anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Caspase-9, a cysteine-aspartate protease traditionally associated with intrinsic apoptosis, has recently emerged as having non-apoptotic roles, including influencing cell migration-an aspect that has received limited attention in existing studies. In our investigation, we aimed to explore the impact of caspase-9 on the migration and invasion behaviors of MDA-MB-231, a triple-negative breast cancer (TNBC) cell line known for its metastatic properties. We established a stable cell line expressing an inducible caspase-9 (iC9) in MDA-MB-231 and assessed their metastatic behavior using both monolayer and the 3D organotypic model in co-culture with human Foreskin fibroblasts (HFF). Our findings revealed that caspase-9 had an inhibitory effect on migration and invasion in both models. In monolayer culture, caspase-9 effectively suppressed the migration and invasion of MDA-MB-231 cells, comparable to the anti-metastatic agent panitumumab (Pan). Notably, the combination of caspase-9 and Pan exhibited a significant additional effect in reducing metastatic behavior. Interestingly, caspase-9 demonstrated superior efficacy compared to Pan in the organotypic model. Molecular analysis showed down regulation of epithelial-mesenchymal transition and migratory markers, in caspase-9 activated cells. Additionally, flow cytometry analysis indicated a cell cycle arrest. Moreover, pre-treatment with activated caspase-9 sensitized cells to the chemotherapy of doxorubicin, thereby enhancing its effectiveness. In conclusion, the anti-metastatic potential of caspase-9 presents avenues for the development of novel therapeutic approaches for TNBC/metastatic breast cancer. Although more studies need to figure out the exact involving mechanisms behind this behavior.
Neovascular disease activity as shown by microaneurysms (MA) turnover (MA formation rate \>= 2, i.e. number of new MA per year) computed from CFP using the RetmarkerDR software.
AIM: (-)-Epicatechin (EPI) has physiological activities such as antioxidant, anti-inflammatory and immune enhancement. In this study, we elucidated the protective effects of EPI in myocardial ischemia/reperfusion injury (MI/RI) and its mechanisms.
METHODS: An in vivo I/R model was constructed by performing left anterior descending coronary artery surgery on rats, and an in vitro I/R model was constructed by subjecting hypoxia/reperfusion treatment on H9C2 cells. The damage of cardiac tissues was detected by 2,3,5-triphenyltetrazolium chloride (TTC) and hematoxylin-eosin (H&E) staining, and expressions of ferroptosis-related proteins were examined by Western blot. Changes in the number of autophagosomes, the levels of oxidative stress and Fe2+ were also examined.
RESULTS: EPI reduced abnormal electrocardiogram waveform and infarct size caused by MI/RI in rats. The increasing trend of levels of reactive oxygen species (ROS) and Fe2+ was reversed by EPI, suggesting that EPI can reduce ferroptosis in vivo. Moreover, the levels of lipid ROS and LC3 in H9C2 cells were decreased with EPI treatment, and autophagy and ferroptosis were also alleviated in a dose-dependent manner in vitro. Co-cultivation of USP14 inhibitor IU1 and EPI further revealed that EPI regulates ferroptosis through the USP14-autophagy pathway.
CONCLUSIONS: EPI can reduce the level of oxidative stress by promoting USP14 to reduce autophagy, thus inhibiting autophagy dependent ferroptosis and reducing oxidative stress, and has a protective effect on myocardial infarction/myocardial infarction.
Doxepin hydrochloride is one of a class of psychotherapeutic agents known as dibenzoxepin tricyclic compounds. The molecular formula of the compound is C19H21NO ∙ HCl having a molecular weight of 315.84. It is a white crystalline powder freely soluble in water, in ethanol (96%), and methylene chloride. It may be represented by the following structural formula:

Chemically, doxepin hydrochloride is a dibenzoxepin derivative and is the first of a family of tricyclic psychotherapeutic agents. Specifically, it is an isomeric mixture of 1-Propanamine, 3-dibenz[b,e] oxepin-11 (6H)ylidene-N,N-dimethyl-hydrochloride.

