anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Online weight loss programs have ambiguous efficacy. There is a growing body of evidence that weight loss programs when combined with apps have better outcomes; however, many apps lack an evidence-based approach to dietary changes for weight loss and do not rely on a theoretical framework for behavior change.
OBJECTIVE: This study aimed to describe the development and the preliminary usability and acceptability testing of a web app that uses behavior change techniques (BCTs) to support users of a comprehensive online weight loss program.
METHODS: The weight loss program intervention components were nutrient and weight tracking charts that needed a remotely accessible and online format. The app was designed by nutrition researchers and developers in a collaborative effort. A review of BCTs in weight loss and web apps was performed as well as an assessment of user needs to inform the initial prototype. A preliminary app prototype, version 1.0, was provided to participants of a weight loss trial (N=30) to assess for feasibility of its use. A full app prototype, version 2.0, was feasibility and acceptability tested by trial participants (n=11) with formal feedback by Likert-scale survey and open-ended questions. In the final round of testing, a user group of scientists and developers (n=11) was selected to provide a structured 3-month review through which the group met weekly for collective feedback sessions.
RESULTS: The process resulted in a fully developed web app, MealPlot, by the Applied Research Institute, for meal planning and weight tracking that can be used by weight loss users and health professionals to track their patients. MealPlot includes a weight chart, a protein-fiber chart, and a chat feature. In addition, MealPlot has 2 distinct platforms, 1 for weight loss users and 1 for health professionals. Selected BCTs for incorporation into the app were goal setting, feedback, problem-solving, self-monitoring, and social support. Version 1.0 was used successfully to provide a functioning, online weight chart over the course of a 1-year trial. Version 2.0 provided a functional weight chart and meal planning page, but 8 out of 11 participants indicated MealPlot was difficult to use. Version 3.0 was developed based on feedback and strategies provided from user group testing.
CONCLUSIONS: The web app, MealPlot, was developed to improve outcomes and functionality of an online weight loss program by providing a remote method of tracking weight, food intake, and connecting users to health professionals for consistent guidance that is not otherwise available in a traditional in-person health care setting. The final version 3.0 of the web app will be refined based on findings of a review study gathering feedback from health professionals and from actual weight loss users who are part of a clinical weight loss trial.
Losartan inhibits the pressor effect of angiotensin II (as well as angiotensin I) infusions. A dose of 100 mg inhibits the pressor effect by about 85% at peak with 25-40% inhibition persisting for 24 hours. Removal of the negative feedback of angiotensin II causes a doubling to tripling in plasma renin activity and consequent rise in angiotensin II plasma concentration in hypertensive patients. Losartan does not affect the response to bradykinin, whereas ACE inhibitors increase the response to bradykinin. Aldosterone plasma concentrations fall following losartan administration. In spite of the effect of losartan on aldosterone secretion, very little effect on serum potassium was observed.

The effect of losartan is substantially present within one week but in some studies the maximal effect occurred in 3 to 6 weeks. In long-term follow-up studies (without placebo control) the effect of losartan appeared to be maintained for up to a year. There is no apparent rebound effect after abrupt withdrawal of losartan. There was essentially no change in average heart rate in losartan-treated patients in controlled trials.
Experimental: Intervention group "Yönetebilirim" Before the initiation of the program, patients who visit the outpatient clinic will be evaluated according to the inclusion-exclusion criteria, their consent will be obtained, and pre-tests will be administered. Then, randomization will be performed and participants will be assigned to the experimental and control groups. Participants in the experimental group will be registered on the web-based program. The individuals in the experimental group will use "Yönetebilirim" for 8 weeks as of the time the program is put into use. "Yönetebilirim" consists of modules and consultancy services. Participants will be able to watch informative videos as much as they want for 8 weeks and receive consultancy service if they wish.
