anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Poor quality diet and physical inactivity are the most prevalent, preventable causes of death in the United States. In particular, high saturated fat diet (Fat), low fruit and vegetable intake (FV), low physical activity (PA), and high sedentary leisure screen time (Sed) co-occur and heighten the risks of cardiovascular disease and cancers. The first Make Better Choices (MBC1) experiment contrasted four strategies to promote healthful change across these four risk behaviors. Each intervention targeted two behaviors (one diet, one activity) simultaneously and either increased healthy or decreased unhealthy responding. The intervention targeting increased FV and decreased Sed was most efficacious, yielding unexpectedly sustained improvement in three out of the four risk behaviors (FV, Sed, Fat). The proposed MBC2 trial tests the efficacy of MBC intervention to promote sustained, healthful change in diet and activity at 6 and 12 months, as contrasted with a stress management control condition. MBC2 tests competing hypotheses about the optimal way to increase PA without undermining the maintenance of FV, Sed, and Fat by changing multiple behaviors either sequentially or simultaneously. Furthermore, MBC2 examines mediators and biomarkers of healthy lifestyle change. Community dwelling adults (N=250) with suboptimal diet and inactive lifestyle will be randomized to the following conditions: 1) Sequential MBC (increasing FV intake and decreasing Sed, followed by increasing PA), 2) Simultaneous MBC (increasing FV, decreasing Sed, and increasing PA), or 3) Control (stress management). Participants in all conditions will use Smartphones equipped with customized behavioral decision support tools to self-monitor health behaviors. These handheld devices will be programmed to automatically transmit these data to our study server to be reviewed by a personal behavior coach. Based on theories of self-regulation and habit strength, the Mastery hypothesis predicts superior health behavior change for participants randomized to the sequential condition. It is anticipated that these effects will be mediated by greater habit strength for healthy eating and physical activity. However, based on goal systems theory, the Synergy hypothesis predicts superior health behavior change among participants randomized to the simultaneous condition. It is anticipated that these effects will be mediated by the establishment of superordinate healthy lifestyle goals. The results of the MBC2 trial will assist researchers in understanding the optimal manner in which to facilitate multiple health behavior change in this population. Furthermore, these data will help to identify the mechanisms that underlie healthy change among prevalent risk behaviors. If successful, this trial will also result in an innovative, highly disseminable technology-supported minimal counseling intervention to address the American unhealthy diet and sedentary lifestyle.
BACKGROUND: During inpatient rehabilitation, physical therapists (PTs) often need to manually advance patients' limbs, adding physical burden to PTs and impacting gait retraining quality. Different electromechanical devices alleviate this burden by assisting a patient's limb advancement and supporting their body weight. However, they are less ideal for neuromuscular engagement when patients no longer need body weight support but continue to require assistance with limb advancement as they recover. The objective of this study was to determine the feasibility of using a hip flexion exosuit to aid paretic limb advancement during inpatient rehabilitation post-stroke.
METHODS: Fourteen individuals post-stroke received three to seven 1-hour walking sessions with the exosuit over one to two weeks in addition to standard care of inpatient rehabilitation. The exosuit assistance was either triggered by PTs or based on gait events detected by body-worn sensors. We evaluated clinical (distance, speed) and spatiotemporal (cadence, stride length, swing time symmetry) gait measures with and without exosuit assistance during 2-minute and 10-meter walk tests. Sessions were grouped by the assistance required from the PTs (limb advancement and balance support, balance support only, or none) without exosuit assistance.
RESULTS: PTs successfully operated the exosuit in 97% of sessions, of which 70% assistance timing was PT-triggered to accommodate atypical gait. Exosuit assistance eliminated the need for manual limb advancement from PTs. In sessions with participants requiring limb advancement and balance support, the average distance and cadence during 2-minute walk test increased with exosuit assistance by 2.2 ± 3.1 m and 3.4 ± 1.9 steps/min, respectively (p < 0.017). In sessions with participants requiring balance support only, the average speed during 10-meter walk test increased with exosuit by 0.07 ± 0.12 m/s (p = 0.042). Clinical and spatiotemporal measures of independent ambulators were similar with and without exosuit (p > 0.339).
CONCLUSIONS: We incorporated a unilateral hip flexion exosuit into inpatient stroke rehabilitation in individuals with varying levels of impairments. The exosuit assistance removed the burden of manual limb advancement from the PTs and resulted in improved gait measures in some conditions. Future work will understand how to optimize controller and assistance profiles for this population.
BACKGROUND: Developmental dyslexia, a complex neurodevelopmental disorder, not only affects children's academic performance but is also associated with increased healthcare costs, lower employment rates, and reduced productivity. The pathogenesis of dyslexia remains unclear and it is generally considered to be caused by the overlap of genetic and environmental factors. Systematically exploring the close relationship between exposure to environmental compounds and susceptibility genes in the development of dyslexia is currently lacking but high necessary.
METHODS: In this study, we systematically compiled 131 publicly reported susceptibility genes for dyslexia sourced from DisGeNET, OMIM, and GeneCards databases. Comparative Toxicogenomics Database database was used to explore the overlap between susceptibility genes and 95 environmental compounds, including metals, persistent organic pollutants, polycyclic aromatic hydrocarbons, and pesticides. Chemical bias towards the dyslexia risk genes was taken into account in the observation/expectation ratios > 1 and the corresponding P value obtained by hypergeometric probability test.
RESULTS: Our study found that the number of dyslexia risk genes targeted by each chemical varied from 1 to 109. A total of 35 chemicals were involved in chemical reactions with dyslexia-associated genes, with significant enrichment values (observed/expected dyslexia risk genes) ranging from 1.147 (Atrazine) to 66.901 (Dibenzo(a, h)pyrene).
CONCLUSION: The results indicated that dyslexia-associated genes were implicated in certain chemical reactions. However, these findings are exploratory, and further research involving animal or cellular experiments is needed.
Participants will receive a Fitbit activity monitor and access to the mHealth physical activity intervention for 6 weeks. The intervention will include regular motivational messages to encourage activity, a social media thread to provide social support, and a series of fun virtual walking races.
Warfarin sodium is a racemic mixture of the R\- and S-enantiomers of warfarin. The S-enantiomer exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer in humans, but generally has a more rapid clearance. 

