anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Risk Summary

SOHONOS is contraindicated during pregnancy. Based on the findings in animal studies and class effects of retinoids, SOHONOS can cause fetal harm when administered during pregnancy [see Warnings and Precautions (5.1) and Use in Specific Populations (8.3)]. In animal reproduction studies, oral administration of palovarotene to pregnant rats during the period of organogenesis resulted in multiple fetal malformations typical of retinoids (e.g., cleft palate, malformed skull bone, shortening of the long bones) at doses ≥0.25 mg/kg/day (less than the clinical exposure) (see Data). There are no available human data on SOHONOS use in pregnant women. If pregnancy occurs during treatment with SOHONOS, discontinue treatment immediately and refer the patient to an obstetrician/gynecologist or other specialist experienced in reproductive toxicity for further evaluation and counseling.

Data

Animal Data

Palovarotene oral administration to pregnant rats during the period of organogenesis (gestation day 6 to 17) at doses of 0.01, 0.25 and 1.25 mg/kg/day resulted in fetal malformations consistent with retinoid-mediated embryopathy. Palovarotene exposure resulted in fetal external, visceral and skeletal malformations typical of retinoids, including defects in the mouth (cleft palate, protruding tongue), eye (anophthalmia, microphthalmia), skull (dilated cerebral ventricle, misshapen brain), skeleton (shortening of the long bones), blood vessels, kidney, and ureters at doses ≥ 0.25 mg/kg/day (less than the clinical exposure). The fetal toxicity was observed at maternal rat exposures well below the range of clinically relevant exposures.
Inhibitors are provided for inhibiting the activity of clathrin. In particular, binding site(s) on the clathrin terminal doman (TD) for binding inhibitors have been identified. The binding sites are defined by amino acid(s) in the group Ile 52, Ile 62, Ile 80, Phe 91, and Ile 93 of the clathrin TD (SEQ ID No. 1). In at least some forms, the binding site may be further defined by amino acid(s) in the group Ile 66, Arg 64, Leu 82 andf Lys 96 of SEQ ID No. 1, or by Val 50 of SEQ ID No.1. There are also provided methods for prophylaxis or treatment of disease and conditions responsive to the inhibition of clathrin.
The Health and Environmental Sciences Institute (HESI) is a nonprofit organization dedicated to resolving global health challenges through collaborative scientific efforts across academia, regulatory authorities and the private sector. Collaborative science across non-clinical disciplines offers an important keystone to accelerate the development of safer and more effective medicines. HESI works to address complex challenges by leveraging diverse subject-matter expertise across sectors offering access to resources, data and shared knowledge. In 2008, the HESI Cardiac Safety Committee (CSC) was established to improve public health by reducing unanticipated cardiovascular (CV)-related adverse effects from pharmaceuticals or chemicals. The committee continues to significantly impact the field of CV safety by bringing together experts from across sectors to address challenges of detecting and predicting adverse cardiac outcomes. Committee members have collaborated on the organization, management and publication of prospective studies, retrospective analyses, workshops, and symposia resulting in 38 peer reviewed manuscripts. Without this collaboration these manuscripts would not have been published. Through their work, the CSC is actively addressing challenges and opportunities in detecting potential cardiac failure modes using in vivo, in vitro and in silico models, with the aim of facilitating drug development and improving study design. By examining past successes and future prospects of the CSC, this manuscript sheds light on how the consortium's multifaceted approach not only addresses current challenges in detecting potential cardiac failure modes but also paves the way for enhanced drug development and study design methodologies. Further, exploring future opportunities and challenges will focus on improving the translational predictability of nonclinical evaluations and reducing reliance on animal research in CV safety assessments.
FIELD: medicine, phytotherapy. SUBSTANCE: medicinal agent is spirituous infusion based on seeds, pulp and peel without the surface layer and juice (in the case of the use of unnatural oranges containing tanning agent in pulp). Vegetable raw is collected in tropic and subtropic regions at long vegetation period of plants for 4 weeks before and 2 weeks after onset of peel separating without pulp. Invention can be used in technology of preparing medicinal infusions and extracts based on vegetable raw. EFFECT: improved technology of preparing. 1 tbl
Individuals will receive pulsed ultrasound with a mechanical index of 1.4 delivered to the splenic hilum and the cervical vagus nerve. The two doses will be administered in separate visits with min. 14 days between each stimulation.
