anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Supporting cell proliferation through nucleotide biosynthesis is an essential requirement for cancer cells. Hence, inhibition of folate-mediated one carbon (1C) metabolism, which is required for nucleotide synthesis, has been successfully exploited in anti-cancer therapy. Here, we reveal that mitochondrial folate metabolism is upregulated in patient-derived leukaemic stem cells (LSCs). We demonstrate that inhibition of mitochondrial 1C metabolism through impairment of de novo purine synthesis has a cytostatic effect on chronic myeloid leukaemia (CML) cells. Consequently, changes in purine nucleotide levels lead to activation of AMPK signalling and suppression of mTORC1 activity. Notably, suppression of mitochondrial 1C metabolism increases expression of erythroid differentiation markers. Moreover, we find that increased differentiation occurs independently of AMPK signalling and can be reversed through reconstitution of purine levels and reactivation of mTORC1. Of clinical relevance, we identify that combination of 1C metabolism inhibition with imatinib, a frontline treatment for CML patients, decreases the number of therapy-resistant CML LSCs in a patient-derived xenograft model. Our results highlight a role for folate metabolism and purine sensing in stem cell fate decisions and leukaemogenesis.
Participants first received Linagliptin 5 mg tablet 1 tablet (Test product) in a fasting state. After a washout period of 1 week, they then received Trajecta 5 mg tablet (Reference product) in a fasting state.
Risk Summary

There is no information on the presence of elagolix or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. When estrogen and progestins are administered to lactating women, these compounds and/or their metabolites are detected in human milk and can reduce milk production in breast-feeding females. This reduction can occur at any time but is less likely to occur once breast-feeding is well established. Advise the nursing female to use non-hormonal contraception until she discontinues breast-feeding. The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for ORIAHNN and any potential adverse effects on the breast-fed child from ORIAHNN or from the underlying maternal condition [see Data]. 

Data

There is no information on the presence of elagolix or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Estrogen administration to nursing women has been shown to decrease the quantity and quality of the breast milk. Detectable amounts of estrogen and progestin have been identified in the breast milk of women receiving estrogen and progestin combinations. 

