Oxygen-independent enzymatic dearomatization of homocyclic aromatic compounds

Abstract: 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.

Zhan T
Breiltgens J
Appel L
Peller L
Husain SM
Müller M
Boll M


Hydrogels: current biomedical applications and future directions

Abstract: 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.

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

Hydrogels
Humans
Tissue Engineering
Animals
Drug Delivery Systems
Regenerative Medicine
Biocompatible Materials


Neurons Die Not by One Hit, but by Signaling Convergence

Abstract: 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.

Humans
Animals
Signal Transduction
Neurons
Oxidative Stress
Neurodegenerative Diseases
Cell Death
Mitochondria


Sensitive detection of unopposed estrogen using estrogen receptor functionalized nanoprobes for cancer diagnosis

Abstract: 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.

Uti DE
Alum EU
Ogbu CO
Ugwu OP
Egbung GE
Atangwho IJ
Dagnaw M
Jan A


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

Abstract: 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.

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


Chronic Myelomonocytic Leukemia: History, Pathobiology, Diagnostic Controversies, and Evolving Classification

Abstract: 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.

Humans
Leukemia, Myelomonocytic, Chronic
Mutation


Habit Formation to Enhance Implementation of Evidence-based Practice

Abstract: 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.

Administration and policy in mental health


Genotypic features of antimicrobial resistance, virulence determinants, and clonal lineages of Enterococcus spp. reported in Brazil: a scoping review with marked regional asymmetry

Abstract: 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.

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology


Microfragmented Adipose Tissue in Pain Management: Bridging Regenerative Biology and Clinical Therapeutics

Abstract: 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.

Van Tran Y
Van Pham P
Encinas MN
Puttini PS
Myrcik D
Dauri P
Farì G
Gharibo CG
Leoni MLG
Mercieri M
Varrassi G


New trends in the overdose epidemic: postural impact on abusers of fentanyl and xylazine and clinical and forensic implications

Abstract: 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.

Forensic science, medicine, and pathology

da Silva MLO
Barbosa J
Dinis-Oliveira RJ


Cardiac magnetic resonance parametric mapping in patients with thalassemia: Clinical insights into native myocardial T1 mapping and its relationship with T2*. A systematic review

Abstract: 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.

The international journal of cardiovascular imaging

Pegoraro N
Carnevale A
Bisi R
Giganti M
Longo F
Cossu A


Bacillus Probiotics in Broiler Nutrition: Mechanisms, Gut Health, Performance, and Practical Considerations

Abstract: 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.


Remote robot-assisted renal surgery: a systematic review and single-arm meta-analysis of real-world evidence

Abstract: 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.

Cao S
Li QL
Qin J
Huang HT
Li HY
Guan RX
Zhou XY
Yin JY
Tan SZ
Zhang XY
Yang XS

Humans
Robotic Surgical Procedures
Nephrectomy
Length of Stay
Operative Time
Kidney
Blood Loss, Surgical
Telemedicine

Journal Article
Systematic Review
Meta-Analysis
Review


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)

Abstract: 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.

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


Unraveling the Multifaceted Roles of Tissue-Resident Macrophages: Focus on Bone Homeostasis and Regeneration

Abstract: 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.

Feng X
Wu Q
Yan Y
Yu B
Zhu Z
Qiao Y
Wei J


Cardiovascular Care in Multiple Myeloma: A Comprehensive Review and Integrated Systems-Based Approach from a UK Cardio-Oncology Centre of Excellence

Abstract: 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.

Akrawi D
Datta S
Hatipoglu S
Wechalekar AD
Ghose A
Alkhateeb A
Walker JM
Ghosh AK

Humans
Multiple Myeloma
Cardio-Oncology
Cardiovascular Diseases
United Kingdom
Delivery of Health Care, Integrated
Cardiotoxicity
Antineoplastic Agents
Risk Factors
Risk Assessment


Global trends in learning curves of robot-assisted urological surgery: a bibliometric analysis of surgical safety and functional recovery

Abstract: 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.

Zhang Y
Wang K
Wang H
Yan R
Gui H
Man J
Yang L

Robotic Surgical Procedures
Urologic Surgical Procedures
Humans
Learning Curve
Bibliometrics
Recovery of Function
Clinical Competence


Early versus delayed oral sialagogues for the prevention of salivary gland dysfunction after radioiodine therapy in differentiated thyroid cancer: a systematic review

Abstract: 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.

