anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Disclosed herein are gel compositions for enhanced transdermal delivery of an active ingredient into a serum of a subject through production of a reservoir of the active ingredient in the stratum corneum of the subject. The gel composition comprises at least one oleogel (organogel), at least one aqueous gel and the active ingredient. The composition further has at least one of the following - (i) the active substance is micronized, (ii) the composition contains a bioadhesive and (iii) the composition contains a C1-8 alcohol in an amount up to 4% w/w. In a preferred embodiment the oleogel is formed from glycerides and ethylcellulose and the aqueous gel is formed from water and sodium carboxymethylcelluose. Exemplary active ingredients include testosterone, estradiol and diclofenac. Also disclosed herein are methods preparing the gel composition, methods of using the gel composition to at least partially ameliorate a condition, and kits comprising the gel composition.
This program is an attention control group, which consists of general health education. Education sessions will be delivered either by zoom or in person. The education sessions will cover the following topics: 1) falls prevention; 2) sleep; 3) healthy eating; 4) cognitive health; and 5) mental and emotional health.
INTRODUCTION: Patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) and concomitant multivessel coronary artery disease (CAD) are considered patients with extremely high-risk atherosclerotic cardiovascular disease (ASCVD), and current guidelines specify a lower low-density lipoprotein cholesterol (LDL-C) target for this population. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to effectively reduce LDL-C levels on a statin background. Additionally, several studies have confirmed the role of PCSK9 inhibitors in plaque regression and reducing residual cardiovascular risk in patients with ACS. However, those studies included coronary lesions with a degree of stenosis <50%. Whether the application of PCSK9 inhibitors in patients with NSTE-ACS with non-culprit artery critical lesions (stenosis degree between 50% and 75%) has a similar effect on plaque regression and improvement of cardiovascular outcomes remains unknown, with a lack of relevant research. This study aims to further investigate the safety and efficacy of evolocumab in patients with NSTE-ACS and concomitant multivessel CAD (non-culprit artery stenosis between 50% and 75%).
METHODS AND ANALYSIS: In this single-centre clinical randomised controlled trial, 122 patients with NSTE-ACS and concomitant multivessel CAD (non-culprit artery stenosis between 50% and 75%) will be randomly assigned to either the evolocumab treatment group or the standard treatment group after completing culprit vessel revascularisation. The evolocumab treatment group will receive evolocumab in addition to statin therapy, while the standard treatment group will receive standard statin therapy. At baseline and week 50, patients in the evolocumab treatment group will undergo coronary angiography and OCT imaging to visualise pre-existing non-lesional vessels. The primary end point is the absolute change in average minimum fibrous cap thickness (FCT) from baseline to week 50. Secondary end points include changes in plaque lipid arc, lipid length, macrophage grading, lipid levels and major adverse cardiovascular events during the 1-year follow-up period.
ETHICS AND DISSEMINATION: Ethics: this study will adhere to the principles outlined in the Helsinki Declaration and other applicable ethical guidelines. This study protocol has received approval from the Medical Research Ethics Committee of the First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital), with approval number 2022-ky214.
DISSEMINATION: we plan to disseminate the findings of this study through various channels. This includes publication in peer-reviewed academic journals, presentation at relevant academic conferences and communication to the public, policymakers and healthcare professionals. We will also share updates on the research progress through social media and other online platforms to facilitate the exchange and application of scientific knowledge. Efforts will be made to ensure widespread dissemination of the research results and to have a positive impact on society.
TRIAL REGISTRATION NUMBER: ChiCTR2200066675.
BACKGROUND: Globally, over 39% of individuals are obese. Metabolic syndrome, usually accompanied by obesity, is regarded as a major contributor to noncommunicable diseases. Given this relationship, the concepts of metabolically healthy and unhealthy obesity, considering metabolic status, have been evolving. Attention is being directed to metabolically healthy people with obesity who have relatively low transition rates to noncommunicable diseases. As obesity rates continue to rise and unhealthy behaviors prevail among young adults, there is a growing need for obesity management that considers these metabolic statuses. A nomogram can be used as an effective tool to predict the risk of transitioning to metabolically unhealthy obesity from a metabolically healthy status.
OBJECTIVE: The study aimed to identify demographic factors, health behaviors, and 5 metabolic statuses related to the transition from metabolically healthy obesity to unhealthy obesity among people aged between 20 and 44 years and to develop a screening tool to predict this transition.
METHODS: This secondary analysis study used national health data from the National Health Insurance System in South Korea. We analyzed the customized data using SAS (SAS Institute Inc) and conducted logistic regression to identify factors related to the transition from metabolically healthy to unhealthy obesity. A nomogram was developed to predict the transition using the identified factors.
