anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: The relationship between peripheral immune cells and immunoglobulin A nephropathy (IgAN) is widely known; however, causal evidence of this link is lacking. Here, we aimed to determine the causal effect of peripheral immune cells, specifically total white blood cells, lymphocytes, monocytes, basophils, eosinophils, and neutrophils, as well as lymphocyte subset traits, on the IgAN risk using a Mendelian randomization (MR) analysis.
METHODS: The inverse-variance weighted (IVW) method was used for the primary analysis. We applied three complementary methods, including the weighted median, MR-Egger regression, and MR-PRESSO, to detect and correct for the effect of horizontal pleiotropy. Additionally, we performed a multivariable MR (MVMR) analysis, adjusting for the effects of C-reactive protein (CRP) levels. The roles of specific lymphocyte subtypes and their significance have garnered interest. Bidirectional two-sample MR analysis was performed to test the potential causal relationships between immune traits, including median fluorescence intensities (MFIs) and the relative cell count (AC), and IgAN.
RESULTS: The IVW-MR analysis suggested a potential causal relationship between lymphocyte counts and IgAN in Europe (OR per 1-SD increase: 1.43, 95% CI: 1.08-1.88, P = 0.0123). The risk effect of lymphocytes remained even after adjusting for CRP levels using the MVMR method (OR per 1-SD increase: 1.44, 95% CI: 1.05-1.96, P = 0.0210). The other sensitivity analyses showed a consistent trend. The largest GWAS published to date was used for peripheral blood immunophenotyping to explore the potential causal relationship between peripheral immune cell subsets and IgAN. Six AC-IgAN and 14 MFI-IgAN pairs that reached statistical significance (P < 0.05) were detected. Notably, CD3, expressed in eight subsets of T cells, consistently showed a positive correlation with IgAN. The bidirectional MR analysis did not reveal any evidence of reverse causality. According to the sensitivity analysis, horizontal pleiotropy was unlikely to distort the causal estimates.
CONCLUSIONS: Genetically determined high lymphocyte counts were associated with IgAN, supporting that high lymphocyte counts is causal risk factor for IgAN.
PROBLEM TO BE SOLVED: To obtain the subject pharmaceutical preparation having high nasty smell-masking effect and reduced in bitter taste by constituting the pharmaceutical preparation so as to have two or more layers different in methol formulation amounts and gradually increase a menthol concentration bringing into contact with tongue. SOLUTION: This solid pharmaceutical preparation is obtained by forming the preparation in such structure that the formulation amount of menthol of a layer more slowly dissolving in oral cavity becomes higher than that of menthol of a layer more quickly dissolving than the layer. For example, a laminated structure comprising three or more layers or a structure comprising two or more layers in which all or a part of inner layer is coated with outer layer is exemplified as the structure. In the menthol blend layer having higher menthol formulation content, the menthol content is preferably <=5wt.%. The difference of menthol blend amount of each layer is preferably >=0.05wt.%.  It is preferable from the viewpoint capable of reducing unpleasant taste such as bitter taste which menthol has that the layer blending menthol is formed as a expandable layer formulating a carbonate with an organic acid.
The R2D2 study will test whether the adverse cognitive effects of anticholinergic medications are reversible by implementing a pharmacist-based deprescribing intervention for older adults within primary care practices. Two groups will be recruited: providers (physicians and advanced practice providers including nurse practitioners), and patients. Primary care providers of those prescribed eligible anticholinergic medications will be recruited for participation in the study, and their patients who also meet eligible criteria will be subsequently approached and recruited. Participants will be randomized to one of two groups: the deprescribing intervention group or usual care; the intervention group will receive a pharmacist-based deprescribing intervention, while the usual care group will receive care as usually provided by their primary and/or specialty care providers. The intervention and follow-up data collection will occur over 24 months in order to test the long-term impact of the intervention on the planned clinical outcomes. Study outcomes include cognition (primary) and safety (secondary) through validated self-reported scales.
