anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Myocardial infarction (MI) induces complex transcriptional changes across diverse cardiac cell types. Single-cell RNA sequencing (scRNA-seq) provides an unparalleled ability to discern cellular diversity during infarction, yet the veracity of these discoveries necessitates confirmation. This investigation sought to elucidate MI mechanisms by integrating scRNA-seq and bulk RNA-seq data.
METHODS: Publicly available scRNA-seq (GSE136088) and bulk RNA-seq (GSE153485) data from mice MI models were analyzed. Cell types were annotated, and differential expression analysis conducted. Bulk RNA-seq underwent quality control, principal component analysis, and differential expression analysis.
RESULTS: In scRNA-seq data, the comparison between MI and sham groups unveiled a reduction in endothelial cell populations, but macrophages and monocytes increased. Within fibroblast subgroups, three distinct categories were discerned, with two exhibiting upregulation in MI. Notably, endothelial cells exhibited an elevated expression of genes associated with apoptosis and ferroptosis. In bulk RNA-seq analysis, distinct patterns emerged when comparing MI and sham groups. Specifically, six genes linked to endothelial ferroptosis exhibited heightened expression in MI group, thereby corroborating the scRNA-seq findings. Moreover, the examination of isolated cardiac macrophages from mice MI model revealed increased expression of Spp1, Col1a2, Col3a1, Ctsd, and Lgals3 compared to sham group, thus substantiating the dysregulation of macrophage apoptosis-related proteins following MI.
CONCLUSION: MI altered the transcriptomic landscapes of cardiac cells with increased expression of apoptotic genes. Moreover, the upregulation of macrophage apoptosis marker was confirmed within MI models. The presence of endothelial cell depletion and ferroptosis in MI has been demonstrated.
OBJECTIVE: This study compared radiographic measures of foot structure between people with and without symptomatic radiographic midfoot osteoarthritis (OA).
METHODS: This was a cross-sectional study of adults aged 50 years and older registered with four UK general practices who reported foot pain in the past year. Bilateral weightbearing dorsoplantar and lateral radiographs were obtained. Symptomatic radiographic midfoot OA was defined as midfoot pain in the last 4 weeks, combined with radiographic OA in one or more midfoot joints (first cuneometatarsal, second cuneometatarsal, navicular-first cuneiform, and talonavicular). Midfoot OA cases were matched 1:1 for sex and age to controls with a 5-year age tolerance. Eleven radiographic measures were extracted and compared between the groups using independent sample t-tests and effect sizes (Cohen's d).
RESULTS: We identified 63 midfoot OA cases (mean ± SD age was 66.8 ± 8.0 years, with 32 male and 31 female participants) and matched these to 63 controls (mean ± SD age was 65.9 ± 7.8 years). There were no differences in metatarsal lengths between the groups. However, those with midfoot OA had a higher calcaneal-first metatarsal angle (d = 0.43, small effect size, P = 0.018) and lower calcaneal inclination angle (d = 0.46, small effect size, P = 0.011) compared with controls.
CONCLUSIONS: People with midfoot OA have a flatter foot posture compared with controls. Although caution is required when inferring causation from cross-sectional data, these findings are consistent with a pathomechanical pathway linking foot structure to the development of midfoot OA. Prospective studies are required to determine the temporal relationships between foot structure, function, and the development of this common and disabling condition.
Isolation and "Ex-Vivo" expansion of Mesenchymal stem cells (MSC) obtained from each patient's bone marrow under GMP conditions at Xcelia-División de Terapias Avanzadas del Banc de Sang I Teixits. After 21 days, approximately 40 millions of autologous MSC will be implanted in the knee by articular injection.
BACKGROUND: DNA methylation may have a regulatory role in monogenic sensorineural hearing loss and complex, polygenic phenotypic forms of hearing loss, including age-related hearing impairment or Meniere disease. The purpose of this systematic review is to critically assess the evidence supporting a functional role of DNA methylation in phenotypes associated with hearing loss.
RESULTS: The search strategy yielded a total of 661 articles. After quality assessment, 25 records were selected (12 human DNA methylation studies, 5 experimental animal studies and 8 studies reporting mutations in the DNMT1 gene). Although some methylation studies reported significant differences in CpG methylation in diverse gene promoters associated with complex hearing loss phenotypes (ARHI, otosclerosis, MD), only one study included a replication cohort that supported a regulatory role for CpG methylation in the genes TCF25 and POLE in ARHI. Conversely, several studies have independently confirmed pathogenic mutations within exon 21 of the DNMT1 gene, which encodes the DNA (cytosine-5)-methyltransferase 1 enzyme. This methylation enzyme is strongly associated with a rare disease defined by autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN). Of note, rare variants in DNMT1 and DNMT3A genes have also been reported in noise-induced hearing loss.
CONCLUSIONS: Evidence supporting a functional role for DNA methylation in hearing loss is limited to few genes in complex disorders such as ARHI. Mutations in the DNMT1 gene are associated with ADCA-DN, suggesting the CpG methylation in hearing loss genes deserves further attention in hearing research.