There are no adequate animal data on excretion of elagolix in milk.
The invention relates to a treatment method for mumps. The method is characterized in that: it involves the following ingredients: 100g of green beans, 30g of wild chrysanthemum, 30g of small red bean powder, 20g of water chestnuts, 20g of raw lotus roots, 20g of fresh couchgrass roots, a bag of radix isatidis, 4 folium isatidis particles, and 4 Vitamin C Yinqiao tablets. The method includes: adding the green beans, wild chrysanthemum, small red bean powder, water chestnuts, raw lotus roots, fresh couchgrass roots and water into a small pot, conduct decoction for 30min by slow fire, pouring out a cup of juice, smashing the radix isatidis, folium isatidis particles, and Vitamin C Yinqiao tablets into powder, and adding the powder into the cup, stirring the mixture evenly, and taking 200ml of the mixture every time, three times every day for 10 days, thus curing mumps. The method can cooperate with external application of drugs to improve the curative effect. Among 50 treatment cases, the method takes effect in 90% of the cases. The method provides a solution to the problems that existing traditional drugs for treating mumps have unobvious and slow effects, and have certain side effect on the human body mechanism, even can disorder patients' metabolism, reduce the human body immunity, and are likely to cause other complications.
BACKGROUND: The residual burden of coronary artery disease (CAD) after percutaneous coronary intervention (PCI) drew a growing interest. The residual SYNTAX Score (rSS) was a strong prognostic factor of adverse events and all-cause mortality in patients who underwent PCI. In addition, the SYNTAX Revascularization Index (SRI), a derivative of rSS, was used to figure out the treated proportion of CAD and could be used as a prognostic utility in PCI for patients with multi-vessel disease (MVD).
PURPOSE: We aimed at the assessment of the use of rSS and the SRI as predictors of in-hospital outcomes and up to two-year cumulative follow-up outcomes in patients with MVD who had PCI for the treatment of ST-Elevation Myocardial Infarction (STEMI) or Non-STEMI (NSTEMI).
METHODS: We recruited 149 patients who had either STEMI or NSTEMI while having MVD and received treatment with PCI. We divided them into tertiles based on their rSS and SRI values. We calculated baseline SYNTAX Score (bSS) and rSS using the latest version of the calculator on the internet, and we used both scores to calculate SRI. The study end-points were In-hospital composite Major Adverse Cardiovascular Events (MACE) and its components, in-hospital death, and follow-up cumulative MACE up to 2 years.
RESULTS: Neither rSS nor SRI were significant predictors of in-hospital adverse events, while female sex, hypertension, and left ventricular ejection fraction were independent predictors of in-hospital MACE. At the two-year follow-up, Kaplan-Meyer analysis showed a significantly increased incidence of MACE within the third rSS tertile (rSS > 12) compared to other tertiles (log rank p = 0.03). At the same time, there was no significant difference between the three SRI tertiles. Unlike SRI, rSS was a significant predictor of cumulative MACE on univariate Cox regression (HR = 1.037, p < 0.001). On multivariate Cox regression, rSS was a significant independent predictor of two-year cumulative MACE (HR = 1.038, p = 0.0025) along with female sex, hypertension, and left ventricular ejection fraction. We also noted that all patients with complete revascularization survived well throughout the entire follow-up period.
CONCLUSIONS: Neither rSS nor SRI could be good predictors of in-hospital MACE, while the rSS was a good predictor of MACE at two-year follow-up. Patients with rSS values > 12 had a significantly higher incidence of cumulative MACE after 2 years. The best prognosis was achieved with complete revascularization.
BACKGROUND: Approximately 60% of patients with colorectal liver metastases (CRLM) experience relapse within 2 years after radical resection, previous studies have proven that repeat local treatment (LT) could prolong survival, however, it is difficult to seize the window for LT due to the lack of a high-sensitive surveillance method. In this study, the authors aim to examine the value of longitudinal circulating tumor DNA (ctDNA) in guiding adjuvant chemotherapy, optimizing clinical surveillance strategy, and thereby improving CRLM outcomes.
