anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The objective of this proposal is to investigate the intra-individual reproducibility (within the same individual, when repeatedly measured) and inter-individual variability (among individuals) of glycemic index (GI) and glycemic load (GL) value determinations for individual foods and food combinations. The specific aims to accomplished this objective are to evaluate reproducibility and variability of GI value determinations in volunteers differing in biologic characteristics - body mass index (BMI), age and gender; assess the effect of macronutrient amounts and combinations, and fiber on variability of GI and GL value determinations; assess the effect of prior meal macronutrient composition ('second meal' effect) on GI value determinations; and relate these data to chronic disease risk factors monitored prior to and during the intervention period. These aims will be accomplished by assessing intra-individual reproducibility and inter-individual variability of repeated GI value determinations for white bread, commonly used as a reference food, relative to glucose, in volunteers selected to represent a range of BMI's (18-24.9, 25-29.9, 30-35) and ages (18-49.9, 50-85 y), and on the basis of gender, and relate these data to body composition and insulin sensitivity (Phase I). This work will then be extended to address issues related to variability potentially introduced by differences in macronutrient and fiber combinations and loads (Phase II), and finally by 'second meal' effects (Phase III). Prior to each set of food challenges (glucose and test food\[s\] in random order) volunteers will be characterized on the basis of fasting HbA1c; lipids and lipoproteins; insulin, glucose and C-reactive protein. During the 5-hour challenge (sampling at 0, 15, 30, 45, 60, and every 30 minutes thereafter) volunteers will be monitored for changes in blood glucose, insulin, triglycerides, total, low density lipoprotein and high density lipoprotein cholesterol, and non-esterified fatty acid levels. Additionally, supplementary data on variation in oral sensation, habitual food intake, food preferences and genes mediating sensory perception and dietary behaviors (supported by a grant from the Tufts Ross Aging Initiative) will be related to the outcomes on the present study. The concepts of both GI and GL are in the public domain and it has been suggested that the concepts be incorporated into U.S. federal dietary guidance (U.S. Dietary Guidelines and Dietary References Intakes) formulated to promote health and reduce chronic disease risk. This proposal addresses some of the understudied areas for which additional information would be useful in order to determine whether GI and GL should be used to classify foods on an individual basis, as has been suggested, and when formulating dietary guidance for the general population.
Cholesterol gallstone disease (CGD) is one of the most common digestive diseases, and it is closely associated with hepatic cholesterol metabolism. Cholesterol gallstones may be caused by abnormal hepatic cholesterol metabolism, such as excessive cholesterol biosynthesis within the liver, interfering with the uptake or export of cholesterol in the liver, and abnormal hepatic cholesterol esterification. In this review, we begin with a brief overview of the clinical diagnosis and treatment of gallstone disease (GSD). Then, we briefly describe the major processes of hepatic cholesterol metabolism and summarize the key molecular expression changes of hepatic cholesterol metabolism in patients with gallstones. We review and analyze the recent advances in elucidating the relationships between these key molecules and CGD, and some targets significantly impacting on CGD via hepatic cholesterol metabolism are also listed. We also provide a significant discussion on the relationship between CGD and nonalcoholic fatty liver disease (NAFLD). Finally, the new discoveries of some therapeutic strategies associated with hepatic cholesterol metabolism to prevent and treat CGD are summarized.
PURPOSE: To obtain a skin preparation for external use containing, as active ingredients, gymnema saponin and at least one kind of compound selected from L-ascorbic acid compounds, placenta extract, kojic acid compounds, azelaic acid compounds, glucosamine compounds, hydroquinone compounds and tranexamic acid compounds. CONSTITUTION: This skin preparation for external use contains, as active ingredients, 0.001-20wt.% of at least one kind of compound selected from L- ascorblc acid and derivatives therefrom, placenta extract, kojic acid and derivatives therefrom, azelaic acid and derivatives therefrom, glucosamine and derivatives therefrom, hydroquinone glycosides and derivatives therefrom, and tranexamic acid and derivatives therefrom and 0.001-20wt.% of gymnema saponin and/or its salt. Combined use of the above two kinds of active ingredients results in the synergistic skin beautifying effect of this skin preparation with both high safety and stability. The skin preparation can be made into such formulations as solubilized system e.g. lotion, emulsified system e.g. milky lotion or cream, ointment or dispersion. The gymnema saponin is a triterpenoid saponin obtainable from the extract of e.g.  Gymnema inodorum.
