anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Rilonacept (Interleukin-1 Trap) has been developed as an antagonist of the cytokine IL-1 in the treatment of rheumatoid arthritis and other inflammatory diseases. IL-1 causes leukocyte accumulation by inducing adhesion receptors on vascular endothelium and stimulating chemokine production. It also stimulates the synthesis of other cytokines, including IL-6, which in turn stimulates synthesis of C-reactive protein (CRP) in the liver. Based on numerous clinical studies, CRP has emerged as a risk marker for the development and clinical expression of atherosclerotic cardiovascular disease, leading to published recommendations for measurement of CRP in screening population subsets for cardiovascular risk. Endothelial function, as evidenced by stimulated nitric oxide release, has also been recognized as a marker of cardiovascular disease risk. Thus, patients with coronary artery disease (CAD) or its risk factors have impaired nitric oxide release from the endothelium compared with healthy subjects. Recent studies have shown that CRP levels were significantly higher in CAD patients compared with healthy subjects, with an inverse correlation between forearm blood flow responses to acetylcholine as a measure of endothelial function and CRP. Endothelial progenitor cells (EPCs) are primitive bone marrow-derived cells that have a capacity to home to sites of vascular injury and differentiate into vascular cell types, and are reduced in number and differentiation capacity in CAD patients relative to healthy subjects. Studies suggest that CRP inhibits viability and endothelial differentiation capacity of EPCs and may account for reduced numbers of EPCs and endothelial dysfunction in CAD patients. The objective of the present study is to demonstrate the potential of an investigational biological agent, rilonacept, as adjunctive treatment for CAD by examining effects of this agent on CRP levels, endothelial progenitor cell mobilization and endothelial function in a randomized, double-blind, placebo-controlled phase I/II clinical trial.
This study will be interventional in nature and employ a crossover, randomized, double-blinded approach. This study will include a maximal oxygen uptake test and three trials: one familiarization trial, and two experimental trials. The familiarization will serve as a practice test to minimize any training effects between experimental trials. The experimental trials will be completed within a 2-week period determined by the luteal phase of the menstrual cycle (days 15-28 of the menstrual cycle, with day 1 being the first day of menstruation). A minimum of 48-72 hours will be provided between testing days.

Experimental trials will consist of baseline testing (height, weight, urinalysis, resting metabolic rate), followed by a treadmill performance protocol. Participants will complete a 3-stage incremental exercise test (at 55%, 65%, and 75% of maximal oxygen uptake respectively). Metabolic data will be collected during this time. Participants will then complete a 10-kilometer running time trial in which markers of intensity are monitored at various time points (blood glucose, blood lactate, heart rate, rating of perceived exertion). Participants and primary researchers will be blinded to all time and speed data. Distance will be the only known measure of progress. Additional blood, urine, and body weight measures will be taken immediately post exercise.
Between 1997-2010 the PALG run three prospective studies. In the most recent PLAG 5-2007 protocol attempts have been made to individualize treatment. In particular, stratification to high and standard risk group was based on both conventional clinical criteria and the level of MRD after induction and consolidation. Patients with unsatisfactory response were referred for allogeneic hematopoietic stem cell transplantation (alloHSCT). Interim analysis showed significant improvement compared to previous PALG 4-2002 protocol with regard to both overall survival and leukemia-free survival. The reasons of failure were relapses and non-relapse mortality (NRM) associated with alloHSCT.