PURPOSE: A composition containing the extract of Euonymus alatus (Thunb.) Sieb. as a main component is provided. The Euonymus alatus extract exhibits antidiabetic activity in OGTT(Oral Glucose Tolerance Tests) and streptozotocin-induced diabetic rats and significantly reduces the glucose level in blood and urine and can be used in prevention and treatment of diabetes. CONSTITUTION: The pharmaceutical composition for the prevention and treatment of diabetes contains 0.1 to 50% by weight of a Euonymus alatus extract, pharmaceutically acceptable carriers or excipients. The Euonymus alatus extract is a crude extract or an extract soluble in a polar solvent such as water, lower alcohol or a mixed solvent thereof. The dosage of the pharmaceutical composition is administered in an amount of 0.1 to 100mg/kg per day. The health food for reducing blood glucose level and preventing diabetes contains a Euonymus alatus extract which is soluble in a polar solvent and a food acceptable additive. The Euonymus is Euonymus alatus (Thunb.) Sieb., Euonymus bungeanus MAXIM. or Euonymus sieboldianus BLUME.
This invention provides for the assessment of susceptibility to disease e.g. HIV-1 by assessment of an individual's FUT2 genotype or associated phenotype. The normal non-variant FUT2 allele codes for an α (1, 2) fucosyltransferase enzyme associated with a characteristic phenotype. Some people are homozygotes for a genetic variant of FUT2 which is characterised by an enzyme-inactivating nonsense change at position 143 of the amino acid sequence, so that a tryptophan codon is converted into a stop codon. Individuals homozygous for the variant form also have a characteristic phenotype. Homozygotes for the less common variant allele (se) are less likely to be susceptible to HIV-1 infection than an individual homozygous for the more common normal allele (SE). Heterozygotes (SE/se) are at most risk of HIV-1 infection in comparison to the other FUT2 genotypes (se/se, SE/SE).
The biology of the cyclin-dependent kinase-like (CDKL) kinase family remains enigmatic. Contrary to their nomenclature, CDKLs do not rely on cyclins for activation and are not involved in cell cycle regulation. Instead, they share structural similarities with mitogen-activated protein kinases and glycogen synthase kinase-3, although their specific functions and associated signaling pathways are still unknown. Previous studies have shown that the activation of CDKL5 kinase contributes to the development of acute kidney injury (AKI) by suppressing the protective SOX9-dependent transcriptional program in tubular epithelial cells. In the current study, we measured the functional activity of all five CDKL kinases and discovered that, in addition to CDKL5, CDKL1 is also activated in tubular epithelial cells during AKI. To explore the role of CDKL1, we generated a germline knockout mouse that exhibited no abnormalities under normal conditions. Notably, when these mice were challenged with bilateral ischemia-reperfusion and rhabdomyolysis, they were found to be protected from AKI. Further mechanistic investigations revealed that CDKL1 phosphorylates and destabilizes SOX11, contributing to tubular dysfunction. In summary, this study has unveiled a previously unknown CDKL1-SOX11 axis that drives tubular dysfunction during AKI.NEW & NOTEWORTHY Identifying and targeting pathogenic protein kinases holds potential for drug discovery in treating acute kidney injury. Our study, using novel germline knockout mice, revealed that Cdkl1 kinase deficiency does not affect mouse viability but provides protection against acute kidney injury. This underscores the importance of Cdkl1 kinase in kidney injury and supports the development of targeted small-molecule inhibitors as potential therapeutics.
The active ingredient in gabapentin capsules isgabapentin, which has the chemical name 1-(aminomethyl) cyclohexaneacetic acid.The molecular formula of gabapentin is C9H17NO2and the molecular weight is 171.24. The structural formula of gabapentin is:

