anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The efficacy of BYLVAY was evaluated in Trial 3 (NCT04674761), a 24-week, randomized, double-blind, placebo-controlled trial. Trial 3 was conducted in 52 pediatric patients, aged 6 months to 15 years, with a confirmed diagnosis of ALGS and presence of pruritus at baseline. Patients who had decompensated liver disease, who had other concomitant liver disease, whose INR was greater than 1.4, whose ALT was greater than 10-times the upper limit of normal (ULN) at screening, whose total bilirubin was greater than 15-times the ULN at screening, or who had received a liver transplant were excluded from Trial 3.

Patients were randomized to placebo (n=17) or 120 mcg/kg (n=35). Study drug was administered once daily with a meal in the morning. In patients weighing less than 19.5 kg or patients who could not swallow the whole capsule, study drug was sprinkled on soft food and then administered orally. 

Median age (range) of the patients in Trial 3 was 6.1 (1.7 to 15.5) years in the BYLVAY group and 4.2 (0.5 to 14.3) years in the placebo group; 5 patients were older than 12 years of age. Of the 52 patients, 52% were male and 83% were white; 92% of patients had the JAG1 mutation and 8% had the NOTCH2 mutation. The mean (standard deviation [SD]) scratching score in the 2 weeks prior to baseline was 2.9 (0.6). Baseline mean (SD) eGFR was 159 (51.4) mL/min/1.73 m2. Baseline median (range) ALT, AST, and total bilirubin were 152 (39-403) U/L, 135 (57-427) U/L, and 2.0 (0.4-11.4) mg/dL, respectively. 

Given the patients' young ages, a single-item observer-reported outcome (ObsRO) was used to measure patients' scratching severity as observed by their caregiver twice daily (once in the morning and once in the evening). Scratching severity was assessed on a 5-point ordinal response scale, with scores ranging from 0 (no scratching) to 4 (worst possible scratching). Patients were included in Trial 3 if the average scratching score was greater than or equal to 2 (medium scratching) in the 14 days prior to baseline.

Table 8 presents the results of the comparison between BYLVAY and placebo on the change from baseline in average scratching score based on ObsRO assessments to Month 6 (Weeks 21 to 24). The average scratching score for each patient for each month post-baseline was calculated by: (Step 1) averaging the morning scores and averaging the evening scores within a week; (Step 2) averaging the morning and evening weekly scores to yield a single weekly score; and finally (Step 3) averaging the 4 weekly scores within the month. The baseline average scratching score for each patient was calculated by averaging the weekly scores obtained in Step 2 across the 2 weeks prior to randomization and initiation of blinded treatment. Patients treated with BYLVAY demonstrated greater improvement in pruritus compared with placebo. Figure 2 displays the means (95% confidence interval) of patients' average scratching scores in each treatment group for each month.
Between 60%-70% of the risk of obesity appears to be heritable. Unfortunately, the exact genes involved have been difficult to identify. New technologies now exist to help researchers discover obesity susceptibility genes. One of these technologies is the Affymetrix Genome-Wide Human SNP (single nucleotide polymorphism) Array 6.0 chips. SNPs are individual base pair differences in genes of different individuals, and they are the main source of human genetic diversity. The "chips" are thumbnail-size silicon surfaces that contain copies of hundreds of thousands of SNPs of the human genome (in this case around 900,000). SNP chips allow researchers to screen thousands of genes in a single experiment and compare genes of subjects with a particular disease or condition with unaffected control subjects. The investigators study utilizes SNP chips to compare the genetic profiles of obese subjects (N = 20, body mass index \> 35 kg/m2) without common obesity-related co-morbidities such as diabetes mellitus or hypertension with well matched, lean controls (N = 20, body mass index 18-25 kg/m2). This is a pilot study intended to explore the following: 1) possible associations between obesity and previously unidentified obesity susceptibility genes; 2) associations between known obesity genes and obesity risk in subjects without obesity-related metabolic co-morbidities; and 3) how well our genetic data conform to other studies in similar populations as a way of assessing if the investigators have identified a representative cohort of obese subjects.
