anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Clinical studies have demonstrated that elevated levels of total-C, LDL-C and Apo B, the major protein constituent of LDL, promote human atherosclerosis. In addition, decreased levels of HDL-C are associated with the development of atherosclerosis. Epidemiologic studies have established that cardiovascular morbidity and mortality vary directly with the level of total-C and LDL-C and inversely with the level of HDL-C. Like LDL, cholesterol-enriched triglyceride-rich lipoproteins, including very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), and remnants, can also promote atherosclerosis. The independent effect of raising HDL-C or lowering TG on the risk of coronary and cardiovascular morbidity and mortality has not been determined.  
  
Ezetimibe reduces total-C, LDL-C, Apo B, non-HDL-C, and TG, and increases HDL-C in patients with hyperlipidemia. Administration of ezetimibe with a statin is effective in improving serum total-C, LDL-C, Apo B, non-HDL-C, TG, and HDL-C beyond either treatment alone. Administration of ezetimibe with fenofibrate is effective in improving serum total-C, LDL-C, Apo B, and non-HDL-C in patients with mixed hyperlipidemia as compared to either treatment alone. The effects of ezetimibe given either alone or in addition to a statin or fenofibrate on cardiovascular morbidity and mortality have not been established.
FIELD: organic chemistry, biochemistry, virology. SUBSTANCE: invention relates to novel substituted pyrimidinethioalkyl or alkylester compounds, their pharmaceutically acceptable salts, hydrates, N-oxides and method of inhibition of viral reverse transcriptase activity. Proposed compounds can be used in treatment of HIV-infected patients. Proposed compounds correspond to the general structural formula (I)   where m = 0 or 1; R 1  is taken among the group consisting of: -C=CH, -CO 2 R 53 , -CONR 54 R 55  or residues of compounds of the formulas (A)  , (B)   and (C)   where radical values are given in the invention claim. Method of inhibition of activity of viral reverse transcriptase involves administration to patients of effective dose of compound of the formula (I). EFFECT: new compounds indicated above, improved method of inhibition. 20 cl, 13 tbl
BACKGROUND: Control of Neisseria gonorrhoeae infection (gonorrhoea) depends on effective testing strategies. Anorectal testing in women is often done on indication of anal sex; however, anorectal infections are seen with and without anal exposure, possibly caused by autoinoculation. This study aims to enhance understanding of anorectal infections in women, by identifying risk factors for anorectal diagnosis.
METHODS: In this retrospective cohort study we used national surveillance data from Dutch sexual health centres from Jan 1, 2016, to Dec 31, 2021. We included cisgender women having sex with men who were tested urogenitally and anorectally for gonorrhoea. Due to different testing policies, we identified three groups: women who had not reported recent anal sex (in the past 6 months), women who had reported recent anal sex, and sex workers. Extracted data for analyses included demographics, sexual behaviour, and diagnosis of a sexually transmitted infection (STI). Per group, multivariable models using Firth's penalised maximum likelihood logistic regression were constructed, identifying determinants of anorectal gonorrhoea among all women and among gonorrhoea-positive women only. Variables included in model construction were age, education level, migration background, number of partners, condom use, partner notification, STI symptoms, having a partner who has sex with men (MSM) or a migrant partner, previous STI test, anal sex, and chlamydia and gonorrhoea diagnoses per anatomical location.
FINDINGS: In total, 117 693 women were included: 43 757 women without reported recent anal sex, 51 728 women with reported recent anal sex, and 22 208 sex workers. In all three groups, around 2% of women were gonorrhoea positive, and 70% or more of women had an anorectal infection. The strongest determinant of anorectal gonorrhoea was a concurrent urogenital gonorrhoea diagnosis (adjusted odds ratios [aOR] 782 [95% CI 605-1018]) among women without reported recent anal sex (612 [490-768] among women with reported recent anal sex, and 464 [335-652] among sex workers). Among gonorrhoea-positive women, determinants of anorectal gonorrhoea were urogenital and anorectal chlamydia co-infection (aOR 2·03 [95% CI 1·38-3·02], for women without reported anal sex) and migration background (1·44 [1·02-2·06], for women with reported anal sex). Determinants among sex workers were condomless sex (2·43 [1·55-3·82]), anal sex (1·71 [1·10-2·66]), MSM or migrant partner (1·78 [1·13-2·79]), and urogenital and anorectal chlamydia co-infection (2·28 [1·11-5·14]).
