anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
AIMS: Cardiac involvement is common in patients hospitalized with COVID-19 and correlates with an adverse disease trajectory. While cardiac injury has been attributed to direct viral cytotoxicity, serum-induced cardiotoxicity secondary to serological hyperinflammation constitutes a potentially amenable mechanism that remains largely unexplored.
METHODS AND RESULTS: To investigate serological drivers of cardiotoxicity in COVID-19 we have established a robust bioassay that assessed the effects of serum from COVID-19 confirmed patients on human embryonic stem cell (hESC)-derived cardiomyocytes. We demonstrate that serum from COVID-19 positive patients significantly reduced cardiomyocyte viability independent of viral transduction, an effect that was also seen in non-COVID-19 acute respiratory distress syndrome (ARDS). Serum from patients with greater disease severity led to worse cardiomyocyte viability and this significantly correlated with levels of key inflammatory cytokines, including IL-6, TNF-α, IL1-β, IL-10, CRP, and neutrophil to lymphocyte ratio with a specific reduction of CD4+ and CD8+ cells. Combinatorial blockade of IL-6 and TNF-α partly rescued the phenotype and preserved cardiomyocyte viability and function. Bulk RNA sequencing of serum-treated cardiomyocytes elucidated specific pathways involved in the COVID-19 response impacting cardiomyocyte viability, structure, and function. The observed effects of serum-induced cytotoxicity were cell-type selective as serum exposure did not adversely affect microvascular endothelial cell viability but resulted in endothelial activation and a procoagulant state.
CONCLUSION: These results provide direct evidence that inflammatory cytokines are at least in part responsible for the cardiovascular damage seen in COVID-19 and characterise the downstream activated pathways in human cardiomyocytes. The serum signature of patients with severe disease indicates possible targets for therapeutic intervention.
Children and adults (10 - 45 years old) with PKU attending the metabolic medicine clinics in the area of National Health Services (NHS) Greater Glasgow and Clyde (GGC) will be approached for recruitment. Participants will be free from history of acute and chronic illness (other than PKU) requiring regular appointments to the doctor and/or chronic use of medication or major gastrointestinal surgery where major part of the gut has been resected as these conditions are known to impact on energy expenditure and dietary intake. Pregnant or lactating women will also be excluded from participation. People with learning or mobility difficulties or those with incapacity to provide informed consent will be excluded too. The clinical treatment team will evaluate patients' capacity to consent before considering them to participate in the study.
Do not start WELLBUTRIN SR in a patient who is being treated with a reversible MAOI such as linezolid or intravenous methylene blue. Drug interactions can increase the risk of hypertensive reactions. In a patient who requires more urgent treatment of a psychiatric condition, non-pharmacological interventions, including hospitalization, should be considered [see Contraindications (4), Drug Interactions (7.6)].

In some cases, a patient already receiving therapy with WELLBUTRIN SR may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of hypertensive reactions in a particular patient, WELLBUTRIN SR should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with WELLBUTRIN SR may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue.

