane extract of Angelicae Sinensis Radix and Hedysari Radix may attenuate renal tissue injury and delay disease progression in DKD rats by restoring mitochondrial dynamics, controlling mitochondrial fission-fusion balance, and improving mitochondrial function.","[""English Abstract"", ""Journal Article""]","[""Yang R"", ""Jia ZQ"", ""Wan SF"", ""Wei ZH"", ""Hu YM""]",10.19540/j.cnki.cjcmm.20260303.801,Yang R,Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica,1001-5302,12,Zhongguo Zhong Yao Za Zhi,chi,Hu YM,"[""Animals"", ""Male"", ""Rats"", ""Mitochondria"", ""Diabetic Nephropathies"", ""Drugs, Chinese Herbal"", ""Rats, Wistar"", ""Angelica sinensis"", ""Ultrafiltration"", ""Humans"", ""Kidney"", ""Apoptosis""]",3459-3467,42543305,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543305/,[Study on mechanism of ultrafiltration membrane extract of Angelicae Sinensis Radix and Hedysari Radix regulates mitochondrial function to ameliorate diabetic kidney disease],51,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Based on a strategy integrating topological feature identification and path priority assessment, this study systematically explored the efficacy targets and differentiated mechanisms of Colquhounia Root Tablets(CRT) in the &quot;homotherapy for heteropathy&quot; of rheumatoid arthritis(RA) and diabetic kidney disease(DKD). Firstly, candidate targets of CRT and disease-specific genes were retrieved by integrating multi-source databases and transcriptomic data. Protein-protein interaction(PPI) networks were constructed to identify key targets shared by or specific to RA and DKD via topological feature identification. Subsequently, a path priority assessment was introduced to calculate the average shortest path(ASP) values from drug targets to various pathological segments, thereby quantifying intervention efficacy to lock onto &quot;dominant pharmacodynamic links&quot;. The predicted key functional axes were validated through animal experiments. The results indicated that the core targets of CRT for both diseases involved shared pathways such as phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt), tumor necrosis factor(TNF), and glycolysis/gluconeogenesis. Notably, path priority assessment revealed distinct dominant intervention links: for RA, CRT preferentially targeted &quot;fibroblast-like synoviocyte(FLS) activation and invasion&quot;(ASP=2.361), which mapped to the TNF-p38 mitogen-activated protein kinase(p38)-LIM domain kinase 1(LIMK1)-Cofilin1 axis to regulate cytoskeleton remodeling; for DKD, the dominant link was &quot;filtration barrier injury and interstitial fibrosis&quot;(ASP=2.295), converging on the TNF-poly(ADP-ribose) polymerase 1(PARP1)-signal transducer and activator of transcription 1(STAT1)-matrix metallopeptidase 9(MMP9) axis to mediate cellular senescence and senescence-associated secretory phenotype(SASP) secretion. Animal experiments confirmed that CRT significantly alleviated RA synovial invasion and DKD renal fibrosis by inhibiting these two differentiated signaling axes, respectively. By employing topological feature identification and path priority assessment, this study elucidates the scientific connotation of &quot;homotherapy for heteropathy&quot; of RA and DKD with CRT through both shared network regulation and intervention in disease-specific differential signaling axes associated with pharmacodynamic links.","[""English Abstract"", ""Journal Article""]","[""Cai BB"", ""Mao X"", ""Ma ZC"", ""Xu MZ"", ""Lin Y"", ""Lin N"", ""Zhang YQ""]",10.19540/j.cnki.cjcmm.20260206.703,Cai BB,Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica,1001-5302,11,Zhongguo Zhong Yao Za Zhi,chi,Zhang YQ,"[""Animals"", ""Arthritis, Rheumatoid"", ""Diabetic Nephropathies"", ""Plant Roots"", ""Drugs, Chinese Herbal"", ""Humans"", ""Protein Interaction Maps"", ""Tablets""]",3284-3293,42543287,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543287/,"[Unveiling efficacy targets and differentiated mechanisms of Colquhounia Root Tablets in ""homotherapy for heteropathy"" of rheumatoid arthritis and diabetic kidney disease: a analysis based on topological feature identification and path priority assessment]",51,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Glycemic control is a critical component in the management of diabetes mellitus among children and adolescents. This narrative review synthesizes existing evidence on the status of glycemic control-both good and poor-and its associated factors among Ethiopian children and adolescents living with diabetes. The objective of the review was to assess the pattern of glycemic control and identify factors associated with both good and poor glycemic outcomes among children and adolescents with diabetes in Ethiopia. Relevant studies reporting on glycemic control and associated factors were identified through searches conducted in Google Scholar, PubMed/MEDLINE, African Journals Online, and the Ethiopian Medical Journal. Additional grey literature sources were also reviewed. Eligible studies were screened and narratively synthesized. The prevalence of poor glycemic control among Ethiopian children and adolescents ranged from 39.3% to 89.3%. Conversely, good glycemic control was reported in 16.4% to 60.7% of participants. Factors associated with glycemic control included socio-demographic characteristics, treatment-related variables, health system constraints, and dietary habits. Poor glycemic control is widespread among Ethiopian children and adolescents with diabetes, underscoring the urgent need for improved management strategies and targeted interventions. Strengthening diabetes education, promoting self-monitoring of blood glucose, and improving access to essential medical supplies and insulin may help enhance glycemic outcomes.","[""Journal Article"", ""Review""]","[""Leake Y"", ""Hagos HH"", ""Reta BK""]",10.11604/pamj.2026.54.5.50512,Leake Y,The Pan African medical journal,1937-8688,,Pan Afr Med J,eng,Reta BK,"[""Humans"", ""Ethiopia"", ""Adolescent"", ""Glycemic Control"", ""Diabetes Mellitus, Type 1"", ""Blood Glucose"", ""Child"", ""Hypoglycemic Agents"", ""Insulin"", ""Blood Glucose Self-Monitoring"", ""Prevalence""]",5,42542856,pmc-id: PMC13428645;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42542856/,Glycemic control and its associated factors among children and adolescents with type 1 diabetes in Ethiopia: a narrative review,54,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Type 1 diabetes mellitus (T1DM) is frequently associated with other autoimmune disorders, particularly autoimmune thyroid disease (AITD) and celiac disease. Guidelines recommend screening for thyroid and celiac disease in T1DM patients. Nevertheless, in case of their positivity, indicating the presence of an autoimmune polyendocrine syndrome (APS), there is a lack of guidance on how to proceed. Should we screen these patients for other autoimmune diseases? This study's aim was to evaluate the prevalence of additional autoimmune conditions in a cohort of T1DM patients with AITD and/or celiac disease. This cross-sectional study includes adult T1DM patients identified through electronic medical records. Patients with concomitant AITD or celiac disease were invited to undergo an extended screening workup for autoimmune disorders. 639 T1DM patients were identified, and 198 (31%) met the clinical criteria for APS (T1DM plus AITD and/or celiac disease), but only 17 (8.6%) had a formal APS diagnosis in their records. After the extended screening in 139/198 patients, 39% exhibited previously unknown autoantibody positivity, and 11.5% had new autoimmune diseases. Overall, among the patients who underwent the extended screening, 32% (44/139) were diagnosed with at least three autoimmune diseases. Our study shows that APS is often under-recognized and rarely formally documented in patients with T1DM. In addition, 32% of T1DM patients with AITD or celiac disease have at least a third autoimmune disease. These findings highlight that the identification of AITD or celiac disease in T1DM marks only one stage of the diagnostic journey. APS recognition should lead to a formal diagnosis and ensure heightened clinical vigilance with tailored evaluation of further autoimmune comorbidities during lifelong patient follow-up.","[""Journal Article""]","[""Velardi V"", ""Sanson L"", ""Toffoli B"", ""Favaro F"", ""Fischetti F"", ""Fabris B"", ""Candido R"", ""Bernardi S""]",10.1007/s12020-026-04716-2,Velardi V,Endocrine,1355-008X,1,Endocrine,eng,Bernardi S,"[""Humans"", ""Polyendocrinopathies, Autoimmune"", ""Female"", ""Diabetes Mellitus, Type 1"", ""Cross-Sectional Studies"", ""Male"", ""Adult"", ""Celiac Disease"", ""Middle Aged"", ""Thyroiditis, Autoimmune"", ""Mass Screening"", ""Prevalence"", ""Autoantibodies"", ""Young Adult""]",,42541639,pmc-id: PMC13428756;,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42541639/,Under-recognition of autoimmune polyendocrine syndromes in T1DM: results from an extended screening workup,91,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder requiring multi-target therapeutic strategies. Traditional Chinese medicine offers potential multi-component interventions, yet the material basis and molecular mechanisms of novel formulations often remain incompletely defined. This study developed an integrated formula (FSV) combining a modified Baihu Jia Renshen Decoction with Sanghuangporus vaninii extract and explored its anti-hyperglycemic potential using chemical profiling, network pharmacology, in vitro α-glucosidase inhibition, and an STZ/HSHFD-induced hyperglycemic mouse model. A total of 2,413 database-matched features were annotated, most of which should be regarded as putative rather than standard-confirmed identifications. Mangiferin and several flavonoids were retained as plant/fungus-compatible candidate constituents, whereas implausible xenobiotic matches were excluded from biological interpretation. Network pharmacology predicted the involvement of inflammation- and insulin-resistance-related targets, including TNF, AKT1, IL6, NFKB1, and MAPK3 (also known as ERK1), whereas ALB was treated as a high-connectivity carrier protein rather than a direct druggable mediator. FSV inhibited α-glucosidase in vitro and was associated with improvements in hyperglycemia, insulin-sensitivity indices, dyslipidemia, and tissue morphology in the mouse model. These phenotypic findings are presented as experimental support accompanying the pathway predictions, while direct pathway validation is left for future mechanistic studies. Overall, the results provide a preliminary basis for further chemical validation and mechanistic investigation of FSV in diabetes-related metabolic dysfunction.","[""Journal Article""]","[""Zhang J"", ""Chen Y"", ""Lin Y"", ""Huang Z"", ""Ge X"", ""Liu B"", ""Huang Z""]",10.1007/s10735-026-10921-0,Zhang J,Journal of molecular histology,1567-2379,4,J Mol Histol,eng,Huang Z,"[""Animals"", ""Mice"", ""Network Pharmacology"", ""Drugs, Chinese Herbal"", ""Hypoglycemic Agents"", ""Tandem Mass Spectrometry"", ""Male"", ""Chromatography, High Pressure Liquid"", ""Diabetes Mellitus, Experimental"", ""Plant Extracts"", ""Blood Glucose"", ""Glycoside Hydrolase Inhibitors"", ""alpha-Glucosidases""]",,42541619,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42541619/,Integrated UPLC-MS/MS profiling and network pharmacology-based analysis of the anti-hyperglycemic potential of Baihu Jia Renshen Decoction combined with Sanghuangporus vaninii extract in mice,57,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Research on whether maternal diabetes and hypertension prior to conception influence their children's health is limited. In Ontario, Canada, ICES is an independent research institute that securely houses population-based administrative health data, including diagnostic information, for individuals covered under the province's universal health insurance program. To determine whether maternal preconception diabetes and hypertension were associated with child age- and sex- standardized body mass index (zBMI). This longitudinal cohort study included children 0 to 12 years enrolled in the TARGet Kids! primary care practice-based cohort (www.targetkids.ca) in Ontario, Canada (2008-2021). Maternal diagnoses of diabetes and hypertension prior to conception were identified through provincial administrative datasets held at ICES, deterministically linked to TARGet Kids! data using individual health insurance numbers. Child zBMI was derived from directly measured height and weight and electronic medical records. Linear mixed effects models were used to assess associations adjusting for confounders. Among 7,351 mothers (mean age at delivery 33 years), 308 (4.6%) had preconception diabetes (2.1%) or hypertension (2.9%). Children (n = 9,087; mean age 4.6 years; 48.4%female) contributed to 28,861 zBMI measures. Maternal preconception hypertension was associated with higher mean child zBMI. The adjusted estimated difference for children of mothers with preconception hypertension with the average duration of hypertension prior to conception was 0.29 units higher in zBMI (95%CI: 0.03;0.55) compared with children of mothers without hypertension. The association between preconception hypertension and higher child zBMI may indicate a potential maternal health target for the prevention of child overweight and obesity.","[""Journal Article""]","[""Li X"", ""Chomka L"", ""Keown-Stoneman C"", ""Allen C"", ""Anderson L"", ""Ara Begum E"", ""D'Annunzio D"", ""Thadani S"", ""Maguire J"", ""Birken C""]",10.23889/ijpds.v11i5.3570,Li X,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Birken C,"[""Humans"", ""Female"", ""Longitudinal Studies"", ""Ontario"", ""Child"", ""Hypertension"", ""Child, Preschool"", ""Pregnancy"", ""Body Mass Index"", ""Adult"", ""Infant"", ""Child Development"", ""Male"", ""Infant, Newborn"", ""Diabetes Mellitus"", ""Pregnancy in Diabetics""]",3570,42541047,pmc-id: PMC13426783;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42541047/,"Using Linked Administrative Health Data to Examine Maternal Preconception Diabetes and Hypertension and Child Growth in Ontario, Canada: A Longitudinal Cohort Study",11,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Understanding the longer-term health impacts of SARS-CoV-2 infection is essential for informing public health policy. While earlier studies suggested increased diabetes risk after infection, evidence for the Omicron period and the modifying effect of vaccination remains limited and inconsistent. A matched cohort study was conducted using a large-scale linked asset covering over 90% of the Australian population, integrating COVID-19 notifications with demographic information and administrative health records. Individuals aged ≥16 years diagnosed with COVID-19 between 15 December 2021 and 31 December 2022 were matched 1:1 to those without COVID-19 by age, sex, and COVID-19 vaccine recency. Cox-models were used to estimate the association between COVID-19 and initiation of diabetes treatment, adjusting for relevant demographic and health-related factors. Negative control outcomes were assessed. Among 5,736,501 matched pairs followed for a median of 200 days, 45,816 initiated diabetes treatment. Compared to those without COVID-19, individuals with COVID-19 had a 14% higher risk of subsequently initiating diabetes treatment (aHR 1.14 [95%CI 1.12; 1.17]), with the highest risk observed among those hospitalised due to COVID-19 (aHR 2.52 [95%CI 2.23; 2.84]). The risk was also higher for individuals with ≤2 COVID-19 vaccine doses compared to those boosted within the last 90 days (aHR of 1.22 [95%CI 1.18; 1.25] vs 1.08 [95%CI 1.04; 1.12]). We found an increased risk of diabetes following SARS-CoV-2 infection during the Omicron dominant period and a protective effect of COVID-19 vaccination. However, the findings should be interpreted with caution considering the potential for unmeasured confounding.","[""Journal Article""]","[""Qian J"", ""Stepien S"", ""Cheng A"", ""Newall A"", ""Wood J"", ""Rowe S"", ""Thompson K"", ""O'Donnell B"", ""Dore G"", ""Macartney K""]",10.23889/ijpds.v11i5.3492,Qian J,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Macartney K,"[""Humans"", ""COVID-19"", ""Female"", ""Adult"", ""Diabetes Mellitus"", ""Cohort Studies"", ""Male"", ""Australia"", ""Middle Aged"", ""Aged"", ""SARS-CoV-2"", ""Risk Factors"", ""Adolescent"", ""Young Adult"", ""COVID-19 Vaccines"", ""Proportional Hazards Models""]",3492,42540994,pmc-id: PMC13426669;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540994/,New-onset diabetes following SARS-CoV-2 Omicron infection: a matched cohort study,11,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"To develop and evaluate a Transformer-based temporal representation learning framework for predicting incident diabetes using longitudinal laboratory data, and to compare its performance with state-of-the-art pretrained models and traditional machine-learning baselines. We deterministically linked a cardiac registry cohort (2015-2019) in Alberta, Canada, and retrieved three years of laboratory tests preceding each patient's diabetes diagnosis. Each laboratory event was modelled as a triplet consisting of test type, test value, and time gap with the previous test, to preserve temporal structure. Our Transformer architecture learned contextual embeddings that capture both intra-test dynamics and inter-test interactions, indicating the onset of diabetes. Performance was benchmarked against two pretrained Transformer models (Moment, PatchTST) and an XGBoost baseline trained on aggregated test summaries (mean, standard deviation, minimum, maximum). The final cohort included 30,462 patients and 19 laboratory test types relevant to diabetes. The proposed method achieved the highest predictive accuracy (AUC = 0.92), outperforming Moment (0.80), PatchTST (0.74), and XGBoost (0.88). It also demonstrated superior sensitivity (0.70) and positive predictive value (0.777) while maintaining high specificity (0.938) and negative predictive value (0.911). Conclusion: Modelling raw laboratory trajectories with a dedicated temporal Transformer substantially improves diabetes prediction compared with both pretrained sequence models and aggregation-based baselines. This framework provides a generalizable pathway for leveraging routine laboratory data in early disease detection. It highlights the clinical value of sequence-level modelling and supports the integration of temporal representation learning into population-level surveillance and decision-support systems.","[""Journal Article""]","[""Pan J"", ""Lee S"", ""Virani A"", ""Riazi K"", ""Martin E"", ""Leung A"", ""Quan H"", ""Li N""]",10.23889/ijpds.v11i5.3567,Pan J,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Li N,"[""Humans"", ""Diabetes Mellitus"", ""Electronic Health Records"", ""Longitudinal Studies"", ""Predictive Learning Models"", ""Alberta"", ""Boosting Machine Learning Algorithms"", ""Registries"", ""Prediction Algorithms""]",3567,42540952,pmc-id: PMC13426693;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540952/,Temporal Signals of Disease: A Transformer Approach for Predicting Diabetes from Longitudinal EHRs,11,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Diabetes is one of the most common chronic diseases in the Netherlands: approximately 1.2 million people have diabetes, of which 1.1 million have type 2 diabetes. Type 2 diabetes is strongly related to lifestyle factors (e.g. unhealthy eating habits, being overweight and smoking), but also to ageing and it has a genetic component. An individual's social environment may influence their lifestyle (choices), and subsequently their chance of having diabetes. This study examines the relationship between an individual's social environment and diabetes with administrative data from the Person Network of Statistics Netherlands. The Person Network includes five types of relationships (so-called network layers) of each inhabitant of the Netherlands in 2022: household members, (extended) family members, colleagues, neighbours and classmates. Individuals' diabetes status was based on whether they were prescribed diabetes medication in 2022. An ""exposure score"" was calculated for each individual indicating to what extent diabetes was present in their (local) network. The exposure score was decomposed to assess the distinct contribution of each network layer to the overall score. The population was limited to individuals aged 40+ years as the prevalence of type 2 diabetes increases rapidly after age 40. Exposure to diabetes was higher for individuals with diabetes than those without. Both before and after adjusting for individual background factors (e.g. age, gender, origin, income, social economic category, household composition, urbanity of the neighbourhood), individuals who had relatively more network members with diabetes were more likely to have diabetes themselves than those with fewer network members with diabetes.","[""Journal Article""]","[""van Hedel K"", ""de Jonge E"", ""van der Laan J"", ""Das M""]",10.23889/ijpds.v11i5.3497,van Hedel K,International journal of population data science,2399-4908,5,Int J Popul Data Sci,eng,Das M,"[""Humans"", ""Netherlands"", ""Diabetes Mellitus, Type 2"", ""Female"", ""Middle Aged"", ""Adult"", ""Male"", ""Life Style"", ""Aged"", ""Social Environment"", ""Socioeconomic Factors""]",3497,42540905,pmc-id: PMC13426636;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42540905/,Exposure to diabetes and own diabetes status using a whole population network of the Netherlands,11,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Diabetes is a chronic metabolic disease characterised by high glucose levels and altered carbohydrate and lipid metabolism, affecting an increasing number of people worldwide. Spain ranks fifth among European countries with the highest incidence of diabetes. Hyperglycaemia causes damage to numerous cell types, including keratinocytes and fibroblasts in the skin. Dermatological manifestations appear in more than 30% of cases of diabetes at the onset of the disease and in up to 100% during the course of the disease. This makes skin examination of patients particularly important, as early treatment of diabetes can slow the progression of the disease and improve its prognosis. In addition, some dermatological changes may alert us to suboptimal metabolic control of previously known diabetes. Some lesions are associated with insulin resistance, others are due to fungal or bacterial infections, there are also alterations due to diabetes itself or to chronic complications of diabetes; finally, there are lesions due to pharmacological treatment of the disease and to devices such as insulin infusion pumps and sensors for interstitial glucose measurement. Knowing and recognising dermatological changes is therefore essential in our daily work, because they guide us towards a better management of the disease and its causes.","[""Journal Article"", ""Review""]","[""Casado-Hoces SV"", ""González-Tejedor D"", ""Martín-Velasco R""]",10.18176/resp.00126,Casado-Hoces SV,Revista espanola de sanidad penitenciaria,1575-0620,2,Rev Esp Sanid Penit,eng,Martín-Velasco R,"[""Humans"", ""Diabetes Complications"", ""Skin Diseases"", ""Diabetes Mellitus"", ""Insulin Resistance""]",67-75,42540556,pmc-id: PMC13426110;,2026 May-Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42540556/,Dermatological lesions in diabetes,28,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Immune checkpoint inhibitors-induced diabetes mellitus (ICI-DM) is a rare but potentially life-threatening endocrine immune-related adverse event, often characterized by abrupt onset of insulin deficiency and frequent presentation with diabetic ketoacidosis and difficulty with daily management with the available therapies. Lung cancer patients represent a substantial proportion of reported cases, reflecting the widespread use of PD-1/PD-L1 inhibitors in thoracic oncology. We report on the case of an elderly patient with metastatic lung adenocarcinoma treated with pembrolizumab who developed severe DM requiring permanent insulin therapy and leading to treatment discontinuation. The patient was subsequently followed over a prolonged period, during which oncological disease remained under sustained control despite immunotherapy interruption. We describe the clinical course, diagnostic workup, and multidisciplinary management, and review current guideline recommendations addressing acute metabolic management, diabetic treatment, and decision-making regarding continuation of immunotherapy. This case highlights the complexity of managing ICI-DM in real-world clinical practice. The current guidelines may help in broad terms. Although guidelines have been published, they remain cursory. Nevertheless, therapeutic decisions should ultimately be individualized through close multidisciplinary collaboration.","[""Case Reports"", ""Journal Article""]","[""Nova D"", ""Pagliari GG"", ""Mambrito S"", ""Cortinovis DL"", ""Canova S""]",10.3389/fimmu.2026.1874841,Nova D,Frontiers in immunology,1664-3224,,Front Immunol,eng,Canova S,"[""Humans"", ""Immune Checkpoint Inhibitors"", ""Lung Neoplasms"", ""Carcinoma, Non-Small-Cell Lung"", ""Antibodies, Monoclonal, Humanized"", ""Diabetes Mellitus"", ""Male"", ""Insulin"", ""Neoplasm Metastasis"", ""Aged""]",1874841,42539567,pmc-id: PMC13423843;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42539567/,Immune checkpoint inhibitor-induced diabetes mellitus in metastatic NSCLC: a case report with extended follow-up and management considerations,17,9lRAwP1dogJpvKfy0,FC5EFQkqYJAwdCVtI
"Persistent pain affects approximately one in five children and adolescents globally and is associated with school absenteeism, reduced academic engagement, psychosocial distress, and long-term health consequences. Schools are important settings for developing health beliefs and self-management behaviors, yet educators receive little formal preparation about pain. This Practitioner's Perspective describes integration of a brief contemporary pain neuroscience education (CPNE) module into an undergraduate teacher preparation course. Two interactive sessions delivered by a physical therapist introduced pain as a protective nervous system output influenced by biological, psychological, and social factors. Participants demonstrated improved pain knowledge and beliefs, increased confidence discussing pain-related concepts, and greater appreciation for the relevance of pain literacy to educational practice. Pain literacy may improve educator responses to student pain, reduce stigma, support appropriate participation, and promote equitable school environments. Physical therapists may be well positioned to collaborate with teachers, school nurses, counselors, coaches, and other school-based professionals. Teacher preparation programs may represent an upstream opportunity to improve pain literacy, support student health and learning, and contribute to the prevention of persistent pain.","[""Journal Article""]","[""Curfman SE"", ""Best WJ"", ""Harrison DA"", ""Austin GP"", ""Finch DC""]",10.1111/josh.70212,Curfman SE,The Journal of school health,0022-4391,8,J Sch Health,eng,Finch DC,"[""Humans"", ""Neurosciences"", ""Health Literacy"", ""School Teachers"", ""Health Knowledge, Attitudes, Practice"", ""Teacher Training"", ""Chronic Pain"", ""Pain Management"", ""Curriculum"", ""School Health Services""]",e70212,42538134,pmc-id: PMC13427623;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42538134/,Improving Pain Literacy Among Future Educators: Contemporary Pain Neuroscience Education in Teacher Preparation,96,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Neurotechnologies are transforming how we measure, interpret, and modulate brain-body interactions, integrating real-time sensing, computation, and stimulation to enable precise physiological control. They hold transformative potential across clinical and nonclinical domains, from treating disorders to enhancing cognition and performance. Realizing this potential requires navigating complex, interdisciplinary challenges spanning neuroscience, materials science, engineering, signal processing, and regulatory and ethical frameworks. This Perspective presents a strategic roadmap for neurotechnology development, created by early-career researchers at the intersection of disciplines. We identify five cross-cutting trade-offs that shape the development and translation of neurotechnology: material functionality versus long-term stability, innovative development versus scalable manufacturing, spatiotemporal resolution versus real-time capability, multiscale multimodal integration versus system adaptability, and technological complexity versus clinical or commercial translatability. Rather than a domain-specific review, we focus on shared challenges and strategic opportunities that transcend disciplines, propose a unified framework for collaborative innovation and education, highlight ethical and regulatory priorities, and outline a timeline for overcoming key bottlenecks.","[""Journal Article"", ""Review""]","[""Serrano RR"", ""Troughton JG"", ""Mirkhani N"", ""Martínez N"", ""Mariello M"", ""Tsigarides J"", ""Williamson S"", ""Sapriza J"", ""Susnoschi Luca I"", ""Dominguez-Alfaro A"", ""Cuttaz E"", ""Thompson N"", ""Swedick S"", ""Almulla L"", ""Güemes A""]",10.1126/sciadv.aee8595,Serrano RR,Science advances,2375-2548,31,Sci Adv,eng,Güemes A,"[""Humans"", ""Neurosciences"", ""Translational Research, Biomedical""]",eaee8595,42536721,pmc-id: PMC13426423;,2026 Jul 31,2026,https://pubmed.ncbi.nlm.nih.gov/42536721/,From trade-offs to translation: An interdisciplinary roadmap for neurotechnology,12,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Helen Willsey is an Associate Professor at the Weill Institute for Neuroscience at the University of California, San Francisco (UCSF), USA. Helen's group uses frog models to dissect how risk genes contribute to psychiatric disorders. We spoke to Helen to learn more about her career trajectory, the importance of mentorship and the value of maintaining a full life both in and out of the lab.","[""Interview"", ""Historical Article""]",[],10.1242/dev.205924,,"Development (Cambridge, England)",0950-1991,15,Development,eng,,"[""Animals"", ""History, 21st Century"", ""History, 20th Century"", ""Humans"", ""Neurosciences"", ""Developmental Biology"", ""Mentors""]",,42529859,,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42529859/,Transitions in development - an interview with Helen Willsey,153,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"The nervous system is now recognized as an enabling hallmark of cancer biology. Neural inputs drive tumor growth in both central nervous system tumors and extracranial tumors through different mechanisms, including synaptic signaling, adrenergic regulation, perineural invasion, neuropeptides, immune remodeling, and bioelectric mechanisms. These insights have facilitated repurposing of neuroactive agents that are now in clinical trials as adjuncts to standard cancer therapy. The central translational challenge now is how to match the right neural circuit to the right patient and to pair appropriate neuromodulators with immunotherapy in combinations designed to restore, rather than merely supplement, antitumor immunity.","[""Journal Article"", ""Review""]","[""Pasvolsky L"", ""Jones GH"", ""Vu Y"", ""Winkler F"", ""Amit M""]",10.1126/scitranslmed.aeh1718,Pasvolsky L,Science translational medicine,1946-6234,860,Sci Transl Med,eng,Amit M,"[""Humans"", ""Neoplasms"", ""Animals"", ""Neurosciences""]",eaeh1718,42525788,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42525788/,Cancer neuroscience: Mechanisms to medicine,18,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Nervous system activity drives both normal neurodevelopment and childhood brain cancers through paracrine and synaptic signaling. In childhood gliomas, cancer cells integrate structurally and electrically into neural networks, and neuron-cancer interactions are strongly growth-promoting. Understanding the neuroscience mechanisms regulating childhood brain cancers opens a previously unexplored avenue for much-needed therapeutic interventions.","[""Journal Article"", ""Review""]","[""Monje M""]",10.1126/scitranslmed.aeg9138,Monje M,Science translational medicine,1946-6234,860,Sci Transl Med,eng,Monje M,"[""Humans"", ""Brain Neoplasms"", ""Neurosciences"", ""Child"", ""Animals"", ""Neurodevelopment"", ""Glioma"", ""Neurons""]",eaeg9138,42525784,,2026 Jul 29,2026,https://pubmed.ncbi.nlm.nih.gov/42525784/,The neuroscience of childhood brain cancers,18,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Alvinocaridid shrimps colonize hydrothermal vent fields along the Mid-Atlantic Ridge (MAR), where they experience extreme environmental conditions including high hydrostatic pressure, steep thermal and chemical gradients, and dim light. While various aspects of the biology of the dominant vent shrimp Rimicaris exoculata, such as general anatomy, microhabitat, symbiotic relationships, or trophic networks, have been extensively studied, little is known about how brain organization varies among alvinocaridid species occupying different ecological niches. Here, we investigated whether vent shrimps share common neuroanatomical features and whether differences in brain and vascular organization reflect ecological diversification among species. Using histology, immunohistochemistry, µCT scans, and 3D reconstruction, we compared the brain and the neurovascular system (cor frontale) in four MAR species with distinct ecologies (R. exoculata, Rimicaris chacei, Mirocaris fortunata, Alvinocaris markensis) and in the coastal relative Palaemon elegans. Our results reveal strong commonalities in brain organization among vent shrimps. All MAR species display a compact brain architecture with hypertrophied mushroom bodies (MBs), suggesting enhanced multisensory integration and memory capacities. Corresponding to the low-light environment, the visual neuropils (lamina, medulla, lobula) are smaller than those of the coastal species P. elegans. In all species living near hydrothermal vents, the retina exhibits modifications; it extends along the dorsal part of the cephalothorax, and its length varies according to the species, being the longest in the genus Rimicaris. The lobula satellite neuropil is absent in all alvinocaridids, suggesting a limited capacity to track moving visual signals. The olfactory lobes exhibit a common glomerular organization but differ among species in quantitative parameters, such as volume and number of glomeruli. The neurovascular system shows marked interspecific variation; the cor frontale differs in size and volume among hydrothermal vent species but retains a conserved subdivision of central arteries surrounding a longitudinal muscle bundle. We conclude that the observed variations in the volume of neuropils and arrangement of the vascular system likely reflect the ecological divergence related to microhabitat conditions and trophic strategies near hydrothermal emissions.","[""Journal Article"", ""Comparative Study""]","[""Mathou A"", ""Machon J"", ""Meth R"", ""Zbinden M"", ""Ravaux J"", ""Harzsch S""]",10.1002/cne.70190,Mathou A,The Journal of comparative neurology,0021-9967,8,J Comp Neurol,eng,Harzsch S,"[""Animals"", ""Brain"", ""Decapoda"", ""Species Specificity"", ""Hydrothermal Vents"", ""Ecosystem"", ""Neuroanatomy""]",e70190,42522123,pmc-id: PMC13415758;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42522123/,Comparative Neuroanatomy of Hydrothermal Vent Shrimps: Ecological Differentiation Among Four Alvinocaridid Species,534,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Pain neuroscience education is recognized as a core component of multidisciplinary chronic pain management. Although meta-analyses report small to medium clinical benefits across a range of chronic pain conditions and delivery settings, further evidence is needed to support implementation. To evaluate changes in knowledge of pain neurophysiology and patient perceptions following participation in a single-session, multidisciplinary ""Introduction to Pain Management"" (IPM) program delivered within a tertiary pain service. This quality improvement study examined outcomes from patients attending one of 16 IPM sessions delivered between February and December 2025. Participants completed the Revised Neurophysiology of Pain Questionnaire (R-NPQ) immediately before and after the program. Rasch analysis was conducted to generate person estimates, and pre-post changes were analyzed using the paired-sample t-test. A post-program survey assessed perceived relevance, clarity, and intended use of self-management strategies. Of the 172 patients who attended the program, paired Rasch person estimates were available for 158 patients following exclusion of those with extreme Rasch scores. Participation in the IPM program was associated with a statistically significant increase in knowledge of pain neurophysiology (p < 0.001), with a moderate-to-large effect size (d = 0.73). Post-program survey responses indicated high levels of perceived relevance, clarity, and intended use of self-management strategies. Participation in a single-session, multidisciplinary pain education program was associated with immediate improvements in pain neurophysiology knowledge and positive patient perceptions. These findings support the role of brief, structured pain education as a foundational component of multidisciplinary tertiary chronic pain services. Further research is needed to determine whether improvements in pain neurophysiology knowledge are maintained over time and associated with longer-term clinical outcomes.","[""Journal Article""]","[""Chan SH"", ""Davis H""]",10.1111/jep.70544,Chan SH,Journal of evaluation in clinical practice,1356-1294,5,J Eval Clin Pract,eng,Davis H,"[""Humans"", ""Pain Management"", ""Female"", ""Patient Education as Topic"", ""Health Knowledge, Attitudes, Practice"", ""Male"", ""Neurosciences"", ""Middle Aged"", ""Adult"", ""Chronic Pain"", ""Quality Improvement"", ""Surveys and Questionnaires"", ""Aged""]",e70544,42507815,pmc-id: PMC13405248;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42507815/,Improvement in Pain Neuroscience Knowledge and Patient Perceptions Following a One-Day Multidisciplinary Pain Education Program,32,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Studies of the oldest-old show great neuropathologic heterogeneity; little is known in diverse populations after age 90. LifeAfter90 is a lifecourse cohort study of individuals aged ≥ 90 years evaluated every 6 months with optional brain donation; this study presents initial neuropathological findings. A total of 124 decedents (mean age 96, 49.2% White, 12.1% Black, 16.9% Asian, 18.5% Latino individuals) came to autopsy. At last evaluation, 35% had dementia, 23% cognitive impairment, and 41% normal cognition. 