anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling is a significant component of the innate immune system and functions as a vital sentinel mechanism to monitor cellular and tissue aberrations in microbial invasion and organ injury. cGAS, a cytosolic DNA sensor, is specialized in recognizing abnormally localized cytoplasmic double-stranded DNA (dsDNA) and catalyzes the formation of a second messenger cyclic-GMP-AMP (cGAMP), which initiates a cascade of type Ⅰ interferon and inflammatory responses mediated by STING. Micronucleus, a byproduct of chromosomal missegregation during anaphase, is also a significant contributor to cytoplasmic dsDNA. These unstable subcellular structures are susceptible to irreversible nuclear envelope rupture, exposing genomic dsDNA to the cytoplasm, which potently recruits cGAS and activates STING-mediated innate immune signaling and its downstream activities, including type Ⅰ interferon and classical nuclear factor-κB (NF-κB) signaling pathways lead to senescence, apoptosis, autophagy activating anti-cancer immunity or directly killing tumor cells. However, sustained STING activation-induced endoplasmic reticulum stress, activated chronic type Ⅰ interferon and nonclassical NF-κB signaling pathways remodel immunosuppressive tumor microenvironment, leading to immune evasion and facilitating tumor metastasis. Therefore, activated cGAS-STING signaling plays a dual role of suppressing or facilitating tumor growth in tumorigenesis and therapy. This review elaborates on research advances in mechanisms of micronucleus inducing activation of cGAS-STING signaling and its implications in tumorigenesis and therapeutic strategies of malignant tumors.
This paper presents evidence that some-but not all-religious experts in a particular faith may have a schizophrenia-like psychotic process which is managed or mitigated by their religious practice, in that they are able to function effectively and are not identified by their community as ill. We conducted careful phenomenological interviews, in conjunction with a novel probe, with okomfo, priests of the traditional religion in Ghana who speak with their gods. They shared common understandings of how priests hear gods speak. Despite this, participants described quite varied personal experiences of the god's voice. Some reported voices which were auditory and more negative; some seemed to describe trance-like states, sometimes associated with trauma and violence; some seemed to be described sleep-related events; and some seemed to be interpreting ordinary inner speech. These differences in description were supported by the way participants responded to an auditory clip made to simulate the voice-hearing experiences of psychosis and which had been translated into the local language. We suggest that for some individuals, the apprenticeship trained practice of talking with the gods, in conjunction with a non-stigmatizing identity, may shape the content and emotional tone of voices associated with a psychotic process.
328,111. Risler, J. Dec. 13, 1928, [Convention date]. Salves; medicinal powders for external use.- Creams or other preparations such as soaps or " poudres de riz," for protection of the skin against ultra-violet light consist of the usual ingredients togetlier with cadmium sulphide. The cadmium sulphide used may contain also zinc sulphide, or other ingredients such as sodium hyposulphite, zinc sulphate, copper bismuth or manganese. As an example a cream with a red phosphorescence consists of neutral 30 per cent glycerine 66 grammes, purified stearic acid 16 grammes, solution of ammonia B.P. 6 grammes, distilled water 8 grammes, 30 per cent phosphorescent cadmium sulphide 4 grammes. By reducing the strength of the phosphorescent cadmium sulphide to 20 per cent and 12 per cent the cream can be made of orange or citron yellow respectively. Perfumes may be added. Fluorescent aniline dyes may also be added and minute quantities of radio-active substances such as radium bromide in extremely dilute solution. Known preparations containing phosphorogenic copper together with zinc sulphide and in some cases the further addition of manganese are referred to.
