anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Clopidogrel is the most broadly utilized platelet P2Y12 receptor inhibitor. However, numerous studies have shown that pharmacodynamics (PD) response profiles vary among clopidogrel treated patients and that individuals with reduced response have an increased risk of recurrent ischemic events. There are multiple factors contributing to clopidogrel response variability. Among these, genetic variations of the cytochrome P450 (CYP) 2C19 enzyme, a key contributor to clopidogrel metabolism, have been involved. In particular, loss-of-function (LOF) alleles of the CYP2C19 enzyme reduce transformation of clopidogrel pro-drug into its active metabolite. Thus, patients carrying LOF alleles have lower levels of clopidogrel's active metabolite as well as diminished platelet inhibition, which translates into an increased rate of adverse cardiovascular events, particularly in the setting of percutaneous coronary intervention (PCI). Because of these findings, drug regulating authorities have provided a boxed warning on the product label of clopidogrel on the potential for reduced efficacy of clopidogrel among CYP2C19 LOF carriers and suggested considering alternative antiplatelet therapies for these individuals. Prasugrel and ticagrelor are novel generation P2Y12 receptor inhibitors characterized by greater PD potency and reduced ischemic event rates compared with clopidogrel, and are not affected by CYP2C19 LOF polymorphisms. However, to date there are limited head-to-head PD comparisons between these two new P2Y12 receptors blockers, and there are no studies assessing on how these agents behave among CYP2C19 LOF carriers. Tailoring antiplatelet therapy according to results of genetic testing has been limited in real world clinical practice because of not having readily accessible results of individual's genetic makeup. The aim of the present study is to compare the PD effects of prasugrel versus ticagrelor in patients undergoing PCI with CYP2C19 LOF alleles using the novel point-of-care genetic testing Spartan RX-CYP2C19 which permits accurate and rapid identification of CYP2C19 genetic status.
Solid dosages of oral medicaments comprise a tetracycline antibiotic and novobiocin, the latter being contained in from 5 to 2000 "pellets," i.e. discrete particles, e.g. granules, pilules, spheres or compressed powders having sufficient integrity to withstand formulation into a single dosage unit such as a hard or soft gelatine capsule or a tablet.  Optionally, the pellets may be coated with a material which will delay the release of novobiocin in the stomach for about 10 to 20 minutes, e.g. styrene-maleic acid copolymer, ethyl cellulose or a fatty or waxy material and they may contain an anionic or non-ionic surfactant.  Specified tetracyclines include the bases tetracycline, chlortetracycline, oxytetracycline and demethyltetracycline and their pharmaceutically acceptable acid addition salts.  The novobiocin may be in any form other than the crystalline free acid.
An area of increasing interest continues to be the interaction between music therapy and its impacts on the autonomic nervous system (ANS) and wound repair in patients who have experienced trauma. This study intended to quantify the effect of music therapy on ANS regulation and wound healing. A cross-sectional observational study from March to December 2023 was undertaken involving 500 trauma patients. A control group received standard care, and an experimental group received daily 30-min music therapy sessions. Heart rate variability (HRV), cortisol levels, wound healing rates and patient-reported outcomes regarding pain, tension and well-being were among the critical parameters assessed. After 1 month, the experimental group exhibited a statistically significant rise in HRV (p < 0.05), suggesting increased parasympathetic activity. The experimental group exhibited a significant decrease in cortisol levels in comparison to the control group, with notable reduction observed after 1 month (p < 0.05). At 9 months, the experimental group exhibited significantly faster wound healing than the control group, with 85% wound recovery as opposed to 75% in control group. There was notable decrease in pain and stress scores at all time intervals in the music therapy group, with the greatest reduction occurring at the 9-month mark (p < 0.05). A significant positive correlation (p < 0.05) was identified between the number of completed music therapy sessions and patient outcomes, with individuals attending more than 20 sessions experiencing 33.6% positive outcomes. In trauma patients, music therapy substantially enhanced ANS regulation and accelerated wound healing. As evidenced by the elevated HRV and decreased cortisol levels, the therapy induced a physiologically tranquil state that is conducive to recovery. The considerable enhancements in the rates of wound healing, in conjunction with the substantial decreases in pain and tension levels, highlighted the therapeutic capacity of music therapy as intervention in trauma care. Additionally, the observed dose-response relationship indicated that customised music therapy regimens are crucial for achieving the best possible results for patients.
