anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
PCT No. PCT/JP94/00007 Sec. 371 Date Nov. 10, 1994 Sec. 102(e) Date Nov. 10, 1994 PCT Filed Jan. 6, 1994 PCT Pub. No. WO94/15934 PCT Pub. Date Jul. 21, 1994A quinoline-3-acetic acid derivative of the formula    <IMAGE>  (I)  wherein R1, R2 and R3 are the same or different and each is a hydrogen atom or a halogen atom, R4 is a hydrogen atom, a halogen atom or a substituted or unsubstituted lower alkyl, R5 is an optionally esterified carboxyl and the broken line means an optional presence of a double bond, and a pharmaceutically acceptable salt thereof. The novel compound of the formula (I) and a pharmaceutically acceptable salt thereof of the present invention have an aldose reductase inhibitory activity in mammals inclusive of human and are highly safe. Accordingly, they are useful as pharmaceutical compositions for the treatment of the complications of diabetes, such as faulty union of corneal injury, cataract, neurosis, retinopathy and nephropathy, particularly cataract and neurosis.
BACKGROUND & AIM: Sleep disorder is a growing concern, and calcium supplementation is often recommended as a potential intervention for sleep disorders. However, the causal relationship between calcium levels and the incidence of sleep disorders remains unclear. Mendelian randomization techniques utilizing genetic variants that affect calcium levels, can provide valuable insights into causality. This study aims to examine the association between calcium levels and sleep disorders in a diverse population that includes both adolescents and adults, and investigate the effects of calcium levels on sleep disorders.
METHODS: Mendelian randomization analysis was conducted using data from UK Biobank and FinnGen datasets. The inverse-variance weighting (IVW) was selected as the primary method. In addition, traditional mediation analysis was performed on a subset of the NHANES data spanning from 2007 to 2018.
RESULTS: Our findings provide evidence supporting a causal relationship between calcium intake and reduced risk of sleep disorders (beta = -0.079, SE = 0.0395, P = 0.0457). While not reaching statistical significance, other MR methods such as weighted median and Mr-Egger exhibited similar directional trends. Analysis of the NHANES cohort revealed a negative association between calcium levels and the prevalence of sleep disorders in male, black, and physically active populations. However, this association was not observed in other demographic groups.
CONCLUSION: Our results suggested that there is no significant correlation between calcium levels and sleep disorder in non-exercise populations. This raises concerns about the long-term high-dose calcium supplementation in clinical practice, which requires further investigation.
Physiotherapy re-education program based on the pre-activation of the transverse abdominal muscle, performed with progressive difficulty and supervised at all times by an expert physiotherapist. The intervention will last 4 weeks, with two weekly sessions of 30-35 minutes each. Sessions will be held individually.
PURPOSE:To make possible the diagnosis of various cancers by using a monoclonal antibody which reacts specifically with the cancer cells of the human gland as a reagent useful for measuring the corresponding antigen in the bodily fluid by immonoassay. CONSTITUTION:The monoclonal antibody which reacts specifically with the cancer cells of the human gland is formed from the hybridoma obtd. by the confluence of the immune cells of the mammal immunized by the cancer cells of the human lung gland and myeloma cells. This method for prepn. consists first in the prepn. of the hybridoma from the body by the conventional method. Mouse, etc. are generally used for the mammal to immunize the cancer cells of the human lung gland. The antibody generative cells are then made confluent with the myeloma cells. The hybridoma obtd. in the above-mentioned manner is cultured in an ordinary hybridoma selecting medium and the necessary hybridoma is separated. The diagnosis of various cancers is made possible by measuring the corresponding specific amtingens in the patient's blood by an immunological method using the monoclonal antibody.