INTERPRETATION: These findings support the possibility of an autoinoculation process from the urogenital to the anorectal location due to the very strong correlation between urogenital and anorectal gonorrhoea, and due to the similarity of results across all three groups. Current testing strategies could miss anorectal infections, which should be considered when developing gonorrhoea prevention and control guidelines.
FUNDING: None.
Optimizing delivery of pharmacological agents (A) involves: (i) synchronizing a living organism in a reference state using a chronoactive agent (B); (ii) synchronizing the release of (A) by interaction of (B) with e.g. growth hormone in plasma; or (iii) inducing endogenous synthesis of (B) by an environmental stimulus before administration of a formulation containing (A). Optimizing delivery of pharmacological agents (A) involves: (i) synchronizing a living organism in a reference state using a chronoactive agent (B); (ii) synchronizing the release of (A) by interaction of (B) with growth hormone, cortisol, melatonin, prolactin, ADH or VIP concentrations in plasma; or (iii) inducing endogenous synthesis of (B) by an environmental stimulus such as exposure to light, darkness, alternation of light and darkness, heat, cold or temperature change (especially by immersion of the subject) before administration of a formulation containing (A). (N.B. In dependent claims (A) include plant protectants, defoliants and insecticides, as well as drugs). An Independent claim is included for a galenic device for carrying out the processes, which ensures the sequential delivery of (A) and (B) (specifically by immediate release of (B) and retarded release of (A)).
In each country, this arm constitute with 6 clusters where 2 from high, 2 from medium and 2 from low shadfly destiny. Each cluster has 50 households. It will receive IWFPL intervention.
Obesity is a complex metabolic disorder, manifesting as excessive accumulation of body fat. Ten-Eleven Translocation-2 (TET2) has garnered significant attention in the context of obesity due to its crucial role in epigenetic regulation and metabolic homeostasis. In this study, we aimed to investigate the effect of endothelial TET2 on obesity and explore the potential mechanism. We generated endothelial cell-specific TET2 deficiency mice and investigated endothelial TET2 using transcriptomic and epigenomic analyses. We determined the downregulation of endothelial TET2 in white adipose tissues. Furthermore, we identified that endothelial TET2 loss aggravated high-fat diet-induced obesity by inhibiting vascularization and thus suppressing white adipose tissue browning. Mechanistically, endothelial TET2 modulates obesity by engaging in endothelial fatty acid oxidation and angiocrine-mediated secretion of bone morphogenetic protein 4 (BMP4), in which nuclear factor-erythroid 2-related factor 2 (NRF2) serves as a key mediator. Our study reveals that endothelial TET2 regulates white adipose tissue browning by interacting with NRF2 to facilitate fatty acid oxidation and lipolysis in adipocytes.
PROBLEM TO BE SOLVED: To obtain the subject stable radix extract composition having good handleability and useful for providing a preparation having high stability by including a polyhydric alcohol fatty acid ester, a hydrophobic Glycyrrhizae Radix extract and oil and fat. SOLUTION: This composition comprises (A) a polyhydric alcohol fatty acid ester (preferably a diglycerol monofatty acid ester such as diglyceryl monoisostearate, especially having <=7.5 HLB), (B) a hydrophobic Glycyrrhizae Radix extract and (C) oil and fat (preferably exhibiting fluidity at ordinary temperature, e.g. a dialkyl carbonate). The component B is obtained by subjecting an extracted solution obtained by extracting root or rhizome of Glycyrrhiza glabra with an organic solvent such as ethanol or an extract obtained by removing the solvent to purification treatment such as decoloring or deodorization. The composition contains glabridin, glabrene, or the like, as main ingredient. The composition comprises 10-50 wt.% component A, 1-20 wt.% component B and the balance of the component C.
Part 1 is a single-arm study. All eligible patients will receive tislelizumab 200 mg intravenously on day 1 every 3 weeks plus regorafenib orally 80 mg per day.