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with WELLBUTRIN SR is unclear. The clinician should, nevertheless, be aware of the possibility of a drug interaction with such use [see Contraindications (4), Drug Interactions (7.6)].
Subjects with moderately severe to severe aortic stenosis (AS), left ventricular hypertrophy (LVH), diastolic dysfunction, preserved ejection fraction, and no planned aortic valve replacement over the next 6 months will be eligible for this randomized, double-blind, placebo-controlled, pilot study. There will be a diabetic cohort (n=32) and non-diabetic cohort (n=24); each cohort will be randomized 1:1 to tadalafil vs. placebo. During a baseline study visit, the following will be obtained: clinical data, 6 minute walk, quality of life questionnaire, blood draw, and an echocardiogram. A 3-day run-in will occur to initially assess tolerability and compliance. If the drug is tolerated during this run-in period, participants will be randomized. An MRI will also be performed during this randomization visit. Follow-up study visits and testing will occur at 6 and 12 weeks and 6 months.
Participants in this arm receive both standard DC Quitline Support and Mobile EX cessation support. Mobile EX cessation support is designed to enhance the Washington D.C. Quitline (DCQL) by giving participants the ability track their cessation attempt on a phone-based app and thus create a profile documenting their progress and set-backs over the days or weeks in between QL contacts. Participants receive summary information and graphics that help them understand what is working best for them. Participants also receive 24-hr, momentary access to a set of interactive cessation tools on their phone.
FIELD: medicine, more particularly stomatologic agents. SUBSTANCE: agent for care of mouth cavity comprises bisphosphonate as active ingredient and physiologically acceptable substrate which determines form of final agent. Said agent further comprises phosphonfumoric acid or salt thereof as second active ingredient components being used in certain ratios. Said agent has high medicinal effect and is stable during storage period and includes no additional preserving agents. EFFECT: improved properties of the agent for care of mouth cavity. 2 tbl
After successful endoscopic hemostasis, the patients are given an 80-mg i.v. omeprazole bolus. The OB group receives a 40-mg i.v. bolus of OME every 12 h.
Subjects will receive oral doses of sobetirome. All subjects will start with a 50 mcg dose, once-daily for 14 days. If this dose proves safe and well tolerated, subjects will receive a 100 mcg dose once-daily for an additional 14 days.
To expand the empirical evidence for the effectiveness of Smart Parents and to explore the implementation factors that might promote or hinder adoption, fidelity, and scalability, the proposed study uses a type 2 hybrid effectiveness-implementation design. Designed to efficiently bridge the research to practice gap, the type 2 hybrid design tests the effectiveness of an intervention while concurrently exploring the viability of an explicit implementation strategy in a real world setting. To determine effectiveness (Aims 1 \& 2), the investigators will conduct a pragmatic, quasi-experimental, stepped wedge cluster randomized trial (SW-CRT; N = 400) of CSA-related awareness (i.e., knowledge and attitudes about CSA and CSA prevention) and intention to use CSA protective behaviors for parents receiving Smart Parents when added to PAT (PAT+Smart Parents) compared to parents receiving PAT treatment as usual (PAT-TAU; Aim 1). The investigators will follow-up participating parents in both conditions at 12- and 24-months to determine retention of awareness (i.e., knowledge and attitudes) and actual use of protective behaviors (Aim 2).

A variation of a crossover experimental design, the SW-CRT is a pragmatic experimental design wherein randomized clusters sequentially transition from control to intervention until all clusters are exposed to the intervention. Once introduced to a cluster, the intervention is never removed. Facilitated by PAT National, 25 PAT sites will be recruited at the start of the study period. Sites will then be randomized into 1 of 5 clustered sequences (or steps) each containing 5 sites (or clusters). At the time on randomization, providers at all sites will begin recruiting eligible parents for participation in research and parents will begin the data collection protocols. At the point of the wedge, sites will be trained to deliver Smart Parents and will transition from control (PAT+TAU) to intervention (PAT+Smart Parents) conditions, the timing of which will be determined by the randomized step assignment.
Dual antiplatelet therapy (DAPT) with ticagrelor or adjusted-dose prasugrel has been used for acute coronary syndrome (ACS). However, few studies have directly compared these two drugs. In this study, we compared the real-world applications and outcomes of these two drugs in patients with ACS who had undergone percutaneous coronary intervention (PCI). This retrospective cohort study was conducted using the data of eligible patients with ACS who had undergone PCI at Chang Gung Memorial Hospital System between June 2019 and December 2021. The primary efficacy-related outcome was the occurrence of major adverse cardiovascular events (MACEs), and the primary safety-related outcome was major bleeding. Inverse probability of treatment weighting based on propensity score was performed to reduce confounding effects. The study included 2,636 patients; of them, 429 received prasugrel and 2,207 received ticagrelor. No significant between-group difference was observed in the risk of MACE (13.1 vs. 13.1 events per 100 person-years, respectively, hazard ratio (HR): 1.01, 95% confidence interval (CI): 0.71-1.43). Both groups exhibited similar rates of major bleeding (3.9 vs. 4.1 events per 100 person-years, respectively, subdistribution HR: 0.96, 95% CI: 0.68-1.35). In real-world settings, adjusted-dose prasugrel and ticagrelor exhibit comparable safety and efficacy profiles in East Asian patients with ACS after PCI. Our findings offer valuable insights for future clinical decision making and patient management strategies.
Concomitant use of opioids, including OBREDON, with benzodiazepines, or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Because of these risks, avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol [ see Drug Interactions ( 7.1, 7.4) ]. 