A Bifidobacterium lactis BL-99 strain capable of enhancing immunity and the use thereof, which belongs to the technical field of microorganisms, is described. The Bifidobacterium lactis BL-99 provided by the present invention is deposited in China General Microbiological Culture Collection Center CGMCC on Apr. 26, 2018 with the deposit number CGMCC No. 15650. The bacteria have gastric acid resistance and intestinal fluid resistance, can significantly promote the growth of Bifidobacterium and Lactobacillus, significantly increase antibody-producing cells and half hemolysis value HC50, activate NK cell activity, and can be used to prepare foods for immunity enhancement. It also has the effects in preventing osteoporosis, increasing blood calcium and/or phosphorus ions, which has a wide range of application prospects.
During aging, changes in body composition can result in sarcopenic obesity, which is a condition in which obesity occurs accompanied by the loss of muscle mass and strength caused by sarcopenia. Although the effects of obesity and sarcopenia on body composition are known, the muscle-specific strength in older women with sarcopenic obesity remains under-researched. The objective of this study was to evaluate community-dwelling older women for the absence or presence of obesity, sarcopenia and sarcopenic obesity and compare them in terms of body composition, functional physical performance and muscle-specific strength. One hundred and fifty-six older women (± 74 years) were evaluated for body composition using Dual X-ray Absorptiometry, handgrip strength with a Jamar dynamometer and functional performance using gait speed and timed up and go tests. The presence of obesity, sarcopenia and sarcopenic obesity was found in 32.7%, 15.4% and 25% of the sample, respectively. Comparing groups, community-dwelling older women with sarcopenic obesity exhibited poorer functional physical performance (TUG ± 14 s), and lower muscle-specific strength (± 1.18). Sarcopenic obesity was associated with muscle-specific strength (95% IC 0.016-0.241), and TUG (95% CI 1.001-1.137). These findings indicate that the combination of obesity and sarcopenia has a negative impact on skeletal muscle, reducing muscle-specific strength and physical performance in older women with more declines than either disease alone. Therefore, this comprehensive assessment gives useful information for incorporating muscle-specific strength into the diagnosis of sarcopenic obesity in the older people.
Sulawesi crested macaques (Macaca nigra) (SCMs) are critically endangered and frequently suffer from chronic intestinal disease in captivity. Often, despite routine diagnostic investigations and confirmation of intestinal inflammation, an aetiology cannot be identified, leading to a non-specific categorization as chronic enterocolitis rather than an aetiological diagnosis. This study evaluates the histological features of gastrointestinal tissues from 23 SCMs, comparing animals with a clinical history suggestive of chronic enterocolitis (n = 14) with those without gastrointestinal clinical signs (n = 9). Tissues were graded according to the Nancy index (NI), a scoring system used in human medicine to evaluate disease activity in ulcerative colitis, a common form of human inflammatory bowel disease (IBD). Additionally, inflammatory cells in the colonic lamina propria were visually identified by type, counted and subsequently compared between diseased and control animals. Moderate to severe lymphoplasmacytic inflammation and structural changes were most common in the colons of affected SCMs, whereas histopathological changes were absent or mild in all examined small intestine (n = 17) and stomach (n = 11) tissues. The colonic NI had a significant positive correlation with clinical disease severity and 57% (n = 8) of animals with clinical signs had a NI grade of ≥2, consistent with moderate to severe, active IBD. Half of SCMs with recurrent rectal prolapse (n = 6) had a NI grade of 0, suggesting that intestinal inflammation is not always part of this condition's pathogenesis. The numbers of colonic lymphocytes, plasma cells, neutrophils, macrophages and total leucocytes were significantly higher in diseased animals. This study validated the use of the NI in SCMs, enabling a more standardized histopathological evaluation of the colon in this species.