Participants will take part in a prospective, single center, randomized, double-blind, clinical study of 2.0 g/day of SRT2104 or placebo (test material) administered orally as 0.25 g capsules. The study will evaluate the effect of 28 days of consecutive SRT2104 dosing upon muscle strength, metabolism and structure of the ankle muscle group following a 14 day leg immobilization period. The study will also evaluate pharmacokinetic parameters as well as the safety and tolerability of 2.0 g/day of SRT2104. Thirty-four (34) healthy male and female subjects aged 18-40, who fulfill the inclusion/exclusion criteria, will be enrolled in this study. Subjects will be randomized 1:1 to receive either 2.0 g/day of SRT2104 or placebo in a fed state for 28 consecutive days. Subjects will remain on a fixed dose of test material for all dosing days in the study.

Subjects will provide written informed consent and undergo screening assessments. If eligible and willing to participate, subjects will undergo baseline strength testing, muscle biopsy, MRI, and MRS evaluations on Day -1 to assess muscle strength, and metabolism. Participants will then commence a 28 day dosing period with test material. On the first day of dosing (Day 1), pharmacokinetic and safety assessments will be performed. On Day 15, after subjects have completed 14 days of dosing with test material, participants will repeat the muscle biopsy, strength testing, MRI evaluations, pharmacokinetic and safety assessments. Following the study assessments on Day 15, subjects will commence a 14 day immobilization period. The leg of the dominant leg will be immobilized with a temporary removable brace, and subjects will be instructed to ambulate using crutches for the duration of the immobilization period. Designated site staff will contact subjects via telephone on Day 18 and Day 24 to check on the subjects' wellbeing and ability to function while immobilized. Subjects will report to the study site on Day 21 during the 14 day immobilization period for assessment of the immobilized leg, including safety evaluations. On Day 28, following completion of the 14 day immobilization period, a muscle biopsy, skeletal muscle evaluations, pharmacokinetic and safety assessments will be performed. Subjects will return to the clinic for an End of Study visit 7 days (+/- 2 days) after the last dose of test material for follow up safety assessments. A follow-up safety call will be made to each subject approximately 30 days following their final dose of SRT2104 or placebo.
The research was carried out in randomized control, pretest-posttest, experimental and control group design. In the sample calculation of the study, 30 of the manager nurses were determined by using G\*Power analysis as the control group and were included randomly. No intervention was made in the control group. At the same time as the experimental group, the nurse administrators in the control group were also administered the Participant Information Form-Nurse Manager, PSI and DMSS.
BACKGROUND AND AIMS: Patients undergoing maintenance hemodialysis (MHD) experience increased mortality and cardiovascular disease (CVD) risks; however, the potential connection between pinch strength (PS) and the prognosis of these patients remains unknown. Consequently, this study aimed to comprehensively assess the influence of PS and handgrip strength (HGS) on both survival and cardiovascular events (CVE) in patients undergoing MHD.
METHODS: Data were gathered from patients undergoing MHD at the Hemodialysis Center of Guangzhou Red Cross Hospital in March 2021. We performed a retrospective follow-up spanning 24 months, with death serving as the primary endpoint for observation and CVE as the secondary endpoint. Multifactorial Cox regression analysis, Kaplan-Meier survival curves, trend tests, and restricted cubic spline were applied to explore the association.
RESULTS: During a 24-month follow-up, data were collected from 140 patients undergoing MHD with an average age of 66.71 ± 12.61 years. Among them, 52 (37.14%) experienced mortality, whereas 36 (40.00%) had CVE without baseline CVD. Kaplan-Meier survival curves demonstrated better survival rates and reduced CVE risk for patients in the second, third, and fourth quartiles compared with those in the first quartile for PS. Adjusted analyses in different models revealed higher PS levels were independently associated with all-cause mortality (major model, model 4, HR, 0.78; 95% CI, 0.64-0.95) but not with CVE risk (unadjusted HR, 0.90; 95% CI, 0.77-1.05). Compared with lower quartile PS levels, higher PS levels significantly reduced all-cause mortality (HR, 0.31; 95% CI, 0.10-1.02), and this trend remained consistent (P for trend = 0.021). Finally, the restricted cubic spline method using different models showed a linear relationship between PS and all-cause mortality (P > 0.05), when PS exceeded 4.99 kg, the all-cause mortality of MHD patients significantly decreased.