Liver fibrosis is a chronic liver disease with progressive wound healing reaction caused by liver injury. Currently, there is no FDA approved drugs for liver fibrosis. Human adipose mesenchymal stem cells (hADSCs) have shown remarkable therapeutic effects in liver diseases. However, few studies have evaluated the therapeutic role of hADSCs in liver fibrosis, and the detailed mechanism of action is unknown. Here, we investigated the in vitro and in vivo anti-fibrosis efficacy of hADSCs and identified important metabolic changes and detailed mechanisms through transcriptomic and metabolomic analyses. We found that hADSCs could inhibit the proliferation of activated hepatic stellate cells (HSCs), promote their apoptosis, and effectively inhibit the expression of pro-fibrotic protein. It can significantly reduce collagen deposition and liver injury, improve liver function and alleviate liver inflammation in cirrhotic mouse models. In addition, transcriptome analysis revealed that the key mechanism of hADSCs against liver fibrosis is the regulation of AGE-RAGE signaling pathway. Metabolic analysis showed that hADSCs influenced changes of metabolites in lipid metabolism. Therefore, our study shows that hADSCs could reduce the activation of hepatic stellate cells and inhibit the progression of liver fibrosis, which has important potential in the treatment of liver fibrosis as well as other refractory chronic liver diseases.
The present invention provides a precursor of a beta-modified phosphoric acid compound having a partial structure represented by formula 1A in the molecule, and a reaction inhibitor and a pharmaceutical product each containing the precursor. (wherein A  1  representation-SR  1  、－S－S－R  1  、－SeR  1  or-X (wherein X is halogen selected from fluorine, chlorine, bromine and iodine), R  1  Hydrogen, alkyl group having 1 to 20 carbon atoms, and the like. L (L)  1  Represents hydrogen, alkyl group having 1 to 20 carbon atoms, or the like, L  2  Alkyl groups having 1 to 20 carbon atoms, and the like. L (L)  1  And L is equal to  2  Can be connected with each other to form a 4-6 membered ring structure. L (L)  1  L and  2  may have a substituent. Is a bond that is phosphorylated to bond to a phosphate group).
Participants in the TDC group will apply a 20 cm2 patch (Xulane: 20µg/d EE,150µg/d norelgestromin) to the abdomen, upper arm or buttock. The patch will be changed once weekly on the same day each week for weeks 1-3 (days 1-21, removed on day 22) and weeks 5-8 (days 29-56). Week 4 (days 22-28) will be a patch-free week. As soon as the post-study testing is complete, subjects will remove the patch.
The gut microbiota-brain axis has been associated with the pathogenesis of numerous disorders, but the mechanism(s) underlying these links are generally poorly understood. Accumulating evidence indicates the involvement of gut microbe-derived metabolites. Circulating levels of the gut microbe/host co-metabolite p-cresol sulfate (pCS) correlate with cerebrovascular event risk in individuals with chronic kidney disease (CKD), but whether this relationship is mechanistic is unclear. We hypothesized that pCS would impair the function of the blood-brain barrier (BBB), the primary brain vasculature interface. We report that pCS exposure impairs BBB integrity in human cells in vitro and both acutely (≤6 hours) and chronically (28 days) in mice, enhancing tracer extravasation, disrupting barrier-regulating tight junction components and ultimately exerting a suppressive effect upon whole-brain transcriptomic activity. In vitro and in vivo mechanistic studies showed that pCS activated epidermal growth factor receptor (EGFR) signaling, sequentially activating the intracellular signaling proteins annexin A1 and STAT3 to induce mobilization of matrix metalloproteinase MMP-2/9 and disruption to the integrity of the BBB. This effect was confirmed as specific to the EGFR through the use of both pharmacological and RNA interference approaches. Confirming the translational relevance of this work, exposure of the cerebromicrovascular endothelia to serum from hemodialysis patients in vitro led to a significant increase in paracellular permeability, with the magnitude of permeabilization closely correlating with serum pCS, but not most other uremic toxin, content. Notably, this damaging effect of hemodialysis patient serum was prevented by pharmacological blockade of the EGFR. Our results define a pathway linking the co-metabolite pCS with BBB damage and suggest that targeting the EGFR may mitigate against cerebrovascular damage in CKD. This work further provides mechanistic evidence indicating the role of gut microbe-derived metabolites in human disease.