35.5% had intermediate AD, 8.1% had high AD neuropathologic changes, 73% had moderate/severe arteriolosclerosis, 23% one or more microinfarcts, 32% Lewy bodies, 24% TDP-43 deposits, and 4% hippocampal sclerosis. There was a high degree of mixed neuropathology, with 69% having three or more pathologies. Cognitive impairment was most strongly associated with AD pathology. Multiple pathologies were common, and many individuals maintained normal cognition indicating substantial neuropathologic burden may be present in the absence of overt cognitive impairment, especially in the oldest-old.","[""Journal Article""]","[""Dugger BN"", ""Luu MN"", ""Patel V"", ""DeCarli C"", ""Jin LW"", ""Gilsanz P"", ""Mungas D"", ""Kawas C"", ""Corrada MM"", ""Whitmer RA""]",10.1002/alz.71634,Dugger BN,Alzheimer's & dementia : the journal of the Alzheimer's Association,1552-5260,7,Alzheimers Dement,eng,Whitmer RA,"[""Humans"", ""Aged, 80 and over"", ""Female"", ""Male"", ""Brain"", ""Cohort Studies"", ""Alzheimer Disease"", ""Hippocampal Sclerosis"", ""Cognitive Dysfunction"", ""Neuropathology""]",e71634,42499153,pmc-id: PMC13400840;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42499153/,Neuropathology in a diverse cohort of oldest-old: The LifeAfter90 study,22,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Computational neuroscience projects often combine simulation code, configuration files, analysis scripts, plotting utilities, and provenance records through loosely coupled and difficult-to-replay workflows. SACS is presented as a configuration-driven research-software framework for reproducible schematic multi-region circuit simulation with integrated analytics, validation checks, deterministic execution, deterministic replay, artifact replay, and graphical inspection. Implemented as the Python package brain_sim, the framework converts declarative model and scenario specifications into standardized run directories containing numerical outputs, machine-readable summaries, figure-generation recipes, validation reports, and provenance metadata. The contribution is methodological and neuroinformatics-oriented. SACS is not presented as a biologically validated model of anxiety, brain function, or treatment response, and its built-in circuit materials are used as configurable demonstration components rather than as evidence of clinical or biological validity. Instead, the framework is evaluated as software for reproducible computational experimentation: hypotheses are encoded as explicit configurations, executed under recorded seeds, inspected through analytics and validation layers, and then used to inform subsequent configurations in an iterative workflow. The manuscript describes the software architecture, configuration and execution model, artifact structure, replay mechanisms, and graphical/programmatic interfaces that support this workflow. The central claim is that SACS improves transparency, inspectability, and reuse for schematic circuit experiments by binding configuration, execution, analytics, provenance, and replay within a single software environment.","[""Journal Article""]","[""Beyene ED"", ""Atmaca E""]",10.1007/s12021-026-09799-w,Beyene ED,Neuroinformatics,1539-2791,3,Neuroinformatics,eng,Atmaca E,"[""Software"", ""Computer Simulation"", ""Humans"", ""Animals"", ""Brain"", ""Models, Neurological"", ""Reproducibility of Results"", ""Neurosciences""]",,42496772,,2026 Jul 24,2026,https://pubmed.ncbi.nlm.nih.gov/42496772/,"SACS: A Reproducible, Configuration-Driven Software Framework for Schematic Multi-Region Circuit Simulation and Integrated Analytics",24,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"This piece provides an overview of my fifty-year career as a neuroscientist. I spent much of this time trying to understand what emotions are and how they relate to human behavior and consciousness. I am pleased that my work on the amygdala helped bring emotion into the field. But late in the game I changed my views about the amygdala and emotions, causing some unrest in the field. Note that this is a personal, not an encyclopedic, overview of the neuroscience of emotion. In other words, this is my story about emotions and the brain, especially in relation to emotional consciousness.","[""Journal Article"", ""Historical Article""]","[""LeDoux JE""]",10.1523/JNEUROSCI.0172-26.2026,LeDoux JE,The Journal of neuroscience : the official journal of the Society for Neuroscience,0270-6474,29,J Neurosci,eng,LeDoux JE,"[""Humans"", ""Consciousness"", ""Emotions"", ""Brain"", ""History, 21st Century"", ""History, 20th Century"", ""Neurosciences"", ""Animals""]",,42486689,pmc-id: PMC13393538;embargo-date: 2027/01/22;,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42486689/,My Fifty Years Thinking about Emotional Consciousness in the Brain,46,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Digital cognitive interventions (DCIs) have emerged as scalable approaches for treating cognitive dysfunction across psychiatric, neurological, and aging populations. Despite growing evidence of efficacy, little is known about which intervention components drive therapeutic effects or through which neurocognitive mechanisms they operate. As a result, null findings are often difficult to interpret, making it unclear whether interventions failed to engage their intended targets, or whether the targets themselves are not causally related to meaningful outcomes. This limits intervention refinement, comparative evaluation, and precision personalization. Here, we argue that DCI research should shift from broad efficacy testing toward mechanistic trials designed to identify active ingredients-the intervention components responsible for engaging prespecified neurocognitive targets and producing clinically meaningful benefits. We propose adapting dismantling design methodology from psychotherapy research in order to integrate Research Domain Criteria constructs, mechanistic neuroscience, and high-resolution digital behavioral data to identify factors driving cognitive and functional outcomes. This approach aligns with the National Institute of Mental Health experimental therapeutics framework by explicitly linking target specification and target engagement with downstream clinical and functional outcomes. Mechanistic dismantling trials can determine whether specific DCI features, including adaptive difficulty, reward schedules, feedback contingencies, task variability, cognitive targets, and human support, are necessary, sufficient, or synergistic for engaging neural circuitry and producing durable and clinically meaningful transfer. Beyond optimizing intervention design, such studies may transform null or negative trials into mechanistically interpretable findings, while clarifying disease mechanisms and supporting the development of personalized, optimized, and usable DCIs.","[""Journal Article""]","[""Morimoto SS"", ""Lindbergh CA"", ""Conley A"", ""Jones DR"", ""Steffens DC""]",10.2196/94246,Morimoto SS,JMIR mental health,2368-7959,,JMIR Ment Health,eng,Steffens DC,"[""Humans"", ""Digital Media"", ""Research Design"", ""Cognitive Dysfunction"", ""Neurosciences"", ""Cognitive Behavioral Therapy""]",e94246,42459150,pmc-id: PMC13373463;,2026 Jul 14,2026,https://pubmed.ncbi.nlm.nih.gov/42459150/,Active Ingredients in Digital Cognitive Interventions: Integrating Dismantling Designs With Mechanistic Neuroscience,13,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"The mind-brain relationship is a foundational yet underexplored dimension of contemporary neuroscience, shaping research framing, data interpretation, and public communication. We conducted a large-scale international survey of 2,657 neuroscientists to assess their views on the mind-brain problem, free will, and the future of the discipline. Our results reveal a complex and sometimes paradoxical worldview. While 64% of participants endorse reductive physicalism-the view that mental activity is fully reducible to brain function-only 17.5% reject free will. Despite estimating that current knowledge covers only a limited portion of brain structure and function (30%), respondents express marked optimism about the future of neuroscience, including the prospect of fully understanding the human being and mental disorders through neuroscience, and even achieving mind reading and mental uploading. A principal component analysis identified five latent dimensions, some of which vary systematically across sociodemographic and disciplinary factors. These findings indicate that neuroscientists hold diverse philosophical commitments that diverge from common narratives of hard determinism. The prevalence of neuroessentialist views further highlights the need for sustained interdisciplinary dialogue to address the conceptual, ethical, and societal implications of neuroscientific progress.","[""Journal Article""]","[""Navarro-Peña F"", ""Arrondo G"", ""Barrett NF"", ""Güell F"", ""Madirolas G"", ""Murillo JI"", ""Sánchez-Cañizares J"", ""Bernacer J""]",10.1073/pnas.2610776123,Navarro-Peña F,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,29,Proc Natl Acad Sci U S A,eng,Bernacer J,"[""Neurosciences"", ""Humans"", ""Philosophy"", ""Brain""]",e2610776123,42455665,pmc-id: PMC13389498;,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42455665/,Divergent philosophical commitments in neuroscience: Evidence from a global survey,123,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"It is now widely appreciated that culture can shape cognition and neural engagement. However, research investigating the effects of culture across the adult lifespan, with a focus on cognitive aging, is lacking. In this article, we consider why this integration of topics is useful and discuss the ways in which culture has been proposed to affect cognition and the cognitive neuroscience of aging. The literature thus far is reviewed from the perspectives of long-term memory and decision-making, which broadly encompass information processing in the brain and reflect a person's worldview and resulting actions. We argue for the importance of integrating aging into the study of cultural neuroscience, making the case from two different perspectives: the importance of studying cultural influences over the trajectory of the adult lifespan and the importance of understanding the cognitive neuroscience of aging across cultural groups. We discuss challenges and opportunities for future research, concluding that studying the cognitive neuroscience of aging across cultures has the potential to broaden understanding of the factors that contribute to successful cognitive aging as well as age-related decline and pathology.","[""Journal Article"", ""Review""]","[""Gutchess A"", ""Tan YS"", ""Qian J"", ""Goh JOS""]",10.1111/nyas.70336,Gutchess A,Annals of the New York Academy of Sciences,0077-8923,1,Ann N Y Acad Sci,eng,Goh JOS,"[""Humans"", ""Cognitive Neuroscience"", ""Aging"", ""Cognition"", ""Culture"", ""Decision Making"", ""Cognitive Aging"", ""Brain"", ""Memory, Long-Term"", ""Neurosciences""]",e70336,42444549,pmc-id: PMC13366456;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42444549/,The Importance of Studying the Cognitive Neuroscience of Aging Across Cultures,1561,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"The steady-state visual evoked potential (SSVEP), the brain's oscillatory response to repetitive visual stimulation (RVS), has emerged as a powerful tool in neuroscience with wide-ranging applications in multiple disciplines. This review provides a scoping, narrative roadmap of SSVEP applications organized into three primary domains: fundamental research in vision and cognition, clinical neuroscience, and neural engineering. Although these fields differ in focus, they often converge in their use of similar research questions, stimulation paradigms, analysis techniques, and application scenarios. At the same time, specialization may have created knowledge silos that limit cross-disciplinary transfer of methods and insights. By bridging findings from seemingly disparate domains, this review highlights the versatility of SSVEPs in investigating neural mechanisms, supporting diagnosis and treatment of neurological and psychiatric conditions, and advancing brain-computer interface technology. We conclude with cross-field insights on how stimulus and analysis choices affect interpretation and usability, and we outline directions for improving the comparability and transferability of SSVEP research and applications.","[""Journal Article"", ""Review""]","[""Tsoneva T"", ""Desain P"", ""Garcia-Molina G"", ""Thielen J""]",10.1016/j.neuroimage.2026.122095,Tsoneva T,NeuroImage,1053-8119,,Neuroimage,eng,Thielen J,"[""Humans"", ""Evoked Potentials, Visual"", ""Cognitive Neuroscience"", ""Electroencephalography"", ""Brain"", ""Brain-Computer Interfaces""]",122095,42431561,,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42431561/,The steady-state visual evoked potential (SSVEP): A review of applications in cognitive and clinical neuroscience and neural engineering,338,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Creutzfeldt-Jakob disease (CJD) is a rapidly progressive neurodegenerative disease characterized by significant changes in EEG and structural alterations on MRI. Both are integrated in the current World Health Organization (WHO) surveillance criteria of CJD. We aimed to re-evaluate the EEG recordings, along with clinical and MRI data, in patients with different subtypes of definite CJD by applying the adapted American Clinical Neurophysiology Society (ACNS) criteria, 2021. Fifty-one routine EEG recordings in 16 patients with sporadic CJD were reanalyzed. Generalized slowing, according to standard terminology, was present in 94% of patients. Generalized periodic discharges (GPDs) and generalized rhythmic delta activity (GRDA), as defined by the 2021 ACNS criteria, occurred frequently (31% and 38%, respectively). The differentiation from ictal activity may be challenging because 25% (4/16) of the patients fulfilled the criteria of the recently proposed ictal-interictal continuum (IIC) in at least 1 EEG. By contrast, no status epilepticus (SE) was observed. The EEG alterations varied among the different CJD molecular subgroups: more cortical involvement in MM/MV1 and mixed MM/MV1 + 2C histotypes was associated with periodic discharges (PDs) (57% and 80%) and also IIC (43% and 20%). We could not detect any PD or IIC in patients with the VV1 or MV2K (predominant subcortical pathology) histotype. Assessing the EEGs according to the 2021 ACNS criteria may help prevent misdiagnosis of nonconvulsive status epilepticus, and repetitive recordings may help in earlier diagnosis of CJD.","[""Journal Article""]","[""Berger-Sieczkowski E"", ""Zulehner G"", ""Klotz S"", ""Regelsberger G"", ""Haider L"", ""Bonelli-Nauer S"", ""Trimmel K"", ""Gelpi E""]",10.1212/CPJ.0000000000200642,Berger-Sieczkowski E,Neurology. Clinical practice,2163-0402,4,Neurol Clin Pract,eng,Gelpi E,"[""Creutzfeldt-Jakob Syndrome"", ""Humans"", ""Electroencephalography"", ""Female"", ""Male"", ""Aged"", ""Middle Aged"", ""Societies, Medical"", ""Magnetic Resonance Imaging"", ""Neurophysiology""]",e200642,42424573,pmc-id: PMC13352215;embargo-date: 2027/08/01;,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42424573/,Altered EEG in Creutzfeldt-Jakob Disease: Improving Diagnostic Accuracy Using American Clinical Neurophysiology Society 2021 Criteria,16,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"We sought to explore outcomes at 1 year in functional neurological disorder (FND) following a neuroscience-informed education and counseling assessment. Patients with FND were assessed at a quaternary neuropsychiatry clinic in Toronto, Canada, and provided education and counseling to build insight into their FND diagnosis. Patient-determined diagnostic agreement at follow-up was categorized as a binary variable: (i) symptoms attributable primarily to FND or (ii) attributable to another cause (neurological disease or unknown). One-year symptom status was patient-reported on a 7-point scale (-3 to +3), with scores ≥2 defined as meaningful improvement. Return to work/school was assessed as an indicator of global improvement of functional status. Univariate tests screened variables for inclusion in multivariate logistic regression models, which evaluated associations between diagnostic agreement and other outcomes. A total of 282 patients with FND were assessed (mean age 38.9 ± 12.0 years; 80.3% female), and of these, 127 had 1-year follow-up data. FND subtypes included functional movement disorder (functional weakness [26.8%], hyperkinetic movement [15.7%]), seizure (15.0%), sensory (16.5%), functional cognitive disorder (7.9%), persistent postural perceptual dizziness (14.2%), and speech/swallowing (3.9%). Diagnostic agreement was significantly associated with symptom improvement (odds ratio [OR] = 3.81, 95% CI: 1.33-11.71, p = 0.015) and global improvement (OR = 5.74, 95% CI: 1.11-37.54, p = 0.047). Psychiatric comorbidity (p = 0.026), childhood trauma (p = 0.015), and psychological triggers (p = 0.013) were associated with diagnostic agreement, while ongoing medical/neurological workup was linked to disagreement (p < 0.001). Diagnostic agreement was associated with symptom improvement and return-to-work/school status in FND patients who received a neuroscience-informed education and counseling assessment. However, given the observational design and lack of baseline measurement of diagnostic agreement, the directionality of this relationship cannot be determined.","[""Journal Article""]","[""Mollica A"", ""Ng E"", ""Nannapaneni S"", ""Bhayat U"", ""Feinstein A"", ""Perez DL"", ""Burke MJ""]",10.1002/brb3.71491,Mollica A,Brain and behavior,2162-3279,7,Brain Behav,eng,Burke MJ,"[""Humans"", ""Female"", ""Male"", ""Adult"", ""Retrospective Studies"", ""Nervous System Diseases"", ""Middle Aged"", ""Counseling"", ""Patient Education as Topic"", ""Neurosciences"", ""Follow-Up Studies"", ""Conversion Disorder""]",e71491,42418303,pmc-id: PMC13344738;,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42418303/,"Diagnostic Agreement and 1-Year Outcomes in Functional Neurological Disorder Following Neuroscience-Informed Assessment, Education, and Counseling: A Retrospective Cohort Study",16,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"This article examines how early twentieth-century comparative psychology treated behaviour as a primary site for studying regulation, dysfunction, and adaptation, using experimental neurosis as a historical case study. Beginning with Pavlov's observation that dogs exposed to irresolvable conflict developed persistent behavioural and autonomic disturbances, the paradigm expanded through mid-century work by Liddell, Gantt, and Masserman, who introduced new species, longitudinal designs, and ecologically grounded conditions revealing dysregulation as a multilevel, temporally extended phenomenon. In this tradition, behaviour was not construed as mechanistic output but as an autonomous level of organisation whose structured patterns, i.e., variability, context-sensitivity, stability, and breakdown, made internal regulatory dynamics experimentally accessible in ways physiology alone could not. Hybrid methodologies integrating laboratory control with naturalistic observation showed that pathological breakdown provides access to organisational features obscured during normal function. By mid-century, however, this behaviourally rich framework was displaced by reductionist approaches based on standardised assays and physiological endpoints. Recent historiography documents this shift as an epistemological transformation in which behaviour was redefined from interface to index, from organised system to dependent variable. These tensions persist in contemporary neuroscience and translational research, where behaviour is routinely subordinated to mechanism despite gaps between circuit-level manipulation and behavioural explanation. This historical analysis supports the claim that mechanistic approaches which bypass behaviour incur explanatory loss, eliminating the domain in which neurophysiological processes acquire functional meaning. Progress in understanding psychopathology requires restoring behaviour to ontological and epistemological centrality as the irreducible interface through which adaptive and pathological regulation become scientifically accessible.","[""Journal Article"", ""Historical Article"", ""Review""]","[""De Marco RJ""]",10.1007/s40656-026-00746-1,De Marco RJ,History and philosophy of the life sciences,0391-9714,3,Hist Philos Life Sci,eng,De Marco RJ,"[""Animals"", ""Dogs"", ""Behavior, Animal"", ""History, 20th Century"", ""Neurosciences"", ""Psychology, Comparative"", ""History, 19th Century""]",,42418096,pmc-id: PMC13346283;,2026 Jul 8,2026,https://pubmed.ncbi.nlm.nih.gov/42418096/,The ontological status of behaviour: lessons from experimental neurosis (1900-1950),48,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Research at the intersection of neuroscience and education has generated substantial empirical findings but has often lacked a unifying theoretical framework capable of explaining why those findings belong together. Predictive processing, a family of accounts characterizing the brain as a hierarchical system that continuously generates expectations and updates internal models in response to prediction errors, has been proposed as a candidate umbrella framework for the cognitive sciences, though it remains actively debated. We examine whether its core concepts transfer meaningfully to educational contexts. Rather than deriving concrete instructional prescriptions, we propose four constraints that are especially relevant when instruction aims to produce conceptual model revision under uncertainty. We further suggest that developmental differences between children and adults can be interpreted as systematic variations in these inferential parameters. The contribution of this paper is primarily integrative: findings from educational research have largely been articulated within separate paradigms, and we argue that predictive processing may offer a common inferential vocabulary for describing them. Future work may derive empirically testable predictions from this framework, though the limitations of these accounts must be kept carefully in view.","[""Journal Article""]","[""Trapp S"", ""Németh D"", ""Janacsek K""]",10.1007/s12124-026-10019-y,Trapp S,Integrative psychological & behavioral science,1932-4502,3,Integr Psychol Behav Sci,eng,Janacsek K,"[""Humans"", ""Learning"", ""Neurosciences"", ""Research"", ""Uncertainty""]",,42418077,,2026 Jul 8,2026,https://pubmed.ncbi.nlm.nih.gov/42418077/,Learning Under Uncertainty: Predictive Processing as an Integrative Framework for Educational Research,60,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Open neuroscience repositories support reuse by making datasets accessible, but event level reuse also depends on whether task and stimulus annotations can be interpreted by software. I audited public latest OpenNeuro BIDS snapshots using public GraphQL metadata, recursive file trees, small events.json sidecars, and bounded events.tsv header ranges. Raw neural data were left untouched. Among 1,713 public latest snapshots, 1,483 had task metadata or observed event TSV files and formed the primary event relevant denominator. Event TSV files were present in 1,175/1,483 snapshots (79.2%; Wilson 95% CI 77.1%-81.2%). Candidate event JSON sidecars were present in 604/1,483 snapshots (40.7%), but an inheritance aware path and entity check found applicable JSON sidecars for 590/1,483 (39.8%), descriptive applicable sidecars for 550/1,483 (37.1%), and experiment specific applicable sidecars for 491/1,483 (33.1%). Across the full recursive file tree, 162,034/301,681 event TSV files (53.7%) had an applicable event JSON sidecar, and 147,412/301,681 (48.9%) had an applicable experiment specific sidecar. HED was detected in event JSON for 45/1,483 snapshots (3.0%) and in sampled TSV headers for 2/1,483 (0.13%). EEG had higher sidecar coverage and HED detection than fMRI, but 21.2% of EEG candidate JSON files were bookkeeping only. These results identify a repository visible metadata gap: event timing is common, but software interpretable event meaning remains uneven.","[""Journal Article""]","[""Xu Y""]",10.1007/s12021-026-09797-y,Xu Y,Neuroinformatics,1539-2791,3,Neuroinformatics,eng,Xu Y,"[""Metadata"", ""Humans"", ""Software"", ""Semantics"", ""Databases, Factual"", ""Neurosciences"", ""Animals""]",,42418054,pmc-id: PMC13346197;,2026 Jul 8,2026,https://pubmed.ncbi.nlm.nih.gov/42418054/,"Event Files are Common, But Semantic Event Metadata Remain Uneven in OpenNeuro BIDS Datasets",24,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Cognitive neuroscience faces a paradox: neural data are abundant, yet conceptual synthesis has stalled because dominant contrast-based approaches show where activity differs but not how cognitive operations relate or transform. Here, we propose a generative-transformational logic grounded in AI and neural geometry, treating cognition as lawful mappings among neural states. Generative models can learn latent transformations linking states across tasks, contexts, and individuals. Because transformation success is testable, this framework enables counterfactual simulation and connects data-driven modeling with theory-driven inference. It moves cognitive neuroscience from mapping correlates toward algorithmic explanations of how the brain generates and reorganizes cognition over time.","[""Journal Article"", ""Review""]","[""Beste C"", ""Safavi S""]",10.1038/s42003-026-10642-w,Beste C,Communications biology,2399-3642,1,Commun Biol,eng,Safavi S,"[""Cognitive Neuroscience"", ""Humans"", ""Generative Artificial Intelligence"", ""Cognition"", ""Brain""]",,42414558,pmc-id: PMC13342655;,2026 Jul 8,2026,https://pubmed.ncbi.nlm.nih.gov/42414558/,Generative AI as a transformational logic for cognitive neuroscience,9,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
The once-obscure Danionella fish will be the focus of an ambitious new Howard Hughes Medical Institute project.,"[""News""]","[""Beketova Z""]",10.1126/science.aek1830,Beketova Z,"Science (New York, N.Y.)",0036-8075,6806,Science,eng,Beketova Z,"[""Animals"", ""Neurosciences"", ""Zebrafish"", ""Brain""]",18-19,42391370,,2026 Jul 2,2026,https://pubmed.ncbi.nlm.nih.gov/42391370/,Transparent fish takes center stage in $1 billion neuroscience initiative,393,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"How a visual stimulus is perceived depends on the context provided by other stimuli in the scene. Fu et al.1 combine imaging, modeling, and innovative closed-loop stimulus generation to identify the brain computations that underlie contextual effects in primary visual cortex (V1) neurons.","[""Journal Article"", ""Comment""]","[""Moon J"", ""Goris RLT""]",10.1016/j.neuron.2026.06.007,Moon J,Neuron,0896-6273,13,Neuron,eng,Goris RLT,"[""Animals"", ""Visual Cortex"", ""Humans"", ""Photic Stimulation"", ""Visual Perception"", ""Neurons"", ""Primary Visual Cortex"", ""Neurosciences"", ""Visual Pathways""]",2296-2297,42385678,,2026 Jul 1,2026,https://pubmed.ncbi.nlm.nih.gov/42385678/,Image space opens up for visual neuroscience,114,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Futrell and Mahowald argue that neural networks have learned non-trivial aspects of language. We argue that these systems have not in fact demonstrated ""mastery"" of syntax, marshalling recent evidence, and that they further obscure explanatory insights with respect to topics in the cognitive neuroscience of language.","[""Journal Article""]","[""Murphy E"", ""Morosi P"", ""Leivada E"", ""Nevins A""]",10.1017/S0140525X26104634,Murphy E,The Behavioral and brain sciences,0140-525X,,Behav Brain Sci,eng,Nevins A,"[""Humans"", ""Linguistics"", ""Language"", ""Large Language Models"", ""Neurosciences"", ""Neural Networks, Computer""]",e217,42380006,,2026 Jul 1,2026,https://pubmed.ncbi.nlm.nih.gov/42380006/,Machine yearning: LLMs do not capture formal linguistic structure and obscure neuroscientific inquiry,49,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"People differ in their tendency to experience negative emotions. This variability is largely captured by broad psychological constructs like neuroticism, whose facets include anxiety, depression, and stress vulnerability, among others. The amygdala and salience network have been assumed to underlie such dispositions, despite inconsistent evidence. We preregistered a comprehensive test of these and other competing hypotheses-accompanied by theory-agnostic machine learning prediction-using neural responses in the two most common emotional neuroimaging tasks (scenes and faces; N = 338/424). Evidence including Bayes factors indicated that neuroticism is not associated with any region, network, affective signature, or machine learning pattern, including the amygdala. Still, a brain-wide machine learning pattern robustly predicted the neuroticism facet stress vulnerability (r = .21), replicated in an independent dataset (r = .19). Predictive performance most strongly depended on somatomotor and visual networks, rather than salience network regions, relating stress vulnerability to cortical perception-action systems. Together with a multiverse analysis spanning 14 trait constructs and 1,176 models, our findings demonstrate the highly selective predictability of emotional dispositions from brain responses to common affective tasks. Therein, they highlight the importance of construct and task selection, while challenging the role of the most commonly used neural markers, including responses of the amygdala and salience network.","[""Journal Article""]","[""Sicorello M"", ""Gianaros PJ"", ""Wright AGC"", ""Petre B"", ""Kraynak TE"", ""Manuck SB"", ""Schmahl C"", ""Wager TD""]",10.1038/s41467-026-74565-0,Sicorello M,Nature communications,2041-1723,1,Nat Commun,eng,Wager TD,"[""Humans"", ""Emotions"", ""Amygdala"", ""Female"", ""Neuroticism"", ""Bayes Theorem"", ""Magnetic Resonance Imaging"", ""Brain"", ""Male"", ""Machine Learning"", ""Neurobiology"", ""Adult"", ""Brain Mapping"", ""Young Adult"", ""Stress, Psychological""]",,42373635,pmc-id: PMC13315715;,2026 Jun 27,2026,https://pubmed.ncbi.nlm.nih.gov/42373635/,The functional neurobiology of dispositions towards negative emotions,17,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Since 2017, the European Journal of Neuroscience has featured interviews with 27 female neuroscientists to showcase and celebrate their excellent scientific contributions and to hear their personal stories and advice for younger neuroscientists. Although these women represent different fields in neuroscience, countries, and levels of seniority, their stories share some remarkable commonalities, which we briefly discuss in this editorial. Highlighted topics include: the circuitous route of some of the careers; the importance of having good mentors and belonging to networks; the role of ""good fortune"" versus abilities and skills; the upsides and downsides of an academic career; some of the aspects in which women's academic careers may differ from those of men; and the advice the interviewees would like to pass on to the next generations. Although it is clear from these personal accounts that some aspects of women's careers in neuroscience have improved over the past decade, other elements seem stagnant. The European Journal of Neuroscience remains committed to equity and will continue to feature the stories of women in neuroscience to inspire future generations.","[""Editorial""]","[""Joëls M"", ""Nicklas PR"", ""Helmreich DL""]",10.1111/ejn.70583,Joëls M,The European journal of neuroscience,0953-816X,1,Eur J Neurosci,eng,Helmreich DL,"[""Humans"", ""Female"", ""Neurosciences"", ""Academia"", ""Mentors"", ""Women"", ""Career Choice"", ""Research Personnel""]",e70583,42357834,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42357834/,The Inspiring Journeys of Women in Science,64,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Neuropharmacology has emerged in recent years as a field of active research, driven by the need to address increasing challenges posed by clinical conditions such as neurodegenerative disorders, which affect more and more elderly people worldwide as the average life expectancy extends progressively [...].","[""Editorial"", ""Introductory Journal Article""]","[""Radu B"", ""Amuzescu B""]",10.3390/biom16060901,Radu B,Biomolecules,2218-273X,6,Biomolecules,eng,Amuzescu B,"[""Humans"", ""Neuropharmacology"", ""Neurodegenerative Diseases"", ""Animals""]",,42352366,pmc-id: PMC13296847;,2026 Jun 18,2026,https://pubmed.ncbi.nlm.nih.gov/42352366/,New Discoveries in the Field of Neuropharmacology,16,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Neural signaling shapes tumor progression, but it is not intrinsically tumor-promoting or tumor-restrictive. We argue that neural directionality is context-dependent and governed by tumor kinetics, tissue architecture, neural state, receptor and target-cell topology, immune-host biology, and treatment history. We propose a mechanistically interpretable and clinically actionable reporting framework for precision neuromodulatory oncology.","[""Journal Article"", ""Review""]","[""Birbrair A"", ""Simon DJ"", ""Talbot S"", ""Zhou S""]",10.1016/j.ccell.2026.05.016,Birbrair A,Cancer cell,1535-6108,7,Cancer Cell,eng,Zhou S,"[""Humans"", ""Neoplasms"", ""Animals"", ""Signal Transduction"", ""Neurosciences""]",1321-1324,42314663,,2026 Jul 13,2026,https://pubmed.ncbi.nlm.nih.gov/42314663/,Context dependency in cancer neuroscience,44,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Many open questions about neural circuit and systems function could be answered if spikes and synaptic potentials could be accurately measured from many neurons simultaneously in a given network with cell-type specificity, cellular resolution, and at the millisecond time scale. Voltage imaging with genetically encoded voltage indicators (GEVIs) has advanced to the point that this is now possible for small networks or sparsely labeled neurons, and emerging optical methods promise to soon enable imaging from larger, dense cell populations. This review describes recent discoveries made using GEVIs to understand local and propagating cortical activity, network oscillations, and cortical and hippocampal microcircuit dynamics, and outlines several promising future applications in systems neuroscience.","[""Journal Article"", ""Review""]","[""Gomez LC"", ""Rodriguez L"", ""Garderes PM"", ""Feldman DE""]",10.1016/j.conb.2026.103238,Gomez LC,Current opinion in neurobiology,0959-4388,,Curr Opin Neurobiol,eng,Feldman DE,"[""Animals"", ""Neurosciences"", ""Humans"", ""Neurons"", ""Voltage-Sensitive Dye Imaging"", ""Nerve Net"", ""Optical Imaging""]",103238,42314366,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42314366/,Optical voltage imaging: ready to spark systems neuroscience,99,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Understanding the neural basis of speech communication is essential for uncovering how sounds are translated into meaning, how that changes with development, ageing and speech-related deficits, as well as contributing to brain-computer interfaces research. While traditional neurophysiological studies have relied on simplified, controlled paradigms, recent advances have shifted the field towards more ecologically valid approaches. Here, we describe the evolving landscape of experimental designs in speech neurophysiology, from discrete to continuous stimuli and from socially isolated listening to dynamic, multiagent communication. Realistic paradigms in that space challenge conventional methods, offering richer insights into neural encoding, functional brain mapping and neural entrainment. At the same time, they introduce significant analytical and technical complexities, particularly when incorporating social interaction. By synthesising findings across studies, we highlight how these ecologically valid speech paradigms have been contributing to refining theories of language processing and open new avenues for research. In doing so, this review critically evaluates of whether the move towards realism in speech neurophysiology represents a technological trend or a transformative leap in understanding the neural underpinnings of speech communication.","[""Journal Article"", ""Review""]","[""Di Liberto GM"", ""Ip EYJ""]",10.1111/ejn.70496,Di Liberto GM,The European journal of neuroscience,0953-816X,12,Eur J Neurosci,eng,Ip EYJ,"[""Humans"", ""Speech"", ""Speech Perception"", ""Brain"", ""Brain Mapping"", ""Neurophysiology""]",e70496,42309989,pmc-id: PMC13275642;,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42309989/,Speech Neurophysiology in Realistic Contexts: Big Hype or Big Leap?,63,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Chronic insomnia, as defined by the DSM-5 and ICSD-3, is characterized by difficulties falling asleep, maintaining sleep, or waking up too early, occurring at least three times a week for more than three months, with daytime consequences. Long considered a secondary symptom, it is now recognized as a distinct condition resulting from a persistent disruption of sleep-wake regulation. Genetic and epigenetic studies show substantial heritability, suggesting a strong biological influence. More than 500 loci have been identified, linking insomnia to both metabolic and psychiatric traits. Gene-environment interactions, particularly through DNA methylation, may explain how stress can durably alter sleep system reactivity and promote chronicity. Brain imaging research highlights hyperactivation of key regions such as the anterior cingulate cortex, thalamus, insula, and precuneus, which are involved in arousal, vigilance, and emotional regulation. Electroencephalography confirms increased cortical activity, particularly in the beta and alpha bands, reflecting a persistent state of wakefulness during sleep. Explanatory models describe a set of mechanisms in which conditioning, stress reactivity, and co-activation of sleep and wake networks maintain the disorder. Insomnia thus appears as a hybrid state between wakefulness and sleep. These advances underline the complexity of insomnia and the need for integrated therapeutic approaches combining cognitive, behavioral, and physiological interventions to restore normal sleep regulation.","[""Journal Article"", ""Review""]","[""Solelhac G"", ""Raffray T"", ""Lombardi AS""]",10.1016/j.encep.2026.03.003,Solelhac G,L'Encephale,0013-7006,3S,Encephale,eng,Lombardi AS,"[""Humans"", ""Sleep Initiation and Maintenance Disorders"", ""Brain"", ""Gene-Environment Interaction"", ""Sleep"", ""Electroencephalography"", ""Neurobiology"", ""Wakefulness""]",S12-S15,42301742,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42301742/,Pathophysiology and neurobiology of insomnia,52,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Much has been elucidated about the neurobiological effects of early childhood trauma and its transgenerational transmission, although its integration into psychodynamic therapy has been challenging. Here we focus on a common area of interest to both areas-emotion and cognition rooted in past trauma experiences and how these experiences produce maladaptive behaviors transmitted to the next generation through parenting behaviors. We explore two mammalian research paradigms of early-life trauma explicitly within attachment, and transmission of transgenerational pathology through the caregiver to the offspring. We suggest that understanding the neurobiology through this mammalian nonhuman research can provide, in part, an understanding for the complex psychodynamic thought processes seen in adulthood, particularly as the mother begins to raise her own child. Specifically, while cognition and complex conscious and unconscious thoughts are characteristic of the human condition following early-life trauma, the mother-infant attachment system is a phylogenetically preserved system with some basic characteristics seen across species. We outline how embracing both the cognition and preserved trauma neural programing within attachment may provide some insight into cases, especially for the parent-child social interactions well documented to program the brain. Using mother-infant attachment, we suggest there is an area of convergence between clinical psychodynamic focus and basic research in brain function and mechanisms. Focusing on this convergence may provide a unique viewpoint to psychodynamics to supplement diagnosis and treatment.","[""Journal Article"", ""Review""]","[""Chambers J"", ""Sullivan R""]",10.1521/pdps.2026.54.2.249,Chambers J,Psychodynamic psychiatry,2162-2590,2,Psychodyn Psychiatry,eng,Sullivan R,"[""Humans"", ""Object Attachment"", ""Mother-Child Relations"", ""Animals"", ""Neurobiology"", ""Female"", ""Brain"", ""Adverse Childhood Experiences""]",249-282,42301161,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42301161/,Trauma in Attachment: Understanding the First Relationship Through Neurobiology and Psychodynamics,54,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Neuromyths-misconceptions arising from misinterpretations of neuroscientific findings-are widely endorsed by educators and students, including those in psychology. Their persistence has been linked to contextual, cognitive, and personality-related factors, but evidence is mixed, especially among psychology students. This study examined predictors of neuromyth endorsement in Argentine psychology undergraduates. To identify contextual (neuroscience training, interest), personality (Need for Cognition; NFC), and cognitive (Cognitive Reflection Test; CRT) predictors of neuromyth beliefs. A convenience sample of 320 psychology students (82.5% women; M_age = 27.39 years) completed online measures assessing neuromyth endorsement, general brain knowledge, NFC, CRT, and self-reported neuroscience training and interest. Spearman correlations and hierarchical regressions were conducted to examine associations and predictive effects. Participants endorsed 41.22% of neuromyths on average, with learning styles (76.25%) and sensory-rich environments benefits (74.37%) being the most accepted. CRT scores negatively predicted neuromyth endorsement (β = -.175, p < .001), whereas the NFC ""enjoyment of thinking"" factor positively predicted endorsement (β = 0.145, p = .024). Age also showed a positive effect (β = 0.175, p = .002). Neuroscience interest, courses taken, and general brain knowledge did not predict neuromyth acceptance, although they were positively associated with neuroscience knowledge. Analytical thinking emerged as the strongest protective factor against neuromyths, while enjoyment of thinking unexpectedly predicted higher endorsement, possibly reflecting exposure to low-quality sources of information and/or Dunning-Kruger effects. Factual neuroscience knowledge and training did not decrease neuromyth endorsement, underscoring the importance of fostering critical thinking skills within psychology education.","[""Journal Article""]","[""Tabullo ÁJ""]",10.1016/j.tine.2026.100284,Tabullo ÁJ,Trends in neuroscience and education,2211-9493,,Trends Neurosci Educ,eng,Tabullo ÁJ,"[""Adult"", ""Female"", ""Humans"", ""Male"", ""Young Adult"", ""Cognition"", ""Cognitive Reflection"", ""Neurosciences"", ""Personality"", ""Psychology"", ""Students"", ""Thinking""]",100284,42285694,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42285694/,"Why do psychology students believe in neuromyths? A study of personality, contextual and cognitive predictors",43,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Brain organoids, as three-dimensional cellular models that recapitulate human brain development and function in vitro, have emerged as a pivotal platform for neuroscience research. However, it still faces many technical challenges in aspects such as the structural and physiological relevance, functional regulation and system analysis, and urgently needs the deep integration of multi-disciplinary technologies to drive paradigm-shifting innovations. Here, we systematically summarize the main technological frameworks that support brain organoid research, including bioengineering and organoid construction technologies, biofabrication and microenvironmental modulation strategies, high-precision detection and multimodal analytical methodologies, as well as intelligent algorithms and data analysis platforms. The cross-integration of multiple technologies not only provides solutions to the existing limitations in brain organoid research, but also opens up cross-technological innovation application scenarios. We further discuss key bottlenecks in technology convergence and propose the development direction of future research. This review aims to provide a comprehensive technical roadmap for brain organoid research, promoting its in-depth application and paradigm innovation in cross-disciplinary fields including neuroscience, precision medicine, and brain-inspired computing.","[""Journal Article"", ""Review""]","[""Zhang Z"", ""Wang Y"", ""Chen L"", ""Ming D""]",10.1016/j.expneurol.2026.115877,Zhang Z,Experimental neurology,0014-4886,,Exp Neurol,eng,Ming D,"[""Humans"", ""Organoids"", ""Brain"", ""Animals"", ""Biomedical Technology"", ""Neurosciences"", ""Biomedical Research"", ""Bioengineering""]",115877,42285251,,2026 Oct,2026,https://pubmed.ncbi.nlm.nih.gov/42285251/,Convergence and innovative applications of cutting-edge biomedical technologies in brain organoid research,404,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Central nervous system (CNS) tumors represent a heterogeneous group of neoplasms associated with significant morbidity and mortality despite their relatively low incidence. Advances in the fifth edition of the World Health Organization (WHO) classification have emphasized the integration of histopathological, immunohistochemical, and molecular features, fundamentally transforming diagnostic and prognostic frameworks in neuro-oncology. This manuscript aims to provide an overview of CNS tumor biology, focusing on key diagnostic markers, genetic and epigenetic alterations, and emerging therapeutic strategies. It further describes recent advances in multi-omics approaches and artificial intelligence, which enable deeper characterization of tumor heterogeneity and support the development of precision medicine strategies. Finally, current and emerging therapeutic modalities, including combination therapies, targeted treatments, and novel molecular targets, are examined with emphasis on overcoming resistance mechanisms and improving clinical outcomes. Overall, the integration of molecular biology, advanced diagnostics, and innovative therapeutic approaches represents a critical step toward personalized management of CNS tumors and improved patient survival.","[""Journal Article"", ""Review""]","[""Leskova B"", ""D'Agostino I"", ""Mattova S"", ""Urbanska N"", ""Blicharova A"", ""Simko P"", ""Toplu A"", ""Karaman M"", ""Kiskova-Simkova T""]",10.3390/ijms27114880,Leskova B,International journal of molecular sciences,1422-0067,11,Int J Mol Sci,eng,Kiskova-Simkova T,"[""Humans"", ""Brain Neoplasms"", ""Epigenesis, Genetic"", ""Neuropharmacology"", ""Biomarkers, Tumor"", ""Precision Medicine"", ""Animals"", ""Artificial Intelligence"", ""Molecular Targeted Therapy"", ""Multiomics"", ""Antineoplastic Agents""]",,42278411,pmc-id: PMC13257304;,2026 May 28,2026,https://pubmed.ncbi.nlm.nih.gov/42278411/,Brain Cancer: Molecular Alterations and Emerging Trends in Neuropharmacology,27,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Sub-Saharan Africa is experiencing a rising burden of neurological and mental disorders. The International Brain Research Organization (IBRO)-funded 2nd School on Neuropharmacology Research and Drug Development (NRDD) was held in Harare, Zimbabwe, 2024. The meeting aimed to (1) provide a theoretical foundation in neuropharmacology; (2) develop skills in experimental design, pharmacokinetics, and drug evaluation; (3) foster interdisciplinary collaboration and networking; and (4) promote cultural and scientific exchange. Thirteen participants from eight African countries attended the 1-week program. This Meeting Review evaluates the extent to which the meeting achieved its goals, drawing on structured reflections from all participants, and describes the scientific, networking, cultural, and logistical dimensions of the experience. The school successfully equipped participants with foundational knowledge in neuropharmacology and drug development. Future editions would benefit from extended hands-on sessions and structured post-program follow-up.","[""Journal Article""]","[""Senanu J"", ""Wanyu BY"", ""Burns J"", ""Archibong VB"", ""Chinheya RM"", ""Ombel Musa NS"", ""Zengeni S"", ""Haj-Khlifa A"", ""Adeniji KO"", ""Kolo RM"", ""Caroline M"", ""Sakhri FZ"", ""Chipofya E""]",10.1242/bio.062217,Senanu J,Biology open,2046-6390,6,Biol Open,eng,Chipofya E,"[""Zimbabwe"", ""Humans"", ""Neuropharmacology"", ""Drug Development""]",,42273748,pmc-id: PMC13382971;,2026 Jun 15,2026,https://pubmed.ncbi.nlm.nih.gov/42273748/,"Perspectives from the 2024 School on Neuropharmacology Research and Drug Development in Harare, Zimbabwe: insights from participants",15,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Research using brain tissue obtained through autopsies is essential for the development of treatments for several neurological disorders and for elucidating their pathophysiologies. However, owing to a decline in the number of autopsies, opportunities to examine central nervous system tissues are diminishing. It is therefore necessary to collaborate with brain banks and establish a system to ensure the proper storage, research utilization, and diagnostic analysis of nervous system tissues obtained through autopsies.","[""Journal Article"", ""English Abstract"", ""Review""]","[""Takao M""]",10.11477/mf.188160960780060739,Takao M,Brain and nerve = Shinkei kenkyu no shinpo,1881-6096,6,Brain Nerve,jpn,Takao M,"[""Autopsy"", ""Humans"", ""Japan"", ""Brain"", ""Neuropathology""]",739-742,42271597,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42271597/,[Neuropathological Autopsies in Japan: Current Scenario and Challenges],78,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"The Simons Collaboration on Ecological Neuroscience (SCENE) seeks to uncover general principles of brain function through an ecological perspective: studying perception, cognition, and action in the context of the affordances available to different agents. Here, we introduce SCENE's goals, hypotheses, and approaches outlining a collaborative vision for the next decade.","[""Journal Article"", ""Review""]","[""Angelaki DE"", ""Batista A"", ""Fitzgerald T"", ""Kominsky JF"", ""Lengyel M"", ""Mathis A"", ""Mathis MW"", ""Moss CF"", ""Niell CM"", ""Noel JP"", ""Pitkow X"", ""Rothkopf CA"", ""Savin C"", ""Stachenfeld K"", ""Suthana N"", ""Tolias A"", ""Ulanovsky N"", ""Wolpert DM"", ""Wong A"", ""Zimmermann J""]",10.1016/j.neuron.2026.04.036,Angelaki DE,Neuron,0896-6273,14,Neuron,eng,Zimmermann J,"[""Brain"", ""Neurosciences"", ""Humans"", ""Animals"", ""Cognition""]",2500-2504,42263677,,2026 Jul 15,2026,https://pubmed.ncbi.nlm.nih.gov/42263677/,The Simons Collaboration on Ecological Neuroscience: Studying how the brain interacts with the world,114,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"New conceptual and technological developments bring neuroscientists closer to other disciplines and other fields in neuroscience with different traditions. Although some neuroscientists may underrate the potential benefits of successful interdisciplinary collaborations, others may be unaware of the typical difficulties of such collaborations or are not trained in skills that render them fruitful. Here, we argue that interdisciplinary interactions have