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. Because of similar pharmacologic properties, it is reasonable to expect similar risk with concomitant use of opioid cough medications and benzodiazepines, other CNS depressants, or alcohol.

Advise both patients and caregivers about the risks of respiratory depression and sedation if OBREDON is used with benzodiazepines, alcohol, or other CNS depressants [ see Patient Counseling Information ( 17) ]. 

Patients must not consume alcoholic beverages, or prescription or non-prescription products containing alcohol, while on OBREDON therapy. The co-ingestion of alcohol with OBREDON may result in increased plasma levels and a potentially fatal overdose of hydrocodone [ see Drug Interactions ( 7.1) ].​
The patient will be trained only skills and discharge education. The patient will be follow up at 2nd, 6th and 12th weeks.
The invention relates to the technical field of nanometer, in particular to an L-ascorbyl palmitate modified small molecule peptide liposome and preparation and application thereof, and solves the problem of poor absorption of small molecule peptide at the present stage. The L-ascorbyl palmitate modified small molecule peptide liposome comprises small molecule peptide, L-ascorbyl palmitate and soybean lecithin, and does not contain cholesterol. The L-ascorbyl palmitate modified small molecule peptide liposome is obtained by gradient decompression spin evaporation film formation and circulating low temperature ultrasonic-high speed centrifugation. The method is simple to operate, and the prepared liposome has small particle size (less than 120 nm). The soybean lecithin can encapsulate the hydrophilic small molecular peptide in the hydrophilic inner core, so that the degradation of the small molecular peptide by intestinal environment and digestive enzymes is reduced. Meanwhile, the L-ascorbyl palmitate is embedded on the surface of soybean lecithin, so that sodium-dependent vitamin C transporter 1 can be targeted, and the absorption of small intestinal cells to small molecular peptides is obviously improved.
Methimazole 15-30mg daily initially, then titrate to maintenance dose. Beta-blocker used when necessary.
###  Carcinogenesis

Long-term carcinogenicity studies in mice and rats were carried out with nevirapine. Mice were dosed with 0, 50, 375, or 750 mg/kg/day for two years. Hepatocellular adenomas and carcinomas were increased at all doses in males and at the two high doses in females. In studies in which rats were administered nevirapine at doses of 0, 3.5, 17.5, or 35 mg/kg/day for two years, an increase in hepatocellular adenomas was seen in males at all doses and in females at the high dose. The systemic exposure (based on AUCs) at all doses in the two animal studies was lower than that measured in humans at the 200 mg twice daily dose. The mechanism of the carcinogenic potential is unknown.

###  Mutagenesis

However, in genetic toxicology assays, nevirapine showed no evidence of mutagenic or clastogenic activity in a battery of in vitro and in vivo studies. These included microbial assays for gene mutation (Ames: Salmonella strains and E. coli), mammalian cell gene mutation assay (CHO/HGPRT), cytogenetic assays using a Chinese hamster ovary cell line and a mouse bone marrow micronucleus assay following oral administration. Given the lack of genotoxic activity of nevirapine, the relevance to humans of hepatocellular neoplasms in nevirapine-treated mice and rats is not known. 