Neoadjuvant and adjuvant cisplatin: patients receive cisplatin IV over 6 hours on day 1. Treatment repeats every 2 weeks for 4 courses. Patients with progressive disease after course 4 are taken off study. Patients without evidence of disease progression proceed to surgery. Beginning within 3 weeks after surgery, patients receive cisplatin IV over 6 hours on day 1. Treatment repeats every 2 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.
Myopia is characterized of maladaptive increases in scleral fibroblast-to-myofibroblast transdifferentiation (FMT). Scleral hypoxia is a significant factor contributing to myopia, but how hypoxia induces myopia is poorly understood. Here, we showed that myopia in mice and guinea pigs was associated with hypoxia-induced increases in key glycolytic enzymes expression and lactate levels in the sclera. Promotion of scleral glycolysis or lactate production induced FMT and myopia; conversely, suppression of glycolysis or lactate production eliminated or inhibited FMT and myopia. Mechanistically, increasing scleral glycolysis-lactate levels promoted FMT and myopia via H3K18la, and this promoted Notch1 expression. Genetic analyses identified a significant enrichment of two genes encoding glycolytic enzymes, ENO2 and TPI1. Moreover, increasing sugar intake in guinea pigs not only induced myopia but also enhanced the response to myopia induction via the scleral glycolysis-lactate-histone lactylation pathway. Collectively, we suggest that scleral glycolysis contributes to myopia by promoting FMT via lactate-induced histone lactylation.
Methods and systems for scheduling wellness based meetings are described. In one embodiment, meeting data associated with a meeting is accessed. A meeting type designation is received. The meeting type designation designates the meeting as a walking meeting, a standing meeting, or a sitting meeting. Updated meeting data based on the meeting data and the meeting type designation is stored. Other methods and systems are described.
Sexual dysfunction, particularly in females, is a complex issue influenced by various factors, including depression and inflammation. The Systemic immune-inflammation index (SII), an inflammatory biomarker, has shown associations with different health conditions, but its relationship with female sexual dysfunction (FSD) remains unclear. This study aimed to investigate the association between SII and FSD in the context of depression, utilizing low sexual frequency as an assessment indicator. Data from the National Health and Nutrition Examination Survey (NHANES) 2005 to 2016, involving 1042 depressed female participants, were analyzed. FSD, indicated by low sexual frequency, and SII, derived from complete blood count results, were assessed. Logistic regression and subgroup analyses were conducted, considering demographic and health-related factors. A total of 1042 individuals were included in our analysis; 11.5163% of participants were categorized as having FSD, which decreased with the higher SII tertiles (tertile 1, 13.8329%; tertile 2, 13.5447%; tertile 3, 7.1839%; p for trend < 0.0001). Multivariate linear regression analysis showed a significant negative association between SII and FSD [0.9993 (0.9987, 0.9999)]. This negative association in a subgroup analysis is distinctly and significantly present in the Mexican American subgroup [0.9959 (0.9923, 0.9996)], while it does not reach statistical significance in other racial categories. Furthermore, the association between SII and FSD was nonlinear; using a 2-segment linear regression model, we found a U-shaped relationship between SII and FSD with an inflection point of 2100 (1000 cells/µL). In summary, in depressed individuals, a higher SII is independently associated with a decreased likelihood of FSD, emphasizing the potential role of inflammation in female sexual health.
