{"id": "converted_2970", "sentence1": "Does allele phasing improve the phylogenetic utility of ultraconserved elements?", "sentence2": "Allele Phasing Greatly Improves the Phylogenetic Utility of Ultraconserved Elements., Our empirical analyses of Ultraconserved Element (UCE) locus data collected from the South American hummingbird genus Topaza demonstrate that phased allele sequences carry sufficient phylogenetic information to infer the genetic structure, lineage divergence, and biogeographic history of a genus that diversified during the last three million years. The phylogenetic results support the recognition of two species, and suggest a high rate of gene flow across large distances of rainforest habitats but rare admixture across the Amazon River. Our simulations provide evidence that analyzing allele sequences leads to more accurate estimates of tree topology and divergence times than the more common approach of using contig sequences., Allele Phasing Greatly Improves the Phylogenetic Utility of Ultraconserved Elements.Advances in high-throughput sequencing techniques now allow relatively easy and affordable sequencing of large portions of the genome, even for nonmodel organisms. [SEP]Relations: male organism has relations: anatomy_anatomy with multicellular organism, anatomy_anatomy with multicellular organism. anatomical entity has relations: anatomy_anatomy with anatomical cluster, anatomy_anatomy with anatomical cluster, anatomy_anatomy with immaterial anatomical entity, anatomy_anatomy with immaterial anatomical entity, anatomy_anatomy with insect mouthpart, anatomy_anatomy with insect mouthpart, anatomy_anatomy with material anatomical entity, anatomy_anatomy with material anatomical entity.", "label": "yes"}
{"id": "converted_3484", "sentence1": "Is Selinexor effective for multiple myeloma?", "sentence2": "Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and Waldenstrom macroglobulinemia., Based on these findings, we conclude that selinexor in combination with dexamethasone is active in heavily pretreated MM and propose a RP2D of 45 mg/m2 (80 mg) plus 20 mg dexamethasone given twice weekly. , Selinexor, an Exportin-1 inhibitor, yielded promising results in quad- or penta-refractory MM including patients resistant to daratumumab. , Selective Inhibition of Nuclear Export With Oral Selinexor for Treatment of Relapsed or Refractory Multiple Myeloma., Conclusion The combination of selinexor and dexamethasone has an ORR of 21% in patients with heavily pretreated, refractory myeloma with limited therapeutic options., Selinexor (KPT-330) is the first-in-human SINE compound. Early phase clinical trials have established the safety profile of this agent and have shown promising efficacy in combination with low-dose dexamethasone and other anti-MM agents. The combination of selinexor and dexamethasone has demonstrated activity in \"penta-refractory\" MM, (ie, MM refractory to the 5 most active anti-MM agents currently used in treatment)., We found that DEX in combination with selinexor, an inhibitor of exportin-1 (XPO1) activity, synergistically inhibits the mTOR pathway and subsequently promotes cell death in MM cells. , The current findings are consistent with the beneficial therapeutic outcome in patients with MM when treated with the combination of selinexor and DEX. , Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma., Selinexor is an oral inhibitor of the nuclear export protein exportin 1 (XPO1). Preclinical studies demonstrated synergistic antimyeloma activity between selinexor and proteasome inhibitors (PI) though suppression of NFκB signaling and nuclear retention of tumor suppressor proteins., Targeting XPO1 with selinexor (the selective inhibitor of nuclear export; SINE compound KPT-330) demonstrates broad antitumor activity also in patient cells resistant to bortezomib; hence, it is a promising target in MM patients. Hypoxia is known to mediate tumor progression and drug resistance (including bortezomib resistance) in MM cells., Selinexor, used as a single agent, delayed tumor initiation and tumor progression, prolonging mice survival. In bortezomib-resistant xenografts, selinexor overcame drug resistance, significantly decreasing tumor burden and extending mice survival when combined with bortezomib., The responses seen with venetoclax in RRMM with t(11;14)(high BCL-2, low BCL-XL and MCL-1) and selinexor in penta-refractory myeloma which fulfills the FDA category of unmet need, opens up newer options for these patients. , The FDA granted accelerated approval to selinexor plus low-dose dexamethasone for triple-class refractory multiple myeloma , despite an advisory panel 's concerns about the drug 's toxicity and the lack of randomized clinical data ., Selinexor ( in combination with dexamethasone ) received accelerated approval in the USA in July 2019 for the treatment of adult patients with relapsed or refractory multiple myeloma ( RRMM) . , CONCLUSIONS\nSelinexor-dexamethasone resulted in objective treatment responses in patients with myeloma refractory to currently available therapies., Selinexor: A First-in-Class Nuclear Export Inhibitor for Management of Multiply Relapsed Multiple Myeloma., Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of selinexor for management of relapsed multiple myeloma (MM)., Selinexor (in combination with dexamethasone) received accelerated approval in the USA in July 2019 for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM).[SEP]Relations: Bortezomib has relations: drug_effect with Multiple myeloma, drug_effect with Multiple myeloma. Multiple myeloma has relations: drug_effect with Melphalan, drug_effect with Melphalan, drug_effect with Melphalan, drug_effect with Melphalan, drug_effect with Pramipexole, drug_effect with Pramipexole, drug_effect with Pramipexole, drug_effect with Pramipexole.", "label": "yes"}
{"id": "converted_1226", "sentence1": "Are there interactomes available for POU5F1 and SOX2?", "sentence2": "The interactomes of POU5F1 and SOX2 enhancers in human embryonic stem cells., We assayed long-range chromosomal interactions on putative enhancers of POU5F1 and SOX2 genes in human embryonic stem cells (hESCs) using 4C-Seq technique. We discovered that their frequent interacting regions mainly overlap with early DNA replication domains. The interactomes are associated with active histone marks and enriched with 5-hydroxymethylcytosine sites. In hESCs, genes within the interactomes have elevated expression. Additionally, some genes associated with the POU5F1 enhancer contribute to pluripotency. Binding sites for multiple DNA binding proteins, including ATF3, CTCF, GABPA, JUND, NANOG, RAD21 and YY1, are enriched in both interactomes.[SEP]Relations: NANOG has relations: protein_protein with SOX2, protein_protein with SOX2, protein_protein with POU5F1, protein_protein with POU5F1, pathway_protein with POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation, pathway_protein with POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation, pathway_protein with POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation, pathway_protein with POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation, protein_protein with PSORS1C3, protein_protein with PSORS1C3.", "label": "yes"}
{"id": "converted_3245", "sentence1": "Is the Fluzone intradermal and the Fluzone intradermal quadrivalent vaccine produced by different companies?", "sentence2": "An intradermal version of Fluzone® split-virion inactivated trivalent influenza vaccine, containing 9 µg hemagglutinin per strain of A/H1N1, A/H3N2, and one B lineage virus (Fluzone Intradermal, Sanofi Pasteur), became available in the US during the 2011-2012 influenza season for adults 18-64 years of age. In advance of the 2015-2016 season, Fluzone Intradermal was replaced with Fluzone Intradermal Quadrivalent vaccine, which contains 9 µg hemagglutinin per strain of the two A-strain viruses and both B-strain lineage viruses (Victoria and Yamagata).[SEP]", "label": "no"}
{"id": "converted_4444", "sentence1": "Can epigenetic modifications be heritable?", "sentence2": "Epigenetic alterations (epimutations) could thus contribute to heritable variation within populations and be subject to evolutionary processes such as natural selection and drift. [SEP]", "label": "yes"}
{"id": "converted_705", "sentence1": "Is Bladder training an effective method to treat  urge incontinence ?", "sentence2": "Mindfulness-based stress reduction appears to be a treatment worthy of further study, as in the short term, it is as effective as historical studies of drug treatment and bladder training in reducing urge incontinence and incontinence-related quality of life., All patients, irrespective of the results of cystometry were subsequently treated with oxybutynin 2.5 mg twice daily along with bladder training., Of the 29 patients with stable bladder and symptoms of OAB, 100% cure rate was achieved in 20 (68.9%) and 06 (20.6%) patients respectively. While in 3 patients in both groups, decrease of symptoms upto 75% after 6 months of treatment was observed., Both urodynamically proven unstable and stable bladder showed nearly equal improvement with treatment, There are 3 types of urine incontinence (urge-, stress-, and overflow-incontinence). Another standardization of urinary incontinence follows dysfunctions of the pelvic floor: detrusor muscle-dependent, due to sphincter spasm, prostate gland dependent. Urge incontinence with a dysfunction of the detrusor muscle is the most common type. Mixed types are frequent. Non-drug measures (e.g. pelvic muscle training, bladder training, toilet training are first choice treatments., Treatment of stress, urge and mixed incontinence can usually be commenced in primary care; pelvic floor exercises and bladder training are preferred. If bladder training is not effective for urge incontinence, anticholinergic drugs should be considered., Sixty patients (age 8 to 12 years) with urge incontinence or dysfunctional voiding were evaluated. After a no-treatment control period (average 6 months), patients underwent a 6-day bladder training course, Six months after training completion, 64.1% and 64.7% of the inpatient and outpatient groups with daytime wetting and 51.5% and 17.7% of the inpatient and outpatient groups with nighttime wetting were cured or had improved, Of the inpatient group with urge incontinence, the functional bladder capacity increased by 15%., To compare the efficacy of tolterodine plus simplified bladder training (BT) with tolterodine alone in patients with an overactive bladder., CONCLUSIONS: Tolterodine 2 mg twice daily is an effective and well tolerated treatment for an overactive bladder, the effectiveness of which can be augmented by a simplified BT regimen., Bladder training is a modification of bladder drill that is conducted more gradually on an outpatient basis and has resulted in significant reduction of incontinence in older, community-dwelling women., OBJECTIVE: To evaluate the long-term effect of treatment of female incontinence by the general practitioner (pelvic floor exercises, and bladder training) in female urinary incontinence., Stress incontinence and urge incontinence were treated by means of pelvic floor exercises and bladder training respectively, while a mixed incontinence was treated by bladder training followed by pelvic floor exercises. T, The treatment consisted of training of pelvic muscles in stress incontinence and bladder training in urge incontinence, RESULTS: After 3 months the mean frequency of urine loss per week diminished from 21 to 8, and after 12 months to 6 times., Some elders suffering from urge incontinence prefer pelvic muscle exercises to bladder training as the behavioral intervention of choice, for eight out of nine women their continence had improved, both subjectively and objectively., Bladder training is a simple, safe, and effective treatment in the management of mild to moderate forms of urinary incontinence in outpatient populations. It can be used as a first-line treatment or in combination with such other interventions as pelvic muscle exercises, bladder pressure biofeedback, electrical stimulation, and drug therapy, Treatment consisted of pelvic floor exercises in the case of stress incontinence and bladder training in the case of urge incontinence., After 3 months about 60% of the patients were either dry or only mildly incontinent, terodiline group shows this drug to be a valuable adjunct to a bladder regimen in children with urge incontinence, Basing on our experience with 39 patients with severe urge incontinence (in one-quarter of the cases pure urge incontinence, in one-half of the cases mixed incontinence and in a further quarter of the cases neurogenic bladder disorders) a supervised programme (mictiogram) and a well-tried therapy (especially in the Anglo-Saxon countries) consisting of the triad hospitalisation/bladder training/medication therapy are presented. After an average hospitalisation period of 14 days, we were able to achieve a symptom-free state in 94% of the patients., Anamnestic and urodynamical results are evaluated before and after bladder retraining drill (BRD) in women suffering from urge incontinence., We could state that the BRD is a good possibility to realize multistep-therapy of female incontinence., Twenty consecutive female patients with urge incontinence and stable detrusor function on provocative rapid fill CO2-cystometry were treated as out-patients with a bladder training programme and with terodiline/placebo in a double-blind cross-over design., In conclusion, female patients with idiopathic urge incontinence and stable detrusor function did respond to treatment as do female patients with urge incontinence and proven instability., The results of in-patient bladder training in 65 women with frequency, urgency and urge incontinence are reported. There was a good initial response in 88%. By 6 months the response rate had fallen to 38%., Patients with sensory urgency appeared to do better than those with detrusor instability and it is suggested that bladder training may be indicated as primary treatment in sensory urgency., Bladder training and/or biofeedback techniques were used to treat 75 patients with frequency, urgency, nocturia and urge incontinence. Significant improvement or cure was obtained in 70 per cent of enuretic children, and 66 per cent of men and 74 per cent of women with unstable detrusor function.[SEP]Relations: Urinary incontinence has relations: drug_effect with Ibuprofen, drug_effect with Ibuprofen, drug_effect with Acamprosate, drug_effect with Acamprosate, drug_effect with Urofollitropin, drug_effect with Urofollitropin, drug_effect with Naproxen, drug_effect with Naproxen, drug_effect with Levonorgestrel, drug_effect with Levonorgestrel.", "label": "yes"}
{"id": "converted_2577", "sentence1": "Is Citrobacter rodentium pathogenic?", "sentence2": "One day after colonization, mice were infected with the colonic pathogen, Citrobacter rodentium., The human pathogen enteropathogenic Escherichia coli (EPEC), as well as the mouse pathogen Citrobacter rodentium, colonize the gut mucosa via attaching and effacing lesion formation and cause diarrheal diseases., EPEC-like mouse pathogen Citrobacter rodentium, Here, we develop a model that provides that link for the investigation of Citrobacter rodentium infection, a mouse model for enteropathogenic Escherichia coli (EPEC). [SEP]Relations: escherichia coli infection has relations: disease_disease with infectious disease, disease_disease with infectious disease, disease_disease with infectious disease, disease_disease with infectious disease, disease_phenotype_positive with Recurrent gram-negative bacterial infections, disease_phenotype_positive with Recurrent gram-negative bacterial infections, disease_phenotype_positive with Recurrent gram-negative bacterial infections, disease_phenotype_positive with Recurrent gram-negative bacterial infections.", "label": "yes"}
{"id": "converted_3466", "sentence1": "Is Hemochromatosis type 4 is caused by a mutation in a recessive gene?", "sentence2": " severely affect iron homeostasis causing type 4 hereditary hemochromatosis, an autosomal dominant iron overload condition with variable phenotypic manifestations, Hemochromatosis type 4, also known as ferroportin disease, is an autosomal dominant genetic disorder caused by pathogenic mutations in the SLC40A1 gene, which encodes ferroportin 1 (FPN1)., Hemochromatosis type 4 is a rare form of primary iron overload transmitted as an autosomal dominant trait caused by mutations in the gene encoding the iron transport protein ferroportin 1 (SLC40A1)., Type 4 hemochromatosis follows an autosomal dominant trait; the corresponding mutation affects the basolateral iron carrier ferroportin 1., Type 4 hemochromatosis follows an autosomal dominant trait; the corresponding mutation affects the basolateral iron carrier ferroportin 1, Type 4 hemochromatosis follows an autosomal dominant trait; the corresponding mutation affects the basolateral iron carrier ferroportin 1.[SEP]Relations: hemochromatosis has relations: disease_phenotype_positive with Autosomal recessive inheritance, disease_phenotype_positive with Autosomal recessive inheritance, disease_disease with hereditary hemochromatosis, disease_disease with hereditary hemochromatosis, disease_phenotype_positive with Autosomal dominant inheritance, disease_phenotype_positive with Autosomal dominant inheritance, disease_protein with BMP6, disease_protein with BMP6. SLC40A1 has relations: pathway_protein with Defective SLC40A1 causes hemochromatosis 4 (HFE4) (duodenum), pathway_protein with Defective SLC40A1 causes hemochromatosis 4 (HFE4) (duodenum).", "label": "no"}
{"id": "converted_3375", "sentence1": "Are breaks in double stranded DNA associated with ionizing radiation?", "sentence2": "DNA double-strand breaks (DSBs) are major DNA lesions that are constantly formed during physiological processes such as DNA replication, transcription, and recombination, or as a result of exogenous agents such as ionizing radiation, radiomimetic drugs, and genome editing nucleases, Whereas most endogenous and exogenous DNA damaging agents typically generate lesions that are relatively isolated and can be repaired easily, ionizing radiation (IR) also induces clustered lesions causing DNA double strand breaks (DSBs), The induction of DNA interstrand cross-links by ionizing radiation has been largely ignored in favour of studies on double-strand break formation and repair., While much is known about radiation-induced DNA double-strand breaks (DSBs) and their repair, , Exposure of cells to ionizing radiation induces DNA double-strand breaks., DNA double-strand breaks are considered to be the most deleterious lesion induced by ionizing radiation., Influence of chromatin structure on the induction of DNA double strand breaks by ionizing radiation., Ionizing radiation and radiomimetic drugs such as bleomycin, calichieamycin, neocarzinostatin chromophore, and other synthetic agents can produce both single and double strand breaks in DNA., RESULTS BRCA2-defective cells were unable to repair the double-strand DNA breaks induced by ionizing radiation., BACKGROUND Induction of DNA double strand breaks and alterations in the repair of these breaks is implicated in breast carcinogenesis., Double-stranded breaks ( DSBs ) are the most injurious type of DNA damage , being induced by ionizing radiation ( IR ) and cytotoxic agents used in cancer treatment, Double-stranded breaks ( DSBs ) are cytotoxic DNA lesions caused by oxygen radicals , ionizing radiation , and radiomimetic chemicals, Gamma-ray irradiation introduces single and/or double strand breaks into the DNA molecule of the cells.[SEP]Relations: Bleomycin has relations: drug_drug with Arsenic trioxide, drug_drug with Arsenic trioxide, drug_effect with Abnormal pulmonary Interstitial morphology, drug_effect with Abnormal pulmonary Interstitial morphology, drug_drug with Isosulfan blue, drug_drug with Isosulfan blue, drug_drug with Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated), drug_drug with Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated), drug_drug with Tetradecyl hydrogen sulfate (ester), drug_drug with Tetradecyl hydrogen sulfate (ester).", "label": "yes"}
{"id": "converted_3498", "sentence1": "Has ProSavin undergone phase IV clinical trials by 2018?", "sentence2": "Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial., We undertook a phase 1/2 open-label trial with 12-month follow-up at two study sites (France and UK) to assess the safety and efficacy of ProSavin after bilateral injection into the putamen of patients with Parkinson's disease. [SEP]Relations: Parkinson disease has relations: contraindication with Prochlorperazine, contraindication with Prochlorperazine, contraindication with Indomethacin, contraindication with Indomethacin, contraindication with Amikacin, contraindication with Amikacin, contraindication with Rivastigmine, contraindication with Rivastigmine, contraindication with Perphenazine, contraindication with Perphenazine.", "label": "no"}
{"id": "converted_2050", "sentence1": "Is Dupilumab used for treatment of atopic dermatitis?", "sentence2": "Dupilumab has demonstrated efficacy in patients with asthma and atopic dermatitis, which are both type 2 helper T-cell-mediated diseases., Background Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis., Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis., Dupilumab is a biologic agent targeted at TH2 cytokines, but indirectly impacts IgE and is an important biologic agent for atopic disease., Dupilumab for the treatment of atopic dermatitis: A clinical trial review., Dupilumab is a novel monoclonal antibody that was recently studied in adult patients with moderate-to-severe AD., Patients treated with dupilumab had marked and rapid improvement in all the evaluated measures of atopic dermatitis disease activity., The robust effects of dupilumab on skin inflammation and pruritus confirm the pathogenic role of IL-4 and IL-13 signaling in adult AD, and further support the application of Th2 cytokine antagonists in the treatment of this disease.[SEP]Relations: Dupilumab has relations: drug_drug with Dusigitumab, drug_drug with Dusigitumab, drug_drug with Teplizumab, drug_drug with Teplizumab, drug_drug with Afelimomab, drug_drug with Afelimomab, drug_drug with Tremelimumab, drug_drug with Tremelimumab, drug_drug with Urelumab, drug_drug with Urelumab.", "label": "yes"}
{"id": "converted_4530", "sentence1": "Are functional tests a good biomarker for Duchenne Muscular Dystrophy?", "sentence2": "North Star Ambulatory Assessment is practical and reliable., allow assessment of high-functioning boys with Duchenne muscular dystrophy., agnosis and tracking of symptom progression of DMD usually relies on creatine kinase tests, evaluation of patient performance in various ambulatory assessments, and detection of dystrophin from muscle biopsies, which are invasive and painful for the patient. While the, Aim: Using baseline data from a clinical trial of domagrozumab in Duchenne muscular dystrophy, we evaluated the correlation between functional measures and quantitative MRI assessments of thigh muscle. Patients & methods: Analysis included timed functional tests, knee extension/strength and North St, A New Functional Scale and Ambulatory Functional Classification of Duchenne Muscular Dystrophy: Scale Development and Preliminary Analyses of Reliability and Validity., his preliminary investigation describes the relationship between community ambulation measured by the StepWatch activity monitor and the current standard of functional assessment, the 6-minute walk test, in ambulatory boys with Duchenne muscular dystrophy (n = 16) and healthy controls (n = 13). All, ith strength assessments. MV index, fat fraction and T2-mapping measures had moderate correlations (r ∼ 0.5) to all functional tests, North Star Ambulatory Assessment and age. Conclusion: The moderate correlation between functional tests, age and baseline MRI measures supports MRI as a biomarker in Duchenn, on with clinically meaningful outcome measures such as North Star Ambulatory Assessment (NSAA) and 6 minute walk test (6MWT) is paramount for biomarker qualification. In this stu, Quantitative muscle strength assessment in duchenne muscular dystrophy: longitudinal study and correlation with functional measures., The 6-minute walk test, timed 10-meter walk/run test, and supine-up time are commonly used timed functional tests that also sufficiently monitor changes in muscle function; however, they strongly depend on patient collaboration, Conclusion: The moderate correlation between functional tests, age and baseline MRI measures supports MRI as a biomarker in Duchenne muscular dystrophy clinical trials., Currently, functional measures continue to serve as the primary outcome for the majority of DMD clinical trials., Patients & methods: Analysis included timed functional tests, knee extension/strength and North Star Ambulatory Assessment., The 6-minute walk test, timed 10-meter walk/run test, and supine-up time are commonly used timed functional tests that also sufficiently monitor changes in muscle function; however, they strongly depend on patient collaboration., We have developed a new scale and the associated classification system, to assess the functional ability of children diagnosed with DMD. Preliminary evaluation of the psychometric properties of the functional scale and classification systems indicate sufficient reliability and concurrent validity., Quantitative MRI is an objective and sensitive biomarker to detect subclinical changes, though the examination costs may be a reason for its limited use. In this study, a high correlation between all clinical assessments and quantitative MRI scans was found. The combinational use of these methods provides a better understanding about disease progression; however, longitudinal studies are needed to validate their reliability., The children's functional performance was assessed using 6-minute walk tests and timed performance tests. The correlations between the flexibilities of the lower limb muscles and the performance tests were examined., The flexibilities of the lower extremity muscles were found to be correlated to the 6-minute walk tests and the timed performance tests. The flexibility of the hamstrings (r = -.825), the gastrocnemius muscles (r = .545), the hip flexors (r = .481), and the tensor fascia latae (r = .445) were found to be correlated with functional performance as measured by the 6-minute walk tests (P < .05), Nine biomarkers have been identified that correlate with disease milestones, functional tests and respiratory capacity. Together these biomarkers recapitulate different stages of the disorder that, if validated can improve disease progression monitoring.,  In conclusion, the motor function measure and timed function tests measure disease severity in a highly comparable fashion and all tests correlated with quantitative muscle MRI values quantifying fatty muscle degeneration.,  This study is to date the most thorough long-term evaluation of QMT in a cohort of DMD patients correlated with other measures, such as the North Star Ambulatory Assessment (NSAA) or three 6-min walk test (6MWT)., The MFM scale was a useful instrument in the follow up of patients with DMD. Moreover, it is a more comprehensive scale to assess patients and very good for conducting trials to evaluate treatment., MD subjects were evaluated using the Vignos lower extremity functional rating, and tests including 6 min walk test (6MWT) and 10 m walk., TFTs appear to be slightly more responsive and predictive of disease progression than the 6MWT in 7-12.9 year olds., herefore, in our group of ambulant patients with DMD, timed functional testing was the most sensitive parameter to determine the extent of disease progression. Timed functional testing may therefore be considered as an additional outcome measure in drug trials to evaluate the effects of therapy in ambulant patients with DMD and possibly in other neuromuscular disorders., Time to rise is a useful and simple tool in the screening of neuromuscular disorders such as Duchenne muscular dystrophy,, he muscle strength of the wrist extensors and the radial deviation range of motion at the wrist were found to be strongly correlated with six of the seven tasks assessed. These two clinical assessments appear to be good indicators of overall wrist and hand function.[SEP]Relations: Duchenne muscular dystrophy has relations: disease_phenotype_positive with Muscular dystrophy, disease_phenotype_positive with Muscular dystrophy, disease_phenotype_positive with Skeletal muscle atrophy, disease_phenotype_positive with Skeletal muscle atrophy, disease_protein with BCHE, disease_protein with BCHE, disease_protein with DMD, disease_protein with DMD, disease_protein with ACHE, disease_protein with ACHE.", "label": "yes"}
{"id": "converted_2800", "sentence1": "Is P. gingivalis bacteria found in brain?", "sentence2": "studies using animal model of periodontitis and human post-mortem brain tissues from subjects with AD strongly suggest that a gram-negative periodontal pathogen, Porphyromonas gingivalis (Pg) and/or its product gingipain is/are translocated to the brain., The polymicrobial dysbiotic subgingival biofilm microbes associated with periodontal disease appear to contribute to developing pathologies in distal body sites, including the brain.[SEP]Relations: periodontal disease has relations: disease_disease with gingival disease, disease_disease with gingival disease, disease_protein with CTSC, disease_protein with CTSC. Periodontitis has relations: phenotype_phenotype with Abnormality of the gingiva, phenotype_phenotype with Abnormality of the gingiva, disease_phenotype_positive with dyskeratosis congenita, disease_phenotype_positive with dyskeratosis congenita, disease_phenotype_positive with cyclic hematopoiesis, disease_phenotype_positive with cyclic hematopoiesis.", "label": "yes"}
{"id": "converted_4053", "sentence1": "Does hypofractionated radiotherapy offers any benefit for DIPG?", "sentence2": "CONCLUSION: Hypofractionated RT for children with newly diagnosed DIPG is well tolerated and feasible from the viewpoint of reducing a patient's burden of treatment. Re-irradiation at first progression is suggested to be beneficial., Median OS and time to progression were similar between conventionally fractionated and hypofractionated RT groups.(9.7 [95% confidence interval(CI): 7.1-11.2] versus 11.0[95% CI: 5.2-13.6] months, P = 0.60; 4.2[95% CI: 1.8-8.3] versus 7.1 [95% CI:4.5-8.7] months, P = 0.38). , The median overall survival (OS) was 11 months (95% CI - 7.5 to 14.5 months) in the conventional arm and 12 months (95% CI - 10.5 to 13.5 months) in the experimental arm (p = 0.208). 28% (n = 5) patients in the experimental arm developed grade 3 or 4 hematological toxicity.CONCLUSION: The above study shows that hypofractionated radiotherapy with concurrent and adjuvant temozolomide does not improve OS and has higher hematological toxicity. , CONCLUSIONS: The results of this meta-analysis suggest that CFRT and HFRT provide similar survival outcomes for patients with DIPG., CONCLUSIONS: Hypofractionated radiotherapy offers lesser burden on the patients, their families and the treating departments, with nearly comparable results to conventional fractionation, though not fulfilling the non-inferiority assumption., xternal radiotherapy with a radical hypofractionated regimen is feasible and well tolerated in children with newly diagnosed DIPG. However, this regimen does not seem to change overall survival in this setting.[SEP]Relations: diffuse intrinsic pontine glioma has relations: disease_disease with childhood brain stem glioma, disease_disease with childhood brain stem glioma.", "label": "no"}
{"id": "converted_835", "sentence1": "Is metabolic syndrome related with cardiovascular disease?", "sentence2": "The metabolic syndrome (MetS) is characterized by a cluster of risk factors including central obesity, hypertension, dyslipidemia and insulin resistance, The MetS is associated with an increased risk for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). , As a molecular link between metabolic signals, inflammation, and vascular dysfunction, resistin can be proposed as playing a significant role in the heightened inflammatory state induced by metabolic stress linked to excessive caloric intake, thus contributing to the risk for metabolic syndrome (MetS), type 2 diabetes (T2DM), and cardiovascular disease (CVD). , The metabolic syndrome (MetS) is associated with a higher risk for both, type 2 diabetes mellitus and cardiovascular disease. , arotid intima-media thickness (CIMT) has been widely used as a surrogate marker of atherosclerosis and cardiovascular disease (CVD)[SEP]Relations: metabolic syndrome X has relations: disease_disease with metabolic syndrome, disease_disease with metabolic syndrome, disease_disease with abdominal obesity-metabolic syndrome, disease_disease with abdominal obesity-metabolic syndrome, disease_disease with inborn errors of metabolism, disease_disease with inborn errors of metabolism. cardiovascular disease has relations: disease_disease with heart disease, disease_disease with heart disease, disease_disease with vascular disease, disease_disease with vascular disease.", "label": "yes"}
{"id": "converted_3291", "sentence1": "Is traditional Chinese medicine associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment?", "sentence2": "Traditional Chinese medicine is associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment,  Using TCM significantly decreased the incidence of CHF in patients with breast cancer who received conventional chemotherapy with or without radiotherapy., Traditional Chinese medicine is associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment., CONCLUSION\n\nUsing TCM significantly decreased the incidence of CHF in patients with breast cancer who received conventional chemotherapy with or without radiotherapy., CONCLUSION\nUsing TCM significantly decreased the incidence of CHF in patients with breast cancer who received conventional chemotherapy with or without radiotherapy., CONCLUSION: Using TCM significantly decreased the incidence of CHF in patients with breast cancer who received conventional chemotherapy with or without radiotherapy., Using TCM significantly decreased the incidence of CHF in patients with breast cancer who received conventional chemotherapy with or without radiotherapy.[SEP]Relations: Congestive heart failure has relations: drug_effect with Doxorubicin, drug_effect with Doxorubicin, drug_effect with Doxazosin, drug_effect with Doxazosin, drug_effect with Celecoxib, drug_effect with Celecoxib, drug_effect with Ofloxacin, drug_effect with Ofloxacin, drug_effect with Rofecoxib, drug_effect with Rofecoxib.", "label": "yes"}
{"id": "converted_1380", "sentence1": "Can chronological age be predicted by measuring telomere length?", "sentence2": "Human somatic cells gradually lose telomeric repeats with age. This study investigated if one could use a correlation between telomere length and age, to predict the age of an individual from their DNA., Therefore, telomere length measurement by real-time quantitative PCR cannot be used to predict age of a person, due to the presence of large inter-individual variations in telomere lengths., ur results provide the first clear and unambiguous evidence of a relationship between telomere length and mortality in the wild, and substantiate the prediction that telomere length and shortening rate can act as an indicator of biological age further to chronological age when exploring life history questions in natural conditions.[SEP]Relations: Telomere Extension By Telomerase has relations: pathway_protein with TERT, pathway_protein with TERT, pathway_protein with CCNA2, pathway_protein with CCNA2, pathway_protein with CCNA1, pathway_protein with CCNA1, pathway_protein with WRAP53, pathway_protein with WRAP53, pathway_protein with ANKRD28, pathway_protein with ANKRD28.", "label": "no"}
{"id": "converted_1283", "sentence1": "Is factor XI deficient in Hemophilia C?", "sentence2": "Factor XI deficiency is a rare hematologic disorder. Hemophilia C (factor XI deficiency) affects both genders and it is usually asymptomatic,, Congenital factor XI deficiency (also known as the Rosenthal syndrome or hemophilia C), rare case of an acute cerebral aneurysm rupture in a patient with a known factor XI deficiency. Aneurysmal subarachnoid hemorrhage (SAH) accounts for a high mortality and morbidity rate. When SAH is associated with an inherited coagulation disorder such as hemophilia C, Factor XI deficiency (Hemophilia C), Factor XI deficiency, also called hemophilia C,[SEP]Relations: factor XI deficiency has relations: disease_disease with hemophilia, disease_disease with hemophilia, disease_disease with congenital factor XI deficiency, disease_disease with congenital factor XI deficiency. hematologic disease has relations: disease_disease with L-ferritin deficiency, disease_disease with L-ferritin deficiency, disease_disease with GATA1-Related X-Linked Cytopenia, disease_disease with GATA1-Related X-Linked Cytopenia, contraindication with Adomiparin, contraindication with Adomiparin.", "label": "yes"}
{"id": "converted_3047", "sentence1": "Is there any approved treatment for NAFLD?", "sentence2": "Non-alcoholic fatty liver disease (NAFLD) is the leading chronic hepatic condition worldwide and new approaches to management and treatment are limited., Non-alcoholic fatty liver disease (NAFLD) has become one of the most prominent forms of chronic liver disease worldwide, reflecting the epidemic of global obesity. Those with the progressive variant of NAFLD, non-alcoholic steatohepatitis (NASH), are at significantly increased risk of multisystem morbidity and mortality. However, there are currently no approved pharmacologic therapies for NASH., Although much progress has been made in enhancing our understanding of NAFLD pathogenesis, development of pharmacologic treatments has been hindered by challenges in clinical trial enrollment and complexities in clinical trial design. , Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and there is no approved pharmacotherapy., Nonalcoholic fatty liver disease (NAFLD) has an increasing prevalence worldwide. At present, no specific pharmacotherapy is approved for NAFLD. [SEP]Relations: non-alcoholic steatohepatitis has relations: contraindication with Efavirenz, contraindication with Efavirenz, contraindication with Zidovudine, contraindication with Zidovudine, contraindication with Entecavir, contraindication with Entecavir, contraindication with Tenofovir disoproxil, contraindication with Tenofovir disoproxil, contraindication with Abacavir, contraindication with Abacavir.", "label": "no"}
{"id": "converted_2783", "sentence1": "Can pets affect infant microbiomed?", "sentence2": "Since there is some evidence that pets also alter the gut microbial composition of infants, changes to the gut microbiome are putative pathways by which pet exposure can reduce these risks to health., The impact of pet ownership varies under different birth scenarios; however, in common, exposure to pets increased the abundance of two bacteria, Ruminococcus and Oscillospira, which have been negatively associated with childhood atopy and obesity., As a common effect in all birth scenarios, pre- and postnatal pet exposure enriched the abundance of Oscillospira and/or Ruminococcus (P < 0.05) with more than a twofold greater likelihood of high abundance. Among vaginally born infants with maternal intrapartum antibiotic prophylaxis exposure, Streptococcaceae were substantially and significantly reduced by pet exposure (P < 0.001, FDRp = 0.03), reflecting an 80% decreased likelihood of high abundance (OR 0.20, 95%CI, 0.06-0.70) for pet exposure during pregnancy alone and a 69% reduced likelihood (OR 0.31, 95%CI, 0.16-0.58) for exposure in the pre- and postnatal time periods., Exposure to household furry pets influences the gut microbiota of infant at 3-4 months following various birth scenarios.[SEP]Relations: Bacteremia has relations: disease_phenotype_positive with listeriosis, disease_phenotype_positive with listeriosis, disease_phenotype_positive with toxic shock syndrome, disease_phenotype_positive with toxic shock syndrome, disease_phenotype_positive with shigellosis, disease_phenotype_positive with shigellosis, disease_phenotype_positive with cyclic hematopoiesis, disease_phenotype_positive with cyclic hematopoiesis. obsolete body mass index quantitative trait locus 19 has relations: disease_phenotype_positive with Insulin resistance, disease_phenotype_positive with Insulin resistance.", "label": "yes"}
{"id": "converted_811", "sentence1": "Is myasthenia gravis associated with osteoporosis?", "sentence2": "We performed PVP in 4 patients with generalized MG associated with recent steroid-induced symptomatic VFs. , In this case report, we used tacrolimus to successfully treat a 13-year-old boy with ocular MG who had suffered from severe steroid complications, including a failure of thrive and osteoporosis.,  INTRODUCTION: Myasthenia gravis (MG) is a neuromuscular disease which has been associated with an increased falls risk and glucocorticoid-induced osteoporosis, recognized determinants of increased fracture risk. , RESULTS: Compared to the control cohort, there was no statistically significant increased risk observed in patients with MG for any fracture (adjusted hazard ratio [AHR] 1.11; 95 % confidence interval [CI], 0.84-1.47) or osteoporotic fractures (AHR 0.98 [95 % CI 0.67-1.41]). Further, use of oral glucocorticoids up to a cumulative dose exceeding 5 g prednisolone equivalents did not increase risk of osteoporotic fracture (AHR 0.99 [95 % CI, 0.31-3.14]) compared with MG patients without glucocorticoid exposure., The RANKL/OPG ratio and indices of bone metabolisms are also not affected by THX, although THX increases the levels of IL-7 and RANKL., Both disorders had been controlled for around 15 years by oral prednisolone and a cholinesterase inhibitor following surgical removal of invasive thymoma and radiotherapy, but muscular weakness due to myalgia and an increase in serum levels of myogenic enzymes, mainly ascribable to the recurrence of PM, reappeared immediately after cessation of these drugs, which was done because the patient had multiple bone fractures and severe osteoporosis due to the long-term corticosteroid therapy. , We measured bone density in 36 patients (26 females and 10 males) who had undergone long-term prednisolone administration, and found a decrease in bone density in 31% of female patients and osteoporosis in only 11.5% (three cases)., In conclusion, prednisolone-treated patients with myasthenia gravis have an acceptable risk of bone loss if prophylactic medication is administered., INTRODUCTION: Myasthenia gravis (MG) is a neuromuscular disease which has been associated with an increased falls risk and glucocorticoid-induced osteoporosis, recognized determinants of increased fracture risk., Alendronate should be used with caution in patients with myasthenia gravis who have corticosteroid-induced osteoporosis, In this paper we present two cases of young women who developed severe PAO with vertebral fractures: a 42-year-old woman with a family history of osteoporosis, and a 21-year-old woman affected with myasthenia gravis, Myasthenia gravis (MG) is a neuromuscular disease which has been associated with an increased falls risk and glucocorticoid-induced osteoporosis, recognized determinants of increased fracture risk[SEP]Relations: myasthenia gravis has relations: disease_phenotype_positive with Acrocyanosis, disease_phenotype_positive with Acrocyanosis, disease_phenotype_positive with Myositis, disease_phenotype_positive with Myositis, disease_protein with FAS, disease_protein with FAS, disease_phenotype_positive with Rheumatoid arthritis, disease_phenotype_positive with Rheumatoid arthritis, disease_protein with MUSK, disease_protein with MUSK.", "label": "yes"}
{"id": "converted_918", "sentence1": "Is oxalate renal excretion increased after bariatric surgery?", "sentence2": "Despite the fact that bariatric surgery-induced weight loss is associated with a significant decrease in morbidity and mortality and improvement in renal function, bariatric surgery has recently been shown to be associated with a significant risk of nephrolithiasis. The main risk factor for nephrolithiasis is increased excretion of urinary oxalate., Enteric hyperoxaluria, nephrolithiasis, and oxalate nephropathy must be considered with the other risks of RYGBP., The urinary excretion of oxalate was high: 1.112 mumol/24 h (normal range: 55-400 mumol/24 h), and citrate excretion was low: 1.48 mmol/24 h (normal range: 2-5 mmol/24 h). , Hyperoxaluria in patients with JIB was found to be a result of hyperabsorption of oxalate, and these patients displayed altered oxalate kinetics with continued urinary excretion of orally administered 14C-oxalate for more than 48 hours. , Malabsorption of calcium and low fasting urinary calcium excretion in the JIB patients were associated with high tubular reabsorption of calcium, the latter presumably attributable to a compensatory increase in circulating parathyroid hormone (PTH). In most recurrent renal stone formers the urinary calcium concentration was increased, with an inverse relationship to serum PTH, indicating intestinal hyperabsorption of calcium. A[SEP]Relations: Nephropathy has relations: drug_effect with Oxaliplatin, drug_effect with Oxaliplatin, drug_effect with Oxacillin, drug_effect with Oxacillin, drug_effect with Irbesartan, drug_effect with Irbesartan, drug_effect with Ioxaglic acid, drug_effect with Ioxaglic acid, drug_effect with Ranitidine, drug_effect with Ranitidine.", "label": "yes"}
{"id": "converted_2277", "sentence1": "Are TAD boundaries in Drosophila depleted in highly-expressed genes?", "sentence2": "Furthermore, we find that these TAD boundaries are present irrespective of the expression and looping of genes located between them., In particular, Hi-C revealed that chromosomes of animals are organized into topologically associating domains (TADs), evolutionary conserved compact chromatin domains that influence gene expression., Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes. , The insulator-like, TAD-boundary-like, and TAD-interior-like regions are each enriched for distinct epigenetic marks and are each correlated with different gene expression levels, We conclude that epigenetic modifications, gene density, and transcriptional activity combine to shape the local packing of the A. thaliana nuclear genome., Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions., Our results demonstrate the functional importance of TADs for orchestrating gene expression via genome architecture and indicate criteria for predicting the pathogenicity of human structural variants, particularly in non-coding regions of the human genome., The three-dimensional organization of a genome plays a critical role in regulating gene expression, yet little is known about the machinery and mechanisms that determine higher-order chromosome structure., Ectopically expressed roX1 and roX2 RNAs target HAS on the X chromosome in trans and, via spatial proximity, induce spreading of the MSL complex in cis, leading to increased expression of neighboring autosomal genes. , Collectively, our results suggest that TADs are condensed chromatin domains depleted in active chromatin marks, separated by regions of active chromatin., However, Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes.[SEP]Relations: insect neurogenic region has relations: anatomy_anatomy with embryonic structure, anatomy_anatomy with embryonic structure. X chromosome has relations: cellcomp_protein with PCGF3, cellcomp_protein with PCGF3, cellcomp_protein with SIN3B, cellcomp_protein with SIN3B, cellcomp_protein with PCGF5, cellcomp_protein with PCGF5. chromosome X structural anomaly has relations: disease_disease with partial deletion of chromosome X, disease_disease with partial deletion of chromosome X.", "label": "no"}
{"id": "converted_545", "sentence1": "Have hESC been tested for the treatment of age-related macular degeneration?", "sentence2": "Development of human embryonic stem cell therapies for age-related macular degeneration, In this review, we describe recent approaches to develop cell-based therapies for the treatment of AMD. Recent research has focused on replacing the retinal pigment epithelium (RPE), a monolayer of cells vital to photoreceptor cell health. We discuss the various methods used to differentiate and purify RPE from human embryonic stem cells (HESC), and describe the surgical approaches being used to transplant these cells in existing and forthcoming clinical trials., Age-related macular degeneration (AMD) is characterized by the loss or dysfunction of retinal pigment epithelium (RPE) and is the most common cause of vision loss among the elderly. Stem-cell-based strategies, using human embryonic stem cells (hESCs) or human-induced pluripotent stem cells (hiPSCs), may provide an abundant donor source for generating RPE cells in cell replacement therapies., This study contributes to our understanding of the utility of hESC/hiPSC-derived RPE in AMD therapy., Two important early potential hESC applications are the use of retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration and Stargardt disease, an untreatable form of macular dystrophy that leads to early-onset blindness., Human embryonic stem cells (hESCs) are a promising source of retinal pigment epithelium (RPE) cells: cells that can be used for the treatment of common and incurable forms of blindness, such as age-related macular degeneration., A potential application of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) is the generation of retinal pigmented epithelium (RPE) to treat age-related macular degeneration (AMD), a common but incurable retinal disease., Human embryonic stem cells (hESCs) are a promising source of retinal pigment epithelium (RPE) cells: cells that can be used for the treatment of common and incurable forms of blindness, such as age-related macular degeneration, A potential application of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) is the generation of retinal pigmented epithelium (RPE) to treat age-related macular degeneration (AMD), a common but incurable retinal disease, Assessments of safety and efficacy are crucial before human ESC (hESC) therapies can move into the clinic. Two important early potential hESC applications are the use of retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration and Stargardt disease, an untreatable form of macular dystrophy that leads to early-onset blindness., A potential application of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) is the generation of retinal pigmented epithelium (RPE) to treat age-related macular degeneration (AMD), a common but incurable retinal disease. RPE cells derived from hESCs (hESC-RPEs) and iPSCs (iPSC-RPEs) express essential RPE markers and can rescue visual function in animal models., Two important early potential hESC applications are the use of retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration and Stargardt disease, an untreatable form of macular dystrophy that leads to early-onset blindness. Here we show long-term functional rescue using hESC-derived RPE in both the RCS rat and Elov14 mouse, which are animal models of retinal degeneration and Stargardt, respectively.[SEP]Relations: macular degeneration, age-related, 3 has relations: disease_disease with macular degeneration, disease_disease with macular degeneration, disease_protein with FBLN5, disease_protein with FBLN5, disease_phenotype_positive with Macular degeneration, disease_phenotype_positive with Macular degeneration, disease_phenotype_positive with Decreased patellar reflex, disease_phenotype_positive with Decreased patellar reflex, disease_phenotype_positive with Choroidal neovascularization, disease_phenotype_positive with Choroidal neovascularization.", "label": "yes"}
{"id": "converted_616", "sentence1": "Is statin use associated with improved outcomes after aneurysmal subarachnoid hemorrhage?", "sentence2": "Statins have been shown in two recent small phase I/II trials to be associated with a marked reduction in clinical and transcranial Doppler (TCD) evidence of vasospasm after aneurysmal subarachnoid haemorrhage (SAH). , Statins did not result in reduced TCD velocities, clinical or angiographic vasospasm, or improvements in global outcome at the time of hospital discharge. , There remains significant uncertainty as to the role of statins in preventing vasospasm after SAH., Although the results of 2 randomized clinical trials demonstrated that statin decreases the incidence of symptomatic cerebral vasospasm after aSAH, retrospective studies have failed to confirm this., There were no differences in the incidence of symptomatic vasospasm (25.3 vs 30.5%; p = 0.277), in-hospital mortality rate (18 vs 15%; p = 0.468), length of hospitalization (21 +/- 15 vs 19 +/- 12 days; p = 0.281), or poor outcome at discharge (Glasgow Outcome Scale Scores 1-2: 21.7 vs 18.2%; p = 0.416) between the simvastatin and nonstatin cohorts. , The uniform introduction of simvastatin did not reduce the incidence of symptomatic cerebral vasospasm, death, or poor outcome in patients with aSAH. Simvastatin was well tolerated, but its benefit may be less than has been previously reported., Cholesterol-reducing agents might improve unfavourable outcomes., We cannot draw any conclusions about the effectiveness and safety of lowering cholesterol in aneurysmal SAH because of insufficient reliable evidence from only one small trial., Experimental evidence has indicated the benefit of simvastatin in the treatment of subarachnoid hemorrhage., There was an improvement in the functional outcome in the simvastatin group at 1, 3 or 6 months in the follow-up; however, this difference was not statistically significant.,  There was benefit of simvastatin in terms of reduction in clinical vasospasm, mortality or improved functional outcome, however, this was not statistically significant., Cerebral vasomotor reactivity, however, is significantly improved after long-term statin administration in most patients with severe small vessel disease, aneurysmal subarachnoid hemorrhage, or impaired baseline CA., Atorvastatin decreases computed tomography and S100-assessed brain ischemia after subarachnoid aneurysmal hemorrhage: a comparative study., In the overall population, cerebral vasospasm was significantly less common in the statin-treated group. Severity of vasospasm, as assessed on the most severe angiogram, was lowered with statin. Statins significantly reduced volume of ischemia in patients with vasospasm and an uncomplicated coiling procedure. S100B levels were significantly lower in statin-treated patients, and the decrease was greatest among high-grade patients (World Federation of Neurological Surgeons 3-5). No differences were found between statin-treated and untreated groups regarding rescue therapy intensity or 1-yr clinical outcomes., Atorvastatin reduces the incidence, the severity and the ischemic consequences of vasospasm as assessed on computed tomography. In high-grade World Federation of Neurological Surgeons patients, atorvastatin decreases serum levels of S100B, a biomarker of brain ischemia. Despite these positive effects on biomarkers, no improvement of outcome was seen in the overall population, although there was a tendency for a better clinical outcome in high-grade patients., 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, have been associated with improved clinical outcomes after ischemic stroke and subarachnoid hemorrhage, but with an increased risk of incidental spontaneous intracerebral hemorrhage (ICH)., Statins are known to have pleiotropic vascular effects, some of which may interrupt the pathogenesis of DNDs. Based on promising preliminary reports, many clinicians routinely administer statins to prevent DNDs., However, observational studies have not revealed an association between statin-use and reduced DNDs or improved neurological outcomes. Results of RCTs have been inconsistent and limited by small sample size, but together suggest that statins may reduce DNDs, with no clear impact on mortality or neurological recovery., the role of statins in the management of patients with SAH remains unclear. Although promising, statins should not, at this time, be considered standard care., In patients with SAH, they may decrease the incidence of symptomatic vasospasm, although the effects on overall outcome are less clear., Statins treatment may have potential clinical impact in vascular disease beyond cholesterol lowering. Its benefits have been documented in cerebral ischaemia and in subarachnoid haemorrhage., A recent meta-analysis investigating the efficacy of statin treatment in patients with aneurysmal subarachnoid hemorrhage reported a reduced incidence of vasospasm, delayed cerebral ischemia, and mortality in statin-treated patients., The results of the present systematic review do not lend statistically significant support to the finding of a beneficial effect of statins in patients with aneurysmal subarachnoid hemorrhage as reported in a previous meta-analysis., Pre-treatment with cholesterol lowering drugs of the statin family may exert protective effects in patients with ischaemic stroke and subarachnoid haemorrhage but their effects are not clear in patients with intracerebral haemorrhage (ICH). , Recently, two randomized controlled phase II studies showed that acute initiation of statin treatment directly after aneurysmal subarachnoid hemorrhage (SAH) decreases the incidence of radiologic vasospasm and clinical signs of delayed cerebral ischemia (DCI), and even reduces mortality., We conclude that both the primary and secondary outcome results of this study do not support a beneficial effect of simvastatin in patients with SAH., Novel uses of their anti-inflammatory properties in sepsis and vasomotor properties in subarachnoid haemorrhage are being further investigated by randomised trials., A trend towards a lower mortality within 14 days in patients receiving solely simvastatin and those receiving statin and magnesium as compared with the control group was found. , Initiation of statin therapy after aneurysmal SAH significantly reduces the incidence of vasospasm, delayed ischemic deficits, and mortality., The addition of statins to standard care was not associated with any reduction in the development of vasospasm or improvement in outcomes after aneurysmal subarachnoid hemorrhage. , We have previously demonstrated that acute pravastatin therapy after aneurysmal subarachnoid hemorrhage ameliorates vasospasm-related delayed ischemic deficits.,  This trial demonstrates that acute statin treatment reduces traditional rescue therapy for vasospasm after aneurysmal subarachnoid hemorrhage. Improvement in early outcome has proved robust at 6 months, particularly in relation to physical and psychosocial (Short Form 36) outcome., The authors previously have demonstrated that acute treatment with pravastatin after aneurysmal subarachnoid hemorrhage (SAH) can ameliorate vasospasm-related delayed ischemic neurological deficits (DINDs)., The neuroprotective effects of acute treatment with pravastatin following aneurysmal SAH are associated with enhancement of autoregulation, Simvastatin reduces vasospasm after aneurysmal subarachnoid hemorrhage: results of a pilot randomized clinical trial., The use of simvastatin as prophylaxis against delayed cerebral ischemia after aneurysmal SAH is a safe and well-tolerated intervention. Its use attenuates serum markers associated with brain injury and decreases the incidence of radiographic vasospasm and delayed ischemic deficit., Acute treatment with pravastatin after aSAH is safe and ameliorates cerebral vasospasm, improves cerebral autoregulation, and reduces vasospasm-related DID.,  SAH statin users demonstrated significant improvement in 14-day functional outcome, a significantly lower incidence of DCI and cerebral infarctions of any type, as well as prevention of TCD highest mean velocity elevation. However, we did not find a significant statin impact on mortality or global outcome (Modified Rankin Scale) in this small sample. [SEP]Relations: acquired aneurysmal subarachnoid hemorrhage has relations: contraindication with Tranexamic acid, contraindication with Tranexamic acid, disease_protein with EDNRB, disease_protein with EDNRB, disease_protein with PPARG, disease_protein with PPARG, disease_protein with NOS2, disease_protein with NOS2, disease_phenotype_positive with Hypopituitarism, disease_phenotype_positive with Hypopituitarism.", "label": "yes"}
{"id": "converted_4368", "sentence1": "Does TIMELESS-TIPIN participate in replisome disassembly?", "sentence2": "TIMELESS-TIPIN and UBXN-3 promote replisome disassembly during DNA replication termination in Caenorhabditis elegans., We show that UBXN-3 is important in vivo for replisome disassembly in the absence of TIMELESS-TIPIN. Correspondingly, co-depletion of UBXN-3 and TIMELESS causes profound synthetic lethality. Since the human orthologue of UBXN-3, FAF1, is a candidate tumour suppressor, these findings suggest that manipulation of CMG disassembly might be applicable to future strategies for treating human cancer.[SEP]Relations: TIMELESS has relations: protein_protein with TIPIN, protein_protein with TIPIN, bioprocess_protein with DNA repair, bioprocess_protein with DNA repair, bioprocess_protein with DNA replication, bioprocess_protein with DNA replication, bioprocess_protein with positive regulation of double-strand break repair via homologous recombination, bioprocess_protein with positive regulation of double-strand break repair via homologous recombination, bioprocess_protein with DNA replication checkpoint signaling, bioprocess_protein with DNA replication checkpoint signaling.", "label": "yes"}
{"id": "converted_4221", "sentence1": "Does a comet assay measure radiation induced mutations?", "sentence2": "Evaluation of primary DNA-damage is one way to identify potential genotoxic agents and for this purpose the Comet assay has, for the last decades, been used to monitor DNA single strand and double strand breaks in individual cells, DNA strand-break frequency was examined by means of the comet assay i, . The comet assay (as this method was subsequently named) was able to measure, for the first time, the fraction of radiobiologically hypoxic cells in mouse and human tumors. It was used to determine that the rate of rejoining of DNA breaks was relatively homogenous within an irradiated population of cells, The comet assay is frequently used to measure DNA damage in individual cells. , Thus a complete repair of DNA damage induced by gamma-irradiation and measurable by the Comet assay was observed, whereas the yield of somatic mutations increased in relation to the radiation dose., xanthi) mutagenicity assay is the ability to analyze and compare on the same plants under identical treatment conditions both the induced acute DNA damage in somatic cells as measured by the Comet assay and the yield of induced leaf somatic mutations., The present study reveals that gamma radiation induces single strand breaks in DNA as measured by alkaline comet assay in bivalves and comet assay serves as a sensitive and rapid method to detect genotoxicity of gamma radiation., The present study is aimed (a) to know the genotoxic effect of gamma radiation on aquatic fauna employing two species of selected bivalves, (b) to evaluate the possible use of 'Comet assay' for detecting genetic damage in haemocytes of bivalves as a biomarker for environmental biomonitoring and also (c) to compare the relative sensitivity of two species of bivalves viz., The single cell gel electrophoresis (SCGE) assay, more commonly known as the comet assay, due to the \"comet-like\" appearance of the cells, was originally developed as a technique to measure the presence of DNA single-strand breaks., BACKGROUND: The neutral comet assay was devised to measure double-stranded DNA breaks, but it has also been used to measure apoptosis based on its characteristic DNA fragmentation patterns., 2, 4, 6, 8 and 10 Gy) of gamma radiation and their genotoxic effects on the haemocytes were studied using the comet assay., PURPOSE: The Deoxyribonucleic Acid (DNA) Comet assay, being a quick, simple, sensitive, reliable and fairly inexpensive method for measuring DNA strand breaks, has been used to assess DNA damage caused by gamma radiation in developmental stages of maize weevil Sitophilus zeamais Motschulsky., This paper attempts a correlation between the induction and repair of DNA damage measured in the comet assay and the clinical observed reaction in order to evaluate the suitability of the comet assay for prediction of radiation sensitivity., gle cell gel electrophoresis (e.g., Comet Assay) and immunofluoresence microscopy to detect the presence of gamma-H2AX foci, we find that Cr[VI] induces DNA double-strand breaks similar to ionizing radiation (IR). We also demo, ir of DNA damage induced by gamma-irradiation and measurable by the Comet assay was observed, whereas the yield of somatic mutations increased in relation to the radiation dose. Data on the kinetic, eased yield of somatic mutations was highly correlated (r = 0.996) with the increased DNA damage measured by the Comet assay immediately after irradiation. With inc, rther assess potential co-mutagenic effects of FA, we exposed A549 human lung cells to FA in combination with various mutagens and measured the induction and removal of DNA damage by the comet assay and the production of chromosomal mutations by the cytokinesis-block micronucleus assay (CBMN assay). The , DNA effects were analysed in leukocytes using the alkaline Comet assay, gene mutations and chromosome aberrations were measured in erythrocytes using the flow cytometric Pig-a gene mutation assay and the micronucleus test (applying both microscopic and flow cytometric evaluation), respectively., A wide variety of mutagens have been shown to cause DNA alterations detectable with the comet assay, but it is not yet clear whether a relationship exists between the DNA effects and the induction of mutations., The transgenerational changes in mutation rates were attributed to the presence of a persistent subset of endogenous DNA lesions (double- and single-strand breaks), measured by the phosphorylated form of histone H2AX (gamma-H2AX) and alkaline Comet assays., The single-cell electrophoresis (comet) assay is an established method for measuring radiation-induced strand breaks in DNA., The COMET assay is recognized as a rapid and sensitive method in quantifying radiation induced DNA damage., The relationship between cellular radiosensitivity and radiation-induced DNA damage measured by the comet assay., Reliable Comet assay measurements for detecting DNA damage induced by ionising radiation and chemicals., Radiation sensitivity of lymphocytes from healthy individuals and cancer patients as measured by the comet assay., The comet assay is a potential tool for use in neutron therapy, as well as a method for the rapid screening of samples from individuals accidentally exposed to radiation., Induction and repair of DNA damage as measured by the Comet assay and the yield of somatic mutations in gamma-irradiated tobacco seedlings., The increased yield of somatic mutations was highly correlated (r = 0.996) with the increased DNA damage measured by the Comet assay immediately after irradiation., The alkaline version of single cell gel electrophoresis (comet) assay is widely used for evaluating DNA damage at the individual cell level., Induction (2 and 5 Gy) of gamma-ray-induced DNA damage and its repair (during 60 min after irradiation) was measured with the alkaline and neutral comet assay., The alkaline single-cell gel electrophoresis (SCGE or Comet) assay appears to be a promising tool for measuring DNA damage at the individual cell level in both in vitro and in vivo studies., Considering our previous studies showing significant increases in the frequency of cytogenetic damage (when measured as micronuclei) in patients treated with relatively low doses of 131I, the results obtained in the present work by using the Comet assay could indicate that 1 week after the exposure most of the radioiodine-induced DNA lesions, that can be detected with this assay, have already been repaired., Hence, we are using the single-cell gel electrophoresis (comet assay) to detect mouse mutants that display a genetic susceptibility to ionizing radiation., We have established the analysis parameters in the comet assay which are currently used to detect radiation-sensitive mouse mutants and to control the variance within the mouse population in the ENU screen., Comet assay as a tool to screen for mouse models with inherited radiation sensitivity.[SEP]Relations: Protein S human has relations: drug_drug with Azithromycin, drug_drug with Azithromycin, drug_drug with Triptolide, drug_drug with Triptolide, drug_drug with Bamet-UD2, drug_drug with Bamet-UD2, drug_drug with Arsenic trioxide, drug_drug with Arsenic trioxide, drug_drug with Trastuzumab emtansine, drug_drug with Trastuzumab emtansine.", "label": "yes"}
{"id": "converted_888", "sentence1": "Does replication timing affect the rate of somatic mutations?", "sentence2": "Here we observe that mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome, ll classes of substitutions are affected, suggesting a generalized mechanism involving replication time-dependent DNA damage, We show that mutation rate varies 6-fold across a single chromosome, that this variation is correlated with replication timing, and we propose a model to explain this variation that relies on the temporal separation of two processes for replicating past damaged DNA: error-free DNA damage tolerance and translesion synthesis., Recent studies revealed a long suspected replication-timing effect on mutation rate, but the mechanisms that regulate the increase in mutation rate as the genome is replicated remain unclear. , DNA repair systems, in general, are less efficient in late replicating heterochromatic regions compared to early replicating euchromatic regions of the genome., The mutational profile of the yeast genome is shaped by replication, the mutation rate increases with the replication timing by more than 30% between the earliest and the latest replicating regions., Thus, we show that the leading replicating strands present an excess of C over G and of A over T in the genome of S. cerevisiae (reciprocally an excess of G + T over C + A in lagging strands), Late-replicating domains have higher divergence and diversity in Drosophila melanogaster, Recent evidence also suggests that late replication is associated with high mutability in yeast., Limited evidence from one chromosome arm in Drosophila melanogaster suggests the opposite pattern, with regions overlapping early-firing origins showing increased levels of diversity and divergence, The mutation rate for DNA mismatch repair null strains was approximately 1 mutation per genome per generation, 225-fold greater than the wild-type rate. The mutations were distributed randomly throughout the genome, independent of replication timing., Many single-nucleotide substitutions in cancer genomes arise because of errors in DNA replication, which is spatio-temporally stratified., Here we propose that DNA replication patterns help shape the mutational landscapes of normal and cancer genomes, Using data on five fully sequenced cancer types and two personal genomes, we determined that the frequency of intergenic single-nucleotide substitution is significantly higher in late DNA replication timing regions, even after controlling for a number of genomic features, we found that genomic regions in close spatial proximity to late-replicating domains display similar mutation spectra as the late-replicating regions themselves, In addition, certain chromosome rearrangements found in cancer cells and in cells exposed to ionizing radiation display a significant delay in replication timing of >3 hours that affects the entire chromosome(2,3). Recent work from our lab indicates that disruption of discrete cis-acting autosomal loci result in an extremely late replicating phenotype that affects the entire chromosome(4)., A conservative estimate is that at least 1-2% of new deleterious mutations affect some aspect of DNA replication, repair, or chromosome segregation. Since deleterious mutations can have an effect even as heterozygotes, this mutation accumulation can create an inherited background of late-acting mutations that themselves enhance mutation rate., Drake calculates that lytic RNA viruses display spontaneous mutation rates of approximately one per genome while most have mutation rates that are approximately 0.1 per genome (Drake 1993). This constancy of germline mutation rates among microbial species need not necessarily mean constancy of the somatic mutation rates., A recent flurry of reports correlates replication timing (RT) with mutation rates during both evolution and cancer., DNA replication timing, genome stability and cancer: late and/or delayed DNA replication timing is associated with increased genomic instability., Since deleterious mutations can have an effect even as heterozygotes, this mutation accumulation can create an inherited background of late-acting mutations that themselves enhance mutation rate., In addition, this method allows for the unambiguous identification of chromosomal rearrangements that correlate with changes in replication timing that affect the entire chromosome.[SEP]Relations: adaptation to pheromone regulating conjugation with mutual genetic exchange has relations: bioprocess_bioprocess with response to pheromone regulating conjugation with mutual genetic exchange, bioprocess_bioprocess with response to pheromone regulating conjugation with mutual genetic exchange, bioprocess_bioprocess with negative adaptation of signaling pathway, bioprocess_bioprocess with negative adaptation of signaling pathway. partial monosomy of the short arm of chromosome X has relations: disease_disease with atypical Norrie disease due to monosomy Xp11.3, disease_disease with atypical Norrie disease due to monosomy Xp11.3. Lacrimation abnormality has relations: disease_phenotype_positive with limbal stem cell deficiency, disease_phenotype_positive with limbal stem cell deficiency, disease_phenotype_positive with Waardenburg syndrome, disease_phenotype_positive with Waardenburg syndrome.", "label": "yes"}
{"id": "converted_3094", "sentence1": "Can cardiospheres be produced from skin fibroblasts?", "sentence2": "Therefore, there is an emerging interest in generating cardiosphere-like stem cells from somatic cells via somatic reprogramming. , Here we provide the detailed protocol for generating induced cardiospheres (iCS) for cardiac regeneration by somatic reprogramming of mouse fibroblasts using a panel of pluripotent transcription factors and cardiotrophic growth factors.[SEP]", "label": "yes"}
{"id": "converted_2509", "sentence1": "Is creatinine assessment included in the MELD score?", "sentence2": "Model For End-Stage Liver Disease (MELD) scores were calculated as 3.78×ln[TB] + 11.2×ln[INR] + 9.57×ln[creatinine] + 6.43. , A corrected creatinine was derived from the mGFR after application of the Modification of Diet in Renal Disease formula. Subsequently, a corrected MELD was calculated and compared with the conventionally calculated MELD., Among patients with MELD score>35, a new prognostic model based on serum creatinine, need for hemodialysis and moderate ascites could identify the sickest one., Patient risk factors evaluated include age, INR (international normalized ratio), creatinine, bilirubin, and MELD score (Model for End-of-stage Liver Disease). , Limited comparability of creatinine assays in patients with liver cirrhosis and their impact on the MELD score., The model of end-stage liver disease (MELD) score is used for this purpose in most countries and incorporates bilirubin, International Normalized ratio, and creatinine. , The MELD score was calculated using international normalized ratio, serum billirubin and creatinine., Regression analysis identified high creatinine and INR, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. , This study aimed to evaluate the impact of two creatinine measurement methods on the Model for End Stage Liver Disease (MELD) score and glomerular filtration rate estimation (eGFR) in cirrhotic patients., <b>OBJECTIVES</b>: The model for end-stage liver disease score (MELD = 3.8*LN[total bilirubin] + 9.6*LN[creatinine] + 11.2*[PT-INR] + 6.4) predicts mortality for tricuspid valve surgery., Simplified MELD score = 3.8*LN[total bilirubin] + 9.6*LN[creatinine] + 6.4.<br><b>METHODS</b>: A total of 172 patients (male: 66, female: 106; mean age, 63.8 ± 10.3 years) who underwent tricuspid replacement (n = 18) or repair (n = 154) from January 1991 to July 2011 at a single centre were included., CONCLUSION Incorporating eGFR obtained by the 6-variable MDRD equation into the MELD score showed an equal predictive performance in in-hospital mortality compared to a creatinine-based MELD score., Simplified MELD score = 3.8*LN[total bilirubin] + 9.6*LN[creatinine] + 6.4.[SEP]Relations: kidney disease has relations: contraindication with Melatonin, contraindication with Melatonin, contraindication with Fingolimod, contraindication with Fingolimod, contraindication with Probenecid, contraindication with Probenecid, contraindication with Meloxicam, contraindication with Meloxicam, contraindication with Melphalan, contraindication with Melphalan.", "label": "yes"}
{"id": "converted_3240", "sentence1": "Can mitochondria transfer from cell to cell?", "sentence2": "Interest in the recently discovered phenomenon of mitochondrial transfer between mammalian cells has gained momentum since it was first described in cell culture systems more than a decade ago., We show evidence that mitochondria transfer from Jurkat cells to MSCs, which is mediated by cell adhesion, This process of mitochondria transfer is mediated by tunneling nanotubes, which are protrusions that extend from the cell membrane .[SEP]Relations: mitochondrion has relations: cellcomp_protein with TH, cellcomp_protein with TH, cellcomp_protein with CS, cellcomp_protein with CS, cellcomp_protein with NNT, cellcomp_protein with NNT, cellcomp_protein with HIBADH, cellcomp_protein with HIBADH, cellcomp_protein with CAT, cellcomp_protein with CAT.", "label": "yes"}
{"id": "converted_1985", "sentence1": "Does HuR bind to the untranslated regions (UTRs) of mRNAs?", "sentence2": "HuR is also overexpressed during tumourigenesis and is abnormally present within the cytoplasm, where it binds to AU-rich elements in the 3'UTRs of target mRNA and post-transcriptionally regulates the expression of its target genes., Human antigen R (HuR) is a ubiquitous 32 kDa protein comprising three RNA Recognition Motifs (RRMs), whose main function is to bind Adenylate and uridylate Rich Elements (AREs) in 3' UnTranslated Regions (UTRs) of mRNAs., Human antigen R (HuR) is a ubiquitously expressed RNA-binding protein that modulates gene expression at the post-transcriptional level., The RNA-binding protein HuR binds at 3' untranslated regions (UTRs) of target transcripts, thereby protecting them against degradation. , ELAV/Hu proteins bind to AU-rich elements (ARE) in mRNAs and regulate their stability from splicing to translation, and the ubiquitous HuR protein has been implicated in cancerous cell growth. , This is achieved by altered expression of the proteins TTP and HuR, which bind 3' untranslated region (UTR) elements in cancer-related genes.[SEP]Relations: ELAVL1 has relations: molfunc_protein with mRNA 3'-UTR AU-rich region binding, molfunc_protein with mRNA 3'-UTR AU-rich region binding, pathway_protein with HuR (ELAVL1) binds and stabilizes mRNA, pathway_protein with HuR (ELAVL1) binds and stabilizes mRNA, molfunc_protein with mRNA 3'-UTR binding, molfunc_protein with mRNA 3'-UTR binding, bioprocess_protein with 3'-UTR-mediated mRNA stabilization, bioprocess_protein with 3'-UTR-mediated mRNA stabilization. protein binding has relations: molfunc_protein with HUS1, molfunc_protein with HUS1.", "label": "yes"}
{"id": "converted_2930", "sentence1": "Do raspberries improve postprandial glucose and acute and chronic inflammation in adults with type 2 Diabetes?", "sentence2": "The NLR family pyrin domain containing 3 (NLRP3) inflammasome plays a critical role in insulin resistance and the pathogenesis of type 2 diabetes. Red raspberry (RB) contains high amounts of dietary fibers and polyphenolic compounds, which are known for their anti-oxidative and anti-inflammatory effects. [SEP]Relations: retinoblastoma has relations: disease_phenotype_positive with Reduced visual acuity, disease_phenotype_positive with Reduced visual acuity, disease_protein with RB1, disease_protein with RB1, disease_phenotype_positive with Ewing sarcoma, disease_phenotype_positive with Ewing sarcoma, disease_phenotype_positive with Subretinal pigment epithelium hemorrhage, disease_phenotype_positive with Subretinal pigment epithelium hemorrhage, disease_phenotype_positive with Hypopyon, disease_phenotype_positive with Hypopyon.", "label": "yes"}
{"id": "converted_4628", "sentence1": "Is tirabrutinib effective for lymphoma?", "sentence2": "In March 2020, oral tirabrutinib was approved in Japan for the treatment of recurrent or refractory primary central nervous system lymphoma. Tirabrutinib is also under regulatory review in Japan for the treatment of Waldenström's macroglobulinemia and lymphoplasmacytic lymphoma. Clinical development is underway in the USA, Europe and Japan for autoimmune disorders, chronic lymphocytic leukaemia, B cell lymphoma, Sjogren's syndrome, pemphigus and rheumatoid arthritis. This article summarizes the milestones in the development of tirabrutinib leading to the first approval of tirabrutinib for the treatment of recurrent or refractory primary central nervous system lymphoma in Japan., CONCLUSION: These data indicate favorable efficacy of tirabrutinib in patients with relapsed/refractory PCNSL., Tirabrutinib was well tolerated and showed promising efficacy for B-cell NHL/CLL., rabrutinib was approved in Japan for the treatment of recurrent or refractory primary central nervous system lymphoma. Tirabrutinib is also , Here, we provide a comprehensive review of the preclinical and clinical activity of tirabrutinib, a drug approved in Japan for relapsed or refractory primary central nervous system lymphoma and all lines of Waldenström macroglobulinemia/lymphoplasmacytic lymphoma., Tirabrutinib (ONO/GS-4059; Ono Pharmaceutical) is a newly developed drug that selectively and irreversibly inhibits Bruton's tyrosine kinase (BTK) and has been approved in Japan for treating relapsed/refractory primary central nervous system lymphoma (PCNSL)., A 64-year-old patient with recurrent PCNSL enrolled in the phase I/II clinical trial of tirabrutinib, a second-generation BTK inhibitor designed for treating relapsed/refractory PCNSL., BACKGROUND: The safety, tolerability, efficacy, and pharmacokinetics of tirabrutinib, a second-generation, highly selective oral Bruton's tyrosine kinase inhibitor were evaluated for relapsed/refractory primary central nervous system lymphoma (PCNSL).M,  2020, oral tirabrutinib was approved in Japan for the treatment of recurrent or refractory primary central nervous system lymphoma. Tirabru, ine kinase inhibitor tirabrutinib (for relapsed and refractory PCNSL) and high-dose chemotherapy with autologous stem cell transplantation support using thiotepa and busulfan (BuTT) were approved by the Japanese Ministry of Health and Welfare in March 2020 and has recently become available for clinical practice. While these novel, BACKGROUND: The safety, tolerability, efficacy, and pharmacokinetics of tirabrutinib, a second-generation, highly selective oral Bruton's tyrosine kinase inhibitor were evaluated for relapsed/refractory primary central nervous system lymphoma (PCNSL).METHODS: Patients with relapsed/refractory PCNSL, Karnofsky performance status ≥70, and normal end-organ function received tirabrutinib 320 and 480 , Histological verification of the treatment effect of tirabrutinib for relapsed/refractory primary central nervous system lymphoma., In March 2020, oral tirabrutinib was approved in Japan for the treatment of recurrent or refractory primary central nervous system lymphoma.[SEP]Relations: Ibrutinib has relations: drug_drug with Ibritumomab tiuxetan, drug_drug with Ibritumomab tiuxetan, drug_drug with Acalabrutinib, drug_drug with Acalabrutinib, drug_drug with Tixocortol, drug_drug with Tixocortol. Thiotepa has relations: drug_drug with Ibritumomab tiuxetan, drug_drug with Ibritumomab tiuxetan, drug_drug with Acalabrutinib, drug_drug with Acalabrutinib.", "label": "yes"}
{"id": "converted_2791", "sentence1": "Is erythropoietin effective for treatment of amyotrophic lateral sclerosis?", "sentence2": "This study was performed to validate the ALS-MITOS as a 6-month proxy of survival in 200 ALS patients followed up to 18 months.METHODS: Analyses were performed on data from the recombinant human erythropoietin RCT that failed to demonstrate differences between groups for both primary and secondary outcomes., CONCLUSIONS: RhEPO 40,000 IU fortnightly did not change the course of ALS., At 12 months, the annualised rate of death (rhEPO 0.11, 95% CI 0.06 to 0.20; placebo: 0.08, CI 0.04 to 0.17), tracheotomy or >23 h NIV (rhEPO 0.16, CI 0.10 to 0.27; placebo 0.18, CI 0.11 to 0.30) did not differ between groups, also after stratification by onset and ALSFRS-R at baseline.[SEP]Relations: amyotrophic lateral sclerosis has relations: disease_protein with OPTN, disease_protein with OPTN, disease_protein with ERBB4, disease_protein with ERBB4, disease_protein with OTOG, disease_protein with OTOG, disease_protein with FOS, disease_protein with FOS, disease_protein with XIAP, disease_protein with XIAP.", "label": "no"}
{"id": "converted_1750", "sentence1": "Is synapsin a phosphoprotein?", "sentence2": "Synapsin is an evolutionarily conserved presynaptic phosphoprotein., Synapsins as a family of presynaptic terminal phosphoprotein participates in neuronal development, Synapsin III (SynIII) is a phosphoprotein, The neuronal phosphoprotein synapsin III, Synapsin II is a member of the neuronal phosphoprotein family., phosphoprotein synapsin[SEP]Relations: phosphoglycoprotein 1 has relations: disease_disease with Mendelian disease, disease_disease with Mendelian disease. neuronal tumor has relations: disease_disease with neuroepithelial neoplasm, disease_disease with neuroepithelial neoplasm, disease_disease with extraventricular neurocytoma, disease_disease with extraventricular neurocytoma, disease_disease with central neurocytoma, disease_disease with central neurocytoma, disease_disease with cerebellar liponeurocytoma, disease_disease with cerebellar liponeurocytoma.", "label": "yes"}
{"id": "converted_1652", "sentence1": "Is cardiac magnetic resonance imaging indicated in the pre-participation screening of athletes?", "sentence2": "As modern imaging further enhances our understanding of the spectrum of athlete's heart, its role may expand from the assessment of athletes with suspected disease to being part of comprehensive pre-participation screening in apparently healthy athletes., Finally we will address the role of CMR in pre-participation screening.[SEP]", "label": "no"}
{"id": "converted_2840", "sentence1": "Is Tisagenlecleucel effective for B-Cell Lymphoma?", "sentence2": "The phase II JULIET trial suggests that the CD19-targeting CAR T-cell therapy tisagenlecleucel produces durable responses in patients with relapsed and refractory diffuse large B-cell lymphoma., Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia., BACKGROUND: In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL)., CONCLUSIONS: In this global study of CAR T-cell therapy, a single infusion of tisagenlecleucel provided durable remission with long-term persistence in pediatric and young adult patients with relapsed or refractory B-cell ALL, with transient high-grade toxic effects., Chimeric antigen receptor T cells demonstrate efficacy in B-cell malignancies, leading to US Food and Drug Administration approval of axicabtagene ciloleucel (October 2017) and tisagenlecleucel (May 2018) for large B-cell lymphomas after 2 prior lines of therapy., This article reviews data of current diffuse large B-cell lymphoma management, focusing on axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel., This article reviews data of current diffuse large B-cell lymphoma management, focusing on axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel.<br>, The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study.<br><b>METHODS</b>: We conducted an international, phase 2, pivotal study of centrally manufactured tisagenlecleucel involving adult patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for or had disease progression after autologous hematopoietic stem-cell transplantation., No differences between response groups in tumor expression of CD19 or immune checkpoint-related proteins were found.<br><b>CONCLUSIONS</b>: In this international study of CAR T-cell therapy in relapsed or refractory diffuse large B-cell lymphoma in adults, high rates of durable responses were produced with the use of tisagenlecleucel., This was a milestone in tumor immunology on account of the significant antitumor effect of tisagenlecleucel for the treatment of relapsed/refractory B-ALL patients., On August 30, 2017, the U.S. Food and Drug Administration (FDA) approved Novartis' tisagenlecleucel (CTL-019, Kymriah), which is a synthetic bioimmune product of anti-CD19 chimeric antigen receptor (CAR) T cells, for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL)., Within the last one year, two anti-CD19 CAR T-cell therapy products, axicabtagene ciloleucel and tisagenlecleucel, were approved by the United States Food and Drug Administration for the treatment of relapsed or refractory large B-cell lymphoma after at least two lines of systemic therapy based on multicenter single-arm phase two clinical trials. , On August 30, 2017, the U.S. Food and Drug Administration approved tisagenlecleucel for treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse., Tisagenlecleucel for the treatment of B-cell acute lymphoblastic leukemia., Background: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy approved for the treatment of children and young adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL).[SEP]Relations: B-cell lymphoma has relations: drug_effect with Lansoprazole, drug_effect with Lansoprazole, drug_effect with Darunavir, drug_effect with Darunavir, drug_effect with Muromonab, drug_effect with Muromonab. precursor T-cell acute lymphoblastic leukemia has relations: disease_protein with BLM, disease_protein with BLM, disease_protein with BLM, disease_protein with BLM.", "label": "yes"}
{"id": "converted_2247", "sentence1": "Does TFIIS affect nucleosome positioning?", "sentence2": "Transcript cleavage factor TFIIS reactivates the backtracked complexes and promotes pol II transcription through the nucleosome. , The same nucleosomes transcribed in the opposite orientation form a weaker, more diffuse barrier that is largely relieved by higher salt, TFIIS, or FACT, The system contains natural or recombinant histones, chromatin assembly factors, the histone-acetyltransferase p300, all components of the general transcription machinery, general coactivators and the elongation factor SII (TFIIS)., Efficient and rapid nucleosome traversal by RNA polymerase II depends on a combination of transcript elongation factors., We now show that although TFIIF or TFIIS alone is modestly stimulatory for nucleosome traversal, both factors together increase transcription through nucleosomes in a synergistic manner., Significantly, we found that nucleosomes with a Sin mutant histone are traversed to the same extent and at nearly the same rate as equivalent pure DNA templates if both TFIIS and TFIIF are present., After partial uncoiling of nucleosomal DNA from histone octamer by Pol II and backtracking of the enzyme, nucleosomal DNA recoils on the octamer, locking Pol II in the arrested state. Histone chaperones and transcription factors TFIIS, TFIIF and FACT facilitate transcription through chromatin using different molecular mechanisms., Transcript cleavage factor TFIIS reactivates the backtracked complexes and promotes pol II transcription through the nucleosome., The highly conserved eukaryotic transcriptional elongation factor TFIIS enables RNA polymerase II (RNAPII) to read though pause or termination sites, nucleosomes and sequence-specific DNA-binding proteins., We also studied the effect of TFIIF and TFIIS on transcription of nucleosomes containing a Sin mutant histone., The same nucleosomes transcribed in the opposite orientation form a weaker, more diffuse barrier that is largely relieved by higher salt, TFIIS, or FACT.[SEP]Relations: nucleosome has relations: cellcomp_protein with IRF4, cellcomp_protein with IRF4, cellcomp_protein with MPHOSPH8, cellcomp_protein with MPHOSPH8, cellcomp_protein with H2AX, cellcomp_protein with H2AX, cellcomp_protein with SLF1, cellcomp_protein with SLF1, cellcomp_protein with GLYR1, cellcomp_protein with GLYR1.", "label": "yes"}
{"id": "converted_3470", "sentence1": "Is overexpression of LY6K associated with better prognosis for non-small cell lung cancer patients?", "sentence2": "Gene expression profile analyses of non-small cell lung carcinomas (NSCLC) and esophageal squamous cell carcinomas (ESCC) revealed that lymphocyte antigen 6 complex locus K (LY6K) was specifically expressed in testis and transactivated in a majority of NSCLCs and ESCCs. Immunohistochemical staining using 406 NSCLC and 265 ESCC specimens confirmed that LY6K overexpression was associated with poor prognosis for patients with NSCLC (P = 0.0003), as well as ESCC (P = 0.0278), and multivariate analysis confirmed its independent prognostic value for NSCLC (P = 0.0035). , Immunohistochemical staining using 406 NSCLC and 265 ESCC specimens confirmed that LY6K overexpression was associated with poor prognosis for patients with NSCLC (P = 0.0003), as well as ESCC (P = 0.0278), and multivariate analysis confirmed its independent prognostic value for NSCLC (P = 0.0035)., Immunohistochemical staining using 406 NSCLC and 265 ESCC specimens confirmed that LY6K overexpression was associated with poor prognosis for patients with NSCLC (P = 0.0003), as well as ESCC (P = 0.0278), and multivariate analysis confirmed its independent prognostic value for NSCLC (P = 0.0035).[SEP]Relations: small cell lung carcinoma has relations: disease_protein with LYRM9, disease_protein with LYRM9, disease_protein with STK31, disease_protein with STK31, disease_protein with CYP2A6, disease_protein with CYP2A6, disease_protein with DMPK, disease_protein with DMPK, disease_protein with PYCARD, disease_protein with PYCARD.", "label": "no"}
{"id": "converted_167", "sentence1": "Is CD84 genetically associated with arthritis?", "sentence2": "The SNP is predicted to disrupt transcription factor binding site motifs in the 3' UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1 × 10(-11) in 228 non-RA patients and P = 0.004 in 132 RA patients), Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity,  Three members of this gene family, Ly108, Ly9, and CD84, exhibit polymorphisms that strongly influence susceptibility to systemic autoimmunity, notably in mice, but also in some human populations[SEP]Relations: Rheumatoid arthritis has relations: disease_phenotype_positive with IgG4-related retroperitoneal fibrosis, disease_phenotype_positive with IgG4-related retroperitoneal fibrosis, disease_phenotype_positive with hereditary xanthinuria, disease_phenotype_positive with hereditary xanthinuria, phenotype_phenotype with Arthritis, phenotype_phenotype with Arthritis, drug_effect with Interferon alfa-2b, drug_effect with Interferon alfa-2b, disease_phenotype_positive with achalasia (disease), disease_phenotype_positive with achalasia (disease).", "label": "yes"}
