anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The current standard of care of patients with moderate to severe COPD is a combination of inhaled corticosteroids, long-acting beta agonist and a long-acting muscarinic agonist (3-5). This treatment recommendation does not consider the heterogeneity of bronchitis in patients with COPD. A third of patients with COPD without asthma may have an eosinophilic bronchitis that is likely to respond to inhaled corticosteroids or prednisone. Approximately 1 in 5 exacerbations are also likely to be associated with an eosinophilic exacerbation (6). This is unlikely to be controlled or prevented by the current recommendations that do not examine bronchitis at the time of exacerbations. None of the major clinical trials that have evaluated treatments that form the basis of current guidelines have examined bronchitis at the time of exacerbations.

Quantitative cell counts in sputum provide a reliable method to assess bronchitis. Sputum can be safely induced with hypertonic saline even in patients with moderate and severe COPD. Similarly to asthma (7), the presence of eosinophils in sputum is a predictor of short-term response in forced expiratory volume at one second (FEV1) and quality of life to inhaled (8) and oral corticosteroids (9). A single study has demonstrated that normalizing eosinophils in sputum in patients with COPD reduces severe exacerbations and hospitalizations by approximately 60% (10). The relative risk reduction in this study is greater than that demonstrated by any study conducted so far in COPD. Long-term studies have not been conducted.

Our recent experience with mepolizumab demonstrated that specifically targeting eosinophils in patient with severe asthma had a prednisone-sparing effect (11) and decrease exacerbations (11,12). In this study it also improved their lung function including in those patients with associated COPD. This is not surprising given that persistent airway eosinophilia can contribute to airway remodeling (13). Indeed, the improvement in FEV1 was associated with a decrease in sputum hyaluron (14) over the six month treatment period. Changes in lung function and symptoms have not been consistently observed in previous mepolizumab trials (12,15). This is clearly related to how precise the patients where phenotyped in terms of sputum eosinophilia. In studies that recruited patients who had persistent sputum eosinophilia, decrease in exacerbations were associated with improvements in FEV1 (16).

It is thus likely that a specific treatment such as anti-IL5 directed against eosinophils would be superior to the current standard treatment in decreasing exacerbations in patients with COPD who continue to have eosinophils in their airway and whose airway disease has an eosinophil-driven component as evidenced by persistent airway eosinophilia.
Immunotherapies, such as chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies or T-cell engagers, have revolutionized the treatment landscape for various B-cell malignancies, including B-acute lymphoblastic leukemia and many non-Hodgkin lymphomas. Despite their significant impact on these malignancies, their application in chronic lymphocytic leukemia (CLL) management is still largely under investigation. Although the initial success of CD19-directed CAR T-cell therapy was observed in 3 multiply relapsed CLL patients, with 2 of them surviving over 10 years without relapse, recent CAR T-cell therapy trials in CLL have shown reduced response rates compared to their efficacy in other B-cell malignancies. One of the challenges with using immunotherapy in CLL is the compromised T-cell fitness from persistent CLL-related antigenic stimulation, and an immunosuppressive tumor microenvironment (TME). These challenges underscore a critical gap in therapeutic options for CLL patients intolerant or resistant to current therapies, emphasizing the imperative role of effective immunotherapy. Encouragingly, innovative strategies are emerging to overcome these challenges. These include integrating synergistic agents like ibrutinib to enhance CAR T-cell function and persistence and engineering newer CAR T-cell constructs targeting diverse antigens or employing dual-targeting approaches. Bispecific antibodies are an exciting "off-the-shelf" prospect for these patients, with their investigation in CLL currently entering the realm of clinical trials. Additionally, the development of allogeneic CAR T-cells and natural killer (NK) cells from healthy donors presents a promising solution to address the diminished T-cell fitness observed in CLL patients. This comprehensive review delves into the latest insights regarding the role of immunotherapy in CLL, the complex landscape of resistance mechanisms, and a spectrum of innovative approaches to surmount therapeutic challenges.
Subject after Coronary Sinus Reducer implantation due to chronic disabling refractory angina pectoris (Canadian Cardiovascular Society \[CCS\] classes 2-4) despite maximally tolerated anti-angina medical therapy. All patients were evaluated by the local Heart Team and considered not amenable to percutaneous or surgical revascularization procedures. After the Heart Team evaluation patients were qualified for the procedure or Coronary Sinus Reducer implantation unless they meet one of the exclusion criteria. Initial patient evaluation (prior to device implantation) consists of past medical history, actual clinical assessment with an evaluation of CCS class, Seattle Angina Questionnaire - 7 items (SAQ-7) scores, 6-min walk distance (6-MWT) test, and echocardiography. First, a follow-up visit is scheduled 1 month after the implantation procedure than the follow-up is planned twice a year.
The pharmacokinetics of RYANODEX was investigated in healthy volunteers following single-dose administration as an intravenous push over 60 seconds (dose range of 1 to 2.5 mg/kg), via a peripheral catheter. There was a dose-proportional increase in plasma exposure of dantrolene and its metabolite, 5-hydroxydantrolene. Table 2 presents pharmacokinetic parameters of dantrolene after administration of a single RYANODEX dose of 2.5 mg/kg. Time to peak dantrolene concentration was observed at the first time point collected (i.e., median Tmax is 1 minute post-dose). The mean half-life (t1/2) for dantrolene was independent of the RYANODEX dose administered and ranged from 8.5 hours to 11.4 hours over the 1 to 2.5 mg/kg dose range.