MYAMBUTOL, following a single oral dose of 25 mg/kg of body weight, attains a peak of 2 to 5 mcg/mL in serum 2 to 4 hours after administration. When the drug is administered daily for longer periods of time at this dose, serum levels are similar. The serum level of MYAMBUTOL falls to undetectable levels by 24 hours after the last dose except in some patients with abnormal renal function. The intracellular concentrations of erythrocytes reach peak values approximately twice those of plasma and maintain this ratio throughout the 24 hours. During the 24-hour period following oral administration of MYAMBUTOL approximately 50 percent of the initial dose is excreted unchanged in the urine, while an additional 8 to 15 percent appears in the form of metabolites. The main path of metabolism appears to be an initial oxidation of the alcohol to an aldehydic intermediate, followed by conversion to a dicarboxylic acid. From 20 to 22 percent of the initial dose is excreted in the feces as unchanged drug. No drug accumulation has been observed with consecutive single daily doses of 25 mg/kg in patients with normal kidney function, although marked accumulation has been demonstrated in patients with renal insufficiency. MYAMBUTOL diffuses into actively growing Mycobacterium cells such as tubercle bacilli. MYAMBUTOL appears to inhibit the synthesis of one or more metabolites, thus causing impairment of cell metabolism, arrest of multiplication, and cell death. No cross resistance with other available antimycobacterial agents has been demonstrated.  
  
MYAMBUTOL has been shown to be effective against strains of Mycobacterium tuberculosis but does not seem to be active against fungi, viruses, or other bacteria. Mycobacterium tuberculosis strains previously unexposed to MYAMBUTOL have been uniformly sensitive to concentrations of 8 or less mcg/mL, depending on the nature of the culture media. When MYAMBUTOL has been used alone for treatment of tuberculosis, tubercle bacilli from these patients have developed resistance to MYAMBUTOL (ethambutol hydrochloride) by in-vitro susceptibility tests; the development of resistance has been unpredictable and appears to occur in a step-like manner. No cross resistance between MYAMBUTOL and other antituberculous drugs has been reported. MYAMBUTOL has reduced the incidence of the emergence of mycobacterial resistance to isoniazid when both drugs have been used concurrently. An agar diffusion microbiologic assay, based upon inhibition of Mycobacterium smegmatis (ATCC 607) may be used to determine concentrations of MYAMBUTOL in serum and urine.
Continuous 28-day cycles of BSC only, azacitidine subcutaneously (SC) plus BSC, low-dose cytarabine (LDAC) SC plus BSC, or intermediate-dose cytarabine (IDAC) intravenously (IV) plus BSC. Subjects will be assigned by the investigator to one of the CCR treatment options based on the investigator's assessment of subjects' eligibility.
FIELD: medicine, psychoneurology. SUBSTANCE: invention proposes agent containing a mixture of 0.15-0.20% of hydrogen peroxide in the amount of 200 ml and 2-4 ml of viburnum decoction. Invention proposes also method of treatment of patients with epilepsy and schizophrenia using the proposed preparation by intravenous infusion. Infusion is carried out by courses by 10-15 infusions at the rate 30-60 drops per minute in 2-3 days. Mixture of hydrogen peroxide in the dose 0.15-0.20% in volume 200 ml and viburnum bark decoction in the dose 1-2 ml in 100 ml of hydrogen peroxide. Proposed preparation and method of treatment give good therapeutic effect, frequency of epileptic seizures is decreased, electroencephalogram is normalized. EFFECT: enhanced effectiveness of preparation and treatment. 2 cl, 2 ex
PURPOSE: This study aimed to compare the effectiveness of Pulsed Radiofrequency Ablation (PRFA) and surgery for treating chronic plantar fasciitis, focusing on pain relief and functional outcomes.
METHODS: A prospective study involved 30 patients with chronic plantar fasciitis unresponsive to 12 months of conservative treatment. Patients were divided into PRFA (n = 17) and surgical (n = 13) groups. Clinical evaluations were conducted preoperatively and at three, six and 12 months postoperatively using VAS, AOFAS, FFI, and RMS scores. Radiological measurements assessed foot structure impact.
RESULTS: Both PRFA and surgery significantly reduced pain and improved function. PRFA had a shorter operative time and quicker return to activities (p < 0.001). At 3 months, PRFA showed superior VAS, FFI, and RMS scores (p < 0.05). Long-term outcomes were similar. No major complications occurred, but minor complications were higher in the surgical group (p < 0.01).
CONCLUSIONS: PRFA is a minimally invasive, effective treatment for chronic plantar fasciitis with quicker recovery and lower complication rates compared to surgery. Both treatments offer comparable long-term benefits. Further studies are needed to confirm these findings.