Participants will receive 2 meals per day for 7 days a week for a duration of 10 weeks and educational materials (e.g., relevant handouts from the SMA) after the completion of the post intervention study assessment. This group will act as our Waitlist Control group.
OBJECTIVE: To analyse the preva lence of complications related to out-of-hospital cardiac arrest patients achieving target temperature management within 360 minutes compared to those taking more than 360 minutes.
METHODS: The retrospective study was conducted at a medical centre in Taiwan, and comprised data from Januar y 1, 2014, to December 31, 2020. Data was retrieved using the International Classification of Diseases version 10 codes I46.2, I46.8 and I46.9 related to adult patients of either gender presenting to the Emergenc y Medicine department with out-of-hospital cardiac arrest. Data included gender, age, medical histor y, body mass index, acute physiology and chronic health evaluation II score, blood glucose levels, electrocardiogram results, and complications occurring within the target temperature management timeframe. Data was divided into group A having patients who achieved target temperature management within 360 minutes, and group B having patients with delayed TTM of more than 360 minutes. Data was analysed using SPSS 22.
RESULTS: Of the 127 patients, 76(59%) were males, 51(41%) were females,, 47(37%) were aged >75 years, and 13(10.3%) were aged <50 years. Of the total, 65(51.2%) patients were in group A, and 62(48.8%) were in group B. Pneumonia, urinary tract infection, septic shock and gastrointestinal bleeding had lower incidence rates in group A than group B (p<0.05). The odds of death were 2.879 times high er in group B patients than group A (95% confidence interval: 1.908-8.916).
CONCLUSIONS: Hypothermia tre atment should be sta rted as soon as pos sible to achieve target temp erature management within 360 minutes to reduce the risk of complications and mortality.
Participants received intravenous (IV) infusions of sebelipase alfa during the open-label treatment. Participants initially received 0.35 milligrams (mg)/kilogram (kg) qw and escalated to 1 mg/kg qw after demonstrating acceptable safety and tolerability during at least 2 infusions. One participant initiated treatment under a Temporary Use Authorization prior to enrollment, wherein the participant's dose was gradually escalated from 0.2 to 1 mg/kg over 4 weeks; the participant started the study at this dose. Participants on treatment for 96 weeks and on stable qw dosing for 24 weeks could be switched to an every other week (qow) dosing schedule. In the event of protocol-defined disease progression at any time during treatment, a participant could receive a dose increase from 1 to 3 mg/kg qw and, if necessary, a dose increase to 5 mg/kg qw with Safety Committee approval. Participants dosed qow who met dose-escalation criteria were reverted to qw dosing or escalated to 1 or 3 mg/kg qow.
Participants will play CCT games at home 5 times per week for two weeks before beginning CBT and for two weeks after the first CBT session. Then participants will have CCT games immediately prior to CBT for nine more weeks (one time a week).
AIM: To investigate the association of sarcopenia with cardiovascular disease (CVD) incidence in people with type 2 diabetes.
MATERIALS AND METHODS: A prospective cohort study with 11 974 White European UK Biobank participants with type 2 diabetes, aged 40-70 years, included. Sarcopenia was defined based on the European Working Group on Sarcopenia in Older People as either non-sarcopenic or sarcopenic. Outcomes included CVD, stroke, heart failure (HF) and myocardial infarction (MI). The association between sarcopenia and the incidence of outcomes was investigated using Cox proportional hazard models adjusted for sociodemographic and lifestyle factors. The rate advancement period was used to estimate the time period by which CVD is advanced because of sarcopenia.
RESULTS: Over a median follow-up of 10.7 years, 1957 participants developed CVDs: 373 had a stroke, 307 had an MI and 742 developed HF. Compared with non-sarcopenia, those with sarcopenia had higher risks of CVD (HR 1.89 [95% CI 1.61; 2.21]), HF (HR 2.59 [95% CI 2.12; 3.18]), stroke (HR 1.90 [95% CI 1.38; 2.63]), and MI (HR 1.56 [95% CI 1.04; 2.33]) after adjustment for all covariates. Those with sarcopenia had CVD incidence rates equivalent to those without sarcopenia who were 14.5 years older. Similar results were found for stroke, HF and MI.
CONCLUSIONS: In people with type 2 diabetes, sarcopenia increased the risk of developing CVD, which might occur earlier than in those without sarcopenia. Therefore, sarcopenia screening and prevention in patients with type 2 diabetes may be useful to prevent the complications of CVD.
This is a randomized, double-blind (neither physician nor participants know the name of the assigned drug), placebo-controlled study of TMC435 in participants who are infected with genotype 1 hepatitis C virus (HCV), who have never received treatment for HCV infection before. Participants in this study will also receive two other drugs for their HCV infection called peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV). The purpose of the study is to investigate if TMC435 is superior to placebo in reducing plasma levels of HCV ribonucleic acid (RNA) to an undetectable level 12 weeks after the end of treatment. For the first 12 weeks, participants will take either TMC435 or placebo, plus PegIFNα-2a and RBV. For the next 12 weeks, participants will take PegIFN alpha-2a and RBV only. After that, some participants will continue to take PegIFN alpha-2a and RBV for up to 24 additional weeks and some will stop taking PegIFN alpha-2a and RBV depending on response-guided treatment criteria. The study doctor will inform each participant about how to take their study medication and when they should stop taking it. After a participant stops taking study medication, they will continue to come to the doctor's office for study visits until a total of 72 weeks after they enroll in the study. The total duration of the study is 78 weeks (including screening). Participants will be monitored for safety throughout the study.