Gabapentin is awhite to off-white crystalline solid with a pKa1 of 3.7 and a pKa2 of 10.7. Itis freely soluble in water and both basic and acidic aqueous solutions. The logof the partition coefficient (n-octanol/0.05M phosphate buffer) at pH 7.4 is–1.25. 

  


Each gabapentin capsule contains 100 mg, 300 mg, or 400 mg of gabapentinand the following inactive ingredients: anhydrous lactose, cornstarch, andtalc. The 100 mg capsule shell contains gelatin, sodium lauryl sulfate, andtitanium dioxide. The 300 mg capsule shell contains gelatin, sodium laurylsulfate, titanium dioxide, and yellow iron oxide. The 400 mg capsule shellcontains gelatin, sodium lauryl sulfate, red iron oxide, titanium dioxide, andyellow iron oxide. The imprinting ink contains shellac, dehydrated alcohol,isopropyl alcohol, butyl alcohol, propyl glycol, strong ammonia solution, andtitanium dioxide.
Background: oral ulceration is the earliest and commonest manifestation of Behcet's disease (BD). Minor aphthous like ulcers (\<10 mm in diameter) are the most common type (85%); major or herpetiform ulcers are less frequent. It is occurred about in Egypt; 3.6/100,000 % and high recurrence rate with traditional treatment. Colchicine is the first line of treatment in mucocutaneous manifestation of BD through its anti-inflammatory effect. Tacrolimus oral gel is safe and effective in treating aphthous ulcers in many diseases. Objectives: to compare the clinical efficacy of topical tacrolimus versus oral colchicine upon disease activity, pain and ulcer severity in oral ulcer associated with BD. Study design: A randomized double -blinded trial.

Setting: Rheumatology clinic, Assiut University Hospital and Faculty of Dental Medicine, AlAzhar University, Assiut branch outpatient's clinic. Methods: 40 BD participants (\> 3 months taken traditional treatment with persistent active oral ulceration). They have been equally randomized into either group I (Colchicine and topically applied Tacrolimus), or group II (Colchicine only). Measurements: Behcet's Disease Current Activity Form (BDCAF), Ulcer Severity Score (USS) and visual analog scale (VAS) pre-injection, then re-evaluated postinjection at four-time points (15 days, 1st, 2nd and 3rd months) and Determination of Natural Killer (NK) cells number in salival wash before treatment (at base line) and after the treatment (after 3 months)
Once the MTD or recommended Phase 2 dose has been determined, an expansion cohort of up to 25 subjects may be enrolled. Subjects will receive ASP1235 (AGS62P1) as an intravenous infusion once weekly for three weeks pf a 4-week cycle.
Placebo is supplied as a sterile, colorless, clear, isotonic solution in a glass cartridge which is pre-assembled into a disposable delivery device (pen) for subcutaneous injection. Each prefilled delivery device is filled with 2.7 mL to deliver 2.4 mL. Each mL contains 0.41 mg glacial acetic acid, 0.1 mg sodium acetate (anhydrous), 45.4 mg mannitol, 3 mg Metacresol, and Water for Injection. In addition, hydrochloric acid solution 10% and/or sodium hydroxide solution 10% may have been added to adjust the product to pH 4.
PROBLEM TO BE SOLVED: To obtain the subject particles capable of effectively inducing a damage to a cute lymphoblastic leukemia (hereinafter ALL) cells, when the ALL cells are cultured in the presence of the particles, by immobilizing an anti-Fas antibody and an anti-CD 10 antibody. SOLUTION: The gelatin particles bound to an anti-Fas antibody (preferably CH 11) and preferably further an anti-CD 10 antibody (preferably NL-1). The Fas is a cell surface antigen as one of the family of TNF receptors, and the CD 10 is a common acute lymphoblastic leukemia antigen. The ratio of the anti-Fas antibody/ the anti-CD 10 antibody bound to the gelatin particles is preferably 1/(0.1-10). A physical adsorption method is preferably used as a method for binding the antibody to the gelatin particles. The culture of ALL cells in the presence of the gelatin particles can induce a specific cell damage to the ALL cells, especially the specific cell damage to the ALL cells in a body fluid, a culture liquid, or the like, containing normal cells.
A composition and therapeutic kit provide a therapeutic azole with increased solubility. The kit includes an aerosol packaging assembly containing a container accommodating a pressurized product and an outlet capable of releasing the pressurized product as a foam. The pressurized product includes a foamable composition including:
         i. a therapeutic azole, wherein the solubility of the azole in the composition before foaming is less than the solubility of the azole in the composition after foaming;   ii. at least one organic carrier selected from the group consisting of a hydrophobic organic carrier, a co-solvent, an emollient and mixtures thereof, at a concentration of about 2% to about 50% by weight;   iii. a surface-active agent;   iv. about 0.01% to about 5% by weight of at least one polymeric additive selected from the group consisting of a bioadhesive agent, a gelling agent, a film forming agent and a phase change agent;   v. water; and   vi. liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the total composition.
OBJECTIVES: I. Compare the response rate or clinical benefit rate in patients with locally advanced or metastatic breast cancer treated with 1 of 2 different doses of arzoxifene hydrochloride. II. Compare the response rates and clinical benefit rates for patients with tamoxifen-sensitive versus tamoxifen-refractory disease. III. Compare the degree of toxicity between the 2 doses of arzoxifene hydrochloride in these patients. IV. Compare the quality of life and survival of these patients receiving high versus low dose arzoxifene hydrochloride. V. Determine the time to progressive disease, time to treatment failure, and response duration of this treatment in these patients. VII. Measure changes in serum estradiol, follicle stimulating hormone, luteinizing hormone, and sex hormone binding globulin in these patients during treatment.