CONCLUSIONS: PS was independently associated with all-cause mortality but not with CVE in patients undergoing MHD.
STELARA ®is an immunosuppressant and may increase the risk of malignancy. Malignancies were reported among subjects who received STELARA ®in clinical trials [see Adverse Reactions (6.1)] . In rodent models, inhibition of IL-12/IL-23p40 increased the risk of malignancy [see Nonclinical Toxicology (13)] . 

The safety of STELARA ®has not been evaluated in patients who have a history of malignancy or who have a known malignancy. 

There have been post-marketing reports of the rapid appearance of multiple cutaneous squamous cell carcinomas in patients receiving STELARA ®who had pre-existing risk factors for developing non-melanoma skin cancer. Monitor all patients receiving STELARA ®for the appearance of non-melanoma skin cancer. Closely follow patients greater than 60 years of age, those with a medical history of prolonged immunosuppressant therapy and those with a history of PUVA treatment [see Adverse Reactions (6.1)] .
FIELD: biochemistry.SUBSTANCE: invention relates to biotechnology. Method for modifying a given target site in a target nucleic acid sequence in a host cell using a programmable nucleoprotein molecular complex is described. Programmable polypeptide or nucleic acid sequence encoding a programmable polypeptide is delivered to the host cell. Polypeptide comprises a functional domain capable of modifying said target site devoid of a specific nucleic acid binding site and a binding domain capable of interacting with a specificity contributing nucleic acid (SCNA), where the binding domain is devoid of the specific binding site of the target nucleic acid. Also specificity contributing nucleic acid (SCNA) molecule comprising at least 18 nucleotides, or a nucleic acid encoding SCNA, is delivered. SCNA molecule contains a nucleotide sequence complementary to the target nucleic acid portion and a recognition site capable of specifically attaching to the binding domain of the programmable polypeptide. Presence of a polypeptide in a host cell containing SCNA makes it possible to attach said polypeptide to SCNA, thereby forming an active, programmed nucleoprotein complex. As a result, the active programmed nucleoprotein complex is targeted to the target site in the target nucleic acid sequence in the host cell, which facilitates the modification of the target site by the said active programmed nucleoprotein complex. Composition comprising such a complex and corresponding vectors is also provided.EFFECT: programmable nucleoprotein molecular complex is capable of specifically modifying and /or correcting the target site in the target nucleic acid sequence and / or modifying the function of the target nucleic acid sequence.33 cl, 16 dwg, 12 ex
Growth faltering among Ethiopian infants and young children is one of the highest in sub-Saharan Africa. Nutrition education on infant and young child feeding has shown good potential to improve growth of young children whenever it is accessible, context-based and integrated with locally available resources. The current nutrition education in Ethiopia, however, appears to be general and lacks the essential components for success. It is mainly didactic and lacks a motivational approach that can enhance the self-efficacy of mothers for behavior change. Another important barrier for nutrition education to become effective is that rural mothers have limited access to nutrient-dense foods that are recommended to be fed to young children. Therefore, it is expected that low food access by poor households together with the less motivational approach used may hamper the effectiveness of the current nutrition education in the country. In Ethiopia, a child-centered counseling approach is hypothesized to be more effective than the current nutrition and health education when investment on home-based food production is used as a platform for nutrition education. This project is proposed to evaluate the efficacy of a food-based package integrating child-centered nutrition counseling and home-based food production using a between-group comparative intervention study. The intervention comprises child-centered nutrition counseling for caretakers and support for 'developed' gardens and improved backyard poultry production; whereas the control will only receive the agriculture extension and the existing health and nutrition education in the area. Two Primary Healthcare Units (one intervention and one control group) will be selected from Jimma Zone using relevant criteria. A total of 404 (i.e. 202 in each of intervention and control areas) households with infants of age \< 12 months will participate in the study for 18 months. The efficacy of the intervention will be assessed by its effect on child growth and infant and child feeding index as primary outcomes. Besides the effect on dietary adequacy and growth, the project aims at evaluating the interactive processes in a longitudinal way to provide evidence on the possible success factors and barriers encountered. Therefore, secondary outcomes include household production, income and expenditure in relation to the home-based food production; diet diversity; feeding and care practices, and morbidity. Data will be compared between intervention and control groups using linear mixed-effects models and generalized linear models.