High priority populations include CKD in the setting of diabetes (diabetic kidney disease, DKD) and hypertension-associated CKD (H-CKD). A special population of people with long-standing type 1 diabetes (more than 25 years) who remain free of clinically-evident DKD will also be included.
<P>PROBLEM TO BE SOLVED: To provide a cosmetic or medical composition for topical application to the skin afflicted with rosacea and treated with a retinoid.  <P>SOLUTION: A cosmetic or medical composition for topical application to the skin afflicted with rosacea and treated with a retinoid. The composition for treating rosacea comprises an anti-irritating component and several other components for treating rosacea. The other components form a mixture of a salicylic acid, a phytosphingosine, green tea, hinokitiol, gorgonian extract, and polysaccharide. A method for decreasing the irritation on the skin caused by the heightened sensitivity experienced by skin suffering from rosacea. The other components are effective in treating the rosacea condition, but particularly, in treating the telangiectasic symptoms of rosacea.  <P>COPYRIGHT: (C)2007,JPO&INPIT
The Sleep Restriction condition will allow 6.5 hours in bed, which in previous research results in an average of 6.1-6.3 hours of nightly sleep. This condition reflects a realistic dose of sleep restriction (similar to the school-night sleep of 15-20% of healthy adolescents) that has been shown to be feasible and to induce daytime sleepiness, inattention, and irritability/moodiness in typically developing adolescents.
BACKGROUND: Malignant gastric outlet obstruction (GOO) poses a substantial symptomatic burden. While various therapeutic options exist, self-expanding metal stents (SEMS) are a common palliative choice for patients who are ineligible for surgery. We studied SEMS outcomes to identify factors influencing stent dysfunction and patient survival.
METHODS: A multi-centre, retrospective review of 190 patients with GOO undergoing SEMS at three tertiary hospitals was performed over 2016-2022. Technical success, clinical success and adverse outcomes were recorded. Predictors of stent dysfunction and survival were evaluated using multivariate regression.
RESULTS: Technical success was achieved in 186/190 (97.9%) and clinical success in 156/186 (83.9%), defined as post-procedural gastric outlet obstruction symptom score (GOOSS) ≥2. Eighty-two (44.1%) patients experienced an adverse event with stent occlusion the most common (23.1%). Approximately one-third (32.3%) underwent a repeat intervention. Mean stent patency time was 67 days (standard deviation=76), and median post-stent survival was 95 days (37-197). Covered and partially covered SEMS carried three times the risk of stent dysfunction compared to uncovered SEMS (odds ratio 3.06, p=0.008). Mortality predictors were Eastern Cooperative Oncology Group score ≥2 (p=0.03), extrinsic outlet obstruction (p=0.05) and presence of ascites (p=<0.001).
CONCLUSION: SEMS demonstrated technical and clinical success but posed a high risk of recurrence, with stent patency time falling short of survival in our cohort. With an evolving landscape of therapeutics for GOO, appropriate patient selection is paramount. Individuals with reduced performance status, extrinsic obstruction and/or ascites may be better candidates for SEMS due to more limited life expectancy. In this setting, uncovered SEMS carry the lowest risk of reintervention.
The lipid synthesis of fatty acid (FA) represents a significant hallmark in the occurrence and progression of malignant tumor, which are associated with lymph node (LN) metastasis. Elucidation of the molecular mechanisms underlying LN metastasis could provide therapeutic strategies for cervical cancer (CCa). N6-Methyladenosine (m6A), the most prevalent and abundant RNA modification, exerts specific regulatory control over a series of oncogene expressions. This study demonstrated a clinical correlation between the upregulation of the m6A reader YTHDF3 and LN metastasis, thereby contributing to poor overall survival probability (OS) among CCa patients. The mechanistic investigation revealed that SREBF1 transcriptionally activated YTHDF3 expression by binding to its promoter. Functional experiments demonstrated that the upregulation of YTHDF3 significantly enhanced the in vitro proliferative, migratory, and invasive capacities of CCa cells, while also promoting lymphangiogenesis and facilitating LN metastasis in vivo. Mechanistically, the upregulation of LRP6 through YTHDF3-mediated m6A modification resulted in increased expression of FASN and ACC1, leading to both lipolysis of lipid droplets and synthesis of free fatty acid. Ultimately, this promoted fatty acid metabolism and enhanced LN metastasis by activating the LRP6-YAP-VEGF-C axis, which could induce lymphangiogenesis in CCa. Our study highlighted that YTHDF3 can serve as a promising therapeutic target and predictive biomarker for CCa patients with LN metastasis.
Treatment for patients with anxiety should be initiated with a dose of 0.25 to 0.5 mg given three times daily. The dose may be increased to achieve a maximum therapeutic effect, at intervals of 3 to 4 days, to a maximum daily dose of 4 mg, given in divided doses. The lowest possible effective dose should be employed and the need for continued treatment reassessed frequently. The risk of dependence may increase with dose and duration of treatment.

