anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
This study is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, efficacy and safety study, designed to document the clinical benefit of ataluren when administered as therapy of participants with CF due to a nonsense mutation (premature stop codon) in the CFTR gene. It is planned that \~208 participants who are ≥6 years of age and have a forced expiratory volume in 1 second (FEV1) ≥40% and ≤90% of predicted will be enrolled. Study participants will be enrolled at sites in North America, Europe, and Israel. They will be randomized in a 1:1 ratio to either ataluren or placebo. Participants will receive study drug 3 times per day (at morning, midday, and evening) for 48 weeks. Participants will be evaluated at clinic visits every 8 weeks. Additional safety laboratory testing, which may be performed at the investigational site or at an accredited local laboratory or clinic, is required every 4 weeks for the first 6 months of study participation. At the completion of blinded treatment, all compliant participants will be eligible to receive open-label ataluren in a separate extension study.
The dietary intervention will be a 10-day feasibility trial, using a honey, spice infused baked good. The participants will receive the baked good on day 1 and will be asked to consume a 50-gram baked good daily for 10 days with or without their meals. The honey, spice infused baked good will contain 15g honey and 3g of spice blend (turmeric and cinnamon). A saliva sample will be taken at the start of the intervention (day 1) before consumption of the baked good and after the intervention ends (day 10), 2 hours after consuming the final baked good. Additionally, participants will provide a urine sample to determine microalbuminuria level, complete a spice-consumption survey and a semi-quantitative food frequency questionnaire (day 1). At day 10, participants will indicate if their spice consumption and dietary intake has changed over the past 10 days. Each day, they will tick off the amount of baked good consumed (100%, 75%, 50%, 25%, 0%).
The subjects will be dosed twice daily (BID); in an on-site setting at dose initiation and at times of dose escalation to evaluate safety, and for specimen collection for routine laboratory and pharmacokinetic analysis. Subjects will be discharged and compliance of BID dosing will be monitored via twice daily phone calls by site staff. The initial dose will be 0.5mg BID with a dose escalation every 2-3 days until a maximum tolerated dose is observed or a maximum of 2.5mg BID dose is obtained.
Stimulus control.45 People with insomnia may fail to associate the bedroom with sleep, and instead may associate it with worrying, planning, or recreation. Stimulus control includes the following instructions: (1) go to bed only when sleepy; (2) only use your bed or bedroom for sleep (or sex); (3) if you do not fall asleep quickly (i.e., 15 minutes), leave the bed, do something in another room, and return to bed only when you feel a strong sleep urge; (4) if you do not fall asleep quickly upon returning to bed, repeat instruction 3; (5) use your alarm to awaken at the same time every morning regardless of duration of sleep obtained; and (6) do not take long naps.
Patients undergo computerized cognitive behavior therapy consisting of 45-60 minute sessions once per week for 8 weeks. Patients also complete the PHQ-9 and GAD7 at weeks 1, 3, 5, 7 and 8 and complete other questionnaires for 15-30 minutes each that assess psychosocial and physical symptoms.
Disclosed is a system and method for assisting in verifying the right medication is provided to the right patient, in the right dose, at the right time, and via the right route. The method may include using a scanner to provide first, second, and third signals to a central computer (108) having data defining a first flow rate and first flow rate tolerance. First signal may include data identifying a medication. Second signal may include data identifying a second flow rate. Third signal may include data identifying the volume of medication in a medication container (124). Central computer (108) authorizes the second flow rate if the second flow rate is withing the first flow rate tolerance. An infusion pump (120) receives new operating parameters to implement the second flow rate if the central computer (108) authorizes the second flow rate and the central computer (108) documents initiation of the second flow rate using a time source.