Each 10 mg, 25 mg, 50 mg, 75 mg and 100 mg doxepin capsule for oral administration contains doxepin hydrochloride, USP equivalent to 10 mg, 25 mg, 50 mg, 75 mg and 100 mg of doxepin, respectively and the following inactive ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, pregelatinized starch and sodium lauryl sulfate. The empty gelatin capsule shells contain gelatin, sodium lauryl sulfate and titanium dioxide. In addition, the 10 mg empty gelatin capsule shells contain iron oxide red and iron oxide yellow, the 25 mg and 50 mg empty gelatin capsule shells contain D&C Yellow 10 and FD&C Yellow 6, and the 75 mg and 100 mg empty gelatin capsule shells contain D&C Yellow 10 and FD&C Blue 1.

The imprinting ink may contain ferrosoferric oxide, potassium hydroxide, propylene glycol and shellac glaze.
Qualitative data collection will occur through one-on-one semi-structured interviews with AYA providers (n=36). Providers will be health professionals who provide supportive care for AYAs to help address financial, body image, and fertility/future parenthood concerns or needs. Psychosocial providers (e.g., social workers, patient navigators, psychologists) will all be eligible to participate. We will also include reproductive endocrinologists, nurse practitioners, and other medical professionals who have expertise in the appropriate area of health-related quality of life (HRQOL). Additional inclusion criteria will be: (1) provision of care to AYAs; (2) ≥2 years practicing; (3) English-speaking.
Mefloquine derivatives, contrary to chloroquine derivatives have not been widely studied to date. Consequently, mefloquine and its derivatives still remain very attractive synthetic targets. Although mefloquine is usually used clinically as a racemic mixture, some studies have shown that its (+)-enantiomer is more potent than the (-)-enantiomer. Moreover, the (-)-enantiomer is responsible for side effects due to reaction with the central nervous system adenosine receptors, while the (+)-enantiomer does no bind at this binding site. Recently, different libraries of racemate 4-aminoalcoholquinolines showed interesting anti-malarial activities. Herein, the present invention describes an enantiopure synthetic and straightforward route to prepare pure enantiomer 4-aminoalcoholquinoline derivatives through the 4-oxirane key-intermediate. A regioselective S N 2 ring opening of this epoxide, by diverse amines, allows to obtain the corresponding (R) or (S) 4-aminoquinolines with good yields and enantiomeric excesses generally superior to 92%. The reported methodology appears suitable for the synthesis of a large number of pure enantiomer 4-aminoalcoholquinoline derivatives.
Given a well-known overlapping prevalence of social isolation with loneliness and depression among older adults, this study aimed to contextually investigate the relationship of these constructs with weight loss of more than 5kg in a year, with a special focus on the intersection of living alone and marital dissolution as key dimensions of isolation. The data were obtained from the Korean Longitudinal Study of Aging (KLoSA) from 2006, 2008, 2010, 2012, 2014, 2016, and 2018, with an adult sample of those aged 65 and older (n = 5,481). The study evaluated several critical dimensions of social isolation: living alone, transition to living alone, infrequent social contact with children or friends, and infrequent social participation. These dimensions were examined individually and as a composite scale, along with loneliness and depressive symptoms, to determine their association with weight loss of 5kg or greater among older men and women. Generalized Estimating Equation (GEE) regression models enabled investigation of whether socially isolated men and women tended to lose 5kg or more in weight, given other confounding factors. Surprisingly, the results showed no evidence of such a trend. However, significant associations were found between weight loss and changes in living alone and marital status. For older men, transitioning to living alone without a change in marital status was linked to significant weight loss. For older women, transitioning to living alone following widowhood or divorce was the risk factor. These relationships remained significant even after adjusting for depression and a wide range of covariates. Additional analysis testing a cumulative effect revealed that only depression was a risk factor for being underweight at the last observation. Therefore, to prevent a clinically risky extent of weight loss, health policies for older Koreans should focus on those who transition to living alone, especially due to spousal bereavement or divorce (among women) and separation from living with children (among men).
Gingival displacement with a gingival cord (#0, #00 or #000) prior to the restoration. Application of total-etch adhesive system: enamel and dentin etched with 35% phosphoric acid, wash, dry, two layers of primer/bond application with a brush and photoactivated for 20 seconds.