In elderly patients, in patients with advanced liver disease or in patients with debilitating disease, the usual starting dose is 0.25 mg, given two or three times daily. This may be gradually increased if needed and tolerated. The elderly may be especially sensitive to the effects of benzodiazepines.

If side effects occur at the recommended starting dose, the dose may be lowered.

In all patients, dosage should be reduced gradually when discontinuing therapy or when decreasing the daily dosage. Although there are no systematically collected data to support a specific discontinuation schedule, it is suggested that the daily dosage be decreased by no more than 0.5 mg every three days. Some patients may require an even slower dosage reduction.
The invention discloses a Chinese medicinal enema for treating a chronic pelvic inflammatory disease. The pelvic inflammatory disease belongs to the field of 'bellyache', 'abnormal vaginal discharge' and the like in traditional Chinese medical science. The pathogenesis of the pelvic inflammatory disease mainly includes 'dampness, heat and stasis'. In the invention, Chinese medicines including baikal skullcap root, ash bark, honeysuckle flower, common andrographis herb, heartleaf houttuynia herb, kadsura pepper stem, kusnezoff monkshood root, nutgrass galingale rhizome, rose, myrrh, twotooth achyranthes root and safflower which have the effects of clearing heat, promoting diuresis, dispersing blood stasis and dredging collateral are selected, and are prepared into an enema by the preparation department of the academy. The enema is applied to a patient every night before sleeping. As proved by clinical test, the total effective rate is 96.7 percent, which is remarkably higher than that of a control group; and moreover, the Chinese medicinal enema is free from toxic and side effects, has low treatment cost, and is safe and reliable.
Because of the risks of hepatotoxicity and birth defects, bosentan is available only through a restricted program called the Bosentan REMS Program. Under the Bosentan REMS, prescribers, patients, and pharmacies must enroll in the program. [see Warnings and Precautions (5.3)].