When prophylactic intravenous dantrolene infusion was administered, whole blood dantrolene concentrations remained at a near steady state level for 3 or more hours after the infusion was completed.

Distribution   
Based on assays of whole blood and plasma, slightly greater amounts of dantrolene are associated with red blood cells than with the plasma fraction of blood. Significant amounts of dantrolene are bound to plasma proteins, mostly albumin, and this binding is readily reversible. Binding to plasma protein is not significantly altered by diazepam, diphenylhydantoin, or phenylbutazone. Binding to plasma proteins is reduced by warfarin and clofibrate and increased by tolbutamide.

Information concerning the passage of dantrolene across the blood-brain barrier is not available.

Metabolism   
Dantrolene is found in measurable amounts in blood and urine. Its major metabolites in body fluids are 5-hydroxy dantrolene and an acetylamino metabolite of dantrolene. Another metabolite with an unknown structure appears related to the latter. Dantrolene may also undergo hydrolysis and subsequent oxidation forming nitrophenylfuroic acid. Following RYANODEX 2.5 mg/kg dose administration in healthy volunteers, mean peak plasma concentration for the primary metabolite, 5-hydroxydantrolene, was 640 ng/mL, and was achieved by approximately 24 hours post-dose, with an average metabolite-to-parent exposure ratio of 0.27 (AUC0-inf = 21.2 μg*h/mL). Median t1/2 for 5-hydroxydantrolene was 10 hours, the clearance was estimated to be 8.9 L/hr and the terminal phase volume of distribution was 144 L.

Dantrolene is metabolized by the liver, and it is possible that its metabolism may be enhanced by drugs known to induce hepatic microsomal enzymes. However, neither phenobarbital nor diazepam appears to affect dantrolene metabolism.
The participants in the intervention group received the intensive care unit diary writing and reading. Participants are required to write at least one sentence daily. The primary writers will be the patients themselves, and in cases where patients are unable to write, their family members will write on their behalf. After completion, the diary will be handed over to the patients to review its contents for at least 10 minutes before bedtime, allowing them to write down their immediate reflections and thoughts on when they read. This process will continue until the 14th day post-operation.
Chronic neck pain is a persistent condition affecting the spinal region, resulting in pain and restricted mobility. The management of neck pain often involves manual therapies, encompassing both passive and active interventions, aimed at alleviating pain, enhancing function, improving mobility, motor control, and reducing inflammatory processes. This pain can persist for at least three months and is considered non-specific when it is not associated with any specific underlying condition, such as inflammatory rheumatic disease, osteoporosis, cancer, or radiculopathy.