RESULTS: Among 3,351,989 people, there was a significant association between the transition from metabolically healthy to unhealthy obesity and general characteristics, health behaviors, and metabolic components. Male participants showed a 1.30 higher odds ratio for transitioning to metabolically unhealthy obesity than female participants, and people in the lowest economic status were also at risk for the transition (odds ratio 1.08, 95% CI 1.05-1.1). Smoking status, consuming >30 g of alcohol, and insufficient regular exercise were negatively associated with the transition. Each relevant variable was assigned a point value. When the nomogram total points reached 295, the shift from metabolically healthy to unhealthy obesity had a prediction rate of >50%.
CONCLUSIONS: This study identified key factors for young adults transitioning from healthy to unhealthy obesity, creating a predictive nomogram. This nomogram, including triglycerides, waist circumference, high-density lipoprotein-cholesterol, blood pressure, and fasting glucose, allows easy assessment of obesity risk even for the general population. This tool simplifies predictions amid rising obesity rates and interventions.
AIMS: Chronic hyperglycemia-induced inflammation of the hippocampus is an important cause of cognitive deficits in diabetic patients. The receptor for advanced glycation end products (RAGE), which is widely expressed in the hippocampus, is a crucial factor in this inflammation and the associated cognitive deficits. We aimed to reveal the underlying mechanism by which RAGE regulates neuroinflammation in the pathogenesis of diabetes-induced cognitive impairment.
METHODS: We used db/db mice as a model for type 2 diabetes to investigate whether receptor-interacting serine/threonine protein kinase 1 (RIPK1), which is expressed in microglia in the hippocampal region, is a key protein partner for RAGE. GST pull-down assays and AutoDock Vina simulations were performed to identify the key structural domain in RAGE that binds to RIPK1. Western blotting, co-immunoprecipitation (Co-IP), and immunofluorescence (IF) were used to detect the levels of key proteins or interaction between RAGE and RIPK1. Cognitive deficits in the mice were assessed with the Morris water maze (MWM) and new object recognition (NOR) and fear-conditioning tests.
RESULTS: RAGE binds directly to RIPK1 via the amino acid sequence (AAs) 362-367, thereby upregulating phosphorylation of RIPK1, which results in activation of the NLRP3 inflammasome in microglia and ultimately leads to cognitive impairments in db/db mice. We mutated RAGE AAs 362-367 to reverse neuroinflammation in the hippocampus and improve cognitive function, suggesting that RAGE AAs 362-367 is a key structural domain that binds directly to RIPK1. These results also indicate that hyperglycemia-induced inflammation in the hippocampus is dependent on direct binding of RAGE and RIPK1.
CONCLUSION: Direct interaction of RAGE and RIPK1 via AAs 362-367 is an important mechanism for enhanced neuroinflammation in the hyperglycemic environment and is a key node in the development of cognitive deficits in diabetes.
PURPOSE: To facilitate analysis, extraction and resolution of the useful ingredient contained in each layer of a bamboo stalk by grinding succulent section of said stalk with a grinder and separately taking the powder for each cuticle section, hypodermic section and succulent section thereof. CONSTITUTION: A bamboo stalk mainly comprises three layers; a blue-green cuticle section, a yellow-white hypodermic section and white succulent section containing many vascular bundles in the order from the outside of said stalk. Each layer contains different types of useful ingredients and they can be separately taken out by each layer with a grinding means. It is recommended that the bamboo stalk be ground by a paper grinder. Different sizes of bamboo powder particle can be taken depending on the particle size of the paper grinder. The grinding depth depends on the thickness of each layer. To this end, the thickness of the bamboo stalk to be ground is measured prior to its grinding and a paper grinder is set to have the required grinding depth matched to the measured thickness. The ground bamboo powder is taken by an aspirator.
The primary aim of this study is to determine the difference between antibody titers in the two study groups and study the relationship between endemic infections, IA, the FRCn, and CD4 and CD8 T cell subsets and the magnitude and durability of neutralizing antibody response to YFV in a cohort shown to have elevated IA, a damaged FRCn, and pan T cell depletion and a cohort that does not. This is a single arm, open-label, two cohort study of healthy adults in Kampala, Uganda and in Minnesota, USA. The cohort in Uganda will be 30 adults (15 men and 15 women) and the cohort in Minnesota will be 16 adults (8 men and 8 women). Everyone will be screened to ensure there are no contraindications to receiving YFV (e.g., immunosuppression) or the planned procedures. The inclusion and exclusion criteria are discussed in detail in the protocol that is included in the appendix. Participants will have an inguinal lymph node and adjacent adipose tissue biopsy and leukapheresis prior to YFV and again 3 weeks after the vaccine administration. The vaccine will be given in the contralateral thigh from the first LN biopsy so that the second biopsy will be from a draining LN. PBMC and plasma as well as urine and stool will be collected at regular intervals over the 18-month follow-up period and leukapheresis will be done again at the month 18 visit.