long been part of neuroscience, although they are often challenging, because neuroscientists may be confronted with concepts, assumptions, and interpretative horizons that differ from their own. This can lead to misunderstandings and little mutual appreciation. Using the historical development of brain imaging techniques, we distinguish between different types of interdisciplinary interactions and illustrate some of their benefits. In addition, we present various challenges for collaborations at the interface between traditional laboratory-type approaches and those of clinical or computational neuroscience or of ecological field approaches. To address these challenges, we invite neuroscientists to consider philosophers as collaboration partners with complementary expertise, which includes special consideration of language use, underlying assumptions and proficiency in conceptual analysis. This expertise can be used by neuroscientists to increase their understanding and address some difficulties in interdisciplinary interactions more effectively. The benefits of these interactions can be expected to outweigh challenges in the dialogue with philosophers. Importantly, neuroscientists can choose between reading philosophical literature, participating in joint events with philosophers, and integrating philosophers into neuroscience projects. This may allow neuroscientists to explore unforeseen possibilities to improve or initiate collaborations with scientists from other fields and disciplines.","[""Journal Article"", ""Review""]","[""Kunze M"", ""Brun C"", ""Badaut J"", ""Darnaudéry M"", ""Gross F"", ""Peltier L"", ""Pradeu T"", ""Sarto-Jackson I"", ""Konsman JP""]",10.1111/ejn.70542,Kunze M,The European journal of neuroscience,0953-816X,11,Eur J Neurosci,eng,Konsman JP,"[""Neurosciences"", ""Humans"", ""Interdisciplinary Communication"", ""Cooperative Behavior"", ""Philosophy"", ""Interdisciplinary Research""]",e70542,42252691,pmc-id: PMC13243816;,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42252691/,How to Foster Challenging Interdisciplinary Collaborations: Can Philosophy Support Neuroscientists?,63,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Pregnancy involves profound physical and psychological changes that may increase the risk of lumbopelvic pain and affect body image. Body surveillance and functionality appreciation are key constructs in this context, yet little is known about interventions targeting them in pregnant women experiencing pregnancy-related pain. This study examined whether standard prenatal education alone or combined with pain neuroscience education could improve functionality appreciation and reduce body surveillance in women with pregnancy-related lumbopelvic pain. A total of 211 third-trimester pregnant women with pregnancy-related lumbopelvic pain were randomly assigned to standard prenatal education or a combined program with pain neuroscience education. Both programs included twelve online lessons delivered over four weeks. Functionality appreciation and body surveillance were measured at baseline and post-intervention using validated questionnaires. Linear mixed models were used for analysis under an intention-to-treat approach. Functionality appreciation improved significantly over time in both groups (p = .018), but no between-group differences were observed (Cohen's d = 0.056). Body surveillance scores remained unchanged in both groups (Cohen's d = 0.00). Adherence was higher in the SPE group (88%) compared to SPE+PNE (77.5%, p = .011). Brief online educational programs, especially standard prenatal education, can enhance functionality appreciation during pregnancy, shifting focus from appearance to bodily capacities.","[""Journal Article"", ""Randomized Controlled Trial""]","[""García-Lucas C"", ""Zamora Á"", ""Amer-Cuenca JJ"", ""Arguisuelas MD"", ""Pardo J"", ""Baños RM"", ""Lisón JF"", ""Biviá-Roig G""]",10.1016/j.midw.2026.104883,García-Lucas C,Midwifery,0266-6138,,Midwifery,eng,Biviá-Roig G,"[""Humans"", ""Female"", ""Pregnancy"", ""Adult"", ""Prenatal Education"", ""Surveys and Questionnaires"", ""Neurosciences"", ""Low Back Pain"", ""Pregnant People"", ""Body Image"", ""Pelvic Pain"", ""Patient Education as Topic""]",104883,42248093,,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42248093/,Effects of standard prenatal education with and without pain neuroscience education on functionality appreciation and body surveillance in pregnant women with lumbopelvic pain: a secondary analysis of a randomized controlled trial,160,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"In this interview with Neuron, Danilo Bzdok argues that artificial intelligence and big data herald a paradigm shift in neuroscience. Leveraging large language models, researchers can overcome traditional, intuition-driven taxonomies, bridge disciplinary silos, and reconcile today's fragmented knowledge into a unified vision of brain function.","[""Interview"", ""Historical Article""]","[""Bzdok D""]",10.1016/j.neuron.2026.04.042,Bzdok D,Neuron,0896-6273,11,Neuron,eng,Bzdok D,"[""Humans"", ""Neurosciences"", ""Artificial Intelligence"", ""Animals"", ""Brain"", ""History, 20th Century"", ""History, 21st Century"", ""Big Data""]",1889-1892,42235489,,2026 Jun 3,2026,https://pubmed.ncbi.nlm.nih.gov/42235489/,Danilo Bzdok,114,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Stroke remains one of the leading causes of death and long-term disability worldwide, often resulting in persistent motor impairments that limit independence and quality of life. This special issue highlights recent advances in stroke assessment and rehabilitation driven by the convergence of engineering, neuroscience, and motor control. The contributions are organized around four themes: (1) the importance of rigorous theoretical and methodological foundations to improve reproducibility and clinical translation; (2) the role of neuroplasticity, neuromodulation, and cognition in enhancing recovery; (3) emerging insights into neurophysiological and motor control mechanisms across cortical and spinal levels; and (4) innovations in assessment tools and rehabilitation technologies, including accessible, low-cost, and real-world solutions. Collectively, these studies demonstrate how interdisciplinary approaches are advancing both the science and practice of stroke rehabilitation, with an emphasis on clinically feasible strategies that can improve functional recovery and outcomes for individuals living with stroke.","[""Introductory Journal Article"", ""Editorial""]","[""Krishnan C"", ""Sulzer J"", ""Patten C"", ""Ranganathan R""]",10.1177/09226028261447080,Krishnan C,Restorative neurology and neuroscience,0922-6028,2,Restor Neurol Neurosci,eng,Ranganathan R,"[""Humans"", ""Stroke Rehabilitation"", ""Neurosciences"", ""Stroke"", ""Recovery of Function"", ""Animals"", ""Neuronal Plasticity""]",51-54,42227879,,2026 May,2026,https://pubmed.ncbi.nlm.nih.gov/42227879/,"Special Issue: Breakthroughs in Stroke Rehabilitation: Bridging Engineering, Neuroscience, and Motor Control",44,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Mobile MRI scanners could transform neuroimaging by expanding accessibility to diverse populations and enabling data collection in remote settings. This study serves as a short-term feasibility and system commissioning report, investigating the reliability and repeatability of two mobile 1.5 T MRI scanners compared to a stationary 1.5 T reference. To evaluate the technical impact of scanner relocation and mobile housing, a comprehensive protocol was implemented: five healthy subjects underwent 10 scans each (N = 50 total sessions) across three 1.5 T systems (one stationary; two mobile). The protocol employed a test-retest design with participant repositioning on each measurement day. Stability was assessed through longitudinal fBIRN phantom scans and human imaging of magnetic field homogeneity (ΔB0), RF flip-angle mapping (B1 +), structural MP-RAGE, and functional EPI-BOLD. Initial commissioning results demonstrated that short-term relocation and mobile operation did not compromise hardware performance. Phantom QA showed stable tSNR and minimal signal drift. In human subjects, magnetic field stability (ΔB0) and B1 + distributions were equivalent across systems, with Bland-Altman plots confirming no systematic bias following transit. Structural MP-RAGE voxel-intensity distributions and tissue volumes were highly consistent, with ICCs between 0.99 and 1 for estimated WM and GM volumes. This technical validation study demonstrates the short-term feasibility of utilizing mobile 1.5 T platforms for high-quality neuroimaging. The results confirm that current mobile shielding and stabilization technologies effectively mitigate the environmental challenges of transit, establishing a reliable baseline for future longitudinal research in remote or underserved settings.","[""Journal Article"", ""Comparative Study""]","[""Aigner CS"", ""Forlim CG"", ""Santoro D"", ""Bodammer NC"", ""Brühl R"", ""Sudimac S"", ""Schmalen K"", ""Schröder S"", ""Mohammadi S"", ""Kühn S""]",10.1002/nbm.70310,Aigner CS,NMR in biomedicine,0952-3480,7,NMR Biomed,eng,Kühn S,"[""Humans"", ""Magnetic Resonance Imaging"", ""Reproducibility of Results"", ""Phantoms, Imaging"", ""Adult"", ""Male"", ""Brain"", ""Female"", ""Neurosciences""]",e70310,42225567,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42225567/,MRI Goes Mobile: Assessing the Reliability and Repeatability of a Mobile vs. Stationary 1.5 T MRI for Functional Neuroscience Studies,39,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Understanding how decision-making changes across the lifespan is a central challenge for neuroscience, yet research on cognitive aging remains largely disconnected from the theoretical and computational advances shaping modern systems neuroscience. Over recent decades, theoretical frameworks have transformed how we study cognition in young, healthy brains. In contrast, aging research has relied on single-metric behavioral measures, cross-sectional comparisons, and descriptive neural analyses, limiting our ability to explain fundamental differences in individual aging trajectories. This gap represents a missed opportunity: aging offers a powerful platform for testing theories of neural computation, stability, and flexibility under changing biological constraints. We argue that closer integration between aging research and contemporary theoretical neuroscience will move the field from descriptive towards mechanistic insights. Here, we outline how recent advances in behavioral quantification, latent-state modeling, dynamical systems, encoding models, representational geometry, and recurrent neural networks offer a rich theoretical toolkit for studying decision-making across the lifespan.","[""Journal Article"", ""Review""]","[""Ryan MB"", ""Ye L"", ""Churchland AK""]",10.1016/j.conb.2026.103223,Ryan MB,Current opinion in neurobiology,0959-4388,,Curr Opin Neurobiol,eng,Churchland AK,"[""Humans"", ""Decision Making"", ""Aging"", ""Animals"", ""Neurosciences"", ""Brain"", ""Models, Neurological""]",103223,42208127,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42208127/,Harnessing theoretical neuroscience to understand decision-making across aging,99,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Unlike any other organ, the brain's role in identity, agency, and experience makes it biologically and culturally unique. The transformative potential of global neuroscience demands robust, integrated ethical engagement across the research life cycle. Neuroscientists and neuroengineers need to be equipped with a neuroethics familiarity that transcends the compliance training of older generations. Neuroethics must be an integral part of their work. This paper advocates for a proactive ""neuroethics-by-design"" (NxbD) approach. NxbD offers a reflective lens as well as an operational methodology that can iteratively shape hypotheses, experiments, technological architectures, and translation of the work to wider society. While NxbD is conceived as a toolkit for researchers, the responsibility of considering and addressing these issues is not theirs alone. NxbD is most effectively conceptualized as a shared responsibility that is evaluated and enacted by multiple communities. Such an approach is an investment in our collective future in which we can all contribute.","[""Journal Article""]","[""Rommelfanger KS""]",10.1523/JNEUROSCI.2165-25.2026,Rommelfanger KS,The Journal of neuroscience : the official journal of the Society for Neuroscience,0270-6474,21,J Neurosci,eng,Rommelfanger KS,"[""Humans"", ""Neurosciences""]",,42203525,pmc-id: PMC13217526;embargo-date: 2026/11/27;,2026 May 27,2026,https://pubmed.ncbi.nlm.nih.gov/42203525/,Designing Globally Inclusive and Ethically Deliberate Neurofutures,46,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Attention deficit hyperactivity disorder (ADHD) is a common and highly heterogeneous neurodevelopmental condition with complex biological underpinnings. Despite substantial progress in identifying genetic and neurobiological correlates, the cellular mechanisms linking genetic variation to functional brain alterations remain poorly understood. Human induced pluripotent stem cell (iPSC) technology provides a powerful platform to investigate these mechanisms by enabling the generation of patient-specific neural cell types and the direct interrogation of molecular, cellular, and network-level phenotypes. In this review, we summarise the current understanding of the neurobiological mechanisms underlying ADHD, including dopaminergic dysregulation, delayed neurodevelopmental maturation, and excitatory/inhibitory imbalance. We then discuss how iPSC-based models, combined with genome engineering and advanced functional assays, can be used to dissect gene-specific effects, study neural circuit development, and establish scalable platforms for therapeutic discovery. Finally, we outline key methodological considerations for designing robust iPSC-based models of ADHD. Together, these approaches provide new opportunities to bridge genetic risk with cellular function and accelerate the development of mechanistically informed therapeutic strategies.","[""Journal Article"", ""Review""]","[""Namipashaki A"", ""Yu H"", ""Bellgrove MA"", ""Hawi Z""]",10.3390/cells15100931,Namipashaki A,Cells,2073-4409,10,Cells,eng,Hawi Z,"[""Humans"", ""Attention Deficit Disorder with Hyperactivity"", ""Induced Pluripotent Stem Cells"", ""Models, Biological"", ""Neurodevelopment"", ""Neurobiology""]",,42193940,pmc-id: PMC13204105;,2026 May 19,2026,https://pubmed.ncbi.nlm.nih.gov/42193940/,Modelling the Neurobiology of ADHD Using Human iPSC Systems: A Multimodal Platform for Mechanistic Discovery,15,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Conscious thought is often treated as a special class of neural processing, distinct from the nonconscious computations that guide most behavior. Here I offer a different perspective, grounded in the neuroscience of decision-making. I argue that conscious thought arises not from a unique mechanism but from a distinctive use of neural representations already engaged in nonconscious thought. Nonconscious thoughts are structured as interrogations that yield provisional intentions-decision-like commitments that guide action or inquiry without entering awareness. Using examples from perceptual decision-making and neurophysiology, I suggest that such thoughts depend on persistent neural representations that encode not only potential actions but the questions that give them meaning. These knowledge states may also preserve source-sensitive structure that supports a minimal experiential organization even when they remain nonconscious. Conscious thought, on this account, emerges when such a state is reformatted for potential report to another mind, or to oneself, recruiting theory of mind and narrative structure and placing its content in a space presumed to be shared. This proposal identifies a tractable bridge from nonconscious decision mechanisms to phenomenal consciousness, thereby placing part of the hard problem within empirical reach.","[""Journal Article""]","[""Shadlen MN""]",10.1073/pnas.2601239123,Shadlen MN,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,22,Proc Natl Acad Sci U S A,eng,Shadlen MN,"[""Decision Making"", ""Consciousness"", ""Humans"", ""Neurosciences"", ""Thinking""]",e2601239123,42189989,pmc-id: PMC13229189;,2026 Jun 2,2026,https://pubmed.ncbi.nlm.nih.gov/42189989/,Conscious and nonconscious thought: Insights from the neuroscience of decision-making,123,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Knee osteoarthritis is a prevalent chronic condition in older adults, particularly postmenopausal women, affecting physical, psychological, social, and economic aspects of life. Existing neuromuscular exercise programs for knee osteoarthritis are often incomplete, focusing on isolated components such as strength or balance, without simultaneously targeting all key elements, including core stability, balance, and lower-limb strength. Additionally, these programs rarely address psychosocial factors or integrate pain neuroscience principles. Evidence suggests that combining a comprehensive neuromuscular exercise program with Pain Neuroscience Education (PNE) may offer superior benefits in reducing pain, improving function, and decreasing fear of movement compared with conventional exercise alone. This study aims to develop and present a novel integrated protocol and to evaluate its effectiveness compared with usual care in older women with knee osteoarthritis. This double-blind randomized controlled trial will enroll 60 women aged 60 years and older with knee osteoarthritis, randomly assigned to either an intervention group or a usual-care control group (30 per group). Outcome assessors and the statistician will be blinded to group allocation. The intervention group will receive an 8-week supervised neuromuscular exercise program combined with PNE, while the control group will receive usual care, defined as continuation of any ongoing medical management without any structured exercise or PNE added. The primary outcome is knee pain intensity, measured using the Visual Analog Scale. Secondary outcomes include functional disability, assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Knee Injury and Osteoarthritis Outcome Score (KOOS); physical performance, evaluated via the Timed Up and Go and Sit-to-Stand tests; balance assessed through plantar pressure analysis and the Berg Balance Scale; fear of falling; and pain-related psychological factors including catastrophizing, self-efficacy, and kinesiophobia. Knee proprioception, lower-limb muscle strength, and muscle activity will also be assessed. This protocol describes a novel, integrated approach that simultaneously targets the physical and psychosocial dimensions of knee osteoarthritis in older women. If the findings demonstrate effectiveness, this low-risk, non-pharmacological intervention has the potential to inform clinical rehabilitation guidelines and offer a scalable, accessible treatment option for this growing population. Study is registered in the Iranian Registry of Clinical Trials (IRCT20190224042827N7), registration date: 17 November 2025.","[""Journal Article"", ""Clinical Trial Protocol""]","[""Saki F"", ""Ramezani F"", ""Eizadi S"", ""Taheri R""]",10.1186/s13018-026-06973-3,Saki F,Journal of orthopaedic surgery and research,1749-799X,1,J Orthop Surg Res,eng,Taheri R,"[""Humans"", ""Osteoarthritis, Knee"", ""Female"", ""Exercise Therapy"", ""Randomized Controlled Trials as Topic"", ""Aged"", ""Double-Blind Method"", ""Patient Education as Topic"", ""Middle Aged"", ""Pain Management"", ""Neurosciences"", ""Kinesiophobia"", ""Combined Modality Therapy"", ""Pain Measurement""]",,42178552,pmc-id: PMC13386617;,2026 May 24,2026,https://pubmed.ncbi.nlm.nih.gov/42178552/,Neuromuscular exercise combined with pain neuroscience education for knee osteoarthritis management in older women: protocol for a randomized controlled trial,21,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"The study of rodent social behavior has shifted in recent years from relying on direct human observation to more nuanced approaches that integrate computational methods from artificial intelligence (AI) and machine learning. While conventional methods introduce bias and can fail to capture the complexity of rodent social interactions, modern approaches bridging computer vision, ethology, and neuroscience provide more multifaceted insights into behavior, which are particularly relevant to social neuroscience. Despite these benefits, integrating AI into social behavior research also poses several challenges. Here, we discuss the main steps involved and the tools available for analyzing rodent social behavior, examining their advantages and limitations. Additionally, we suggest practical solutions to address common hurdles, aiming to guide young investigators in adopting these methods and to stimulate further discussion among researchers regarding the evolving requirements of these tools in scientific applications.","[""Journal Article"", ""Review""]","[""Chindemi G"", ""Bellone C"", ""Girard B""]",10.1016/j.neubiorev.2026.106766,Chindemi G,Neuroscience and biobehavioral reviews,0149-7634,,Neurosci Biobehav Rev,eng,Girard B,"[""Animals"", ""Social Behavior"", ""Machine Learning"", ""Behavior, Animal"", ""Rodentia"", ""Artificial Intelligence"", ""Soft Computing"", ""Humans"", ""Neurosciences""]",106766,42177927,,2026 Sep,2026,https://pubmed.ncbi.nlm.nih.gov/42177927/,From eye to AI: Studying rodent social behavior in the era of machine learning,188,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Over the past two decades, zebrafish have become an increasingly prominent model organism for basic research, drug discovery, and toxicology. Its advantages combine low cost, high throughput amenability, high gene homology to humans, genetic flexibility and widespread use in academia. This animal model combines the ease of use of smaller animals (such as C. elegans and D. melanogaster) with the complexity of its vertebrate/mammalian counterparts, adding access to comprehensive phenotypic and behavioral studies without compromising high throughput and low cost. Similar to rodent models, a growing number of assays have recently been developed for zebrafish. This repertoire is rapidly growing and recent advancements in high-throughput techniques, computer-driven simulations, and automated tracking technologies/devices are starting to open new doors of research while simplifying the analysis of previously difficult-to-detect phenotypes. In parallel, the integration of artificial intelligence (AI) holds great promise for more effectively detecting and characterizing even the most subtle behavioral changes. Despite this rapid progress, the field would benefit from greater standardization of nomenclature, assays, and data formats. Here, we reviewed the literature associated with comprehensive zebrafish behavioral assays, with a particular focus on their applications in drug discovery and toxicology. We compiled the automated devices developed or adapted for these assays. We further discussed the advantages and limitations of these technologies and outlined potential future directions and needs in the field.","[""Journal Article"", ""Review""]","[""Nguyen QTN"", ""Giacomotto J""]",10.1016/j.neubiorev.2026.106774,Nguyen QTN,Neuroscience and biobehavioral reviews,0149-7634,,Neurosci Biobehav Rev,eng,Giacomotto J,"[""Animals"", ""Zebrafish"", ""Drug Discovery"", ""Phenotype"", ""Artificial Intelligence"", ""Behavior, Animal"", ""Neurosciences"", ""Humans"", ""Toxicology"", ""Models, Animal""]",106774,42176767,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42176767/,"Zebrafish behavioral phenotyping: Current assays, automated platforms, and the emerging need for AI in neuroscience, drug discovery and toxicology",187,PIgM9m77TgVQyiyw9,E5ItlhoU1SRxvUojQ
"Collaborative assessment formats have gained increasing attention in medical education due to their potential to foster clinical reasoning, teamwork, and to reduce examination-related stress. However, evidence for their feasibility and acceptance within summative undergraduate medical curricula remains limited. This study aimed to evaluate the feasibility and student perceptions of a case-based, collaborative summative examination (""whisper exam"") in undergraduate medical education. Specifically, we explored students' perceptions of stress, preparation effort, teamwork, and the alignment between self-assessement and actual examination performance. A single-center, descriptive feasibility study was conducted with third-year medical students (n = 350) following a laboratory course in hygiene, microbiology, and virology. Students completed a digital, case-based examination using key-feature questions in pairs. Examination performance was recorded at the team level. Student perceptions were collected via a post-exam voluntary questionnaire and analyzed descriptively. The overall pass rate was 93.1% (326/350 students). Survey responses were obtained from 190 students (54.3%). Most respondents reported lower perceived stress compared to individual examinations and described teamwork as constructive and enjoyable. Preparation effort was reported to be comparable to that required for individual examinations. Self-assessment of performance broadly aligned with examination outcomes, although a tendency toward underestimation was observed. The whisper exam was feasible to implement within a summative undergraduate curriculum and positively perceived by the majority of participating students. Findings suggest that collaborative, case-based examinations may complement existing assessment formats. Further research using comparative and multi-institutional designs is required to evaluate educational impact and validity.","[""Journal Article""]","[""Vorbeck L"", ""Ruesseler M"", ""Steinmetzer J"", ""Kohmer N"", ""Kempf VAJ"", ""Brandt C""]",10.1186/s12909-026-10018-y,Vorbeck L,BMC medical education,1472-6920,1,BMC Med Educ,eng,Brandt C,"[""Humans"", ""Feasibility Studies"", ""Education, Medical, Undergraduate"", ""Educational Measurement"", ""Students, Medical"", ""Clinical Competence"", ""Clinical Decision-Making"", ""Virology"", ""Microbiology"", ""Male"", ""Female"", ""Curriculum"", ""Surveys and Questionnaires""]",,42542555,pmc-id: PMC13428416;,2026 Aug 1,2026,https://pubmed.ncbi.nlm.nih.gov/42542555/,"The Frankfurt 'whisper exam' - a case-based collaborative summative examination to assess clinical decision-making skills in hygiene, microbiology and virology- feasibility and evaluation",26,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"The Pradhan Mantri Ayushman Bharat Health Infrastructure Mission (PM-ABHIM) scheme, supported by the World Bank, is establishing four zonal National Institutes of Virology (NIVs) in India. It is essential to identify the zonal disease and research priorities so as to focus research at zonal levels. This study reports a zonal viral disease prioritisation exercise to support outbreak response and collaborative research. It describes zonal-prioritised viral diseases, assesses concordance and differences in zonal priority lists and, and identifies cross‑cutting research themes and preparedness gaps using an multicriteria decision analysis (MCDA)‑based consensus process. We conducted a cross-sectional, multi-stakeholder consultative study across four geographical zones of India in March 2024. The zonal-level consultative workshops employed a systematic consensus-building approach using the modified One Health Zoonotic Disease Prioritisation (OHZDP) tool, adapted for emerging viral diseases and applied via MCDA. We identified zonal-level stakeholders, listed 40 viral diseases and categorised them into three groups: common occurrence (Group A), limited occurrence (Group B), and rare occurrences with a chance of emergence, evolution or importation (Group C). The stakeholders from state health departments, medical colleges, research institutes and the Virus Research and Diagnostic Laboratory (VRDL) network ranked the viral diseases and research themes in each zone. Spearman rank correlation was used to assess concordance of priority rankings between zones. A total of 186 participants (42-48 per zone) contributed to the four zonal workshops including collaborators from VRDL laboratories (26%), public health stakeholders from Integrated Disease Surveillance programme(IDSP) (28%), invited experts (21%), organisers (19%) and Indian Council of Medical Research (ICMR) representatives (6%). The key outcomes included the zone-specific lists of priority viral diseases in Groups A, B and C. There were zonal variations in viral disease prioritisation, reflecting local epidemiological patterns. Spearman rank correlation analysis showed moderate positive correlation between the Central and East zones (rho = 0.697, P = 0.031), whereas other pairwise comparisons were not statistically significant, which indicated both shared and distinct priority patterns within the zones. The top five priority viral diseases across zones included dengue, influenza, measles, Japanese encephalitis and hepatitis A. The research themes and subthemes were then decided for collaborative research. These multistakeholder consultations provided a novel, replicable template for prioritising viral diseases to develop strategies for mitigating the impact of future outbreaks through collaborative research. These zonal priorities may guide similar exercises at national, regional and global levels in future.","[""Journal Article""]","[""Pise K"", ""Tandale B"", ""Kumar N"", ""Barde P"", ""Munivenkatappa A"", ""Mathapati B"", ""Jadhav A"", ""Rawat P"", ""Basavaraj S"", ""Gaikwad S"", ""Deoshatwar A"", ""Pattassery SA"", ""Kutteyil S"", ""Pulinchani A""]",10.1186/s40249-026-01484-z,Pise K,Infectious diseases of poverty,2095-5162,1,Infect Dis Poverty,eng,Pulinchani A,"[""India"", ""Humans"", ""Pandemic Preparedness"", ""Cross-Sectional Studies"", ""Virus Diseases"", ""Disease Outbreaks"", ""Virology"", ""Research"", ""Academies and Institutes"", ""Stakeholder Participation"", ""Animals""]",,42522023,pmc-id: PMC13411115;,2026 Jul 28,2026,https://pubmed.ncbi.nlm.nih.gov/42522023/,Strengthening India's pandemic preparedness with the four zonal institutes of virology: stakeholder consultations for outbreak response and collaborative research priorities,15,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Artificial intelligence (AI) has rapidly emerged as a transformative tool in virology, offering new opportunities for the detection, classification, and surveillance of viral pathogens. Recent advances in machine learning, deep neural networks, and multimodal data analysis now enable the identification of viral signatures from genomic sequences, medical images, environmental samples, and social-media-derived epidemiological signals. This review provides a comprehensive overview of state-of-the-art AI methodologies applied to viral pathogen research, with a particular focus on image-based diagnostics, automated quality assessment of virology-related digital content, and predictive modelling for outbreak monitoring. We discuss how convolutional and transformer-based architectures are being used to classify infected tissues, detect viral particles, and support laboratory workflows. Furthermore, we highlight the emerging role of AI in evaluating the reliability of user-generated images and short videos related to infectious diseases, an area increasingly relevant in the age of misinformation. Challenges such as dataset bias, limited annotated virological images, ethical concerns, and the need for standardized quality-assessment pipelines are critically examined. Finally, we outline future research directions, including hybrid AI-biological models, AI-supported viral surveillance in healthcare environments, and the integration of explainable AI to enhance clinical trust.","[""Journal Article"", ""Review""]","[""Khelil H"", ""Palumbo R"", ""Roviello GN""]",10.3390/pathogens15070761,Khelil H,"Pathogens (Basel, Switzerland)",2076-0817,7,Pathogens,eng,Roviello GN,"[""Artificial Intelligence"", ""Humans"", ""Virus Diseases"", ""Viruses"", ""Virology"", ""Machine Learning""]",,42515088,pmc-id: PMC13415249;,2026 Jul 20,2026,https://pubmed.ncbi.nlm.nih.gov/42515088/,"AI-Driven Approaches for the Detection, Classification, and Surveillance of Viral Pathogens: Current Advances, Challenges, and Future Directions",15,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Intestinal organoids have emerged as a transformative model system in virology, bridging the gap between conventional cell lines and animal models by recapitulating the complex cellular diversity, three-dimensional architecture, and key functions of the human intestinal epithelium. This review highlights how this technology has enabled groundbreaking studies of enteric viruses, including the successful cultivation of previously uncultivable human norovirus, and has provided critical insights into the infection mechanisms of rotavirus, enterovirus A71, and Severe Acute Respiratory Syndrome Coronavirus 2. We discuss how emerging technologies, such as co-culture systems for host-microbiome interactions, vascularization techniques, and CRISPR/Cas9 gene editing, are being integrated with organoids to create more physiologically relevant microphysiological systems. Despite challenges related to immune component integration and model standardization, intestinal organoids offer a promising platform for elucidating virus-host interactions, advancing antiviral drug screening, and promoting personalized infectious disease research.","[""Journal Article"", ""Review""]","[""Ruting W"", ""Jiale L"", ""Hongxi W"", ""Zhenjin H"", ""Ruohan Z"", ""Yuanbo S"", ""Rongxin Z"", ""Hongzhen T"", ""Feng J""]",10.4014/jmb.2603.03016,Ruting W,Journal of microbiology and biotechnology,1017-7825,,J Microbiol Biotechnol,eng,Feng J,"[""Organoids"", ""Humans"", ""Animals"", ""Intestines"", ""Viruses"", ""Virology"", ""Intestinal Mucosa"", ""Host Microbial Interactions"", ""Models, Biological"", ""Microphysiological Systems"", ""Host-Pathogen Interactions"", ""Coculture Techniques""]",e2603016,42482485,pmc-id: PMC13389515;,2026 Jul 7,2026,https://pubmed.ncbi.nlm.nih.gov/42482485/,Intestinal Organoids as Models to Study Viruses: Current Application and Future Perspective,36,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"The 9th National Congress of the Italian Society for Virology (SIV-ISV), entitled ""One Virology-One Health"", took place in Turin at the Centro Congressi Lingotto from 22 to 24 June 2025. The meeting highlighted recent multidisciplinary and translational developments in virology, with a strong focus on the integration of the One Health perspective. Major themes included viral emergence and surveillance, genomic sequencing and bioinformatics, virus-host interactions, viral immunology and vaccines, structural and physical virology, environmental and food virology, zoonoses and animal infections, diagnostics and antiviral therapy, virus-based biotechnology and plant virology. The Congress aimed to: (i) bring together clinicians, basic researchers, veterinarians, environmental microbiologists, bioinformaticians, public-health professionals and industry to share methodologies and best practices; (ii) provide an interactive scientific environment promoting discussion and collaboration between senior investigators and trainees through plenaries, joint society sessions, invited talks, oral communications selected from abstracts, poster sessions, and mentoring panels; and (iii) identify priorities and inspire new research directions at the interface of human, animal and environmental health. More than 400 participants from national and international institutions attended the meeting, featuring distinguished plenary speakers, joint sessions with global networks, and numerous presentations of original unpublished data. This report summarizes the meeting's scientific highlights, cross-disciplinary discussions, and proposed actions to strengthen One Health surveillance, computational infrastructures, and translational applications of viral biology.","[""Conference Proceedings""]","[""De Filippis A"", ""Donalisio M"", ""Luganini A"", ""Caccuri F"", ""Esposito F"", ""Grandi N"", ""Zannella C"", ""Rubino L"", ""Tramontano E"", ""Vaccari G"", ""Galdiero M"", ""Caruso A""]",10.3390/v18060684,De Filippis A,Viruses,1999-4915,6,Viruses,eng,Caruso A,"[""Humans"", ""Virology"", ""Animals"", ""One Health"", ""Italy"", ""Societies, Scientific"", ""Virus Diseases"", ""Zoonoses"", ""Viruses""]",,42357693,pmc-id: PMC13307661;,2026 Jun 18,2026,https://pubmed.ncbi.nlm.nih.gov/42357693/,Report from the 9th Italian Society for Virology (SIV-ISV) 2025 Annual Meeting,18,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Studying the effects of mutations is central to virology. Deep mutational scanning (DMS) is a technique that couples high-throughput mutagenesis with deep sequencing to measure the effects of mutations in pooled assays. When adapted to viruses, DMS accelerates comprehensive measurement of mutational effects across viral genomes, mapping evolutionary constraints on viral proteins. Recently, DMS has been applied to a wider variety of problems in virology and viral evolution, quantifying the effects of mutation across host species, tissue environments, and immunological pressures. Since DMS was first applied to virology, synthetic biology has transformed the engineering of mutational libraries, opening new questions to exploration. With the technology now matured, DMS is poised to transform our understanding of viral evolution in new, exciting ways. This review will synthesize recent technological and conceptual advances in DMS methods being applied to virology, the insights it is yielding, and the opportunities for future studies.","[""Journal Article"", ""Review""]","[""Dorman J"", ""Bakhache W"", ""Dolan PT""]",10.1128/jvi.01784-25,Dorman J,Journal of virology,0022-538X,7,J Virol,eng,Dolan PT,"[""High-Throughput Nucleotide Sequencing"", ""Virology"", ""Viruses"", ""Mutation"", ""Genome, Viral"", ""Evolution, Molecular"", ""DNA Mutational Analysis"", ""Mutagenesis""]",e0178425,42267826,pmc-id: PMC13386985;,2026 Jul 21,2026,https://pubmed.ncbi.nlm.nih.gov/42267826/,Scanning the horizon: deep mutational scanning approaches in virology,100,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Significant advances in microscopy methods for biomedical applications have been made in the past two decades, and these methods are now being actively pursued for virus research [...].","[""Editorial"", ""Introductory Journal Article""]","[""Ray K""]",10.3390/v18050551,Ray K,Viruses,1999-4915,5,Viruses,eng,Ray K,"[""Microscopy"", ""Virology"", ""Viruses"", ""Humans"", ""Animals""]",,42198754,pmc-id: PMC13211748;,2026 May 12,2026,https://pubmed.ncbi.nlm.nih.gov/42198754/,Special Issue: Microscopy Methods for Virus Research,18,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"United States seeks to debar Ralph Baric for misleading NIAID on old coronavirus studies, which he disputes.","[""News""]","[""Cohen J""]",10.1126/science.aej0204,Cohen J,"Science (New York, N.Y.)",0036-8075,6800,Science,eng,Cohen J,"[""Humans"", ""Biomedical Research"", ""COVID-19"", ""National Institute of Allergy and Infectious Diseases (U.S.)"", ""Research Support as Topic"", ""SARS-CoV-2"", ""United States"", ""Virology"", ""Gain of Function Mutation""]",795-796,42166576,,2026 May 21,2026,https://pubmed.ncbi.nlm.nih.gov/42166576/,Virologist accused of starting COVID-19 fights funding ban,392,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Current generations are living through a historical event in virology: the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. If you asked people when the last major pandemic was, many would probably say the Spanish flu of 1918-1920. Pandemics happen more frequently than most people think (Sampath et al., Cureus 13:e18136-18144, 2021). There have been at least five recorded pandemics between the Spanish flu and the recent SARS-CoV-2 pandemic. While the SARS-CoV-2 pandemic has brought with it indescribable sorrow and pain, it has also increased people's awareness of the impact viruses can have on life on Earth. Terms such as hygiene, modes of infection, community spread, quarantine, vaccines, etc. have become part of our daily conversations. As this book's first chapter provided a basic review of proteomic technologies for virologists, this chapter provides a basic review of virology for proteomic scientists. While virologist may find this chapter unsatisfying, hopefully proteomic scientists will learn enough to be able to understand how proteomic technology can be used to further detail the structure, function, and life cycle of viruses. This chapter will provide both generic and specific examples of viral structures, how they infect cells, and their effects on both the infected cell and the entire organism.","[""Journal Article"", ""Review""]","[""Veenstra TD""]",10.1007/978-3-032-22340-1_2,Veenstra TD,Advances in experimental medicine and biology,0065-2598,,Adv Exp Med Biol,eng,Veenstra TD,"[""Humans"", ""SARS-CoV-2"", ""Virology"", ""Proteomics"", ""COVID-19"", ""Genome, Viral"", ""Viral Proteins"", ""Animals""]",29-49,42129070,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42129070/,Basic Virology,1511,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Just over 125 years has passed since the 'filterable' agents of tobacco mosaic disease and foot-and-mouth disease were first described as infectious, replicating entities smaller than bacteria. Today, viruses are formally classified into more than 16,000 species ranked into genera, families and higher taxa. The development of an official virus taxonomy has been overseen by an International Committee, first constituted in 1966 and renamed as the International Committee on Taxonomy of Viruses (ICTV) in 1975. Despite the engagement of the ICTV in virus taxonomy over the last 60 years, many aspects of virus classification and nomenclature may seem odd or sometimes incomprehensible to virologists more familiar with the taxonomy of cellular organisms. Who runs the ICTV? What are virus species demarcation criteria? Why have all virus species names become binomial? How can a sequence in a metagenomic dataset be assigned to a virus species? This article attempts to answer several such questions and outlines how a large, inclusive and global community of virologists has developed new and responsive policies for virus taxonomy in a decade when the pace of virus discovery has dramatically accelerated.","[""Journal Article"", ""Review""]","[""Smith DB"", ""Simmonds P"", ""Siddell SG""]",10.1099/jgv.0.002243,Smith DB,The Journal of general virology,0022-1317,5,J Gen Virol,eng,Siddell SG,"[""Viruses"", ""Virology"", ""Terminology as Topic"", ""Classification"", ""Genome, Viral""]",,42126918,pmc-id: PMC13170759;,2026 May,2026,https://pubmed.ncbi.nlm.nih.gov/42126918/,Virus taxonomy and the ICTV - 21 FAQs for the perplexed virologist,107,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"The use of plant virus vectors to express reporter genes has significantly enhanced the study of virus biology. In this communication we expand the list of virus vectored reporter systems to include the RUBY visible reporter. RUBY utilizes a three-enzyme system to produce betalain from the amino acid tyrosine, a natural pigment responsible for the bright red coloration in beets. To adapt this system for virus expression one of the three enzymes, L-DOPA 4,5-dioxygenase (DODA), was engineered into tobacco mosaic virus (TMV) and turnip mosaic virus (TuMV) vectors. The two remaining enzymes required for betalain production, P450 oxygenase CYP76AD1 and glucosyltransferase (GT), were transformed for expression in the host plant Nicotiana benthamiana. Inoculation of TMV and TuMV vectors expressing DODA onto transgenic CYP76AD1-GT plants resulted in the production of visible red tissues that corresponded with virus infection. The development of this system provides a non-invasive and robust means to directly visualize virus infection without the need for destructive sampling, special lighting equipment or enzymatic substrates.","[""Journal Article""]","[""Nunna H"", ""Lin J"", ""Koretsky M"", ""Culver JN""]",10.1016/j.virol.2026.110944,Nunna H,Virology,0042-6822,,Virology,eng,Culver JN,"[""Genes, Reporter"", ""Nicotiana"", ""Plant Diseases"", ""Genetic Vectors"", ""Tobacco Mosaic Virus"", ""Plants, Genetically Modified"", ""Potyvirus"", ""Glucosyltransferases"", ""Plant Viruses"", ""Virology""]",110944,42119419,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42119419/,A two-component RUBY reporter system to assess plant virus infection,621,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Protein language models (PLMs) enable functional analysis of divergent viral sequences without homology alignment. This review covers PLM architectures from sequence encoders through structure-aware architectures to generative models and assesses their application to orphan protein structure resolution, virosphere-wide functional classification, host factor identification, and therapeutic antibody optimization. Finally, the limitations of the current model in terms of interpretability and