anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. There have been case reports of withdrawal, ranging from mild to severe, following discontinuation of illicit use of GHB at frequent repeated doses (18 g to 250 g per day) in excess of the recommended dosage range. Signs and symptoms of GHB withdrawal following abrupt discontinuation included insomnia, restlessness, anxiety, psychosis, lethargy, nausea, tremor, sweating, muscle cramps, tachycardia, headache, dizziness, rebound fatigue and sleepiness, confusion, and, particularly in the case of severe withdrawal, visual hallucinations, agitation, and delirium. These symptoms generally abated in 3 to 14 days. In cases of severe withdrawal, hospitalization may be required. The discontinuation effects of Xyrem have not been systematically evaluated in controlled clinical trials. In the clinical trial experience with Xyrem in narcolepsy/cataplexy patients at recommended doses, two patients reported anxiety and one reported insomnia following abrupt discontinuation at the termination of the clinical trial; in the two patients with anxiety, the frequency of cataplexy had increased markedly at the same time.

Tolerance

Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). Tolerance to Xyrem has not been systematically studied in controlled clinical trials. There have been some case reports of symptoms of tolerance developing after illicit use at dosages far in excess of the recommended Xyrem dosage regimen. Clinical studies of sodium oxybate in the treatment of alcohol withdrawal suggest a potential cross-tolerance with alcohol. The safety and effectiveness of Xyrem in the treatment of alcohol withdrawal have not been established.
Alcohol use and abuse have been associated with increased risky sexual behavior, poor adherence to antiretroviral therapy (ARVs) and toxicity from ARVs among those with HIV infection. As such, alcohol use and abuse have a major impact on HIV transmission and disease progression. Because alcohol abuse is widespread in Kenya, with estimates of hazardous drinking as high as 68% in general medicine clinics and 53% in HIV clinics, this Stage 1 pilot project will develop and evaluate a paraprofessionally led group cognitive behavioral treatment (CBT) targeting alcohol use among HIV infected Kenyans who were initiated on ARV therapy in the past year. Although CBT is well-suited to the Kenyan setting because it is comparatively structured and consistent with the Kenyan conceptual model of drinking behavior, it requires adaptation for group paraprofessional delivery due to the extremely limited supply of Kenyan mental health professionals. The goal of this 24-month capacity-building R21 study is to evaluate the efficacy of a novel application of CBT, a 6-session paraprofessionally led group in Eldoret, Kenya, when compared against a usual care support group, to reduce hazardous and binge drinking among adult persons infected with HIV. This work will be conducted via the Kenya-U.S. HIV and Alcohol Research and Prevention Partnership-an experienced team of Kenyan and U.S. physicians, behavioral scientists, recovered substance users and persons infected with HIV. The team expands on well-established ties between the Academic Model for Providing Access to Health Care (AMPATH) and the Veterans Aging Cohort Study (VACS), a longitudinal clinical study of HIV and alcohol. AMPATH treats more than 65,000 HIV patients in 19 clinics in western Kenya. Our goals are to: 1) train Kenyan staff and investigators in research methods and train paraprofessionals in group CBT delivery; 2) pilot the CBT adaptation; and 3) evaluate the feasibility of the paraprofessionally led group CBT via a Stage 1 trial in which 56 HIV infected Kenyans are randomized to same-sex CBT or usual care HIV support groups.
The clinical outcome of lymphocytic leukemia (CLL) is quite heterogeneous. The purpose of this observational study was to investigate the clinical merit of measuring plasma galectin-9 and CXCL-13 concentrations as predictors of CLL activity, prognosis, and early indicators of therapeutic response. These biomarkers were compared with other prognostic indicators, progression-free survival (PFS), time to first treatment (TTT), and overall survival (OS) over a follow-up period (4 years). First, plasma galectin-9 and CXCL-13 concentrations were analyzed in CLL patients at the time of diagnosis as well as healthy controls. Compared to controls, CLL patients had significantly higher serum levels of CXCL-13 and galectin-9. Second, we observed that CLL patients with high soluble CXCL-13 and galectin-9 levels had advanced clinical stages, poor prognosis, 17p del, short PFS, short TTT, and therapy resistance. The levels of CXCL-13, β2-microglobulin, LDH, CD38%, and high grade of Rai-stage were all strongly correlated with the galectin-9 levels. Soluble CXCL-13 and galectin-9 had very good specificity and sensitivity in detecting CLL disease progression and high-risk patients with the superiority of galectin-9 over CXCL-13. Although the two biomarkers were equal in prediction of TTT and treatment response, the soluble CXCL13 was superior in prediction of OS. High CXCL-13 and galectin-9 plasma levels upon CLL diagnosis are associated with disease activity, progression, advanced clinical stages, short periods of PFS, short TTT, and unfavorable treatment response.