INTRODUCTION: Accurate risk scoring in emergency general surgery (EGS) is vital for consent and resource allocation. The emergency surgery score (ESS) has been validated as a reliable preoperative predictor of postoperative outcomes in EGS but has been studied only in the US population. Our primary aim was to perform an external validation study of the ESS in a UK population. Our secondary aim was to compare the accuracy of ESS and National Emergency Laparotomy Audit (NELA) scores.
METHODS: We conducted an observational cohort study of adult patients undergoing emergency laparotomy over three years in two UK centres. ESS was calculated retrospectively. NELA scores and all other variables were obtained from the prospectively collected Emergency Laparotomy and Laparoscopic Scottish Audit (ELLSA) database. The primary and secondary outcomes were 30-day mortality and postoperative intensive care unit (ICU) admission, respectively.
RESULTS: A total of 609 patients were included. Median age was 65 years, 52.7% were female, the overall mortality was 9.9% and 23.8% were admitted to ICU. Both ESS and NELA were equally accurate in predicting 30-day mortality (c-statistic=0.78 (95% confidence interval (CI), 0.71-0.85) for ESS and c-statistic=0.83 (95% CI, 0.77-0.88) for NELA, p=0.196) and predicting postoperative ICU admission (c-statistic=0.76 (95% CI, 0.71-0.81) for ESS and 0.80 (95% CI, 0.76-0.85) for NELA, p=0.092).
CONCLUSIONS: In the UK population, ESS and NELA both predict 30-day mortality and ICU admission with no statistically significant difference but with higher c-statistics for NELA score. Both scores have certain advantages, with ESS being validated for a wider range of outcomes.
Lower back pain is a common disorder that include any discomfort in the lumbar area below the origin of ribs and above the area of buttocks.Lower back pain with disability is 2nd most often reason for the wastage of time \& money.Almost all people suffer from lower back pain at some age of their life .Both genders are effected equally by low back pain. The common problem of lower back pain are when you lift a heavy object prolonged unsupported sitting, accidents, sedentary life style. Sedentary life style could be the cause of low back pain usually when strenuous workout done on weekends as compared to minimal activities on week days. Lumbar area of the back hold and support the weight of the upper body and body do twisting and bending at this area. Specific or non-specific lower back pain is the classifications. Pain caused by any deformity, injury or any physical activity is called non-specific lower back pain.Non-specific lower back pain cannot be having any specific pathology, changes in behavior of movement pattern due to fear avoidance having bad postural control cause this non-specific pain.Lower back pain is one of the general health setbacks globally. It is the leading cause of people's absence from work and limits their activities.Prevalence and burden of low back pain increased with aging.Spinal decompression can create a opposite intradiscal pressure to promote led back of the herniated or bulging disc material and this oppsosity in the disc will cause influx of healing nutrients and other substances into the disc Core stability program improves functional status; reduce pain, increases quality of life and endurance of muscles in lumbar disk herniation patients.A strong core is important to the healthy spine. Abdominal muscle can help the back muscle supporting supine. If core muscle are weak, supine carry extra pressure on your back muscles. For this stabilizing and core exercises are important to strengthen back spine. By increasing endurance of these muscles core muscle should be strong. Core stability program improves functional status; reduce pain, increases quality of life and endurance of muscles in lumbar disk herniation patients.In 2008, a researcher found that stabilization exercises helpful in spinal rehabilitation to prevent from any sports injury. Another study by Hodges in 2003 stated that exercises for central muscle is an developing process; additional work necessary to purify and authenticate move forward, mainly with reference to understand the neurobiology of chronic pain.A study in 2011 on comparison between stabilization plan and Pilates technique for treating Low back pain. Their results showed that, Pereira technique is not is not helpful in get better back pain and function, in comparison with control and lumbar stabilization exercise groups.In exercise plan Mat and gym ball exercise for strength training and step box were used to develop an independent habit of exercise .these exercise plan intend to increase strength of muscle and decrease pain. As a main exercise walking is, safe, suitable and easy to decrease low back pain because it does not involve forceful and twisting forward flexion.
