anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
P/Q-type (Cav2.1) calcium channels mediate Ca2+ influx essential for neuronal excitability and synaptic transmission. The CACNA1A gene, encoding the Cav2.1 pore forming subunit, is highly expressed throughout the mammalian central nervous system. Alternative splicing of Cav2.1 pre-mRNA generates diverse channel isoforms with distinct biophysical properties and drug affinities, which are differentially expressed in nerve tissues. Splicing variants can also affect channel function under pathological conditions although their phenotypic implication concerning inherited neurological disorders linked to CACNA1A mutations remains unknown. Here, we quantified the expression of Cav2.1 exon 24 (e24) spliced transcripts in human nervous system samples, finding different levels of expression within discrete regions. The corresponding Cav2.1 variants, differing by the presence (+) or absence (Δ) of Ser-Ser-Thr-Arg residues (SSTR) in the domain III S3-S4 linker, were functionally characterized using patch clamp recordings. Further, the + /ΔSSTR isoforms were used to demonstrate the differential impact of the Familial Hemiplegic Migraine Type 1 (FHM-1) S218L mutation, located in the domain I S4-S5 linker, on the molecular structure and electrophysiological properties of Cav2.1 isoforms. S218L has a prominent effect on the voltage-dependence of activation of +SSTR channels when compared to ΔSSTR, indicating a differential effect of the mutation depending on splice-variant context. Structural modeling based upon Cav2.1 cryo-EM data provided further insight reflecting independent contributions of amino acids in distant regions of the channel on gating properties. Our modelling indicates that by increasing hydrophobicity the Leu218 mutation contributes to stabilizing a structural conformation in which the domain I S4-S5 linker is oriented alongside the inner plasma membrane, similar to that occurring when S4 is translocated upon activation.The SSTR insertion appears to exert an influence in the local electric field of domain III due to an change in the distribution of positively charged regions surrounding the voltage sensing domain, which we hypothesize impacts its movement during the transition to the open state. In summary, we reveal molecular changes correlated with distinct functional effects provoked by S218L FHM-1 mutation in hCav2.1 splice isoforms whose differential expression could impact the manifestation of the neurological disorder.
Crohn's disease is an inflammatory condition of the intestine characterized by largely unknown etiology and a relapse remission cycle of disease control. While possible triggers have been identified, research is inconsistent on the precise cause of these relapses, especially in the under-researched pediatric population. We hypothesized that patients in remission would have persistent microbial and inflammatory changes in small intestinal tissue that might trigger relapse. To this end, we analyzed intestinal biopsy samples from six patients with pediatric Crohn's disease in remission and a control group of 16 pediatric patients with no evident pathogenic abnormality. We identified compositional microbiota differences, including decreases in the genera Streptococcus and Actinobacillus as well as increases in Oribacterium and Prevotella in patients with controlled Crohn's disease compared to controls. Further, a histologic analysis found that patients with controlled Crohn's disease had increased epithelial integrity, and decreased intraepithelial lymphocytes compared with controls. Additionally, we observed increased peripheral CD4+ T cells in patients with pediatric Crohn's disease. These results indicate that markers of intestinal inflammation are responsive to Crohn's disease treatment, however the interventions may not resolve the underlying dysbiosis. These findings suggest that persistent dysbiosis may increase vulnerability to relapse of pediatric Crohn's disease. This study used a nested cohort of patients from the Bangladesh Environmental Enteric Dysfunction (BEED) study (ClinicalTrials.gov ID: NCT02812615 Date of first registration: 24/06/2016).
PURPOSE: A pharmaceutical composition containing recombinant expression vector containing a gene encoding TASK-3 proteins is provided to effectively suppress cancer metastasis. CONSTITUTION: A pharmaceutical composition for suppressing cancer metastasis contains TASK-3 protein, a gene encoding the protein, or expression vector for gene therapy as an active ingredient and further contains pharmaceutically acceptable protein. The TASK-3 protein has an amino acid sequence of sequence number 21. The gene encoding TASK-3 contains a base sequence of sequence number 22. The recombinant expression vector contains the gene. A composition additionally contains an anticancer agent.