High-grade osteosarcoma (OS) is the most common primary bone tumor mainly affecting children and young adults. First-line treatment consists of neo-adjuvant chemotherapy with doxorubicin, cisplatin, and methotrexate and surgery. The mean long-term survival rate for localized disease at diagnosis is 65-70%, dropping down to 20% when metastases are present at diagnosis. Therefore, curing OS is a clinical challenge, particularly for patients that do not respond to standard treatments. MYC has frequently been reported to be involved in the pathogenesis of OS and its high expression may be associated with drug resistance and patients' worse prognosis. Moreover, MYC is a master regulator of ribosomal proteins (RPs) synthesis and ribosome biogenesis (RiBi), which is often up-regulated in human tumors. In recent years, RPs have been recognized not only for their traditional role in ribosome assembly but also for their extra-ribosomal functions, many of which are linked to the onset and progression of cancer. In this review we focus on the role and possible interplay of MYC and RPs expression in association with drug resistance and worse prognosis in OS and discuss therapeutic options that target de-regulated MYC, RiBi, or RPs, which are already clinically available or under evaluation in clinical trials.
BACKGROUND: Although stroke is prevalent among Chinese, individuals with stroke may become more disabling if they have concomitant neck pain (NP) and low back pain (LBP). However, the prevalence and factors associated with post-stroke spinal pain among Chinese remain unknown. The current study used the 2018 cohort data from the China Health and Aged Care Tracking Survey (CHARLS) to determine the prevalence and factors associated with increased post-stroke NP and LBP in China.
METHODS: The CHARLS study was conducted on four cohorts of nationally representative samples of individuals aged 45 years and above from 30 provincial-level administrative units in China. We used data from the 2018 cohort of the CHARLS survey to determine the prevalence and factors associated with NP and LBP in the non-stroke and post-stroke populations. Participants aged 45 years or older who reported to have NP, and/or LBP were identified. The study was statistically analyzed using t-test, and ANOVA analysis of variance. A multiple logistic regression model was used to identify factors significantly associated with NP and/or LBP in the non-stroke and post-stroke populations.
RESULTS: A total of 19,816 individuals participated in the 2018 survey. The final inclusion of 17,802 subjects who met the criteria included 16,197 non-stroke and 885 stroke participants. The prevalence of NP and LBP in non-stroke population was 17.80% (95% CI: 17.21-18.39) and 37.22% (95% CI: 36.47-37.96), respectively. The prevalence of NP and LBP in the target stroke population was 26.44% (95% CI: 23.53-29.35) and 45.42% (95% CI: 42.14-48.71), respectively, and the difference was statistically significant (p < 0.05). Factors associated with increased post-stroke NP included female, short sleep duration, long lunch break, physical dysfunction, and depression. Factors associated with increased post-stroke LBP included female, comorbidities of two or more chronic diseases, physical dysfunction, and depression.
CONCLUSION: The current study highlighted the high prevalence of post-stroke neck pain (26.44%) and LBP (45.42%) in China. While slightly different associated factors were found to be associated with a higher prevalence of post-stroke NP and LBP, female and individuals with more physical dysfunction or depression were more likely to experience post-stroke spinal pain. Clinicians should pay more attention to vulnerable individuals and provide pain management measures.