MATERIALS AND METHODS: The authors conducted a prospective clinical trial using a personalized, tumor-informed ctDNA assay to monitor 60 CRLM patients undergoing resection with curative intent. Formalin-fixed paraffin-embedded tumor samples were collected after surgery. Blood samples were collected before surgery, 30 days after surgery (post-OP), and every third month until relapse or up to 2 years.
RESULTS: A total of 394 plasma samples from 60 eligible patients were analyzed, with a median follow-up time of 31.3 months. Landmark analyses revealed that detectable ctDNA at post-OP (HR, 4.8), postadjuvant chemotherapy (HR, 6.0), and end-of-treatment (HR, 5.6) were associated with higher recurrence risk ( P <0.001). Post-OP ctDNA positivity served as the only independent prognostic marker in the multivariant analysis (HR, 5.1; P <0.001). Longitudinal ctDNA analysis identified relapsed patients at both sensitivity and specificity of 100%. Most (75%) patients were found with radiological relapse within 6 months after the first detectable ctDNA with a median lead time of 3.5 months. In relapsed patients, 73.2% had oligometastatic disease and 61% were liver-restricted, of which 72.0% received repeat LTs, and 60.0% achieved a secondary no evidence of disease status.
CONCLUSIONS: Longitudinal ctDNA monitoring assists in early prediction of relapse, and thereby improves survival of CRLM patients by increased secondary resection rate and secondary no evidence of disease rate.
Minocycline (Min), as an antibiotic, possesses various beneficial properties such as anti-inflammatory, antioxidant, and anti-apoptotic effects. Despite these known qualities, the precise cardioprotective effect and mechanism of Min in protecting against sepsis-induced cardiotoxicity (SIC) remain unspecified. To address this, our study sought to assess the protective effects of Min on the heart. Lipopolysaccharide (LPS) was utilized to establish a cardiotoxicity model both in vivo and in vitro. Min was pretreated in the models. In the in vivo setting, evaluation of heart tissue histopathological injury was performed using hematoxylin and eosin (H&E) staining and TUNEL. Immunohistochemistry (IHC) was employed to evaluate the expression levels of NLRP3 and Caspase-1 in the heart tissue of mice. During in vitro experiments, the viability of H9c2 cells was gauged utilizing the CCK8 assay kit. Intracellular ROS levels in H9c2 cells were quantified using a ROS assay kit. Both in vitro and in vivo settings were subjected to measurement of oxidative stress indexes, encompassing glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) levels. Additionglly, myocardial injury markers like lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB) activity were quantified using appropriate assay kits. Western blotting (WB) analysis was conducted to detect the expression levels of NOD-like receptor protein-3 (NLRP3), caspase-1, IL-18, and IL-1β, alongside apoptosis-related proteins such as Bcl-2 and Bax, and antioxidant proteins including superoxide dismutase-1 (SOD-1) and antioxidant proteins including superoxide dismutase-1 (SOD-2), both in H9c2 cells and mouse heart tissues. In vivo, Min was effective in reducing LPS-induced inflammation in cardiac tissue, preventing cell damage and apoptosis in cardiomyocytes. The levels of LDH and CK-MB were significantly reduced with Min treatment. In vitro studies showed that Min improved the viability of H9C2 cells, reduced apoptosis, and decreased ROS levels in these cells. Further analysis indicated that Min decreased the protein levels of NLRP3, Caspase-1, IL-18, and IL-1β, while increasing the levels of SOD-1 and SOD-2 both in vivo and in vitro. Min alleviates LPS-induced SIC by suppressing the NLRP3/Caspase-1 signalling pathway in vivo and in vitro.
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Rats treated with nicardipine in the diet (at concentrations calculated to provide daily dosage levels of 5, 15, or 45 mg/kg/day) for two years showed a dose-dependent increase in thyroid hyperplasia and neoplasia (follicular adenoma/carcinoma). One- and three-month studies in the rat have suggested that these results are linked to a nicardipine-induced reduction in plasma thyroxine (T4) levels with a consequent increase in plasma levels of thyroid stimulating hormone (TSH). Chronic elevation of TSH is known to cause hyperstimulation of the thyroid. 