BACKGROUND: Several prognostic factors for primary cutaneous melanoma (PCM) have been identified, and these predict metastasis and survival, to a certain extent. We sought to determine the frequency of angiotropism (AT) and lymphovascular invasion (LVI) in PCM and the relationship between AT, LVI, and other clinicopathological parameters and patient's prognosis.
METHODS: This study included 538 cases of PCM diagnosed between 2003 and 2016. It comprised 246 females and 292 males whose clinicopathological variables were evaluated with respect to LVI and AT using univariate and multivariate analyses. Overall survival (OS) was assessed by Kaplan-Meier (KM) analysis and Cox regression multivariate analysis.
RESULTS: AT occurred more frequently than LVI. Ulceration, mitotic rate, and Breslow thickness were found to be highly associated with both LVI and AT (p < 0.01). All LVI+ cases had AT, with a significant positive correlation (p < 0.01). Both AT and LVI predicted lymph node (LN) metastasis (odds ratio [OR] = 1.47, 1.12, respectively). Multivariate analysis showed LN metastasis, Breslow thickness, LVI, and AT as predictors of OS. LVI and AT independently predicted adverse OS by Cox regression analysis (hazard ratio [HR] = 1.66, 1.49, respectively) and with KM survival analysis.
CONCLUSION: AT is a marker for angiotropic extravascular migratory tumor spread (angiotropic EVMM), and LVI is a marker for intra-lymphovascular tumor spread. Both predict poor prognosis. Given its ease of detection, AT could be adopted as a histologpathological feature in the routine assessment of primary cutaneous malignant melanoma cases.
AIMS/HYPOTHESIS: Regulatory factor X 6 (RFX6) is crucial for pancreatic endocrine development and differentiation. The RFX6 variant p.His293LeufsTer7 is significantly enriched in the Finnish population, with almost 1:250 individuals as a carrier. Importantly, the FinnGen study indicates a high predisposition for heterozygous carriers to develop type 2 and gestational diabetes. However, the precise mechanism of this predisposition remains unknown.
METHODS: To understand the role of this variant in beta cell development and function, we used CRISPR technology to generate allelic series of pluripotent stem cells. We created two isogenic stem cell models: a human embryonic stem cell model; and a patient-derived stem cell model. Both were differentiated into pancreatic islet lineages (stem-cell-derived islets, SC-islets), followed by implantation in immunocompromised NOD-SCID-Gamma mice.
RESULTS: Stem cell models of the homozygous variant RFX6-/- predictably failed to generate insulin-secreting pancreatic beta cells, mirroring the phenotype observed in Mitchell-Riley syndrome. Notably, at the pancreatic endocrine stage, there was an upregulation of precursor markers NEUROG3 and SOX9, accompanied by increased apoptosis. Intriguingly, heterozygous RFX6+/- SC-islets exhibited RFX6 haploinsufficiency (54.2% reduction in protein expression), associated with reduced beta cell maturation markers, altered calcium signalling and impaired insulin secretion (62% and 54% reduction in basal and high glucose conditions, respectively). However, RFX6 haploinsufficiency did not have an impact on beta cell number or insulin content. The reduced insulin secretion persisted after in vivo implantation in mice, aligning with the increased risk of variant carriers to develop diabetes.
CONCLUSIONS/INTERPRETATION: Our allelic series isogenic SC-islet models represent a powerful tool to elucidate specific aetiologies of diabetes in humans, enabling the sensitive detection of aberrations in both beta cell development and function. We highlight the critical role of RFX6 in augmenting and maintaining the pancreatic progenitor pool, with an endocrine roadblock and increased cell death upon its loss. We demonstrate that RFX6 haploinsufficiency does not affect beta cell number or insulin content but does impair function, predisposing heterozygous carriers of loss-of-function variants to diabetes.
DATA AVAILABILITY: Ultra-deep bulk RNA-seq data for pancreatic differentiation stages 3, 5 and 7 of H1 RFX6 genotypes are deposited in the Gene Expression Omnibus database with accession code GSE234289. Original western blot images are deposited at Mendeley ( https://data.mendeley.com/datasets/g75drr3mgw/2 ).