The stimulant methylphenidate (MPH) is the most commonly prescribed psychoactive medication in children. An abundance of studies attest to the efficacy of MPH for attenuating inattentive, hyperactive, and impulsive symptoms in children with ADHD. Despite its efficacy, most children with ADHD who are prescribed MPH have poor continuity of treatment for a variety of reasons, including forgetting to administer the medication and delays obtaining refills. In addition, it is an accepted clinical practice for physicians to omit MPH for periods of time, such as during the summer or on weekends (i.e., drug holidays). Since MPH discontinuation is considered to be benign, many clinicians do not employ any special procedures or inform families of any special precautions in regard to its cessation. However, increasing evidence suggests that the pharmacological effects of MPH cause lasting changes in brain neurochemistry that persist beyond medication discontinuation. Moreover, these neurobiological effects of discontinuation appear to have neurobehavioral consequences. There is a critical need to better understand the breadth and magnitude of the neurobehavioral effects caused by MPH discontinuation as well as to better understand the temporal trajectory of these deleterious effects. Hence, the primary goal of the proposed research is to conduct the first randomized, double-blind, placebo-controlled trial specifically designed to study the negative effects of MPH discontinuation at multiple time points. 180 children diagnosed with ADHD will participate across two recruitment sites. After undergoing a 4-week MPH titration trial and 4-week MPH maintenance phase, participants will be randomized to either discontinue MPH (and receive placebo) OR remain on MPH for 4 weeks. Comprehensive multi-time point, multi-informant (parents, teachers, study staff) and multi-modal (behavior/mood/affect ratings scales, direct behavior observations, standardized testing) assessments will be used to assess a broad range of neurobehavioral outcomes. We will examine the magnitude and time course of effects of MPH discontinuation on behavioral as well as cognitive and academic functioning in children with ADHD. Furthermore, we will examine moderators of the adverse effects of MPH discontinuation on these outcomes to aid in the identification of those who are at increased risk.
The present invention relates to stereocomplex hydrogels for drug delivery and tissue engineering. The hydrogels comprise block or graft polymers with at least one hydrophilic region and at least two enantiomerically enriched degradable regions, which may represent grafts or terminal blocks. In the hydrogels, degradable regions of opposite chirality form racemic crystallites, leading to the physical crosslinking of the polymers. Furthermore, the significance of the terminal groups of the degradable blocks for the degradability of the hydrogel is disclosed. Hydrogels from polymers whose degradable regions are characterised by the absence of terminal hydroxyl groups are shown to be particularly stable, having long lifetimes and a high potential for sustained drug release over extended periods such as weeks or months. In other aspects, the invention provides methods for the preparation of hydrogel compositions, kits from which the hydrogels can be prepared, and uses of the hydrogels.
The present invention relates to a composition comprising a pharmaceutically active ingredient susceptible to or having abuse potential. The present invention provides an oral pharmaceutical composition comprising a first population of beads and a second population of beads. The first population of beads comprises a pharmaceutically active ingredient that is susceptible to, or has the potential to, abuse. The second bead population comprises a gelling agent and a coating substantially surrounding the gelling agent, but does not contain a pharmaceutically active ingredient. The first bead population and the second bead population are physically separable, but visually indistinguishable to the naked eye. Upon entry of water into the second bead population, the gelling agent is caused to swell, forming a viscous substance that impedes or prevents extraction of the active ingredient.
OBJECTIVE: Erythropoietin-producing hepatocellular (Eph)/Ephrin cell-cell signaling is emerging as a key player in tissue fibrogenesis. The aim of this study was to test the hypothesis that the receptor tyrosine kinase EphB2 mediates dermal fibrosis in systemic sclerosis (SSc).
METHODS: We assessed normal and SSc human skin biopsies for EphB2 expression. The in vivo role of EphB2 in skin fibrosis was investigated by subjecting EphB2-knockout mice to both bleomycin-induced and tight skin (Tsk1/+) genetic mouse models of skin fibrosis. EphB2 kinase-dead and overactive point mutant mice were used to evaluate the role of EphB2 forward signaling in bleomycin-induced dermal fibrosis. In vitro studies were performed on dermal fibroblasts from patients with SSc and healthy controls, which was followed by in vivo analysis of fibroblast-specific Ephb2-deficient mice.