{"id": "converted_520", "sentence1": "Does ziconotide bind to N-type calcium channels?", "sentence2": "Since this region partially overlaps with residues previously implicated in block of the channel by omega-conotoxin GVIA, we assessed the effects of mutations in the putative EF hand domain on channel block by omega-conotoxin GVIA and the structurally related omega-conotoxin MVIIA. Both of the toxins irreversibly block the activity of wild type alpha(1B) N-type channels. , Despite their high sequence homology, the peptide neurotoxins omega-conotoxin MVIIA and MVIIC selectively block N- and P/Q-type calcium channels, respectively. ,  Binding assay for both N- and P/Q-type calcium channels showed that amino acid residues restricted to the N-terminal half are important for the recognition of N-type channels, whereas essential residues for P/Q-type channel recognition are widely spread over the whole omega-conotoxin molecule., Ziconotide is a novel peptide that blocks the entry of calcium into neuronal N-type voltage-sensitive calcium channels, preventing the conduction of nerve signals., Ziconotide is a selective, potent and reversible blocker of neuronal N-type voltage-sensitive calcium channels (VSCCs)., The therapeutic benefit of ziconotide derives from its potent and selective blockade of neuronal N-type voltage-sensitive calcium channels., Interactions of intrathecally administered ziconotide, a selective blocker of neuronal N-type voltage-sensitive calcium channels, with morphine on nociception in rats., Ziconotide, a new N-type calcium channel blocker, administered intrathecally for acute postoperative pain., Ziconotide, an intrathecally administered N-type calcium channel antagonist for the treatment of chronic pain., Thus, ziconotide is the first of a new class of agents--N-type calcium channel blockers, or NCCBs., Ziconotide, formerly known also as SNX- 111, represents a new class of agents, the N-type calcium channel blockers., The selective N-type calcium channel blocker ziconotide ameliorates severe chronic pain but has a narrow therapeutic window and requires intrathecal administration., A selective N-type calcium channel inhibitor, ziconotide (Prialt), is a neuroactive peptide recently marketed as a novel nonopioid treatment for severe chronic pain., As the clinically available analgesics, pregabalin (alpha2delta-subunit calcium channel ligand), ziconotide (N-type calcium channel blocker), mexiletine (sodium channel blocker), and duloxetine (serotonin and norepinephrine reuptake inhibitors) were evaluated in these neurochemically-induced allodynia models., The present investigation was designed to assess the safety and analgesic efficacy of ziconotide, a new N-type calcium channel blocker, when administered intrathecally to patients with acute postoperative pain., Inhibition of the N-type calcium channel by intrathecal administration of the channel-specific blocker omega-conotoxin MVIIA (ziconotide) is efficacious in the treatment of severe chronic pain., Ziconotide is a powerful analgesic drug that has a unique mechanism of action involving potent and selective block of N-type calcium channels, which control neurotransmission at many synapses., In conclusion, present findings provide implication that the spinal anti-nociceptive mechanistic site of pregabalin is different from that of ziconotide, mexiletine, and duloxetine, and pregabalin could have a broader anti-nociceptive mechanism other than N-type calcium channel blockade., Ziconotide (SNX-111), a selective blocker of neuronal N-type voltage-sensitive calcium channels, is antinociceptive when it is administered intrathecally., Effects of intrathecal administration of ziconotide, a selective neuronal N-type calcium channel blocker, on mechanical allodynia and heat hyperalgesia in a rat model of postoperative pain., A state-dependent Ca(V)2.2 inhibitor may provide an improved therapeutic window over ziconotide, the peptidyl Ca(V)2.2 inhibitor used clinically. , There is also human validation data from ziconotide, the CaV2.2-selective peptidyl inhibitor used clinically to treat refractory pain. , A selective N-type calcium channel inhibitor, ziconotide (Prialt), is a neuroactive peptide recently marketed as a novel nonopioid treatment for severe chronic pain. , The neuroprotective effects of intrathecal administration of the selective N-type calcium channel blocker ziconotide in a rat model of spinal ischemia.[SEP]Relations: Ziconotide has relations: drug_drug with Calcium, drug_drug with Calcium, drug_drug with Calcium cation, drug_drug with Calcium cation, drug_drug with Calcium acetate, drug_drug with Calcium acetate, drug_drug with Calcium chloride, drug_drug with Calcium chloride, drug_drug with Calcium gluconate, drug_drug with Calcium gluconate.", "label": "yes"}
{"id": "converted_824", "sentence1": "is pharmacological treatment of subclinical hypothyroidism effective in reducing cardiovascular events?", "sentence2": "The decision to treat elderly people is still an unresolved clinical challenge--first, due to a lack of appropriately powered randomized controlled trials of L-T4 in sHT patients, examining cardiovascular hard endpoints in various classes of age; and second, because of the negative effects of possible overtreatment., The lack of specific randomized trials enrolling either old or very old subjects, aimed at evaluate the efficacy of hormonal replacement on overall survival and cardiovascular risk reduction along with the negative effects of possible over-treatment, makes the decision to treat older people a still unresolved clinical challenge, In patients with type 2 DM, the presence of SH serves as an additional risk factor for endothelial dysfunction., Treatment of SCH with levothyroxine was associated with fewer IHD events in younger individuals, but this was not evident in older people., Subclinical hyperthyroidism seems to be a risk factor of developing major cardiovascular events, especially stroke in older adults from the general population with normal left ventricular function., SCH appears to influence the postoperative outcome for patients by increasing the development of postoperative atrial fibrillation. However, it is still unproven whether preoperative thyroxine replacement therapy for patients with SCH might prevent postoperative atrial fibrillation after CABG., In CHF patients TSH levels even slightly above normal range are independently associated with a greater likelihood of heart failure progression., In current RCTs, levothyroxine replacement therapy for subclinical hypothyroidism did not result in improved survival or decreased cardiovascular morbidity. Data on health-related quality of life and symptoms did not demonstrate significant differences between intervention groups., However, the actual effectiveness of thyroid hormone substitution in reducing the risk of cardiovascular events remains to be elucidated. In conclusion, the multiplicity and the possible reversibility of subclinical hypothyroidism-associated cardiovascular abnormalities suggest that the decision to treat a patient should depend on the presence of risk factors, rather than on a TSH threshold. , However, whether SH confers a high risk for cardiovascular disease, and whether LT4 therapy has a long-term benefit that clearly outweighs the risks of overzealous treatment in these individuals, remain topics of controversy.[SEP]Relations: Levothyroxine has relations: contraindication with cardiovascular disease, contraindication with cardiovascular disease, drug_effect with Hypoglycemia, drug_effect with Hypoglycemia. cardiovascular disease has relations: contraindication with Levothyroxine, contraindication with Levothyroxine, contraindication with Phenobarbital, contraindication with Phenobarbital, contraindication with Liothyronine, contraindication with Liothyronine.", "label": "no"}
{"id": "converted_2854", "sentence1": "Is pacritinib effective for treatment of myelofibrosis?", "sentence2": "Pacritinib and its use in the treatment of patients with myelofibrosis who have thrombocytopenia., Pacritinib, a dual JAK2 and FLT3 inhibitor which also inhibits IRAK1, has demonstrated the ability to favorably impact MF-associated splenomegaly and symptom burden, while having limited myelosuppression with manageable gastrointestinal toxicity., Other JAKis, such as fedratinib and pacritinib, proved to be useful in MF. , Conclusions and Relevance: In patients with myelofibrosis and thrombocytopenia, including those with prior anti-JAK therapy, pacritinib twice daily was more effective than BAT, including ruxolitinib, for reducing splenomegaly and symptoms., Developments of JAK inhibitors, such as ruxolitinib, pacritinib, momelotinib, and febratinib enabled the effective management in MF patients. ,  Pacritinib (PAC), a multi-kinase inhibitor with specificity for JAK2, FLT3, and IRAK1 but sparing JAK1, has demonstrated clinical activity in MF with minimal myelosuppression. , Pacritinib could be a treatment option for patients with myelofibrosis, including those with baseline cytopenias for whom options are particularly limited., Conclusions and Relevance\nIn patients with myelofibrosis and thrombocytopenia, including those with prior anti-JAK therapy, pacritinib twice daily was more effective than BAT, including ruxolitinib, for reducing splenomegaly and symptoms., Expert commentary: Pacritinib has demonstrated promising results in patients with myelofibrosis and thrombocytopenia., Pacritinib, a dual JAK2 and FLT3 inhibitor, improves disease-related symptoms and signs with manageable gastrointestinal toxicity in patients with myelofibrosis with splenomegaly and high-risk features, without causing overt myelosuppression, and therefore may provide an important treatment option for a range of patients with myelofibrosis., Pacritinib is an active agent in patients with MF, offering a potential treatment option for patients with preexisting anemia and thrombocytopenia., Pacritinib (PAC), a multi-kinase inhibitor with specificity for JAK2, FLT3, and IRAK1 but sparing JAK1, has demonstrated clinical activity in MF with minimal myelosuppression., This article examines the role of JAK2 and FLT3 signaling in myelofibrosis and provides an overview of the clinical development of pacritinib as a new therapy for myelofibrosis., Pacritinib appears to be an effective agent for the control of MF-related symptoms and splenomegaly with potentially fewer haematological side-effects when compared with ruxolitinib and seems a particularly promising agent for anaemic and thrombocytopenic patients. , Expert commentary: Pacritinib has demonstrated promising results in patients with myelofibrosis and thrombocytopenia.[SEP]Relations: Pacritinib has relations: drug_drug with Dibromotyrosine, drug_drug with Dibromotyrosine, drug_drug with Thyrotropin, drug_drug with Thyrotropin, drug_drug with Carbimazole, drug_drug with Carbimazole, drug_drug with Liothyronine, drug_drug with Liothyronine, drug_drug with Follitropin, drug_drug with Follitropin.", "label": "yes"}
{"id": "converted_1955", "sentence1": "Does oculocutaneous albinism show an autosomal recessive inheritance?", "sentence2": "Oculocutaneous albinism (OCA) is an autosomal recessive disorder characterized by hypopigmentation in eyes, hair and skin, accompanied with vision loss. , Oculocutaneous albinism (OCA) is an autosomal recessive hereditary pigmentation disorder affecting humans and several other animal species. , Oculocutaneous albinism type 2 (OCA2) is a human autosomal-recessive hypopigmentation disorder associated with pathological mutations of the OCA2 gene., Oculocutaneous albinism type1 (OCA1) is characterized by the absence of melanin pigmentation. The mutation on TYR gene makes OCA1 as an autosomal recessive genetic disorder. , Our patients were diagnosed as affected with Oculocutaneous albinism type1a. Analysis of pedigree pattern showed an autosomal recessive inheritance. , Oculocutaneous albinism (OCA) is an autosomal recessive disorder of melanin biosynthesis that results in congenital hypopigmentation of ocular and cutaneous tissues., Oculocutaneous albinism is an autosomal recessive genetic disorder., Melanin biosynthesis is reduced in oculocutaneous albinism, an autosomal recessive disorder., The pedigrees were consistent with an autosomal recessive inheritance pattern.CONCLUSION: This unique type of oculocutaneous albinism has heterogeneous clinical features., BACKGROUND: Oculocutaneous albinism (OCA) is an autosomal recessive hereditary pigmentation disorder affecting humans and several other animal species., The Q402 allele has been associated with autosomal recessive ocular albinism when it is in trans with a tyrosinase gene mutation associated with oculocutaneous albinism type 1., Analysis using the POINTER program showed that this type of oculocutaneous albinism was inherited in an autosomal recessive pattern, with an estimated gene frequency of 0.025 +/- 0.007 in this population., We have identified 12 families with oculocutaneous albinism type 1 that exhibit segregation of the c.1205G>A variant with a known pathologic mutation on the homologous chromosome, and demonstrate no genetic association between autosomal recessive oculocutaneous albinism and the Q402 variant., BACKGROUND: Type II (tyrosinase-positive) oculocutaneous albinism is an autosomal recessive disorder that has recently been mapped to chromosome segment 15q11-q13., The child with ocular albinism was heterozygous for two different mutations in the P gene.CONCLUSIONS: Abnormalities of the P gene are associated with a wide range of clinical phenotypes, including type II oculocutaneous albinism, albinism associated with the Prader-Willi syndrome, and at least some cases of autosomal recessive ocular albinism., Mutations in the TYR gene (TYR, 11q14-21, MIM 606933) cause oculocutaneous albinism type 1 (OCA1, MIM 203100), a developmental disorder having an autosomal recessive mode of inheritance, The pedigrees were consistent with an autosomal recessive inheritance pattern.This unique type of oculocutaneous albinism has heterogeneous clinical features, Oculocutaneous albinism (OCA) is an autosomal recessive disorder, Oculocutaneous albinism (OCA) is an autosomal recessive disorder of abnormal melanin formation, which results in hypopigmentation of skin, hair and eyes, The mutation of the tyrosinase (TYR) gene results in oculocutaneous albinism type 1 (OCA1), an autosomal recessive genetic disorder, We found oculo-cutaneous albinism in two brothers and granular dystrophy in three brothers, the mother and a son.Corneal dystrophy is an autosomal dominant disorder inherited independently of oculocutaneous albinism, which is inherited as an autosomal recessive condition, Oculocutaneous albinism (OCA) type 4 is a newly identified human autosomal recessive hypopigmentary disorder that disrupts pigmentation in the skin, hair and eyes, Analysis using the POINTER program showed that this type of oculocutaneous albinism was inherited in an autosomal recessive pattern, with an estimated gene frequency of 0.025 +/- 0.007 in this population. , DISCUSSION: Corneal dystrophy is an autosomal dominant disorder inherited independently of oculocutaneous albinism, which is inherited as an autosomal recessive condition. , BACKGROUND: Oculocutaneous albinism type II (OCA2) is an autosomal recessively inherited disorder, characterized by white hair and skin, and loss of pigment in the eyes. , Is autosomal recessive deafness associated with oculocutaneous albinism a \"coincidence syndrome\"?, Oculocutaneous albinism, immunodeficiency, hematological disorders, and minor anomalies: a new autosomal recessive syndrome?, Mutations in the TYR gene (TYR, 11q14-21, MIM 606933) cause oculocutaneous albinism type 1 (OCA1, MIM 203100), a developmental disorder having an autosomal recessive mode of inheritance., Oculocutaneous albinism (OCA) is an autosomal recessive disorder characterized by hypopigmentation in eyes, hair and skin, accompanied with vision loss., Oculocutaneous albinism (OCA) is an autosomal recessive hereditary pigmentation disorder affecting humans and several other animal species.[SEP]Relations: autosomal recessive disease has relations: disease_disease with autosomal recessive ocular albinism, disease_disease with autosomal recessive ocular albinism. Autosomal recessive inheritance has relations: disease_phenotype_positive with oculoosteocutaneous syndrome, disease_phenotype_positive with oculoosteocutaneous syndrome. autosomal dominant oculocutaneous albinism has relations: disease_disease with autosomal dominant disease, disease_disease with autosomal dominant disease. autosomal dominant disease has relations: disease_disease with autosomal dominant oculocutaneous albinism, disease_disease with autosomal dominant oculocutaneous albinism. ocular albinism (disease) has relations: disease_disease with autosomal recessive ocular albinism, disease_disease with autosomal recessive ocular albinism.", "label": "yes"}
{"id": "converted_2008", "sentence1": "Is Meis1 implicated in microphthalmia?", "sentence2": "Meis1 coordinates a network of genes implicated in eye development and microphthalmia., Here we show that haploinsufficiency of Meis1, which encodes a transcription factor with evolutionarily conserved expression in the embryonic trunk, brain and sensory organs, including the eye, causes microphthalmic traits and visual impairment in adult mice., We propose that Meis1 is at the core of a genetic network implicated in eye patterning/microphthalmia, and represents an additional candidate for syndromic cases of these ocular malformations., We propose that Meis1 is at the core of a genetic network implicated in eye patterning/microphthalmia, and represents an additional candidate for syndromic cases of these ocular malformations., In the eye primordium, Meis1 coordinates, in a dose-dependent manner, retinal proliferation and differentiation by regulating genes responsible for human microphthalmia and components of the Notch signaling pathway., Meis1 coordinates a network of genes implicated in eye development and microphthalmia, We propose that Meis1 is at the core of a genetic network implicated in eye patterning/microphthalmia, and represents an additional candidate for syndromic cases of these ocular malformations. <CopyrightInformation>© 2015, In the eye primordium, Meis1 coordinates, in a dose-dependent manner, retinal proliferation and differentiation by regulating genes responsible for human microphthalmia and components of the Notch signaling pathway, We propose that Meis1 is at the core of a genetic network implicated in eye patterning/microphthalmia, and represents an additional candidate for syndromic cases of these ocular malformations. <CopyrightInformation>© 2015., In the eye primordium, Meis1 coordinates, in a dose-dependent manner, retinal proliferation and differentiation by regulating genes responsible for human microphthalmia and components of the Notch signaling pathway., Meis1 coordinates a network of genes implicated in eye development and microphthalmia.[SEP]Relations: microphthalmia has relations: disease_protein with HMX1, disease_protein with HMX1, disease_protein with TENM3, disease_protein with TENM3, disease_protein with RBP4, disease_protein with RBP4, disease_protein with CRB1, disease_protein with CRB1, disease_protein with BEST1, disease_protein with BEST1.", "label": "yes"}
{"id": "converted_4114", "sentence1": "Is YKL-40 used as a biomarker for Alzheimer's disease?", "sentence2": "Recently, cerebrospinal fluid (CSF) YKL-40 levels were reported to be a promising candidate biomarker of glial inflammation in Alzheimer's disease (AD). , Disease groups differed between them except AD versus FTD for YKL-40. , YKL-40 appears to be a more reliable biomarker in neurological diseases than NSE.[SEP]Relations: familial Alzheimer disease has relations: disease_disease with Alzheimer disease, disease_disease with Alzheimer disease, disease_protein with PRNP, disease_protein with PRNP, disease_phenotype_positive with Perseveration, disease_phenotype_positive with Perseveration, disease_phenotype_positive with Attention deficit hyperactivity disorder, disease_phenotype_positive with Attention deficit hyperactivity disorder, disease_disease with inherited prion disease, disease_disease with inherited prion disease.", "label": "yes"}
{"id": "converted_4511", "sentence1": "Is thalidomide used as an immunomodulatory drug nowadays?", "sentence2": "Potential immunomodulatory, antiinflammatory, anti-angiogenic and sedative properties make thalidomide a good candidate for the treatment of several diseases such as multiple myeloma., In 1990s, however, thalidomide received attention due to the discovery of its anticancer potential derived from antiangiogenic and immunomodulatory activities, and its therapeutic effect on myeloma., Thalidomide is an immunomodulatory agent; although its mechanisms of action are not fully understood, many authors have described its anti-inflammatory and immunosuppressive properties, Thalidomide has antiangiogenic and immunomodulatory properties and has recently been used in the management of human malignancies, After nearly decades of extinction as a sedative and antiemetic, thalidomide reemerged as the parent compound of a novel and promising class of therapeutics termed the immunomodulatory drugs (IMiDs), Thalidomide has antiangiogenic and immunomodulatory properties and has recently been used in the management of human malignancies., Thalidomide is a drug that, since its development, has made history in the world of medicine--having been withdrawn and now has returned with a boom as an anticancer and immunomodulatory drug., Thalidomide was developed in the 1950s as a sedative drug and withdrawn in 1961 because of its teratogenic effects, but has been rediscovered as an immuno-modulatory drug., Thalidomide is attracting growing interest because of its reported immunomodulatory and anti-inflammatory properties., Only in the last several years has thalidomide been aggressively investigated for its antiangiogenic potential and immunomodulatory properties in various tumor types., After nearly decades of extinction as a sedative and antiemetic, thalidomide reemerged as the parent compound of a novel and promising class of therapeutics termed the immunomodulatory drugs (IMiDs)., In the present review an attempt is made to highlight the immunomodulatory action of thalidomide in various pathologic conditions., Thalidomide and its immunomodulatory analogues have numerous effects on the body's immune system, including potential anti-cancer and anti-inflammatory activities., Thalidomide is an immunomodulatory agent; although its mechanisms of action are not fully understood, many authors have described its anti-inflammatory and immunosuppressive properties., Thalidomide (Thal) has antiangiogenic and immunomodulatory activity., Thalidomide is an immunomodulatory drug (IMiD) with proven therapeutic action in several autoimmune/inflammatory diseases;, The immunomodulatory agents thalidomide and lenalidomide and the proteasome inhibitor bortezomib are now routine components of MM therapy, Although thalidomide was withdrawn in the 1960s after its teratogenic property was recognized, it was subsequently found that this drug possesses immunomodulatory and anti-inflammatory effects.,  Its immunological effects were known already from earlier studies. Nowadays its use is accepted in myeloma therapy., Therapeutics that have proven to be highly effective include the immunomodulatory drug thalidomide and its newer analogs, lenalidomide and pomalidomide, as well as the proteasome inhibitors bortezomib and carfilzomib, As immunomodulatory drugs, thalidomide and its analogues have been used to effectively treat various diseases, Its effectiveness in the clinic has been ascribed to wide-ranging properties, including anti-TNF-alpha, T-cell costimulatory and antiangiogenic activity., Thalidomide has various immunomodulatory effects. Thalidomide inhibits TNF alpha production, has T-cell costimulatory properties and modulates the expression of cell surface molecules on leukocytes in vivo.,  thalidomide has been a target of active investigation in both malignant and inflammatory conditions. Although initially developed for its sedative properties, decades of investigation have identified a multitude of biological effects that led to its classification as an immunomodulatory drug (IMiD)., The mechanism of action of thalidomide is probably based on its immunomodulatory effect, namely the suppression of production of tumor necrosis factor alpha and the modulation of interleukins., This effect is probably due to a direct influence on the immune system[SEP]Relations: Thalidomide has relations: drug_drug with Etomidate, drug_drug with Etomidate, drug_drug with Desomorphine, drug_drug with Desomorphine, drug_drug with Dipyridamole, drug_drug with Dipyridamole, drug_drug with Practolol, drug_drug with Practolol, drug_drug with Felodipine, drug_drug with Felodipine.", "label": "yes"}
{"id": "converted_3073", "sentence1": "Is the NLM medical text indexer (MTI) still useful and relevant?", "sentence2": "12 years on - Is the NLM medical text indexer still useful and relevant?, Facing a growing workload and dwindling resources, the US National Library of Medicine (NLM) created the Indexing Initiative project in 1996. This cross-library team's mission is to explore indexing methodologies for ensuring quality and currency of NLM document collections. The NLM Medical Text Indexer (MTI) is the main product of this project and has been providing automated indexing recommendations since 2002. After all of this time, the questions arise whether MTI is still useful and relevant.METHODS: To answer the question about MTI usefulness, we track a wide variety of statistics related to how frequently MEDLINE indexers refer to MTI recommendations, how well MTI performs against human indexing, and how often MTI is used. To answer the question of MTI relevancy compared to other available tools, we have participated in the 2013 and 2014 BioASQ Challenges. The BioASQ Challenges have provided us with an unbiased comparison between the MTI system and other systems performing the same task.RESULTS: Indexers have continually increased their use of MTI recommendations over the years from 15.75% of the articles they index in 2002 to 62.44% in 2014 showing that the indexers find MTI to be increasingly useful. The MTI performance statistics show significant improvement in Precision (+0.2992) and F1 (+0.1997) with modest gains in Recall (+0.0454) over the years. MTI consistency is comparable to the available indexer consistency studies. MTI performed well in both of the BioASQ Challenges ranking within the top tier teams.CONCLUSIONS: Based on our findings, yes, MTI is still relevant and useful, and needs to be improved and expanded. The BioASQ Challenge results have shown that we need to incorporate more machine learning into MTI while still retaining the indexing rules that have earned MTI the indexers' trust over the years. We also need to expand MTI through the use of full text, when and where it is available, to provide coverage of indexing terms that are typically only found in the full text. The role of MTI at NLM is also expanding into new areas, further reinforcing the idea that MTI is increasingly useful and relevant., The role of MTI at NLM is also expanding into new areas, further reinforcing the idea that MTI is increasingly useful and relevant., CONCLUSIONS\nBased on our findings, yes, MTI is still relevant and useful, and needs to be improved and expanded., 12 years on - Is the NLM medical text indexer still useful and relevant?Based on our findings, yes, MTI is still relevant and useful, and needs to be improved and expanded. , The role of MTI at NLM is also expanding into new areas, further reinforcing the idea that MTI is increasingly useful and relevant., After all of this time, the questions arise whether MTI is still useful and relevant.<br><b>METHODS</b>: To answer the question about MTI usefulness, we track a wide variety of statistics related to how frequently MEDLINE indexers refer to MTI recommendations, how well MTI performs against human indexing, and how often MTI is used., The MTI performance statistics show significant improvement in Precision (+0.2992) and F<br><b>CONCLUSIONS</b>: Based on our findings, yes, MTI is still relevant and useful, and needs to be improved and expanded., The role of MTI at NLM is also expanding into new areas, further reinforcing the idea that MTI is increasingly useful and relevant.<br>, After all of this time, the questions arise whether MTI is still useful and relevant., The role of MTI at NLM is also expanding into new areas, further reinforcing the idea that MTI is increasingly useful and relevant., Based on our findings, yes, MTI is still relevant and useful, and needs to be improved and expanded.[SEP]Relations: F11 has relations: anatomy_protein_absent with vastus lateralis, anatomy_protein_absent with vastus lateralis, drug_protein with Coagulation Factor IX (Recombinant), drug_protein with Coagulation Factor IX (Recombinant), anatomy_protein_absent with biceps brachii, anatomy_protein_absent with biceps brachii, anatomy_protein_present with lung, anatomy_protein_present with lung, drug_protein with Zinc sulfate, unspecified form, drug_protein with Zinc sulfate, unspecified form.", "label": "yes"}
{"id": "converted_3701", "sentence1": "Have toll-like receptor 2 activators been found in food?", "sentence2": "Toll-like receptor 2 (TLR2) is a widely expressed pattern recognition receptor critical for innate immunity. TLR2 is also a key regulator of mucosal immunity implicated in the development of allergic disease. TLR2 activators are found in many common foods,, TLR2 activators are found in many common foods, but the role of TLR2 in oral tolerance and allergic sensitization to foods is not well understood., TLR2 activators are found in many common foods, but the role of TLR2 in oral tolerance and allergic sensitization to foods is not well understood.[SEP]Relations: sensitization has relations: bioprocess_protein with DRD5, bioprocess_protein with DRD5, bioprocess_bioprocess with nonassociative learning, bioprocess_bioprocess with nonassociative learning.", "label": "yes"}
{"id": "converted_2496", "sentence1": "Does prolactinoma increase osteoporosis risk?", "sentence2": "Prolactinoma: A Massive Effect on Bone Mineral Density in a Young Patient., Osteoporosis has been noted to be an issue in postmenopausal women with prolactinomas. This case shows a similar impact on bone health in a young male resulting in low bone mineral density for age based on Z-score. This case report highlights the possible mechanisms for the bone loss in the setting of prolactinoma and the need for assessing bone health in such patients.,  Hyperprolactinaemia related to prolactinoma significantly (more than functional hyperprolactiaemia) increases the risk of osteopenia, osteoporosis and bone fractures. , Prolactinomas are the most common type of functional pituitary tumor. Effective hyperprolactinemia treatment is of great importance, due to its potential deleterious effects including infertility, gonadal dysfunction and osteoporosis. , Prolactinomas cause hypogonadism, infertility, osteoporosis, and tumor mass effects, and are the most common type of neuroendocrine tumor., We present a 22-year-old man with multiple osteoporotic fractures associated with prolactinoma despite the use of teriparatide for 18 months. We emphasize and highlight the importance of hyperprolactinemia and fractures caused by high prolactin levels., OBJECTIVE: Patients with prolactinoma seem to be at high risk for osteopenia. , RESULTS: Compared to the matched controls, BMD of patients with prolactinoma or craniopharyngioma significantly decreased. , CONCLUSION: In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma., Data on osteoporotic fractures in hyperprolactinemia are limited. An increased prevalence of radiological vertebral fractures was recently observed in women with prolactin (PRL)-secreting adenoma, whereas it is unknown whether this observation may reflect a more general increased risk of fractures in this disease and whether the prevalence of fractures in males is affected by gonadal status., Prolactinoma presenting as chronic anaemia with osteoporosis: a case report., Six years later, he was evaluated and diagnosed with a prolactinoma and resultant osteoporosis. Prolactinoma in old people may present insidiously with chronic anaemia and osteoporosis with or without sexual dysfunction., The relative risk for developing osteoporosis in women with prolactinoma was found to be 4.5, indicating that hyperprolactinemia in women is a major risk factor for osteoporosis.<br>, <b>INTRODUCTION</b>: Osteopenia and osteoporosis because of hyperprolactinaemia caused by prolactinoma may be followed by an increased risk of fracture., Univariate and multivariate regression analysis indicated that the bone loss in prolactinomas was significantly correlated to disease duration and hypogonadism.<br><b>CONCLUSION</b>: In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma., High serum prolactin levels lead to increase of the risk of osteopenia or/and osteoporosis., Prolactinoma in old people may present insidiously with chronic anaemia and osteoporosis with or without sexual dysfunction.<br><b>CASE PRESENTATION</b>: We describe the case of a 70-year-old Caucasian man who presented with mild anaemia and tiredness., In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma., The relative risk for developing osteoporosis in women with prolactinoma was found to be 4.5, indicating that hyperprolactinemia in women is a major risk factor for osteoporosis., CONCLUSION In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma., Prolactinoma in old people may present insidiously with chronic anaemia and osteoporosis with or without sexual dysfunction., Hyperprolactinaemia related to prolactinoma significantly (more than functional hyperprolactiaemia) increases the risk of osteopenia, osteoporosis and bone fractures., INTRODUCTION Osteopenia and osteoporosis because of hyperprolactinaemia caused by prolactinoma may be followed by an increased risk of fracture., In conclusion, men with prolactinoma have high prevalence of osteopenia and osteoporosis., Humans with prolactinoma are at risk for osteoporosis., Osteopenia and osteoporosis because of hyperprolactinaemia caused by prolactinoma may be followed by an increased risk of fracture., The relative risk for developing osteoporosis in women with prolactinoma was found to be 4.5, indicating that hyperprolactinemia in women is a major risk factor for osteoporosis.., In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma.[SEP]Relations: craniopharyngioma has relations: disease_phenotype_positive with Increased susceptibility to fractures, disease_phenotype_positive with Increased susceptibility to fractures. Osteopenia has relations: disease_phenotype_positive with prolactin producing pituitary gland tumor, disease_phenotype_positive with prolactin producing pituitary gland tumor. Prolactinoma has relations: disease_phenotype_positive with growth hormone secreting pituitary adenoma 1, disease_phenotype_positive with growth hormone secreting pituitary adenoma 1, disease_phenotype_positive with prolactin producing pituitary gland tumor, disease_phenotype_positive with prolactin producing pituitary gland tumor, disease_phenotype_positive with multiple endocrine neoplasia, disease_phenotype_positive with multiple endocrine neoplasia.", "label": "yes"}
{"id": "converted_2166", "sentence1": "Is intraoperative radiotherapy used for treatment of glioblastoma?", "sentence2": " 1) Intraoperative radiotherapy ( IOR , 1,000-2,000 rad) was applied in 13 cases; the 2-year survival was 41.6%. , The median survival time after IORT was 12 months for 9 patients with glioblastoma or anaplastic astrocytoma, while it was 51 months for 8 patients with less infiltrative tumors (ependymoma, anaplastic ependymoma, and anaplastic oligodendroglioma). , It is concluded that IORT combined with extensive tumor removal has an acceptable toxicity in previously irradiated patients and can be effective for selected recurrent malignant brain tumors., CONCLUSIONS: The results of this study indicate that IORT can contribute to successful tumor treatment while neither increasing peri-operative morbidity nor subacute sequelae., This review compiles preclinical and clinical evidence for a dedicated treatment of both residual cancer cells and regional microenvironment using intraoperative radiotherapy (IORT).,  Intraoperative radiotherapy (IORT) is a pragmatic and effective approach to sterilize the margins from persistent tumor cells, abrogate post-injury proliferative stimuli and to bridge the therapeutic gap between surgery and radiochemotherapy. , [Surgical treatment and radiation therapy for glioblastoma multiforme, with special reference to intraoperative radiotherapy]., Rationale for intraoperative radiotherapy in glioblastoma., Intraoperative radiotherapy (IORT) was performed in 20 of 36 patients with glioma; 11 glioblastomas, 7 malignant astrocytomas, 2 benign astrocytomas., [Surgical treatment and radiation therapy for glioblastoma multiforme, with special reference to intraoperative radiotherapy], INTRAGO: intraoperative radiotherapy in glioblastoma multiforme—a phase I/II dose escalation study, Intraoperative cobalt-60 treatment of glioblastoma multiforme, An intraoperative remote afterloading endocurietherapy (ECT) technique with high-activity 60cobalt (60Co) for the treatment of glioblastoma multiforme (GM) is described, [Surgical treatment and radiation therapy for glioblastoma multiforme, with special reference to intraoperative radiotherapy]., Rationale for intraoperative radiotherapy in glioblastoma., Intraoperative cobalt-60 treatment of glioblastoma multiforme., INTRAGO: intraoperative radiotherapy in glioblastoma multiforme—a phase I/II dose escalation study., Intraoperative remote afterloading endocurietherapy with high-activity 60cobalt for treatment of glioblastoma multiforme., Combining intraoperative carmustine wafers and Stupp regimen in multimodal first-line treatment of primary glioblastomas., The intraoperative use of carmustine wafers in combination with Stupp regimen is a viable first-line treatment option of glioblastomas., An intraoperative remote afterloading endocurietherapy (ECT) technique with high-activity 60cobalt (60Co) for the treatment of glioblastoma multiforme (GM) is described., The study investigated if intraoperative use of carmustine wafers, particularly in combination with Stupp regimen, is a viable and safe first-line treatment option of glioblastomas.[SEP]Relations: adult glioblastoma has relations: disease_disease with glioblastoma (disease), disease_disease with glioblastoma (disease), disease_disease with glioblastoma (disease), disease_disease with glioblastoma (disease), disease_disease with adult infiltrating astrocytic neoplasm, disease_disease with adult infiltrating astrocytic neoplasm, disease_disease with adult infiltrating astrocytic neoplasm, disease_disease with adult infiltrating astrocytic neoplasm. anaplastic oligodendroglioma has relations: disease_disease with grade III glioma, disease_disease with grade III glioma.", "label": "no"}
{"id": "converted_2790", "sentence1": "Is the PINES framework being used for the prediction of coding variants?", "sentence2": "PINES: phenotype-informed tissue weighting improves prediction of pathogenic noncoding variants., Here, we introduce the computational framework PINES (Phenotype-Informed Noncoding Element Scoring), which predicts the functional impact of noncoding variants by integrating epigenetic annotations in a phenotype-dependent manner. PINES enables analyses to be customized towards genomic annotations from cell types of the highest relevance given the phenotype of interest. We illustrate that PINES identifies functional noncoding variation more accurately than methods that do not use phenotype-weighted knowledge, while at the same time being flexible and easy to use via a dedicated web portal., Here, we introduce the computational framework PINES (Phenotype-Informed Noncoding Element Scoring), which predicts the functional impact of noncoding variants by integrating epigenetic annotations in a phenotype-dependent manner., We illustrate that PINES identifies functional noncoding variation more accurately than methods that do not use phenotype-weighted knowledge, while at the same time being flexible and easy to use via a dedicated web portal.<br>, PINES enables analyses to be customized towards genomic annotations from cell types of the highest relevance given the phenotype of interest.[SEP]", "label": "no"}
{"id": "converted_876", "sentence1": "Can fetal aneuploidy be detected with non-invasive prenatal testing?", "sentence2": "Non-invasive prenatal testing with cell-free DNA: US physician attitudes toward implementation in clinical practice., The aim of this study was to assess awareness, potential adoption, and current utilization of non-invasive prenatal testing (NIPT) analysis for common fetal aneuploidies among obstetricians, Cell-free DNA has been used for fetal rhesus factor and sex determination, fetal aneuploidy screening, cancer diagnostics and monitoring, and other applications., The recent release of new, non-invasive prenatal tests for fetal aneuploidy using cell-free fetal DNA (cffDNA) has been hailed as a revolution in prenatal testing and has triggered significant commercial interest in the field., Non-invasive prenatal testing (NIPT) for aneuploidy using cell-free DNA in maternal plasma is revolutionizing prenatal screening and diagnosis., SNP-based non-invasive prenatal testing detects sex chromosome aneuploidies with high accuracy., Non-invasive prenatal testing (NIPT) of cell-free fetal DNA in maternal plasma is a novel approach, designed for detecting common aneuploidies in the fetus., This study aimed to develop a single-nucleotide polymorphism-based and informatics-based non-invasive prenatal test that detects sex chromosome aneuploidies early in pregnancy., RAPIDR: an analysis package for non-invasive prenatal testing of aneuploidy., Non-invasive prenatal testing for aneuploidy: current status and future prospects., Non-invasive prenatal testing of fetal whole chromosome aneuploidy by massively parallel sequencing., Attitudes towards non-invasive prenatal testing for aneuploidy among US adults of reproductive age., [Non-invasive prenatal test in the diagnosis of aneuploidy 13, 18 and 21--theoretical and practical aspects]., To track and analyze two false positive cases from non-invasive prenatal testing for potential fetal aneuploidy., Non-invasive prenatal testing (NIPT) of fetal aneuploidy using cell-free fetal DNA is becoming part of routine clinical practice., To report secondary or additional findings arising from introduction of non-invasive prenatal testing (NIPT) for aneuploidy by whole genome sequencing as a clinical service., Israeli Society of Medical Genetics NIPT Committee Opinion 072013: Non-invasive prenatal testing of cell-free DNA in maternal plasma for detection of fetal aneuploidy., In recent years, technical advances in the molecular analysis of fetal DNA (e.g., digital PCR and massively parallel sequencing (MPS)) has enabled the successful implementation of noninvasive testing into clinical practice, such as fetal sex assessment, RhD genotyping, and fetal chromosomal aneuploidy detection.With the ability to decipher the entire fetal genome from maternal plasma DNA, we foresee that an increased number of non-invasive prenatal tests will be available for detecting many single-gene disorders in the near future, First identified in 1997, cell-free fetal DNA (cffDNA) has just recently been used to detect fetal aneuploidy of chromosomes 13, 18, and 21, showing its potential to revolutionize prenatal genetic testing as a non-invasive screening tool, Non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma has been developed for the detection of fetal aneuploidy, Israeli Society of Medical Genetics NIPT Committee Opinion 072013: Non-invasive prenatal testing of cell-free DNA in maternal plasma for detection of fetal aneuploidy, Non-invasive prenatal testing for fetal aneuploidies in the first trimester of pregnancy, To explore the value of next-generation sequencing for the non-invasive prenatal testing of fetal chromosomal aneuploidies, Secondary findings from non-invasive prenatal testing for common fetal aneuploidies by whole genome sequencing as a clinical service, To report secondary or additional findings arising from introduction of non-invasive prenatal testing (NIPT) for aneuploidy by whole genome sequencing as a clinical service, Secondary findings from non-invasive prenatal testing for common fetal aneuploidies by whole genome sequencing as a clinical service., Motivations for undertaking DNA sequencing-based non-invasive prenatal testing for fetal aneuploidy: a qualitative study with early adopter patients in Hong Kong., OBJECTIVE: To determine whether non-invasive prenatal testing by maternal plasma DNA sequencing can uncover all fetal chromosome aneuploidies in one simple sequencing event. , Non-invasive prenatal diagnosis of fetal aneuploidies using massively parallel sequencing-by-ligation and evidence that cell-free fetal DNA in the maternal plasma originates from cytotrophoblastic cells., Non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma has been developed for the detection of fetal aneuploidy., Non-invasive prenatal testing (NIPT) of cell-free fetal DNA in maternal plasma is a novel approach, designed for detecting common aneuploidies in the fetus., non-invasive prenatal tests for fetal aneuploidy using cell-free fetal DNA (cffDNA) has been hailed as a revolution in prenatal testing and has triggered significant commercial interest in the field.,  Non-invasive prenatal testing (NIPT) of fetal aneuploidy using cell-free fetal DNA is becoming part of routine clinical practice. RAPIDR (Reliable Accurate Prenatal non-Invasive Diagnosis R package) is an easy-to-use open-source R package that implements several published NIPT analysis methods., The clinical data collected thus far indicate that NIPT is highly sensitive in detecting trisomies 21 and 18, and fairly sensitive in detecting trisomy 13 and sex chromosome aneuploidies. Because false-positive results may occur, an abnormal result must be validated by invasive prenatal testing., When non-invasive prenatal screening for aneuploidy is available, maternal age alone should not be an indication for invasive prenatal diagnosis in a twin pregnancy. (II-2A) If non-invasive prenatal screening is not available, invasive prenatal diagnosis in twins should be offered to women aged 35 and over., Therefore, methods with high sensitivity and precision are required to detect and differentiate fetal DNA from the large background of maternal DNA. In recent years, technical advances in the molecular analysis of fetal DNA (e.g., digital PCR and massively parallel sequencing (MPS)) has enabled the successful implementation of noninvasive testing into clinical practice, such as fetal sex assessment, RhD genotyping, and fetal chromosomal aneuploidy detection.With the ability to decipher the entire fetal genome from maternal plasma DNA, we foresee that an increased number of non-invasive prenatal tests will be available for detecting many single-gene disorders in the near future., Non-invasive prenatal testing for fetal aneuploidies in the first trimester of pregnancy., Secondary findings from non-invasive prenatal testing for common fetal aneuploidies by whole genome sequencing as a clinical service., To explore the value of next-generation sequencing for the non-invasive prenatal testing of fetal chromosomal aneuploidies., [Cell-free nucleic acid-based non-invasive prenatal diagnosis of fetal aneuploidies]., Maternal age alone is a poor minimum standard for prenatal screening for aneuploidy, and it should not be used a basis for recommending invasive testing when non-invasive prenatal screening for aneuploidy is available., Israeli Society of Medical Genetics NIPT Committee Opinion 072013: Non-invasive prenatal testing of cell-free DNA in maternal plasma for detection of fetal aneuploidy., Attitudes towards non-invasive prenatal testing for aneuploidy among US adults of reproductive age., The recent release of new, non-invasive prenatal tests for fetal aneuploidy using cell-free fetal DNA (cffDNA) has been hailed as a revolution in prenatal testing and has triggered significant commercial interest in the field., Non-invasive prenatal testing (NIPT) of fetal aneuploidy using cell-free fetal DNA is becoming part of routine clinical practice., Non-invasive prenatal testing (NIPT) by massively parallel sequencing is a useful clinical test for the detection of common fetal aneuploidies., The clinical data collected thus far indicate that NIPT is highly sensitive in detecting trisomies 21 and 18, and fairly sensitive in detecting trisomy 13 and sex chromosome aneuploidies.[SEP]Relations: sex chromosome has relations: cellcomp_protein with SMC6, cellcomp_protein with SMC6, cellcomp_protein with SMC5, cellcomp_protein with SMC5. somatic recombination of T cell receptor gene segments has relations: bioprocess_bioprocess with T cell receptor V(D)J recombination, bioprocess_bioprocess with T cell receptor V(D)J recombination, bioprocess_bioprocess with somatic diversification of T cell receptor genes, bioprocess_bioprocess with somatic diversification of T cell receptor genes, bioprocess_bioprocess with somatic diversification of immune receptors via germline recombination within a single locus, bioprocess_bioprocess with somatic diversification of immune receptors via germline recombination within a single locus.", "label": "yes"}
{"id": "converted_3068", "sentence1": "Has the protein SIRT2 been associated to cervical cancer?", "sentence2": " A progressive increase in the expression of both SIRT2 and SIRT7 was noted during cancer progression in the following order: normal < preneoplasia < cancer.,  We demonstrate that treatment of cervical cancer cells with a RhoGDIα-derived K52-trifluoroacetylated, substrate-derived peptidic sirtuin inhibitor severely impairs cell proliferation. [SEP]Relations: PPP1R1A has relations: disease_protein with liver cancer, disease_protein with liver cancer, protein_protein with ACTA2, protein_protein with ACTA2, protein_protein with ZPBP2, protein_protein with ZPBP2, anatomy_protein_present with spinal cord, anatomy_protein_present with spinal cord. NAD-dependent protein deacetylase activity has relations: molfunc_protein with SIRT2, molfunc_protein with SIRT2.", "label": "yes"}
{"id": "converted_815", "sentence1": "Is indicated the use of antioxidant supplements in patients at risk for coronary artery disease?", "sentence2": "We and others have published observational epidemiologic studies in support of vitamins in the primary prevention of CVD, but the results from intervention studies are mixed., For vitamin E, observational data suggest benefit at doses of 100 to 400 IU/d. Results from recent large-scale trials are mixed, with some showing modest benefit but others suggesting no benefit, especially for secondary prevention. Results for B vitamins are also mixed and further complicated by the recent folate fortification of the flour supply. If greater B vitamin intake does reduce CVD, the benefits are likely to be greatest for primary prevention and in populations with intake below dietary reference standards. , In the dose-response meta-analysis, each 30 mg/day increase in vitamin C, 30 IU/day increase in vitamin E, and 1 mg/day increase in beta-carotene yielded the estimated overall relative risk for CHD of 1.01 (95% CI, 0.99-1.02), 0.96 (95% CI, 0.94-0.99), and 1.00 (95% CI, 0.88-1.14), respectively. CONCLUSIONS: Our findings in this meta-analysis suggest that an increase in dietary intake of antioxidant vitamins has encouraging prospects for possible CHD prevention., High levels of α-tocopherol in serum were associated with 30% lower CAD risk in another study (HR 0.71; 95%CI 0.53-0.94). Among minerals (zinc, selenium, and chromium), an inverse association between zinc and CAD was observed; levels lower than 14.1 µmol/L were associated with an increased risk for CAD (RR 1.70; 95%CI 1.21-2.38)., The information available on this issue is scarce. Further prospective studies are needed to elucidate the role of these nutrients in the cardiovascular risk of patients with diabetes., Coenzyme Q10 supplementation at a dosage of 150 mg appears to decrease the inflammatory marker IL-6 in patients with CAD.,  Coenzyme Q10 supplements at a dose of 150 mg can decrease oxidative stress and increase antioxidant enzyme activity in patients with CAD. A higher dose of coenzyme Q10 supplements (>150 mg/d) might promote rapid and sustainable antioxidation in patients with CAD., Alpha-tocopherol or beta-carotene supplementation has no protective effect on macrovascular outcomes or total mortality of diabetic male smokers., Sodium selenite supplementation increases GPx-1 activity in endothelial cells and in CAD patients. Future studies have to demonstrate whether long-term CAD outcome can be improved., After 7.3 years of treatment and follow-up, a combination pill of folic acid, vitamin B6, and vitamin B12 did not reduce a combined end point of total cardiovascular events among high-risk women, despite significant homocysteine lowering.,  In this population-based study, vitamin E use was unrelated to mortality, but this apparently null finding seems to represent a combination of increased mortality in those with severe cardiovascular disease and a possible protective effect in those without.,  In this large cohort of apparently healthy US male physicians, self-selected supplementation with vitamin E, vitamin C, or multivitamins was not associated with a significant decrease in total CVD or CHD mortality. , The American Heart Association has recommended consumption of a balanced diet with emphasis on antioxidant-rich fruits and vegetables but has made no recommendations regarding vitamin E supplementation for the general population. Although vitamin E supplementation seems to be safe for most people, recommendations from health care professionals should reflect the uncertainty of established benefit as demonstrated in clinical trials, Recent studies show that supplementation with antioxidant vitamins E and C have benefits in CHD prevention; however, supplementation with beta-carotene may have deleterious effects and is not recommended. Current evidence suggests that patients with CHD would probably benefit from taking vitamin E in a dosage of 400 IU per day and vitamin C in a dosage of 500 to 1,000 mg per day. Clinicians may also want to consider vitamin supplementation for CHD prevention in high-risk patients. Folate lowers elevated homocysteine levels, but evidence for routine supplemental use does not yet exist. , In patients at high risk for cardiovascular events, treatment with vitamin E for a mean of 4.5 years had no apparent effect on cardiovascular outcomes.[SEP]Relations: cardiovascular disease has relations: contraindication with Antipyrine, contraindication with Antipyrine, contraindication with Amoxapine, contraindication with Amoxapine, contraindication with Methionine, contraindication with Methionine, contraindication with Fentanyl, contraindication with Fentanyl, contraindication with Carbinoxamine, contraindication with Carbinoxamine.", "label": "no"}
{"id": "converted_724", "sentence1": "Are there any clinical trials of the effect of evening primrose oil on postmenopausal symptoms ?", "sentence2": "To analyze whether the time (morning/evening) of administration of a compound containing 60 mg of dry soy seed extract (glycine max) with 40% of total isoflavones, primrose oil and α-tocopherol modifies the effect on the climacteric syndrome., The object of this study was to evaluate the effect of different doses of a compound containing isoflavones 60 mg, primrose oil 440 mg and vitamin E 10 mg. (IOVE) on menopausal complaints. This was an open, multicentre, randomised, group comparative, efficacy and safety trial., Emphasis was placed on randomized, double-blind, placebo-controlled clinical trials, as these provide the best efficacy and safety data, Nonprescription therapies reviewed include black cohosh, dong quai, evening primrose oil, physical activity, phytoestrogens, and red clover, The effect of oral evening primrose oil on menopausal hot flashes: a randomized clinical trial., The aim of this study was to compare the efficacy of evening primrose with placebo in improvement of menopausal hot flashes. ,  The application of oral evening primrose oil compared with placebo for controlling hot flashes may decrease more the intensity of attacks , Our search identified 58 randomised controlled trials of which 11 involved the use of clonidine, six for SSRIs, four for gabapentin, seven for black cohosh, seven for red clover, 18 for phytoestrogens, two for ginseng, one for evening primrose,, Single clinical trials have found no benefit for dong quai, evening primrose oil,, Single clinical trials have found that dong quai, evening primrose oil,, To evaluate the efficacy of gamolenic acid provided by evening primrose oil in treating hot flushes and sweating associated with the menopause. DESIGN: Randomised, double blind, placebo controlled study.[SEP]Relations: Evening primrose oil has relations: drug_drug with Primidone, drug_drug with Primidone, drug_drug with Estradiol, drug_drug with Estradiol, drug_drug with Acetaminophen, drug_drug with Acetaminophen, drug_drug with Prednisone, drug_drug with Prednisone, drug_drug with Antipyrine, drug_drug with Antipyrine.", "label": "yes"}
{"id": "converted_712", "sentence1": "Is PER3 required for CHK2 activation in human cells?", "sentence2": "Per3, a circadian gene, is required for Chk2 activation in human cells., Depletion of Per3 by siRNA almost completely abolished activation of checkpoint kinase 2 (Chk2) after inducing DNA damage in human cells., Per3 overexpression induced Chk2 activation in the absence of exogenous DNA damage,, Per3 overexpression also led to the inhibition of cell proliferation and apoptotic cell death., These combined results suggest that Per3 is a checkpoint protein that plays important roles in checkpoint activation, cell proliferation and apoptosis., Depletion of Per3 by siRNA almost completely abolished activation of checkpoint kinase 2 (Chk2) after inducing DNA damage in human cells, Per3 overexpression induced Chk2 activation in the absence of exogenous DNA damage, and this activation depended on ATM, In addition, Per3 physically interacted with ATM and Chk2[SEP]Relations: PER3 has relations: protein_protein with CHEK2, protein_protein with CHEK2, protein_protein with PER2, protein_protein with PER2, molfunc_protein with kinase binding, molfunc_protein with kinase binding, protein_protein with BTK, protein_protein with BTK, protein_protein with DHRS2, protein_protein with DHRS2.", "label": "yes"}
{"id": "converted_539", "sentence1": "Are integrins part of the extracellular matrix?", "sentence2": "Several constituents of the ECM provide adhesive cues, which serve as binding sites for cell trans-membrane receptors, such as integrins., We also determined that blocking β1integrins, the major class of receptors for all ECM proteins tested,, Here, we elucidate a cross-scale mechanism for tissue assembly and ECM remodeling involving Cadherin 2, the ECM protein Fibronectin, and its receptor Integrin α5. , due to the diverse functions and variable expression of proteoglycans, matrix proteins, and integrins, it is rather difficult to identify a comprehensive therapeutic target among ECM components., Integrin-dependent cell-extracellular matrix (ECM) adhesion is a determinant of spindle orientation., The extracellular matrix component periostin is a secreted protein that functions as both a cell attachment protein and an autocrine or paracrine factor that signals through the cell adhesion molecule integrins αvβ3 and αvβ5. , Integrin receptors connect the extracellular matrix to the cell cytoskeleton to provide essential forces and signals. ,  the integrin, talin, and actin filament form a linear complex of which both ends are typically anchored to the extracellular matrices via integrins., Integrins, a central family of cellular ECM receptors, have been implicated in these processes but their specific role in ES cell self-renewal remains unclear., Attachment to the extracellular matrix is mediated by a complex of adhesion proteins, including integrins, signaling molecules, actin and actin-binding proteins, and scaffolding proteins., Beta 1 integrin binding plays a role in the constant traction force generation in response to varying stiffness for cells grown on mature cardiac extracellular matrix.[SEP]Relations: extracellular matrix has relations: cellcomp_protein with IGFALS, cellcomp_protein with IGFALS, cellcomp_protein with IHH, cellcomp_protein with IHH, cellcomp_protein with COMP, cellcomp_protein with COMP, cellcomp_protein with NYX, cellcomp_protein with NYX, cellcomp_protein with VEGFA, cellcomp_protein with VEGFA.", "label": "yes"}
{"id": "converted_4416", "sentence1": "Is periampullary carcinoma (PAC) a relatively rare genitourinary malignancy", "sentence2": "Pancreaticobiliary subtype of Periampullary carcinoma (PAC) has a poor prognosis in comparison to the intestinal subtype., MUC1, CK20, and CDX2 immunohistochemical markers can sub-classify periampullary carcinomas into pancreaticobiliary, intestinal, and mixed subtypes., Pancreaticoduodenectomy (PD) is a complex surgical procedure involving resection of the duodenum, the pancreatic head and uncinate process, and the distal common bile duct. It is most commonly performed for periampullary malignancy but may also be indicated in select cases of chronic pancreatitis or benign periampullary tumors., In patients suspected of pancreatic or periampullary cancer, abdominal contrast-enhanced computed tomography (CT) is the standard diagnostic modality., The pre-operative neutrophil-to-lymphocyte ratio (NLR), when ≥5 has been associated with reduced survival for patients with various gastrointestinal tract cancers, however, it's prognostic value in patients with periampullary tumour has not been reported to date., Comparison Of Biliary Stenting And Surgical Bypass In Palliative Management Of Irresectable Periampullary Carcinoma.,  Some 20-40% of the periampullary carcinoma is irresectable at the time of diagnosis. Biliary stenting and surgical bypass are commonly used palliative procedure., Whereas Periampulary AdenoCarcinoma (PAC) having four anatomic subtypes, pancreatic, Common Bile Duct (CBD), ampullary and duodenum shows relative better prognosis, DEFINITION: Periampullary carcinomas are rare and constitute a special entity, as diagnosed earlier and having a better prognosis than other duodenal tumors.METHODS: In the present study, we retrospectively reviewed the medical records of 16 patients with periampullary carcinomas over 10 years.RESULTS: 16 patients, 10 men and 6 women (median age 66.7 years, range 42-80) had a , Periampullary carcinomas: a special entity of duodenal tumors., Periampullary adenocarcinomas are rare neoplasm that originates from the pancreatic head, the ampulla of vater, the distal bile duct or the duodenum.[SEP]Relations: periampullary adenocarcinoma has relations: disease_disease with ampulla of vater adenocarcinoma, disease_disease with ampulla of vater adenocarcinoma. intestine has relations: anatomy_protein_present with PACS2, anatomy_protein_present with PACS2, anatomy_protein_present with PACS1, anatomy_protein_present with PACS1, anatomy_protein_present with PACSIN2, anatomy_protein_present with PACSIN2. duodenum has relations: anatomy_protein_present with PACS1, anatomy_protein_present with PACS1.", "label": "no"}
{"id": "converted_1520", "sentence1": "Is there any data to suggest that TRH (thyrotropin releasing hormone) administration can improve symptom severity of amyotrophic lateral sclerosis patients?", "sentence2": "These central nervous system (CNS)-mediated effects provide the rationale for use of TRH and its analogs in the treatment of brain and spinal injury, and CNS disorders like schizophrenia, Alzheimer's disease, epilepsy, amyotrophic lateral sclerosis, Parkinson's disease, depression, shock and ischemia., The Effect of TRH to correct the abnormal F responses in SSP might be consistent with effects of TRH to reduce spasticity in amyotrophic lateral sclerosis described previously, Agents undergoing therapeutic trials at present include CNTF, IGF1 glutamate antagonists, branched-chain amino acids and TRH analogue., Evidence that thyrotropin-releasing hormone (TRH) has prominent trophic effects on the motor system led to several negative therapeutic trials in amyotrophic lateral sclerosis, a disease of the motor system., The results of the clinical evaluation at the beginning and end of the treatment as well as after patient follow up demonstrated that beneficial effects do not occur equally in all patients but rather are transitory and do not improve the natural evolution of the disease., The neurological evaluation after acute TRH-T treatment showed an objective improvement in 3 of the 8., The outcome of the study, in agreement with some and at variance with other studies, was that TRH induced a statistically significant neurological improvement in 17 of the 23 ALS patients but little or none in the other ALS patients and in patients with other neurological diseases., [A case of amyotrophic lateral sclerosis with disturbance of vertical ocular movement responding to thyrotropin releasing hormone (TRH)]., TRH injections resulted in improvement of disturbance of vertical ocular movement, but no effect was seen on the weakness of the limb., 13 patients with amyotrophic lateral sclerosis (ALS) were treated with intravenous infusion of thyrotropin-releasing hormone (TRH). , Similar improvements in speech, swallowing and in tongue and jaw movements were seen after iv and oral administration in nine, five and eight patients respectively. , No clinical improvement was detected. , A trial of Thyrotropin Releasing Hormone (TRH) 5.0 mg/kg body weight subcutaneously every other day for two weeks produced transient increased tone in muscles, along with other (side-) effects in patients with Amyotrophic Lateral Sclerosis (ALS)., Although the mechanism is not known, several reports of the effectiveness of thyrotropin releasing hormone (TRH) in ALS were recently published., Protirelin (thyrotropin-releasing hormone) appears to be a neuromodulator in the extrahypothalamic nervous system and has been suggested as an adjunct in the treatment of amyotrophic lateral sclerosis (ALS). , Clinical studies have shown that response to TRH is state dependent, that is, it depends on whether the patient has bulbar or nonbulbar signs and is male or female. Future studies must take into consideration this state dependence as a specific feature of the pharmacological action of TRH and its analogues., Three of the studies showed a transient, statistically significant effect in at least some muscles. The two studies that demonstrated no such effect both used TRH in very small doses. It therefore seems reasonable to conclude that the effect of TRH in ALS is a definite, acute, and transient response. , It was found that in only 3 out of 14 patients with moderately progressed disease no improvement was achieved, while in 11 cases the improvement was from 10 to 20%. However, the improvement was transient, and TRH treatment failed to stop the progression of the disease., Only 3 patients noted subjective improvement of strength., In 6 of the 9, TRH induced a significant increase in vibratory inhibition. This suggests that the TRH-induced reduction of spasticity might be due to an increase in presynaptic inhibition acting on Ia fibres., However, 2 mg DN-1417, IM twice a day for 1 month in an open-label trial, produced no objective improvement of strength in nine patients with ALS. , Our experience suggests that this approach is safe, has high patient acceptance, and is worthy of more careful evaluation., Focal, small-to-moderate and transient improvement occurred in the muscle strength and function of patients with ALS who received TRH in dose-response and screening studies. In a small pilot study of 12 patients, 3 months administration of TRH at 10 mg per kg on alternate days resulted in localized increased strength of jaw muscles as well as significant improvement in lower extremity function. Aerobic exercise capacity was particularly improved in patients with ALS following administration of TRH. , Mild to moderate improvement was found in 9 (56%) of 16 patients. , We thought such action of TRH to be useful to the therapy of ALS., With daily TRH, 10 patients noted subjective improvement without objective evidence, and 10 patients complained of worsening of the disease with objective decline after TRH was stopped. Statistical analysis, however, showed no beneficial effects from either acute or chronic TRH trials., A temporary increase in the strength of some muscles was detected following the administration of TRH, but no change in functional performance was noted. Neither the patients nor the investigators believed the effects were of any marked clinical significance., Nevertheless, statistically significant improvement was seen only in dynametric strength 1 hour after subcutaneous injection (p less than 0.05). Significant improvement occurred, in one patient only, on subjective speech testing during IV infusion of TRH. In none of six other ratings was there a significant difference between TRH and placebo. Subjective improvement was noted by 11 of 12 patients., Significant improvement, as shown by statistical analysis, was noted in muscle strength in the 9 patients by 5 infusions over a 4-week period and a sub-group of 5 patients treated by 8 infusions over 10 weeks., The progressive course of this disease, manifested by increasing atrophy, paralysis and disability score, was not altered. , Very high intravenous doses (2-19 mg/min) of thyrotropin-releasing hormone (TRH, L-pyroglutamyl-L-histidyl-L-prolinamide) given to 12 patients with amyotrophic lateral sclerosis (ALS) produced a moderate to marked improvement of functions caused by deficiency of lower motor neurons (weakness) and upper motor neurons (spasticity). The improvement was sustained throughout the infusion and for about 1 h thereafter; sometimes a slight improvement was evident 20 h after infusion., Aerobic exercise capacity was particularly improved in patients with ALS following administration of TRH[SEP]Relations: amyotrophic lateral sclerosis has relations: disease_protein with TRPM7, disease_protein with TRPM7, disease_protein with NEFH, disease_protein with NEFH, disease_disease with progressive muscular atrophy, disease_disease with progressive muscular atrophy, disease_protein with TARDBP, disease_protein with TARDBP, disease_protein with TREM2, disease_protein with TREM2.", "label": "yes"}
{"id": "converted_375", "sentence1": "Is lambrolizumab effective for treatment of patients with melanoma ?", "sentence2": "However, through parallel efforts that have showcased the efficacy of small-molecule BRAF and MAP-ERK kinase (MEK) inhibitors, as well as the immune checkpoint inhibitors, namely ipilimumab and the anti-PD1/PDL1 antibodies (lambrolizumab, nivolumab, MPDL3280), an opportunity exists to transform the treatment of melanoma specifically and cancer generally by exploring rational combinations of molecularly targeted therapies, immunotherapies, and molecular targeted therapies with immunotherapies. , Programmed death-1 receptor (PD-1)/its ligand (PD-L1) antibodies have changed the landscape in oncology in 2013. The most mature results have been obtained in advanced melanoma patients. , Merck's lambrolizumab (MK-3475) monoclonal antibody received \"Breakthrough Therapy\" designation from the U.S. Food and Drug Administration in April for treating patients with advanced melanoma., The programmed death 1 (PD-1) receptor is a negative regulator of T-cell effector mechanisms that limits immune responses against cancer. We tested the anti-PD-1 antibody lambrolizumab (previously known as MK-3475) in patients with advanced melanoma. , In patients with advanced melanoma, including those who had had disease progression while they had been receiving ipilimumab, treatment with lambrolizumab resulted in a high rate of sustained tumor regression, with mainly grade 1 or 2 toxic effects. , Because of all these reasons PD-1/PD-L1 antibodies are considered 'drug of the year'.[SEP]Relations: Pembrolizumab has relations: drug_drug with Catumaxomab, drug_drug with Catumaxomab, drug_drug with Basiliximab, drug_drug with Basiliximab, drug_drug with Golimumab, drug_drug with Golimumab, drug_drug with Afelimomab, drug_drug with Afelimomab, drug_drug with Ibalizumab, drug_drug with Ibalizumab.", "label": "yes"}
{"id": "converted_2788", "sentence1": "Is pembrolizumab effective against Ewing's sarcoma?", "sentence2": "None of the 13 patients with Ewing's sarcoma had an objective response. , Between March 13, 2015, and Feb 18, 2016, we enrolled 86 patients, 84 of whom received pembrolizumab (42 in each disease cohort) and 80 of whom were evaluable for response (40 in each disease cohort). [SEP]Relations: Ewing sarcoma of bone has relations: disease_disease with Ewing sarcoma, disease_disease with Ewing sarcoma, disease_disease with bone sarcoma, disease_disease with bone sarcoma, disease_disease with Ewing sarcoma/peripheral primitive neuroectodermal tumor of bone, disease_disease with Ewing sarcoma/peripheral primitive neuroectodermal tumor of bone.", "label": "no"}
{"id": "converted_4037", "sentence1": "Is Tocilizumab (Actemra) used to block/antagonize the  IL-6 receptor?", "sentence2": "Preliminary clinical results have indicated that antagonism of the IL-6 receptor (IL-6R), including with the FDA-approved humanized monoclonal antibody tocilizumab, can improve the outcomes of patients with severe or critical COVID-19 while maintaining a good safety profile., Tocilizumab, an anti-IL-6 receptor antibody, and corticosteroids were initially used to treat the increase in acute inflammatory proteins and the anasarca, resulting in decreased cytokine levels. , Tocilizumab, a monoclonal antibody against the IL-6 receptor, was initiated at a dose of 8 mg/kg every 4 weeks., we randomly assigned patients with type 2 diabetes or obesity to intravenous tocilizumab (an IL-6 receptor antagonist) ,  Clinical studies are investigating whether tocilizumab (anti-IL-6 receptor) can help preserve beta cell function in patients recently diagnosed with T1D, Tocilizumab (RoActemra or Actemra) is a recombinant humanized monoclonal antibody that acts as an interleukin (IL)-6 receptor antagonist., To increase the number of cycles of antigen binding and lysosomal degradation, we engineered tocilizumab (Actemra), an antibody against the IL-6 receptor (IL-6R), to rapidly dissociate from IL-6R within the acidic environment of the endosome (pH 6.0) while maintaining its binding affinity to IL-6R in plasma (pH 7.4)., Tocilizumab (Actemra; Genentech, Inc) is the first biologic therapy targeting the cytokine interleukin 6 (IL-6)., over, our findings showed that combination of tocilizumab (Actemra; Roche), an anti-IL-6R monoclonal antibody, with carboplatin synergistically inhibited growth and proliferation of the EOC cells and the most direct axis for IL-6 gene expression was NF-κB pathway.CONC, Roche is co-developing tocilizumab (Actemra, RoActemra), a humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody, with Chugai Pharmaceutical., Tocilizumab (TCZ) is a compound that inhibits the IL-6 receptor., Tocilizumab (TCZ), is a recombinant humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody which has a main use in the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis (sJIA) and polyarticular juvenile idiopathic arthritis (pJIA)., the US Food and Drug Administration accepted a complete-response submission for the use of Actemra (tocilizumab), the first humanized IL-6 receptor-inhibiting monoclonal antibody, for the treatment of RA. Although thi, increase the number of cycles of antigen binding and lysosomal degradation, we engineered tocilizumab (Actemra), an antibody against the IL-6 receptor (IL-6R), to rapidly dissociate from IL-6R within the acidic environment of the endosome (pH 6.0) while maintaining its binding affinity to IL-6R in plasma (pH 7.4). Studies usin,  present study, we have shown that the humanized anti-IL-6 receptor tocilizumab (Actemra) is also a potent inhibitor of IL-8 in TNBC cells. Similar ef, Roche is co-developing tocilizumab (Actemra, RoActemra), a humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody, with Chugai Pharmaceutical. Tocili, tory gene activation is inhibited in vitro by tocilizumab, a humanized antibody to IL6 receptor (IL6R). Tocilizumab, These lines of evidence indicate that tocilizumab is able to bind to both sIL-6R and mIL-6R and to inhibit IL-6 binding to its receptors, leading to the blockade of the IL-6 signaling through both sIL-6R and mIL-6R, but not block the signaling of other IL-6 family cytokines., Tocilizumab inhibits signal transduction mediated by both mIL-6R and sIL-6R, but not by the receptors of other members of IL-6 cytokine family., In addition, tocilizumab had the ability to bind to human IL-6R expressing COS-7 cells and to suppress the growth of the IL-6-dependent myeloma cell line, KPMM2., To characterize the biological activity of tocilizumab, a humanized anti-human interleukin-6 receptor (IL-6R) monoclonal antibody, we examined its binding activity to both soluble IL-6R (sIL-6R) and membrane bound IL-6R (mIL-6R) and its neutralizing activity to other IL-6 family cytokines., Tocilizumab inhibited the proliferation of BaF/IL-6R induced by IL-6, but did not inhibit the proliferation of BaF/IL-11R, BaF/OSMR, BaF/LIFR and BaF/CNTFR cells induced by their corresponding cytokines., Moreover, tocilizumab suppressed the IL-6/sIL-6R complex-induced proliferation of human gp130-transfected cell, BAF-h130., In addition, tocilizumab had the ability to dissociate IL-6 and sIL-6R from their preformed complex., ELISA assay demonstrated that tocilizumab bound to sIL-6R and inhibited IL-6 binding to sIL-6R in a dose-dependent manner., Tocilizumab recognizes both the membrane-bound and the soluble form IL-6R and specifically blocks IL-6 actions., Humanized antihuman IL-6 receptor antibody, tocilizumab., Tocilizumab is a humanized antihuman IL-6 receptor antibody designed using genetic engineering technology., Tocilizumab is expected to ameliorate the autoimmune inflammatory diseases with IL-6 overproduction and has been clinically developed as a therapeutic agent for RA, systemic-onset and articular types of JIA, Crohn's disease, etc., Tocilizumab/Actemra is an anti-IL-6R antibody, which can competitively block IL-6 binding to the IL-6R., Tocilizumab (TCZ; RoActemra® or Actemra®) is a recombinant humanized monoclonal antibody that acts as an interleukin 6 (IL-6) receptor antagonist., In 2009 the US Food and Drug Administration accepted a complete-response submission for the use of Actemra (tocilizumab), the first humanized IL-6 receptor-inhibiting monoclonal antibody, for the treatment of RA., Tocilizumab binds to the interleukin-6 receptor (IL-6R) and thereby blocks signaling of the pro-inflammatory cytokine IL-6., Tocilizumab (RoActemra(®); Actemra(®)) is a recombinant humanized monoclonal antibody that acts as an interleukin-6 receptor antagonist.[SEP]Relations: Tocilizumab has relations: drug_protein with IL6R, drug_protein with IL6R, drug_drug with Elagolix, drug_drug with Elagolix, drug_drug with Acteoside, drug_drug with Acteoside, drug_drug with Metronidazole, drug_drug with Metronidazole, drug_drug with Atezolizumab, drug_drug with Atezolizumab.", "label": "yes"}
{"id": "converted_2279", "sentence1": "Is there increased recombination rate in human regulatory domains?", "sentence2": "Evidence of reduced recombination rate in human regulatory domains., We study the relationship between recombination rate and gene regulatory domains, defined by a gene and its linked control elements. We define these links using expression quantitative trait loci (eQTLs), methylation quantitative trait loci (meQTLs), chromatin conformation from publicly available datasets (Hi-C and ChIA-PET), and correlated activity links that we infer across cell types. Each link type shows a \"recombination rate valley\" of significantly reduced recombination rate compared to matched control regions. This recombination rate valley is most pronounced for gene regulatory domains of early embryonic development genes, housekeeping genes, and constitutive regulatory elements, which are known to show increased evolutionary constraint across species. Recombination rate valleys show increased DNA methylation, reduced doublestranded break initiation, and increased repair efficiency, specifically in the lineage leading to the germ line. Moreover, by using only the overlap of functional links and DNA methylation in germ cells, we are able to predict the recombination rate with high accuracy.CONCLUSIONS: Our results suggest the existence of a recombination rate valley at regulatory domains and provide a potential molecular mechanism to interpret the interplay between genetic and epigenetic variations.[SEP]Relations: Geneticin has relations: drug_drug with Antihemophilic Factor (Recombinant), PEGylated, drug_drug with Antihemophilic Factor (Recombinant), PEGylated, drug_drug with Antithrombin III human, drug_drug with Antithrombin III human, drug_drug with Botulinum Toxin Type B, drug_drug with Botulinum Toxin Type B, drug_drug with Certolizumab pegol, drug_drug with Certolizumab pegol, drug_drug with Tubocurarine, drug_drug with Tubocurarine.", "label": "no"}
{"id": "converted_364", "sentence1": "Is alemtuzumab effective for remission induction in patients diagnosed with T-cell prolymphocytic leukemia?", "sentence2": "Sequential chemoimmunotherapy of fludarabine, mitoxantrone, and cyclophosphamide induction followed by alemtuzumab consolidation is effective in T-cell prolymphocytic leukemia, A central need in this historically refractory tumor is the controlled evaluation of multiagent chemotherapy and its combination with the currently most active single agent, alemtuzumab. , FMC-A is a safe and efficient protocol in T-PLL, which compares favorably to published data., Currently, the best treatment for T-PLL is IV alemtuzumab, which has resulted in very high response rates of more than 90% when given as frontline treatment and a significant improvement in survival. , The patient failed to respond to standard ALL induction chemotherapy, but achieved complete remission following treatment with a fludarabine and alemtuzumab-based regimen., Here we present a rare case of concurrent T-PLL and Kaposi sarcoma who achieved a complete hematologic and cytogenetic remission after a very short course of treatment with alemtuzumab.,  Recent studies with single-agent alemtuzumab, an anti-CD52 monoclonal antibody, have shown improved response rates and survival in patients with T-cell prolymphocytic leukemia and cutaneous T-cell lymphoma. , The CD52 antigen is expressed at high density on the malignant T-cells and therapy with alemtuzumab, a humanized IgG1 antibody that targets this antigen, has produced promising results. , With the introduction of alemtuzumab, most patients who progressed despite treatment with pentostatin had a major response with a complete remission rate higher than that obtained with pentostatin when used as a first line., Alemtuzumab (anti-CD52, Campath-1H) has recently been shown to be effective in the treatment of a range of hematological malignancies, including B-cell chronic lymphocytic leukemia and T-cell prolymphocytic leukemia., Here we report the outcome of two patients with CD4-positive T cell prolymphocytic leukemia treated with CAMPATH-1H. Both patients responded rapidly to treatment and subsequently developed CD4 lymphopenia., T-cell prolymphocytic leukemia (T-PLL) is a chemotherapy-resistant malignancy with a median survival of 7.5 months. Preliminary results indicated a high remission induction rate with the human CD52 antibody, CAMPATH-1H. , CAMPATH-1H (30 mg) was administered intravenously 3 times weekly until maximal response. The overall response rate was 76% with 60% CR and 16% partial remission (PR). These responses were durable with a median disease-free interval of 7 months (range, 4-45 months). , The conclusion is that CAMPATH-1H is an effective therapy in T-PLL, producing remissions in more than two thirds of patients. , For example, most patients with T-cell prolymphocytic leukemia, including those with large tumor burdens and high peripheral white blood cell counts, will enter complete remission using the antibody CAMPATH-1H without any evidence of tumor lysis., Overall response rate to FMC was 68%, comprising 6 complete remissions (all bone-marrow confirmed) and 11 partial remissions. Alemtuzumab consolidation increased the intent-to-treat overall response rate to 92% (12 complete remissions; 11 partial remissions). [SEP]Relations: Alemtuzumab has relations: drug_drug with Catumaxomab, drug_drug with Catumaxomab, drug_drug with Otelixizumab, drug_drug with Otelixizumab, drug_drug with Mogamulizumab, drug_drug with Mogamulizumab, drug_drug with Golimumab, drug_drug with Golimumab, drug_drug with Lumiliximab, drug_drug with Lumiliximab.", "label": "yes"}
{"id": "converted_3189", "sentence1": "Have apolipoprotein mimetics been used in clinical trials?", "sentence2": "One of these (AEM-28) has recently been given orphan drug status and is undergoing clinical trials.[SEP]", "label": "yes"}
{"id": "converted_3810", "sentence1": "Can AGY be used as antidiuretic replacement therapy?", "sentence2": "AGY, a Novel Egg Yolk-Derived Anti-gliadin Antibody, Is Safe for Patients with Celiac Disease., Oral egg yolk anti-gliadin antibody (AGY) is a novel treatment to neutralize gluten and may improve the efficacy of the GFD., To determine the safety, tolerability, and potential efficacy of AGY in patients with CD., Most patients had fewer celiac symptoms (especially tiredness, headache, and bloating), improved quality of life, lowered antibodies, and lowered LMER when taking AGY compared to the run-in period., In our cohort, AGY was safe and potentially associated with improved CD-related outcome measures in patients on a GFD. [SEP]Relations: Headache has relations: drug_effect with Acyclovir, drug_effect with Acyclovir, drug_effect with Azithromycin, drug_effect with Azithromycin, drug_effect with Oxybutynin, drug_effect with Oxybutynin. Fatigue has relations: drug_effect with Acyclovir, drug_effect with Acyclovir, drug_effect with Oxybutynin, drug_effect with Oxybutynin.", "label": "no"}
{"id": "converted_1340", "sentence1": "Are there enhancer RNAs (eRNAs)?", "sentence2": "active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription,  eRNAs may then facilitate enhancer-promoter interaction or activate promoter-driven transcription, Enhancer RNAs: a class of long noncoding RNAs synthesized at enhancers, Enhancer RNAs and regulated transcriptional programs, enhancers have been found to be broadly transcribed, resulting in the production of enhancer-derived RNAs, or eRNAs, The emerging roles of eRNAs in transcriptional regulatory networks, we found certain enhancer RNAs (eRNAs) regulate chromatin accessibility of the transcriptional machinery at loci encoding master regulators of myogenesis (i.e., MyoD/MyoG), thus suggesting their significance and site-specific impact in cellular programming, Enhancer RNAs: the new molecules of transcription,  the discovery that distal regulatory elements known as enhancers are transcribed and such enhancer-derived transcripts (eRNAs) serve a critical function in transcriptional activation has added a new dimension to transcriptional regulation, eRNAs reach the heart of transcription, Recent studies have disclosed the function of enhancer RNAs (eRNAs), which are long non-coding RNAs transcribed from gene enhancer regions, in transcriptional regulation., Since the discovery that many transcriptional enhancers are transcribed into long noncoding RNAs termed \"enhancer RNAs\" (eRNAs), their putative role in enhancer function has been debated., Recent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs)., Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers, whose function and action mechanism are yet to be firmly established., In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs)., In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). , A subset of enhancers are occupied by RNA polymerase II (RNAP II) and transcribed to produce long non-coding RNAs termed eRNAs. , Very recent evidence has indicted that some eRNAs play a role in initiating or activating transcription, possibly by helping recruit and/or stabilize binding of the general transcription machinery to the proximal promoter of their target genes. , In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). However, it has remained unclear whether these eRNAs are functional or merely a reflection of enhancer activation. , Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4. The level of eRNA expression at neuronal enhancers positively correlates with the level of messenger RNA synthesis at nearby genes, suggesting that eRNA synthesis occurs specifically at enhancers that are actively engaged in promoting mRNA synthesis., A function of CBP at enhancers may be to recruit RNA polymerase II (RNAPII), as we also observed activity-regulated RNAPII binding to thousands of enhancers. Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4.,  Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers, whose function and action mechanism are yet to be firmly established. Here we show that eRNAs facilitate the transition of paused RNA polymerase II (RNAPII) into productive elongation by acting as a decoy for the negative elongation factor (NELF) complex upon induction of immediate early genes (IEGs) in neurons., Recent studies have disclosed the function of enhancer RNAs (eRNAs), which are long non-coding RNAs transcribed from gene enhancer regions, in transcriptional regulation., Recent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription., Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers,, In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). However, it has remained unclear whether these eRNAs are functional or merely a reflection of enhancer activation.,  Recent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription.[SEP]Relations: mRNA transcription has relations: bioprocess_protein with EREG, bioprocess_protein with EREG, bioprocess_protein with HIPK3, bioprocess_protein with HIPK3, bioprocess_bioprocess with mRNA transcription by RNA polymerase II, bioprocess_bioprocess with mRNA transcription by RNA polymerase II, bioprocess_protein with HSF1, bioprocess_protein with HSF1. RNA localization to chromatin has relations: bioprocess_protein with HNRNPU, bioprocess_protein with HNRNPU.", "label": "yes"}
{"id": "converted_1674", "sentence1": "Has field-programmable gate array (FPGA) technology been used to solve sequence alignment problems?", "sentence2": "A linear error model for the raw intensity data and Burrows-Wheeler transform (BWT) based alignment are combined utilizing a Bayesian score function, which is then globally optimized over all possible genomic locations using an efficient branch-and-bound approach. The algorithm has been implemented in soft- and hardware [field-programmable gate array (FPGA)] to achieve real-time performance., we have designed and built a high-performance FPGA-accelerated version of BLASTP, Mercury BLASTP. In this paper, we describe the architecture of the portions of the application that are accelerated in the FPGA, and we also describe the integration of these FPGA-accelerated portions with the existing BLASTP software. We have implemented Mercury BLASTP on a commodity workstation with two Xilinx Virtex-II 6000 FPGAs., This paper shows how reconfigurable architectures can be used to derive an efficient fine-grained parallelization of the dynamic programming calculation. We describe how this technique leads to significant runtime savings for HMM database scanning on a standard off-the-shelf field-programmable gate array (FPGA)., We have constructed a linear systolic array to perform pairwise sequence distance computations using dynamic programming. This results in an implementation with significant runtime savings on a standard FPGA., in this paper, we focused on accelerating the Smith-Waterman algorithm by modifying the computationally repeated portion of the algorithm by FPGA hardware custom instructions., We present a reconfigurable systolic architecture that can be applied for the efficient treatment of several dynamic programming methods for resolving well-known problems, such as global and local sequence alignment, approximate string matching and longest common subsequence. The dynamicity of the reconfigurability was found to be useful for practical applications in the construction of sequence alignments. A VHDL (VHSIC hardware description language) version of this new architecture was implemented on an APEX FPGA (Field programmable gate array)., This results in an implementation of ClustalW with significant runtime savings on a standard off-the-shelf FPGA., The accelerator implements a version of the Needleman-Wunsch algorithm for nucleotide sequence alignment. Sequence lengths are constrained only by available memory; the product of sequence lengths in the current implementation can be up to 2(22). The machine is implemented as two NuBus boards connected to a Mac IIf/x, using a mixture of TTL and FPGA technology clocked at 10 MHz.[SEP]", "label": "yes"}
{"id": "converted_3830", "sentence1": "Should tirilazad be used for treatment of ischemic stroke?", "sentence2": "CONCLUSION: Tirilazad had no effect on clinical outcome but did decrease symptomatic vasospasm in five trials of aneurysmal SAH. , Tirilazad did not significantly decrease unfavorable clinical outcome on the GOS (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.89-1.20) or cerebral infarction (OR 1.04, 95% CI 0.89-1.22). , The authors investigated whether the lack of effect of tirilazad on clinical outcome in patients with acute ischemic stroke is explained by failure of tirilazad to reduce infarct volume. , Tirilazad did not alter early case fatality (odds ratio [OR] 1.11, 95% confidence interval [CI] 0.79 to 1.56) or end-of-trial case fatality (OR 1.12, 95% CI 0.88 to 1.44). A just-significant increase in death and disability, assessed as either the expanded Barthel Index (OR 1.23, 95% CI 1.01 to 1.51) or Glasgow Outcome Scale (OR 1. 23, 95% CI 1.01 to 1.50) was observed., CONCLUSIONS: Tirilazad mesylate increases death and disability by about one fifth when given to patients with acute ischemic stroke. Although further trials of tirilazad are now unwarranted, analysis of individual patient data from the trials may help elucidate why tirilazad appears to worsen outcome in acute ischemic stroke.[SEP]Relations: Ischemic stroke has relations: drug_effect with Aripiprazole, drug_effect with Aripiprazole, drug_effect with Sitaxentan, drug_effect with Sitaxentan, drug_effect with Ramipril, drug_effect with Ramipril, drug_effect with Tramadol, drug_effect with Tramadol, drug_effect with Pazopanib, drug_effect with Pazopanib.", "label": "no"}