The invention relates to conjugates obtained by reductive amination of serotype 5 pneumococcus capsular polysaccharide. The reductive amination conditions differ from conventional conditions in that they avoid the creation of an undesired compound which is harmful to the immunogenicity of the conjugates. In carbon NMR spectrometry, the undesired compound is characterized by a resonance signal of 13 -14 ppm. The aminated polysaccharides involved in the production of the conjugates have a carbon NMR  spectrum devoid of a resonance signal of 13 -14 ppm. The reductive amination conditions according to the invention are twofold. According to a first method, the reductive amination is performed at a pH which is slightly acidic (4-6, 5) for a maximum of 4 hours. According to a second method, the polysaccharide is initially reduced, then fragmented and finally undergoes the reductive amination per se in conventional or unconventional conditions.  According to the method used, the structure of the aminated polysaccharide can vary (conversion or not of the Sug residue of the repeater unit into N-acetyl quinovosamine and N-acetyl fucosamine) but said variations, as recorded in carbon NMR spectrometry, have no effect on immunogenicity.
Due to the increasing scientific efforts in recent years, a variety of HET are now available for patients with MS. In addition to long-term clinical assessment, monitoring by means of magnetic resonance imaging (MRI) has also become increasingly established. No evidence of disease activity under appropriate immunotherapy has thus been defined in a wide variety of concepts using clinical and MRI parameters. These medical achievements have positively influenced the natural course of MS, especially by significantly reducing the relapse activity. In contrast, however, the risk of potential complications under long-term immunotherapy should not be underestimated. This concerns in particular infection risks but also an increased malignancy risk for various, mostly highly effective immunotherapies.

Therefore, the question increasingly arises in clinical practice as to what extent HET should be continued or should be de-escalated in case of long-term disease course. As patients and doctors take clinical decision to de-escalate their therapies, often after many years of little or even no disease activity, the central question of how to best monitor patients subsequently remains. Digital smartwatch-based measurements or app-based regular assessments could add high-frequency real-world data to the picture and thus improve the understanding of individual disease courses. Additionally, novel serological markers to detect neuronal damage are becoming more widely available. Consequently, this study aims to evaluate different digital measurements and blood-based analyses to monitor disease activity in MS patients, which have independently with their treating physicians decided to discontinue or de-escalate their disease-modifying treatment of MS.

Data captured by the used smartwatches (Withings Scanwatch) includes activity-related data (step count, minutes in certain intensity levels), basic cardiovascular measurements such as heart rate, and sleep-related data (total time asleep, sleep efficiency and quality etc.). Blood-based measurements include serum neurofilament-light-chain (sNfL), glial fibrillary acidic protein (GFAP) and proteomic data. The investigators will attempt to closely analyze MS patients after de-escalating or discontinuation of immunotherapy using digital and serological biomarkers in order to detect possible increased disease activity. In addition to clinical assessment, structural MRI examinations will be optionally conducted in patients from core center at baseline and in month 12 and 24. Measurement parameters from clinical MRI examinations (lesion load) are also taken into account from the other study centers. In addition to that, patients from core center will undergo an Optical coherence tomography (OCT) measurement. OCT is a non-invasive, interferometric method that allows for detailed visualization of retinal morphology and is known to reveal abnormalities in various central nervous system (CNS) disorders. Data will be collected for a 24-month prospective period.
The aim of this study was to elucidate the specific mechanism through which 7-difluoromethoxy-5,4'-dimethoxygenistein (DFMG) inhibits angiogenesis in atherosclerosis (AS) plaques, given its previously observed but poorly understood inhibitory effects. In vitro, a model using Human Umbilical Vein Endothelial (HUVEC-12) cells simulated the initial lesion in the atherosclerotic pathological process, specifically oxidative stress injury, by exposing cells to 30 μmol/L LPC. Additionally, an AS mouse model was developed in ApoE knockout mice through a 16-week period of high-fat feeding. DFMG demonstrated a reduction in tubule quantities in the tube formation assay and neovascularization induced by oxidative stress-damaged endothelial cells in the chicken embryo chorioallantoic membrane assay. Furthermore, DFMG decreased lipid levels in the blood of ApoE knockout mice with AS, along with a decrease in atherosclerotic plaques and neovascularizations in the aortic arch and descending aorta of AS animal models. DFMG treatment upregulated microRNA140 (miR-140) expression and suppressed VEGF secretion in HUVEC-12 cells. These effects were counteracted by Toll-like receptor 4 (TLR4) overexpression in HUVEC-12 cells subjected to oxidative injury or in a mouse model of AS. Dual-luciferase reporter assays demonstrated that miR-140 directly targeted TLR4. Immunohistochemical assay findings indicated a significant inverse relationship between miR-140 expression and TLR4 expression in ApoE knockout mice subjected to a high-fat diet. The study observed a close association between DFMG inhibitory effects on angiogenesis and plaque stability in AS, and the inhibition of the TLR4/NF-κB/VEGF signaling pathway, negatively regulated by miR-140.