Voxelotor was not carcinogenic in a 26-week study in RasH2 transgenic mice at oral doses of 30, 150, or 500 mg/kg/day.

Voxelotor was not genotoxic in the reverse mutation bacterial (Ames) test, rat Comet assay, or rat micronucleus assay.

In a fertility and early embryonic development study, voxelotor was administered orally to rats at 15, 50, and 250 mg/kg/day. Males were dosed 28 days prior to mating through cohabitation and females were dosed 14 days prior to mating through gestation Day 7. Voxelotor had no effect on fertility or reproductive function. Sperm motility was decreased and changes in sperm morphology occurred at 250 mg/kg/day (approximately 5-times the human exposure at 1,500 mg/day).
Congenital or early-onset unilateral hearing loss (UHL) can disrupt the normal development of the auditory system. In extreme cases of UHL (i.e., single sided deafness), consistent cochlear implant use during sensitive periods resulted in cortical reorganization that partially reversed the detrimental effects of unilateral sensory deprivation. There is a gap in knowledge, however, regarding cortical plasticity i.e. the brain's capacity to adapt, reorganize, and develop binaural pathways in milder degrees of UHL rehabilitated by a hearing aid (HA). The current study was set to investigate early-stage cortical processing and electrophysiological manifestations of binaural processing by means of cortical auditory evoked potentials (CAEPs) to speech sounds, in children with moderate to severe-to-profound UHL using a HA. Fourteen children with UHL (CHwUHL), 6-14 years old consistently using a HA for 3.5 (±2.3) years participated in the study. CAEPs were elicited to the speech sounds /m/, /g/, and /t/ in three listening conditions: monaural [Normal hearing (NH), HA], and bilateral [BI (NH + HA)]. Results indicated age-appropriate CAEP morphology in the NH and BI listening conditions in all children. In the HA listening condition: (1) CAEPs showed similar morphology to that found in the NH listening condition, however, the mature morphology observed in older children in the NH listening condition was not evident; (2) P1 was elicited in all but two children with severe-to-profound hearing loss, to at least one speech stimuli, indicating effective audibility; (3) A significant mismatch in timing and synchrony between the NH and HA ear was found; (4) P1 was sensitive to the acoustic features of the eliciting stimulus and to the amplification characteristics of the HA. Finally, a cortical binaural interaction component (BIC) was derived in most children. In conclusion, the current study provides first-time evidence for cortical plasticity and partial reversal of the detrimental effects of moderate to severe-to-profound UHL rehabilitated by a HA. The derivation of a cortical biomarker of binaural processing implies that functional binaural pathways can develop when sufficient auditory input is provided to the affected ear. CAEPs may thus serve as a clinical tool for assessing, monitoring, and managing CHwUHL using a HA.
A web-based intervention (CONNECT) to empower and connect caregivers of newly diagnosed cancer patients to supportive care resources A randomized pilot study will be conducted to assess feasibility and acceptability and obtain data on caregiver and patient outcomes. CONNECT e-tool, re-education and optional referral (2 weeks post CONNECT e-tool). Baseline, one month post randomization data collection, three months post randomization data collection, quantitative and qualitative measures.
Certain disclosed embodiments of the present invention concern a method for making biaryl compounds by combining a diene with a dienophile under reaction conditions that facilitate a Diels-Alder reaction. Certain embodiments are particularly directed to making a tetra-ortho-substituted biaryl compounds. The disclosed method may involve using novel dienes, dienophiles, or both. Similarly, certain of the biaryl compounds are novel compounds too. Additional disclosed embodiments concern a method for making useful compounds by first making a Diels-Alder adduct. The Diels-Alder adduct is then further modified or coupled to other compounds. The method can be used to make carbazoles, such as Siamenol. Disclosed biaryl compounds are useful for a number of applications, such as pharmacophores and organocatalysts.
An implantable left ventricular assist device (LVAD) is indicated as a bridge to transplantation or recovery in the United Kingdom (UK). The mechanism of action of the LVAD results in a unique state of haemodynamic stability with diminished arterial pulsatility. The clinical assessment of an LVAD recipient can be challenging because non-invasive blood pressure, pulse and oxygen saturation measurements may be hard to obtain. As a result of this unusual situation and complex interplay between the device and the native circulation, resuscitation of LVAD recipients requires bespoke guidelines. Through collaboration with key UK stakeholders, we assessed the current evidence base and developed guidelines for the recognition of clinical deterioration, inadequate circulation and time-critical interventions. Such guidelines, intended for use in transplant centres, are designed to be deployed by those providing immediate care of LVAD patients under conditions of precipitous clinical deterioration. In summary, the Joint British Societies and Transplant Centres LVAD Working Group present the UK guideline on management of emergencies in implantable LVAD recipients for use in advanced heart failure centres. These recommendations have been made with a UK resuscitation focus but are widely applicable to professionals regularly managing patients with implantable LVADs.