BACKGROUND: Permanent health impairments after a COVID-19 infection can lead to a lack of social participation and pronounced emotional stress. The aim of this study was to find out how Long COVID affects the social activities of those affected and understand the role that medical support and the immediate social environment play in this.
METHODS: Between January and May 2022, 25 participants with long COVID were interviewed about their health situation, their perception of health care in Germany, and their social and professional context. The interviews, which were mainly conducted online, were analyzed for content, and the results were assessed using lifeworld-theoretical approaches.
RESULTS: The participants reported a variety of health symptoms such as fatigue, shortness of breath, and cognitive impairments. The majority of respondents had a pessimistic attitude toward a timely recovery. Most participants perceived the medical support for long COVID as inadequate. Long waiting times for specialist appointments and the lack of acceptance of the health impairment by some doctors lead to an increase in existing uncertainties. Long COVID also had a major impact on respondents' social life. Many participants referred to a burdensome decline in the number of meetings with family and friends. Many respondents avoided physical contact with friends and family members due to a high level of fear of infection. Some participants explained that they separated themselves from people in their environment because they did not take their precarious situation seriously. However, an important resource was the close circle of family and friends from whom the majority of the interviewees received support.
DISCUSSION: While other research studies particularly emphasize the comprehensive psychological and emotional consequences of long COVID, such as identity conflicts, existential angst, or depression, the present study shows that a lack of understanding from medical professionals as well as heavily delayed treatment leave the interviewees in a state of emotional void.
CONCLUSIONS: The findings show a considerable need for support among people with health impairments after a COVID-19 infection. Empathic and empirically based counseling and support by general practitioners as well as improvement of access to rehabilitative services can provide substantial support for people with long COVID.
Participants will receive their usual medical care and an educational booklet with information about Aromatase Inhibitors (AIs), side effects they cause including painful arthralgia, methods for managing arthralgia, and tips for talking with doctors about arthralgia and other AI side effects. They will also be given access to an online pain coping skills training program and asked to complete it at home over 8 to 10 weeks. This interactive, web-based program teaches cognitive and behavioral skills that research has shown can reduce pain and pain-related interference with daily activities. The program includes eight sessions that participants will complete at a rate of about 1 per week. Each session takes 35-45 minutes. Participants will be shown how to use the program and can contact the study team if they have any problems with it. Participants who do not have a device capable of accessing the program will be loaned a tablet computer for the study.
This is a Phase II, randomized (the study medication is assigned by chance), open-label (all people know the identity of the intervention), controlled, single centre study. The study consists of 3 phases including, the screening phase (4 weeks before administration of study medication), treatment phase (48 weeks), and the follow-up phase (4 weeks). In the treatment phase, HIV-infected participants who have not changed their first-line treatment of highly active antiretroviral therapy (HAART) for at least 8 weeks and have documented evidence of their HIV- ribonucleic acid (RNA) measurements being virologically suppressed (HIV-RNA less than 50 copies/mL) for at least 24 weeks prior to the screening, will be randomly assigned equally in two treatment arms: triple combination therapy arm (DRV/r 800/100 mg once daily plus 2 NRTIs) or monotherapy arm (DRV/r 800/100 mg once daily). Participants in the triple combination arm who are already on 2 NRTIs prior to randomization may remain on these or switch them at baseline, where the participants on the monotherapy arm will discontinue HAART at baseline and will start DRV/r 800/100 mg once daily. Safety evaluations will include assessment of adverse events, significant vital signs, and significant laboratory tests. The total duration of the study will be 56 weeks.
The present invention relates to solid forms of 13-(N-Boc-β-isobutylserinyl)-14-β-hydroxybaccatin III 1,14-carbonate (Ortataxel). Amorphous Form A, crystalline Form B, mixtures thereof and processes for preparing them are disclosed. Amorphous Form A is prepared by fast precipitation of Ortataxel from a mixture of acetone and water. Form A transforms in Form B when suspended and stirred in a mixture of ethanol and water for 4-8 hours. If the suspension is stirred for less than 4 hours, mixtures of Form B and Form A are obtained. Form B or mixtures of Forms A and B can also be obtained dissolving Ortataxel in a protic organic solvent, followed by addition of water.