INTRODUCTION: The pathogenesis of chronic subdural hematoma (CSDH) has not been completely understood. However, different mechanisms can result in space-occupying subdural fluid collections, one pathway can be the transformation of an original trauma-induced acute subdural hematoma (ASDH) into a CSDH.
MATERIALS AND METHODS: All patients with unilateral CSDH, requiring burr hole trephination between 2018 and 2023 were included. The population was distributed into an acute-to-chronic group (group A, n = 41) and into a conventional group (group B, n = 282). Clinical and radiographic parameters were analyzed. In analysis A, changes of parameters after trauma within group A are compared. In analysis B, parameters between the two groups before surgery were correlated.
RESULTS: In group A, volume and midline shift increased significantly during the progression from acute-to-chronic (p < 0.001, resp.). Clinical performance (modified Rankin scale, Glasgow Coma Scale) dropped significantly (p = 0.035, p < 0.001, resp.). Median time between trauma with ASDH and surgery for CSDH was 12 days. Patients treated up to the 12th day presented with larger volume of ASDH (p = 0.012). Before burr hole trephination, patients in group A presented with disturbance of consciousness (DOC) more often (p = 0.002), however less commonly with a new motor deficit (p = 0.014). Despite similar midline shift between the groups (p = 0.8), the maximal hematoma width was greater in group B (p < 0.001).
CONCLUSION: If ASDH transforms to CSDH, treatment may become mandatory early due to increase in volume and midline shift. Close monitoring of these patients is crucial since DOC and rapid deterioration is common in this type of SDH.
The present invention is based on the purification and sequencing of isozymes of plasma hyaluronidase (pHAse) found in urine. Specifically, urine contains two hyaluronidases (HAses): 1) a 57 kDa HAse that is apparently the same as the 57 kDa HAse found in plasma; and 2) a 45 kDa HAse, which is found in urine but not plasma. The smaller urine isozyme is composed of two disulfide-linked polypeptides produced by endoproteolytic cleavage of the 57 kDa isoform. The present invention thus features a urinary hyaluronidase (uHAse) polypeptide and nucleotide sequences encoding a Chain A polypeptide and a Chain B polypeptide, the two polypeptides of which uHAse is composed. In a particular aspect, the uHAse is a human uHAse (huHAse), preferably a huHAse composed of the Chain A and B polypeptides having SEQ ID NOS: 2 and 4, respectively. In related aspects the invention features polynucleotide sequence encoding Chain A and Chain B polypeptides, preferably having the sequences of SEQ ID NOS: 1 and 3, respectively. In addition, the invention features polynucleotide sequences that hybridize under stringent conditions to SEQ ID NOS: 1 and 3. In related aspects the invention features expression vectors and host cells comprising polynucleotides that encode uHAse polypeptide Chains A and B. The present invention also features antibodies that bind specifically to uHAse, and methods for producing uHAse.
Peripheral blood lymphocytes will be collected and neoantigen reactive T cells(NRTs) will be generated in the laboratory;nab-paclitaxel 100-200mg/m2/D will be i.v. for 7 days before cell infusion; Cyclophosphamide 300mg/m2/D will be i.v. for 2 and 3 days before cell infusion; NRTs 0.5\~1 x 10\^10, will be i.v.Q3 weeks for total 4 doses;Interleukin-2 (IL-2) will be continuous intravenous infused since the first day of the cell infusion for 5 consecutive days, 1000,000 international unit per day.All Patients will receive a total of 4 cycles of treatment.