insufficient data representation are discussed while exploring future trends toward multimodal integration and the ""dry-wet"" experimental loop to accelerate the adoption of artificial intelligence in precision virology.","[""Journal Article"", ""Review""]","[""Luo L"", ""Li Y"", ""Huang T""]",10.1007/978-1-0716-5264-0_18,Luo L,"Methods in molecular biology (Clifton, N.J.)",1064-3745,,Methods Mol Biol,eng,Huang T,"[""Humans"", ""Virology"", ""Viruses"", ""Generative Artificial Intelligence"", ""Viral Proteins"", ""Large Language Models"", ""Models, Molecular""]",331-344,42108305,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42108305/,Protein Language Models in Virology: A Review of Advances and Applications,3033,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"The viral gene sequence is regarded as a kind of special text, which constitutes a core innovation in the application of large language models to virus research. This idea breaks free from the shackles of the traditional analysis framework and opens up a new way of computing to understand the evolution of the virus. Using this method, researchers can quickly and accurately locate the key mutation sites of the virus. This helps to detect emerging variant strains in time and assess their potential impact on transmissibility and pathogenicity. Especially importantly, this technology can also reconstruct the evolutionary path of the virus and realize real-time tracking of the mutation process. This provides a powerful tool for a systematic understanding of the adaptive evolution of the virus. These profound insights based on the big language model can be used as a theoretical basis for the development of targeted vaccines and drugs. Although the relevant computing technology is in the development stage, it has shown great potential to promote the transformation of virological research to a predictable direction.","[""Journal Article""]","[""Shen W"", ""Zhu L"", ""Li Y"", ""Huang T""]",10.1007/978-1-0716-5264-0_17,Shen W,"Methods in molecular biology (Clifton, N.J.)",1064-3745,,Methods Mol Biol,eng,Huang T,"[""Large Language Models"", ""Virology"", ""Mutation"", ""Evolution, Molecular"", ""Genome, Viral"", ""Viruses"", ""RNA, Viral"", ""Humans""]",321-329,42108304,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42108304/,RNA Large Language Models in Virology,3033,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"HIV env-pseudotyped viruses have become invaluable tools in HIV research. These recombinant viral particles are generated by co-transfecting HEK293T cells with an envelope cassette containing a heterologous HIV envelope glycoprotein and an envelope-deficient backbone that lacks one or more essential genes, to facilitate only single round infection. The non-infective, replication-deficient nature of env-pseudotyped viruses allows them to be safely handled in a BSL-2 facility. Because of their ability to express heterogeneously derived HIV envelopes, they serve as versatile tools for investigating co-receptor usage and tropism, screening of novel anti-HIV agents, studying neutralizing antibody responses, identifying novel broadly neutralizing antibodies (bNAbs), and for understanding the infectivity and mechanistic potential of different HIV strains. This review summarizes the current methods of generating HIV env-pseudotyped viruses using diverse packaging systems, and their varied applications, sources and limitations.","[""Journal Article"", ""Review""]","[""Vivekanandan S"", ""Sonawane A"", ""Hanna LE""]",10.1016/j.virusres.2026.199738,Vivekanandan S,Virus research,0168-1702,,Virus Res,eng,Hanna LE,"[""Humans"", ""env Gene Products, Human Immunodeficiency Virus"", ""Viral Pseudotyping"", ""HIV Infections"", ""HEK293 Cells"", ""HIV-1"", ""Virology""]",199738,42061759,pmc-id: PMC13188107;,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42061759/,HIV envelope pseudotyped virus- an indispensable tool in HIV research,368,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Located on the traditional and ancestral homelands of the Arapaho, Cheyenne, and Ute Nations, Colorado State University's Mountain Campus hosted the 25th Annual Rocky Mountain Virology Association meeting. The three-day event, held from 26 September to 28 September 2025, welcomed 152 participants focused on the following topics: viruses, prions, immunology, transmission, structural biology, and vector biology. This year's Randall Jay Cohrs Keynote Presentation summarized ongoing research on viral glycoproteins in relation to viral entry and assembly. Understanding the role of viral glycoproteins is essential in vaccine and antiviral development for enveloped RNA viruses. Alongside rigorous scientific discourse and networking, attendees made the most of their time by hiking amidst beautiful fall colors, wildlife, and young aspens starting the forest anew. On behalf of the Rocky Mountain Virology Association, this report summarizes select presentations from the 25th annual meeting.","[""Conference Proceedings""]","[""Byrne-Haber TJ"", ""Pham KN"", ""Joob A"", ""Pinto SM"", ""Ratnayake OC"", ""Thompson R"", ""Rovnak J"", ""Perera R""]",10.3390/v18040464,Byrne-Haber TJ,Viruses,1999-4915,4,Viruses,eng,Perera R,"[""Animals"", ""Humans"", ""Virology"", ""Prions"", ""Viruses"", ""Virus Diseases"", ""Virus Internalization"", ""Glycoproteins""]",,42043253,pmc-id: PMC13120276;,2026 Apr 14,2026,https://pubmed.ncbi.nlm.nih.gov/42043253/,25th Annual Meeting of the Rocky Mountain Virology Association,18,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Feline calicivirus (FCV) is widely used as a surrogate model to study calicivirus biology, including human noroviruses, for which robust cell culture systems are limited. The availability of concentrated and purified viral preparations is essential for structural, biochemical, and infectivity studies. Here, we describe and validate a polyethylene glycol (PEG-8000) precipitation method for the enrichment and purification of FCV from infected cell culture supernatants. PEG-8000 precipitation resulted in a more than 2-log increase in viral titers while markedly reducing contaminating cellular proteins. Purified viral particles retained infectivity and exhibited typical cytopathic effects, viral protein expression, and subcellular localization patterns during infection. Transmission electron microscopy confirmed the presence of non-enveloped viral particles with preserved morphology. Notably, both PEG-8000-purified and non-purified FCV preparations remained stable upon storage at -80 °C, maintaining infectivity after freezing. Compared with conventional ultracentrifugation-based approaches, this method is rapid, cost-effective, and does not require specialized equipment. Overall, PEG-8000 precipitation provides a reliable and straightforward strategy for FCV enrichment and purification and may be readily adapted for other members of the family Caliciviridae.","[""Journal Article""]","[""Gómez de la Madrid J"", ""Sosa-Mondragon SI"", ""Salazar-Villatoro L"", ""Gutiérrez-Escolano AL""]",10.1016/j.jviromet.2026.115390,Gómez de la Madrid J,Journal of virological methods,0166-0934,,J Virol Methods,eng,Gutiérrez-Escolano AL,"[""Polyethylene Glycols"", ""Calicivirus, Feline"", ""Animals"", ""Cats"", ""Chemical Precipitation"", ""Cell Line"", ""Virology"", ""Microscopy, Electron, Transmission""]",115390,41935580,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/41935580/,PEG-8000 precipitation as a rapid method for enrichment and purification of feline calicivirus,344,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"This review discusses pseudoviruses, which are chimeric viral particles constructed by replacing the envelope glycoproteins of viruses such as human immunodeficiency virus (HIV) or vesicular stomatitis virus (VSV) with those of target viruses, and their advantages in the study of highly pathogenic respiratory viruses. These systems serve as valuable tools for elucidating viral entry mechanisms, screening antiviral drugs, quantitatively assessing virus-neutralizing antibodies, and evaluating vaccine efficacy, while reducing the safety risks associated with live viruses. Despite limitations such as applicability primarily to enveloped viruses, ongoing technological advances continue to improve pseudovirus systems, increasing their utility in vaccine development, antiviral research, and rapid response to emerging infectious diseases.","[""Journal Article"", ""Review""]","[""Ota M"", ""Sano K"", ""Yoshihara K"", ""Watanabe S"", ""Hasegawa H"", ""Miyakawa K""]",10.1007/978-3-032-04153-1_22,Ota M,Advances in experimental medicine and biology,0065-2598,,Adv Exp Med Biol,eng,Miyakawa K,"[""Virology"", ""Viral Envelope"", ""Glycoproteins"", ""Orthomyxoviridae"", ""SARS-CoV-2"", ""Vaccine Development""]",361-372,41917406,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/41917406/,Applications of Pseudoviruses Bearing Glycoproteins of SARS-CoV-2 and Influenza Virus,1491,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Lumpy skin disease (LSD) poses a significant threat to cattle populations in India and worldwide, owing to its rapid spread, high morbidity rate, and continuous emergence of new variants. Reliable in vitro systems for LSD virus (LSDV) isolation are essential for diagnostic applications, virological studies, and vaccine development. Primary ruminant cells are commonly used for initial virus isolation; however, they suffer from limited availability and poor reproducibility. In this study, we systematically evaluated the susceptibility of five cell lines, Vero, MA-104, MDBK, BHK-21, and goat testis (GT) cells for the direct isolation and propagation of LSDV. Viral replication and infectivity were assessed using cytopathic effect (CPE) monitoring, conventional multi-target PCR, 50% tissue culture infectious dose (TCID₅₀) assay, and an indirect immunoperoxidase test (IPT) for antigen detection. Direct virus isolation from clinical scab material was successful only in MA-104 and GT cells. In contrast, Vero, MDBK, and BHK-21 cells did not support primary isolation but readily propagated LSDV after prior adaptation to GT cells. Subsequent one-step growth kinetics, performed at multiplicities of infection (MOI) of 0.1 and 0.01, further elucidated the distinct cell line-dependent replication patterns. Vero cells yielded the highest titers (106.33 TCID50/mL), whereas MA-104 cells supported sustained replication with peak titers of 105.5 TCID50/mL, demonstrating their strong capacity for propagation, comparable to other permissive continuous cell lines (MDBK and BHK-21 cells), which required prior viral adaptation. Unlike primary GT cells, MA-104 is a novel, permissive continuous cell line offering benefits such as reproducibility, ready availability, and reduced ethical concerns, making it a robust alternative for primary cell isolation. This study provides practical insights into the selection of appropriate cell lines and determination of optimal harvesting time points for efficient LSDV isolation and propagation, as well as downstream applications, such as pathogenesis studies and vaccine development.","[""Journal Article"", ""Evaluation Study""]","[""Todkari AM"", ""Kumar AP"", ""Kelwan AP"", ""Sahoo B"", ""Gurav A"", ""Mondal B"", ""Kumar A""]",10.1016/j.jviromet.2026.115389,Todkari AM,Journal of virological methods,0166-0934,,J Virol Methods,eng,Kumar A,"[""Animals"", ""Lumpy skin disease virus"", ""Cell Line"", ""Virus Cultivation"", ""Lumpy Skin Disease"", ""Cattle"", ""Virus Replication"", ""Goats"", ""Chlorocebus aethiops"", ""Cytopathogenic Effect, Viral"", ""Virology"", ""India""]",115389,41911978,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/41911978/,Identification of MA-104 cells as a novel continuous cell line for the direct primary isolation of lumpy skin disease virus,343,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Diagnostic inaccuracies are a major yet often overlooked threat to global health, leading to delayed treatment, preventable harm and systemic gaps in disease control. Among the most affected domains are Orthoflavivirus infections, which pose ongoing diagnostic challenges due to antigenic cross-reactivity, overlapping clinical symptoms and the narrow temporal sensitivity of standard tools such as serology and reverse transcription polymerase chain reaction. These constraints have led to widespread misdiagnoses and underreporting, ultimately hampering both effective clinical management and public health response. Recent advances in metagenomic and metatranscriptomic sequencing offer a transformative solution by enabling unbiased, simultaneous pathogen detection and real-time profiling of viral and host transcriptomics. In this review, we assess the diagnostic performance and translational value of these approaches in resolving Orthoflavivirus infections, with case examples from clinical settings in countries like the USA, UK, China and Germany which have already implemented these approaches into routine diagnosis in some settings. We examine key methodological considerations, including optimal sample timing, sample types and processing, sequencing strategy selection and the diagnostic performance of various platforms. We highlight the growing use of metatranscriptomics for detecting active infections, profiling viral and host responses, identifying coinfections and supporting real-time surveillance. We also discuss the key challenges such as technical expertise, lack of standardization, cost, turnaround time and regulatory approval that currently limit global implementation. Finally, we highlight emerging international efforts to integrate sequencing-based diagnostics into routine hospital workflows. Together, these innovations mark a critical shift toward precision diagnostics for Orthoflavivirus infections, with broad implications for clinical settings.","[""Journal Article"", ""Review""]","[""Hosen ME"", ""Horwood PF"", ""Sarker S""]",10.1099/jgv.0.002247,Hosen ME,The Journal of general virology,0022-1317,3,J Gen Virol,eng,Sarker S,"[""Metagenomics"", ""Humans"", ""RNA Viruses"", ""Virology"", ""Gene Expression Profiling"", ""RNA Virus Infections"", ""Transcriptome""]",,41911008,pmc-id: PMC13035173;,2026 Mar,2026,https://pubmed.ncbi.nlm.nih.gov/41911008/,Integrating metagenomics and metatranscriptomics into Orthoflavivirus diagnosis: a transformative approach for clinical virology,107,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Animal models are a cornerstone of basic and translational virology research, widely used to study viral pathogenesis and evaluate vaccines and therapeutics. However, growing ethical and scientific concerns, alongside recent National Institutes of Health (NIH) and Food and Drug Administration (FDA) initiatives, are accelerating a shift toward non-animal, human-relevant alternatives. Advanced cell- and tissue-based systems now offer powerful platforms to model human disease. This Gem outlines emerging tools and highlights their promise for virology research in a rapidly evolving regulatory and technological landscape.","[""Journal Article"", ""Review""]","[""Liu M"", ""Faris JG"", ""Panfil AR"", ""Warren CJ""]",10.1128/jvi.01326-25,Liu M,Journal of virology,0022-538X,4,J Virol,eng,Warren CJ,"[""Humans"", ""Animals"", ""Virology"", ""Translational Research, Biomedical"", ""Disease Models, Animal"", ""United States"", ""Virus Diseases""]",e0132625,41837642,pmc-id: PMC13098269;,2026 Apr 21,2026,https://pubmed.ncbi.nlm.nih.gov/41837642/,How new approach methods are reshaping virology research,100,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Organoids have revolutionized human biomedical research since their development in 2010. However, as nearly 75% of human infectious diseases originate in animals, animal-derived organoids are essential to complement human models, yet their development in veterinary contexts remains scarce. Organoids replicate native tissue architecture, enabling species-specific and comparative studies of viral infection and host response. Thus, animal organoids represent a powerful field in organoid technology, advancing cross-species virology research and strengthening strategies for zoonotic disease preparedness.","[""Journal Article"", ""Review""]","[""García-Rodríguez I"", ""García-Dorival I"", ""Alonso C"", ""Cuesta-Geijo MÁ""]",10.1128/jvi.02197-25,García-Rodríguez I,Journal of virology,0022-538X,3,J Virol,eng,Cuesta-Geijo MÁ,"[""Animals"", ""Organoids"", ""Humans"", ""Virus Diseases"", ""Zoonoses"", ""Viral Zoonoses"", ""Biomedical Research"", ""Host-Pathogen Interactions"", ""Virology""]",e0219725,41773860,pmc-id: PMC13011349;,2026 Mar 24,2026,https://pubmed.ncbi.nlm.nih.gov/41773860/,Animal organoids as transformative platforms for viral infections and zoonotic cross-species viral research,100,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"The Virology Department of the Czechoslovak army, established in response to the need for a specific approach to biological threats, was initially subordinated to the Military Institute of Hygiene and Epidemiology (founded in 1957), and later to the Central Military Medical Institute. Within this department, a systematic Virus Strain Bank was established that contained highly contagious viruses and bacteria used for diagnostic purposes and to develop defensive methods against biological threats. The preserved strains included viruses causing hemorrhagic fevers, encephalitis, yellow fever, and Rocky Mountain spotted fever, as well as the variola minor virus. The Virus Strain Bank enabled testing of the capabilities to detect and identify dangerous agents, as well as the development of specific and neutralizing antibodies against them. It was therefore essential for defensive and diagnostic purposes in the context of protection against the use of biological weapons. Keywords: virus strains; viral infection diagnosis, biological threat.","[""Journal Article"", ""Historical Article"", ""English Abstract""]","[""Holub M"", ""Mankovecký L"", ""Kubátová H"", ""Pavliš O"", ""Pajer P""]",,Holub M,Klinicka mikrobiologie a infekcni lekarstvi,1211-264X,3,Klin Mikrobiol Infekc Lek,cze,Pajer P,"[""Humans"", ""History, 20th Century"", ""Virus Diseases"", ""Czechoslovakia"", ""Military Medicine"", ""Virology""]",101-104,41734221,,2025 Sep,2025,https://pubmed.ncbi.nlm.nih.gov/41734221/,[A brief history and significance of the Czechoslovak army's Antiviral Serum Bank],31,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Hepatitis A virus (HAV) remains a significant global public health concern, particularly as a foodborne pathogen. Despite advances in vaccination and sanitation, HAV continues to cause outbreaks, especially in regions with uneven immunization coverage or inadequate hygiene infrastructure. This review comprehensively examines HAV from virological, clinical, and epidemiological perspectives, highlighting its pathogenesis, transmission routes, genomic diversity, and foodborne risks. We discuss the evolving global epidemiology of HAV, emphasizing the shift from high to low endemicity in vaccinated populations and the emergence of susceptible cohorts in moderately developed regions. The review underscores the challenges in foodborne HAV detection, including the limitations of current methods and the promise of emerging technologies like reverse transcription digital polymerase chain reaction (RT-dPCR) for enhanced sensitivity. Additionally, we summarize emerging antiviral approaches in food safety control, including plant-derived bioactive compounds and edible coatings, for controlling HAV transmission through the food chain. Finally, we present an overview of WHO-recommended vaccination strategies based on endemicity levels-targeted immunization for high-risk groups in low-endemic areas, universal childhood vaccination in moderate-endemic regions, and reliance on naturally acquired immunity in high-endemic zones. Our synthesis aims to bridge gaps between virology, clinical medicine, and food safety, offering insights for interdisciplinary collaboration in HAV prevention and control.","[""Journal Article"", ""Review""]","[""Shi JM"", ""Zhou SY"", ""Ren F""]",10.1007/s10482-026-02264-3,Shi JM,Antonie van Leeuwenhoek,0003-6072,3,Antonie Van Leeuwenhoek,eng,Ren F,"[""Humans"", ""Hepatitis A"", ""Hepatitis A virus"", ""Public Health"", ""Food Safety"", ""Foodborne Diseases"", ""Virology"", ""Animals""]",,41718774,,2026 Feb 20,2026,https://pubmed.ncbi.nlm.nih.gov/41718774/,"Bridging virology, public health, and food safety: a comprehensive review of hepatitis A virus",119,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Viruses are obligate parasites that rely extensively on host cellular machinery to complete their life cycles. Therefore, examining the fundamental nature behind how viruses interact with their hosts can teach us more about the pathogenesis of these microbes while also contributing to our overall understanding of essential cell biological processes. In a 2021 mSphere of Influence article, the use of live-cell imaging to uncover a unique mechanism of viral assembly was discussed. In this Full Circle review, we highlight the high-resolution imaging techniques currently revolutionizing virology research and discuss how they can be utilized to advance our ability to identify and interrogate novel virus-host interactions.","[""Journal Article"", ""Review""]","[""Amaya I"", ""Spriggs CC""]",10.1128/msphere.00816-25,Amaya I,mSphere,2379-5042,3,mSphere,eng,Spriggs CC,"[""Host-Pathogen Interactions"", ""Host Microbial Interactions"", ""Viruses"", ""Humans"", ""Virology"", ""Animals"", ""Virus Assembly"", ""Microscopy"", ""Virus Physiological Phenomena""]",e0081625,41711433,pmc-id: PMC13037411;,2026 Mar 31,2026,https://pubmed.ncbi.nlm.nih.gov/41711433/,High-resolution imaging techniques to interrogate virus-host interactions,11,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Oncolytic viruses (OVs) constitute a promising class of cancer therapeutics engineered to selectively replicate in and lyse malignant cells while sparing normal tissues. Among these, recombinant Herpes Simplex Virus type 1 (HSV-1), generated through targeted deletion of immediate-early (IE) genes, has emerged as a leading candidate, with several vectors currently advancing to phase III clinical trials. Genetic alterations are typically introduced into the HSV-1 genome via homologous recombination using shuttle vectors; however, isolation of recombinant viruses from parental populations by plaque purification remains labor-intensive and technically demanding. This limitation primarily results from the low efficiency of homologous recombination and the frequent persistence of parental virus, which often exhibits a replicative advantage over recombinant variants. In this study, a novel purification protocol incorporating a GFP-PAC co-expression cassette was developed and optimized to enable simultaneous puromycin selection and fluorescence-based identification of recombinant viral constructs. This dual-selection approach significantly accelerates and simplifies the isolation of recombinant HSV-1, enhancing both efficiency and purity. The optimized protocol provides a robust, scalable strategy for generating recombinant HSV-1 with broad applicability in vaccine development, gene therapy, and fundamental virology research.","[""Journal Article""]","[""Kelishadi M"", ""Tabarraei A"", ""Azadmanesh K""]",10.1016/j.jviromet.2026.115364,Kelishadi M,Journal of virological methods,0166-0934,,J Virol Methods,eng,Azadmanesh K,"[""Herpesvirus 1, Human"", ""Green Fluorescent Proteins"", ""Animals"", ""Recombination, Genetic"", ""Genetic Vectors"", ""Virology"", ""Humans"", ""Staining and Labeling"", ""Genes, Reporter"", ""Cell Line""]",115364,41687970,,2026 May,2026,https://pubmed.ncbi.nlm.nih.gov/41687970/,Optimization of a GFP-PAC co-expression cassette-based purification system for efficient construction and rapid screening of recombinant HSV-1,342,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Detecting and measuring HIV reservoirs, neutralizing antibodies, and restriction factors are important for HIV cure research and the development of new therapeutics and vaccines. Here we describe the development and validation of several HIV Rev-dependent indicator cell lines for these purposes. These reporter cells derive from different T-lymphoblast cell lines, including Molt4-CCR5, SupT1-CCR5, CEM-SS, A3R5, and from the adherent TZM cell platform based on HeLa clone JC53. These cells express CD4, CXCR4, and various levels of CCR5. We compared these cell lines for responsiveness to both X4 and R5-tropic viruses, and confirmed that reporter expression in these cells is not affected by stimulation from mitogens but is responsive to HIV Tat and Rev, reducing non-specific reporter induction from the leaky LTR promoter. To validate the sensitivity of the Rev-dependent reporter cell systems, we conducted a viral dilution assay with three primary HIV-1 clade C swarms from an adult in Malawi. We also validated the systems for quantifying antibody neutralization and screening restriction factors; these systems are also sensitive for viral outgrowth assays for quantifying viral reservoirs in clinical and basic research settings. Given that the systems can measure HIV accurately in complex environments with mitogens or other substances, they can be used for versatile applications, such as quantifying latent reservoirs, testing inhibitory compounds, conducting neutralizing antibody assays, and identifying new restriction factors.","[""Journal Article""]","[""Spear M"", ""Choi J"", ""Hetrick B"", ""Lee J"", ""Lê-Bury G"", ""Vo TT"", ""Han Y"", ""Liang H"", ""Guo J"", ""Yu D"", ""Iyer S"", ""Mwandumba HC"", ""Russell DG"", ""Wu Y"", ""Gludish DW""]",10.1186/s12977-026-00675-8,Spear M,Retrovirology,1742-4690,1,Retrovirology,eng,Gludish DW,"[""Humans"", ""HIV-1"", ""Genes, Reporter"", ""Antibodies, Neutralizing"", ""Cell Line"", ""HIV Antibodies"", ""rev Gene Products, Human Immunodeficiency Virus"", ""HIV Infections"", ""Virology"", ""Receptors, CCR5""]",3,41673644,pmc-id: PMC12903711;,2026 Feb 11,2026,https://pubmed.ncbi.nlm.nih.gov/41673644/,"Versatile HIV Rev-dependent reporter cell system for stringent and sensitive quantification of viral reservoirs, neutralizing antibodies, and restriction factors",23,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Human noroviruses (hNoVs) are the leading cause of foodborne gastroenteritis worldwide, yet progress in infectivity-based studies has been hindered by the lack of robust virus purification methods that preserve infectivity. Here, we evaluated porcine gastric mucin (PGM)-coated magnetic beads as a sample preparation tool for concentrating and purifying infectious hNoVs from complex clinical and food matrices for use in two emerging infectivity models, human intestinal enteroids (HIEs) and zebrafish embryos/larvae. Using 18 hNoV strains across multiple genotypes, we observed variable recovery efficiencies (0.03–40%) from stool suspensions, with PGM beads often enhancing viral binding to HIEs but sometimes reducing replication (ten hNoV strains replicated without beads but only seven demonstrated replication with addition of beads), likely due to partial blocking of cell entry. In oyster homogenates spiked with hNoV GII.4[P16], bead aggregation and toxicity issues were mitigated by sample dilution, use of zebrafish larvae instead of embryos, and incorporation of an additional purification step, enabling detection at 105 to 106 genome copies per reaction. No significant cytotoxicity was detected in HIEs or zebrafish larvae under optimized conditions. Our findings indicate that PGM bead-based purification can be a valuable optional step for infectivity assays when working with samples containing strong inhibitors. This protocol provides a practical bridge between environmental/food hNoV detection and infectivity assessment in advanced model systems.","[""Journal Article"", ""Evaluation Study""]","[""Tan MTH"", ""Wales SQ"", ""Li D""]",10.1007/s12560-026-09681-7,Tan MTH,Food and environmental virology,1867-0334,1,Food Environ Virol,eng,Li D,"[""Animals"", ""Zebrafish"", ""Humans"", ""Gastric Mucins"", ""Norovirus"", ""Swine"", ""Caliciviridae Infections"", ""Feces"", ""Intestines"", ""Virology"", ""Gastroenteritis"", ""Ostreidae""]",9,41619096,,2026 Jan 31,2026,https://pubmed.ncbi.nlm.nih.gov/41619096/,Using Porcine Gastric Mucin Coated Magnetic Beads to Concentrate and Purify Infectious Human Noroviruses for Infectivity Assays with Human Intestinal Enteroids and Zebrafish,18,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Ever since the advent of recombinant DNA technology in the early 1970s concerns have been expressed about the misuse potential of this and subsequent biotechnology breakthroughs. This article focuses on the securitization of gain-of-function (GOF) virology research in the United States, utilizing an updated theoretical framework that distinguishes between ""riskification"" and ""threatification."" The paper examines three distinct cases, two historical, one ongoing. It argues that early attempts to govern GOF research primarily employed a riskification approach, characterized by self-governance by the scientific community. However, the controversy over the origins of the COVID-19 pandemic led to a shift toward threatification, bringing in high-level political actors like the U.S. President and Congress, resulting in the adoption of more restrictive, legally-enforced oversight measures. The article concludes that the application of this theoretical distinction provides a better understanding of how the governance of dual-use research has evolved in the United States.","[""Journal Article""]","[""Kelle A"", ""Dando M""]",10.1017/pls.2025.10018,Kelle A,Politics and the life sciences : the journal of the Association for Politics and the Life Sciences,0730-9384,1,Politics Life Sci,eng,Dando M,"[""United States"", ""Virology"", ""Humans"", ""COVID-19"", ""Politics"", ""SARS-CoV-2""]",141-158,41612816,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/41612816/,Gain-of-function virology as dual-use research of concern: Variations of securitization in the United States,45,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Cell lines are essential tools in virology for propagating viruses for characterization studies. However, reliance on a few historically popular lines-such as Vero, BHK-21, and MDCK-can introduce bias and obscure important aspects of viral biology, such as entry mechanisms and replication dynamics. A review of over 6,000 publications revealed that a small number of cell lines are used disproportionately, often due to historical precedence and general permissiveness for viral infection. Gene expression analysis showed that while these lines are enriched for pro-viral process genes, many underutilized cell lines from diverse tissue types also exhibit similar profiles. This review calls for a more strategic, molecularly informed approach to cell line selection, including the development of molecular databases for non-human cell lines, identification of virologically relevant traits, and broader use of biologically diverse panels. Such a data-driven strategy is especially vital for studying emerging and zoonotic viruses, where accurate modeling of host-virus interactions is important. Expanding and refining cell line use will improve reproducibility and yield more accurate insights into viral pathogenesis.","[""Journal Article"", ""Review""]","[""Kim JV"", ""Pickering BS""]",10.3389/fcimb.2025.1675100,Kim JV,Frontiers in cellular and infection microbiology,2235-2988,,Front Cell Infect Microbiol,eng,Pickering BS,"[""Animals"", ""Humans"", ""Cell Line"", ""Virology"", ""Viruses"", ""Virus Replication"", ""Virus Cultivation"", ""Host-Pathogen Interactions""]",1675100,41586304,pmc-id: PMC12827766;,2025,2025,https://pubmed.ncbi.nlm.nih.gov/41586304/,Cell line bias in virus research: implications for viral propagation and biological interpretation,15,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Fifty years ago, at the remarkably young age of 37, David Baltimore received the Nobel Prize (with Howard Temin and Renato Dulbecco) for ""discoveries concerning the interaction between tumor viruses and the genetic material of the cell."" David was a prolific scientist whose work spanned many topics, but he was first and foremost a virologist. His recent passing invites us to reflect on a remarkable intellectual trajectory that began with seminal discoveries in virology, broadened to encompass major advances in cancer biology and immunology, and culminated in a legacy-sustained by the many scientists he trained-that will continue to shape modern biomedicine for years to come.","[""Journal Article"", ""Historical Article""]","[""Andrews NC"", ""Daley GQ""]",10.1073/pnas.2528373123,Andrews NC,Proceedings of the National Academy of Sciences of the United States of America,0027-8424,4,Proc Natl Acad Sci U S A,eng,Daley GQ,"[""Virology"", ""Humans"", ""Male"", ""History, 20th Century"", ""History, 21st Century"", ""Mentors"", ""Nobel Prize"", ""Oncogenic Viruses"", ""Host-Pathogen Interactions"", ""Neoplasms""]",e2528373123,41557805,pmc-id: PMC12846782;,2026 Jan 27,2026,https://pubmed.ncbi.nlm.nih.gov/41557805/,"David Baltimore: Scientist, leader, and mentor",123,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Artificial intelligence (AI), including machine learning (ML) and deep learning (DL), has become a crucial element in medical virology, transforming the research and treatment of viral illnesses. AI is transforming viral research and clinical practice by improving genomic analysis, diagnostic accuracy, treatment innovation, and epidemiological modeling. AI's contributions are significant and extensive, encompassing the analysis of intricate viral genomes, the expedited development of antiviral treatments, and the forecasting of disease evolution. Notwithstanding obstacles like data privacy, algorithmic bias, and ethical dilemmas, the amalgamation of AI with advanced technologies, including quantum computing and protein language models, is poised to herald a new epoch of virological advancement. This letter emphasizes the necessity for interdisciplinary collaboration to use AI's transformational capabilities while maintaining stringent ethical monitoring in combating viral infections.","[""Letter""]","[""Ibrahim MN""]",10.7754/Clin.Lab.2025.250474,Ibrahim MN,Clinical laboratory,1433-6510,1,Clin Lab,eng,Ibrahim MN,"[""Humans"", ""Artificial Intelligence"", ""Deep Learning"", ""Machine Learning"", ""Virology"", ""Virus Diseases""]",,41543085,,2026 Jan 1,2026,https://pubmed.ncbi.nlm.nih.gov/41543085/,Artificial Intelligence as a Catalyst for Advancements in Medical Virology,72,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"The 3rd International Conference of the World Society for Virology (WSV 2025) was held in May 6-8, 2025, in Kuala Lumpur, Malaysia. WSV2025 adopted the integrative theme ""The Virosphere of Our Cellular World."" This theme denotes the universal and intricate relationships between viruses and their cellular hosts across all domains of life. The conference attracted 291 participants from 27 countries, featuring a scientific program of 83 talks and numerous poster presentations spanning human, animal, plant, insect, and bacterial viruses at basic, clinical and applied levels. This report summarizes the program highlights, key scientific discussions, and significant outcomes of the conference, confirming the WSV's role as a unifying platform for the global virology community since its founding in 2017.","[""Conference Proceedings""]","[""Söderlund-Venermo M"", ""Johari NAB"", ""Muhamad A"", ""Yusoff K"", ""Abdelwahab SF"", ""Moore MD"", ""Wilson WC"", ""Venter M"", ""Malik YS"", ""Saxena SK"", ""Abdelwhab EM"", ""Winter S"", ""Fielding BC"", ""Vakharia VN"", ""Varma A"", ""Kuhn RJ"", ""Abdel-Moneim AS""]",10.1016/j.virol.2026.110792,Söderlund-Venermo M,Virology,0042-6822,,Virology,eng,Abdel-Moneim AS,"[""Animals"", ""Humans"", ""Societies, Scientific"", ""Virology"", ""Virus Diseases"", ""Viruses""]",110792,41530010,,2026 Mar,2026,https://pubmed.ncbi.nlm.nih.gov/41530010/,Meeting report: The 3(rd) international conference of the World Society for Virology (WSV 2025) - The Virosphere of Our Cellular World,616,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"In recent decades, there has been an increased interest in viruses of microorganisms (VoM) and international efforts to gather researchers interested in them. Here, we describe the 1st Brazilian Symposium on Viruses of Microorganisms (BrVoM), held on 1 August 2025 at the Federal University of Minas Gerais (UFMG, Belo Horizonte, Brazil) with institutional support from the Federal University of Alfenas (UNIFAL) and the Brazilian Society for Virology (SBV). The symposium greatly surpassed expectations, gathering nearly 300 attendees from all Brazilian geographical regions. The scientific program included keynote and thematic lectures covering bacteriophages, fungal viruses, giant viruses, and microbial resources regulation. The event was remarkable for its collaborative spirit and inclusion of early career attendees. The success of this first edition highlights the vitality of the Brazilian community working on microbial viruses and sets the stage for future editions.","[""Conference Proceedings""]","[""Abrahão JS"", ""Coelho LFL"", ""Witt ASA"", ""Alves AKDNN"", ""Guimarães ACDS"", ""Silva BSR"", ""Neiva BN"", ""Oliveira BF"", ""Dias J"", ""Carvalho JVRP"", ""Lopes LP"", ""Rodrigues MFDR"", ""Barcelos MG"", ""Arias NEC"", ""Zerbini P"", ""Santos VLD"", ""Leal-Dutra CA"", ""de Farias ST"", ""Rodrigues RAL"", ""Cortines JR"", ""Thiemann OH"", ""Boratto P"", ""Freitas MHA"", ""Almeida GMF""]",10.3390/v17121603,Abrahão JS,Viruses,1999-4915,12,Viruses,eng,Almeida GMF,"[""Brazil"", ""Viruses"", ""Virology"", ""Bacteriophages"", ""Humans"", ""Fungal Viruses"", ""Giant Viruses""]",,41472273,pmc-id: PMC12737712;,2025 Dec 11,2025,https://pubmed.ncbi.nlm.nih.gov/41472273/,First Brazilian Symposium on Viruses of Microorganisms (BrVoM 2025),17,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"The yeast Saccharomyces cerevisiae has long been an essential model in molecular biology. Its exceptional recombination capacity and efficiency in propagating large DNA fragments surpass those of organisms such as Escherichia coli or Bacillus subtilis. These properties make S. cerevisiae the preferred choice for cloning and manipulating bacterial and viral genomes. Among the available methods, transformation-associated recombination (TAR) cloning has established itself as a reliable and effective approach for isolating and manipulating large DNA molecules. To date, numerous viral genomes have been successfully cloned in yeast. The ability to modify these cloned genomes and reconstitute infectious viral particles highlights the role of S. cerevisiae as a powerful bioengineering platform. Its versatility addresses various biomedical needs, including virus research, vaccine production, and gene therapy. Combining efficiency, reliability, and flexibility, S. cerevisiae stands out as an invaluable tool for advancing biomedical applications and tackling modern biological challenges.","[""Journal Article"", ""Review"", ""English Abstract""]","[""Rey C"", ""Agaoua A"", ""Erbs P""]",10.1684/vir.2025.1114,Rey C,"Virologie (Montrouge, France)",1267-8694,6,Virologie (Montrouge),fre,Erbs P,"[""Saccharomyces cerevisiae"", ""Synthetic Biology"", ""Cloning, Molecular"", ""Genome, Viral"", ""Recombination, Genetic"", ""Transformation, Genetic"", ""Virology""]",397-410,41457956,,2025 Dec 1,2025,https://pubmed.ncbi.nlm.nih.gov/41457956/,[Contribution of yeast to synthetic virology],29,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"The yeast Saccharomyces cerevisiae has long been an essential model in molecular biology. Its exceptional recombination capacity and efficiency in propagating large DNA fragments surpass those of organisms such as Escherichia coli or Bacillus subtilis. These properties make S. cerevisiae the preferred choice for cloning and manipulating bacterial and viral genomes. Among the available methods, transformation-associated recombination (TAR) cloning has established itself as a reliable and effective approach for isolating and manipulating large DNA molecules. To date, numerous viral genomes have been successfully cloned in yeast. The ability to modify these cloned genomes and reconstitute infectious viral particles highlights the role of S. cerevisiae as a powerful bioengineering platform. Its versatility addresses various biomedical needs, including virus research, vaccine production, and gene therapy. Combining efficiency, reliability, and flexibility, S. cerevisiae stands out as an invaluable tool for advancing biomedical applications and tackling modern biological challenges.","[""Journal Article"", ""Review"", ""English Abstract""]","[""Rey C"", ""Agaoua A"", ""Erbs P""]",10.1684/vir.2025.1121,Rey C,"Virologie (Montrouge, France)",1267-8694,6,Virologie (Montrouge),fre,Erbs P,"[""Saccharomyces cerevisiae"", ""Synthetic Biology"", ""Cloning, Molecular"", ""Genome, Viral"", ""Recombination, Genetic"", ""Transformation, Genetic"", ""Virology""]",77-88,41457953,,2025 Dec 1,2025,https://pubmed.ncbi.nlm.nih.gov/41457953/,[Contribution de la levure à la virologie synthétique],29,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Northern Australia has long been a hotbed of arboviral discovery, and collections of viral isolates from Northern Australia represent an invaluable resource for both our knowledge of viral diversity and for disease preparedness and treatment. While discovery of novel viruses via classical virology methods is on the decline, next generation sequencing offers the possibility to speed up viral discovery, albeit at the expense of the collection of valuable life history data. By sequencing unknown isolates from historical viral collections, we may leverage both the rich data collected through classical virology and the power of identification using contemporary sequencing technologies. In the present study, we sequenced 76 historical viral isolates held at the Berrimah Veterinary Laboratory in Darwin, northern Australia, for which serological typing had yielded ambiguous results. We determined that 43 of these isolates belong to the genera Hapavirus, Orbivirus, and Orthobunyavirus. Several of these isolates are putatively novel genotypes or potential taxa, which has significant potential implications for human and animal health. This study demonstrates the utility of historical collections for viral discovery and characterisation and how considerable past efforts to isolate and characterise viruses can be enhanced using next generation sequencing approaches.","[""Journal Article""]","[""Sistrom M"", ""Neave M"", ""Joseph A"", ""Newberry K"", ""Andrews H"", ""Shilton C"", ""Bhardwaj V"", ""Weir R""]",10.3390/v17111513,Sistrom M,Viruses,1999-4915,11,Viruses,eng,Weir R,"[""High-Throughput Nucleotide Sequencing"", ""Animals"", ""Phylogeny"", ""Australia"", ""Genome, Viral"", ""Viruses"", ""Virology"", ""Orbivirus"", ""Genotype"", ""Orthobunyavirus"", ""Humans""]",,41305533,pmc-id: PMC12656724;,2025 Nov 18,2025,https://pubmed.ncbi.nlm.nih.gov/41305533/,Leveraging Classical Virology and High Throughput Sequencing for Viral Discovery Using a Historical Viral Collection,17,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Nucleus-forming jumbo bacteriophages display a surprisingly intricate replication cycle inside of bacterial host cells, challenging the long-standing paradigm of prokaryotic simplicity. The phage nucleus encloses phage DNA in a protein shell, strictly uncouples transcription from translation, and facilitates selective protein import and messenger RNA (mRNA) export, serving the same major functions as the eukaryotic nucleus. Infection of host cells by these phages begins with the formation of a transcriptionally active membrane-bound early phage infection vesicle, demonstrating that these phages are capable of constructing subcellular compartments composed of lipids and proteins. Here, we review the current body of literature revealing the complexities of nucleus-forming phages and the history of the major discoveries. Studies of these phages are revealing new insights into basic principles of subcellular organization, viral speciation, and intracellular viral competition.","[""Journal Article"", ""Review"", ""Research Support, Non-U.S. Gov't"", ""Research Support, N.I.H., Extramural""]","[""Birkholz EA"", ""Armbruster EG"", ""Pogliano J""]",10.1146/annurev-genet-111523-102019,Birkholz EA,Annual review of genetics,0066-4197,1,Annu Rev Genet,eng,Pogliano J,"[""Bacteriophages"", ""Viral Replicase Complex Proteins"", ""Virology"", ""Viral Genome Packaging"", ""Virus Internalization""]",51-68,41290383,pmc-id: PMC12908238;manuscript-id: NIHMS2142351;,2025 Nov,2025,https://pubmed.ncbi.nlm.nih.gov/41290383/,The Biology of Nucleus-Forming Jumbo Phages,59,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Super-resolution microscopy (SRM) has exerted a pivotal influence on virology by surpassing the diffraction limits of conventional optical microscopy, enabling unprecedented visualization of viral structures and dynamics. Techniques such as stimulated emission depletion, photoactivated localization microscopy, stochastic optical reconstruction microscopy, and