{"id": "converted_2265", "sentence1": "Does echinacea increase anaphylaxis risk?", "sentence2": "Chicoric acid (dicaffeoyl-tartaric acid), is a natural phenolic compound found in a number of plants, such as chicory (Cichorium intybus) and Echinacea (Echinacea purpurea), which possesses antioxidant, anti-inflammatory, antiviral, and analgesic activities. Although these biological effects of chicoric acid have been investigated, there are no reports of its antiallergic-related anti-inflammatory effects in human mast cells (HMC)-1 or anaphylactic activity in a mouse model., BACKGROUND: Fifty percent of Australians use complementary and alternative medicines (other than vitamins) in any 12-month period, of which echinacea-containing products are increasingly popular. Recent reports have highlighted the risk of allergic reactions to complementary medicines in atopic patients., Two patients suffered anaphylaxis and a third had an acute asthma attack 10 minutes after their first ever dose of echinacea., Fifty-one Australian adverse drug reports implicating echinacea were also reviewed. There were 26 cases suggestive of possible immunoglobulin E-mediated hypersensitivity (4 anaphylaxis, 12 acute asthma, 10 urticaria/angioedema). , Echinacea-associated anaphylaxis., A woman with atopy experienced anaphylaxis after taking, among other dietary supplements, a commercial extract of echinacea., Risk of anaphylaxis in complementary and alternative medicine., Several culprits identified including Andrographis paniculata, Echinacea species, bee products, Ginkgo biloba and Ginseng are discussed here.SUMMARY: Knowing the factors that increase the risk of anaphylaxis allows reactions to be recognized, reported and further investigated.[SEP]Relations: anaphylaxis has relations: disease_disease with exercise-induced anaphylaxis, disease_disease with exercise-induced anaphylaxis, contraindication with Paclitaxel, contraindication with Paclitaxel, contraindication with Esmolol, contraindication with Esmolol, contraindication with Acebutolol, contraindication with Acebutolol, contraindication with Atenolol, contraindication with Atenolol.", "label": "yes"}
{"id": "converted_581", "sentence1": "Is CD99 encoded by MIC2 gene?", "sentence2": "We report 2 unusual cytogenetic findings in a pediatric Ewing sarcoma, an insertion of the MIC2 gene encoding CD99 from Xp to 10p and a submicroscopic deletion of the well-known tumor supressor gene KLF6, We obtained the final diagnosis of ES/PNET by immunohistochemical molecular study with positive staining for the MIC2 gene product (CD99) and a Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangement, CD99, a transmembrane protein encoded by MIC2 gene is involved in multiple cellular events including cell adhesion and migration, apoptosis, cell differentiation and regulation of protein trafficking either in physiological or pathological conditions, CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene, The surgical specimens showed small round cell tumor with positive staining for MIC2 gene product (CD99), CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene., The leukocyte surface molecule CD99 is an integral membrane glycoprotein encoded by the E2/MIC2 gene., Human CD99, which is encoded by the mic2 gene, is a ubiquitous 32 kDa transmembrane protein., Human CD99 is a 32-kDa cell surface protein that is encoded by the MIC2 gene localized to the PAR1., The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene., CD99, a transmembrane protein encoded by MIC2 gene is involved in multiple cellular events including cell adhesion and migration, apoptosis, cell differentiation and regulation of protein trafficking either in physiological or pathological conditions., CD99, the product of the MIC2 gene, exhibits an erythroid-specific quantitative polymorphism coregulated with the polymorphism of the XG blood group gene., CD99, the product of the MIC2 gene, exhibits an erythroid-specific quantitative polymorphism co-regulated with the Xga blood group polymorphism., Homology searches resulted in finding homologous sequences (totally about 40% homology) in the human MIC2 gene product (CD99; 32-kDa) of T lymphocytes., Although considered a specific marker for Ewing's sarcoma/peripheral neuroectodermal tumour, the MIC2 gene product (CD99) has been immunolocalised in a variety of human tumours., MIC2, the gene encoding the CD99 antigen, is found in the pseudoautosomal region of both the X and Y chromosomes., Human CD99 is a 32-kDa cell surface protein that is encoded by the MIC2 gene localized to the PAR1., The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene., CD99 (MIC2) regulates the LFA-1/ICAM-1-mediated adhesion of lymphocytes, and its gene encodes both positive and negative regulators of cellular adhesion., Relation of neurological marker expression and EWS gene fusion types in MIC2/CD99-positive tumors of the Ewing family., The Ewing family of tumors (EFT) is characterized by high MIC2/CD99 expression and specific EWS/ETS gene rearrangements, resulting in different chimeric transcripts., The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene., Monoclonal antibody (MAb) HBA71, which was raised against Ewing's sarcoma cells, recognizes a cell-surface glycoprotein, p30/32MIC2, that is encoded by the MIC2 gene in the pseudoautosomal region of human chromosomes X and Y., Monoclonal antibodies (mAbs) directed against E2, a 32-kDa transmembrane protein encoded by the MIC2 gene located in the pseudoautosomal region, induce a transbilayer movement of phosphatidylserine and, to a lesser extent, phosphatidylethanolamine in human thymocytes and a Jurkat T lymphocytes., Homology searches resulted in finding homologous sequences (totally about 40% homology) in the human MIC2 gene product (CD99; 32-kDa) of T lymphocytes., CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene, CD99, a transmembrane protein encoded by MIC2 gene is involved in multiple cellular events including cell adhesion and migration, apoptosis, cell differentiation and regulation of protein trafficking either in physiological or pathological conditions, The surgical specimens showed small round cell tumor with positive staining for MIC2 gene product (CD99), We report 2 unusual cytogenetic findings in a pediatric Ewing sarcoma, an insertion of the MIC2 gene encoding CD99 from Xp to 10p and a submicroscopic deletion of the well-known tumor supressor gene KLF6, MIC2, the gene encoding the CD99 antigen, is found in the pseudoautosomal region of both the X and Y chromosomes, Immunohistochemical analysis showed weak to moderate and partial staining for MIC2 (CD99) and WT1, respectively, Human CD99, which is encoded by the mic2 gene, is a ubiquitous 32 kDa transmembrane protein, The leukocyte surface molecule CD99 is an integral membrane glycoprotein encoded by the E2/MIC2 gene, The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene, Human CD99 is a 32-kDa cell surface protein that is encoded by the MIC2 gene localized to the PAR1, MIC2, the gene encoding the CD99 antigen, is found in the pseudoautosomal region of both the X and Y chromosomes, CD99, the product of the MIC2 gene, exhibits an erythroid-specific quantitative polymorphism co-regulated with the Xga blood group polymorphism[SEP]Relations: EWSR1 has relations: protein_protein with CDK12, protein_protein with CDK12, protein_protein with CD177, protein_protein with CD177, protein_protein with CUEDC2, protein_protein with CUEDC2. SLC52A2 has relations: protein_protein with ADRB2, protein_protein with ADRB2, protein_protein with CDC23, protein_protein with CDC23.", "label": "yes"}
{"id": "converted_3357", "sentence1": "Is SARS virus interacting with ACE2 encoded protein?", "sentence2": "The trimeric SARS coronavirus (SARS-CoV) surface spike (S) glycoprotein consisting of three S1-S2 heterodimers binds the cellular receptor angiotensin-converting enzyme 2 (ACE2) and mediates fusion of the viral and cellular membranes through a pre- to postfusion conformation transition, The viral spike glycoprotein (S) utilizes angiotensin-converting enzyme 2 (ACE2) as a host protein receptor and mediates fusion of the viral and host membranes, making S essential to viral entry into host cells and host species tropism., Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, Angiotensin-converting enzyme 2 (ACE2), a relatively new member of the RAS, has drawn extensive attention since 2003, because of the findings that ACE2 is the receptor for SARS Corona virus and that maintenance of normal ACE2 levels in the lung is beneficial for the host to combat inflammatory lung disease., The infection of target cells by the SARS CoV is mediated through the interaction of the viral Spike (S) protein (1255 amino acids) and its cellular receptor, angiotensin-converting enzyme 2 (ACE2).[SEP]Relations: severe acute respiratory syndrome has relations: disease_protein with ACE, disease_protein with ACE. Protein S human has relations: drug_drug with Saruplase, drug_drug with Saruplase, drug_drug with Sarpogrelate, drug_drug with Sarpogrelate. peptidyl-dipeptidase activity has relations: molfunc_protein with ACE2, molfunc_protein with ACE2, molfunc_protein with ACE, molfunc_protein with ACE.", "label": "yes"}
{"id": "converted_3959", "sentence1": "Are PDXK mutations linked to polyneuropathy?", "sentence2": "PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation., To identify disease-causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy.METHODS: We performed genome-wide sequencing, homozygosity mapping, and segregation analysis for novel disease-causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient-derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating scales, electrophysiology, and biochemical quantification.RESULTS: We identified biallelic mutations in PDXK in 5 individuals from 2 unrelated families with primary axonal polyneuropathy and optic atrophy. The natural history of this disorder suggests that untreated, affected individuals become wheelchair-bound and blind. We identified conformational rearrangement in the mutant enzyme around the ATP-binding pocket. Low PDXK ATP binding resulted in decreased erythrocyte PDXK activity and low pyridoxal 5'-phosphate (PLP) concentrations. We rescued the clinical and biochemical profile with PLP supplementation in 1 family, improvement in power, pain, and fatigue contributing to patients regaining their ability to walk independently during the first year of PLP normalization.INTERPRETATION: We show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We show that the biochemical profile can be rescued with PLP supplementation associated with clinical improvement. As B6 is a cofactor in diverse essential biological pathways, our findings may have direct implications for neuropathies of unknown etiology characterized by reduced PLP levels. ANN NEUROL 2019;86:225-240., RETATION: We show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We sh, PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation, Hereditary polyneuropathy with optic atrophy due to PDXK variant leading to impaired Vitamin B6 metabolism, INTERPRETATION: We show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP., RESULTS: We identified biallelic mutations in PDXK in 5 individuals from 2 unrelated families with primary axonal polyneuropathy and optic atrophy., show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We[SEP]Relations: polyneuropathy has relations: disease_disease with polyneuropathy due to drug, disease_disease with polyneuropathy due to drug, disease_disease with peripheral neuropathy, disease_disease with peripheral neuropathy, disease_protein with PNPLA6, disease_protein with PNPLA6, disease_disease with idiopathic progressive polyneuropathy, disease_disease with idiopathic progressive polyneuropathy, disease_disease with polyneuritis, disease_disease with polyneuritis.", "label": "yes"}
{"id": "converted_1876", "sentence1": "Has small pox been eradicated from the world?", "sentence2": "small pox has been eradicated., smallpox is now eradicated, In May 1980 the World Health Assembly in Geneva announced in solemn form the world-wide eradication of the small-pox and gave recommendations to the member countries for concluding measures concerning the small-pox vaccination, the foundation of vaccine reserves and the control of the epidemiological situation in the world., As a result of vaccination, diseases such as polio and measles have been controlled and small pox has been eradicated, Small pox eradication from the world is the perfect example of the role of mass vaccination of the entire community of the universe. , The French owe a lot to this Central Committee of Vaccine, which greatly contributed to fighting small pox and eradicating the disease finally., Small pox eradication from the world is the perfect example of the role of mass vaccination of the entire community of the universe., Also, the vaccine that Jenner used, which decreased the prevalence of Small Pox worldwide in his own time, and later was used to eradicate Small Pox altogether, is discussed in light of recent data.., the only known cases of smallpox happened from an outbreak in Birmingham, England caused by a laboratory accident in the year of 1979. On May the 8 th 1980 the disease was declared as eliminated from the world by the WHO (WHO-Resolution 33.33).[SEP]Relations: BCG vaccine has relations: drug_drug with Ponatinib, drug_drug with Ponatinib, drug_drug with Paclitaxel, drug_drug with Paclitaxel, drug_drug with Ubenimex, drug_drug with Ubenimex, drug_drug with Ebola Zaire vaccine (live, attenuated), drug_drug with Ebola Zaire vaccine (live, attenuated), drug_drug with Aspoxicillin, drug_drug with Aspoxicillin.", "label": "yes"}
{"id": "converted_813", "sentence1": "Does a selective sweep increase genetic variation?", "sentence2": "An East African population that gave rise to non-Africans underwent a selective sweep affecting the subcentromeric region where MTMR8 is located. This and similar sweeps in four other regions of the X chromosome, documented in the literature, effectively reduced genetic diversity of non-African chromosomes, a selective sweep that has removed genetic variation from much of the drive X chromosome., evidence of reduced diversity and an excess of fixed replacement sites, consistent with a species-wide selective sweep., recent independent selective sweeps in AGO2 have reduced genetic variation, episodes of natural selection (likely a selective sweep) predating the coalescent of human lineages, within the last 25 million years, account for the observed reduced diversity, reduced variation or deviations from neutrality that might indicate a recent selective sweep, Consider a genetic locus carrying a strongly beneficial allele which has recently fixed in a large population. As strongly beneficial alleles fix quickly, sequence diversity at partially linked neutral loci is reduced. This phenomenon is known as a selective sweep., a local selective sweep or demographic process that reduced variability, reduced variation (a selective sweep), the mtDNA diversity, but not the nuclear DNA diversity, has been reduced relative to the neutral expectation of molecular evolution, suggesting the action of a selective sweep, Furthermore, the amount of genetic variation after a selective sweep is expected to be unequal over demes: a greater reduction in expected heterozygosity occurs in the subpopulation from which the beneficial mutation originates than in its neighboring subpopulations., Our observation of reduction in variation at both intragenic and flanking loci of mutant pfcrt gene confirmed the selective sweep model of natural selection in chloroquine resistant P., A selective sweep describes the reduction of linked genetic variation due to strong positive selection., In these situations, adaptation should commonly produce 'soft' selective sweeps, where multiple adaptive alleles sweep through the population at the same time, either because the alleles were already present as standing genetic variation or arose independently by recurrent de novo mutations., CONCLUSIONS: The severe reduction in nucleotide variation at OsAMT1;1 in rice was caused by a selective sweep around OsAMT1;1, which may reflect the nitrogen uptake system under strong selection by the paddy soil during the domestication of rice., A selective sweep describes the reduction of linked genetic variation due to strong positive selection[SEP]Relations: adaptation to pheromone regulating conjugation with mutual genetic exchange has relations: bioprocess_bioprocess with response to pheromone regulating conjugation with mutual genetic exchange, bioprocess_bioprocess with response to pheromone regulating conjugation with mutual genetic exchange, bioprocess_bioprocess with regulation of conjugation, bioprocess_bioprocess with regulation of conjugation, bioprocess_bioprocess with negative adaptation of signaling pathway, bioprocess_bioprocess with negative adaptation of signaling pathway. Lacrimation abnormality has relations: phenotype_phenotype with Decreased lacrimation, phenotype_phenotype with Decreased lacrimation, phenotype_phenotype with Gustatory lacrimation, phenotype_phenotype with Gustatory lacrimation.", "label": "no"}
{"id": "converted_3035", "sentence1": "Is Lasmiditan effective for migraine?", "sentence2": "Amongst the ditans, lasmiditan: (i) fails to constrict human coronary arteries; and (ii) is effective for the acute treatment of migraine in preliminary Phase III clinical trials., Although ongoing phase III clinical trials are needed to confirm its efficacy and safety, lasmiditan might offer an alternative to treat acute migraine with no associated cardiovascular risk., Lasmiditan is considered to be the first member of a new drug category, the neurally acting anti-migraine agent (NAAMA), Lasmiditan for the treatment of acute migraine: a review and potential role in clinical practice., Lasmiditan, a highly selective 5-HT1F agonist, has completed two Phase III randomized, double blind, placebo-controlled clinical trials, with a third - a long-term, open-label safety study - still underway. Research to date suggests lasmiditan lacks vasoconstrictive properties and may be a safe and effective treatment option in patients refractory to current acute migraine medications or who have cardiovascular risk factors., Lasmiditan is an effective acute treatment for migraine: A phase 3 randomized study., Compared with placebo, more patients dosed with lasmiditan 200 mg were free of headache pain at 2 hours after dosing (32.2% vs 15.3%; odds ratio [OR] 2.6, 95% confidence interval [CI] 2.0-3.6, p< 0.001), similar to those dosed with lasmiditan 100 mg (28.2%; OR 2.2, 95% CI 1.6-3.0, p< 0.001). Furthermore, compared with those dosed with placebo, more patients dosed with lasmiditan 200 mg (40.7% vs 29.5%; OR 1.6, 95% CI 1.3-2.1, p< 0.001) and lasmiditan 100 mg (40.9%; OR 1.7, 95% CI, 1.3-2.2, p< 0.001) were free of their MBS at 2 hours after dosing., CONCLUSIONS: Lasmiditan dosed at 200 and 100 mg was efficacious and well tolerated in the treatment of acute migraine among patients with a high level of cardiovascular risk factors, CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for adult patients with migraine, lasmiditan increases the proportion of subjects who are headache pain free at 2 hours after treating a migraine attack., For the understanding of migraine pathophysiology, it is very important to note that a selective 5-HT(1F) receptor agonist like lasmiditan is effective in the acute treatment of migraine. , While lasmiditan most likely is effective in the treatment of migraine attacks it had, unfortunately, a high incidence of CNS related AEs in the oral RCT. , Acute treatment of migraine with the selective 5-HT1F receptor agonist lasmiditan--a randomised proof-of-concept trial.At intravenous doses of 20 mg and higher, lasmiditan proved effective in the acute treatment of migraine. , Lasmiditan for the treatment of acute migraine: a review and potential role in clinical practice. , BACKGROUND\nLasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a proof-of-concept migraine study., INTERPRETATION\nOral lasmiditan seems to be safe and effective in the acute treatment of migraine., The 5-HT1F receptor agonist lasmiditan, a drug acting through non-vasoconstrictive mechanisms, represents a promising safe, effective and tolerated acute migraine therapy also for patients at cardiovascular risk., For the understanding of migraine pathophysiology, it is very important to note that a selective 5-HT(1F) receptor agonist like lasmiditan is effective in the acute treatment of migraine., The 5-HT1F receptor agonist lasmiditan as a potential treatment of migraine attacks: a review of two placebo-controlled phase II trials., Within the past few years, new and promising drugs such as more specific 5-HT 1F receptor agonists (that is, lasmiditan) and monoclonal calcitonin gene-related peptide (CGRP) receptor antibodies entered advanced development phases while non-invasive neuromodulatory approaches were suggested to be potentially effective as non-pharmaceutical interventions for migraine., CLASSIFICATION OF EVIDENCE\nThis study provides Class I evidence that for adult patients with migraine, lasmiditan increases the proportion of subjects who are headache pain free at 2 hours after treating a migraine attack., BACKGROUND Lasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a proof-of-concept migraine study., INTERPRETATION Oral lasmiditan seems to be safe and effective in the acute treatment of migraine., Research to date suggests lasmiditan lacks vasoconstrictive properties and may be a safe and effective treatment option in patients refractory to current acute migraine medications or who have cardiovascular risk factors., The non-vascular, neural mechanism of action of lasmiditan may offer an alternative means to treat migraine especially in patients who have contra-indications for agents with vasoconstrictor activity., Compared with placebo, more patients dosed with lasmiditan 200 mg were free of headache pain at 2 hours after dosing (32.2% vs 15.3%; odds ratio [OR] 2.6, 95% confidence interval [CI] 2.0-3.6, <br><b>CONCLUSIONS</b>: Lasmiditan dosed at 200 and 100 mg was efficacious and well tolerated in the treatment of acute migraine among patients with a high level of cardiovascular risk factors.<br><b>CLINICALTRIALSGOV IDENTIFIER</b>: NCT02439320.<br><b>CLASSIFICATION OF EVIDENCE</b>: This study provides Class I evidence that for adult patients with migraine, lasmiditan increases the proportion of subjects who are headache pain free at 2 hours after treating a migraine attack.<br>, The most common adverse events were CNS related and included dizziness, fatigue, vertigo, paraesthesia, and somnolence.<br><b>INTERPRETATION</b>: Oral lasmiditan seems to be safe and effective in the acute treatment of migraine., Dizziness, paresthesia and sensations of heaviness (usually limb) were more common on lasmiditan.<br><b>CONCLUSIONS</b>: At intravenous doses of 20 mg and higher, lasmiditan proved effective in the acute treatment of migraine., <b>BACKGROUND</b>: Lasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a proof-of-concept migraine study., For the understanding of migraine pathophysiology, it is very important to note that a selective 5-HT(1F) receptor agonist like lasmiditan is effective in the acute treatment of migraine., This study provides Class I evidence that for adult patients with migraine, lasmiditan increases the proportion of subjects who are headache pain free at 2 hours after treating a migraine attack., While lasmiditan most likely is effective in the treatment of migraine attacks it had, unfortunately, a high incidence of CNS related AEs in the oral RCT.[SEP]Relations: Lasmiditan has relations: drug_drug with Fendiline, drug_drug with Fendiline, drug_drug with Hypericin, drug_drug with Hypericin, drug_drug with Benzoctamine, drug_drug with Benzoctamine, drug_drug with Fimasartan, drug_drug with Fimasartan, drug_drug with Methadone, drug_drug with Methadone.", "label": "yes"}
{"id": "converted_3768", "sentence1": "Is tocilizumab a tumor necrosis factor inhibitor?", "sentence2": "For the first-line bDMARD/tsDMARD, either tumor necrosis factor inhibitors (TNFi), non-TNFi (abatacept, tocilizumab, rituximab), or tsDMARDs, may be considered.[SEP]Relations: Tocilizumab has relations: drug_drug with Necitumumab, drug_drug with Necitumumab, drug_drug with Nemolizumab, drug_drug with Nemolizumab, drug_drug with Cemiplimab, drug_drug with Cemiplimab, drug_drug with Tositumomab, drug_drug with Tositumomab, drug_drug with Otelixizumab, drug_drug with Otelixizumab.", "label": "no"}
{"id": "converted_4565", "sentence1": "Is Sotrovimab effective for COVID-19?", "sentence2": "It seems that monoclonal antibodies (e.g., low dosage bamlanivimab, baricitinib, imatinib, and sotrovimab) are a better choice for treating severe or non-severe COVID-19 patients. , The Food and Drug Administration has granted emergency use authorization to sotrovimab for the treatment of mild to moderate COVID-19 in patients at increased risk for progression to severe illness., Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab., Sotrovimab is a pan-sarbecovirus monoclonal antibody that was designed to prevent progression of Covid-19 in high-risk patients early in the course of disease, CONCLUSIONS: Among high-risk patients with mild-to-moderate Covid-19, sotrovimab reduced the risk of disease progression., The Food and Drug Administration has granted emergency use authorization to sotrovimab for the treatment of mild to moderate COVID-19 in patients at increased risk for progression to severe illness.Sotrovimab is a monoclonal antibody that works directly against the spike protein of SARS-CoV-2 to block its attachment and entry into a human cell., In patients with non-severe covid-19, casirivimab-imdevimab probably reduces hospitalisation; bamlanivimab-etesevimab, bamlanivimab, and sotrovimab may reduce hospitalisation. Convalescen, ms that monoclonal antibodies (e.g., low dosage bamlanivimab, baricitinib, imatinib, and sotrovimab) are a better choice for treating severe or non-severe COVID-19 patients. Clini, Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab, The Food and Drug Administration has granted emergency use authorization to sotrovimab for the treatment of mild to moderate COVID-19 in patients at increased risk for progression to severe illness[SEP]Relations: Baricitinib has relations: drug_drug with Sofosbuvir, drug_drug with Sofosbuvir, drug_drug with Cortivazol, drug_drug with Cortivazol, drug_drug with Somatostatin, drug_drug with Somatostatin, drug_drug with Efalizumab, drug_drug with Efalizumab. Imatinib has relations: drug_drug with Sofosbuvir, drug_drug with Sofosbuvir.", "label": "yes"}
{"id": "converted_1826", "sentence1": "Is the protein lefty an inhibitor of nodal?", "sentence2": "The expression of lefty, an inhibitor of nodal is often reduced in tumor cells.,  Nodal, and an inhibitor, Lefty., as well as the expression of Lefty, an inhibitor of nodal signaling,, he Nodal inhibitor lefty, The morphogen Nodal was proposed to form a long-range signaling gradient via a reaction-diffusion system, on the basis of differential diffusion rates of Nodal and its antagonist Lefty.[SEP]Relations: malignancy in giant cell tumor of bone has relations: disease_disease with bone sarcoma, disease_disease with bone sarcoma, disease_disease with malignant giant cell tumor, disease_disease with malignant giant cell tumor.", "label": "yes"}
{"id": "converted_213", "sentence1": "Is protein M3/6 a dual specificity phosphatase?", "sentence2": "Involvement of the dual-specificity phosphatase M3/6 in c-Jun N-terminal kinase inactivation following cerebral ischemia in the rat hippocampus., The results revealed upregulation of dual-specificity phosphatase M3/6 (DUSP8) activity at 4 h of reperfusion in rat hippocampi. , This study examines the molecular mechanism underlying JNK dephosphorylation and inactivation evoked by dual-specificity phosphates following cerebral ischemia., Phosphatases play a particularly important role in this respect, by tightly controlling MAPK phosphorylation and activation. M3/6 (DUSP8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of JNK and, to a lesser extent, p38 MAPKs and is found in a complex with these kinases, along with other pathway components, held together by scaffold proteins. , Dual-specificity phosphatases (DUSPs) play a very important role in these events by modulating the extent of JNK phosphorylation and activation and thus regulating cellular responses to stress. M3/6 (DUSP8) is one of the dual-specificity protein phosphatases with distinct specificity towards JNK., M3/6 is a dual-specificity phosphatase selective for JNK [7, 8]. , Here we describe two new dual specificity phosphatases of the CL100/MKP-1 family that are selective for inactivating ERK or JNK/SAPK and p38 MAP kinases when expressed in COS-7 cells. M3/6 is the first phosphatase of this family to display highly specific inactivation of JNK/SAPK and p38 MAP kinases. , We previously demonstrated that the dual specificity phosphatases (DSPs) MKP7 and M3/6 bind the scaffold JNK-interacting protein-1 (JIP-1) and inactivate the bound subset of JNK (1)., the dual-specificity phosphatase M3/6,  dual-specificity phosphatase M3/6 (DUSP8), M3/6 (DUSP8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of JNK , the M3/6 dual-specificity phosphatase, M3/6 (DUSP8) is one of the dual-specificity protein phosphatases with distinct specificity towards JNK, M3/6 is a dual-specificity phosphatase selective for JNK, The dual specificity phosphatases M3/6 and MKP-3 are highly selective for inactivation of distinct mitogen-activated protein kinases., Phosphorylation of the M3/6 dual-specificity phosphatase enhances the activation of JNK by arsenite., Indeed, expanded polyglutamine impaired the solubility of the dual-specificity JNK phosphatase M3/6., Regulation of dual-specificity phosphatases M3/6 and hVH5 by phorbol esters., M3/6 (DUSP8) is one of the dual-specificity protein phosphatases with distinct specificity towards JNK., M3/6 is a dual-specificity phosphatase selective for JNK [7, 8], M3/6 (DUSP8) is one of the dual-specificity protein phosphatases with distinct specificity towards JNK, Here we describe how diverse cellular stresses affect differently the stability and activity of a JNK-inactivating dual-specificity threonine-tyrosine phosphatase M3/6, M3/6 is a dual-specificity phosphatase selective for JNK [7, 8], Regulation of dual-specificity phosphatases M3/6 and hVH5 by phorbol esters. Analysis of a delta-like domain., The results revealed upregulation of dual-specificity phosphatase M3/6 (DUSP8) activity at 4 h of reperfusion in rat hippocampi, Indeed, expanded polyglutamine impaired the solubility of the dual-specificity JNK phosphatase M3/6, Here we report that JIP-1 also binds the dual-specificity phosphatases MKP7 and M3/6 via a region independent of its JNK binding domain., Differential regulation of M3/6 (DUSP8) signaling[SEP]Relations: MAPK8IP1 has relations: disease_protein with type 2 diabetes mellitus, disease_protein with type 2 diabetes mellitus, protein_protein with LRP2, protein_protein with LRP2, bioprocess_protein with JUN phosphorylation, bioprocess_protein with JUN phosphorylation, protein_protein with MAP2K7, protein_protein with MAP2K7, protein_protein with LRP8, protein_protein with LRP8.", "label": "yes"}
{"id": "converted_2602", "sentence1": "Is Rucaparib effective for ovarian cancer?", "sentence2": "INTERPRETATION: In patients with BRCA mutant or BRCA wild-type and LOH high platinum-sensitive ovarian carcinomas treated with rucaparib, progression-free survival was longer than in patients with BRCA wild-type LOH low carcinomas., High LOH is associated with response to the PARP inhibitor rucaparib in BRCA wild-type ovarian cancer., Rucaparib Approved for Ovarian Cancer., The FDA approved the PARP inhibitor rucaparib to treat women with advanced ovarian cancer who have already been treated with at least two chemotherapies and have a BRCA1 or BRCA2 gene mutation identified by an approved companion diagnostic test., Rucaparib (Rubraca™) is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor being developed by Clovis Oncology, Inc. (Boulder, CO, USA) for the treatment of solid tumours. It has been approved in the USA as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies. , In 2016, the US Food and Drug Administration approved three novel drugs for the treatment of solid malignancies-olaratumab in selected patients with soft-tissue sarcoma, atezolizumab for the treatment of bladder cancer, and rucaparib for the treatment of ovarian cancer; also in 2016, the use of previously approved anticancer agents (including atezolizumab) was expanded into 11 new patient populations. , Conclusions:Rucaparib was tolerable and had activity in patients with platinum-sensitive germlineBRCA1/2-mutated HGOC., <b>OBJECTIVE</b>: To review the pharmacology, safety, efficacy, and the role of rucaparib in the treatment of relapsed, advanced ovarian cancer.<br><b>SUMMARY</b>: A total of 2 phase I/II trials and 1 phase II trial have evaluated the safety and efficacy of oral rucaparib in ovarian cancer., Rucaparib was found to be relatively well tolerated in clinical trials, with the most common adverse events being anemia, fatigue, and nausea.<br><b>CONCLUSION</b>: Rucaparib appears to be a safe and effective new option in the treatment of relapsed, advanced BRCA1/2 mutant ovarian cancer., In patients with deleterious BRCA1/2 mutation, an overall response rate of 80% was achieved in the phase II trial Assessment of Rucaparib in Ovarian CancEr Trial 2 (ARIEL2)., This article summarizes the milestones in the development of rucaparib leading to this first approval for ovarian cancer.<br>, These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer.<br>, Rucaparib: a Poly(ADP-Ribose) Polymerase Inhibitor for BRCA-Mutated Relapsed Ovarian Cancer., CONCLUSION Rucaparib appears to be a safe and effective new option in the treatment of relapsed, advanced BRCA1/2 mutant ovarian cancer., These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer., Rucaparib received US FDA Breakthrough Therapy designation for treatment of platinum-sensitive BRCA-mutated advanced ovarian cancer patients who received greater than two lines of platinum-based therapy., BACKGROUND Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity., Rucaparib appears to be a safe and effective new option in the treatment of relapsed, advanced BRCA1/2 mutant ovarian cancer., Rucaparib: A Poly(ADP-Ribose) Polymerase Inhibitor for BRCA-Mutated Relapsed Ovarian Cancer., Rucaparib: the past, present, and future of a newly approved PARP inhibitor for ovarian cancer., FDA Approval Summary: Rucaparib for the Treatment of Patients with Deleterious BRCA Mutation-Associated Advanced Ovarian Cancer., Olaparib and rucaparib have been approved by the US FDA as monotherapy for advanced recurrent ovarian cancer.[SEP]Relations: Rucaparib has relations: drug_drug with Lobucavir, drug_drug with Lobucavir, drug_drug with Estradiol, drug_drug with Estradiol, drug_drug with Capsaicin, drug_drug with Capsaicin, drug_drug with Olaparib, drug_drug with Olaparib, drug_drug with Lopinavir, drug_drug with Lopinavir.", "label": "yes"}
{"id": "converted_3540", "sentence1": "Is TIM-3 a target for cancer immunotherapy in NSCLC?", "sentence2": " Our results imply that implementing combined treatment on CIK cells before transfusion via antibodies targeting PD-L1, LAG-3, TIM-3, and CEACAM-1 might improve the efficiency of CIK therapy for NSCLC patients., Furthermore, TIM-3 and CEACAM1 were strongly expressed simultaneously during long-term CIK culture and showed a significant and mutually positive correlation. , In present study, we detected the dynamic expression of eight major checkpoint molecules (CTLA-4, PD-1, PD-L1, TIM- 3, CEACAM-1, LAG-3, TIGIT and BTLA) on CIK cells from NSCLC patients., Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors on T cells and other approaches such as adoptive cell transfer are tested for clinical efficacy in melanoma as well., We found immune activation coexistent with elevation of multiple targetable immune checkpoint molecules, including PD-L1, PD-L2, PD-1, TIM-3, B7-H3, BTLA, and CTLA-4, along with increases in tumor infiltration by CD4(+)Foxp3(+) regulatory T cells in lung adenocarcinomas that displayed an EMT phenotype, Cytometric profiling identified an immunologically \"hot\" cluster with abundant CD8+ T cells expressing high levels of PD-1 and TIM-3 and an immunologically \"cold\" cluster with lower relative abundance of CD8+ T cells and expression of inhibitory markers,  Interestingly, CD161+ CD4+ T cells highly express OX40 co-stimulatory receptor, less frequently 4-1BB, and display an activated but not completely exhausted PD-1-positive Tim-3-negative phenotype., . Furthermore, overexpression of targetable immune checkpoints, such as CTLA-4 and TIM-3 were associated with EMT in both NSCLCs. [SEP]Relations: small cell lung carcinoma has relations: disease_protein with ASCL1, disease_protein with ASCL1, disease_protein with TP73, disease_protein with TP73, disease_protein with EPHB3, disease_protein with EPHB3. Protein S human has relations: drug_drug with NS-398, drug_drug with NS-398, drug_drug with Antithrombin III human, drug_drug with Antithrombin III human.", "label": "yes"}
{"id": "converted_2486", "sentence1": "Is vorinostat effective for glioblastoma?", "sentence2": "Conclusions: Vorinostat combined with standard chemoradiation had acceptable tolerability in newly diagnosed glioblastoma. Although the primary efficacy endpoint was not met, vorinostat sensitivity and resistance signatures could facilitate patient selection in future trials., LESSONS LEARNED: Combination regimen with bevacizumab (BEV) and vorinostat is well tolerated in patients with recurrent glioblastoma., CONCLUSION: Combination treatment of BEV and VOR was well tolerated. This combination therapy for this study population did not improve PFS6 or median OS when compared with BEV monotherapy., We present two patients with glioblastoma multiforme who developed severe hemolytic anemia shortly after initiating therapy with vorinostat, a pan-active histone deacetylase inhibitor, while on prophylactic dapsone., Vorinostat is the most advanced HDAC inhibitor that entered clinical trials in glioblastoma, showing activity in recurrent disease. Multiple phase II trials with vorinostat in combination with targeted agents, temozolomide and radiotherapy are currently recruiting. , . On the basis of the results of this phase II study, further evaluation of the vorinostat-bortezomib combination in GBM patients in this dose and schedule is not recommended., ith the increased toxicities associated with CPT-11 coupled with its unclear clinical significance, investigating the efficacy of vorinostat combined with bevacizumab alone may represent a more promising strategy to evaluate in the context of a phase II clinical trial., CONCLUSION: Vorinostat in combination with temozolomide is well tolerated in patients with HGG. A phase I/II trial of vorinostat with radiotherapy and concomitant TMZ in newly diagnosed glioblastoma is underway.[SEP]Relations: Vorinostat has relations: drug_effect with Cholecystitis, drug_effect with Cholecystitis, drug_effect with Erythroderma, drug_effect with Erythroderma, drug_effect with T-cell lymphoma, drug_effect with T-cell lymphoma, drug_drug with Entinostat, drug_drug with Entinostat, drug_effect with Xerostomia, drug_effect with Xerostomia.", "label": "no"}
{"id": "converted_4540", "sentence1": "Do only changes in coding regions of MEF2C cause developmental disorders?", "sentence2": "Non-coding region variants upstream of MEF2C cause severe developmental disorder through three distinct loss-of-function mechanisms., Clinical genetic testing of protein-coding regions identifies a likely causative variant in only around half of developmental disorder (DD) cases. The contribution of regulatory variation in non-coding regions to rare disease, including DD, remains very poorly understood. We screened 9,858 probands from the Deciphering Developmental Disorders (DDD) study for de novo mutations in the 5' untranslated regions (5' UTRs) of genes within which variants have previously been shown to cause DD through a dominant haploinsufficient mechanism. We identified four single-nucleotide variants and two copy-number variants upstream of MEF2C in a total of ten individual probands. We developed multiple bespoke and orthogonal experimental approaches to demonstrate that these variants cause DD through three distinct loss-of-function mechanisms, disrupting transcription, translation, and/or protein function. These non-coding region variants represent 23% of likely diagnoses identified in MEF2C in the DDD cohort, but these would all be missed in standard clinical genetics approaches. Nonetheless, these variants are readily detectable in exome sequence data, with 30.7% of 5' UTR bases across all genes well covered in the DDD dataset. Our analyses show that non-coding variants upstream of genes within which coding variants are known to cause DD are an important cause of severe disease and demonstrate that analyzing 5' UTRs can increase diagnostic yield. We also show how non-coding variants can help inform both the disease-causing mechanism underlying protein-coding variants and dosage tolerance of the gene.[SEP]Relations: developmental disability has relations: disease_protein with MECP2, disease_protein with MECP2. MEF2C has relations: disease_protein with intellectual disability, disease_protein with intellectual disability, disease_protein with autism spectrum disorder, disease_protein with autism spectrum disorder, disease_protein with autism (disease), disease_protein with autism (disease), disease_protein with autism susceptibility 1, disease_protein with autism susceptibility 1.", "label": "no"}
{"id": "converted_1861", "sentence1": "Is treatment resistant depression related to vitamin B9?", "sentence2": "Suboptimal serum and red blood cell folate levels have been associated with a poorer response to antidepressant therapy, a greater severity of symptoms, later onset of clinical improvement, and overall treatment resistance. This article reviews the evidence for L-methylfolate and folic acid as antidepressive agents in depression and discusses their clinical use, Although further randomized controlled trials in this area appear warranted, SAMe and L-methylfolate may represent a useful addition to the AD armamentarium., Patients with depression have consistently been found to have lower levels of serum and red blood cell folate than normal or nondepressed psychiatric patients. Decreased folate levels have been associated with lowered response rates to standard antidepressant pharmacotherapy. Recent studies have shown that augmentation with a folate supplement increases medication response in both treatment-naïve and treatment-resistant depressed patients irrespective of whether there is folate deficiency., Depressed patients with both low and normal folate levels may benefit from augmenting a primary antidepressant medication either initially, at the onset of treatment, or later after some degree of treatment resistance has been recognized., The results of this study suggest that intake of vitamin B9 may modulate the total score of Center for Epidemiological Studies Depression Scale (CES-D) and two subscales of the CES-D including depressive affect and interpersonal difficulties., The results of this study suggest that intake of vitamin B9 may modulate the total score of Center for Epidemiological Studies Depression Scale (CES-D) and two subscales of the CES-D including depressive affect and interpersonal difficulties. , This article reviews the metabolic and clinical importance of folate, vitamin B12, and SAMe, as well as clinical trials in relation to depression and dementia, In particular, vitamins B1, B3, B6, B9 and B12 are essential for neuronal function and deficiencies have been linked to depression.[SEP]Relations: Folic acid has relations: drug_drug with Amphotericin B, drug_drug with Amphotericin B, contraindication with diabetes mellitus (disease), contraindication with diabetes mellitus (disease), drug_drug with Blonanserin, drug_drug with Blonanserin, drug_drug with Brincidofovir, drug_drug with Brincidofovir. Thiamine has relations: drug_protein with SLC19A2, drug_protein with SLC19A2.", "label": "yes"}
{"id": "converted_579", "sentence1": "Is there any link between the aurora B kinase and the polycomb protein ring1B?", "sentence2": "The aurora B kinase and the polycomb protein ring1B combine to regulate active promoters in quiescent lymphocytes., We show that the Aurora B kinase and the polycomb protein Ring1B have essential roles in regulating transcriptionally active genes in quiescent lymphocytes. Ring1B and Aurora B bind to a wide range of active promoters in resting B and T cells. Conditional knockout of either protein results in reduced transcription and binding of RNA Pol II to promoter regions and decreased cell viability. Aurora B phosphorylates histone H3S28 at active promoters in resting B cells as well as inhibiting Ring1B-mediated ubiquitination of histone H2A and enhancing binding and activity of the USP16 deubiquitinase at transcribed genes. Our results identify a mechanism for regulating transcription in quiescent cells that has implications for epigenetic regulation of the choice between proliferation and quiescence., We show that the Aurora B kinase and the polycomb protein Ring1B have essential roles in regulating transcriptionally active genes in quiescent lymphocytes., We show that the Aurora B kinase and the polycomb protein Ring1B have essential roles in regulating transcriptionally active genes in quiescent lymphocytes. Ring1B and Aurora B bind to a wide range of active promoters in resting B and T cells. Conditional knockout of either protein results in reduced transcription and binding of RNA Pol II to promoter regions and decreased cell viability. , We show that the Aurora B kinase and the polycomb protein Ring1B have essential roles in regulating transcriptionally active genes in quiescent lymphocytes. Ring1B and Aurora B bind to a wide range of active promoters in resting B and T cells.[SEP]Relations: Protein S human has relations: drug_drug with Peginterferon alfa-2b, drug_drug with Peginterferon alfa-2b, drug_drug with Cepeginterferon alfa-2B, drug_drug with Cepeginterferon alfa-2B, drug_drug with Interferon alfa-2b, drug_drug with Interferon alfa-2b. histone H2A acetylation has relations: bioprocess_protein with MORF4L1, bioprocess_protein with MORF4L1, bioprocess_protein with RUVBL1, bioprocess_protein with RUVBL1.", "label": "yes"}
{"id": "converted_2005", "sentence1": "Is Doxorubicin cardiotoxic?", "sentence2": "Doxorubicin (DOXO) is widely used to treat solid tumors. However, its clinical use is limited by side effects including serious cardiotoxicity due to cardiomyocyte damage. , The results provide direct evidence for the role of catalase in doxorubicin cardiotoxic responses., These results do not support the possibility that mitomycin C potentiates the acute cardiotoxic effects produced by doxorubicin., The anthracycline chemotherapeutic agent doxorubicin is converted by the enzyme carbonyl reductase 1 (CBR1) into its cardiotoxic metabolite doxorubicinol, The clinical efficiency of the highly potent antitumor agent doxorubicin is limited by cardiotoxic effects, Doxorubicin (DOX), a highly active chemotherapeutic drug, faces limitations in clinical application due to severe cardiotoxic effects (mainly through increased oxidative stress), Clinical uses of doxorubicin (DOX), a highly active anticancer agent, are limited by its severe cardiotoxic side effects associated with increased oxidative stress and apoptosis, Doxorubicin (DOX) and trastuzumab (TRZ) are highly effective chemotherapeutic agents in the breast cancer setting, limited by their cardiotoxic side effects, Twisting and ironing: doxorubicin cardiotoxicity by mitochondrial DNA damage., Cardiotoxic effects were reported in 15 (5%) of 291 children receiving treatment including doxorubicin., On the other hand, pretreatment of rats with hesperidin protected cardiac tissues against the cardiotoxic effects of doxorubicin as evidenced from amelioration of histopathological changes and normalization of cardiac biochemical parameters.Hesperidin may have a protective effect against DOX-induced cardiotoxicity., However, with cumulative doses, doxorubicin also is known to have cardiotoxic effects, including cardiomyopathy and heart failure., Methods of reducing or preventing doxorubicin-induced cardiotoxicity have been suggested, including an investigational doxorubicin analog, mitoxantrone ( Novantrone )., The most cardiotoxic drug, doxorubicin, is the most potent inducer of superoxide generation, while epirubicin, which is less cardiotoxic, has a relatively limited effect on superoxide production., The mechanism of doxorubicin cardiotoxicity is likely multifactorial and most importantly, the genetic factors predisposing to doxorubicin cardiotoxicity are unknown., As doxorubicin cardiotoxicity is considered irreversible, early detection of cardiotoxicity and prevention of overt heart failure is essential., Although there are monitoring guidelines for cardiotoxicity, optimal timing for early detection of subclinical doxorubicin cardiotoxicity is still obscure., Quercetin attenuates doxorubicin cardiotoxicity by modulating Bmi-1 expression., However, doxorubicin cardiotoxicity of the heart has largely limited its clinical use., Mitochondrial topoisomerase I (top1mt) is a novel limiting factor of doxorubicin cardiotoxicity., Doxorubicin-based chemotherapy induces cardiotoxicity, which limits its clinical application., he clinical use of doxorubicin (DOX) and other anthracyclines is limited by a dosage-dependent cardiotoxicity, which can lead to cardiomyopathy. , Besides its cardiotoxic effect, doxorubicin also elicits inflammatory effects in vivo. 7-Monohydroxyethylrutoside (monoHER) has recently been used as a protector against doxorubicin-induced cardiotoxicity in vivo., Doxorubicin is an effective antineoplastic agent, but it frequently causes dose-related cardiotoxic effects. , Among these analogs, idarubicin (4-demethoxy-daunorubicin) was shown to be less cardiotoxic than doxorubicin i, Verapamil has also been suggested to potentiate the cardiotoxicity of doxorubicin. , Doxorubicin treatment is associated with both acute and chronic cardiotoxicity. , cardiac effects of diclofenac sodium on doxorubicin-induced cardiomyopathy in rats[SEP]Relations: Doxorubicin has relations: drug_effect with Cardiogenic shock, drug_effect with Cardiogenic shock, drug_effect with Cardiomyopathy, drug_effect with Cardiomyopathy, contraindication with cardiomyopathy, contraindication with cardiomyopathy, drug_effect with Cardiomegaly, drug_effect with Cardiomegaly, drug_drug with Epirubicin, drug_drug with Epirubicin.", "label": "yes"}
{"id": "converted_3003", "sentence1": "Is verubecestat effective for Alzheimer’s Disease?", "sentence2": " The lack of efficacy of verubecestat in mild-to-moderate AD raises important questions about the timing of intervention with BACE-1 inhibitors, and anti-amyloid therapies in general, in AD treatment., This reaction was applied to the preparation of verubecestat, which is currently undergoing clinical evaluation for the treatment of Alzheimer's disease., Verubecestat is an inhibitor of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) being evaluated in clinical trials for the treatment of Alzheimer's disease. , CONCLUSIONS: Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events. , Randomized Trial of Verubecestat for Mild-to-Moderate Alzheimer's Disease.Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events. , CONCLUSIONS\nVerubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events., Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events.[SEP]Relations: familial Alzheimer disease has relations: disease_disease with Alzheimer disease, disease_disease with Alzheimer disease, disease_disease with inherited prion disease, disease_disease with inherited prion disease, disease_protein with PRNP, disease_protein with PRNP, disease_phenotype_positive with Sleep disturbance, disease_phenotype_positive with Sleep disturbance, disease_phenotype_positive with Perseveration, disease_phenotype_positive with Perseveration.", "label": "no"}
{"id": "converted_2", "sentence1": "Is the protein Papilin secreted?", "sentence2": "Using expression analysis, we identify three genes that are transcriptionally regulated by HLH-2: the protocadherin cdh-3, and two genes encoding secreted extracellular matrix proteins, mig-6/papilin and him-4/hemicentin. , We found that mig-6 encodes long (MIG-6L) and short (MIG-6S) isoforms of the extracellular matrix protein papilin, each required for distinct aspects of DTC migration. Both MIG-6 isoforms have a predicted N-terminal papilin cassette, apilins are homologous, secreted extracellular matrix proteins which share a common order of protein domains. , The TSR superfamily is a diverse family of extracellular matrix and transmembrane proteins, many of which have functions related to regulating matrix organization, cell-cell interactions and cell guidance. This review samples some of the contemporary literature regarding TSR superfamily members (e.g. F-spondin, UNC-5, ADAMTS, papilin, and TRAP) where specific functions are assigned to the TSR domains., Papilins are extracellular matrix proteins , Papilin is an extracellular matrix glycoprotein ,  Collagen IV, laminin, glutactin, papilin, and other extracellular matrix proteins were made primarily by hemocytes and were secreted into the medium. , A sulfated glycoprotein was isolated from the culture media of Drosophila Kc cells and named papilin.[SEP]Relations: ADAMTS4 has relations: anatomy_protein_present with saliva-secreting gland, anatomy_protein_present with saliva-secreting gland, protein_protein with ITPA, protein_protein with ITPA, protein_protein with ACAN, protein_protein with ACAN, protein_protein with TIMP3, protein_protein with TIMP3. extracellular matrix has relations: cellcomp_protein with PAPLN, cellcomp_protein with PAPLN.", "label": "yes"}
{"id": "converted_74", "sentence1": "Do patients with Pendred syndrome present congenital deafness?", "sentence2": "Pendred Syndrome can be characterized by the triad composed of familial goitre, abnormal perchlorate discharge and congenital deafness., Pendred syndrome is an autosomal recessive disorder characterized by congenital deafness and goiter. , Pendred syndrome comprises congenital sensorineural hearing loss, thyroid goiter, and positive perchlorate discharge test. , The cause of the congenital deafness in Pendred syndrome is obscure, although a Mondini type malformation of the cochlea exists in some patients., Pendred syndrome is an autosomal recessive disorder characterized by congenital deafness and goiter., Pendred syndrome is the autosomal recessively transmitted association of familial goiter and congenital deafness., Pendred syndrome (PDS) is an autosomal recessive disorder characterized by congenital deafness, goiter and iodide organification defect., Pendred syndrome is a recessively inherited disorder with the hallmark features of congenital deafness and thyroid goitre., Pendred syndrome, a common autosomal-recessive disorder characterized by congenital deafness and goiter, is caused by mutations of SLC26A4, which codes for pendrin., These studies provide compelling evidence that defects in pendrin cause Pendred syndrome thereby launching a new area of investigation into thyroid physiology, the pathogenesis of congenital deafness and the role of altered sulphate transport in human disease., Mutations in the Pendred syndrome gene have been observed in patients with deafness and vestibular aqueduct dilatation, in the absence of other Pendred syndrome features., The occurrence of congenital deafness, mutism and goitre unassociated with cretinism or mental retardation in euthyroid patients is known as Pendred's Syndrome., The autosomal recessive Pendred's syndrome is defined by congenital sensorineural deafness, goiter, and impaired iodide organification., Pendred's syndrome is an autosomal recessive disease characterized by goiter, impaired iodide organification, and congenital sensorineural deafness., Pendred syndrome is an autosomal recessive disorder characterized by congenital sensorineural deafness, goiter, and impaired iodide organification., Pendred's syndrome is manifested by congenital sensorineural deafness in association with familial goiter due to defective organic binding of iodine in the thyroid gland., Although the textbook view of the Pendred syndrome is that of an autosomal recessive condition characterised by deafness and goitre, it is increasingly clear that not all patients present this classical clinical description., Pendred's syndrome may account for up to 10% of the cases with hereditary hearing loss, and pendrin mutations have also been found in a kindred with non-syndromic deafness., Pendred syndrome comprises the association of severe congenital sensorineural deafness with thyroid pathology., The first one is named Pendred Syndrome (PS) when deafness is associated with thyroid goiter; the second is called DFNB4, when no other symptoms are present., Pendred syndrome is an autosomal recessive disorder characterized by sensorineural deafness, a partial defect in iodide organification, and dyshormonogenetic goiter., Pendred syndrome and non-syndromic recessive deafness associated with enlarged vestibular aqueduct (NSRD with EVA) are caused by mutations in the SLC26A4 (PDS) gene., Although the textbook view of Pendred syndrome is that of an autosomal recessive condition characterized by deafness and goitre, it is increasingly clear that not all such patients present this classical clinical picture. , The occurrence of congenital deafness, mutism and goitre unassociated with cretinism or mental retardation in euthyroid patients is known as Pendred's Syndrome. , The cause of the congenital deafness in Pendred syndrome is obscure, although a Mondini type malformation of the cochlea exists in some patients. , The discovery of mutations in the SLC26A4 gene in patients with Pendred syndrome (congenital deafness, goiter, and defective iodide organification) suggested a possible role for the encoded protein, pendrin, as an apical iodide transporter. , Pendred syndrome is a recessively inherited disorder with the hallmark features of congenital deafness and thyroid goitre. , Pendred&apos;s syndrome is manifested by congenital sensorineural deafness in association with familial goiter due to defective organic binding of iodine in the thyroid gland. The majority of patients with Pendred&apos;s syndrome are euthyroid. We report on an unusual case of a patient with Pendred&apos;s syndrome presenting with amenorrhea and late-onset hypothyroidism.,  Although the textbook view of Pendred syndrome is that of an autosomal recessive condition characterized by deafness and goitre, it is increasingly clear that not all such patients present this classical clinical picture. Malformations of the inner ear, specifically enlargement of the vestibular aqueduct, are common in Pendred syndrome and mutations in the PDS (Pendred Syndrome) gene have been recorded in patients presenting with deafness and vestibular aqueduct dilatation only, without other features of Pendred syndrome., The occurrence of congenital deafness, mutism and goitre unassociated with cretinism or mental retardation in euthyroid patients is known as Pendred&apos;s Syndrome. It has been estimated that 4-10 % of children with congenital deafness suffer from this condition., Malformations of the inner ear, specifically enlargement of the vestibular aqueduct, are common in Pendred syndrome and mutations in the PDS (Pendred Syndrome) gene have been recorded in patients presenting with deafness and vestibular aqueduct dilatation only, without other features of Pendred syndrome. Since this is the most common radiological malformation of the cochlea in deaf patients, we investigated what proportion of such cases were due to mutation of the PDS gene., Although the textbook view of Pendred syndrome is that of an autosomal recessive condition characterized by deafness and goitre, it is increasingly clear that not all such patients present this classical clinical picture. Malformations of the inner ear, specifically enlargement of the vestibular aqueduct, are common in Pendred syndrome and mutations in the PDS (Pendred Syndrome) gene have been recorded in patients presenting with deafness and vestibular aqueduct dilatation only, without other features of Pendred syndrome.[SEP]Relations: Pendred syndrome has relations: disease_disease with syndromic genetic deafness, disease_disease with syndromic genetic deafness, disease_phenotype_positive with Congenital sensorineural hearing impairment, disease_phenotype_positive with Congenital sensorineural hearing impairment, disease_phenotype_positive with Neurological speech impairment, disease_phenotype_positive with Neurological speech impairment, disease_disease with syndromic hypothyroidism, disease_disease with syndromic hypothyroidism. Congenital sensorineural hearing impairment has relations: disease_phenotype_positive with Pendred syndrome, disease_phenotype_positive with Pendred syndrome.", "label": "yes"}
{"id": "converted_3280", "sentence1": "Is Protoporphyrinogen oxidase localized to the mitochondrium?", "sentence2": "We showed that 28 amino acids in the amino terminus of PPOX contain an independently functioning signal for mitochondrial targeting., Based on our results we propose a mechanism for protoporphyrinogen oxidase targeting to the mitochondrion., Mitochondrial targeting of human protoporphyrinogen oxidase., In the present study, PfPPO has been cloned, expressed and shown to be localized to the mitochondrion by immunofluorescence microscopy. [SEP]Relations: Mitochondrial inheritance has relations: disease_phenotype_positive with mitochondrial myopathy with reversible cytochrome C oxidase deficiency, disease_phenotype_positive with mitochondrial myopathy with reversible cytochrome C oxidase deficiency, disease_phenotype_positive with cytochrome-c oxidase deficiency disease, disease_phenotype_positive with cytochrome-c oxidase deficiency disease, disease_phenotype_positive with striatonigral degeneration, disease_phenotype_positive with striatonigral degeneration, disease_phenotype_positive with ophthalmoplegic neuromuscular disorder with abnormal mitochondria, disease_phenotype_positive with ophthalmoplegic neuromuscular disorder with abnormal mitochondria, disease_phenotype_positive with Kearns-Sayre syndrome, disease_phenotype_positive with Kearns-Sayre syndrome.", "label": "yes"}
{"id": "converted_3970", "sentence1": "Does erenumab target the calcitonin gene-related peptide?", "sentence2": "Four monoclonal antibodies have been developed: one targeting the calcitonin gene-related peptide receptor (erenumab) and three targeting the calcitonin gene-related peptide (eptinezumab, fremanezumab, and galcanezumab).[SEP]Relations: CALCRL has relations: drug_protein with Erenumab, drug_protein with Erenumab, molfunc_protein with calcitonin gene-related peptide receptor activity, molfunc_protein with calcitonin gene-related peptide receptor activity, bioprocess_protein with calcitonin gene-related peptide receptor signaling pathway, bioprocess_protein with calcitonin gene-related peptide receptor signaling pathway. Human calcitonin has relations: drug_protein with ANPEP, drug_protein with ANPEP, drug_effect with Erythema, drug_effect with Erythema.", "label": "no"}
{"id": "converted_4408", "sentence1": "Does UBE4B promote renal cancer?", "sentence2": "UBE4B might act as an oncogene in regulating RCC development. Therefore it could be served as an effective indicator to predict OS and a potential biomarker for targeted therapy of RCC patients.[SEP]Relations: UBE4B has relations: anatomy_protein_present with kidney, anatomy_protein_present with kidney, protein_protein with UBC, protein_protein with UBC, protein_protein with UBE2C, protein_protein with UBE2C, anatomy_protein_present with renal glomerulus, anatomy_protein_present with renal glomerulus, protein_protein with UBE2V1, protein_protein with UBE2V1.", "label": "yes"}
{"id": "converted_1139", "sentence1": "Are ACTA1 (alpha actin) and NEB (nebulin) genes related to nemaline myopathy?", "sentence2": "Nemaline myopathy (NM) is a group of congenital myopathies, characterized by the presence of distinct rod-like inclusions \"nemaline bodies\" in the sarcoplasm of skeletal muscle fibers. To date, ACTA1, NEB, TPM3, TPM2, TNNT1, and CFL2 have been found to cause NM., Nemaline myopathy (NM) is the most common congenital myopathy and is caused by mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3 (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin). 20-25% of NM cases carry ACTA1 defects and these particular mutations usually induce substitutions of single residues in the actin protein. , Nemaline myopathy (NM) is a genetically and clinically heterogenous muscle disorder, which is myopathologically characterized by nemaline bodies. Mutations in six genes have been reported to cause NM: Nebulin (NEB Pelin 1999), alpha-skeletal muscle actin (ACTA1 Nowak 1999), alpha-slow tropomyosin (TPM3 Laing 1995), beta-tropomyosin (TPM2 Donner 2002), slow troponin T (TNNT1 Johnston 2000) and cofilin 2 (CFL2 Agrawal 2007). The majority of cases are due to mutation in NEB and ACTA1. , Nemaline myopathy is a heterogenous form of congenital myopathy characterised by a variable spectrum of clinical features, predominated in the severe form by profound muscle hypotonia and weakness accompanied by respiratory insufficiency. The clinical variability, with differing age of onset and severity of symptoms makes the diagnosis of nemaline myopathy difficult in some cases. Severe forms of nemaline myopathy may be caused by mutation of a number of different genes: skeletal muscle actin (ACTA1), nebulin (NEB) and alpha-tropomyosin (TPM3), all of which encode components of the sarcomeric thin filaments of skeletal muscle. , Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes. , We report muscle MRI findings of 10 patients from 8 families with nemaline myopathy. Patients with involvement of the nebulin (NEB) gene showed a consistent pattern of selective muscle involvement corresponding to clinical severity., Patients with nemaline myopathy secondary to mutations in the skeletal muscle alpha-actin (ACTA1) gene showed diffuse involvement of thigh and leg muscles with relative sparing of the gastrocnemii., Congenital myopathies are clinical and genetic heterogeneous disorders characterized by skeletal muscle weakness ranging in severity. Three major forms have been identified: actin myopathy, intranuclear rod myopathy, and nemaline myopathy. Nemaline myopathy is the most common of these myopathies and is further subdivided into seven groups according to severity, progressiveness, and age of onset. At present, five genes have been linked to congenital myopathies. These include alpha-actin (ACTA1), alpha- and beta-tropomyosin (TPM3 and TPM2), troponin T (TNNT1), and nebulin (NEB). , Nemaline myopathy is a structural congenital myopathy which may show both autosomal dominant and autosomal recessive inheritance patterns. Mutations in three different genes have been identified as the cause of nemaline myopathy: the gene for slow alpha-tropomyosin 3 (TPM3) at 1q22-23, the nebulin gene (NEB) at 2q21.1-q22, and the actin gene (ACTA1) at 1q42., Nemaline myopathy is a clinically and genetically heterogeneous condition. The clinical spectrum ranges from severe cases with antenatal or neonatal onset and early death to late onset cases with only slow progression. Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42. , Nemaline myopathy (NM) is the most common congenital myopathy and is caused by mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3 (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin)., Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42., Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1)., Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes., Severe forms of nemaline myopathy may be caused by mutation of a number of different genes: skeletal muscle actin (ACTA1), nebulin (NEB) and alpha-tropomyosin (TPM3), all of which encode components of the sarcomeric thin filaments of skeletal muscle., Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1)., Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42., Mutations in three different genes have been identified as the cause of nemaline myopathy: the gene for slow alpha-tropomyosin 3 (TPM3) at 1q22-23, the nebulin gene (NEB) at 2q21.1-q22, and the actin gene (ACTA1) at 1q42., Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes, Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1), Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42, Nemaline myopathy (NM) is the most common congenital myopathy and is caused by mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3 (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin), Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1), Nemaline myopathy (NM) is the most common congenital myopathy and is caused by mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3 (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin), Mutations in three different genes have been identified as the cause of nemaline myopathy: the gene for slow alpha-tropomyosin 3 (TPM3) at 1q22-23, the nebulin gene (NEB) at 2q21.1-q22, and the actin gene (ACTA1) at 1q42, Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42, Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes, Severe forms of nemaline myopathy may be caused by mutation of a number of different genes: skeletal muscle actin (ACTA1), nebulin (NEB) and alpha-tropomyosin (TPM3), all of which encode components of the sarcomeric thin filaments of skeletal muscle[SEP]Relations: nemaline myopathy has relations: disease_protein with ACTA1, disease_protein with ACTA1, disease_disease with alpha-actinopathy, disease_disease with alpha-actinopathy, disease_protein with NEB, disease_protein with NEB, disease_disease with qualitative or quantitative defects of alpha-actin, disease_disease with qualitative or quantitative defects of alpha-actin. alpha-actinopathy has relations: disease_disease with nemaline myopathy, disease_disease with nemaline myopathy.", "label": "yes"}
{"id": "converted_2561", "sentence1": "Has intepirdine been evaluated in clinical trials? (November 2017)", "sentence2": "Using small molecules blocking 5-HT6serotonin receptor (intepirdine), inhibiting BACE activity (E2609, AZD3293, and verubecestat), or reducing tau aggregation (TRx0237) are also currently in Phase III clinical trials.[SEP]", "label": "yes"}
{"id": "converted_2391", "sentence1": "Does the association of PARP1 and CTCF follow a circadian rhythm?", "sentence2": "here we uncovered an inter-chromosomal network connecting active loci enriched in circadian genes to repressed lamina-associated domains (LADs)., Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation, PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity., Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation. Furthermore, depletion of H3K9me2/3, inhibition of PARP activity by olaparib, or downregulation of PARP1 or CTCF expression counteracts both recruitment to the envelope and circadian transcription. PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity., transcriptionally active and inactive chromatin domains tend to segregate into separate sub nuclear compartments to maintain stable expression patterns however here we uncovered an inter chromosomal network connecting active loci enriched in circadian genes to repressed lamina associated domains lads the interactome is regulated by parp1 and its co factor ctcf they not only mediate chromatin fiber interactions but also promote the recruitment of circadian genes to the lamina synchronization of the circadian rhythm by serum shock induces oscillations in parp1 ctcf interactions which is accompanied by oscillating recruitment of circadian loci to the lamina followed by the acquisition of repressive h3k9me2 marks and transcriptional attenuation furthermore depletion of h3k9me2 3 inhibition of parp activity by olaparib or downregulation of parp1 or ctcf expression counteracts both recruitment to the envelope and circadian transcription parp1 and ctcf regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity., Synchronization of the circadian rhythm by serum shock induces oscillations in PARP1-CTCF interactions, which is accompanied by oscillating recruitment of circadian loci to the lamina, followed by the acquisition of repressive H3K9me2 marks and transcriptional attenuation.[SEP]Relations: Olaparib has relations: drug_protein with PARP1, drug_protein with PARP1, drug_protein with PARP3, drug_protein with PARP3, drug_protein with PARP2, drug_protein with PARP2, drug_drug with Peginterferon beta-1a, drug_drug with Peginterferon beta-1a, drug_drug with Parnaparin, drug_drug with Parnaparin.", "label": "yes"}
{"id": "converted_1377", "sentence1": "Is there a relation between ANP and transcapillary albumin escape?", "sentence2": "Thus, in a large ethnically homogeneous cohort of diabetic subjects, our data show: (1) a significant association of C708/T polymorphism with microalbuminuria in long-term diabetes and with both lower plasma ANP levels and widespread albumin leakage, hese results suggest a possible role of PND gene in conferring protection from nephropathy and microvascular damage in type 1 diabetes., Moreover, the increased susceptibility of the glomerular capillaries in diabetics to ANP seems to be part of a more generalized capillary abnormality, because ANP also increases the transcapillary escape of albumin., In summary, low dose ANP infusion in healthy subjects caused a shift of plasma water and electrolytes from the circulation, with albumin escape as a secondary phenomenon.[SEP]Relations: Albuminuria has relations: drug_effect with Entacapone, drug_effect with Entacapone, drug_effect with Epirubicin, drug_effect with Epirubicin, drug_effect with Allopurinol, drug_effect with Allopurinol, drug_effect with Sibutramine, drug_effect with Sibutramine, drug_effect with Mycophenolic acid, drug_effect with Mycophenolic acid.", "label": "yes"}
{"id": "converted_87", "sentence1": "Can Levoxyl (levothyroxine sodium) cause insomnia?", "sentence2": "METHODS: Seventy-one patients diagnosed with primary hypothyroidism were randomly allocated into two study groups: the first group received usual dose of levothyroxine and the second group received combination of levothyroxine and liothyronine for at least 4 months. The main outcomes were psychosocial problems (Goldberg's General Health Questionnaire, GHQ-28), bodyweight, heart rate, blood pressure, and serum lipid levels. RESULTS: In both groups serum thyroid-stimulating hormone levels remained unchanged compared with baseline. Psychosocial scores, body weight, heart rate, blood pressure, and lipid profile in the two groups remained constant. The only exception was a small but significant reduction in anxiety/insomnia in combined treatment group as compared with monotherapy. [SEP]Relations: Levothyroxine has relations: drug_effect with Alopecia, drug_effect with Alopecia, drug_drug with Omeprazole, drug_drug with Omeprazole, drug_effect with Coma, drug_effect with Coma, drug_effect with Dyspnea, drug_effect with Dyspnea, drug_effect with Arrhythmia, drug_effect with Arrhythmia.", "label": "yes"}
{"id": "converted_1754", "sentence1": "Could BRCA gene test used for breast and ovarian cancer risk?", "sentence2": "Participation of Korean families at high risk for hereditary breast and ovarian cancer in BRCA1/2 genetic testing., The prevalence of BRCA1/2 mutations in Korean ovarian cancer patients irrespective of the family history was significantly higher than previously reported. Possible founder mutations in Korean ovarian cancer patients were identified., Germline Mutations of BRCA1 and BRCA2 in Korean Ovarian Cancer Patients: Finding Founder Mutations., The assessment of BRCA1 and BRCA2 coding sequences to identify pathogenic mutations associated with inherited breast/ovarian cancer syndrome has provided a method to identify high-risk individuals, allowing them to seek preventative treatments and strategies. , Maximising survival: the main concern of women with hereditary breast and ovarian cancer who undergo genetic testing for BRCA1/2.,  Little is known about how women with hereditary breast and/or ovarian cancer who test positive for a BRCA gene manage the impact of a positive test result on their everyday lives and in the longer term. This study defined the experience and needs of women with hereditary breast and ovarian cancer and a positive BRCA test over time., The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 × 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3))., Female BRCA (breast cancer gene)-1 and BRCA-2 mutations are significantly associated with risk of developing breast and ovarian cancers, in turn, associated with female infertility. , Large BRCA1 and BRCA2 genomic rearrangements in Polish high-risk breast and ovarian cancer families., BRCA1 and BRCA2 are two major genes associated with familial breast and ovarian cancer susceptibility., Until 2006, she supervised a diagnostic unit for BRCA gene testing at the Interdisciplinary Center for Hereditary Breast Cancer (Max Delbrück Center, Berlin, Germany). , Inherited BRCA gene mutations convey a high risk for breast and ovarian cancer, but current guidelines limit BRCA mutation testing to women with early-onset cancer and relatives of mutation-positive cases. , Women who carry a BRCA1 or BRCA2 gene mutation face a risk of developing breast or ovarian cancer at an earlier age than women without such a mutation., In 2006, participants were recruited from Web sites for women with breast cancer or BRCA gene mutations. , About 20 % of hereditary breast cancers are caused by mutations in BRCA1 and BRCA2 genes. Since BRCA1 and BRCA2 mutations may be spread throughout the gene, genetic testing is usually performed by direct sequencing of entire coding regions., Suggestion of an association between BRCA2 c.7806-2A>G and risk of breast cancer in males has emerged. , The presence of deleterious mutations in breast cancer (BRCA)-1 or BRCA-2 gene has a decisive influence on the development of various types of neoplasms, such as breast, ovarian, tubal, and peritoneal cancers. , OBJECTIVE: Female BRCA (breast cancer gene)-1 and BRCA-2 mutations are significantly associated with risk of developing breast and ovarian cancers, in turn, associated with female infertility., BRCA1 and BRCA2 genes are responsible for 5-10% of breast and ovarian cancer cases., She was daughter of a woman, a carrier of BRCA 1 gene mutation, with early onset of breast cancer and positive family history.CONCLUSIONS: BRCA 1 and BRCA 2 gene mutations are of particular importance in the increasing risk of ovarian cancer and early onset of breast cancer as well as some other malignancies., BACKGROUND: Women who are diagnosed with a deleterious mutation in either breast cancer (BRCA) gene have a high risk of developing breast and ovarian cancers at young ages., We identified AJ individuals with breast and/or ovarian cancer undergoing hereditary breast/ovarian cancer risk assessment since 2006 without evidence of a deleterious mutation on BRCA gene sequencing who were screened for major gene rearrangements in BRCA1 and BRCA2., Germline BRCA gene mutations are reportedly associated with hereditary breast and ovarian cancers., [Detection and occurrence of BRCA 1 gene mutation in patients with carcinoma of the breast and ovary]., We investigated the relationship between BRCA mutations and the distribution of familial cancers other than breast or ovary in high-risk breast cancer patients.PATIENTS WITH BREAST CANCER WHO HAD AT LEAST ONE OF THE FOLLOWING RISK FACTORS WERE ENROLLED: reported family history of breast or ovarian cancer; 40 years of age or younger age at diagnosis; bilateral breast cancer; or male gender, Mutations in breast cancer susceptibility genes (BRCA1 and BRCA2) are associated with increased risks for breast, ovarian, and other types of cancer.To review new evidence on the benefits and harms of risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women.MEDLINE and PsycINFO between 2004 and 30 July 2013, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews from 2004 through the second quarter of 2013, Health Technology Assessment during the fourth quarter of 2012, Scopus, and reference lists.English-language studies about accuracy of risk assessment and benefits and harms of genetic counseling, genetic testing, and interventions to reduce cancer incidence and mortality., The objective of this study was to assess the incidence of primary breast cancer (PBC) and contralateral breast cancer (CBC) in patients who had BRCA1/BRCA2-associated epithelial ovarian cancer (OC).From the database of the Rotterdam Family Cancer Clinic, patients who had BRCA-associated OC without a history of unilateral breast cancer (BC) (at risk of PBC; n = 79) or with a history of unilateral BC (at risk of CBC; n = 37) were selected, Statistically significant earlier ages at diagnosis also were observed within subgroups of BRCA1 and BRCA2 mutations, maternal inheritance, paternal inheritance, breast cancer only, and breast cancer-identified and ovarian cancer-identified families.Breast and ovarian cancers in BRCA mutation carriers appeared to be diagnosed at an earlier age in later generations, The USPSTF also reviewed interventions aimed at reducing the risk for BRCA-related cancer in women with potentially harmful BRCA mutations, including intensive cancer screening, medications, and risk-reducing surgery.This recommendation applies to asymptomatic women who have not been diagnosed with BRCA-related cancer.The USPSTF recommends that primary care providers screen women who have family members with breast, ovarian, tubal, or peritoneal cancer with 1 of several screening tools designed to identify a family history that may be associated with an increased risk for potentially harmful mutations in breast cancer susceptibility genes (BRCA1 or BRCA2), If a woman bearing a mutation develops cancer in one breast, her risk of developing cancer in the other breast depends on the particular gene that is mutated and on her age at the onset of disease.About half of all monogenically determined carcinomas of the breast and ovary are due to a mutation in one or the other of the highly penetrant BRCA genes (BRCA1 and BRCA2), A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk.Mutations of BRCA1 or BRCA2.Breast and ovarian cancer risks.Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer, This study defined the experience and needs of women with hereditary breast and ovarian cancer and a positive BRCA test over time.METHODS: A grounded theory approach was taken using qualitative interviews (n = 49) and reflective diaries. , Little is known about how women with hereditary breast and/or ovarian cancer who test positive for a BRCA gene manage the impact of a positive test result on their everyday lives and in the longer term., This study defined the experience and needs of women with hereditary breast and ovarian cancer and a positive BRCA test over time.A grounded theory approach was taken using qualitative interviews (n = 49) and reflective diaries., Women with a harmful mutation in the BReast CAncer (BRCA) gene are at significantly increased risk of developing hereditary breast and ovarian cancer (HBOC) during their lifetime, compared to those without., Genetic testing for BRCA genes, associated with hereditary breast-ovarian cancer risk, is an accepted cancer control strategy., Younger patients, those with a family history of breast or ovarian cancer, and those diagnosed more recently were more likely to be BRCA tested., Mutations in BRCA genes elevate risk for breast and ovarian cancer., Observational studies of prophylactic surgeries report reduced risks for breast and ovarian cancer in mutation carriers.No data describe the range of risk associated with BRCA mutations, genetic heterogeneity, and moderating factors; studies conducted in highly selected populations contain biases; and information on adverse effects is incomplete.A primary care approach to screening for inherited breast and ovarian cancer susceptibility has not been evaluated, and evidence is lacking to determine benefits and harms for the general population., We identified AJ individuals with breast and/or ovarian cancer undergoing hereditary breast/ovarian cancer risk assessment since 2006 without evidence of a deleterious mutation on BRCA gene sequencing who were screened for major gene rearrangements in BRCA1 and BRCA2. For each proband, the pre-test probability of identifying a deleterious BRCA mutation was estimated using the Myriad II model. We identified 108 affected individuals who underwent large rearrangement testing (80 breast cancer, 19 ovarian cancer, nine both breast and ovarian cancer)., Truncated proteins are easily discriminated from full size.RESULTS: Three BRCA 1 gene alterations were identified in the investigated group of women suffering from ovarian or breast cancer. One asymptomatic person--carrier of BRCA 1 gene mutation--was identified in this study. She was daughter of a woman, a carrier of BRCA 1 gene mutation, with early onset of breast cancer and positive family history.CONCLUSIONS: BRCA 1 and BRCA 2 gene mutations are of particular importance in the increasing risk of ovarian cancer and early onset of breast cancer as well as some other malignancies., Germline BRCA gene mutations are reportedly associated with hereditary breast and ovarian cancers. Identification of BRCA mutations greatly improves the preventive strategies and management of breast cancer., Statistically significant earlier ages at diagnosis also were observed within subgroups of BRCA1 and BRCA2 mutations, maternal inheritance, paternal inheritance, breast cancer only, and breast cancer-identified and ovarian cancer-identified families.CONCLUSIONS: Breast and ovarian cancers in BRCA mutation carriers appeared to be diagnosed at an earlier age in later generations., Truncated proteins are easily discriminated from full size.RESULTS: Three BRCA 1 gene alterations were identified in the investigated group of women suffering from ovarian or breast cancer., However, some single risk factors without family histories (early-onset breast cancer, male breast cancer, or multiple organ cancers) may limit the utility of BRCA gene testing in the Korean population., BRCA Mutations Increase Fertility in Families at Hereditary Breast/Ovarian Cancer Risk., Because infertility is associated with breast and ovarian cancer risks, we hypothesized that the mutations in the BRCA gene may be associated with low response to fertility treatments., Moreover, in families of breast cancer patients without BRCA mutations, breast cancer risk depends on the patient's age at diagnosis., Among the 554 women who underwent genetic testing for BRCA mutation, 78 were found to have a deleterious mutation in the BRCA1 gene, and 54 had a mutation in the BRCA 2 gene., Frequent recurrent mutations in the breast and ovarian cancer susceptibility (BRCA) genes BRCA1 and BRCA2 among Hispanics, including a large rearrangement Mexican founder mutation (BRCA1 exon 9-12 deletion [ex9-12del]), suggest that an ancestry-informed BRCA-testing strategy could reduce disparities and promote cancer prevention by enabling economic screening for hereditary breast and ovarian cancer in Mexico., Individuals who carry a BRCA gene mutation have increased lifetime risks of developing hereditary breast and ovarian cancer syndrome-related cancers., BRCA gene mutations have been well described to carry an increased risk of both breast and ovarian cancer., Ovarian cancer among 8,005 women from a breast cancer family history clinic: no increased risk of invasive ovarian cancer in families testing negative for BRCA1 and BRCA2., Women who were BRCA carriers, women who had a history of breast cancer, DCIS, or breast biopsy, or had a family history of ovarian cancer were more likely to have undergone surgery for cancer risk reduction., Genetic testing for breast cancer susceptibility became a reality after two cancer predisposition genes, BRCA1 and BRCA2, were identified., Germline mutations in BRCA genes are associated with breast and ovarian cancer susceptibility., We used person-years at risk to assess ovarian cancer rates in the study population, subdivided by genetic status (BRCA1, BRCA2, BRCA negative, BRCA untested) compared with the general population.[SEP]Relations: carcinoma has relations: disease_protein with BRCA1, disease_protein with BRCA1. Breast carcinoma has relations: disease_phenotype_positive with ovarian cancer, disease_phenotype_positive with ovarian cancer, disease_phenotype_positive with hereditary breast ovarian cancer syndrome, disease_phenotype_positive with hereditary breast ovarian cancer syndrome, disease_phenotype_positive with breast-ovarian cancer, familial, susceptibility to, disease_phenotype_positive with breast-ovarian cancer, familial, susceptibility to, disease_phenotype_positive with hereditary breast carcinoma, disease_phenotype_positive with hereditary breast carcinoma.", "label": "yes"}
{"id": "converted_2236", "sentence1": "Is sonidegib effective for basal cell carcinoma?", "sentence2": "This review of the literature aims to describe previous and current treatment options for oral therapy in locally advanced and metastatic NMSC otherwise unamenable to standard treatment. Oral Smoothened (Smo) inhibitors Vismodegib, Sonidegib, and Taladegib have shown to be effective in several trials. , Sonidegib is a new smoothened inhibitor currently under investigation for treatment of laBCC, which demonstrates a comparable safety profile to vismodegib. , The recent development of novel hedgehog pathway inhibitors for high-risk BCC (including oral vismodegib and sonidegib) may represent a paradigm shift towards medical management of NMSC., Sonidegib (Odomzo®), an oral smoothened (SMO) antagonist, is indicated for the treatment of adults with locally advanced basal cell carcinoma (laBCC) who are not candidates for surgery or radiation therapy, or adults with recurrent laBCC following surgery or radiation therapy. , The acceptable benefit-risk profile of sonidegib, along with a paucity of treatment options and the seriousness of the condition, makes sonidegib an emerging option for the treatment of adults with laBCC that has recurred following surgery or radiation therapy, or in those who are not candidates for surgery or radiation therapy., Sonidegib phosphate: new approval for basal cell carcinoma., Sonidegib, a novel smoothened inhibitor for the treatment of advanced basal cell carcinoma., Serious adverse events occurred in 11 (14%) of 79 patients in the 200 mg group and 45 (30%) of 150 patients in the 800 mg group.The benefit-to-risk profile of 200 mg sonidegib might offer a new treatment option for patients with advanced basal cell carcinoma, a population that is difficult to treat.Novartis Pharmaceuticals Corporation.<CopyrightInformation>Copyright © 2015 Elsevier Ltd. All rights reserved.</, However, to date, Hh inhibitors, specifically those targeting Smoothened [such as vismodegib, BMS-833923, saridegib (IPI-926), sonidegib/erismodegib (LDE225), PF-04449913, LY2940680, LEQ 506, and TAK-441], have demonstrated good efficacy as monotherapy in patients with basal cell carcinoma and medulloblastoma, but have shown limited activity in other tumor types., The hedgehog pathway inhibitor sonidegib demonstrated meaningful tumor shrinkage in more than 90% of patients with locally advanced basal cell carcinoma (BCC) or metastatic BCC in the BCC Outcomes with LDE225 Treatment study.This report provides long-term follow-up data collected up to 12 months after the last patient was randomized.In this multicenter, randomized, double-blind phase II study, patients were randomized 1:2 to sonidegib 200 or 800 mg. The primary end point was objective response rate assessed by central review.Objective response rates in the 200- and 800-mg arms were 57.6% and 43.8% in locally advanced B, Serious adverse events occurred in 11 (14%) of 79 patients in the 200 mg group and 45 (30%) of 150 patients in the 800 mg group.The benefit-to-risk profile of 200 mg sonidegib might offer a new treatment option for patients with advanced basal cell carcinoma, a population that is difficult to treat.Novartis Pharmaceuticals Corporation.<CopyrightInformation>Copyright © 2015 Elsevier Ltd. All rights reserved.</C, Oral sonidegib is approved in Switzerland for the treatment of adult patients with advanced basal cell carcinoma (BCC) and in the US and EU for the treatment of adult patients with locally advanced BCC that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy., Sonidegib phosphate: new approval for basal cell carcinoma.[SEP]Relations: Sonidegib has relations: drug_drug with Carbamazepine, drug_drug with Carbamazepine, drug_drug with Carbomycin, drug_drug with Carbomycin, drug_drug with Afelimomab, drug_drug with Afelimomab. basal cell carcinoma has relations: contraindication with Methoxsalen, contraindication with Methoxsalen, disease_disease with carcinoma, disease_disease with carcinoma.", "label": "yes"}