OUTLINE: This is a randomized, double blind study. Patients are stratified according to number of metastatic sites (less than 3 vs 3 or more), tamoxifen sensitivity (sensitive vs refractory), and degree of estrogen receptor positivity (high vs low vs unknown). Patients are randomized to receive 1 of 2 doses of arzoxifene hydrochloride. Patients receive arzoxifene hydrochloride orally once daily for 12 weeks. Treatment continues in the absence of toxicity and disease progression. Quality of life is assessed before, during, and at the completion of the study. Patients are followed every 4 weeks for 12 weeks, at 30 days after the last treatment, and every 2-3 months after the last treatment.

PROJECTED ACCRUAL: This study will accrue 104-114 patients.
Rare and low-frequency variants contribute to schizophrenia (SCZ), and may influence its age-at-onset (AAO). We examined the association of rare or low-frequency deleterious coding variants in Chinese patients with SCZ. We collected DNA samples in 197 patients with SCZ spectrum disorder and 82 healthy controls (HC), and performed exome sequencing. The AAO variable was ascertained in the majority of SCZ participants for identify the early-onset (EOS, AAO<=18) and adult-onset (AOS, AAO>18) subgroups. We examined the overall association of rare/low-frequency, damaging variants in SCZ versus HC, EOS versus HC, and AOS versus HC at the gene and gene-set levels using Sequence Kernel Association Test. The quantitative rare-variant association test of AAO was conducted. Resampling was used to obtain empirical p-values and to control for family-wise error rate (FWER). In binary-trait association tests, we identified 5 potential candidate risk genes and 10 gene ontology biological processes (GOBP) terms, among which PADI2 reached FWER-adjusted significance. In quantitative rare-variant association tests, we found marginally significant correlations of AAO with alterations in 4 candidate risk genes, and 5 GOBP pathways. Together, the biological and functional profiles of these genes and gene sets supported the involvement of perturbations of neural systems in SCZ, and altered immune functions in EOS.
BACKGROUND: Chlorhexidine gluconate solution is superior to povidone-iodine for prevention of surgical site infection. However, the overall efficacy of chlorhexidine gluconate for surgical site infection prevention in various types of gastroenterological surgery, as well as the optimal concentration of chlorhexidine gluconate, remain unclear. The aim of the present study was to clarify whether subcutaneous wound soaking with chlorhexidine gluconate would reduce the incidence of surgical site infection associated with gastroenterological surgery in patients with wound classes Ⅱ to Ⅳ.
METHODS: Patients were randomly assigned (1:1) to either wound soaking with chlorhexidine gluconate (chlorhexidine gluconate group) or no chlorhexidine gluconate soaking (control group). After closure of the abdominal fascia, gentle subcutaneous soaking of the wound was performed using gauze fully soaked in aqueous 0.05% chlorhexidine gluconate before skin closure. Incisional surgical site infection was diagnosed using the Centers for Disease Control and Prevention criteria. The primary end point was the occurrence of incisional surgical site infection.
RESULTS: Among 363 patients, 245 (67%) underwent laparoscopic surgery. All 363 patients were included-181 in the chlorhexidine gluconate group (49.9%) and 182 (50.1%) in the control group. There were no significant inter-group differences in patient background, the type of procedure, or wound classification. The incidence proportion of incisional surgical site infection was significantly lower in the chlorhexidine gluconate group than in the control group (9.4% vs 19.2%; P = .008).
CONCLUSION: Subcutaneous wound soaking with chlorhexidine gluconate reduces the incidence of incisional surgical site infection in patients undergoing gastroenterological surgery.
Caesarean scar endometriosis is a rare condition characterised by the presence of endometrial tissue within a surgical scar following a caesarean section. A woman in her late 30s presented with a painful lump beneath her caesarean section skin scar, worsening during menstruation. Despite a previous incision and drainage procedure for a 'scar abscess', the symptoms persisted. Ultrasound imaging revealed a cystic lesion beneath the scar. A diagnosis of scar endometriosis was made, and surgical excision was performed. The patient remained symptom-free at 2-year follow-up postsurgery. Histopathology confirmed the presence of endometrial glands and stroma within the scar tissue. This case demonstrates that a reliable diagnosis of caesarean section endometriosis could be made with a triad of symptoms of a cyclic painful mass at the site of a caesarean section scar. Imaging is helpful in excluding other differential diagnoses. Diagnosis can be confirmed with histopathology and treated with complete surgical excision.
Multiple Myeloma