structured illumination microscopy facilitate nanoscale imaging of viruses, providing critical insights into the viral life cycle and virus-host interactions. We examine the principles and advancements in SRM techniques and their applications in virology. We discuss the development and selection of fluorescent probes, highlighting specific labeling methods. Key applications of SRM are illustrated through case studies of viruses such as influenza, HIV, and SARS-CoV-2, demonstrating the technology's impact on understanding viral mechanisms. We also explore future developments in SRM, including enhanced spatial and temporal resolution, and integration with technologies such as single-molecule imaging and fluorescence resonance energy transfer, positioning SRM as a pivotal tool for advancing viral research and therapeutic development.","[""Journal Article"", ""Review""]","[""Liu M"", ""Zhang L"", ""Huang S"", ""Xu Y"", ""Jin C""]",10.1002/jbio.202500461,Liu M,Journal of biophotonics,1864-063X,3,J Biophotonics,eng,Jin C,"[""Humans"", ""Viruses"", ""Microscopy"", ""Virology"", ""SARS-CoV-2"", ""Microscopy, Fluorescence"", ""Fluorescent Dyes""]",e202500461,41239836,,2026 Mar,2026,https://pubmed.ncbi.nlm.nih.gov/41239836/,"Application of Super-Resolution Microscopy in Virology Research: Principles, Technological Advances, and Analysis of the Viral Life Cycle",19,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Pandemic preparedness is critical as we face potential threats of infectious diseases. Systems virology and collaborative/responsive science are key infrastructures that facilitated scientific advances during the SARS-CoV-2 pandemic. As discussed here, G2P-Japan and other consortia are examples of systems virology-based research collaborations that can guide future responses.","[""Journal Article""]","[""Sato K""]",10.1016/j.chom.2025.10.007,Sato K,Cell host & microbe,1931-3128,11,Cell Host Microbe,eng,Sato K,"[""Humans"", ""COVID-19"", ""SARS-CoV-2"", ""Pandemics"", ""Japan"", ""Virology""]",1807-1810,41232511,,2025 Nov 12,2025,https://pubmed.ncbi.nlm.nih.gov/41232511/,Systems virology as a cornerstone for pandemic responsiveness: A G2P-Japan perspective,33,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Medical virology requires students to master complex concepts in a limited timeframe, yet traditional lectures often struggle to sustain engagement and ensure long-term retention. Serious games have emerged as promising tools to promote active learning. Building on the success of BacteriaGame, ViroGame was developed to reinforce virology knowledge through gamification. This study evaluated its effectiveness in enhancing student engagement, knowledge mobilization, and supervisor-perceived feasibility for curricular integration. A total of 318 learners participated in ViroGame sessions during the 2023-2024 academic year. Of these, 266 students/residents completed a structured questionnaire assessing with likert scale [1-5] gameplay fluidity, knowledge consolidation, perceived difficulty and potential integration with BacteriaGame. Nine supervisors also provided evaluations on rule clarity, session management and educational value. Data were analyzed using descriptive statistics, Mann-Whitney U tests and Chi-squared tests, with qualitative feedback examined thematically. Residents rated gameplay fluidity significantly higher than students (4.4/5 vs. 4.1/5; p = 0.039). Both groups reported high knowledge mobilization scores (students 4.5/5; residents 4.3/5; p = 0.378). Nearly half perceived some content as exceeding expected knowledge, despite alignment with national standards (47.4% vs. 41.8%; p = 0.482). A greater proportion of students than residents reported difficulties with virological concepts (78.9% vs. 60.3%; p = 0.021), particularly regarding diagnostic methods and viral structures. Supervisors rated the game positively, endorsing its use primarily as a revision tool. ViroGame is a well-received, effective and engaging tool for teaching medical virology. It promotes active learning, collaboration and knowledge retention while addressing the inherent complexity of virology. Further controlled studies are planned to evaluate its long-term impact on learning outcomes and exam performance.","[""Journal Article""]","[""Portet Sulla V"", ""Marot S"", ""Dutkiewicz M"", ""Berti V"", ""Grimal A"", ""Ghelfenstein-Ferreira T"", ""Solis M"", ""Charre C"", ""Salmona M"", ""Thibault V"", ""Pronier C"", ""Pineros N"", ""Lescat M"", ""Besombes J"", ""Vauloup-Fellous C""]",10.1186/s12909-025-08086-7,Portet Sulla V,BMC medical education,1472-6920,1,BMC Med Educ,eng,Vauloup-Fellous C,"[""Humans"", ""Virology"", ""Students, Medical"", ""Female"", ""Male"", ""Problem-Based Learning"", ""Video Games"", ""Surveys and Questionnaires"", ""Curriculum"", ""Adult"", ""Education, Medical, Undergraduate"", ""Educational Measurement""]",1485,41131602,pmc-id: PMC12548107;,2025 Oct 23,2025,https://pubmed.ncbi.nlm.nih.gov/41131602/,ViroGame: a serious game for medical virology education - a feedback report,25,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"The integration of computational advances in microscopy has enhanced our ability to visualise immunological events at scales. However, data generated with these techniques is often complex, multi-dimensional, and multi-modal. Data science and artificial intelligence (AI) play a key role in untangling the wealth of information hidden in microscopy data by enhancing image processing, automating image analysis, and assisting in interpreting the results. With this Review, we aim to inform the reader about the advances in the fields of fluorescence and electron microscopy with a focus on their applications to immunology and virology, and the AI approaches to aid image acquisition, analysis, and data interpretation. We also outline the open-source tools for image acquisition and analysis and how these tools can be programmed for an image-informed, AI-assisted acquisition.","[""Journal Article"", ""Review""]","[""Morone D"", ""D'Antuono R""]",10.3389/fimmu.2025.1610345,Morone D,Frontiers in immunology,1664-3224,,Front Immunol,eng,D'Antuono R,"[""Humans"", ""Artificial Intelligence"", ""Software"", ""Image Processing, Computer-Assisted"", ""Virology"", ""Allergy and Immunology"", ""Animals"", ""Microscopy""]",1610345,41098742,pmc-id: PMC12518252;,2025,2025,https://pubmed.ncbi.nlm.nih.gov/41098742/,AI-based hardware and software tools in microscopy to boost research in immunology and virology,16,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"My arrival into this world came quickly, according to my mother, and it feels like my life has mirrored that rapid beginning. I have enjoyed a rich, varied, and stimulating life and career that have gone through several phases. I credit genetics, my family, technological advances, and many environmental factors for shaping my career. Being a virologist allowed me to be curious and creative and to make several unexpected discoveries. This has been a fun and rewarding journey, but it wasn't always easy. I am not accustomed to talking about myself, but I am happy to share some scientific achievements and professional challenges with the hope that they illustrate the joy of research and the need for resilience and persistence to assure progress and acceptance of unexpected results.","[""Journal Article"", ""Historical Article"", ""Review"", ""Research Support, N.I.H., Extramural"", ""Research Support, U.S. Gov't, Non-P.H.S.""]","[""Estes MK""]",10.1146/annurev-virology-092623-111211,Estes MK,Annual review of virology,2327-056X,1,Annu Rev Virol,eng,Estes MK,"[""Humans"", ""History, 20th Century"", ""History, 21st Century"", ""Gastrointestinal Tract"", ""Viruses"", ""Virology""]",1-21,40998740,,2025 Sep,2025,https://pubmed.ncbi.nlm.nih.gov/40998740/,A Fascination with Gastrointestinal Viruses,12,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Electron microscopy (EM) and especially three-dimensional (3D) EM techniques have become established methods in structural virology. Investigation of virus-induced alteration of the cellular ultrastructure, such as Zika virus (ZIKV)-induced replication factories or coronavirus replication organelles, demands 3D imaging. Transmission electron microscopy (TEM) tomography is a widely used method, despite its limitation to samples with a thickness of up to 200 nm. Focused ion beam-scanning electron microscopy (SEM)-tomography can produce 3D data of larger volumes with isotropic, albeit typically lower resolution. Alternative techniques, such as block face-scanning electron microscopy (BF-SEM), SEM array tomography, or TEM imaging of serial sections are used for imaging of larger volumes. However, compared to the previously mentioned techniques, these techniques come at the cost of much lower resolution along the Z-axis of the sample. A technique that provides 3D information of samples up to 1 µm thickness with isotropic resolution of a few nanometers is scanning transmission electron microscopy (STEM) tomography. Here, we present a protocol for the preparation of high-pressure frozen, freeze-substituted, and resin-embedded virological specimens and their analysis using STEM tomography. This protocol benefits from the advantages of room temperature imaging while preserving the biological ultrastructure in a near-native state. We show two representative examples for questions that can be answered using STEM tomography. First, we apply the protocol for studying virion morphogenesis of a recombinant vesicular stomatitis virus (VSV). The STEM tomograms offer information on recombinant VSV budding that is otherwise not accessible by 2D imaging. Second, we show correlative light and electron microscopy (CLEM) using Foerster resonance energy transfer (FRET) imaging and STEM tomography (FRET-3D-CLEM) of EF-C peptide nanofibrils. This recently published combination gives new insights into the uptake and disassembly of infection-enhancing peptide nanofibrils, especially profiting from the large volume that is accessible by STEM tomography.","[""Journal Article"", ""Video-Audio Media"", ""Research Support, Non-U.S. Gov't""]","[""Wieland JG"", ""La Roche J"", ""Bergner T"", ""Habisch R"", ""Puschmann E"", ""Soza-Ried J"", ""Schütz D"", ""Münch J"", ""Walther P"", ""Dass M"", ""Read C""]",10.3791/68568,Wieland JG,Journal of visualized experiments : JoVE,1940-087X,222,J Vis Exp,eng,Read C,"[""Virology"", ""Microscopy, Electron, Scanning Transmission"", ""Electron Microscope Tomography"", ""Imaging, Three-Dimensional"", ""Cell Culture Techniques"", ""Preservation, Biological""]",,40853940,,2025 Aug 6,2025,https://pubmed.ncbi.nlm.nih.gov/40853940/,"Scanning Transmission Electron Microscopy Tomography in Virology: 3D Imaging of High-pressure Frozen, Freeze-substituted Samples",,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Virus infections in plants are a major threat to crop production and sustainable agriculture, which results in significant yield losses globally. The past decade has seen the development and deployment of sophisticated high-throughput omics technologies including genomics, transcriptomics, proteomics, and metabolomics, in order to try to understand the mechanisms underlying plant-virus interactions and implement strategies to ameliorate crop losses. In this review, we discuss the current state-of-the-art applications of such key omics techniques, their challenges, future, and combinatorial use (e.g., single cell and spatial omics coupled with super-resolution high-throughput imaging methods and artificial intelligence-based predictive models) to obtain new mechanistic insights into plant-virus interactions, which could be exploited for more effective plant disease management and monitoring.","[""Journal Article"", ""Review"", ""Research Support, Non-U.S. Gov't""]","[""Samarskaya V"", ""Spechenkova N"", ""Kalinina NO"", ""Love AJ"", ""Taliansky M""]",10.3390/v17070986,Samarskaya V,Viruses,1999-4915,7,Viruses,eng,Taliansky M,"[""Plant Diseases"", ""Plant Viruses"", ""Proteomics"", ""Genomics"", ""Metabolomics"", ""Plants"", ""Host-Pathogen Interactions"", ""Virology""]",,40733603,pmc-id: PMC12299024;,2025 Jul 15,2025,https://pubmed.ncbi.nlm.nih.gov/40733603/,The Emerging Role of Omics-Based Approaches in Plant Virology,17,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"The term 'entomo-virology' arose because of the confluence of entomology and virology, focused on deepening the knowledge about the interactions between vectors and viruses and the aspects that involve hosts and the environment. Based on this, entomo-virological surveillance was proposed, aiming to develop tools that strengthen prevention for arboviral disease and vector control strategies. This review aims to present a narrative synthesis regarding the component elements of the concept of entomo-virology. In addition, the applications and tools for the surveillance of viruses and vectors, their implementation challenges, and perspectives are discussed.","[""Journal Article"", ""Review""]","[""Lemos PDS"", ""Pacheco MMM"", ""Nascimento BLSD"", ""Coelho MS"", ""Franco Filho LC"", ""Dias DD"", ""Sena L"", ""Silva SPD"", ""Sallum MAM""]",10.3390/pathogens14070699,Lemos PDS,"Pathogens (Basel, Switzerland)",2076-0817,7,Pathogens,eng,Sallum MAM,"[""Animals"", ""Insect Vectors"", ""Humans"", ""Virology"", ""Entomology""]",,40732745,pmc-id: PMC12299351;,2025 Jul 15,2025,https://pubmed.ncbi.nlm.nih.gov/40732745/,The Frontier of Entomo-Virology: Applications and Tools for Virus and Vector Surveillance,14,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"During the 56th annual meeting of the International Committee on Taxonomy of Viruses (ICTV), held in Bari, Italy, in August 2024, two technical proposals were presented. The first called for amended versions of accepted taxonomic proposals to be named in such a way to ensure that they are readily accessible on the ICTV website (2024.001G). The second proposed a substantial reformatting of the ICTV statutes and codes to produce a more unified text after the numerous changes made to both documents in previous years (2024.002G). Finally, the ICTV Executive Committee (EC) nominated Professor Stuart Siddell as a Life Member of the ICTV for his work over four decades on virus taxonomy, including 16 years as a member of the EC (2024.003G).","[""Journal Article"", ""Research Support, N.I.H., Extramural""]","[""Zerbini FM"", ""Crane A"", ""Kuhn JH"", ""Simmonds P"", ""Lefkowitz EJ"", ""Ictv Taxonomy Summary Consortium"", ""ICTV Taxonomy Summary Consortium""]",10.1099/jgv.0.002116,Zerbini FM,The Journal of general virology,0022-1317,7,J Gen Virol,eng,Ictv Taxonomy Summary Consortium,"[""Viruses"", ""Classification"", ""Terminology as Topic"", ""Virology"", ""Humans"", ""Italy""]",,40711893,pmc-id: PMC12446860;,2025 Jul,2025,https://pubmed.ncbi.nlm.nih.gov/40711893/,"Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses (ICTV) - General taxonomy proposals, 2025",106,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Environmental sampling of photosynthetic microorganisms and their viruses plays a critical role in understanding contemporary marine and freshwater biodiversity and ecosystem dynamics as well as the impacts of climate change-related factors (e.g., rising temperatures and acidification) on evolutionary trajectories of species and community composition. Unfortunately, the diversity of the virosphere does not support a single universal sampling and experimental workflow. Indeed, each virus system has unique features, which require modifications to standard protocols in virology to accomplish research goals. Although virus discovery and characterization require approaches that are specific to the target system, for all viruses, the research aims are similar: isolate the virus; determine host range; confirm productive infection; and characterize the virus, the host, and virus-host dynamics. Robust descriptions of virus-host systems consist minimally of elucidating morphology, physiology, biochemistry, and omics profiles. Further information may be obtained by manipulating the system by changing factors such as multiplicity of infection, temperature, pH, host-switch, directed evolution, or applying drugs to observe virus-host system response. Our laboratory studies viruses across domains of life (Archaea, Bacteria, and Eukarya). In this report, we detail methods for sampling photosynthetic microbes from the euphotic zone of freshwater and marine environments with focus on isolating bacteriophage (i.e., cyanophage) of cyanobacteria. Cyanobacteria are keystone species critical to primary production and nutrient cycling in these aquatic ecosystems. The described workflow extends from sampling waters at different depths to characterizing virus-host system features using liquid and solid media culture, advanced molecular/genetic methods, and analytical approaches. The methods described are adaptable to bacteriophage and virus discovery in virus-host systems across domains of life.","[""Journal Article"", ""Video-Audio Media"", ""Research Support, U.S. Gov't, Non-P.H.S.""]","[""Heng S"", ""Ceballos RM""]",10.3791/68379,Heng S,Journal of visualized experiments : JoVE,1940-087X,221,J Vis Exp,eng,Ceballos RM,"[""Photosynthesis"", ""Viruses"", ""Virology""]",,40690404,,2025 Jul 3,2025,https://pubmed.ncbi.nlm.nih.gov/40690404/,Environmental Sampling of Photosynthetic Microbes and Their Viruses: From Field to Lab,,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"The Global Virus Network (GVN) is a voluntary consortium of virology laboratories and affiliated scientists that seek to prevent and control global viral threats. The meetings of the GVN are characterized by academic, health center, government, and industry participation, sharing information that is designed to further the mutual mission. In September 2024, the meeting in Durban, South Africa, highlighted diseases and investigators from Africa, and paid special attention to pandemic preparedness. Selected highlights from the meeting are presented here, along with a call-to-action in defense of global partnerships for research in the origins of human and animal viruses, the risk to humans from other animal sources, the pathogenesis of given viruses, and their prevention and treatment. Discussions of laboratory discovery science are juxtaposed with development of vaccines, antiviral drugs, immunotherapies, and innovative field strategies for control of viral diseases.","[""Conference Proceedings""]","[""Bartlett ML"", ""Perumal R"", ""Vermund SH"", ""Abdool Karim S""]",10.3390/v17060819,Bartlett ML,Viruses,1999-4915,6,Viruses,eng,Abdool Karim S,"[""Humans"", ""Virus Diseases"", ""Africa"", ""Virology"", ""Animals"", ""Viruses"", ""Antiviral Agents"", ""South Africa"", ""Pandemics""]",,40573408,pmc-id: PMC12197373;,2025 Jun 5,2025,https://pubmed.ncbi.nlm.nih.gov/40573408/,Navigating Virology's Frontiers in Africa: Global Virus Network 2024 Durban Meeting,17,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"The Epstein-Barr virus, was discovered in 1964, and was the first identified human oncogenic virus that can persist asymptomatically for life. It is associated with a broad spectrum of diseases in the pediatric population, including benign pathologies such as infectious mononucleosis or severe ones such as hemophagocytic lymphohistiocytosis, among others.Professor Sir Anthony Epstein (1921-2024), an English pathologist and virologist, was its co-discoverer with the Irish virologist Yvonne Barr (1932-2016). We will review the history, and the particularities of the serendipitous character that ended with the virus identification, together with the biography of both scientists who gave rise to this famous eponym, which endures to this day.","[""Journal Article"", ""Historical Article""]","[""Donoso Fuentes A"", ""Arriagada Santis D""]",10.5546/aap.2025-10694.eng,Donoso Fuentes A,Archivos argentinos de pediatria,0325-0075,6,Arch Argent Pediatr,eng,Arriagada Santis D,"[""History, 20th Century"", ""History, 21st Century"", ""Virology"", ""Herpesvirus 4, Human"", ""Humans"", ""Epstein-Barr Virus Infections""]",e202510694,40526683,,2025 Dec 1,2025,https://pubmed.ncbi.nlm.nih.gov/40526683/,A Fog-Delayed Flight and the Story of Sir Michael Anthony Epstein (1921-2024) and Yvonne Margaret Barr (1932-2016),123,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Viral reverse genetics involves the process of generating synthetic viruses from purified DNA or RNA, enabling the artificial engineering of viral genes. In recent decades, viral reverse genetics has been effectively implemented for numerous viruses that pose significant threats to public health and the global economy. Viral reverse genetics techniques enable researchers to elucidate the molecular mechanisms of viral infection and transmission, trace viral evolution and replication, and study the impact of viral mutations on the virus life cycle. In this chapter, we describe a general reverse genetic strategy for rescuing DNA and RNA viruses.","[""Journal Article""]","[""Zhang Y"", ""Zhang T"", ""Xiong Y"", ""Zheng C"", ""Li L""]",10.1007/978-1-0716-4615-1_26,Zhang Y,"Methods in molecular biology (Clifton, N.J.)",1064-3745,,Methods Mol Biol,eng,Li L,"[""Reverse Genetics"", ""RNA Viruses"", ""DNA Viruses"", ""Virus Replication"", ""RNA, Viral"", ""Humans"", ""Virology"", ""Genome, Viral""]",307-318,40515921,,2025,2025,https://pubmed.ncbi.nlm.nih.gov/40515921/,Reverse Genetics-Based Methodology for Molecular Virology Study,2940,A5OsI3uyAB4Upt7u9,g711jAsWSxe1ygsfg
"Isoquercitrin (ISO), a neuroprotective flavonoid, alleviates ischemic stroke (IS) by inhibiting ferroptosis. In present study, we explored the mechanism of ISO attenuates neuronal ferroptosis in IS. HT22 cells and primary neurons underwent oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic in vitro IS. Dual‑luciferase reporter assays detected luciferase activity. H3K9 acetylation levels at the RBM15 promoter were assessed by ChIP. The m6A modification of SLC25A28 mRNA was analyzed by MeRIP. The binding of RBM15 and IGF2BP3 to SLC25A28 mRNA was examined via RIP. Lipid and intracellular ROS levels were measured by C11-BODIPY and DCFH-DA staining. The levels of ferroptosis-related indicators were determined with commercial kits. Cell viability was examined using the CCK-8 assay. In vivo, the middle cerebral artery occlusion (MCAO) rat model was used to explore the effect of ISO. ISO protected against OGD/R-induced ferroptosis and restored viability. ISO inhibited neuronal ferroptosis by reducing RBM15 expression. ISO suppressed RBM15 via SIRT1-mediated H3K9 deacetylation. Subsequently, RBM15 promoted m6A modification of SLC25A28 mRNA to enhance its stability. Reversal of ISO-mediated ferroptosis suppression by SLC25A28 overexpression was partly counteracted by RBM15 knockdown. In the MCAO model, ISO reduced infarct volume, lowered MDA levels, and restored GPX4 expression, which were partly reversed by RBM15 overexpression. ISO promoted SIRT1-mediated H3K9 deacetylation at the RBM15 promoter to suppress its transcription. RBM15 downregulation inhibited SLC25A28 stability by m6A-IGF2BP3-dependent, ultimately attenuating neuronal ferroptosis in IS.","[""Journal Article""]","[""Cai S"", ""Zhou S"", ""Wang Y"", ""Li Z"", ""Long H"", ""Chen Y"", ""Wu M"", ""Li X""]",10.1007/s40199-026-00629-7,Cai S,"Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences",1560-8115,2,Daru,eng,Li X,"[""Animals"", ""Ferroptosis"", ""Sirtuin 1"", ""RNA-Binding Proteins"", ""Quercetin"", ""Neurons"", ""Promoter Regions, Genetic"", ""Ischemic Stroke"", ""Rats"", ""Neuroprotective Agents"", ""Acetylation"", ""Male"", ""Mice"", ""Histones"", ""Rats, Sprague-Dawley"", ""Cell Line"", ""Cell Survival""]",,42545594,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545594/,Isoquercitrin suppresses neuronal ferroptosis in ischemic stroke via SIRT1-mediated deacetylation of H3K9 at the RBM15 promoter,34,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Subdural hematoma (SDH) represents a growing hemorrhagic concern among ischemic stroke survivors receiving long-term antithrombotic therapy. Although aging, multimorbidity, and antithrombotic exposure are all contributors to SDH, there is limited evidence on subtype-specific risk factors in stroke populations, and existing studies have often overlook competing mortality. Practical tools to guide individualized antithrombotic stewardship remain absent from contemporary guidelines. A nationwide retrospective cohort study was conducted using Korean National Health Insurance Service data from 2010 to 2023. Adults with incident ischemic stroke were followed for traumatic and non-traumatic SDH using Fine-Gray competing risk regression and cause-specific hazard models. Variables were selected using the Akaike information criterion to develop integer-based prediction scores. Internal validation used cross-validation, and external validation applied the models to an independent ischemic stroke cohort from the UK Biobank. A web-based calculator was employed to facilitate clinical use. Among 506,746 ischemic stroke survivors (median follow-up 57.9 months), 7,425 developed traumatic SDH and 1,705 developed non-traumatic SDH. The 10-year cumulative incidences were 1.94% for traumatic and 0.43% for non-traumatic SDH. Older age, multimorbidity, and antithrombotic exposure were independently associated with increased risk. Traumatic SDH demonstrated stronger associations with antiplatelet therapy and diabetes, whereas non-traumatic SDH was most strongly linked to warfarin use. Warfarin emerged as the only modifiable risk factor. Prediction models showed clear risk-gradient separation for both subtypes and maintained stratification performance in the UK Biobank cohort. A web-enabled platform provided individualized 10-year cumulative incidence estimates using routinely available clinical variables. This nationwide competing-risk analysis identified subtype-specific associations of aging, comorbidities, and antithrombotic exposure with SDH risk among ischemic stroke survivors. Because the models predict SDH specifically rather than overall intracranial hemorrhage, they are intended to support risk-stratified surveillance, monitoring, and patient counseling rather than to guide antithrombotic cessation in isolation, as such decisions require balancing ischemic recurrence against the full spectrum of major bleeding risk.","[""Journal Article""]","[""Kim J"", ""Choi S"", ""Jung S"", ""Lee JH"", ""Ha J"", ""Eun J""]",10.1007/s10143-026-04414-7,Kim J,Neurosurgical review,0344-5607,1,Neurosurg Rev,eng,Eun J,"[""Humans"", ""Hematoma, Subdural"", ""Aged"", ""Ischemic Stroke"", ""Female"", ""Risk Factors"", ""Retrospective Studies"", ""Male"", ""Middle Aged"", ""Aged, 80 and over"", ""Republic of Korea"", ""Risk Assessment"", ""Incidence""]",,42545518,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545518/,Risk prediction of traumatic and non-traumatic subdural hematoma after ischemic stroke: a nationwide competing-risk model with external validation,49,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Blood proteins may play causal roles in cardiovascular diseases (CVDs) such as heart failure (HF) and peripheral artery disease (PAD). Proteome-wide Mendelian randomization (MR) has been widely used to prioritize drug targets for CVD in European populations, but its application to non-European populations remains limited. We conducted a proteome-wide MR analysis to evaluate the potential causal effects of 2,922 plasma proteins on five CVDs-atrial fibrillation (AF), coronary artery disease (CAD), HF, ischemic heart disease (IHD), and PAD. Analyses were performed across African (n = 931), East Asian (n = 262), and European (n = 10,840) populations using genetic instrument data from the UK Biobank cohort. Significant associations were further examined with genetic colocalization to strengthen causal inference. Using MR and colocalization analyses, we identified 53 significant protein-CVD associations across multi-populations, including 16 in African, six in East Asian, and 31 in European populations, respectively. Cross-population comparisons revealed four protein-CVD associations unique to African population and another four specific to East Asian population. Integration with clinical trial data prioritized 14 protein-disease pairs as promising candidates for therapeutic development or drug repurposing. Our findings highlight the value of proteome-wide MR in evaluating drug target applicability across populations. Several protein-disease associations were population-specific, emphasizing the need for inclusive genetic research to inform precision medicine in CVD prevention and treatment.","[""Journal Article""]","[""Zhong H"", ""Zhu J"", ""Liu S"", ""Wong HTH"", ""Zhang Y"", ""Luu HN"", ""Wu Q"", ""Wang X"", ""Wu L""]",10.1007/s00438-026-02458-4,Zhong H,Molecular genetics and genomics : MGG,1617-4623,1,Mol Genet Genomics,eng,Wu L,"[""Humans"", ""Mendelian Randomization Analysis"", ""Cardiovascular Diseases"", ""Proteome"", ""Blood Proteins"", ""Genome-Wide Association Study"", ""Polymorphism, Single Nucleotide"", ""Genetic Predisposition to Disease"", ""European People""]",,42545500,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545500/,Cross-population proteome-wide mendelian randomization study identifies likely causal proteins for cardiovascular diseases,301,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Inherited hypertrophic cardiomyopathy (HCM) is considered a disease of the cardiac sarcomere and caused by pathogenic variants present in genes that encode sarcomeric proteins. The human TNNC1 gene is a designated HCM-susceptibility gene encoding the troponin C (TnC) protein, which is expressed in both cardiac and type I slow skeletal muscles and abbreviated as cTnC and ssTnC respectively. HCM patients have been reported to exhibit skeletal muscle weakness and reduced exercise tolerance. Patients bearing TNNC1 cardiac pathogenic variants also express it in type I fibers of their slow skeletal muscles. We hypothesized that the presence of TNNC1 HCM variants in type I fibers may decrease force generating capabilities and alter fatigue resistance of slow skeletal muscles. To address this, we examined the impact of HCM Tnnc1 variants in the soleus muscles of two HCM knock-in mouse models A8V+/-, A8V-/-, and C84Y+/- and their respective wild type (WT) controls. At high stimulation frequencies, we found that A8V-/- soleus muscles had lower tetanic force production than WT, however no differences in fatigue when comparing fatigue indices for either of the variants. The muscles were evaluated by comparing % specific force (N/cm2)-variant and both A8V-/- and C84+/- had increased responsiveness at low stimulation frequencies. Fiber type analysis uncovered an increase in abundance of type I fibers in A8V-/- soleus, however no other differences were observed in fiber-type percentage of either mouse model. Comparison of the cross-sectional areas (CSA) of type I fibers in soleus muscles revealed lower average values for A8V+/+ and A8V-/-, however an increase in C84Y+/- relative to controls. Examination of the CSA of type IIa fibers uncovered decreased values for both A8V+/- and A8V-/- with no changes in C84Y+/- soleus. Histological evaluation of A8V+/- and A8V-/- soleus muscles revealed central nucleation and the detection of embryonic myosin heavy chain by immunofluorescence suggested the presence of mild regeneration. In contrast, no histopathological changes were detected in the C84Y+/- soleus muscle. Serum myokines were also measured to assess systemic impacts of the pathogenic variants and alterations in the physical activity of the mice but no significant changes were found. Taken together our results suggest that the HCM A8V variant alters force production in soleus muscle that may be attributed to fiber atrophy and heightened pathophysiology.","[""Journal Article""]","[""Patel S"", ""da Silva Santos GL"", ""Florence J"", ""Kahmini AR"", ""Shi Y"", ""Garcia MR"", ""Gordon BS"", ""Chase PB"", ""Solís C"", ""Laitano O"", ""Pinto JR"", ""Parvatiyar MS""]",10.1007/s10974-026-09736-z,Patel S,Journal of muscle research and cell motility,0142-4319,3,J Muscle Res Cell Motil,eng,Parvatiyar MS,"[""Animals"", ""Mice"", ""Cardiomyopathy, Hypertrophic"", ""Muscle Fibers, Slow-Twitch"", ""Troponin C"", ""Muscle, Skeletal"", ""Humans"", ""Male""]",,42545432,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545432/,Hypertrophic cardiomyopathy-linked Tnnc1 variants are associated with distinct myopathic changes in slow skeletal muscle of mice,47,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"To investigate the characteristics of blood pressure (BP) circadian rhythm disruption and its relationship with prognosis in patients with acute anterior ST-elevation myocardial infarction (STEMI) after emergency percutaneous coronary intervention (PCI). A total of 330 patients with anterior STEMI who underwent emergency PCI were enrolled in this study (MI group). Additionally, 131 physical examination patients were selected as the control group. Based on 24-h ambulatory blood pressure monitoring (ABPM) results, BP rhythm in both groups was classified into Extreme dipper, Dipper, Non-dipper, and Reverse dipper. The characteristics of BP rhythm were compared between the two groups. Patients with anterior MI were followed up for 1 year postoperatively. The occurrence of major adverse cardiovascular events (MACE) was compared among subgroups with different BP rhythms. The proportion of dipper BP in the study group (11.21%) was significantly lower than that of the control group (63.36%) (p = 0.001). The proportions of non-dipper (43.03%) and reverse dipper (40%) BP in the MI group were higher than the control group (22.90% and 7.63%, respectively; all p < 0.001). Multivariate Cox regression analysis, using dipper BP as the reference, showed that reverse dipper BP was independently associated with MACE (HR = 6.417, p = 0.002). The cumulative risk of the primary endpoint event (Log Rank p = 0.021) was significantly higher in the reverse dipper group compared to the dipper group. Patients with anterior STEMI are still under the burden of disrupted BP circadian rhythm and reduced dipper BP rhythm. The reverse dipper BP rhythm may serve as an independent factor of MACE.","[""Journal Article""]","[""Shao Y"", ""Yang Y"", ""Wang C"", ""Yu Z"", ""Wang R""]",10.1002/clc.70377,Shao Y,Clinical cardiology,0160-9289,8,Clin Cardiol,eng,Wang R,"[""Humans"", ""Circadian Rhythm"", ""Blood Pressure"", ""Male"", ""Female"", ""Percutaneous Coronary Intervention"", ""Prognosis"", ""Blood Pressure Monitoring, Ambulatory"", ""ST Elevation Myocardial Infarction"", ""Risk Factors"", ""Middle Aged"", ""Anterior Wall Myocardial Infarction"", ""Time Factors"", ""Follow-Up Studies"", ""Retrospective Studies"", ""Treatment Outcome"", ""Aged""]",e70377,42545175,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42545175/,Association Between Disruption of Blood Pressure Circadian Rhythm and Prognosis After Acute Anterior Myocardial Infarction,49,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"To investigate the association between the change in D-dimer levels (ΔD-dimer) and the development of localized intravascular coagulation (LIC) following surgical intervention in patients with venous malformations. This retrospective cohort study enrolled 267 patients with venous malformations who underwent surgical treatment at Fujian Maternity and Child Health Hospital between June 2021 and December 2025. The primary exposure variable was the preoperative-to-postoperative ΔD-dimer. The principal outcome was postoperative LIC. Multivariable logistic regression analysis was employed to estimate the effect size, adjusted for potential confounders. The incidence of LIC was 31.1% (83/267). Each unit increase in ΔD-dimer was significantly associated with a higher risk of LIC (adjusted odds ratio [aOR] = 2.51; 95% confidence interval [CI]: 1.93-3.26; p < 0.001). This association was consistent across stratified subgroups, including sex, age, number of lesions, tissue layer involvement, lesion volume, lesion location, surgical approach, and anticoagulation status (all P for interaction > 0.05), with a borderline interaction by head/neck involvement (P for interaction = 0.054). ΔD-dimer is independently associated with postoperative LIC in patients with venous malformations, with a monotonic dose-response relationship. A threshold near 4.8 mg/L FEU is suggested by exploratory segmented analysis but requires external validation before any clinical use. ΔD-dimer is independently associated with postoperative LIC in patients with venous malformations, demonstrating a significant dose-response relationship. Collectively, these findings suggest that ΔD-dimer is independently associated with postoperative LIC and may serve as a risk marker for perioperative coagulation monitoring.","[""Journal Article""]","[""Zhang R"", ""Luo H"", ""Jiang L"", ""Jiang C"", ""Cai T"", ""He J"", ""Chen K"", ""Chen D"", ""Zhan T""]",10.1080/07853890.2026.2711537,Zhang R,Annals of medicine,0785-3890,1,Ann Med,eng,Zhan T,"[""Humans"", ""Fibrin Fibrinogen Degradation Products"", ""Female"", ""Male"", ""Retrospective Studies"", ""Vascular Malformations"", ""Veins"", ""Adult"", ""Risk Factors"", ""Child"", ""Infant"", ""Postoperative Complications"", ""Perioperative Period"", ""Child, Preschool"", ""Adolescent""]",2711537,42544951,,2026 Dec,2026,https://pubmed.ncbi.nlm.nih.gov/42544951/,Association between perioperative D-dimer dynamics and post-treatment localized intravascular coagulation in venous malformations,58,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"To investigate the risk factors and tempral distribution of lower extremity deep vein thrombosis(DVT) formation after surgery in patients with cervical spine fracture and paraplegia. A total of 98 patients with cervical fracture and paraplegia admitted between January 2020 and January 2023 were enrolled in this study, including 50 males and 48 females. The age ranged from 18 to 80 years with a mean of (63.39±7.26) years, and the body mass index (BMI) ranged from 22.35 to 28.17 with a mean of (24.64±1.71) kg·m-2. Patients were divided into a DVT group (n=22) and a non-DVT group (n=76) based on the occurrence of postoperative DVT. General clinical data were compared between the two groups. The tempral distribution of DVT occurrence was analyzed in DVT patients at preoperation and on postoperative days 1,3,7, and 14, along with management strategies for different types of thrombus formation. Logistic regression analysis was performed to identify independent risk factors associated with postoperative DVT in patients with cervical fracture and paraplegia. A nomogram model was then constructed based on these identified independent predictors to estimate the risk of postoperative DVT in this patient population. Among the 98 patients who underwent surgical treatment for cervical fractures, 22 developed DVT, yielding an incidence rate of 22.45% (22/98). The peak onset of DVT occurred on the first postoperative day. The number of DVT cases detected preoperatively and on postoperative days 1,3,7, and 14 were 0,16,1,1, and 4, respectively. BMI≥25 kg·m-2, comorbid hypertension, elevated hemoglobin levels, high hematocrit, and the presence of large vascular atherosclerotic plaques were identified as independent risk factors for postoperative DVT in patients with cervical fracture and paraplegia (P<0.05). A nomogram model was constructed based on these indicators. Internal validation using Bootstrap resampling (1 000 replications) demonstrated that the model yielded an area under the curve (AUC) of 0.928, 95%CI(0.829, 0.990), with a specificity of 0.942 and a sensitivity of 0.872 for predicting postoperative DVT. Postoperative day 1 is the peak time for DVT occurrence. It is recommended that thromboprophylaxis measures be implemented as early as during or immediately after surgery. BMI, hypertension, hemoglobin, hematocrit, and atherosclerotic plaques in major vessels are independent risk factors for postoperative DVT. The nomogram constructed based on these factors can effectively predict the occurrence of postoperative DVT in patients with cervical spine fractures and paraplegia.","[""English Abstract"", ""Journal Article""]","[""Wang J"", ""Kang X"", ""Zhu W""]",10.12200/j.issn.1003-0034.20230426,Wang J,Zhongguo gu shang = China journal of orthopaedics and traumatology,1003-0034,7,Zhongguo Gu Shang,chi,Zhu W,"[""Humans"", ""Female"", ""Venous Thrombosis"", ""Spinal Fractures"", ""Middle Aged"", ""Lower Extremity"", ""Male"", ""Risk Factors"", ""Paraplegia"", ""Cervical Vertebrae"", ""Adult"", ""Aged"", ""Postoperative Complications"", ""Aged, 80 and over"", ""Adolescent"", ""Young Adult""]",670-6,42544802,,2026 Jul 25,2026,https://pubmed.ncbi.nlm.nih.gov/42544802/,[Factor analysis and tempral distribution of postoperative lower limb deep venous thrombosis in patients with cervical spine fracture and paraplegia],39,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"BackgroundInherited thrombophilia, particularly Factor V Leiden (FVL) mutation, globally, stands as a known contributing factor for venous thromboembolism (VTE). However, there are minimal case-control studies about the genetic composition and risk of these mutations within the Kurdistan Region of Iraq (KRI). This study's goal was to analyze the frequency and clinical significance of FVL, Prothrombin G20210A, and MTHFR C677T mutations in patients from Sulaymaniyah province.MethodsWithin this prospective case-control study, we analyzed 147 unselected patients (aged 18-49) with documented VTE (DVT, PE, or PVT) and 100 age and sex matched healthy controls. Molecular analysis was performed using multiplex PCR and reverse hybridization.ResultsIn the patient cohort, 55.8% had at least one prothrombotic mutation. The frequency of FVL was 14.3% in the patient cohort compared to 8% in the control group. FVL carriers showed a remarkably higher rate of recurrent thrombosis compared to non-carriers (71% vs. 40%; p = 0.041). Furthermore, FVL carriers had a five-fold increased risk for recurrent DVT (OR 5.4, 95% CI 0.778-37.505) and were significantly more likely to have a positive family history (p = 0.005). While MTHFR C677T was highly prevalent in both groups (48% patients, 49% controls), it was not identified to be an independent risk factor for VTE.ConclusionFVL is classified as a strong contributing factor for recurrent thrombosis in Sulaymaniyah. The high regional prevalence of FVL shows the need for targeted genetic screening in young patients, presenting with unprovoked or recurrent DVT, particularly when a family history is present.","[""Journal Article""]","[""Abdulqader AMR"", ""Noori AS"", ""Noori AS"", ""Mohammed NH"", ""Abdalla HS"", ""Mohammed RS"", ""Mahmood SN""]",10.1177/10760296261475425,Abdulqader AMR,Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis,1076-0296,,Clin Appl Thromb Hemost,eng,Mahmood SN,"[""Humans"", ""Methylenetetrahydrofolate Reductase (NADPH2)"", ""Factor V"", ""Thrombophilia"", ""Iraq"", ""Female"", ""Male"", ""Adult"", ""Prothrombin"", ""Case-Control Studies"", ""Prospective Studies"", ""Middle Aged"", ""Adolescent"", ""Mutation"", ""Thrombosis"", ""Risk Factors"", ""Young Adult""]",10760296261475425,42544730,,2026 Jan-Dec,2026,https://pubmed.ncbi.nlm.nih.gov/42544730/,"Clinical Impact of Inherited Thrombophilia in Patients With Thrombosis: Evaluating the Real Risk of FVL, PTG20210A, and MTHFR Mutations in the Kurdistan Region of Iraq",32,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"To explore the risk factors of lower extremity deep vein thrombosis (DVT) in patients with iliac vein compression syndrome (IVCS) and to construct a risk prediction model. A total of 187 patients with IVCS admitted to The First Hospital of Lanzhou University from January 2023 to December 2024 were selected as the research subjects. Clinical data such as gender, age, underlying diseases, surgical history, anticoagulation history, body mass index (BMI), and laboratory test results of all patients were collected. According to whether the patients were combined with lower extremity DVT, they were divided into the DVT group (90 cases) and the non-DVT group (97 cases). Univariate and multivariate Logistic regression analyses were used to analyze the risk factors of lower extremity DVT in patients with IVCS. One hundred patients with IVCS admitted to our hospital from January 2025 to July 2025 were selected as the validation group for model validation. The Hosmer-Lemeshow test was used to evaluate the goodness-of-fit of the model, and the predictive performance of the model was evaluated based on the area under the receiver operating characteristic (ROC) curve (AUC). There were statistically significant differences between the DVT group and the non-DVT group in terms of age, BMI, lower extremity mobility disorder, postoperative infection, previous history of thrombosis, D-dimer levels, anticoagulation history, bed rest time, uric acid levels, prothrombin time, and fibrinogen levels (P < 0.05). Multivariate Logistic regression analysis revealed advanced age (OR =1.107, 95%CI : 1.033-1.187, P =0.004), plasma D-dimer >0.5 mg/L (OR =12.799, 95%CI : 1.124-145.782, P =0.040), BMI >25 kg/m2 (OR =5.695, 95%CI : 1.474-22.008, P =0.012), previous history of thrombosis (OR =40.453, 95%CI : 7.234-226.214, P < 