{"id": "converted_8", "sentence1": "Has Denosumab (Prolia) been approved by FDA?", "sentence2": "Denosumab is a RANK-ligand antibody that was approved by the FDA in 2010 for the prevention of skeletal fractures in patients with bone metastases from solid tumors.,  The authors present the imaging findings and technical report of an attempted percutaneous vertebroplasty in the only patient found to be actively under treatment with denosumab after a retrospective review of the databank of patients with pathological fractures referred to the Department Radiology of the Ohio State University for percutaneous vertebroplasty (a total sample of 20 patients) since the FDA approval of denosumab (November 2010) until June of 2013 (a 30-month period)., On the basis of this data, the FDA approved denosumab for the treatment of patients whose GCTB is unresectable, or when surgery is likely to result in severe morbidity., Denosumab (Prolia®) is a fully human monoclonal antibody for RANKL, which selectively inhibits osteoclastogenesis, being recently approved for the treatment of postmenopausal osteoporosis in women at a high or increased risk of fracture by the FDA in the United Sates and by the European Medicines Agency in Europe since June 2010., Recent phase II clinical trials with denosumab in skeletally mature adolescents over age 12 years and adults with GCTB, have shown both safety and efficacy, leading to its accelerated US FDA approval on 13 June 2013. , Zoledronic acid (ZA), an intravenously administered bisphosphonate, and Denosumab, a subcutaneously administered inhibitor of nuclear factor B ligand (RANKL), have already been approved by Food and Drug Administration (FDA) for their use in treatment of bone metastases., These results led to the approval of denosumab by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA), for the prevention of SREs in adults with bone metastases from solid tumors, including breast cancer., Alendronate, risedronate, zoledronic acid, denosumab, and teriparatide are Food and Drug Administration (FDA)-approved therapeutic options. , Several of these therapies have recently been approved by the FDA to treat bone cancer pain (bisphosphonates, denosumab) and others are currently being evaluated in human clinical trials (tanezumab)., A fourth agent, denosumab (bone targeted therapy) was also recently approved by the FDA for patients with bone metastasis after showing a reduction in the occurrence of skeletal-related events. , AHRQ published an updated review in March 2012 that summarized the benefits and risks of osteoporosis medications in treatment and prevention of osteoporosis, including bisphosphonates (aledronate, risedronate, ibandronate, zoledronic acid), parathyroid hormone, teriparatide, calcitonin, estrogens (for prevention in postmenopausal women), selective estrogen receptor modulators (raloxifene), and denosumab(approved by the FDA in 2010). , Four new drugs have received U.S. Food and Drug Administration (FDA)-approval in 2010 and 2011: sipuleucel-T, an immunotherapeutic agent; cabazitaxel, a novel microtubule inhibitor; abiraterone acetate, a new androgen biosynthesis inhibitor; and denosumab, a bone-targeting agent. , Recently, the US FDA and the EMA approved denosumab (a fully human monoclonal antibody) to treat skeletal-related events in bone-metastatic prostate cancer., In addition to these new and emerging therapeutic agents, denosumab was approved for the prevention of skeletal complications in patients with bone metastases due to solid tumor malignancies, providing an alternative to zoledronic acid. , Recently, denosumab was FDA-approved for prevention of SREs in patients with bone metastases from solid tumors. , In the 2010s to date, an additional 3 antibodies (denosumab, belimumab, ipilimumab) have been approved and one antibody-drug conjugate (brentuximab vedotin) is undergoing regulatory review and may be approved in the US by August 30, 2011., We also review the evidence supporting the FDA's approval of denosumab (bone-targeted therapy) as a treatment option for men with CRPC and bony metastases. ,  It has been approved for clinical use by the FDA in the US and by the European Medicines Agency in Europe since June 2010 (trade name Prolia(™), Amgen, Thousand Oaks, CA, USA). , The fully human monoclonal antibody denosumab (Prolia(®)) has been recently approved by the European Medical Agency (EMEA) and the Food and Drug Administration (FDA) for the treatment of postmenopausal osteoporosis. , Raloxifene and denosumab are only FDA approved for postmenopausal osteoporosis., The new antiresorptive drug, denosumab, although FDA-approved only for postmenopausal women, has been shown in a study of men on ADT to increase bone density in spine, hip, and forearm and decrease vertebral fractures on x-ray. ,  Since then, an additional six human mAbs have received FDA approval: panitumumab, golimumab, canakinumab, ustekinumab, ofatumumab and denosumab. [SEP]Relations: Denosumab has relations: drug_drug with Erenumab, drug_drug with Erenumab, drug_drug with Avelumab, drug_drug with Avelumab, drug_drug with Fasinumab, drug_drug with Fasinumab, drug_drug with Siponimod, drug_drug with Siponimod, drug_drug with Conatumumab, drug_drug with Conatumumab.", "label": "yes"}
{"id": "converted_3799", "sentence1": "Can SMAD6 variants cause craniosynostosis?", "sentence2": "SMAD6 variants in craniosynostosis: genotype and phenotype evaluation., Enrichment of heterozygous missense and truncating SMAD6 variants was previously reported in nonsyndromic sagittal and metopic synostosis, and interaction of SMAD6 variants with a common polymorphism nearBMP2 (rs1884302) was proposed to contribute to inconsistent penetrance. We determined the occurrence of SMAD6 variants in all types of craniosynostosis, evaluated the impact of different missense variants on SMAD6 function, and tested independently whether rs1884302 genotype significantly modifies the phenotype.METHODS: We performed resequencing of SMAD6 in 795 unsolved patients with any type of craniosynostosis and genotyped rs1884302 in SMAD6-positive individuals and relatives. We examined the inhibitory activity and stability of SMAD6 missense variants.RESULTS: We found 18 (2.3%) different rare damaging SMAD6 variants, with the highest prevalence in metopic synostosis (5.8%) and an 18.3-fold enrichment of loss-of-function variants comparedwith gnomAD data (P < 10-7). Combined with eight additional variants, ≥20/26 were transmitted from an unaffected parent but rs1884302 genotype did not predict phenotype.CONCLUSION: Pathogenic SMAD6 variants substantially increase the risk of both nonsyndromic and syndromic presentations of craniosynostosis, especially metopic synostosis. Functional analysis is important to evaluate missense variants. Genotyping of rs1884302 is not clinically useful. Mechanisms to explain the remarkable diversity of phenotypes associated with SMAD6 variants remain obscure.[SEP]Relations: craniosynostosis Fontaine type has relations: disease_disease with craniosynostosis, disease_disease with craniosynostosis. Metopic synostosis has relations: disease_phenotype_positive with six2-related frontonasal dysplasia, disease_phenotype_positive with six2-related frontonasal dysplasia, disease_phenotype_positive with neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome due to 9q21 microdeletion, disease_phenotype_positive with neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome due to 9q21 microdeletion, disease_phenotype_positive with cranioectodermal dysplasia, disease_phenotype_positive with cranioectodermal dysplasia, disease_phenotype_positive with neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome due to a point mutation, disease_phenotype_positive with neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome due to a point mutation.", "label": "yes"}
{"id": "converted_462", "sentence1": "Does melanoma  occur in people of African origin ?", "sentence2": "ALM is the most common type of melanoma amongst Asians, Africans,, ALM develops on palmar, plantar, and subungual skin, and its biology is different from that of other cutaneous melanomas, where sunlight is the major known environmental determinant, We present four albinos with histologic diagnoses of skin cancer, Four Nigerian albinos (two men and two women) with skin cancer, The sites of the lesions included the head [squamous cell carcinoma (SCC) in two patients and basal cell carcinoma (BCC) in one patient] and the upper limb (melanoma, wenty-nine patients (18 males and 11 females) with skin cancer were identified, Kaposi sarcoma associated with HIV represented 81.8 percent of KS cases found. Squamous cell carcinoma (SCC) ranked second and malignant melanoma third, Earlier studies have shown frequent mutations in the BRAF and NRAS genes in cutaneous melanoma, but these alterations have not been examined in the rare category of melanoma from black Africans., In a series of melanomas from black Africans (n=26), only two BRAF mutations (8%) were found, both being different from the common T1799A substitution. Moreover, melanomas from black Africans exhibited mutations in NRAS exon 1 only (12%), whereas NRAS exon 2 mutations were predominant in melanomas from Caucasians. Thus, the frequencies of BRAF and NRAS mutations were particularly low in melanomas from black Africans, supporting a different pathogenesis of these tumors., Malignant melanoma (MM) remains a pediatric rarity world-wide, but perhaps more so in black Africans. To the best of our knowledge, the current report of MM in a two-and-a-half-year-old Nigerian who had a pre-existing congenital giant hairy nevus is probably the first (in an accessible literature) in a black African child., Malignant melanomas in black Africans are predominantly located on the lower extremities, Thus, our findings indicate that melanomas located on the lower extremities in black Africans show several features of aggressiveness; in particular, the proliferative activity was high, and p16 alterations was frequent as evidenced by loss of protein staining. Our findings also indicated that the diagnosis is delayed among black Africans., Africans with dark skin have a reduced risk of getting all types of skin cancer as compared with Caucasians, but the ratio of their incidence rates of cutaneous malignant melanoma to that of squamous cell carcinoma is larger than the corresponding ratio for Caucasians. (, Albino Africans, as compared with normally pigmented Africans, seem to have a relatively small risk of getting cutaneous malignant melanomas compared to nonmelanomas. This is probably also true for albino and normally pigmented Caucasians., Scant data exists on melanoma in blacks from Africa, The mean age at presentation of the 39 women and 24 men was 60.5 years (range of 30 to 85 years), with a peak incidence in the sixth decade. The foot was the most common site of disease (45 patients). Seven patients had subungual melanoma, seven had primary mucosal lesions, and in six, the primary lesion could not be found., The poor prognosis in black patients in South Africa is the result of delayed presentation with thick primary lesions and advanced disease, The outcome of treatment in 40 black patients (27 women, 13 men; mean age 62.9 years) with plantar melanoma over a 13-year period was analysed, Delay in presentation and locally advanced disease may explain the poor prognosis of plantar melanoma in black South Africans., Eighteen cases of malignant skin tumors seen at the University of Port Harcourt Teaching Hospital over 3 years (1984 to 1987) were analyzed for diagnoses, site of tumors, sex, and age. Seven patients (39%) had malignant melanomas affecting only the soles of the feet, while the same number had squamous cell carcinomas widely distributed in various parts of the body, Non-white populations experienced in general a much lower incidence of melanoma although there was some overlap of white and non-white rates., Populations of African descent were found to have a higher incidence than those of Asiatic origin, but it was concluded that this was due largely to the high frequency of tumours among Africans on the sole of the foot., Pathological features of twenty-one cases of malignant melanoma studied in the University of Nigeria Teaching Hospital, Enugu during the period January, 1974 to December, 1975 are presented. Malignant melanoma accounted for 2.4% of all tumours and 4.5% of all malignant tumours, greatest age incidence being in the fifth to seventh decades., 81% melanomas occurred on the sole of feet validating the hypothesis that the pigmented skin in Africans is resistant to malignant melanoma., This paper reports the incidence of this lesion in association with invasive malignant melanomas of the feet and hands of Black Africans., Follow-up data (over a 3-year period) and the histological appearances of primary lesion were studied and related in 40 Black patients with malignant melanoma., Malignant melanoma of the skin in Blacks in formidable and sinister tumour., The incidence of malignant melanoma in Johannesburg Black was 1,2 per 100 000 and accounted for 2% of all cancers. The largest number of cases occurred in the 50- 70-year age group and there was a female preponderance. As in previous studies, the sites predominantly affected were the foot and the hand, mainly on the plantar and palmar surfaces., Twenty-one cases of malignant melanoma occurring in the Igbos of Nigeria have been analysed. The site of predilection is the sole of the foot. This result supports the conclusion that Negroes tend to have the disease in the non-pigmented parts., A case of leptomeningeal melanoma in an African child of 7 years is presented together with a survey of pigmentation in the normal African brain.[SEP]Relations: melanoma has relations: disease_disease with melanomatosis, disease_disease with melanomatosis, disease_disease with familial melanoma, disease_disease with familial melanoma, disease_disease with childhood malignant melanoma, disease_disease with childhood malignant melanoma, disease_disease with skin cancer, disease_disease with skin cancer, disease_disease with amelanotic skin melanoma, disease_disease with amelanotic skin melanoma.", "label": "yes"}
{"id": "converted_38", "sentence1": "Does physical activity influence gut hormones?", "sentence2": "Increases in blood PYY(3-36) levels were dependent on the exercise intensity (effect of session: P<0.001 by two-way ANOVA), whereas those in GLP-1 levels were similar between two different exercise sessions., A decrease in serum leptin levels (-48.4%, p < 0.001) was observed after intervention without changes in total peptide YY and insulin levels., ur data suggest that the control of spontaneous physical activity by gut hormones or their neuropeptide targets may represent an important mechanistic component of energy balance regulation, Hunger and gut hormones remained unchanged during the bed rest., weight-bearing exercise has a greater exercise-induced appetite suppressive effect compared with non-weight-bearing exercise, and both forms of exercise lowered acylated ghrelin and increased total PYY, but the changes did not differ significantly between exercise modes., Appetite (P < 0.0005) and acylated ghrelin (P < 0.002) were suppressed during exercise but more so during SIE. Peptide YY increased during exercise but most consistently during END (P < 0.05). Acylated ghrelin was lowest in the afternoon of SIE (P = 0.018) despite elevated appetite, Following the pre-exercise meal, ghrelin was suppressed ~17% and insulin and PYY were elevated ~157 and ~40%, respectively, relative to fasting (day 7). Following exercise, PYY, ghrelin, and GH were significantly (p < 0.0001) increased by ~11, ~16 and ~813%, respectively. The noted disruption in the typical inverse relationship between ghrelin and PYY following exercise suggests that interaction of these peptides may be at least partially responsible for post-exercise appetite suppression, Plasma levels of PYY and GLP-1 were increased by exercise, whereas plasma ghrelin levels were unaffected by exercise, These findings suggest ghrelin and PYY may regulate appetite during and after exercise,, significant (P < 0.05) interaction effects for hunger, acylated ghrelin, and PYY, indicating suppressed hunger and acylated ghrelin during aerobic and resistance exercise and increased PYY during aerobic exercise, 'exercise-induced anorexia' may potentially be linked to increased PYY, GLP-1 and PP levels., Hunger scores and PYY, GLP-1 and PP levels showed an inverse temporal pattern during the 1-h exercise/control intervention, Exercise significantly increased mean PYY, GLP-1 and PP levels, and this effect was maintained during the post-exercise period for GLP-1 and PP. No significant effect of exercise was observed on postprandial levels of ghrelin, following blood donation the strenuous exercise resulted in a marked reduction in the plasma leptin, We conclude that strenuous physical exercise; 1) fails to affect plasma leptin level but when performed after meal but not after blood withdrawal it results in an increase and fall in plasma leptin, and 2) the release of gut hormones (gastrin, CCK and PP) and stress hormones (norepinephrine, cortisol, GH) increase immediately after exercise independently of feeding or blood donation, the unrestricted exercise group has a significantly elevated SRIF-LI concentration, Exercise has recently been reported to influence ghrelin and PYY concentrations.[SEP]Relations: Norepinephrine has relations: drug_effect with Aggressive behavior, drug_effect with Aggressive behavior, drug_effect with Lactic acidosis, drug_effect with Lactic acidosis, drug_effect with Anxiety, drug_effect with Anxiety. Hydrocortisone has relations: drug_effect with Increased body weight, drug_effect with Increased body weight, drug_effect with Emotional lability, drug_effect with Emotional lability.", "label": "yes"}
{"id": "converted_4699", "sentence1": "Are there roles for cohesin mutations in AML?", "sentence2": "Several landmark studies have shown that cohesin mutations perturb the balance between self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPC). Emerging data now begin to uncover the molecular mechanisms that underpin this phenotype. Among these mechanisms is a role for cohesin in the control of inflammatory responses in HSPCs and myeloid cells. Inflammatory signals limit HSPC self-renewal and drive HSPC differentiation. Consistent with this, cohesin mutations promote resistance to inflammatory signals, and may provide a selective advantage for AML progression. [SEP]Relations: acute promyelocytic leukemia has relations: disease_protein with PML, disease_protein with PML, disease_phenotype_positive with Somatic mutation, disease_phenotype_positive with Somatic mutation, disease_protein with ASXL1, disease_protein with ASXL1, disease_protein with GLI2, disease_protein with GLI2, disease_phenotype_positive with Gingival bleeding, disease_phenotype_positive with Gingival bleeding.", "label": "yes"}
{"id": "converted_3874", "sentence1": "Is isradipine effective for Parkinson's disease?", "sentence2": "Adjusted least-squares mean changes in total UPDRS score in the antiparkinson medication ON state over 36 months for isradipine and placebo recipients were 2.99 (95% CI, 0.95 to 5.03) points versus 3.26 (CI, 1.25 to 5.26) points, respectively, with a treatment effect of -0.27 (CI, -3.02 to 2.48) point (P = 0.85)., Conclusion: Long-term treatment with immediate-release isradipine did not slow the clinical progression of early-stage PD.[SEP]Relations: Isradipine has relations: contraindication with liver disease, contraindication with liver disease, drug_effect with Vertigo, drug_effect with Vertigo, drug_effect with Hepatitis, drug_effect with Hepatitis, drug_effect with Hyperhidrosis, drug_effect with Hyperhidrosis, contraindication with hypotensive disorder, contraindication with hypotensive disorder.", "label": "no"}
{"id": "converted_3777", "sentence1": "Does protein ALEX1 contain armadillo repeats?", "sentence2": "ALEX1 (Arm protein lost in epithelial cancers, on chromosome X), contains two armadillo repeats domains, is expressed different in normal and carcinomas tissues., Arm protein lost in epithelial cancers, on chromosome X 1 (ALEX1) is a novel member of the Armadillo family which has two Armadillo repeats as opposed to more than six repeats in the classical Armadillo family members.[SEP]Relations: carcinoma has relations: disease_protein with S1PR1, disease_protein with S1PR1, disease_protein with TSC22D1, disease_protein with TSC22D1, disease_protein with MC1R, disease_protein with MC1R, disease_protein with MPZL1, disease_protein with MPZL1, disease_protein with BCL2L1, disease_protein with BCL2L1.", "label": "yes"}
{"id": "converted_3849", "sentence1": "Can ATAC-Seq be employed in single-cell mode?", "sentence2": "Single-cell ATAC-seq: strength in numbers., Assembly, and Single-Cell ATAC-Seq., Single cell RNA-seq and ATAC-seq analysis of cardiac progenitor cell transition states and lineage settlement.,  Here, we comprehensively characterize mouse cardiac progenitor cells (CPCs) marked by Nkx2-5 and Isl1 expression from E7.5 to E9.5 using single-cell RNA sequencing and transposase-accessible chromatin profiling (ATAC-seq)., Classifying cells with Scasat, a single-cell ATAC-seq analysis tool., When done at single-cell resolution, ATAC-seq provides an insight into the cell-to-cell variability that emerges from otherwise identical DNA sequences by identifying the variability in the genomic location of open chromatin sites in each of the cells., Single-cell ATAC-Seq in human pancreatic islets and deep learning upscaling of rare cells reveals cell-specific type 2 diabetes regulatory signatures., THODS: We present genome-wide single-cell chromatin accessibility profiles in >1,600 cells derived from a human pancreatic islet sample using single-cell combinatorial indexing ATAC-seq (sci-ATAC-seq). W, Contiguity-Preserving Transposition Sequencing (CPT-Seq) for Genome-Wide Haplotyping, Assembly, and Single-Cell ATAC-Seq., SCALE method for single-cell ATAC-seq analysis via latent feature extraction., Single-cell ATAC-seq (scATAC-seq) profiles the chromatin accessibility landscape at single cell level, thus revealing cell-to-cell variability in gene regulation., The recently developed low-input and single-cell regulome mapping technologies such as ATAC-seq and single-cell ATAC-seq (scATAC-seq) allow analyses of small-cell-number and single-cell samples, but their signals remain highly discrete or noisy., This paper presents Scasat (single-cell ATAC-seq analysis tool), a complete pipeline to process scATAC-seq data with simple steps., Here, we comprehensively characterize mouse cardiac progenitor cells (CPCs) marked by Nkx2-5 and Isl1 expression from E7.5 to E9.5 using single-cell RNA sequencing and transposase-accessible chromatin profiling (ATAC-seq)., Single-cell ATAC-seq (scATAC-seq) technology has also been developed to study cell type-specific chromatin accessibility in tissue samples containing a heterogeneous cellular population., Here we combined sequencing of the TCR-encoding genes with assay for transposase-accessible chromatin with sequencing (ATAC-seq) analysis at the single-cell level to provide information on the TCR specificity and epigenomic state of individual T cells., Substantial advances of this work include the optimization of a single-cell combinatorial indexing assay for transposase accessible chromatin (sci-ATAC-seq); a software suite,, The accessible chromatin landscape of the murine hippocampus at single-cell resolution., Here we present a comprehensive map of the accessible chromatin landscape of the mouse hippocampus at single-cell resolution., We expect this review will provide a guideline for successful data generation and analysis methods using appropriate software tools and databases for the study of chromatin accessibility at single-cell resolution., Single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) is the state-of-the-art technology for analyzing genome-wide regulatory landscapes in single cells., Single-cell ATAC-seq data are sparse and noisy, and analyzing such data is challenging., Here, we introduce a method for analyzing scATAC-seq data, called Single-Cell ATAC-seq analysis via Latent feature Extraction (SCALE)., Single-cell ATAC-seq signal extraction and enhancement with SCATE., Single-cell ATAC-seq detects open chromatin in individual cells., Currently data are sparse, but combining information from many single cells can identify determinants of cell-to-cell chromatin variation., Predictions based on single-cell RNA-seq (scRNA-seq) can more accurately reconstruct bulk chromatin accessibility than using scATAC-seq., Global prediction of chromatin accessibility using small-cell-number and single-cell RNA-seq., Single-cell ATAC-seq (scATAC-seq) maps from hundreds of single cells in aggregate closely resemble accessibility profiles from tens of millions of cells and provide insights into cell-to-cell variation., However, very few studies have been performed at the single cell level (scATAC-seq) due to technical challenges., Here, we present Perturb-ATAC, a method that combines multiplexed CRISPR interference or knockout with genome-wide chromatin accessibility profiling in single cells based on the simultaneous detection of CRISPR guide RNAs and open chromatin sites by assay of transposase-accessible chromatin with sequencing (ATAC-seq)., Additionally, the same workflow can be used to aid de novo assembly (Adey et al., Genome Res 24(12):2041-2049, 2014), detect structural variants, and perform single cell ATAC-seq analysis (Cusanovich et al., Science 348(6237):910-914, 2015)., ChromA can analyze single cell ATAC-seq data, correcting many biases generated by the sparse sampling inherent in single cell technologies.,  circuits. Existing chromatin profiling methods such as ATAC-seq and DNase-seq, applied to islets in bulk, produce aggregate profiles that mask important cellular and regulatory heterogeneity.METHODS: We present genome-wide single-cell chromatin accessibility profiles in >1,600 cells derived from a human pancreatic islet sample using single-cell combinatorial indexing ATAC, ATAC-seq has become a leading technology for probing the chromatin landscape of single and aggregated cells.[SEP]Relations: transcription-coupled nucleotide-excision repair has relations: bioprocess_protein with AQR, bioprocess_protein with AQR, bioprocess_protein with XRCC1, bioprocess_protein with XRCC1, bioprocess_protein with POLR2C, bioprocess_protein with POLR2C, bioprocess_protein with CDK7, bioprocess_protein with CDK7, bioprocess_protein with ERCC1, bioprocess_protein with ERCC1.", "label": "yes"}
{"id": "converted_4213", "sentence1": "Is capmatinib effective for glioblastoma?", "sentence2": "CONCLUSION: The combination of INC280/buparlisib resulted in no clear activity in patients with recurrent PTEN-deficient glioblastoma. [SEP]Relations: adult glioblastoma has relations: disease_disease with glioblastoma (disease), disease_disease with glioblastoma (disease), disease_disease with adult infiltrating astrocytic neoplasm, disease_disease with adult infiltrating astrocytic neoplasm, disease_disease with adult spinal cord glioblastoma, disease_disease with adult spinal cord glioblastoma.", "label": "no"}
{"id": "converted_3925", "sentence1": "Are the major royal jelly proteins similar to the yellow proteins?", "sentence2": "Major royal jelly proteins (named MRJP1-5) of honeybee (Apis mellifera), yellow proteins of Drosophila, together with putative proteins found in several bacteria, form a protein family termed the MRJP/yellow family., Analysis of Drosophila yellow-B cDNA reveals a new family of proteins related to the royal jelly proteins in the honeybee, he Yellow proteins are related to the Royal Jelly proteins and have no relatives in other non-insect metazoan species. [SEP]Relations: Bacteremia has relations: disease_phenotype_positive with listeriosis, disease_phenotype_positive with listeriosis, disease_phenotype_positive with cyclic hematopoiesis, disease_phenotype_positive with cyclic hematopoiesis, disease_phenotype_positive with toxic shock syndrome, disease_phenotype_positive with toxic shock syndrome, disease_phenotype_positive with nocardiosis, disease_phenotype_positive with nocardiosis, disease_phenotype_positive with shigellosis, disease_phenotype_positive with shigellosis.", "label": "yes"}
{"id": "converted_2455", "sentence1": "Is LDB1-mediated enhancer looping dependent on cohesin?", "sentence2": "LDB1-mediated enhancer looping can be established independent of mediator and cohesin., Moreover, ENCODE data and our chromatin immunoprecipitation results indicate that cohesin is almost completely absent from validated and predicted LDB1-regulated erythroid enhancer-gene pairs. Thus, lineage specific factors largely mediate enhancer-promoter looping in erythroid cells independent of mediator and cohesin., Moreover, ENCODE data and our chromatin immunoprecipitation results indicate that cohesin is almost completely absent from validated and predicted LDB1-regulated erythroid enhancer-gene pairs., Moreover, ENCODE data and our chromatin immunoprecipitation results indicate that cohesin is almost completely absent from validated and predicted LDB1-regulated erythroid enhancer-gene pairs., LDB1-mediated enhancer looping can be established independent of mediator and cohesin.[SEP]", "label": "no"}
{"id": "converted_3239", "sentence1": "Is TNF-α an activator of pancreatic stellate cells?", "sentence2": "TNF-α is the prime factor responsible for the activation of pancreatic stellate cells, Activated PSCs expressed IL-33 in the nucleus, and the expression was increased by IL-1β, TNF-α, PDGF-BB, and IFN-γ, but not TGF-β1. [SEP]Relations: pancreatic stellate cell proliferation has relations: bioprocess_bioprocess with fibroblast proliferation, bioprocess_bioprocess with fibroblast proliferation. Becaplermin has relations: drug_protein with PDGFRA, drug_protein with PDGFRA, drug_protein with A2M, drug_protein with A2M, drug_protein with PDGFRB, drug_protein with PDGFRB.", "label": "yes"}
{"id": "converted_1219", "sentence1": "Can ferric carboxymaltose be used to treat anemia in inflammatory bowel disease patients?", "sentence2": "Intravenous iron should be preferred where oral iron is poorly tolerated or where it has failed in moderate to severe anemia, and in combination with erythropoietin, Ferric carboxymaltose is much more convenient, and has been shown to be more effective than iron sucrose in a large randomized tria, nemia and iron deficiency anemia are very common in inflammatory bowel disease (IBD, Ferric carboxymaltose was associated with cost savings of 30-44 % per patient per treatment cycle compared to iron sucrose. , Iron deficiency is common in pregnancy, postpartum, inflammatory bowel disease, chronic kidney disease, chronic heart failure, heavy uterine bleeding, cancer and following surgery. We estimate the budget impact (BI) on the Swiss mandatory health insurance associated with substituting iron sucrose (standard) with ferric carboxymaltose (new treatment) using real-life data., reating iron deficiency involves substantial costs to the Swiss MHI which may be reduced by substituting iron sucrose with ferric carboxymaltose., e aim of this study was to observe, in a non-interventional way, how Swedish gastroenterologists adhere to guidelines in IBD outpatients treated with intravenous ferric carboxymaltose (FCM), and the result of treatment, FCM lowers platelet counts and platelet activation in patients with IBD-associated secondary thrombocytosis., We performed a randomized, single-blinded placebo-controlled trial testing the effect of ferric carboxymaltose (FCM) in patients with IBD with secondary thrombocytosis (platelets > 450 G/L), e performed a randomized, placebo-controlled trial to determine if administration of ferric carboxymaltose (FCM) prevents anemia in patients with IBD and low levels of serum ferritin, FCM prevents recurrence of anemia in patients with IBD, compared with placebo. ,  A subgroup was analyzed regarding efficacy and side effects of iron supplementation with ferric carboxymaltose., Iron deficiency and anemia are frequent in IBD patients. Treatment with ferric carboxymaltose is efficious, safe and well tolerated in iron-deficient IBD patients.,  Intravenous iron avoids these concerns, especially with the development of ferric carboxymaltose, which allow up to 1000mg to be given rapidly., What is the optimal treatment for anemia in inflammatory bowel disease?, We compared the efficacy and safety of a novel fixed-dose ferric carboxymaltose regimen (FCM) with individually calculated iron sucrose (IS) doses in patients with inflammatory bowel disease (IBD) and IDA, Study drugs were well tolerated and drug-related adverse events were in line with drug-specific clinical experience,  The simpler FCM-based dosing regimen showed better efficacy and compliance, as well as a good safety profile, compared with the Ganzoni-calculated IS dose regimen., Ferric carboxymaltose can be rapidly administered in doses of 15 mg/kg body weight, up to a ceiling dose of 1000 mg. A test dose is not required, and it can be used more widely across a spectrum of iron deficiency and iron deficiency anemia indication,  Intravenous iron offers a rapid means of iron repletion and is superior to oral iron in many circumstances, especially in the presence of anemia of chronic disease, where it appears to overcome the block to absorption of iron from the gastrointestinal tract and immobilization of stored iron. The clinical situations where high doses of iron are commonly required are reviewed. These include nondialysis-dependent chronic kidney disease, inflammatory bowel disease, obstetrics, menorrhagia, and anemia associated with cancer and its treatment. , Ferric carboxymaltose can be administered at 15 mg/kg body weight to a maximum dose of 1000 mg, whereas iron isomaltoside 1000 can be administered at 20 mg/kg body weight. The ability to give high doses of iron is important in the context of managing iron deficiency anemia in a number of clinical conditions where demands for iron are high (including chronic blood loss associated with inflammatory bowel disease, menorrhagia, and chronic kidney disease), erric carboxymaltose (FCM, Ferinject) was effective and well tolerated in the treatment of iron-deficiency anemia (IDA) in nine, Phase III, randomized, controlled, multicenter trials in a diverse range of indications, including patients with inflammatory bowel disease (IBD), post-partum anemia (PPA) or abnormal uterine bleeding (AUB), chronic heart failure (CHF), non-dialysis-dependent chronic kidney disease (CKD) and those undergoing hemodialysis (HD, In patients with IBD or PPA, improvements in Hb levels were more rapid with FCM than with FeSulf. , CM improved patient quality of life to an equivalent extent to oral FeSulf in patients with IBD or PPA, and to a greater extent than oral FeSulf in women with AUB, Four different products are principally used in clinical practice, which differ in their pharmacokinetic properties and safety profiles: iron gluconate and iron sucrose (lower single doses), and iron dextran and ferric carboxymaltose (higher single doses)., he prevalence of anemia across studies on patients with inflammatory bowel disease (IBD) is high (30%).,  novel intravenous iron formulation for treatment of anemia in inflammatory bowel disease: the ferric carboxymaltose (FERINJECT) randomized controlled trial., FeCarb is effective and safe in IBD-associated anemia. It is noninferior to FeSulf in terms of Hb change over 12 wk, and provides a fast Hb increase and a sufficient refill of iron stores., Treatment-related adverse events (AEs) occurred in 28.5% of the FeCarb and 22.2% of the FeSulf groups, with discontinuation of study medication due to AEs in 1.5% and 7.9%, respectively., The median Hb improved from 8.7 to 12.3 g/dL in the FeCarb group and from 9.1 to 12.1 g/dL in the FeSulf group, demonstrating noninferiority (P= 0.6967). , Ferric carboxymaltose prevents recurrence of anemia in patients with inflammatory bowel disease., Ferric carboxymaltose (FCM, Ferinject) was effective and well tolerated in the treatment of iron-deficiency anemia (IDA) in nine, Phase III, randomized, controlled, multicenter trials in a diverse range of indications, including patients with inflammatory bowel disease (IBD), post-partum anemia (PPA) or abnormal uterine bleeding (AUB), chronic heart failure (CHF), non-dialysis-dependent chronic kidney disease (CKD) and those undergoing hemodialysis (HD)., Ferric carboxymaltose (FCM, Ferinject) was effective and well tolerated in the treatment of iron-deficiency anemia (IDA) in nine, Phase III, randomized, controlled, multicenter trials in a diverse range of indications, including patients with inflammatory bowel disease (IBD), post-partum anemia (PPA) or abnormal uterine bleeding (AUB), chronic heart failure (CHF), non-dialysis-dependent chronic kidney disease (CKD) and those undergoing hemodialysis (HD)[SEP]Relations: Ferric carboxymaltose has relations: drug_drug with Ofloxacin, drug_drug with Ofloxacin, drug_drug with Fleroxacin, drug_drug with Fleroxacin, drug_drug with Ferric pyrophosphate citrate, drug_drug with Ferric pyrophosphate citrate, drug_drug with Ferric pyrophosphate, drug_drug with Ferric pyrophosphate, drug_drug with Enoxacin, drug_drug with Enoxacin.", "label": "yes"}
{"id": "converted_360", "sentence1": "Have thyronamines  effects on fat tissue?", "sentence2": "In conclusion, trace amines and thyronamines are negative inotropic agents., Their in vivo administration induces effects opposite to those induced by thyroid hormone, including lowering of body temperature.[SEP]Relations: response to thyroid hormone has relations: bioprocess_protein with GBA, bioprocess_protein with GBA, bioprocess_bioprocess with response to thyroxine, bioprocess_bioprocess with response to thyroxine, bioprocess_protein with SLC26A5, bioprocess_protein with SLC26A5, bioprocess_protein with SLC34A1, bioprocess_protein with SLC34A1, bioprocess_protein with HPN, bioprocess_protein with HPN.", "label": "no"}
{"id": "converted_2101", "sentence1": "Is Obeticholic Acid used for treatment of Primary Biliary Cholangitis?", "sentence2": "Obeticholic acid in primary biliary cholangitis., In a double-blind, randomized, placebo-controlled study including 217 patients with primary biliary cholangitis, the authors show that obeticholic acid (a potent farnesoid X agonist) administered with ursodeoxycholic acid or as monotherapy significantly decreases serum alkaline phosphatase and bilirubin when compared to placebo., Obeticholic acid (Ocaliva(TM)) is a farnesoid-X receptor (FXR) agonist that is being developed by Intercept Pharmaceuticals for the treatment of various liver diseases, and has recently been granted accelerated approval in the USA for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid in adults with an inadequate response to ursodeoxycholic acid, or as monotherapy in adults unable to tolerate ursodeoxycholic acid. , Obeticholic Acid (OCA) is a farnesoid X receptor (FXR) agonist which has been evaluated as a second line therapy in PBC and has recently been licenced by the FDA., OCA will be the first stratified therapy introduced in PBC, however confirmatory trial and real life data are needed to confirm that suggestive biochemical improvements are matched by improvement in key clinical outcomes., Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection., A series of clinical trials of OCA in PBC, primarily in combination with UDCA, have established that OCA leads to significant reductions in serum alkaline phosphatase that are predicted to lead to improved clinical outcomes, while dose-dependent pruritus has been the most common adverse effect. On the basis of these studies, OCA was given conditional approval by the US Food and Drug Administration with plans to establish the long-term clinical efficacy of OCA in patients with advanced PBC., Although obeticholic acid was approved by the FDA for the treatment of PBC in May 2016, this development occurred after the symposium presentation. , While several agents are being studied in combination with UDCA, monotherapy with the novel agent obeticholic acid, a farnesoid X receptor agonist, has also shown promising results., Obeticholic acid (Ocaliva(TM)) is a farnesoid-X receptor (FXR) agonist that is being developed by Intercept Pharmaceuticals for the treatment of various liver diseases, and has recently been granted accelerated approval in the USA for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid in adults with an inadequate response to ursodeoxycholic acid, or as monotherapy in adults unable to tolerate ursodeoxycholic acid., Obeticholic acid for the treatment of primary biliary cholangitis., Long-term clinical impact and cost-effectiveness of obeticholic acid for the treatment of primary biliary cholangitis., A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis., This article summarizes the milestones in the development of obeticholic acid leading to this first approval for primary biliary cholangitis., Obeticholic acid for the treatment of primary biliary cholangitis., Long-term Clinical Impact and Cost-Effectiveness of Obeticholic Acid for the Treatment of Primary Biliary Cholangitis., Obeticholic acid in primary biliary cholangitis., A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis., This article summarizes the milestones in the development of obeticholic acid leading to this first approval for primary biliary cholangitis.[SEP]Relations: primary biliary cholangitis has relations: contraindication with Cholic Acid, contraindication with Cholic Acid, contraindication with Fenofibric acid, contraindication with Fenofibric acid, contraindication with Chenodeoxycholic acid, contraindication with Chenodeoxycholic acid, contraindication with Fenofibrate, contraindication with Fenofibrate. Obeticholic acid has relations: drug_drug with Cholic Acid, drug_drug with Cholic Acid.", "label": "yes"}
{"id": "converted_4633", "sentence1": "Is PCAT6 a microRNA?", "sentence2": "In this work, we investigated the role and regulatory mechanism of lncRNA prostate cancer-associated transcript 6 (PCAT6) in breast cancer progression.[SEP]Relations: long noncoding RNA binding has relations: molfunc_protein with MIR384, molfunc_protein with MIR384. benign neoplasm of male breast has relations: disease_disease with breast benign neoplasm, disease_disease with breast benign neoplasm.", "label": "no"}
{"id": "converted_3677", "sentence1": "Has the Spanich flu virus been reconstructed?", "sentence2": "Reconstruction of the 1918 influenza virus has facilitated considerable advancements in our understanding of this extraordinary pandemic virus., These viral RNA sequences eventually permitted reconstruction of the complete 1918 virus, which has yielded, almost a century after the deaths of its victims, novel insights into influenza virus biology and pathogenesis and has provided important information about how to prevent and control future pandemics., Reconstruction of the 1918 virus and studies elucidating the exceptional virulence and transmissibility of the virus are providing exciting new insights into this devastating pandemic strain. [SEP]Relations: Cessation of head growth has relations: disease_phenotype_positive with leukoencephalopathy with vanishing white matter, disease_phenotype_positive with leukoencephalopathy with vanishing white matter, disease_phenotype_positive with Angelman syndrome due to a point mutation, disease_phenotype_positive with Angelman syndrome due to a point mutation, disease_phenotype_positive with Angelman syndrome due to paternal uniparental disomy of chromosome 15, disease_phenotype_positive with Angelman syndrome due to paternal uniparental disomy of chromosome 15, disease_phenotype_positive with Angelman syndrome due to maternal 15q11q13 deletion, disease_phenotype_positive with Angelman syndrome due to maternal 15q11q13 deletion, disease_phenotype_positive with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, disease_phenotype_positive with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies.", "label": "yes"}
{"id": "converted_1917", "sentence1": "Is there a role for gamma knife in treatment of Obsessive-Compulsive Disorder?", "sentence2": "OBJECTIVE Functional Gamma Knife radiosurgery (GKRS) procedures have been increasingly used for treating patients with tremor, trigeminal neuralgia (TN), and refractory obsessive-compulsive disorder., METHODS The authors constructed a linear-quadratic model of BED in functional GKRS with a dose-protraction factor to correct for intrafraction DNA-damage repair and used standard single-fraction doses for trigeminal nerve ablation for TN (85 Gy), thalamotomy for tremor (130 Gy), and capsulotomy for obsessive-compulsive disorder (180 Gy). , Gamma knife for obsessive compulsive disorder: can it be detrimental?, Gamma knife radiosurgery (GKRS) is also being practised to treat refractory obsessive- compulsive disorder (OCD)., Radio and neurosurgical procedures, including gamma knife radiation and deep brain stimulation, are reserved for severe, treatment-refractory disease that has not responded to multiple treatments, and some patients may benefit from transcranial magnetic stimulation.,  We close with a discussion of gamma knife capsulotomy, a modality with deep historical roots., Results following gamma knife radiosurgical anterior capsulotomies for obsessive compulsive disorder., Gamma knife radiosurgery (GKRS) is also being practised to treat refractory obsessive- compulsive disorder (OCD)., Lesion topography and outcome after thermocapsulotomy or gamma knife capsulotomy for obsessive-compulsive disorder: relevance of the right hemisphere., Neuropsychological outcome of ventral capsular/ventral striatal gamma capsulotomy for refractory obsessive-compulsive disorder: a pilot study, Gamma ventral capsulotomy for treatment of resistant obsessive-compulsive disorder: a structural MRI pilot prospective study, Results following gamma knife radiosurgical anterior capsulotomies for obsessive compulsive disorder, At 28 months, the third patient is living and working independently, and her YBOCS score is 18.CONCLUSION: Within a strict protocol, gamma knife radiosurgery provided improvement of OCD behavior with no adverse effects., Gamma knife for obsessive compulsive disorder: can it be detrimental?[SEP]Relations: obsessive-compulsive disorder has relations: contraindication with Riboflavin, contraindication with Riboflavin, contraindication with Ibuprofen, contraindication with Ibuprofen, disease_protein with SLITRK5, disease_protein with SLITRK5, contraindication with Pheniramine, contraindication with Pheniramine, contraindication with Isometheptene, contraindication with Isometheptene.", "label": "yes"}
{"id": "converted_2372", "sentence1": "Is there any linear-time and linear-space algorithm for the computation of avoided words in biological sequences?", "sentence2": "The systematic search for avoided words is particularly useful for biological sequence analysis. We present a linear-time and linear-space algorithm for the computation of avoided words of lengthkin a given sequencex. We suggest a modification to this algorithm so that it computes all avoided words ofx, irrespective of their length, within the same time complexity. We also present combinatorial results with regards to avoided words and absent words., We present a linear-time and linear-space algorithm for the computation of avoided words of length <br>, <b>BACKGROUND</b>: The deviation of the observed frequency of a word <br><b>RESULTS</b>: In this article, we propose an [Formula: see text]-time and [Formula: see text]-space algorithm to compute all [Formula: see text]-avoided words of length <br><b>CONCLUSIONS</b>: The systematic search for avoided words is particularly useful for biological sequence analysis., We present a linear-time and linear-space algorithm for the computation of avoided words of length, We present a linear-time and linear-space algorithm for the computation of avoided words of length k in a given sequence x., Hence, computing all such words naïvely can be a very time-consuming procedure, in particular for large k.   RESULTS In this article, we propose an [Formula: see text]-time and [Formula: see text]-space algorithm to compute all [Formula: see text]-avoided words of length k in a given sequence of length n over a fixed-sized alphabet., We also present a time-optimal [Formula: see text]-time algorithm to compute all [Formula: see text]-avoided words (of any length) in a sequence of length n over an integer alphabet of size [Formula: see text]., the deviation of the observed frequency of a word from its expected frequency in a given sequence is used to determine whether or not the word is this concept is particularly useful in dna linguistic analysis the value of the deviation of denoted by formula see text effectively characterises the extent of a word by its edge contrast in the context in which it occurs a word of length formula see text is a formula see text avoided word in if formula see text for a given threshold formula see text notice that such a word may be completely from hence computing all such words naïvely can be a very time consuming procedure in particular for large in this article we propose an formula see text time and formula see text space algorithm to compute all formula see text avoided words of length in a given sequence of length over a fixed sized alphabet we also present a time optimal formula see text time algorithm to compute all formula see text avoided words of any length in a sequence of length over an integer alphabet of size formula see text in addition we provide a tight asymptotic upper bound for the number of formula see text avoided words over an integer alphabet and the expected length of the longest one we make available an implementation of our algorithm experimental results using both real and synthetic data show the efficiency and applicability of our implementation in biological sequence analysis the systematic search for avoided words is particularly useful for biological sequence analysis we present a linear time and linear space algorithm for the computation of avoided words of length in a given sequence we suggest a modification to this algorithm so that it computes all avoided words of irrespective of their length within the same time complexity we also present combinatorial results with regards to avoided words and absent words.[SEP]Relations: response to nickel cation has relations: bioprocess_protein with CACNA1G, bioprocess_protein with CACNA1G, bioprocess_bioprocess with cellular response to nickel ion, bioprocess_bioprocess with cellular response to nickel ion, bioprocess_bioprocess with response to metal ion, bioprocess_bioprocess with response to metal ion.", "label": "yes"}
{"id": "converted_687", "sentence1": "Is the Miller-Fisher syndrome considered to be a variant of Guillain-Barré?", "sentence2": "Miller Fisher syndrome is a variant of Guillain-Barre syndrome characterized by the classic triad of ophthalmoplegia, ataxia, and areflexia, We are reporting a rare case of Miller-Fisher (MFS) variant of Guillain-Barré syndrome (GBS) as the first manifestation of SLE in a 41-year-old female, Miller-Fisher syndrome is defined as ophthalmoplegia, ataxia and areflexia. Considered as a variant of Guillain-Barré syndrome, it differs in its clinical presentation and by anti-GQ1b antibody positivity, Guillain-Barré syndrome (GBS) and its variant, Miller Fisher syndrome (MFS), exist as several clinical subtypes with different neurological features and presentations, Using in vitro and in vivo models of the Guillain-Barré syndrome variant, Miller Fisher syndrome, we have shown previously that anti-GQ1b ganglioside antibodies target the presynaptic motor nerve terminal axon and surrounding perisynaptic Schwann cells, thereby mediating destructive injury through deposition of membrane attack complex., Miller Fisher syndrome is a variant of Guillain-Barré syndrome, characterized by ophthalmoplegia, ataxia and areflexia., Miller Fisher syndrome is a localized variant of Guillain-Barré syndrome, characterized by ophthalmoplegia, areflexia and ataxia., Miller Fisher syndrome, a variant of Guillain-Barré syndrome, is associated with IgG antibody to GQ1b ganglioside., Miller Fisher syndrome (MFS), a variant of Guillain-Barré syndrome, is a rare disorder typically characterized by a triad of ataxia, areflexia, and ophthalmoplegia, which may have a highly variable clinical presentation., Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barré syndrome and is characterized by the clinical triad of ataxia, areflexia, and ophthalmoplegia., The objective of this study was to review the occurrence and clinical features of Guillain-Barré syndrome and its variant, the Miller Fisher syndrome, during TNFalpha antagonist therapy., Miller Fisher variant of Guillain-Barré syndrome masquerading as acute sphenoid sinusitis with orbital apex syndrome., Controversy exists concerning whether Miller Fisher syndrome (MFS) is the result of a predominantly axonal or demyelinating polyneuropathy and whether the Guillain-Barré syndrome variant of acute ataxia and areflexia without ophthalmoplegia, ataxic Guillain-Barré syndrome (atxGBS), has a distinct pathophysiology., Miller Fisher syndrome is characterised by the triad ophthalmoparesis, ataxia and areflexia and is considered to be a variant of Guillain-Barré syndrome; its differential diagnosis includes Wernicke&apos;s encephalopathy, Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barré syndrome and is characterized by the clinical triad of ataxia, areflexia, and ophthalmoplegia, Miller-Fisher syndrome is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia and is considered a variant form of Guillain-Barré syndrome, The syndrome of ataxia, areflexia and ophthalmoplegia, or Miller-Fisher syndrome, has been considered to be a variant of Guillain-Barré syndrome with pathology restricted to the peripheral nervous system, Miller-Fisher syndrome (MFS) is considered the most common variant of Guillain-Barré syndrome (GBS) and is characterized by the clinical triad of ophthalmoplegia, ataxia and areflexia, Miller Fisher syndrome (MFS), characterized as ataxia, areflexia and ophthalmoplegia, is generally considered as a variant of Guillain-Barré syndrome (GBS), Miller Fisher Syndrome (MFS), which is characterized by ophthalmoplegia, ataxia and tendon areflexia, is generally considered as a clinical variant of Guillain-Barré Syndrome, Miller-Fisher syndrome (MFS), a variant of Guillain-Barré syndrome (GBS) is a self-limiting demyelinating disease of the peripheral nervous system, BACKGROUND: Miller-Fisher syndrome is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia and is considered a variant form of Guillain-Barré syndrome. , BACKGROUND AND OBJECTIVE: Miller-Fisher syndrome (MFS) is considered the most common variant of Guillain-Barré syndrome (GBS) and is characterized by the clinical triad of ophthalmoplegia, ataxia and areflexia. , Miller Fisher syndrome is characterised by the triad ophthalmoparesis, ataxia and areflexia and is considered to be a variant of Guillain-Barré syndrome; its differential diagnosis includes Wernicke's encephalopathy. , A recent report described serum anti-GQ1b ganglioside antibodies in Miller Fisher syndrome (MFS), a clinical variant of Guillain-Barré syndrome (GBS)., The syndrome of ataxia, areflexia and ophthalmoplegia, or Miller-Fisher syndrome, has been considered to be a variant of Guillain-Barré syndrome with pathology restricted to the peripheral nervous system., Guillain-Barré syndrome (GBS), an acute inflammatory polyneuropathy, is preceded in most cases by an infectious illness, and Campylobacter jejuni, a leading cause of acute gastroenteritis, is the most common antecedent to GBS and its ocular variant, Miller Fisher syndrome (MFS)., Miller-Fisher syndrome is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia and is considered a variant form of Guillain-Barré syndrome., Miller-Fisher syndrome is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia and is considered a variant form of Guillain-Barré syndrome.,  The syndrome of ataxia, areflexia and ophthalmoplegia, or Miller-Fisher syndrome, has been considered to be a variant of Guillain-Barré syndrome with pathology restricted to the peripheral nervous system. A patient with Miller-Fisher syndrome and bilateral demyelinating optic neuropathy suggesting associated central nervous system pathology is presented., Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barré syndrome and is characterized by the clinical triad of ataxia,,  Miller Fisher syndrome is an uncommon disease and it is a variant of Guillain-Barre syndrome. Miller Fisher syndrome also has rarer variants., Miller Fisher syndrome is characterised by the triad ophthalmoparesis, ataxia and areflexia and is considered to be a variant of Guillain-Barré syndrome; its differential diagnosis includes Wernicke's encephalopathy., Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barré syndrome and is characterized by the clinical triad of ataxia, areflexia, and ophthalmoplegia., Data were separately analysed for Miller Fisher syndrome and other Guillain-Barré syndrome variants., Guillain-Barré syndrome variants alone (excluding Miller Fisher syndrome) accounted for 10.5% of total cases., The syndrome of ataxia, areflexia and ophthalmoplegia, or Miller-Fisher syndrome, has been considered to be a variant of Guillain-Barré syndrome with pathology restricted to the peripheral nervous system.[SEP]Relations: Miller Fisher syndrome has relations: disease_disease with regional variant of Guillain-Barre syndrome, disease_disease with regional variant of Guillain-Barre syndrome, disease_disease with cerebellar disease, disease_disease with cerebellar disease. Guillain-Barre syndrome has relations: disease_disease with variant of Guillain-Barre syndrome, disease_disease with variant of Guillain-Barre syndrome, disease_protein with PMP22, disease_protein with PMP22, disease_disease with syndromic disease, disease_disease with syndromic disease.", "label": "yes"}
{"id": "converted_432", "sentence1": "Is it possible to detect survivin protein expression in normal human adult tissues?", "sentence2": "Survivin (BIRC5) is one of the members of IAP-family apoptosis inhibitors. The BIRCS gene is expressed in most human embryonic tissues and malignant tumors but not in normal differentiated tissues of adult human., Survivin is an inhibitor of apoptosis that is undetectable in most terminally differentiated normal human tissues, strongly expressed in embryonic and fetal organs and is strongly expressed in many different human cancers., Survivin is a member of the inhibitor apoptosis family that is overexpressed in many malignancies. It has five known alternative splice forms, some of which differ in their antiapoptotic properties and expression levels in human cancers., survivin is usually not expressed in normal adult tissues,, AZD1152-hQPA induced caspase-dependent apoptosis of some cell lines, demonstrated by loss of mitochondrial membrane potential, activation of caspase-9, followed by activation of caspase-3. This effect was accompanied by the inhibition of survivin expression. In vivo efficacy was determined in NOD/SCID/γc(null) mice implanted with the Ramos human BL cell line. AZD1152 had anti-tumour effects in this murine xenograft model. There preclinical data suggest that the inhibition of Aurora B kinase is a potentially useful therapeutic strategy in BL and HL., a novel antiapoptosis gene, i.e., survivin, was identified as a structurally unique member of the inhibitor of apoptosis protein family. Survivin expression is turned off during fetal development and not found in non-neoplastic adult human tissues but is again turned on in the most common human cancers. The antiapoptotic properties of survivin might provide a significant growth advantage in tumors and possibly also contribute to chemoresistance of cancer., Further comparison of the distribution of PDEF with other widely recognized cancer-associated molecules showed that PDEF has more restricted distributions than Her-2/neu, Bcl-2, survivin or telomerase in cDNA libraries from normal human tissues and more increased distribution than Her-2/neu, CA-125, Bcl-2, survivin and telomerase in cDNA libraries from brain (except survivin), breast, lung and ovarian tumors. These data together show a better tumor-association for PDEF and suggest that PDEF is a more suitable target for developing specific cancer therapies., we identified decreased FHIT expression resulting in apoptosis inhibition and decreasing apoptosis associated with abnormal levels of some pro- and anti-apoptotic proteins (Bax, Bcl-2 and Survivin) by TUNEL and TMA. Our results demonstrated that the mutation in the FHIT gene significantly reduced FHIT expression in human CRC. Both TUNEL and TMA experiments demonstrated significantly inhibited apoptosis by down-regulation of Bax and up-regulation of Survivin and Bcl-2. Collectively, these studies identify the mechanism by which an important tumor suppressor gene, FHIT, inactivated specifically in human CRC, and contributes to our understanding of the mechanism of colorectal carcinogenesis.[SEP]Relations: PPP1R1A has relations: anatomy_protein_present with adult mammalian kidney, anatomy_protein_present with adult mammalian kidney, anatomy_protein_present with adipose tissue, anatomy_protein_present with adipose tissue, anatomy_protein_present with muscle tissue, anatomy_protein_present with muscle tissue, anatomy_protein_present with blood, anatomy_protein_present with blood. breast has relations: anatomy_protein_present with VIM, anatomy_protein_present with VIM.", "label": "no"}
{"id": "converted_3749", "sentence1": "Is the TFR1 gene dispensable for erythropoiesis?", "sentence2": "These studies describe how point mutations of the transferrin receptor can cause a microcytic anemia that does not respond to iron therapy and would not be detected by routine iron studies, such as serum ferritin., Ret-He was the only red cell marker affected prior to the onset of brain ID. The clinical practice of using anemia as the preferred biomarker for diagnosis of iron deficiency may need reconsidering., The restoration of EPO production and EPOR mRNA expression with ASP treatment activated EPOR downstream JAK2/STAT5 and PI3K/Akt signaling, induced their target genes, such as Bcl-xL, Fam132b and Tfrc, and increased Bcl-2/Bax ratio in bone marrow-derived mononuclear cells of CKD rats., Transferrin-bound iron binding to transferrin receptor 1 (TfR1) is essential for cellular iron delivery during erythropoiesis. , aken together, decreasing TfR1 expression during β-thalassemic erythropoiesis, either directly via induced haploinsufficiency or via exogenous apotransferrin, decreases ineffective erythropoiesis and provides an endogenous mechanism to upregulate hepcidin, leading to sustained iron-restricted erythropoiesis and preventing systemic iron overload in β-thalassemic mice., The type 1 transferrin receptor (TfR1) is well known as a key player in erythroid differentiation through its role in iron uptake. , The signaling functions of both TfR1 and TfR2 in erythroid cells were unexpected and these recent findings open a new field of research regarding the last steps of erythroid differentiation and their regulation., Erythropoiesis requires large amounts of iron for hemoglobin synthesis, which is mainly provided by macrophages and the intestines in a transferrin (Tf)-bound form.,  In humans, hematopoietic erythroid precursor cells express high levels of TFR1 and specifically take up the FTH homopolymer (H-ferritin)., We found decreased expression of hepcidin and TfR2 and increased expression of TfR1 and NGAL in the beta-thalassemia mouse models, compared with the control mice., Soluble transferrin receptor-1 (sTfR1) concentrations are increased in the plasma under two conditions that are associated with increased iron absorption, i.e. iron deficiency and increased erythropoiesis., Hemochromatosis is caused by mutations in HFE, a protein that competes with transferrin (TF) for binding to transferrin receptor 1 (TFR1)., Here we report that sorting nexin 3 (Snx3) facilitates the recycling of transferrin receptor (Tfrc) and thus is required for the proper delivery of iron to erythroid progenitors., These findings provide direct evidence that Tfr1 is essential for hematopoiesis through binding diferric transferrin to supply iron to cells.[SEP]Relations: hemochromatosis has relations: disease_protein with TFR2, disease_protein with TFR2. hemopoiesis has relations: bioprocess_protein with TWSG1, bioprocess_protein with TWSG1, bioprocess_protein with L3MBTL1, bioprocess_protein with L3MBTL1, bioprocess_protein with GFI1, bioprocess_protein with GFI1. Erythropoietin has relations: drug_protein with EPOR, drug_protein with EPOR.", "label": "no"}
{"id": "converted_1216", "sentence1": "Can desvenlafaxine be used at a dose of 50mg/day?", "sentence2": "Long-term use of desvenlafaxine was safe and well tolerated, with a clinical benefit/risk profile similar to that in other populations., e objective of this study was to evaluate the long-term safety of desvenlafaxine for continuation treatment of major depressive disorder (MDD) in Japanese patients. This was a phase 3, multicenter, 10-month, open-label study with flexible dosing of desvenlafaxine (25, 50, 100 mg/day), n an effort to establish the lowest effective dose of desvenlafaxine (administered as desvenlafaxine succinate), we assessed the efficacy, safety, and tolerability of 10- and 50-mg/day desvenlafaxine vs placebo for the treatment of major depressive disorder, Change from baseline to final evaluation in adjusted HAM-D(17) total scores was not significantly different comparing desvenlafaxine 10 mg/day (-9.28) and desvenlafaxine 50 mg/day (-8.92) with placebo (-8.42), Overall rates of treatment-emergent adverse events with both doses were similar to placebo, However, in a companion study reported separately, desvenlafaxine 50 mg, but not 25 mg, separated from placebo. Taken together, these studies suggest that 50 mg is the minimum effective dose of desvenlafaxine for the treatment of major depressive disorder. , Desvenlafaxine XR was dosed at 50 mg/day for 10 days., Desvenlafaxine therapy is initiated at the therapeutic dose (50 mg/day) without a need for dose titration., Clinical studies have investigated the efficacy of DVS in doses ranging from 50 to 400 mg/day for the treatment of MDD in adult outpatients. The effects of DVS 50 mg/day have been clearly distinguished from placebo in the reduction of MDD symptoms in such clinical trials. No additional therapeutic benefits were found at doses > 50 mg/day. The recommended dose of DVS ranges from 50 to 100 mg., Adult outpatients with major depressive disorder received desvenlafaxine doses ranging from 50-400 mg/day or placebo for 8 weeks,  At the recommended therapeutic dose of 50 mg/day, discontinuation due to adverse events was similar to placebo, atients received fixed (50, 100, 200, or 400 mg/day; n=1,342) or flexible doses (100-400 mg/day; n=463) of desvenlafaxine or placebo (n=1,108), Desvenlafaxine demonstrated short-term efficacy for treating major depressive disorder across the range of doses studied. No evidence of greater efficacy was observed with doses >50 mg/day; a strong dose-response effect on tolerability was observed., To assess the efficacy, safety, and tolerability of 50- and 100-mg/day doses of desvenlafaxine (administered as desvenlafaxine succinate), a serotonin-norepinephrine reuptake inhibitor, for the treatment of major depressive disorder (MDD), Patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) MDD and 17-item Hamilton Rating Scale for Depression (HAM-D(17)) scores > or =20 were randomly assigned to double-blind placebo or desvenlafaxine treatment (fixed dose of 50 mg/day or 100 mg/day) for 8 weeks., Desvenlafaxine 50 mg was associated with a significantly greater adjusted mean change from baseline on the HAM-D(17) (-11.5) compared with placebo (-9.5, p=0.018),  These results demonstrate efficacy, safety, and tolerability of desvenlafaxine 50 mg/day for treating MDD. , CONCLUSIONS: Desvenlafaxine at the recommended dose of 50 mg/d was effective in relapse prevention of depression during a 6-month period in patients who demonstrated stable response after 20 weeks of open-label desvenlafaxine treatment.[SEP]Relations: Desvenlafaxine has relations: drug_drug with Dosulepin, drug_drug with Dosulepin, drug_drug with Colistimethate, drug_drug with Colistimethate, drug_drug with Etonogestrel, drug_drug with Etonogestrel, drug_drug with Nomifensine, drug_drug with Nomifensine, drug_drug with Pemetrexed, drug_drug with Pemetrexed.", "label": "yes"}
{"id": "converted_3697", "sentence1": "Is SATB1 necessary for T-cell maturation?", "sentence2": "Special AT-rich binding protein 1 (SATB1) nuclear protein, expressed predominantly in T cells, regulates genes through targeting chromatin remodeling during T-cell maturation., the transcription factor SATB1 that regulates the T-cell maturation, SATB1 is a transcriptional regulator controlling the gene expression that is essential in the maturation of the immune T-cell. , Special AT-rich sequence binding protein 1 (SATB1) regulates gene expression essential in immune T-cell maturation and switching of fetal globin species, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin remodeling. [SEP]Relations: Tat protein binding has relations: molfunc_protein with GABARAPL1, molfunc_protein with GABARAPL1, molfunc_protein with NPM1, molfunc_protein with NPM1, molfunc_protein with SMARCB1, molfunc_protein with SMARCB1, molfunc_protein with DLL1, molfunc_protein with DLL1, molfunc_protein with DNAJA1, molfunc_protein with DNAJA1.", "label": "yes"}
{"id": "converted_2229", "sentence1": "Does PCSK9 (Proprotein convertase subtilisin/kexin type 9) binds with HDL-receptor (HDL-R)?", "sentence2": "Recently it was revealed that the secreted Proprotein Convertase Subtilisin Kexin 9 (PCSK9) binds with LDL-receptor (LDL-R) causing its degradation in the lysosome with the result of LDL-C accumulating in the blood., The major goal of this study is to identify peptide/s from the catalytic domain of hPCSK9 that can block the binding of hPCSK9 and LDL-R and therefore can reduce LDL-R degradation leading to the clearance of LDL-C from the plasma., In vitro administration of SRT3025 to cultured AML12 hepatocytes attenuated Pcsk9 secretion and its binding to Ldlr, thereby reducing Pcsk9-mediated Ldlr degradation and increasing Ldlr expression and LDL uptake., Proprotein convertase subtilisin/kexin type 9 (PCSK9), which involves in low-density lipoprotein cholesterol (LDL-C) metabolism by interacting with the LDL receptor, is considered as a potent therapeutic target for treating hypercholesterolemia. , Taken together, these results suggested that the IgG1-PA4 can be served as a potential candidate for the treatment of hypercholesterolemia by inhibiting PCSK9-mediated degradation of cell surface LDLRs., Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein receptor, escorting it to its destruction in the lysosome and thereby preventing the recirculation of the low-density lipoprotein receptor to the hepatocyte cell surface. , However, statins have low efficiency because they also increase PCSK9 which targets LDLR for degradation., Inhibition of the enzyme PCSK9 (proprotein convertase subtilisin/kexin type 9), which is involved in depletion of the LDL-receptor, is a new pharmacologic approach. , Proprotein convertase subtilisin kexin type 9 (PCSK9) modulates LDL-c through post-translational degradation of the LDLR., Mechanistically, hepatic S1P KD was shown to decrease the liver and plasma levels of the protein proprotein convertase subtilisin/kexin type 9 (PCSK9), which degrades LDLR protein. , We report here the development of sdAbs targeting human PCSK9 (proprotein convertase subtilisin/kexin type 9) as an alternative to anti-PCSK9 mAbs., PCSK9 proprotein convertase subtilisin/kexin type (PCSK9) protein plays an important role in LDL cholesterol (LDL-C) metabolism, due to its role in the degradation of the LDL receptor., Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to LDL receptors, leading to their degradation, Low density lipoprotein binds to proprotein convertase subtilisin/kexin type-9 (PCSK9) in human plasma and inhibits PCSK9-mediated low density lipoprotein receptor degradation, Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a secreted protein that binds to the epidermal growth factor-like-A domain of the low density lipoprotein receptor (LDLR) and mediates LDLR degradation in liver, Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds LDL receptors, targeting them for degradation, Proprotein convertase subtilisin/kexin type 9 (PCSK9), which binds the low-density lipoprotein receptor and targets it for degradation, has emerged as an important regulator of serum cholesterol levels and cardiovascular disease risk, Secreted proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein receptor (LDLR) at the cell surface and disrupts the normal recycling of the LDLR, Proprotein convertase, subtilisin/kexin type 9 (PCSK9), a key regulator of plasma LDL-cholesterol (LDL-c) and cardiovascular risk, is produced in liver and secreted into plasma where it binds hepatic LDL receptors (LDLR), leading to their degradation, Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the hepatic low-density lipoprotein receptor (LDL-R) and is therefore a prominent therapeutic target for reducing LDL-cholesterol, In the present study we scanned the related gene of a clinically diagnosed autosomal genetic hypercholesterolemia family for the possible mutations and established eukaryotic expression vector of mutation of proprotein convertase subtilisin/kexin type 9 (PCSK9) gene with gene recombination technique to investigate the contributions of the variation on low density lipoprotein receptor (LDL-R) metabolism and function alternation.Mutation detection was conducted for LDL-R, apolipoprotein B(100) (apoB(100)) and PCSK9 gene with nucleotide sequencing in a Chinese FH family, Proprotein convertase subtilisin-kexin type 9 (PCSK9) provides a key step in LDL metabolism by stimulating LDL receptor degradation., The proprotein convertase subtilisin-kexin type 9 (PCSK9) pathway plays a key role in lipoprotein metabolism by promoting LDL-receptor degradation., Proprotein convertase subtilisin-kexin type 9 (PCSK9) plays a key role in LDL receptor processing., Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the LDL receptor (LDLr) in hepatocytes, and its expression in mouse liver has been shown to decrease with fenofibrate treatment.We developed a sandwich ELISA using recombinant human PCSK9 protein and 2 affinity-purified polyclonal antibodies directed against human PCSK9., Proprotein convertase subtilisin kexin type 9 (PCSK9) enhances the degradation of the LDLR and modulates liver CD81 levels., Low-density lipoprotein (LDL) metabolism is governed by proprotein convertase subtilisin-kexin type 9 (PCSK9), which down-regulates LDL receptor expression, resulting in higher LDL cholesterol (LDL-C)., Proprotein convertase subtilisin kexin type 9 (PCSK9) is gaining attention as a key regulator of serum LDL-cholesterol (LDLC)., The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene regulates cholesterol homoeostasis by accelerating low-density lipoprotein receptor (LDLR) degradation resulting in the decreased catabolism of low-density lipoprotein (LDL) leading to hypercholesterolaemia., Low density lipoprotein binds to proprotein convertase subtilisin/kexin type-9 (PCSK9) in human plasma and inhibits PCSK9-mediated low density lipoprotein receptor degradation., Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a secreted protein that binds to the epidermal growth factor-like-A domain of the low density lipoprotein receptor (LDLR) and mediates LDLR degradation in liver., Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of LDL-cholesterol receptor homeostasis and emerges as a therapeutic target in the prevention of cardiovascular (CV) disease., The present study was conducted to investigate the role of plasma proprotein convertase subtilisin kexin type 9 (PCSK9) levels, a regulator of LDL-receptor expression, in the occurrence of diabetic dyslipidemia.[SEP]Relations: cell surface has relations: cellcomp_protein with PCSK9, cellcomp_protein with PCSK9, cellcomp_protein with PCSK6, cellcomp_protein with PCSK6, cellcomp_protein with KLRC4-KLRK1, cellcomp_protein with KLRC4-KLRK1. lysosome has relations: cellcomp_protein with PCSK9, cellcomp_protein with PCSK9. low-density lipoprotein particle has relations: cellcomp_protein with LDLR, cellcomp_protein with LDLR.", "label": "no"}
{"id": "converted_1929", "sentence1": "Can NADPH oxidase be inhibited by apocynin and diphenylene iodonium?", "sentence2": "Ang II treatment also led to a significant increment in intracellular reactive oxygen species generation, which could be fully abolished by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors apocynin or diphenylene iodonium, indicating that Ang II enhanced oxidative stress via a NADPH oxidase-dependent manner., NOX inhibitors (diphenylene iodonium (DPI) or apocynin) were able to achieve similar results to that of ML-7 except no effect on MLCK activity and MLC20 phosphorylation. , Significant reductions of AII effects on podocyte TRPC6 were also observed after pretreatment with NADPH oxidase inhibitors apocynin or diphenylene iodonium (DPI). , Furthermore, inhibition of NOX-mediated ROS production with apocynin, diphenylene iodonium (DPI) or NOX2 docking sequence (Nox2ds)-tat peptide during these first 4h of PE stimulation significantly inhibited PE-induced hypertrophy of H9c2 cells, both after 24 and 48h of PE stimulation. , Remarkably, Ang-II induced reactive oxygen species (ROS) via a NAD(P)H oxidase-dependent mechanism, as shown by inhibition of ROS production via the NAD(P)H oxidase inhibitors diphenylene iodonium (DPI) and apocynin. , Moreover, NADPH oxidase activation by beta CD (145.5+/-9.0%; control: 98.6+/-1.6%) was also abrogated by the NADPH oxidase inhibitors apocynin (100.4+/-3.2%) and diphenylene iodonium (9.5+/-3.3%)., We used structurally diverse NADPH oxidase inhibitors, aminoethyl-benzenesulfonylfluoride (AEBSF, 100-1000microM), apocynin (100-1000microM), and diphenylene iodonium (DPI, 3-30microM), to inhibit intrinsic NADPH oxidase activity in N27 cells., Paraquat-induced ROS production was inhibited by NADPH oxidase inhibitors, apocynin and diphenylene iodonium (DPI), but not the xanthine/xanthine oxidase inhibitor, allopurinol., With the use of dihydroethidium as a superoxide indicator, C(2)-ceramide was found to increase superoxide production in the endothelial cells of small coronary arteries, which was inhibited by the NADPH oxidase inhibitors N-vanillylnonanamide, apocynin, and diphenylene iodonium., The contractile responses to U46619 in isolated PA were inhibited by PEG-catalase and the NADPH oxidase inhibitors diphenylene iodonium (DPI) and apocynin., The effects of diphenylene iodonium (DPI) and apocynin, inhibitors of NADPH oxidase, on key parameters of PSC activation were evaluated in vitro., These effects could be inhibited by diphenylene iodonium and apocynin, indicating a self-cycle regulated by NADPH oxidase in microglial activation in response to oAâ., Diphenylene iodonium is an inhibitor of the respiratory burst-generating NADPH oxidase of phagocytes., NADPH oxidase inhibitors [diphenylene iodonium (DPI) and apocynin (4-hydroxy-3-methoxy-acetophenone)] prevented the microglial activation induced by oAâ, suggesting that NADPH oxidase activation was involved in microglial activation., In addition, inhibitors of NADPH oxidase (diphenylene iodonium or apocynin) also prevented microglia proliferation, suggesting that this may be the source of hydrogen peroxide., Inhibitors of NADPH oxidase (diphenylene iodonium, apocynin, D-(+)-neopterine) also significantly blunted the generation of reactive oxygen species, activation of K(+), Cl(-)-cotransport and apoptosis induced by N-ethylmaleimide., With the use of dihydroethidium as a superoxide indicator, C(2)-ceramide was found to increase superoxide production in the endothelial cells of small coronary arteries, which was inhibited by the NADPH oxidase inhibitors N-vanillylnonanamide, apocynin, and diphenylene iodonium., NADPH-dependent superoxide production by the solubilized oxidase of neutrophils was inhibited 36% by diphenylene iodonium at a 1:1 stoichiometry with the enzyme flavoprotein content., These effects could be inhibited by diphenylene iodonium and apocynin, indicating a self-cycle regulated by NADPH oxidase in microglial activation in response to oAβ, Moreover, CSE-regulated COX-2, PGE(2), and IL-6 generation was inhibited by pretreatment with TLR4 Ab; inhibitors of c-Src (PP1), NADPH oxidase (diphenylene iodonium chloride and apocynin), p38 MAPK (SB202190), MEK1/2 (U0126), JNK1/2 (SP600125), and NF-kappaB (helenalin); a ROS scavenger (N-acetyl-l-cysteine); and transfection with siRNA of TLR4, MyD88, TRAF6, Src, p47(phox), p38, p42, JNK2, or p65, Treatment of the cells with the NADPH oxidase inhibitors, apocynin and diphenylene iodonium, inhibited these effects, With the use of dihydroethidium as a superoxide indicator, C(2)-ceramide was found to increase superoxide production in the endothelial cells of small coronary arteries, which was inhibited by the NADPH oxidase inhibitors N-vanillylnonanamide, apocynin, and diphenylene iodonium, UVB irradiation generated ROS in a dose-dependent manner, and this was significantly inhibited by diphenylene iodonium (DPI), apocynin (Apo) and neopterine (Neo), inhibitors of the NADPH oxidase, and indomethacin (Indo), a cyclooxygenase (COX) inhibitor, but not by the mitochondrial electron transport inhibitors and other cytosolic enzyme inhibitors, In RBA-1 cells, JEV induced MMP-9 expression and promoter activity, which was inhibited by pretreatment with inhibitors of NADPH oxidase (diphenylene iodonium chloride or apocynin), MAPKs (U0126, SB203580 or SP600125) and a ROS scavenger (N-acetylcysteine), or transfection with siRNAs of p47(phox) , ERK1, JNK2 and p38, Such discharge of Dectin-1-reactive β-glucan from macrophage cells was inhibited by either NADPH oxidase inhibitors (apocynin and diphenylene iodonium) or radical scavengers (N-acetyl cysteine and MCI-186), The contractile responses to U46619 in isolated PA were inhibited by PEG-catalase and the NADPH oxidase inhibitors diphenylene iodonium (DPI) and apocynin, ANG II further increased superoxide production in LP only, and this was inhibited by coincubation with diphenylene iodonium or apocynin (inhibitor of NADPH oxidase complex), Our results showed that IL-1beta enhanced HTSMCs-monocyte adhesion through up-regulation of VCAM-1, which was inhibited by pretreatment with selective inhibitors of PKCalpha (Gö6976), c-Src (PP1), NADPH oxidase [diphenylene iodonium (DPI) and apocynin (APO)], intracellular calcium chelator (BAPTA/AM), PI-PLC (U73122), CaM (calmidazolium chloride), CaM kinase II (KN62), p300 (garcinol), NF-kappaB (Bay11-7082), HDAC (trichostatin A), and ROS scavenger [N-acetyl-L-cysteine (NAC)] or transfection with siRNAs of MyD88, PKCalpha, Src, p47(phox), p300, and HDAC4., Here we show that cAMP-dependent decidualization can be attenuated or enhanced upon treatment of primary cultures with a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor (diphenylen iodonium) or activator (apocynin), respectively. , With the use of dihydroethidium as a superoxide indicator, C(2)-ceramide was found to increase superoxide production in the endothelial cells of small coronary arteries, which was inhibited by the NADPH oxidase inhibitors N-vanillylnonanamide, apocynin, and diphenylene iodonium. , The inhibition of NAD(P)H oxidase by apocynin and diphenylene iodonium, and of the mitochondrial electron transport system at complex II by thenoyltrifluoroacetone (TTFA), significantly inhibited both AGE-induced ROS production and VCAM-1 expression, whereas these effects were potentiated by rotenone and antimycin A, specific inhibitors of mitochondrial complex I and III, respectively. , Paraquat-induced ROS production was inhibited by NADPH oxidase inhibitors, apocynin and diphenylene iodonium (DPI), but not the xanthine/xanthine oxidase inhibitor, allopurinol. , Treatment of the cells with the NADPH oxidase inhibitors, apocynin and diphenylene iodonium, inhibited these effects. , The G6PD inhibitor DHEA and the inhibitors of NADPH oxidase apocynin and diphenylene iodonium (DPI) prevented both superoxide generation and capacitation in human spermatozoa, but whereas DPI and DHEA inhibited PPP, apocynin did not influence it, suggesting that PPP activation during capacitation is not a response to increased oxidative stress but exerts a role by supplying reducing equivalents to oxygen., Ang II induced a time-dependent increase in Rac1 activation and O(2)(*-) production in Neuro-2A cells, and this was abolished by pretreatment with AdN17Rac1 or the NADPH oxidase inhibitors apocynin or diphenylene iodonium. , Paraquat-induced ROS production was inhibited by NADPH oxidase inhibitors, apocynin and diphenylene iodonium (DPI), but not the xanthine/xanthine oxidase inhibitor, allopurinol., In RBA-1 cells, JEV induced MMP-9 expression and promoter activity, which was inhibited by pretreatment with inhibitors of NADPH oxidase (diphenylene iodonium chloride or apocynin), MAPKs (U0126, SB203580 or SP600125) and a ROS scavenger (N-acetylcysteine), or transfection with siRNAs of p47(phox) , ERK1, JNK2 and p38., These effects could be inhibited by diphenylene iodonium and apocynin, indicating a self-cycle regulated by NADPH oxidase in microglial activation in response to oAβ., Treatment of the cells with the NADPH oxidase inhibitors, apocynin and diphenylene iodonium, inhibited these effects., UVB irradiation generated ROS in a dose-dependent manner, and this was significantly inhibited by diphenylene iodonium (DPI), apocynin (Apo) and neopterine (Neo), inhibitors of the NADPH oxidase, and indomethacin (Indo), a cyclooxygenase (COX) inhibitor, but not by the mitochondrial electron transport inhibitors and other cytosolic enzyme inhibitors., Such discharge of Dectin-1-reactive β-glucan from macrophage cells was inhibited by either NADPH oxidase inhibitors (apocynin and diphenylene iodonium) or radical scavengers (N-acetyl cysteine and MCI-186)., Our results showed that IL-1beta enhanced HTSMCs-monocyte adhesion through up-regulation of VCAM-1, which was inhibited by pretreatment with selective inhibitors of PKCalpha (Gö6976), c-Src (PP1), NADPH oxidase [diphenylene iodonium (DPI) and apocynin (APO)], intracellular calcium chelator (BAPTA/AM), PI-PLC (U73122), CaM (calmidazolium chloride), CaM kinase II (KN62), p300 (garcinol), NF-kappaB (Bay11-7082), HDAC (trichostatin A), and ROS scavenger [N-acetyl-L-cysteine (NAC)] or transfection w, Moreover, CSE-regulated COX-2, PGE(2), and IL-6 generation was inhibited by pretreatment with TLR4 Ab; inhibitors of c-Src (PP1), NADPH oxidase (diphenylene iodonium chloride and apocynin), p38 MAPK (SB202190), MEK1/2 (U0126), JNK1/2 (SP600125), and NF-kappaB (helenalin); a ROS scavenger (N-acetyl-l-cysteine); and transfection with siRNA of TLR4, MyD88, TRAF6, Src, p47(phox), p38, p42, JNK2, or p65., The use of diphenylene iodonium, an inhibitor of NADPH oxidase, to investigate the antimicrobial action of human monocyte derived macrophages., NADPH oxidase inhibitors [diphenylene iodonium (DPI) and apocynin (4-hydroxy-3-methoxy-acetophenone)] prevented the microglial activation induced by oAβ, suggesting that NADPH oxidase activation was involved in microglial activation., Furthermore, inhibition of NOX-mediated ROS production with apocynin, diphenylene iodonium (DPI) or NOX2 docking sequence (Nox2ds)-tat peptide during these first 4h of PE stimulation significantly inhibited PE-induced hypertrophy of H9c2 cells, both after 24 and 48h of PE stimulation., We compared the pharmacological profiles of the commonly used NADPH oxidase inhibitors, diphenylene iodonium (DPI), apocynin and 4-(2-amino-ethyl)-benzolsulphonyl-fluoride (AEBSF), as well as the novel triazolo pyrimidine VAS3947., IL-1beta and TNF-alpha rapidly stimulated the rate of hydrogen peroxide produced by isolated microglia, and this was inhibited by diphenylene iodonium, implying that the cytokines were acting directly on microglia to stimulate the NADPH oxidase., The fractions achieved the same effects that known NADPH oxidase inhibitors, such as diphenylene iodonium and apocynin, but they presented better hydrosolubility., Ang II induced a time-dependent increase in Rac1 activation and O(2)(*-) production in Neuro-2A cells, and this was abolished by pretreatment with AdN17Rac1 or the NADPH oxidase inhibitors apocynin or diphenylene iodonium.[SEP]Relations: NADPH oxidase complex has relations: cellcomp_protein with NOX4, cellcomp_protein with NOX4, cellcomp_protein with NOX4, cellcomp_protein with NOX4, cellcomp_protein with NOX3, cellcomp_protein with NOX3, cellcomp_protein with NOX3, cellcomp_protein with NOX3, cellcomp_protein with CYBA, cellcomp_protein with CYBA.", "label": "yes"}
{"id": "converted_1962", "sentence1": "Do normal cells express the protein TERT?", "sentence2": "Since telomerase has been recognized as a relevant factor distinguishing cancer cells from normal cells, it has become a very promising target for anti-cancer therapy, Telomerase plays a pivotal role in cellular immortality and tumorigenesis. Its activity is normally not detectable in most somatic cells while it is reactivated in the vast majority of cancer cells. Therefore, inhibition of telomerase has been viewed as a promising anticancer approach due to its specificity for cancer cells., Telomerase activity is found in 85%-90% of all human cancers but not in their adjacent normal cells. Human telomerase reverse transcriptase (hTERT) is an essential component in the telomerase complex that plays an important role in telomerase activity., elomerase activation is considered to be a critical step in carcinogenesis and its activity correlates closely with human telomerase reverse transcriptase (hTERT) expression. Since only tumor cells that express telomerase activity would activate this promoter, the hTERT proximal promoter allows for preferential expression of viral genes in tumor cells, leading to selective viral replication[SEP]Relations: Protein S human has relations: drug_drug with Platelet Activating Factor, drug_drug with Platelet Activating Factor, drug_protein with PROC, drug_protein with PROC, drug_drug with Iloprost, drug_drug with Iloprost, drug_drug with Dienogest, drug_drug with Dienogest, drug_drug with Sarpogrelate, drug_drug with Sarpogrelate.", "label": "no"}
{"id": "converted_1853", "sentence1": "Could hypophosphatemic rickets cause craniosynostosis?", "sentence2": "This study examines a series of patients with hypophosphatemic rickets and craniosynostosis to characterize the clinical course and associated craniofacial anomalies. , Hypophosphatemic rickets and craniosynostosis: a multicenter case series., A 20-year retrospective review identified patients with hypophosphatemic rickets and secondary craniosynostosis at 3 major craniofacial centers. , Secondary craniosynostosis develops postnatally due to metabolic or mechanical factors. The most common metabolic cause is hypophosphatemic rickets, which has a variety of etiologies. Head shape changes occur later and with a more heterogeneous presentation compared with that of primary craniosynostosis., Patients with multisutural involvement or X-linked hypophosphatemic rickets had a significant delay in presentation for craniosynostosis. , Craniosynostosis can be gene-linked, or caused by metabolic diseases, such as rickets, which results from a deficiency or impaired metabolism of vitamin D, magnesium, phosphorus or calcium leading to hypomineralization of the bone. X-linked dominant hypophosphatemic rickets (XLHR) is the most prevalent genetic type of hypophosphatemic rickets and is caused by germ line mutations in the PHEX-gene. In XLHR, only few case reports of craniosynostosis were described., Papilledema in the setting of x-linked hypophosphatemic rickets with craniosynostosis., Case report of a 3-year-old female presenting with papilledema resulting from craniosynostosis secondary to XLH., X-linked hypophosphatemic rickets and craniosynostosis., X-linked hypophosphatemic (XLH) rickets is the most common form of metabolic rickets, and there have been reports linking XLH rickets to craniosynostosis. A clinical report of a patient with XLH rickets and craniosynostosis is presented with a review of literature. , This may be the reason for the common association of craniosynostosis and XLH rickets. , Craniosynostosis and associated craniofacial deformities, such as frontal bossing, often occur as symptoms of vitamin D-resistant rickets in children. Similar skull deformities develop in mice with X-linked dominant hypophosphatemia, the most common form of vitamin D-resistant rickets. , The x-linked hypophosphatemic mouse is an animal model that can be used to study the role of vitamin D-resistant rickets in the development of craniosynostosis, to relate craniosynostosis to the development of associated skull deformities, and to test new treatment procedures., Craniosynostosis secondary to rickets is rarely reported, but since neither rickets nor craniosynostosis is a reportable disease, the exact incidence of both diseases is unknown., X-linked hypophosphatemic (XLH) rickets is the most common form of metabolic rickets, and there have been reports linking XLH rickets to craniosynostosis., A clinical report of a patient with XLH rickets and craniosynostosis is presented with a review of literature., METHODS A 20-year retrospective review identified patients with hypophosphatemic rickets and secondary craniosynostosis at 3 major craniofacial centers., Bilateral coronal and sagittal synostosis in X-linked hypophosphatemic rickets: a case report., X-linked hypophosphatemic rickets and sagittal craniosynostosis: three patients requiring operative cranial expansion: case series and literature review, X-linked hypophosphatemic rickets and craniosynostosis, X-linked hypophosphatemic (XLH) rickets is the most common form of metabolic rickets, and there have been reports linking XLH rickets to craniosynostosis, The recent observations of two new cases of X-linked hypophosphatemic rickets associated with premature closure of the sagittal suture prompted a review of similar cases seen in this institution.To review the clinical records and skull radiographs of 28 children with hypophosphatemic rickets in order to investigate the frequency and type of craniosynostosis and other cranial vault changes seen in these conditions and to review the literature for relevant findings.Clinical and imaging records were reviewed on 28 patients with hypophosphatemic rickets, all younger than 18 years, Those with multisutural synostosis presented at a significantly older age than patients with sagittal or bicoronal synostosis.Patients with multisutural involvement or X-linked hypophosphatemic rickets had a significant delay in presentation for craniosynostosis, Papilledema in the setting of x-linked hypophosphatemic rickets with craniosynostosis, INTRODUCTION TO THE OPHTHALMIC LITERATURE OF AN UNUSUAL CAUSE OF PAPILLEDEMA AND SUBSEQUENT OPTIC ATROPHY: X-linked hypophosphatemic rickets (XLH).Case report of a 3-year-old female presenting with papilledema resulting from craniosynostosis secondary to XLH.Early intervention with craniofacial surgery prevented the development of optic atrophy.Children with XLH should be screened for ophthalmic evidence of elevated intracranial pressure to aid early intervention and prevention of permanent loss of vision, CONCLUSIONS: Patients with multisutural involvement or X-linked hypophosphatemic rickets had a significant delay in presentation for craniosynostosis. , Craniosynostosis can be gene-linked, or caused by metabolic diseases, such as rickets, which results from a deficiency or impaired metabolism of vitamin D, magnesium, phosphorus or calcium leading to hypomineralization of the bone. , Similar skull deformities develop in mice with X-linked dominant hypophosphatemia, the most common form of vitamin D-resistant rickets., Craniosynostosis in vitamin D-resistant rickets., Craniosynostosis can be gene-linked, or caused by metabolic diseases, such as rickets, which results from a deficiency or impaired metabolism of vitamin D, magnesium, phosphorus or calcium leading to hypomineralization of the bone., X-linked hypophosphatemic rickets and craniosynostosis., X-linked hypophosphatemic (XLH) rickets is the most common form of metabolic rickets, and there have been reports linking XLH rickets to craniosynostosis., Hypophosphatemic rickets and craniosynostosis: a multicenter case series.[SEP]Relations: Craniosynostosis has relations: disease_phenotype_positive with hypophosphatemic rickets, disease_phenotype_positive with hypophosphatemic rickets, disease_phenotype_positive with hereditary hypophosphatemic rickets, disease_phenotype_positive with hereditary hypophosphatemic rickets. hypophosphatemic rickets has relations: disease_phenotype_positive with Craniosynostosis, disease_phenotype_positive with Craniosynostosis, disease_phenotype_positive with Craniosynostosis, disease_phenotype_positive with Craniosynostosis, disease_disease with rickets (disease), disease_disease with rickets (disease).", "label": "yes"}