Run-in period (28 days): participants will receive vemurafenib 960 mg orally BID for 21 days, then vemurafenib 720 mg orally BID for 7 days in combination with cobimetinib (Cob) 60 mg IV once daily, 21 days on/7 days off schedule (21/7). Combination treatment period: Participants will receive fixed dose of atezolizumab 800 mg IV every 2 weeks (q2w) in combination with vemurafenib 720 mg orally BID and cobimetinib 60 mg orally once daily 21/7 in 28 days cycle.
Increasing prevalence of non-communicable diseases (NCDs) has become the leading cause of death and disability in Bangladesh. Therefore, this study aimed to measure the prevalence of and risk factors for double and triple burden of NCDs (DBNCDs and TBNCDs), considering diabetes, hypertension, and overweight and obesity as well as establish a machine learning approach for predicting DBNCDs and TBNCDs. A total of 12,151 respondents from the 2017 to 2018 Bangladesh Demographic and Health Survey were included in this analysis, where 10%, 27.4%, and 24.3% of respondents had diabetes, hypertension, and overweight and obesity, respectively. Chi-square test and multilevel logistic regression (LR) analysis were applied to select factors associated with DBNCDs and TBNCDs. Furthermore, six classifiers including decision tree (DT), LR, naïve Bayes (NB), k-nearest neighbour (KNN), random forest (RF), and extreme gradient boosting (XGBoost) with three cross-validation protocols (K2, K5, and K10) were adopted to predict the status of DBNCDs and TBNCDs. The classification accuracy (ACC) and area under the curve (AUC) were computed for each protocol and repeated 10 times to make them more robust, and then the average ACC and AUC were computed. The prevalence of DBNCDs and TBNCDs was 14.3% and 2.3%, respectively. The findings of this study revealed that DBNCDs and TBNCDs were significantly influenced by age, sex, marital status, wealth index, education and geographic region. Compared to other classifiers, the RF-based classifier provides the highest ACC and AUC for both DBNCDs (ACC = 81.06% and AUC = 0.93) and TBNCDs (ACC = 88.61% and AUC = 0.97) for the K10 protocol. A combination of considered two-step factor selections and RF-based classifier can better predict the burden of NCDs. The findings of this study suggested that decision-makers might adopt suitable decisions to control and prevent the burden of NCDs using RF classifiers.
Chimeric antigen receptor (CAR)-modified T cells targeted against CD19 have demonstrated unprecedented successes in treating patients with hematopoietic and lymphoid malignancies. Besides CD19, many other molecules such as CD22, CD30,BCMA,CD123, etc. may have the potential to develop the corresponding CAR-T cells to treat patients whose tumors express those markers. In this study, investigators will evaluate the safety and efficacy of CAR-T targeting CD33/CD123 in patients with Acute Myelocytic Leukemia. The primary goal is safety assessment including cytokine storm response and any other adverse effects. In addition, disease status after treatment will also be evaluated.

The purpose of this clinical trial is to assess the feasibility, safety, and efficacy of multiple CAR T-cell therapy which combines CAR T cells against AML Cells with CAR T cells targeting CD123 or CD33 in patients with relapsed and refractory AML. The study also aims to learn more about the function of CAR T cells and their persistence in AML patients.
General anesthesia, the patient will be put in the prone and abdomen-free position. A 4-cm midline longitudinal incision will be made over the spinous processes of the L3-5 levels. It will be deepened through the fat and fascia in line with the skin incision to reach the spinous processes.The paraspinous muscles will be dissected subperiosteally down the spinous processes and along the lamina to the facet joints. Laminectomy will be done carefully at the herniated disc level for posterior decompression. The ligamentum flavum will be excised to expose the dural sac.Using blunt dissection, the investigators carefully continue down the lateral side of the dura to the floor of the spinal canal; the investigators retract the dura and its nerve root medially. After the posterior aspect of the disc space is revealed, the affected disc will be removed and discotomy will be performed.The wound will be closed in the routine fashion after meticulous hemostasis and normal saline irrigation.