Hepatotoxicity

In clinical studies, bosentan caused at least 3-fold upper limit of normal (ULN) elevation of liver aminotransferases (ALT and AST) in about 11% of patients, accompanied by elevated bilirubin in a small number of cases. Because these changes are a marker for potential serious hepatotoxicity, serum aminotransferase levels must be measured prior to initiation of treatment and then monthly [see Dosage and Administration (2.4), Warnings and Precautions (5.1)]. In the postmarketing period, in the setting of close monitoring, rare cases of unexplained hepatic cirrhosis were reported after prolonged (>12 months) therapy with bosentan in patients with multiple comorbidities and drug therapies. There have also been reports of liver failure. The contribution of bosentan in these cases could not be excluded. 

In at least one case, the initial presentation (after > 20 months of treatment) included pronounced elevations in aminotransferases and bilirubin levels accompanied by non-specific symptoms, all of which resolved slowly over time after discontinuation of bosentan. This case reinforces the importance of strict adherence to the monthly monitoring schedule for the duration of treatment and the treatment algorithm, which includes stopping bosentan with a rise of aminotransferases accompanied by signs or symptoms of liver dysfunction [see Dosage and Administration (2.4)]. 

Elevations in aminotransferases require close attention [see Dosage and Administration (2.4)]. Bosentan should generally be avoided in patients with elevated aminotransferases (> 3 x ULN) at baseline because monitoring for hepatotoxicity may be more difficult. If liver aminotransferase elevations are accompanied by clinical symptoms of hepatotoxicity (such as nausea, vomiting, fever, abdominal pain, jaundice, or unusual lethargy or fatigue) or increases in bilirubin ≥ 2 x ULN, treatment with bosentan should be stopped. There is no experience with the reintroduction of bosentan in these circumstances. 

Embryo-Fetal Toxicity

Bosentan is likely to cause major birth defects if used by pregnant females based on animal data [see Warnings and Precautions (5.2), Use in Specific Populations (8.1)]. Therefore, pregnancy must be excluded before the start of treatment with bosentan. Throughout treatment and for one month after stopping bosentan, females of reproductive potential must use two reliable methods of contraception unless the patient has an intrauterine device (IUD), or tubal sterilization, in which case no other contraception is needed. Hormonal contraceptives, including oral, injectable, transdermal, and implantable contraceptives should not be used as the sole means of contraception because these may not be effective in patients receiving bosentan [see Drug Interactions (7.2)]. Obtain monthly pregnancy tests.
This is a prospective, multicenter, randomized, parallel controlled and superiority clinical trial. It is planned to be carried out in hospitals with qualifications as a national-level clinical trial institution. Subjects who have signed the ICF, meet all inclusion criteria and do not meet any exclusion criteria will be included in this study. Subjects included will be randomly assigned into the experimental group and the control group at a ratio of 1:1. Those in the control group will receive microfracture, and those in the experimental group will receive microfracture plus Chondro-Gide® bilayer collagen membrane. The primary efficacy evaluation indicator of this clinical study is the MOCART score at 24 months postoperative. The secondary efficacy evaluation indicators are IKDC score (before operation, 3, 6, 12 and 24 months postoperative), MOCART score (6 and 12 months postoperative), hyaline cartilage production (T2 mapping ratio) (12 and 24 months postoperative), Lysholm score (before operation, 3, 6, 12 and 24 months postoperative), and device performance evaluation of the investigational product. Safety evaluation indicators include adverse events (or serious adverse events), device-related adverse events (or serious adverse events), device deficiencies and laboratory examination.