In the current protocol we intend to further adjust the therapy for individual patients needs. We assume that this way we will be able to reduce the risk of relapse and NRM and improve the cure rate. All patients will receive multiagent induction and consolidation chemotherapy. The type and intensity of the therapy, as well as indications for allogeneic and autologous HSCT will depend on age, status of MRD, immunophenotype and the presence of BCR/ABL fusion gene.
PURPOSE:The titled fomentation, obtained by distributing bentonite absorbing water to be an integrated in a continuous phase, containing stably existing water even in high anhydrous condition and having high cold sense in applica tion, high developing rate of the refrigerant feeling and powerful effect. CONSTITUTION:An adhesive fomentation obtained by distributing bentonite adsorbing water to be an integrated state in a continuous phase consisting of a rubber ingredient, preferably A-B-A teleblock copolymer elastomer consisting of styrene-isoprene-styrene, oil ingredient, e.g. liquid paraffin, tackifier ingredient, e.g. rosin or polybutene, and a drug active ingredient, e.g. methyl salicylate menthol, peppermint oil, etc., as principal ingredients. The amount of the water is preferably 5-70wt% based on the total fomentation and the amount of the bentonite is preferably 5-100pts.wt. water. The bentonite absorbing the water is distributed in the form of a lump material and part thereof is exposed to the surface of the fomentation to exhibit improved effect.
Fluid therapy before and under surgery can be guided by measurement of the hearts ability to eject blood (cardiac output). By doing this it has been shown that the occurrence of nausea,vomiting and complications generally can be reduced. The function of the heart has been measured with a probe in the esophagus in in earlier studies. We want to correlate these results with other techniques by which fluid therapy also is guided in daily practice. These are: SVO2, modelflow (finapres)and NIRS.

