anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
This is an open-label, single-arm, investigator-initiated study (IIT) to evaluate the safety an JWCAR201 in adult patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). The study employs a two-stage, Continual Reassessment Method (CRM)-like dose escalation design. In the first stage, each dose cohort will use an accelerated titration approach, escalating to the dose level at which a Dose-Limiting Toxicity (DLT) occurs or the 50 × 10\^6 CAR+ T-cell dose level (whichever is reached first). The second stage will start at observed DLT dose level or the 50\^6 CAR+ T-cell dose level, an model-based CRM method using a single-parameter Logistic model will be used to describe the relationship between the JWCAR201 dose and the probability of observed DLTs. The Maximum Tolerated Dose (MTD) is defined as the highest an estimated DLT probability below the 25% target toxicity level. For each dose level, a prior mean DLT risk (skeleton) will be set based on historical data. After enrolling ≥3 patients perort, the prior DLT risk will be updated based on the available study data, and the DLT risk will be communicated to the Data Safety Monitoring Committee to recommend the next cohort dose. The study plans to start at 25 × 10\^6 CAR+ T cells as the initial dose, with exploration across three dose levels (25 × 10\^6, 50 × 10\^6, 75 × 10\^6 CAR+ T cells), and 15 × 10\^6 CAR+ T cells or lower and 100 × 10\^6 CAR+ T cells or higher as backup doses, aiming to evaluate the safety, tolerability of JWCAR201 in r/r DLBCL and determine the recommended dose for expansion. Additionally, pharmacokinetic and pharmacodynamic characteristics are also study objectives.
Patients with Parkinson’s disease treated with ZELAPAR or other drugs increasing dopaminergic tone have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes resulted in accidents. Although many of these patients reported somnolence, some did not perceive warning signs, such as excessive drowsiness, and believed that they were alert immediately prior to the event. Some of these events have been reported as late as one year after initiation of treatment. 

It has been reported that falling asleep while engaged in activities of daily living always occurs in a setting of pre-existing somnolence, although patients may not give such a history. For this reason, prescribers should reassess patients for drowsiness or sleepiness especially since some of the events occur well after the start of treatment.

Somnolence may occur in patients receiving ZELAPAR. There was an increased risk for somnolence in geriatric patients (≥65 years) vs. non-geriatric patients treated with ZELAPAR. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. Patients should be advised to exercise caution while driving, operating machines, or working at heights during treatment with ZELAPAR. Patients who have already experienced somnolence and/or an episode of sudden sleep onset should not participate in these activities during treatment with ZELAPAR.

Before initiating treatment with ZELAPAR, advise patients about the potential to develop drowsiness and specifically ask about factors that may increase this risk, such as concomitant sedating medications and the presence of sleep disorders. If a patient develops daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.), ZELAPAR should ordinarily be discontinued. If a decision is made to continue ZELAPAR, patients should be advised not to drive and to avoid other potentially dangerous activities. There is insufficient information to establish whether dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.
Trans women carry the largest population burden of HIV in San Francisco and have low utilization of mental health and substance use services. The investigators' goal is to use lessons learned in a prior previously-funded Special Projects of National Significance to conduct a pilot peer delivered mHealth support and navigation intervention for trans women living with HIV. The investigators will work with partners in San Francisco Department of Public Health (SFDPH) clinics. The SFDPH is a HRSA-funded entity with trans-specific clinics and a host of in-house referrals to trans-competent mental health and substance use services. Despite availability of trans-specific services, considerable systems barriers exist. Trans clinics have limited clinic hours, and providers have large patient loads wherein medical gender affirmation and HIV care needs must be attended to in short visits. Visit and clinic time and large patient volume leaves providers with little time to ensure continuity in mental health and substance use referrals. To overcome these issues, a peer navigator will deliver mobile and in-person support and navigation to increase substance use and mental health service initiation and engagement among trans women living with HIV in trans health clinics. The research team has already conducted formative research with community members, key stakeholders and providers in San Francisco to help shape and refine the intervention model during the implementation phase of the research.In the implementation phase, the research team will pilot the mSN intervention to improve initiation and engagement in mental health and substance use (MHSU) services.
Constricting pythons, known for their ability to consume infrequent, massive meals, exhibit rapid and reversible cardiac hypertrophy following feeding. Our primary goal was to investigate how python hearts achieve this adaptive response after feeding. Isolated myofibrils increased force after feeding without changes in sarcomere ultrastructure and without increasing energy cost. Ca2+ transients were prolonged after feeding with no changes in myofibril Ca2+ sensitivity. Feeding reduced titin-based tension, resulting in decreased cardiac tissue stiffness. Feeding also reduced the activity of sirtuins, a metabolically linked class of histone deacetylases, and increased chromatin accessibility. Transcription factor enrichment analysis on transposase-accessible chromatin with sequencing revealed the prominent role of transcription factors Yin Yang1 and NRF1 in postfeeding cardiac adaptation. Gene expression also changed with the enrichment of translation and metabolism. Finally, metabolomics analysis and adenosine triphosphate production demonstrated that cardiac adaptation after feeding not only increased energy demand but also energy production. These findings have broad implications for our understanding of cardiac adaptation across species and hold promise for the development of innovative approaches to address cardiovascular diseases.