Plasmodium vivax represents 50-80% of all malarial cases in Latin America and South East Asia. It is able to establish a dormant liver stage called the hypnozoite. Hypnozoite activation after initial infection can cause a relapse. Currently the only widely available drug is primaquine which requires administration over 14 days, resulting in poor compliance and treatment failure. Tafenoquine (an 8-aminoquinoline anti-malarial drug) has been shown to possess activity against all stages of the plasmodium life cycle, including the dormant stage in the liver. This is a multi-centre, double dummy, double blind, parallel group, randomized, active control study which is conducted in two parts. For both parts, subjects are treated with Chloroquine on days 1 to 3 (600mg, 600mg, and 300mg) to treat the blood stage vivax malaria. Part 1 will include at least 324 subjects and part 2 at least 600 subjects. Part 1 has 6 treatment arms, arms 1 to 4 contain different doses of Tafenoquine (50mg, 100mg, 300mg, and 600mg) dosed on day 1 or 2, arm 5 contains primaquine (15mg) dosing over 14 days (days 2-15 (15mg)) and arm 6 contains chloroquine only. The aim of this is to find a dose of Tafenoquine which meets the defined dose criteria. Based on Part 1 efficacy and safety, a single Tafenoquine dose (300 mg) will be studied in the pivotal Part 2. Part 2 contains 3 treatment arms one with the selected Tafenoquine dose (300 mg), the second arm will be 15mg Primaquine which will again be dosed over 14 days and the final arm contains chloroquine only dosed days 1-3 (600mg, 600mg, 300mg). Therefore as with Part 1, in Part 2 all subjects will receive Chloroquine. The aim of Part 2 is to investigate the safety and efficacy of the selected Tafenoquine/Chloroquine dose in the treatment and radical cure of Plasmodium vivax malaria. In addition to the Primary and Secondary endpoints stated below we will also be collecting; other efficacy endpoints (gametocyte clearance time, Recrudescence defined as any Plasmodium vivax parasitemia occurring on or before Day 29 (blood stage treatment failure), Incidence of Plasmodium falciparum malaria and Incidence of recrudescence and new Plasmodium vivax infection, determined by Polymerase Chain Reaction (PCR), safety endpoints (clinically relevant haemolysis leading to drops in haemoglobin / haematocrit or complications thereof (required transfusions, acute renal failure), changes in methaemoglobin, gastrointestinal (GI) tolerability - incidence of abdominal pain, heartburn, diarrhoea, constipation, nausea and vomiting and ophthalmic safety - incidence of corneal deposits, retinal and visual field abnormalities. Data collected at up to four centres . Additionally, the incidence and severity of adverse events and abnormal laboratory observations will be presented).Pharmacokinetic endpoints (Population pharmacokinetic parameters for tafenoquine including but not limited to oral clearance (CL/F) and volume of distribution (V/F)and Pharmacokinetic/Pharmacodynamic endpoints (e.g. tafenoquine plasma concentrations) and selected Pharmacodynamic endpoints (e.g. relapse efficacy, change in methaemoglobin) if appropriate, will be explored.
INTRODUCTION: Outcomes of deceased donor kidney transplant (DDKT) recipients from the same donor with donor-recipient sex discordance have been studied with inconsistent results.
METHODS: Adult DDKT where both kidneys from the same donor occurred at our center in two different recipients of different sexes were included. Outcomes were analyzed separately for male and female donors, based on the concordance or discordance between donor-recipient sex: Male-male (M-m) versus Male to female (M-f) or vice versa, F-f versus F-m. Acute rejection (AR) and uncensored graft failure were primary outcomes of interest. The univariate and multivariate risks for AR and graft failure were conducted using the Cox proportional hazards model and log-rank tests.
RESULTS: A total of 130 donors, 84 male and 46 female fulfilled our selection criteria and were transplanted in 260 recipients. With respect to the concordant groups (M-m or F-f), sex discordance was not significantly associated with the risk of rejection in multivariate analysis (M-f vs. M-m HR 1.15 [0.53-2.53, P = 0.72]; F-m vs. F-f HR 1.77 [0.71-4.39, P = 0.23]). Sex discordance was also not significantly associated with graft failure in multivariate analysis. Interestingly, risk factors for AR differed among male donors and female donors. The higher calculated panel reactive antibodies (cPRA) and nonwhite recipients were at increased risk for AR in F-m, but not in M-f.
CONCLUSIONS: Donor-recipient sex discordance was not significantly associated with AR or graft failure. Risk factors for AR may differ across male and female donors.
FIELD: drug production. SUBSTANCE: homogenate of brain cortex is subjected for enzymatic hydrolysis at pH 6.8-8.4 for 4-5 hr. Then proteins were separated by alcohol precipitation, prepared hydrolyzate is filtered successively through membrane filters at pore size 0.22-0.5 mcm at threshold retention of substances 5-15 kDa. Alcohol and water were distilled off, preserving agent is added 0.3% phenol followed by sterile filtration through membrane at pore size 0.2-0.32 mcm. EFFECT: simplified technology, high clinic effectiveness of preparation. 1 tbl
Zolpidem was given orally for basic treatment, with the treatment dose of 10mg/tablet per day, one tablet per time, once a day, before sleep, for 8 consecutive weeks. Placebo was given orally, with a therapeutic dose of 0.36g/capsule, 2 capsules each time, twice a day, and once after breakfast and dinner.