###  Impairment of Fertility

In reproductive toxicology studies, evidence of impaired fertility was seen in female rats at doses providing systemic exposure, based on AUC, approximately equivalent to that provided with the recommended clinical dose of nevirapine.
Questionnaires and scales will be filled out by the researcher 5 minutes before vaccination. Only routine applications will be made. The scales will be filled again 5 minutes after vaccination.
Disclosed herein are multimeric molecular complexes and compounds that are multivalent, i.e., they have two or more targeting elements directed to a ligand that confers paracellular transporting properties and/or transcytotic properties to complexes and compounds to which it is bound. The complexes and compounds have properties that are different from the properties of monomers, complexes and compounds having only one targeting element directed to a paracellular and/or transcytotic ligand. The complexes and compounds of the invention undergo endocytosis, transcytosis and exocytosis; following endocytosis, the complexes or compounds may be transported into the cytosol or an organelle of a cell. In polarized cells, transcytosis can proceed in a “forward” or “reverse” direction. Reverse transcytosis is used for the non-invasive delivery of biologically active agents from the lumen of, e.g., the gastrointestinal tract or the airways of lungs, to the circulatory system. The complexes and compounds are incorporated in various compositions and medical devices suitable for medicinal or veterinary use.
PURPOSE: An external use skin composition containing Arenaria kansuensis Maxim. fermentation is provided to improve antioxdiation, anti-wrinkling, whitening, and moisturizing effects and to promoter collagen synthesis. CONSTITUTION: An external use skin composition contains Arenaria kansuensis Maxim. fermentation as an active ingredient. A method for preparing the fermentation comprises: a step of preparing Arenaria kansuensis Maxim.extract; a step of mixing the extract and Grifolafrondosa (KCTC 10337BP) mycelium or culture liquid of the mycelium and culturing the mixture; and a step of removing the mycelium from the culture liquid and collecting filtered liquid. The composition contains 0.001-30.0 wt% of the filtered liquid. An extraction solvent is 85-99%(v/v) ethanol. The composition is used for skin whitening, anti-aging, skin irritation relieving, atopic dermatitis treatment, or acne prevention.
INTRODUCTION: A stoma will cause nutrients loss which could result in impaired growth. Impaired growth can negatively impact long-term development. This study aims to evaluate: (1) the effect of stomas on growth comparing small bowel stoma versus colostomy and (2) if early closure (within 6 weeks), proximal small bowel stoma (within 50 cm of Treitz), major small bowel resection (≥ 30 cm), or adequate sodium supplementation (urinary level ≤ 30 mmol/L) influences growth.
METHODS: Young children (≤ 3 years) treated with stomas between 1998 and 2018 were retrospectively identified. Growth was measured with weight-for-age Z-scores. Malnourishment was defined using the World Health Organization's definition. Comparison between changes in Z-scores at creation, closure, and a year following closure was done by Friedman's test with post hoc Wilcoxon's signed rank test or Wilcoxon's rank-sum test when necessary.
RESULTS: In the presence of a stoma in 172 children, 61% showed growth decline. Severe malnourishment was seen at the time of stoma closure in 51% of the patients treated by small bowel stoma and 16% of those treated by colostomy. Within a year following stoma closure, 67% showed a positive growth trend. Having a proximal small bowel stoma and undergoing major small bowel resection led to significantly lower Z-scores at closure. Adequate sodium supplementation and early closure did not lead to significant changes in Z-scores.
CONCLUSION: Stomas have a negative impact on growth in the majority of children. This impact might be decreased by preventing small bowel stomas when possible, specifically proximal stomas, and limiting small bowel resection. Since stoma closure is essential in reversing the negative effect on growth, we opt that early closure might result in an early shift to catch-up growth.
Adolescents will receive 16h of training (2h healthy lifestyle training, social marketing and communication, 6h to design activities, 2h session together with all intervention high-schools, 6h to practice and standardize activities) and 4h (1h/activity) to implement 4 activities in schools. The scholars will receive 4 activities designed by adolescents, focusing on: 1) increasing fruit consumption, 2) increasing vegetable consumption, 3) increasing physical activity practice and to reduce sedentary lifestyles and, 4) decreasing sugary drinks and fast-food consumption.
OBJECTIVE: Primary antiphospholipid syndrome (PAPS) is a rare autoimmune disease characterized by the presence of antiphospholipid antibodies and the occurrence of thrombotic events and pregnancy complications. Our study aimed to identify novel genetic susceptibility loci associated with PAPS.
METHODS: We performed a genome-wide association study comprising 5,485 individuals (482 affected individuals) of European ancestry. Significant and suggestive independent variants from a meta-analysis of approximately 7 million variants were evaluated for functional and biological process enrichment. The genetic risk variability for PAPS in different populations was also assessed. Hierarchical clustering, Mahalanobis distance, and Dirichlet Process Mixtures with uncertainty clustering methods were used to assess genetic similarities between PAPS and other immune-mediated diseases.
RESULTS: We revealed genetic associations with PAPS in a regulatory locus within the HLA class II region near HLA-DRA and in STAT1-STAT4 with a genome-wide level of significance; 34 additional suggestive genetic susceptibility loci for PAPS were also identified. The disease risk allele near HLA-DRA is associated with overexpression of HLA-DRB6, HLA-DRB9, HLA-DQA2, and HLA-DQB2 in immune cells, vascular tissue, and nervous tissue. This association is independent of the association between PAPS and HLA-DRB1*1302. Functional analyses highlighted immune-related pathways in PAPS-associated loci. The comparison with other immune-mediated diseases revealed a close genetic relatedness to neuromyelitis optica, systemic sclerosis, and Sjögren syndrome, suggesting co-localized causal variations close to STAT1-STAT4, TNPO3, and BLK.
CONCLUSION: This study represents a comprehensive large-scale genetic analysis for PAPS and provides new insights into the genetic basis and pathophysiology of this rare disease.
Cilostazol Tablets, USP is absorbed after oral administration. A high fat meal increases absorption, with an approximately 90% increase in Cmax and a 25% increase in AUC. Absolute bioavailability is not known. Cilostazol is extensively metabolized by hepatic cytochrome   
P-450 enzymes, mainly 3A4, and, to a lesser extent, 2C19, with metabolites largely excreted in urine. Two metabolites are active, with one metabolite appearing to account for at least 50% of the pharmacologic (PDE III inhibition) activity after administration of Cilostazol Tablets, USP. Pharmacokinetics are approximately dose proportional. Cilostazol and its active metabolites have apparent elimination half-lives of about 11 to 13 hours. Cilostazol and its active metabolites accumulate about 2-fold with chronic administration and reach steady state blood levels within a few days. The pharmacokinetics of cilostazol and its two major active metabolites were similar in healthy normal subjects and patients with intermittent claudication due to peripheral arterial disease (PAD).