The use of lasers and LEDs for photobiomodulation (PBM) represents an advantageous approach to treating neck pain, given their demonstrated therapeutic efficacy in the literature. Moreover, these resources are non-invasive and easy to apply, making them an attractive option for both patients and healthcare professionals. Therefore, the aim of this study is to evaluate the effects of Pompage associated or not with PBM, using a cluster of LEDs, on pain and neck disability. This controlled, randomized, and double-blinded clinical study includes participants of both genders, aged 18 to 62, with non-specific chronic neck pain will be included. Participants will be randomized into two groups: (1) Pompage (n=28) focusing only on manual therapy through Pompage technique and (2) Pompage + PBM Group (n=28) involving the same procedures as the first group, followed by PBM with a LED cluster applied for 10 minutes to the neck region. The treatment protocol consists of 10 sessions, three times weekly, excluding weekends. For PBM, a cluster comprising 264 LEDs (8 mW; 4.89J; 9.6 J/cm2; 16 mW/cm² per LED) will be used, with 132 red (660nm) and 132 infrared (850nm) LEDs. Pain and functional disability will be assessed using the visual analog scale (VAS) and Neck Pain Disability Index before and after the intervention. The resulting data will be submitted to statistical analysis considering α=0.05.
The present invention relates to a new method to obtain more effective CAR-T cells. Here, the inventors worked on the function of FOXO1 in T lymphocyte physiology for many years. They recently described, using a FOXO1 pharmacological inhibitor, that the acute block of this transcription factor induces a drastic metabolism modification of quiescent T cells, notably allowing their infection with lentiviruses (Roux et al., 2019). Thanks to permissivity induced by FOXO1 inhibition, the inventors explored the possibility that a simple pharmacological treatment during ex vivo culture can generate CAR-T cells lacking the exhausted characteristics of classical CAR-T cells. They showed for the first time that the inhibition of FOXO1 potentiates the ability to induce lysis of a target cell thanks to the increased expression of TNF-α and other inflammatory cytokines, induces spontaneous cell polarization comparable to that obtained by stimulation with chemokines and thus improves the motility of the cells, induces a sharp increase of memory T cells and allows to obtain more efficient CAR- T cells to treat solid tumors than classical CAR-T cells obtained with the known protocol. Thus, the present invention relates to an  ex vivo  method to obtain improved CAR-T cells comprising the following steps i) cultivate T cells obtained from a subject with a FOXO1 inhibitor during a time of 2 to 10 days; ii) transforming the T cells into CAR-T cells thanks to a known method.
BACKGROUND: The HPV-automated visual evaluation (PAVE) Study is an extensive, multinational initiative designed to advance cervical cancer prevention in resource-constrained regions. Cervical cancer disproportionally affects regions with limited access to preventive measures. PAVE aims to assess a novel screening-triage-treatment strategy integrating self-sampled HPV testing, deep-learning-based automated visual evaluation (AVE), and targeted therapies.
METHODS: Phase 1 efficacy involves screening up to 100,000 women aged 25-49 across nine countries, using self-collected vaginal samples for hierarchical HPV evaluation: HPV16, else HPV18/45, else HPV31/33/35/52/58, else HPV39/51/56/59/68 else negative. HPV-positive individuals undergo further evaluation, including pelvic exams, cervical imaging, and biopsies. AVE algorithms analyze images, assigning risk scores for precancer, validated against histologic high-grade precancer. Phase 1, however, does not integrate AVE results into patient management, contrasting them with local standard care.Phase 2 effectiveness focuses on deploying AVE software and HPV genotype data in real-time clinical decision-making, evaluating feasibility, acceptability, cost-effectiveness, and health communication of the PAVE strategy in practice.
RESULTS: Currently, sites have commenced fieldwork, and conclusive results are pending.
CONCLUSIONS: The study aspires to validate a screen-triage-treat protocol utilizing innovative biomarkers to deliver an accurate, feasible, and cost-effective strategy for cervical cancer prevention in resource-limited areas. Should the study validate PAVE, its broader implementation could be recommended, potentially expanding cervical cancer prevention worldwide.
FUNDING: The consortial sites are responsible for their own study costs. Research equipment and supplies, and the NCI-affiliated staff are funded by the National Cancer Institute Intramural Research Program including supplemental funding from the Cancer Cures Moonshot Initiative. No commercial support was obtained. Brian Befano was supported by NCI/ NIH under Grant T32CA09168.
Fatigue, cognition and quality of life measurements with different kind of tests and forms. EDSS and SFMC. Daily physical activity measurement 7days. Berg´s scale. Sit-Up 30 s and 6-minutes walking test. Length, weight and waist measurements.
The main objective of the POWER study is to investigate the effects of a 12-week moderate to high-intensity, partially supervised exercise program on cardiorespiratory fitness (VO2peak) in children and adolescents who have completed acute cancer treatment. This randomized controlled trial will include n=56 patients. Patients will be randomly assigned to the intervention or the control group. Patients in the intervention group will perform two supervised exercise sessions per week, one personal training session and one group-based training session. During an initial consultation, both groups receive recommendations for individual physical activity goals and a brochure with exercise recommendations as well as a fitness tracker to monitor their daily physical activity. Only the intervention group will receive daily activity targets, which will be adjusted on a regular basis. The study starts 6 weeks after completion of the patient's acute cancer treatment.

Secondary aims of this interventional study are to evaluate additional performance markers, including muscle strength, functional mobility, balance, body composition and patient-reported outcomes including QoL, fatigue, and cognitive function as well as blood markers to evaluate changes in metabolic, immune, and heart health.
To reconstitute, aseptically add 3 mL of preservative free 0.9% sodium chloride to the vial and swirl. This solution may be kept at room temperature and should be used within 8 hours of reconstitution, after which time any unused portion should be discarded.

The vial should be inspected visually for particulate matter and discoloration prior to administration.

For prompt contraction of the gallbladder, a dose of 0.02 mcg sincalide per kg (1.4 mcg/70 kg) is injected intravenously over a 30- to 60-second interval; if satisfactory contraction of the gallbladder does not occur in 15 minutes, a second dose, 0.04 mcg sincalide per kg, may be administered. To reduce the intestinal side effects, an intravenous infusion may be prepared at a dose of 0.12 mcg/kg in 100 mL of Sodium Chloride Injection USP and given at a rate of 2 mL per minute; alternatively, an intramuscular dose of 0.1 mcg/kg may be given.

