anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Cardiovascular diseases (CVD) are closely linked to protein homeostasis (proteostasis) and its failure. Beside genetic mutations that impair cardiac protein quality control, obesity is a strong risk factor for heart disease. In obesity, adipose tissue becomes dysfunctional and impacts heart function and CVD progression by releasing cytokines that contribute to systemic insulin resistance and cardiovascular dysfunction. In addition, chronic inflammation and lipotoxicity compromise endoplasmic reticulum (ER) function, eliciting stress responses that overwhelm protein quality control beyond its capacity. Impairment of proteostasis-including dysfunction of the ubiquitin-proteasome system (UPS), autophagy, and the depletion of chaperones-is intricately linked to cardiomyocyte dysfunction. Interventions targeting UPS and autophagy pathways are new potential strategies for re-establishing protein homeostasis and improving heart function. Additionally, lifestyle modifications such as dietary interventions and exercise have been shown to promote cardiac proteostasis and overall metabolic health. The pursuit of future research dedicated to proteostasis and protein quality control represents a pioneering approach for enhancing cardiac health and addressing the complexities of obesity-related cardiac dysfunction.
BACKGROUND: Oxidative stress has been implicated in the pathogenesis of chronic kidney disease (CKD), prompting the exploration of antioxidants as a potential therapeutic avenue for mitigating disease progression. This study aims to investigate the beneficial impact of Tempol on the progression of CKD in a rat model utilizing oxidized albumin as a biomarker.
METHODS: After four weeks of treatment, metabolic parameters, including body weight, left ventricle residual weight, kidney weight, urine volume, and water and food intake, were measured. Systolic blood pressure, urinary protein, oxidized albumin level, serum creatinine (Scr), blood urea nitrogen (BUN), 8-OHdG, TGF-β1, and micro-albumin were also assessed. Renal fibrosis was evaluated through histological and biochemical assays. P65-NF-κB was quantified using an immunofluorescence test, while Smad3, P65-NF-κB, and Collagen I were measured using western blot. TNF-α, IL-6, MCP-1, TGF-β1, Smad3, and P65-NF-κB were analyzed by RT-qPCR.
RESULTS: Rats in the high-salt diet group exhibited impaired renal function, characterized by elevated levels of blood urea nitrogen, serum creatinine, 8-OHdG, urine albumin, and tubulointerstitial damage, along with reduced body weight. However, these effects were significantly ameliorated by Tempol administration. In the high-salt diet group, blood pressure, urinary protein, and oxidized albumin levels were notably higher compared to the normal diet group, but Tempol administration in the treatment group reversed these effects. Rats in the high-salt diet group also displayed increased levels of proinflammatory factors (TNF-α, IL-6, MCP1) and profibrotic factors (NF-κB activation, Collagen I), elevated expression of NADPH oxidation-related subunits (P65), and activation of the TGF-β1/Smad3 signaling pathway. Tempol treatment inhibited NF-κB-mediated inflammation and TGF-β1/Smad3-induced renal fibrosis signaling pathway activation.
CONCLUSION: These findings suggest that Tempol may hold therapeutic potential for preventing and treating rats undergoing 5/6 nephrectomy. Further research is warranted to elucidate the mechanisms underlying Tempol's protective effects and its potential clinical applications. Besides, there is a discernible positive relationship between oxidized albumin and other biomarkers, such as 8-OHG, urinary protein levels, mALB, Scr, BUN, and TGF-β1 in a High-salt diet combined with 5/6 nephrectomy rat model. These findings suggest the potential utility of oxidized albumin as a sensitive indicator for oxidative stress assessment.
The present disclosure relates to a method for determining a completion score for a record object based on electronic activities. The method includes accessing record objects, each of which corresponds to a record object type and includes object fields having object field-values. The method includes selecting one of the record objects. The method includes identifying electronic activities transmitted or received associated with the record object. Each of the electronic activities has a timestamp indicating a receipt time or transmission time of the respective electronic activity. The method includes determining a participant of each of the electronic activities. The method includes determining a completion score indicating a likelihood of completing an event associated with the record object based on the timestamp of each of the electronic activities and the participant of each of the electronic activities. The method includes storing an association between the record object and the completion score.