The balance between the tumor-necrosis factor α (TNFα) and type-I interferon (T1IFN) pathways is crucial for proper immune function. Dysregulation of either pathway can contribute to autoimmune diseases development. Even though TNFα blockade has shown promising results in various autoimmune diseases, the effect on the balance between TNFα and T1IFN is elusive. We used targeted anti-TNFα therapies in juvenile idiopathic arthritis (JIA) as an experimental approach to study the cross-regulation between TNFα and type-I IFN. We found that TNFα-rich environment affected viral defense through the attenuation of T1IFN responses and affected the phenotype and distribution of myeloid dendritic cells, which are engaged in early viral infections. Anti-TNFα therapy normalized the observed deviations in JIA patients. We hypothesize that the inadequate immune response caused by a high TNFα environment could be projected to more frequent or lengthy viral infections and possibly play a role in the process of JIA disease development.
It remains to be elucidated whether Ca2+ antagonists induce pharmacological preconditioning to protect the heart against ischemia/reperfusion injury. The aim of this study was to determine whether and how pretreatment with a Ca2+ antagonist, azelnidipine, could protect cardiomyocytes against hypoxia/reoxygenation (H/R) injury in vitro. Using HL-1 cardiomyocytes, we studied effects of azelnidipine on NO synthase (NOS) expression, NO production, cell death and apoptosis during H/R. Action potential durations (APDs) were determined by the whole-cell patch-clamp technique. Azelnidipine enhanced endothelial NOS phosphorylation and NO production in HL-1 cells under normoxia, which was abolished by a heat shock protein 90 inhibitor, geldanamycin, and an antioxidant, N-acetylcysteine. Pretreatment with azelnidipine reduced cell death and shortened APDs during H/R. These effects of azelnidipine were diminished by a NOS inhibitor, L-NAME, but were influenced by neither a T-type Ca2+ channel inhibitor, NiCl2, nor a N-type Ca2+ channel inhibitor, ω-conotoxin. The azelnidipine-induced reduction in cell death was not significantly enhanced by either additional azelnidipine treatment during H/R or increasing extracellular Ca2+ concentrations. RNA sequence (RNA-seq) data indicated that azelnidipine-induced attenuation of cell death, which depended on enhanced NO production, did not involve any significant modifications of gene expression responsible for the NO/cGMP/PKG pathway. We conclude that pretreatment with azelnidipine protects HL-1 cardiomyocytes against H/R injury via NO-dependent APD shortening and L-type Ca2+ channel blockade independently of effects on gene expression.
Our study investigated the causal relationship between immune cells, metabolites, and epilepsy using two-sample Mendelian Randomization (MR) and mediation MR analysis of 731 immune cell traits and 1400 metabolites. Our core methodology centered on inverse-variance weighted MR, supplemented by other methods. This approach was crucial in clarifying the potential intermediary functions of metabolites in the genetic links between traits of immune cells and epilepsy. We found a causal relationship between immune cells and epilepsy. Specifically, the genetically predicted levels of CD64 on CD14-CD16- are positively correlated with the risk of epilepsy (p < 0.001, OR = 1.0826, 95% CI 1.0361-1.1312). Similarly, metabolites also exhibit a causal relationship with both immune cells (OR = 1.0438, 95% CI 1.0087-1.0801, p = 0.0140) and epilepsy (p = 0.0334, OR = 1.0897, 95% CI 1.0068-1.1795), and sensitivity analysis was conducted to further validate these relationships. Importantly, our intermediate MR results suggest that the metabolite Paraxanthine to linoleate (18:2n6) ratio may mediate the causal relationship between immune cell CD64 on CD14-CD16- and epilepsy, with a mediation effect of 5.05%. The results suggest the importance of specific immune cell levels and metabolites in understanding epilepsy's pathogenesis, which is significant for its prevention and treatment.
The three aims for this study are: 1. To develop an electronic version of the revised B-RST (Breast Cancer Genetics Referral Screening Tool) with a HIPAA compliant database for integration within the Winship Cancer Institute at Emory website. 2. To identify the most effective means of follow-up to maximize the number of screen positive individuals who are referred to and complete cancer genetics counseling. 3. Evaluate the clinical utility of B-RST 3.0 by analyzing the number of individuals who were referred to and received genetic counseling and were considered appropriate for genetic testing and underwent genetic testing, and were identified with a BRCA1/2 mutation, and/or were identified with a mutation in a different hereditary cancer gene, or were not appropriate for genetic testing, but were appropriate for referral to high-risk follow-up services.