Frankowski Dagostin A
Rehandhika NY
Potiguara de Souza AL
Holland S

Humans
Thyroid Neoplasms
Iodine Radioisotopes
Sialadenitis
Salivary Gland Diseases
Time Factors
Salivary Glands


Calreticulin as a stress-responsive integrator of ER proteostasis, calcium homeostasis, and immune clearance

Abstract: 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.

Calreticulin
Humans
Proteostasis
Calcium
Endoplasmic Reticulum
Animals
Homeostasis
Endoplasmic Reticulum Stress
Cellular Senescence


Global research trends in robotic applications in cosmetic dermatology: a bibliometric analysis

Abstract: 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.

Öktem R
Yıldırım KPH
Tanaçan E
Hasanbeyzade S
Ünal E
Rota DD

Humans
Dermatology
Bibliometrics
Robotic Surgical Procedures
Cosmetic Techniques
Robotics


A kinetic-based framework for the selection of in vitro osteoarthritis models: integrating temporal dynamics of inflammatory inducers

Abstract: 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.

Cheng G
Atheeqah-Hamzah N
Liu X
Lv F
Loh KW
Aziz A
Tan HL
Tunku K

Osteoarthritis
Humans
Interleukin-1beta
Tumor Necrosis Factor-alpha
Lipopolysaccharides
Kinetics
Inflammation
Matrix Metalloproteinase 13
ADAMTS5 Protein
Chondrocytes
Animals
Models, Biological
Signal Transduction


Astragalus polysaccharides in aquaculture: a comprehensive review on growth, immunity, and disease resistance

Abstract: 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.

Animals
Astragalus Plant
Polysaccharides
Aquaculture
Disease Resistance
Fishes
Animal Feed
Antioxidants


Assessment methods for surgeons' ergonomics in the operating room: a scoping review

Abstract: 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.

Hayashi S
Watanabe J
Hayashi K
Matsui R
Kinoshita J
Inaki N


The efficacy of ERAS-related components in orthopedic trauma surgery: a systematic review and meta-analysis of randomized controlled trials

Abstract: 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.

European journal of orthopaedic surgery & traumatology : orthopedie traumatologie

Das DL
Aiman U
Shahzad UB
Malik T
Khan TI
Ahmed M
Talha M
Sheikh AR
Zahoor RMW
Saleem MF
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


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

Abstract: 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.

Humans
Intestinal Perforation
Diverticulitis, Colonic
Treatment Outcome
Conservative Treatment

Journal Article
Systematic Review
Letter


Transcatheter Pulmonary Valve Replacement in the Native Dysfunctional Right Ventricular Outflow Tract: Strategies for Optimal Prosthesis Selection, Valve Deployment and Lifetime Management

Abstract: 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.


Improving T-cell engager efficacy in glioblastoma with multi-antigen targeting and novel delivery approaches

Abstract: 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.

Humans
Glioblastoma
T-Lymphocytes
Brain Neoplasms
Animals
Immunotherapy
Antigens, Neoplasm


Adaptive cascading artificial intelligence for Alzheimer's disease assessment: a clinically oriented narrative review and implementation framework

Abstract: 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.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

Hooshmandi S
Rahimi Jaberi K
Kamalov F
Nami M

Humans
Alzheimer Disease
Artificial Intelligence
Biomarkers


The incidence and epidemiology of patellar fractures following medial patellofemoral ligament reconstruction: a systematic review and meta-analysis

Abstract: 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.

Archives of orthopaedic and trauma surgery

Abelleyra Lastoria DA
Hunt A
Ross CK
Yemane M
Keynes S
Ghosh A
Hing CB

Humans
Patella Fracture
Incidence
Patellofemoral Joint
Plastic Surgery Procedures
Joint Instability
Ligaments, Articular
Postoperative Complications
Risk Factors
Patella


Injectable Filler-Based Chin Augmentation: A Systematic Review of Non-Surgical Volumetric Techniques

Abstract: 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 .

Shome D
Bose D
Prabhughate A
Shah R
Kapoor R


[Perioperative management of trochanteric femoral fractures : Fasting, fluid therapy and multimodal pain management as underappreciated factors]

Abstract: 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.

Link BC
Haefeli PC
Rohner-Spengler M
van de Wall B
Beeres FJP


Minimally invasive surgery in adult spinal deformity: sagittal alignment correction potential and clinical outcomes. A systematic review of the literature

Abstract: 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.