These methods are noninvasive except SVO2 measurement which requires a central venous catheter (CVK). Therefore we have chosen a population in which CVK is standard in our institution. We thereby don´t apply any further risks than daily practice and the project is considered as a quality assessment of used standards.
INTRODUCTION: Intensive weight management programs are effective but often have low enrollment and high attrition. Lack of motivation is a key psychological barrier to enrollment, engagement, and weight loss. Mental Contrasting with Implementation Intentions (MCII) is a unique imagery technique that increases motivation for behavior change. We describe our study protocol to assess the efficacy and implementation of MCII to enhance the effectiveness of VA's MOVE! or TeleMOVE! weight management programs using a procedure called "WOOP" (Wish, Outcome, Obstacle, Plan) for Veterans. We hypothesize that WOOP+MOVE! or TeleMOVE! (intervention) will lead to greater MOVE!/TeleMOVE! program engagment and consequently weight loss than MOVE!/TeleMOVE! alone (control).
METHOD: Veterans are randomized to either the intervention or control. Both arms receive the either MOVE! or TeleMOVE! weight management programs. The intervention group receives an hour long WOOP training while the control group receives patient education. Both groups receive telephone follow up calls at 3 days, 4 weeks, and 2 months post-baseline. Eligible participants are Veterans (ages 18-70 years) with either obesity (BMI ≥ 30 kg/m2) or overweight (BMI ≥ 25 kg/m2) and an obesity-associated co-morbidity. At baseline, 6 and 12 months, we assess weight, diet, physical activity in both groups. The primary outcome is mean percent weight change at 6 months. Secondary outcomes include changes in waist circumference, diet, physical activity, and dieting self-efficacy and engagement in regular physical activity. We assess implementation using the RE-AIM framework.
CONCLUSION: If WOOP VA is found to be efficacious, it will be an important tool to facilitate weight management and improve weight outcomes.
CLINICAL TRIAL REGISTRATION: NCT05014984.
OBJECTIVE: Child developmental rate holds predictive value for early-stage developmental trajectories, yet few studies explored how sleep problems during different infancy stages impact this rate. This study aims to investigate the correlation between sleep problems and child developmental trajectories.
METHODS: This study utilized a prospective national cohort of 5006 children in Taiwan. The developmental inventories covering motor, cognitive, language, and socioemotional domains were collected through questionnaire-based in-person home interviews conducted at 3, 12, 24, and 36 months. Sleep problems data, encompassing bedtime regularity, sleep duration, and sleep quality, were collected at 3 and 12 months. Child developmental rate was assessed by analyzing the slope of developmental ability estimates over a period of time.
RESULTS: Bedtime regularity and high-quality sleep at 3 and 12 months were found to be significantly associated with intercepts across all domains (estimate = -0.196∼0.233, p < 0.033). Children with high-quality sleep at 3 months showed enhanced developmental slopes in socioemotional domains (estimate = 0.032, p < 0.001). Atypical sleep duration at 3 and 12 months had differential detrimental association with child development in various domains (estimate = -0.108∼-0.016, p < 0.048).
CONCLUSION: The relationship between sleep problems and child development exhibited variability based on the timing of exposure to these issues. Early exposure to low-quality sleep was significantly related to developmental functions and socioemotional developmental rate, potentially leading to increased developmental disparities as children age. Inadequate sleep duration in late infancy and excessive sleep duration in early infancy were both negatively associated with child development trajectories. Policymakers can use these findings to design targeted sleep programs for optimal child development.
MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression and which play important roles in many cell types, including as described herein, the pancreatic .beta.-cell.  Glucagon like peptide-1 (GLP-1), a hormone released from intestinal L-cells following meal intake, exerts pleiotropic effects on .beta.-cell function including raising intracellular cAMP levels and now represents an important therapy for type 2 diabetes.    Expression of miR-132 and miR212 is upregulated by CREB protein in response increased cAMP levels in the cell; therefore, methods for detecting and evaluating .beta.-cell engagement by GLP-1 receptor agonists by monitoring miR- 132 and miR-212 expression in a subject is described. The methods herein are particularly useful in the context of longitudinal clinical trials, such as those designed for testing the durability of any single or combination therapy in type 2 diabetes populations. Because the expression of these miRNAs is not affected by glucose, fatty acid, insulin, or .beta.-cell function, monitoring miR- 132 and miR-212 expression can be used to monitor the efficacy of any agent that effects an increase cAMP in .beta.-cells. Such agents include for example, GLP- 1, glucagon, GPR- 119, and GIP receptor agonists; dipeptidyl peptidase N(DPP IV) inhibitors; and phosphodiesterase inhibitors.
Studies on the role of the gut microbiota in the associations between per- and polyfluoroalkyl substance (PFAS) exposure and adverse neurodevelopment are limited. Umbilical cord serum and faeces samples were collected from children, and the Strengths and Difficulties Questionnaire (SDQ) was conducted. Generalized linear models, linear mixed-effects models, multivariate analysis by linear models and microbiome regression-based kernel association tests were used to evaluate the associations among PFAS exposure, the gut microbiota, and neurobehavioural development. Perfluorohexane sulfonic acid (PFHxS) exposure was associated with increased scores for conduct problems and externalizing problems, as well as altered gut microbiota alpha and beta diversity. PFHxS concentrations were associated with higher relative abundances of Enterococcus spp. but lower relative abundances of several short-chain fatty acid-producing genera (e.g., Ruminococcus gauvreauii group spp.). PFHxS exposure was also associated with increased oxidative phosphorylation. Alpha and beta diversity were found significantly associated with conduct problems and externalizing problems. Ruminococcus gauvreauii group spp. abundance was positively correlated with prosocial behavior scores. Increased alpha diversity played a mediating role in the associations of PFHxS exposure with conduct problems. Our results suggest that the gut microbiota might play an important role in PFAS neurotoxicity, which may have implications for PFAS control.
Being regularly physically active is a basic component of a healthy lifestyle. However, a large amount of the Flemish population does not reach the prescribed guidelines and cannot enjoy the health benefits related to an active lifestyle. One part of the population is physically active but makes no use of the existing, structured and supervised exercise and sports programs. Therefore the chance on lifetime participation in sports and exercise is quite low in this group. Another group consists of sedentary people that does not participate in any exercise or sports activity at all.

A physical activity counselor can possibly deliver a crucial service for the above mentioned groups. He/she can design an individualized sports- or exercise approach and program. In the short term, the physical activity counselor can guide the participant into his first success experiences regarding exercise and sports. In the long term, the chance of remaining physically active will increase by improving the understanding and the self-confidence of these participants.