Quantitating exercise ventilatory and gas exchange dynamics affords insights into physiological control processes and cardiopulmonary dysfunction. We designed a novel waveform, the chirp waveform, to efficiently extract moderate-intensity exercise response dynamics. In the chirp waveform, work rate fluctuates sinusoidally with constant amplitude as sinusoidal period decreases progressively from ∼8.5 to 1.4 min over 30 min of cycle ergometry. We hypothesized that response dynamics of pulmonary ventilation (V̇e) and gas exchange [oxygen uptake (V̇o2) and carbon dioxide output (V̇co2)] extracted from chirp waveform are similar to those obtained from stepwise transitions. Thirty-one participants [14 young healthy, 7 older healthy, and 10 patients with chronic obstructive pulmonary disease (COPD)] exercised on three occasions. Participants first performed ramp-incremental exercise for gas exchange threshold (GET) determination. In randomized order, the next two visits involved either chirp or stepwise waveforms. Work rate amplitude (20 W to ∼95% GET work rate) and exercise duration (30 min) were the same for both waveforms. A first-order linear transfer function with a single system gain (G) and time constant (τ) characterized response dynamics. Agreement between model parameters extracted from chirp and stepwise waveforms was established using Bland-Altman analysis and Rothery's concordance coefficient (RCC). V̇e, V̇o2, and V̇co2 Gs showed no systematic bias (P > 0.178) and moderate-to-good agreement (RCC > 0.772, P < 0.01) between waveforms. Similarly, no systematic bias (P = 0.815) and good agreement (RCC = 0.837, P < 0.001) was found for τV̇o2. Despite moderate agreement for τV̇co2 (RCC = 0.794, P < 0.001) and τV̇e (RCC = 0.722, P = 0.083), chirp τ was less [-6.9(11.7) s and -12.2(22.5) s, respectively]. We conclude that the chirp waveform is a promising method for measuring exercise response dynamics and investigating physiological control mechanisms.NEW & NOTEWORTHY We investigated the ability of a novel waveform to extract exercise ventilatory and gas exchange dynamics. In the chirp waveform, work rate fluctuates sinusoidally with constant amplitude as sinusoidal period decreases progressively over 30 min of exercise. In a study of 31 healthy individuals and patients with COPD, comparison of exercise dynamics derived from chirp to those from stepwise waveforms suggests that the chirp waveform is a promising method for derivation of exercise response dynamics.
Plantaginis semen is the dried ripe seed of Plantago asiatica L. or Plantago depressa Willd., which has a long history in alleviating hyperuricemia (HUA) and chronic kidney diseases. While the major chemical ingredients and mechanism remained to be illustrated. Therefore, this work aimed to elucidate the chemicals and working mechanisms of PS for HUA. UPLC-QE-Orbitrap-MS was applied to identify the main components of PS in vitro and in vivo. RNA sequencing (RNA-seq) was conducted to explore the gene expression profile, and the genes involved were further confirmed by real-time quantitative PCR (RT-qPCR). A total of 39 components were identified from PS, and 13 of them were detected in the rat serum after treating the rat with PS. The kidney tissue injury and serum uric acid (UA), xanthine oxidase (XOD), and cytokine levels were reversed by PS. Meanwhile, renal urate anion transporter 1 (Urat1) and glucose transporter 9 (Glut9) levels were reversed with PS treatment. RNA-seq analysis showed that the PPAR signaling pathway; glycine, serine, and threonine metabolism signaling pathway; and fatty acid metabolism signaling pathway were significantly modified by PS treatment. Further, the gene expression of Slc7a8, Pck1, Mgll, and Bhmt were significantly elevated, and Fkbp5 was downregulated, consistent with RNA-seq results. The PPAR signaling pathway involved Pparα, Pparγ, Lpl, Plin5, Atgl, and Hsl were elevated by PS treatment. URAT1 and PPARα proteins levels were confirmed by Western blotting. In conclusion, this study elucidates the chemical profile and working mechanisms of PS for prevention and therapy of HUA and provides a promising traditional Chinese medicine agency for HUA prophylaxis.
