anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Various heart diseases ultimately lead to chronic heart failure (CHF). In CHF, the inflammatory response is associated with pyroptosis, which is mediated by the NOD-like receptor protein 3 (NLRP3) inflammasome. Fu Xin decoction (FXD) is commonly used in clinical practice to treat CHF and improve inflammatory conditions. However, the specific pharmacological mechanisms of action for FXD in these processes have yet to be fully understood.
PURPOSE: The objective of this study was to examine the protective mechanism of FXT against CHF, both in H9c2 cells and mice.
METHOD: A CHF mouse model was established, and the effect of FXD was observed via gavage. Cardiac function was evaluated using echocardiography, while serum BNP and LDH levels were analyzed to assess the severity of CHF. Hematoxylin and eosin staining (H&E) and Masson staining were performed to evaluate myocardial pathological changes, and TdT-mediated dUTP Nick-End Labeling staining was used to detect DNA damage. Additionally, doxorubicin was utilized to induce myocardial cell injury in H9c2 cells, establishing a relevant model. CCK8 was used to observe cell viability and detect LDH levels in the cell supernatant. Subsequently, the expression of pyroptosis-related proteins was detected using immunohistochemistry, immunofluorescence, and western blotting. Finally, the pharmacological mechanism of FXD against CHF was further validated by treating H9c2 cells with an NLRP3 activator and inducing NLRP3 overexpression.
RESULT: According to current research findings, echocardiography demonstrated a significant improvement of cardiac function by FXD, accompanied by reduced levels of BNP and LDH, indicating the amelioration of cardiac injury in CHF mice. FXD exhibited the ability to diminish serum CRP and MCP inflammatory markers in CHF mice. The results of HE and Masson staining analyses revealed a significant reduction in pathological damage of the heart tissue following FXD treatment. The CCK8 assay demonstrated the ability of FXD to enhance H9c2 cell viability, improve cell morphology, decrease LDH levels in the cell supernatant, and alleviate cell damage. Immunohistochemistry, Western blotting, and immunofluorescence staining substantiated the inhibitory effect of FXD on the NLRP3/caspase-1/GSDMD pyroptosis signaling pathway in both CHF and H9c2 cell injury models. Ultimately, the administration of the NLRP3 activator (Nigericin) and the overexpression of NLRP3 counteract the effects of FXD on cardiac protection and pyroptosis inhibition in vitro.
CONCLUSION: FXD exhibits a cardioprotective effect, improving CHF and alleviating pyroptosis by inhibiting the NLRP3/caspase-1/GSDMD pathway.
INTRODUCTION: Global chronic kidney disease is now epidemic, with substantial health and economic consequences. While scientific support for living donor renal transplants (LDRT) is strong, donor shortages necessitate consideration of expanded criteria, including obese individuals. Bariatric surgery (BS) may mitigate obesity-related risks, but research on living donor candidates is scarce. Our scoping review aims to compile evidence, identify gaps, and formulate an algorithm to guide healthcare professionals in evaluating BS for obese living donors.
EVIDENCE ACQUISITION: We did a systematic search of studies on living kidney donors and obesity. We searched the MEDLINE Ovid, Embase Ovid, CENTRAL and Web of Science databases for studies from database inception to March 30, 2023. All English-language articles available in full text have been considered. Excluded are commentaries, editorials, letters, and abstracts.
EVIDENCE SYNTHESIS: Obesity in LDRT raises long-term ESRD risk. Current high BMI donor admission raises ethical and clinical concerns. Encouraging timely weight loss can make obese candidates suitable donors, reducing risks. Sleeve gastrectomy is the most reported and preferable approach, since it minimizes hyperoxaluria risk. Re-evaluation for donation is possible 6-12 months post-BS, with BMI<35 for three months. Cost-benefit analysis favors BS over nephrectomy in obese donors (cost-benefit ratio: 3.64) when graft survival is equal.
CONCLUSIONS: BS shows promise with short-term effectiveness and potential long-term outcomes. However, it should not be perceived as a means to expand the donor pool but rather as a personalized approach to address obesity and improve individuals' health.