Absorption 

Warfarin is essentially completely absorbed after oral administration, with peak concentration generally attained within the first 4 hours. 

Distribution 

Warfarin shows a volume of distribution of about 0.14 L/kg. Approximately 99% of the drug is bound to plasma proteins. 

Metabolism 

The elimination of warfarin is almost entirely by metabolism. Warfarin is stereoselectively metabolized by hepatic cytochrome P-450 (CYP450) microsomal enzymes to inactive hydroxylated metabolites (predominant route) and by reductases to reduced metabolites (warfarin alcohols) with minimal anticoagulant activity. Identified metabolites of warfarin include dehydrowarfarin, two diastereoisomer alcohols, and 4′-, 6-, 7-, 8-, and 10- hydroxywarfarin. The CYP450 isozymes involved in the metabolism of warfarin include CYP2C9, 2C19, 2C8, 2C18, 1A2, and 3A4. CYP2C9, a polymorphic enzyme, is likely to be the principal form of human liver CYP450 that modulates the in vivo anticoagulant activity of warfarin. Patients with one or more variant CYP2C9 alleles have decreased S-warfarin clearance [see Clinical Pharmacology (12.5)]. 

Excretion 

The terminal half-life of warfarin after a single dose is approximately 1 week; however, the effective half-life ranges from 20 to 60 hours, with a mean of about 40 hours. The clearance of R-warfarin is generally half that of S-warfarin, thus as the volumes of distribution are similar, the half-life of R-warfarin is longer than that of S-warfarin. The half-life of R-warfarin ranges from 37 to 89 hours, while that of S-warfarin ranges from 21 to 43 hours. Studies with radiolabeled drug have demonstrated that up to 92% of the orally administered dose is recovered in urine. Very little warfarin is excreted unchanged in urine. Urinary excretion is in the form of metabolites. 