Young healthy males will ingest Rapamycin (blinded) and perform a single bout of knee-extensor exercise and insulin action is investigated 4 hours after cessation of exercise. Insulin action towards muscle glucose uptake and protein synthesis will be investigated during a 120 min euglycemic hyperinsulinemic clamp.
South Asians, who originate from the Indian subcontinent and make up one-fifth of the world's population, are among the highest number who suffer from heart disease and diabetes. The results of many research studies suggest that genes play a role in developing heart disease and diabetes that is made worse by the diet in the United States. Fructose is a sugar widely used in the American diet, and when consumed, it is taken up by the liver and changed into fats through a process called de novo lipogenesis (DNL). The current study will compare this change into fats in the liver between South Asians and Caucasians. The participants will be screened on the initial visit, and on the second visit, the DNL response will be measured in the blood over four hours after drinking one sweetened beverage, containing half glucose, half fructose, similar to a soft drink. We expect that DNL in response to fructose intake is higher in South Asians when compared to Caucasians and may partially explain why South Asians have earlier heart disease and diabetes.
Subjects will be screened to assess their eligibility to enter the study within approximately 4 weeks prior to dose administration. Subjects will be confined to the Clinical Research Unit (CRU) for their entire participation in this study. Eight subjects will be enrolled to allow 6 subjects to complete the study. Each subject will report to the CRU and be confined from Day -1 (the day before dosing) through at least Day 8 (168 hours postdose). A single dose of study drug will be administered on Day 1 (0 hour). On Day 8, subjects can be asked to remain as a resident within the CRU for an additional period to allow for ongoing 24-hour urine, fecal, and blood sample collections. These collections can continue up to a maximum of 336 hours postdose (Day 15). Subjects can be discharged prior to Day 15 if the following individual subject discharge criteria have been satisfied: ≥ 90% of the 14C dose recovered in combined urine and feces, and ≤ 1% of the total radioactive dose is recovered in combined excreta (urine and feces) in 3 consecutive 24-hour periods in which a fecal sample is provided.
The occurrence of myocardial ischemia/reperfusion injury is commonly observed during cardiac surgery; however, there remains a dearth of effective therapeutic strategies to mitigate this injury. The a disintegrin and metallopeptidase domain 10 (ADAM10) is a transmembrane protein anchored on the cell membrane surface, and its precise mechanism of action in myocardial ischemia/reperfusion injury remains incompletely understood. This study aims to investigate the impact of ADAM10 on cardiomyocyte injury induced by hypoxia/reoxygenation (H/R) and elucidate the underlying mechanisms. The ADAM10 overexpression plasmid was transfected into H9c2 cells, which were subsequently treated with the Notch signaling pathway inhibitor DAPT and cultured under H/R conditions. Cell proliferation activity was assessed using the CCK-8 assay. The levels of LDH, SOD, and MDA were quantified through colorimetric analysis. The levels of ROS and the rate of apoptosis were measured using flow cytometry. The morphological changes in the nucleus of H9c2 cells were observed by employing Hoechst 33258 staining. The mRNA expression levels of ADAM10, Notch1, NICD, and Hes1 in H9c2 cells were determined using qRT-PCR. The expressions of Notch signaling pathway and apoptosis-related proteins were analyzed by Western blot. Overexpression of ADAM10 provided protection to H9c2 cells against injury induced by H/R, leading to an increase in SOD levels and alleviation of oxidative stress caused by the accumulation of ROS and the decrease of SOD activity. Meanwhile, overexpression of ADAM10 inhibited apoptosis in H9c2 cells exposed to H/R by regulating the expression of apoptosis-related proteins, such as Bax, Bcl-2 and Cleaved-caspase-3. Additionally, overexpression of ADAM10 facilitated the activation of the Notch1 signaling pathway in H9c2 cells exposed to H/R by upregulating the protein expression of Notch1, NICD, and Hes1. However, the protective effect of ADAM10 on H/R-induced H9c2 cells was partially reversed by DAPT. Our findings demonstrate that ADAM10 exerts protective effects in H/R-induced H9c2 cells by suppressing oxidative stress and apoptosis via the activation of the Notch signaling pathway.