NEW MATERIAL:The compound of formula I (R<1> is H, halogen, lower alkyl, etc.; R<2> is H, lower alkyl, aryl, etc.; R<3> and R<4> are H, lower alkyl, aralkyl, etc.) and its acid addition salt. EXAMPLE:5-Chloro-3-(2,3-dihydroxypropyloxy)-1,2-benzisoxazole. USE:A central muscle relaxant. Useful for the treatment of the sequela of cerebral apoplexy and head lesion. PREPARATION:The compound of formula I can be produced according to the reaction formula by heating an epoxide compound of formula II in an aqueous solution of an alkali metal carbonate (e.g., K2CO3 or Na2CO3) or an alkali metal hydroxide in the presence of an organic solvent, adding the resultant diol compound of formula III with phosgene or a halocarbonic acid ester and then with a tert-amine in the presence of an organic solvent and reacting the product with an amine of formula IV.
Metformin is the first-line medication for type 2 diabetes. It is effective and safe, provided some caution is taken in specific populations. In patients with chronic kidney disease, metformin may provide long-term benefits, and it is a first-line therapy for diabetes, but the estimated glomerular filtration rate (eGFR) must be assessed regularly, to minimize the risk for metformin accumulation. When eGFR is 30-60 mL/min/1.73m2, the dose should be reconsidered, and sick-days education provided. Metformin should be discontinued when eGFR falls below 30 mL/min/1.73m2. Metformin accumulation may increase the risk for lactic acidosis if concomitant risk factors for hyperlactataemia (liver or respiratory insufficiency, sepsis, acute heart failure) are present; in these conditions, metformin is contraindicated, even although the available evidence is reassuring. Patients on metformin often complain of gastrointestinal side effects (mainly diarrhoea and nausea) during therapy initiation, but they may sometimes occur after years of stable therapy. These usually resolve if the dose is carefully titrated, or by switching to the extended-release formulation. Patients with obesity may benefit from the significant, although modest, metformin-associated weight loss and appetite reduction. During pregnancy, metformin is associated with a reduction of pregnancy complications, especially in obese women, but some concern remains, because metformin crosses the placenta, and it is associated with a significantly lower mean birth weight than insulin. In the elderly, gastrointestinal tolerability and renal function must be reassessed more often. Vitamin B-12 should be screened regularly in long-time metformin users because metformin may induce clinical vitamin B-12 deficiency.
Healthy participants will be enrolled into 1 of 6 planned SAD cohorts to receive single dose of RO6889678/matching placebo in fasted state as per anticipated dose escalation sequence (30 milligrams \[mg\], 100 mg, 300 mg, 600 mg, 1000 mg and 1500 mg). Cohort 1 will be split in 2 groups: 2 participants will be dosed 1 day (1 on RO6889678 and 1 on matching placebo) and 3 participants (2 on RO6889678 and 1 on matching placebo) will be dosed at least 24 hours afterward following satisfactory safety assessment for first 2 participants. Cohort 2 \& beyond will include 8 healthy participants with 6 participants randomly assigned to RO6889678 \& 2 randomly assigned to placebo. Participants who will tolerate fasted dose and agree to continue in food-effect SAD cohort, will receive single dose (dose level, either 300 mg or 600 mg, decided based on PK and safety data of first 2 SAD cohorts) of RO6889678/matching placebo with US FDA recommended high-fat and high-calorie breakfast on Day 16.
Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by progressive degeneration of motor neurons, muscle atrophy and paralysis. There is no reliable early diagnostic test for ALS making identification of the disease difficult at its earliest stages. Early detection is critical to the initiation of early neuroprotective therapy. By the time a reliable diagnosis can be made, substantial damage to motor neurons and muscle has already occurred. The purpose of the current project is to establish a bank of blood samples (serum and protein/RNA/DNA from blood cells) and CSF for use in the development of an early diagnostic test for ALS and to better understand the progression of this disease.

Samples from patients that have a confirmed or unknown diagnosis of motor neuron disease will be examined. ALS and suspected neuromuscular disease (control) samples will be collected for comparison. Investigators will examine various biochemical, metabolic and genetic markers from these samples in hopes of finding differences in the expression between control subjects and ALS patients and how these biomarkers vary during disease progression. Participants will be asked to complete an optional questionnaire to collect data including medication and vitamin use and medical and disease history. This data will be linked to the patient's samples; however, all samples will be deidentified and coded to avoid the possibility of linking results to the patient. Results will not be stored in the patient's medical record.
Introduction: Thyroid hormone transporters are essential for thyroid hormones to enter target cells. Monocarboxylate transporter (MCT) 8 is a key transporter and is expressed at the blood-brain barrier (BBB), in neural cells and many other tissues. Patients with MCT8 deficiency have severe neurodevelopmental delays because of cerebral hypothyroidism and chronic sequelae of peripheral thyrotoxicosis. The T3 analog 3,3',5-triiodothyroacetic acid (TRIAC) rescued neurodevelopmental features in animal models mimicking MCT8 deficiency and improved key metabolic features in patients with MCT8 deficiency. However, the identity of the transporter(s) that facilitate TRIAC transport are unknown. Here, we screened candidate transporters that are expressed at the human BBB and/or brain-cerebrospinal fluid barrier and known thyroid hormone transporters for TRIAC transport. Materials and Methods: Plasma membrane expression was determined by cell surface biotinylation assays. Intracellular accumulation of 1 nM TRIAC was assessed in COS-1 cells expressing candidate transporters in Dulbecco's phosphate-buffered saline (DPBS)/0.1% glucose or Dulbecco's modified Eagle's medium (DMEM) with or without 0.1% bovine serum albumin (BSA). Expression of Slc22a8 was determined by fluorescent in situ hybridization in brain sections from wild-type and Mct8/Oatp1c1 knockout mice at postnatal days 12, 21, and 120. Results: In total, 59 plasma membrane transporters were selected for screening of TRIAC accumulation (n = 40 based on expression at the human BBB and/or brain-cerebrospinal fluid barrier and having small organic molecules as substrates; n = 19 known thyroid hormone transporters). Screening of the selected transporter panel showed that 18 transporters facilitated significant intracellular accumulation of TRIAC in DPBS/0.1% glucose or DMEM in the absence of BSA. In the presence of BSA, substantial transport was noted for SLCO1B1 and SLC22A8 (in DPBS/0.1% glucose and DMEM) and SLC10A1, SLC22A6, and SLC22A24 (in DMEM). The zebrafish and mouse orthologs of these transporters similarly facilitated intracellular accumulation of TRIAC. Highest Slc22a8 mRNA expression was detected in mouse brain capillary endothelial cells and choroid plexus epithelial cells at early postnatal time points, but was reduced at P120. Conclusions: Human SLC10A1, SLCO1B1, SLC22A6, SLC22A8, and SLC22A24 as well as their mouse and zebrafish orthologs are efficient TRIAC transporters. These findings contribute to the understanding of TRIAC treatment in patients with MCT8 deficiency and animal models thereof.
BACKGROUND AND OBJECTIVES: Pain management for patients undergoing the Nuss procedure for treatment of pectus excavatum can be challenging. In an effort to improve pain management, our institution added bilateral single injection erector spinae plane (ESP) blocks to surgeon placed intercostal nerve cryoablation. We aimed to assess the efficacy of this practice change.