There will be a washout of at least 5 days between MK-5684 dosing in Period 1 and the first diltiazem dosing in Period 2. In Period 2, diltiazem will be administered once daily (QD) for 6 consecutive days with a single dose of MK-5684 coadministered on Day 2 under fasting conditions. HRT (prednisone and fludrocortisone) will be administered under fed conditions QD on Days 2 through 5, approximately 4.5 hours after MK-5684 and/or diltiazem dosing.
PURPOSE: Core body temperature has been extensively investigated as a thereuptic target in care after cardiac arrest. Nevertheless, the integrity of thermoregulation in patients after cardiac arrest has not been well studied. We sought to evaluate whether low spontaneous body temperature after cardiac arrest is associated with increased death and a worse neurologic outcome, and whether patients with low spontaneous body temperature exhibit features suggestive of impaired thermoregulation.
METHODS: We conducted a single-centre retrospective cohort study. We included all adult patients who underwent temperature control with hypothermia after cardiac arrest between 1 January 2014 and 30 June 2020. The primary exposure was low spontaneous core body temperature (< 35 °C) at initiation of hypothermia therapy. The primary outcome was in-hospital death and the secondary outcome was poor neurologic outcomes at discharge.
RESULTS: Five hundred and ninety-seven adult patients, comprising both in- and out-of-hospital cardiac arrests, were included. Patients with low spontaneous body temperature also had slightly lower average temperature, and more frequent transient but controlled breakthrough fever episodes in the first 24 hr. In the multivariable logistic regression analysis, low spontaneous body temperature was associated with higher odds of in-hospital death (odds ratio, 2.9; 95% confidence interval, 1.9 to 4.2; P < 0.001).
CONCLUSION: In this single-centre retrospective cohort study, low spontaneous core body temperature was associated with poor outcomes in patients after cardiac arrest. Patients with low spontaneous body temperature also exhibited features suggestive of impaired thermoregulation. Further research is needed to determine whether body temperature upon presentation reflects the robustness of the patient's underlying physiology and severity of brain insult after a cardiac arrest.
The aim of this study was to investigate the utility of serum soluble B7-H3 (sB7-H3) as a diagnostic marker for early-stage nonsmall cell lung cancer (NSCLC) and its potential for evaluating the prognosis of patients with advanced-stage NSCLC. In this study, an ELISA was employed to detect the expression levels of sB7-H3 in a cohort of patients diagnosed with NSCLC ( n  = 122) and a control group ( n  = 42) during the same observation period. Comparative analyses were conducted to ascertain the variations in sB7-H3 concentrations between the NSCLC cohort and the healthy control group, as well as across pathological types and the presence and absence of lymph node metastasis. (1) The concentration of sB7-H3 in patients diagnosed with NSCLC exhibited a statistically significant increase compared to that observed in the healthy control group ( P  < 0.05). Elevated expression levels of sB7-H3 demonstrated a significant correlation with pathological type, lymph node metastasis, tumor, node and metastasis stage and programmed cell death ligand (PD-L1) expression ( P  < 0.05). (2) The diagnostic utility of sB7-H3 for the diagnosis of NSCLC and the heightened expression of PD-L1 demonstrated high levels of sensitivity and specificity. (3) Elevated levels of sB7-H3 emerged as an independent risk factor impacting the overall survival of patients diagnosed with advanced NSCLC. The findings of this study suggest that sB7-H3 holds promise as a diagnostic tool for early-stage NSCLC. The elevated expression of sB7-H3 appears to serve as a reliable indicator for assessing the prognosis of patients diagnosed with advanced NSCLC.
NUVIGIL is indicated to improve wakefulness in patients with excessive sleepiness associated with obstructive sleep apnea, narcolepsy and shift work disorder.