OBJECTIVE: To develop a machine learning-based prediction model for identifying hyperuricemic participants at risk of developing gout.
METHODS: A retrospective nationwide Israeli cohort study used the Clalit Health Insurance database of 473 124 individuals to identify adults 18 years or older with at least two serum urate measurements exceeding 6.8 mg/dl between January 2007 and December 2022. Patients with a prior gout diagnosis or on gout medications were excluded. Patients' demographic characteristics, community and hospital diagnoses, routine medication prescriptions and laboratory results were used to train a risk prediction model. A machine learning model, XGBoost, was developed to predict the risk of gout. Feature selection methods were used to identify relevant variables. The model's performance was evaluated using the receiver operating characteristic area under the curve (ROC AUC) and precision-recall AUC. The primary outcome was the diagnosis of gout among hyperuricemic patients.
RESULTS: Among the 301 385 participants with hyperuricemia included in the analysis, 15 055 (5%) were diagnosed with gout. The XGBoost model had a ROC-AUC of 0.781 (95% CI 0.78-0.784) and precision-recall AUC of 0.208 (95% CI 0.195-0.22). The most significant variables associated with gout diagnosis were serum uric acid levels, age, hyperlipidemia, non-steroidal anti-inflammatory drugs and diuretic purchases. A compact model using only these five variables yielded a ROC-AUC of 0.714 (95% CI 0.706-0.723) and a negative predictive value (NPV) of 95%.
CONCLUSIONS: The findings of this cohort study suggest that a machine learning-based prediction model had relatively good performance and high NPV for identifying hyperuricemic participants at risk of developing gout.
Worldwide exposure to fluoxetine hydrochloride is estimated to be over 38 million patients (circa 1999). Of the 1578 cases of overdose involving fluoxetine hydrochloride, alone or with other drugs, reported from this population, there were 195 deaths. 

Among 633 adult patients who overdosed on fluoxetine hydrochloride alone, 34 resulted in a fatal outcome, 378 completely recovered, and 15 patients experienced sequelae after overdosage, including abnormal accommodation, abnormal gait, confusion, unresponsiveness, nervousness, pulmonary dysfunction, vertigo, tremor, elevated blood pressure, impotence, movement disorder, and hypomania. The remaining 206 patients had an unknown outcome. The most common signs and symptoms associated with non-fatal overdosage were seizures, somnolence, nausea, tachycardia, and vomiting. The largest known ingestion of fluoxetine hydrochloride in adult patients was 8 grams in a patient who took fluoxetine alone and who subsequently recovered. However, in an adult patient who took fluoxetine alone, an ingestion as low as 520 mg has been associated with lethal outcome, but causality has not been established.

Among pediatric patients (ages 3 months to 17 years), there were 156 cases of overdose involving fluoxetine alone or in combination with other drugs. Six patients died, 127 patients completely recovered, 1 patient experienced renal failure, and 22 patients had an unknown outcome. One of the six fatalities was a 9-year-old boy who had a history of OCD, Tourette’s syndrome with tics, attention deficit disorder, and fetal alcohol syndrome. He had been receiving 100 mg of fluoxetine daily for 6 months in addition to clonidine, methylphenidate, and promethazine. Mixed-drug ingestion or other methods of suicide complicated all 6 overdoses in children that resulted in fatalities. The largest ingestion in pediatric patients was 3 grams which was nonlethal.

Other important adverse reactions reported with fluoxetine overdose (single or multiple drugs) include coma, delirium, ECG abnormalities (such as nodal rhythm, QT interval prolongation and ventricular arrhythmias, including Torsades de Pointes-type arrhythmias), hypotension, mania, neuroleptic malignant syndrome-like reactions, pyrexia, stupor, and syncope.