METHODS: Retrospective clinical data from a single academic medical center were evaluated. Due to an institutional change in clinical management, we were able to perform a before and after study. Twenty patients undergoing Nuss procedure who received bilateral ultrasound-guided single-shot T6 level ESP blocks and intercostal nerve cryoablation were compared with a historical control cohort of 20 patients who underwent Nuss procedure with intercostal nerve cryoablation alone. The primary outcome variables included postoperative pain scores, total hospital opioid use, and hospital length of stay.
RESULTS: Median total hospital intravenous morphine milligram equivalents was lower for the ESP group than for the control group (0.60 (IQR 0.35-0.88) vs 1.15 mg/kg (IQR 0.74-1.68), p<0.01). There was no difference in postoperative pain scores between the two groups. Mean hospital length of stay was 2.45 (SD 0.69) days for the control group and 1.95 (SD 0.69) days for the ESP group (p=0.03). No adverse events related to block placement were identified.
CONCLUSIONS: In a single-center academic practice, the addition of bilateral single injection ESP blocks at T6 to surgeon performed cryoablation reduced opioid consumption without a change in subjectively reported pain scores. The results from this pilot study can provide effect size estimates to guide the design of future randomized trials.
This was a two phase feasibility study exploring appropriate management, setting, participants including inclusion and exclusion criteria, attrition rates, protocol, and retention. Outcome data for each stage were collected during baseline, acquisition, short-term, and long-term retention.

There were two primary objectives of this two phase feasibility study. The first was to uncover some potential short comings in research designs used in this area. The second was to explore the feasibility of a study in both the chronic and acute stroke populations in a rural community. Topics of feasibility include recruitment, retention, and specific inclusion and exclusion criteria. Extending the work by Muckel and Merholz, this feasibility study examined performance of individuals post stroke during a seated lateral weight shifting task and incorporated retention trials, quality of movement exploration, and bilateral weight shifting.

During Phase I, individuals in both groups sat unsupported on a hi-lo mat table which was adjusted so participants were sitting at 90 degrees hip and knee flexion with feet shoulder width apart. Tape marks were used to mark initial set up ensuring standardized positioning for each trial. Following baseline trials, all participants watched the same instructional video describing lateral weight shifting. The instructions included correct mechanics that should be used when weight shifting laterally with focus on correct form needed for the movement.

Testing included baseline, acquisition, short term retention (5 minutes later), and long-term retention (7-10 days later). Participants performed three trials of seated weight shifting to each side at all timepoints. During acquisition, the internal focus group was instructed to "shift your weight as much as possible towards your right or left hip without using your arms". The external focus group sat with targets one arm length away at shoulder height and were instructed to "shift your body weight as much as possible towards the blue/orange target without using your arms." During baseline and retention trials, adults were instructed to "lean as far as you can to the right/left without using your arms." During Phase II, the protocol was similar except 6 trials were performed for acquisition to potentially improve motor learning, which was not significant in Phase I per retention data. Other changes to the protocol included allowing participants to move their feet when weight-shifting. Instructions were also revised. The external focus group was told to "move your shoulder as close to the blue/orange target as possible", while the internal focus group was told to "shift your body weight as much as possible towards your right/left hip without using your arms."
The World Health Organization has updated their classification system for the diagnosis of gliomas, combining histological features with molecular data including isocitrate dehydrogenase 1 and codeletion of chromosomal arms 1p and 19q. 1p/19q codeletion analysis is commonly performed by fluorescence in situ hybridization (FISH). In this study, we developed a 57-gene targeted next-generation sequencing (NGS) panel including 1p/19q codeletion detection mainly to assess diagnosis and potential treatment response in melanoma, gastrointestinal stromal tumor, and glioma patients. Loss of heterozygosity analysis was performed using the NGS method on 37 formalin-fixed paraffin-embedded glioma tissues that showed 1p and/or 19q loss determined by FISH. Conventional methods were applied for the validation of some glioma-related gene mutations. In 81.1% (30 of 37) and 94.6% (35 of 37) of cases, 1p and 19q were found to be in agreement whereas concordance for 1p/19q codeletion and no 1p/19q codeletion was found in 94.7% (18 of 19) and 94.4% (17 of 18) of cases, respectively. Overall, comparing NGS results with those of conventional methods showed high concordance. In conclusion, the NGS panel allows reliable analysis of 1p/19q codeletion and mutation at the same time.