The present invention relates to a liver-protecting sobering-up capsule and a production method thereof by utilizing grape peel. The liver-protecting sobering-up capsule comprises the following raw materials according to weight percent: lactose, mannitol, grape peel dregs extract and yeast powder. The production method comprises the following steps: fully mixing the lactose, the mannitol, the grape peel dregs extract and the yeast powder according to the required amount, granulating with 40 to 95% ethanol, sterilizing, drying for 15 to 60 minutes at 45 to 95 DEG C, granulating and filling in blank capsules, and then obtaining the liver-protecting sobering-up capsule. The liver-protecting sobering-up capsule of the present invention is a pure natural liver-protecting sobering-up health food mainly adopting the grape peel dregs extract extracted from natural plant grapes and the yeast powder rich in natural group B vitamins and protein as the raw materials. The liver-protecting sobering-up capsule not only has the functions for preventing people from being drunk and sobering up, but also has a protection function for acute alcoholic liver injury and chronic alcoholic liver injury. The production method of the liver-protecting sobering-up capsule is one of the preferable methods for producing the liver-protecting sobering-up capsule.
BACKGROUND: Chronic kidney disease (CKD) is highly prevalent among Indigenous Australians, especially those in remote regions. The Tiwi population has been isolated from mainland Australia for millennia and exhibits unique genetic characteristics that distinguish them from other Indigenous and non-Indigenous populations. Notably, the rate of end-stage renal disease is up to 20 times greater in this population compared to non-Indigenous populations. Despite the identification of numerous genetic loci associated with kidney disease through GWAS, the Indigenous population such as Tiwi remains severely underrepresented and the increased prevalence of CKD in this population may be due to unique disease-causing alleles/genes.
METHODS: We used albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) to estimate the prevalence of kidney disease in the Tiwi population (N = 492) in comparison to the UK Biobank (UKBB) (N = 134,724) database. We then performed an exploratory factor analysis to identify correlations among 10 CKD-related phenotypes and identify new multi-phenotype factors. We subsequently conducted a genome-wide association study (GWAS) on all single and multiple phenotype factors using mixed linear regression models, adjusted for age, sex, population stratification, and genetic relatedness between individuals.
RESULTS: Based on ACR, 20.3% of the population was at severely increased risk of CKD progression and showed elevated levels of ACR compared to the UKBB population independent of HbA1c. A GWAS of ACR revealed novel association loci in the genes MEG3 (chr14:100812018:T:A), RAB36 (rs11704318), and TIAM2 (rs9689640). Additionally, multiple phenotypes GWAS of ACR, eGFR, urine albumin, and serum creatinine identified a novel variant that mapped to the gene MEIS2 (chr15:37218869:A:G). Most of the identified variants were found to be either absent or rare in the UKBB population.
CONCLUSIONS: Our study highlights the Tiwi population's predisposition towards elevated ACR, and the collection of novel genetic variants associated with kidney function. These associations may prove valuable in the early diagnosis and treatment of renal disease in this underrepresented population. Additionally, further research is needed to comprehensively validate the functions of the identified variants/genes.
Volunteers will receive 15 mcg intramuscularly (IM). Subjects who received previous clade 1 vaccine will get 1 dose, clade 1 vaccine-naive subjects receive 2 doses 28 days apart.
Table 4. enumerates adverse events that occurred at an incidence of 1% or more, and were more frequent than in the placebo group, among mirtazapine-treated patients who participated in short-term US placebo-controlled trials in which patients were dosed in a range of 5 to 60 mg/day. This table shows the percentage of patients in each group who had at least 1 episode of an event at some time during their treatment. Reported adverse events were classified using a standard COSTART-based dictionary terminology.

The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other investigations involving different treatments, uses and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side-effect incidence rate in the population studied.

Events reported by at least 1% of patients treated with mirtazapine are included, except the following events which had an incidence on placebo greater than or equal to mirtazapine: headache, infection, pain, chest pain, palpitation, tachycardia, postural hypotension, nausea, dyspepsia, diarrhea, flatulence, insomnia, nervousness, libido decreased, hypertonia, pharyngitis, rhinitis, sweating, amblyopia, tinnitus, taste perversion. *