0.001), no history of anticoagulation (OR =8.020, 95%CI : 2.274-28.279, P =0.001), bed rest time >72 hours (OR =38.500, 95%CI : 2.696-549.888, P =0.007), hyperuricemia (OR =1.026, 95%CI : 1.016-1.035, P < 0.001) and hyperfibrinogen (OR =3.786, 95%CI : 1.366-10.491, P =0.010) were independent risk factor for lower extremity DVT in patients with IVCS. The Hosmer-Lemeshow test showed that, χ2 =9.608, the P value was 0.294, the goodness-of-fit of the model was good. ROC curve analysis showed that the AUC of the model was 0.946 (95%CI : 0.914-0.978), the specificity was 0.918, and the sensitivity was 0.833. The prediction accuracy of this model was 90.00%, and the Kappa consistency coefficient was 0.780. Advanced age, elevated D-dimer, BMI >25 kg/m2, previous history of thrombosis, no anticoagulation prevention, bed rest time >72 hours, hyperuricemia and hyperfibrinogen are all independent risk factors for lower extremity DVT in patients with IVCS. In clinical work, these factors should be emphasized and active intervention measures should be taken to prevent the occurrence of lower extremity DVT, and improve the prognosis of diseases.","[""English Abstract"", ""Journal Article""]","[""Zhu H"", ""Xi YM"", ""Ma HJ"", ""Qin LN"", ""Li SX"", ""Xu WY"", ""Bai YW""]",10.19746/j.cnki.issn1009-2137.2026.03.025,Zhu H,Zhongguo shi yan xue ye xue za zhi,1009-2137,3,Zhongguo Shi Yan Xue Ye Xue Za Zhi,chi,Bai YW,"[""Humans"", ""Venous Thrombosis"", ""Risk Factors"", ""May-Thurner Syndrome"", ""Lower Extremity"", ""Iliac Vein"", ""Logistic Models"", ""Female"", ""Fibrin Fibrinogen Degradation Products""]",806-812,42544670,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42544670/,[Analysis of Risk Factors and Construction of Predictive Model for Iliac Vein Compression Syndrome Combined with Deep Vein Thrombosis of the Lower Extremities],34,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"To construct a risk assessment model for venous thromboembolism (VTE) in children with acute lymphoblastic leukemia (ALL) after transplantation, and to explore the value of this new model in predicting the risk of post-transplant VTE in children with ALL. A total of 113 children with ALL who underwent allogeneic hematopoietic stem cell transplantation (HSCT) at Children's Hospital of Soochow University were enrolled. According to the occurrence of VTE within 30 days after transplantation, the children were divided into VTE group and non-VTE group. Differences in the levels of coagulation markers and the distribution of other thromboembolism-related clinical risk factors were compared between the two groups. Logistic regression analysis was used to screen independent risk factors for post-transplant VTE. Based on these factors, a new VTE risk assessment model was established, and receiver operating characteristic (ROC) curves were plotted to evaluate the predictive performance of the new model for VTE in children with ALL after transplantation, as well as to compare its advantages over traditional methods. In the VTE group, the plasma levels of tissue plasminogen activator-inhibitor complex (t-PAIC), thrombin-antithrombin complex (TAT), plasmin-α2-plasmin inhibitor complex (PIC), prothrombin time (PT), activated partial thromboplastin time (APTT), and D-dimer (DD) were significantly higher than those in the non-VTE group, while the fibrinogen (FIB) level was significantly lower (all P < 0.05). In the VTE group, the duration of ALL was generally longer, and the detection rates of granulocytopenia, agranulocytosis, and peripherally inserted central catheter (PICC)-related bloodstream infection (CRBSI) were significantly higher than those in the non-VTE group (all P < 0.05). Multivariate analysis showed that t-PAIC >4.3 ng/ml (OR =30.19, P =0.005) and APTT >31.8 s (OR =12.17, P =0.015) were independent risk factors for post-transplant VTE in children with ALL. A new VTE risk assessment model was established based on these two risk factors. The model showed significantly superior performance in predicting post-transplant VTE in children with ALL compared with individual coagulation and fibrinolysis indicators, as well as the traditional Caprini score and DIC score, with an AUC of 0.90 (P =0.001). The novel thrombotic marker t-PAIC has important clinical value in the early prediction of VTE in children with ALL after HSCT. Compared with the traditional thrombosis risk assessment models, the new model established based on t-PAIC and APTT exhibits superior diagnostic performance and clinical applicability in the pediatric ALL population.","[""English Abstract"", ""Journal Article""]","[""Wei J"", ""Chen F"", ""Tan QX"", ""Wang ZZ"", ""Xue J"", ""Shen HJ""]",10.19746/j.cnki.issn1009-2137.2026.03.022,Wei J,Zhongguo shi yan xue ye xue za zhi,1009-2137,3,Zhongguo Shi Yan Xue Ye Xue Za Zhi,chi,Shen HJ,"[""Humans"", ""Hematopoietic Stem Cell Transplantation"", ""Precursor Cell Lymphoblastic Leukemia-Lymphoma"", ""Venous Thromboembolism"", ""Child"", ""Female"", ""Male"", ""Child, Preschool"", ""Risk Assessment"", ""Risk Factors"", ""Biomarkers"", ""Adolescent"", ""Infant"", ""Logistic Models"", ""Predictive Value of Tests"", ""Antithrombin III""]",786-792,42544667,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42544667/,[Predictive Value of a Risk Assessment Model Based on Coagulation Biomarkers for Venous Thromboembolism after Hematopoietic Stem Cell Transplantation in Children with Acute Lymphoblastic Leukemia],34,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"To validate the predictive ability of the International Myeloma Working Group (IMWG) venous thromboembolism (VTE) scoring system, the IMPEDE VTE scoring system, and the SAVED scoring system for VTE in Chinese multiple myeloma (MM) patients. A total of 415 patients with MM who visited The First Affiliated Hospital of Soochow University from January 1, 2019 to June 30, 2023 were included in the research cohort, and a retrospective analysis of their data was conducted. These patients were scored according to the IMWG, IMPEDE, and SAVED thrombosis risk models, respectively, and the predictive value of these three scoring models for VTE events was evaluated. The cumulative incidence of VTE events was 7.0% in the 415 patients. Both the IMWG score and the IMPEDE score demonstrated predictive value for VTE events. Each 1-point increase in the IMWG score was significantly associated with VTE events after treatment initiation (HR=3.41, 95%CI : 2.48-4.69, P < 0.001). Similarly, each 1-point increase in the IMPEDE score was also significantly associated with VTE events after treatment initiation (HR=2.46, 95%CI : 1.95-3.10, P < 0.001). In contrast, the SAVED score did not show significant predi- ctive value for VTE events in Chinese MM patients (P =0.693). However, according to the IMWG risk stratification, the vast majority of patients (97.3%) were classified into the high-risk group; in contrast, only 1 case (0.2%) was categorized into the high-risk group based on the IMPEDE risk stratification, indicating that these two risk stratification criteria are not suitable for Chinese patients. Therefore, patients were regrouped according to the IMWG score: ≤2 points as low-risk (163 cases), 3-4 points as intermediate-risk (214 cases), and ≥5 points as high-risk (38 cases); The 6-month cumulative incidence of VTE events in the high-risk group was 36.8%, which was significantly higher than that in the intermediate- and low-risk groups (P < 0.001, log-rank test). Patients were regrouped according to the IMPEDE score: ≤3 points as low-risk (265 cases), 4-5 points as intermediate-risk (131 cases), and ≥6 points as high-risk (19 cases); The 6-month cumulative incidence of VTE events in the high-risk group was 42.1%, which was significantly higher than that in the intermediate- and low-risk groups (P < 0.001, log-rank test). The IMWG score and the IMPEDE score have predictive value for VTE events in Chinese patients with MM, but restratification of patients based on these scores is required, while the SAVED score is not applicable to Chinese MM patients.","[""English Abstract"", ""Journal Article""]","[""Huang Y"", ""Wu XY"", ""Shen HM"", ""You HY"", ""Yan Z"", ""Zhai YY"", ""Shi XL"", ""Shang JJ"", ""Jin S"", ""Yan LZ"", ""Wu DP"", ""Fu CC""]",10.19746/j.cnki.issn1009-2137.2026.03.020,Huang Y,Zhongguo shi yan xue ye xue za zhi,1009-2137,3,Zhongguo Shi Yan Xue Ye Xue Za Zhi,chi,Fu CC,"[""Humans"", ""Multiple Myeloma"", ""Venous Thromboembolism"", ""Retrospective Studies"", ""Risk Assessment"", ""Risk Factors"", ""East Asian People""]",773-780,42544665,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42544665/,"[Validation of the Predictive Ability of IMWG, IMPEDE and SAVED Thrombosis Risk Stratification Systems for Venous Thromboembolism in Chinese Multiple Myeloma Patients]",34,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"To analyze the clinical characteristics of patients with multiple myeloma (MM) complicated with light chain amyloidosis (AL), particularly those with cardiac amyloidosis (CA), in order to provide evidence for early identification. Clinical data were retrospectively collected from 359 newly diagnosed MM patients at the First Affiliated Hospital of Soochow University from August 2017 to December 2023. Based on histopathological results, patients were grouped to compare the clinical characteristics between the multiple myeloma with amyloid light-chain (MM-AL) group and the multiple myeloma without amyloid light-chain (MM without AL) group, as well as between the cardiac involvement and non-cardiac involvement subgroups within the MM-AL cohort. MM-AL patients accounted for 19.5% (70/359), of whom 30.0% had cardiac involvement. Compared with the MM without AL group, the MM-AL group had a higher proportion of λ light chain type (65.7% vs. 45.0%), a higher proportion of frail patients (45.7% vs. 29.1%), a lower proportion of DS stage III (84.3% vs. 93.4%), fewer patients presenting with bone pain as the initial symptom (45.7% vs. 69.2%), and higher proportions of patients with heart failure (12.8% vs. 4.2%) and non-hypoproteinemia polyserositis (27.2% vs. 5.9%) (all P < 0.05). Electrocardiogram abnormalities (low voltage, pseudo-infarction) were observed only in the MM-AL group. Compared with those without cardiac involvement, MM-CA patients had a higher proportion of light chain type (47.6% vs. 18.4%), a higher proportion of congestive heart-failure at onset (33.3% vs. 4.1%), a higher incidence of major adverse cardiovascular events during treatment (33.3% vs. 2.0%), and significantly elevated levels of NT-proBNP and hs-TnT, as well as a higher incidence of electrocardiogram abnormalities (all P < 0.05). Multivariate analysis showed that non-hypoproteinemia polyserositis (OR =7.66, P < 0.001) and λ light chain type (OR =2.40, P =0.017) were independent risk factors for MM complicated with AL. In terms of cytogenetics, the proportion of high-risk cytogenetic abnormalities was lower in MM-CA patients compared with those without cardiac involvement (14.3% vs. 36.7%, P =0.047). Patients with MM complicated by AL present with distinct clinical and cytogenetic features. The presence of λ light chain type and non-hypoproteinemic polyserous effusions are independent risk factors. Electrocardiographic findings of low voltage and pseudoinfarction patterns are suggestive of early recognition of AL and cardiac involvement.","[""English Abstract"", ""Journal Article""]","[""Shen HM"", ""Huang Y"", ""Wu XY"", ""Xie Y"", ""Wu DP"", ""Fu CC""]",10.19746/j.cnki.issn1009-2137.2026.03.019,Shen HM,Zhongguo shi yan xue ye xue za zhi,1009-2137,3,Zhongguo Shi Yan Xue Ye Xue Za Zhi,chi,Fu CC,"[""Humans"", ""Multiple Myeloma"", ""Retrospective Studies"", ""Immunoglobulin Light-chain Amyloidosis"", ""Immunoglobulin Light Chains"", ""Amyloidosis"", ""Female""]",763-772,42544664,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42544664/,[Analysis of Clinical Features of Newly Diagnosed Multiple Myeloma Complicated with Light Chain Amyloidosis],34,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"To analyze the expression level of heterogeneous nuclear ribonucleoprotein U (hnRNP U) and its correlation with prognosis in patients with multiple myeloma (MM), and explore the functional role as well as molecular mechanism of hnRNP U, thereby providing a theoretical basis for development of hnRNP U as a novel therapeutic target for MM. Based on Gene Expression Omnibus (GEO) database, the expression of hnRNP U in plasma cell diseases and healthy controls was compared. Based on the GSE9782 dataset (n =264), patients were divided into high expression group (n =114) and low expression group (n =150) according to the median expression level of hnRNP U . Overall survival (OS) between the two groups was compared. RPMI 8226, NCI-H929 and MM.1S cell lines were selected as tool cell lines. Following knockdown of hnRNP U by shRNA, the cell proliferation was detected by CCK-8. The apoptosis of MM cells was analyzed by Annexin V/7-AAD staining, and cell cycle was detected by BrdU/DAPI staining followed by flow cytometric analysis. The effect of hnRNP U on the biological characteristics of human MM cells was explored. The effect of knockdown of hnRNP U on DNA damage response pathways was analyzed by Western blot. Analysis of GSE5900 and GSE2113 datasets showed that the mRNA level of hnRNP U rose with the increased degree of malignancy of plasma cell diseases. Survival curve analysis of GSE9782 dataset showed that the high expression group of hnRNP U had a shorter OS than that of the low expression group. Down-regulation of hnRNP U in MM cell lines RPMI 8226, NCI-H929 and MM.1S could inhibit the cell proliferation, promote cell apoptosis and arrest the cell cycle. After knocking down hnRNP U, the expression levels of cleaved PARP and p-H2A.X, as the important markers of activated DNA damage pathway, were significantly increased in MM cells. hnRNP U is highly expressed in several plasma cell diseases including MM, and the high expression of hnRNP U in MM patients predicts poor prognosis. Knocking down hnRNP U can inhibit the malignant progression of MM cells, which is possibly associated with aggravated DNA damage.","[""English Abstract"", ""Journal Article""]","[""Qi WH"", ""Xu CL"", ""Zhang LL"", ""Tang KK"", ""Lei L"", ""Chu JH"", ""Zhu TT""]",10.19746/j.cnki.issn1009-2137.2026.03.018,Qi WH,Zhongguo shi yan xue ye xue za zhi,1009-2137,3,Zhongguo Shi Yan Xue Ye Xue Za Zhi,chi,Zhu TT,"[""Multiple Myeloma"", ""Humans"", ""Apoptosis"", ""Cell Line, Tumor"", ""Prognosis"", ""Cell Proliferation"", ""Heterogeneous-Nuclear Ribonucleoprotein U"", ""Cell Cycle"", ""Gene Expression Regulation, Neoplastic""]",754-762,42544663,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42544663/,[The Clinical Significance and in vitro Experimental Study of hnRNP U in Multiple Myeloma],34,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"To retrospectively analyze the early death of patients with newly diagnosed multiple myeloma (NDMM) treated with daratumumab, build a risk warning model and verify its clinical decision-making benefits. The clinical data of 112 NDMM patients treated with daratumumab combination therapy in Tangshan Gongren Hospital from June 2018 to June 2022 were retrospectively collected as the training set, and the clinical data of 78 NDMM patients who received daratumumab combination therapy in the same period were collected as the validation set. According to whether early death occurred during regular follow-up (OS <24 months), the patients were divided into early death group (26 cases) and non-early death group (86 cases). The differences of clinical data between the two groups were analyzed, and Kaplan-Meier survival curves were used to analyze the survival difference of patients with different efficacy. Univariate and multivariate Cox regression analysis were used to analyze the independent risk factors affecting early death of NDMM patients treated with daratumumab. A warning nomogram model for the risk of early death was established, and the predictive performance was analyzed by receiver operating characteristic (ROC) curve and verified internally. According to whether the efficacy of daratumumab treatment achieved partial response (PR), the patients were divided into <PR group (32 cases) and ≥PR group (80 cases). Kaplan-Meier analysis found that the median OS of both groups were not reached, while the OS of patients with efficacy ≥PR was significantly longer than that of patients with efficacy <PR (log-rank χ2=14.225, P <0.001). Multivariate Cox regression analysis showed that older age, R-ISS stage Ⅲ, elevated hs-CRP, and efficacy <PR were independent risk factors for early death in NDMM patients (all P <0.05), and a nomogram model for early death risk in NDMM patients was constructed. ROC analysis and DeLong test showed that the AUC of the nomogram model was 0.894(95%CI : 0.828-0.959), which was higher than that of each individual model, and the differences were statistically significant (all P <0.05). Internal and external validation showed that the nomogram model was stable and had a positive net benefit. The OS of NDMM patients who did not reach PR after daratumumab treatment can be affected. Daratumumab treatment early death risk warning model for NDMM has good efficacy, and can be targeted at high-risk population for intensive treatment to improve prognosis.","[""English Abstract"", ""Journal Article""]","[""Wang BW"", ""Sun H"", ""Chen X"", ""Wang H"", ""Li XL""]",10.19746/j.cnki.issn1009-2137.2026.03.017,Wang BW,Zhongguo shi yan xue ye xue za zhi,1009-2137,3,Zhongguo Shi Yan Xue Ye Xue Za Zhi,chi,Li XL,"[""Humans"", ""Multiple Myeloma"", ""Antibodies, Monoclonal"", ""Retrospective Studies"", ""Risk Factors"", ""Clinical Decision-Making"", ""Nomograms""]",744-753,42544662,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42544662/,[Multi Model Study and Clinical Decision Analysis of Early Death Risk Warning in Patients with Newly Diagnosed Multiple Myeloma Treated with Daratumumab],34,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"To explore the correlation between CD269 expression patterns in multiple myeloma (MM) cells and the expression of other antigens and molecular cytogenetics. Flow cytometry was used to detect the expression level of CD269 in bone marrow plasma cells of 115 newly diagnosed MM patients. The patients were subsequently divided into CD269- group (<20%), CD269 partial expression group (20%-80%), and CD269 high expression group (>80%). The CD269 partial expression group and high expression group were combined as the CD269+ group. The immunophenotype of bone marrow plasma cells was analyzed by flow cytometry. Molecular cytogenetic analysis was performed using combined probe fluorescence in situ hybridization technology. There were 27 patients (23.5%) in the CD269- group, 42 patients (36.5%) in the CD269 partial expression group, and 46 patients (40.0%) in the CD269 high expression group. The expression rate of CD56 antigen was 72.7% in the CD269+ group, which was higher than 48.1% in the CD269- group (P <0.05). The expression rates of CD56 and CD117 antigen in the CD269 high expression group were 76.1% and 47.8%, respectively, which were higher than 69.0% and 16.7% in the CD269 partial expression group (both P <0.05). The CD56/CD117 co-expression rate in the CD269 high expression group was 39.1%, which was higher than 14.8% in the CD269- group and 14.3% in the CD269 partial expression group (both P <0.05). The positive rate of IgH/CCND1 gene fusion in the CD269- group was 63.0%, which was higher than 31.0% in the CD269 partial expression group, 19.6% in the CD269 high expression group, and 25.0% in the CD269+ group (all P <0.05). The IgH deletion rate was 13.0% in the CD269 high expression group, while no IgH deletion was observed in the CD269 partial expression group, with a statistically significant difference between the two groups (P <0.05). The expression of CD269 on bone marrow plasma cells in MM patients is significantly correlated with the expression of CD56 and CD117, as well as IgH/CCND1 gene fusion and IgH deletion. The high expression of CD269 is associated with better prognosis related biological indicators.","[""English Abstract"", ""Journal Article""]","[""Wang XF"", ""Shao M"", ""Liang C"", ""Wen JW"", ""Shi YP"", ""Liu YR""]",10.19746/j.cnki.issn1009-2137.2026.03.016,Wang XF,Zhongguo shi yan xue ye xue za zhi,1009-2137,3,Zhongguo Shi Yan Xue Ye Xue Za Zhi,chi,Liu YR,"[""Humans"", ""Multiple Myeloma"", ""Female"", ""Flow Cytometry"", ""Dipeptidyl Peptidase 4"", ""Middle Aged"", ""Immunophenotyping"", ""CD56 Antigen"", ""Aged"", ""In Situ Hybridization, Fluorescence"", ""Male"", ""Plasma Cells"", ""Chromosome Aberrations""]",739-743,42544661,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42544661/,[Correlation of CD269 Expression Patterns with Antigen Expression and Molecular Cytogenetics Abnormalities in Patients with Multiple Myeloma],34,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"To explore the clinical features, treatment strategies, and prognostic factors of patients with new diagnosed Lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM), thereby enhancing the diagnostic and therapeutic understanding of this disease. Comprehensive clinical data were collected from 35 newly diagnosed LPL/WM patients at our hospital between December 2015 and June 2024. A systematic analysis was conducted on baseline characteristics, laboratory parameters, treatment regimens, and follow-up information. Survival analysis was performed using the Kaplan-Meier method, and a Cox regression model was applied to assess prognostic factors. A total of 35 LPL/WM patients were enrolled, with a male predominance (91.4%) and a median age at diagnosis of 69 years (range: 32-83). The most common clinical manifestations were fatigue (45.7%), lower limb edema (28.5%), and lymphadenopathy (62.9%). Laboratory findings revealed anemia in 88.6% of patients. The vast majority (94.3%) secreted monoclonal IgM, one patient secreted monoclonal IgG, and one patient had both monoclonal IgM and IgG. The light chain type was predominantly kappa (77.1%). Molecular genetic testing showed a MYD88 L265P mutation rate of 82.4% (28/34), while the CXCR4 mutation rate was lower (17.6%, 3/17). The overall response rate was 82.4% in the treatment group containing Bruton's tyrosine kinase inhibitors (BTKi) and 66.7% in the non-BTKi treatment group. With a median follow-up of 70 months, one patient was lost to follow-up and 14 patients died. The median overall survival (OS) for the entire cohort was 71 months. Univariate analysis identified β2-microglobulin ≥4 mg/L at diagnosis was associated with OS (P =0.036) and PFS (P =0.021). Multivariate analysis confirmed β2-microglobulin ≥4 mg/L at diagnosis as an independent adverse prognostic factor for OS (HR =3.854, P =0.025) and PFS (HR=3.201, P =0.030), while receiving BTKi-containing therapy was identified as a protective factor for OS (HR=0.312, P =0.047). This study confirms that elevated β2-microglobulin levels are an independent adverse prognostic factor in patients with LPL/WM. In our center's cohort, patients receiving BTKi therapy achieve higher response rates and longer OS.","[""English Abstract"", ""Journal Article""]","[""Pan Y"", ""Yao CY"", ""Gao WX"", ""Zhu MZ"", ""Dong Y""]",10.19746/j.cnki.issn1009-2137.2026.03.012,Pan Y,Zhongguo shi yan xue ye xue za zhi,1009-2137,3,Zhongguo Shi Yan Xue Ye Xue Za Zhi,chi,Dong Y,"[""Humans"", ""Waldenstrom Macroglobulinemia"", ""Prognosis"", ""Male"", ""Aged"", ""Middle Aged"", ""Adult"", ""Female"", ""Aged, 80 and over""]",713-718,42544657,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42544657/,[Clinical Characteristics and Prognosis of Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia],34,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Myxomatous degeneration of the mitral valve (MDMV) is a common cardiovascular manifestation of Marfan syndrome (MFS), yet the role of lymphatic vessels in the disease progression remains unknown. In this Commentary, we discuss the study by Tan, Kume, and colleagues, which identifies defective lymphangiogenesis as a previously unrecognized driver of MDMV. Their work demonstrates that impaired lymphatic development and drainage promote valve inflammation through reduced ZFP36-mediated antiinflammatory signaling, whereas restoration of lymphatic function or pharmacological activation of ZFP36 with the FDA-approved drug FTY720 ameliorates disease progression. These findings establish lymphatic vessels as critical regulators of mitral valve homeostasis and support exploration of lymphatic-targeted therapeutic opportunities for MFS-associated valvular disease.","[""Journal Article"", ""Comment""]","[""Tian Y"", ""Caron KM""]",10.1172/JCI209169,Tian Y,The Journal of clinical investigation,0021-9738,15,J Clin Invest,eng,Caron KM,"[""Marfan Syndrome"", ""Humans"", ""Animals"", ""Mitral Valve"", ""Lymphangiogenesis"", ""Fingolimod Hydrochloride"", ""Lymphatic Vessels"", ""Heart Valve Diseases""]",,42544580,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42544580/,Lymphatic therapies open the valve in Marfan syndrome,136,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Cerebral ischemia-reperfusion injury (CIRI) involves complex pathogenesis with limited therapeutic options. This study investigated whether dexmedetomidine liposomes (Dex-lip) exert neuroprotective effects by modulating astrocytic aerobic glycolysis via calcium signaling. In vivo CIRI model mice received Dex-lip, with or without the aerobic glycolysis inhibitor 2-deoxy-D-glucose (2-DG). Neurological function, cortical calcium levels, aerobic glycolysis-related protein expression, lactate production, and hippocampal neuronal damage were assessed. In vitro, astrocytes were treated with the calcium channel blocker nifedipine to evaluate intracellular calcium, lactate levels, and glycolysis-related gene expression. Dex-lip treatment reduced cortical calcium overload, upregulated aerobic glycolysis key proteins, increased lactate production, and attenuated hippocampal neuronal injury. These neuroprotective effects were abolished by 2-DG. In vitro, nifedipine lowered astrocytic calcium concentration, which paradoxically increased lactate production, elevated ECAR, and upregulated HK1, HK2, and PFK1 mRNA expression, confirming that calcium reduction promotes aerobic glycolysis. Dex-lip ameliorates CIRI by reducing astrocytic calcium overload, enhancing aerobic glycolysis and lactate supply to neurons, thereby preventing apoptosis. This study provides a mechanistic basis and therapeutic strategy for CIRI.","[""Journal Article""]","[""Wang S"", ""Lian Y"", ""Wu T"", ""Li Y""]",10.2147/IJN.S611089,Wang S,International journal of nanomedicine,1176-9114,,Int J Nanomedicine,eng,Li Y,"[""Animals"", ""Dexmedetomidine"", ""Reperfusion Injury"", ""Neuroprotective Agents"", ""Glycolysis"", ""Liposomes"", ""Calcium"", ""Mice"", ""Astrocytes"", ""Brain Ischemia"", ""Male"", ""Mice, Inbred C57BL"", ""Hippocampus"", ""Neurons"", ""Lactic Acid""]",611089,42544301,pmc-id: PMC13429122;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42544301/,Neuroprotective Delivery of Dexmedetomidine Liposomes Mitigates Cerebral Energy Crisis by Modulating Calcium-Driven Aerobic Glycolysis in Cerebral Ischemia-Reperfusion Injury,21,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Deep vein thrombosis (DVT) is a common thrombotic condition with substantial morbidity when not identified early. Machine learning (ML)-based predictive models may improve early identification of patients at high risk for DVT, but few clinically applicable early-risk models exist. To develop and internally validate a ML model using routinely available clinical and laboratory indicators for early risk prediction of DVT, and to identify the most influential predictors using model explainability techniques. We retrospectively analyzed clinical data from 231 patients evaluated at the Fifth Affiliated Hospital of Southern Medical University between January 2017 and June 2024. Patients were labeled as DVT occurrence (n = 159) or non-occurrence (n = 72). Seven candidate predictors were selected by Least Absolute Shrinkage and Selection Operator (LASSO) regression. The dataset was split into training (70%, n = 162) and test (30%, n = 69) sets. Five ML algorithms were trained: XGBoost, CatBoost, Random Forest (RF), Logistic Regression, and Support Vector Machine, with hyperparameter tuning on the training set. Model performance was assessed by 5-fold cross-validation and on the held-out test set using Area Under the Receiver Operating Characteristic Curve (AUC), accuracy, recall, and F1 score. The best model was further interpreted via feature importance and Shapley Additive Explanations (SHAP). LASSO selected seven predictors: hemoglobin, platelet count, leukocyte count, fibrinogen, prothrombin time, D-dimer (DD), and glucose. The Random Forest model showed the best discrimination (test-set AUC = 0.874), with favorable accuracy, recall, and F1 compared with other classifiers (detailed metrics reported in the manuscript). In the RF model, D-dimer had the highest feature-importance contribution; SHAP analysis confirmed DD as the dominant risk driver and characterized the directions and relative effects of other features. We developed an internally validated ML model for early DVT risk prediction using seven routine clinical variables; Random Forest achieved the best performance and identified D-dimer as the most influential predictor. This model may support earlier identification and intervention for patients at risk of DVT, pending external validation and prospective evaluation.","[""Journal Article""]","[""Wang X"", ""Chen X"", ""Mao J"", ""Liu M"", ""Yan L"", ""Sun W"", ""Song J""]",10.7717/peerj.21524,Wang X,PeerJ,2167-8359,,PeerJ,eng,Song J,"[""Humans"", ""Venous Thrombosis"", ""Predictive Learning Models"", ""Retrospective Studies"", ""Female"", ""Machine Learning"", ""Random Forest"", ""Boosting Machine Learning Algorithms"", ""Risk Assessment"", ""Male"", ""Middle Aged"", ""Risk Factors"", ""Prediction Algorithms"", ""Aged"", ""Classification Algorithms"", ""Fibrin Fibrinogen Degradation Products"", ""ROC Curve"", ""Hospitalization"", ""Logistic Models""]",e21524,42544207,pmc-id: PMC13429103;,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42544207/,A machine learning-based risk prediction model for Hospitalized patients with deep vein thrombosis,14,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Poisoning with Taxus baccata (common yew) is a life-threatening emergency due to its major cardiotoxicity. The taxines it contains block cardiac sodium channels, rapidly leading to severe arrhythmias, cardiogenic shock, and often cardiac arrest. Management is exclusively symptomatic and relies on intensive hemodynamic support, including advanced resuscitation and, in some cases, the use of extracorporeal circulatory support (ECMO). The administration of antidotes such as DigiFab®, although experimental and not formally validated for this indication, may be considered based on pharmacological analogies with digoxin.","[""Case Reports"", ""English Abstract"", ""Journal Article""]","[""Ait Moussa N"", ""Delcour A"", ""Morimont P"", ""Lambermont B""]",,Ait Moussa N,Revue medicale de Liege,0370-629X,7-8,Rev Med Liege,fre,Lambermont B,"[""Taxus"", ""Humans"", ""Plant Poisoning"", ""Fatal Outcome"", ""Shock, Cardiogenic""]",471-474,42544073,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42544073/,[Volontary poisoning with yew ( Taxus baccata) : a fatal case],81,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Austrian syndrome is characterized by the triad of pneumonia, meningitis, and endocarditis due to Streptococcus pneumoniae («pneumococcus»). Endocarditis, often occurring in the background, is frequently diagnosed late and requires prompt medical and sometimes surgical management. We report the case of a 51-year-old man admitted for confusion. The initial evaluation revealed bacterial meningitis documented by purulent cerebrospinal fluid, associated with right basal pneumonia. Blood cultures and cerebrospinal fluid cultures identified Streptococcus pneumoniae. The clinical course was marked by hemodynamic deterioration with circulatory shock, multiorgan failure, and cardiac arrhythmias, prompting the performance of transoesophageal echocardiography. This revealed aortic valve endocarditis complicated by a mitro-aortic curtain abscess and severe aortic regurgitation due to valvular perforation. Intensive care management with targeted antibiotic therapy and urgent valve surgery was required. This case illustrates the importance of systematically investigating for endocarditis in any patient with pneumococcal meningitis, particularly when pneumonia is present, to avoid diagnostic delay with potentially fatal consequences.","[""Case Reports"", ""English Abstract"", ""Journal Article""]","[""Schwab AS"", ""Collin V""]",,Schwab AS,Revue medicale de Liege,0370-629X,7-8,Rev Med Liege,fre,Collin V,"[""Humans"", ""Male"", ""Middle Aged"", ""Endocarditis, Bacterial"", ""Meningitis, Pneumococcal"", ""Syndrome"", ""Streptococcus pneumoniae"", ""Pneumonia, Pneumococcal"", ""Pneumococcal Infections""]",428-432,42544065,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42544065/,[Austrian Syndrome : when Pneumococcus strikes three times],81,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Carbon monoxide poisoning is one of the most common types of intoxication and is linked to a high mortality rate when not managed appropriately. We are discussing the case of a patient found unconscious after a house fire, presenting a smoke inhalation injury and particularly carbon monoxide poisoning. The clinical course was marked by the development of a massive bilateral pulmonary embolism despite thromboprophylaxis. This case highlights the increased thromboembolic risk, which can persist up to 90 days after carbon monoxide poisoning. We analyse the cardiovascular manifestations while focusing on the thromboembolic risks. Finally, we provide a brief overview of the pathophysiology and management of this condition.","[""Case Reports"", ""English Abstract"", ""Journal Article""]","[""Yassine J"", ""Faniel M"", ""Germonpré P""]",,Yassine J,Revue medicale de Liege,0370-629X,7-8,Rev Med Liege,fre,Germonpré P,"[""Humans"", ""Pulmonary Embolism"", ""Smoke Inhalation Injury"", ""Carbon Monoxide Poisoning"", ""Male""]",420-423,42544063,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42544063/,[Pulmonary embolism following smoke inhalation],81,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Bicuspid aortic valve (BAV) is the most common congenital heart disease. It is often associated with aortic abnormalities and, more rarely, with coronary anomalies that may influence surgical strategy. We describe a 38-year-old patient with a Sievers type I BAV. Coronary CT angiography revealed an abnormally high proximal origin of the right coronary artery, with a 10 mm ectatic dilation at its origin followed by a return to normal caliber. This feature prompted a change in operative strategy: mechanical aortic valve replacement instead of a Ross procedure, more distal aortic clamping, and a «lazy-S» aortotomy. The procedure was completed without complications. Coronary anomalies are more frequent in patients with BAV than in the general population. Their preoperative identification is essential to prevent intraoperative complications. Multimodal imaging plays a key role in optimizing surgical planning in line with current recommendations. Coronary anomalies associated with BAV should be systematically screened for before any valve surgery. This case highlights the importance of thorough preoperative assessment and appropriate technical adaptation to ensure operative safety.","[""Case Reports"", ""English Abstract"", ""Journal Article""]","[""Damès S"", ""Madani S"", ""Durieux R"", ""Tchana-Sato V"", ""Radermecker M""]",,Damès S,Revue medicale de Liege,0370-629X,7-8,Rev Med Liege,fre,Radermecker M,"[""Humans"", ""Bicuspid Aortic Valve Disease"", ""Aortic Valve"", ""Coronary Vessel Anomalies"", ""Heart Valve Diseases"", ""Adult"", ""Male""]",411-414,42544061,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42544061/,[Coronary artery anomalies associated with bicuspid aortic valve],81,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Idiopathic intracranial hypertension (IIH) is a syndrome identified by raised intracranial pressure (ICP), with absence of a mass lesion/hydrocephalus, typically affecting obese women of childbearing age.1 It may present with similar symptoms such as headache, visual disturbances, and papilledema, making clinical differentiation challenging.1 IIH primarily threatens vision, and treatment focuses on lowering ICP using medications like acetazolamide, serial lumbar punctures, or surgical interventions such as optic nerve sheath fenestration or CSF shunting in refractory cases.2 Misdiagnosing IIH as CVST can lead to unnecessary anticoagulation, which may prove to be harmful for the patient.","[""Journal Article"", ""Case Reports""]","[""Gupta N"", ""Batra T"", ""Kakar A"", ""Chandra AA""]",10.59556/japi.74.1594,Gupta N,The Journal of the Association of Physicians of India,0004-5772,7,J Assoc Physicians India,eng,Chandra AA,"[""Humans"", ""Sinus Thrombosis, Intracranial"", ""Pseudotumor Cerebri"", ""Diagnosis, Differential"", ""Female"", ""Adult""]",90-92,42544001,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42544001/,Idiopathic Intracranial Hypertension Masquerading as Cerebral Venous Sinus Thrombosis: A Diagnostic Challenge,74,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Thrombotic events are a major morbidity among Philadelphia chromosome-negative myeloproliferative neoplasm (Ph-MPN) patients. There is a lack of data from Kerala regarding the profile of Ph-MPN and the prevalence of thrombosis among these patients. To study the clinical profile, driver mutations, incidence of thrombotic events among Ph-MPN patients, and the response to hydroxyurea therapy. We reviewed the medical records of 84 Ph-MPN patients who were on follow-up from April 2019 to June 2023 in a tertiary care hospital in Kerala. There were 48 polycythemia vera (PV), 16 essential thrombocythemia (ET), 14 primary myelofibrosis (PMF), and six unclassifiable MPN (MPN-u) patients. The incidence of Janus kinase 2 (JAK2) mutation was 96, 62.5, and 79% among PV, ET, and PMF patients, respectively. The incidence of calreticulin (CALR) mutation was 37.5 and 21% among ET and PMF patients, respectively. The incidence of thrombotic events was 23/48 (48%), 7/16 (43.5%), and 6/14 (42.8%) among PV, ET, and PMF patients, respectively. All ET and PMF patients with thrombotic events were JAK2V617F-mutated. Eighty-seven percent of the evaluable patients on hydroxyurea for PV achieved freedom from therapeutic phlebotomies. ET patients who were on hydroxyurea achieved a median platelet count of 4.3 lakhs/µL (3.16-6.08). There is a higher incidence of thrombosis among Ph-MPN patients from Kerala, which needs to be ascertained in a population-based study. JAK2V617F mutation is the major determinant of thrombotic episodes in ET and PMF. Hydroxyurea is an effective cytoreductive therapy in PV and ET.","[""Journal Article""]","[""Prabhu RS"", ""Nameera RS"", ""Thangal K SML"", ""Nair PR""]",10.59556/japi.74.1583,Prabhu RS,The Journal of the Association of Physicians of India,0004-5772,7,J Assoc Physicians India,eng,Nair PR,"[""Humans"", ""Thrombocythemia, Essential"", ""Polycythemia Vera"", ""Male"", ""Female"", ""Janus Kinase 2"", ""Middle Aged"", ""Thrombosis"", ""Hydroxyurea"", ""Adult"", ""Calreticulin"", ""India"", ""Aged"", ""Mutation"", ""Philadelphia Chromosome"", ""Retrospective Studies"", ""Incidence"", ""Myeloproliferative Disorders"", ""Cytoreduction Surgical Procedures"", ""Primary Myelofibrosis""]",24-27,42543987,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543987/,Profile of Philadelphia Chromosome Negative (Ph-) Myeloproliferative Neoplasm with Special Emphasis on Vascular Thrombotic Events and the Response to Cytoreductive Therapy in Polycythemia Vera and Essential Thrombocythemia Patients: A Single Center Study from Kerala,74,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Imatinib is the standard first-line therapy for chronic myeloid leukemia (CML) and is generally well tolerated. Gastrointestinal adverse effects are common; however, gastric antral vascular ectasia (GAVE) is an extremely rare complication. We report a 77-year-old woman with chronic-phase CML who developed severe upper gastrointestinal bleeding 1 month after the initiation of imatinib therapy. Endoscopy revealed classic features of GAVE, and no alternative etiology was identified. Discontinuation of imatinib resulted in complete clinical and endoscopic resolution. Clinicians should consider this rare complication in patients receiving imatinib who present with unexplained anemia or gastrointestinal bleeding.","[""Case Reports"", ""Journal Article""]","[""Sharma KL"", ""Veerwal R"", ""Kaur G"", ""Otwani S""]",10.59556/japi.74.1577,Sharma KL,The Journal of the Association of Physicians of India,0004-5772,6S,J Assoc Physicians India,eng,Otwani S,"[""Humans"", ""Female"", ""Imatinib Mesylate"", ""Gastric Antral Vascular Ectasia"", ""Aged"", ""Leukemia, Myelogenous, Chronic, BCR-ABL Positive"", ""Antineoplastic Agents"", ""Benzamides"", ""Pyrimidines"", ""Gastrointestinal Hemorrhage"", ""Piperazines""]",72-73,42543981,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543981/,Gastric Antral Vascular Ectasia in a Patient with Chronic Myeloid Leukemia on Imatinib Treatment: A Rare Case Report,74,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Scorpion envenomation is common in India but rarely leads to neurovascular complications. We present a rare case of a 72-year-old male who developed acute transverse myelitis, subarachnoid hemorrhage, and pulmonary thromboembolism following a scorpion sting. The patient presented with sudden-onset paraparesis. Magnetic resonance imaging (MRI) of the spine revealed longitudinal hyperintensity from T5 to T12, suggestive of transverse myelitis, along with evidence of spinal subarachnoid hemorrhage. Computed tomography (CT) pulmonary angiography confirmed bilateral pulmonary thromboembolism. Cerebrospinal fluid analysis showed a hemorrhagic tap with elevated protein and lactate dehydrogenase (LDH), but no infectious or malignant cells. Neuromyelitis optica (NMO) and myelin oligodendrocyte glycoprotein (MOG) antibodies were negative. Nerve conduction studies showed bilateral sensorimotor axonal polyneuropathy. The patient was treated with corticosteroids and anticoagulants and showed gradual improvement. This case underscores the systemic toxicity of scorpion venom and highlights the importance of early recognition and multidisciplinary management of rare neurovascular complications.","[""Journal Article"", ""Case Reports""]","[""Rijhwani P"", ""Jain S"", ""Gupta D"", ""Agarwal P"", ""Swami D"", ""Agarwal A""]",10.59556/japi.74.1340,Rijhwani P,The Journal of the Association of Physicians of India,0004-5772,6S,J Assoc Physicians India,eng,Agarwal A,"[""Humans"", ""Male"", ""Aged"", ""Scorpion Stings"", ""Myelitis, Transverse"", ""Pulmonary Embolism"", ""Animals"", ""Scorpion Venoms"", ""Magnetic Resonance Imaging""]",70-71,42543980,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543980/,Acute Transverse Myelitis and Pulmonary Thromboembolism Following Scorpion Envenomation: A Rare Case Report,74,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Systemic sclerosis (SSc) is a complex autoimmune disease marked by vasculopathy, fibrosis, and multisystem involvement. Interstitial lung disease (ILD) and pulmonary hypertension (PH) are major mortality contributors. Importantly, SSc is associated with an increased risk of malignancy. This report presents a challenging case of SSc with severe Raynaud's phenomenon (RP), digital gangrene, calcinosis cutis, extensive ILD, severe PH, and right heart failure. The patient underwent mesenchymal stem cell therapy (MST), following which she developed breast cancer and chemotherapy-related complications, ultimately leading to death. This case highlights the need for timely intervention, screening for malignancy, and awareness of potential therapy-related risks in SSc.","[""Journal Article"", ""Case Reports""]","[""Parimi VP"", ""Tejaswini RN""]",10.59556/japi.74.1350,Parimi VP,The Journal of the Association of Physicians of India,0004-5772,6S,J Assoc Physicians India,eng,Tejaswini RN,"[""Humans"", ""Female"", ""Scleroderma, Systemic"", ""Breast Neoplasms"", ""Hypertension, Pulmonary"", ""Raynaud Disease"", ""Fatal Outcome"", ""Lung Diseases, Interstitial"", ""Mesenchymal Stem Cell Transplantation"", ""Middle Aged""]",68-69,42543979,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543979/,A Complex Case of Systemic Sclerosis with Concurrent Breast Malignancy and Treatment-related Complications,74,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Bidirectional ventricular tachycardia (BDVT) is a rare arrhythmia marked by beat-to-beat QRS axis alteration. We report a 36-year-old female with recurrent palpitations who presented with BDVT degenerating into polymorphic ventricular tachycardia and ventricular fibrillation. An extensive evaluation, including cardiac magnetic resonance imaging (MRI), stress and adrenaline