In trials 1 and 2 in patients who received POMALYST + Low-dose Dex, neutropenia was the most frequently reported Grade 3 or 4 adverse reaction, followed by anemia and thrombocytopenia. Neutropenia of any grade was reported in 51% of patients in both trials. The rate of Grade 3 or 4 neutropenia was 46%. The rate of febrile neutropenia was 8%.

Monitor patients for hematologic toxicities, especially neutropenia. Monitor complete blood counts weekly for the first 8 weeks and monthly thereafter. Patients may require dose interruption and/or modification [see Dosage and Administration (2.4)].

Kaposi Sarcoma

In Trial 12-C-0047, hematologic toxicities were the most common (all grades and Grade 3 or 4) adverse reactions [see Adverse Reactions (6.1)]. Fifty percent of patients had Grade 3 or 4 neutropenia. Monitor patients for hematologic toxicities, especially decreased neutrophils. Monitor complete blood counts every 2 weeks for the first 12 weeks and monthly thereafter. Withhold, reduce the dose, or permanently discontinue POMALYST based on the severity of the reaction [see Dosage and Administration (2.4)].
Hypobaric Hypoxia (HH) negatively affects the cardiovascular and respiratory systems as well as gonadal development and the therefore next generation. This study investigated the effects of HH on zebrafish and SD rats, by exposing them to a low-pressure environment at 6000 m elevation for 30 days to simulate high-altitude conditions. It was indicated that parental zebrafish reared amh under HH had increased embryo mortality, reduced hatchability, and abnormal cartilage development in the offspring. Furthermore, the HH-exposed SD rats had fewer reproductive cells and smaller litters. Moreover, the transcriptome analysis revealed the down-regulation of steroid hormone biosynthesis pathways. The expression of the gonad-associated genes (amh, pde8a, man2a2 and lhcgr), as well as the gonad and cartilage-related gene bmpr1a, were also down-regulated. In addition, Western blot analysis validated reduced bmpr1a protein expression in the ovaries of HH-treated rats. In summary, these data indicate the negative impact of HH on reproductive organs and offspring development, emphasizing the need for further research and precautions to protect future generations' health.
Acute respiratory distress syndrome (ARDS is a severe form of acute lung injury. ARDS is characterized by an increase in pulmonary vascular permeability resulting from a non-cardiogenic cause, leading to an increased vascular water volume, pulmonary inflammation, and severe hypoxemia. Conventional therapy for ARDS is primarily respiratory management by mechanical ventilation using positive end-expiratory pressure (PEEP). Mechanical ventilation is the major management concern in patients with ARDS, due to its higher risk of infections and morbidity. Treatment with Carperitide may reduce time on the ventilator by reducing pulmonary edema and by improving gas exchange. The results of Carperitide studies in animals and humans support the idea that the hormone will be effective in managing the acute pulmonary complications and hypoxemia seen in ARDS.