{"id": "converted_2227", "sentence1": "Is Downs syndrome associated with decreased risk of leukemia?", "sentence2": "The association of Down's syndrome and leukemia has been documented for over 50 years. Multiple studies have established the incidence of leukemia in Down's syndrome patients to be 10- to 20-fold higher than that in the general population., We present a case of congenital acute myeloid leukemia manifesting from the very first day of birth. Diagnosis of acute myeloid leukemia was suspected by the presence of blasts in the peripheral blood smear and was confirmed on bone marrow by flowcytometry. Karyotyping revealed Trisomy 21., Juvenile myelomonocytic leukemia (JMML) and a solitary cases of acute myeloid leukemia (AML) in Downs syndrome. , This was thus confirmed to be a case with transient leukemia with Downs syndrome.[SEP]Relations: Down syndrome has relations: disease_phenotype_positive with Decreased fertility, disease_phenotype_positive with Decreased fertility, disease_phenotype_positive with Acute megakaryocytic leukemia, disease_phenotype_positive with Acute megakaryocytic leukemia, disease_phenotype_positive with Sporadic, disease_phenotype_positive with Sporadic, disease_phenotype_positive with Short palm, disease_phenotype_positive with Short palm, disease_phenotype_positive with Short neck, disease_phenotype_positive with Short neck.", "label": "no"}
{"id": "converted_2140", "sentence1": "Is it feasible to obtain DNA read lengths that exceed 30 Kb?", "sentence2": "Single-molecule, real-time sequencing (SMRT) developed by Pacific BioSciences produces longer reads than secondary generation sequencing technologies such as Illumina. The long read length enables PacBio sequencing to close gaps in genome assembly, reveal structural variations, and identify gene isoforms with higher accuracy in transcriptomic sequencing.,  Third-generation sequencing, with read lengths>10 kb, will improve the assembly of complex genomes, but these techniques require high-molecular-weight genomic DNA (gDNA), and gDNA extraction protocols used for obtaining smaller fragments for short-read sequencing are not suitable for this purpose., The emergence and development of so called third generation sequencing platforms such as PacBio has permitted exceptionally long reads (over 20 kb) to be generated.[SEP]", "label": "no"}
{"id": "converted_296", "sentence1": "is intense physical activity associated with longevity ?", "sentence2": "We found a very significant increase in average longevity (17%) of the cyclists when compared with the general population. The age at which 50% of the general population died was 73.5 vs. 81.5 years in Tour de France participants. Our major finding is that repeated very intense exercise prolongs life span in well trained practitioners., Competitive exercise does not induce cardiac damage in individuals with healthy hearts, but does induce physiological functional and structural cardiac adaptations which have positive effects on life expectancy., Medallists lived an average of 2.8 years longer than controls. Medallists in eight of the nine country groups had a significant survival advantage compared with controls. Gold, silver, and bronze medallists each enjoyed similar sized survival advantages. Medallists in endurance sports and mixed sports had a larger survival advantage over controls at 30 years (1.13, 1.09 to 1.17; 1.11, 1.09 to 1.13) than that of medallists in power sports (1.05, 1.01 to 1.08). CONCLUSIONS: Olympic medallists live longer than the general population, irrespective of country, medal, or sport. This study was not designed to explain this effect, but possible explanations include genetic factors, physical activity, healthy lifestyle, and the wealth and status that come with international sporting glory., Long-term endurance training induces in elderly subjects an increased HRV and a higher exercise working capacity, which are well-established predictors of cardiovascular and overall mortality., Sports activity in adolescents and young adults was associated with an increased risk of SD, both in males and females. Sports, per se, was not a cause of the enhanced mortality, but it triggered SD in those athletes who were affected by cardiovascular conditions predisposing to life-threatening ventricular arrhythmias during physical exercise.[SEP]Relations: SLC17A5 has relations: molfunc_protein with transmembrane transporter activity, molfunc_protein with transmembrane transporter activity, molfunc_protein with carbohydrate:proton symporter activity, molfunc_protein with carbohydrate:proton symporter activity. Ventricular arrhythmia has relations: drug_effect with Ganciclovir, drug_effect with Ganciclovir, drug_effect with Sildenafil, drug_effect with Sildenafil. Silver has relations: drug_effect with Inflammatory abnormality of the skin, drug_effect with Inflammatory abnormality of the skin.", "label": "yes"}
{"id": "converted_745", "sentence1": "Is rivaroxaban metabolized in kidneys?", "sentence2": "The novel oral anticoagulants (i.e., dabigatran, apixaban, rivaroxaban) all undergo renal metabolism to varying degrees, and hence dosing, efficacy, and safety require special consideration in CKD patients., The new oral anticoagulants have relatively little data in patients with severe renal impairment, and all have an element of renal excretion., Now new anticoagulant drugs(dabigatran and rivaroxaban) can become available. Therefore, we have to learn how to use those drugs. They have to carefully be used because they discharge from kidney and old aged patients have potential renal dysfunction. , In the everyday practice it will be necessary to be very cautious in patients with impaired renal function, as all these drugs are eliminated by kidneys., Dabigatran etexilate and rivaroxaban carry the highest risk due to a high degree of renal excretion, whereas the risk for apixaban, edoxaban and betrixaban seems lower., However, all these agents undergo renal clearance to varying degrees, and hence dosing, efficacy, and safety require special consideration in patients with CKD. , Rivaroxaban being excreted via kidney and liver, some precautions should apply in case of liver insufficiency. , Rivaroxaban elimination is mainly renal, but also through faecal matter and by hepatic metabolism. [SEP]Relations: Rivaroxaban has relations: contraindication with kidney disease, contraindication with kidney disease, drug_drug with Carboplatin, drug_drug with Carboplatin, drug_drug with Conjugated estrogens, drug_drug with Conjugated estrogens, drug_drug with Colistin, drug_drug with Colistin, drug_drug with Metaxalone, drug_drug with Metaxalone.", "label": "yes"}
{"id": "converted_1372", "sentence1": "Does nimotuzumab improve survival of glioblastoma patients?", "sentence2": "The survival times were similar to those seen in historical data of standard therapy., The survival time of a matched population treated at the same hospital with irradiation alone was decreased (median 8.0 and 12.2 mo for GBM and AA patients, respectively) compared with that of the patients who received nimotuzumab and curative-intent radiotherapy., This study, in a poor prognosis population, validates the previous data of survival gain after combining nimotuzumab and radiotherapy, in newly diagnosed high-grade glioma patients., The mean and median survival time for subjects treated with nimotuzumab was 31.06 and 17.76 vs. 21.07 and 12.63 months for the control group. CONCLUSIONS: In this randomized trial, nimotuzumab showed an excellent safety profile and significant survival benefit in combination with irradiation., Nimotuzumab was well-tolerated and treatment with the antibody yielded a survival benefit: median survival time was 32.66 mo and the 2-y survival rate was 54.2%. This study demonstrated the feasibility of prolonged administration of nimotuzumab and showed preliminary evidence of clinical benefit in HGG patients with poor prognosis.,  Recent clinical studies show that patients with malignant gliomas could benefit from nimotuzumab treatment., CONCLUSIONS: Nimotuzumab in combination with chemotherapy has moderate activity in patients with malignant gliomas and the toxicities are well tolerable, therefore, worth further investigation., It has been evaluated in malignant brain tumors in adults and children, and shown to be therapeutically safe and effective in terms of increased survival and improved quality of life. , Conclusions As used in this study, nimotuzumab demonstrated a broad safety profile, making it acceptable for chronic use, and implied clinical benefits in terms of increased survival and improved functional status in these patients, compared to findings described in the literature. , Nimotuzumab prolongs survival in patients with malignant gliomas: A phase I/II clinical study of concomitant radiochemotherapy with or without nimotuzumab., Conclusions As used in this study, nimotuzumab demonstrated a broad safety profile, making it acceptable for chronic use, and implied clinical benefits in terms of increased survival and improved functional status in these patients, compared to findings described in the literature., This study, in a poor prognosis population, validates the previous data of survival gain after combining nimotuzumab and radiotherapy, in newly diagnosed high-grade glioma patients, Conclusions As used in this study, nimotuzumab demonstrated a broad safety profile, making it acceptable for chronic use, and implied clinical benefits in terms of increased survival and improved functional status in these patients, compared to findings described in the literature, A multicenter exploratory study combining nimotuzumab and radiotherapy showed disease control and an overall patient survival similar to previous experiences along with an improvement in the quality of patient survival and no severe side effects., Combining craniospinal irradiation (CSI) with concurrent temozolomide and nimotuzumab therapy may slightly improve tumor control and overall survival[SEP]Relations: Nimotuzumab has relations: drug_drug with Afelimomab, drug_drug with Afelimomab, drug_drug with Nemolizumab, drug_drug with Nemolizumab, drug_drug with Eculizumab, drug_drug with Eculizumab, drug_drug with Obiltoxaximab, drug_drug with Obiltoxaximab, drug_drug with Visilizumab, drug_drug with Visilizumab.", "label": "yes"}
{"id": "converted_2357", "sentence1": "Is Kummell’s disease an avascular necrosis of the vertebral body?", "sentence2": " Kummell's disease is an avascular necrosis of the vertebral body, secondary to a vertebral compression fracture. This entity is characterised by the gradual development in time of a vertebral body collapse following a trivial spinal trauma, involving a worsening back pain associated with a progressive kyphosis., Kummell's disease is a rare spinal disorder characterized as avascular necrosis of a vertebral body occurring in a delayed fashion after minor trauma., Kummell's disease is a spinal disorder characterized by delayed post-traumatic collapse of a vertebral body with avascular necrosis., Kummell disease, or avascular necrosis of a vertebral body, presents as vertebral osteonecrosis typically affecting a thoracic vertebra with compression deformity, intravertebral vacuum cleft, and exaggerated kyphosis weeks to months after a minor traumatic injury., INTRODUCTION Kummell's disease is an avascular necrosis of the vertebral body, secondary to a vertebral compression fracture., Kummel disease is the eponym for avascular necrosis of the vertebral body after a vertebral compression fracture., kummell s disease delayed post traumatic osteonecrosis of the vertebral body, Kummell's disease, caused by osteonecrosis of the vertebral body, is a cause of vertebral collapse., Kummell's disease is a post-traumatic vertebral body collapse, Kummell's disease is a rare, delayed posttraumatic collapse of a vertebral body that can occur several months or even years after an osteoporotic compression fracture. , Avascular necrosis of a vertebral body, a relatively uncommon entity, is caused by malignancy, infection, radiation, systemic steroid treatment, trauma, and the like.1 Vertebral osteonecrosis induced by trauma is called Kvmell's disease[SEP]Relations: Vertebral compression fractures has relations: disease_phenotype_positive with Cushing disease due to pituitary adenoma, disease_phenotype_positive with Cushing disease due to pituitary adenoma, disease_phenotype_positive with multicentric osteolysis, nodulosis, and arthropathy, disease_phenotype_positive with multicentric osteolysis, nodulosis, and arthropathy, disease_phenotype_positive with Gaucher disease, disease_phenotype_positive with Gaucher disease, disease_phenotype_positive with osteogenesis imperfecta, disease_phenotype_positive with osteogenesis imperfecta, disease_phenotype_positive with geroderma osteodysplastica, disease_phenotype_positive with geroderma osteodysplastica.", "label": "yes"}
{"id": "converted_2409", "sentence1": "Are mouse chromosomes acrocentric?", "sentence2": " Based on combined fluorescence in situ hybridization and linkage mapping, the gene order on CFA9 is similar to that of the homologous genes on HSA17q and mouse chromosome 11 (MMU11), but in the dog the gene order is inverted with respect to the centromere. , In murine models of human carcinogenesis, however, karyotype analysis is technically demanding because mouse chromosomes are acrocentric and of similar size., The minor satellite is closer to the short arms of the acrocentric chromosomes than the major satellite,  These cells contain Robertsonian translocated chromosomes 1 and 7 as the only submetacentric chromosome in an otherwise acrocentric genome.,  The resulting metacentric chromosomes are very different in size and in morphology from normal mouse acrocentric chromosomes.,  Because of 35 independent primary hybrids used in this study were derived from two types of feral mice, each with a different combination of Robertsonian translocation chromosomes, as well as from mice with a normal complement of acrocentric chromosomes, analysis of 16 selected mouse enzyme markers provided data on the segregation of all 20 mouse chromosomes in these hybrids, The two mouse stocks exhibit karyotypes consisting of nine pairs of metacentric chromosomes as a result of centric fusions of acrocentric chromosomes in different combinations., Physical gene mapping by in situ hybridization is a difficult task in an all-acrocentric mouse karyotype, because all of the chromosomes are morphologically very similar., The resulting metacentric chromosomes are very different in size and in morphology from normal mouse acrocentric chromosomes., murine models of human carcinogenesis are exceedingly valuable tools to understand genetic mechanisms of neoplastic growth the identification of recurrent chromosomal rearrangements by cytogenetic techniques serves as an initial screening test for tumour specific aberrations in murine models of human carcinogenesis however karyotype analysis is technically demanding because mouse chromosomes are acrocentric and of similar size fluorescence in situ hybridization fish with mouse chromosome specific painting probes can complement conventional banding analysis although sensitive and specific fish analyses are restricted to the visualization of only a few mouse chromosomes at a time here we apply a novel imaging technique that we developed recently for the visualization of human chromosomes to the simultaneous discernment of all mouse chromosomes the approach is based on spectral imaging to measure chromosome specific spectra after fish with differentially labelled mouse chromosome painting probes utilizing a combination of fourier spectroscopy ccd imaging and conventional optical microscopy spectral imaging allows simultaneous measurement of the fluorescence emission spectrum at all sample points a spectrum based classification algorithm has been adapted to karyotype mouse chromosomes we have applied spectral karyotyping sky to chemically induced plasmocytomas mammary gland tumours from transgenic mice overexpressing the c myc oncogene and thymomas from mice deficient for the ataxia telangiectasia atm gene results from these analyses demonstrate the potential of sky to identify complex chromosomal aberrations in mouse models of human carcinogenesis.[SEP]Relations: chromosome has relations: cellcomp_protein with MBD6, cellcomp_protein with MBD6, cellcomp_protein with HOXA13, cellcomp_protein with HOXA13, cellcomp_protein with TEX12, cellcomp_protein with TEX12, cellcomp_protein with CBX6, cellcomp_protein with CBX6, cellcomp_protein with CCDC86, cellcomp_protein with CCDC86.", "label": "yes"}
{"id": "converted_4316", "sentence1": "Is fusobacterium associated with Lemierre's syndrome?", "sentence2": "Invasive infections with Fusobacterium necrophorum including Lemierre's syndrome: an 8-year Swedish nationwide retrospective study., Lemierre's syndrome is defined as an oropharyngeal infection due to Fusobacterium necrophorum,, Lemierre's syndrome is a rare but life-threatening condition characterized by an oropharyngeal infection typically secondary to Fusobacterium necrophorum resulting in septic thrombophlebitis of the internal jugular vein. ,  Lemierre's syndrome is a rare condition that results from oropharyngeal infection with the gram-negative, anaerobic Fusobacterium necrophorum., INTRODUCTION: Like Fusobacterium necrophorum, Fusobacterium nucleatum is capable causing Lemierre's syndrome., [Lemierre syndrome variant: Hepatic abscesses and hepatic venous thrombosis due to Fusobacterium nucleatum septicemia]., Fusobacterium necrophorum-induced sepsis: an unusual case of Lemierre's syndrome., F necrophorum is most commonly associated with Lemierre's syndrome: a septic thrombophlebitis of the internal jugular vein., Fusobacterium necrophorum Septicemia Leading to Lemierre's Syndrome in an Immunocompetent Individual: A Case Report., We present a case of a patient with Lemierre's syndrome caused by Fusobacterium necrophorum who developed a right frontal lobe brain abscess., Lemierre's syndrome secondary to Fusobacterium necrophorum infection, a rare cause of hepatic abscess., Lemierre's syndrome is an uncommon complication of pharyngitis commonly associated with an anaerobic gram negative bacterium, Fusobacterium necrophorum., The following presentation is a case of Lemierre's syndrome in a 23-year-old healthy individual who is infected by a rare species: Fusobacterium nucleatum., However, Fusobacterium species causing Lemierre's variant gastrointestinal syndrome has only been reported in case reports., Fusobacterium species is known for being a causative agent for Lemierre's syndrome, which is characterized by thrombophlebitis of the jugular vein., The Fusobacterium species is known for its association with septic thrombophlebitis of the internal jugular vein (Lemierre's syndrome). Lemierre's syndrome is as, Lemierre's syndrome due to Fusobacterium necrophorum., Fusobacterium species are well described as the causative pathogen in Lemierre's syndrome, a suppurative thrombophlebitis of the jugular vein. However, they are less r, Introduction: Lemierre's syndrome is a rare but serious complication of an oral infection mostly related to Fusobacterium necrophorum. This condition combines j, Fusobacterium necrophorum is a gram-negative anaerobic bacterium that is the causative agent of the invasive disease Lemierre's syndrome., INTRODUCTION: Lemierre's syndrome is defined as an oropharyngeal infection due to Fusobacterium necrophorum, associated with septic thrombophlebitis of the internal , Fusobacterium nucleatum is a gram-negative bacillius commonly found in oropharynx and is traditionally associated with Lemierre syndrome, which is characterized by history of recent oropharyngeal infection, internal jugular vein thrombosis, and isolation of anaerobic pathogens, mainly Fuosobacterium necrophorum. Ho, Lemierre's syndrome is an uncommon complication of pharyngitis commonly associated with an anaerobic gram negative bacterium, Fusobacterium necrophorum. , Fusobacterium species is known for being a causative agent for Lemierre's syndrome, which is characterized by thrombophlebitis of the jugular vein. , Lemierre's syndrome is a systemic complication commonly caused by oropharyngeal infection by Fusobacterium species, which manifests itself as an internal jugular vein thrombosis formation. , Lemierre's syndrome is a rare but serious condition, characterized by disseminated infection with Fusobacterium necrophorum, most often originating from the oropharynx. T, Lemierre's syndrome is a rare clinical condition that generally develops secondary to oropharyngeal infection caused by Fusobacterium necrophorum, which is an anaerobic bacteria. , Lemierre's syndrome, a systemic anaerobic infection caused by Fusobacterium necrophorum, is characterized by an acute oropharyngeal infection, septic thrombophlebitis of the internal jugular veins, sepsis, and multiple metastatic infections. It c, Lemierre's syndrome, a systemic anaerobic infection caused by Fusobacterium necrophorum, is characterized by an acute oropharyngeal infection, septic thrombophlebitis of the internal jugular vein, sepsis, and multiple metastatic infections. It c, Fusobacterium necrophorum is a rare infection most notable for causing Lemierre's syndrome., We present a patient with an atypical presentation of Fusobacterium infection, the genus responsible for Lemierre's syndrome., INTRODUCTION: Like Fusobacterium necrophorum, Fusobacterium nucleatum is capable causing Lemier, Fusobacterium necrophorum, a well‐known cause of Lemierre's syndrome, was identified., We report an unusual case of Lemierre's syndrome due to a rare species of Fusobacterium, that is, Fusobacterium nucleatum preceded by Mycoplasma pneumoniae pharyngitis and followed later by Epstein-Barr virus infectious mononucleosis., We present a case of invasive Fusobacterium infection that meets all criteria for Lemierre syndrome except lacking internal jugular thrombosis., Fusobacterium necrophorum is ananaerobic Gram-negative bacillus and is the most common organism reported to cause Lemierre's syndrome which usually occurs one to three weeks post pharyngitis or oropharyngeal surgery., Lemierre's disease: postanginal bacteremia and pulmonary involvement caused by Fusobacterium necrophorum., Increased diagnosis of Lemierre syndrome and other Fusobacterium necrophorum infections at a Children's Hospital., The Fusobacterium species is known for its association with septic thrombophlebitis of the internal jugular vein (Lemierre's syndrome)., Fusobacterium species have rarely been implicated in cases of gastrointestinal variant of Lemierre's syndrome., Fusobacterium species are well described as the causative pathogen in Lemierre's syndrome, a suppurative thrombophlebitis of the jugular vein., F. necrophorum is unique among non-spore-forming anaerobes, first for its virulence and association with Lemierre's syndrome as a monomicrobial infection and second because it seems probable that it is an exogenously acquired infection., Fusobacteria are most often associated with the classic presentation of Lemierre's syndrome consisting of a sore throat, internal jugular vein thrombophlebitis, and septic emboli to the lungs., Fusobacterium necrophorum plays a causal role in a rare and life-threatening condition, Lemierre's syndrome., Lemierre's syndrome is a rare disorder of young adults caused by the anaerobic bacterium, Fusobacterium necrophorum and occasionally by other Fusobacterium species (F. nucleatum, F. mortiferum and F. varium etc)., Lemierre's syndrome is a severe complication of Fusobacterium necrophorum oropharyngeal infection associated with metastatic foci of infection, internal jugular vein thrombosis, and septicemia., Short blood culture time-to-positivity in Fusobacterium necrophorum bacteremia is associated with Lemierre's syndrome., The causative organisms are the anaerobic fusobacteria, most commonly Fusobacterium necrophorum., In a 3-year prospective study, all cases of disseminated Fusobacterium necrophorum infections found in Denmark from 1998 to 2001 were analysed, with the aim of describing the epidemiology and clinical features of the variants of Lemierre's syndrome and disseminated non-head-and-neck-associated F. necrophorum infections.[SEP]Relations: Lemierre syndrome has relations: disease_disease with commensal bacterial infectious disease, disease_disease with commensal bacterial infectious disease, disease_disease with bacterial infectious disease with sepsis, disease_disease with bacterial infectious disease with sepsis. Fusobacterium infectious disease has relations: disease_disease with anaerobic bacteria infectious disease, disease_disease with anaerobic bacteria infectious disease, disease_disease with anaerobic bacteria infectious disease, disease_disease with anaerobic bacteria infectious disease, disease_disease with gram-negative bacterial infections, disease_disease with gram-negative bacterial infections.", "label": "yes"}
{"id": "converted_3260", "sentence1": "Can leuprorelin acetate be used as androgen deprivation therapy?", "sentence2": "We investigated the health-related quality of life (HRQoL) of long-term prostate cancer patients who received leuprorelin acetate in microcapsules (LAM) for androgen-deprivation therapy (ADT)., Long-term ADT with LAM is a well-accepted, tolerated, effective, and low-burden treatment option for patients with advanced, hormone-sensitive PCa.[SEP]Relations: lymphangioleiomyomatosis has relations: disease_phenotype_positive with Cognitive impairment, disease_phenotype_positive with Cognitive impairment, disease_phenotype_positive with Ascites, disease_phenotype_positive with Ascites, disease_phenotype_positive with Restrictive ventilatory defect, disease_phenotype_positive with Restrictive ventilatory defect, disease_phenotype_positive with Macule, disease_phenotype_positive with Macule, disease_phenotype_positive with Seizure, disease_phenotype_positive with Seizure.", "label": "yes"}
{"id": "converted_2786", "sentence1": "Do yeast LTR give rise to circular DNA?", "sentence2": "Circular retrotransposition products generated by a LINE retrotransposon, Formation of Extrachromosomal Circular DNA from Long Terminal Repeats of Retrotransposons in Saccharomyces cerevisiae, Ty eccDNA can arise from the circularization of extrachromosomal linear DNA during the transpositional life cycle of retrotransposons, or from circularization of genomic Ty DNA, Circularization may happen through nonhomologous end-joining (NHEJ) of long terminal repeats (LTRs) flanking Ty elements, by Ty autointegration, or by LTR-LTR recombination, We have recently shown that yeast LTR elements generate circular DNAs through recombination events between their flanking long terminal repeats (LTRs)., Similarly, circular DNAs can be generated by recombination between LTRs residing at different genomic loci, in which case the circular DNA will contain the intervening sequence., A recent study on circular DNAs in yeast found that transposable element sequence residing in circular structures mostly corresponded to full-length transposable elements.[SEP]Relations: Nonhomologous End-Joining (NHEJ) has relations: pathway_protein with XRCC6, pathway_protein with XRCC6, pathway_protein with XRCC5, pathway_protein with XRCC5, pathway_protein with RAD50, pathway_protein with RAD50, pathway_protein with XRCC4, pathway_protein with XRCC4, pathway_protein with TDP2, pathway_protein with TDP2.", "label": "yes"}
{"id": "converted_2150", "sentence1": "Is skin color affected by variations of the SLC24A5 gene?", "sentence2": "the alleles of single-nucleotide polymorphisms rs1426654 and rs1834640 (SLC24A5) associated with light skin pigmentation in Eurasian populati, Associations between five single nucleotide polymorphisms (SNPs) known to play a role in pigmentation (rs1426654-SLC24A5, rs1042602-TYR, rs16891982-SLC45A2, rs6058017-ASIP, and rs642742-KITLG) and MI measures were tested using standard one-way analysis of variance (ANOVA) within each population.[SEP]Relations: Sodium/Calcium exchangers has relations: pathway_protein with SLC24A5, pathway_protein with SLC24A5, pathway_protein with SLC24A4, pathway_protein with SLC24A4, pathway_protein with SLC24A2, pathway_protein with SLC24A2, pathway_protein with SLC24A3, pathway_protein with SLC24A3, pathway_protein with SLC24A1, pathway_protein with SLC24A1.", "label": "yes"}
{"id": "converted_1937", "sentence1": "Does NADPH oxidase 5 require any subunit for function?", "sentence2": "Nox5 forms a functional oligomer mediated by self-association of its dehydrogenase domain.,  While Nox1-4 require regulatory subunits, including p22phox, Nox5 activity does not depend on any subunits. ,  Thus, Nox5 forms a catalytically active oligomer in the membrane that is mediated by its dehydrogenase domain. , Coexpression of specific Nox catalytic subunits (Nox1, Nox2, Nox3, Nox4, or Nox5) along with their corresponding regulatory subunits (NOXO1/NOXA1 for Nox1; p47phox/p67phox/Rac for Nox2; NOXO1 for Nox3; no subunits for Nox4 or Nox5) resulted in marked production of reactive oxygen. [SEP]Relations: NOXO1 has relations: cellcomp_protein with NADPH oxidase complex, cellcomp_protein with NADPH oxidase complex, molfunc_protein with superoxide-generating NADPH oxidase activator activity, molfunc_protein with superoxide-generating NADPH oxidase activator activity, pathway_protein with RHO GTPases Activate NADPH Oxidases, pathway_protein with RHO GTPases Activate NADPH Oxidases. membrane has relations: cellcomp_protein with CHD5, cellcomp_protein with CHD5, cellcomp_protein with CDH5, cellcomp_protein with CDH5.", "label": "no"}
{"id": "converted_393", "sentence1": "Is there an association between bruxism and reflux?", "sentence2": "Sleep bruxism is prevalent in GERD patients, and GERD is highly associated with SB., There was a statistical trend towards tooth wear progression being associated with gastric risk factors (p < 0.05). , This article presents a case report of a 27-year-old male smoker with tooth wear and dentin sensitivity caused by GERD associated with bruxism. , The aim of this cross-over, randomized, single-blinded trial was to examine whether intra-esophageal acidification induces sleep bruxism (SB). , RMMA episodes including SB were induced by esophageal acidification. , Chronic regurgitation of gastric acids in patients with gastroesophageal reflux disease may cause dental erosion, which can lead in combination with attrition or bruxism to extensive loss of coronal tooth tissue., This clinical report describes treatment of severe tooth wear of a gastroesophageal reflux disease patient who is 54-year-old Turkish male patient. After his medical treatment, severe tooth wear, bruxism and decreased vertical dimensions were determined. , Gastroesophageal reflux disease by itself or in combination with attrition, abrasion or bruxism may be responsible for the loss., The association between bruxism, feeding and smoking habits and digestive disorders may lead to serious consequences to dental and related structures, involving dental alterations (wear, fractures and cracks), periodontal signs (gingival recession and tooth mobility) and muscle-joint sensitivity, demanding a multidisciplinary treatment plan. This paper presents a case report in which bruxism associated with acid feeding, smoking habit and episodes of gastric reflow caused severe tooth wear and great muscular discomfort with daily headache episodes. , The frequencies of RMMA, single short-burst, and clenching episodes were significantly higher during decreased esophageal pH episodes than those during other times. , These results suggest that most jaw muscle activities, ie, RMMA, single short-burst, and clenching episodes, occur in relation to gastroesophageal reflux mainly in the supine position., Nocturnal bruxism may be secondary to nocturnal gastroesophageal reflux, occurring via sleep arousal and often together with swallowing.[SEP]Relations: Gastroesophageal reflux has relations: disease_phenotype_positive with Joubert syndrome with Jeune asphyxiating thoracic dystrophy, disease_phenotype_positive with Joubert syndrome with Jeune asphyxiating thoracic dystrophy, disease_phenotype_positive with citrullinemia, disease_phenotype_positive with citrullinemia, disease_phenotype_positive with atrioventricular defect-blepharophimosis-radial and anal defect syndrome, disease_phenotype_positive with atrioventricular defect-blepharophimosis-radial and anal defect syndrome. gastroesophageal reflux disease has relations: contraindication with Racementhol, contraindication with Racementhol, contraindication with Butabarbital, contraindication with Butabarbital.", "label": "yes"}
{"id": "converted_1543", "sentence1": "Is there a mouse model for Fanconi anemia?", "sentence2": "Cyclophosphamide promotes engraftment of gene-modified cells in a mouse model of Fanconi anemia without causing cytogenetic abnormalities, We compared Cy preconditioning with fludarabine (Flu) or cytarabine (AraC) or no conditioning as a control in fanca ( -/- ) mutant mice receiving gene-modified bone marrow cells, We conclude that Cy is an effective and superior preparative regimen with respect to engraftment of lentivirus-transduced cells and functional correction in fanca ( -/- ) mice, To study whether there is a causal relationship between FA pathway defects and tumour development, we have generated a mouse model with a targeted disruption of the FA core complex gene Fancf, Fancf-deficient mouse embryonic fibroblasts displayed a phenotype typical for FA cells: they showed an aberrant response to DNA cross-linking agents as manifested by G(2) arrest, chromosomal aberrations, reduced survival, and an inability to monoubiquitinate FANCD2, Fancf homozygous mice were viable, born following a normal Mendelian distribution, and showed no growth retardation or developmental abnormalities. The gonads of Fancf mutant mice functioned abnormally, showing compromised follicle development and spermatogenesis as has been observed in other FA mouse models and in FA patients, In a cohort of Fancf-deficient mice, we observed decreased overall survival and increased tumour incidence, To provide further experimental access to the FA-M complementation group we have generated Fancm-deficient mice by deleting exon 2, FANCM deficiency caused hypogonadism in mice and hypersensitivity to cross-linking agents in mouse embryonic fibroblasts (MEFs), thus phenocopying other FA mouse models, Fancm(Delta2/Delta2) mice also showed unique features atypical for FA mice, including underrepresentation of female Fancm(Delta2/Delta2) mice and decreased overall and tumor-free survival, Fancm-deficient mice reveal unique features of Fanconi anemia complementation group M, Fancf-deficient mice are prone to develop ovarian tumours, In vivo proliferation advantage of genetically corrected hematopoietic stem cells in a mouse model of Fanconi anemia FA-D1, Using an FA mouse model with a marked hematopoietic phenotype, the FA-D1 (Brca2(Delta27/Delta27)) mice, we demonstrate that the lentivirus-mediated gene therapy of FA HSCs results in the progressive expansion of genetically corrected clones in mild-conditioned FA-D1 recipients, Consistent with these data, hematopoietic progenitors from FA recipients progressively became mitomycin C resistant and their chromosomal instability was reverted, Hematopoietic dysfunction in a mouse model for Fanconi anemia group D1, We have investigated the hematopoietic phenotype of mice with a hypomorphic mutation in the Brca2/Fancd1 gene (Brca2(Delta27/Delta27) mutation), Conventional BM competition experiments showed a marked repopulation defect in Brca2(Delta27/Delta27) hematopoietic stem cells (HSCs), compared to wild-type HSCs, Moreover, we have observed for the first time in a DNA repair disease model a very significant proliferation defect in Brca2(Delta27/Delta27) HSCs maintained in their natural physiological environment, The hematopoietic phenotype associated with the Brca2(Delta27/Delta27) mutation suggests that this FA-D1 mouse model will constitute an important tool for the development of new therapies for FA, including gene therapy, In vitro phenotypic correction of hematopoietic progenitors from Fanconi anemia group A knockout mice, In this study we characterized the hematopoietic phenotype of a Fanca knockout mouse model and corrected the main phenotypic characteristics of the bone marrow (BM) progenitors using retroviral vectors, The hematopoiesis of these animals was characterized by a modest though significant thrombocytopenia, consistent with reduced numbers of BM megakaryocyte progenitors, As observed in other FA models, the hematopoietic progenitors from Fanca(-/-) mice were highly sensitive to mitomycin C (MMC), Aiming to correct the phenotype of Fanca(-/-) progenitors, purified Lin(-)Sca-1(+) cells were transduced with retroviral vectors encoding the enhanced green fluorescent protein (EGFP) gene and human FANCA genes. Lin(-)Sca-1(+) cells from Fanca(-/-) mice were transduced with an efficiency similar to that of samples from wild-type mice. More significantly, transductions with FANCA vectors corrected both the MMC hypersensitivity as well as the impaired ex vivo expansion ability that characterized the BM progenitors of Fanca(-/-) mice,  The Btbd12 knockout mouse therefore establishes a disease model for Fanconi anemia and genetically links a regulator of nuclease incision complexes to the Fanconi anemia DNA crosslink repair pathway., Hematopoietic dysfunction in a mouse model for Fanconi anemia group D1., Bone marrow failure in the Fanconi anemia group C mouse model after DNA damage., In vivo proliferation advantage of genetically corrected hematopoietic stem cells in a mouse model of Fanconi anemia FA-D1., Assessment of the flexed-tail mouse as a possible model for Fanconi anemia: analysis of mitomycin C-induced micronuclei., The Btbd12 knockout mouse therefore establishes a disease model for Fanconi anemia and genetically links a regulator of nuclease incision complexes to the Fanconi anemia DNA crosslink repair pathway., Cyclophosphamide promotes engraftment of gene-modified cells in a mouse model of Fanconi anemia without causing cytogenetic abnormalities., Mouse models of Fanconi anemia., Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia., This review summarizes the phenotype of each of the Fanconi anemia mouse models and highlights how genetic and interventional studies using the strains have yielded novel insight into therapeutic strategies for Fanconi anemia and into how the Fanconi anemia pathway protects against genomic instability., To study FA complementation group A using the mouse as a model system, we cloned and characterized the mouse homolog of the human FANCA cDNA., Here we describe the phenotype of the Btbd12 knockout mouse, the mouse ortholog of SLX4, which recapitulates many key features of the human genetic illness Fanconi anemia., Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia, In contrast to observations made in other Fanconi anemia (FA) mouse models, low numbers of hematopoietic colony-forming cells (CFCs) were noted in Brca2(Delta27/Delta27) mice, either young or adult, Fanconi anemia group A and C double-mutant mice: functional evidence for a multi-protein Fanconi anemia complex., In addition, mouse models are also useful for testing treatments for FA., Development and characterization of immortalized fibroblastoid cell lines from an FA(C) mouse model., These mouse models display the characteristic FA feature of cellular hypersensitivity to DNA cross-linking agents[SEP]Relations: Fanconi anemia complementation group has relations: disease_disease with Fanconi anemia, disease_disease with Fanconi anemia, disease_disease with Fanconi anemia, disease_disease with Fanconi anemia, disease_disease with Fanconi anemia, disease_disease with Fanconi anemia, disease_phenotype_positive with Abnormal facial shape, disease_phenotype_positive with Abnormal facial shape, disease_phenotype_positive with Abnormal facial shape, disease_phenotype_positive with Abnormal facial shape.", "label": "yes"}
{"id": "converted_4367", "sentence1": "Can bergapten cross the blood-brain barrier?", "sentence2": "Moreover, pharmacokinetic studies showed that bergapten has higher absolute bioavailability and can cross the blood-brain barrier and has a great potential for treating brain disease, but the mechanism needs further clarification to make greater use of its ability to treat brain diseases. [SEP]Relations: blood brain barrier has relations: anatomy_anatomy with glial blood brain barrier, anatomy_anatomy with glial blood brain barrier, anatomy_anatomy with cell layer, anatomy_anatomy with cell layer. brain disease has relations: contraindication with Cefepime, contraindication with Cefepime, contraindication with Cyclopentolate, contraindication with Cyclopentolate, contraindication with Edrophonium, contraindication with Edrophonium.", "label": "yes"}
{"id": "converted_905", "sentence1": "Are viruses involved in the etiology of human subacute thyroiditis?", "sentence2": "he etiology of subacute (de Quervain's) thyroiditis (SAT) is uncertain, although it probably represents a nonspecific inflammatory response by the thyroid to a variety of viruses., Subacute thyroiditis is an inflammatory disorder of the thyroid caused probably by viruses. I, We believe that the etiologic agent was the Epstein-Barr virus because heterophile and Epstein-Barr virus-specific antibodies were positive., ltogether, these results indicate that the mechanism of inhibition of Spumavirinae infection by interferon differs from that described for the other Retroviridae, and particularly for types B, C and D viruses. Our data is of therapeutic interest since Spumavirinae have been linked to pathological processes such as de Quervain thyroiditis.[SEP]Relations: subacute thyroiditis has relations: disease_disease with thyroiditis (disease), disease_disease with thyroiditis (disease). regulation of excitatory postsynaptic membrane potential involved in skeletal muscle contraction has relations: bioprocess_bioprocess with modulation of excitatory postsynaptic potential, bioprocess_bioprocess with modulation of excitatory postsynaptic potential.", "label": "yes"}
{"id": "converted_4331", "sentence1": "Are Epoxyeicosatrienoic acids (EETs) synthesized by cytochrome P450 epoxygenases from arachidonic acid?", "sentence2": "Biologically active epoxyeicosatrienoic acid (EET) regioisomers are synthesized from arachidonic acid by cytochrome P450 epoxygenases of endothelial, myocardial, and renal tubular cells., epoxyeicosatrienoic acids (EETs), synthesized by cytochrome P450 epoxygenases from arachidonic acid. , Epoxyeicosatrienoic acids (EETs), synthesized from arachidonic acid by cytochrome P450 epoxygenases, Epoxyeicosatrienoic acids (EETs), which are synthesized from arachidonic acid by cytochrome P450 epoxygenases, function primarily as autocrine and paracrine effectors in the cardiovascular system and kidney. , Epoxyeicosatrienoic acids (EETs) are synthesized from arachidonic acid by cytochrome P450 epoxygenases in endothelial cells. I, Epoxyeicosatrienoic acids (EETs), the eicosanoid biomediators synthesized from arachidonic acid by cytochrome P450 epoxygenases,, Epoxyeicosatrienoic acids (EETs) are bioactive eicosanoids produced from arachidonic acid by cytochrome P450 epoxygenases., Arachidonic acid is metabolized to epoxyeicosatrienoic acids (EETs) by cytochrome (CYP) P450 epoxygenases, and to ω-terminal hydroxyeicosatetraenoic acids (HETEs) by ω-hydroxylases., Epoxyeicosatrienoic acids (EETs), synthesized from arachidonic acid by cytochrome P450 epoxygenases, are converted to dihydroxyeicosatrienoic acids by soluble epoxide hydrolase., Epoxyeicosatrienoic acids (EETs), which are synthesized from arachidonic acid by cytochrome P450 epoxygenases, function primarily as autocrine and paracrine effectors in the cardiovascular system and kidney., Epoxygenases metabolize arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EETs) and selected monohydroxyeicosatetraenoic acids (HETEs)., Epoxyeicosatrienoic acids (EETs) are potent lipid mediators formed by cytochrome P450 epoxygenases from arachidonic acid. , Epoxyeicosatrienoic acids (EETs) are bioactive eicosanoids produced from arachidonic acid by cytochrome P450 epoxygenases. , Epoxyeicosatrienoic acids (EETs), derived from arachidonic acid by cytochrome P450 epoxygenases, are potent vasodilators that function as endothelium-derived hyperpolarizing factors in some vascular beds. E, Epoxyeicosatrienoic acids (EETs), which are synthesized from arachidonic acid by cytochrome P450 epoxygenases, function primarily as autocrine and paracrine effectors in the cardiovascular system and kidney. T, poxyeicosatrienoic acids (EETs) are epoxy lipids derived from metabolism of arachidonic acid by cytochrome P450 epoxygenases. W, he vascular endothelium metabolizes arachidonic acid by cytochrome P450 epoxygenases to epoxyeicosatrienoic acids or EETs., Epoxyeicosatrienoic acids (EETs) are the epoxidation products of arachidonic acid catalyzed by cytochrome P450 (CYP) epoxygenases, which possess multiple biological activities. In , OBJECTIVE: Arachidonic acid metabolism by cytochrome P450 (CYP) epoxygenases leads to epoxyeicosatrienoic acids (EETs), which are eicosanoids with vasodilator and anti-inflammatory pro, Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play important and diverse roles in the cardiovascular system. Th, Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites produced by cytochrome P450 epoxygenases which are highly expressed in hepatocytes. , Epoxyeicosatrienoic acids (EETs) are epoxides of arachidonic acid generated by cytochrome P450 (CYP) epoxygenases., Although eicosanoids, including prostaglandins and leukotrienes, are best known as products of arachidonic acid metabolism by cyclooxygenases and lipoxygenases, arachidonic acid is also a substrate for another enzymatic pathway, the cytochrome P450 (CYP) system., Epoxyeicosatrienoic acids (EETs), lipid mediators synthesized from arachidonic acid by cytochrome P-450 epoxygenases, are converted by soluble epoxide hydrolase (SEH) to the corresponding dihydroxyeicosatrienoic acids (DHETs)., Epoxyeicosatrienoic acids (EETs) are synthesized from arachidonic acid by cytochrome P450 epoxygenases in endothelial cells., Epoxyeicosatrienoic acids (EETs), the eicosanoid biomediators synthesized from arachidonic acid by cytochrome P450 epoxygenases, are inactivated in many tissues by conversion to dihydroxyeicosatrienoic acids (DHETs)., Epoxyeicosatrienoic acids (EETs) are potent lipid mediators formed by cytochrome P450 epoxygenases from arachidonic acid., Recent studies show that mouse epidermis expresses CYP2B19, a keratinocyte-specific epoxygenase that generates 11,12- and 14,15-epoxyeicosatrienoic (EET) acids from arachidonate., Identification of rabbit cytochromes P450 2C1 and 2C2 as arachidonic acid epoxygenases., Epoxyeicosatrienoic acids (EETs) are formed from arachidonic acid by the action of P450 epoxygenases (CYP2C and CYP2J)., Epoxyeicosatrienoic acids (EETs) are generated from arachidonic acid by cytochrome P450 (CYP) epoxygenases.[SEP]Relations: Arachidonic Acid has relations: drug_drug with Aprepitant, drug_drug with Aprepitant, drug_drug with Phenylbutazone, drug_drug with Phenylbutazone, drug_drug with Apremilast, drug_drug with Apremilast, drug_drug with Ethinylestradiol, drug_drug with Ethinylestradiol. arachidonate 5-lipoxygenase activity has relations: molfunc_protein with ALOX5AP, molfunc_protein with ALOX5AP.", "label": "yes"}
{"id": "converted_222", "sentence1": "Is there any association between Jarid2 and miR-155 in Th17 cells?", "sentence2": "Jarid2 links MicroRNA and chromatin in Th17 cells., In this issue of Immunity, Escobar et al. (2014) bring microRNAs and chromatin together by showing how activation-induced miR-155 targets the chromatin protein Jarid2 to regulate proinflammatory cytokine production in T helper 17 cells., miR-155 activates cytokine gene expression in Th17 cells by regulating the DNA-binding protein Jarid2 to relieve polycomb-mediated repression., Mir155 was bound by Th17 cell transcription factors and was highly expressed during Th17 cell differentiation. miR-155-deficient Th17 and T regulatory (Treg) cells expressed increased amounts of Jarid2, a DNA-binding protein that recruits the Polycomb Repressive Complex 2 (PRC2) to chromatin. PRC2 binding to chromatin and H3K27 histone methylation was increased in miR-155-deficient cells, coinciding with failure to express Il22, Il10, Il9, and Atf3. Defects in Th17 cell cytokine expression and Treg cell homeostasis in the absence of Mir155 could be partially suppressed by Jarid2 deletion. Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2., Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2., Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2., Defects in Th17 cell cytokine expression and Treg cell homeostasis in the absence of Mir155 could be partially suppressed by Jarid2 deletion. Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2., Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2.[SEP]Relations: MIR155 has relations: disease_protein with lung cancer, disease_protein with lung cancer, disease_protein with lung neoplasm, disease_protein with lung neoplasm, bioprocess_protein with negative regulation of gene expression, bioprocess_protein with negative regulation of gene expression, disease_protein with goblet cell carcinoma, disease_protein with goblet cell carcinoma, disease_protein with carcinoid tumor (disease), disease_protein with carcinoid tumor (disease).", "label": "yes"}
{"id": "converted_2599", "sentence1": "A bite from the Lone Star Tick Amblyomma americanum, can cause the victim to become allergic to red meat, yes or no?", "sentence2": "A recent discovery of an IgE antibody specific to galactose-α-1,3-galactose, which is a carbohydrate abundantly expressed on cells and tissues of beef, pork, and lamb, adds one more tool to aid the clinician in making the appropriate diagnosis. A link has been discovered between the bite of the Lone Star Tick (Amblyomma americanum) and the development of sensitivity to galactose-α-1,3-galactose. , . Recently described conditions such as Southern tick-associated rash illness and anaphylaxis to red meat following tick bites have been attributed to the lone star tick., Recently described conditions such as Southern tick-associated rash illness and anaphylaxis to red meat following tick bites have been attributed to the lone star tick.[SEP]Relations: Bite cells has relations: phenotype_phenotype with Poikilocytosis, phenotype_phenotype with Poikilocytosis, disease_phenotype_positive with hereditary stomatocytosis, disease_phenotype_positive with hereditary stomatocytosis. anaphylaxis has relations: disease_disease with hypersensitivity reaction disease, disease_disease with hypersensitivity reaction disease, contraindication with Brimonidine, contraindication with Brimonidine. injury has relations: contraindication with Amlodipine, contraindication with Amlodipine.", "label": "yes"}
{"id": "converted_3359", "sentence1": "Is the FIP virus thought to be a mutated strain for the Feline enteric Coronavirus?", "sentence2": "Feline infectious peritonitis (FIP) results from mutations in the viral genome during a common feline enteric coronavirus (FECV) infection., It is caused by FIP virus (FIPV), a virulent mutant strain of Feline Enteric Coronavirus (FECV)., Feline infectious peritonitis virus (FIPV) was presumed to arise from mutations in the 3c of a ubiquitous and largely nonpathogenic feline enteric coronavirus (FECV)., Feline enteric coronavirus (FECV) causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP), can arise through mutation of FECV to FIP virus (FIPV)., Feline infectious peritonitis (FIP) is a lethal systemic disease caused by FIP virus (FIPV), a virulent mutant of apathogenic feline enteric coronavirus (FECV)., Feline infectious peritonitis (FIP) is an almost invariably fatal feline coronavirus (FCoV)-induced disease thought to arise from a combination of viral mutations and an overexuberant immune response., BACKGROUND\n\nFeline Infectious Peritonitis (FIP) is a lethal systemic disease, caused by the FIP Virus (FIPV); a virulent mutant of Feline Enteric Coronavirus (FECV)., BACKGROUND Feline Infectious Peritonitis (FIP) is a lethal systemic disease, caused by the FIP Virus (FIPV); a virulent mutant of Feline Enteric Coronavirus (FECV)., This coronavirus is a virulent mutant of the harmless, ubiquitous feline enteric coronavirus (FECV)., Feline infectious peritonitis virus (FIPV) was presumed to arise from mutations in the 3c of a ubiquitous and largely nonpathogenic feline enteric coronavirus (FECV)., Whilst intact in all FECVs, the 3c gene was mutated in the majority (71.4 %) of FIPVs, but not in all, implying that mutation in 3c is not the (single) cause of FIP.[SEP]Relations: feline infectious peritonitis has relations: disease_disease with Orthocoronavirinae infectious disease, disease_disease with Orthocoronavirinae infectious disease, disease_disease with Orthocoronavirinae infectious disease, disease_disease with Orthocoronavirinae infectious disease, disease_disease with cat disease, disease_disease with cat disease, disease_disease with cat disease, disease_disease with cat disease. Rotavirus infection has relations: disease_disease with Reoviridae infectious disease, disease_disease with Reoviridae infectious disease.", "label": "yes"}
{"id": "converted_3898", "sentence1": "Can saponins be used as adjuvant?", "sentence2": "We report the design, synthesis, immunological evaluation, and conformational analysis of new saponin variants as promising vaccine adjuvants, The purified active fraction of Albizia julibrissin saponin (AJSAF) is an ideal adjuvant candidate, BALB/c mice immunized with subcutaneous injections of the recombinant protein with or without liposome/saponin (Lip/Sap) as an adjuvant.,  a saponin-based Matrix-M™ adjuvant, . These results confirm that Momordica saponins are a viable natural source to provide potent saponin adjuvants[SEP]Relations: adaptation of signaling pathway by response to pheromone involved in conjugation with cellular fusion has relations: bioprocess_bioprocess with adaptation of signaling pathway, bioprocess_bioprocess with adaptation of signaling pathway, bioprocess_bioprocess with re-entry into mitotic cell cycle after pheromone arrest, bioprocess_bioprocess with re-entry into mitotic cell cycle after pheromone arrest.", "label": "yes"}
{"id": "converted_319", "sentence1": "Is microRNA(miRNA) 29 involved in post-ischemic cardiac remodeling?", "sentence2": "Myocardial ischaemia/reperfusion (I/R)-induced remodelling generally includes cell death (necrosis and apoptosis), myocyte hypertrophy, angiogenesis, cardiac fibrosis, and myocardial dysfunction. I, In addition, miR-21, -24, -133, -210, -494, and -499 appear to protect myocytes against I/R-induced apoptosis, whereas miR-1, -29, -199a, and -320 promote apoptosis, Myocardial fibrosis can be regulated by the miR-29 family, Studies using various in vivo, ex vivo, and in vitro models have suggested the possible involvement of miR-1, miR-21, miR-29, miR-92a, miR-133, miR-199a, and miR-320 in ischemia-reperfusion injury and/or remodeling after myocardial infarction., Among the MI-regulated miRNAs are members of the miR-29 family, which are down-regulated in the region of the heart adjacent to the infarct. The miR-29 family targets a cadre of mRNAs that encode proteins involved in fibrosis, including multiple collagens, fibrillins, and elastin. Thus, down-regulation of miR-29 would be predicted to derepress the expression of these mRNAs and enhance the fibrotic response. Indeed, down-regulation of miR-29 with anti-miRs in vitro and in vivo induces the expression of collagens, whereas over-expression of miR-29 in fibroblasts reduces collagen expression. We conclude that miR-29 acts as a regulator of cardiac fibrosis and represents a potential therapeutic target for tissue fibrosis in general.[SEP]Relations: ischemia reperfusion injury has relations: disease_protein with MIR148B, disease_protein with MIR148B, disease_protein with EFNA5, disease_protein with EFNA5. myocardial infarction has relations: disease_protein with MIR145, disease_protein with MIR145, disease_protein with MIR145, disease_protein with MIR145, disease_protein with MIR761, disease_protein with MIR761.", "label": "yes"}
{"id": "converted_4512", "sentence1": "Does p85α homodimerize?", "sentence2": "homodimerized p85α, p110α-free p85α homodimerizes, homodimeric but not monomeric p85α[SEP]", "label": "yes"}
{"id": "converted_983", "sentence1": "Have mutations in the ZEB2 gene been found in any human syndrome?", "sentence2": "Mowat-Wilson syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene, Mowat-Wilson syndrome (MWS; OMIM#235730) have characteristic facial features, a variety of congenital anomalies such as Hirschsprung disease, and intellectual disabilities caused by mutation or deletion of ZEB2 gene., owat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene, MWS is caused by de novo heterozygous mutations in the ZEB2 gene, The cause of MWS is a de novo mutation in the ZEB2 gene, owat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene, MWS have a heterozygous loss-of-function mutation in the zinc finger E-box protein 2 (ZEB2) gene, also called SIP1 (Smad-interacting protein 1) and ZFHX1B,,  human Mowat-Wilson syndrome, we suggest that deletion of ZEB2, is responsible for most of the effects of the mutation, Mutations at the hZeb2 locus cause Mowat-Wilson syndrome (MWS), Mowat-Wilson syndrome and a mutation in ZEB2, owat-Wilson syndrome (MWS) is caused by a heterozygous mutation or deletion of the ZEB2 gene, The syndrome is caused by mutations or deletions of the ZEB2 gene, owat-Wilson syndrome (MWS) is an autosomal dominant intellectual disability syndrome, single-copy ZEB2 gene deletion at 2q22.3 consistent with Mowat-Wilson syndrome, Mowat-Wilson syndrome, confirmed by molecular analysis as a heterozygous deletion of the ZEB2 gene., deletion encompassing ZEB2, the gene responsible for the Mowat-Wilson syndrome,  Six patients had deletions in the ZEB2 gene, ZEB2 gene analysis for Mowat-Wilson syndrome, Mowat-Wilson syndrome (MWS) like appearance was noted. The disease is caused by mutation or deletion of ZEB2 gene, owat-Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene, owat-Wilson syndrome (MWS) is an autosomal dominant developmental disorder with mental retardation and variable multiple congenital abnormalities due to mutations of the ZEB2 (ZFHX1B) , MWS is caused by heterozygous mutations or deletions in the Zinc finger E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1), owat-Wilson syndrome (MWS) is a multiple congenital anomaly-mental retardation complex caused by mutations in the Zinc Finger Homeobox 1 B gene (ZFHX1B), the ZFHX1B gene, which is known to be involved in the Mowat-Wilson syndrom, de novo heterozygous mutations or deletions of the ZFHX1B gene located at 2q22, owat-Wilson syndrome (MWS) is a recently delineated mental retardation (MR)-multiple congenital anomaly syndrome, FHX1B mutations in patients with Mowat-Wilson syndrome, Mutations leading to haploinsufficiency of the ZFHX1B gene, mutation in the ZFHX1B gene associated with an atypical Mowat-Wilson syndrome phenotype, ZFHX1B mutation associated with a mild Mowat-Wilson syndrome, Patients with zinc finger homeo box 1B (ZFHX1B) mutations or deletions develop multiple congenital anomalies including Hirschsprung disease, known as Mowat-Wilson syndrome (MWS), Heterozygous mutations or deletions involving the gene ZFHX1B (previously SIP1) [OMIM 605802] have recently been found to cause MWS,  ZFHX1B deletions, splice site or truncating mutations were detected in all 28 patients classified as typical MWS, Mowat-Wilson syndrome with deletion/mutation in the zinc finger homeo box 1B gene (ZFHX1B),  mutations in the zinc finger homeo box 1B gene, ZFHX1B (SIP1), ZFHX1B gene transcripts during mouse and human development supports the various clinical manifestations of the \"Mowat-Wilson\" syndrome,  ZFHX1B mutations cause a complex developmental phenotype characterized by severe mental retardation (MR) and multiple congenital defects, mutation of the zinc finger homeo box 1 B gene in syndromic corpus callosum agenesis (Mowat-Wilson syndrome, syndrome is the result of heterozygous deletions or truncating mutations of the ZFHX1B (SIP1) gene, humans with Zfhx1b mutations (Mowat-Wilson syndrome, syndrome occurs as a result of heterozygous mutations or deletions in the zinc finger E-box-binding homeobox 2 gene, ZEB2, previously called ZFHX1B (SIP1), owat-Wilson syndrome (MWS) is a recently delineated mental retardation;, Mowat-Wilson syndrome is a congenital syndrome caused by a defect of the transcriptional repressor ZFHX1B (SIP1), Mowat-Wilson syndrome patients, and all siblings had the same E87X nonsense mutation in ZFHX1B[SEP]Relations: ZEB2 has relations: disease_protein with Mowat-Wilson syndrome due to a ZEB2 point mutation, disease_protein with Mowat-Wilson syndrome due to a ZEB2 point mutation, protein_protein with SMAD2, protein_protein with SMAD2, anatomy_protein_present with blood, anatomy_protein_present with blood, anatomy_protein_present with brain, anatomy_protein_present with brain, anatomy_protein_present with embryo, anatomy_protein_present with embryo.", "label": "yes"}
{"id": "converted_3804", "sentence1": "Have the rotavirus vaccines changed the predominant rotavirus genotypes?", "sentence2": "This study describes the distribution and diversity of rotavirus genotypes before and after rotavirus vaccine introduction into the Australian NIP., G1P[8] was the dominant genotype nationally in the prevaccine era (1995-2006). Following vaccine introduction (2007-2015), greater genotype diversity was observed with fluctuating genotype dominance. Genotype distribution varied based on the vaccine implemented, with G12P[8] dominant in states using RotaTeq, and equine-like G3P[8] and G2P[4] dominant in states and territories using Rotarix., The increased diversity and differences in genotype dominance observed in states using RotaTeq (G12P[8]), and in states and territories using Rotarix (equine-like G3P[8] and G2P[4]), suggest that these vaccines exert different immunological pressures that influence the diversity of rotavirus strains circulating in Australia.[SEP]Relations: Rotavirus vaccine has relations: drug_drug with Flunisolide, drug_drug with Flunisolide, drug_drug with Hypericin, drug_drug with Hypericin, drug_drug with Flucytosine, drug_drug with Flucytosine, drug_drug with Fluocortin, drug_drug with Fluocortin, drug_drug with Corticotropin, drug_drug with Corticotropin.", "label": "yes"}
{"id": "converted_1585", "sentence1": "Can Preimplantation Genetic Diagnosis (PGD) be used for gender selection?", "sentence2": "This testing is used for identifying singlegene disorders, chromosomal abnormalities, mitochondrial disorders, gender selection in non-mendelian disorders with unequal gender distribution, aneuploidy screening, and other preconceptually identified genetic abnormalities in prospective parents. ,  Although many clinics offer PGD for HA by gender selection, an approach that detects the presence of the underlying F8 mutation has several advantages. , Preimplantation genetic diagnosis (PGD) for gender selection for non-medical reasons has been considered an unethical procedure by several authors and agencies in the Western society on the basis that it could disrupt the sex ratio, that it discriminates against women and that it leads to disposal of normal embryos of the non-desired gender. In this study, the analysis of a large series of PGD procedures for gender selection from a wide geographical area in the USA shows that, in general, there is no deviation in preference towards any specific gender except for a preference of males in some ethnic populations of Chinese, Indian and Middle Eastern origin that represent a small percentage of the US population. ,  In response to one specific question, one-third of the couples agreed to use the donor child as a lifetime organ donor and supported the use of PGD for non-medical gender selection. , More specifically, I illustrate how the prescriptions of deliberative democracy can be applied to the issue of regulating non-medical uses of pre-implantation genetic diagnosis (PGD), such as gender selection. , Private clinics were more likely than other programs to be on either the East or West Coast, list certain PGD risks (e.g., diagnostic error), note that PGD was new or controversial, reference source of PGD information, provide accuracy rates of genetic testing of embryos, and offer gender selection for social reasons., The purpose of this article is to ascertain and appraise the ethical issues inherent to the utilisation of preimplantation genetic diagnosis for gender selection in infertile patients anticipating undergoing a medically indicated assisted reproductive technique procedure. Performance of preimplantation genetic diagnosis per request specifically for gender selection by an infertile couple undergoing medically indicated assisted reproductive technique may not breach the principles of ethics, and is unlikely to alter the population balance of sexes., One possible use of PGD is to perform gender selection for couples whose offspring are at increased risk of disorders that do not follow Mendelian inheritance, but which are substantially more common in one sex than another (unequal sex incidence). Here, we examine the clinical and ethical issues to be considered prior to offering PGD gender selection to reduce the risk of a child being affected by a non-Mendelian condition with unequal sex incidence. , New uses of PGD have been reported in the past year for screening embryos for susceptibility to cancer, for late-onset diseases, for HLA-matching for existing children, and for gender. , This article describes current and likely future uses of PGD, and then analyses the ethical issues posed by new uses of PGD to screen embryos for susceptibility and late-onset conditions, for HLA-matching for tissue donation to an existing child, and for gender selection., The use of PGD for sex selection arouses considerable debate, especially in countries like India that have a marked cultural preference for boys. It is argued that using PGD for sex selection is a treatment option that can be ethically offered to couples who desire to use this technology to plan their families., Another concern is the use of this technology for nongenetic disorders such as gender selection. [SEP]Relations: chromosome separation has relations: bioprocess_protein with SMARCAD1, bioprocess_protein with SMARCAD1, bioprocess_protein with RECQL5, bioprocess_protein with RECQL5. Prostaglandin D2 has relations: drug_protein with PTGDR2, drug_protein with PTGDR2, drug_drug with Magnesium salicylate, drug_drug with Magnesium salicylate, drug_drug with Pirprofen, drug_drug with Pirprofen.", "label": "yes"}
{"id": "converted_2876", "sentence1": "Does tremelimumab improve survival of mesothelioma patients?", "sentence2": "BACKGROUND: Tremelimumab, an anti-CTLA4 monoclonal antibody, initially showed good activity when used alone in patients with mesothelioma, but did not improve the overall survival of patients who failed on first-line or second-line chemotherapy compared with placebo in the DETERMINE study. , INTERPRETATION: The combination of tremelimumab and durvalumab appeared active, with a good safety profile in patients with mesothelioma, warranting further exploration., Biological and clinical considerations rule out the use of tremelimumab as single agent for MM and, more generally, the use of immune checkpoint inhibitors for MM is still largely questionable and not supported by evidences., At the data cutoff date (Jan 24, 2016), 307 (80%) of 382 patients had died in the tremelimumab group and 154 (81%) of 189 patients had died in the placebo group. Median overall survival in the intention-to-treat population did not differ between the treatment groups: 7·7 months (95% CI 6·8-8·9) in the tremelimumab group and 7·3 months (5·9-8·7) in the placebo group (hazard ratio 0·92 [95% CI 0·76-1·12], p=0·41). , INTERPRETATION: Tremelimumab did not significantly prolong overall survival compared with placebo in patients with previously treated malignant mesothelioma., BACKGROUND\nTremelimumab, an anti-CTLA4 monoclonal antibody, initially showed good activity when used alone in patients with mesothelioma, but did not improve the overall survival of patients who failed on first-line or second-line chemotherapy compared with placebo in the DETERMINE study., INTERPRETATION\nTremelimumab did not significantly prolong overall survival compared with placebo in patients with previously treated malignant mesothelioma., Median overall survival in the intention-to-treat population did not differ between the treatment groups: 7·7 months (95% CI 6·8-8·9) in the tremelimumab group and 7·3 months (5·9-8·7) in the placebo group (hazard ratio 0·92 [95% CI 0·76-1·12], p=0·41)., BACKGROUND Tremelimumab, an anti-CTLA4 monoclonal antibody, initially showed good activity when used alone in patients with mesothelioma, but did not improve the overall survival of patients who failed on first-line or second-line chemotherapy compared with placebo in the DETERMINE study., INTERPRETATION Tremelimumab did not significantly prolong overall survival compared with placebo in patients with previously treated malignant mesothelioma., Median overall survival in the intention-to-treat population did not differ between the treatment groups: 7·7 months (95% CI 6·8-8·9) in the tremelimumab group and 7·3 months (5·9-8·7) in the placebo group (hazard ratio 0·92 [95% CI 0·76-1·12], p=0·41). , <b>BACKGROUND</b>: Tremelimumab, an anti-CTLA4 monoclonal antibody, initially showed good activity when used alone in patients with mesothelioma, but did not improve the overall survival of patients who failed on first-line or second-line chemotherapy compared with placebo in the DETERMINE study.[SEP]Relations: Tremelimumab has relations: drug_drug with Afelimomab, drug_drug with Afelimomab, drug_drug with Cemiplimab, drug_drug with Cemiplimab, drug_drug with Canakinumab, drug_drug with Canakinumab, drug_drug with Eculizumab, drug_drug with Eculizumab, drug_drug with Lumiliximab, drug_drug with Lumiliximab.", "label": "no"}
{"id": "converted_353", "sentence1": "Are there any functional differences between Mfd and its human Cocaine syndrome protein B (CSB) homolog?", "sentence2": "In humans, the TCR coupling factor, CSB, plays a critical role in restoring transcription following both UV-induced and oxidative DNA damage. It also contributes indirectly to the global repair of some forms of oxidative DNA damage. The Escherichia coli homolog, Mfd, is similarly required for TCR of UV-induced lesions., Mfd may be functionally distinct from its human CSB homolog in that it does not detectably contribute to the recovery of gene expression or global repair following oxidative damage., CSB has an ATPase activity that is stimulated strongly by DNA; however, it neither acts as a helicase nor does it dissociate stalled RNA polymerase II, suggesting a coupling mechanism in humans different from that in prokaryotes. , In addition, these findings imply that Mfd may be functionally distinct from its human CSB homolog in that it does not detectably contribute to the recovery of gene expression or global repair following oxidative damage., In addition, these findings imply that Mfd may be functionally distinct from its human CSB homolog in that it does not detectably contribute to the recovery of gene expression or global repair following oxidative damage., In contrast, no difference was detected in the rate of transcription recovery in mfd, uvrA, fpg, nth, or polB dinB umuDC mutants relative to wild-type cells following oxidative damage[SEP]Relations: Adenosine phosphate has relations: drug_protein with FBP1, drug_protein with FBP1, drug_protein with PRKAB2, drug_protein with PRKAB2, drug_protein with PDE4D, drug_protein with PDE4D, drug_protein with PRKAB1, drug_protein with PRKAB1, drug_protein with AMPD1, drug_protein with AMPD1.", "label": "yes"}
{"id": "converted_2407", "sentence1": "Has the proteome of mice hippocampus been analysed?", "sentence2": "We employed a discovery-based proteomic approach in subcellular fractions of hippocampal tissue from chronic intermittent alcohol (CIE)-exposed C57Bl/6J mice to gain insight into alcohol-induced changes in GluN2B signaling complexes. ,  We employed shotgun liquid chromatography-mass spectrometry (LC-MS) proteomic and metabonomic profiling approaches on prefrontal cortex (PFC) and hippocampal (HPC) tissue from Df(16)A+/-mice, a model of the 22q11.2 deletion syndrome. ,  Molecular alterations in the frontal cortex and hippocampus ofTsc1+/-and control mice, with or without rapamycin treatment, were investigated. A quantitative mass spectrometry-based shotgun proteomic approach (LC-MSE) was employed as an unbiased method to detect changes in protein levels., This dataset reports on the analysis of mouse hippocampus by LC-MS/MS, from mice fed a diet that was either deficient in n-3 FA (n-3 Def) or sufficient in n-3 FA (n-3 Adq). , Using isobaric tags for relative and absolute quantitation (iTRAQ) and proteomic methods, here we identified learning-induced changes in the hippocampal proteome of non-transgenic (NonTg) and 3 × Tg-AD mice, a widely used animal model of AD. [SEP]Relations: hippocampus fimbria has relations: anatomy_anatomy with central nervous system cell part cluster, anatomy_anatomy with central nervous system cell part cluster. frontal cortex has relations: anatomy_protein_present with HIPK3, anatomy_protein_present with HIPK3, anatomy_protein_present with HIPK4, anatomy_protein_present with HIPK4, anatomy_protein_present with HIPK2, anatomy_protein_present with HIPK2, anatomy_protein_present with HIPK1, anatomy_protein_present with HIPK1.", "label": "yes"}
{"id": "converted_4434", "sentence1": "Is Satb1 a transcription factor?", "sentence2": "Special AT-rich sequence binding protein-1 (SATB1) is localized to the nucleus and remodels chromatin structure in T cells, chromatin organizers SATB2 and SATB1 , transcription factor complexes. These MYB complexes assemble aberrantly with LYL1, E2A, C/EBP family members, LMO2, and SATB1. , Staining for the transcription factors Foxp2, Satb1 and Satb2 labeled most ganglion cells in the avian ganglion cell layer.[SEP]Relations: Tat protein binding has relations: molfunc_protein with DNAJA1, molfunc_protein with DNAJA1, molfunc_protein with DNAJA1, molfunc_protein with DNAJA1, molfunc_protein with GABARAPL1, molfunc_protein with GABARAPL1, molfunc_protein with GABARAPL1, molfunc_protein with GABARAPL1. Protein S human has relations: drug_drug with Factor XIII (human), drug_drug with Factor XIII (human).", "label": "yes"}
{"id": "converted_2135", "sentence1": "Are hepadnaviral minichromosomes free of nucleosomes?", "sentence2": "Several nucleosome-protected sites in a region of the DHBV genome [nucleotides (nt) 2000 to 2700], known to harbor various cis transcription regulatory elements, were consistently identified in all DHBV-positive liver samples., In addition, we observed other nucleosome protection sites in DHBV minichromosomes that may vary among individual ducks, but the pattern of MNase mapping in those regions is transmittable from the adult ducks to the newly infected ducklings., nucleosomes along viral cccDNA in the minichromosomes are not random but sequence-specifically positioned., Investigators studying the structure and function of hepadnaviral CCC DNA (3) have provided evidence that suggests that this structure exists in the nucleus of infected hepatocytes as a heterogeneous population of viral minichromosomes, which range from half to fully chromatinized, thought to be owing to their association with variable numbers of nucleosomes., Characterization of nucleosome positioning in hepadnaviral covalently closed circular DNA minichromosomes., To obtain insight on the structure of hepadnaviral cccDNA minichromosomes, we utilized ducks infected with the duck hepatitis B virus (DHBV) as a model and determined the in vivo nucleosome distribution pattern on viral cccDNA by the micrococcal nuclease (MNase) mapping and genome-wide PCR amplification of isolated mononucleosomal DHBV DNA., Mature SV40 minichromosomes are estimated to contain about 27 nucleosomes (error +/- 2), except for those molecules with a nucleosome-free gap, which are interpreted to contain 25 nucleosomes (error +/- 2)., In vitro replication in the presence of protein-free competitor DNA shows that replicating trypsinized minichromosomes do not lose nucleosomes and replicating competitor DNA does not gain nucleosomes., In vitro replication in the presence of protein-free competitor DNA shows that replicating trypsinized minichromosomes do not lose nucleosomes and replicating competitor DNA does not gain nucleosomes., We conclude that in both cases parental nucleosomes are transferred to progeny DNA, and, in addition, that an assembly of new nucleosomes occurs during the replication of native minichromosomes., In contrast, the replicated untreated minichromosomes were found to be densely packed with nucleosomes, indicating that an assembly of new nucleosomes occurred during in vitro replication., Investigators studying the structure and function of hepadnaviral CCC DNA (3) have provided evidence that suggests that this structure exists in the nucleus of infected hepatocytes as a heterogeneous population of viral minichromosomes, which range from half to fully chromatinized, thought to be owing to their association with variable numbers of nucleosomes, To obtain insight on the structure of hepadnaviral cccDNA minichromosomes, we utilized ducks infected with the duck hepatitis B virus (DHBV) as a model and determined the in vivo nucleosome distribution pattern on viral cccDNA by the micrococcal nuclease (MNase) mapping and genome-wide PCR amplification of isolated mononucleosomal DHBV DNA, Characterization of nucleosome positioning in hepadnaviral covalently closed circular DNA minichromosomes., To obtain insight on the structure of hepadnaviral cccDNA minichromosomes, we utilized ducks infected with the duck hepatitis B virus (DHBV) as a model and determined the in vivo nucleosome distribution pattern on viral cccDNA by the micrococcal nuclease (MNase) mapping and genome-wide PCR amplification of isolated mononucleosomal DHBV DNA., Investigators studying the structure and function of hepadnaviral CCC DNA (3) have provided evidence that suggests that this structure exists in the nucleus of infected hepatocytes as a heterogeneous population of viral minichromosomes, which range from half to fully chromatinized, thought to be owing to their association with variable numbers of nucleosomes..[SEP]Relations: nucleosome has relations: cellcomp_protein with MPHOSPH8, cellcomp_protein with MPHOSPH8, cellcomp_protein with PRM3, cellcomp_protein with PRM3, cellcomp_protein with KAT6B, cellcomp_protein with KAT6B, cellcomp_protein with PRM1, cellcomp_protein with PRM1, cellcomp_protein with PRM2, cellcomp_protein with PRM2.", "label": "no"}
{"id": "converted_4168", "sentence1": "Are enhancers directional in their targeting of gene promoters?", "sentence2": "Novel bi-directional duplex promoters (BDDP) were constructed by placing two identical core promoters divergently on both upstream and downstream sides of their duplicated enhancer elements., These promoters initiate transcription in opposite directions and are separated only by a short enhancer region, which is likely to regulate both promoters simultaneously. [SEP]Relations: promoter clearance from RNA polymerase I promoter has relations: bioprocess_bioprocess with promoter clearance during DNA-templated transcription, bioprocess_bioprocess with promoter clearance during DNA-templated transcription, bioprocess_bioprocess with promoter clearance from RNA polymerase I promoter for nuclear large rRNA transcript, bioprocess_bioprocess with promoter clearance from RNA polymerase I promoter for nuclear large rRNA transcript.", "label": "no"}
{"id": "converted_1690", "sentence1": "Is the JNK pathway activated during liver regeneration?", "sentence2": "analysis of the role of JNK signaling pathway in regulating cell proliferation and apoptosis of rat liver regeneration, paths of JNK signaling pathway regulate cell proliferation and apoptosis in both LR, c-jun is not mandatory for mouse hepatocyte proliferation , Mice lacking c-jun in the liver display impaired regeneration after partial hepatectomy (PH), initial activity of the JNK pathway, use of Drosophila for the study of regeneration , Loss of macroautophagy led to overactivation of the c-Jun N-terminal kinase (JNK)/c-Jun signaling pathway that induced cell death., stress induced during intermittent selective clamping accelerates rat liver regeneration through JNK pathway, JNK2 promotes injury after mouse LT via the MPT, Jun N-terminal kinase 2 promotes graft injury via the mitochondrial permeability transition after mouse liver transplantation, add45beta promotes hepatocyte survival during liver regeneration in mice by modulating JNK signaling, basis for JNK suppression during liver regeneration and identify Gadd45beta as a potential therapeutic target in liver diseases,  genetic inactivation of the JNK pathway results in impaired proliferation of fetal hepatoblasts in vitro and defective adult liver regeneration in vivo, enhancement of the activation of Jun N-terminal kinase and p38 mitogen-activated protein kinase caused by partial hepatectomy,  arsenite induced apoptosis in the hepatocytes in vivo, through the enhancement of the activation of JNK and p38 MAPK caused by partial hepatectomy, Jun N-terminal kinase and p38 MAPK, but not Akt, was altered., Although mechanical stress has been implicated in hepatic cirrhosis and liver regeneration following hepatectomy, the signaling pathway(s) that may be activated in hepatocytes in response to mechanical stress have not been determined,  JNK, ERK and JAK2 inhibitors partially abrogated apoptosis and when used in combination reduced it to basal levels, induction of CD40-mediated cholangiocyte apoptosis requires JAK2-mediated phosphorylation of STAT3 as well as sustained JNK1/2, ERK1/2 activation, Jun-N-terminal kinase drives cyclin D1 expression and proliferation during liver regeneration, c-Jun-N-terminal kinase (JNK) pathway is strongly activated after partial hepatectomy (PH), growth factors and cytokines are involved in liver regeneration, JAB1 (Jun activation domain-binding protein 1), a co-activator of AP-1, which is essential for liver regeneration, specifically interacts with intracellular HPO[SEP]Relations: mitogen-activated protein kinase binding has relations: molfunc_protein with PTPRJ, molfunc_protein with PTPRJ, molfunc_protein with PTPRJ, molfunc_protein with PTPRJ, molfunc_protein with PTAFR, molfunc_protein with PTAFR, molfunc_protein with PTAFR, molfunc_protein with PTAFR, molfunc_protein with CDK5RAP3, molfunc_protein with CDK5RAP3.", "label": "yes"}
{"id": "converted_4165", "sentence1": "Is belimumab effective for the lupus nephritis?", "sentence2": "Long-term effects of combined B-cell immunomodulation with rituximab and belimumab in severe, refractory systemic lupus erythematosus: 2-year results., CONCLUSIONS: Combined B-cell targeted therapy with RTX and BLM prevented full B-cell repopulation including DN B cells, with concomitant specific reduction of SLE-relevant autoantibodies. , Clinical Efficacy of Routinely Administered Belimumab on Proteinuria and Neuropsychiatric Lupus., Conclusions: In our series, BEL led to a decrease of proteinuria in patients with proteinuria of more than 1,000 mg/g creatinine despite standard of care treatment, and led to a marked clinical improvement in one patient with NPSLE. No adverse events were observed. Routinely administered BEL shows clinical efficacy on non-approved manifestations, but careful patient selection is warranted., Phase II Randomized Trial of Rituximab Plus Cyclophosphamide Followed by Belimumab for the Treatment of Lupus Nephritis., OBJECTIVE: To assess the safety, mechanism of action, and preliminary efficacy of rituximab followed by belimumab in the treatment of refractory lupus nephritis (LN)., CONCLUSION: The addition of belimumab to a treatment regimen with rituximab and CYC was safe in patients with refractory LN., RECENT FINDINGS: Recently, the Belimumab in Subjects with Systemic Lupus Erythematosus - Lupus Nephritis trial tested belimumab, an inhibitor of B-cell activating factor, as an add-on therapy to steroids and either mycophenolate mofetil (MMF) or cyclophosphamide when given IV monthly over a period of 104 weeks at an effect size of 11% for a Primary Efficacy Renal Response. , Case report: successful treatment of membranous lupus nephritis with belimumab in an African female immigrant., Recently introduced into the market, belimumab (Benlysta) is a monoclonal antibody that has potential clinically efficacious applications for the treatment of lupus nephritis., Successful treatment of a mycophenolate mofetil-refractory proliferative lupus nephritis with Belimumab in a 19-year-old woman., Following treatment with belimumab, proteinuria rapidly improved to almost normal levels and clinical remission lasted. Belimumab might hold promise for this indication.[SEP]Relations: Belimumab has relations: drug_drug with Lumiliximab, drug_drug with Lumiliximab, drug_drug with Luspatercept, drug_drug with Luspatercept, drug_drug with Tremelimumab, drug_drug with Tremelimumab, drug_drug with Dupilumab, drug_drug with Dupilumab, drug_drug with Rituximab, drug_drug with Rituximab.", "label": "yes"}
{"id": "converted_3595", "sentence1": "Can LB-100 sensitize ovarian carcinoma to cisplatin?", "sentence2": "The protein phosphatase 2A inhibitor LB100 sensitizes ovarian carcinoma cells to cisplatin-mediated cytotoxicity., LB100 sensitized ovarian carcinoma lines to cisplatin-mediated cell death. , Our results suggest that LB100 sensitizes ovarian cancer cells to cisplatin in vitro and in vivo by modulation of the DDR pathway and cell-cycle checkpoint abrogation.[SEP]Relations: Cisplatin has relations: drug_effect with Erythema, drug_effect with Erythema, drug_effect with Pancreatitis, drug_effect with Pancreatitis, drug_drug with SC-236, drug_drug with SC-236, drug_effect with Papilledema, drug_effect with Papilledema, drug_drug with SRP 299, drug_drug with SRP 299.", "label": "yes"}
{"id": "converted_2259", "sentence1": "Does TUC.338 inhibit colorectal cancer?", "sentence2": "TUC.338 promotes invasion and metastasis in colorectal cancer., Until now, the role of TUC.338 in colorectal cancers remains undefined. This study revealed that TUC.338 is significantly up-regulated in colorectal cancers (CRC) tissue and CRC cell lines, and the up-regulated TUC.338 is associated with lymph node metastasis.,  Thus, these findings suggested that TUC.338 acts as a novel oncogene by targeting the TIMP-1 gene thus promoting colorectal cancer cell migration and invasion., Thus, these findings suggested that TUC.338 acts as a novel oncogene by targeting the TIMP-1 gene thus promoting colorectal cancer cell migration and invasion., This study revealed that TUC.338 is significantly up-regulated in colorectal cancers (CRC) tissue and CRC cell lines, and the up-regulated TUC.338 is associated with lymph node metastasis., TUC.338 promotes invasion and metastasis in colorectal cancer.[SEP]Relations: colorectal carcinoma has relations: disease_protein with UNC13B, disease_protein with UNC13B, disease_protein with WAC, disease_protein with WAC, disease_protein with MIR1273C, disease_protein with MIR1273C, disease_protein with CXCL8, disease_protein with CXCL8, disease_protein with TFEC, disease_protein with TFEC.", "label": "no"}
{"id": "converted_2016", "sentence1": "Is ocular melanosis a risk factor for uveal melanoma?", "sentence2": "Ocular/oculodermal (oculo[dermal]) melanocytosis is a congenital periocular pigmentary condition that can lead to the development of uveal melanoma, estimated at 1 in 400 affected patients., Melanosis oculi is often underestimated as a risk factor for uveal melanoma and glaucoma. Ophthalmic surveillance, every 6 or 12 months is important, in patients with ocular melanocytosis for early detection of high risk diseases.,  One of about 400 patients with ODM followed for life is estimated to develop uveal melanoma. Excessive melanocytes in the uveal tract in ODM may provide the biologic basis for susceptibility to the development of uveal melanoma. Patients with ODM should be monitored ophthalmoscopically, especially during the susceptible period, for the development of uveal melanoma. The authors suggest that a national registry of ODM patients be created and prospective data collected to better assess the risk of developing uveal melanoma., In the white population, an association between oculo(dermal) melanocytosis (ODM) and uveal melanoma is well recognized. , Malignant melanomas may arise in the uveal tract, the conjunctiva, the skin of the eyelid, or the orbit. Risk factors so far identified include pre-existing choroidal naevi for uveal melanomas, primary acquired melanosis (PAM) for conjunctival tumours, and ocular and oculodermal melanocytosis for uveal and orbital lesions. , Risk factors so far identified include pre-existing choroidal naevi for uveal melanomas, primary acquired melanosis (PAM) for conjunctival tumours, and ocular and oculodermal melanocytosis for uveal and orbital lesions., Phacomatosis pigmentovascularis of cesioflammea type in 7 patients: combination of ocular pigmentation (melanocytosis or melanosis) and nevus flammeus with risk for melanoma., In the fourth case the melanoma was detected in a routine examination and we were able to apply a preserving treatment with I125 brachytherapy.DISCUSSION: Melanosis oculi is often underestimated as a risk factor for uveal melanoma and glaucoma., Association of ocular and oculodermal melanocytosis with the rate of uveal melanoma metastasis: analysis of 7872 consecutive eyes., Risk factors so far identified include pre-existing choroidal naevi for uveal melanomas, primary acquired melanosis (PAM) for conjunctival tumours, and ocular and oculodermal melanocytosis for uveal and orbital lesions, In the fourth case the melanoma was detected in a routine examination and we were able to apply a preserving treatment with I125 brachytherapy.Melanosis oculi is often underestimated as a risk factor for uveal melanoma and glaucoma, In this study, patients with melanocytosis who developed uveal melanoma were found to have double the risk for metastasis compared with those without melanocytosis.To determine the relationship of oculo(dermal) melanocytosis to the prognosis of patients with uveal melanoma.Retrospective chart review of 7872 patients with uveal melanoma treated at the Ocular Oncology Service, Wills Eye Institute, from August 25, 1970, through August 27, 2008.Enucleation, plaque radiotherapy, local resection, or thermotherapy.Metastasis and death.Of 7872 patients with uveal melanoma, oculo(dermal) melanocytosis was present in 230 (3%), By multivariable analysis, the factors predictive of metastasis in patients harboring uveal melanoma associated with oculo(dermal) melanocytosis were increased tumor thickness (P = .001) and the presence of subretinal fluid (P = .05), and the only factor predictive of death was increased tumor thickness (P = .009). , In the fourth case the melanoma was detected in a routine examination and we were able to apply a preserving treatment with I125 brachytherapy.Melanosis oculi is often underestimated as a risk factor for uveal melanoma and glaucoma., Risk factors so far identified include pre-existing choroidal naevi for uveal melanomas, primary acquired melanosis (PAM) for conjunctival tumours, and ocular and oculodermal melanocytosis for uveal and orbital lesions., CONCLUSIONS AND RELEVANCE Patients with uveal melanoma associated with oculo(dermal) melanocytosis have double the risk for metastasis compared with those with no melanocytosis., By multivariable analysis, the factors predictive of metastasis in patients harboring uveal melanoma associated with oculo(dermal) melanocytosis were increased tumor thickness (P = .001) and the presence of subretinal fluid (P = .05), and the only factor predictive of death was increased tumor thickness (P = .009)., CONCLUSIONS AND RELEVANCE Patients with uveal melanoma associated with oculo(dermal) melanocytosis have double the risk for metastasis compared with those with no melanocytosis.[SEP]Relations: melanoma has relations: disease_disease with ocular melanoma, disease_disease with ocular melanoma, disease_phenotype_positive with Uveal melanoma, disease_phenotype_positive with Uveal melanoma, disease_disease with eyelid melanoma, disease_disease with eyelid melanoma, disease_disease with skin cancer, disease_disease with skin cancer, disease_disease with amelanotic skin melanoma, disease_disease with amelanotic skin melanoma.", "label": "yes"}
{"id": "converted_903", "sentence1": "Does Rad9 interact with Aft1 in S.cerevisiae?", "sentence2": "Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae., Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast. Aft1 regulates iron homeostasis and is also involved in genome integrity having additional iron-independent functions. Using genome-wide expression and chromatin immunoprecipitation approaches, we found Rad9 to be recruited to 16% of the yeast genes, often related to cellular growth and metabolism, while affecting the transcription of ∼2% of the coding genome in the absence of exogenously induced DNA damage. Importantly, Rad9 is recruited to fragile genomic regions (transcriptionally active, GC rich, centromeres, meiotic recombination hotspots and retrotransposons) non-randomly and in an Aft1-dependent manner. Further analyses revealed substantial genome-wide parallels between Rad9 binding patterns to the genome and major activating histone marks, such as H3K36me, H3K79me and H3K4me. Thus, our findings suggest that Rad9 functions together with Aft1 on DNA damage-prone chromatin to facilitate genome surveillance, thereby ensuring rapid and effective response to possible DNA damage events., Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast, Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae, Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast. Aft1 regulates iron homeostasis and is also involved in genome integrity having additional iron-independent functions. Using genome-wide expression and chromatin immunoprecipitation approaches, we found Rad9 to be recruited to 16% of the yeast genes, often related to cellular growth and metabolism, while affecting the transcription of ?2% of the coding genome in the absence of exogenously induced DNA damage. , Importantly, Rad9 is recruited to fragile genomic regions (transcriptionally active, GC rich, centromeres, meiotic recombination hotspots and retrotransposons) non-randomly and in an Aft1-dependent manner. Further analyses revealed substantial genome-wide parallels between Rad9 binding patterns to the genome and major activating histone marks, such as H3K36me, H3K79me and H3K4me. Thus, our findings suggest that Rad9 functions together with Aft1 on DNA damage-prone chromatin to facilitate genome surveillance, thereby ensuring rapid and effective response to possible DNA damage events.[SEP]Relations: centromere clustering has relations: bioprocess_bioprocess with chromosome localization, bioprocess_bioprocess with chromosome localization, bioprocess_bioprocess with centromere clustering at the mitotic interphase nuclear envelope, bioprocess_bioprocess with centromere clustering at the mitotic interphase nuclear envelope, bioprocess_bioprocess with centromere localization, bioprocess_bioprocess with centromere localization, bioprocess_bioprocess with meiotic centromere clustering, bioprocess_bioprocess with meiotic centromere clustering. anatomical entity has relations: anatomy_anatomy with insect mouthpart, anatomy_anatomy with insect mouthpart.", "label": "yes"}