BACKGROUND: Sesn2 (Sestrin2) is a stress-induced protein that provides protective effects during myocardial ischemia and reperfusion (I/R) injury, while endoplasmic reticulum (ER) stress may be a pivotal mediator of I/R injury. The goal of this study was to determine whether Sesn2-mTOR (mammalian target of rapamycin) signaling regulates ER stress during myocardial I/R.
METHODS AND RESULTS: In vivo cardiac I/R was induced by ligation and subsequent release of the left anterior descending coronary artery in wild-type (WT) and cardiac-specific Sesn2 knockout (Sesn2cKO) mice. At 6 hours and 24 hours after reperfusion, cardiac function was evaluated, and heart samples were collected for analysis. I/R induced cardiac ER stress and upregulated Sesn2 mRNA and protein levels. Inhibiting ER stress with 4-phenylbutyric acid reduced infarct size by 37.5%, improved cardiac systolic function, and mitigated myocardial cell apoptosis post-I/R. Hearts from Sesn2cKO mice displayed increased susceptibility to ER stress during I/R compared with WT. Notably, cardiac mTOR signaling was further increased in Sesn2cKO hearts compared with WT hearts during I/R. In mice with cardiac Sesn2 deficiency, compared with WT, ER lumen was significantly expanded after tunicamycin-induced ER stress, as assessed by transmission electron microscopy. Additionally, pharmacological inhibition of mTOR signaling with rapamycin improved cardiac function after tunicamycin treatment and significantly attenuated the unfolded protein response and apoptosis in WT and Sesn2cKO mice.
CONCLUSIONS: Sesn2 attenuates cardiac ER stress post-I/R injury via regulation of mTOR signaling. Thus, modulation of the mTOR pathway by Sesn2 could be a critical factor for maintaining cardiac ER homeostasis control during myocardial I/R injury.
INTRODUCTION: There is an urgent unmet medical need for a safe, effective, nonopioid analgesic agent for postoperative pain control.
METHODS: This first-in-man study was designed to explore a data-informed, model-based candidate dosage regimen and safety of a novel formulation of ketorolac tromethamine (NTM-001) delivered as a 12.5-mg intravenous (IV) bolus followed immediately by 3.5 mg/h continuous infusion over 24 h compared versus IV bolus dosing of 30 mg generic ketorolac every 6 h. The study evaluated pharmacokinetic parameters and safety profiles based on a targeted product profile. A graphical overlay method and model-based comparisons were used to assess the concentration-time curve.
RESULTS: Healthy adults (n = 28, 50% men) received NTM-001 and bolus dosing in an open-label crossover design. Observed plasma concentrations were tightly aligned with predicted values with no outliers. Graphical overlay comparisons showed low between-subject variability and agreed with forecasted concentration-time targets. The pharmacokinetic (PK) base models fit with preliminary PK data from both the NTM-001 and bolus groups with model fit median profiles within 95% prediction limits and no updating of the models. Consistent with serum concentration-time profiles, pain relief scores fell within predicted limits, with initial pain relief scores of NTM-001 slightly above the target profile, likely because the initial serum ketorolac concentrations were somewhat higher than predicted. The 24-h pain relief predicted for NTM-001 based on the area under the median ketorolac pain relief versus time curve was about 6% below that of the pain relief target. Both treatments were well tolerated and no subject withdrew because of adverse events.