The B-RST is a simple yet effective screening tool to identify individuals who may be at risk for hereditary breast and ovarian cancer. This study will seek to determine the most effective method of follow-up to maximize referral to and completion of cancer genetic counseling services following a screen positive result on the B-RST tool, and to understand clinical outcomes following participation in genetic counseling (i.e., whether patients who receive counseling undergo genetic testing, genetic testing results, and recommendations for enhanced screening and preventions).
Pembrolizumab, 200mg IV every 3 weeks. Treatment will continue, in the absence of prohibitive toxicities or disease progression, for up to 24 months.
The active ingredient in esomeprazole sodium for injection is (S)-5-methoxy-2[[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methyl]sulfinyl]-1 H-benzimidazole sodium, a PPI. Esomeprazole is the S-isomer of omeprazole, which is a mixture of the S- and R-isomers. Its molecular formula is C17H18N3O3SNa with molecular weight of 367.4 g/mol (sodium salt) and 345.4 g/mol (parent compound). Esomeprazole sodium is a white or almost white, hygroscopic powder. It is very soluble in water and freely soluble in ethanol (95%). The structural formula is: 

  


  


Esomeprazole sodium for injection is supplied as a sterile, freeze-dried, white to off-white, porous cake or powder in a 5 mL single-dose vial, intended for intravenous administration after reconstitution with 0.9% Sodium Chloride Injection, USP; Lactated Ringer’s Injection, USP or 5% Dextrose Injection, USP. Esomeprazole sodium for injection contains 40 mg esomeprazole (equivalent to 42.5 mg esomeprazole sodium), edetate disodium 1.5 mg and sodium hydroxide q.s. for pH adjustment. The pH of reconstituted solution of esomeprazole sodium for injection depends on the reconstitution volume and is in the pH range of 9 to 11. The stability of esomeprazole sodium in aqueous solution is strongly pH dependent. The rate of degradation increases with decreasing pH.
Exercise consultation will be realised only at 3 months in the control group(group B). Furthermore, patients of group B will not received any physical activity counseling at baseline.
Antiangiogenic therapy targeting VEGF-A has become the standard of first-line therapy for non-small cell lung cancer (NSCLC). However, its clinical response rate is still less than 50%, and most patients eventually develop resistance, even when using combination therapy with chemotherapy. The major cause of resistance is the activation of complex bypass signals that induce angiogenesis and tumor progression. Therefore, exploring novel proangiogenic mechanisms and developing promising targets for combination therapy are crucial for improving the efficacy of antiangiogenic therapy. Immunoglobulin-like transcript (ILT) 4 is a classic immunosuppressive molecule that inhibits myeloid cell activation. Recent studies have shown that tumor cell-derived ILT4 drives tumor progression via the induction of malignant biologies and creation of an immunosuppressive microenvironment. However, whether and how ILT4 participates in NSCLC angiogenesis remain elusive. Herein, we found that enriched ILT4 in NSCLC is positively correlated with high microvessel density, advanced disease, and poor overall survival. Tumor cell-derived ILT4 induced angiogenesis both in vitro and in vivo and tumor progression and metastasis in vivo. Mechanistically, ILT4 was upregulated by its ligand angiopoietin-like protein 2 (ANGPTL2). Their interaction subsequently activated the ERK1/2 signaling pathway to increase the secretion of the proangiogenic factors VEGF-A and MMP-9, which are responsible for NSCLC angiogenesis. Our study explored a novel mechanism for ILT4-induced tumor progression and provided a potential target for antiangiogenic therapy in NSCLC.
Eleven healthy, normal body weight (male: 6, female: 5) adults after a 12hr fast, consumed 50g available carbohydrates from mixed fruit juice enriched with probiotics, tested once, in random order, along with 300mL water. Fingertip capillary blood glucose samples were collected at baseline and 15, 30, 45, 60, 90, 120, 150, and 180 min after test drink consumption. Salivary insulin samples were collected at baseline, 15, 30, 45, 60, 90, 120, and 180 min after test drink consumption.