RESULTS: Expression of EphB2 is up-regulated in SSc skin tissue and explanted SSc dermal fibroblasts compared with healthy controls. EphB2 expression is elevated in two animal models of dermal fibrosis. In mice, EphB2 drives dermal fibrosis in both the bleomycin and the Tsk1/+ models of skin fibrosis. EphB2 forward signaling is a critical mediator of dermal fibrosis. Transforming growth factor-β (TGF-β) cytokines up-regulate EphB2 in dermal fibroblasts via noncanonical TGF-β/mother against decapentaplegic signaling, and silencing EPHB2 in human dermal fibroblasts is sufficient to dampen TGF-β-induced fibroblast-to-myofibroblast differentiation. Moreover, mice with fibroblast-specific deletion of EphB2 showed impaired fibroblast-to-myofibroblast differentiation and reduced skin fibrosis upon bleomycin challenge.
CONCLUSION: Our data implicate TGF-β regulation of EphB2 overexpression and kinase-mediated forward signaling in the development of dermal fibrosis in SSc. EphB2 thus represents a potential new therapeutic target for SSc.
Comorbid epilepsy and challenging behaviours is quiet common in patients with ID (intellectual disability). This study aims to determine the frequency and mutual association between epilepsy and challenging behaviours. In this cross-sectional analytical study, 252 patients were enrolled through convenient sampling technique. Comorbid epilepsy and CB (challenging behaviour) were seen in 111 (44.6%) and 116 (46.6%) patients, respectively. Epilepsy and severity of intellectual disability (ID) are statistically and significantly associated with challenging behaviour. This study concluded that comorbid epilepsy is more common among people with ID as compared to the general population. The clinical variables, i.e. comorbid epilepsy and severity of ID have statistically significant association with the CB.
The present invention relates to a chemical and pharmaceutical technology, and in particular to a STAT3 and ERK signal pathway inhibitor and a use thereof. On the one hand, provided is a STAT3 and ERK signal pathway inhibitor. The inhibitor mainly consists of a mogroside and/or an analogue thereof. The mogroside and the analogue thereof inhibit the phosphorylation of a transcription factor STAT3 and inhibit the phosphorylation of an ERK. In the method for preparing the mogroside and the analogue thereof, a high-purity target product is prepared by means of the steps of pretreatment, resin separation, hydrolysis, chromatographic purification, etc., the process has the characteristics of simpleness and strong operability, and the purity of the product is greater than 96%. On the other hand, provided is a use of the STAT3 and ERK signal pathway inhibitor in the preparation of drugs for treating tumours, which effectively induces the cyclic arrest of cancer cells and promotes the apoptosis of cancer cells, realizes the purposes of inhibiting the proliferation of cancer cells and promoting the apoptosis of cancer cells, and has a very good inhibition effect on cancers.
Participants will receive a single high dose intravitreal injection of JNJ-81201887 in the study eye on Day 4. In addition, participants will receive a 20-day oral prednisone course starting on Day 1 and a single, long acting periocular triamcinolone (corticosteroid injection) on Day 4 for prophylaxis of intraocular inflammation.
Virus-associated cytokine storm syndrome (CSS) has been recognized for a long time and the classic viruses associated are the herpes viruses EBV, CMV, and HHV-8 as described in chapters IVa,b. In addition, pandemic viruses such as influenza, SARS, and MERS can result in severe CSS that might ultimately lead to severe acute respiratory distress syndrome (ARDS) and death [1-3]. A new pandemic caused by SARS-CoV-2 that started in 2019 has defined another chapter in the virus-associated CSS. The clinical spectrum of SARS-CoV-2 infection has many faces. In most people, it will be asymptomatic, but it can also result in severe COVID-19 pneumonia, ARDS, and multiorgan failure depending on age, comorbidities, and immune status [4]. In addition, this pandemic has known many different stages and developed in a unique way in the first 2 years. It started in a setting where there was no immunity to the virus and after a year, highly effective vaccines were introduced and herd immunity built up over time. However, vaccine effectiveness was waning over time depending on multiple factors, and novel variant strains of the virus circulated across different areas in the world. Antiviral therapy was developed and introduced, and treatment changed from giving no immunomodulatory treatment, followed by the introduction of corticosteroids [5], and later the addition of more targeted strategies such as JAK inhibitors [6] and blocking IL-6 signaling [7]. Therefore, the scientific literature published on COVID-19 must be seen in the context of a highly dynamic and rapidly changing pandemic, making it difficult to compare results from early studies to more recent reports even within 2 years. Still, a lot has been learned over a very short period. It has become apparent that severe COVID-19 is predominantly a disease of immune dysregulation with components that can be defined as CSS. It has unique features and overlapping characteristics with other CSSs, and immunological treatment addressing the CSS has been extensively explored, which will be described here.