Pain affects one-third of the global population and is a significant public health issue. The use of opioid drugs, which are the strongest painkillers, is associated with several side effects, such as tolerance, addiction, overdose, and even death. An increasing demand for novel, safer analgesic agents is a driving force for exploring natural sources of bioactive peptides with antinociceptive activity. Since the G protein-coupled receptors (GPCRs) play a crucial role in pain modulation, the discovery of new peptide ligands for GPCRs is a significant challenge for novel drug development. The aim of this review is to present peptides of human and animal origin with antinociceptive potential and to show the possibilities of their modification, as well as the design of novel structures. The study presents the current knowledge on structure-activity relationship in the design of peptide-based biomimetic compounds, the modification strategies directed at increasing the antinociceptive activity, and improvement of metabolic stability and pharmacodynamic profile. The procedures employed in prolonged drug delivery of emerging compounds are also discussed. The work summarizes the conditions leading to the development of potential morphine replacements.
Calcium 500 mg by mouth everyday for 12 months. Vitamin D 400 units by mouth 2 times a day for 12 months.
Patients receive paclitaxel IV over 1 hour on day 1 followed by bryostatin 1 IV over 1 hour on day 2 of weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
PURPOSE:To obtain stable human urokinase precursor useful for treating thrombosis, etc. economically in high purity, by purifying a substance containing the human urokinase precursor with an adsorbent carrier containing a specific high polymer and a specific chain substance cleavage inhibitor. CONSTITUTION:A substance containing human urokinase precursor is brought into contact with an adsorbent carrier containing an acrylonitrile polymer to adsorb the above-mentioned precursor specifically therein, and eluted with an aqueous solution of an inorganic or organic substance, e.g. NaCl, from the adsorbent carrier to give the stable human urokinase precursor. Furthermore, a chain substance cleavage inhibitor for the human urokinase precursor, e.g. aprotinin, is present therein to inhibit the cleavage of the single-stranded structure into double-stranded structure and give a urkinaselike substance. The above-mentioned precursor differs from the human urokinase and is a very favorable remedy, because the precursor dissolves coagulated fibrin, etc., without decomposing and consuming plasminogen in the blood.
Resatorvid (TAK-242), a small-molecule inhibitor of Toll-like receptor 4 (TLR4), has the ability to cross the blood-brain barrier (BBB). In this study, we explored the role of TAK-242 on glioblastoma (GBM) invasion, migration, and proneural-mesenchymal transition (PMT). RNA sequencing (RNA-Seq) data and full clinical information of glioma patients were downloaded from the Chinese Glioma Genome Atlas (CGGA) and the Cancer Genome Atlas (TCGA) cohorts and then analyzed using R language; patients were grouped based on proneural (PN) and mesenchymal (MES) subtypes. Bioinformatics analysis was used to detect the difference in survival and TLR4-pathway expression between these groups. Cell viability assay, wound-healing test, and transwell assay, as well as an intracranial xenotransplantation mice model, were used to assess the functional role of TAK-242 in GBM in vitro and in vivo. RNA-Seq, Western blot, and immunofluorescence were employed to investigate the possible mechanism. TLR4 expression in GBM was significantly higher than in normal brain tissue and upregulated the expression of MES marker genes. Moreover, TAK-242 inhibited GBM progression in vitro and in vivo via linking with PMT, which could be a novel treatment strategy for inhibiting GBM recurrence.
Many studies have shown that green tea may have anti-cancer and anti-inflammatory effects in cancer cells and animal models of breast cancer. Some studies have found that Asian women who drink many cups of green tea have lower rates of breast cancer. Green tea may have an effect on proliferative and inflammatory pathways. Women with ductal carcinoma in situ (DCIS) have been found to have inflammation in the breast tissue surrounding DCIS lesions. Inflammatory pathways are being studied for a possible link to cancer. This study is designed to evaluate changes in biomarkers of proliferation, inflammation, and angiogenesis in response to green tea intake.