The inherited myotonias are a complex group of diseases caused by variations in genes that encode or modulate the expression of ion channels that regulate muscle excitability. These variations alter muscle membrane excitability allowing mild depolarization, causing myotonic discharges. There are two groups of inherited myotonia, the dystrophic and the nondystrophic myotonias (NDM). Patients with NDM have a pure muscle phenotype with variations in channel genes expressed in muscle. The dystrophic myotonias are caused by genes that alter splicing leading to more systemic effects with myotonia being one of a number of systemic symptoms. This chapter therefore focuses on the key aspects of the NDMs. The NDMs manifest with varying clinical phenotypes, which change from infancy to adulthood. The pathogenicity of different variants can be determined using heterologous expression systems to understand the alteration in channel properties and predict the likelihood of causing disease. Myotonia itself can be managed by lifestyle modifications. A number of randomized controlled trials demonstrate efficacy of mexiletine and lamotrigine in treating myotonia, but there is an evidence that specific variants may be more or less well-treated by the different agents because of how they alter the channel kinetics. More work is needed to develop more targeted genetic treatments.
BACKGROUND: Tolvaptan preserves kidney function in adults with autosomal dominant polycystic kidney disease (ADPKD) at elevated risk of rapid progression. A trial (NCT02964273) evaluated tolvaptan safety and pharmacodynamics in children (5-17 years). However, progression risk was not part of study eligibility criteria due to lack of validated criteria for risk assessment in children. As risk estimation is important to guide clinical management, baseline characteristics of the study participants were retrospectively evaluated to determine whether risk of rapid disease progression in pediatric ADPKD can be assessed and to identify parameters relevant for risk estimation.
METHODS: Four academic pediatric nephrologists reviewed baseline data and rated participant risk from 1 (lowest) to 5 (highest) based on clinical judgement and the literature. Three primary reviewers independently scored all cases, with each case reviewed by two primary reviewers. For cases with discordant ratings (≥ 2-point difference), the fourth reviewer provided a secondary rating blinded to the primary evaluations. Study participants with discordant ratings and/or for whom data were lacking were later discussed to clarify parameters relevant to risk estimation.
RESULTS: Of 90 evaluable subjects, primary reviews of 69 (77%) were concordant. The proportion considered at risk of rapid progression (final mean rating ≥ 3.5) by age group was: 15-17 years, 27/34 (79%); 12- < 15, 9/32 (28%); 4- < 12, 8/24 (33%). The panelists agreed on characteristics important for risk determination: age, kidney imaging, kidney function, blood pressure, urine protein, and genetics.
CONCLUSIONS: High ratings concordance and agreement among reviewers on relevant clinical characteristics support the feasibility of pediatric risk assessment.
<P>PROBLEM TO BE SOLVED: To provide a method for producing chitosan nanoparticles using a simple operation and reduced amount of organic solvents.  <P>SOLUTION: The method for producing chitosan nanoparticles comprises dissolving chitosan in an aqueous acid solution to obtain an aqueous chitosan solution and adding the aqueous chitosan solution to an aqueous alkali solution. The chitosan particles are obtained by the production method. The coating composition contains the chitosan particles. The sustained release preparation (for example, microcapsule) is wet-coated with the composition. The injection contains the sustained preparation.  <P>COPYRIGHT: (C)2006,JPO&NCIPI
Background: The place of death of cancer patients is an important aspect of end-of-life care. However, little research has been conducted regarding factors that may influence the preferred and actual place of death in cancer patients and whether the patients die at their preferred place of death. In this study, we aimed to investigate the preferred and actual place of death for palliative cancer patients, and factors influencing these variables. Methods: Patients diagnosed with cancer and admitted to a palliative care team across three Swedish cities between 2019 and 2022 were asked for participation. Participants completed a questionnaire capturing sociodemographic data and preferred place of death. Further data regarding age, sex, and cancer type were collated at inclusion, and the actual place of death recorded for those deceased by 5-May-2023. Results: The study included 242 patients. A majority (79%) wanted to die at home which was the actual death location for 76% of the patients. When the place-of-death decision was made by the patient alone, 75% chose home, compared to 96% when decided jointly with relatives-a statistically significant variation (p = 0.0037). For the patients who wanted to die at home, 80% actually died at home, with insignificant disparities among subgroups. Conclusions: Most palliative cancer patients in this Swedish cohort preferred and achieved death at home. Involving relatives in decision-making may influence the preferred place of death, however larger studies are needed to comprehensively assess factors affecting the preferred and actual place of death in different subgroups of patients.