The mean ± SEM plasma concentration-time profile at steady state after multiple dosing of Cilostazol Tablets, USP 100 mg b.i.d. is shown below:

Plasma Concentration Time profile
An important goal in the opioid field is to discover effective analgesic drugs with minimal side effects. MCRT demonstrated potent antinociceptive effects with limited side effects, making it a promising candidate. However, its pharmacological properties and how it minimizes side effects remain unknown. Various mouse pain and opioid side effect models were used to evaluate the antinociceptive properties and safety at the spinal level. The targets of MCRT were identified through cAMP measurement, isolated tissue assays, and pharmacological experiments. Immunofluorescence was employed to visualize protein expression. MCRT displayed distinct antinociceptive effects between acute and chronic inflammatory pain models due to its multifunctional properties at the μ opioid receptor (MOR), µ-δ heterodimer (MDOR), and neuropeptide FF receptor 2 (NPFFR2). Activation of NPFFR2 reduced MOR-mediated antinociception, leading to bell-shaped response curves in acute pain models. However, activation of MDOR produced more effective antinociception in chronic inflammatory pain models. MCRT showed limited tolerance and opioid-induced hyperalgesia in both acute and chronic pain models and did not develop cross-tolerance to morphine. Additionally, MCRT did not exhibit addictive properties, gastrointestinal inhibition, and effects on motor coordination. Mechanistically, peripheral chronic inflammation or repeated administration of morphine and MCRT induced an increase in MDOR in the spinal cord. Chronic administration of MCRT had no apparent effect on microglial activation in the spinal cord. These findings suggest that MCRT is a versatile compound that provides potent antinociception with minimal opioid-related side effects. MDOR could be a promising target for managing chronic inflammatory pain and addressing the opioid crisis.