PROBLEM TO BE SOLVED: To provide a method of transporting antigen peptide to endoplasmic reticulum by fusion protein.SOLUTION: A method of transporting antigen peptide to endoplasmic reticulum by fusion protein includes the following steps. Sequence of fusion protein contains Tat peptide, (His)peptide, ubiquitin protein, and antigen peptide in order from N-terminal to C-terminal. In a step a, fusion protein is manufactured. In a step b where fusion protein is transported from outside a cell into cytoplasm, fusion protein is introduced from outside a cell into the cytoplasm of the cell by Tat peptide. In a step c where antigen peptide is cut out, antigen peptide is cut out from fusion protein by ubiquitin protein C-terminal hydrolase in cytoplasm. In a step d where antigen peptide is transported to the endoplasmic reticulum, the antigen peptide cut out by TAP1/2 transport protein of membrane of the endoplasmic reticulum in the cytoplasm is transported into the endoplasmic reticulum.
Cassava is one of the important industrial crops in Thailand. The leftover fiber of cassava is still valuable and can be used as a dietary fiber. The previous study demonstrated that dietary fiber containing cassava fiber was safe for consumption without any contamination of the cyanide and heavy metals. Moreover, the microbial contaminations were within the safety range. The toxicity study revealed that the LD50 of the cassava dietary fiber was more than 5 g/kg body weight (BW) and NOAEL was 3 g/kg BW. The NOAEL was used to calculate the human equivalent dose for determining the effect of cassava dietary fiber in a clinical study.

Cassava dietary fiber consists of water-insoluble fiber such as cellulose more than 50%. The previous study showed that insoluble fiber decreased the risk of type 2 diabetes and increased insulin release. Moreover, a high fiber diet also decreased the fasting glucose and HbA1C in type 2 diabetes volunteer. In addition, the effect of dietary fiber on the reduction of cholesterol was also reported. The previous study reported that the cassava dietary fiber could decrease the total cholesterol, triglyceride but increase high-density lipoprotein in a dyslipidemia rat model. Therefore, the cassava fiber might be the potential food supplement for the control of blood sugar and lipid profiles in human. However, less scientific data support the effect of cassava dietary fiber in human.
The present invention relates to diagnosis of decreased immunity through analysis of intestinal flora of a gastric cancer patient and a theragnosis composition using the intestinal flora. According to the present invention, it is confirmed that diversity of the intestinal flora is reduced in the gastric cancer patient, and a composition ratio of the intestinal flora in healthy adults is different from a composition ratio thereof in a patient with a benign tumor. It is confirmed that in a gastric cancer patient group, an immune function is decreased, and the patient's immune function decreased as gastric cancer progresses. In addition, it is confirmed that PD-L1 and IL-10, which are increased due to the decreased immunity, are effectively suppressed when patient-derived macrophages are treated with a Faecalibacterium prausnitzii strain and butyrate, a metabolite thereof, which are found to be reduced in the gastric cancer patient group. Moreover, it is confirmed that cell death is effectively induced when gastric cancer cell lines are treated with the Faecalibacterium prausnitzii strain and butyrate, a metabolite thereof. It is confirmed that butyrate inhibits tumor growth and reduces expression of a tumor marker and an immunodeficiency marker in an avatar animal model for gastric cancer patients which reflects a patient's immune status and is transplanted with the gastric cancer cell lines. Accordingly, it is confirmed that by diagnosing collapse of the intestinal flora and decreased immunity in the gastric cancer patient group, and confirming an effect of increasing immunity and restoring the intestinal flora according to treatment with an active substance of the present invention, personalized medicine is feasible. The present invention provides a pharmaceutical composition for preventing or treating cancer, containing butyrate or a microbiome as an active ingredient.
Postmenopausal osteoporosis is diagnosed using Dual-X-ray Absorptiometry (DXA), which measures bone mineral density (BMD) and provides a T-score. A T-score of -2.5 or lower confirms the diagnosis of osteoporosis.
CONTEXT: Monocarboxylate transporter 8 (MCT8) deficiency is a rare genetic disease that leads to severe global developmental delay. MCT8 facilitates thyroid hormone (TH) transport across the cell membrane, and the serum TH profile is characterized by high T3 and low T4 levels. Recent studies have shown that the chemical chaperone sodium phenylbutyrate (NaPB) restored mutant MCT8 function and increased TH content in patient-derived induced pluripotent stem cells, making it a potential treatment for MCT8 deficiency.
OBJECTIVE: We aimed to assess the efficacy and safety of glycerol phenylbutyrate (GPB) in MCT8 deficiency.
METHODS: We treated 2 monozygotic twins aged 14.5 years with MCT8 deficiency due to P321L mutation with escalating doses of GPB over 13 months. We recorded TH, vital signs, anthropometric measurements, and neurocognitive functions. Resting metabolic rate (RMR) was measured by indirect calorimetry. Serum metabolites of GPB were monitored as a safety measure. In vitro effects of NaPB were evaluated in MDCK1 cells stably expressing the MCT8P321L mutation. The effects of GPB were compared to the effects of DITPA and TRIAC, thyromimetic medications that the patients had received in the past.