Participants in this group will perform breathing exercises using a resistive breathing device. The training will take place in the FMS lab. After training, participants will perform the exercise for 20 minutes daily (5days each week for 6 weeks) in their home.
NEW MATERIAL:A cell growth promoting substance which is a water-soluble protein, extracted from a bovine spleen, having 41,000 estimated molecular weight as well as about 6.0-6.5 isoelectric point. USE:A hepatotonic agent, drug for gastric and duodenal ulcer, damage reparative agent and culture medium additive. PREPARATION:For example, a bovine spleen is finely cut and homogenized at a low temperature. Water or sodium chloride solution, etc., is added to allow the homogenate to stand for 6hr-a whole day and night. The homogenate is then centrifuged to separated and collect the obtained supernatant liquid. Ammonium sulfate is subsequently added to the supernatant liquid so as to provide 40% saturated concentration and centrifugation is carried out to separate and collect the resultant supernatant liquid. Ammonium sulfate is then added to the supernatant liquid so as to provide 60% saturated concentration. Formed precipitates are then purified by gel filtration and ion exchange chromatography in combination and heat-treated at 60 deg.C for 10hr to carry out inactivation of viruses and afford the aimed cell growth promoting substance.
The present study is designed primarily to compare continuation rates after three months of use of NuvaRing® and OrthoEvra® in women who had been previously using oral contraceptives. The study attempts to evaluate the possible choices for women who are content with their current or recent method of oral combined hormonal contraception but would be considering a change in their method to a non-daily delivery system. Continuation rates should demonstrate the overall acceptance of both methods as women who find that the method is convenient and has few side effects are likely to continue using the method. Sexual functioning is another important aspect to investigate. The Female Sexual Function Index (FSFI) will be administered to participants along with the planned study questionnaires at the enrollment visit and at the final visit. Additionally, this study will compare side effects, the incidence of bacterial vaginosis, and direct measures of acceptability between the two groups. Efficacy over the three-month study period will also be evaluated; however, since both methods are highly effective and the study is relatively short in duration, the study is not designed to be large enough to detect any differences in efficacy.

This open-label, prospective, multicenter, randomized comparative trial will be conducted in approximately 500 women in the United States who are currently or recently have used a combined oral contraceptive and have no past experience using NuvaRing® or OrthoEvra®. Subjects will be enrolled once they have provided informed consent, had a baseline blood pressure and breast and pelvic examinations, and had negative endocervical testing for gonorrhea and chlamydia. Participants will be randomized to use either NuvaRing® or OrthoEvra® for four continuous cycles beginning with the first day of menses following the enrollment visit. Subjects are to contact the research office by phone to confirm that they initiated the method as instructed. The researchers will contact subjects during the second week of the second cycle of study medication. A final visit will occur during the first week of the fourth cycle of study medication (or sooner if the subject requires or requests early discontinuation). An acceptability questionnaire will be administered at the subject's final visit. This questionnaire has been modified from a questionnaire validated in women using NuvaRing®.
The trial will be a double blinded, placebo control trial of two uric acid lowering agents. The endpoints for this trial will be, endothelial function, systemic vascular resistance, plasma renin activity, MCP-1 and CRP. Upon recruitment and informed consent, children will undergo initial screening. This will include medical history, family history, dietary history, review of systems (questionnaire used and validated in pediatric hypertension clinic) and pediatric quality of life questionnaire. They will have a physical exam, casual and ambulatory blood pressure monitoring (see below) and screening laboratory analysis that will include CBC, electrolytes, BUN, Cr, Uric acid, AST, ALT and urinary micro-albumin to creatinine ratio. Children with serum uric acid less than 5.0mg per dl will be enrolled as controls and only have baseline studies at Screening and Visit 1. Children with serum uric acid equal to or greater than 5.0mg per dl will be randomized (in a one to one to one ratio) to receive placebo, allopurinol or probenecid.

Study drug (or placebo) will be administered for 2 months. During the first week, subjects will take one tablet (placebo, 150mg allopurinol or 250mg probenecid) twice daily. At the end of one week subjects will be instructed to increase to 2 tablets (placebo, 300mg allopurinol or 500mg probenecid) twice daily. Data collection will occur during screening, after one and two months on the study drug and one month after completion of the study drug.