{"id": "converted_3356", "sentence1": "Is golimumab effective for sarcoidosis?", "sentence2": "Introduced monoclonal antibodies (infliximab, etanercept, adaluimumab, golimumab, rituximab), tested for efficacy in other pathologies associated with the formation of granulomas, have a limited application in patients with SA. , Although treatment was well tolerated, neither ustekinumab nor golimumab demonstrated efficacy in pulmonary sarcoidosis. , Although treatment was well tolerated, neither ustekinumab nor golimumab demonstrated efficacy in pulmonary sarcoidosis.[SEP]Relations: Golimumab has relations: drug_drug with Sarilumab, drug_drug with Sarilumab, drug_drug with Sirukumab, drug_drug with Sirukumab, drug_drug with Seribantumab, drug_drug with Seribantumab, drug_drug with Patritumab, drug_drug with Patritumab, drug_drug with Pomalidomide, drug_drug with Pomalidomide.", "label": "no"}
{"id": "converted_1486", "sentence1": "Does ventriculoperitoneal shunt improve normal pressure hydrocephalus?", "sentence2": "Clinical improvement depends not only on the capability to restore the cerebrospinal fluid dynamic, but also on the ability of cerebral parenchyma to recover the metabolic function.,  After shunting, the global CMRglu significantly increased (2.95 ± 0.44 vs 4.38 ± 0.68, p = 10(-7)) in all INPH patients with a mean percentage value of 48.7%. , Our preliminary data show that changes in the CMRglu are promptly reversible after surgery and that there is a relationship between the early metabolic changes and clinical symptoms, independently from the simultaneous changes in the ventricular size. The remarkable and prompt improvement in the global CMRglu and in symptoms may also have important implications for the current concept of \"neuronal plasticity\" and for the cells' reactivity in order to recover their metabolic function., Outcome of shunting in INPH is most often successful when patients are accurately diagnosed, suitably evaluated for surgical candidacy, and managed carefully throughout the preoperative, surgical, and postoperative periods., The decision to perform the only efficient procedure, i.e., a ventricular shunt operation, depends upon a number of established arguments in favor of that procedure. Clinical improvement, which is often spectacular, can then confirm the diagnosis. , During the 1st postoperative year, there was improvement in the condition of 22 patients (96%) who had received a ventricular shunt; 21 of these patients (91%) remained improved until death or for at least 5 years., Shunt treatment showed an effect on cognitive functions of distractibility of attention and motor speed, but not on intelligence of memory. Three patients deteriorated, eleven remained stable and sixteen showed significant improvement on psychological tests, mainly those for attention, motor speed and memory, but rarely did any improvement of intelligence occur.[SEP]Relations: Cessation of head growth has relations: phenotype_phenotype with Secondary microcephaly, phenotype_phenotype with Secondary microcephaly, disease_phenotype_positive with Angelman syndrome due to a point mutation, disease_phenotype_positive with Angelman syndrome due to a point mutation, disease_phenotype_positive with leukoencephalopathy with vanishing white matter, disease_phenotype_positive with leukoencephalopathy with vanishing white matter, disease_phenotype_positive with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, disease_phenotype_positive with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies. cerebrospinal fluid has relations: anatomy_anatomy with transudate, anatomy_anatomy with transudate.", "label": "yes"}
{"id": "converted_309", "sentence1": "Is TREM2 associated with Alzheimer's disease in humans?", "sentence2": "Genetic deficits and loss of function for the triggering receptor expressed in myeloid cells 2 (TREM2; encoded at chr6p21.1), a transmembrane spanning stimulatory receptor of the immunoglobulin/lectin-like gene superfamily, have been associated with deficiencies in phagocytosis and the innate immune system in Alzheimer's disease., Recent works have demonstrated a rare functional variant (R47H) in triggering receptor expressed on myeloid cells (TREM) 2 gene, encoding TREM2 protein, increase susceptibility to late-onset Alzheimer's disease (AD),, possible involvement of TREM2 in AD pathogenesis., TREM2 is associated with the risk of Alzheimer's disease in Spanish population., Two recent studies have reported the association of rs75932628-T in the TREM2 gene with the risk for Alzheimer's disease (AD)., we report the first positive replication study in a Spanish population and confirm that TREM2 rs75932628-T is associated with the risk for AD., (TREM2) has recently been identified as a rare risk factor for late-onset Alzheimer's disease (AD)., In this study we examined the association between TREM2 exon 2 variants and early-onset AD in a sample of Caucasian subjects of French origin including 726 patients with age of onset ≤65 years and 783 controls., We found significantly more variants in exon 2 of TREM2 in patients with Alzheimer's disease than in controls in the discovery set, The most commonly associated variant, rs75932628 (encoding R47H), showed highly significant association with Alzheimer's disease (P<0.001)., Our findings strongly implicate variant TREM2 in the pathogenesis of Alzheimer's disease. Given the reported antiinflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer's disease, Recent works have demonstrated a rare functional variant (R47H) in triggering receptor expressed on myeloid cells (TREM) 2 gene, encoding TREM2 protein, increase susceptibility to late-onset Alzheimer's disease (AD), with an odds ratio similar to that of the apolipoprotein E ε4 allele., The rs75932628-T variant of the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) has recently been identified as a rare risk factor for late-onset Alzheimer's disease (AD)., BACKGROUND: Homozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early-onset dementia., CONCLUSIONS: Heterozygous rare variants in TREM2 are associated with a significant increase in the risk of Alzheimer's disease., RESULTS: A rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in an R47H substitution, was found to confer a significant risk of Alzheimer's disease in Iceland (odds ratio, 2.92; 95% confidence interval [CI], 2.09 to 4.09; P=3.42×10(-10)).[SEP]Relations: TREM2 has relations: disease_protein with Alzheimer disease, disease_protein with Alzheimer disease, disease_protein with dementia (disease), disease_protein with dementia (disease), disease_protein with semantic dementia, disease_protein with semantic dementia, disease_protein with frontotemporal dementia, disease_protein with frontotemporal dementia, disease_protein with dystonia, disease_protein with dystonia.", "label": "yes"}
{"id": "converted_4203", "sentence1": "Does AZD3759 cross the blood brain barrier?", "sentence2": "AZD3759, an EGFR tyrosine kinase inhibitors (TKIs) with excellent blood-brain barrier (BBB) penetration,, AZD3759, a BBB-penetrating EGFR inhibitor for the treatment of EGFR mutant NSCLC with CNS metastases, We report the discovery and early clinical development of AZD3759, a selective EGFR inhibitor that can fully penetrate the blood-brain barrier (BBB),, AZD3759 is a novel EGFR tyrosine kinase inhibitor with high capability to penetrate the blood-brain barrier. , We report the discovery and early clinical development of AZD3759, a selective EGFR inhibitor that can fully penetrate the blood-brain barrier (BBB), with equal free concentrations in the blood, cerebrospinal fluid, and brain tissue., Another promising class of EGFR TKI such as AZD3759 has been designed to penetrate blood brain barrier to treat brain metastases and leptomeningeal disease and has showed promising responses in patients with brain metastases., AZD3759 is a novel EGFR tyrosine kinase inhibitor with high capability to penetrate the blood-brain barrier., In our study, we demonstrated that AZD3759, an EGFR tyrosine kinase inhibitors (TKIs) with excellent blood-brain barrier (BBB) penetration, combined with radiation enhanced the antitumor efficacy in BM model from EGFR mutant (EGFRm) NSCLC., sing class of EGFR TKI such as AZD3759 has been designed to penetrate blood brain barrier to treat brain metastases and leptomeningeal disease and has showed promising responses in patients with brain metastases. Acquired re,  discovery and early clinical development of AZD3759, a selective EGFR inhibitor that can fully penetrate the blood-brain barrier (BBB), with equal free concentrations in the blood, cerebrospinal fluid, and brain tissue. Treatment with A, AZD3759, a BBB-penetrating EGFR inhibitor for the treatment of EGFR mutant NSCLC with CNS metastases., our study, we demonstrated that AZD3759, an EGFR tyrosine kinase inhibitors (TKIs) with excellent blood-brain barrier (BBB) penetration, combined with radiation enhanced the antitumor efficacy in BM model from EGFR mutant (EGFRm) NSCLC. Besides, t,  in patients with BM and LM treated with AZD3759 confirms its BBB-penetrant properties and antitumor activities. Our data demonstrate , ood penetration of the blood-brain barrier by AZD3759, and its promising clinical activity, support further assessment of this compound in studies.FUNDI, The next generation EGFR TKIs osimertinib and AZD3759 have improved BBB penetration and the BLOOM study of osimertinib and AZD3759 has reported highly promising intracranial efficacy and may herald a new frontier to treat this therapeutically challenging subset of advanced EGFR mutant patients., The results showed the BBB penetration of AZD3759 was decreased within 24 hr after radiation, however, the free concentration of AZD3759 in brain kept at a high level in the context of radiation., We also detected the BBB penetration of AZD3759 when combined with cranial radiation.,  good penetration of the blood-brain barrier by AZD3759, and its promising clinical activity, support further assessment of this compound in studies.FUND, n pretreated with a tyrosine kinase inhibitor. The good penetration of the blood-brain barrier by AZD3759, and its promising clinical activity, support further asse, An early clinical study in patients with BM and LM treated with AZD3759 confirms its BBB-penetrant properties and antitumor activities.[SEP]Relations: blood brain barrier has relations: anatomy_anatomy with glial blood brain barrier, anatomy_anatomy with glial blood brain barrier, anatomy_anatomy with cell layer, anatomy_anatomy with cell layer. central nervous system has relations: anatomy_protein_present with AZIN1, anatomy_protein_present with AZIN1, anatomy_protein_present with ZNF609, anatomy_protein_present with ZNF609, anatomy_protein_present with TBC1D9, anatomy_protein_present with TBC1D9.", "label": "yes"}
{"id": "converted_3703", "sentence1": "Does radiotherapy for Hodgkin disease increases risk for lung cancer?", "sentence2": "Risks of lung, breast, and gastrointestinal (GI) cancers increase with higher radiation dose. , CONCLUSIONS: RT treatment, especially with doses higher than 42 Gy, and smoking increase the risk of SN after HL. In this series, LC patients with early stages had a shorter elapsed time from HL diagnosis and longer OS, therefore the role of LC screening in HL survivors should be prospectively evaluated and smoking cessation counseling ought to be a key aspect during follow-up., BACKGROUND: Long-term Hodgkin lymphoma (HL) survivors have an increased risk of late cardiac morbidity and secondary lung cancer after chemotherapy and mediastinal radiotherapy. , PURPOSE: Hodgkin lymphoma (HL) survivors have an increased risk of cardiovascular disease (CD), lung cancer, and breast cancer., Lung cancer (LC) represents the most common solid tumor in survivors of Hodgkin's disease (HD), and the assessment of the mutational status of oncogenic driver mutations in LC is now standard. , PURPOSE: Hodgkin lymphoma (HL) survivors face an increased risk of treatment-related lung cancer. , Increased risk of second lung cancer in Hodgkin's lymphoma survivors: a meta-analysis., BACKGROUND: Patients treated for Hodgkin's lymphoma (HL) have a higher risk of developing second lung cancer (SLC) compared with the general population. , The pooled relative risk (RR) of SLC was 4.62 (95 % confidence interval [CI], 3.18-6.70], I (2) = 98 %), with a median absolute excess rate of 10.4 per 10,000 person-years. , CONCLUSIONS: The current meta-analysis provided a detailed estimate of the risk of SLC among HL survivors. , CONCLUSIONS\n\nThe excess risk of lung cancer in Hodgkin's disease patients treated with radiotherapy is related to the radiation dose received by the affected area of the lung., BACKGROUND\n\nLung cancer is a frequent cause of death in patients cured of Hodgkin's disease, but the contributions of chemotherapy, radiotherapy, and smoking are not well described., CONCLUSIONS\n\nPast treatments with alkylating agents and radiation therapy for Hodgkin's disease were associated with an increased risk of lung cancer in a dose-dependent and additive fashion., BACKGROUND\n\nSeveral studies have shown that survivors of Hodgkin's disease have increased risk of lung cancer, but the factors responsible for this excess risk are not well known., PURPOSE\n\nThis study was undertaken to investigate the effects of radiation dose, chemotherapy, and smoking on the risk of lung cancer following treatment of Hodgkin's disease., Increased risk of lung cancer, non-Hodgkin's lymphoma, and leukemia following Hodgkin's disease., It is recognized that survivors of Hodgkin's disease are at a substantially increased risk of lung cancer., The risk of lung and breast cancer is significantly increased after therapy for Hodgkin 's disease ( HD) , but there are few data that describe the molecular profiles of these tumors . , Hodgkin lymphoma ( HL ) survivors have an increased risk of cardiovascular disease ( CD) , lung cancer , and breast cancer . , BACKGROUND\nLung cancer is a frequent cause of death in patients cured of Hodgkin's disease, but the contributions of chemotherapy, radiotherapy, and smoking are not well described., CONCLUSIONS\nPast treatments with alkylating agents and radiation therapy for Hodgkin's disease were associated with an increased risk of lung cancer in a dose-dependent and additive fashion., Lung cancer in Hodgkin's disease: association with previous radiotherapy., Twenty-eight (94%) of 30 patients developing metachronous lung cancer received supradiaphragmatic irradiation as primary therapy for HD., The risk ratio for the development of lung cancer among HD patients was 5.6 times that expected in the general population., Seven cases of lung cancer were observed in patients with Hodgkin's disease (HD) since 1970., BACKGROUND\nSeveral studies have shown that survivors of Hodgkin's disease have increased risk of lung cancer, but the factors responsible for this excess risk are not well known., The excess risk of lung cancer in Hodgkin's disease patients treated with radiotherapy is related to the radiation dose received by the affected area of the lung., Lung cancer is a frequent cause of death in patients cured of Hodgkin's disease, but the contributions of chemotherapy, radiotherapy, and smoking are not well described., Past treatments with alkylating agents and radiation therapy for Hodgkin's disease were associated with an increased risk of lung cancer in a dose-dependent and additive fashion., Several studies have shown that survivors of Hodgkin's disease have increased risk of lung cancer, but the factors responsible for this excess risk are not well known.[SEP]Relations: Non-Hodgkin lymphoma has relations: drug_effect with Bortezomib, drug_effect with Bortezomib, drug_effect with Bortezomib, drug_effect with Bortezomib, drug_effect with Fluoxetine, drug_effect with Fluoxetine, drug_effect with Fluoxetine, drug_effect with Fluoxetine, drug_effect with Raltegravir, drug_effect with Raltegravir.", "label": "yes"}
{"id": "converted_2106", "sentence1": "Does GATA-1 regulate ribosomal protein genes?", "sentence2": "Mutations in exon 2 interfere with the synthesis of the full-length isoform of GATA-1 and lead to the production of a shortened isoform, GATA-1s. These mutations have been found in patients with Diamond-Blackfan anemia (DBA), a congenital erythroid aplasia typically caused by mutations in genes encoding ribosomal proteins., Sixteen of the corresponding transcription factors are of particular interest, as they are housekeeping genes or show a direct link to hematopoiesis, tumorigenesis or leukemia (e.g. GATA-1/2, PU.1, MZF-1)., Deletion of PKC1 relieves the repression of both ribosomal protein and rRNA genes that occurs in response to a defect in the secretory pathway., This stress is monitored by Pkc1p, which initiates a signal transduction pathway that leads to repression of transcription of the rRNA and ribosomal protein genes., The importance of the transcription of the 137 ribosomal protein genes to the economy of the cell is apparent from the existence of at least three distinct pathways that can effect the repression of this set of genes.[SEP]Relations: GATA1 has relations: protein_protein with DNASE2, protein_protein with DNASE2, protein_protein with GNA12, protein_protein with GNA12, protein_protein with SPTA1, protein_protein with SPTA1, protein_protein with SPIB, protein_protein with SPIB, protein_protein with DNAI2, protein_protein with DNAI2.", "label": "yes"}
{"id": "converted_949", "sentence1": "Do R-loops tend to form at sites of DNA replication?", "sentence2": "Escherichia coli rnhA mutants devoid of RNase HI exhibit constitutive stable DNA replication, cSDR, which is thought to be initiated from R-loops stabilized in the absence of RNase HI., We propose that the organized structure of the R-loop is critical for primer RNA function in vivo with important implications for the RNA processing and DNA replication machinery., The precursor primer RNA exists as a persistent RNA-DNA hybrid, known as an R-loop, formed during transcription through the replication origin (Xu, B., and Clayton, D. A. (1996) EMBO J. 15, 3135-3143)., We found that overproduction of RecG protein drastically decreased copy numbers of ColE1-type plasmids, which require R-loop formation between the template DNA and a primer RNA transcript (RNA II) for the initiation of replication., These results suggest that overproduced RecG inhibits the initiation of replication by prematurely resolving the R-loops formed at the replication origin region of these plasmids with its unique helicase activity. The possibility that RecG regulates the initiation of a unique mode of DNA replication, oriC-independent constitutive stable DNA replication, by its activity in resolving R-loops is discussed., We propose that downstream of a replication block, RNA at R-loops is extended by DNA polymerase I, opening up the DNA duplex and leading to the recruitment of the replisome. This would allow replication to proceed while the original block is repaired or bypassed, Furthermore, increased RNaseH expression significantly alleviated genomic instability in deficient fibroblasts suggesting that cotranscriptional R-loops formation contributes to the genesis of replication-dependent DSBs in these cells., Transcription is an important source of replicative stress and consequently, maintenance of genome integrity requires the protection of chromosomes from the deleterious effects arising from the interaction between nascent RNAs and template DNA, leading to stable DNA-RNA hybrids (R-loop) formation., Strikingly, we found that attenuation of replication strongly suppresses R-loop-mediated DNA rearrangements in both E. coli and HeLa cells., More importantly, we then show that R-loop formation causes DNA replication fork stalling, and that this in fact underlies the effects of R loops on genomic stabilit, R-loop-mediated genomic instability is caused by impairment of replication fork progression, When any of these processes are not properly coordinated, aberrant outcomes such as fork reversal and R-loop formation arise and trigger unscheduled recombinogenic events and genome rearrangements. , Many studies show that cells can manage R loop formation with efficiency, and can also process the R-loops already formed in the cell, and by which, the bad effects of R-loops on DNA replication, gene mutation and homologous recombination can be regulated., Here we propose that physiological R-loop formation at CpG island promoters can contribute to DNA replication origin specification at these regions, the most efficient replication initiation sites in mammalian cells. , In agreement with this, we found that R-loops co-localize with the ORC within the same CpG island region in a significant fraction of these efficient replication origins, precisely at the position displaying the highest density of G4 motifs. , connection between transcription and replication in human cells and suggests that R-loop dysregulation at CpG island promoter-origins might contribute to the phenotype of DNA replication abnormalities and loss of genome integrity detected in cancer cells., We show that RNA:DNA hybrids (R-loops) form at sites of transcription/replication collisions and that RNase H1 functions to suppress CFS instability., R-loops and initiation of DNA replication in human cells: a missing link?, Stable RNA-DNA hybrids (R-loops) prime the initiation of replication in Escherichia coli cells., We propose that downstream of a replication block, RNA at R-loops is extended by DNA polymerase I, opening up the DNA duplex and leading to the recruitment of the replisome., Immediately after infection, RNA-DNA hybrids (R-loops) occur on (at least some) replication origins, with the annealed RNA serving as a primer for leading-strand synthesis in one direction., Here we propose that physiological R-loop formation at CpG island promoters can contribute to DNA replication origin specification at these regions, the most efficient replication initiation sites in mammalian cells., ColE1 plasmid origins of replication and oriK sites initiate primosome assembly by an RNA-DNA hybrid structure known as R-loop., This scenario builds on the connection between transcription and replication in human cells and suggests that R-loop dysregulation at CpG island promoter-origins might contribute to the phenotype of DNA replication abnormalities and loss of genome integrity detected in cancer cells., The multiple cleavage sites on the R-loop substrate match the priming sites observed in vivo, suggesting that RNase MRP alone is capable of generating virtually all of the leading-strand replication primers., Mechanisms of primer RNA synthesis and D-loop/R-loop-dependent DNA replication in Escherichia coli., Alternative oriC-independent modes of replication initiation are possible, one of which is constitutive stable DNA replication (cSDR) from transcription-associated RNA-DNA hybrids or R-loops., Our results suggest that Top1 execute this function by suppressing the formation of DNA-RNA hybrids during transcription, these so-called R-loops interfering with the progression of replication forks., Critical role of R-loops in processing replication blocks., The possibility that RecG regulates the initiation of a unique mode of DNA replication, oriC-independent constitutive stable DNA replication, by its activity in resolving R-loops is discussed., Competition between the RNA transcript and the nontemplate DNA strand during R-loop formation in vitro: a nick can serve as a strong R-loop initiation site., More importantly, we then show that R-loop formation causes DNA replication fork stalling, and that this in fact underlies the effects of R loops on genomic stability. , Consistent with this hypothesis, the 3' ends of the mitochondrial R-loop formed by in vitro transcription are located close to the initiation sites of the mitochondrial DNA replication. , A hybrid G-quadruplex structure formed between RNA and DNA explains the extraordinary stability of the mitochondrial R-loop., Previous studies have shown that the newly synthesized primers form a stable and persistent RNA-DNA hybrid, a R-loop, near the leading-strand origin of DNA replication. , Escherichia coli rnhA mutants devoid of RNase HI exhibit constitutive stable DNA replication, cSDR, which is thought to be initiated from R-loops stabilized in the absence of RNase HI. [SEP]Relations: HELLS has relations: bioprocess_protein with DNA methylation-dependent heterochromatin assembly, bioprocess_protein with DNA methylation-dependent heterochromatin assembly, anatomy_protein_present with lymph node, anatomy_protein_present with lymph node, bioprocess_protein with maintenance of DNA methylation, bioprocess_protein with maintenance of DNA methylation. snRNA transcription by RNA polymerase III has relations: bioprocess_protein with ZC3H8, bioprocess_protein with ZC3H8, bioprocess_protein with ELL, bioprocess_protein with ELL.", "label": "yes"}
{"id": "converted_2423", "sentence1": "Is Solanezumab effective for Alzheimer's Disease?", "sentence2": "An analysis of publicly available data from the Phase II studies for bapineuzumab and solanezumab indicates that neither compound produced compelling evidence of drug-like behavior that would justify their progression into pivotal trials. , Notably, a recent study of solanezumab, an amyloid β monoclonal antibody, raises hope for the further therapeutic potential of immunotherapy, not only in Alzheimer's disease, but also for other neurodegenerative disorders, including Parkinson's disease. , For example, Eli Lilly announced a major change to its closely watched clinical trial for the Alzheimer's drug solanezumab which failed to reach statistical significance. , Areas covered: This contradiction prompted us to review all study phases of Intravenous Immunoglobulin (IVIG), Bapineuzumab, Solanezumab, Avagacestat and Dimebolin to shed more light on these recent failures. ,  Results from phase III clinical trials in mild-to-moderate Alzheimer's disease (AD) patients with two monoclonal antibodies bapineuzumab and solanezumab and intravenous immunoglobulin have been disappointing. Subsequent analysis of pooled data from both phase III trials with solanezumab showed a reduction in cognitive decline in patients with mild AD., Secondary analyses of EXPEDITION studies suggested a smaller functional effect of solanezumab relative to cognition. An increasing effect of solanezumab over 18 months was shown for cognition and function., RESULTS: In the mild AD population, less cognitive and functional decline was observed with solanezumab (n = 659) versus placebo (n = 663), measured by Alzheimer's Disease Assessment Scale Cognitive subscale, Mini-Mental State Examination, and Alzheimer's Disease Cooperative Study-Activities of Daily Living functional scale Instrumental ADLs. , The promising results obtained with aducanumab and solanezumab against Alzheimer's disease (AD) strengthen the vaccine approach to prevent AD, despite of the many clinical setbacks. , CONCLUSIONS: Solanezumab, a humanized monoclonal antibody that binds amyloid, failed to improve cognition or functional ability. , Results from phase III clinical trials in mild-to-moderate Alzheimer's disease (AD) patients with two monoclonal antibodies bapineuzumab and solanezumab and intravenous immunoglobulin have been disappointing.[SEP]Relations: Solanezumab has relations: drug_drug with Adalimumab, drug_drug with Adalimumab, drug_drug with Eldelumab, drug_drug with Eldelumab, drug_drug with Idarucizumab, drug_drug with Idarucizumab, drug_drug with Alemtuzumab, drug_drug with Alemtuzumab, drug_drug with Refanezumab, drug_drug with Refanezumab.", "label": "no"}
{"id": "converted_2308", "sentence1": "Is there an RNAi drug being developed to treat amyloidosis?", "sentence2": "Patisiran is an investigational RNA interference (RNAi) therapeutic in development for the treatment of hereditary ATTR (hATTR) amyloidosis, a progressive disease associated with significant disability, morbidity, and mortality.[SEP]Relations: primary amyloidosis has relations: disease_disease with AL amyloidosis, disease_disease with AL amyloidosis.", "label": "yes"}
{"id": "converted_2410", "sentence1": "Is overproduction of transthyretin is associated with amyloidosis associated neuropathy?", "sentence2": "Transthyretin-associated familial amyloid polyneuropathy (TTR-FAP) is a disease caused by the deposit of abnormal transthyretin on tissues, mainly nerves, transthyretin familial amyloid polyneuropathy, We report a new transthyretin (ATTR) gene c.272C>G mutation and variant protein, p.Leu32Val, in a kindred of Bolivian origin with a rapid progressive peripheral neuropathy and cardiomyopat, Hereditary transthyretin amyloidosis is an autosomal dominant inherited disorder, first described in families with sensorimotor and autonomic neuropathy., Abnormal deposition of aggregated wild-type (WT) human transthyretin (TTR) and its pathogenic variants is responsible for cardiomyopathy and neuropathy related to TTR amyloidosis. , Transthyretin (TTR), normally a plasma circulating protein, can become misfolded and aggregated, ultimately leading to extracellular deposition of amyloid fibrils usually targeted to heart or nerve tissues. Referred to as TTR-associated amyloidoses (ATTR), this group of diseases is frequently life threatening and fatal if untreated, Hereditary transthyretin amyloidosis is an autosomal dominant inherited disorder, first described in families with sensorimotor and autonomic neuropathy., Hereditary transthyretin amyloidosis (ATTR) is usually characterised by a progressive peripheral and autonomic neuropathy often with associated cardiac failure and is due to dominantly inherited transthyretin mutations causing accelerated amyloid deposition.[SEP]Relations: hereditary ATTR amyloidosis has relations: disease_disease with familial amyloid neuropathy, disease_disease with familial amyloid neuropathy, disease_disease with hereditary amyloidosis, disease_disease with hereditary amyloidosis. Optic neuropathy has relations: disease_phenotype_positive with fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3, disease_phenotype_positive with fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3, disease_phenotype_positive with combined oxidative phosphorylation deficiency, disease_phenotype_positive with combined oxidative phosphorylation deficiency. Cardiomyopathy has relations: disease_phenotype_positive with familial amyloid neuropathy, disease_phenotype_positive with familial amyloid neuropathy.", "label": "yes"}
{"id": "converted_2947", "sentence1": "Are there tools for reviewing variant calls?", "sentence2": "VIPER: a web application for rapid expert review of variant calls., With the rapid development in next-generation sequencing, cost and time requirements for genomic sequencing are decreasing, enabling applications in many areas such as cancer research. Many tools have been developed to analyze genomic variation ranging from single nucleotide variants to whole chromosomal aberrations. As sequencing throughput increases, the number of variants called by such tools also grows. Often employed manual inspection of such calls is thus becoming a time-consuming procedure. We developed the Variant InsPector and Expert Rating tool (VIPER) to speed up this process by integrating the Integrative Genomics Viewer into a web application. Analysts can then quickly iterate through variants, apply filters and make decisions based on the generated images and variant metadata. VIPER was successfully employed in analyses with manual inspection of more than 10 000 calls.Availability and implementation: VIPER is implemented in Java and Javascript and is freely available at https://github.com/MarWoes/viper., Variant Review with the Integrative Genomics Viewer., VIPER: a web application for rapid expert review of variant calls.Supplementary data are available at Bioinformatics online., We developed the Variant InsPector and Expert Rating tool (VIPER) to speed up this process by integrating the Integrative Genomics Viewer into a web application.[SEP]", "label": "yes"}
{"id": "converted_1523", "sentence1": "Can siRNA affect response to afatinib treatment?", "sentence2": "On the other hand, miR-146a enhanced the inhibition of cell proliferation by drugs targeting EGFR, including both TKIs (gefitinib, erlotinib, and afatinib) and a monoclonal antibody (cetuximab), These effects were independent of the EGFR mutation status (wild type, sensitizing mutation or resistance mutation), but were less potent compared to the effects of siRNA targeting of EGFR, Among the anti-EGFR agents tested, the strongest biological effect was observed when afatinib was combined with T790M-specific-siRNAs, The combination of a potent, irreversible kinase inhibitor such as afatinib, with T790M-specific-siRNAs should be further investigated as a new strategy in the treatment of lung cancer containing the resistant T790M mutation., The strongest biological effect was observed when afatinib was combined with an EGFR-specific siRNA, The addition of EGFR siRNA to either TKIs or cetuximab additively enhanced growth inhibition and induction of apoptosis in all five cell lines, independent of the EGFR mutation status (wild-type or sensitizing mutation or resistant mutation)., The combination of a potent, irreversible kinase inhibitor such as afatinib, with EGFR-specific siRNAs should be further investigated as a new strategy in the treatment of lung cancer and other EGFR dependent cancers, including those with downstream resistance mutations.[SEP]Relations: Afatinib has relations: drug_drug with Sirolimus, drug_drug with Sirolimus, drug_drug with Cannabidiol, drug_drug with Cannabidiol, drug_drug with Lapatinib, drug_drug with Lapatinib, drug_drug with Binimetinib, drug_drug with Binimetinib, drug_drug with Dovitinib, drug_drug with Dovitinib.", "label": "yes"}
{"id": "converted_3776", "sentence1": "Is MAGE-A3 immunotherapeutic effective for non-small-cell lung cancer?", "sentence2": "INTERPRETATION: Adjuvant treatment with the MAGE-A3 immunotherapeutic did not increase disease-free survival compared with placebo in patients with MAGE-A3-positive surgically resected NSCLC. Based on our results, further development of the MAGE-A3 immunotherapeutic for use in NSCLC has been stopped., In the overall population, median disease-free survival was 60·5 months (95% CI 57·2-not reached) for the MAGE-A3 immunotherapeutic group and 57·9 months (55·7-not reached) for the placebo group (hazard ratio [HR] 1·02, 95% CI 0·89-1·18; p=0·74). Of the patients who did not receive chemotherapy, median disease-free survival was 58·0 months (95% CI 56·6-not reached) in those in the MAGE-A3 group and 56·9 months (44·4-not reached) in the placebo group (HR 0·97, 95% CI 0·80-1·18; p=0·76). Because of the absence of treatment effect, we could not identify a gene signature predictive of clinical benefit to MAGE-A3 immunotherapeutic. , uvant treatment with the MAGE-A3 immunotherapeutic did not increase disease-free survival compared with placebo in patients with MAGE-A3-positive surgically resected NSCLC. Ba[SEP]Relations: small cell lung carcinoma has relations: disease_protein with GRIK3, disease_protein with GRIK3, disease_protein with CSF3, disease_protein with CSF3, disease_protein with TP73, disease_protein with TP73, disease_protein with EPHB3, disease_protein with EPHB3, disease_protein with TAOK3, disease_protein with TAOK3.", "label": "no"}
{"id": "converted_3255", "sentence1": "Can Daptacel be used instead of IPOL?", "sentence2": "Our goal was to compare the safety and immunogenicity of a combination vaccine (DTaP(5)-IPV-Hib; Pentacel) with that of its separately administered, US-licensed equivalent vaccines (diphtheria, tetanus, 5-component acellular pertussis vaccine [DTaP(5); Daptacel], inactivated poliovirus vaccine [IPV; IPOL], and Haemophilus influenzae type b [Hib] vaccine [ActHIB]), when administered to infants and toddlers concomitantly with other routinely recommended vaccines and to assess antibody persistence from the fourth dose in toddlers to the fifth (preschool) DTaP(5) dose., DTaP(5)-IPV-Hib is a suitable replacement for separately administered DTaP, IPV, and Hib vaccines.,  In this randomized, multicenter study, 1939 healthy infants were immunized at 2, 4, and 6 months of age with 1 of 3 lots of DTaP(5) coadministered with IPV and Hib vaccines or 1 lot of DTaP(5)-IPV-Hib combination vaccine., DTaP(5)-IPV-Hib elicited similar or fewer solicited injection-site and systemic reactions as compared with the separate administration of US-licensed DTaP(5), IPV, and Hib vaccines. [SEP]Relations: Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) has relations: drug_drug with Certolizumab pegol, drug_drug with Certolizumab pegol, drug_drug with Dactinomycin, drug_drug with Dactinomycin, drug_drug with Dacarbazine, drug_drug with Dacarbazine, drug_drug with Clobetasol, drug_drug with Clobetasol. Clostridium tetani toxoid antigen (formaldehyde inactivated) has relations: drug_drug with Dactinomycin, drug_drug with Dactinomycin.", "label": "no"}
{"id": "converted_1594", "sentence1": "Is Tuberous Sclerosis a genetic disease?", "sentence2": "Tuberous sclerosis complex (TSC) is a genetic disease, Tuberous sclerosis is a rare genetic disease, Tuberous sclerosis complex (TSC) is a multisystem genetic disease, Tuberous sclerosis complex (TSC) is a genetic disease, The disease is caused by mutational inactivation of the tumor suppressor gene tuberous sclerosis complex 1 (TSC1) or TSC2., mTOR inhibitors have antiepileptogenic and antiseizure effects in animal models of the genetic disease, tuberous sclerosis complex., Tuberous sclerosis (TSC) is an autosomal-dominant genetic disease, Tuberous sclerosis is a rare genetic disease, Tuberous Sclerosis Complex (TSC) is a genetic disease, Tuberous sclerosis complex (TSC) is a multiorgan genetic disease, Tuberous sclerosis complex (TSC) is a genetic disease, Tuberous Sclerosis Complex (TSC) is a multiorgan genetic disease, Tuberous sclerosis complex (TSC) is a genetic disease, Tuberous sclerosis complex (TSC) is a multiorgan genetic disease, In all these lesions, genetic alterations related to the tuberous sclerosis complex (TSC) have been demonstrated., Although epilepsy affects most patients with tuberous sclerosis complex (TSC), little is known about the natural history of epilepsy in this genetic disease., The tuberous sclerosis gene 2 product tuberin is an important regulator of the mammalian target of rapamycin (mTOR)., Tuberous sclerosis complex (TSC) is a genetic disease, Tuberous Sclerosis Complex (TSC) is a multiorgan genetic disease, Tuberous sclerosis complex (TSC) is a relatively rare autosomal dominant disorder, Tuberous sclerosis is a genetic disease with autosomal dominant inheritance,, PEComas are related to the genetic alterations of tuberous sclerosis complex (TSC), an autosomal dominant genetic disease due to losses of TSC1 (9q34) or TSC2 (16p13.3) genes which seem to have a role in the regulation of the Rheb/mTOR/p70S6K pathway., Tuberous sclerosis complex (TSC) is a multiorgan genetic disease, Tuberous sclerosis complex (TSC) is a genetic disease, Tuberous sclerosis is a rare genetic disease, Tuberous sclerosis complex (TSC) is a genetic disease, Tuberous sclerosis complex (TSC) is a genetic disease caused by mutation in either TSC1 or TSC2., Tuberous sclerosis complex (TSC) is a genetic disease caused by mutations in either TSC1 or TSC2 tumor suppressor genes., Mutation in either the TSC1 or TSC2 tumor suppressor gene is responsible for the inherited genetic disease of tuberous sclerosis complex., Tuberous sclerosis (TSC) is a frequent autosomal-dominant condition (affecting 1 in 6000 individuals) caused by various mutations in either the hamartin (TSC1) or the tuberin gene (TSC2)., Tuberous sclerosis is a rare genetic disease, Tuberous sclerosis (TS) is a genetic disease with prominent cutaneous and brain involvement , TSC was recognized to be a genetic disease with autosomal dominant inheritance, On average TSC families are very small; in most cases there are fewer than two informative meioses. The size distribution of chromosome 9 linked families was similar to that of non-linked families., The effects of missense changes and small in-frame deletions and insertions on protein function are not easy to predict, and the identification of such variants in individuals at risk of a genetic disease can complicate genetic counselling. One option is to perform functional tests to assess whether the variants affect protein function. We have used this strategy to characterize variants identified in the TSC1 and TSC2 genes in individuals with, or suspected of having, Tuberous Sclerosis Complex (TSC)., Tuberous sclerosis is a dominant hereditary disease, Many of these advances originated from studies of the genetic disease tuberous sclerosis complex (TSC)[SEP]Relations: tuberous sclerosis has relations: disease_disease with genetic nervous system disorder, disease_disease with genetic nervous system disorder, disease_disease with genetic nervous system disorder, disease_disease with genetic nervous system disorder, disease_disease with genetic nervous system disorder, disease_disease with genetic nervous system disorder, disease_disease with genetic nervous system disorder, disease_disease with genetic nervous system disorder, disease_disease with inherited neurodegenerative disorder, disease_disease with inherited neurodegenerative disorder.", "label": "yes"}
{"id": "converted_1447", "sentence1": "Has silicon been used in treatment of  incontinence ?", "sentence2": "an artificial anal sphincter. Worldwide, there are two established devices on the market: the artificial bowel sphincter® (ABS) from A. M. S. (Minnetonka, MN, USA) and the soft anal band® from A. M. I. (Feldkirch, Austria). How to implant the artificial anal sphincter? Both devices consist of a silicon cuff which can be filled with fluid., The InVance™ system uses a silicon-coated polyester sling positioned under the bulbar urethra via a perineal incision., Through a perineal incision three titanium screws with a polipropylene suture were inserted in each ischiopubic rami, and a silicon/polipropylene mesh (Invance) is affixed to them, compressing the bulbar urethra, surgical treatment of female stress urinary incontinence with a trans-obturator sub-urethral tape of Uratape (Porgés). METHODS: Treatment and follow up of their complication were performed at the CHRU of Lille. RESULTS: In both cases, this complication is related to prolonged vaginal exposition of the tape. Vaginal erosion always occurs next to the silicon coated section of the tape, A non-elastic, polypropylene tape (UraTape, Mentor-Porgès) with a silicon coated central part was placed under the mid-urethra.,  Stress incontinence is a rare complication in men, usually following prostatic surgery. It can be treated conservatively with pelvic floor training and alpha-adrenergic receptor agonists and if necessary surgically with submucosal collagen or silicon injections in the sphincter area or implantation of a sphincter prosthesis, The Femassist is a medical-grade silicon dome-shaped device, worn over the urethra and held securely via suction and a commercially available adhesive lotion., To examine the performance of a silicon urinary control device for nonsurgical management of women with genuine stress incontinence, The \"FemAssist\" is a dome-shaped medical grade silicon device intended to be worn over the external urethral meatus and held in place by suction and an adhesive gel. Thirty eight women with varying degrees of genuine stress urinary incontinence (GSUI) or mixed incontinence on multichannel urodynamic testing were fitted with one of two sizes of \"FemAssist[SEP]Relations: Stress urinary incontinence has relations: phenotype_phenotype with Urinary incontinence, phenotype_phenotype with Urinary incontinence, disease_phenotype_positive with cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy,, disease_phenotype_positive with cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy,. Bulbar urethral stricture has relations: disease_phenotype_positive with urethral stricture (disease), disease_phenotype_positive with urethral stricture (disease). annular constricting bands has relations: disease_disease with syndromic disease, disease_disease with syndromic disease. regulation of establishment of actomyosin contractile ring localization involved in mitotic cell cycle has relations: bioprocess_bioprocess with regulation of establishment of actomyosin contractile ring localization, bioprocess_bioprocess with regulation of establishment of actomyosin contractile ring localization.", "label": "yes"}
{"id": "converted_3539", "sentence1": "Are gut microbiota profiles altered by irradiation?", "sentence2": "Specific Members of the Gut Microbiota are Reliable Biomarkers of Irradiation Intensity and Lethality in Large Animal Models of Human Health., Irradiation profoundly impacted gut microbiota profiles in both animals., Our findings suggest that gut symbiont-based probiotics can be used as agents for reversing radiation-induced ecological fitness decrease.[SEP]Relations: Gastrointestinal obstruction has relations: disease_phenotype_positive with cryptosporidiosis, disease_phenotype_positive with cryptosporidiosis, drug_effect with Imatinib, drug_effect with Imatinib, phenotype_phenotype with Functional abnormality of the gastrointestinal tract, phenotype_phenotype with Functional abnormality of the gastrointestinal tract, phenotype_phenotype with Intestinal obstruction, phenotype_phenotype with Intestinal obstruction, phenotype_phenotype with Functional intestinal obstruction, phenotype_phenotype with Functional intestinal obstruction.", "label": "yes"}
{"id": "converted_2364", "sentence1": "Are Conserved Nonexonic Elements (CNEEs) important in phylogenomics research?", "sentence2": "Overall, CNEEs appear to be promising as phylogenomic markers, yielding phylogenetic resolution as high as for UCEs and introns but with fewer gaps, less ambiguity in alignments and with patterns of nucleotide substitution more consistent with the assumptions of commonly used methods of phylogenetic analysis., Conserved Nonexonic Elements: A Novel Class of Marker for Phylogenomics., Target capture for vertebrate animals is currently dominated by two approaches-anchored hybrid enrichment (AHE) and ultraconserved elements (UCE)-and both approaches have proven useful for addressing questions in phylogenomics, phylogeography and population genomics., conserved nonexonic elements a novel class of marker for phylogenomics[SEP]", "label": "yes"}
{"id": "converted_2565", "sentence1": "Does armodafinil improve fatigue of glioma patients?", "sentence2": "CONCLUSIONS: While treatment was well-tolerated, an 8-week course of armodafinil did not improve fatigue or QOL in glioma patients undergoing RT in this pilot study. , We evaluated whether armodafinil, a wakefulness-promoting medication, improves fatigue in glioma patients undergoing RT., Armodafinil did not significantly improve fatigue or QOL based on the 42-day change in FACIT-F fatigue subscale, FACT-G, CFS, or BFI. Further analysis suggests no difference between the arms even after accounting for the potential bias of missing data. , Treatment was well tolerated with few grade 3 or 4 toxicities.<br><b>CONCLUSIONS</b>: While treatment was well-tolerated, an 8-week course of armodafinil did not improve fatigue or QOL in glioma patients undergoing RT in this pilot study., Armodafinil did not significantly improve fatigue or QOL based on the 42-day change in FACIT-F fatigue subscale, FACT-G, CFS, or BFI., While treatment was well-tolerated, an 8-week course of armodafinil did not improve fatigue or QOL in glioma patients undergoing RT in this pilot study.[SEP]Relations: Fatigue has relations: drug_effect with Flumazenil, drug_effect with Flumazenil, drug_effect with Lapatinib, drug_effect with Lapatinib, drug_effect with Sildenafil, drug_effect with Sildenafil, drug_effect with Amiodarone, drug_effect with Amiodarone, drug_effect with Fosinopril, drug_effect with Fosinopril.", "label": "no"}
{"id": "converted_831", "sentence1": "Have 5q35 microdeletions been implicated in Sotos syndrome development?", "sentence2": "Loss-of-function mutations of NSD1 and 5q35 microdeletions encompassing NSD1 are a major cause of Sotos syndrome (Sos), which is characterized by overgrowth, macrocephaly, characteristic facies, and variable intellectual disability (ID), We observed a novel 3.5 Mb 5q subtelomeric deletion in a 3-year-old girl with developmental delay, hypotonia and multiple minor anomalies. Comparison of her phenotype with the few published patients with terminal 5q35 deletions revealed several overlapping features, but also showed remarkable differences such as shortness of stature versus macrosomia. After the report of 5q35.3 microdeletions in Sotos syndrome we integrated the published BACs into the public draft sequence and exactly mapped the deletion size in our patient by FISH analysis with 15 BAC probes. We demonstrated that the deletion in our patient is immediately adjacent to the reported Sotos syndrome deletion site, Switch in FGFR3 and -4 expression profile during human renal development may account for transient hypercalcemia in patients with Sotos syndrome due to 5q35 microdeletions., Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome., After the report of 5q35.3 microdeletions in Sotos syndrome we integrated the published BACs into the public draft sequence and exactly mapped the deletion size in our patient by FISH analysis with 15 BAC probes., Clinical and genetic spectrum of 18 unrelated Korean patients with Sotos syndrome: frequent 5q35 microdeletion and identification of four novel NSD1 mutations., Here we describe a new case of Sotos syndrome with a 5q35 microdeletion, affecting the fibroblast growth factor receptor 4 (FGFR4) gene, presenting with infantile hypercalcemia., Microdeletions at 5q35.3, encompassing NSD1, are responsible for approximately 10% of non-Japanese cases of Sotos., Alu-related 5q35 microdeletions in Sotos syndrome., Most cases of Sotos syndrome are caused by intragenic NSD1 mutations or 5q35 microdeletions., Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome, Clinical and genetic spectrum of 18 unrelated Korean patients with Sotos syndrome: frequent 5q35 microdeletion and identification of four novel NSD1 mutations, Microdeletions at 5q35.3, encompassing NSD1, are responsible for approximately 10% of non-Japanese cases of Sotos, A case of Sotos syndrome with 5q35 microdeletion and novel clinical findings., Here we describe a new case of Sotos syndrome with a 5q35 microdeletion, affecting the fibroblast growth factor receptor 4 (FGFR4) gene, presenting with infantile hypercalcemia. , There are two types of mutations that cause NSD1 haploinsufficiency: mutations within the NSD1 gene (mutation type) and a 5q35 submicroscopic deletion encompassing the entire NSD1 gene (deletion type). , aCGH and metaphase FISH are useful for rapid diagnosis of 5q35 microdeletion associated with Sotos syndrome., Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome., Switch in FGFR3 and -4 expression profile during human renal development may account for transient hypercalcemia in patients with Sotos syndrome due to 5q35 microdeletions., A case of Sotos syndrome with 5q35 microdeletion and novel clinical findings., Most cases of Sotos syndrome are caused by intragenic NSD1 mutations or 5q35 microdeletions., aCGH and metaphase FISH are useful for rapid diagnosis of 5q35 microdeletion associated with Sotos syndrome., Alu-related 5q35 microdeletions in Sotos syndrome.[SEP]Relations: Sotos syndrome has relations: disease_protein with SETD2, disease_protein with SETD2, disease_protein with NSD1, disease_protein with NSD1, disease_disease with partial deletion of the long arm of chromosome 5, disease_disease with partial deletion of the long arm of chromosome 5, disease_protein with APC2, disease_protein with APC2, disease_protein with NRK, disease_protein with NRK.", "label": "yes"}
{"id": "converted_2780", "sentence1": "Is cariprazine effective for treatment of bipolar disorder?", "sentence2": "BACKGROUND: We evaluated the safety/tolerability of longer-term open-label treatment with cariprazine in patients who had responded to cariprazine for acute bipolar mania., Clinically relevant response and remission outcomes in cariprazine-treated patients with bipolar I disorder., Cariprazine is FDA approved for the acute treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder in adults., DISCUSSION: Cariprazine-treated patients with bipolar I disorder attained clinically significant improvement in manic symptoms as shown by significantly greater rates of response and remission versus placebo; improvement in manic symptoms did not induce depressive symptoms., OBJECTIVE: Cariprazine, a dopamine D3/D2 partial agonist atypical antipsychotic with preferential binding to D3 receptors, is approved for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder., <b>BACKGROUND</b>: Cariprazine was approved for treating schizophrenia and bipolar disorder, and currently is being evaluated for treating depression in clinical trials in the United States.[SEP]Relations: bipolar disorder has relations: contraindication with Desipramine, contraindication with Desipramine, contraindication with Desipramine, contraindication with Desipramine, contraindication with Trimipramine, contraindication with Trimipramine, contraindication with Trimipramine, contraindication with Trimipramine, contraindication with Imipramine, contraindication with Imipramine.", "label": "yes"}
{"id": "converted_1450", "sentence1": "Does the 3D structure of  the genome remain stable during cell differentiation?", "sentence2": "We identify large, megabase-sized local chromatin interaction domains, which we term 'topological domains', as a pervasive structural feature of the genome organization., The domains are stable across different cell types and highly conserved across species, indicating that topological domains are an inherent property of mammalian genomes, Insulators are involved in 3D genome organization at multiple spatial scales and are important for dynamic reorganization of chromatin structure during reprogramming and differentiation., The relation between alterations in chromatin structure and changes in gene expression during cell differentiation has served as a paradigm to understand the link between genome organization and function., Architectural proteins orchestrate higher-order chromatin organization through the establishment of interactions between regulatory elements across multiple spatial scales. The regulation of these proteins, their interaction with DNA, and their co-occurrence in the genome, may be responsible for the plasticity of 3D chromatin architecture that dictates cell and time-specific blueprints of gene expression., The role of 3D genome organisation in the control and execution of lineage-specific transcription programmes during the development and differentiation of multipotent stem cells into specialised cell types remains poorly understood., Chromatin structural states and their remodelling, including higher-order chromatin folding and three-dimensional (3D) genome organisation, play an important role in the control of gene expression, Here, we show that substantial remodelling of the higher-order chromatin structure of the epidermal differentiation complex (EDC), a keratinocyte lineage-specific gene locus on mouse chromosome 3, occurs during epidermal morphogenesis., Many studies have suggested a link between the spatial organization of genomes and fundamental biological processes such as genome reprogramming, gene expression, and differentiation., Moreover, we reveal that formation of such highly condensed, transcriptionally repressed heterochromatin promotes transcriptional activation of differentiation genes and loss of pluripotency., The open chromatin of embryonic stem cells (ESCs) condenses into repressive heterochromatin as cells exit the pluripotent state., we find that localized heterochromatin condensation of ribosomal RNA genes initiates establishment of highly condensed chromatin structures outside of the nucleolus, We focus on the emerging relationship between genome organization and lineage-specific transcriptional regulation, which we argue are inextricably linked., Cells face the challenge of storing two meters of DNA in the three-dimensional (3D) space of the nucleus that spans only a few microns. The nuclear organization that is required to overcome this challenge must allow for the accessibility of the gene regulatory machinery to the DNA and, in the case of embryonic stem cells (ESCs), for the transcriptional and epigenetic changes that accompany differentiation, In this review we summarize some of the recent findings illuminating the 3D structure of the eukaryotic genome, as well as the relationship between genome topology and function from the level of whole chromosomes to enhancer-promoter loops with a focus on features affecting genome organization in ESCs and changes in nuclear organization during differentiation, We observe that although self-associating chromatin domains are stable during differentiation, chromatin interactions both within and between domains change in a striking manner, altering 36% of active and inactive chromosomal compartments throughout the genome[SEP]Relations: LORICRIN has relations: bioprocess_protein with keratinocyte differentiation, bioprocess_protein with keratinocyte differentiation, pathway_protein with Formation of the cornified envelope, pathway_protein with Formation of the cornified envelope, cellcomp_protein with cornified envelope, cellcomp_protein with cornified envelope, molfunc_protein with structural constituent of cytoskeleton, molfunc_protein with structural constituent of cytoskeleton. heterochromatin has relations: cellcomp_protein with BEND3, cellcomp_protein with BEND3.", "label": "no"}
{"id": "converted_577", "sentence1": "Is paramyxovirus involved in human subacute thyroiditis?", "sentence2": "Most cases of subacute thyroiditis are caused by a variety of viruses, for example, Coxsackie, cytomegalovirus, Epstein-Barr virus, and adenovirus. Influenza immunization or infection may cause subacute thyroiditis., Coxsackie virus has been reported to be one of the viruses associated with the disease., The etiology of subacute granulomatous thyroiditis (SAT) is obscure, although it is postulated to be associated with viral infections and genetic factors., The results suggest that SAT is not usually associated with acute infections, No evidence was obtained to support the proposed role of enteroviruses as an important etiologic agent of SAT., The viral antibodies evaluated were those of Influenza A and B, Coxsackie A9, B1, B2, B3, B4, B5 and B6, Echo 3, 7, 11 and 12, Parainfluenza 1, 2, 3 and 4, and Adeno 8 virus. The following results were obtained: In class I HLA typing, the frequency of HLA-Bw35 in SAT was 67.4%, which was significantly (p less than 0.0001) higher than that in the control (14.1%). On the other hand, the frequency of Cw1 in SAT (14.6%) was significantly (p less than 0.01) lower than that of the control (32.1%), and that of Cw3 (65.2%) was significantly (p less than 0.01) higher than that of the control (46.5%).[SEP]Relations: adenovirus renal infection has relations: disease_disease with adenoviridae infectious disease, disease_disease with adenoviridae infectious disease, disease_disease with kidney disease, disease_disease with kidney disease. Nipah virus disease has relations: disease_disease with henipavirus infectious disease, disease_disease with henipavirus infectious disease, disease_phenotype_positive with Myoclonus, disease_phenotype_positive with Myoclonus. coxsackievirus infectious disease has relations: disease_disease with enterovirus infectious disease, disease_disease with enterovirus infectious disease.", "label": "no"}
{"id": "converted_1206", "sentence1": "Is the SDHAF2 gene encoding a protein necessary for flavination of SDHA?", "sentence2": "Pheochromocytoma-paraganglioma syndrome is caused by mutations in SDHB, SDHC, and SDHD, encoding subunits of succinate dehydrogenase (SDH), and in SDHAF2, required for flavination of SDHA. , At present, these are RET proto-oncogene, von Hippel-Lindau disease tumor suppressor gene (VHL), neurofibromatosis type 1 tumor suppressor gene (NF1), genes encoding the succinate dehydrogenase (SDH) complex subunits SDHB, SDHC, and SDHD, but also SDHA, the gene encoding the enzyme responsible for the flavination of SDHA (SDHAF2 or hSDH5), and the newly described TMEM127 and MAX tumor suppressor genes., the gene encoding the enzyme responsible for the flavination of SDHA (SDHAF2 or hSDH5), SDHAF2, required for flavination of SDHA, At present, these are RET proto-oncogene, von Hippel-Lindau disease tumor suppressor gene (VHL), neurofibromatosis type 1 tumor suppressor gene (NF1), genes encoding the succinate dehydrogenase (SDH) complex subunits SDHB, SDHC, and SDHD, but also SDHA, the gene encoding the enzyme responsible for the flavination of SDHA (SDHAF2 or hSDH5), and the newly described TMEM127 and MAX tumor suppressor genes., Pheochromocytoma-paraganglioma syndrome is caused by mutations in SDHB, SDHC, and SDHD, encoding subunits of succinate dehydrogenase (SDH), and in SDHAF2, required for flavination of SDHA., In a recent issue of Science, Rutter and coworkers showed that SDH5 is required for the flavination of SDHA, which is necessary for SDH assembly and function., At present, these are RET proto-oncogene, von Hippel-Lindau disease tumor suppressor gene (VHL), neurofibromatosis type 1 tumor suppressor gene (NF1), genes encoding the succinate dehydrogenase (SDH) complex subunits SDHB, SDHC, and SDHD, but also SDHA, the gene encoding the enzyme responsible for the flavination of SDHA (SDHAF2 or hSDH5), and the newly described TMEM127 and MAX tumor suppressor genes, Pheochromocytoma-paraganglioma syndrome is caused by mutations in SDHB, SDHC, and SDHD, encoding subunits of succinate dehydrogenase (SDH), and in SDHAF2, required for flavination of SDHA, CONTEXT: Pheochromocytoma-paraganglioma syndrome is caused by mutations in SDHB, SDHC, and SDHD, encoding subunits of succinate dehydrogenase (SDH), and in SDHAF2, required for flavination of SDHA. , This gene is co-expressed with a number of genes encoding mitochondrial proteins, including SDH1-1, and has low partial sequence similarity to human SDHAF2, a protein required for flavin-adenine dinucleotide (FAD) insertion into SDH. , At present, these are RET proto-oncogene, von Hippel-Lindau disease tumor suppressor gene (VHL), neurofibromatosis type 1 tumor suppressor gene (NF1), genes encoding the succinate dehydrogenase (SDH) complex subunits SDHB, SDHC, and SDHD, but also SDHA, the gene encoding the enzyme responsible for the flavination of SDHA (SDHAF2 or hSDH5), and the newly described TMEM127 and MAX tumor suppressor genes., Pheochromocytoma-paraganglioma syndrome is caused by mutations in SDHB, SDHC, and SDHD, encoding subunits of succinate dehydrogenase (SDH), and in SDHAF2, required for flavination of SDHA.[SEP]Relations: Flavin adenine dinucleotide has relations: drug_protein with AIFM1, drug_protein with AIFM1, drug_protein with NQO2, drug_protein with NQO2, drug_protein with DLD, drug_protein with DLD, drug_protein with CYB5R3, drug_protein with CYB5R3, drug_protein with ACAD8, drug_protein with ACAD8.", "label": "yes"}
{"id": "converted_2832", "sentence1": "Is durvalumab used for lung cancer treatment?", "sentence2": " In the phase III PACIFIC trial consolidation with durvalumab, an anti-PDL-1 antibody, was associated with survival benefit in patients diagnosed with LA-NSCLC who responded to concurrent chemoradiotherapy., METHODS: An electronic literature search was performed of public databases (MEDLINE, Excerpta Medica dataBASE [EMBASE], and Cochrane) and conference proceedings for trials using PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab, durvalumab, and avelumab) in patients with NSCLC., Durvalumab in non-small-cell lung cancer patients: current developments., Single-agent durvalumab showed clinical efficacy and a manageable safety profile in advanced non-small-cell lung cancer, particularly the ≥25% PD-L1+ population., Six drugs including one CTLA-4 blocker (ipilimumab), two PD-1 blockers (nivolumab and pembrolizumab) and three PD-L1 blockers (atezolizumab, avelumab and durvalumab) are approved for the treatment of different types of cancers including both solid tumors such as melanoma, lung cancer, head and neck cancer, bladder cancer and Merkel cell cancer as well as hematological tumors such as classic Hodgkin's lymphoma. , PURPOSE OF REVIEW: The therapeutic armamentarium for advanced non-small-cell lung cancer has evolved considerably over the past years. Immune checkpoint inhibitors targeting programmed cell death-1 such as pembrolizumab and nivolumab or programmed cell death ligand 1 such as atezolizumab, durvalumab and avelumab have shown favorable efficacy results in this patient population in the first-line and second-line setting., In addition, preclinical and early clinical evidence suggests that chemotherapy and radiation may work synergistically with anti-PD-1/PD-L1 therapy to promote antitumor immunity, which has led to the initiation of clinical trials testing these drugs in patients with stage III NSCLC. A preliminary report of a randomized phase III trial, the PACIFIC trial, demonstrated an impressive increase in median progression-free survival with consolidative durvalumab, a PD-L1 inhibitor, compared with observation after cCRT. , ICI, such as the PD-1 inhibitors nivolumab and pembrolizumab and the PD-L1 inhibitor atezolizumab, have already been marketed for the treatment of pretreated patients with advanced NSCLC., The PACIFIC trial assessing durvalumab after standard chemoradiotherapy for locally advanced NSCLC has already met its primary endpoint and the potential of durvalumab will be reinforced if phase III randomized studies of first-line (MYSTIC trial) and second or subsequent (ARCTIC trial) lines of therapy demonstrate superiority over the current standard of care.<br>[SEP]Relations: Ipilimumab has relations: drug_drug with Durvalumab, drug_drug with Durvalumab, drug_drug with Dusigitumab, drug_drug with Dusigitumab, drug_drug with Lerdelimumab, drug_drug with Lerdelimumab. Nivolumab has relations: drug_drug with Durvalumab, drug_drug with Durvalumab, drug_drug with Dusigitumab, drug_drug with Dusigitumab.", "label": "yes"}
{"id": "converted_3639", "sentence1": "Is poliosis circumscripta another term for a white or unpigmented patch of hair or skin?", "sentence2": "\"white forelock,\" poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicle, Although traditionally known as \"white forelock,\" poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicles, can involve any hairy area on the body including the scalp, eyebrows, and eyelashes., Although traditionally known as \" white forelock , \" poliosis circumscripta , defined as a localized patch of white hair in a group of hair follicles , can involve any hairy area on the body including the scalp , eyebrows , and eyelashes, Although traditionally known as \"white forelock,\" poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicles, can involve any hairy area on the body including the scalp, eyebrows, and eyelashes.[SEP]Relations: eyelash has relations: anatomy_anatomy with strand of hair, anatomy_anatomy with strand of hair. muscle structure has relations: anatomy_anatomy with insect adult somatic muscle, anatomy_anatomy with insect adult somatic muscle, anatomy_anatomy with somatic muscle, anatomy_anatomy with somatic muscle, anatomy_anatomy with urethra muscle tissue, anatomy_anatomy with urethra muscle tissue, anatomy_anatomy with anatomical structure, anatomy_anatomy with anatomical structure.", "label": "yes"}
{"id": "converted_825", "sentence1": "Could Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)\ncause sudden cardiac death?", "sentence2": "Two siblings died suddenly at the ages of 9 and 10 years, Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a type of cardiac arrhythmia that occurs in people with a structurally normal heart. Stress or anxiety-induced release of endogenous catecholamines causes a dysfunction in the myocytic calcium-ion channel, leading to ventricular arrhythmias that can cause dizziness, syncope, or sudden cardiac death. , During a follow-up of 48±94 months, arrhythmia events (sudden cardiac death and aborted cardiac arrest) associated with noncompliance occurred in 2 patients. , We report a family with repeat events of sudden cardiac death and recurrent ventricular fibrillation in a teenage girl, where autopsy data and clinical investigations were inconclusive. The diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT) was established only following finding a gene mutation in the cardiac ryanodine receptor. , Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a devastating inherited disorder characterized by episodic syncope and/or sudden cardiac arrest during exercise or acute emotion in individuals without structural cardiac abnormalities. Although rare, CPVT is suspected to cause a substantial part of sudden cardiac deaths in young individuals. , catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada syndrome (BrS), leave no evidence to be found at autopsy, a spectrum of sudden cardiac death (SCD)-predisposing heritable cardiac arrhythmia syndromes, including long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome (BrS), and catecholaminergic polymorphic ventricular tachycardia (CPVT). , CPVT is a familial arrhythmogenic syndrome characterized by abnormal calcium (Ca(2+)) handling, ventricular arrhythmias, and sudden cardiac death, Mutations in RyR2 are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT) and sudden cardiac death., Patients with CPVT often present with exercise- or emotion induced syncope, the first presentation can also be sudden cardiac death., Among the five major arrhythmogenic disorders occurring in the absence of a structural heart disease is catecholaminergic polymorphic ventricular tachycardia (CPVT), which is a highly lethal form of inherited arrhythmias. , Patients with CPVT are at high risk of developing life-threatening ventricular arrhythmias when untreated. , Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by VT induced by adrenergic stress in the absence of structural heart disease and high incidence of sudden cardiac death. , CPVT is an inherited arrhythmia syndrome caused by gene mutations that destabilize cardiac ryanodine receptor Ca(2+) release channels. Sudden cardiac death is incompletely prevented by conventional drug therapy with β-blockers with or without Ca(2+) channel blockers. , Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease that can cause sudden cardiac death due to ventricular fibrillation (VF)., Important potential causes of sudden cardiac deaths in the absence of heart disease are primary electrical diseases such as Brugada syndrome, long QT syndrome (LQTS), short QT syndrome and catecholaminergic polymorphic ventricular tachyarrhythmias. , catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada syndrome (BrS) are primary inherited arrhythmia syndromes that may cause syncope and sudden cardiac death in young individuals. , Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a cardiac channelopathy characterized by altered intracellular calcium handling resulting in ventricular arrhythmias and high risk of cardiac sudden death in young cases with normal structural hearts. , Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disorder that causes syncopal episodes related with stress or emotion and even sudden cardiac deaths., Catecholaminergic polymorphic ventricular tachycardia caused by mutations in the RyR2 gene manifests as severe arrhythmias, and may provide a candidate for sudden cardiac deaths., Patients diagnosed with an electrical cardiomyopathy have an increased risk of syncope and sudden cardiac death (SCD). , Patients with CPVT present with exercise-induced syncope and sudden cardiac death but normal resting electrocardiograms. , Over 80% of SCD occurs in patients with organic heart disease. However, approximately 10-15% of SCD occurs in the presence of structurally normal heart and the majority of those patients are young. In this group of patients, changes in genes encoding cardiac ion channels produce modification of the function of the channel resulting in an electrophysiological substrate of VA and SCD. Collectively these disorders are referred to as Cardiac Ion Channelopathies. The 4 major syndromes in this group are: The Long QT Syndrome (LQTS), the Brugada Syndrome (BrS), the Short QT Syndrome (SQTS), and the Catecholaminergic Polymorphic VT (CPVT). , Important potential causes of sudden cardiac deaths in the absence of heart disease are primary electrical diseases such as Brugada syndrome, long QT syndrome (LQTS), short QT syndrome (SQTS), and catecholaminergic polymorphic ventricular tachyarrhythmias (CPVT). , Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial cardiac arrhythmia that is related to RYR2 or CASQ2 gene mutation. It occurs in patients with structurally normal heart and causes exercise-emotion-triggered syncope and sudden cardiac death., Potentially lethal ion channel disorders (channelopathies) such as the long QT syndromes (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), Aberrant spontaneous, diastolic Ca2+ leak from the SR due to dysfunctional RyR2 contributes to the formation of delayed after-depolarisations, which are thought to underlie the fatal arrhythmia that occurs in both heart failure (HF) and in catecholaminergic polymorphic ventricular tachycardia (CPVT). , Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an uncommon heritable disease presenting with syncope or sudden cardiac death., Mutations in RyR2 have been linked to exercise-induced sudden cardiac death (catecholaminergic polymorphic ventricular tachycardia [CPVT])., Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a heritable arrhythmia unmasked by exertion or stress, characterized by triggered activity and sudden cardiac death in affected patients., families that exhibit CPVT (catecholaminergic polymorphic ventricular tachycardia), a condition in which physical or emotional stress can trigger severe tachyarrhythmias that can lead to sudden cardiac death., that often leads to sudden death in HF and in CPVT., Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by adrenergically mediated polymorphic ventricular tachycardia leading to syncope and sudden cardiac death., Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an autosomal dominant inherited disorder characterized by adrenergic induced polymorphic ventricular tachycardias and associated with sudden cardiac death. , These data suggest that \"leaky\" RyR2 channels can trigger fatal cardiac arrhythmias, providing a possible explanation for CPVT., Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare arrhythmogenic disorder characterized by syncopal events and sudden cardiac death at a young age during physical stress or emotion, in the absence of structural heart disease. ,  catecholaminergic polymorphic ventricular tachycardia (CPVT), idiopathic ventricular fibrillation (VF), and arrhythmogenic right ventricular cardiomyopathy (ARVC) account for a relevant proportion of sudden cardiac death cases in young patients cohorts. , has recently been shown to be involved in at least two forms of sudden cardiac death (SCD): (1) Catecholaminergic polymorphic ventricular tachycardia (CPVT) [SEP]Relations: catecholaminergic polymorphic ventricular tachycardia has relations: disease_phenotype_positive with Sudden cardiac death, disease_phenotype_positive with Sudden cardiac death, disease_phenotype_positive with Sudden death, disease_phenotype_positive with Sudden death, disease_phenotype_positive with Cardiac arrest, disease_phenotype_positive with Cardiac arrest, disease_phenotype_positive with Prolonged QT interval, disease_phenotype_positive with Prolonged QT interval. Sudden cardiac death has relations: disease_phenotype_positive with catecholaminergic polymorphic ventricular tachycardia, disease_phenotype_positive with catecholaminergic polymorphic ventricular tachycardia.", "label": "yes"}
{"id": "converted_697", "sentence1": "Are there randomised controlled trials on sevoflurane?", "sentence2": "After Ethics Review Board approval, 44 ASA I-III patients undergoing elective gynaecological surgery were randomised after surgery to either hypercapnic hyperpnoea or control groups., Hypercapnic hyperpnoea in spontaneously breathing patients halves the time of recovery from sevoflurane-induced anaesthesia in the operating room., A total of 200 women undergoing first trimester abortion (American Society of Anesthesiologists physical status I) participated in the study. Patients were randomly assigned to receive either sevoflurane or propofol for short-term sedation., The results showed the incidence of dreaming was significantly different between anaesthesia groups with 60% (60/100) of the sevoflurane group and 33% (33/100) of the propofol group (P=0.000), Anaesthesia administered had no effect on patient satisfaction. The results suggest that the incidence of dreaming was not affected by recovery time. Patient satisfaction was not influenced by choice of sedative and/or by the occurrence of dreaming during sevoflurane or propofol short-term sedation., Prior reports suggest that dreaming during anaesthesia is dependent on recovery time. Dreaming during sedation may impact patient satisfaction, Sevoflurane vs. propofol in patients with coronary disease undergoing mitral surgery: a randomised study., We therefore performed a randomised controlled trial (sevoflurane vs. propofol) to compare cardiac troponin release in patients with coronary disease undergoing mitral surgery., Myocardial injury in remifentanil-based anaesthesia for off-pump coronary artery bypass surgery: an equipotent dose of sevoflurane versus propofol, This randomised controlled trial compared the effect of equipotent anaesthetic doses of sevoflurane (S group) versus propofol (P group), during remifentanil-based anaesthesia for off-pump coronary artery bypass surgery, on myocardial injury. Either sevoflurane or propofol was titrated to maintain bispectral index values between 40 and 50., This randomised, multicentre, parallel-group trial included 98 adult patients. Patients received intravenous propofol for induction followed by sevoflurane maintenance anaesthesia., Patients were randomly allocated to receive sugammadex 2.0 mg kg(-1) or neostigmine 50 microg, We compared the haemodynamics, emergence and recovery characteristics of total intravenous anaesthesia using propofol/remifentanil with sevoflurane/remifentanil anaesthesia, under bispectral index guidance, in 103 patients undergoing surgical procedures lasting > 3.5 h, A randomised controlled trial of paediatric conscious sedation for dental treatment using intravenous midazolam combined with inhaled nitrous oxide or nitrous oxide/sevoflurane, Intravenous midazolam, especially in combination with inhaled nitrous oxide or sevoflurane and nitrous oxide, are effective techniques, with the combination of midazolam and sevoflurane the one most likely to result in successful treatment., We randomly assigned 1063 adult and 322 paediatric elective patients to one of four (adult) or two (paediatric) anaesthesia groups, In both studies, there was no difference in postdischarge outcomes at Day 7. Sevoflurane/sevoflurane was more costly with higher PONV rates in both studies. In adults, the cost per extra episode of PONV avoided was pound 296 (propofol/propofol vs. propofol/ sevoflurane) and pound 333 (propofol/sevoflurane vs. propofol/isoflurane)., Comparison of sevoflurane and nitrous oxide mixture with nitrous oxide alone for inhalation conscious sedation in children having dental treatment: a randomised controlled trial., We studied 411 children aged 3-10 years who were referred for dental treatment. They were randomly allocated to have inhalation conscious sedation with either sevoflurane/nitrous oxide mixture or nitrous oxide alone[SEP]Relations: Sevoflurane has relations: drug_drug with Enflurane, drug_drug with Enflurane, drug_drug with Propanidid, drug_drug with Propanidid, drug_drug with Ancrod, drug_drug with Ancrod, drug_drug with Selegiline, drug_drug with Selegiline, drug_drug with Cannabidiol, drug_drug with Cannabidiol.", "label": "yes"}
{"id": "converted_1899", "sentence1": "Have the promoter regions of the genes implicated in Rett Syndrome been characterized with CAGE?", "sentence2": "CAGE-defined promoter regions of the genes implicated in Rett Syndrome., Mutations in three functionally diverse genes cause Rett Syndrome. Although the functions of Forkhead box G1 (FOXG1), Methyl CpG binding protein 2 (MECP2) and Cyclin-dependent kinase-like 5 (CDKL5) have been studied individually, not much is known about their relation to each other with respect to expression levels and regulatory regions. Here we analyzed data from hundreds of mouse and human samples included in the FANTOM5 project, to identify transcript initiation sites, expression levels, expression correlations and regulatory regions of the three genes.RESULTS: Our investigations reveal the predominantly used transcription start sites (TSSs) for each gene including novel transcription start sites for FOXG1. We show that FOXG1 expression is poorly correlated with the expression of MECP2 and CDKL5. We identify promoter shapes for each TSS, the predicted location of enhancers for each gene and the common transcription factors likely to regulate the three genes. Our data imply Polycomb Repressive Complex 2 (PRC2) mediated silencing of Foxg1 in cerebellum.CONCLUSIONS: Our analyses provide a comprehensive picture of the regulatory regions of the three genes involved in Rett Syndrome., CAGE-defined promoter regions of the genes implicated in Rett Syndrome, CAGE-defined promoter regions of the genes implicated in Rett Syndrome.[SEP]Relations: Rett syndrome has relations: disease_protein with NTNG1, disease_protein with NTNG1, disease_phenotype_positive with Increased serum leptin, disease_phenotype_positive with Increased serum leptin, disease_disease with X-linked complex neurodevelopmental disorder, disease_disease with X-linked complex neurodevelopmental disorder, disease_protein with MECP2, disease_protein with MECP2, disease_phenotype_positive with Increased serum pyruvate, disease_phenotype_positive with Increased serum pyruvate.", "label": "yes"}
{"id": "converted_2934", "sentence1": "Have machine learning methods been used to predict the severity of major depressive disorder(MDD)?", "sentence2": "Here, we conduct a meta-review to identify predictors of response to antidepressant therapy in order to select robust input features for machine learning models of treatment response. , machine learning framework involving EEG-based functional connectivity to diagnose major depressive disorder (MDD)., Identification of risk factors of treatment resistance may be useful to guide treatment selection, avoid inefficient trial-and-error, and improve major depressive disorder (MDD) care. We extended the work in predictive modeling of treatment resistant depression (TRD) via partition of the data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) cohort into a training and a testing dataset., persistence and severity of major depressive disorder from baseline self-reports,  These results confirm that clinically useful MDD risk-stratification models can be generated from baseline patient self-reports and that ML methods improve on conventional methods in developing such models, Furthermore, machine learning weighting factors may reflect an objective biomarker of major depressive disorder illness severity, based on abnormalities of brain structure., Notably, while the only information provided for training the classifiers was T(1)-weighted scans plus a categorical label (major depressive disorder versus controls), both relevance vector machine and support vector machine 'weighting factors' (used for making predictions) correlated strongly with subjective ratings of illness severity., BACKGROUND\nAlthough variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods., BACKGROUND Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods., BACKGROUND Growing evidence documents the potential of machine learning for developing brain based diagnostic methods for major depressive disorder (MDD)., OBJECTIVE We aimed to integrate neural data and an advanced machine learning technique to predict individual major depressive disorder (MDD) patient severity., Furthermore, machine learning weighting factors may reflect an objective biomarker of major depressive disorder illness severity, based on abnormalities of brain structure., <b>BACKGROUND</b>: Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods.[SEP]Relations: major depressive disorder has relations: disease_protein with MDM4, disease_protein with MDM4, disease_disease with anxiety disorder, disease_disease with anxiety disorder, disease_protein with DRD4, disease_protein with DRD4, disease_protein with DDC, disease_protein with DDC, disease_protein with PCNT, disease_protein with PCNT.", "label": "yes"}
{"id": "converted_1995", "sentence1": "Are there canonical marks of active chromatin in developmentally regulated genes?", "sentence2": "Absence of canonical marks of active chromatin in developmentally regulated genes., The interplay of active and repressive histone modifications is assumed to have a key role in the regulation of gene expression. In contrast to this generally accepted view, we show that the transcription of genes temporally regulated during fly and worm development occurs in the absence of canonically active histone modifications. Conversely, strong chromatin marking is related to transcriptional and post-transcriptional stability, an association that we also observe in mammals. Our results support a model in which chromatin marking is associated with the stable production of RNA, whereas unmarked chromatin would permit rapid gene activation and deactivation during development. In the latter case, regulation by transcription factors would have a comparatively more important regulatory role than chromatin marks., Absence of canonical marks of active chromatin in developmentally regulated genes, Absence of canonical marks of active chromatin in developmentally regulated genes., In contrast to this generally accepted view, we show that the transcription of genes temporally regulated during fly and worm development occurs in the absence of canonically active histone modifications.[SEP]Relations: RNA localization to chromatin has relations: bioprocess_protein with HNRNPU, bioprocess_protein with HNRNPU. histone modification has relations: bioprocess_bioprocess with covalent chromatin modification, bioprocess_bioprocess with covalent chromatin modification. transcription factor binding has relations: molfunc_protein with METTL23, molfunc_protein with METTL23, molfunc_protein with PSMD10, molfunc_protein with PSMD10, molfunc_protein with ZNF618, molfunc_protein with ZNF618.", "label": "no"}
{"id": "converted_4344", "sentence1": "Does trimetazidine protect from myocardial injury after percutaneous coronary intervention?", "sentence2": "After a median follow-up of 47·5 months (IQR 42·3-53·3), incidence of primary endpoint events was not significantly different between the trimetazidine group (700 [23·3%] patients) and the placebo group (714 [23·7%]; hazard ratio 0·98 [95% CI 0·88-1·09], p=0·73). When analysed individually, there were no significant differences in the incidence of the components of the primary endpoint between the treatment groups. , INTERPRETATION: Our results show that the routine use of oral trimetazidine 35 mg twice daily over several years in patients receiving optimal medical therapy, after successful PCI, does not influence the recurrence of angina or the outcome; these findings should be taken into account when considering the place of trimetazidine in clinical practice. [SEP]Relations: Trimetazidine has relations: drug_drug with Metoclopramide, drug_drug with Metoclopramide, drug_drug with Patent Blue, drug_drug with Patent Blue, drug_protein with ACAA1, drug_protein with ACAA1, drug_drug with Isosorbide mononitrate, drug_drug with Isosorbide mononitrate. negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator has relations: bioprocess_protein with CD44, bioprocess_protein with CD44.", "label": "no"}
{"id": "converted_409", "sentence1": "Does a linker histone exist in the yeast genome?", "sentence2": "Hho1p is a bona fide linker histone, In Saccharomyces cerevisiae, HHO1 encodes a putative linker histone with very significant homology to histone H1, HHO1p may play a similar role to linker histones, but at restricted locations in the chromatin, The putative linker histone in Saccharomyces cerevisiae, Hho1p, has two regions of sequence (GI and GII) that are homologous to the single globular domains of linker histones H1 and H5 in higher eukaryotes. , The Saccharomyces cerevisiae homologue of the linker histone H1, Hho1p, has two domains that are similar in sequence to the globular domain of H1 (and variants such as H5), Two homologous domains of similar structure but different stability in the yeast linker histone, Hho1p, Saccharomyces cerevisiae encodes a single linker histone, Hho1p, with two globular domains. , The Saccharomyces cerevisiae linker histone Hho1p, with two globular domains, can simultaneously bind to two four-way junction DNA molecules, Here, we show in yeast, that the presence of yeast linker histone Hho1p represses expression of a pol II transcribed gene (MET15) embedded in the rDNA., Yeast linker histone Hho1p is required for efficient RNA polymerase I processivity and transcriptional silencing at the ribosomal DNA, Saccharomyces cerevisiae linker histone Hho1p is not essential for cell viability, and very little is known about its function in vivo. , Saccharomyces cerevisiae linker histone Hho1p functionally interacts with core histone H4 and negatively regulates the establishment of transcriptionally silent chromatin,  Unlike canonical linker histones in higher eukaryotes that have a single conserved globular domain, Hho1p possesses two globular domains. We show that the carboxyl-terminal globular domain of Hho1p is dispensable for its function, suggesting that the mode of Hho1p action is similar to that of canonical linker histones, To identify new proteins involved in spore nuclear organization, we purified chromatin from mature spores and discovered a significant enrichment of the linker histone (Hho1), Hho1 chromatin immunoprecipitation followed by sequencing (ChIP-seq) revealed increased genome-wide binding in mature spores and provides novel in vivo evidence of the linker histone binding to nucleosomal linker DNA, One of the peculiarities of S. cerevisiae cells is the unusual and less abundant linker histone, Hho1p., Hho1p, the linker histone of Saccharomyces cerevisiae, is important for the proper chromatin organization in vivo, Characteristically, linker histone depleted chromatin generally exhibited longer chromatin loops than the wild-type. , Saccharomyces cerevisiae linker histone-Hho1p maintains chromatin loop organization during ageing., Database homology searching against the complete yeast genome has identified a gene, HHO1, (or YPL127C, formerly LPI17) which encodes a protein that has two regions that show similarity to the pea histone H1 globular domain., Database homology searching against the complete yeast genome has identified a gene, HHO1, (or YPL127C, formerly LPI17) which encodes a protein that has two regions that show similarity to the pea histone H1 globular domain. , Biochemical studies to date have not been able to identify the linker histone H1 protein in the budding yeast Saccharomyces cerevisiae. Database homology searching against the complete yeast genome has identified a gene, HHO1, (or YPL127C, formerly LPI17) which encodes a protein that has two regions that show similarity to the pea histone H1 globular domain., Database homology searching against the complete yeast genome has identified a gene, HHO1, (or YPL127C, formerly LPI17) which encodes a protein that has two regions that show similarity to the pea histone H1 globular domain.[SEP]Relations: FGFR1 has relations: molfunc_protein with heparin binding, molfunc_protein with heparin binding, drug_protein with Heparin, drug_protein with Heparin, disease_protein with isolated cloverleaf skull syndrome, disease_protein with isolated cloverleaf skull syndrome, anatomy_protein_present with connective tissue, anatomy_protein_present with connective tissue, anatomy_protein_present with putamen, anatomy_protein_present with putamen.", "label": "yes"}
{"id": "converted_3544", "sentence1": "Is AND-1/Ctf4 essential for proliferation?", "sentence2": "AND-1 fork protection function prevents fork resection and is essential for proliferation., AND-1/Ctf4 bridges the CMG helicase and DNA polymerase alpha, facilitating replication. Using an inducible degron system in avian cells, we find that AND-1 depletion is incompatible with proliferation, owing to cells accumulating in G2 with activated DNA damage checkpoint. Replication without AND-1 causes fork speed slow-down and accumulation of long single-stranded DNA (ssDNA) gaps at the replication fork junction, with these regions being converted to DNA double strand breaks (DSBs) in G2. Strikingly, resected forks and DNA damage accumulation in G2, but not fork slow-down, are reverted by treatment with mirin, an MRE11 nuclease inhibitor. Domain analysis of AND-1 further revealed that the HMG box is important for fast replication but not for proliferation, whereas conversely, the WD40 domain prevents fork resection and subsequent DSB-associated lethality. Thus, our findings uncover a fork protection function of AND-1/Ctf4 manifested via the WD40 domain that is essential for proliferation and averts genome instability., Thus , our findings uncover a fork protection function of AND-1/Ctf4 manifested via the WD40 domain that is essential for proliferation and averts genome instability, Thus, our findings uncover a fork protection function of AND-1/Ctf4 manifested via the WD40 domain that is essential for proliferation and averts genome instability.[SEP]Relations: HMG box domain binding has relations: molfunc_protein with TCF12, molfunc_protein with TCF12, molfunc_protein with SP1, molfunc_protein with SP1, molfunc_protein with POU3F3, molfunc_protein with POU3F3, molfunc_protein with ALX4, molfunc_protein with ALX4, molfunc_protein with EGR2, molfunc_protein with EGR2.", "label": "yes"}