In OSA, NUVIGIL is indicated as an adjunct to standard treatment(s) for the underlying obstruction. If continuous positive airway pressure (CPAP) is the treatment of choice for a patient, a maximal effort to treat with CPAP for an adequate period of time should be made prior to initiating NUVIGIL. If NUVIGIL is used adjunctively with CPAP, the encouragement of and periodic assessment of CPAP compliance is necessary. 

In all cases, careful attention to the diagnosis and treatment of the underlying sleep disorder(s) is of utmost importance. Prescribers should be aware that some patients may have more than one sleep disorder contributing to their excessive sleepiness.

The effectiveness of NUVIGIL in long-term use (greater than 12 weeks) has not been systematically evaluated in placebo-controlled trials. The physician who elects to prescribe NUVIGIL for an extended time in patients should periodically re-evaluate long-term usefulness for the individual patient.
A previously healthy 22-year-old woman was admitted to our hospital after an out-of-hospital cardiac arrest. Spontaneous circulation was restored prior to arrival at the hospital. However, the patient's vital signs remained unstable. Vasopressors and hyperhydration therapy were administered. Computed tomography did not reveal a cause of the cardiac arrest. Antibiotics were initiated after obtaining blood culture samples. The patient was admitted to the intensive care unit (ICU). High-dose vasopressors and hyperhydration therapy were continued and fresh frozen plasma was transfused. Two hours after ICU admission, gram staining of a blood smear revealed the presence of Streptococcus, and the antibiotics were switched to penicillin G potassium and clindamycin, and immunoglobulins were administered. Extracorporeal membrane oxygenation was initiated 10 h after ICU admission owing to respiratory failure caused by fluid overload; however, the patient's condition did not improve and she died 40 h after admission. Blood culture results confirmed the presence of Streptococcus pyogenes; the T and M serotypes were unclassifiable. The emm genotype was emm22. Sequencing revealed the presence of streptococcal pyrogenic toxin genes, speA and speB, whereas speC was absent. CsrS, CsrR, and Rgg amino acid sequencing revealed the presence of a CsrS mutation.
PURPOSE: To evaluate the degree of lung hyperinflation (LH) in patients with stable chronic obstructive pulmonary disease (COPD) by lung ultrasound score (LUS) and assess its value.
PATIENTS AND METHODS: We conducted a study of 149 patients with stable COPD and 100 healthy controls recruited by the Second Affiliated Hospital of Fujian Medical University. The pleural sliding displacement (PSD) was measured, the sliding of the pleura in different areas was observed, and LUS was calculated from both of them. The diaphragm excursion (DE), residual capacity (RV), total lung capacity (TLC), inspiratory capacity (IC) and functional residual capacity (FRC) were measured. We described the correlation between ultrasound indicators and pulmonary function indicators reflecting LH. Multiple linear regression analysis was used. The ROC curves of LUS and DE were drawn to evaluate their diagnostic efficacy, and De Long method was used for comparison.
RESULTS: (1) The LUS of patients with stable COPD were positively correlated with RV, TLC, RV/TLC and FRC and negatively correlated with IC and IC/TLC (r1=0.72, r2=0.41, r3=0.72, r4=0.70, r5=-0.56, r6=-0.65, P < 0.001). The correlation was stronger than that between DE at maximal deep inspiration and the corresponding pulmonary function indices (r1=-0.41, r2=-0.26, r3=-0.40, r4=-0.43, r5=0.30, r6=0.37, P < 0.001). (2) Multiple linear regression analysis showed that LUS were significantly correlated with IC/TLC and RV/TLC. (3) With IC/TLC<25% and RV/TLC>60% as the diagnostic criterion of severe LH, the areas under the ROC curves of LUS and DE at maximal deep inspiration for diagnosing severe LH were 0.914 and 0.385, 0.845 and 0.543, respectively (P < 0.001).
CONCLUSION: The lung ultrasound score is an important parameter for evaluating LH. LUS is better than DE at maximal deep inspiration for diagnosing severe LH and is expected to become an effective auxiliary tool for evaluating LH.