Geriatric Patients 

Patients 60 years or older appear to exhibit greater than expected INR response to the anticoagulant effects of warfarin. The cause of the increased sensitivity to the anticoagulant effects of warfarin in this age group is unknown but may be due to a combination of pharmacokinetic and pharmacodynamic factors. Limited information suggests there is no difference in the clearance of S-warfarin; however, there may be a slight decrease in the clearance of R-warfarin in the elderly as compared to the young. Therefore, as patient age increases, a lower dose of warfarin is usually required to produce a therapeutic level of anticoagulation [see Dosage and Administration (2.3, 2.4)]. 

Asian Patients 

Asian patients may require lower initiation and maintenance doses of warfarin. A non-controlled study of 151 Chinese outpatients stabilized on warfarin for various indications reported a mean daily warfarin requirement of 3.3 ± 1.4 mg to achieve an INR of 2 to 2.5. Patient age was the most important determinant of warfarin requirement in these patients, with a progressively lower warfarin requirement with increasing age.
FIELD: chemical-pharmaceutical industry. SUBSTANCE: invention relates to liquid composition for oral use. Composition has ondansetron or its pharmaceutically acceptable derivative, sweetening agent and one or some pharmaceutically acceptable excipients. Sweetening agent is one or some polyhydric alcohols and pH value of the composition is at the range from 2.0 to 5.0. Invention describes also the method of use of these compositions for treatment of patients with states mediated with effect of 5-hydroxytryptamine on 5-HT 3 -receptors. EFFECT: quick effect, retained activity and good availability. 12 cl, 5 ex
Membrane transporters are important determinants of drug bioavailability. Their expression and activity affect the intracellular drug concentration in leukemic cells impacting response to therapy. Pharmacogenomics represents genetic markers that reflect allele arrangement of genes encoding drug transporters associated with treatment response. In previous work, we identified SNP rs460089 located in the promotor of SLC22A4 gene encoding imatinib transporter OCTN1 as influential on response of patients with chronic myeloid leukemia treated with imatinib. Patients with rs460089-GC pharmacogenotype had significantly superior response to first-line imatinib treatment compared to patients with rs460089-GG. This study investigated whether pharmacogenotypes of rs460089 are associated with sustainability of treatment-free remission (TFR) in patients from the EUROpean Stop Kinase Inhibitor (EURO-SKI) trial. In the learning sample, 176 patients showed a significantly higher 6-month probability of molecular relapse free survival (MRFS) in patients with GC genotype (73%, 95% CI: 60-82%) compared to patients with GG (51%, 95% CI: 41-61%). Also over time, patients with GC genotype had significantly higher MRFS probabilities compared with patients with GG (HR: 0.474, 95% CI: 0.280-0.802, p = 0.0054). Both results were validated with data on 93 patients from the Polish STOP imatinib study. In multiple regression models, in addition to the investigated genotype, duration of TKI therapy (EURO-SKI trial) and duration of deep molecular response (Polish study) were identified as independent prognostic factors. The SNP rs460089 was found as an independent predictor of TFR.
During Cohort 1, participants will receive a single dose of GSK2330811 100 mg by SC injection via needle and syringe in to the abdomen, thigh or upper arm by the investigator or designee at every other week from D1 to D71 (total 6 doses) for 10 weeks. Participants will be followed-up up to W28 D197.
Participants assigned to the M-DMT group condition will receive care as usual plus 12 weekly 90-minute group M-DMT sessions delivered online by a board-certified dance/movement therapist. The therapist is instructed to follow the M-DMT manualized protocol.
Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous disease with distinct molecular subtypes described as classical/progenitor and basal-like/squamous PDAC. We hypothesized that integrative transcriptome and metabolome approaches can identify candidate genes whose inactivation contributes to the development of the aggressive basal-like/squamous subtype. Using our integrated approach, we identified endosome-lysosome associated apoptosis and autophagy regulator 1 (ELAPOR1/KIAA1324) as a candidate tumor suppressor in both our NCI-UMD-German cohort and additional validation cohorts. Diminished ELAPOR1 expression was linked to high histological grade, advanced disease stage, the basal-like/squamous subtype, and reduced patient survival in PDAC. In vitro experiments demonstrated that ELAPOR1 transgene expression not only inhibited the migration and invasion of PDAC cells but also induced gene expression characteristics associated with the classical/progenitor subtype. Metabolome analysis of patient tumors and PDAC cells revealed a metabolic program associated with both upregulated ELAPOR1 and the classical/progenitor subtype, encompassing upregulated lipogenesis and downregulated amino acid metabolism. 1-Methylnicotinamide, a known oncometabolite derived from S-adenosylmethionine, was inversely associated with ELAPOR1 expression and promoted migration and invasion of PDAC cells in vitro. Taken together, our data suggest that enhanced ELAPOR1 expression promotes transcriptome and metabolome characteristics that are indicative of the classical/progenitor subtype, whereas its reduction associates with basal-like/squamous tumors with increased disease aggressiveness in PDAC patients. These findings position ELAPOR1 as a promising candidate for diagnostic and therapeutic targeting in PDAC.
During double-blind treatment, participants receive olanzapine at a dose of 5 milligram (mg) which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.
For the comparison condition, after the baseline assessment, parents will receive a handbook on nutrition and physical activity entitled: "Healthy Eating \& Physical Activity Across Your Lifespan: Helping your Child - Tips for Parents". This handbook, which is adapted from the handbook developed by the National Institute of Diabetes and Digestive and Kidney Diseases and the Weight Control Information Network, is approximately the same length as the intervention handbook and is available in English and Spanish. It is given with an insert on reducing weight talk and weight teasing in the family. Parents will also receive a magnet with a message about nutrition and exercise. To control for contact time, these participants will meet live with a study staff member two weeks after receiving the handbook, complete an action plan, and have the 30-minute call, as well as receive two text messages twice per week for 13 weeks with tips and reminders from the comparison handbook and insert.
A vaccine utilizing purified mutant alpha toxins from Clostridium septicum for humans and animals against infections caused by C. septicum. Persons potentially affected by C. septicum infections include colonic cancer patients, diabetics, leukemia patients, and neutropenics. The alpha toxin mutant of the vaccine lacks the toxicity of a native C. septicum alpha toxin. A serum comprising antibodies raised to the alpha toxin mutant is also available for treating humans or animals against C. septicum infections. The serum may be used in a method for conferring passive immunity against C. septicum. Antibodies to the alpha toxin mutant may be used in diagnostic tests or in treatments to clear alpha toxin from bodily fluids. The mutant alpha toxin may be produced by recombinant methods using cDNA encoding the toxin, the cDNA contained for example in a plasmid or host cell.
1. Technical Result Prevention of cracks formation in valaciclovir tablets.         2. Essence A tablet comprising valaciclovir or the salts thereof in the form of granules, colloidal silicon dioxide, a filler and a lubricant; at least small part of the colloidal silicon dioxide, the filler and the lubricant are present extragranularly. These tablets are used for treatment of viral infections.          3. Field of Application Medicine.
The present invention belongs to the technical field of immunotherapy. A method of using dimethylarginine derivatives to inhibit the proliferation of lymphocyte. ADMA, SDMA, and their derivative DMGV can inhibit T cells and/or B cells proliferation in vitro by inducing mitochondrial ROS. ADMA and SDMA can induce mitochondrial ROS generation by the action of alanine-glyoxylate aminotransferase 2 (AGXT2), which converts both ADMA and SDMA into dimethylguanidino valeric acid (DMGV) in the mitochondria. The dimethylarginine dimethylamino hydrolase (DDAH) inhibitor PD404182 also inhibits T cell proliferation by allowing more ADMA and SDMA to be converted to DMGV. As a clinical relevance, DMGV effectively treated arthritis in mice which was caused by activated T cells.