A process for preparing CaCO3 abrasive coated with pyrophosphate comprises contacting unhalogenated pulverized CaCO3 having an everage particle size of 0.2-30μ in a liq. dispersion with an alkali metal pyrophosphate source at the reaction temp. to produce a pyrophosphate deriv., to chemisorb 0.42-21 wt.% of P2O5 based on total wt. of abrasive on the CaCO3 particle surface.  The CaCO3 abrasive is used in dentifrice compsns. e.g. tooth powders and toothpastes.
This study investigates the sensory processing of typically developing toddlers with and without sleep problems. The research group consisted of typically developing toddlers with sleep problems (n = 110, mean age=18.35 ± 3.4 months), while the control group included typically developing toddlers without sleep problems (n = 110, mean age=18.67 ± 3.5 months) and their mothers. Toddlers were assigned to the research and control groups based on their sleep problems, as determined by the Brief Infant Sleep Questionnaire. The sensory processing of the toddlers was evaluated using the Infant/Toddler Sensory Profile 2. Sensory patterns and sensory processing sub-parameters of the research and control groups were compared. The sensory processing of the research group showed atypical behavioral responses in low registration (low awareness or indifferent attitude to sensory stimuli), sensory sensitivity (distracted or irritable attitude, intensely stimulated by sensory stimuli), and sensory avoiding (intentional avoidance of sensory stimuli or attitudes that produce out-of-norm responses) patterns compared to the control group (p < 0.05). Behavioral responses were similar in the sensory seeking (disturbing or dangerous attitude to the environment in search of sensory stimuli) pattern (p > 0.309). Statistically significant differences were observed in all sub-parameters of sensory processing compared to the control group. Our findings indicate that toddlers with sleep problems are at risk for sensory processing issues. Toddlers with sleep problems exhibit atypical sensory responses related to sensory sensitivity, low registration, and sensory avoiding. It should be considered that toddlers with sleep problems may show sensitivity to different sensory stimuli, avoidance or may not be able to recognize sensory stimuli. These findings suggest that the inclusion of sensory profile assessments in interdisciplinary care for toddlers with sleep problems may contribute to parent-infant well-being.
The study includes one session that will last approximately 2 - 3 hours. The study involves interactions with digital assistants developed by the research team, the participants will answer structured interview questions regarding their experiences using the system. The researchers will assess the participants' comments along dimensions such as type of information requested, preference for format of information, points of confusion, and likes and dislikes of features, which will form the basis for a prioritized list of features/functions to be modified for the next prototype iteration.
A deep sea water organic extract comprises solid organic substances. The solid organic substances are obtained by extracting sea water with C18 filtration film. The solid organic substances do not pass the C18 filtration film and are kept and accumulated on a surface of the C18 filtration film. The sea water constituents comprise at least one type of sea water formed of the following group: deep sea water and processed deep sea water, wherein the processed deep sea water is formed by introducing the deep sea water into at least one filtration unit that comprises a microfiltration membrane to conduct a filtration operation. The deep sea water organic extracts have effects of suppressing activity of NO synthetase or cyclooxygenase, suppressing growth of Helicobacter pylori, suppressing atherosclerosis, suppressing vascular hyperplasia and mobility, and reducing blood fat. The present invention also provides a fabrication method of the deep sea water organic extracts and a use of the deep sea water organic extracts.
Functional constipation, a highly prevalent functional gastrointestinal disorder, often accompanies by mental and psychological disorders. Previous neuroimaging studies have demonstrated brain functional and structural alterations in patients with functional constipation. However, little is known about whether and how regional homogeneity is altered in these patients. Moreover, the potential genetic mechanisms associated with these alterations remain largely unknown. The study included 73 patients with functional constipation and 68 healthy controls, and regional homogeneity comparison was conducted to identify the abnormal spontaneous brain activities in patients with functional constipation. Using Allen Human Brain Atlas, we further investigated gene expression profiles associated with regional homogeneity alterations in functional constipation patients with partial least squares regression analysis applied. Compared with healthy controls, functional constipation patients demonstrated significantly decreased regional homogeneity in both bilateral caudate nucleus, putamen, anterior insula, thalamus and right middle cingulate cortex, supplementary motor area, and increased regional homogeneity in the bilateral orbitofrontal cortex. Genes related to synaptic signaling, central nervous system development, fatty acid metabolism, and immunity were spatially correlated with abnormal regional homogeneity patterns. Our findings showed significant regional homogeneity alterations in functional constipation patients, and the changes may be caused by complex polygenetic and poly-pathway mechanisms, which provides a new perspective on functional constipation's pathophysiology.