The stimulation characteristics for this arm include a continuous frequency of 5 Hz, pulsewidth 0.2 ms, and intensity 2-4 times the threshold voltage required for finger twitching - or the intensity that the subject feels comfortable with. Subjects will be asked to use the stimulator for a minimum of 60 minutes prior to bedtime for two weeks, or longer if they can tolerate it, have the time, and accurately record the total duration. Stimulation will be performed during the first, second, and third weeks of the study.
The incidence of preoperatively diagnosed multiple ipsilateral breast cancer (MIBC) is increasing due to improved sensitivity of screening and preoperative staging modalities including digital breast tomosynthesis (3D breast mammography) and magnetic resonance imaging (MRI). The surgical management of MIBC remains controversial. Many surgeons continue to recommend mastectomy due to high local recurrence rates in patients with MIBC undergoing breast conservation therapy reported in historic, retrospective studies. More recent retrospective studies report acceptable rates of local recurrence. Yet concerns persist due to a paucity of prospective data regarding recurrence as well as concerns for margin positivity, cosmetic outcomes and the feasibility of adequate and safe delivery of radiation following breast conserving surgery. Breast conservation has emerged as the preferred surgical strategy for eligible patients with unifocal disease. Benefits include improved quality of life, body image and sexual function and lower surgical complication rates. A recent prospective clinical trial has corroborated a large body of retrospective data confirming the safety of breast conserving therapy and adjuvant radiation in women with MIBC with good oncologic control, low rates of conversion to mastectomy and satisfactory patient-reported cosmetic outcomes. With the current rise in MIBC diagnoses, it is imperative that surgeons understand the existent evidence in order to guide shared decision-making conversations with patients diagnosed with MIBC. This comprehensive review synthesizes the best available data and offers current recommendations for management of both the primary sites of disease as well as management of the axilla in patients with MIBC.
BACKGROUND AND OBJECTIVES: Parkinson disease (PD) exhibits a characteristic pattern of brain perfusion or metabolism, thereby being considered network disorder. Using dual-phase N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (18F-FP-CIT) PET, we investigated the role of brain perfusion in motor symptoms and disease progression, independent of striatal dopamine depletion.
METHODS: We recruited patients with de novo PD and healthy controls (HCs) who underwent dual-phase 18F-FP-CIT PET and brain MRI. All patients underwent the Unified PD Rating Scale (UPDRS) and were followed up for ≥5 years. A subset of patients (n = 51) underwent follow-up UPDRS and brain MRI. Early-phase images evaluated brain perfusion, while delayed-phase images evaluated dopamine transporter availability. We compared early-phase 18F-FP-CIT uptakes (SUVRE) between PD and HC groups. Then, we investigated the association of SVURE and delayed-phase 18F-FP-CIT uptakes (SUVRD) with motor symptoms in PD. Standardized residuals (SRs) of the SUVRE in the hyperperfusion region (SUVRE-HYPER) were obtained from the linear regression of the SUVRD in the posterior putamen (SUVRD-PP), the main region of dopamine deficit. Subsequently, we investigated the association of the SR with baseline and longitudinal motor symptoms and brain atrophy.
RESULTS: Compared with HC (n = 30), patients with PD (n = 168) showed relative hyperperfusion in the primary motor cortex, thalamus, pons, hippocampus, and cerebellum and relative hypoperfusion in the prefrontal and temporo-parieto-occipital cortices, which is consistent with a PD-related metabolic pattern. Motor symptoms were negatively correlated with SUVRD-PP (standardized β = 0.402, p < 0.001) and positively correlated with SUVRE-HYPER (standardized β = 0.292, p < 0.001), but not with SUVRE in the hypoperfusion regions. Regardless of SUVRD-PP, SUVRE-HYPER was independently associated with motor dysfunction, especially rigidity (standardized β = 0.214, p = 0.012). The SR of SUVRE-HYPER was significantly associated with the UPDRS part III total score. Longitudinally, the baseline SR of SUVRE-HYPER was not associated with long-term motor complications but with an increase in the UPDRS part III total score (p = 0.017) and a decrease in brain volume.