Bronchopulmonary dysplasia (BPD) is a severe lung disease in preterm infants, the abnormal proliferate and differentiate ability of type II epithelial cells (AEC II) is the key to the pathological basis of BPD. Mechanisms regarding abnormal AEC II in BPD remain unclear. The present work investigated the role and mechanisms of invariant natural killer T (iNKT) cells in lung disorder in BPD using public datasets, clinical samples, a hyperoxia-induced BPD mouse model and AEC II-iNKT cells transwell co-culture system. Firstly, we found that the NKT cells development factor IL-15 increased over time in patients with BPD in public databases, and clinically collected peripheral blood NKT cells in patients with BPD were increased. Subsequently, the percentage of iNKT cells increased in hyperoxia group compared with normoxia group, with the highest at P7, accompanied by increased activation with abnormal lung development. The administration of anti-CD1d neutralizing antibody to inhibit iNKT cells could alleviate the abnormal lung development of hyperoxia group mice, while α-GalCer administration could aggravate lung injury in hyperoxia group mice, and adoptive transfer of iNKT cells could aggravate the abnormal lung development in hyperoxia group mice. In addition, to further verify the role of iNKT cells on AEC II, AEC II-iNKT cells co-culture system was established. The presence of iNKT cells could aggravate the abnormal expression of SP-C and T1α under hyperoxia. Meanwhile, RNA-seq analysis showed that ferroptosis-related genes were highly expressed in AEC II co-cultured with iNKT cells under hyperoxia. We further validated the effect of the presence of iNKT cells under hyperoxia environment on AEC II ferroptosis levels, suggested that iNKT cells promote AEC II ferroptosis under hyperoxia, accompanied by decreased expression of SP-C and T1α. Our study found that the recruitment of iNKT cells in the lung may be an important cause of alveolarization disorder in BPD.
PROBLEM TO BE SOLVED: To obtain a cosmetic, free from stickiness and glittering, excellent in feeling of use and humectant effects and causing low irritation to the skin, etc., by dissolving a specified phosphoric triester in a lower alcohol/water system for use. SOLUTION: This cosmetic is produced by blending (A) a phosphoric triester of formula I (R<1> to R<3> are each an >=11C alkyl, with the proviso that at least one of R<1> to R<3> is a >=13C alkyl and at least one thereof is a branched alkyl) with (B) a lower alcohol and (C) water. Compounds in which at least one of R<1> to R<3> is a 13-20C alkyl; the rest are 11-18C alkyls and at least two thereof are branched alkyls, e.g. compounds of formulas II and III are preferred as the phosphoric triester. The cosmetic preferably comprises 1-40wt.% component (A), 10-98wt.% component (B) and 1-80wt.% component (C). This cosmetic can be prepared into skin cosmetics such as a skin lotion, a milky lotion, a cosmetic solution or an after-shaving lotion and hair cosmetics such as a hair tonic or a hair tonic and treatment/hair growth agent.
Transforming growth factor-beta (TGFβ) is a pleiotropic cytokine which belongs to a superfamily of ligands, including bone morphogenetic proteins and activins \[1-5\]. Under normal conditions, members of the TGFβ family maintain homeostasis in many organ systems. In normal and non-cancerous cells, TGFβ limits the growth of epithelial, endothelial, neuronal, and hematopoietic cell lineages through anti-proliferative and apoptotic responses. In addition, TGFβ exerts potent effects that influence immune function, cell proliferation/ functional differentiation, cell adhesion, extracellular matrix production, cell motility, angiogenesis, and cytokine production. TGFβ has been implicated as an important factor in the growth, progression, and metastatic potential of advanced cancers. Although TGFβ has been shown to suppress the growth of epithelial cells in the early stages of tumor development (premalignant conditions), the effect on advanced cancers is more complex \[1, 5-6\]. Increased production of TGFβ has been found in many neoplasms such as breast, prostate, gastric, renal, and epidermal carcinomas, and elevated plasma TGFβ levels in patients have been correlated with advanced disease, metastases, and lower survival rates \[7-13\]. In these later stage cancers, TGFβ induced growth suppression is lost, and instead, TGFβ promotes tumor growth and metastasis.