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

Quarto E
Zanirato A
Marston SJ
Alhourani H
Armani L
Massarini E
Vandenbulcke A
Luyet A
Dimitriou J
Formica M
Le Huec JC


Death by neurologic criteria: a nuclear medicine approach based on the 2023 AAN/AAP/CNS/SCCM Guideline and 2025 SNMMI Procedure Standard

Abstract: 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.


Artificial intelligence in the radiologic diagnosis of major urological cancers: a meta-analysis

Abstract: 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.

Humans
Artificial Intelligence
Urologic Neoplasms
Sensitivity and Specificity

Journal Article
Meta-Analysis
Systematic Review


Antiaromaticity by on-surface synthesis

Abstract: 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.


Overview of the DREADDs chemogenetics and the patent landscape of their actuators

Abstract: 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.

Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents


Topical strategies for antimicrobial delivery of peptide medicines for the management of chronic wounds

Abstract: 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.

Murthy S
Zhao TY
Neela VK
Hassan M
Selvaraja M
Palanirajan VK


Biomarkers of Lyme neuroborreliosis: a systematic review

Abstract: 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.

Fjordside L
Florescu A
Dos AH
Ørbaek M
Mens H
Lebech AM


Acute respiratory distress syndrome in scrub typhus: a systematic review and meta-analysis

Abstract: 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).

Chaudhuri S
Adhikari SD
Boodman C
Schmiedel Y
Grobusch MP
Gupta N


Mechanistic and molecular insights into emerging anti-virulence therapeutics

Abstract: 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.


The future of meat: innovations in production within an expanding and sustainable food system

Abstract: 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.


Management of anterior shoulder instability in patients aged 40 and older: a systematic review

Abstract: 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.

Ybema S
Khan W
Vivekanantha P
Bouchard MD
Kotipalli S
Kay J

Humans
Joint Instability
Shoulder Joint
Adult
Rotator Cuff Injuries
Middle Aged
Shoulder Injuries
Shoulder Dislocation
Aged
Range of Motion, Articular

Journal Article
Systematic Review
Review


Advances in TMDs-Based Electromagnetic Wave Absorbers: From Structural Engineering to Multicomponent Synergy

Abstract: 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.

Yan Y
Lun A
Gao B
Liu Y
Jia D
Zhou Y
Huang X


Exosome-mediated siRNA delivery in cancer: Loading strategies, targeting approaches, and therapeutic outcomes

Abstract: 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.

Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences

Abdelgawwad El-Sehrawy AAM
Youssef Hussein H
Nematov O
Baig MR
Patel DN
Priyadarshini Nayak P
Alkayyat S
Bainsal N
Singh G
Basunduwah TS

Humans
Exosomes
RNA, Small Interfering
Neoplasms
Animals
Tumor Microenvironment
Gene Silencing
Nanoparticles


Thrombolytic resistance: an important factor leading to the failure of intravenous thrombolytic therapy

Abstract: 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.

Liu J
Gao X
Sun Y
Shang Y
Guo J
Cheng J
Bi X
Zhang X

Humans
Thrombolytic Therapy
Fibrinolytic Agents
Tissue Plasminogen Activator
Drug Resistance
Ischemic Stroke
Animals
Treatment Failure


Nicotine in Neurodegenerative and Neuropsychiatric Disorders: Mechanisms and Clinical Evidence

Abstract: 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.

Humans
Nicotine
Animals
Neurodegenerative Diseases
Mental Disorders
Receptors, Nicotinic
Nicotinic Agonists


Efflux-mediated carbapenem resistance: unveiling genetic drivers, clinical implications, and strategies for global antimicrobial stewardship

Abstract: 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.

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


The effect of water immersion thermotherapy on sleep quality: a systematic review and meta-analysis of randomized controlled trials

Abstract: 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.

Humans
Randomized Controlled Trials as Topic
Sleep Quality
Hyperthermia, Induced
Water
Sleep Duration
Immersion


Oligometastatic esophageal squamous cell carcinoma: a systematic review of current definitions and meta-analysis of local therapy outcomes

Abstract: 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.

Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus

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

Humans
Esophageal Neoplasms
Esophageal Squamous Cell Carcinoma
Treatment Outcome
Neoplasm Metastasis
Female
Male

Systematic Review
Journal Article
Meta-Analysis