PURPOSE: This study aimed to analyze the incidence and characteristics of intraocular lens (IOL) dislocation after cataract surgery in South Korea.
METHODS: We retrospectively analyzed the incidence of IOL dislocation after cataract surgery in patients diagnosed between 2002 and 2021. Data of all pseudophakic patients who underwent secondary IOL or IOL exchange surgeries due to IOL dislocation were extracted from the Korean National Health Insurance System database and the Korean Standard Classification of Diseases 7th Revision codes. The incidence per 1,000,000 person-years and corresponding 95% confidence intervals (CIs) were calculated.
RESULTS: Between 2002 and 2021, 39,965 of the 4,848,125 pseudophakic patients (0.82%) were diagnosed with IOL dislocation and surgically treated. The incidence of IOL dislocation requiring surgery in pseudophakic patients was 28,900 per 1,000,000 person-years (95% CI, 28,431-29,369), comprising 57,800 cases in male (95% CI, 56,730-58,870) and 10,800 in female patients (95% CI, 10,523-11,077), and the mean male to female ratio was 5.35. The incidence rate peaked in younger age group below 40 years, showing 107,000 per 1,000,000 person-years (95% CI, 102,900-111,100), and the average age of IOL dislocation requiring surgery was 68.1 ± 10.7 years. The average time lapse from cataract surgery to secondary IOL surgery due to IOL dislocation was 4.1 ± 4.7 years (median, 2.2 years), and the number of secondary IOL surgery due to dislocation of artificial lensrapidly occurred 10 years after cataract surgery among all age groups.
CONCLUSIONS: The incidence of IOL dislocation requiring surgery was higher in younger and male patients. Our findings could be expected to aid establishing future healthcare policies for South Korean populations with an increased risk of IOL dislocation after cataract surgery.
The invention relates to traditional Chinese medicine red sage root-motherwort powder for treating infertility. The traditional Chinese medicine red sage root-motherwort powder is mainly used for solving the problem that the current drugs for treating infertility are poor in treatment effect and have side effects. The traditional Chinese medicine red sage root-motherwort powder is prepared through the steps of weighing 9g of prepared monkshood, 9g of prepared kusnezoff monkshood, 15g of red sage root and 15g of motherwort, baking all the traditional Chinese medicines except for asarum, and then, co-grinding into fine powder together with asarum. The usage and dosage are as follows: the powder is orally taken once in the morning, noon and evening of a day by 17g every time, and liquor is taken as a guide; the powder is orally taken about one week after menstruation; a treatment course comprises the continuous taking of two prescriptions; in case of not work, the powder can be orally taken in such a way at next menstrual onset. The traditional Chinese medicine red sage root-motherwort powder has the aims and advantages that the total effective rate for infertility treatment is over 95%, and the cure rate is over 80%. The traditional Chinese medicine red sage root-motherwort powder is free from toxic and side effects.
UNLABELLED: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a KRAS-driven inflammatory program and a desmoplastic stroma, which contribute to the profoundly chemoresistant phenotype. The tumor stroma contains an abundance of cancer-associated fibroblasts (CAF), which engage in extensive paracrine cross-talk with tumor cells to perpetuate protumorigenic inflammation. IL1α, a pleiotropic, tumor cell-derived cytokine, plays a critical role in shaping the stromal landscape. To provide insights into the molecular mechanisms regulating IL1A expression in PDAC, we performed transcriptional profiling of The Cancer Genome Atlas datasets and pharmacologic screening in PDAC cells and identified p38α MAPK as a key positive regulator of IL1A expression. Both genetic and pharmacologic inhibition of p38 MAPK significantly diminished IL1α production in vitro. Chromatin- and coimmunoprecipitation analyses revealed that p38 MAPK coordinates the transcription factors Sp1 and the p65 subunit of NFκB to drive IL1A overexpression. Single-cell RNA sequencing of a highly desmoplastic murine PDAC model, Ptf1aCre/+; LSL-KrasG12D/+; Tgfbr2flox/flox (PKT), confirmed that p38 MAPK inhibition significantly decreases tumor cell-derived Il1a and attenuates the inflammatory CAF phenotype in a paracrine IL1α-dependent manner. Furthermore, p38 MAPK inhibition favorably modulated intratumoral immunosuppressive myeloid populations and augmented chemotherapeutic efficacy to substantially reduce tumor burden and improve overall survival in PKT mice. These findings illustrate a cellular mechanism of tumor cell-intrinsic p38-p65/Sp1-IL1α signaling that is responsible for sustaining stromal inflammation and CAF activation, offering an attractive therapeutic approach to enhance chemosensitivity in PDAC.