{"id": "converted_828", "sentence1": "Is muscle lim protein (MLP) involved in cardiomyopathies?", "sentence2": "Muscle LIM protein (MLP) has been proposed to be a central player in the pathogenesis of heart muscle disease. In line with this notion, the homozygous loss of MLP results in cardiac hypertrophy and dilated cardiomyopathy. Moreover, MLP is induced in several models of cardiac hypertrophy such as aortic banding and myocardial infarction. , Muscle LIM protein (MLP) null mice are often used as a model for human dilated cardiomyopathy., A lack of MLP leads to an age-dependent impairment of excitation-contraction coupling with resulting contractile dysfunction and secondary fibrosis., Loss of murine MLP results in dilated cardiomyopathy, and mutations in human MLP lead to cardiac hypertrophy, indicating a critical role for MLP in maintaining normal cardiac function., Our data indicate that MLP contributes to muscle stiffness and is necessary for maximum work and power generation., Interestingly, MLP was also found to be down-regulated in humans with heart failure (Zolk et al. Circulation 101:2674-2677, 2000) and MLP mutations are able to cause hypertrophic and dilated forms of cardiomyopathy in humans (Bos et al. Mol Genet Metab 88:78-85, 2006; Geier et al. Circulation 107:1390-1395, 2003; Hershberger et al. Clin Transl Sci 1:21-26, 2008; Knöll et al. Cell 111:943-955, 2002; Knöll et al. Circ Res 106:695-704, 2010; Mohapatra et al. Mol Genet Metab 80:207-215, 2003)., MLP soon became an important model for experimental cardiology when it was first demonstrated that MLP deficiency leads to myocardial hypertrophy followed by a dilated cardiomyopathy and heart failure phenotype (Arber et al. Cell 88:393-403, 1997). , Previous studies have shown an association between CSRP3 missense mutations and either dilated cardiomyopathy (DCM) or HCM, but all these studies were unable to provide comprehensive genetic evidence for a causative role of CSRP3 mutations. , We used a newly designed monoclonal antibody to show that muscle LIM protein (MLP), the protein encoded by CSRP3, is mainly a cytosolic component of cardiomyocytes and not tightly anchored to sarcomeric structures. Our functional data from both in vitro and in vivo analyses suggest that at least one of MLP's mutated forms seems to be destabilized in the heart of HCM patients harbouring a CSRP3 missense mutation., Muscle LIM protein (MLP) is a cytoskeletal protein located at the Z-disc of sarcomeres. Mutations in the human MLP gene are associated with hypertrophic and dilated cardiomyopathy., Our data demonstrate that Mlp84B is essential for normal cardiac function and establish the Drosophila model for the investigation of the mechanisms connecting defective cardiac Z-disc components to the development of cardiomyopathy., Muscle LIM protein (MLP) is a cytoskeletal LIM-only protein expressed in striated muscle. Mutations in human MLP are associated with cardiomyopathy;, TTN-encoded titin, CSRP3-encoded muscle LIM protein, and TCAP-encoded telethonin are Z-disc proteins essential for the structural organization of the cardiac sarcomere and the cardiomyocyte's stretch sensor. All three genes have been established as cardiomyopathy-associated genes for both dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). , Approximately 4.1% of unrelated patients had HCM-associated MLP or TCAP mutations. MLP/TCAP-HCM phenotypically mirrors myofilament-HCM and is more severe than the subset of patients who still remain without a disease-causing mutation. The precise role of W4R-MLP in the pathogenesis of either DCM or HCM warrants further investigation., MLP (muscle-LIM-protein) deficient mice develop DCM and changes in the mechanical coupling of cardiomyocytes result in alterations at the intercalated disks and enhanced accumulation of adherens junction proteins., Targeted deletion of cytoskeletal muscle LIM protein (MLP) in mice consistently leads to dilated cardiomyopathy (DCM) after one or more months. , In summary, young MLPKO mice revealed substantial alterations in passive myocardial properties and relaxation time, but not in most systolic characteristics. These results indicate that the progression to heart failure in the MLPKO model may be driven by diastolic myocardial dysfunction and abnormal passive properties rather than systolic dysfunction., Mice lacking the muscle LIM protein (MLP) develop morphological and clinical signs resembling human dilated cardiomyopathy and heart failure., Our results show that the absence of MLP causes a local loss of mitochondria. We hypothesize that this is caused by a disturbed interaction between cytoskeleton and mitochondria, which interferes with energy sensing and energy transfer. Recovery of energy depletion by stimulating mitochondrial biogenesis might be a useful therapeutic strategy for improving the energy imbalance in heart failure., Previous work has shown that mutations in muscle LIM protein (MLP) can cause hypertrophic cardiomyopathy (HCM). In order to gain an insight into the molecular basis of the disease phenotype, we analysed the binding characteristics of wild-type MLP and of the (C58G) mutant MLP that causes hypertrophic cardiomyopathy., The molecular basis for HCM-causing mutations in the MLP gene might therefore be an alteration in the equilibrium of interactions of the ternary complex MLP-N-RAP-alpha-actinin., Muscle LIM protein (MLP) is a member of the cysteine-rich protein (CRP) family and has been implicated in both myogenesis and sarcomere assembly. In the latter role, it binds zyxin and alpha-actinin, both of which are involved in actin organization. An MLP-deficient mouse has been described; these mice develop dilated cardiomyopathy and heart failure., We identified a patient with DCM and EFE, having a mutation in MLP with the residue lysine 69 substituted by arginine (K69R). , MLP-knockout mice develop a marked cardiac hypertrophy reaction and dilated cardiomyopathy (DCM). MLP is therefore a candidate gene for heritable forms of hypertrophic cardiomyopathy (HCM) and DCM in humans., Family studies revealed cosegregation of clinically affected individuals with the respective mutations in MLP. CONCLUSION: Here, we present evidence that mutations in the CRP3/MLP gene can cause HCM., The skeletal muscle LIM protein 1 (SLIM1) is highly expressed in skeletal and cardiac muscle, and its expression is downregulated significantly in dilated human cardiomyopathy. , Targeted disruption of muscle LIM protein (MLP) has previously been shown to result in dilated cardiomyopathy with many of the clinical signs of heart failure, although the effects of MLP disruption on passive ventricular mechanics and myocyte architecture are not known., These results suggest that the disruption of the cytoskeletal protein MLP results in less compliant passive tissue and concomitant structural alterations in the three-dimensional myocyte architecture that may in part explain the ventricular dysfunction in the dilated heart.,  Mutations in cysteine and glycine-rich protein 3 (CSRP3), the gene encoding MLP, have been directly associated with human cardiomyopathies, whereas aberrant expression patterns are reported in human cardiac and skeletal muscle diseases., Muscle LIM protein (MLP) has been proposed to be a central player in the pathogenesis of heart muscle disease., Previous work has shown that mutations in muscle LIM protein (MLP) can cause hypertrophic cardiomyopathy (HCM)[SEP]Relations: muscle tissue has relations: anatomy_protein_present with MLXIP, anatomy_protein_present with MLXIP, anatomy_protein_present with LIMS1, anatomy_protein_present with LIMS1, anatomy_protein_present with MLIP, anatomy_protein_present with MLIP, anatomy_protein_present with LIMS3, anatomy_protein_present with LIMS3, anatomy_protein_present with MLPH, anatomy_protein_present with MLPH.", "label": "yes"}
{"id": "converted_488", "sentence1": "Can exosomes be detected in urine?", "sentence2": "Exosomes are nanovesicles secreted into the extracellular environment upon internal vesicle fusion with the plasma membrane. The molecular content of exosomes is a fingerprint of the releasing cell type and of its status. For this reason, and because they are released in easily accessible body fluids such as blood and urine, they represent a precious biomedical tool. , Exosomes are vesicles that are released from the kidney into urine., Quantification of human urinary exosomes by nanoparticle tracking analysis., Urinary extracellular vesicles (uEVs) are released by cells throughout the nephron and contain biomolecules from their cells of origin., Urinary exosomes have been proposed as potential diagnostic tools., Urinary exosomes as a source of kidney dysfunction biomarker in renal transplantation, . Here we sought to optimize the methodologies for the isolation and quantification of urinary exosomal microRNA as a prelude to biomarker discovery studies. , Exosomes are small (30-150 nm) vesicles containing unique RNA and protein cargo, secreted by all cell types in culture. They are also found in abundance in body fluids including blood, saliva, and urine. , Urinary exosome-like vesicles (ELVs) are a heterogenous mixture (diameter 40-200 nm) containing vesicles shed from all segments of the nephron including glomerular podocytes, Exosomes are cytoplasm containing vesicles released by many cells that can be found in several biological fluids including urine., Proteomic analysis of urinary exosomes in cardiovascular and associated kidney diseases by two-dimensional electrophoresis and LC-MS/MS[SEP]Relations: cytoplasm has relations: cellcomp_protein with EXOSC10, cellcomp_protein with EXOSC10, cellcomp_protein with PSME1, cellcomp_protein with PSME1. kidney disease has relations: contraindication with Entacapone, contraindication with Entacapone, contraindication with Cisapride, contraindication with Cisapride. plasma membrane has relations: cellcomp_protein with EXO1, cellcomp_protein with EXO1.", "label": "yes"}
{"id": "converted_3835", "sentence1": "Do exon 38 or 39 KMT2D missense variants cause Kabuki syndrome type 1 (KS1)?", "sentence2": "A restricted spectrum of missense KMT2D variants cause a multiple malformations disorder distinct from Kabuki syndrome., To investigate if specific exon 38 or 39 KMT2D missense variants (MVs) cause a condition distinct from Kabuki syndrome type 1 (KS1).METHODS: Multiple individuals, with MVs in exons 38 or 39 of KMT2D that encode a highly conserved region of 54 amino acids flanked by Val3527 and Lys3583, were identified and phenotyped. Functional tests were performed to study their pathogenicity and understand the disease mechanism.RESULTS: The consistent clinical features of the affected individuals, from seven unrelated families, included choanal atresia, athelia or hypoplastic nipples, branchial sinus abnormalities, neck pits, lacrimal duct anomalies, hearing loss, external ear malformations, and thyroid abnormalities. None of the individuals had intellectual disability. The frequency of clinical features, objective software-based facial analysis metrics, and genome-wide peripheral blood DNA methylation patterns in these patients were significantly different from that of KS1. Circular dichroism spectroscopy indicated that these MVs perturb KMT2D secondary structure through an increased disordered to ɑ-helical transition.CONCLUSION: KMT2D MVs located in a specific region spanning exons 38 and 39 and affecting highly conserved residues cause a novel multiple malformations syndrome distinct from KS1. Unlike KMT2D haploinsufficiency in KS1, these MVs likely result in disease through a dominant negative mechanism.[SEP]Relations: Kabuki syndrome has relations: disease_protein with KMT2D, disease_protein with KMT2D, disease_protein with KDM6A, disease_protein with KDM6A, disease_phenotype_positive with Generalized hypotonia, disease_phenotype_positive with Generalized hypotonia, disease_protein with RAP1B, disease_protein with RAP1B, disease_protein with RAP1A, disease_protein with RAP1A.", "label": "no"}
{"id": "converted_3058", "sentence1": "Is Miller-Dieker syndrome associated with abnormalities of chromosome 1?", "sentence2": "A complete ophthalmic examination is not routinely performed on infants with Miller-Dieker syndrome (MDS, chromosome 17p13.3 microdeletion). , Chromosome microdeletions within 17p13.3 can result in either isolated lissencephaly sequence (ILS) or Miller-Dieker syndrome (MDS). , We report a fetus with lissencephaly diagnosed as Miller-Dieker Syndrome postnatally. G banded chromosome analysis revealed 45,X,psu dic(17;Y)(p13;p11.32).ish dic (17;Y)(LIS1-,RARA+, SRY+, DYZ3+) by G-banding analysis using high resolution banding technique. Fetal delayed cortical development will be the findings to perform further investigations including fluorescence in situ hybridization analysis for MDS, a 17p13.3 microdeletion syndrome, pre/postnatally. This will be the first case of MDS with unbalanced translocation between deleted short arm of chromosome 17 and Y chromosome.,  We report the finding of a 2.5-Mb gene region quadruplication of Chromosome 17p13.3. This region is well characterized for the deletion leading to Miller-Dieker syndrome but has an unclear replication phenotype. , Both deletions have overlapped with the critical region of Miller-Dieker syndrome (MDS) and involved candidate genes such as PAFAH1B1, YWHAE and CRK. In addition, SNP array and FISH analyses on the parental peripheral blood samples demonstrated that both 17p13.3 and 17p13.3p13.2 deletions were of de novo origin., Miller-Dieker syndrome (MDS) is caused by a heterozygous deletion of chromosome 17p13.3 involving the genes LIS1 and YWHAE (coding for 14.3.3ε) and leads to malformations during cortical development., We studied after death a 3-month-old girl whose karyotype was 45,XX,-15,-17,+der(17),t(15;17)(q13;p13.3) and thus combines abnormalities of chromosome 15 associated with the Prader-Willi syndrome and of chromosome 17 associated with the Miller-Dieker syndrome., The Miller-Dieker syndrome (MDS), a syndrome with lissencephaly, distinctive craniofacial features, growth impairment, and profound developmental failure, has been associated with a deletion of the distal part of chromosome band 17p13., The Miller-Dieker syndrome (type I lissencephaly) is a neuronal migration disorder which is associated with microdeletions in the short arm of chromosome 17., Detection of submicroscopic deletions in band 17p13 in patients with the Miller-Dieker syndrome., A 15-month-old girl with Miller-Dieker syndrome, a contiguous gene deletion syndrome involving chromosome 17p13.3 and resulting in lissencephaly, was diagnosed with precursor B-cell acute lymphoblastic leukemia., A computed tomography scan revealed evidence of lissencephaly, and chromosomal analysis showed a microdeletion on the short arm of chromosome 17 (17p13.3), confirming the diagnosis as Miller-Dieker syndrome., Familial Miller-Dieker syndrome associated with pericentric inversion of chromosome 17., The Miller-Dieker syndrome (MDS), a rare congenital disorder manifested by characteristic facial abnormalities and lissencephaly (smooth brain), is associated with microdeletions of the distal 17p region., Miller-Dieker syndrome (MDS), a disorder manifesting the severe brain malformation lissencephaly (\"smooth brain\"), is caused, in the majority of cases, by a chromosomal microdeletion of the distal short arm of chromosome 17., The Miller-Dieker syndrome (MDS), composed of characteristic facial abnormalities and a severe neuronal migration disorder affecting the cerebral cortex, is caused by visible or submicroscopic deletions of chromosome band 17p13., Microdeletions including YWHAE in the Miller-Dieker syndrome region on chromosome 17p13.3 result in facial dysmorphisms, growth restriction, and cognitive impairment., Identification of the functional profilin gene, its localization to chromosome subband 17p13.3, and demonstration of its deletion in some patients with Miller-Dieker syndrome., HIC1 is a candidate tumor suppressor gene which is frequently hypermethylated in human tumors, and its location within the Miller-Dieker syndrome's critical deletion region at chromosome 17p13.3 makes it a candidate gene for involvement in this gene deletion syndrome., A complete ophthalmic examination is not routinely performed on infants with Miller-Dieker syndrome (MDS, chromosome 17p13.3 microdeletion)., About 15% of patients with isolated lissencephaly and more than 90% of patients with Miller-Dieker syndrome have microdeletions in a critical 350-kilobase region in chromosome 17p13.3 (ref., Chromosome aberrations in which epilepsy is a major and consistent finding include Angelman syndrome due to loss of the maternal 15q11.2-q12 segment, tetrasomy of the maternal segment 15pter-q13 due to an additional inv dup chromosome, Miller-Dieker syndrome due to deletion of the 17p13.3 segment including the lissencephaly1 gene, ring chromosome 20, and Wolf-Hirschhorn syndrome due to deletion of at least the 4p16.3 segment., Miller-Dieker syndrome and trisomy 5p in a child carrying a derivative chromosome with a microdeletion in 17p13.3 telomeric to the LIS1 and the D17S379 loci., The Miller-Dieker syndrome, a disorder of neuronal migration, is caused by deletions of chromosome 17p13.3., The girl was diagnosed by subtelomeric FISH and array-CGH, showing a 4.43-Mb heterozygous deletion on chromosome 10p that involved 14 genes and a 3.22-Mb single-copy gain on chromosome 17p, which includes the critical region of the Miller-Dieker syndrome and 61 genes., Detection of submicroscopic deletions in band 17p13 in patients with the Miller-Dieker syndrome.The Miller-Dieker syndrome (MDS), a syndrome with lissencephaly, distinctive craniofacial features, growth impairment, and profound developmental failure, has been associated with a deletion of the distal part of chromosome band 17p13. , Microdeletions including YWHAE in the Miller-Dieker syndrome region on chromosome 17p13.3 result in facial dysmorphisms, growth restriction, and cognitive impairment.Microdeletions of chromosome 17p13.3 involving YWHAE present with growth restriction, craniofacial dysmorphisms, structural abnormalities of brain and cognitive impairment. , Unbalanced translocation (15;17)(q13;13.3) with apparent Prader-Willi syndrome but without Miller-Dieker syndrome.We studied after death a 3-month-old girl whose karyotype was 45,XX,-15,-17,+der(17),t(15;17)(q13;p13.3) and thus combines abnormalities of chromosome 15 associated with the Prader-Willi syndrome and of chromosome 17 associated with the Miller-Dieker syndrome. , The Miller-Dieker syndrome (MDS), a rare congenital disorder manifested by characteristic facial abnormalities and lissencephaly (smooth brain), is associated with microdeletions of the distal 17p region. , A revision of the lissencephaly and Miller-Dieker syndrome critical regions in chromosome 17p13.3.Miller-Dieker syndrome (MDS) is a multiple malformation syndrome characterized by classical lissencephaly and a characteristic facies. , Case Report of Proliferative Peripheral Retinopathy in Two Familial Lissencephaly Infants with Miller-Dieker Syndrome.A complete ophthalmic examination is not routinely performed on infants with Miller-Dieker syndrome (MDS, chromosome 17p13.3 microdeletion). , Identification of the functional profilin gene, its localization to chromosome subband 17p13.3, and demonstration of its deletion in some patients with Miller-Dieker syndrome.Profilin is a conserved actin-monomer-binding protein which is found in all eukaryotes, including yeast. , We propose that essentially no loss of 17p material has occurred and confirm previous reports that the critical region for the production of the Miller-Dieker phenotype is located subterminally in the 17p13.3 region.<br>, A review of the literature revealed five additional patients in three families, who had Miller-Dieker syndrome and an abnormality of 17p., We propose that essentially no loss of 17p material has occurred and confirm previous reports that the critical region for the production of the Miller-Dieker phenotype is located subterminally in the 17p13.3 region., Miller-Dieker syndrome: lissencephaly and monosomy 17p., Thus, we propose that monosomy of distal 17p may be the cause of Miller-Dieker syndrome in some patients., Miller-Dieker syndrome with der(17)t(12;17)(q24.33;p13.3)pat presenting with a potential risk of mis-identification as a de novo submicroscopic deletion of 17p13.3., Most cases of Miller-Dieker syndrome have a de novo deletion involving 17p13.3.[SEP]Relations: partial monosomy of the short arm of chromosome 17 has relations: disease_disease with Miller-Dieker lissencephaly syndrome, disease_disease with Miller-Dieker lissencephaly syndrome. PAFAH1B1 has relations: disease_protein with Miller-Dieker lissencephaly syndrome, disease_protein with Miller-Dieker lissencephaly syndrome. Contiguous gene syndrome has relations: disease_phenotype_positive with Miller-Dieker lissencephaly syndrome, disease_phenotype_positive with Miller-Dieker lissencephaly syndrome. Miller Fisher syndrome has relations: disease_protein with PMP22, disease_protein with PMP22. congenital nervous system disorder has relations: disease_disease with Say-Barber-Miller syndrome, disease_disease with Say-Barber-Miller syndrome.", "label": "no"}
{"id": "converted_3399", "sentence1": "Does CXorf21 escape X chromosome inactivation?", "sentence2": "This revealed a 637-kb tandem duplication that in addition to DAX1 includes the four MAGEB genes, the hypothetical gene CXorf21, GK, and part of the MAP3K7IP3 gene, Among statin users, diabetes cases had marginal but insignificantly different expression of ZNF532 (up-regulated 15%, Q-value=0.0584), CXORF21 (up-regulated 11%, Q-value=0.0584), and ZNHIT3 (up-regulated 19%, Q-value=0.0959), compared with controls.,  For this, we selected five SNPs (rs1801274 in FCGR2A and rs2286672 in PLD2, rs887369 in CXorf21, rs9782955 in LYST, and rs3794060 in NADSYN1), Examination of X-linked DEGs, such as GTPBP6, TAF9L, and CXORF21, that show verbal cognition-gene expression correlations may establish a causal link between these genes, neurodevelopment, and language function.[SEP]Relations: ZNHIT3 has relations: protein_protein with XRCC3, protein_protein with XRCC3, bioprocess_protein with box C/D snoRNP assembly, bioprocess_protein with box C/D snoRNP assembly. NADSYN1 has relations: protein_protein with NOXA1, protein_protein with NOXA1, anatomy_protein_absent with cerebellar vermis, anatomy_protein_absent with cerebellar vermis. Protein S human has relations: drug_drug with Coagulation Factor IX (Recombinant), drug_drug with Coagulation Factor IX (Recombinant).", "label": "yes"}
{"id": "converted_4366", "sentence1": "Is there a genetic cause of craniostenosis?", "sentence2": "Apert syndrome - acrocephalosyndactyly - is a rare autosomal dominant disorder representing 1:65 000 cases of living newborns. Characteristic malformations of the Apert syndrome are early craniostenosis, microviscerocranium and II-V finger syndactyly of hand and toes with proximal phalanx of the bilateral thumb \"in delta\"., A 3-year-old child with tertiary trisomy (14 (+14q--), daughter of a mother with a balanced reciprocal translocation [46,XX,t(14;16)(q11;q24) is presented. Craniostenosis and developmental retardation were the primary presenting features in this patient., Saethre-Chotzen syndrome is an autosomal dominant disease characterized by craniosynostosis, ptosis, and limb and external ear abnormalities, . For 98 patients (15%) a syndrome is associated. Third part of them has Apert syndrome, an other third part has Crouzon syndrome, and for the last third more exceptional acrocephalosyndactyly syndrome (Saethre-Chotzen, Pfeiffer) or others atypical associations, sometimes not yet described, but with an autosomal dominant inheritance., Coronal craniostenosis seems to be a dominant autosomal character, when scaphocephaly is more often sporadic; for both, an autosomal dominant inheritance is not excluded for some pedigrees.,  genetic origins are not completely clear although mutations in the genes that code for fibroblast growth factor receptors have been described; depending upon the gene involved, the type of mutation and the embryological period in which the mutation itself occurs, a type of craniosynostosis arises that may involve one or more cranial sutures. The, Saethre-Chotzen syndrome is an autosomal dominant disease characterized by craniosynostosis, ptosis, and limb and external ear abnormalities. , Identification and analysis of the genetic causes in nine unrelated probands with syndromic craniosynostosis., To identify and analyze causative genetic variants in nine unrelated probands mainly manifested as syndromic craniosynostosis, we reviewed the relevant medical information of the patients and performed the whole exome sequencing, further verified with Sanger sequencing and parental background., [Genetic counseling in craniostenosis. Results of a prospective study performed with a group of studies on craniofacial malformations]., Constitutional 11q interstitial deletion syndrome presents with congenital anomalies including microcephaly with craniostenosis, minor dysmorphic features, vitreoretinopathy, and renal anomalies., A suckling baby with microcephaly, craniostenosis, downward slanting palpebral fissues, malformed ears, cerebral, cardiac and intestinal malformation, and partial 6q25 leads to 6qter trisomy is presented., Its genetic origins are not completely clear although mutations in the genes that code for fibroblast growth factor receptors have been described; depending upon the gene involved, the type of mutation and the embryological period in which the mutation itself occurs, a type of craniosynostosis arises that may involve one or more cranial sutures., through which skull growth abnormalities are seen. It is becoming clearer that in most patients with craniosynostosis, there is regional imbalance of skull growth, which co-exists with a variety of other equally important factors, such as genetic defects, raised intracranial pressure, venous hypertension, and other brain parenchymal a, Recent genetic studies have identified several novel genes and pathways that cause nonsyndromic craniosynostosis, providing genetic evidence linking the causes of syndromic and nonsyndromic craniosynostoses, and allowing for genotype-based prediction of risk of recurrence in some nonsyndromic families.[SEP]Relations: Craniosynostosis has relations: phenotype_phenotype with Abnormality of cranial sutures, phenotype_phenotype with Abnormality of cranial sutures, disease_phenotype_positive with hereditary hypophosphatemic rickets, disease_phenotype_positive with hereditary hypophosphatemic rickets, disease_phenotype_positive with mucolipidosis, disease_phenotype_positive with mucolipidosis, phenotype_phenotype with Coronal craniosynostosis, phenotype_phenotype with Coronal craniosynostosis, disease_phenotype_positive with congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency, disease_phenotype_positive with congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency.", "label": "yes"}
{"id": "converted_725", "sentence1": "Is acid alpha-glucosidase the enzyme that causes Pompe disease when mutant?", "sentence2": "Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme responsible for degradation of lysosomal glycogen (acid α-glucosidase (GAA)), Pompe disease is a systemic metabolic disorder characterized by lack of acid-alpha glucosidase (GAA) resulting in ubiquitous lysosomal glycogen accumulation, Pompe disease is an autosomal recessive myopathic disorder caused by the deficiency of lysosomal acid α-glucosidase (GAA), Acid α-glucosidase deficiency, that is, Pompe disease, is a glycogenosis for which enzyme replacement therapy (ERT) is available, The analysis revealed that the amino acid substitutions causing a processing or transport defect responsible for Pompe disease were widely spread over all of the five domains comprising the acid alpha-glucosidase., Pompe disease is a lysosomal storage disease (LSD) caused by a deficiency in the lysosomal enzyme acid alpha-glucosidase., Glycogen storage disease type II (GSDII; Pompe disease or acid maltase deficiency) is an autosomal recessive disorder caused by lysosomal acid alpha-glucosidase (AalphaGlu) deficiency and manifests predominantly as skeletal muscle weakness., Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease., The nature of mutant acid alpha-glucosidase (AAG) in muscle was studied in 6 patients with Pompe disease, consisting of 2 each of the infantile, childhood and adult types., Pompe disease (glycogen storage disease II) is caused by mutations in the acid alpha-glucosidase gene., Glycogen storage disease type II (Pompe disease) is inherited by autosomal recessive transmission and caused by a deficiency of acid alpha-glucosidase (GAA), resulting in impaired degradation and lysosomal accumulation of glycogen., Pompe disease is a lysosomal storage disorder (LSD) caused by mutations in the gene that encodes acid alpha-glucosidase (GAA)., Demonstration of acid alpha-glucosidase in different types of Pompe disease by use of an immunochemical method., Acid alpha-glucosidase (GAA) deficiency causes Pompe disease, a lethal lysosomal glycogen storage disease for which no effective treatment currently exists., Deficiency of acid alpha glucosidase (GAA) causes Pompe disease, which is usually fatal if onset occurs in infancy., Ambulatory electrocardiogram analysis in infants treated with recombinant human acid alpha-glucosidase enzyme replacement therapy for Pompe disease., Infantile Pompe disease is caused by deficiency of lysosomal acid alpha-glucosidase., Determination of acid alpha-glucosidase activity in blood spots as a diagnostic test for Pompe disease., The pharmacological chaperone AT2220 increases the specific activity and lysosomal delivery of mutant acid alpha-glucosidase, and promotes glycogen reduction in a transgenic mouse model of Pompe disease, Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease, Glycogen stored in skeletal but not in cardiac muscle in acid alpha-glucosidase mutant (Pompe) mice is highly resistant to transgene-encoded human enzyme, Although many lysosomal disorders are corrected by a small amount of the missing enzyme, it has been generally accepted that 20-30% of normal acid alpha-glucosidase (GAA) activity, provided by gene or enzyme replacement therapy, would be required to reverse the myopathy and cardiomyopathy in Pompe disease, The nature of mutant acid alpha-glucosidase (AAG) in muscle was studied in 6 patients with Pompe disease, consisting of 2 each of the infantile, childhood and adult types, As in the severe human infantile disease (Pompe Syndrome), mice homozygous for disruption of the acid alpha-glucosidase gene (6(neo)/6(neo)) lack enzyme activity and begin to accumulate glycogen in cardiac and skeletal muscle lysosomes by 3 weeks of age, with a progressive increase thereafter, Glycogen-storage disease type II, Pompe disease, is caused by the deficiency of acid alpha-D-glucosidase in lysosome, Pompe disease (glycogen storage disease II) is caused by mutations in the acid alpha-glucosidase gene, Glycogen storage disease type II (Pompe disease) is inherited by autosomal recessive transmission and caused by a deficiency of acid alpha-glucosidase (GAA), resulting in impaired degradation and lysosomal accumulation of glycogen, Glycogen stored in skeletal but not in cardiac muscle in acid alpha-glucosidase mutant (Pompe) mice is highly resistant to transgene-encoded human enzyme., Structural modeling of mutant alpha-glucosidases resulting in a processing/transport defect in Pompe disease., Replacing acid alpha-glucosidase in Pompe disease: recombinant and transgenic enzymes are equipotent, but neither completely clears glycogen from type II muscle fibers., The pharmacological chaperone AT2220 increases the specific activity and lysosomal delivery of mutant acid alpha-glucosidase, and promotes glycogen reduction in a transgenic mouse model of Pompe disease., Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase. , Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease., We describe an improved method for detecting deficiency of the acid hydrolase, alpha-1,4-glucosidase in leukocytes, the enzyme defect in glycogen storage disease Type II (Pompe disease)., Acid alpha-glucosidase (GAA) deficiency causes Pompe disease,,  Infantile Pompe disease is caused by deficiency of lysosomal acid alpha-glucosidase. Trials with recombinant human acid alpha-glucosidase enzyme replacement therapy (ERT) show a decrease in left ventricular mass and improved function.,  Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase. Due to virtual absence of acid alpha-glucosidase, patients with classical infantile Pompe disease develop progressive cardiomyopathy, skeletal muscle weakness and respiratory insufficiency leading to death in early infancy., Pompe disease is caused by the congenital deficiency of the lysosomal enzyme acid alpha-glucosidase., The nature of mutant acid alpha-glucosidase (AAG) in muscle was studied in 6 patients with Pompe disease,,  Pompe disease is a lysosomal storage disorder (LSD) caused by mutations in the gene that encodes acid alpha-glucosidase (GAA). Recently, small molecule pharmacological chaperones have been shown to increase protein stability and cellular levels for mutant lysosomal enzymes and have emerged as a new therapeutic strategy for the treatment of LSDs., Acid alpha-glucosidase (GAA) deficiency causes Pompe disease, a lethal lysosomal glycogen storage disease for which no effective treatment currently exists., Infantile Pompe disease is caused by deficiency of lysosomal acid alpha-glucosidase., Glycogen-storage disease type II, Pompe disease, is caused by the deficiency of acid alpha-D-glucosidase in lysosome., Structural modeling of mutant alpha-glucosidases resulting in a processing/transport defect in Pompe disease., Pompe disease is a lysosomal storage disorder (LSD) caused by mutations in the gene that encodes acid alpha-glucosidase (GAA)., Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease., Ambulatory electrocardiogram analysis in infants treated with recombinant human acid alpha-glucosidase enzyme replacement therapy for Pompe disease., Mutations in alpha-glucosidase cause accumulation of glycogen in lysosomes, resulting in Pompe disease, a lysosomal storage disorder., Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase., Infantile Pompe disease is a fatal genetic muscle disorder caused by a deficiency of acid alpha-glucosidase, a glycogen-degrading lysosomal enzyme.[SEP]Relations: glycogen storage disease has relations: disease_disease with glycogen storage disease due to muscle beta-enolase deficiency, disease_disease with glycogen storage disease due to muscle beta-enolase deficiency, disease_disease with glycogen storage disease due to acid maltase deficiency, late-onset, disease_disease with glycogen storage disease due to acid maltase deficiency, late-onset, disease_disease with glycogen storage disease due to acid maltase deficiency, infantile onset, disease_disease with glycogen storage disease due to acid maltase deficiency, infantile onset. GAA has relations: disease_protein with glycogen storage disease due to acid maltase deficiency, late-onset, disease_protein with glycogen storage disease due to acid maltase deficiency, late-onset, disease_protein with glycogen storage disease due to acid maltase deficiency, infantile onset, disease_protein with glycogen storage disease due to acid maltase deficiency, infantile onset.", "label": "yes"}
{"id": "converted_3", "sentence1": "Are long non coding RNAs spliced?", "sentence2": "Our analyses indicate that lncRNAs are generated through pathways similar to that of protein-coding genes, with similar histone-modification profiles, splicing signals, and exon/intron lengths., For alternative exons and long noncoding RNAs, splicing tends to occur later, and the latter might remain unspliced in some cases., bosome-mapping data to identify lncRNAs of Caenorhabditis elegans. We found 170 long intervening ncRNAs (lincRNAs), which had single- or multiexonic structures that did not overlap protein-coding transcripts, and about sixty antisense lncRNAs (ancRNAs), which were complementary to protein-coding transcripts, We introduce an approach to predict spliced lncRNAs in vertebrate genomes combining comparative genomics and machine learning., Owing to similar alternative splicing pattern to mRNAs, the concept of lncRNA genes was put forward to help systematic understanding of lncRNAs. , Our synthesis of recent studies suggests that neither size, presence of a poly-A tail, splicing, direction of transcription, nor strand specificity are of importance to lncRNA function.[SEP]Relations: long noncoding RNA binding has relations: molfunc_protein with MIR384, molfunc_protein with MIR384.", "label": "yes"}
{"id": "converted_2105", "sentence1": "Does the word ovine refers to goats?", "sentence2": "Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA), a transmissible lung cancer of sheep that has rarely been found in goats. , In sheep, a bronchiolo-alveolar carcinoma, known as ovine pulmonary carcinoma (OPC), is caused by jaagsiekte sheep retrovirus (JSRV), an exogenous type D retrovirus. [SEP]Relations: protein complex oligomerization has relations: bioprocess_protein with OPA1, bioprocess_protein with OPA1, bioprocess_protein with BOK, bioprocess_protein with BOK, bioprocess_protein with MCU, bioprocess_protein with MCU, bioprocess_protein with ADCY8, bioprocess_protein with ADCY8, bioprocess_protein with NOL3, bioprocess_protein with NOL3.", "label": "no"}
{"id": "converted_528", "sentence1": "Is there any software for automated analysis of immuno-histochemistry images?", "sentence2": "The LIM homeobox gene Lhx2 is expressed in cortical progenitors during development and also in the superficial layers of the neocortex in maturity. However, analysis of Lhx2 function at later stages of cortical development has been hampered by severe phenotypes associated with early loss of function. , The vein graft samples were obtained on each time point after surgery. The expression of the EDRz transfected in the vein graft was detected using a fluorescent microscope. Early growth response gene-1 (Egr-1) mRNA was measured using reverse transcription-PCR and in situ hybridization. And the protein expression of Egr-1 was detected by using western blot and immunohistochemistry analyses., Tissue Transglutaminase (TG2) is a multifunctional enzyme, which amongst other functions, is involved in cell differentiation. Therefore, we hypothesized that TG2 contributes to differentiation of OPCs into OLGs and thereby stimulates remyelination. [SEP]Relations: neocortex has relations: anatomy_protein_present with ENO2, anatomy_protein_present with ENO2, anatomy_protein_present with TMCO3, anatomy_protein_present with TMCO3, anatomy_protein_present with TMCO6, anatomy_protein_present with TMCO6. Protein S human has relations: drug_drug with Ifosfamide, drug_drug with Ifosfamide, drug_drug with Ifosfamide, drug_drug with Ifosfamide.", "label": "yes"}
{"id": "converted_3904", "sentence1": "Is Ixodes a species of tick?", "sentence2": "ixodid ticks, ixodid ticks ,  ixodid ticks, tick, Ixodes ricinus, hard ticks (family Ixodidae), The two enzootic tick vectors, Ixodes affinis and Ixodes minor, rarely bite humans but are more important than the human biting \"bridge\" vector, Ixodes scapularis, in maintaining the enzootic spirochete cycle in nature., is more common in coastal habitats, where a greater diversity of Ixodes species ticks are found feeding on small mammal hosts (four species when compared with only I. pacificus in other sampled habitats)., We found three of five previously reported tick species as well as a tick resembling the eastern North American tick Ixodes minor Neumann (which we here designate Ixodes \"Mojave morphotype\") on isolated Amargosa voles and Owens Valley voles (Microtus californicus vallicola Bailey) in Inyo County in 2012 and 2014., THODS: We focused on the well-studied tick genus Ixodes from which many species are known to transmit zoonotic diseases to humans. W, Ectoparasites of Microtus californicus and Possible Emergence of an Exotic Ixodes Species Tick in California., Since 2007, non-native tick species have been documented in the state every year, including Amblyomma americanum, Dermacentor andersoni, Dermacentor occidentalis, Dermacentor variabilis, Ixodes pacificus, Ixodes ricinus, Ixodes scapularis, Ixodes texanus, and Rhipicephalus sanguineus sensu lato (s.l.)., in 1.5% of Ixodes species ticks and 3.6% of small mammals., Data-driven predictions and novel hypotheses about zoonotic tick vectors from the genus Ixodes., spirochetes and transmitted by Ixodes species ticks., In this study, cutaneous bite-site lesions were analyzed using Affymetrix mouse genome 430A 2.0 arrays and histopathology at 1, 3, 6, and 12 hours after uninfected Ixodes scapularis nymphal tick attachment., The minimally vegetated, extremely arid desert surrounding the pools is essentially uninhabitable for Ixodes species ticks., Biology of Ixodes species ticks in relation to tick-borne zoonoses., Borrelia miyamotoi is a newly described emerging pathogen transmitted to people by Ixodes species ticks and found in temperate regions of North America, Europe, and Asia., Rickettsia conorii was found in virtually all non- Ixodes tick species from Albania and Turkey., Ixodes anatis is a species of endophilic (nidicolous) tick species parasitizing brown kiwi (Apteryx mantelli). Even, Ixodes ariadnae is a tick species of bats so far reported only in Central Europe, with its description based on the female and nymph. Th, BACKGROUND: Ixodes collaris Hornok, 2016 is a recently discovered tick species associated with bats, Ixodes holocyclus (Acarina: Ixodidae) and Ixodes cornuatus (Acarina: Ixodidae) are two tick species found in the more densely populated areas of Australia and are known to be the cause of the neurotoxic disease tick paralysis in humans and mammals. Borre, Ixodes affinis Neumann (Acari: Ixodidae) is a hard-bodied tick species distributed throughout much of the southeastern United States. Alt, ixodid tick fauna consists of 241 species in the genus Ixodes and 442 species in the genera Amblyomma, Anomalohimalaya, Bothriocroton, Cosmiomma, Dermacentor, Haemaphysalis, Hyalomma, Margaropus, Nosomma, Rhipicentor and Rhipicephalus in the family Ixodidae, with the genus Boophilus becoming a subgenus of the genus Rhipicephalus. The family Nutt, e following 16 ixodid tick species were identified: Ixodes fuscipes, Amblyomma auricularium, Amblyomma coelebs, Amblyomma dubitatum, Amblyomma geayi, Amblyomma humerale, Amblyomma latepunctatum, Amblyomma longirostre, Amblyomma naponense, Amblyomma nodosum, Amblyomma oblongoguttatum, Amblyomma ovale, Amblyomma romitii, Amblyomma rotundatum, Amblyomma scalpturatum, and Amblyomma varium. From these, A. aur, In 2014, a new tick species, Ixodes inopinatus, was described, which is closely related to Ixodes ricinus. So fa, ontinent. Zoonotic Babesia is vectored by Ixodes ticks and is commonly transmitted in North America by Ixodes scapularis, the tick species responsible for transmitting the pathogens that also cause Lyme disease, Powassan virus, and anaplasmosis in hu, In addition to identifying novel, testable hypotheses about intrinsic features driving vectorial capacity across Ixodes tick species, our model identifies particular Ixodes species with the highest probability of carrying zoonotic diseases, offering specific targets for increased zoonotic investigation and surveillance., To date, the tick fauna of this area consists of 117 species in the following families: Argasidae-Argas (7 species), Carios (4 species) and Ornithodoros (2 species); Ixodidae-Amblyomma (8 species), Anomalohimalaya (2 species), Dermacentor (12 species), Haemaphysalis (44 species), Hyalomma (6 species), Ixodes (24 species) and Rhipicephalus (8 species)., During a 3-yr comprehensive study, 196 ixodid ticks (9 species) were collected from 89 passerine birds (32 species) from 25 localities across Canada to determine the distribution of avian-associated tick species and endogenous Lyme disease spirochetes, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt, and Brenner., In the Polish fauna there are 19 species of ticks (Ixodida) recognized as existing permanently in our country: Argas reflexus, Argas polonicus, Carios vespertilionis, Ixodes trianguliceps, Ixodes arboricola, Ixodes crenulatus, Ixodes hexagonus, Ixodes lividus, Ixodes rugicollis, Ixodes caledonicus, Ixodes frontalis, Ixodes simplex, Ixodes vespertilionis, Ixodes apronophorus, Ixodes persulcatus, Ixodes ricinus, Haemaphysalis punctata, Haemaphysalis concinna, Dermacentor reticulatus., Occasionally, alien species of ticks transferred to the territory of Poland are recorded: Amblyomma sphenodonti, Amblyomma exornatum, Amblyomma flavomaculatum, Amblyomma latum, Amblyomma nuttalli, Amblyomma quadricavum, Amblyomma transversale, Amblyomma varanensis, Amblyomma spp., Dermacentor marginatus, Hyalomma aegyptium, Hyalomma marginatum, Ixodes eldaricus, Ixodes festai, Rhipicephalus rossicus, Rhipicephalus sanguineus., Haemaphysalis leporispalustris (Packard) (one nymph, 14 larvae); the bird tick Ixodes brunneus Koch (two larvae); the American dog tick, Dermacentor variabilis (Say) (one nymph); and Ixodes affinis Neumann (one larva)., Four members of the Ixodes ricinus species complex, Ixodes pacificus, Ixodes persulcatus, Ixodes ricinus and Ixodes scapularis, have, between them, a worldwide distribution within the northern hemisphere., Diapause in ticks of the medically important Ixodes ricinus species complex., Herein, we report these ticks to represent three different species: Ixodes catarinensis n. sp., We found that 430 endemic ticks were from 3 Ixodes species: Ixodes pacificus, Ixodes spinipalpis, and Ixodes angustus, whereas Ixodes scapularis (n = 111) was the most common species among the 119 nonendemic ticks., In total, 549 human-biting Ixodes ticks were submitted comprising both endemic and nonendemic species., Human-Biting Ixodes Ticks and Pathogen Prevalence from California, Oregon, and Washington., In this study, we show that many nonendemic Ixodes ticks (119/549) are most likely acquired from travel to a different geographic region., The Ixodes ricinus species complex is a group of ticks distributed in almost all geographic regions of the world., We report a tick associated with the enhancement of mammalian meat anaphylaxis after tick bite which is novel for both Australia and the world and establishes Ixodes (Endopalpiger) australiensis as a second tick species associated with mammalian meat allergy in Australia., Among the various species of hard ticks, Ixodes ricinus is the most frequently found tick throughout Europe.,  in humans. We aimed to identify intrinsic traits that predict which Ixodes tick species are confirmed or strongly suspected to be vectors of zoonotic pathogens.METHODS: We focused on the well-studied tick genus Ixodes from which many species are known to transmit zoonoti, A list of the 70 species of Australian ticks; diagnostic guides to and species accounts of Ixodes holocyclus (paralysis tick), Ixodes cornuatus (southern paralysis tick) and Rhipicephalus australis (Australian cattle tick); and consideration of the place of Australia in the evolution of ticks with comments on four controversial ideas., Differentiation of medically important Euro-Asian tick species Ixodes ricinus, Ixodes persulcatus, Ixodes hexagonus, and Dermacentor reticulatus by polymerase chain reaction., All these I. granulatus ticks collected from Taiwan and Japan were genetically affiliated to a monophyletic group with highly homogeneous sequences (95.8-99.5% similarity), and can be discriminated from other species and subgenera of Ixodes ticks with a sequence divergence ranging from 13.6% to 62.9%., The phylogenetic relationships were analyzed by comparing the sequences of mitochondrial 16S ribosomal DNA gene obtained from 19 strains of ticks representing seven species of Ixodes and two outgroup species (Rhipicephalus sanguineus and Haemaphysalis inermis)., e, I. woyliei n. sp. was only found on two I. o. fusciventer.CONCLUSIONS: Morphological and molecular data have confirmed the first new Australian Ixodes tick species described in ov, More than 800 tick species have been reported world-wide however only about 30 tick species feed on humans, among them Ixodes ricinus, which is the most frequent tick species biting humans in Europe., Description of a new tick species, Ixodes collaris n. sp. (Acari: Ixodidae), from bats (Chiroptera: Hipposideridae, Rhinolophidae) in Vietnam.[SEP]Relations: Lyme disease has relations: disease_disease with tick-borne infectious disease, disease_disease with tick-borne infectious disease, disease_disease with spirochaetales infections, disease_disease with spirochaetales infections. anaplasmosis has relations: disease_disease with tick-borne infectious disease, disease_disease with tick-borne infectious disease. Rickettsiosis has relations: disease_disease with tick-borne relapsing fever, disease_disease with tick-borne relapsing fever. Dental malocclusion has relations: disease_phenotype_positive with enthesitis-related juvenile idiopathic arthritis, disease_phenotype_positive with enthesitis-related juvenile idiopathic arthritis.", "label": "yes"}
{"id": "converted_1980", "sentence1": "Could divalent metal transporter 1 deficiency lead to anemia?", "sentence2": "The divalent metal transporter 1 (DMT1) is a major iron transporter required for iron absorption and erythropoiesis. Loss of DMT1 function results in microcytic anemia. , Dysfunction of human DMT1 is associated with several pathologies such as iron deficiency anemia hemochromatosis, Parkinson's disease and Alzheimer's disease, as well as colorectal cancer and esophageal adenocarcinoma, making DMT1 an attractive target for drug discovery., Deficiency of the divalent metal transporter 1 (DMT1) leads to hypochromic microcytic anemia. We have previously shown that DMT1 deficiency impairs erythroid differentiation and induces apoptosis of erythroid cells. , We propose that DMT1 deficiency negatively affects metabolism and life span of mature erythrocytes; two other aspects of defective erythropoiesis which contribute to the pathophysiology of the disease., Hypochromic microcytic anemia associated with ineffective erythropoiesis caused by recessive mutations in divalent metal transporter 1 (DMT1) can be improved with high-dose erythropoietin supplementation. , Belgrade rats exhibit microcytic, hypochromic anemia and systemic iron deficiency due to a glycine-to-arginine mutation at residue 185 in a metal ion transporter of a divalent metal transporter/divalent cation transporter/solute carrier 11 group A member 2 or 3 (DMT1/DCT1/SLC11A2), a member of the natural-resistance-associated macrophage protein (Nramp) family., Deficiency of the divalent metal transporter 1 (DMT1) leads to hypochromic microcytic anemia, Belgrade rats exhibit microcytic, hypochromic anemia and systemic iron deficiency due to a glycine-to-arginine mutation at residue 185 in a metal ion transporter of a divalent metal transporter/divalent cation transporter/solute carrier 11 group A member 2 or 3 (DMT1/DCT1/SLC11A2), a member of the natural-resistance-associated macrophage protein (Nramp) family, BACKGROUND/AIMS: Deficiency of the divalent metal transporter 1 (DMT1) leads to hypochromic microcytic anemia. , Microcytic anemia (mk/mk) mice defective in DMT1 and wild-type mice were exposed to either bleomycin or saline via intratracheal instillation and the resultant lung injury was compared. , Deficiency of the divalent metal transporter 1 (DMT1) leads to hypochromic microcytic anemia., The divalent metal transporter 1 (DMT1) is a major iron transporter required for iron absorption and erythropoiesis., This mutation severely impairs the iron transport capability of DMT1, leading to systemic iron deficiency and anemia.[SEP]Relations: SLC11A2 has relations: pathway_protein with Defective SLC11A2 causes hypochromic microcytic anemia, with iron overload 1 (AHMIO1), pathway_protein with Defective SLC11A2 causes hypochromic microcytic anemia, with iron overload 1 (AHMIO1), disease_protein with iron deficiency anemia, disease_protein with iron deficiency anemia, disease_protein with deficiency anemia, disease_protein with deficiency anemia, disease_protein with microcytic anemia with liver iron overload, disease_protein with microcytic anemia with liver iron overload. microcytic anemia has relations: disease_phenotype_positive with Anemia of inadequate production, disease_phenotype_positive with Anemia of inadequate production.", "label": "yes"}
{"id": "converted_1987", "sentence1": "Is H4K20 methylation associated with DNA replication?", "sentence2": "It seems likely that continued study of the methylation of H4K20 will yield extremely valuable insights concerning the regulation of histone modifications before and during cell division and the impact of these modifications on subsequent gene expression., Aberrant rereplication correlates with decreased levels of H4K20me1 and increased levels of H4K20 trimethylation (H4K20me3)., Consistent with this, H4K20 methylation status plays a direct role in recruiting ORC through the binding properties of ORC1 and ORCA/LRWD1. Thus, coordinating the status of H4K20 methylation is pivotal for the proper selection of DNA replication origins in higher eukaryotes., H4K20 methylation regulates quiescence and chromatin compaction., Mass spectrometry analysis of histone modifications reveals that H4K20me2 and H4K20me3 increase in quiescence and other histone modifications are present at similar levels in proliferating and quiescent cells., Analysis of cells in S, G2/M, and G1 phases shows that H4K20me1 increases after S phase and is converted to H4K20me2 and H4K20me3 in quiescence. , Overexpression of Suv4-20h1, the enzyme that creates H4K20me2 from H4K20me1, results in G2 arrest, consistent with a role for H4K20me1 in mitosis. The results suggest that the same lysine on H4K20 may, in its different methylation states, facilitate mitotic functions in M phase and promote chromatin compaction and cell cycle exit in quiescent cells., Histone H4 lysine 20 methylation: key player in epigenetic regulation of genomic integrity.,  Intense research during the past few years has revealed histone H4 lysine 20 methylation (H4K20me) as critically important for the biological processes that ensure genome integrity, such as DNA damage repair, DNA replication and chromatin compaction., Disruption of these H4K20-specific histone methyltransferases leads to genomic instability, demonstrating the important functions of H4K20 methylation in genome maintenance. , Both H4K20 mono-methylation and H3K56 acetylation mark transcription-dependent histone turnover in fission yeast., Histone turnover is often associated with various histone modifications such as H3K56 acetylation (H3K56Ac), H3K36 methylation (H3K36me), and H4K20 methylation (H4K20me)., These results together indicate that H4K20me1 as well as H3K56Ac are bona fide marks for transcription-dependent histone turnover in fission yeast., Methylation of histone H4 lysine 20 by PR-Set7 ensures the integrity of late replicating sequence domains in Drosophila., However, these studies were limited to only a handful of mammalian origins, and it remains unclear how PR-Set7 and H4K20 methylation impact the replication program on a genomic scale., The methylation state of lysine 20 on histone H4 (H4K20) has been linked to chromatin compaction, transcription, DNA repair and DNA replication. Monomethylation of H4K20 (H4K20me1) is mediated by the cell cycle-regulated histone methyltransferase PR-Set7,  We find that deregulation of H4K20 methylation had no impact on origin activation throughout the genome. Instead, depletion of PR-Set7 and loss of H4K20me1 results in the accumulation of DNA damage and an ATR-dependent cell cycle arrest., We review the signaling pathways and functions associated with a single residue, H4K20, as a model chromatin and clinically important mark that regulates biological processes ranging from the DNA damage response and DNA replication to gene expression and silencing., Thus, coordinating the status of H4K20 methylation is pivotal for the proper selection of DNA replication origins in higher eukaryotes., We employed genetic, cytological, and genomic approaches to better understand the role of PR-Set7 and H4K20 methylation in regulating DNA replication and genome stability in Drosophila cells., The methylation state of lysine 20 on histone H4 (H4K20) has been linked to chromatin compaction, transcription, DNA repair and DNA replication., However, these studies were limited to only a handful of mammalian origins, and it remains unclear how PR-Set7 and H4K20 methylation impact the replication program on a genomic scale., Methylation of histone H4 lysine-20 has been implicated in DNA repair, transcriptional silencing, genomic stability and regulation of replication., Thus, coordinating the status of H4K20 methylation is pivotal for the proper selection of DNA replication origins in higher eukaryotes, Methylation of histone H3 on lysine 79 associates with a group of replication origins and helps limit DNA replication once per cell cycle, We employed genetic, cytological, and genomic approaches to better understand the role of PR-Set7 and H4K20 methylation in regulating DNA replication and genome stability in Drosophila cells., We review the signaling pathways and functions associated with a single residue, H4K20, as a model chromatin and clinically important mark that regulates biological processes ranging from the DNA damage response and DNA replication to gene expression and silencing. <CopyrightInformation>© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.</C, Thus, coordinating the status of H4K20 methylation is pivotal for the proper selection of DNA replication origins in higher eukaryotes.., Intense research during the past few years has revealed histone H4 lysine 20 methylation (H4K20me) as critically important for the biological processes that ensure genome integrity, such as DNA damage repair, DNA replication and chromatin compaction.[SEP]Relations: histone H4 acetylation has relations: bioprocess_protein with MORF4L2, bioprocess_protein with MORF4L2, bioprocess_protein with ACTL6B, bioprocess_protein with ACTL6B, bioprocess_protein with MORF4L1, bioprocess_protein with MORF4L1, bioprocess_bioprocess with histone H4 acetylation involved in response to DNA damage stimulus, bioprocess_bioprocess with histone H4 acetylation involved in response to DNA damage stimulus, bioprocess_protein with NAA50, bioprocess_protein with NAA50.", "label": "yes"}
{"id": "converted_4631", "sentence1": "Is taxilin a cancer marker?", "sentence2": "Αlpha-Taxilin (α-Taxilin) has been found as one of the novel, significantly up regulated protein in RA, Expression of α-taxilin has been implicated in the development of human glioblastoma, hepatocellular carcinoma and renal cell carcinoma. , α-Taxilin, a binding partner of the syntaxin family, is a candidate tumor marker. , Expression of α-taxilin in hepatocellular carcinoma correlates with growth activity and malignant potential of the tumor.[SEP]Relations: Clear cell renal cell carcinoma has relations: disease_phenotype_positive with Blau syndrome, disease_phenotype_positive with Blau syndrome, disease_phenotype_positive with renal cell carcinoma (disease), disease_phenotype_positive with renal cell carcinoma (disease). liver carcinoma in situ has relations: disease_disease with in situ carcinoma, disease_disease with in situ carcinoma, disease_disease with bile duct carcinoma in situ, disease_disease with bile duct carcinoma in situ, disease_disease with carcinoma of liver and intrahepatic biliary tract, disease_disease with carcinoma of liver and intrahepatic biliary tract.", "label": "yes"}
{"id": "converted_2274", "sentence1": "Is autophagy modulated in a circadian fashion?", "sentence2": "TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in behavior and plasticity of L2 interneurons in the brain of Drosophila melanogaster.,  Our results indicate that the TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in the behavior and plasticity of neurons in the brain of adult flies., the pathways of autophagy, mTOR, SIRT1, and Wnt that control mammalian circadian rhythm, Metabolic pathways, bile acid synthesis, and autophagic and immune/inflammatory processes are driven by the biological clock. , our findings suggest that the clock geneBmal1is a positive regulator of autophagy through the mTOR signaling pathway and protects cardiomyocytes against high-glucose toxicity., Autophagy is a highly conserved intracellular degradation system, and recently was shown to display circadian rhythms in mice. [SEP]Relations: Protein S human has relations: drug_drug with Protocatechualdehyde, drug_drug with Protocatechualdehyde, drug_drug with Thalidomide, drug_drug with Thalidomide, drug_drug with Pargyline, drug_drug with Pargyline, drug_drug with Cephaloglycin, drug_drug with Cephaloglycin, drug_drug with Procarbazine, drug_drug with Procarbazine.", "label": "yes"}
{"id": "converted_2197", "sentence1": "Is Pfh1 a component of the replisome?", "sentence2": "Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity, Although the Schizosaccharomyces pombe 5'-to-3' DNA helicase Pfh1 is known to promote fork progression, its genomic targets, dynamics, and mechanisms of action are largely unknown. Here we address these questions by integrating genome-wide identification of Pfh1 binding sites, comprehensive analysis of the effects of Pfh1 depletion on replication and DNA damage, and proteomic analysis of Pfh1 interaction partners by immunoaffinity purification mass spectrometry., DNA replication through hard-to-replicate sites, including both highly transcribed RNA Pol II and Pol III genes, requires the S. pombe Pfh1 helicase., Here, we show that Pfh1 is required for efficient fork movement in the ribosomal DNA, the mating type locus, tRNA, 5S ribosomal RNA genes, and genes that are highly transcribed by RNA polymerase II. ,  Thus, Pfh1 promotes DNA replication and separation of converged replication forks and suppresses DNA damage at hard-to-replicate sites., Cells depleted of Pfh1 were inviable if they also lacked the human TIMELESS homolog Swi1, a replisome component that stabilizes stalled forks., Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity., Thus, we conclude that Pfh1 is an accessory DNA helicase that interacts with the replisome and promotes replication and suppresses DNA damage at hard-to-replicate sites., Consistent with this interpretation, Pfh1 co-purified with many key replisome components, including the hexameric MCM helicase, replicative DNA polymerases, RPA, and the processivity clamp PCNA in an S phase dependent manner., Although Pfh1 affected replication and suppressed DNA damage at discrete sites throughout the genome, Pfh1 and the replicative DNA polymerase bound to similar extents to both Pfh1-dependent and independent sites, suggesting that Pfh1 is proximal to the replication machinery during S phase., Cells depleted of Pfh1 were inviable if they also lacked the human TIMELESS homolog Swi1, a replisome component that stabilizes stalled forks, Here, we show that Pfh1 is required for efficient fork movement in the ribosomal DNA, the mating type locus, tRNA, 5S ribosomal RNA genes, and genes that are highly transcribed by RNA polymerase II, Thus, Pfh1 promotes DNA replication and separation of converged replication forks and suppresses DNA damage at hard-to-replicate sites, Cells depleted of Pfh1 were inviable if they also lacked the human TIMELESS homolog Swi1, a replisome component that stabilizes stalled forks., Thus, we conclude that Pfh1 is an accessory DNA helicase that interacts with the replisome and promotes replication and suppresses DNA damage at hard-to-replicate sites., Consistent with this interpretation, Pfh1 co-purified with many key replisome components, including the hexameric MCM helicase, replicative DNA polymerases, RPA, and the processivity clamp PCNA in an S phase dependent manner., Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity.[SEP]Relations: replisome has relations: cellcomp_protein with PCNA, cellcomp_protein with PCNA, cellcomp_protein with DONSON, cellcomp_protein with DONSON. RNA polymerase II transcribes snRNA genes has relations: pathway_protein with GTF2E1, pathway_protein with GTF2E1, pathway_protein with SP1, pathway_protein with SP1, pathway_protein with GTF2F1, pathway_protein with GTF2F1.", "label": "no"}
{"id": "converted_1992", "sentence1": "Is there a role of proton beam therapy in medulloblastoma treatment?", "sentence2": "All papers directly compared outcomes from protons with photons, five papers included medulloblastoma, four papers each included craniopharyngioma and low grade gliomas and three papers included ependymoma., There are many indications of protontherapy for paediatric brain tumours in curative intent, either for localized treatment of ependymomas, germ-cell tumours, craniopharyngiomas, low-grade gliomas; or panventricular irradiation of pure non-secreting germinoma; or craniospinal irradiation of medulloblastomas and metastatic pure germinomas., Cost-effectiveness analysis of cochlear dose reduction by proton beam therapy for medulloblastoma in childhood., BACKGROUND: The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood.METHODS: We developed a Markov model to describe health states of 6-year-old children with medulloblastoma after treatment with proton or X-ray radiotherapy., Evaluation of permanent alopecia in pediatric medulloblastoma patients treated with proton radiation., BACKGROUND: To precisely calculate skin dose and thus to evaluate the relationship between the skin dose and permanent alopecia for pediatric medulloblastoma patients treated with proton beams., CONCLUSIONS: Our results based on 12 patients provide a relationship between the skin dose and permanent alopecia for pediatric medulloblastoma patients treated with protons. , Proton beam craniospinal irradiation reduces acute toxicity for adults with medulloblastoma., PURPOSE: Efficacy and acute toxicity of proton craniospinal irradiation (p-CSI) were compared with conventional photon CSI (x-CSI) for adults with medulloblastoma., CONCLUSIONS: This report is the first analysis of clinical outcomes for adult medulloblastoma patients treated with p-CSI. , Dilemmas concerning dose distribution and the influence of relative biological effect in proton beam therapy of medulloblastoma., OBJECTIVE: To improve medulloblastoma proton therapy., The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood., The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood.We developed a Markov model to describe health states of 6-year-old children with medulloblastoma after treatment with proton or X-ray radiotherapy, All patients completed therapy without interruption.Our proton-beam technique for craniospinal irradiation of pediatric medulloblastoma has successfully reduced normal-tissue doses and acute treatment-related sequelae, Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuro-ectodermal tumors: spinal theca irradiation, For 6 MV x-rays > 60% of the dose prescribed to the target was delivered to 44% of the heart volume, while the proton beam was able to completely avoid the heart, the liver, and in all likelihood the thyroid and gonads as well.The present study demonstrates a potential role of proton therapy in decreasing the dose (and toxicity) to the critical structures in the irradiation of the spinal neuraxis in medulloblastoma/PNET, Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuroectodermal tumors: reduction of the supratentorial target volume, This review describes the role of radiation in general and proton therapy in particular for the treatment of medulloblastoma, central nervous system primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors, and the recently described embryonal tumor with multilayered rosettes, Reducing toxicity from craniospinal irradiation: using proton beams to treat medulloblastoma in young children., Intensity-modulated radiotherapy did show more bladder dose reduction than the other techniques in pelvic sarcoma irradiation.CONCLUSIONS: In the diseases studied, using various techniques of 3D-CRT, electrons, IMRT, and protons, protons are most optimal in treating retinoblastomas, medulloblastomas (posterior fossa and craniospinal), and pelvic sarcomas., For 6 MV x-rays>60% of the dose prescribed to the target was delivered to 44% of the heart volume, while the proton beam was able to completely avoid the heart, the liver, and in all likelihood the thyroid and gonads as well.CONCLUSION: The present study demonstrates a potential role of proton therapy in decreasing the dose (and toxicity) to the critical structures in the irradiation of the spinal neuraxis in medulloblastoma/PNET., In medulloblastoma, three posterior fossa irradiation techniques were analyzed: 3D-CRT, IMRT, and protons., Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuro-ectodermal tumors: spinal theca irradiation., Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuroectodermal tumors: reduction of the supratentorial target volume., The present study demonstrates a potential role of proton therapy in decreasing the dose (and toxicity) to the critical structures in the irradiation of the spinal neuraxis in medulloblastoma/PNET., Cost-effectiveness analysis of cochlear dose reduction by proton beam therapy for medulloblastoma in childhood., Dilemmas concerning dose distribution and the influence of relative biological effect in proton beam therapy of medulloblastoma., To improve medulloblastoma proton therapy., Our proton-beam technique for craniospinal irradiation of pediatric medulloblastoma has successfully reduced normal-tissue doses and acute treatment-related sequelae., Treatment planning with protons for pediatric retinoblastoma, medulloblastoma, and pelvic sarcoma: how do protons compare with other conformal techniques?[SEP]Relations: Medulloblastoma has relations: disease_phenotype_positive with mismatch repair cancer syndrome, disease_phenotype_positive with mismatch repair cancer syndrome, disease_phenotype_positive with medulloblastoma, disease_phenotype_positive with medulloblastoma, disease_phenotype_positive with pleuropulmonary blastoma, disease_phenotype_positive with pleuropulmonary blastoma, disease_phenotype_positive with Li-Fraumeni syndrome, disease_phenotype_positive with Li-Fraumeni syndrome, disease_phenotype_positive with Gardner syndrome, disease_phenotype_positive with Gardner syndrome.", "label": "yes"}
{"id": "converted_1536", "sentence1": "Are OATP1B1 and OATP1B3 associated with bilirubin transport?", "sentence2": "OATP1B1 and OATP1B3-mediated transport of bilirubin was confirmed and inhibition was determined for atazanavir, rifampicin, indinavir, amprenavir, cyclosporine, rifamycin SV and saquinavir. , Examples of adaptive nontoxic changes in liver function, which may elevate direct (conjugated) and/or indirect (unconjugated) bilirubin above baseline levels, include reversible inhibition of UGT1A1-mediated bilirubin metabolism and OATP1B1-, OATP1B3-, or MRP2-mediated transport (Keogh., Due to limited solubility and poor ionization of bilirubin and its glucuronide, the formation of estradiol 3-glucuronide was used as a surrogate to assess UGT1A1 activity, while the transport of pitavastatin, CDCF, and taurocholate were used as surrogate probe substrates to monitor the function of OATP1B1/OATP1B3, MRP2, and BSEP, respectively., OATP1B1 and OATP1B3-mediated transport of bilirubin was confirmed and inhibition was determined for atazanavir, rifampicin, indinavir, amprenavir, cyclosporine, rifamycin SV and saquinavir., However, because drug transporters also contribute to bilirubin elimination, the purpose of this work was to investigate the in vitro inhibition of OATP1B1, OATP1B3, MRP2, and BSEP of select test drugs known to elicit hyperbilirubinemia., Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia.Moreover, OATP1B1 and OATP1B3 null mutations may confer substantial drug toxicity risks., Bilirubin elimination is a multifaceted process consisting of uptake of bilirubin into the hepatocytes facilitated by OATP1B1 and OATP1B3., Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver., Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia., The data show that a substantial fraction of bilirubin conjugates is primarily secreted by MRP3 at the sinusoidal membrane into the blood, from where they are subsequently reuptaken by sinusoidal membrane-bound organic anion transporting polypeptides OATP1B1 and OATP1B3., Evaluating the in vitro inhibition of UGT1A1, OATP1B1, OATP1B3, MRP2, and BSEP in predicting drug-induced hyperbilirubinemia., OATP1B1 and OATP1B3-mediated transport of bilirubin was confirmed and inhibition was determined for atazanavir, rifampicin, indinavir, amprenavir, cyclosporine, rifamycin SV and saquinavir, Bilirubin elimination is a multifaceted process consisting of uptake of bilirubin into the hepatocytes facilitated by OATP1B1 and OATP1B3, Due to limited solubility and poor ionization of bilirubin and its glucuronide, the formation of estradiol 3-glucuronide was used as a surrogate to assess UGT1A1 activity, while the transport of pitavastatin, CDCF, and taurocholate were used as surrogate probe substrates to monitor the function of OATP1B1/OATP1B3, MRP2, and BSEP, respectively, Examples of adaptive nontoxic changes in liver function, which may elevate direct (conjugated) and/or indirect (unconjugated) bilirubin above baseline levels, include reversible inhibition of UGT1A1-mediated bilirubin metabolism and OATP1B1-, OATP1B3-, or MRP2-mediated transport (Keogh, In vitro, faldaprevir inhibited key processes involved in bilirubin clearance: UDP glucuronosyltransferase (UGT) 1A1 (UGT1A1) (IC50 0.45 µM), which conjugates bilirubin, and hepatic uptake and efflux transporters, organic anion-transporting polypeptide (OATP) 1B1 (IC50 0.57 µM), OATP1B3 (IC50 0.18 µM), and multidrug resistance-associated protein (MRP) 2 (IC50 6.2 µM), which transport bilirubin and its conjugates, Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia, Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia.Moreover, OATP1B1 and OATP1B3 null mutations may confer substantial drug toxicity risks, OATP1B1 (a.k.a. OATP-C, OATP2, LST-1, or SLC21A6) is a liver-specific organic anion uptake transporter and has been shown to be a higher affinity bilirubin uptake transporter than OATP1B3, In vitro OATP1B1 and OATP1B3 inhibition is associated with observations of benign clinical unconjugated hyperbilirubinemia., Examples of adaptive nontoxic changes in liver function, which may elevate direct (conjugated) and/or indirect (unconjugated) bilirubin above baseline levels, include reversible inhibition of UGT1A1-mediated bilirubin metabolism and OATP1B1-, OATP1B3-, or MRP2-mediated transport (Keogh. Adv Pharmacol 63:1-42, 2012). , Using mice deficient in Oatp1a/1b and in the multispecific sinusoidal export pump Abcc3, we found that Abcc3 secretes bilirubin conjugates into the blood, while Oatp1a/1b transporters mediate their hepatic reuptake. , Bilirubin elimination is a multifaceted process consisting of uptake of bilirubin into the hepatocytes facilitated by OATP1B1 and OATP1B3. , OATP1B1 polymorphism is a major determinant of serum bilirubin level but not associated with rifampicin-mediated bilirubin elevation., Unconjugated bilirubin (UCB) is taken up into hepatocytes by human organic anion transporting polypeptide 1B1 (OATP1B1; encoded for by the SLCO1B1 gene)., However, because drug transporters also contribute to bilirubin elimination, the purpose of this work was to investigate the in vitro inhibition of OATP1B1, OATP1B3, MRP2, and BSEP of select test drugs known to elicit hyperbilirubinemia. Test drugs investigated in this study were atazanavir and indinavir, which are associated with hyperbilirubinemia and elevations in serum transaminase; ritonavir and nelfinavir, which are not associated with hyperbilirubinemia; and bromfenac, troglitazone, and trovafloxacin, which are associated with severe idiosyncratic hepatotoxicity exhibiting elevations in serum bilirubin and transaminase., Test drugs investigated in this study were atazanavir and indinavir, which are associated with hyperbilirubinemia and elevations in serum transaminase; ritonavir and nelfinavir, which are not associated with hyperbilirubinemia; and bromfenac, troglitazone, and trovafloxacin, which are associated with severe idiosyncratic hepatotoxicity exhibiting elevations in serum bilirubin and transaminase. Due to limited solubility and poor ionization of bilirubin and its glucuronide, the formation of estradiol 3-glucuronide was used as a surrogate to assess UGT1A1 activity, while the transport of pitavastatin, CDCF, and taurocholate were used as surrogate probe substrates to monitor the function of OATP1B1/OATP1B3, MRP2, and BSEP, respectively., In vitro, faldaprevir inhibited key processes involved in bilirubin clearance: UDP glucuronosyltransferase (UGT) 1A1 (UGT1A1) (IC50 0.45 µM), which conjugates bilirubin, and hepatic uptake and efflux transporters, organic anion-transporting polypeptide (OATP) 1B1 (IC50 0.57 µM), OATP1B3 (IC50 0.18 µM), and multidrug resistance-associated protein (MRP) 2 (IC50 6.2 µM), which transport bilirubin and its conjugates., In vitro OATP1B1 and OATP1B3 inhibition is associated with observations of benign clinical unconjugated hyperbilirubinemia., 3.  The results indicated that in vivo Fi values >0.2 or R-values >1.5 for OATP1B1 or OATP1B3, but not UGT1A1, are associated with previously reported clinical cases of drug-induced unconjugated hyperbilirubinemia., OATP1B1 and OATP1B3-mediated transport of bilirubin was confirmed and inhibition was determined for atazanavir, rifampicin, indinavir, amprenavir, cyclosporine, rifamycin SV and saquinavir.[SEP]Relations: UGT1A1 has relations: disease_protein with bilirubin encephalopathy, disease_protein with bilirubin encephalopathy, bioprocess_protein with bilirubin conjugation, bioprocess_protein with bilirubin conjugation, protein_protein with B3GALT1, protein_protein with B3GALT1, drug_protein with Alvocidib, drug_protein with Alvocidib. SLCO1B1 has relations: molfunc_protein with bile acid transmembrane transporter activity, molfunc_protein with bile acid transmembrane transporter activity.", "label": "yes"}
{"id": "converted_523", "sentence1": "Is stop codon bypass possible?", "sentence2": "In 1999, proof-of-concept for treating these disorders was obtained in a mouse model of muscular dystrophy, when administration of aminoglycosides restored protein translation by inducing the ribosome to bypass a PTC., Aminoglycosides can bypass nonsense mutations and are the prototypic agents for translational bypass therapy (TBT)., Expression of retroviral replication enzymes (Pol) requires a controlled translational recoding event to bypass the stop codon at the end of gag. This recoding event occurs either by direct suppression of termination via the insertion of an amino acid at the stop codon (readthrough) or by alteration of the mRNA reading frame (frameshift)., Recent studies on translation termination in the yeast Saccharomyces cerevisiae have not only enabled the identification of the key components of the termination machinery, but have also revealed several regulatory mechanisms that might enable the controlled synthesis of C-terminally extended polypeptides via stop-codon readthrough. , The effects of all possible single-base mutations in the codons flanking the stop indicated that 3' contexts of the form CAR-YYA confer leakiness and that the 3' context permits read through of UAA and UGA stop codons as well as UAG., As a first step to elucidate the mechanism(s) by which ribosomes bypass leaky stop codons in vivo, we have devised a system in which readthrough is coupled to the transient expression of beta-glucuronidase (GUS) in tobacco protoplasts. [SEP]Relations: beta-glucuronidase activity has relations: molfunc_protein with HPSE, molfunc_protein with HPSE, molfunc_protein with KL, molfunc_protein with KL, molfunc_protein with GUSB, molfunc_protein with GUSB, molfunc_protein with GUSBP3, molfunc_protein with GUSBP3. Muscular dystrophy has relations: disease_phenotype_positive with fatal infantile hypertonic myofibrillar myopathy, disease_phenotype_positive with fatal infantile hypertonic myofibrillar myopathy.", "label": "yes"}
{"id": "converted_1187", "sentence1": "Is there any link between conserved noncoding elements and alternative splicing in vertebrates?", "sentence2": "Some of the most highly conserved sequences occur in genes encoding RNA binding proteins, particularly the RNA splicing-associated SR genes. Differences in sequence conservation between plants and animals are likely to reflect differences in the biology of the organisms, with plants being much more able to tolerate genomic deletions and whole-genome duplication events due, in part, to their far greater fecundity compared with vertebrates.[SEP]Relations: vertebra has relations: anatomy_anatomy with non-transverse process-bearing vertebra, anatomy_anatomy with non-transverse process-bearing vertebra. protein binding has relations: molfunc_protein with SPRYD7, molfunc_protein with SPRYD7, molfunc_protein with SPG7, molfunc_protein with SPG7, molfunc_protein with SPIC, molfunc_protein with SPIC, molfunc_protein with SP7, molfunc_protein with SP7.", "label": "yes"}
{"id": "converted_4629", "sentence1": "Is covid-19 induced anosmia caused by disruption of nuclear architecture?", "sentence2": "Disruption of nuclear architecture as a cause of COVID-19 induced anosmia., Here, using molecular evaluation of human olfactory epithelium (OE) from subjects succumbing to COVID-19 and a hamster model of SARS-CoV-2 infection, we discovered widespread downregulation of olfactory receptors (ORs) as well as key components of their signaling pathway. OR downregulation likely represents a non-cell autonomous effect, since SARS-CoV-2 detection in OSNs is extremely rare both in human and hamster OEs. A likely explanation for the reduction of OR transcription is the striking reorganization of nuclear architecture observed in the OSN lineage, which disrupts multi-chromosomal compartments regulating OR expression in humans and hamsters. Our experiments uncover a novel molecular mechanism by which a virus with a very selective tropism can elicit persistent transcriptional changes in cells that evade it, contributing to the severity of COVID-19.[SEP]Relations: olfactory receptor activity has relations: molfunc_protein with OR2M7, molfunc_protein with OR2M7, molfunc_protein with OR2L13, molfunc_protein with OR2L13, molfunc_protein with OR2A7, molfunc_protein with OR2A7. colitis (disease) has relations: disease_protein with NOS2, disease_protein with NOS2, disease_protein with IL17A, disease_protein with IL17A.", "label": "yes"}
{"id": "converted_3845", "sentence1": "Do polycomb group proteins (PcG) mediate the formation of chromatin loops?", "sentence2": "A chromatin insulator driving three-dimensional Polycomb response element (PRE) contacts and Polycomb association with the chromatin fiber, the Drosophila gypsy insulator behaves as a conformational chromatin border that is able to prohibit contacts between a Polycomb response element (PRE) and a distal promoter, Polycomb action at a distance can be organized by local chromatin topology, Polycomb repressive complex 2 is recruited through the interaction of CTCF, CTCF governs gene expression by orchestrating chromatin loop structures and by serving as a DNA-binding protein scaffold to recruit and bind polycomb repressive complexes, The chromatin loops completely dissolve, accompanied by loss of PcG proteins and H3K27me3 marks, when Tera-2 cells receive differentiation signals which induce a approximately 60-fold increase in GATA-4 expression., Polycomb-mediated chromatin loops revealed by a subkilobase-resolution chromatin interaction map., es or \"anchors\" are associated with CTCF protein in mammals, loop anchors in Drosophila were found most often in association with the polycomb group (PcG) protein Polycomb (Pc), a subunit of polycomb repressive complex 1 (PRC1). Loops were frequently located within domains of PcG, We also provide novel insight that PcG-occupied and H3K27me3-enriched regions can form chromatin loops and physically interact in cis around a single gene in mammalian cells., Repressive loops within polycomb domains are formed after the midblastula transition between polycomb response elements by the action of GAGA factor and polycomb proteins., PcG proteins, DNA methylation, and gene repression by chromatin looping., Loops were frequently located within domains of PcG-repressed chromatin., iation to proliferation control. Our results revealed a chromatin looping mechanism of long-range control and argue against models involving homogeneous spreading of PcG silencers [SEP]Relations: protein binding has relations: molfunc_protein with PCP4, molfunc_protein with PCP4, molfunc_protein with PCTP, molfunc_protein with PCTP, molfunc_protein with PCCA, molfunc_protein with PCCA, molfunc_protein with PCNP, molfunc_protein with PCNP, molfunc_protein with PCDHA4, molfunc_protein with PCDHA4.", "label": "yes"}
{"id": "converted_1274", "sentence1": "Is Fanconi anemia presented as a genetically and clinically heterogeneous disease entity?", "sentence2": "Fanconi anaemia (FA) is a rare, autosomal recessive, genetically complex, DNA repair deficiency syndrome in man. Patients with FA exhibit a heterogeneous spectrum of clinical features. The most significant and consistent phenotypic characteristics are stem cell loss, causing progressive bone marrow failure and sterility, diverse developmental abnormalities and a profound predisposition to neoplasia. To date, 15 genes have been identified, biallelic disruption of any one of which results in this clinically defined syndrome, Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder, Significant phenotypic differences were found. FA-G patients had more severe cytopenia and a higher incidence of leukemia. Somatic abnormalities were less prevalent in FA-C, but more common in the rare groups FA-D, FA-E, and FA-F. In FA-A, patients homozygous for null mutations had an earlier onset of anemia and a higher incidence of leukemia than those with mutations producing an altered protein, Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease. At least eight complementation groups (FA-A to FA-H) have been identified, Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease. At least eight complementation groups (FA-A to FA-H) have been identified with their relative prevalence varying among the ethnical backgrounds, Fanconi anemia is a rare autosomal recessive disorder characterized clinically by congenital abnormalities, progressive bone marrow failure, and a predisposition to malignancy. FA cells are sensitive to DNA cross-linking agents. Complementation analysis of FA cells using somatic cell fusion has facilitated the identification of eight complementation groups, suggesting that FA is a genetically heterogeneous disorder. Six genes (FANCA, FANCC, FANCD2, FANCE, FANGF, FANCG) have been cloned so far, Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease., Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease., Among patients with bone marrow failure (BMF) syndrome, some are happened to have underlying Fanconi anemia (FA), a genetically heterogeneous disease, which is characterized by progressive pancytopenia and cancer susceptibility., Fanconi anemia (FA) is a genetically and phenotypically heterogeneous inherited disease., Fanconi anemia is a genetically heterogeneous recessive disease characterized mainly by bone marrow failure and cancer predisposition., INTRODUCTION: Fanconi anemia (FA) is a genetically and phenotypically heterogeneous inherited disease., Fanconi anemia (FA) is a genetically heterogeneous, autosomal recessive disorder characterized by pediatric bone marrow failure and congenital anomalies., Fanconi anemia (FA) is a heterogeneous disease associated with a bone marrow failure, cancer predisposition and hypersensitivity to DNA crosslinking agents., Fanconi anemia is a genetically heterogeneous chromosomal instability syndrome, characterized by multiple congenital anomalies, progressive bone marrow failure, and a predisposition to malignancy., Fanconi anemia (FA) is a heterogeneous disease characterized by spontaneous chromosomal breaks and abnormal DNA repair., Fanconi anemia (FA) is a genetically heterogeneous disease with at least eight genes on the basis of complementation groups (FAA to FAH)., Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder., Fanconi anaemia (FA) is a genetically heterogeneous disease with at least eight complementation groups (A-H)., FA is a genetically heterogeneous disease with at least seven genes so far identified., Fanconi anemia (FA) is an autosomal recessive rare disease characterized by progressive pancytopenia, congenital malformations and predisposition to acute myeloid leukemia., Fanconi anemia is genetically heterogeneous, with at least eight complementation groups of FA (FAA to FAD2)., Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease, Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease, The disease is clinically heterogeneous; eight different complementation groups (FA A-H) and, thus, genetic loci have been discovered, The hereditary genetic disorder Fanconi anemia (FA) belongs to the heterogeneous group of diseases associated with defective DNA damage repair, The clinical manifestations of FA are heterogeneous, but one common outcome in the majority of patients is the development of life-threatening hematologic disease, Fanconi anemia is a genetically heterogeneous chromosomal breakage disorder exhibiting a high degree of clinical variability, Fanconi anemia (FA) is a genetically heterogeneous chromosomal instability syndrome associated with multiple congenital abnormalities, aplastic anemia, and cancer, Fanconi anemia (FA) is a genetically heterogeneous autosomal recessive syndrome associated with chromosomal instability, hypersensitivity to DNA cross-linking agents, and predisposition to malignancy, Fanconi anemia (FA) is a rare autosomal recessive disease characterized by progressive pancytopenia, congenital malformations, and predisposition to acute myeloid leukemia, Fanconi anemia (FA) is a heterogeneous disease characterized by spontaneous chromosomal breaks and abnormal DNA repair, Fanconi anemia (FA) is a genetically and phenotypically heterogeneous recessive disorder characterized by diverse congenital malformations, progressive pancytopenia and predisposition to both hematologic malignancies and solid tumors, Fanconi anemia is a genetically heterogeneous chromosomal instability syndrome, characterized by multiple congenital anomalies, progressive bone marrow failure, and a predisposition to malignancy[SEP]Relations: Fanconi anemia has relations: disease_disease with congenital anemia, disease_disease with congenital anemia, disease_disease with genetic skin disease, disease_disease with genetic skin disease. Fanconi anemia complementation group has relations: disease_disease with Fanconi anemia, disease_disease with Fanconi anemia, disease_disease with Fanconi anemia, disease_disease with Fanconi anemia, disease_disease with Fanconi anemia, disease_disease with Fanconi anemia.", "label": "yes"}
{"id": "converted_2171", "sentence1": "Is tirilazad effective for treatment of aneurysmal subarachnoid haemorrhage?", "sentence2": "There was no significant difference between the two groups at the end of follow up for the primary outcome, death (odds ratio (OR) 0.89, 95% confidence interval (CI) 0.74 to 1.06), or in poor outcome (death, vegetative state or severe disability) (OR 1.04, 95% CI 0.90 to 1.21). During the treatment period, fewer patients developed delayed cerebral ischaemia in the tirilazad group than in the control group (OR 0.80, 95% CI 0.69 to 0.93). Subgroup analyses did not demonstrate any significant difference in effects of tirilazad on clinical outcomes. , AUTHORS' CONCLUSIONS: There is no evidence that tirilazad, in addition to nimodipine, reduces mortality or improves poor outcome in patients with aneurysmal SAH., This clinical trial suggest that tirilazad mesylate, at a dosage of 6 mg/kg/day, improves overall outcome in aneurysmal subarachnoid hemorrhage patients., Tirilazad is ineffective.There are many possible successful treatment options for preventing vasospasm, delayed ischemic neurologic deficits, and poor neurologic outcome following aneurysmal subarachnoid hemorrhage; however, further multicenter RCTs need to be performed to determine if there is a significant benefit from their use, Findings from previous multicenter clinical trials have suggested that tirilazad mesylate, a synthetic nonhormonal 21-aminosteroid, might be effective in preventing delayed cerebral ischemia following subarachnoid hemorrhage (SAH)., This clinical trial suggest that tirilazad mesylate, at a dosage of 6 mg/kg/day, improves overall outcome in aneurysmal subarachnoid hemorrhage patients.[SEP]Relations: subarachnoid hemorrhage (disease) has relations: contraindication with Tranexamic acid, contraindication with Tranexamic acid, disease_disease with acquired aneurysmal subarachnoid hemorrhage, disease_disease with acquired aneurysmal subarachnoid hemorrhage, disease_protein with EDNRB, disease_protein with EDNRB, disease_protein with PPARG, disease_protein with PPARG, disease_protein with ADORA1, disease_protein with ADORA1.", "label": "no"}
{"id": "converted_207", "sentence1": "Does administration of triiodothyronine improve outcome following coronary artery bypass grafting?", "sentence2": "Serum T3 concentrations were significantly higher with fewer patients having T3 concentrations below the normal range in the T3 group than the placebo group throughout the postoperative period. Hemodynamic variables, postoperative inotrope requirement, and outcome variables showed no differences between the groups, We conclude that although widespread interest has been shown on the use of thyroid hormones in the perioperative period, and the effect of cardiopulmonary bypass on thyroid hormone metabolism widely studied, there is no substantial evidence to justify routine use of thyroid hormones in patients undergoing coronary artery bypass grafting., Treatment with GIK, T3, and GIK/T3 improves hemodynamic performance and results in reduced cTnI release in patients undergoing on-pump CABG surgery., Perioperative administration of triiodothyronine increased cardiac output slightly and decreased systemic vascular resistance, but it had no effect on operative outcome., Parenteral triiodothyronine given after crossclamp removal during elective coronary artery bypass grafting significantly improved postoperative ventricular function, reduced the need for treatment with inotropic agents and mechanical devices, and decreased the incidence of myocardial ischemia. The incidence of atrial fibrillation was slightly decreased, and the need for postoperative pacemaker support was reduced., Perioperative T3 administration decreased the incidence and need for treatment of postoperative atrial fibrillation.,  Intravenous T(3) does not have dramatic effects on hemodynamic variables in this setting as has been previously suggested. , Raising serum triiodothyronine concentrations in patients undergoing coronary-artery bypass surgery increases cardiac output and lowers systemic vascular resistance, but does not change outcome or alter the need for standard postoperative therapy., No significant differences were noted in the pre and post CPB hemodynamics between the two groups for the most part of the study except that heart rate was increased in T3 group., The haemodynamic parameters were no different between the two groups at any postoperative time point. Likewise, density and affinity of lymphocyte beta-adrenoceptors were not significantly different from pre-operative values in either group.[SEP]Relations: Coronary artery atherosclerosis has relations: drug_effect with Rivastigmine, drug_effect with Rivastigmine, drug_effect with Vincristine, drug_effect with Vincristine, drug_effect with Varenicline, drug_effect with Varenicline, drug_effect with Ropinirole, drug_effect with Ropinirole, drug_effect with Fenofibrate, drug_effect with Fenofibrate.", "label": "no"}