The invention discloses a compound traditional Chinese medicine extract preparation for preventing and treating proventriculitis of chickens and a preparation method thereof. The compound traditional Chinese medicine extract preparation is prepared from drugs including astragalus membranaceus, codonopsis pilosula, radix paeoniae alba, rhizoma atractylodis macrocephalae, dandelion, radix aucklandiae and fructus aurantii in certain proportions. The preparation is suitable for prevention and treatment of proventriculitis of the chickens. After the drugs are conjugated, the compound traditional Chinese medicine extract preparation has the effects of clearing heat, diminishing inflammation, tonifying qi, invigorating the stomach, promoting mucosa healing and reducing the damage of hazardous substances. Meanwhile, drug residues and drug resistance caused by antibiotics are effectively avoided. The compound traditional Chinese medicine extract preparation can be administrated by drinking water, is convenient to absorb and is capable of achieving the effect of treating quickly and good in economic benefits and social benefits.
Effective treatments for patients with degenerative spinocerebellar ataxia are scarce. It has recently been shown that intensive coordinative training based on either physiotherapy or exergames (= whole-body controlled videogames; might improve degenerative ataxia, but its effectiveness is still disputed. This situation is even more complicated for degenerative ataxia subjects in advanced disease stages and with high multisystemic disease load. Here, underlying neurodegeneration has progressed to many irreversible states and includes many additional extra-cerebellar systems, making functional plasticity and therapeutic success much less likely. Moreover, intervention outcome assessment in subjects unable to walk freely is more delicate. Correspondingly, nonambulatory ataxia subjects in advanced disease stages are currently often excluded from treatment trials, thus leaving them without prospects of access to novel treatments.

The investigators here hypothesized that exergame training might offer a novel treatment approach even in largely nonambulatory subjects with multisystemic degenerative spinocerebellar ataxia. Using a rater-blinded, intraindividual control study design, the investigators show that an individualized exergame training strategy, tailored to individuals' disease stage, improves postural control and ataxia-specific control functions even in advanced disease.
The present disclosure relates to a dialysis machine, external medical equipment and to methods for establishing an authenticated connection between a dialysis machine and external medical equipment. The dialysis machine is caused to establish S2 a short-range wireless connection between the dialysis machine and external medical equipment. A first shared key is associated with the short-range wireless connection. The dialysis machine is further configured to obtain S5 a second shared key generated using the first shared key and to generate S6 a first signature, using the obtained second shared key. The dialysis machine is further configured to send S7, to the external medical equipment, an authentication request comprising the generated first signature and to receive S8 in return an authentication accept comprising a second signature. Furthermore, the control unit is configured to verify S9 the authenticity of the external medical equipment using the second signature. The present disclosure also relates to a computer program and a computer program product implementing the method.
After the Investigators and the Sponsor considers the study treatment with PEGCISGEM during the Run-in portion safe and tolerable, new participants will be enrolled to receive 3.0 mcg/kg PEGPH20 on Days 1, 8, and 15 in combination with 25 mg/m\^2 CIS and 1000 mg/m\^2 GEM on Days 2 and 9 of each 21-day cycle by IV infusion. Treatment will continue until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity.
The 1-heterocyclylmethyl-substituted pyrazole of the formula (I-I) is described, wherein: R1 is an optionally substituted 5-membered aromatic heterocyclic ring having one heteroatom selected from S, N and O; R2 and R3, including the double bond, form a 5-membered aromatic heterocyclic ring having one heteroatom selected from S, N and O, or a phenyl ring, which are optionally substituted; A1 is an optionally substituted 5- or 6- membered aromatic or saturated heterocyclic ring having up to three heteroatoms selected from S, N and O. The 1-heterocyclylmethyl-substituted pyrazole or 1-benzyl-substituted pyrazole of formula (II-I) is also described, wherein: R20 is an optionally substituted 6-membered aromatic heterocyclic ring having up to three nitrogen atoms; R21 and R22, including the double bond, form a 5-membered aromatic heterocyclic ring having one heteroatom selected from S, N and O, or a phenyl ring, which are optionally substituted; A2 represents optionally substituted phenyl or optionally substituted 5- or 6-membered aromatic or saturated heterocyclic ring having up to three heteroatoms selected from S, N and O. The 3-Heterocyclyl-substituted pyrazole derivative of the general formula (III-I) (as well as isomers thereof) is also described, wherein: R42 is an optionally substituted saturated 6-membered heterocyclic ring having up to 2 heteroatoms selected from S, N and O or an optionally substituted 5-membered aromatic or saturated heterocyclic ring having 2-3 heteroatoms selected from S, N and O, which can also be bonded via a nitrogen atom and which are optionally substituted; R43 and R44, including the double bond, form a 5-membered aromatic heterocyclic ring having one heteroatom selected from S, N and O, or a phenyl ring, which are optionally substituted; A3 is a 5- to 6-membered aromatic or saturated heterocyclic ring having up to three heteroatoms selected from S, N and O, or phenyl, which are optionally substituted; with the proviso that R42 is not pyrrolidinyl or piperidinyl. 1-Benzyl-3-(substituted phenyl or heteroaryl)-fused pyrazole derivatives of the formula (IV-I) (as well as isomers thereof) is also described, wherein: R69 is optionally substituted pyrrole, furan, thienyl or phenyl. R70 and R71 form together an optionally substituted pyrrole, furan, thienyl or phenyl ring; A4 is optionally substituted phenyl. The compounds of formulae (I-I), (II-I), (III-I) and (IV-I) are useful for inhibiting the breakdown of cyclic guanosine monophosphate (cGMP).