SIGNIFICANCE: Inhibition of p38 MAPK suppresses tumor cell-derived IL1α and attenuates the inflammatory stroma and immunosuppressive tumor microenvironment to overcome chemotherapeutic resistance in pancreatic cancer.
BACKGROUND: Although chimeric antigen receptor T (CAR-T) cells have been proven to be an effective way of treating B cell malignancies, a lot of patients could not benefit from it because of failure in CAR-T cell manufacturing, disease progression, and unaffordable price. The study aimed to explore universal CAR-T cell products to extend the clinical accessibility.
METHODS: The antitumor activity of CRISPR/Cas9-edited allogeneic anti-CD19 CAR-T (CAR-T19) cells was assessed in vitro, in animal models, and in patients with relapsed/refractory (R/R) acute B cell lymphoblastic leukemia (B-ALL) or diffuse large B cell lymphoma.
RESULTS: B2M-/TRAC- universal CAR-T19 (U-CAR-T19) cells exhibited powerful anti-leukemia abilities both in vitro and in animal models, as did primary CD19+ leukemia cells from leukemia patients. However, expansion, antitumor efficacy, or graft-versus-host-disease (GvHD) was not observed in six patients with R/R B cell malignancies after U-CAR-T19 cell infusion. Accordingly, significant activation of natural killer (NK) cells by U-CAR-T19 cells was proven both clinically and in vitro. HLA-A-/B-/TRAC- novel CAR-T19 (nU-CAR-T19) cells were constructed with similar tumoricidal capacity but resistance to NK cells in vitro. Surprisingly, robust expansion of nU-CAR-T19 cells, along with rapid eradication of CD19+ abnormal B cells, was observed in the peripheral blood and bone marrow of another three patients with R/R B-ALL. The patients achieved complete remission with no detectable minimal residual disease 14 days after the infusion of nU-CAR-T19 cells. Two of the three patients had grade 2 cytokine release syndrome, which were managed using an IL-6 receptor blocker. Most importantly, GvHD was not observed in any patient, suggesting the safety of TRAC-disrupted CAR-T cells generated using the CRISPR/Cas9 method for clinical application.
CONCLUSIONS: The nU-CAR-T19 cells showed a strong response in R/R B-ALL. nU-CAR-T19 cells have the potential to be a promising new approach for treating R/R B cell malignancies.
The present invention is related to benzoxazole acetonitriles as well as to pharmaceutical formulations containing such benzoxazole acetonitriles pof formula (I). Said benzoxazole acetonitriles are useful in the treatment of metabolic disorders mediated by insulin resistance or hyperglycemia, comprising diabetes type II, inadequate glucose tolerance, insulin resistance, obesity, polycystic ovary syndrome (PCOS). The present invention is furthermore related to methods of preparing benzoxazole acetonitriles (I). A is a pyrimidinyl.L is a secondary or tertiary amino group, or a 3-8 membered heterocycloalkyl, containing at least one heteroatom. selected from N, O, S or L is an acylamino moiety. R 1  is selected from the group comprising or consisting of hydrogen, sulfonyl, amino, C 1 C 6 -alkYl, C 2 -C 6 -alkenYl, C 2 -C 6 -alkynyl or C 1 -C 6 -alkoxy, aryl, halogen, carboxy, aminocarbonyl, cyano or hydroxy.
BACKGROUND: Chronic kidney disease (CKD) presents a significant clinical and economic burden to healthcare systems worldwide, which increases considerably with progression towards kidney failure. The Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial demonstrated that patients with or without type 2 diabetes who were treated with dapagliflozin experienced slower progression of CKD versus those receiving placebo. Understanding the effect of long-term treatment with dapagliflozin on the timing of kidney failure beyond trial follow-up can assist informed decision-making by healthcare providers and patients. The study objective was therefore to extrapolate the outcome-based clinical benefits of treatment with dapagliflozin in patients with CKD via a time-to-event analysis using trial data.