CONCLUSIONS: The PK parameters for NTM-001 and comparator bolus were similar to the modeling targets with no updating of the base model. There were no outliers and little intersubject variability. NTM-001 delivered as a bolus of 12.5 mg IV followed immediately by continuous infusion of 3.5 mg/h using a standard hospital infusion pump may offer an alternative to opioids for acute postoperative pain control.
This is a multicenter (when more than one hospital or medical school team work on a medical research study), open-label (all people know the identity of the intervention), randomized (the study drug is assigned by chance), parallel-group (Each group of participants will be treated at the same time), comparison study to assess the pharmacokinetics and safety of paliperidone palmitate (study medication) in participants with schizophrenia. The study comprises a 64-day Treatment period and a 155-day Follow-up period. The participants will be randomly assigned to one of the four study groups. The study medication will be administered on Days 1, 8, 36 and 64. Pharmacokinetics of the study medication will be assessed as primary outcome. Participants' safety will be monitored throughout the study.
The investigators propose to perform a 6-month pilot study in Northwest Arkansas in collaboration of two EMS providers; Central EMS and AirEvac. These local providers operate in the WRMC catchment area and transport over 90% of patients with a suspected stroke to WRMC comprehensive stroke center. Thus no changes to their standard operations would be implemented. The aim of this pilot study would be to test the accuracy of VAN-screening in the area in patients treated at WRMC - thus only patients who are brought to WRMC as per current protocol would be included in the study.

The investigators would train Central EMS and AirEvac personnel to perform the V.A.N screen, over a 2-month period (estimated June-July 2020) in several sessions at the Central EMS training center at 800 S. School Ave. in Fayetteville. This training would be performed by study investigators, assisted by medical students, residents, and advanced practice nurses (APNs). The training would consist of a training video, hands-on instruction, and sample scenarios.The investigators would survey all training participants to gather feedback on the format, delivery, and understanding of the training material. The PowerPoint presentation planned for the training session, as well as the post-training quiz, are attached as Appendices to this application. The investigators would expect a rate of 80% correct answers in the post-training quiz. All questions and scenarios would be discussed with all trainees after the quiz, and re-takes would be allowed.
Nasal administration can bypass the blood-brain barrier and directly deliver drugs to the brain, providing a non-invasive route for central nervous system (CNS) diseases. Inspired by the appearance that a gate can block the outside world and the characteristics of the sol-gel transition can form a "gate" in the nasal cavity, a Drop to Gate nasal drop (DGND) is designed to set a gate in nose, which achieves protecting role from the influence of nasal environment. The DGND demonstrates the efficiency and application prospect of delivering drugs to the brain through the N-to-B. The effective concentration of single administration is increased through the hydrophobic interaction between C8-GelMA and SRT1720 (SA), and then cross-linked under UV to form nanogel, which can respond to MMP in the inflammatory microenvironment of sepsis-induced cognitive dysfunction. Finally, the SA/nanogel is compounded into the thermogel, which can respond to the nasal cavity temperature to form DGND in situ, increasing the residence time and delivery efficiency of drugs in the nasal cavity. In vitro, the DGND alleviates lipopolysaccharides (LPS)-induced BV2 inflammation. In vivo, DGND effectively targets the nasal mucosa and deliver drugs to the brain, which activate Sirt1 to alleviate inflammation mediated by microglia and improve cognitive dysfunction in sepsis mice.
Conventional multiple TESE is performed under general or locoregional anesthesia. Through a small vertical incision in the median scrotal raphe, the skin, dartos muscle, and tunica vaginalis are opened to expose the tunica albuginea. The tunica albuginea is ordinarily incised for about 4 mm at the medium region of the testis. A similar biopsy will be systematically performed in the contralateral testis. The biopsy is analyzed by the biologist in the theatre in order to precise if sufficient spermatozoa is retrieved.