BACKGROUND: QRS morphology can change during ventricular arrhythmias (VAs) with the appearance of bundle branch block (BBB).
METHODS: We retrospectively investigated 195 consecutive patients who underwent an initial ablation of VA. The study inclusion criteria were VAs that were successfully ablated in the outflow tract (OT) and in whom right bundle branch block (RBBB) was induced by catheter manipulation close to the His bundle area during sinus rhythm, before any radiofrequency application. We analyzed the QRS morphology of the VAs with and without RBBB during sinus beats.
RESULTS: Twenty-four patients (age 59 ± 17 years, female 14) developed RBBB at some point during their procedure. The successful ablation sites of the VAs were the right ventricular outflow tract (RVOT) in 12 patients, pulmonary artery in one, left coronary cusp in five, right coronary cusp in three, right-left cusp junction in two, and great cardiac vein in two. QRS-morphology change was observed in five (20%) cases. The successful ablation sites in that group were the left coronary cusp in three cases, right coronary cusp in one, and RVOT septum in one. The QRS duration of the VAs increased during RBBB.
CONCLUSIONS: There are some cases of OT-VAs in which the QRS waveform changes with the appearance of catheter induced RBBB. We need to be aware that when QRS morphology changes during an OT-VA ablation, it does not necessarily mean that the origin or exit of the VA has changed.
BACKGROUND: The comorbidity rate of inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) is high; nevertheless, the reasons behind this high rate remain unclear. Their similar genetic makeup probably contributes to this comorbidity.
METHODS: Based on data obtained from the genome-wide association study of IBD and RA, we first assessed an overall genetic association by performing the linkage disequilibrium score regression (LDSC) analysis. Further, a local correlation analysis was performed by estimating the heritability in summary statistics. Next, the causality between the two diseases was analyzed by two-sample Mendelian randomization (MR). A genetic overlap was analyzed by the conditional/conjoint false discovery rate (cond/conjFDR) method.LDSC with specific expression of gene analysis was performed to identify related tissues between the two diseases. Finally, GWAS multi-trait analysis (MTAG) was also carried out.
RESULTS: IBD and RA are correlated at the genomic level, both overall and locally. The MR results suggested that IBD induced RA. We identified 20 shared loci between IBD and RA on the basis of a conjFDR of <0.01. Additionally, we identified two tissues, namely spleen and small intestine terminal ileum, which were commonly associated with both IBD and RA.
CONCLUSION: Herein, we proved the presence of a polygenic overlap between the genetic makeup of IBD and RA and provided new insights into the genetic architecture and mechanisms underlying the high comorbidity between these two diseases.
Multiple sclerosis (MS) is a chronic and progressive neurological disorder, characterized by neuroinflammation and demyelination within the central nervous system (CNS). The etiology and the pathogenesis of MS are still unknown. Till now, no satisfactory treatments, diagnostic and prognostic biomarkers are available for MS. Therefore, we aimed to investigate metabolic alterations in patients with MS compared to controls and across MS subtypes. Metabolic profiles of serum samples from patients with MS (n = 90) and healthy control (n = 30) were determined by Nuclear Magnetic Resonance (1H-NMR) Spectroscopy using cryogenic probe. This approach was also utilized to identify significant differences between the metabolite profiles of the MS groups (primary progressive, secondary progressive, and relapsing-remitting) and the healthy controls. Concentrations of nine serum metabolites (adenosine triphosphate (ATP), tryptophan, formate, succinate, glutathione, inosine, histidine, pantothenate, and nicotinamide adenine dinucleotide (NAD)) were significantly higher in patients with MS compared to control. SPMS serum exhibited increased pantothenate and tryptophan than in PPMS. In addition, lysine, myo-inositol, and glutamate exhibited the highest discriminatory power (0.93, 95% CI 0.869-0.981; 0.92, 95% CI 0.859-0.969; 0.91, 95% CI 0.843-0.968 respectively) between healthy control and MS. Using NMR- based metabolomics, we identified a set of metabolites capable of classifying MS patients and controls. These findings confirmed untargeted metabolomics as a useful approach for the discovery of possible novel biomarkers that could aid in the diagnosis of the disease.