DISCUSSION: These results suggest that aberrant relative brain hyperperfusion, independent of striatal dopamine depletion, was associated with baseline and longitudinal motor deficits and progression of neurodegeneration in PD.
BACKGROUND AND AIMS: The predominantly progressive, indeterminate, and predominantly regressive (P-I-R) classification extends beyond staging and provides information on dynamic changes of liver fibrosis. However, the prognostic implication of P-I-R classification is not elucidated. Therefore, in the present research, we investigated the utility of P-I-R classification in predicting the on-treatment clinical outcomes.
APPROACH AND RESULTS: In an extension study on a randomized controlled trial, we originally enrolled 1000 patients with chronic hepatitis B and biopsy-proven histological significant fibrosis, and treated them for more than 7 years with entecavir-based therapy. Among the 727 patients with a second biopsy at treatment week 72, we compared P-I-R classification and Ishak score changes in 646 patients with adequate liver sections for the histological evaluation. Progressive, indeterminate, and regressive cases were observed in 70%, 17%, and 13% of patients before treatments and 20%, 14%, and 64% after 72-week treatment, respectively, which could further differentiate the histological outcomes of patients with stable Ishak scores. The 7-year cumulative incidence of HCC was 1.5% for the regressive cases, 4.3% for the indeterminate cases, and 22.8% for the progressive cases ( p <0.001). After adjusting for age, treatment regimen, platelet counts, cirrhosis, Ishak fibrosis score changes, and Laennec staging, the posttreatment progressive had a HR of 17.77 (vs. posttreatment regressive; 95% CI: 5.55-56.88) for the incidence of liver-related events (decompensation, HCC, and death/liver transplantation).
CONCLUSIONS: The P-I-R classification can be a meaningful complement to the Ishak fibrosis score not only in evaluating the histological changes but also in predicting the clinical outcomes.
Excessive reactive oxygen species production during acute lung injury (ALI) will aggravate the inflammatory process and endothelial barrier dysfunction. Carnosol is a natural phenolic diterpene with antioxidant and anti-inflammatory properties, but its role in treating sepsis-induced ALI remains unclear. This study aims to explore the protective effects and underlying mechanisms of carnosol in sepsis-induced ALI. C57BL/6 mouse were preconditioned with carnosol for 1 h, then the model of lipopolysaccharide (LPS)-induced sepsis was established. The degree of pulmonary edema, oxidative stress, and inflammation were detected. Endothelial barrier function was evaluated by apoptosis and cell junctions. In vitro, Mito Tracker Green probe, JC-1 staining, and MitoSOX staining were conducted to investigate the effect of carnosol on mitochondria. Finally, we investigated the role of nuclear factor-erythroid 2-related factor (Nrf2)/sirtuin-3 (SIRT3) in carnosol against ALI. Carnosol alleviated LPS-induced pulmonary oxidative stress and inflammation by inhibiting excess mitochondrial reactive oxygen species production and maintaining mitochondrial homeostasis. Furthermore, carnosol also attenuated LPS-induced endothelial cell barrier damage by reducing vascular endothelial cell apoptosis and restoring occludin, ZO-1, and vascular endothelial-Cadherin expression in vitro and in vivo. In addition, carnosol increased Nrf2 nuclear translocation to promote SIRT3 expression. The protective effects of carnosol on ALI were largely abolished by inhibition of Nrf2/SIRT3. Our study has provided the first evidence that the Nrf2/SIRT3 pathway is a protective target of the endothelial barrier in ALI, and carnosol can serve as a potential therapeutic candidate for ALI by utilizing its ability to target this pathway.
INTRODUCTION: Obesity has been identified as a significant risk factor for several chronic conditions, including diabetes, tumours and cardiovascular disease, and has been associated with increased mortality rates. Despite the well-established clinical practice of electroacupuncture (EA) as a potential treatment option for obesity, its efficacy remains questionable, primarily due to the paucity of empirical evidence supporting its therapeutic benefits.