Schoolchildren aged 12-13 years in the first year of Compulsory Secondary Education (Enseñanza Secundaria Obligatoria in the Spanish educational system) in the city of Terrassa. The CONTROL arm is formed by schoolchildren in schools that willnot receive the intervention and will continue with ongoing (usual) health education sessions.
In a randomized controlled trial including 340 people living with obesity, with and without type 2 diabetes, digital coaching has induced significant long-term weight loss compared to the usual methods of care. We investigated whether education level influenced this weight loss and which lifestyle changes supported the digital lifestyle coaching program. The intervention consisted of a 1 h face-to-face motivational interview followed by digital coaching using behavioral change techniques. At 6 months, the weight loss in the intervention group was significantly larger in participants with short education (6.0 vs. 2.2 kg, p < 0.01) (p = 0.006). Participants with long education experienced initially a modest weight loss, but the effect was maintained, leading to the largest weight loss at 24 months (5.06 [-11.98-1.86] kg), even though there were fewer coaching sessions in the maintenance period. In multiple regression analyses, the greater weight loss in the intervention group was associated with short education (β = 1.81, p = 0.02), improvements in everyday physical activity (β = 2.60, p = 0.014) and improvements in dietary habits (β = 3.84, p = 0.013). In conclusion, at 6 months, the effect of the intervention was more pronounced in people with short education through improvements in everyday physical activity and dietary habits. However, participants with long education sustained their weight loss at 24 months.
The gastrointestinal microbiome has been shown to be altered in critically-ill children such that there is a larger shift toward pathogenic bacteria. Previous studies have shown that probiotics, fecal transplants, antibiotic decontamination, and dietary interventions can shift the gastrointestinal microbiome toward a metabolically favorable microbiome profile and be associated with improvements in disease burden.

This study will randomize critically-ill children who are stable enough for enteral tube feedings to receive either Pediasure or Nourish. Pediasure is a commercially-made formula that is used commonly in pediatric patients. Nourish is an organic, whole-food formula with a high fiber content. High-fiber diets have been correlated with metabolically favorable microbiome profiles. This study will look at the microbiome before and after initiation of enteral tube feedings to determine if either formula is associated with a shift in the microbiome toward a favorable profile.
Patients receive an optimized conventional treatment for 12 weeks, including lifestyle changes, toilet training and weight-adjusted medication. Conventional medical options include oral laxative medication with polyethyleneglycol or rectal medication with saline enemas in possible combination with a stimulant laxative (glycerin or bisacodyl).
Therapy-related myeloid neoplasms (t-MNs) are a group of hematologic diseases that arise after chemotherapy and/or radiation therapy for a previous cancer or rarely autoimmune diseases. t-MNs had been included in the group of AMLs and remain as a distinct category also in the recent 2016 revision of the WHO classification of myeloid neoplasm and acute leukemia. The latency between exposition to anticancer drugs and development of t-MN may vary from some months up to 10 years, even considering the age at diagnosis of the primary malignancy, the kind of cytotoxic treatment previously used, and the cumulative dose and dose intensity. The prognosis of s-AML is generally considered to be poorer than that of de novo AML. The disease tends to be refractory to chemotherapy, and patients' tolerance of treatment generally is reduced because of prior therapies. 5-year event-free survival (EFS) and overall survival (OS) rates of pediatric t-AML/t-MDS have been reported to be 14% to 30%. However, the results are conflicting and overall lacking when compared with those in adults. The purpose of this national observatory is to record scientific and medical information on cases of secondary Acute Myeloid Leukemias that have occurred in France since 2013 in order to improve the treatment of children and adolescents with this disease in the years to come. The primary objective is to evaluate the association of potential prognostic factors (including clinical-biological factors) with the overall survival of children and adolescents aged 0-18 years diagnosed with secondary AML. The secondary objectives are to test the feasibility of setting up a French national database of secondary AMLs for children and adolescents as a first step towards European implementation, to assess the association of potential prognostic factors with event free survival and the occurrence of treatment-related toxicities, to characterize the molecular abnormalities associated with secondary AMLs in children and adolescents.