{"id": "converted_2420", "sentence1": "SGOT is an abbreviation for an enzyme other wise known as alanine amino transferase, yes or no?", "sentence2": "patients with aspartate amino transferase (SGOT), alanine amino transferase (SGPT),, Alanine amino transferase (SGPT), , aspartate aminotransferase (AST-SGOT), alanine amino-transferase (ALT-SGPT), Mean values of glutamate dehydrogenase (GDH), serum aspartate and alanine transferase (SGOT and SGPT), ornithine carbamoyltransferase (OCT), and gamma-glutamyltranspeptidase (gamma-GTP) tended to rise with increasing liver cell necrosis, though values of SGOT, SGPT, OCT, and gamma-GTP showed considerable overlap between the 32 patients with histologically proved hepatitis and the 68 without., Serum aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT), creatinine phosphokinase (CPK), and butyric acid dehydrogenase (BDH) were determined in 94 patients before, 1(1/2) hours, and 24 hours after cardioversion., The study excluded by screening for AntiHCV, HBsAg and patients with aspartate amino transferase (SGOT), alanine amino transferase (SGPT), GGT levels more than three times the normal and subject with a total leukocyte count more than 10,000/microl., Complete blood picture, differential leukocyte count, and serum levels of Estrogen, Alanine amino transferase (SGPT), Aspartate amino transferase (SGOT), total protein and albumin were estimated.[SEP]Relations: glutamate pyruvate transaminase 2 deficiency has relations: disease_protein with GPT2, disease_protein with GPT2, disease_disease with syndromic intellectual disability, disease_disease with syndromic intellectual disability, disease_phenotype_positive with Nasogastric tube feeding in infancy, disease_phenotype_positive with Nasogastric tube feeding in infancy, disease_phenotype_positive with Broad-based gait, disease_phenotype_positive with Broad-based gait, disease_phenotype_positive with Absent speech, disease_phenotype_positive with Absent speech.", "label": "no"}
{"id": "converted_727", "sentence1": "Is the optogenetics tool ChR2 light-sensitive?", "sentence2": "Channelrhodospin-2 (ChR2), a light-sensitive ion channel, and its variants have emerged as new excitatory optogenetic tools not only in neuroscience, but also in other areas, including cardiac electrophysiology., Light-sensitive genes chiefly including the genetically targeted light-gated channels channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR) cause intracellular ion flow during optical illumination., Computational optogenetics: empirically-derived voltage- and light-sensitive channelrhodopsin-2 model., The versatility and the electrophysiologic characteristics of the light-sensitive ion-channels channelrhodopsin-2 (ChR2), halorhodopsin (NpHR), and the light-sensitive proton pump archaerhodopsin-3 (Arch) make these optogenetic tools potent candidates in controlling neuronal firing in models of epilepsy and in providing insights into the physiology and pathology of neuronal network organization and synchronization., Channelrhodopsins-2 (ChR2) are a class of light sensitive proteins that offer the ability to use light stimulation to regulate neural activity with millisecond precision., The most widely used optogenetic tool, Channelrhodopsin2 (ChR2), is both light- and voltage-sensitive., Channelrhodospin-2 (ChR2), a light-sensitive ion channel, and its variants have emerged as new excitatory optogenetic tools not only in neuroscience, but also in other areas, including cardiac electrophysiology. , Optogenetic methods have emerged as a powerful tool for elucidating neural circuit activity underlying a diverse set of behaviors across a broad range of species. Optogenetic tools of microbial origin consist of light-sensitive membrane proteins that are able to activate (e.g., channelrhodopsin-2, ChR2) or silence (e.g., halorhodopsin, NpHR) neural activity ingenetically-defined cell types over behaviorally-relevant timescales. , Virus-mediated expression of a ChR2 variant with greater light sensitivity in SGNs reduced the amount of light required for responses and allowed neuronal spiking following stimulation up to 60 Hz. , Channelrhodopsin-2 (ChR2) from the green alga Chlamydomonas reinhardtii functions as a light-gated cation channel that has been developed as an optogenetic tool to stimulate specific nerve cells in animals and control their behavior by illumination. , Here, we used animal models to characterize optogenetic stimulation, which is the optical stimulation of neurons genetically engineered to express the light-gated ion channel channelrhodopsin-2 (ChR2). , The versatility and the electrophysiologic characteristics of the light-sensitive ion-channels channelrhodopsin-2 (ChR2), halorhodopsin (NpHR), and the light-sensitive proton pump archaerhodopsin-3 (Arch) make these optogenetic tools potent candidates in controlling neuronal firing in models of epilepsy and in providing insights into the physiology and pathology of neuronal network organization and synchronization., The most widely used optogenetic tool, Channelrhodopsin2 (ChR2), is both light- and voltage-sensitive. A light-triggered action potential or light-driven perturbations of ongoing electrical activity provide instant voltage feedback, shaping ChR2 current.,  Optogenetic methods have emerged as a powerful tool for elucidating neural circuit activity underlying a diverse set of behaviors across a broad range of species. Optogenetic tools of microbial origin consist of light-sensitive membrane proteins that are able to activate (e.g., channelrhodopsin-2, ChR2) or silence (e.g., halorhodopsin, NpHR) neural activity ingenetically-defined cell types over behaviorally-relevant timescales., Channelrhodospin-2 (ChR2), a light-sensitive ion channel, and its variants have emerged as new excitatory optogenetic tools not only in neuroscience, but also in other areas, including cardiac electrophysiology., It allows neurons to express light-sensitive genes that enable the identification, dissection, and manipulation of specific neural populations and their connections in the tissues and organs of awake animals with unprecedented spatial and temporal precision. Light-sensitive genes chiefly including the genetically targeted light-gated channels channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR) cause intracellular ion flow during optical illumination., Channelrhodopsin-2 (ChR2) from the green alga Chlamydomonas reinhardtii functions as a light-gated cation channel that has been developed as an optogenetic tool to stimulate specific nerve cells in animals and control their behavior by illumination. The molecular mechanism of ChR2 has been extensively studied by a variety of spectroscopic methods, including light-induced difference Fourier transform infrared (FTIR) spectroscopy, which is sensitive to structural changes in the protein upon light activation.[SEP]Relations: epilepsy has relations: disease_protein with CHRM2, disease_protein with CHRM2, disease_protein with CHD2, disease_protein with CHD2, disease_protein with P2RX2, disease_protein with P2RX2, disease_protein with TANC2, disease_protein with TANC2, disease_protein with RARS2, disease_protein with RARS2.", "label": "yes"}
{"id": "converted_471", "sentence1": "Is there a crystal structure of the full-length of the flaviviridae NS5(Methyltransferase - RNA depended RNA Polymerase) ?", "sentence2": " flavivirus NS5 harbors a methyltransferase (MTase) in its N-terminal ≈ 265 residues and an RNA-dependent RNA polymerase (RdRP) within the C-terminal part. One of the major interests and challenges in NS5 is to understand the interplay between RdRP and MTase as a unique natural fusion protein in viral genome replication and cap formation. Here, we report the first crystal structure of the full-length flavivirus NS5 from Japanese encephalitis virus. , (DENV) nonstructural protein 5 (NS5) is composed of two globular domains separated by a 10-residue linker. The N-terminal domain participates in the synthesis of a mRNA cap 1 structure ((7Me)GpppA(2'OMe)) at the 5' end of the viral genome and possesses guanylyltransferase, guanine-N7-methyltransferase, and nucleoside-2'O-methyltransferase activities. The C-terminal domain is an RNA-dependent RNA polymerase responsible for viral RNA synthesis. Although crystal structures of the two isolated domains have been obtained, there are no structural data for full-length NS5. It is also unclear whether the two NS5 domains interact with each other to form a stable structure in which the relative orientation of the two domains is fixed. To investigate the structure and dynamics of DENV type 3 NS5 in solution, we conducted small-angle X-ray scattering experiments with the full-length protein. NS5 was found to be monomeric and well-folded under the conditions tested., West Nile virus (WNV) NS5 protein contains a methyltransferase (MTase) domain involved in RNA capping and an RNA-dependent RNA polymerase (RdRp) domain essential for virus replication. Crystal structures of individual WNV MTase and RdRp domains have been solved; however, the structure of full-length NS5 has not been determined. To gain more insight into the structure of NS5 and interactions between the MTase and RdRp domains, we generated a panel of seven monoclonal antibodies (mAbs) to the NS5 protein of WNV (Kunjin strain) and mapped their binding sites using a series of truncated NS5 proteins and synthetic peptides. Binding sites of four mAbs (5D4, 4B6, 5C11 and 6A10) were mapped to residues 354-389 in the fingers subdomain of the RdRp. This is consistent with the ability of these mAbs to inhibit RdRp activity in vitro and suggests that this region represents a potential target for RdRp inhibitors. Using a series of synthetic peptides, we also identified a linear epitope (bound by mAb 5H1) that mapped to a 13 aa stretch surrounding residues 47 and 49 in the MTase domain, a region predicted to interact with the palm subdomain of the RdRp. The failure of one mAb (7G6) to bind both N- and C-terminally truncated NS5 recombinants indicates that the antibody recognizes a conformational epitope that requires the presence of residues in both the MTase and RdRp domains. [SEP]Relations: RNA-directed DNA polymerase activity has relations: molfunc_protein with TERC, molfunc_protein with TERC, molfunc_protein with ERVK-7, molfunc_protein with ERVK-7, molfunc_protein with ERVK-6, molfunc_protein with ERVK-6, molfunc_protein with ERVK-8, molfunc_protein with ERVK-8, molfunc_protein with TERT, molfunc_protein with TERT.", "label": "yes"}
{"id": "converted_2670", "sentence1": "The TRPM2 gene is associated with development of spontaneous thromboembolism?", "sentence2": "TheTransientReceptorPotentialMelastatin 2 (TRPM2) is a member of G protein coupled receptor superfamily and a novel dual-function protein that possesses both ion channel andAdenosine 5'-DiphosPhataseRibose (ADPR) hydrolase function. TRPM2 is involved in Ca2+signaling in various cells as an endogenous redox sensor for oxidative stress and reactive oxygen species, and contributes to cytokine production, insulin release, motility, Ca2+entry and Ca2+-dependent cellular reactions such as endothelial hyper-permeability and apoptosis., We show here that the redox-sensitive transient receptor potential (TRP) cation channel TRPM2 is expressed in the phagosomal membrane and regulates macrophage bactericidal activity through the activation of phagosomal acidification, The transient receptor potential melastatin-2 (TRPM2) is an oxidative stress sensing channel that is expressed in a number of inflammatory cells and therefore it has been suggested that inhibition of TRPM2 could lead to a beneficial effect in COPD patients., TRPM2 is a recently identified TRPM family cation channel which is unique among known ion channels in that it contains a C-terminal domain which is homologous to the NUDT9 ADP-ribose hydrolase and possesses intrinsic ADP-ribose hydrolase activity, These results suggest that TRPM2 may participate in antigen-induced extracellular Ca(2+) influx and subsequent degranulation. In addition, TRPM2 inhibitors were shown to improve food allergic reactions in a mouse model. Together, these results suggest that TRPM2 inhibitors suppress MMC degranulation via regulation of the increase in [Ca(2+)]cyt. Thus, TRPM2 may play a key role in degranulation by modulating intracellular Ca(2+) in MMCs., he Na+ and Ca(2+)-permeable melastatin related transient receptor potential 2 (TRPM2) channels can be gated either by ADP-ribose (ADPR) in concert with Ca(2+) or by hydrogen peroxide (H(2)O(2)), an experimental model for oxidative stress, binding to the channel's enzymatic Nudix domain, hese alterations of the extracellular milieu change the activity of transient receptor potential melastatin subfamily member 2 (TRPM2), a nonselective cation channel expressed in the central nervous system and the immune system. , TRPM2 (Transient Receptor Potential Melastatin 2) is a Ca2+-permeable ion channel that is activated under conditions of oxidative stress. , Transient receptor potential melastatin 2 (TRPM2) is a thermosensitive, Ca2+-permeable cation channel. TRPM2 contributes to the pathogenesis of inflammatory bowel disease, and inflammatory and neuropathic pain. We hypothesized that TRPM2 is important for visceral nociception and the development of visceral hypersensitivity., Here, we describe the computational identification of a melanoma-enriched antisense transcript, TRPM2-AS, mapped within the locus of TRPM2, an ion channel capable of mediating susceptibility to cell death, The transient receptor potential melastatin 2 (TRPM2) channel, a Ca(2+)-permeable nonselective cation channel activated by oxidative stress, has been implicated in neurodegenerative diseases, and more recently in amyloid-induced toxicity, Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable cation channel activated by ADP-ribose or reactive oxygen species.,  Transient receptor potential melastatin type 2 (TRPM2) is a Ca2+ permeable non-selective cation channel expressed in several cell types including hippocampal pyramidal neurons. Moreover, activation of TRPM2 during oxidative stress has been linked to cell death. [SEP]Relations: TRPM2-AS has relations: anatomy_protein_present with blood, anatomy_protein_present with blood, anatomy_protein_present with brain, anatomy_protein_present with brain, anatomy_protein_present with lymph node, anatomy_protein_present with lymph node, anatomy_protein_present with spleen, anatomy_protein_present with spleen, anatomy_protein_present with neocortex, anatomy_protein_present with neocortex.", "label": "no"}
{"id": "converted_2965", "sentence1": "There is no drug available to prevent HIV infection, Pre-exposure prophylaxis (PrEP), yes or no?", "sentence2": "pre-exposure prophylaxis with generic tenofovir disoproxil fumarate/emtrictabine in London - analysis of pharmacokinetics, safety and outcomes., The antiviral agent tenofovir is highly effective for the treatment of HIV and hepatitis B virus infections, and the older prodrug tenofovir disoproxil fumarate (TDF) is also a component of daily preexposure prophylaxis (PrEP) to reduce the risk of HIV infection in high-risk populations. , Following US Food and Drugs Administration approval in July 2012 of daily oral tenofovir and emtricitabine for pre-exposure prophylaxis (PrEP) to prevent HIV infection in high-risk individuals in the USA, there has been much controversy about the implementation of this PrEP regimen in other countries throughout the world, and in Europe in particular., Daily oral pre-exposure prophylaxis (PrEP) is the use of antiretroviral drugs by HIV-negative people to prevent HIV infection., HIV pre-exposure prophylaxis (PrEP) is a new approach that involves the ongoing use of antiretroviral medications by HIV-negative individuals to reduce the risk of HIV infection., CONCLUSIONS Combined ART + PrEP is likely to prevent more HIV infections than either strategy alone, but with higher prevalence of drug resistance., INTRODUCTION Use of pre-exposure prophylaxis (PrEP) among people who inject drugs (PWID) has been shown to be effective in preventing HIV transmission., Pre-exposure prophylaxis (PrEP) is an experimental approach to HIV prevention and consists of antiretroviral drugs to be taken before potential HIV exposure in order to reduce the risk of HIV infection and continued during periods of risk., HIV pre-exposure prophylaxis (PrEP) is the use of one or more antiretroviral medications (in combination) to prevent HIV infection., The most commonly used PrEP medication (Truvada<br>, The use of antiretrovirals as pre-exposure prophylaxis (PrEP) is highly efficacious in HIV prevention.[SEP]Relations: Tenofovir disoproxil has relations: contraindication with hepatitis C virus infection, contraindication with hepatitis C virus infection, contraindication with chronic hepatitis C virus infection, contraindication with chronic hepatitis C virus infection. Tenofovir has relations: contraindication with hepatitis C virus infection, contraindication with hepatitis C virus infection, contraindication with chronic hepatitis C virus infection, contraindication with chronic hepatitis C virus infection. Emtricitabine has relations: contraindication with hepatitis C virus infection, contraindication with hepatitis C virus infection.", "label": "no"}
{"id": "converted_2476", "sentence1": "Can canagliflozin cause euglycemic diabetic ketoacidosis?", "sentence2": "CASE REPORT: We present a case of a 57-year-old woman with type 2 diabetes mellitus taking a combination of canagliflozin and metformin who presented with progressive altered mental status over the previous 2 days. Her work-up demonstrated a metabolic acidosis with an anion gap of 38 and a venous serum pH of 7.08. The serum glucose was 168 mg/dL. The urinalysis showed glucose>500 mg/dL and ketones of 80 mg/dL. Further evaluation demonstrated an elevated serum osmolality of 319 mOsm/kg and an acetone concentration of 93 mg/dL. She was treated with intravenous insulin and fluids, and the metabolic abnormalities and her altered mental status resolved within 36 h. This was the first episode of diabetic ketoacidosis (DKA) for this patient. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Diabetic patients on SGLT2 inhibitor medications are at risk for ketoacidosis. Due to the renal glucose-wasting properties of these drugs, they may present with ketoacidosis with only mild elevations in serum glucose, potentially complicating the diagnosis. , Euglycemic Diabetic Ketoacidosis with Persistent Diuresis Treated with Canagliflozin., We herein report the case of a 27-year-old Asian woman with type 2 diabetes who was treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor (canagliflozin) who developed euglycemic diabetic ketoacidosis and persistent diuresis in the absence of hyperglycemia., Canagliflozin raised the risk of amputations and the rate of fractures in the CANVAS trial, although more data are necessary before drawing definite conclusions. The risk of euglycemic diabetic ketoacidosis seems to be minimal when the drugs are prescribed properly., Severe Ketoacidosis Associated with Canagliflozin (Invokana): A Safety Concern.,  However, some serious side effects, including severe anion gap metabolic acidosis and euglycemic diabetic ketoacidosis (DKA), have been reported. , At present, the Food and Drug Administration (FDA) has only approved three medications (canagliflozin, dapagliflozin and empagliflozin) in this drug class for the management of Type 2 diabetes. In May 2015, the FDA issued a warning of ketoacidosis with use of this drug class., We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient., Nonconvulsive Status Epilepticus in Elderly Patients Receiving SSRIs; Euglycemic Diabetic Ketoacidosis Associated with Canagliflozin Use in a Type 1 Diabetic Patient; Duloxetine-Induced Galactorrhea; Canagliflozin-Associated Severe Hypercalcemia and Hypernatremia; Vemurafenib-Induced Fanconi Syndrome., Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1-Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin., We are reporting a timely case of atypical euglycemic diabetic ketoacidosis in a type 1 diabetic patient treated with sodium-glucose cotransporter-2 (SGLT-2) inhibitor canagliflozin., Euglycemic ketoacidosis did not recur in our patient after discontinuing canagliflozin. , Euglycemic Diabetic Ketoacidosis With Prolonged Glucosuria Associated With the Sodium-Glucose Cotransporter-2 Canagliflozin., In this article, we present a case of a 50-year-old woman with type 2 diabetes who developed euglycemic DKA after initiating therapy with canagliflozin. , SGLT2 inhibitors such as canagliflozin may predispose patients not only to diabetic ketoacidosis but also to prolonged glucosuria., We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient.<br>, We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient., CONCLUSION Treatment with canagliflozin was associated with development of euglycemic ketoacidosis., Euglycemic Diabetic Ketoacidosis with Persistent Diuresis Treated with Canagliflozin., We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient.., Euglycemic Diabetic Ketoacidosis With Prolonged Glucosuria Associated With the Sodium-Glucose Cotransporter-2 Canagliflozin., Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1-Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin.[SEP]Relations: Canagliflozin has relations: drug_drug with Carbetocin, drug_drug with Carbetocin, drug_drug with Ketobemidone, drug_drug with Ketobemidone. diabetic ketoacidosis has relations: contraindication with Norfloxacin, contraindication with Norfloxacin, contraindication with Inositol, contraindication with Inositol, contraindication with Inositol nicotinate, contraindication with Inositol nicotinate.", "label": "yes"}
{"id": "converted_646", "sentence1": "Are chromomethylases present in animal genomes?", "sentence2": "Many plant, animal, and fungal genomes contain cytosine DNA methylation in asymmetric sequence contexts (CpHpH, H = A, T, C)., However, at the SUPERMAN locus, asymmetric methylation was only completely abolished in drm1 drm2 chromomethylase 3 (cmt3) triple mutant plants., Although neither the drm1 drm2 double mutants nor the cmt3 single mutants show morphological defects, drm1 drm2 cmt3 triple mutant plants show pleiotropic effects on plant development., Arabidopsis cmt3 chromomethylase mutations block non-CG methylation and silencing of an endogenous gene., The lack of CMT homologs in animal genomes could account for the observation that in contrast to plants, animals maintain primarily CG methylation., Dual binding of chromomethylase domains to H3K9me2-containing nucleosomes directs DNA methylation in plants., A role for CHROMOMETHYLASE3 in mediating transposon and euchromatin silencing during egg cell reprogramming in Arabidopsis., During embryogenesis there is a major switch from dependence upon maternally-deposited products to reliance on products of the zygotic genome., Expression analysis of eight putative tomato DNA methyltransferases encoding genes showed that one chromomethylase (CMT) and two rearranged methyltransferases (DRMs) are preferentially expressed in the pericarp during fruit growth and could be involved in the locus-specific increase of methylation observed at this developmental phase in the pericarp., Natural variation for alleles under epigenetic control by the maize chromomethylase zmet2., Arabidopsis has two types of methyltransferases with demonstrated maintenance activity: MET1, which maintains CpG methylation and is homologous to mammalian DNMT1, and CHROMOMETHYLASE 3 (CMT3), which maintains CpNpG (N = A, T, C, or G) methylation and is unique to the plant kingdom., Maize chromomethylase Zea methyltransferase2 is required for CpNpG methylation., A cytosine DNA methyltransferase containing a chromodomain, Zea methyltransferase2 (Zmet2), was cloned from maize. The sequence of ZMET2 is similar to that of the Arabidopsis chromomethylases CMT1 and CMT3, with C-terminal motifs characteristic of eukaryotic and prokaryotic DNA methyltransferases., We have detected a chromodomain embedded within the catalytic region of a predicted Arabidopsis DNA methyltransferase that is diverged from other eukaryotic enzymes. The 791 residue \"chromomethylase\" (CMT1) is encoded by a floral transcript that is spliced from 20 exons and is present at only approximately 1/10(-7) of total mRNA.[SEP]Relations: Animal protein allergy has relations: phenotype_phenotype with Allergy, phenotype_phenotype with Allergy. Choline magnesium trisalicylate has relations: drug_drug with Amediplase, drug_drug with Amediplase, drug_drug with Chromic nitrate, drug_drug with Chromic nitrate, drug_drug with Cephaloglycin, drug_drug with Cephaloglycin, drug_drug with Chromous sulfate, drug_drug with Chromous sulfate.", "label": "no"}
{"id": "converted_4604", "sentence1": "Is Daprodustat effective for anemia?", "sentence2": "CONCLUSIONS: Oral daprodustat was noninferior to CERA in achieving and maintaining target hemoglobin levels in Japanese ND patients. , BACKGROUND: The Anemia Studies in chronic kidney disease (CKD): Erythropoiesis via a Novel prolyl hydroxylase inhibitor (PHI) Daprodustat-Dialysis (ASCEND-D) trial will test the hypothesis that daprodustat is non-inferior to comparator epoetin alfa or darbepoetin alfa for two co-primary endpoints: haemoglobin efficacy and cardiovascular safety., Daprodustat is one of the orally administrated small-molecule HIF-PH inhibitors, leading to an increase in erythropoietin production, which is regulated by HIF. Also, daprodustat is expected to improve iron metabolism. Recently, several clinical trials showed its efficacy and safety in both hemodialysis- and non-hemodialysis- dependent CKD patients. , Once-daily oral daprodustat treatment was generally well tolerated and mean hemoglobin was achieved and maintained within the target range in Japanese peritoneal dialysis participants., Daprodustat is a hypoxia-inducible factor-prolyl hydroxylase inhibitor for the treatment of anemia of chronic kidney disease. , Daprodustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, is being investigated for treatment of anemia in chronic kidney disease., Daprodustat for the Treatment of Anemia in Patients Not Undergoing Dialysis., ONCLUSIONS: Among patients with CKD and anemia who were not undergoing dialysis, daprodustat was noninferior to darbepoetin alfa with respect to the change in the hemoglobin level from baseline and with respect to cardiovascular outcomes. , Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis., CONCLUSIONS: Among patients with CKD undergoing dialysis, daprodustat was noninferior to ESAs regarding the change in the hemoglobin level from baseline and cardiovascular outcomes., Daprodustat (GSK1278863) is a hypoxia-inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitor in development for treatment of anemia of chronic kidney disease., BACKGROUND: Daprodustat (GSK1278863) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor being developed for treatment of anemia associated with chronic kidney disease (CKD)., Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor developed for treating anemia of chronic kidney disease., Daprodustat is under development as an emerging new class of agents for the treatment of anemia associated with chronic kidney disease (CKD)., Conclusion: Daprodustat was efficacious and well tolerated for anemia in both NDD and DD patients in the short term based on current RCTs., And daprodustat may become an effective alternative for treatment of anemia with CKD.[SEP]Relations: Erythropoietin has relations: drug_drug with Dacarbazine, drug_drug with Dacarbazine, drug_drug with Dacomitinib, drug_drug with Dacomitinib, drug_drug with Dabrafenib, drug_drug with Dabrafenib, drug_drug with Dacetuzumab, drug_drug with Dacetuzumab. Darbepoetin alfa has relations: drug_drug with Dacarbazine, drug_drug with Dacarbazine.", "label": "yes"}
{"id": "converted_3570", "sentence1": "Is palbociclib effective for glioblastoma?", "sentence2": "Although further research is needed, cyclin-dependent kinase 4/6 inhibitors represent intriguing developments in the treatment of various malignancies, including those with such poor prognoses as glioblastoma multiforme, mantle cell lymphoma, and metastatic melanoma., CONCLUSION: In this trial, despite adequate tissue PK, palbociclib monotherapy was not an effective treatment for recurrent glioblastoma., CONCLUSION\n\nIn this trial, despite adequate tissue PK, palbociclib monotherapy was not an effective treatment for recurrent glioblastoma., CONCLUSION In this trial, despite adequate tissue PK, palbociclib monotherapy was not an effective treatment for recurrent glioblastoma., CONCLUSION\nIn this trial, despite adequate tissue PK, palbociclib monotherapy was not an effective treatment for recurrent glioblastoma.[SEP]Relations: adult glioblastoma has relations: disease_disease with glioblastoma (disease), disease_disease with glioblastoma (disease), disease_disease with adult infiltrating astrocytic neoplasm, disease_disease with adult infiltrating astrocytic neoplasm, disease_disease with adult spinal cord glioblastoma, disease_disease with adult spinal cord glioblastoma. mantle cell lymphoma has relations: disease_protein with CREBBP, disease_protein with CREBBP, disease_protein with UBR5, disease_protein with UBR5.", "label": "no"}
{"id": "converted_1640", "sentence1": "Is Turcot syndrome associated with glioblastoma?", "sentence2": "Turcot syndrome is an autosomal recessive disorder clinically characterized by the occurrence of primary tumors of the central nervous system and adenomatous colonic polyps during the first or second decades of life, with a spectrum of clinical features such as \"café-au-lait\" spots, axillary freckling, and hyperpigmented spots. , We present the case of a 20-year-old male with a clinical presentation of both glioblastoma multiforme and multiple adenomatous colonic polyps. , Turcot syndrome (TS) is a rare hereditary disorder clinically characterized by the occurrence of primary tumors of the colon and the central nervous system (CNS). Here we present the case of an 11-year-old boy with a synchronous clinical presentation of both glioblastoma multiforme (GBM) and colonic adenocarcinoma., Based on this case study, the synchronous presentation of glioblastoma multiforme and adenocarcinoma of the colon might suggest a shorter survival rate for patients with Turcot syndrome. , A 15-year-old boy was admitted with the diagnosis of colonic polyposis, and during a 2-year follow-up, he underwent operation for right parieto-occipital anaplastic astrocytoma, left-side colonic non-Hodgkin lymphoma (NHL) and cerebella glioblastoma which were all confirmed by histology. Although cases of Turcot's syndrome (TS) (colonic polyposis and primary brain tumour occurring in the same patient) have been previously described, association with haematological malignancy is rare. We hereby report such a case with TS., Type A microsatellite instability in pediatric gliomas as an indicator of Turcot syndrome.,  Biallelic mutations of MMR genes are associated with pediatric cancers, including glial tumors, in Turcot syndrome type 1 (TS1)., Glioblastomas with giant cell and sarcomatous features in patients with Turcot syndrome type 1: a clinicopathological study of 3 cases., Turcot syndrome (TS) is a rare genetic disorder of DNA mismatch repair predisposing to glioblastoma (GBM) in the type 1 variant. , We report the clinicopathological and genetic features of 3 gliomas in TS type 1 patients., We conclude that 1) the giant cell variant of GBM is overrepresented in TS; 2) gliosarcomas may also be encountered; and 3) survival is often favorable, despite histological anaplasia and exuberant proliferation., Malignant transformation of high-grade astrocytoma associated with neurocysticercosis in a patient with Turcot syndrome., A 45-year-old woman with anaplastic astrocytoma was clinically diagnosed with Turcot syndrome, and subsequently developed simultaneous neurocysticercosis and malignant transformation to glioblastoma. , Familial glioblastoma multiforme is a rather uncommon entity, being in most cases associated to known genetic disorders (as Turcot syndrome, Li-Fraumeni syndrome, neurofibromatosis, etc.). , Turcot syndrome (MIM276300) has been described as the association of central nervous system malignant tumors and familial colorectal cancer and has been reported to be both a dominant and recessive disorder., We report here the first identification of a homozygous mutation in MSH6 in a family with childhood-onset brain tumor, lymphoma, colorectal cancer, and neurofibromatosis type 1 phenotype. , Of the 21 patients, 12 have died (10 after relapse, with a median time to progression for the whole series of 14 months; one with intratumoral bleeding at 40 months after diagnosis; and one affected by Turcot syndrome for duodenal cancer relapse)., [Glioblastoma multiforme as a manifestation of Turcot syndrome]., In the present case, a 60-year-old patient with glioblastoma multiforme and a history of hereditary malignomas is described as an example of a HNPCC-associated Turcot's syndrome., Computed tomography brain scan and computed tomography-guided biopsy revealed a left frontoparietal glioblastoma multiforme. This case illustrates the rare presentation of Turcot syndrome-a hereditary colorectal polyposis syndrome-in an older adult., Turcot syndrome is the association of colorectal polyposis with primary neuroepithelial tumors of the central nervous system such as glioblastoma and medulloblastoma. , Brain tumor is mainly diagnosed as glioblastoma or astrocytoma and mismatch repair genes might be involved. , Patients with Turcot syndrome (TS) are predisposed to colon tumors and primary brain tumors, typically glioblastomas or medulloblastomas. The authors describe a patient with TS featuring a known germline mutation of exon 5 of the hPMS2 mismatch repair gene who developed two metachronous glioblastomas, both with distinct oligodendroglial features., Because this patient had an unusual underlying condition and his tumor had a unique histological appearance for TS, it was hypothesized that this genetic defect may predispose to malignant gliomas with oligodendroglial features. , Turcot Syndrome caused by APC gene develops medulloblastoma and Turcot Syndrome caused by mismatch repair gene develops glioblastoma. , It is characterized by central nervous system (CNS) neoplasms and gastrointestinal polyposis., Seven months after resection of this Dukes' C2 adenocarcinoma, she presented with a second primary CNS tumor, a glioblastoma multiforme., The Turcot syndrome has been defined as the simultaneous presence of multiple polyposis of the colon and a malignant brain tumor., The case of a 47-year-old man submitted to a right hemicolectomy for cancer and polyposis, following a series of endoscopic polypectomies and, finally, removal of left temporal glioma is here presented.,  Two of 13 showed microsatellite instability, one of which in a patient with Turcot syndrome, the other in gliomatosis cerebri., The Turcot syndrome (TS) is a rare, probably autosomal recessive, disorder characterized by development of primary neuroepithelial tumors of the central nervous system (CNS) and numerous adenomatous colorectal polyps. , However, no somatic mutations in APC were found among 91 neuroepithelial tumors (medulloblastoma, glioblastoma, astrocytoma, and oligodendroglioma), whether sporadic or associated with TS. , Such syndromes include neurofibromatosis type 2, neurofibromatosis type 1, Li-Fraumeni syndrome, as well as von Hippel-Lindau disease, tuberous sclerosis, and Turcot syndrome. , This patient's case deals with the association between a glioblastoma, anaplastic glioma (WHO Grade III) and colonic adenocarcinoma based on familial polyposis coli. , The authors describe two patients with the association of polyposis-coli and central nervous system tumor (Turcot's syndrome). , We report a case of Turcot's syndrome in a 20-year old man with multiple adenomatous polyps of the colon and glioblastoma multiforme. , Another unusual autopsy case of the Turcot syndrome is reported in a 23-year-old woman with polyposis coli, who developed primary carcinoma of the jejunum and glioblastoma multiforme of the left frontal lobe. , Turcot syndrome represents the unique and discrete occurrence of polyposis coli with glioblastoma multiforme, medulloblastoma, or both.[SEP]Relations: Glioma has relations: disease_phenotype_positive with Turcot syndrome with polyposis, disease_phenotype_positive with Turcot syndrome with polyposis. Medulloblastoma has relations: disease_phenotype_positive with Turcot syndrome with polyposis, disease_phenotype_positive with Turcot syndrome with polyposis. Lymphoma has relations: disease_phenotype_positive with Turcot syndrome with polyposis, disease_phenotype_positive with Turcot syndrome with polyposis. Brain neoplasm has relations: disease_phenotype_positive with Turcot syndrome with polyposis, disease_phenotype_positive with Turcot syndrome with polyposis. Astrocytoma has relations: disease_phenotype_positive with Turcot syndrome with polyposis, disease_phenotype_positive with Turcot syndrome with polyposis.", "label": "yes"}
{"id": "converted_1871", "sentence1": "Can NEECHAM Confusion Scale be used for evaluation of postoperative delirium?", "sentence2": "Sampling was achieved in a nonrandomized targeted manner and delirium was assessed using NeeCham questionnaire. , Delirium in older patients: a diagnostic study of NEECHAM Confusion Scale in surgical intensive care unit., AIMS AND OBJECTIVES: To estimate the diagnostic value and determine the feasibility of the NEECHAM Confusion Scale on critically ill older patients., CONCLUSIONS: Findings from this study confirm the good diagnostic value and ease of application of the NEECHAM scale with nonventilated intensive care patients.RELEVANCE TO CLINICAL PRACTICE: The NEECHAM scale can be used to detect delirium during the routine nursing assessment of nonintubated older patients as it requires minimal demand and stress on the patient as well as on the bedside nurse., The NEECHAM Confusion Scale and the validated chart review instrument were used for diagnosis of delirium. , Among the various screening instruments, NEECHAM confusion scale and delirium observation scale appear to be most suitable screening instrument for patients' in general medical and surgical wards, depending on the type of rater (physician or nurse). , Use of NEECHAM scaling enabled medical staff to identify cases of possible confusion early, indicating that the NEECHAM confusion scale should be useful for the detection of postoperative delirium and confusion in the surgical ward., Early detection of postoperative delirium and confusion in a surgical ward using the NEECHAM confusion scale., In this study, we investigated whether the early detection of postoperative delirium in elderly patients is possible using a simple, useful behavior-assessing scale, the NEECHAM Confusion Scale, and a method for comprehensively evaluating elderly persons' stress related to surgery, E-PASS., Assessment of the risk of postoperative delirium in elderly patients using E-PASS and the NEECHAM Confusion Scale., The aim of this study was to determine which of the two delirium observation screening scales, the NEECHAM Confusion Scale or the Delirium Observation Screening (DOS) scale, has the best discriminative capacity for diagnosing delirium and which is more practical for daily use by nurses., For delirium diagnosis and severity assessment, we used the NEECHAM Confusion Scale., Use of NEECHAM scaling enabled medical staff to identify cases of possible confusion early, indicating that the NEECHAM confusion scale should be useful for the detection of postoperative delirium and confusion in the surgical ward., The NEECHAM Confusion Scale was performed upon admission and prior to discharge.RESULTS: The incidence of DSM-IV related delirium was 24%., A comparison of the CAM-ICU and the NEECHAM Confusion Scale in intensive care delirium assessment: an observational study in non-intubated patients., Predictive value and validation of the NEECHAM Confusion Scale using DSM-IV criteria for delirium as gold standard., Early detection of postoperative delirium and confusion in a surgical ward using the NEECHAM confusion scale, The aim of this study was to determine which of the two delirium observation screening scales, the NEECHAM Confusion Scale or the Delirium Observation Screening (DOS) scale, has the best discriminative capacity for diagnosing delirium and which is more practical for daily use by nurses.The project was conducted on four wards of a university hospital; 87 patients were included, In addition, we scored the participants on the NEECHAM Scale and evaluated their postoperative delirium and postoperative arrhythmia.On the nights of Days 4 and 5, the amount of activity of the exposure group was significantly lower and The sympathetic nervous index was significantly lower on the night of Day 5, In this study, we investigated whether the early detection of postoperative delirium in elderly patients is possible using a simple, useful behavior-assessing scale, the NEECHAM Confusion Scale, and a method for comprehensively evaluating elderly persons' stress related to surgery, E-PASS. , The cut-off value of the NEECHAM score was established as 20 points, and patients showing values less than this after surgery were regarded as having postoperative delirium. , Identification of delirium was based on evaluation of the level of consciousness with the NEECHAM Confusion Scale and/or a chart-based instrument for delirium., For delirium diagnosis and severity assessment, we used the NEECHAM Confusion Scale., In this study, we investigated whether the early detection of postoperative delirium in elderly patients is possible using a simple, useful behavior-assessing scale, the NEECHAM Confusion Scale, and a method for comprehensively evaluating elderly persons' stress related to surgery, E-PASS.The subjects were 160 patients aged more than 75 years who underwent surgery., In this study a nursing screening instrument, the NEECHAM confusion scale, was studied for early recognition of delirium ICU patients., The psychometric characteristics and the ease of use of the NEECHAM confusion scale enables ICU nurses to early recognize delirium., The trends of the NEECHAM scores in the 3 groups were compared, and the relationship between the NEECHAM scores and suspected clinical risk factors for delirium was investigated., In groups showing an MMSE score of less than 25 or a preoperative NEECHAM score of less than 27, the incidence of postoperative delirium was 76%.CONCLUSION: The results suggest that E-PASS and the NEECHAM score facilitate assessment of the risk of postoperative delirium in elderly patients, contributing to early prevention/treatment., In this study, we investigated whether the early detection of postoperative delirium in elderly patients is possible using a simple, useful behavior-assessing scale, the NEECHAM Confusion Scale, and a method for comprehensively evaluating elderly persons' stress related to surgery, E-PASS., Use of NEECHAM scaling enabled medical staff to identify cases of possible confusion early, indicating that the NEECHAM confusion scale should be useful for the detection of postoperative delirium and confusion in the surgical ward.., Early detection of postoperative delirium and confusion in a surgical ward using the NEECHAM confusion scale., Assessment of the risk of postoperative delirium in elderly patients using E-PASS and the NEECHAM Confusion Scale., For delirium diagnosis and severity assessment, we used the NEECHAM Confusion Scale., The Neecham Confusion Scale and the Delirium Observation Screening Scale: capacity to discriminate and ease of use in clinical practice., The aim of this study was to determine which of the two delirium observation screening scales, the NEECHAM Confusion Scale or the Delirium Observation Screening (DOS) scale, has the best discriminative capacity for diagnosing delirium and which is more practical for daily use by nurses.[SEP]Relations: delirium has relations: contraindication with Trolnitrate, contraindication with Trolnitrate, disease_disease with cognitive disorder, disease_disease with cognitive disorder, disease_disease with subacute delirium, disease_disease with subacute delirium, contraindication with Tacrolimus, contraindication with Tacrolimus, contraindication with Olanzapine, contraindication with Olanzapine.", "label": "yes"}
{"id": "converted_618", "sentence1": "Does molindone affect body weight?", "sentence2": "Mean weight increased by 0.54 kg, and mean body mass index by 0.24 kg/m(2). , A large-scale trial comparing a first-generation antipsychotic (molindone) with newer agents did not find significant differences in treatment response, although the newer antipsychotics were associated with more severe weight gain. , No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. , The three treatment arms did not significantly differ in symptom decrease or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment. , Olanzapine and risperidone were associated with significantly greater weight gain. Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol, low density lipoprotein, insulin, and liver transaminase levels. Molindone led to more self-reports of akathisia. , Molindone is no more or less likely than typical drugs to cause movement disorders, but it does cause significantly more weight loss (2RCTs n=60 RR 2.78, CI 1.10 to 6.99, NNH 5 CI 2 to 77). , Molindone may be an effective antipsychotic but its adverse effect profile does not differ significantly from that of typical antipsychotics (apart from the event of weight loss). , Convergent evidence suggests a hierarchy in the magnitude of BWG that may be induced by diverse agents, being very high for clozapine and olanzapine; high for quetiapine, zotepin, chlorpromazine, and thioridazine; moderate for risperidone and sertindole; and low for ziprazidone, amisulpiride, haloperidol, fluphenazine, pimozide, and molindone. , Loxapine and molindone induce weight decreases, and these exceptions are difficult to explain., It is no more or less likely than typical drugs to cause movement disorders, but causes significantly more weight loss (RR 2.78, CI 1.10 to 6.99)., Molindone may be an effective antipsychotic; however, its adverse effect profile does not differ significantly from that of typical antipsychotics, apart from the event of weight loss. , Among conventional agents, mean weight change ranged from a reduction of 0.39 kg with molindone to an increase of 3.19 kg with thioridazine., Weight gain has been reported with nearly every antipsychotic drug on the market (molindone is an exception). , Although almost all antipsychotics induce bodyweight gain, molindone and loxapine appear to induce bodyweight loss. , Clozapine and low-potency phenothiazines are associated with the largest gains and molindone with weight loss, but the mechanism is not known. , On average, molindone patients lost 5 pounds over the 6 weeks of treatment, whereas thioridazine patients gained 6 pounds. , Clinically, molindone has a tendency to cause weight loss and may have less effect on seizure threshold than conventional antipsychotic agents,  Monthly weights and neuroleptic dosages during the first three months of psychiatric hospitalization were compared between matched groups of patients receiving molindone, a combination of molindone and other neuroleptics, or other neuroleptic drugs. We found no significant differences in weight gain among the three groups. , The weight-reducing property of molindone, a recently introduced antipsychotic drug, was tested in 9 hospitalized chronic schizophrenic patients. There was an average weight loss of 7.6 kg after 3 months on molindone; most of the loss occurred during the first month.[SEP]Relations: Molindone has relations: drug_effect with Increased body weight, drug_effect with Increased body weight, drug_effect with Nausea, drug_effect with Nausea, drug_effect with Tremor, drug_effect with Tremor, drug_effect with Hyperkinetic movements, drug_effect with Hyperkinetic movements, drug_effect with Dyspnea, drug_effect with Dyspnea.", "label": "yes"}
{"id": "converted_3144", "sentence1": "Is the protein Asporin related to disease?", "sentence2": "Accumulating evidence demonstrates the involvement of asporin in OA pathogenesis., Asporin has been reported as a tumor suppressor in breast cancer, while asporin-activated invasion has been described in gastric cancer., Asporin has been implicated as an oncogene in various types of human cancers; ,  These results suggested that asporin promoted the tumor growth and metastasis of CRC, and it could be a potential therapeutic target for CRC patients in future., Our results suggest that ASPN is a stromally expressed biomarker that correlates with disease progression, and is observed in reactive stroma. [SEP]Relations: osteoarthritis susceptibility has relations: disease_protein with ASPN, disease_protein with ASPN, disease_protein with ETFA, disease_protein with ETFA, disease_protein with ACTB, disease_protein with ACTB, disease_protein with ASTN2, disease_protein with ASTN2, disease_protein with COMP, disease_protein with COMP.", "label": "yes"}
{"id": "converted_1689", "sentence1": "Is Achondroplasia associated with hearing loss?", "sentence2": "A hearing screening program was performed to determine the prevalence of hearing loss and abnormal tympanometry in individuals with short-stature skeletal dysplasias attending a national meeting. Behavioral audiometry, otoacoustic emission testing, and tympanometry were used to assess hearing. Failed hearing screen was defined as hearing ≥ 35 dB at one or more frequencies or by \"fail\" on otoacoustic emissions. One hundred ten of 112 subjects completed the screening. 58 (51.8%) were children. Seventy-three (65.2%) had achondroplasia, 34 (30.4%) had one of 11 other diagnoses, and 5(4.4%) were undiagnosed. 25.8% of children failed hearing screening in one or both ears, while 46.3% of adults failed in one or both ears. 55.1% of adults and 25.0% of children with achondroplasia failed screening., Forty-four children had achondroplasia, and 31 had normal hearing in both ears (71%); 8 failed hearing screening in 1 ear (18%), and 3 in both ears (7%). Tympanometry was performed in 45 children, with normal tympanograms found in 21 (47%), bilateral abnormal tympanograms in 15 (33%), and unilateral abnormal tympanograms in 9 (20%). Fourteen children with achondroplasia had normal tympanograms (42%); 11 had bilateral abnormal tympanograms (33%); and 8 had unilateral abnormal tympanograms (24%). For those children without functioning tympanostomy tubes, there was a 9.5 times greater odds of hearing loss if there was abnormal tympanometry (P = .03)., Achondroplasia (MIM 100800) is the most common non-lethal skeletal dysplasia. Its incidence is between one in 10,000 and one in 30,000. The phenotype is characterized by rhizomelic disproportionate short stature, enlarged head, midface hypoplasia, short hands and lordotic lumbar spine, associated with normal cognitive development. This autosomal-dominant disorder is caused by a gain-of-function mutation in the gene encoding the type 3 receptor for fibroblast growth factor (FGFR3); in more than 95% of cases, the mutation is G380R. The diagnosis is suspected on physical examination and confirmed by different age-related radiological features. Anticipatory and management care by a multidisciplinary team will prevent and treat complications, including cervical cord compression, conductive hearing loss and thoracolumbar gibbosity., The report includes information on otitis media, ventilation tubes, hearing loss, tonsillectomy, speech problems, tibial bowing and osteotomy, ventricular shunting, apnoea, cervicomedullary decompression, and neurological signs attributable to spinal stenosis., We conclude that verbal comprehension is significantly impaired in children with achondroplasia. This partial deficiency is probably related to frequent middle ear infections and resulting conductive hearing loss., In order to determine whether these morphologic changes are the cause of the hearing deficit in achondroplasia, audiometric studies and ENT evaluation were performed in eight of the nine patients., Audiograms were obtained in six of the nine achondroplastic subjects (two adults and four children). There was evidence of mixed hearing loss in the four children, but only of sensorineural hearing loss in the adults. We believe that the persistent hearing loss in achondroplasia is not due to sequelae of otitis media as some authors have suggested. , The AA report a clinical and radiological study performed in 18 achondroplastic patients in order to achieve a nosological settlement of the otological impairments. [SEP]Relations: achondroplasia has relations: disease_phenotype_positive with Hearing impairment, disease_phenotype_positive with Hearing impairment, disease_phenotype_positive with Conductive hearing impairment, disease_phenotype_positive with Conductive hearing impairment, disease_phenotype_positive with Functional abnormality of the middle ear, disease_phenotype_positive with Functional abnormality of the middle ear. Hearing impairment has relations: disease_phenotype_positive with achondroplasia, disease_phenotype_positive with achondroplasia, disease_phenotype_positive with severe achondroplasia-developmental delay-acanthosis nigricans syndrome, disease_phenotype_positive with severe achondroplasia-developmental delay-acanthosis nigricans syndrome.", "label": "yes"}
{"id": "converted_4570", "sentence1": "Is AGO2 related to cytokinesis?", "sentence2": "AGO2 localizes to cytokinetic protrusions in a p38-dependent manner and is needed for accurate cell division., We suggest that AGO2 is part of a regulatory mechanism triggered by cytokinetic stress to generate the appropriate micro-environment for local transcript homeostasis.[SEP]Relations: Protein S human has relations: drug_drug with Bamet-UD2, drug_drug with Bamet-UD2, drug_drug with Peginterferon alfa-2b, drug_drug with Peginterferon alfa-2b, drug_drug with Interferon alfa-2b, drug_drug with Interferon alfa-2b, drug_drug with Peginterferon beta-1a, drug_drug with Peginterferon beta-1a, drug_drug with Cepeginterferon alfa-2B, drug_drug with Cepeginterferon alfa-2B.", "label": "yes"}
{"id": "converted_2187", "sentence1": "Is edema a symptom of nephrotic syndrome?", "sentence2": "Nephrotic syndrome (NS) is a common clinical disease with four main clinical manifestations: hypoalbuminemia (<30 g/L), macro-proteinuria (>3.5 g/24 h), edema, and hyperlipidemia. , Nephrotic syndrome is an unusual manifestation of IgA Nephropathy (IgAN)., Twelve patients with IgAN with steroid-responsive nephrotic syndrome were evaluated and followed up. All patients presented with generalized edema. , The clinical features of sudden onset of generalized edema, initial heavy proteinuria and initial severe hypoalbuminemia might help identify the subset of patients, especially in low grade IgAN., Most patients presented within 3 months duration (61.4%) and the most common symptom was puffiness of face (98.45%) followed by pedal edema (91%). , We analyzed medical records of 290 patients with diagnosis of nephrotic syndrome as defined by International Study of Kidney Disease in Children (ISKDC), between January 1987 and December 2000, at the Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar. , He was admitted because of systemic edema and dyspnea on effort Laboratory data revealed renal failure and nephrotic syndrome, whereas there was no symptom of diabetic retinopathy., Nephrotic syndrome: more than just oedema., Oedema is the commonest presenting symptom and sign in nephrotic syndrome. , One of these five clinical syndromes is the nephrotic syndrome, which is characterized by proteinuria > 3.5 g/day accompanied by hypalbuminemia, hyperlipoproteinemia and pronounced edema, Tolvaptan therapy for massive edema in a patient with nephrotic syndrome, Nephrotic syndrome (NS) is characterized by water and sodium retention, which leads to edema, The non-osmotic stimulation of arginine vasopressin release from the pituitary gland has been implicated as one of the important factors in abnormal water retention in patients with NS.We present the initial description of a patient with massive edema caused by refractory nephrotic syndrome, which was effectively treated with tolvaptan, a selective oral vasopressin V2 receptor antagonist.Tolvaptan is effective for the treatment of massive edema caused by NS, We report a child with steroid-resistant nephrotic syndrome with diuretic-resistant nephrotic edema treated successfully using acute peritoneal dialysis as a means of UF, Albumin and Furosemide Combination for Management of Edema in Nephrotic Syndrome: A Review of Clinical Studies, The treatment of edema in patients with nephrotic syndrome is generally managed by dietary sodium restriction and loop diuretics, Nine months after introduction of tiopronin, the boy manifested generalized edema, oliguria, and biochemical indices of nephrotic syndrome, Blessed were the days when it all made sense and the apparent mechanism for edema formation in nephrotic syndrome was straightforward: the kidneys lost protein in the urine, which lowered the plasma oncotic pressure, The nephrotic syndrome is characterized by a combination of pathological lab values and clinical symptoms, i. e. pronounced proteinuria (usually more than 3 - 3,5 g protein/24 h), hypoalbuminemia, edema and hyperlipidemia., The patient was admitted with edema of both legs, and the nephrotic syndrome was discovered, leading to the diagnosis of AA amyloidosis on kidney biopsy., Linear regression to relate measures.Other signs and symptoms of nephrotic syndrome at baseline (serum albumin < 3.5 g/dL, serum total cholesterol > 260 mg/dL or use of a statin, and edema or use of a loop diuretic); progression of chronic kidney disease during follow-up (doubling of baseline serum creatinine level or requirement for dialysis or kidney transplantation)., A case of interstitial shadows associated with oral cyclophosphamide therapy in a 32-month-old girl with steroid-resistant nephrotic syndrome, who was admitted to the Nishi-Kobe Medical Center with systemic edema, is reported., Nephrotic syndrome represents a constellation of symptoms including hyperalbuminuria, hypoalbuminemia, edema formation, hypercholesterolemia, hypertension, hypercoagulopathy, and increased infection risk., Pathophysiology of edema formation in children with nephrotic syndrome not due to minimal change disease., To study the evidence-based therapy of edema in nephrotic syndrome by analyzing the literatures systematically., Edema is the prominent feature of nephrotic syndrome and initially develops around the eyes and legs., Intussusception should be considered in the differential diagnosis of abdominal pain in patients with nephrotic syndrome, especially in patients exhibiting prolonged edema., Oedema is the commonest presenting symptom and sign in nephrotic syndrome., Other signs and symptoms of nephrotic syndrome at baseline (serum albumin < 3.5 g/dL, serum total cholesterol > 260 mg/dL or use of a statin, and edema or use of a loop diuretic); progression of chronic kidney disease during follow-up (doubling of baseline serum creatinine level or requirement for dialysis or kidney transplantation).[SEP]Relations: Edema has relations: disease_phenotype_positive with nephrotic syndrome,, disease_phenotype_positive with nephrotic syndrome,, disease_phenotype_positive with congenital nephrotic syndrome, Finnish type, disease_phenotype_positive with congenital nephrotic syndrome, Finnish type. Nephrotic syndrome has relations: phenotype_phenotype with Abnormal renal physiology, phenotype_phenotype with Abnormal renal physiology, phenotype_phenotype with Transient nephrotic syndrome, phenotype_phenotype with Transient nephrotic syndrome, phenotype_phenotype with Congenital nephrotic syndrome, phenotype_phenotype with Congenital nephrotic syndrome.", "label": "yes"}
{"id": "converted_3620", "sentence1": "Are tumour specific antigens originating from known protein coding genes?", "sentence2": "It is well established that MHC class I molecules present peptides from endogenous proteins, such as virus or tumour antigens, to CD8+ T lymphocytes. , So far, human tumour specific antigens that can be presented by HLA molecules have not been identified on the molecular level., These CTLs recognize short peptides derived from tumour-associated antigens in conjunction with class I molecules expressed on tumour cells.,  The focus on cellular immune responses, combined with rapid biotechnological advances, resulted in the identification of tumour specific antigens, such as MART-1 and gp100, that could be recognised by autologous TIL,  Tumour antigens are mostly of weak immunogenicity, because the vast majority are tumour-associated differentiation antigens already 'seen' by the patient's immune system., Tumour-specific antigens, which could be a more potent target for immunotherapy, mostly arise by point mutations and have the disadvantage of being not only tumour-specific, but also individual-specific., The pioneering studies of Srivastava and colleagues led to the proposal that heat-shock proteins (HSPs) function as ubiquitous tumour-specific antigens, with the specificity residing in a population of bound peptides that identify the tissue of origin of the HSP., Therefore, we propose that CD4(+) T cells that recognize secreted TSA may be superior for immunotherapy by T cell transfer, because the local extracellular antigen concentration will be higher for secreted TSA. ,  Here, we wondered whether these frame-shifted peptide (FSP) sequences represent tumour-specific antigens also for MSI(+) leukaemia and lymphomas (L/L)., Data presented here expand the importance of FSPs as shared and general tumour-specific antigens.[SEP]Relations: germ cell tumor has relations: disease_protein with ATF7IP, disease_protein with ATF7IP, disease_protein with SCNN1A, disease_protein with SCNN1A, disease_protein with KITLG, disease_protein with KITLG, disease_protein with ERCC1, disease_protein with ERCC1, disease_protein with PHC1, disease_protein with PHC1.", "label": "yes"}
{"id": "converted_3373", "sentence1": "Is the drug Exubera currently (March 2020) available?", "sentence2": "Despite discontinuation of the first inhalable insulin, Exubera®, due to suboptimal market acceptance, development of orally inhaled insulin delivery systems has been galvanized by the recent approval of Afrezza® and several others awaiting approval.[SEP]", "label": "no"}
{"id": "converted_1901", "sentence1": "Is there any role for Pds5b in cohesion establishment?", "sentence2": "Pds5B is required for cohesion establishment and Aurora B accumulation at centromeres., Here, we demonstrate that Pds5 proteins are essential for cohesion establishment by allowing Smc3 acetylation by the cohesin acetyl transferases (CoATs) Esco1/2 and binding of Sororin. While both proteins contribute to telomere and arm cohesion, Pds5B is specifically required for centromeric cohesion. Furthermore, reduced accumulation of Aurora B at the inner centromere region in cells lacking Pds5B impairs its error correction function, promoting chromosome mis-segregation and aneuploidy. Our work supports a model in which the composition and function of cohesin complexes differs between different chromosomal regions., Pds5B is required for cohesion establishment and Aurora B accumulation at centromeres., Here, we demonstrate that Pds5 proteins are essential for cohesion establishment by allowing Smc3 acetylation by the cohesin acetyl transferases (CoATs) Esco1/2 and binding of Sororin.[SEP]Relations: Protein S human has relations: drug_drug with Coagulation Factor IX (Recombinant), drug_drug with Coagulation Factor IX (Recombinant), drug_drug with Platelet Activating Factor, drug_drug with Platelet Activating Factor, drug_drug with p-Coumaric acid, drug_drug with p-Coumaric acid, drug_drug with Peginterferon alfa-2b, drug_drug with Peginterferon alfa-2b. centromere clustering has relations: bioprocess_bioprocess with chromosome localization, bioprocess_bioprocess with chromosome localization.", "label": "yes"}
{"id": "converted_1729", "sentence1": "Are mutations in the STXBP1 gene associated with epilepsy?", "sentence2": "Folinic acid responsive epilepsy in Ohtahara syndrome caused by STXBP1 mutation., A novel mutation in STXBP1 gene in a child with epileptic encephalopathy and an atypical electroclinical pattern., Mutations in STXBP1 gene, encoding the syntaxin binding protein 1, have been recently described in Ohtahara syndrome, or early infantile epileptic encephalopathy with suppression-burst pattern, and in other early-onset epileptic encephalopathies., STXBP1 (MUNC18.1), encoding syntaxin binding protein 1, has been reported in Ohtahara syndrome, a rare epileptic encephalopathy with suppression burst pattern on EEG, in patients with infantile spasms and in a few patients with nonsyndromic mental retardation without epilepsy. , ed with severe developmental delay and poor prognosis. Mutations and deletions in the STXBP1 gene are associated with Ohtahara syndrome, also known as \"early infantile epileptic encephalopathy, Here we show that de novo heterozygous mutations in the gene encoding STXBP1, also known as MUNC18-1, which is essential in synaptic vesicle release in multiple species, cause OS, STXBP1 haploinsufficiency results in progressive encephalopathy characterized by intellectual disability and may be accompanied by epilepsy, movement disorders, and autism. , Mutations of the syntaxin binding protein 1 (STXBP1) have been associated with severe infantile epileptic encephalopathies (Ohtahara syndrome and West syndrome), but also with moderate to severe cognitive impairment and nonsyndromic epilepsy., A novel STXBP1 mutation causes focal seizures with neonatal onset., STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern., e novo STXBP1 mutations have been found in individuals with early infantile epileptic encephalopathy with suppression-burst pattern (EIEE), Mutations in STXBP1 are relatively frequent in patients with infantile epileptic encephalopathies. STXBP1-related encephalopathy may present as drug-responsive infantile spasms with focal/lateralized discharges., De novo SCN1A mutations in migrating partial seizures of infancy., De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy., Mutations in STXBP1 have been identified in a subset of patients with early onset epileptic encephalopathy (EE), but the full phenotypic spectrum remains to be delineated, and STXBP1-related West/Ohtahara syndromes, are due to a mutation in a unique gene., This is the first case report showing that STXBP1 mutations caused West syndrome from the onset of epilepsy. [SEP]Relations: epilepsy has relations: disease_protein with STXBP1, disease_protein with STXBP1, disease_protein with STX1B, disease_protein with STX1B, disease_protein with TGFB1, disease_protein with TGFB1, disease_protein with ADCYAP1, disease_protein with ADCYAP1, disease_protein with MIB1, disease_protein with MIB1.", "label": "yes"}
{"id": "converted_4482", "sentence1": "Is neurofilament light marker for disease?", "sentence2": "sNfL levels during the first demyelinating event of MS are associated with greater impairment of BBB integrity, immune cell extravasation, and brain lesion activity on MRI., Neurofilament light chain (NfL) has recently been proposed as a promising biomarker in frontotemporal dementia (FTD). We investigated the correlation of both cerebrospinal fluid (CSF) and serum NfL with detailed neuropsychological data and cognitive decline in a cohort of sporadic and familial FTD., Neurofilament light chain has a potential role in differentiating patients with frontotemporal dementia from healthy controls, patients with Alzheimer's dementia, and psychiatric disorders. ,  Serum neurofilament light chain (sNfL) is a marker of neuroaxonal injury., sNfL is associated with ongoing neuroinflammation and predictive of future neurodegeneration in early MS., Neurofilament light chain (NfL) is a relatively new biomarker for MS diagnosis and follow up. [SEP]Relations: Frontotemporal dementia has relations: disease_phenotype_positive with PRKAR1B-related neurodegenerative dementia with intermediate filaments, disease_phenotype_positive with PRKAR1B-related neurodegenerative dementia with intermediate filaments. Alzheimer disease has relations: disease_protein with MAPT, disease_protein with MAPT, disease_phenotype_positive with Neurofibrillary tangles, disease_phenotype_positive with Neurofibrillary tangles, disease_phenotype_positive with Senile plaques, disease_phenotype_positive with Senile plaques. Mental deterioration has relations: disease_phenotype_positive with neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset, disease_phenotype_positive with neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset.", "label": "yes"}
{"id": "converted_1874", "sentence1": "Is there an association between Muenke Syndrome and FGFR3 gene mutation?", "sentence2": "RESULTS: Forty-four with a positive FGFR3 mutation, median age 9 years, range 7 months to 52 years were enrolled. In addition, 10 unaffected siblings served as controls (5 males, 5 females; median age, 13 years; range, 3-18 years)., Muenke is a fibroblast growth factor receptor 3 (FGFR-3)-associated syndrome, which was first described in late 1990 s. , The syndrome is defined molecularly by a unique point mutation c.749C>G in exon 7 of the FGFR3 gene which results to an amino acid substitution p.Pro250Arg of the protein product. , Muenke syndrome caused by point mutation (C749G) in the FGFR3 gene affects 1 in 30,000 newborns and accounts for 25% to 30% of genetic causes of craniosynostosis., Phenotypic variability in two families of Muenke syndrome with FGFR3 mutation., PURPOSE: There are a number of craniosynostosis syndromes with hearing loss-including Muenke, Apert, Pfeiffer, Crouzon, Beare-Stevenson, Crouzon with acanthosis nigricans, and Jackson-Weiss syndromes-that result from mutations in the fibroblast growth factor receptor (FGFR) genes. , Muenke syndrome is an autosomal dominant craniosynostosis syndrome resulting from a defining point mutation in the Fibroblast Growth Factor Receptor3 (FGFR3) gene., Talocalcaneal coalition in Muenke syndrome: report of a patient, review of the literature in FGFR-related craniosynostoses, and consideration of mechanism., To better understand the pathophysiology of the Muenke syndrome, we present collective findings from several recent studies that have characterized a genetically equivalent mouse model for Muenke syndrome (FgfR3 (P244R)) and compare them with human phenotypes., We show in this study that knock-in mice harboring the mutation responsible for the Muenke syndrome (FgfR3(P244R)) display postnatal shortening of the cranial base along with synchondrosis growth plate dysfunction characterized by loss of resting, proliferating and hypertrophic chondrocyte zones and decreased Ihh expression., Muenke syndrome is caused by a single defining point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene., The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes., Epilepsy in Muenke syndrome: FGFR3-related craniosynostosis., Muenke syndrome (FGFR3-related craniosynostosis): expansion of the phenotype and review of the literature., The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes., PURPOSE: The Muenke syndrome mutation (FGFR3 (P250R)), which was discovered 15 years ago, represents the single most common craniosynostosis mutation., The heterozygous Pro250Arg substitution mutation in fibroblast growth factor receptor 3 (FGFR3), which increases ligand-dependent signalling, is the most common genetic cause of craniosynostosis in humans and defines Muenke syndrome., P250R mutation in the FGFR3 gene also known as Muenke syndrome is associated with coronal craniosynostosis, sensorineural deafness, craniofacial, and digital abnormalities., Muenke syndrome caused by the FGFR3 Pro250Arg mutation is associated with craniosynostosis, hearing loss, and various bony anomalies., Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene., Muenke syndrome, defined by heterozygosity for a Pro250Arg substitution in fibroblast growth factor receptor 3 (FGFR3), is the most common genetic cause of craniosynostosis in humans., In addition, sensorineural hearing loss is detected in all FgfR3 (P244R) mutant mice as in the majority of Muenke syndrome patients., Genetic testing identifies a pathogenic mutation or chromosomal abnormality in ∼ 21% of cases, but it is likely that further causative mutations remain to be discovered.To identify a shared signature of genetically determined craniosynostosis by comparing the expression patterns in three monogenic syndromes with a control group of patients with non-syndromic sagittal synostosis.Fibroblasts from 10 individuals each with Apert syndrome (FGFR2 substitution S252W), Muenke syndrome (FGFR3 substitution P250R), Saethre-Chotzen syndrome (various mutations in TWIST1) and non-syndromic sagittal synostosis (no mutation detected) were cultured, The craniosynostosis syndromes: Apert syndrome, Beare-Stevenson syndrome, Crouzon syndrome, Jackson-Weiss syndrome, Muenke syndrome, Pfeiffer syndrome and Saethre-Chotzen syndrome can be caused by mutation in either FGFR1, FGFR2, or FGFR3, Identical proline-->arginine gain-of-function mutations in fibroblast growth factor receptor (FGFR) 1 (Pro252Arg), FGFR2 (Pro253Arg) and FGFR3 (Pro250Arg), result in type I Pfeiffer, Apert and Muenke craniosynostosis syndromes, respectively, The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes, Mutation analysis of FGFR-3 revealed a missense mutation in exon 6, c.749 C>G, with a resultant amino acid change from proline to arginine at codon 250 (P250R), in keeping with Muenke syndrome (Am J Hum Genet 1997;60:555-564), In an attempt to delineate functional features separating SCS from Muenkes syndrome, we screened patients presenting with coronal suture synostosis for mutations in the TWIST 1 gene, and for the Pro250Arg mutation in FGFR3, Since the Gly380Arg achondroplasia mutation was recognized, similar observations regarding the conserved nature of FGFR mutations and resulting phenotype have been made regarding other skeletal phenotypes, including hypochondroplasia, thanatophoric dysplasia, and Muenke coronal craniosynostosis, Mutations in the gene that encodes Fibroblast Growth Factor Receptor 3 (FGFR3) are associated with Achondroplasia (MIM 100800), Hypochondroplasia (MIM 146000), Muenke Syndrome (MIM 602849), Thanatophoric Dysplasia (MIM 187600, MIM 187601) and Lacrimo-Auriculo-Dento-Digital Syndrome (MIM 149730).Here we report a clinical and molecular study in a large cohort of 125 Portuguese patients with these skeletal disorders. , The Muenke syndrome (MS) is characterized by unicoronal or bicoronal craniosynostosis, midfacial hypoplasia, ocular hypertelorism, and a variety of minor abnormalities associated with a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. , P250R mutation in the FGFR3 gene also known as Muenke syndrome is associated with coronal craniosynostosis, sensorineural deafness, craniofacial, and digital abnormalities. , METHODS: Fibroblasts from 10 individuals each with Apert syndrome (FGFR2 substitution S252W), Muenke syndrome (FGFR3 substitution P250R), Saethre-Chotzen syndrome (various mutations in TWIST1) and non-syndromic sagittal synostosis (no mutation detected) were cultured. , Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene. , Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3). , In spite of a variable phenotype, Muenke syndrome has been related to a unique mutation on the FGFR3 gene, Pro 250 to Arg, which is characteristic of this disease. , Skeletal analysis of the Fgfr3(P244R) mouse, a genetic model for the Muenke craniosynostosis syndrome., Muenke syndrome is caused by a single defining point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene., Epilepsy in Muenke syndrome: FGFR3-related craniosynostosis., Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3)., The Muenke syndrome mutation (FGFR3 (P250R)), which was discovered 15 years ago, represents the single most common craniosynostosis mutation.[SEP]Relations: Muenke syndrome has relations: disease_protein with FGFR3, disease_protein with FGFR3. FGFR3 has relations: disease_protein with Muenke syndrome, disease_protein with Muenke syndrome, disease_protein with apert syndrome, disease_protein with apert syndrome, disease_protein with LADD syndrome, disease_protein with LADD syndrome. apert syndrome has relations: disease_protein with FGFR3, disease_protein with FGFR3.", "label": "yes"}
{"id": "converted_704", "sentence1": "Are CD44 variants (CD44v) associated with poor prognosis of metastasis?", "sentence2": "CD44 variants and prognosis, The CD44 variant (CD44v) isoforms have been noted as markers for tumour metastasis and prognosis in several adenocarcinomas., Positive CD44v3 expression was associated with more advanced pathological stage and poorer prognosis than negative CD44v3 expression, CD44v6 expression in the adenocarcinoma component may directly affect the behavior of carcinoma and the prognosis of patients, D44 variant 6 in endometrioid carcinoma of the uterus: its expression in the adenocarcinoma component is an independent prognostic marker, CD44v5 expression is independently positively correlated with the aggressiveness of thymic epithelial tumors. The expression of CD44v5 may be a potential trigger of tumor invasion in thymomas, analysis of CD44v expression provides indications of biological and clinical relevance also in low grade lymphoproliferative disorders, clinical relevance of CD44 variant isoform expression on B-cell chronic lymphocytic leukemia, CD44 variants and its association with survival in pancreatic cancer, CD44 variant 6(v6) molecule has been noted as a marker for tumor metastasis and prognosis in several tumors, CD44v2 and CD44v6 may be useful markers for poor prognosis in curatively resected primary pancreatic cancer, CD44v8-10 may play an important role in the adhesion of tumor cells to the capillaries of distant organs in the metastatic process, and that immunohistochemical detection of CD44v8-10 may be a biologic marker of prognostic significance., combined expression of CD44v8-10 and SLX may be a biologic marker of prognostic significance, variant isoforms (CD44v) are expressed on different malignant cells and tissues. Their upregulation has been implicated, in the progression and metastasis of malignomas., expression of the CD44 variant exon 6 is associated with lymph node metastasis in non-small cell lung cancer, a number of variant forms of CD44 are frequently expressed, although these variants are infrequently expressed in normal lung tissue, and that the expression of CD44v6 is particularly associated with lymph node metastasis in NSCLC, Expression of CD44v6 may suggest an increased risk for local lymph node metastasis in NSCLCs, different CD44 isoforms are found in human skin cancers and are modulated during carcinogenesis, D44 isoforms correlate with cellular differentiation but not with prognosis in human breast cancer, Correlations between prognosis and expression of CD44v have been reported for gastric and colon carcinoma, for non-Hodgkin's lymphoma, and recently for breast carcinoma, Certain splice variants (CD44v) can promote the metastatic behaviour of cancer cells. In human colon and breast cancer the presence of epitopes encoded by exon v6 on primary resected tumour material indicates poor prognosis, In human mammary carcinomas and colorectal carcinomas, the expression of CD44v has also been correlated with more progressed tumor stages.[SEP]Relations: thymoma has relations: disease_protein with CD274, disease_protein with CD274. colorectal carcinoma has relations: disease_protein with CD93, disease_protein with CD93, disease_protein with CD46, disease_protein with CD46. carcinoma has relations: disease_protein with CDS1, disease_protein with CDS1, disease_protein with CDK4, disease_protein with CDK4.", "label": "yes"}
{"id": "converted_885", "sentence1": "Does  thyroid hormone receptor beta1 affect insulin secretion?", "sentence2": "We demonstrated that thyroid hormone T3 rapidly induces Akt activation in pancreatic beta cells rRINm5F and hCM via thyroid hormone receptor (TR) beta1., The silencing of TRbeta1 expression through RNAi confirmed this receptor to be crucial for the T3-induced activation of Akt., T3 is able to specifically activate Akt in the islet beta cells rRINm5F and hCM through the interaction between TRbeta1 and PI3K p85alpha, demonstrating the involvement of TRbeta1 in this novel T3 non-genomic action in islet beta cells.[SEP]Relations: response to thyroid hormone has relations: bioprocess_protein with AKR1B1, bioprocess_protein with AKR1B1. thyroid hormone receptor binding has relations: molfunc_protein with GAS2L1, molfunc_protein with GAS2L1, molfunc_protein with MED1, molfunc_protein with MED1, molfunc_protein with NR0B2, molfunc_protein with NR0B2, molfunc_protein with NCOR1, molfunc_protein with NCOR1.", "label": "no"}
{"id": "converted_827", "sentence1": "Are histone deacetylase (HDAC) inhibitors good candidates to control metastasis of solid tumors?", "sentence2": "JNJ-26481585 also fully inhibited the growth of C170HM2 colorectal liver metastases, whereas again 5-fluorouracil/Leucovorin showed modest activity., Although not meeting the RECIST response criteria for adequate single-agent activity, the observed tolerable toxicities and the potential for clinical benefit in terms of stable disease suggest that further assessment of vorinostat as a part of combination therapy with either chemotherapeutic or targeted agents in metastatic breast might be undertaken., Treatments of different structural classes of HDACi simultaneously induced cell death and promoted cell migration and metastasis in multiple cancer cell types. Suppression of HDACi-induced PKCs leads to development of low toxic and long-term therapeutic strategies to potentially treat cancer as a chronic disease., mRNA expression analysis of lung tumor bearing mice suggested that the enhanced chemopreventive activity of the combination is related to atorvastatin modulation of DNA repair, SAHA modulation of angiogenesis, and both drugs modulating invasion and metastasis pathways., Histone deacetylase (HDAC) inhibitors induced morphologic differentiation, cell-cycle exit, and a shift to a differentiated, melanocytic gene expression profile in cultured UM cells. VPA inhibited the growth of UM tumors in vivo., When both drugs were used in concert additive effects were observed on the migratory and invasive behavior but not on tumor-endothelium and tumor-matrix interaction. Separate mTOR or HDAC inhibition slows processes related to tumor metastasis. The RAD001-VPA combination showed advantage over VPA monotreatment with particular respect to migration and invasion., In conclusion, sequential treatments of mice with MS-275 followed by TRAIL may target multiple pathways to reverse EMT and inhibit tumor progression, angiogenesis, and metastasis and represent a novel therapeutic approach to treat cancer., In vivo, AA98 synergized with vorinostat to inhibit tumor growth and metastasis., We report the first preclinical data for the prevention of brain metastasis of triple-negative breast cancer. Vorinostat is brain permeable and can prevent the formation of brain metastases by 62%. Its mechanism of action involves the induction of DNA double-strand breaks, suggesting rational combinations with DNA active drugs or radiation., Combining vorinostat with radiation may be a potential treatment option for patients with breast cancer who develop brain metastases., Although single-agent PCI-24781 had modest effects on STS growth and metastasis, marked inhibition was observed when combined with chemotherapy., In a 4T1 metastatic breast carcinoma model, AN-7 inhibited the formation of lung lesions by 76% and AN-9 by 47%, further demonstrating the greater efficacy of AN-7 compared to AN-9 (P<0.02). Both AN-7 and AN-9 exhibited antimetastatic and antiangiogenic activities by reducing vascularization, bFGF expression and HIF-1alpha., Since prolonged oral administration with 50 mg/kg or a single oral dose of 1.2 g/kg AN-7 did not cause adverse effects and the former exhibited significant anticancer activity, AN-7 is likely to display a high therapeutic index and may be beneficial for prostate cancer patients., We show that apicidin significantly inhibits H-ras-induced invasive phenotype of MCF10A human breast epithelial cells in parallel with a specific downregulation of matrix metalloproteinase (MMP)-2, but not MMP-9. We also show that apicidin induces a morphological reversal and growth inhibition of H-ras MCF10A cells similar to that induced by other HDAC inhibitors., We also found that NaB induced three genes, which are known metastatic suppressors, and downregulated 11 genes, which have been shown to promote metastasis.[SEP]Relations: Valproic acid has relations: drug_protein with HDAC9, drug_protein with HDAC9, drug_protein with HDAC2, drug_protein with HDAC2. Vorinostat has relations: drug_protein with HDAC3, drug_protein with HDAC3, drug_protein with HDAC1, drug_protein with HDAC1, drug_protein with HDAC6, drug_protein with HDAC6.", "label": "yes"}
{"id": "converted_784", "sentence1": "Can NXY-059 be used for treatment of acute ischemic stroke patients?", "sentence2": "Even when the international recommendations for preclinical stroke research, the Stroke Academic Industry Roundtable (STAIR) criteria, were followed, we have still seen limited success in the clinic, examples being NXY-059 and haematopoietic growth factors which fulfilled nearly all the STAIR criteria, This occurred during 1993-2006, when the 2,4-disulfonylphenyl PBN derivative, called NXY-059 in the stroke studies, was shown to be safe in humans and was taken all the way through clinical phase 3 trials and then was deemed to be ineffective. , The nitrone-based compound NXY-059, which is the first drug to reach clinical trials for the treatment of acute ischemic stroke, has provided promise for the development of more robust pharmacological agents. , OKN-007 is a proprietary compound that has had extensive commercial development (designated as NXY-059) for another indication, acute ischemic stroke, and after extensive clinical studies was shown to lack efficacy for this indication but was shown to be very safe for human use. , NXY-059, a polar compound with limited transport across the blood-brain barrier, has demonstrated neuroprotection in several animal models of acute ischemic stroke but failed to confirm clinical benefit in the second phase III trial (SAINT-II)., NXY-059 is no longer in development following a lack of efficacy found in a Phase III trial in patients with acute ischemic stroke. , We analyzed the quality and adequacy of animal studies supporting the efficacy of NXY-059 and other neuroprotective agents that are currently being investigated in phase II/III trials,  In the aftermath of the failed stroke clinical trials with the nitrone spin trap/radical scavenger, NXY-059, a number of articles raised the question: are we doing the right thing? ,  In 2006, the first positive trial of neuroprotection was published: the SAINT I (Stroke-Acute Ischemic NXY Treatment) study. In February 2008, the SAINT II study was published, indicating that NXY-059 was not effective for AIS treatment., CONCLUSIONS: NXY-059 is ineffective for treatment of AIS within 6 hours of symptom onset. , BACKGROUND AND PURPOSE: The SAINT I trial that showed a significant benefit of the neuroprotectant NXY-059 used a novel outcome for acute ischemic stroke trials: a shift toward good functional outcome on the 7-category modified Rankin scale (mRS)., BACKGROUND: The free-radical-trapping agent NXY-059 showed promise as a neuroprotectant in the Stroke-Acute Ischemic NXY Treatment I (SAINT I) trial, reducing disability when given to patients who had acute ischemic stroke. , CONCLUSIONS: NXY-059 is ineffective for the treatment of acute ischemic stroke within 6 hours after the onset of symptoms., The continued failure in approving new drugs for treatment of acute stroke has been recently set back by the failure of the NXY-059 (Stroke-Acute Ischemic NXY Treatment (SAINT) II) trial., The SAINT II Trial, a large randomized multicenter clinical trial of the putative neuroprotectant, NXY-059, failed to demonstrate a treatment benefit in acute ischemic stroke. , The positive results from the first Stroke-Acute-Ischaemic-NXY-Treatment (SAINT-I) trial of the free-radical spin-trap drug, NXY-059, which followed many of the STAIR guidelines, reinvigorated enthusiasm in neuroprotection, but the SAINT-II trial did not replicate the positive effect on the same primary prespecified outcome measure. , NXY-059, a free radical spin trap agent, was felt by many to have followed these criteria and it was recently shown to improve outcome in AIS patients in the SAINT I trial. However, the repeat, SAINT II trial was a neutral study, the results of which cast doubt on neuroprotection as a viable strategy for AIS. , NXY-059 is a novel free radical-trapping neuroprotectant that reduces infarct size and preserves brain function in animal models of acute ischemic stroke. It is the first neuroprotectant to demonstrate a reduction in global disability in a phase III clinical trial, as measured by the modified Rankin Scale., BACKGROUND AND PURPOSE: NXY-059 is a free radical-trapping neuroprotectant demonstrated to reduce disability from ischemic stroke., CONCLUSIONS: NXY-059 within 6 hours of acute ischemic stroke significantly reduced disability. , CONCLUSIONS: The administration of NXY-059 within six hours after the onset of acute ischemic stroke significantly improved the primary outcome (reduced disability at 90 days), but it did not significantly improve other outcome measures, including neurologic functioning as measured by the NIHSS score. Additional research is needed to confirm whether NXY-059 is beneficial in ischemic stroke. , BACKGROUND: The free-radical-trapping agent NXY-059 showed promise as a neuroprotectant in the Stroke-Acute Ischemic NXY Treatment I (SAINT I) trial, reducing disability when given to patients who had acute ischemic stroke., NXY-059 is no longer in development following a lack of efficacy found in a Phase III trial in patients with acute ischemic stroke., The free-radical-trapping agent NXY-059 showed promise as a neuroprotectant in the Stroke-Acute Ischemic NXY Treatment I (SAINT I) trial, reducing disability when given to patients who had acute ischemic stroke, The continued failure in approving new drugs for treatment of acute stroke has been recently set back by the failure of the NXY-059 (Stroke-Acute Ischemic NXY Treatment (SAINT) II) trial[SEP]Relations: Ischemic stroke has relations: drug_effect with Naltrexone, drug_effect with Naltrexone, drug_effect with Naltrexone, drug_effect with Naltrexone, disease_phenotype_positive with stroke disorder, disease_phenotype_positive with stroke disorder, disease_phenotype_positive with stroke disorder, disease_phenotype_positive with stroke disorder, drug_effect with Ramipril, drug_effect with Ramipril.", "label": "no"}
{"id": "converted_874", "sentence1": "Is cystatin C or cystatin 3 used as a biomarker of kidney function?", "sentence2": "to explore the effect of ageing on renal function with cystatin C as the marker of glomerular filtration rate (GFR) in the general population without vascular disease or diabetes., Cystatin C, a more specific kidney function biomarker, was also elevated at 24 h after CLP., This study evaluated FGF-23 as well as traditional markers of kidney disease, namely urine albumin-to-creatinine ratio (UACR) and creatinine-cystatin C estimated GFR (eGFRCrCyC), as risk factors for AKI in elderly individuals. , he primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFR(cys))., A number of recent reports have suggested that the cystatin C/creatinine (CysC/Cr) ratio might be a useful biomarker of renal function in pediatric patients., The CKD-EPI equation using cystatin C was the most precise method of renal function evaluation in patients with neurogenic bladder., Serum cystatin C (CysC) is an endogenous marker of kidney function., The urinary content of CysC reflects tubular epithelial dysfunction whereas that of NGAL also characterizes tubular atrophy., Estimated kidney function based on serum cystatin C , : Several formulas for glomerular filtration rate (GFR) estimation, based on serum creatinine or cystatin C, have been proposed. , he highest and lowest eGFR levels corresponded to the cystatin C-based and MDRD-4 equations, respectively. , The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently proposed an equation to estimate GFR in subjects without cirrhosis using both serum creatinine and cystatin C levels., Emerging evidence has shown that cystatin C may improve classification of glomerular filtration rate for defining chronic kidney disease in certain clinical populations and assist in understanding the complications of chronic kidney disease, Beta-trace protein (BTP) and cystatin C (CysC) are novel biomarkers of renal function. , Cystatin C could improve chronic kidney disease (CKD) classification in HIV-infected women relative to serum creatinine.,  Iohexol clearance and cystatin C formulae identify a greater proportion of patients with a GFR <60 mL/min/1.73 m(2), which also predicts the development of AKI.,  Cystatin C was recently reported to be an endogenous surrogate of kidney function, and a high level of cystatin C is reported to be a strong predictor of CVD;, Studies that have simultaneously compared measured GFR and estimated GFR (using endogenous filtration markers such as creatinine, or newer ones such as cystatin C or β-trace protein)[SEP]Relations: kidney disease has relations: contraindication with Biotin, contraindication with Biotin, contraindication with Pravastatin, contraindication with Pravastatin, contraindication with Cyclacillin, contraindication with Cyclacillin, contraindication with Isotretinoin, contraindication with Isotretinoin, contraindication with Phenacetin, contraindication with Phenacetin.", "label": "yes"}