Eli Lilly has developed and produced a Transforming Growth Factor-beta (TGF-β) receptor type-1 kinase inhibitor. LY2157299 monohydrate (LY2157299) is a small molecule that inhibits the TGF-β receptor type 1 kinase activity. LY2157299 was developed to investigate its activity in patients with glioblastoma where TGF-β has been demonstrated to play a specific role in tumor progression. In addition, LY2157299 was investigated in other patient populations, either as a stand-alone therapy or in combination with standard anti-tumor treatment regimens for indications including hepatocellular carcinoma and pancreatic cancer. Future investigations include indications with likely TGF-β associated pathway activation, such as melanoma, breast and prostate cancer as well as hematologic malignancies.
INTRODUCTION: Racial/ethnic differences exist in the prevalence of adverse childhood experiences (ACEs). However, few studies have examined racial/ethnic differences in the association between ACEs and poor mental health outcomes in young adulthood.
METHODS: Data on 10 self-reported, recalled ACEs (prior to age 18) and current symptoms of depression, anxiety, post-traumatic stress disorder, and sleep problems in early adulthood were collected from 2,020 young adults (age 20-23 years) between January and June 2021 enrolled in a Southern California prospective community-based cohort. Logistic regression models run in 2022-2023 evaluated the association of cumulative (0, 1, 2, 3, 4+ ACEs), grouped (abuse, neglect, household dysfunction), and individual ACE exposure with mental health outcomes; interaction models tested for differences by race/ethnicity.
RESULTS: All ACE exposures (cumulative, grouped, individual ACEs) were associated with increased odds of most mental health symptoms. Significant differences by race/ethnicity emerged for individual and grouped (but not cumulative) ACEs. For example, associations of any abuse-related ACE and emotional and physical abuse with depressive symptoms were greater for Hispanic participants than for those of another race/ethnicity. Further, associations of emotional abuse with sleep problems were greater for Hispanic participants than for Asian American and Pacific Islander participants (interaction ps<0.05). Though not significant, the association of familial incarceration with depression symptoms was higher for AAPI participants than for other racial/ethnic groups (interaction p-value=0.06).
CONCLUSIONS: Evaluation of individual and grouped ACEs reveals important racial/ethnic heterogeneity in associations with mental health outcomes. Findings have implications for targeted prevention efforts for racial/ethnic groups at higher risk for poor mental health.
OBJECTIVE: Chronic constriction injury (CCI) of the infraorbital nerve induces neuropathic pain, such as allodynia and hyperalgesia, in the orofacial area. However, the changes in the local circuits of the central nervous system following CCI remain unclear. This study aimed to identify the changes following CCI in Thy1-GCaMP6s transgenic mice.
METHODS: Neural activity in the primary somatosensory cortex (S1) and motor cortex (M1) following whisker stimulation was assessed using in vivo Ca2+ imaging. CCI-induced changes in responses were analyzed.
RESULTS: Before CCI, whisker stimulation induced a greater Ca2+ response in the contralateral S1 than in the ipsilateral S1 and contralateral M1. The peak Ca2+ response amplitude in the bilateral S1 and contralateral M1 decreased two days after CCI compared to before CCI. Decreased Ca2+ response amplitude in these regions was observed until four days after CCI. Seven days after CCI, the Ca2+ response amplitude in the contralateral S1 decreased, whereas that in the ipsilateral S1 and contralateral M1 recovered to control levels.
CONCLUSION: These results suggest that neural activity in regions receiving excitatory inputs via corticocortical pathways recovers earlier than in regions receiving thalamocortical inputs. (185/250 words).
Increasing shortage of donor organs leads to the acceptance of less than optimal grafts for transplantation, up to and including organs donated after circulatory standstill of the donor. Therefore, protective strategies and pharmacological interventions destined to reduce ischemia induced tissue injury are considered a worthwhile focus of research. The present study evaluates the potential of a multidrug pharmacological approach as single flush at the end of static preservation to protect the liver from reperfusion injury. Livers were retrieved from male Wistar rats 20 min after cardiac standstill. The organs were cold stored for 18 h, flushed with 20 ml of saline, kept at room temperature for 20 min, and reperfused at 37 °C with oxygenated Williams E solution. In half of the cases, the flush solution was supplemented with a cocktail containing metformin, bucladesine and cyclosporin A. Upon reperfusion, treated livers disclosed a massive mitigation of hepatic release of alanine aminotransferase and aspartate aminotransferase, along with a significant approximately 50 % reduction of radical mediated lipid peroxidation, caspase activation and release of TNF-alpha. Even after preceding cold preservation, a pharmacological cocktail given as single flush is capable to mitigate manifestations of reperfusion injury in the present model.