RESULTS: NaPB restored mutant MCT8 expression in MDCK1 cells and increased T3 transport into cells carrying the P321L mutation. GPB treatment reduced high T3 and increased low T4 levels. The patients showed a significant weight gain simultaneously with a reduction in RMR. Only minor neurocognitive improvement was observed, in hyperreflexia score and in cognitive functions. Serum metabolites did not exceed the toxic range, but elevated liver transaminases were observed.
CONCLUSION: In the first report of GPB treatment in MCT8 deficiency we found an improvement in TH profile and body mass index, with minor neurodevelopmental changes.
The present invention relates to stable, ophthalmic pharmaceutical formulations of the phosphodiesterase-4 inhibitor, roflumilast, and methods of making the same. Novel ophthalmic pharmaceutical formulations of roflumilast can comprise a viscosity agent, a surfactant, and a buffer. In preferred embodiments, the pH of the ophthalmic pharmaceutical composition is between 6.0 and 6.7. Methods of making stable, ophthalmic pharmaceutical formulations of roflumilast can include separate active and inactive ingredient processes. Further, the methods can include clarity filtration to mitigate particle size aggregation and to create an optimized suspension. Further, the methods can include terminal sterilization of the final drug product.
To provide materials that have excellent ammonia metabolism improving action and are effective in endurance enhancement and anti-fatigue.SOLUTION: An ammonia metabolism promoting agent contains catechins and ornithine as active ingredients. The endurance enhancer contains catechins and ornithine as active ingredients. The anti-fatigue agent contains catechins and ornithine as active ingredients. The inhibitor of decreased blood glucose level during motion contains catechins and ornithine as active ingredients. The promoting agent of recovery from decreased blood glucose level during motion contains catechins and ornithine as active ingredients. The inhibitor of decreased muscle glycogen during motion contains catechins and ornithine as active ingredients. The muscular endurance enhancer contains catechins and ornithine as active ingredients. The preventive or the improving agent of hyperammonemia, hepatic encephalopathy, or chronic fatigue syndrome contains catechins and ornithine as active ingredients.SELECTED DRAWING: None
Chronic Non-specific LBP is located in region below lower costal margins and above inferior gluteal margins with or without any referred pain in legs, an essentially non-attributable to any specific cause. It may lasting for more than 7-12 months and affect individual over a long period of time once in a lifetime at least. METs is useful in increasing extensibility and range of motion of various joints and provides good results in the patients with back pain. These techniques are used as the treatment of weakened muscles, restricted joints, reducing pain reliving muscle tension \& spasm, \& increased strength of the muscle. MET is a verstile, safe, gentle technique traditionally used to address muscular strain, PAIN, local edema and joint dysfunction. It was reported that post isometric relaxation is considered a highly effective therapy for back dysfunction patients.
All patients will receive standardised dietary advice in addition to the ONS prescribed daily for 28 days. The ONS prescription will be determined on an individual basis by the investigating dietitian/nurse responsible for the patient's nutritional management (1-3 ONS per day; aligned with guidelines set out within the Malnutrition Pathway). The ONS prescribed will be the same throughout the 28 days and will be taken orally.
This will be a single center, open label, exploratory research study to evaluate the BE of already marketed formulations of acyclovir in dermal interstitial fluid (ISF) in healthy volunteers using dOFM. The study will be conducted at the Clinical Research Center at the Medical University Graz. dOFM represents the most reliable way to sample interstitial fluid from skin, since it provides diluted but otherwise unchanged dermal interstitial fluid. To assess BE and non-BE, we have designed the experiments in such a way that each subject can serve as its own control. Each subject will have two sets of BE and non-BE pairs in parallel. This study is designed to test dOFM, a new sampling method that allows measurement of skin penetration. Measurement of skin penetration enables the reduction of the impact of inter-subject variability and therefore decreases the number of subjects needed to achieve statistical significance.
Pervasive developmental disorders (PDDs) are characterized by severe impairments in social interaction and communication in addition to restricted patterns of interests and activities. Research suggests that a dysregulation of the dopamine and serotonin systems contributes to these interfering behaviors in individuals with PDD. After benefits of typical neuroleptics were reported in subjects with PDD, research shifted to the atypical antipsychotics which have been shown to be better tolerated and effective in this population. However, the atypical antipsychotics have also been associated with adverse effects. Thus there remains a need for a novel pharmacotherapy that would be safe and effective for children and adolescents with PDDs. The primary objectives of this study are to determine whether aripiprazole is effective and well tolerated for irritability in children and adolescents with PDD not otherwise specified (NOS) during an 8-week acute phase and whether the effectiveness and tolerability of aripiprazole is maintained during a 16-week continuation phase.