METHODS: Patient-level data from the DAPA-CKD trial were used to parameterize a closed cohort-level partitioned survival model that predicted time-to-event for key trial endpoints (kidney failure, all-cause mortality, sustained decline in kidney function and hospitalization for heart failure). Data were pooled with a subpopulation of the Dapagliflozin Effect on Cardiovascular Events - Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) trial to create a combined CKD population spanning a range of CKD stages; a parallel survival analysis was conducted in this population.
RESULTS: In the DAPA-CKD and pooled CKD populations, treatment with dapagliflozin delayed time to first event for kidney failure, all-cause mortality, sustained decline in kidney function and hospitalization for heart failure. Attenuation of CKD progression was predicted to slow the time to kidney failure by 6.6 years [dapagliflozin: 25.2, 95% confidence interval (CI) 19.0-31.5; standard therapy: 18.5, 95% CI 14.7-23.4] in the DAPA-CKD population. A similar result was observed in the pooled CKD population with an estimated delay of 6.3 years (dapagliflozin: 36.0, 95% CI 31.9-38.3; standard therapy: 29.6, 95% CI 25.5-34.7).
CONCLUSION: Treatment with dapagliflozin over a lifetime time horizon may considerably delay the mean time to adverse clinical outcomes for patients who would go on to experience them, including those at modest risk of progression.
Patients will receive 30 - 40 Gy in 4 - 5 fractions. For high risk patients who also receive external beam radiotherapy, the SBRT will be given as 19 - 21 Gy in 2 - 3 fractions.
The multiplace HBOT unit at Asaf Harofeh. The inside looks like an airplane, with comfortable chairs for 11 subjects and the nurse who stays throughout the session. The HBOT protocol is 90 minutes, 5 times/week, 60 sessions, 100% oxygen at 2 ATA with 5 minute air breaks every 30 minutes.
OBJECTIVE: Chronic kidney disease (CKD) is a condition influenced by both genetic and environmental factors and has been a focus of extensive research. Utilizing Mendelian randomization, researchers have begun to untangle the complex causal relationships underlying CKD. This review delves into the advances and challenges in the application of MR in the field of nephrology, shifting from a mere summary of its principles and limitations to a more nuanced exploration of its contributions to our understanding of CKD.
METHODS: Key findings from recent studies have been pivotal in reshaping our comprehension of CKD. Notably, evidence indicates that elevated testosterone levels may impair renal function, while higher sex hormone-binding globulin (SHBG) levels appear to be protective, predominantly in men. Surprisingly, variations in plasma glucose and glycated hemoglobin levels seem unaffected by genetically induced changes in the estimated glomerular filtration rate (eGFR), suggesting an independent pathway for renal function impairment.
RESULTS: Furthermore, lifestyle factors such as physical activity and socioeconomic status emerge as significant influencers of CKD risk and kidney health. The relationship between sleep duration and CKD is nuanced; short sleep duration is linked to increased risk, while long sleep duration does not exhibit a clear causal effect. Additionally, lifestyle factors, including diet, exercise, and mental wellness activities, play a crucial role in kidney health. New insights also reveal a substantial causal connection between both central and general obesity and CKD onset, while no significant links were found between genetically modified LDL cholesterol or triglyceride levels and kidney function.
CONCLUSION: This review not only presents the recent achievements of MR in CKD research but also illuminates the path forwards, underscoring critical unanswered questions and proposing future research directions in this dynamic field.
We propose a parametric model for describing chronic disease mortality from cohort data and illustrate its use for Type 2 diabetes. The model uses ideas from accelerated life testing in reliability theory and conceptualizes the occurrence of a chronic disease as putting the observational unit to an enhanced stress level, which is supposed to shorten its lifetime. It further addresses the issue of semi-competing risk, that is, the asymmetry of death and diagnosis of disease, where the disease can be diagnosed before death, but not after. With respect to the cohort structure of the data, late entry into the cohort is taken into account and prevalent as well as incident cases inform the analysis. We finally give an extension of the model that allows age at disease diagnosis to be observed not exactly, but only partially within an interval. Model parameters can be straightforwardly estimated by Maximum Likelihood, using the assumption of a Gompertz distribution we show in a small simulation study that this works well. Data of the Cardiovascular Disease, Living and Ageing in Halle (CARLA) study, a population-based cohort in the city of Halle (Saale) in the eastern part of Germany, are used for illustration.