provocation testing, and a comprehensive genetic arrhythmia panel, revealed no definitive etiology. Given the concern for proarrhythmic implantable cardioverter-defibrillator (ICD) shocks in a potential channelopathy and after shared decision-making, the patient was managed with high-dose beta blocker therapy. This case underscores the diagnostic and management challenges of BDVT in a structurally normal heart, particularly when balancing guideline recommendations against individualized patient factors.","[""Journal Article"", ""Case Reports""]","[""Limaye SV"", ""Anand AB"", ""Nathani PJ"", ""Lokhandwala YY""]",10.59556/japi.74.1356,Limaye SV,The Journal of the Association of Physicians of India,0004-5772,6S,J Assoc Physicians India,eng,Lokhandwala YY,"[""Humans"", ""Female"", ""Adult"", ""Heart Arrest"", ""Electrocardiography"", ""Tachycardia, Ventricular"", ""Tachycardia"", ""Adrenergic beta-Antagonists"", ""Defibrillators, Implantable"", ""Ventricular Fibrillation""]",56-58,42543975,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543975/,Bidirectional Ventricular Tachycardia Culminating in Cardiac Arrest: A Diagnostic and Management Conundrum,74,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Ask-Upmark kidney was originally described as a congenital segmental hypoplasia of the kidney, but recent data suggest it to be a sequela of vesicoureteral reflux or pyelonephritis in early age. This segmental hypoplasia leads to hypertension in young people. This hypertension is treatable with a partial nephrectomy. This reported patient presented with hypertensive urgency in the OPD. On evaluation, he was found to have Ask-Upmark kidney. The patient was managed conservatively. In case of severe and progressive renal damage, surgical resection with or without transplant can be considered. If the disease is nonprogressive with normal kidney function, the patient can be managed with antihypertensive treatment alone. This is one of the rare causes of hypertension in young that should be kept in mind while evaluating such cases.","[""Journal Article"", ""Case Reports""]","[""Prakash J"", ""Kumari P""]",10.59556/japi.74.1535,Prakash J,The Journal of the Association of Physicians of India,0004-5772,6S,J Assoc Physicians India,eng,Kumari P,"[""Humans"", ""Hypertension"", ""Male"", ""Kidney"", ""Antihypertensive Agents"", ""Nephrectomy""]",45-46,42543971,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543971/,Ask-Upmark Kidney: A Rare Cause of Hypertension in Young Patients,74,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Lateral medullary syndrome is a collection of different neurological symptoms after ischemic/hemorrhagic insult to either the posterior inferior cerebellar artery/vertebral artery or rarely the anterior inferior cerebellar artery, causing infarction of ipsilateral cerebellum and posterolateral medulla (Tiedt and Weidauer, 2013). Dizziness, nausea, vertigo, vomiting, nystagmus, ataxia, dysphagia, hoarseness of voice, ptosis, and sensory impairment of face and body are typical. Here we report an unusual presentation of a 47-year-old female who was hypertensive and diabetic and who complained of vertigo, nausea, vomiting, slurring of speech, facial deviation toward the left, and loss of pain and temperature over the right side of the face and body without any difficulty in swallowing or nasal regurgitation. The patient was eventually diagnosed with left lateral medullary syndrome, drawing attention to the rare and unusual presentation of the same.","[""Journal Article"", ""Case Reports""]","[""Ballabh R"", ""Chakraborty A"", ""Kumar S"", ""Maraskole PA"", ""Rohatgi A"", ""Kumar N""]",10.59556/japi.74.1549,Ballabh R,The Journal of the Association of Physicians of India,0004-5772,6S,J Assoc Physicians India,eng,Kumar N,"[""Humans"", ""Female"", ""Lateral Medullary Syndrome"", ""Middle Aged"", ""Magnetic Resonance Imaging"", ""Medulla Oblongata""]",34-36,42543968,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543968/,An Unusual Case Report of Pseudothalamic Pattern of Sensory Loss in Lateral Medullary Syndrome,74,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary condition characterized by widespread bleeding into the alveoli, leading to respiratory failure. It can result from various etiologies, including autoimmune disorders, drug reactions, and infections. Here is a rare case of a 37-year-old male who presented with progressive dyspnea, hemoptysis, and hypoxemia. Chest imaging and bronchoscopy confirmed the diagnosis of DAH, while laboratory tests revealed ANCA-associated vasculitis. On diagnosis, the patient with granulomatosis with polyangiitis was initiated on corticosteroids and cyclophosphamide. Early initiation of immunosuppressive therapy and supportive care plays a crucial role in disease management, reducing morbidity in such cases.","[""Journal Article"", ""Case Reports""]","[""Shaily KP"", ""Mandadi M"", ""Navothna S"", ""Barthwal M""]",10.59556/japi.74.1553,Shaily KP,The Journal of the Association of Physicians of India,0004-5772,6S,J Assoc Physicians India,eng,Barthwal M,"[""Humans"", ""Male"", ""Granulomatosis with Polyangiitis"", ""Adult"", ""Hemorrhage"", ""Lung Diseases"", ""Pulmonary Alveoli"", ""Immunosuppressive Agents"", ""Cyclophosphamide"", ""Hemoptysis""]",25-27,42543965,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543965/,Diffuse Alveolar Hemorrhage in a Case of Granulomatosis with Polyangiitis: A Case Report,74,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Milroy's disease is a rare hereditary primary lymphedema, typically presenting at birth or early infancy with chronic lower limb swelling due to mutations in the FLT4 gene encoding VEGFR-3. While congenital lymphedema is the hallmark, its association with tubercular pericardial effusion leading to tamponade is extremely rare. We report an 18-year-old female with longstanding bilateral lower limb lymphedema who presented with progressive dyspnea and fever. Evaluation revealed tubercular pericardial effusion, and genetic testing confirmed an FLT4 mutation. The patient improved with antitubercular therapy and supportive care. This case emphasizes the need to consider rare systemic complications in congenital lymphedema syndromes to optimize early diagnosis and management.","[""Journal Article"", ""Case Reports""]","[""Khan K"", ""Quazi T"", ""Jalgaonkar P"", ""Bhrushundi M"", ""Quazi S""]",10.59556/japi.74.1536,Khan K,The Journal of the Association of Physicians of India,0004-5772,6S,J Assoc Physicians India,eng,Quazi S,"[""Humans"", ""Female"", ""Adolescent"", ""Pericardial Effusion"", ""Lymphedema"", ""Antitubercular Agents"", ""Vascular Endothelial Growth Factor Receptor-3""]",20-21,42543963,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42543963/,Successful Management of Milroy's Disease: A Rare Condition Complicated by Tuberculous Pericardial Effusion,74,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Among ischemic stroke patients, prehospital delay is the most common reason for underutilization of thrombolysis. The study assessed prehospital factors contributing to delay and timely arrival among study participants. A cross-sectional study was carried out at the casualty department of Government Stanley Medical College and Hospital, South India. We selected 212 study participants by consecutive sampling. Data were collected by interviewing patients or accompanying family members using a semistructured questionnaire. Univariate analysis was followed by multivariate logistic regression to examine prehospital factors contributing to delay and timely arrival. Follow-up of eligible study participants for thrombolysis was performed using the National Institutes of Health Stroke Scale (NIHSS) and American Heart Association (AHA)-2019 checklist. The most common factors contributing to prehospital delay and timely arrival were found to be ""unawareness regarding benefits of timely arrival among patients/relatives (48.7%)"" and ""apprehension of some serious health issue (50%),"" respectively. The distance between the hospital and the place of onset of symptoms, stroke during sleep, mode of transport, National Institutes of Health Stroke Scale (NIHSS), and slurring of speech were found to have significant odds for timely arrival for intravenous thrombolysis (IVT). Among those who arrived on time (n = 60), 13 study participants could not undergo thrombolysis. The most common reason for this was refusal of thrombolysis (4, 6.7%), and other criteria, such as minor neurological deficits (4, 6.7%), rendered them ineligible for it. The study highlights factors associated with timely arrival at the hospital and further reasons for not undergoing IVT despite timely arrival among cases of acute ischemic stroke (AIS). There is also a need to generate awareness and disseminate information on the benefits of IVT, timely arrival, and prehospital factors; provide training in stroke preparedness; and strengthen the referral system to ensure maximum eligibility and utilization.","[""Journal Article""]","[""P S NS"", ""Vadanere NP"", ""Mugundhan K"", ""Velayudham S"", ""Jeyaraj M"", ""Sowmini PR""]",10.59556/japi.74.1582,P S NS,The Journal of the Association of Physicians of India,0004-5772,7E,J Assoc Physicians India,eng,Sowmini PR,"[""Humans"", ""Male"", ""Cross-Sectional Studies"", ""India"", ""Thrombolytic Therapy"", ""Tertiary Care Centers"", ""Female"", ""Middle Aged"", ""Time-to-Treatment"", ""Ischemic Stroke"", ""Treatment Delay"", ""Aged"", ""Emergency Medical Services"", ""Adult"", ""Time Factors"", ""Fibrinolytic Agents"", ""Stroke""]",e9-e17,42543956,,2026 Jul,2026,https://pubmed.ncbi.nlm.nih.gov/42543956/,A Study on Prehospital Factors Determining the Timely Arrival for Thrombolysis among Patients Presenting with Acute Ischemic Stroke at a Tertiary Care Center in South India,74,oGkmoe5cKsverJu7p,YSPtgdNgx1St6jSnB
"Colorectal cancer (CRC) incidence is increasing in sub-Saharan Africa, including Nigeria, where more than half of patients die within 1 year due to late diagnosis and limited treatment. Without ready access to screening, identifying risk factors is critical. However, regional data are scarce, and it is unclear whether risk factors from high-income populations apply to Nigerians, who may have distinct clinicodemographic patterns and tumor characteristics. To assess whether 13 CRC risk factors identified in high-income populations are associated with CRC in adults in Nigeria. This multicenter case-control study was conducted in 6 hospitals across 3 of Nigeria's 6 geopolitical zones, with recruitment from April 2020 to September 2024. Participants were patients newly diagnosed with CRC and cancer-free controls matched on age, sex, location, education, and recruitment site. Data were analyzed from April 2023 to November 2025. Family history of cancer, anthropometric factors (adult height, body mass index [BMI], and somatotype or body size over the life course), physical activity, and dietary and lifestyle factors (processed meat, red meat, fruit, vegetables, fiber, alcohol, smoking, and diabetes). The associations of risk factors with CRC were assessed using odds ratios (ORs) and 95% CIs, estimated using multivariable unconditional logistic regression. Among 2063 participants (1103 [53.5%] male; median [IQR] age, 54 [42-64] years) enrolled, most had secondary education or higher (1756 participants [85.2%]), lived in urban areas (1817 participants [88.1%]), and were Yoruba (1524 participants [73.9%]). Cases were older than controls (median [IQR] age, 56 [45-66] vs 52 [41-63] years) but were otherwise similar. Family history of cancer (OR, 1.55; 95% CI, 1.06-2.26), adult height (OR per 5-cm increase, 1.09; 95% CI, 1.00-1.20), body size or type over the life course (tertile 3 vs tertile 1: OR, 1.88; 95% CI, 1.30-2.72), and processed meat intake (lowest vs highest tertile of intake: OR, 1.43; 95% CI, 1.07-1.91) were positively associated with CRC risk, and an inverse U-shaped association was identified between physical activity and CRC risk (OR vs first quartile of activity, quartile 2: 0.63; 95% CI, 0.44-0.88; quartile 3: 0.52; 95% CI, 0.34-0.79; quartile 4: 0.77; 95% CI, 0.58-1.02), consistent with data from high-income populations. BMI was inversely associated with CRC risk (OR vs BMI 18.5-24.9, BMI <18.5: 2.63; 95% CI, 1.79-3.86; BMI ≥30: 0.42; 95% CI, 0.28-0.63), likely reflecting prediagnostic weight loss. No associations with diabetes, smoking, or intakes of red meat, fruit, vegetables, fiber, or alcohol were observed, likely due to low prevalence or variability. This case-control study of CRC risk factors in adults in Nigeria found CRC risk patterns similar to those observed in high-income populations. These insights offer immediate opportunity to tailor education, prevention, and early detection in the region, especially as economic development leads to lifestyles more similar to high-income populations. These data provide a foundation for prospective research and investigations in other African populations.","[""Journal Article"", ""Multicenter Study""]","[""Alatise OI"", ""Peeri NC"", ""Abdulkareem FB"", ""Badejo OA"", ""Gali BM"", ""Oludara M"", ""Okereke CE"", ""Olatoke SA"", ""Ademakinwa OR"", ""Alabi A"", ""Aderounmu A"", ""Adeomi A"", ""Mohammed T"", ""Adegboyega O"", ""Adisa A"", ""Ajewole O"", ""Famurewa OC"", ""Agodirin SO"", ""Ariyibi O"", ""Nggada HA"", ""Babatunde OJ"", ""Badmos K"", ""Balogun OS"", ""Bamidele CO"", ""Batta CS"", ""Betiku OA"", ""Bojuwoye MO"", ""Choonawala NR"", ""Cookey C"", ""Daji FY"", ""Egberongbe A"", ""Esan O"", ""Folaranmi OO"", ""Fasiku OK"", ""Fatusi A"", ""Fodero R"", ""Francis AO"", ""Gallagher G"", ""Habeeb MYM"", ""Shittu HA"", ""Iasonos A"", ""Ige OE"", ""Ikujenlola AV"", ""Igetei R"", ""Jackman JM"", ""Kahn R"", ""Katung A"", ""Koiki MA"", ""Komolafe AO"", ""Lawrence AP"", ""Lawal A"", ""Lawal NOO"", ""Makanjuola A"", ""Mobolaji J"", ""Omodele F"", ""Na'aya HU"", ""Nganjiwa US"", ""Njokanma I"", ""Nuhu A"", ""Nwachukwu E"", ""O'Connell K"", ""Odunafolabi T"", ""Ogunleye SO"", ""Olaofe OO"", ""Olcese C"", ""Ologunagba PO"", ""Olokoba A"", ""Olasehinde O"", ""Olajide TO"", ""Osinowo AO"", ""Omoyiola OZ"", ""Omisore AD"", ""Onyekwere C"", ""Owoade IA"", ""Oyesegun R"", ""Samson ML"", ""Sanni A"", ""Sharma A"", ""Sowunmi A"", ""Sulaiman AT"", ""Adebukola OT"", ""Wuraola F"", ""Adeleye AO"", ""Adewunmi OL"", ""Zarami AB"", ""Kingham TP"", ""Du M""]",10.1001/jamanetworkopen.2026.26716,Alatise OI,JAMA network open,2574-3805,8,JAMA Netw Open,eng,Du M,"[""Humans"", ""Risk Factors"", ""Nigeria"", ""Male"", ""Case-Control Studies"", ""Female"", ""Colorectal Neoplasms"", ""Middle Aged"", ""Adult"", ""Aged"", ""Diet"", ""Life Style"", ""Incidence""]",e2626716,42545699,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545699/,Colorectal Cancer Risk Factors in Adults in Nigeria,9,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"We evaluated the impact of chronological age on early urinary continence recovery following robot-assisted radical prostatectomy (RARP) using EPIC-26 and quantified discordance between patient-reported and surgeon-assessed continence. A total of 144 consecutive patients underwent RARP and were stratified into Group A (< 70 years, n = 74), Group B (70-<75 years, n = 36), and Group C (≥ 75 years, n = 34). Continence was assessed using EPIC-26 and independent surgeon evaluation at 1, 2, 3, 4, and 6 months postoperatively. Time-to-event analyses were performed using Kaplan-Meier methods and Cox proportional hazards models; proportional hazards assumptions were verified using Schoenfeld residuals. Longitudinal domain trajectories were analyzed using generalized estimating equations (GEE). Social continence rates at 3 months were 85.1%, 72.2%, and 58.1% in Groups A, B, and C, increasing to 97.3%, 94.4%, and 77.4% at 6 months (p = 0.0004). Pad-free rates increased from 39.7%, 36.7%, and 29.4% to 77.8%, 76.7%, and 52.9% (p = 0.110). Age independently predicted delayed social continence recovery (HR 0.953, 95% CI: 0.933-0.973; p < 0.001). Recovery trajectories were slower in Group C (p = 0.008), whereas Groups A and B showed comparable trajectories. At 3 months, surgeon-assessed pad-free continence was 69.3% compared with 37.3% by EPIC-26, representing a 32-percentage-point difference with only fair agreement (κ = 0.38; p = 0.034). Although age was associated with delayed early recovery, meaningful recovery with partial narrowing of between-group differences was observed. Age alone should not automatically preclude surgical consideration in appropriately selected elderly patients, and surgeon assessments substantially overestimated patient-reported continence, supporting routine use of validated PROMs.","[""Journal Article""]","[""Yoon SG"", ""Yun SW"", ""Jin HJ"", ""Noh TI"", ""Shim JS"", ""Park MG"", ""Kang SH"", ""Kang SG""]",10.1007/s11701-026-03577-1,Yoon SG,Journal of robotic surgery,1863-2483,1,J Robot Surg,eng,Kang SG,"[""Humans"", ""Male"", ""Prostatectomy"", ""Robotic Surgical Procedures"", ""Aged"", ""Urinary Incontinence"", ""Recovery of Function"", ""Middle Aged"", ""Patient Reported Outcome Measures"", ""Prostatic Neoplasms"", ""Age Factors"", ""Time Factors""]",,42545635,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545635/,Patient-reported early continence recovery after robot-assisted radical prostatectomy in elderly men,20,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with limited therapeutic options, driven in part by its immunosuppressive tumor microenvironment (TME). Tumor-associated macrophages (TAMs) and neutrophils (TANs) contribute to tumor progression and immune evasion. A Disintegrin and Metalloproteinase 8 (ADAM8), a zinc-dependent protease, is strongly upregulated in PDAC and correlates with poor clinical outcomes, suggesting a regulatory role in tumor progression. Wild-type (WT) and Adam8 knockout (A8KO) PDAC cell lines were generated using the CRISPR-Cas9 technique, and PDAC mouse models with or without Adam8 expression were established to investigate the role of ADAM8 in tumor and immune cells. In vitro assays, including Western blotting, qPCR, migration and invasion assays, proliferation assays, ELISA, cytokine and proteome analyses, as well as co-culture experiments with PDAC cells and either macrophages or neutrophils, were employed to assess the effects of ADAM8 on tumor-immune cell crosstalk. In parallel, in vivo WT and A8KO KPC models were generated, genotyped, and monitored to evaluate the impact of ADAM8 on survival, tumor growth, and immune cell recruitment within the PDAC TME. ADAM8 deletion reduced tumor cell proliferation and migration, associated with reduced activation of FAK/Src/STAT3 signaling and altered secretion of cytokines including GM-CSF, M-CSF, ICAM-1, and TNF-α. Co-culture assays demonstrated that ADAM8 enhanced reciprocal signaling between tumor cells and TAMs/TANs, promoting pro-oncogenic activation. Migration assays and in vivo analyses revealed that ADAM8 facilitated recruitment of macrophages and neutrophils in PDAC TME, while Adam8KO tumors exhibited reduced immune infiltration and altered macrophage polarization. Our findings demonstrate that ADAM8 promotes PDAC aggressiveness by enhancing tumor cell proliferation and migration, activating FAK/Src/STAT3 signaling, and driving macrophage and neutrophil recruitment through cytokine regulation. By orchestrating both tumor-intrinsic pathways and tumor-immune interactions, ADAM8 emerges as a key determinant of PDAC progression and a systemic target for therapeutic intervention.","[""Journal Article""]","[""Zandieh K"", ""Cook L"", ""Zhao K"", ""Nagl C"", ""Gao Y"", ""diFazio P"", ""Bartsch DK"", ""Bauer UM"", ""Meixner M"", ""Yildiz D"", ""Keber C"", ""Nimsky C"", ""Bartsch JW""]",10.1007/s13402-026-01266-7,Zandieh K,"Cellular oncology (Dordrecht, Netherlands)",2211-3428,4,Cell Oncol (Dordr),eng,Bartsch JW,"[""Animals"", ""Tumor Microenvironment"", ""Humans"", ""ADAM Proteins"", ""Membrane Proteins"", ""Cell Line, Tumor"", ""Carcinoma, Pancreatic Ductal"", ""Cell Movement"", ""Pancreatic Neoplasms"", ""Cell Proliferation"", ""Signal Transduction"", ""Neutrophils"", ""Mice, Knockout"", ""STAT3 Transcription Factor"", ""Mice"", ""Macrophages"", ""src-Family Kinases"", ""Focal Adhesion Kinase 1"", ""Antigens, CD""]",,42545624,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545624/,Deciphering the regulatory role of ADAM8 in the PDAC tumor microenvironment,49,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"Medullary thyroid carcinoma (MTC) is characterized by frequent RET mutations, while non-RET alterations remain less well studied. Previous reports have identified a recurrent STK11 c.1062 C > G (p.Phe354Leu) variant in MTC, but its clinicopathologic and functional significance remains uncertain. A total of 129 MTCs (128 families) were analyzed by Sanger sequencing to screen for the STK11 c.1062 C > G variant. Germline status was assessed in cases with available normal tissue. Targeted next-generation sequencing was performed in 30 tumors (29 families). Functional effects of the STK11 c.1062 C > G variant were evaluated using an overexpression model in TT cells, with assessment of AMPKα phosphorylation. Progression-free survival was analyzed using Kaplan-Meier methods. The STK11 c.1062 C > G variant was identified in 12 of 129 MTCs (9.3%) and in 11 of 128 families (8.6%). It was significantly enriched in hereditary cases compared with sporadic tumors: 27.8% (5/18) vs. 7.7% (1/12) for individual MTC cases, and 23.5% (4/17) vs. 7.7% (1/12) for families. In evaluable cases, the variant was confirmed to be germline. Tumors harboring STK11 c.1062 C > G showed a mutational spectrum predominantly involving RET, whereas variant-negative tumors exhibited more heterogeneous alterations, including genes related to DNA repair and chromatin remodeling. No significant difference in progression-free survival was observed between groups (P = 0.54). In vitro, the STK11 c.1062 C > G variant was associated with reduced AMPKα phosphorylation compared with wild-type STK11. Given the population frequency and ClinVar benign/likely benign classification of this variant, our data do not support STK11 c.1062 C > G as a primary driver of MTC; rather, it may represent a recurrent germline variant that could act as a low-penetrance modifier in a subset of patients, warranting cautious interpretation and further validation.","[""Journal Article""]","[""Kong W"", ""Bao L"", ""Wang M"", ""Zhao X"", ""Gu H"", ""Pan X"", ""Zhang X"", ""Zhang T"", ""Xing X"", ""Wang J""]",10.1007/s12020-026-04729-x,Kong W,Endocrine,1355-008X,1,Endocrine,eng,Wang J,"[""Humans"", ""Thyroid Neoplasms"", ""Protein Serine-Threonine Kinases"", ""Germ-Line Mutation"", ""AMP-Activated Protein Kinase Kinases"", ""Female"", ""Carcinoma, Neuroendocrine"", ""Genetic Predisposition to Disease"", ""Male"", ""Middle Aged"", ""Adult"", ""Aged"", ""Young Adult""]",,42545603,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545603/,STK11 c.1062 C > G germline variant in medullary thyroid carcinoma: implications for familial predisposition and genetic counseling,91,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"This study describes the development and analytical validation of a DNA-based quantitative PCR (qPCR) assay for detecting the NPM1 Type A mutation (NPM1-A mut) in acute myeloid leukemia (AML). The assay employs a modified wild-type blocker (WTB) to preferentially suppress amplification of wild-type (WT) alleles, thereby enriching mutant targets. The modified WTB was synthesized as a 3'-ddC-terminated LNA/DNA chimera and used together with a 6-FAM-MGB-Eclipse hydrolysis probe. The analytical performance of the WTB-qPCR assay was compared with that of an otherwise identical qPCR assay lacking WTB. Key parameters such as linearity, precision, limit of detection (LoD), and limit of quantification (LoQ) were evaluated following the guidelines outlined in CLSI EP17-A2. Concurrently, modified WTB was implemented in Sanger sequencing to improve the sensitivity of mutation detection. Incorporation of WTB yielded an LoD of 0.00302% and an LoQ of 0.00528%, corresponding to approximately 3.02 and 5.28 NPM1-Amut copies, respectively, per 100,000 WT copies. This represented a clear improvement over the non-WTB assay. The WTB-qPCR showed excellent linearity (R2 > 0.999) and precision (CV < 5%), with 100% analytical specificity and no detectable cross-reactivity. Application of modified WTB in Sanger sequencing increased analytical sensitivity to ~ 0.1% mutant allele frequency. The modified WTB-qPCR assay offers a rapid, highly sensitive, and cost-effective DNA-based method for MRD monitoring in NPM1-A-mutated AML. Its strong analytical performance and straightforward workflow support its implementation as a routine diagnostic tool in clinical laboratories.","[""Journal Article"", ""Validation Study""]","[""Hamedi-Asl P"", ""Hamedi-Asl D"", ""Rostami S"", ""Barati M"", ""Amini A"", ""Jafari D"", ""Damerchiloo F"", ""Manafi R"", ""Safa M""]",10.1007/s11033-026-12471-w,Hamedi-Asl P,Molecular biology reports,0301-4851,1,Mol Biol Rep,eng,Safa M,"[""Nucleophosmin"", ""Leukemia, Myeloid, Acute"", ""Humans"", ""Nuclear Proteins"", ""Mutation"", ""Real-Time Polymerase Chain Reaction"", ""Limit of Detection"", ""Sensitivity and Specificity"", ""Alleles"", ""Reproducibility of Results"", ""DNA Mutational Analysis""]",,42545548,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545548/,Analytical validation of a modified wild-type blocker qpcr assay for the sensitive DNA-based detection of NPM1 type A in acute myeloid leukemia,53,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"Pediatric oncology clinical trials (POCTs) are the cornerstone of therapeutic progress in childhood cancer. Yet, poor accrual and retention remain persistent challenges contributing to early termination of POCTs, limiting the advancement of novel therapies. These challenges reflect a convergence of system, protocol, clinician, and family-level factors, among which caregivers' psychosocial decision-making processes represent a potentially modifiable but underexplored contributor. Caregivers making POCT-related decisions must navigate complex medical information under conditions of heightened emotional distress and uncertainty. Psychosocial factors such as distress, comprehension, trust, values, and social context are known to influence decision-making. However, the field still lacks an integrated framework to explain how these factors may shape decisional trajectories and outcomes throughout POCT participation. This commentary reframes POCT enrollment not as a discrete informed-consent event, but as a dynamic, psychosocial decision-making process that unfolds over time. We present an outline of a conceptual Precision Communication Framework designed to support care teams in aligning communication priorities with caregivers' psychosocial and decisional contexts at key decision points throughout trial participation. Rather than seeking to address all causes of poor accrual or withdrawal, this framework focuses on reducing preventable decisional uncertainty and regret in contexts where psychosocial processes are central drivers of caregiver experiences. By presenting an outline of a conceptual model that would link psychosocial-decisional profiles to communication strategies to prioritize, this commentary aims to inform future empirical research and lay the groundwork for identifying communication strategies to prioritize to reduce caregiver decisional burden and promote sustained participation in POCTs.","[""Journal Article""]","[""Levesque A"", ""Blackall G"", ""Axson SA"", ""Van Scoy LJ"", ""Sholler GS""]",10.1007/s00520-026-11048-4,Levesque A,Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer,0941-4355,8,Support Care Cancer,eng,Sholler GS,"[""Humans"", ""Caregivers"", ""Decision Making"", ""Neoplasms"", ""Clinical Trials as Topic"", ""Communication"", ""Child"", ""Uncertainty""]",,42545516,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545516/,Moving toward precision communication in pediatric oncology clinical trials: An outline of a conceptual framework to support caregiver decision-making,34,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"Craniopharyngioma is histologically benign yet locally aggressive, with frequent recurrence. Long-term multicenter outcomes after stereotactic radiosurgery (SRS) remain incompletely defined. We performed a retrospective multi-institutional cohort study through the International Radiosurgery Research Foundation including 296 patients from 13 centers. Median age at first SRS was 33.6 years. Median tumor volume was 1.32 cm³ and median margin dose was 12.0 Gy. The primary endpoint was local control (LC); secondary endpoints were progression-free survival (PFS) and overall survival (OS). Kaplan-Meier methods estimated outcomes, and Cox proportional hazards models evaluated predictors of LC. Actuarial 1-, 5-, and 10-year LC was 93.5%, 76.2%, and 70.1%. Actuarial 1-, 5-, and 10-year OS was 98.2%, 93.6%, and 85.2%, and PFS was 92.4%, 73.6%, and 64.8%. Mixed solid-cystic phenotype had worse LC than non-mixed tumors (log-rank p = 0.025); non-mixed phenotype remained independently associated with improved LC (HR 0.53, p = 0.026). Visual fields improved in 10%, were unchanged in 86%, and deteriorated in 4%; visual acuity improved in 6%, was unchanged in 91%, and worsened in 3%. Ten-year freedom from endocrine deterioration was 96.7%. Diabetes insipidus improved in 6.3%, worsened in 0.5% and other pituitary dysfunction was noted in 2.6%, CONCLUSION: In this international multi-institutional experience, SRS achieved durable long-term control with favorable survival and low incidence of visual and endocrinologic dysfunction. Mixed phenotype was an important determinant of LC. Not applicable.","[""Journal Article"", ""Multicenter Study""]","[""Niranjan A"", ""Reyes JS"", ""Hadjipanayis CG"", ""Bernstein K"", ""Speckter H"", ""Gonzalez I"", ""Chytka T"", ""Liscak R"", ""Bowden GN"", ""Sumi T"", ""Narita K"", ""Kano H"", ""Martínez-Moreno N"", ""Martínez-Álvarez R"", ""Picozzi P"", ""Franzini A"", ""Tripathi M"", ""Rai A"", ""Kumar N"", ""Douri K"", ""Mathieu D"", ""Dono A"", ""Amezquita-Contreras C"", ""Blanco AI"", ""Esquenazi Y"", ""Tos SM"", ""Mantziaris G"", ""Peker S"", ""Samanci Y"", ""Duzkalir AH"", ""Meng Y"", ""Sheehan JP"", ""Kondziolka D"", ""Lunsford LD""]",10.1007/s11060-026-05718-w,Niranjan A,Journal of neuro-oncology,0167-594X,1,J Neurooncol,eng,Lunsford LD,"[""Humans"", ""Craniopharyngioma"", ""Radiosurgery"", ""Female"", ""Pituitary Neoplasms"", ""Retrospective Studies"", ""Male"", ""Adult"", ""Adolescent"", ""Child"", ""Young Adult"", ""Middle Aged"", ""Follow-Up Studies"", ""Child, Preschool"", ""Treatment Outcome"", ""Aged""]",,42545447,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545447/,Stereotactic radiosurgery offers long-term tumor control for craniopharyngioma: a multi-institutional analysis of clinical and imaging outcomes from the International Radiosurgery Research Foundation (IRRF),179,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"Cancer mortality remains high in part because tumor-immune interactions can be unpredictable and may exhibit multistability, making malignant progression difficult to anticipate. We develop and analyze a tumor-immune model incorporating chemotherapy-induced toxicity and a Norton-Simon type tumor response, and show via deterministic analysis and continuation that increasing toxicity can generate hysteresis and bistability separating tumor dormancy from an uncontrolled full-growth state, so that small perturbations may precipitate abrupt progression. To capture uncertainty, we study environmental and demographic stochasticity and observe noise-induced switching in both cases; however, demographic noise sustains higher resilience of the tumor-dominant state under bistability, whereas stronger environmental noise tends to suppress uncontrolled tumor growth. We further assess early-warning signals using single and composite rolling-window indicators and find that they can provide advance warning of transitions from dormancy to full growth, with composite measures offering greater robustness across noise levels. Finally, we formulate an optimal control problem for combination immunotherapy and radiotherapy and demonstrate that appropriately timed treatment can substantially reduce tumor burden when initiated from either dormancy or full-growth conditions, highlighting how stochasticity-aware monitoring and optimized interventions may help prevent catastrophic tumor progression.","[""Journal Article""]","[""Panda S"", ""Karmakar S"", ""Halder S"", ""Chattopadhyay J"", ""Wang H""]",10.1007/s11538-026-01706-3,Panda S,Bulletin of mathematical biology,0092-8240,8,Bull Math Biol,eng,Wang H,"[""Neoplasms"", ""Stochastic Processes"", ""Humans"", ""Mathematical Concepts"", ""Immunotherapy"", ""Combined Modality Therapy"", ""Models, Immunological"", ""Computer Simulation"", ""Animals"", ""Disease Progression"", ""Tumor Microenvironment""]",,42545438,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545438/,Noise-Driven Tipping in a Tumor-Immune Model with Optimal Combination Therapy,88,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"Pelvic lymph-node dissection (PLND) during robot-assisted radical prostatectomy (RARP) is important for nodal staging, but its optimal extent, morbidity profile, and integration with precision-guided techniques remain unsettled. This study mapped the knowledge structure and thematic evolution of RARP-associated PLND research. A single-database search of the Web of Science Core Collection was performed for English-language articles and reviews formally published through 2025. Two reviewers independently screened records directly evaluating PLND, nodal staging, lymphatic morbidity, or related preventive and guidance strategies during RARP according to predefined eligibility criteria. Bibliometrix, VOSviewer, CiteSpace, and Scimago Graphica were used to assess publication trends, collaboration patterns, citation structure, and keyword evolution. The final dataset comprised 225 eligible records, including 208 original research articles and 17 review articles published during 2006-2025. Output increased markedly after 2019 and peaked at 27 publications in 2024. The United States received the most citations, whereas the Netherlands Cancer Institute was the most productive institution. van der Poel H.G. was the most productive author. The knowledge base initially focused on PLND templates, anatomical extent, and lymph-node yield, then expanded toward risk-adapted nodal staging, oncologic implications, lymphatic morbidity, and precision-guided nodal assessment. Keyword analysis identified eight thematic clusters and showed recent attention to peritoneal flap and fixation strategies, node-positive disease, and image- or radioguided nodal approaches. This bibliometric analysis characterizes a shift in RARP-associated PLND research from surgical extent and staging yield toward individualized selection, morbidity reduction, and precision-guided nodal strategies. Further prospective studies are needed to clarify how preventive reconstruction and targeted nodal techniques should be integrated with anatomically defined extended PLND.","[""Journal Article"", ""Review""]","[""Zhao Y"", ""Wang W"", ""Dong Z""]",10.1007/s11701-026-03759-x,Zhao Y,Journal of robotic surgery,1863-2483,1,J Robot Surg,eng,Dong Z,"[""Lymph Node Excision"", ""Humans"", ""Male"", ""Prostatectomy"", ""Robotic Surgical Procedures"", ""Pelvis"", ""Bibliometrics"", ""Prostatic Neoplasms"", ""Lymph Nodes"", ""Neoplasm Staging"", ""Lymphatic Metastasis""]",,42545410,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545410/,"Pelvic lymph node dissection during robot-assisted radical prostatectomy: a bibliometric analysis of surgical extent, nodal staging, and lymphatic morbidity",20,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"Osteosarcoma (OS) is the most common bone cancer, known for its aggressive nature, high chemoresistance, and strong metastatic potential responsible for poor clinical outcomes. In this context, identifying reliable biomarkers and therapeutic targets is therefore critical. This study investigates the role of paraoxonase-2 (PON2), an intracellular enzyme known for its anti-oxidative and anti-apoptotic properties. PON2 overexpression has been observed in various cancers and is implicated in tumor development and progression. PON2 expression was evaluated by immunohistochemistry in bone tissue samples from OS patients and control subjects. shRNA-mediated PON2 silencing was performed in U-2 OS and Saos-2 cells to assess proliferation, viability, migration, chemosensitivity, ROS production, apoptosis activation, glucose uptake, and GLUT1 expression. PON2 overexpression and N-acetylcysteine (NAC) pre-treatment in CDDP-treated U-2 OS cells were used as rescue approaches. Preliminary analyses showed markedly higher PON2 expression in OS than in control bone specimens. PON2 knockdown reduced proliferation, viability, and migration, while enhancing sensitivity to cisplatin (U-2 OS and Saos-2) and doxorubicin (U-2 OS only); these effects were reversed by PON2 upregulation. PON2 silencing also increased ROS levels and caspase expression, and impaired glucose uptake by reducing GLUT1 expression and intracellular glucose levels. Since NAC did not fully rescue these alterations, PON2 appears to sustain chemoresistance by affecting important mechanisms related to ROS detoxification, glucose metabolism, and anti-apoptotic signaling. Obtained data clearly illustrate the potential of PON2 as promising biomarker and molecular therapeutic target for human OS.","[""Journal Article""]","[""Gerini E"", ""Pompei V"", ""Cecati M"", ""Campagna R"", ""Pozzi V"", ""Filosa A"", ""Goteri G"", ""Salvolini E"", ""Emanuelli M"", ""Sartini D""]",10.1007/s11033-026-12528-w,Gerini E,Molecular biology reports,0301-4851,1,Mol Biol Rep,eng,Sartini D,"[""Humans"", ""Osteosarcoma"", ""Aryldialkylphosphatase"", ""Cell Line, Tumor"", ""Bone Neoplasms"", ""Cell Proliferation"", ""Apoptosis"", ""Up-Regulation"", ""Gene Expression Regulation, Neoplastic"", ""Cell Movement"", ""Female"", ""Reactive Oxygen Species"", ""Male"", ""Cell Survival"", ""Cisplatin"", ""Doxorubicin"", ""Drug Resistance, Neoplasm"", ""Glucose Transporter Type 1""]",,42545402,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545402/,Upregulation of paraoxonase-2 enzyme in human osteosarcoma and its involvement in mechanisms promoting the aggressive behavior of tumor cells,53,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"Monodispersed highly magnetic iron oxide nanocubes and nanospheres with magnetization (78.72 emu/gcubic and 72.08 emu/gsphere with an average size of 17.45 ± 5.13 nm for spherical (IONPs) and with edge lengths ranging from 20.85 ± 6.60 nm for nanocubes (IONCs) have been successfully synthesized and functionalized with methoxy-polyethylene glycol (m-PEG). The specific absorption rate (SAR) has been observed to be 351.5 W/g for IONPs and 415.06 W/g for the IONCs. The antimicrobial activity of the synthesized nanoparticles (NPs) against Staphylococcus aureus and Escherichia coli was evaluated using the agar well diffusion method. Anti-angiogenic effects were evaluated via the Chick Chorioallantoic Membrane (CAM) assay, an extensively used in vivo model. Additionally, m-PEG-coated IONCs were functionalized with doxorubicin (DOX) and the tumor-targeting aptamer AS1411 to enable targeted magneto-chemotherapy (MCT) in 3D breast cancer models. The results show that magneto-chemotherapy (MCT) reduces cancer cell viability to 76.41% in 2D cultures and 77.27% in 3D cultures, highlighting the potential of 3D models for enhancing the effectiveness of targeted therapies in breast cancer.","[""Journal Article""]","[""Phalake SS"", ""Patil AP"", ""Patil AR"", ""Salunkhe AB"", ""Park JP"", ""Thorat ND"", ""Khot VM""]",10.1007/s00604-026-08315-w,Phalake SS,Mikrochimica acta,0026-3672,8,Mikrochim Acta,eng,Khot VM,"[""Doxorubicin"", ""Humans"", ""Female"", ""Breast Neoplasms"", ""Animals"", ""Polyethylene Glycols"", ""Cell Survival"", ""Drug Resistance, Neoplasm"", ""Staphylococcus aureus"", ""Escherichia coli"", ""Magnetite Nanoparticles"", ""Magnetic Iron Oxide Nanoparticles"", ""Anti-Bacterial Agents"", ""Antineoplastic Agents"", ""Cell Line, Tumor""]",,42545398,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545398/,Synergistic magnetic nano-chemotherapy overcomes chemoresistance in 3D breast cancer models,193,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"Describe the implementation of robotic-assisted surgery for pediatric cysts and neoplasms and characterize perioperative outcomes. A retrospective review was performed of pediatric patients undergoing robotic-assisted resection of cysts or neoplasms at a quaternary children's hospital from 2011 to 2026. Demographic, lesion, operative, and outcome data were analyzed. Thirty-eight pediatric robotic cases were reviewed. Median age was 13 years (IQR 8.25-16). Eighteen intracavitary cysts and 20 neoplasms were resected. Operations for solid neoplasms consisted of thymectomies (n = 3), mediastinal teratoma excision, lung lobectomy, partial gastrectomy, left hepatectomy, distal pancreatectomy (n = 2), pancreatic uncinate resection, pancreaticoduodenectomy, nephrectomies (2 partial, 2 radical), adrenalectomy, periadrenal mass resection, ovarian cystectomy (n = 2), and radical cystoprostatectomy. Median EBL was 15 mL (IQR 5-25) and day of discharge 1 (IQR 0-2). The median opioid dose prescribed at discharge was 0.28 mg/kg oral morphine equivalents with duration of 1 (0-3) day. Thirty-one (82%) patients experienced no complications. Major complications occurred after pancreatic resections, including hemorrhagic pancreatitis following uncinate resection and delayed biliary stenosis with ductal leak after pancreaticoduodenectomy requiring revision 1.5 years later. Robotic-assisted surgery is a safe and feasible option for selected pediatric cysts and neoplasms, offering low blood loss, short hospitalization, and minimal postoperative opioid requirements.","[""Journal Article""]","[""Chara AO"", ""Gupta VS"", ""Rogers JL"", ""D'Cruz RJ"", ""Stout M"", ""Frainey B"", ""Corona L"", ""Clayton DB"", ""Lovvorn HN"", ""Zamora IJ""]",10.1007/s00383-026-06560-x,Chara AO,Pediatric surgery international,0179-0358,1,Pediatr Surg Int,eng,Zamora IJ,"[""Humans"", ""Robotic Surgical Procedures"", ""Retrospective Studies"", ""Female"", ""Child"", ""Adolescent"", ""Minimally Invasive Surgical Procedures"", ""Male"", ""Treatment Outcome"", ""Neoplasms""]",,42545396,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545396/,Robotic-assisted resection of pediatric intracavitary lesions: expanding the boundaries of minimally invasive surgery,42,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"Differentiated thyroid carcinoma (DTC) in children is a rare malignancy characterized by a high propensity for regional and distant metastases yet generally associated with a favorable long-term prognosis. Radioiodine-refractory (RAIR) disease represents a distinct clinical challenge, accounting for approximately 10-30% of pediatric DTC cases, and warrants comprehensive investigation of its clinical course, prognostic factors, and therapeutic options. This study aimed to perform an integrated assessment of treatment outcomes in children undergoing combined therapy for DTC (surgery and radioiodine therapy, RAI), with a particular focus on advanced and RAIR disease. We retrospectively analyzed medical records of 278 patients aged 5-18 years who underwent primary surgical treatment between 2008 and 2022, followed by one or more courses of RAI at the Endocrinology Research Centre (Moscow, Russia) from December 2015 to March 2024. The study included patients with advanced disease (high risk of recurrence at diagnosis) fulfilling at least one RAIR criterion, with a median follow-up of 48.0 months [21.5; 62.0]. Among 278 patients, 39 (14%) were diagnosed with advanced disease. Of these, 4 achieved remissions, 29 had stable disease, and 6 experienced biochemical and/or structural progression. Progression-free survival in the RAIR cohort was 85%, while the 5-year overall survival reached 100%. Based on study findings, we propose a novel classification system integrating both the baseline ability of metastases to accumulate ¹³¹I and the dynamic response to RAI (progression vs. stabilization). This framework is designed to optimize treatment and follow-up algorithms. The management of RAIR pediatric DTC should remain balanced: avoiding overtreatment in stable disease, while ensuring timely initiation of modern systemic therapies in patients with risk factors for progression.","[""English Abstract"", ""Journal Article""]","[""Slaschuk KY"", ""Reinberg MV"", ""Rumyantsev PO"", ""Nikiforovich PA"", ""Konokikhina AP"", ""Pershina-Milyutina AP"", ""Aredov AV"", ""Sheremeta MS"", ""Degtyarev MV"", ""Trukhin AA"", ""Chikulaeva OA"", ""Nagaeva EV"", ""Brovin DN"", ""Chernikov RA"", ""Bezlepkina OB"", ""Peterkova VA"", ""Mokrysheva NG"", ""Dedov II""]",10.14341/probl13649,Slaschuk KY,Problemy endokrinologii,0375-9660,3,Probl Endokrinol (Mosk),rus,Dedov II,"[""Humans"", ""Adolescent"", ""Child"", ""Thyroid Neoplasms"", ""Iodine Radioisotopes"", ""Retrospective Studies"", ""Female"", ""Child, Preschool"", ""Male"", ""Prognosis"", ""Treatment Outcome""]",66-79,42545325,,2026 Jul 22,2026,https://pubmed.ncbi.nlm.nih.gov/42545325/,[Radioiodine-Refractory Differentiated Thyroid Carcinoma in Children and Adolescents: A Retrospective Study],72,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"The evidence linking occupational exposure to lead and cancer in humans is suggestive. Existing studies examine individual exposure to lead, ignoring the potential joint effects of mixed metal exposure. We analyzed the data of a case-control study of lung cancer conducted in seven European countries and comprising 2,861 cases and 2,936 controls, with a detailed assessment of occupational exposure to arsenic, cadmium, chromium (VI), and lead, to estimate the odds ratio (OR) of lung cancer for combined exposure to lead and these other carcinogenic metals, after adjustment for potential confounders. The results suggested a synergism between lead and arsenic or cadmium: ORs were around 1.0 for lead alone and above 2.0 for combined exposure. No interaction was suggested between lead and chromium (VI). Our results provide suggestive evidence of a possible interaction between occupational exposure to lead, arsenic, or cadmium and lung cancer risk, and highlight the importance of considering mixed metal exposures in occupational epidemiology.","[""Journal Article""]","[""Boffetta P"", ""Zaridze D"", ""Świątkowska B"", ""Pándics T"", ""Lissowska J"", ""Fabiánová E"", ""Field JK"", ""Mates D"", ""Schejbalová M"", ""Foretova L"", ""Janout V"", ""Mukheria A"", ""Yang C"", ""Seyyedsalehi MS""]",10.23749/mdl.2026.18905,Boffetta P,La Medicina del lavoro,0025-7818,4,Med Lav,eng,Seyyedsalehi MS,"[""Humans"", ""Lung Neoplasms"", ""Occupational Exposure"", ""Lead"", ""Occupational Diseases"", ""Cadmium"", ""Case-Control Studies"", ""Arsenic"", ""Male"", ""Middle Aged"", ""Chromium"", ""Female"", ""Europe"", ""Risk Factors"", ""Aged""]",18905,42545244,,2026 Aug 3,2026,https://pubmed.ncbi.nlm.nih.gov/42545244/,Combined Occupational Exposure to Lead and Other Metals and Risk of Lung Cancer,117,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"While the radiation dose to left anterior descending (LAD) artery is associated with overall survival (OS) in NSCLC patients, manual segmentation is labor-intensive. Several auto-segmentation models were developed on average 4DCT with promising geometric agreement, yet their feasibility in clinical outcome analysis on lung CT remains unclear. This study evaluates whether automated LAD segmentation can reproduce, at the group level, the established dose-survival association in a multi-institutional clinical trial dataset. Three deep learning-based auto-segmentation (DLAS) models for automatic segmentation of the LAD coronary artery were applied to 460 patients from the NRG Oncology/RTOG 0617 dataset. Kaplan-Meier curves and Cox proportional hazard ratio (HR) were calculated using each model's segmentation. The LAD V15 Gy was used to stratify patients into high-and low-risk groups, and the cut-off values were determined by minimizing mean absolute error (MAE) between DLAS-derived and manual OS curves. All three models demonstrated significantly different OS curves between the high risk and low risk groups (p < 0.05). The HR was 1.40 (95% CI: 1.02-1.93; p = 0.0381; MAE = 7.1%), 1.32 (95% CI: 1.03-1.68; p = 0.0258; MAE = 9.6%), and 1.37 (95% CI: 1.03-1.84; p = 0.0331; MAE = 7.9%) for the three models using a common V15 Gy ≥ 10% cut-off. After optimizing the cut-off, one model aligned well with what was derived from manual segmentation (MAE = 4.3%). Among the evaluated models, one DL model showed the strongest performance of survival groups separation and achieved group-level overall survival stratification comparable to that previously reported using manual contours in the multi-institutional cohort. Further validation with paired manual contours and pre-specified cutoffs is warranted.","[""Journal Article"", ""Evaluation Study"", ""Multicenter Study""]","[""Zhu L"", ""Rong Y"", ""Tao R"", ""Bai Y"", ""Yu NY"", ""Chen Q""]",10.1002/mp.70621,Zhu L,Medical physics,0094-2405,8,Med Phys,eng,Chen Q,"[""Humans"", ""Lung Neoplasms"", ""Carcinoma, Non-Small-Cell Lung"", ""Coronary Vessels"", ""Radiation Dosage"", ""Neoplasm Staging"", ""Survival Analysis"", ""Image Processing, Computer-Assisted"", ""Artificial Intelligence"", ""Radiotherapy Dosage"", ""Deep Learning""]",e70621,42545172,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42545172/,Evaluation of AI-derived LAD artery dose metrics for survival stratification in stage III NSCLC: A secondary analysis of RTOG 0617 trial,53,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"Deep-learning neural network algorithms for detecting prostate cancer in MRI have proliferated in the literature. However, out of 30+ studies published since the PROSTATEx challenge, no studies tested the performance of their algorithm against using true external image data sets (studies came from an outside institution that did not supply any training data to the algorithm) while validating against MR-US fusion biopsy or whole-mount prostatectomy. Using true external data sets paints a much clearer picture of real-world clinical performance of an algorithm. This work will assess the performance of a published deep learning (DL) neural network algorithm to detect prostate cancer using external studies. The main difference from other studies is the combination of using only MR-US fusion biopsy results as a gold standard; using test data from an institution that did not supply any training data for this version of the algorithm (including studies acquired with an endorectal coil, which were not in the original training set); and comparing the performance of algorithm-generated regions-of-interest (ROIs) versus algorithm heat maps. Patients were included in the study if they had a prostate MRI with at least one radiologist-drawn target on MRI and underwent MR-US fusion biopsy where the target was sampled for pathological analysis. Patients were excluded if they had any history of prostate cancer treatment, had previously undergone MR-US fusion biopsy at our institution, were missing MRI acquisitions, had artifacts in image sets, or if the study had been shared for future algorithm development. MR image data was assessed using a DL research prototype (XProstate) from Siemens Healthineers that produced (a) ROIs in suspected cancer areas with a level of suspicion (LoS) score and (b) heat maps with LoS scores across the entire gland. The XProstate prototype had been trained with 2170 studies from eight different academic institutions. Clinical radiologist, XProstate ROI, and XProstate Heat Map scores were assessed with ROC analysis using pathology results from biopsy as a gold standard. 