However it is questioned how the physical activity counselor can reach these target groups in an efficient way, as the traditional sports and exercise promotion seems to have no impact on these persons. A first alternative may be the setting of the general practitioners. The general practitioner is, as a care provider in primary health care, in a good position to refer sedentary people or those who are active in a non-organized context to a physical activity counselor for 'minimal' coaching. A second alternative can be the setting of the social-cultural associations (e.g. seniors association, women association, neighborhood actions, ...). The social context and the local networks in these associations facilitate the proper forms of motivation to exercise with other people and to adapt to a healthy lifestyle.
Risk Summary

Available data from clinical trials and postmarketing reports on REPATHA use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, there were no effects on pregnancy or neonatal/infant development when monkeys were subcutaneously administered evolocumab from organogenesis through parturition at dose exposures up to 12 times the exposure at the maximum recommended human dose of 420 mg every month. In a similar study with another drug in the PCSK9 inhibitor antibody class, humoral immune suppression was observed in infant monkeys exposed to that drug in utero at all doses. The exposures where immune suppression occurred in infant monkeys were greater than those expected clinically. No assessment for immune suppression was conducted with evolocumab in infant monkeys. Measurable evolocumab serum concentrations were observed in the infant monkeys at birth at comparable levels to maternal serum, indicating that evolocumab, like other IgG antibodies, crosses the placental barrier. Monoclonal antibodies are transported across the placenta in increasing amounts especially near term; therefore, evolocumab has the potential to be transmitted from the mother to the developing fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

There is a pregnancy safety study for REPATHA. If REPATHA is administered during pregnancy, healthcare providers should report REPATHA exposure by contacting Amgen at 1-800-77-AMGEN (1-800-772-6436) or https://wwwext.amgen.com/products/global-patient-safety/adverse-event-reporting.