A Herbal Tea for Type II diabetes mellitus patient is made by a specific method mentioned in the Fig. 1 and Fig 2 of the drawing from  Gymnema lactiferum  leaf used in this randomized double-blind controlled clinical trial. 320 Type II Diabetes patients will be randomly collected from the Type II Diabetes mellitus patients coming to the Diabetic center TH Jaffna and randomly divided in to two groups. One group will be given one cup of Herbal Tea per day in addition to the conventional drugs and other group will be given one cup of green tea as an active control for 3 months. Blood samples will be analyzed according to the schedule mentioned in the mode of invention. Blood pressure and body weight will be analyzed to find out supplementary effect of herbal tea on better glycemic control and control of hyperlipidemia, Blood pressure and body weight.
Rationale: Asthma inception occurs only in susceptible individuals, and is often triggered by specific environmental factors, such as respiratory viruses and aeroallergens. Although asthma is generally viewed as a chronic persistent disease, remission of asthma is possible in a subset of patients. This is highly relevant, since understanding mechanisms that contribute to asthma inception and remission may teach us how asthma can be stopped and thus may provide novel avenues for the treatment of asthma. In adulthood, average remission rates of asthma are approximate 2% per year 1. We observed that remission in adulthood is more likely with earlier onset of asthma, less airway obstruction, more severe bronchial hyperresponsiveness, and smoking cessation. A proper definition of remission is very important; we therefore introduced the terms 'clinical remission' and 'complete remission' 2. Clinical remission was defined as the absence of asthma symptoms and no use of asthma medication, complete remission as the absence of asthma symptoms, no use of asthma medication, normal lung function and no bronchial hyperresponsiveness. In a longitudinal study of 119 allergic asthmatic children followed-up for 30 years, our group found that clinical remission occurred in 30% and complete remission in 22% of all cases.

Objective: to determine the underlying mechanisms and molecular events involved in the inception and remission of asthma.

Methods: We will include a 40 subjects divided over the following 4 groups: i) clinical asthma remission (10 subjects), ii) complete asthma remission (10 subjects), iii) ongoing asthma (10 patients), iv) non-asthmatic healthy controls (10 subjects) in a cross-sectional study. All subjects will be extensively clinically characterized including respiratory symptoms/questionnaires, in- and expiratory CT-scans, and parameters of large and small airway function and inflammation. In addition, blood and nasal epithelial brushes will be obtained to study the genetic and epigenetic mechanisms of asthma remission. Finally, bronchoscopy with bronchial biopsies and brushes will be performed under conscious sedation. Bronchial biopsies from all four patient groups will be used for index FACS sorting of the three most important cell types orchestrating the asthmatic inflammatory process: i.e. B lymphocytes, CD4+ T cells and CD8+ T cells. We will perform single cell whole-genome transcriptome sequencing on at least 100 cells of each type and the primary outcome of the study is to identify how the transcriptomic profile of bronchial epithelial cells is changed between asthma patients and healthy controls as a consequence of asthma inception and what transcriptomic profile changes occur in CD4+ CD8+ and B lymphocytes in the airways from subjects with asthma remission compared to patients with ongoing asthma and healthy controls.