OBJECTIVE: To develop preoperative nomograms using risk factors based on clinicopathological and MRI for predicting the risk of positive surgical margin (PSM) after radical prostatectomy (RP).
PATIENTS AND METHODS: This study retrospectively enrolled patients who underwent prostate MRI before RP at our center between January 2015 and November 2022. Preoperative clinicopathological factors and MRI-based features were recorded for analysis. The presence of PSM (overall PSM [oPSM]) at pathology and the multifocality of PSM (mPSM) were evaluated. LASSO regression was employed for variable selection. For the final model construction, logistic regression was applied combined with the bootstrap method for internal verification. The risk probability of individual patients was visualized using a nomogram.
RESULTS: In all, 259 patients were included in this study, and 76 (29.3%) patients had PSM, including 40 patients with mPSM. Final multivariate logistic regression revealed that the independent risk factors for oPSM were tumor diameter, frank extraprostatic extension, and annual surgery volume (all p < 0.05), and the nomogram for oPSM reached an area under the curve (AUC) of 0.717 in development and 0.716 in internal verification. The independent risk factors for mPSM included the percentage of positive cores, tumor diameter, apex depth, and annual surgery volume (all p < 0.05), and the AUC of the nomogram for mPSM was 0.790 in both development and internal verification. The calibration curve analysis showed that these nomograms were well-calibrated for both oPSM and mPSM.
CONCLUSIONS: The proposed nomograms showed good performance and were feasible in predicting oPSM and mPSM, which might facilitate more individualized management of prostate cancer patients who are candidates for surgery.
Sildenafil is an inhibitor of cGMP specific phosphodiesterase type-5 (PDE-5) in the smooth muscle of the pulmonary vasculature, where PDE-5 is responsible for degradation of cGMP. Sildenafil, therefore, increases cGMP within pulmonary vascular smooth muscle cells resulting in relaxation. In patients with PAH, this can lead to vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation.

Studies in vitro have shown that sildenafil is selective for PDE-5. Its effect is more potent on PDE-5 than on other known phosphodiesterases (10-fold for PDE-6, greater than 80-fold for PDE-1, greater than 700-fold for PDE-2, PDE-3, PDE-4, PDE-7, PDE-8, PDE-9, PDE-10, and PDE-11). The approximately 4,000-fold selectivity for PDE-5 versus PDE-3 is important because PDE-3 is involved in control of cardiac contractility. Sildenafil is only about 10-fold as potent for PDE-5 compared to PDE-6, an enzyme found in the retina and involved in the phototransduction pathway of the retina. This lower selectivity is thought to be the basis for abnormalities related to color vision observed with higher doses or plasma levels [see Clinical Pharmacology (12.2)].

In addition to pulmonary vascular smooth muscle and the corpus cavernosum, PDE-5 is also found in other tissues including vascular and visceral smooth muscle and in platelets. The inhibition of PDE-5 in these tissues by sildenafil may be the basis for the enhanced platelet anti-aggregatory activity of nitric oxide observed in vitro, and the mild peripheral arterial-venous dilatation in vivo.
Between 20 and 40% of extremity fractures in children require a closed reduction, often necessitating procedural sedation and analgesia (PSA) (3, 4). Intravenous (IV) ketamine is the most commonly used sedative agent used to perform a closed reduction (5). However, children rate IV insertion as the most painful hospital experience, second only to the injury itself (6). Intranasal (IN) ketamine may provide effective sedation for children undergoing a closed reduction without the distress and pain related to IV insertion. Although the proportion of children with adequate sedation using IN ketamine at doses of 9-10 mg/kg has been reported to be at least 75% (9-11), there is the possibility of inadequate sedation because IN ketamine 10 mg/kg has not been used for procedural sedation for fracture reduction. A multi-centre, two-arm, randomized, blinded, controlled, non-inferiority trial designed to test the hypothesis that intranasal (IN) ketamine is non-inferior to intravenous (IV) ketamine is being planned for launch in Spring 2019 and a stopping rule for futility will ensure that patients are not unduly enrolled and that resources are not wasted in a futile trial. Creating of a methodologically rigorous stopping rule depends on the results of a small cohort study to provide a more accurate and informed estimate of the probability of adequate sedation with IN ketamine 10 mg/kg.