METHODS AND ANALYSIS: The present study aims to investigate the efficacy and safety of EA for weight loss in obese individuals with pre-diabetes, using a randomised, placebo-controlled clinical trial design. A total of 256 eligible patients will be randomly assigned to one of two groups: EA (comprising EA treatment with health education) or superficial acupuncture (SA) (comprising SA treatment with health education). The intervention will be administered three times per week for the initial 12 weeks, two times per week for the subsequent 8 weeks and one time per week for the final 4 weeks, with a 24-week follow-up period. The primary outcome measure will be the percentage of patients who achieve a reduction of 10% or more in their body weight at week 24. Secondary outcome measures will include changes in body weight and body mass index, blood test results, data collected by the body composition analyser, size of adipose tissue scanned by MRI of the abdomen and the Impact of Weight on Quality of Life, the 21-item Three-Factor Eating Questionnaire-Revised and the Food Craving Questionnaire-Trait. The Treatment Emergent Symptom Scale will be employed to monitor every adverse reaction from baseline to follow-up.
ETHICS AND DISSEMINATION: This trial has received ethical clearance from the Ethics Committee of Shanghai Municipal Hospital of Traditional Chinese Medicine under the registration number 2021SHL-KY-74. All participants will provide their written informed consent prior to their enrolment. The findings of this investigation will be disseminated through peer-reviewed publications and scholarly conferences.
TRIAL REGISTRATION NUMBER: NCT05237089.
The mechanisms underlying the many phenotypic manifestations of post-acute COVID-19 syndrome (PACS) are poorly understood. Herein, we characterized the gut microbiome in heterogeneous cohorts of subjects with PACS and developed a multi-label machine learning model for using the microbiome to predict specific symptoms. Our processed data covered 585 bacterial species and 500 microbial pathways, explaining 12.7% of the inter-individual variability in PACS. Three gut-microbiome-based enterotypes were identified in subjects with PACS and associated with different phenotypic manifestations. The trained model showed an accuracy of 0.89 in predicting individual symptoms of PACS in the test set and maintained a sensitivity of 86% and a specificity of 82% in predicting upcoming symptoms in an independent longitudinal cohort of subjects before they developed PACS. This study demonstrates that the gut microbiome is associated with phenotypic manifestations of PACS, which has potential clinical utility for the prediction and diagnosis of PACS.
In this group patients will undergo balloon-blowing exercises in the 90/90 bridge position with a ball. In this intervention, patients lie on back with feet against a wall and knee bent at 90 degrees, holding a ball between their knees. While extending one arm overhead and holding a balloon in the other hand, perform a pelvic tilt without lifting their backoff the mat. Inhale through the nose, exhale into the balloon for four breaths, then remove the balloon and repeat the sequence four times. The 4-week protocol includes three supervised sessions per week, each supervised by a physiotherapist. Progress will be monitored regularly to evaluate improvements throughout the intervention.
Primary objective: to assess the safety and tolerability of multiple doses of orally administered CC100 in subjects with amyotrophic lateral sclerosis (ALS). Secondary objectives: to determine pharmacokinetics and pharmacodynamics of CC100 in plasma after single and after multiple doses; and to determine short-term effects of CC100 on potential blood-cell ALS biomarkers.

Study Design: Phase 1 double-blind, randomized, placebo-controlled multiple-dose of three CC100-dose cohorts. Approximately 18 subjects will receive CC100. Approximately 3 subjects will be randomized to placebo (across 3 cohorts). Periodic Assessment Committee safety reviews. Note: Participation will not exclude subjects from future CC100 studies Criteria for Evaluation: Safety Endpoints: Adverse events, blood chemistry, hematology, urinalysis, vital signs, 12-lead ECGs. Pharmacokinetic (PK)/Pharmacodynamic (PD): Plasma for CC100 concentrations (PK). Blood collected at baseline and after each subject's last dose will be assayed for potential biomarker(s). Stored specimens will be de-identified or combined for validating diagnostic tools/assays related to ALS. Statistical Methods: A minimum of 6 subjects per CC100 dose group and 3 placebo-dosed subjects (total across cohorts) are considered sufficient to evaluate initial safety and tolerability for the cohorts. Pharmacokinetic parameter estimates will be calculated by standard noncompartmental methods of analysis. Absolute bioavailability of administration will be estimated based on the total area under the time- concentration curve (AUC0-∞).