Fatal and serious myelosuppression occurs in decitabine-treated patients. Myelosuppression (anemia, neutropenia, and thrombocytopenia) is the most frequent cause of decitabine for injection dose reduction, delay, and discontinuation. Neutropenia of any grade occurred in 90% of decitabine-treated patients with grade 3 or 4 occurring in 87% of patients. Grade 3 or 4 febrile neutropenia occurred in 23% of patients. Thrombocytopenia of any grade occurred in 89% of patients with grade 3 or 4 occurring in 85% of patients. Anemia of any grade occurred in 82% of patients. Perform complete blood count with platelets at baseline, prior to each cycle, and as needed to monitor response and toxicity. Manage toxicity using dose-delay, dose-reduction, growth factors, and anti-infective therapies as needed [see Dosage and Administration (2.2)]. Myelosuppression and worsening neutropenia may occur more frequently in the first or second treatment cycles and may not necessarily indicate progression of underlying MDS.
PURPOSE:To obtain the titled drug preparation having constant rate of dissolution and high and stable durability of the drug action and effective to prevent the fit of epilepsy, by coating a core granule of valproate sodium with a carboxyvinyl polymer and further coating with ethylcellulose. CONSTITUTION:A core granule consisting of valproate sodium is coated with a hydrophilic carboxyvinyl polymer having high viscosity and then with a water- insoluble film of ethylcellulose to obtain the objective long-acting granular drug preparation. The amount of carboxyvinyl polymer is 0.01-0.05pts.wt.per 1pt.wt. of the core granule and that of the ethylcellulose is 0.1-0.5pts.wt. per 1pt.wt. of the primary coated core granule. A durable and extremely stable dissolution rate can be achieved compared with the granule coated simply with ethylcellulose. Effective administration every twice a day or less is possible. Since the drug is long-acting granule, the dose can be controlled and the side effect and the fit of epilepsy can be easily prevented.
The effectiveness of RYKINDO as an adjunct to treatment with lithium or valproate for the maintenance treatment of bipolar I disorder is based on an adequate and well-controlled study of risperidone long-acting injection (intramuscular). The results of the adequate and well-controlled study are presented below.

The efficacy of risperidone long-acting injection (intramuscular) was established in a multi-center, randomized, double-blind, placebo-controlled study of adult patients who met DSM-IV criteria for Bipolar Disorder Type I and who experienced at least 4 episodes of mood disorder requiring psychiatric/clinical intervention in the previous 12 months, including at least 2 episodes in the 6 months prior to the start of the study.

A total of 240 patients were treated during a 16-week open-label period with risperidone long-acting injection (intramuscular) (starting dose of 25 mg, and titrated, if deemed clinically desirable, to 37.5 mg or 50 mg), as adjunctive therapy in addition to continuing their usual treatment for bipolar disorder, which consisted of mood stabilizers (primarily lithium and valproate), antidepressants, and/or anxiolytics. All oral antipsychotics were discontinued after the first three weeks after the initial injection of risperidone long-acting injection (intramuscular). In the open-label phase, 124 (51.7%) were judged to be stable for at least the last 4 weeks and were randomized to double-blind treatment with either the same dose of risperidone long-acting injection (intramuscular) or placebo in addition to continuing their usual treatment and monitored for relapse during a 52-week period. The primary endpoint was time to relapse to any new mood episode (depression, mania, hypomania, or mixed).