Myocardial infarction (MI) is the leading cause of death worldwide. The most effective way to treat myocardial infarction is to rescue ischemic cardiomyocytes. After an ischemic event, the overproduction of reactive oxygen species (ROS) is a key driver of myocardial injury. The produced ROS affects mitochondrial function and induces apoptosis in cardiomyocytes. This was accomplished by constructing platelet-membrane-encapsulated ROS-responsive drug-releasing nanoparticles (PMN@NIC-MalNPs) to deliver malonate and niclosamide (NIC). The results revealed that PMN@NIC-MalNPs degraded and released malonate and niclosamide in a high-level ROS microenvironment, effectively reducing the oxidative stress and apoptosis rate. By enhancing basal mitochondrial oxygen consumption rate (OCR), adenosine triphosphate (ATP) production, and spare respiratory capacity (SRC) in vitro, reduced the oxidative stress levels and restored mitochondrial function. In vivo studies revealed that the PMN@NIC-MalNPs improved cardiac dysfunction, inhibited succinate dehydrogenase (SDH) activity, increased ATP production, and reduced the myocardial infarct size in myocardial infarction model mice. Further, transcriptome analysis and Western blot revealed that PMN@NIC-MalNPs prevented apoptosis by activating the expressions of the signal transducer and activator of transcription 3 (STAT3) and Bcl-2, and inhibiting the expression of Bax. Thus, this study provides a novel therapeutic solution for treating myocardial infarction and predicting the viability of an antioxidant and antiapoptotic therapeutic solution in the treatment of myocardial injury.
PURPOSE: Cholesterol metabolism reprograming has been acknowledged as a novel feature of cancers. Pancreatic ductal adenocarcinoma (PDAC) is a cancer with a high demand of cholesterol for rapid growth. The underlying mechanism of how cholesterol metabolism homestasis are disturbed in PDAC is explored.
EXPERIMENTAL DESIGN: The relevance between PDAC and cholesterol was confirmed in TCGA database. The expression and clinical association were discovered in TCGA and GEO datasets. Knockdown and overexpression of AGFG1 was adopted to perform function studies. RNA sequencing, cholesterol detection, transmission electron microscope, co-immunoprecipitation, and immunofluorescence et al. were utilized to reveal the underlying mechanism.
RESULTS: AGFG1 was identified as one gene positively correlated with cholesterol metabolism in PDAC as revealed by bioinformatics analysis. AGFG1 expression was then found associated with poor prognosis in PDAC. AGFG1 knockdown led to decreased proliferation of tumor cells both in vitro and in vivo. By RNA sequencing, we found AGFG1 upregulated expression leads to enhanced intracellular cholesterol biosynthesis. AGFG1 knockdown suppressed cholesterol biosynthesis and an accumulation of cholesterol in the ER. Mechanistically, we confirmed that AGFG1 interacted with CAV1 to relocate cholesterol for the proceeding of cholesterol biosynthesis, therefore causing disorders in intracellular cholesterol metabolism.
CONCLUSIONS: Our study demonstrates the tumor-promoting role of AGFG1 by disturbing cholesterol metabolism homestasis in PDAC. Our study has present a new perspective on cancer therapeutic approach based on cholerstrol metabolism in PDAC.
Pioglitazone is a thiazolidinedione that depends on the presence of insulin for its mechanism of action. Pioglitazone decreases insulin resistance in the periphery and in the liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. Pioglitazone is not an insulin secretagogue. Pioglitazone is an agonist for peroxisome proliferator-activated receptor-gamma (PPARγ). PPAR receptors are found in tissues important for insulin action such as adipose tissue, skeletal muscle and liver. Activation of PPARγ nuclear receptors modulates the transcription of a number of insulin responsive genes involved in the control of glucose and lipid metabolism. 

In animal models of diabetes, pioglitazone reduces the hyperglycemia, hyperinsulinemia and hypertriglyceridemia characteristic of insulin-resistant states such as type 2 diabetes. The metabolic changes produced by pioglitazone result in increased responsiveness of insulin-dependent tissues and are observed in numerous animal models of insulin resistance. 

Because pioglitazone enhances the effects of circulating insulin (by decreasing insulin resistance), it does not lower blood glucose in animal models that lack endogenous insulin.