In rats on an iodine deficient diet, nicardipine administration for one month was associated with thyroid hyperplasia that was prevented by T4 supplementation. Mice treated with nicardipine in the diet (at concentrations calculated to provide daily dosage levels of up to 100 mg/kg/day) for up to 18 months showed no evidence of neoplasia of any tissue and no evidence of thyroid changes.

There was no evidence of thyroid pathology in dogs treated with up to 25 mg nicardipine/kg/day for one year and no evidence of effects of nicardipine on thyroid function (plasma T4 and TSH) in man.

There was no evidence of a mutagenic potential of nicardipine in a battery of genotoxicity tests conducted on microbial indicator organisms, in micronucleus tests in mice and hamsters, or in a sister chromatid exchange study in hamsters.

No impairment of fertility was seen in male or female rats administered nicardipine at oral doses as high as 100 mg/kg/day (human equivalent dose about 16 mg/kg/day, 8 times the maximum recommended oral dose).

13.3 Reproductive and Developmental Toxicology

Embryotoxicity, but no teratogenicity, was seen at intravenous doses of 10 mg nicardipine/kg/day in rats and 1 mg/kg/day in rabbits. These doses in the rat and rabbit are equivalent to human IV doses of about 1.6 mg/kg/day and 0.32 mg/kg/day respectively. (The total daily human dose delivered by a continuous IV infusion ranges from 1.2 to 6 mg/kg/day, depending on duration at different infusion rates ranging from 3 to 15 mg/hr as individual patients are titrated for optimal results.) Nicardipine was also embryotoxic when administered orally to pregnant Japanese White rabbits, during organogenesis, at 150 mg/kg/day (a dose associated with marked body weight gain suppression in the treated doe), but not at 50 mg/kg/day (human equivalent dose about 16 mg/kg/day or about 8 times the maximum recommended human oral dose). No adverse effects on the fetus were observed when New Zealand albino rabbits were treated orally, during organogenesis, with up to 100 mg nicardipine/kg/day (a dose associated with significant mortality in the treated doe). In pregnant rats administered nicardipine orally at doses of up to 100 mg/kg/day (human equivalent dose about 16 mg/kg/day) there was no evidence of embryotoxicity or teratogenicity. However, dystocia, reduced birth weight, reduced neonatal survival and reduced neonatal weight gain were noted.
Specific aims of this project are: 1) to establish a primary care based and parent-mediated childhood overweight intervention program based on the Chronic Care Model in the primary care setting, 2) to explore the efficacy of this intervention in improving the weight status of children, 3) to examine the acceptability and feasibility of the approach among primary care providers and parents. Clinic providers and study personnel will be trained in the use of brief motivational interviewing (brief MI) for the visits and phone calls. The American Academy of Pediatrics 15-Minute Obesity Prevention Protocol will be used for individual visits while the NIH We Can! curriculum and materials will be used for group visits. Parents in the control group will receive the We Can! Parent Handbook and usual care. The intervention is designed to facilitate efficient communication of advice about behavior change, nutrition, and physical activity to parents. Partnership of primary care providers with parents and use of brief intervention techniques and group visits can be a practical approach. If proven to be effective, this approach can serve as an exportable model to other primary care practices and will reach a large proportion of the population and have far-reaching effects.
BACKGROUND: Information about follow-up care in blood cancer survivors is limited. The questionnaire-based "Aftercare in Blood Cancer Survivors" (ABC) study aimed to identify patterns of follow-up care in Germany and compare different types of follow-up institutions.
METHODS: The study's 18-month prospective part compared the follow-up institutions identified in the preceding retrospective part (academic oncologists, community oncologists, primary care physicians). The questionnaires were completed by the follow-up physicians.
RESULTS: Of 1070 physicians named by 1479 blood-cancer survivors, 478 (44.7%) consented to participate. For provision of care, most oncologists relied on published guidelines, while most primary care physicians depended on information from other physicians. Survivors with a history of allogeneic transplantation or indolent lymphoma were mainly seen by academic oncologists, whereas survivors with monoclonal gammopathy, multiple myeloma, or myeloproliferative disorders were often seen by community oncologists, and survivors with a history of aggressive lymphoma or acute leukemia by primary care physicians. Detection of relapse and secondary diseases was consistently viewed as the most important follow-up goal. Follow-up visits were most extensively documented by academic oncologists (574 of 1045 survivors cared for, 54.9%), followed by community oncologists (90/231, 39.0%) and primary care physicians (51/203, 25.1%). Relapse and secondary disease detection rates and the patients' quality of life were similar at the three institutions. Laboratory tests were most often ordered by academic oncologists, and imaging by primary care physicians. Psychosocial issues and preventive care were more often addressed by primary care physicians than by oncologists.
CONCLUSIONS: Patients at high risk of relapse or late complications were preferentially treated by academic oncologists, while patients in stable condition requiring continuous monitoring were also seen by community oncologists, and patients with curable diseases in long-term remission by primary care physicians. For the latter, transfer of follow-up care from oncologists to well-informed primary care providers appears feasible.