Time to relapse was delayed in patients receiving adjunctive therapy with risperidone long-acting injection (intramuscular) compared with patients receiving adjunctive therapy with placebo. The relapse types were about half depressive and half manic or mixed episodes.
### Teratogenic Effects: Pregnancy Category C

Teratogenic studies were performed with labetalol in rats and rabbits at oral doses up to approximately six and four times the maximum recommended human dose (MRHD), respectively. No reproducible evidence of fetal malformations was observed. Increased fetal resorptions were seen in both species at doses approximating the MRHD. A teratology study performed with labetalol in rabbits at intravenous doses up to 1.7 times the MRHD revealed no evidence of drug-related harm to the fetus. There are no adequate and well-controlled studies in pregnant women. Labetalol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

### Nonteratogenic Effects

Hypotension, bradycardia, hypoglycemia, and respiratory depression have been reported in infants of mothers who were treated with labetalol for hypertension during pregnancy. Oral administration of labetalol to rats during late gestation through weaning at doses of two to four times the MRHD caused a decrease in neonatal survival.
The invention relates to the technical field of antibodies, in particular to an anti-novel coronavirus humanized multivalent binding protein and application thereof. The multivalent binding proteins provided by the present invention comprise at least two epitope binding domains, wherein the epitope binding domains are VHHs; the amino acid sequence of the VHH is shown as SEQ ID NO. 1 or SEQ ID NO. 2, or is shown as an amino acid sequence which has at least 95% similarity with SEQ ID NO. 1 or SEQ ID NO. 2. The multivalent binding protein can effectively block the combination of a wild strain, a Delta variant strain and an Omicron variant strain SARS-COV-2RBD protein and a human ACE2 receptor protein, has more obvious neutralizing activity of novel coronavirus compared with a monovalent binding protein, and can be widely used for preventing and treating the novel coronavirus.
Part 2: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, intolerance or two years of treatment. A fixed dose of CDX-301 is injected once a day for five days before cycles 1 and 2 of CDX-1140.
In recent years, due to the rapid increase in the prevalence of autism spectrum disorder (ASD), early detection of these children is helpful for early diagnosis and intervention and better prognosis. Recent research supports the intervention in the daily life of children with autism in a naturalized way. Parents learn intervention skills and implement them in their lives, providing positive effects on children with autism. This type of intervention is called parent-mediated intervention. Pivot Response Training (PRT) is a home-based parent-child intervention model that uses "Applied Behavior Analysis" to integrate into children's daily life situations and teach children to respond appropriately to the many learning opportunities and social interactions in natural situations, reducing reliance on therapist supervision, and care services that hinder children from natural situations. However, there are many obstacles at present. In addition to insufficient resources, long waiting time for accessing services, and the COVID-19 Pandemic or future emerging infections interrupting in-person face-to-face services, remote guidance of parents to implement the intervention at home (telehealth) is another way to help children and families with developmental disabilities. This way of giving patients holistic health care is a new trend in providing early intervention services. Therefore, this study plans to first conduct team education and discussion, and then use our highly reliable screening tool to screen children aged 24-72 months for autism screening in the community and institutes. Those screened with a positive result will be referred to our early intervention center for comprehensive child development and behavioral follow-up. A total of 60 children over 24 months old diagnosed with ASD will participate in the telehealth intervention program. They will be randomly assigned to the intervention group or the comparison group. The intervention group (the telehealth group) will also receive a 16-week telehealth intervention with guidance, digital learning platform, teaching parents to learn intervention skills to improve children's attention and play ability, social communication, cognition, perceptual movement, and improve parents' management of children's behavior problems. The comparison group (telephone group) will receive 16-weeks of child development counseling through phone calls. This project aims to enhance the education and cooperation of the team, increase the awareness and understanding of ASD in the community, strengthen the use of relevant screening tools, provide an easy-accessed E-learning platform for parents, daycare or kindergarten caregivers or professionals to learn, and establish an evidence-based telehealth early intervention for autistic children. In this way, parents of autistic children would have more confidence and support to go for screening and intervention to achieve patient- and family-centered holistic care and enhance their compliance.