Data

Animal Data

In cynomolgus monkeys, no effects on embryo-fetal or postnatal development (up to 6 months of age) were observed when evolocumab was dosed during organogenesis to parturition at 50 mg/kg once every 2 weeks by the subcutaneous route at exposures 30- and 12-fold the recommended human doses of 140 mg every 2 weeks and 420 mg once monthly, respectively, based on plasma AUC. No test of humoral immunity in infant monkeys was conducted with evolocumab.
There is no universally accepted definition for rare diseases: in Europe a disease is considered to be rare when affecting fewer than 1 in 2000 people. European Reference Networks (ERNs) have been the concrete response to address the unmet needs of rare disease patients and many pan-European issues in the field, reducing inequities, and significantly increasing accessibility to high-quality healthcare across Europe. ERNs are virtual networks, involving centres and patient representatives with the general scope to facilitate discussion on complex cases requiring highly specialised competences and trained expertise. ERN BOND - the European Reference Network on rare BONe Diseases - is one of these 24 approved networks with the specific ongoing mission to implement measures facilitating multidisciplinary, holistic, continuous, patient-centred, and participative care provision to patients, and supporting them in the full realisation of their fundamental human rights. ERN BOND includes in 2023 a total of 53 centres of expertise from 20 European countries. Its governing structure installed in March 2017 includes decision-making, operative and consultative committees, which comprise experts in the field and patient representatives ensuring patient's voice and perspectives are taken into account. Over the years, ERN BOND has worked hard to achieve its mission and valuably contribute to the advancement of diagnosis, management, treatment, and research in rare diseases. The network activities are mainly related to (i) the provision of care which collectively involves averagely 2800 patients diagnosed per year, (ii) the development of education for and training of the healthcare personnel consisting until now in the realisation of 7 thematic workshops and 19 webinars, (iii) the dissemination and exchange and spread of knowledge via network's website (https://ernbond.eu/), social media channels, and newsletters, (iv) the management of related data through a disease registry currently mapping over 2300 cases and recording over 600 reported cases, and (v) the enhancement of research which now include two clinical trials endorsed by the network. ERN BOND represents therefore an unprecedented move to improve the healthcare management of patients suffering from rare bone diseases through European collaborations. This network, through the support from the European Health Programme, will continue to pursue its efforts to achieve its goals, always maintaining the patients and their families at the centre of healthcare services.
Hypoxic pulmonary vasoconstriction (HPV) rapidly and reversibly matches lung ventilation (V) and perfusion (Q), optimizing oxygen uptake and systemic oxygen delivery. HPV occurs in small pulmonary arteries (PA), which uniquely constrict to hypoxia. Although HPV is modulated by the endothelium the core mechanism of HPV resides in PA smooth muscle cells (PASMC). The PASMC's mitochondrial oxygen sensor lies within the electron transport chain (ETC) and includes NDUFS2 in ETC Complex-I. PASMC mitochondria respond to hypoxia by varying production of reactive oxygen species (ROS) and hydrogen peroxide in proportion to alveolar oxygen tension. Hypoxic ROS inhibition results in a state of reduction which triggers a redox-mediated inhibition of oxygen-sensitive, voltage-gated, potassium channels, including Kv1.5 and Kv2.1. Kv channel inhibition depolarizes the PASMC, opening of large-conductance calcium channels (CaL), elevating cytosolic calcium and activating the contractile apparatus. HPV is strongest in small PAs where sensors (hypoxia-responsive mitochondria) and effectors (oxygen-sensitive K+ channels) are enriched. Oxygenation at birth reverses fetal HPV, contributing to the rapid neonatal drop in pulmonary vascular resistance (PVR). A similar mitochon-drial-K+ channel sensor-effector mechanism exists in the ductus arteriosus (DA), however in DASMC it is oxygen-induced increases in mitochondrial ROS that inhibit DASMC K+ channels, causing DA constriction. Atelectasis and pneumonia elicit HPV, which optimises V/Q matching, increasing systemic oxygenation. Whilst HPV in response to localized hypoxia in a single lung lobe does not increase PA pressure; global airway hypoxia, as occurs with altitude or sleep apnea, causes pulmonary hypertension. HPV can be inhibited by drugs, including calcium channel blockers, or used to maintain a dry operative field during single lung anesthesia for lung surgery. HPV does not normally cause lung edema but excessive, heterogenous HPV contributes to high altitude pulmonary edema. HPV is suppressed in COVID-19 pneumonia by a SARS-CoV-2 mitochondriopathy. HPV is a component of the body's homeostatic oxygen sensing system. Keywords: Ductus arteriosus, Redox, NDUFS2, Oxygen sensitive potassium, Channels, High altitude pulmonary edema (HAPE), Mitochondrial electron transport chain, COVID-19 pneumonia, Atelectasis.
The maintenance infusion of 125 mL/hr of Lactated Ringers will be given with no additional fluid bolus. The dose of oxytocin being administered at time of epidural placement was halved and not increased for 60 minutes until after placement.
The invention discloses a water solubility platinum complex containing deoxyglucose and a preparation method and application. The water solubility platinum complex containing the deoxyglucose is shown as the formula (1) (please see the formula in the specifications). The water solubility platinum complex containing the deoxyglucose has an excellent tumor selective drug accumulation effect, and drug resistance formed by a repulsive effect of a tumor to drugs is overcome through targeting performance transmission to tumor cells. Compared with clinical drugs, the water solubility platinum complex containing the deoxyglucose has higher water solubility and is capable of achieving clinical preparation easily. Compared with the clinical drug, namely, oxaliplatin, the water solubility platinum complex containing the deoxyglucose has superiority in the aspect of cytotoxicity. In conclusion, according to the water solubility platinum complex containing the deoxyglucose, not only is the problem of poor preparation stability and the shortcoming of inconvenient clinical using in existing platinum drugs because of lacking in water solubility solved, but also targeting performance of the drugs to tumor cells can be improved, and the deficiency of the existing clinical drugs in the aspects of the tumor therapy effect, the drug resistance and toxic and side effects is solved.