BACKGROUND: The therapeutic potential of adipose-derived mesenchymal stromal cells (AMSCs) in the treatment of intestinal fibrosis occured in patients with Crohn's disease (CD) remains unclear. Tumor necrosis factor-stimulated gene 6 (TSG6) protein plays a critical role in inflammation regulation and tissue repair. This study aimed to determine if AMSCs attenuate intestinal fibrosis by secreting paracrine TSG6 protein and explore the underlying mechanisms.
METHODS: Two murine models for intestinal fibrosis were established using 2,4,6-trinitrobenzene sulfonic acid in BALB/c mice and dextran sulfate sodium in C57BL/6 mice. Primary human fibroblasts and CCD-18co cells were incubated with transforming growth factor (TGF)-β1 to build two fibrosis cell models in vitro.
RESULTS: Intraperitoneally administered AMSCs attenuated intestinal fibrosis in the two murine models, as evidenced by significant alleviation of colon shortening, collagen protein deposits, and submucosal thickening, and also decrease in the endoscopic and fibrosis scores (P < 0.001). Although intraperitoneally injected AMSCs did not migrate to the colon lesions, high levels of TSG6 expression and secretion were noticed both in vivo and in vitro. Similar to the role of AMSCs, injection of recombinant human TSG6 attenuated intestinal fibrosis in the mouse models, which was not observed with the administration of AMSCs with TSG6 knockdown or TSG6 neutralizing antibody. Mechanistically, TSG6 alleviates TGF-β1-stimulated upregulation of α-smooth muscle actin (αSMA) and collagen I by inhibiting Smad2 phosphorylation. Furthermore, the expression of TSG6 is lower in intestinal fibrosis tissue of patients with Crohn's disease and can reduce pro-fibrotic protein (αSMA) secretion from primary ileal fibrotic tissue.
CONCLUSIONS: AMSCs attenuate intestinal fibrosis by secreting paracrine TSG6 protein, which inhibits Smad2 phosphorylation. TSG6, a novel anti-fibrotic factor, could potentially improve intestinal fibrosis treatments.
The specific aim of this project is to test the hypothesis that BRCA1 haploinsufficiency regulates gene expression on the X chromosome. This hypothesis will be examined by determining if X chromosome gene expression profiles, derived from lymphocyte RNA, of BRCA1 mutation carriers (cases) can be distinguished from an age-matched group of women who do not have BRCA1 mutations (controls). Neither cases nor controls will have a history of cancer. This investigation will provide valuable insight into the biologic function of BRCA1 and its role in breast and/or ovarian tumorigenesis. Blood samples from cases will be collected from patients who have previously undergone genetic counseling through the Clinical Genetics Service at MSKCC and tested positive for a germline mutation in BRCA1. Blood samples from controls will be obtained from two sources.

First from specimens already collected under IRB Protocol #99-030, entitled "Collection of Tissue, Blood, and Cells to be Used for Studying the Causes, Prevention, Diagnosis, and Treatment of Breast Cancer (T. King, PI). Controls will also be collected from patients who have previously undergone genetic counseling through the Clinical Genetics Service at MSKCC and tested negative for germline mutations in BRCA1. Isolation of total RNA from blood will be performed using the PAXgene™ Blood RNA System. This study will use lymphocyte RNA samples from 50 individuals with BRCA1 mutations and 50 age-matched controls. Gene expression profiling will be performed in the Genomics Core Laboratory of MSKCC under the supervision of Agnes Viale, PhD. Class comparison analysis will be performed on the gene expression data in the Biostatistics Department under the supervision of Adam Olshen, PhD. It is anticipated that this study will be completed in approximately 1 year.
All patients in the study receive the same treatment. All will have 2 polar body biopsies and all embryos biopsied prior to transfer.