202 unique patients were included for assessment of the XProstate research prototype. The ROC curve for the XProstate Heat Map LoS score generated the highest AUC (0.76, 95% CI: 0.70, 0.82) followed by clinical radiologist PI-RADS score (0.73, 95% CI: 0.68, 0.79) and by XProstate ROI LoS score (0.71, 95% CI: 0.65, 0.77). Neither the XProstate Heat Map (AUC difference = 0.03, 95% CI: -0.04, 0.10, p = 0.38) nor the XProstate ROI (AUC difference = -0.02, 95% CI: -0.09, 0.04, p = 0.43) was significantly different from the radiologist PI-RADS score. The XProstate prototype demonstrated equivalent performance as clinical radiologists when presented with de novo cases that would mirror a real-world clinical deployment. The automatic ROI delineation more closely matched clinical radiologist performance when using a cutoff of PI-RADS 5 for annotating suspicious regions. Overall, the XProstate prototype provided reasonable clinical performance and this study demonstrated the need to assess Deep Learning prototypes with external institutional test data.","[""Journal Article""]","[""Shea SM"", ""Wesolowski M"", ""Hashem A"", ""Goldberg A"", ""Joyce C"", ""Gupta G"", ""Grimm R"", ""von Busch H"", ""Lou B"", ""Kamen A""]",10.1002/mp.70614,Shea SM,Medical physics,0094-2405,8,Med Phys,eng,Kamen A,"[""Prostatic Neoplasms"", ""Humans"", ""Male"", ""Deep Learning"", ""Magnetic Resonance Imaging"", ""Image Processing, Computer-Assisted"", ""Algorithms""]",e70614,42545169,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42545169/,Real-world assessment of a deep learning neural network algorithm for prostate cancer detection in MRI using true de novo data,53,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"The NOTCH1 gene and its signaling pathway play a critical role in the oncogenesis and progression of various carcinomas through complex cellular and molecular mechanisms. This integrative literature review examines 21 selected studies across multiple carcinoma types, including head and neck, prostate, penis, breast, and hepatocellular carcinomas, to elucidate the functional impact of notch1 alterations on tumor behavior and clinical outcomes. NOTCH1 functions as a context-dependent regulator, acting either as an oncogene or tumor suppressor according to cellular environment and molecular context. Aberrations in notch1 signaling influence cell proliferation, differentiation, apoptosis, and angiogenesis, thereby contributing to cancer initiation and progression. Despite some variability in findings, the majority of studies indicate that notch1-related molecular changes have significant implications for prognosis and potential therapeutic targeting. This review highlights the importance of understanding notch1 signaling pathways in the cellular and molecular biology of carcinomas, aiming to pave the way for novel diagnostic and treatment strategies.","[""Journal Article"", ""Review""]","[""Silva LMSD"", ""Matos AGM"", ""Kwang Ii Marciaga Teófilo"", ""Carvalho JV"", ""Duarte DRD"", ""Sousa BLN"", ""Carmo JMDGRD"", ""Beltrammi DGM"", ""Lages JS"", ""Frazão RDGC"", ""Teixeira Júnior AAL"", ""Pinho JD"", ""Silva GEB""]",10.14715/cmb/2026.72.4.1,Silva LMSD,"Cellular and molecular biology (Noisy-le-Grand, France)",0145-5680,4,Cell Mol Biol (Noisy-le-grand),eng,Silva GEB,"[""Humans"", ""Receptor, Notch1"", ""Signal Transduction"", ""Disease Progression"", ""Carcinoma"", ""Animals"", ""Gene Expression Regulation, Neoplastic""]",1-6,42545144,,2026 Apr 30,2026,https://pubmed.ncbi.nlm.nih.gov/42545144/,NOTCH1 gene signaling pathway in the development and progression of carcinomas: an integrative review in cellular and molecular contexts,72,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"Colon cancer is one of the most prevalent cancers globally, characterized by the abnormal growth of cells in the intestines. Numerous studies have explored the effects of pomegranate-derived products, such as pomegranate seed oil (PSO), as anti-proliferative, anti-invasive, and pro-apoptotic agents against various cancer cell lines. Additionally, previous research has highlighted the anti-cancer properties of low-frequency electromagnetic fields (LF-EMF). In the present study, we investigated the combined effects of these two factors on the expression of the Caspase 3, Caspase 9, BAX, and Bcl2 genes. Human colon cancer cells of the HT29 line were sourced from the Pasteur Institute of Iran cell bank and maintained in a complete culture medium. The cells were categorized into four groups: control, PSO, EMF, and PSO+EMF. To assess cell viability and the type of cell death, MTT and Annexin V-FITC assays were employed. Changes in the expression levels of Caspase 3, Caspase 9, BAX, and Bcl2 were analyzed using Real-Time PCR. The results from the MTT and Annexin V-FITC assays indicated that both PSO and EMF reduced cell viability and promoted apoptosis in colon cancer cells. The Real-Time PCR results showed an upregulation of Caspase 3, Caspase 9, and BAX genes, along with a downregulation of Bcl2 expression in the treatment groups compared to the control group. This study demonstrated that the combination of PSO and EMF enhances apoptotic gene expression, thereby diminishing the proliferation and viability of cancer cells. Based on these findings, both PSO and LF-EMF exhibit cytotoxic effects on colon cancer cells, suggesting their potential as candidates for future research in the field of colon cancer.","[""Journal Article""]","[""Ghorbani N"", ""Baharara J"", ""Lotfi M""]",10.14715/cmb/2026.72.4.2,Ghorbani N,"Cellular and molecular biology (Noisy-le-Grand, France)",0145-5680,4,Cell Mol Biol (Noisy-le-grand),eng,Lotfi M,"[""Humans"", ""Apoptosis"", ""bcl-2-Associated X Protein"", ""Caspase 3"", ""Proto-Oncogene Proteins c-bcl-2"", ""Plant Oils"", ""Caspase 9"", ""HT29 Cells"", ""Pomegranate"", ""Seeds"", ""Colonic Neoplasms"", ""Electromagnetic Fields"", ""Gene Expression Regulation, Neoplastic"", ""Cell Survival"", ""Cell Proliferation""]",7-14,42545143,,2026 Apr 30,2026,https://pubmed.ncbi.nlm.nih.gov/42545143/,"Pomegranate seed oil combined with low-frequency electromagnetic field enhances apoptosis in HT29 colon cancer cells via modulating caspase-3, caspase-9, Bax, and Bcl-2 expression",72,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"Emerging evidence indicates that mitochondrial dysfunction is not merely a consequence but a driving force in cancer progression. Unlike normal cells, cancer cells rewire their mitochondrial metabolism to support uncontrolled proliferation, a process that includes aerobic glycolysis, persistent reactive oxygen species production, and adaptation to hypoxic conditions. A common hallmark across many tumors is the suppression of the intrinsic apoptotic pathway, primarily achieved through an imbalance between anti-apoptotic and pro-apoptotic BCL-2 family proteins. This evasion of cell death not only facilitates tumor initiation and metastasis but also contributes to resistance against conventional therapies. Here, we provide an overview of major mitochondrial alterations in cancer, with a detailed focus on how the mitochondrial apoptotic machinery is disabled in malignant cells. We then discuss current therapeutic strategies designed to re-activate mitochondria-mediated apoptosis, including BH3 mimetics, direct activators of pro-apoptotic proteins like BAX, immune checkpoint inhibitors, CAR‑T cell therapy, and mitochondria-targeted nanomedicine. Finally, we address the limitations and safety concerns of existing pro-apoptotic drugs and propose future directions to develop more selective and effective cancer treatments. Understanding the molecular mechanisms that govern mitochondrial apoptosis may open new avenues for inducing tumor cell death while minimizing harm to normal tissues.","[""Journal Article"", ""Review""]","[""Blagov AV"", ""Orekhov NA"", ""Rozhkova U"", ""Antonov S"", ""Utkina A"", ""Orekhov AN""]",10.14715/cmb/2026.72.4.6,Blagov AV,"Cellular and molecular biology (Noisy-le-Grand, France)",0145-5680,4,Cell Mol Biol (Noisy-le-grand),eng,Orekhov AN,"[""Humans"", ""Apoptosis"", ""Mitochondria"", ""Neoplasms"", ""Animals"", ""Mitochondrial Diseases"", ""Proto-Oncogene Proteins c-bcl-2"", ""Reactive Oxygen Species""]",41-55,42545139,,2026 Apr 30,2026,https://pubmed.ncbi.nlm.nih.gov/42545139/,The pivotal role of mitochondrial disorders in cancer development with a special focus on mitochondria-mediated apoptosis,72,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"Epidemiological data show that approximately 80% of cancer patients experience pain of varying degrees throughout the course of their disease, with nearly one-third experiencing severe pain, significantly impacting their quality of life and the effectiveness of antitumor treatment. Triple-negative (TN) breast cancer tissues typically exhibit increased stromal stiffness and abnormally elevated mechanical stress; these biomechanical alterations may amplify pain signals by activating mechanosensitive channels. Utilizing single-cell RNA sequencing analysis, this study aims to elucidate the potential biological links between fibroblast mechanotransduction and cancer-associated pain, thereby providing a theoretical basis for clinical diagnosis and treatment. Dimensionality reduction and unsupervised clustering were used to identify cell types in TN breast cancer single-cell RNA sequencing data. To assess the association between pain and mechanical stimulation, we constructed a set of gene signatures associated with mechanical stimulation and pain and calculated scores using the Area Under the Curve Cell (AUCell). CellChat and SCENIC were used to reveal the communication networks and transcription factor regulatory mechanisms of fibroblast subtypes. COL3A1+ fibroblasts derived from TN breast cancer are highly involved in biological processes such as extracellular matrix remodeling, collagen fiber formation, and mechanotransduction. To assess the association between pain and mechanical stimulation, we constructed a gene signature set related to mechanical stimuli and pain and calculated corresponding scores using the AUCell tool. Cell communication studies showed that COL3A1+ fibroblasts interact extensively with epithelial cells and other cells through laminin and collagen signaling pathways, potentially leading to mechanotransduction remodeling of the TN breast cancer microenvironment. COL3A1+ fibroblasts demonstrate enhanced transcriptional profiles pertinent to collagen deposition and cytoskeletal reorganization, which are correlated with mechanotransduction signaling and may be connected with mechanical sensitivity in cancer-related pain. This study systematically characterizes the potential relationship between fibroblast-associated mechanotransduction characteristics and pain-related gene signatures at the single-cell level in TN breast cancer. These findings offer hypothesis-generating insights into the molecular landscape of tumor-associated pain, although additional experimental and clinical validation is necessary.","[""Journal Article""]","[""Zhong Y"", ""Sun Q"", ""Sun C""]",10.1155/prm/8480126,Zhong Y,Pain research & management,1203-6765,1,Pain Res Manag,eng,Sun C,"[""Humans"", ""Triple Negative Breast Neoplasms"", ""Female"", ""Fibroblasts"", ""Transcriptome"", ""Pain"", ""Mechanotransduction, Cellular"", ""Collagen Type III""]",e8480126,42545099,,2026,2026,https://pubmed.ncbi.nlm.nih.gov/42545099/,Transcriptomic Association of COL3A1(+) Fibroblasts With Mechanical Pain-Related Gene Signatures in Triple-Negative Breast Cancer,2026,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"Automatic segmentation of ultrasound-based thyroid nodules can assist physicians in more efficiently and accurately assessing thyroid diseases. However, thyroid ultrasound imaging presents certain unique challenges, such as blurred boundaries of nodules, strong heterogeneity in tissue echoes, and limited contrast between the lesions and adjacent normal thyroid tissue, which hinder the precise identification of nodules in clinical assessment. To overcome these obstacles, we propose a deep hybrid convolutional network, named UTNseg, for precisely automatic segmentation of ultrasound-based thyroid nodules. UTNseg contains four newly designed modules upon TransUNet: (1) the spatial-channel feature strong capture (STransformer) module is designed to reinforce the ability of encoder on capturing spatial and channel features, (2) the redundant feature map utilization (RMU) module is devised to mitigate redundant information in the skip connections, (3) the composite convolution (CConv) module is newly designed to further preserve the key multi-scale features of the target thyroid nodules, (4) the lightweight edge refinement (LER) module is newly proposed to refine the initial segmentation outputs. UTNseg was evaluated on two publicly available ultrasound datasets of thyroid nodules (TN3K with 3493 images and DDTI with 637 images). Datasets were divided at the patient level, with 4000 training images (2000 images from TN3K and 2000 images from DDTI, augmented by random rotation, scaling, and horizontal flipping on 445 images), 761 validation images (698 images from TN3K and 63 images from DDTI), and 924 test images (795 images from TN3K and 129 images from DDTI). Additionally, separate experiments were performed on these two datasets in comparative experiments. And the performance was compared with six state-of-the-art segmentation methods (U-Net, TransUNet, TRFENet, UNeXt, TRFE+ and BPAT-UNet). Evaluation metrics mainly included Dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (HD95). Statistical significance level was analyzed through the Wilcoxon signed-rank test, and the effect size was quantified by Cohen's d . Holm-Bonferroni correction was employed to correct for multiple comparisons. On the TN3K dataset, UTNseg achieved 79.52% DSC and 16.32 HD95. On the DDTI dataset, UTNseg achieved 86.21% DSC and 12.76 HD95. On the hybrid dataset, UTNseg achieved 80.77% DSC and 14.56 HD95. These results showed that UTNseg achieved superior performance. Compared with state-of-the-art approaches, UTNseg was statistically significant ( p < 0.05  ), and the corresponding effect sizes were mostly medium or large, further quantifying the practical importance of the improvements. UTNseg demonstrated excellent segmentation performance on the public dataset. Statistical significance and effect size analysis both indicate that the improvements are reliable and have practical significance.","[""Journal Article""]","[""Lu F"", ""Sun H"", ""Jiang B"", ""Zhang Z"", ""Ren G"", ""Cai J"", ""Gu Y"", ""Ren P"", ""Peng T""]",10.1002/mp.70548,Lu F,Medical physics,0094-2405,8,Med Phys,eng,Peng T,"[""Thyroid Nodule"", ""Ultrasonography"", ""Humans"", ""Image Processing, Computer-Assisted"", ""Convolutional Neural Networks""]",e70548,42545090,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42545090/,Ultrasound-based thyroid nodule segmentation with deep hybrid convolutional network,53,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"Radium-223 dichloride (Ra-223) is an effective treatment for metastatic castration-resistant prostate cancer (mCRPC) with bone metastases. However, predictive factors associated with treatment efficacy remain unclear. This study evaluated prognostic factors associated with the efficacy of Ra-223 and investigated outcomes according to enzalutamide (ENZ) combination patterns. We retrospectively analyzed 34 patients with mCRPC treated with Ra-223 between 2016 and 2024. Progression-free survival (PFS) and overall survival (OS) were evaluated according to time to CRPC, pre-treatment prostate-specific antigen (PSA), PSA doubling time (PSADT), metastatic burden, and ENZ treatment patterns. Cutoff values were determined using the Contal-O'Quigley method. This study was approved by the Institutional Review Board of Gunma University (Approval No. 1662). The median time to CRPC, pre-treatment PSA level, and PSADT were 17 months, 6.2 ng/mL, and 2.2 months, respectively. Shorter time to CRPC (≤ 19 months), higher pre-treatment PSA (> 2.67 ng/mL), and shorter PSADT (≤ 2 months) were significantly associated with shorter PFS. Patients with ≥ 4 bone metastatic regions had significantly worse OS than those with ≤ 3 regions. Among the ENZ treatment patterns, continuous ENZ administration combined with Ra-223 was associated with significantly longer PFS than discontinuation of ENZ. Time to CRPC, pre-treatment PSA, and PSADT may represent potentially useful candidate markers for identifying patients more likely to benefit from Ra-223 therapy. Continued ENZ administration during Ra-223 therapy was associated with favorable PFS in selected patients; however, this finding should be considered exploratory and requires validation in larger cohorts.","[""Journal Article""]","[""Abe K"", ""Miyazawa Y"", ""Nakazawa S"", ""Onose M"", ""Maeno Y"", ""Tsuji Y"", ""Kanayama A"", ""Ohtsu A"", ""Fujizuka Y"", ""Arai S"", ""Nomura M"", ""Sekine Y"", ""Koike H"", ""Matsui H"", ""Suzuki K""]",10.1111/iju.70591,Abe K,International journal of urology : official journal of the Japanese Urological Association,0919-8172,8,Int J Urol,eng,Suzuki K,"[""Humans"", ""Male"", ""Prostatic Neoplasms, Castration-Resistant"", ""Benzamides"", ""Nitriles"", ""Radium"", ""Prostate-Specific Antigen"", ""Retrospective Studies"", ""Bone Neoplasms"", ""Phenylthiohydantoin"", ""Aged"", ""Aged, 80 and over"", ""Progression-Free Survival"", ""Antineoplastic Agents"", ""Treatment Outcome"", ""Prognosis"", ""Time Factors"", ""Middle Aged"", ""Radioisotopes"", ""Kallikreins"", ""Predictive Value of Tests""]",e70591,42544862,,2026 Aug,2026,https://pubmed.ncbi.nlm.nih.gov/42544862/,Real-World Outcomes of Radium-223 Therapy in Metastatic Castration-Resistant Prostate Cancer: Predictive Value of PSA Doubling Time and Enzalutamide Continuation,33,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"Blinatumomab is the first globally approved bispecific T cell engager targeting the B-cell surface antigen CD19, and numerous clinical trials have demonstrated its significant efficacy in B-acute lymphoblastic leukemia (B-ALL) patients. However, with its widespread application, the problem of drug resistance is gradually becoming apparent. The specific mechanisms of drug resistance mainly include antigen escape, lineage switch, immune checkpoint pathway dysregulation and T cell exhaustion. In this review, the mechanisms of resistance to blinatumomab in B-ALL are systematically described, and relevant therapeutic strategies targeting these resistance factors are summarized to provide a reference for clinical diagnosis and treatment.","[""Journal Article"", ""Review"", ""English Abstract""]","[""Jing XR"", ""Cheng J""]",10.19746/j.cnki.issn1009-2137.2026.03.043,Jing XR,Zhongguo shi yan xue ye xue za zhi,1009-2137,3,Zhongguo Shi Yan Xue Ye Xue Za Zhi,chi,Cheng J,"[""Antibodies, Bispecific"", ""Humans"", ""Drug Resistance, Neoplasm"", ""Precursor Cell Lymphoblastic Leukemia-Lymphoma""]",926-930,42544688,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42544688/,[Study on the Resistance Mechanism of Blinatumomab in the Treatment of Acute Lymphoblastic Leukemia--Review],34,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"Cellular senescence is fundamentally characterized as an irreversible cell cycle arrest state. Studies have revealed that cellular senescence plays a significant role in the pathogenesis and progression of hematological malignancies. Consequently, inducing cellular senescence has emerged as a therapeutic strategy for these malignancies. Traditional Chinese herbal medicine, characterized by its high efficacy and relatively low toxicity, has shown unique potential in inducing senescence in hematological tumor cells. Previous studies have shown that traditional Chinese herbal medicine can induce cellular senescence through mechanisms such as telomere shortening, DNA damage induction, and regulation of the senescence-associated secretory phenotype (SASP) to treat hematological malignancies. This review aims to summarize the recent advances in the mechanisms by which cellular senescence contributes to the pathogenesis of hematological malignancies and the role of traditional Chinese herbal medicine in inducing cellular senescence for therapeutic purposes, thereby providing novel insights and theoretical support for the application of traditional Chinese herbal medicine in the treatment of hematological malignancies.","[""Journal Article"", ""Review"", ""English Abstract""]","[""Wang MY"", ""Zhu XJ""]",10.19746/j.cnki.issn1009-2137.2026.03.041,Wang MY,Zhongguo shi yan xue ye xue za zhi,1009-2137,3,Zhongguo Shi Yan Xue Ye Xue Za Zhi,chi,Zhu XJ,"[""Cellular Senescence"", ""Humans"", ""Hematologic Neoplasms"", ""Drugs, Chinese Herbal"", ""Medicine, Chinese Traditional""]",917-921,42544686,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42544686/,[Cellular Senescence in Hematological Malignancies: Pathogenesis and Traditional Chinese Medicine Treatment Strategies--Review],34,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"Chimeric antigen receptor T cell (CAR-T) therapy is a revolutionary progress in the current field of tumor treatment, especially showing remarkable potential in relapsed/refractory hematological malignancies. However, there are significant differences in efficacy among different patients, and such differences are affected by multiple clinical and biomedical factors. This review will discuss the current application status of CAR-T therapy in hematological malignancies, analyze the key factors influencing the efficacy, and summarize the latest research trends and development directions in this field, so as to provide references for clinical decision - making and scientific research innovation.","[""Review"", ""Journal Article"", ""English Abstract""]","[""Li LM"", ""Lai X"", ""Yin HJ""]",10.19746/j.cnki.issn1009-2137.2026.03.040,Li LM,Zhongguo shi yan xue ye xue za zhi,1009-2137,3,Zhongguo Shi Yan Xue Ye Xue Za Zhi,chi,Yin HJ,"[""Humans"", ""Hematologic Neoplasms"", ""Immunotherapy, Adoptive"", ""Receptors, Chimeric Antigen"", ""T-Lymphocytes""]",910-916,42544685,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42544685/,[Advances in the Study of Factors Influencing the Efficacy of CAR-T Cell Therapy in Hematologic Oncology Treatment--Review],34,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"The development and progression of leukemia are driven not only by intrinsic genetic and epigenetic alterations in leukemia cells, but also by the dynamic remodeling of immune niches within the bone marrow microenvironment (BMM). Accumulating evidence has indicated that leukemic cells can reshape the immune microenvironment through cytokine secretion, metabolic reprogramming, and other mechanisms, inducing T-cell dysfunction/exhaustion, impaired NK-cell effector functions, and immunosuppressive polarization of myeloid cells, thereby establishing a protective niche that facilitates disease progression, drug resistance, and relapse. In parallel, epigenetic mechanisms such as DNA methylation, histone modification, and RNA modifications bridge the phenotypic plasticity of leukemic cells and immune evasion processes by regulating antigen presentation, interferon signaling pathways, chemokine profiles, and immune checkpoint expression, thereby influencing the response to immunotherapy. This review centers on the core conceptual framework of ""immune microenvironment remodeling - epigenetic regulation - drug resistance and relapse - combination therapy strategies"". It systematically outlines the key immunosuppressive networks and their epigenetic foundations across different leukemia subtypes. Emphasis is placed on the advances and challenges in combining epigenetic drugs, such as demethylating agents and histone deacetylase inhibitors, with immune checkpoint inhibitors, BCL-2 inhibitors, and microenvironment-targeted therapies. Furthermore, it outlines future directions in microenvironment subtyping and precision interventions driven by single-cell and spatial multi-omics technologies, aiming to provide a theoretical basis for optimizing combination treatment strategies in leukemia.","[""Journal Article"", ""Review"", ""English Abstract""]","[""Liu BH"", ""Zhang XZ"", ""Yang FF""]",10.19746/j.cnki.issn1009-2137.2026.03.039,Liu BH,Zhongguo shi yan xue ye xue za zhi,1009-2137,3,Zhongguo Shi Yan Xue Ye Xue Za Zhi,chi,Yang FF,"[""Tumor Microenvironment"", ""Epigenesis, Genetic"", ""Humans"", ""Leukemia"", ""DNA Methylation"", ""Immunotherapy""]",906-909,42544684,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42544684/,[Research Progress on Epigenetic Regulation of the Leukemia Microenvironment --Review],34,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"Acute myeloid leukemia (AML) is a highly heterogeneous disease. This heterogeneity often leads to treatment failure or unsustainable efficacy, and high relapse rates as well as short progression-free survival (PFS) are closely associated with poor prognosis. Cyclin-dependent kinases (CDKs) play a central role in cell cycle regulation, transcription regulation, and metabolic processes, and their aberrant expression or dysfunction is considered as one of the key drivers of AML progression. Recent studies have increasingly focused on CDK inhibitors, aiming to address drug resistance and improve prognosis. Although some CDK inhibitors have shown promising anti-AML potential, challenges such as off-target effects and systemic toxicity remain daunting. This review systematically summarized the research progress of CDK inhibitors in the treatment of AML, with a particular focus on the results of preclinical studies and clinical trials targeting CDKs in AML, such as CDK2, CDK4/6, CDK7, and CDK9. In addition, the limitations of current therapeutic applications of CDK inhibitors were discussed, and potential strategies to overcome these challenges were explored, aiming to provide a reference for optimizing AML treatment regimens.","[""Journal Article"", ""Review"", ""English Abstract""]","[""Liu YF"", ""Liu H""]",10.19746/j.cnki.issn1009-2137.2026.03.038,Liu YF,Zhongguo shi yan xue ye xue za zhi,1009-2137,3,Zhongguo Shi Yan Xue Ye Xue Za Zhi,chi,Liu H,"[""Leukemia, Myeloid, Acute"", ""Humans"", ""Protein Kinase Inhibitors"", ""Cyclin-Dependent Kinases""]",899-905,42544683,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42544683/,[Research Progress of CDK Inhibitors in Acute Myeloid Leukemia --Review],34,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"To investigate the clinical characteristics, drug resistance and prognosis of Enterobacteriaceae bloodstream infection (BSI) in children with acute leukemia (AL) following chemotherapy. A retrospective analysis was performed on children with Enterobacteriaceae BSI after AL chemotherapy in four hospitals in Fujian Province from January 2015 to December 2023. The clinical characteristics, drug resistance and prognosis of these children were analyzed. A total of 140 children were enrolled, including 117 cases of acute lymphoblastic leukemia and 23 cases of acute myeloid leukemia. BSI occurred in 52.14% of the children during the induction chemotherapy phase, 35.00% during the intensive chemotherapy phase, and 12.86% during the maintenance chemotherapy phase. All children manifested fever, 81.43% had neutropenia, 21.43% had septic shock, 16.43% had no clear infectious lesions, 83.57% had infectious lesions, and 45.71% had two or more multi-site infections. Among the 140 strains of Enterobacteriaceae bacteria, 50.71% were Klebsiella bacteria, 35.00% were Escherichia bacteria, 10.00% were Enterobacter bacteria, and 4.29% were Salmonella bacteria. The highest proportion of multidrug-resistant bacteria (MDRB) and carbapenem-resistant Enterobacteriaceae (CRE) were found in Escherichia (68.89% and 14.89%). Amikacin had the lowest resistance rate among Klebsiella, Escherichia, and Enterobacter. There were no significant differences in pathogen distribution, proportions of MDRB and CRE between the first 4 year group (2015-2018) and the last 5 year group (2019-2023) (P >0.05). There were significant differences in albumin levels, the proportion of anti-infective treatment one week before BSI, proportion of carbapenem anti-infective treatment before BSI, and proportion of deaths between CRE group and non-CRE group (all P <0.05). Among the 140 children, except for 2 children who gave up treatment and the outcomes were unknown, 123 children were cured and 15 children died of BSI. The attributable mortality rate was 10.87% (15/138), and the mortality related to septic shock was 33.33% (10/30). Univariate analysis showed that gender, proportion of septic shock, proportion of CRE strain, albumin level, C-reactive protein (CRP) level and procalcitonin level were significantly different between the cure group and the death group (all P <0.05). Multivariate logistic regression analysis showed that septic shock, lower albumin level and higher CRP level were independent risk factors for death in children with Enterobacteriaceae BSI. In children with Enterobacteriaceae BSI following AL chemotherapy, CRE infection is associated with higher mortality. Septic shock, low albumin, and high CRP are independent risk factors for death caused by Enterobacteriaceae BSI.","[""English Abstract"", ""Journal Article""]","[""Huang SX"", ""Wu CP"", ""LE SH"", ""Zhuang SQ"", ""Wang XF"", ""Guo BY"", ""Lian ZL"", ""Zheng YZ"", ""Weng KZ""]",10.19746/j.cnki.issn1009-2137.2026.03.034,Huang SX,Zhongguo shi yan xue ye xue za zhi,1009-2137,3,Zhongguo Shi Yan Xue Ye Xue Za Zhi,chi,Weng KZ,"[""Humans"", ""Prognosis"", ""Enterobacteriaceae"", ""Retrospective Studies"", ""Enterobacteriaceae Infections"", ""Anti-Bacterial Agents"", ""Drug Resistance, Bacterial"", ""Child"", ""Precursor Cell Lymphoblastic Leukemia-Lymphoma"", ""Female"", ""Bacteremia"", ""Child, Preschool"", ""Leukemia"", ""Infant""]",870-877,42544679,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42544679/,"[Clinical Characteristics, Drug Resistance, and Prognosis Analysis of Enterobacteriaceae Bloodstream Infection in Children with Acute Leukemia]",34,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"To investigate the relationship between TP53 and MYD88 mutations and treatment efficacy in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based standard chemoimmunotherapy. The clinical data of 92 patients with newly diagnosed DLBCL who were treated in the Department of Hematology of the Huai'an No.1 People's Hospital and Yancheng No.1 People's Hospital from January 1, 2015 to December 30, 2023 were retrospectively analyzed. Chi-square test, univariate and multivariate logistic regression analyses were used to identify risk factors associated with treatment efficacy, and a predictive model was further established. Survival curves were plotted using the Kaplan-Meier method, and differences in survival between groups were compared by the log-rank test. Among the 92 patients, 71 (77.2%) achieved post-induction remission (remission group) and 21 (22.8%) did not respond to treatment (non-remission group). The proportions of patients with elevated lactate dehydrogenase (LDH) (P =0.022) and those with MYD88 mutation (P =0.021) were significantly higher in the non-remission group than in the remission group. Univariate analysis showed that LDH (OR =3.482, P =0.027) and MYD88 mutation (OR =3.175, P =0.024) were factors influencing treatment efficacy in DLBCL patients receiving chemoimmunotherapy. Multivariate analysis showed that TP53 mutation （P =0.031） and MYD88 mutation （P =0.010） were independent risk factors for poor treatment efficacy in DLBCL patients. A treatment efficacy prediction model for DLBCL was established based on TP53 and MYD88 mutations, with an area under the receiver operating characteristic (ROC) curve of 0.705. According to the novel predictive model, the enrolled patients were divided into high-risk and low-risk groups. Treatment efficacy analysis showed that the objective response rate (ORR) of the low-risk group was significantly higher than that of the high-risk group (92.3% vs. 66.0%, P =0.006), and the progression-free survival (PFS) and overall survival (OS) of patients in the high-risk group were significantly poorer than those in the low-risk group (PFS: P =0.024; OS: P =0.004). TP53 mutation and MYD88 mutation are independent risk factors for poor efficacy in DLBCL patients receiving first-line immunochemotherapy. The novel predictive model constructed based on these two mutations can identify patients with potential poor response to first-line chemoimmunotherapy, which may provide a reference for optimizing the first-line individualized treatment strategy for DLBCL.","[""English Abstract"", ""Journal Article""]","[""Yao YM"", ""Shi YY"", ""Deng Y"", ""Li YJ"", ""Chen QN"", ""Miao YQ"", ""Wang CL""]",10.19746/j.cnki.issn1009-2137.2026.03.015,Yao YM,Zhongguo shi yan xue ye xue za zhi,1009-2137,3,Zhongguo Shi Yan Xue Ye Xue Za Zhi,chi,Wang CL,"[""Lymphoma, Large B-Cell, Diffuse"", ""Humans"", ""Myeloid Differentiation Factor 88"", ""Tumor Suppressor Protein p53"", ""Mutation"", ""Retrospective Studies"", ""Treatment Outcome"", ""Rituximab"", ""Female"", ""Male"", ""Prognosis""]",732-738,42544660,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42544660/,[Impact of TP53 and MYD88 Mutations on Treatment Efficacy in Diffuse Large B-Cell Lymphoma],34,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"To evaluate the predictive value of peripheral blood CD4+/CD8+ ratio immediately prior to chimeric antigen receptor T-cell (CAR-T) infusion (Day 0) for treatment efficacy in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). A retrospective analysis was conducted on data from 49 R/R DLBCL patients who received CAR-T therapy at The First Affiliated Hospital of Soochow University between January 2017 and June 2024. The relationship between the Day 0 peripheral blood CD4+/CD8+ ratio and treatment efficacy was evaluated. At 3 months post-CAR-T infusion, the objective response rate of the 49 patients was 75.5% (37/49), comprising a complete response rate of 55.1% (27/49) and a partial response rate of 20.4% (10/49). Patients with a Day 0 peripheral blood CD4+/CD8+ ratio ≥1 had a significantly higher 90-day response rate than those with a ratio <1 (88.2% vs. 46.7%, P =0.002). Multivariate analysis showed that the Day 0 peripheral blood CD4+/CD8+ ratio was an independent predictor of both progression-free survival (PFS) and overall survival (OS) (P =0.025； P =0.037). Patients with a ratio ≥1 had significantly longer median PFS (11.0 vs. 3.0 months, P =0.011) and median OS (32.1 vs. 8.5 months, P =0.003) compared to those with a ratio <1. Peripheral blood CD4+/CD8+ ratio ≥1 immediately prior to CAR-T infusion can predict a higher CAR-T treatment response rate and superior survival outcomes in R/R DLBCL patients.","[""English Abstract"", ""Journal Article""]","[""Xia F"", ""Zhu Q"", ""Li JH"", ""Zhang X"", ""Qu CJ"", ""Ping NN""]",10.19746/j.cnki.issn1009-2137.2026.03.013,Xia F,Zhongguo shi yan xue ye xue za zhi,1009-2137,3,Zhongguo Shi Yan Xue Ye Xue Za Zhi,chi,Ping NN,"[""Humans"", ""Lymphoma, Large B-Cell, Diffuse"", ""Retrospective Studies"", ""Immunotherapy, Adoptive"", ""CD4-CD8 Ratio"", ""Receptors, Chimeric Antigen"", ""Treatment Outcome"", ""Female"", ""CD8-Positive T-Lymphocytes""]",719-725,42544658,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42544658/,[The Impact of CD4(+)/CD8(+) Ratio on the Efficacy of CAR-T Therapy in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma],34,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm
"To summarize the clinicopathological characteristics and survival outcomes of pediatric non-Hodgkin lymphoma (NHL) in Fujian Province. Clinical data of 294 newly diagnosed pediatric NHL patients treated at multiple centers in Fujian Province from January 2011 to December 2023 were collected. The characteristics of different pathological subtypes were summarized, Kaplan-Meier survival analysis were performed and Cox proportional hazards regression model was used for prognostic analysis. A total of 294 pediatric NHL patients were included in this study, with a male-to-female ratio of 3.03∶1 and a median age of 7 years (range, 0.9-14 years). The most common subtype was mature B-cell lymphoma, accounting for 59.2% of cases. The majority of patients were diagnosed at stage III/IV (86.2%), with 32 cases (10.9%) involving central nervous system (CNS) infiltration and 89 cases (30.3%) showing bone marrow involvement. The rate of voluntary abandonment significantly decreased after 2018 (abandonment rates before and after 2018: 6/110 (5.45%) vs. 1/184 (0.54%), P =0.012). Furthermore, excluding cases of voluntary abandonment, the 5-year EFS and OS of newly diagnosed pediatric NHL patients from 2018 to 2023 were still significantly higher than those diagnosed from 2011 to 2017 (EFS: 79.3%±3.7% vs. 70.2%±4.5%, P =0.032; OS: 87.7%±2.6% vs. 70.2%±4.5%, P < 0.001). OS improvements after 2018 were significant in patients with BL and LBL (BL: 89.3%±3.6% vs. 73.5%±7.6%, P =0.033; LBL: 89.3%±5.3% vs. 56.5%±10.3%, P =0.001). However, there were no statistically significant differences in EFS or OS for patients with ALCL or DLBCL (all P >0.05). Multivariate survival analysis identified concurrent hemophagocytic lymphohistiocytosis syndrome was an independent risk factors for both EFS and OS in pediatric NHL patients. Over the past six years, OS and EFS in children with NHL in Fujian Province have improved markedly, with more pronounced gains in BL and LBL. This trend may be related to the combined effects of reduced voluntary treatment abandonment, more standardized diagnostic and therapeutic pathways, treatment optimization, and updated protocols. HLH at initial diagnosis is an independent risk factor for poor prognosis in pediatric NHL, while remission after two chemotherapy cycles suggests a favorable outcome.","[""English Abstract"", ""Journal Article""]","[""Pan LL"", ""Zheng YZ"", ""Li J"", ""Guo BY"", ""Zhu Y"", ""Weng KZ"", ""Luo JH"", ""Zhuang SQ"", ""Wang XF"", ""Sun GY"", ""Wu XG"", ""LE SH""]",10.19746/j.cnki.issn1009-2137.2026.03.011,Pan LL,Zhongguo shi yan xue ye xue za zhi,1009-2137,3,Zhongguo Shi Yan Xue Ye Xue Za Zhi,chi,LE SH,"[""Humans"", ""Lymphoma, Non-Hodgkin"", ""Child"", ""Male"", ""Prognosis"", ""Adolescent"", ""China"", ""Child, Preschool"", ""Female"", ""Infant"", ""Survival Analysis"", ""Survival Rate"", ""Proportional Hazards Models""]",705-712,42544656,,2026 Jun,2026,https://pubmed.ncbi.nlm.nih.gov/42544656/,[Clinical Characteristics and Survival Analysis of Pediatric Non-Hodgkin Lymphoma in Fujian Province],34,Go7K2JVpSvk8eVRte,jpygUiz3jdWfPL1dm