To accelerate the transit time of a barium meal through the small bowel, administer Sincalide after the barium meal is beyond the proximal jejunum. (Sincalide, like cholecystokinin, may cause pyloric contraction.) The recommended dose is 0.04 mcg sincalide per kg (2.8 mcg/70 kg) injected intravenously over a 30- to 60- second interval; if satisfactory transit of the barium meal has not occurred in 30 minutes, a second dose of 0.04 mcg sincalide per kg may be administered. For reduction of side effects, a 30-minute IV infusion of sincalide [0.12 mcg per kg (8.4 mcg/70 kg) diluted to approximately 100 mL with Sodium Chloride Injection USP] may be administered
The invention relates to a nanocapsule, a preparation method and application thereof, in particular to an encapsulated catalase nanocapsule, a preparation method and application thereof, and belongs to the technical field of biological medicines. The invention provides a nano-capsule for encapsulating catalase, which consists of a high molecular polymer and the catalase. First, it can effectively prolong the circulation time of catalase in vivo to deliver catalase to liver and prevent ischemia reperfusion injury of liver during liver transplantation. In addition, the activity of smoke-induced apoptosis cells can be effectively improved, so that the tobacco smoke-induced apoptosis cells can be used for preventing and treating the damage of tobacco smoke to lung cells. Meanwhile, the preparation method can also effectively remove excessive hydrogen peroxide in bone regeneration, so that the formation of downstream oxygen free radicals is reduced to the greatest extent, old bone absorption is effectively inhibited, new bone generation is increased, and the osteoporosis is relieved. Besides the above indications, the invention can also be used for researching medicaments for treating other oxygen free radical related diseases.
Patients in this group will be treated by 3 months' independent home computerized exercise program. Each patient will receive a personal access code for the exercise program. The duration of each practice is 5-10 minutes per day.
Detailed clinical examination of cases with pes planus will be performed. Inky foot analysis of both feet will be performed to confirm the diagnosis of pes planus in the subjects included in the study. Staheli arch index and Chippaux-Smirak Index will be calculated for each foot based on the footprints obtained. According to the Staheli Arc Index 1 and above, according to the Chippaux-Smirak Index 0.45 and above will be considered as pes planus, static foot pressure measurement will be performed with a pedobarography device in all cases. Peak pressure, maximum force and total foot area values will be obtained. Balance assessment of the patients will be performed with a computerized static posturography device. Individuals will be graded according to the fall index results, as low, medium and high risk. It will be determined whether there is a fall risk with the Timed Up and Go Test, which is one of the clinical balance tests.
The number of older adults with Alzheimer's disease (AD) and related forms of dementia is increasing in Canada and the majority of individuals with dementia develop neuropsychiatric symptoms (NPS) such as agitation, psychosis, depression and anxiety at some time during their illness. NPS are particularly problematic in long-term care (LTC) where approximately 60% of individuals have dementia, and 80% of individuals with dementia have NPS at any time. Adverse outcomes associated with NPS include increased use of psychotropic medications, stress for families and nursing staff, increased costs of care, and decreased quality of life. A novel approach to implementing non-pharmacological interventions for LTC residents with NPS is the use of volunteers. Volunteer-led programs have been demonstrated to be an effective, inexpensive, and sustainable method of implementing psychosocial interventions for older adults in acute care. The objectives of our project are to: 1.) Recruit and train approximately 40 volunteers in the VALID program; 2.) Conduct a cluster-randomized controlled trial of the VALID program in 6 LTC facilities (3 intervention and 3 control LTC sites; 60 individuals with dementia in each of the experimental and control arms) to determine the effect of the VALID program on symptoms of NPS, patient quality of life, volunteer's experience, and LTC staff stress, 3.) Determine key components of the VALID program that served as facilitators and barriers to implementation.
Efficacy Study - We will use stratified block randomization based on race to ensure that the treatment groups maintain comparable race composition. Participants will be randomly assigned to one of the intervention groups or to usual care. Intervention Group 1 will receive, by mail, a DVD version of the interactive computer program; based on responses to its queries, the program will supply immediate feedback to promote mammography. Intervention Group 2 will receive a telephone version of the tailored intervention delivered by a counselor stationed at a computer. The counselor will use questions from the interactive program and deliver messages the program generates in response to each woman's answers. A third group will receive usual care. All women will be asked to participate in 6-month and 21-month follow-up telephone interviews querying stage of mammography adherence and beliefs.
Participants received 60 mg denosumab subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.