The invention relates to human antibodies, preferably recombinant human antibodies which are specifically bound to human tumour necrotic factor alpha(TNFalpha). The antibodies have high afinity to hTNFalpha, e.g. Kd = 10-8 M or less, low hTNFalpha dissociate velocity, e.g. Koff = 10-3sec-1 or less, and neutralize the hTNFalpha activity in vitro and in vivo. Antibody of this invention can be an antibody with its full length or its antigene-binding part. The antibodies or parts thereof are applicable for the detection of hTNFalpha and for the inhibition of hTNFalpha activity, for example in patients suffering from indispositions where the hTNFalpha activity is harmfull. The invention also relates to nucleinic acids, vectors and host cells for the expression of recombinant human antibodies and to methods for their synthetization.
OBJECTIVE: Diabetes in the course of lifetime is related to a higher risk for mental disorders. The present study addresses the comparison of individuals with diabetes and non-diabetic individuals in depressive symptoms, generalized anxiety symptoms, and health-related quality of life. Furthermore, mediator effect of BMI and health-related quality of life (HRQOL) on the association between diabetes, depression, and generalized anxiety was analyzed.
METHODS: In this cross-sectional study, the three questionnaires PHQ-9, GAD-7, EQ-5D-5L were measured in a representative sample of the German population (N = 2386). In addition, the presence of diabetes and BMI were assessed via self-report.
RESULTS: There were higher values in depressive and anxiety symptoms as well as lower score in HRQOL in individuals with diabetes compared to non-diabetic individuals. Obese individuals with diabetes showed the highest rates in depressive symptoms and generalized anxiety as well as lowest score in HRQOL. With regard to the mediator analyses, association between diabetes, depressive symptoms, and anxiety symptoms is partially mediated by the BMI and fully mediated by the HRQOL.
CONCLUSIONS: In conclusion, individuals with diabetes have an increased risk in the development of depressive and anxiety symptoms as well as lower health-related quality of life. Future research and strategies in the public health policies among individuals with diabetes should take into account that the association between diabetes, depression, and anxiety is mediated by BMI and HRQOL.
Various in vitro and limited in vivo human studies have shown that cytokines and cytokine modulators can influence the expression and activity of specific cytochrome P450 (CYP) enzymes and therefore have the potential to alter the pharmacokinetics of concomitantly administered drugs that are substrates of these enzymes. Elevated interleukin-6 (IL-6) concentration may down-regulate CYP activity such as in patients with RA and hence increase drug levels compared to subjects without RA. Blockade of IL-6 signaling by IL-6Rα antagonists such as KEVZARA might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to altered drug concentrations.

The modulation of IL-6 effect on CYP enzymes by KEVZARA may be clinically relevant for CYP substrates with a narrow therapeutic index, where the dose is individually adjusted. Upon initiation or discontinuation of KEVZARA, in patients being treated with CYP substrate medicinal products, perform therapeutic monitoring of effect (e.g., warfarin) or drug concentration (e.g., theophylline) and adjust the individual dose of the medicinal product as needed.

Exercise caution when co-administering KEVZARA with CYP3A4 substrate drugs where decrease in effectiveness is undesirable, e.g., oral contraceptives, lovastatin, atorvastatin, etc. The effect of KEVZARA on CYP450 enzyme activity may persist for several weeks after stopping therapy [see Clinical Pharmacology (12.3)].
Study drug will be provided as 50 mg tablets. Patients will be instructed to take 2 tablets orally once a day during the evening at least 60 minutes after a meal. Thalidomide will be administered starting at 100 mg (Group 1) for 6 weeks. Thereafter, the dose will be increased every week by 50mg until reaching the dose of 400 mg/day. This treatment is continued for 12 weeks. Thalidomide is administered in conjunction with the standard treatment of riluzole (100mg/day).
BACKGROUND: Prior studies have demonstrated a prevalent occurrence of depression among the middle-aged and older Chinese individuals with chronic diseases. Nevertheless, there is limited research on the specific subgroups of depression trajectories within this population and the factors influencing these subgroups.
OBJECTIVE: To explore the changing trajectory and influencing factors of depression in the middle-aged and older individuals with chronic disease in China, and provide the data reference for the health management of the older adult population in China.