This Phase 1 study is designed to assess the safety, tolerabilty and pharmcokinetics of different dose levels of PRV-002 in Healthy Volunteers. The study will evaluate 3 dose levels of the investigational product, PRV-002, in 5 cohorts of 8 healthy volunteers per cohort. In each cohort, 6 volunteers will receive the investigational product and 2 volunteers will receive placebo. Dose levels will be evaluated in a sequential manner starting at the lowest dose level. Cohorts 1 - 3 will receive a single dose of PRV-002 or placebo. Cohorts will receive one dose of PRV-002 or placebo per day for 5 consecutive days.
The present invention discloses an alcohol-dissolving liver-protecting healthy food which comprises the following raw materials: 35 to 45 parts by weight of hedgehog fungus, 25 to 35 parts by weight of kudzuvine root, 16 to 24 parts by weight of oyster, 8 to 12 parts by weight of licorice root, 8 to 12 parts by weight of white peony root and 8 to 12 parts by weight of nutgrass flatsedge rhizome. The alcohol-dissolving liver-protecting healthy food can be made into capsules, tablets, pills, medicinal granules or other dosage forms. The alcohol-dissolving liver-protecting healthy food of the present invention has the efficiency of sobering up, promoting digestion, smoothing the liver, relieving acid making, diminishing inflammation, alleviating pain, relieving flatulence, removing the sensation of fullness and improving appetite, and has peculiar therapeutic effect on gastrointestinal symptoms caused by excess wine drinking. After being taken, the alcohol-dissolving liver-protecting healthy food can quickly relieve discomfort, and the total effective rate of the alcohol-dissolving liver-protecting healthy food can reach 93.8%. The alcohol-dissolving liver-protecting healthy food has an obvious protective function for alcoholic liver injury and can be used for treating alcoholism and alcoholic fatty livers. The alcohol-dissolving liver-protecting healthy food has the advantages of high safety and reliability of administration and no toxic or side effect.
BACKGROUND: The global hypomethylation of CD4+ T cells in systemic lupus erythematosus (SLE) patients has been previously reported. However, potential influencing factors are unclear. This study aimed to uncover the potential influence of obese on hypomethylated CD4+ T cells in SLE patients.
METHODS: Obese SLE patients with Body Mass Index (BMI)>30 (N.=15) and normal weight SLE patients with 18<BMI<25 (N.=20) were included. SLEADI, antinuclear-ribonuclear-protein (nRNP) and dsDNA levels in them were detected. Methylation rate of CD4+ T cells isolated from SLE patients was assessed, as well as its correlation to BMI and Systemic Lupus Erythematosus Disease Activity Index (SLEADI) in SLE patients. Subsequently, relative level and catalytic activity of DNA (cytosine-5)-methyltransferase 1 (DNMT1) were examined. New Zealand black/white (NZB/W) mice were fed high-fat diet for generating obesity model or normal diet, followed by detection of antinuclear-ribonuclear-protein (nRNP) immunoglobulin G (IgG), antidouble-stranded (ds) DNA IgG, methylation rate of CD4+ T cells and DNMT1 level.
RESULTS: SLEADI, nRNP and dsDNA levels were higher in obese SLE patients than normal weight cases. SLEADI was positively correlated to BMI in included SLE patients. Compared with normal weight SLE patients, methylation rate of CD4+ T cells was lower in obese patients. DNMT1 was downregulated in obese SLE patients, and its level was negatively correlated to BMI in SLE patients. Consistently, methylation rate of CD4+ T cells and DNMT1 level remained lower in obese SLE mice than those normally fed mice with SLE.
CONCLUSIONS: Hypomethylated CD4+ T cells extensively occur in SLE patients, which are much more pronounced in obese cases. DNMT1 level is found to be negatively correlated to the methylation rate of CD4+ T cells in SLE patients.
Perifosine is a drug that in particular inhibits Akt thought to be important for initiation and progression of malignancies, specifically in lymphomas. In laboratory experiments of WM and lymphoma cell lines, perifosine has shown to have cytotoxic and anti-proliferative activity as a single agent. This drug has been used in clinical research studies of other types of cancers including soft tissue sarcomas, head and neck cancers and prostate cancer. This study uses a two-stage design to evaluate efficacy of perifosine based on overall response (OR). The null and alternative OR rates are 20% and 40%. If 4 or more patients enrolled in the stage one cohort (n=17 patients) achieve OR than accrual will proceed to stage two (n=20 patients). If fewer than 10 ORs are observed then the regimen will be considered ineffective.