While sickle cell anemia (SCA) and hereditary spherocytosis (HS) share common features of increased spleen erythrophagocytosis due to increased red blood cell (RBC) turnover, SCA is specifically characterized by susceptibility to infections. In this study, histological lesions in the spleens of pediatric patients with SCA were analyzed, in close correlation with past clinical history and comparatively to HS, healthy and transfused β-thalassemia patients (TDT). An evaluation of red pulp elementary lesions (red pulp fibrosis, iron deposition, number of Gandy-Gamna, and RBC trapping) combined into a severity score was established, as well as B-cell follicles analysis. Quantification on digitalized slides of iron deposition, RBC trapping, and red pulp fibrosis was additionally performed. Spleens from 22 children with SCA, eight with HS, eight with TDT, and three healthy controls (HC) were analyzed. Median age at splenectomy was not different between SCA and HS patients, 6.05 years (range: 4.5-16.0) versus 4.75 (range: 2.2-9.5). Marked heterogeneity was found in SCA spleens in contrast to other conditions. Contrary to previous reports, B-cell follicles were generally preserved in SCA. While RBC trapping was significantly increased in both SCA and HS (compared to TDT and HC), quantitative fibrosis and overall red pulp severity score were significantly increased in SCA spleens compared to other conditions. Moreover, there was an inverse correlation between quantitative fibrosis and number of B-cell follicles, linking these two compartments as well as spleen fibrosis to infectious susceptibility in SCA, potentially through impaired red pulp macrophage scavenging and B-cell subpopulations defects.
Provided are compositions containing engineered particles, and methods of making such engineered particles. Polymeric articles, such as contact lenses, prepared from such compositions are also provided. Such engineered particles are dispersible in hydrophilic systems such as monomer systems for preparation of contact lenses. Each of the engineered particles comprises a hydrophobic core and a hydrophilic shell. The hydrophobic core comprises a silicone-based polymer that can have multiple cross-links and/or polymer-polymer entanglement, and the hydrophilic shell is formed from a reactive stabilizer. A residue of the reactive stabilizer or a hydrophilic segment of the reactive stabilizer can form the shell. The particles have an average particle size of less than about 500 nm.
BACKGROUND: Sepsis-induced cardiomyopathy (SICM) is a common and life-threatening complication of sepsis, significantly contributing to elevated mortality. This study aimed to identify crucial indicators for the prompt and early assessment of SICM.
METHODS: Patients diagnosed with sepsis or SICM within 24 h of intensive care unit (ICU) admission were enrolled in this prospective observational study. Patients were assigned to the training set, validation set and external test set. The primary endpoint was 7-day ICU mortality, and the secondary endpoint was 28-day ICU mortality. Three machine learning algorithms were utilized to identify relevant indicators for diagnosing SICM, incorporating 64 indicators including serum biomarkers associated with cardiac, renal, and liver function, lipid metabolism, coagulation, and inflammation. Internal and external validations were performed on the screening results. Patients were then stratified based on the cut-off value of the most diagnostically effective biomarker identified, and their prognostic outcomes were observed and analyzed.
RESULTS: A total of 270 patients were included in the training and validation set, and 52 patients were included in the external test set. Age, sex, and comorbidities did not significantly differ between the sepsis and SICM groups (P > 0.05). The support vector machine (SVM) algorithm identified six indicators with an accuracy of 84.5%, the random forest (RF) algorithm identified six indicators with an accuracy of 81.9%, and the logistic regression (LR) algorithm screened out seven indicators. Following rigorous selection, a diagnostic model for sepsis-induced cardiomyopathy was established based on heart-type fatty acid binding protein (H-FABP) (OR 1.308, 95% CI 1.170-1.462, P < 0.001) and retinol-binding protein (RBP) (OR 1.020, 95% CI 1.006-1.034, P < 0.05). H-FABP alone exhibited the highest diagnostic performance in both the internal (AUROC 0.689, P < 0.05) and external sets (AUROC 0.845, P < 0.05). Patients with SICM were further stratified based on an H-FABP diagnostic cut-off value of 8.335 ng/mL. Kaplan-Meier curve analysis demonstrated that elevated H-FABP levels at admission were associated with higher 7-day ICU mortality in patients with SICM (P < 0.05).
CONCLUSIONS: This study revealed that H-FABP concentrations measured within 24 h of patient admission could serve as a crucial biomarker for the early and rapid diagnosis and short-term prognostic evaluation of SICM.