METHODS: A longitudinal cohort study was conducted using the data from the China Health and Retirement Longitudinal Study (CHARLS) in 2011, 2013, 2015, 2018, and 2020. A total of 2,178 participants with complete data were included. The level of depression was evaluated using the Center for Epidemiologic Studies Depression Scale (CESD-10). The Latent Class Mixed Models (LCMM) were employed to estimate trajectories of depressive symptoms. The Kruskal-Wallis H test and the Pearson χ 2 test were used to determine the significant factors affecting trajectory grouping. Subsequently, the multinomial logistic regression model was utilized to perform a multifactorial analysis of the variables impacting the trajectory subgroup of change in depressive symptoms.
RESULTS: The LCMM-analysis revealed three distinct subgroups of depression trajectories: the "Low stable group" comprising 36.7% of the sample, the "Medium growth group" comprising 34.4% of the sample, and the "High growth group" comprising 28.9% of the sample. Among the baseline characteristics of different depression trajectory subgroups, there were significant differences in gender, residence, education, marital status, social activity participation, number of chronic diseases, smoking status, BMI, midday napping (minutes) and nighttime sleep duration (hours). Through multiple logistic regression analysis, our findings demonstrate that among the middle-aged and older Chinese individuals with chronic diseases, the following individuals should be the key groups for the prevention and treatment of depressive symptoms: Those who are young, female, residing in rural areas, having primary school education and below, being single, not participating in social activities, suffering from multiple chronic diseases, and having shorter naps and sleeping at night.
CONCLUSION: There is heterogeneity in the subgroups of depression trajectories among the Chinese middle-aged and older individuals with chronic diseases. The focus should be on the distinct characteristics of various trajectories of depression within the realm of health management.
BACKGROUND: Advanced age has been widely identified as a risk factor for recurrent Clostridioides difficile infection (CDI), but most related studies were performed before the introduction of novel therapies. The aim of this study was to compare CDI characteristics and outcomes in patients over and under 80 years old with CDI and their outcomes in the era of new treatments.
METHODS: This was a retrospective cohort study of patients diagnosed with CDI from January 2021 to December 2022 in an academic hospital. We compared recurrence and mortality at 12 weeks after the end of treatment. An extension of the Fine and Grey model adjusted for competing events was used to assess the effect of age on recurrence.
RESULTS: Four hundred seventy-six patients were considered to have CDI (320 in patients <80 years and 156 in ≥80 years). CDI in older patients was more frequently healthcare-associated and was more severe. Although the Charlson index was almost identical between populations, comorbidities clearly differed. New treatments (bezlotoxumab, fidaxomicin and faecal microbiota transplantation) were more frequently used in older patients without statistical significance (41.3% vs. 33.4%, P = .053). There were 69 (14.5%) recurrences, with no differences by age group after adjusting for competing events. Mortality was greater in the oldest (35.3%) than in the youngest (13.1%); P < .001.
CONCLUSIONS: No differences in CDI recurrence rates were found between age groups. However, there was a high mortality rate in patients ≥80 years old, which emphasises the urgent need to improve the prevention and treatment of CDI in this group.
Participants with BRAFV600 mutation-positive disease will be administered cobimetinib, atezolizumab and vemurafenib in 28-day treatment cycles. Treatment includes a 28-day run-in period where participants will receive cobimetinib and vemurafenib only. Upon completion of the 28-day run-in period, atezolizumab will be added to their treatment regimen.
The present invention provides a viscous hydrogel mask pack composition. Hydrogel for a mask pack is extracted from a heating unit, and the mask pack composition comprises: 50-80 wt% of extracted hydrogel, 10-45 wt% of a nutritional component concentrate, and 0.5-7 wt% of oil. Morphological standardization is not performed in a mask type, and hydrogel is directly coated on skin by a user. Thus, the original excellent moisturization and skin adhesion of hydrogel having the properties of a hydrophilic polymer material can be improved. Compared to conventional mask-shaped hydrogel, the viscous hydrogel mask pack composition of the present invention has more excellent adhesion. Heated warm hydrogel is directly coated on skin, so transferring power of active ingredients can be improved.