Vaccine for the prophylactic treatment of equine trichophytosis consists of a suspension of microconidia of an immunogenic strain of Trichophyton equinum in physiological soln. at pH 6.2-7.0, the concn. being 30-45 millions units per ml. of sterile physiological soln. The immunogenic strain is typically trichophyton equinum NL-2251/70 (USSR). In an example, the microorganism was cultured on agar-beer must, and this was used to seed a sucrose-gelatin medium. The prod. after culture was freeze-dried and was tested for immunogenic activity and innocuity.
This resubmission responds to "PAR-16-365-Pilot Clinical Trials for the Spectrum of Alzheimer's Disease and Age-related Cognitive Decline (R01)". It will examine the efficacy of hyperbaric oxygen therapy (HBOT) in improving cognitive functioning in cognitively impaired elderly with diabetes (T2D), who have high risk for dementia. It is a collaboration of the Icahn School of Medicine at Mount Sinai, NY, the University of Wisconsin, the Sagol Center for Hyperbaric Medicine and Research at Asaf Harofeh Medical Center, Israel-one of the world's largest and busiest hyperbaric units-and the Sheba Medical Center, Israel.

HBOT is a treatment in which oxygen-enriched air (up to 100%) is administered to patients at a pressure above the ambient atmosphere. The combined action of hyperoxia and hyperbaric pressure leads to significant improvements in tissue oxygenation, resulting in cerebrovascular benefits with improved ischemic damage and cerebral blood flow. Recently, the researchers of this group published compelling evidence from clinical trials indicating HBOT neurotherapeutic effects in stroke, with better cognitive function and elevated brain activity in SPECT. New preliminary data suggests potential neurotherapeutic effects of HBOT on T2D elderly with mild cognitive impairment (MCI), showing better cognitive performance and brain activity. The researchers propose a randomized controlled clinical trial examining the short (12 weeks) and long-term (12 months) efficacy of HBOT. The researchers will test hypotheses that HBOT compared to a sham condition improves cognitive function and increases cerebral blood flow and glucose utilization in MCI patients with T2D. Such patients are at high dementia risk and enriched in cerebrovascular disease, and thus have high potential for benefitting from HBOT. Aim 1 examines the potential beneficial effects of HBOT on cognition (with a primary composite measure of executive functions and episodic memory, both affected by T2D). Aim 2 examines effects of HBOT on ischemic injury which will be measured by CBF at the level of capillaries in gray matter (by MRI arterial spin labeling), and in macrovessels (by a novel 4D Flow MRI technology developed by the researchers of this group). Aim 3 focuses on effects of HBOT on cerebral glucose utilization using \[F18\]FDG-PET. Finally, Aim 4 investigates mediation by the biomarkers, i.e. whether their inclusion in a mediation model will attenuate the effect of HBOT on cognition, suggesting them as underlying mechanisms. This study will be performed in Israel, where there is optimal infrastructure and expertise for all the study components at significantly lower costs. HBOT can be widely deployed in the US so if successful, this pilot study will provide the basis for a multi-center large-scale clinical trial for definitive evidence of its benefits to cognition in T2D patients at high dementia risk. Despite advances in the understanding of risk factors and the pathologic basis for dementia, treatments are of very limited effects. As the proportion of elderly increases, the accelerating prevalence of T2D and dementia amplifies this application's public health impact.
This invention provides a composition matter comprising rare earth-doped up-conversion nanoparticles (UCNPs) encapsulated with a silica shell. In one embodiment, a photosensitizer is incorporated into the silica shell. In another embodiment, the composition further comprises a targeting molecule. In still another embodiment, a small interfering RNA (siRNA) molecule is also attached to the silica shell with the targeting molecule. The invention further provides methods for synthesizing such compositions and for using them in therapeutic and diagnostic applications. These applications use infrared or near infrared activation to excite the UCNPs.