Group B is serving as the control group who will not have the ensoETM device used.Control group patients will be managed as per standard of care currently utilized in the ICU, which will include the use of other methods of temperature management as warranted. This would include warming with a forced air blanket only in hypothermic patients (core temperature \< 36°C) or antipyretic therapy for febrile patients, as requested by the treating physician.
Disclosed are a hydrogen persulfide prodrug and a pharmaceutical use thereof, belonging to the field of pharmaceutics. The structure of the hydrogen persulfide prodrug is as shown in formula I. The provided hydrogen persulfide prodrug can release H2S2 under the action of an esterase; the hydrogen persulfide prodrug has good stability in PBS, and will not degrade and release H2S2 in the absence of the esterase. In addition to releasing H2S2 under the action of the esterase, most of the remaining by-products of the hydrogen persulfide prodrug are endogenous substances or drug excipients or food additives approved by the FDA, and thus said prodrug has high safety. The provided hydrogen persulfide prodrug can exert an effective analgesic effect in vivo, and the analgesic effect in vivo is better than that of reference compound 301. The hydrogen persulfide prodrug has good clinical application prospects in the preparation of analgesic drugs.
Evidence-based public health approaches to prevent and control diabetes and other chronic diseases have been identified in recent decades, and could have a profound effect on diabetes incidence and quality and length of life of those diagnosed. However, barriers to implement approaches continue because of lack of organizational support, limited resources, competing priorities, and limited skill among the public health workforce. The purpose of this study is to determine effective ways to promote the adoption of evidence based public health practice related to diabetes and chronic disease prevention and control among local health departments (LHDs). This stepped-wedge cluster randomized trial aims to evaluate active dissemination strategies on local-level public health practitioners to increase adoption and use of evidence-based programs and policies for diabetes and chronic disease prevention and control among LHDs in Missouri. Twelve LHDs will be recruited and randomly assigned to one of three groups that cross over from usual practice to receive the intervention (dissemination) strategies at 8-month intervals; the intervention duration for groups ranges from 8 to 24 months. LHD staff and the university-based study team are jointly identifying, refining and selecting dissemination strategies. Intervention strategies may include multi-day in-person training workshops, electronic information exchange modalities, and remote technical assistance. Evaluation methods include surveys at baseline and at each 8-month interval, abstraction of LHD chronic disease prevention program plans and progress reports, and social network analysis.
Duchenne muscular dystrophy (DMD) is a progressive muscle disease that is caused by severe defects in the dystrophin gene and results in the patient's death by the third decade. The present invention utilizes the Double Mutant mice (DM) as an appropriate human model for DMD as these mice are deficient for both dystrophin and utrophin (mdxl+, utrn -/-), die at 3 months of age and suffer from severe muscle weakness, pronounced growth retardation, kyphosis, weight loss, slack posture, and immobility. Expression from a transgene of novel human retinal dystrophin Dp260 was shown to prevent premature death and reduce the severe muscular dystrophy phenotype to a mild clinical myopathy. Electromyography, histology, radiography, magnetic resonance imaging, and behavior studies concluded that DM transgenic mice grew normally, had normal spinal curvature and mobility, and had reduced muscle pathology. EMG and histologic data from transgenic DM mice showed decreased abnormalities to levels typical of mild myopathy, while the DM mice exhibited severe abnormalities commonly seen in human dystrophinopathies. The transgenic DM mice also has measurable movement levels comparable to those of untreated mdx mice and controls.
Chemotherapeutic agents generally accompany by severe side effects to the patients especially by destroying bone marrow cells. In the other hand there is a new trend in fighting cancer by activation of immunosystem. Based on this concept we start to test pleurotus ostreatas mushroom. The present work was designed to isolate and identify anticancer substance accruing in mushroom cultivated on rice straw. The extracted substance had been identified using different spectroscopical technique ( UV, 2D NMR, X-ray Crystallography ) the primary structure was shown to be glucan. Our study showed that mushroom glucan can act as host defense potentiator by increasing maturation, differentiation and proliferation of most cells involved in immunoresponse.