FIELD: organic chemistry and technology. SUBSTANCE: invention relates to new methods of synthesis of compound of the general formula (I) where R - lower alkyl; R 1  - hydrogen atom; R 2  - lower alkyl, lower cycloalkyl; lower cycloalkyl-lower alkyl, lower bicycloalkyl, aryl or aryl-lower alkyl, or R 1  and R 2  form with nitrogen atom to which they are bound the group 3,4-dihydro-2(1H)-isoquinoline; X - lower alkyl, lower alkoxy, halogen atom or trifluoromethyl group; m = 0, 1 or 2. Synthesis is carried out by interaction of compound of the general formula (II) where R, X and m have values indicated above and R 3  - lower alkyl with alkyl-lithium or alkaline metal alcoholate followed by interaction with carboxylic acid of the general formula R 5 -COOH where R 5  - lower alkyl and compound of the general formula (III) where R, X and m have values indicated above is obtained. Then synthesis involves interaction of reaction mass containing compound of the general formula (III) with isocyanate of the general formula R 2 -NCO and compound of the general formula (I) where R 1  - hydrogen atom is obtained, or compound of the general formula (IV) where R 4  - hydrogen atom or lower alkyl in the presence of carboxylic acid of the general formula R 5 -COOH where R 5  has value indicated above and compound of the general formula (V) where R, R 4 , X and m have values indicated above is obtained by contact of reaction mixture containing the compound of the general formula (V) with compound of the general formula R 1 R 2 -NH where R 1  and R 2  have values indicated above and isolation of compound of the general formula (I). EFFECT: improved method of synthesis. 19 cl, 1 tbl
This is a two-centre prospective cohort study in very preterm infants born below 32 0/7 weeks PMA and hospitalised in the neonatal intensive care units at the University Children's Hospital Basel and the Inselspital Berne during two years. After informed consent a sample of 0.5 mL ethylenediaminetetraacetic acid (EDTA) full blood will be taken on day 7 of life (+/- 2 days) during routine blood sampling. The biomarkers which are planned to measure include the C-terminal portion of the proendothelin-1 precursor (CT-proendothelin (proET)-1) and other plasma biomarkers of respiratory distress. At 36 weeks PMA, lung function testing will be performed during quiet unsedated sleep in supine position approximately 30 minutes post feeding. After placement of a facemask, tidal breathing will be recorded at the bedside using a commercially available ultrasonic flow meter (Spiroson, Exhalyzer D, Ecomedics, CH) according to American Thoracic Society (ATS) and European Respiratory Society (ERS) standards of infant lung function testing. Different capnographic indices will be calculated to investigate if they reflect the degree of lung disease at 36 weeks PMA.
The invention discloses a nano-molybdenum sulfide antibacterial material and a synthetic method thereof and application thereof. The synthetic method comprises the following steps: (1) dissolving polyethylene glycol solid in water, performing ultrasonic processing in an ultrasonic pool until the polyethylene glycol is dissolved completely, adding ammonium heptamolybdate solid, and performing ultrasonic processing until the ammonium heptamolybdate is dissolved completely to obtain a mixed solution; and (2) dissolving thiourea solid in water, dissolving the thiourea with stirring, adding the dissolved thiourea into the mixed solution, stirring the mixture, putting the mixture into a hydrothermal reactor having a polytetrafluoroethylene inner container, sealing the reactor, and performing heating reaction to obtain a black precipitate which is the nano-molybdenum sulfide antibacterial material. The invention also provides the nano-molybdenum sulfide antibacterial material which is prepared by the synthetic method. The invention also provides application of the nano-molybdenum sulfide antibacterial material on synergistic anti-microbial combining biomimetic catalysis hydrogen peroxide and near-infrared optothermal. The nano-molybdenum sulfide antibacterial material prepared by the synthetic method in the invention has high yield, and can be captured easily by bacteria. Moreover, the antibacterial effect of the material is obviously better than that of single biomimetic catalysis anti-microbial or single near-infrared optothermal anti-microbial.
Participants randomized to the Intervention Group will be engaged in a 3-month randomized controlled trial and receive the PLP+SDoH curriculum from a trained Community Health Worker (CHW). Each week during the 3 months, participants will meet for approximately 1-1.5 hours and be taught a PLP Lesson or engage in an SDoH activity. Participants will also be asked to undergo an assessment collection point at baseline recruitment and 3-month completion time.
The purpose of this action research, scholarship of teaching and learning study was to develop and integrate effective, student-informed teaching methods for voice acoustics instruction in a graduate speech-language pathology voice disorders course. An online focus group was used to determine what aspects of voice acoustics to include in the course as well as how these aspects were to be covered. A blend of face-to-face, technology-assisted, and practice-based teaching/learning activities resulted from the focused group and were employed in the course. An open-ended application question was used to measure student learning regarding application of voice acoustics to the understanding of human voice. A summative assessment of student recall and application of voice acoustics to speech-language pathology practice was also administered. Results showed significant, positive change pre- to post-course on the open-ended application question. Results of the summative assessment revealed that the largest distribution of student scores was in the 90%-100% range. While individual classes in different programs will differ, this project provides instructors with a baseline format from which to work to tailor acoustics instruction in their own classrooms.