An hydrohalide salt of oxytetracycline is obtained by dissolving up to about 0.3 g./ml. amphoteric oxytetracycline in an aliphatic alcohol of up to six carbon atoms in the presence of a solubilizing agent consisting of (a) 0.01 to 0.05 g./ml. of a hydrogen halide, (b) 0.02 to 0.3 g./ml. of a soluble alkali metal halide, (c) 0.02 to 0.3 g./ml. of a soluble alkaline earth metal halide other than calcium chloride, or (d) 0.02 to 0.3 g./ml. of a soluble zinc halide, and subsequently treating said solution with 0.02 to 0.06 g./ml. of a hydrogen halide thereby precipitating said oxytetracycline hydrohalide salt.  The metal halide should be soluble in the particular solvent selected to the extent of at least 0.02 g./ml. at ordinary temperatures.  Useful combinations are calcium bromide in methanol or ethanol, strontium chloride in methanol, magnesium chloride in methanol, sodium bromide in methanol, zinc chloride in methanol and lithium chloride in methanol.  Suitable hydrogen halides are anhydrous hydrogen chloride, concentrated hydrochloric acid and concentrated hydrobromic acid.  Amphoteric oxytetracycline may be produced in situ by treating a suspension of crude oxytetracycline hydrohalide with an organic amino in the aliphatic alcohol.  The suspension of oxytetracycline so produced is then treated with an alcohol solution of the metal halide, filtered and the hydrohalide salt precipitated by the addition of the appropriate acid.  Suitable amines are pyridine, piperidine, triethylamine, trimethylamine and ethanolamine.  Specification 684,417 is referred to.
PURPOSE:To provide a carcinostatic agent composed of gamma-aminobutyric acid or its ester and an immunopromoting agent, and having excellent carcinostatic effect by the synergistic effect. CONSTITUTION:The objective carcinostatic agent is produced by compounding a gamma-aminobutyric acid (abbreviated as GABA) such as the compound of formula H2NCH2CH2CH2COOH or its salt and an immunopromoting agent such as Piscivanyl [OK-432 (Chugai Pharmaceuticals)], Maruyama vaccine [SSM (Zeria Co.)], Krestin [PSK (Kureha Chemical Ind.)], etc. GABA has antitumor activity by single use, however, a remarkably excellent carcinostatic effect can be attained by the synergistic effect with an immunopromoting agent. GABA is effective to nonspecifically enhance the effect of nonspecific active immunizing agent. Excellent remedying effect is expected to the cancer of various organs and malignant tumors.
Phosphodiesterase 4 (PDE4) inhibitors are expected to exhibit efficacy against inflammatory diseases due to their broad pharmacological activity. The launched PDE4 inhibitors apremilast, crisaborole, and roflumilast have not exhibited sufficient inhibitory potential due to poor margins of effectiveness and tolerability. In this report, we describe the non-clinical efficacy, brain translocation, and vomit-inducing effects of ME3183 compared with apremilast. ME3183 showed extensive cytokine suppression in vitro studies using human peripheral blood mononuclear cells and T cells. ME3183 also significantly suppressed skin inflammation in a chronic oxazolone-induced dermatitis model and showed antipruritic effects in a substance P-induced mouse pruritus model. In these in vitro and in vivo studies, ME3183 also significantly suppressed cytokines, and focusing on tumor necrosis factor-α as a psoriasis-related cytokine and interleukin-4 as an atopic dermatitis-related cytokine, ME3183 potently inhibited both cytokines. ME3183 showed in vivo efficacy at lower doses than apremilast. The brain distribution of ME3183 was sufficiently low in mice and rats. The effective dose of ME3183 for emesis was similar to that of apremilast in ferrets. Given its high-potency inhibitory effects, ME3183 would have a wide margin of efficacy and tolerability. These wide margins demonstrate the effectiveness of ME3183 in treating many inflammatory diseases, such as psoriasis and atopic dermatitis. An on-going phase 2 trial is expected to further demonstrate the efficacy and safety of ME3183.