anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Similar to bariatric surgery, incretin receptor agonists have revolutionized the treatment of obesity, achieving up to 15-25 % weight loss in many patients, i.e., at a rate approaching that achieved with bariatric surgery. However, over 25 % of total weight lost from both surgery and pharmacotherapy typically comes from fat-free mass, including skeletal muscle mass, which is often overlooked and can impair metabolic health and increase the risk of subsequent sarcopenic obesity. Loss of muscle and bone as well as anemia can compromise physical function, metabolic rate, and overall health, especially in older adults. The myostatin-activin-follistatin-inhibin system, originally implicated in reproductive function and subsequently muscle regulation, appears to be crucial for muscle and bone maintenance during weight loss. Activins and myostatin promote muscle degradation, while follistatins inhibit their activity in states of negative energy balance, thereby preserving lean mass. Novel compounds in the pipeline, such as Bimagrumab, Trevogrumab, and Garetosmab-which inhibit activin and myostatin signaling-have demonstrated promise in preventing muscle loss while promoting fat loss. Either alone or combined with incretin receptor agonists, these medications may enhance fat loss while preserving or even increasing muscle and bone mass, offering a potential solution for improving body composition and metabolic health during significant weight loss. Since this dual therapeutic approach could help address the challenges of muscle and bone loss during weight loss, well-designed studies are needed to optimize these strategies and assess long-term benefits. For the time being, considerations like advanced age and prefrailty may affect the choice of suitable candidates in clinical practice for current and emerging anti-obesity medications due to the associated risk of sarcopenia.
Behavioral Activation (BA) as acute treatment (5 wk. inpatient and 5 wk. either inpatient or dayclinic) followed by continuation treatment (6 wk. outpatient group therapy).
The present tool creates a direct extension to patients outside and within the office setting. As used with a mobile device, the tool provides guidance on prescription of drugs or supplements as affected by a known genotype. The disclosed tool will collect, tabulate and report back to the medical practice or practitioner critical live-time information that will help in their medical decision-making. The collective data on patients may be segmented to evaluate various similar attributes among patients. The results of this collection of data may be graphically displayed to illustrate variants. Some examples may be the evaluation of diagnoses, guidance on prescription of drugs or supplements as affected by a known genotype, and the effects and side effects of a treatment on functionality, mental status and its associated complications and adverse reactions.
The invention relates to GLP-1 receptor agonist compounds with a modified N- terminus. The compounds are of the formula Chem. 1: Y-Z-P, wherein P represents a fragment of a GLP-1 receptor agonist peptide lacking the two N-terminal amino acid residues; and Y-Z represents novel His-Ala mimetics. Examples of GLP-1 receptor agonist compounds are derived from human GLP-1 (7-37), exendin-4(1-39), or GLP-1 A (1-37). The invention also relates to derivatives of these compounds, in particular compounds with one or more albumin binding side chains capable of protracting the duration of action in vivo of these compounds. The peptides and derivatives of the invention have a good potency, a protracted pharmacokinetic profile, are stable against degradation by gastro intestinal enzymes, and/or have a high oral bioavailability. These properties are of importance in the development of GLP-1 receptor agonist compounds for subcutaneous, intravenous, and/or in particular oral administration. The invention also relates to intermediate products for use in the preparation of the GLP-1 receptor agonist compounds of the invention.
PURPOSE: Bone marrow mesenchymal stem cells (BMSCs) have emerged as promising candidate for postoperative therapeutics in chronic limb-threatening ischemia (CLTI). Nevertheless, their effectiveness is limited by their low survival rate and impaired functionality in the ischemic microenvironment. To overcome these challenges, we have devised an innovative delivery approach to support the utilization of BMSCs in CLTI therapy.
METHODS: We synthesized oxygen-releasing nanospheres and self-healing hydrogels. The in vivo functionality of the hydrogel-nanosphere delivery system was evaluated via a multimodality animal live imaging system. A unilateral lower limb ischemia model was established in mice, and a delivery system loaded with BMSCs was administered. The experimental groups included normal mice, ischemic mice, ischemic mice treated with BMSCs in PBS, and ischemic mice treated with BMSCs in the delivery system. Blood perfusion was quantitatively measured via a laser doppler flowmeter (LDF). Immunofluorescence, Masson's trichrome staining, immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were also used.
RESULTS: For cell viability analysis 80 μg.mL-1 was considered the optimal concentration for cell survival. In vivo, 18 days after injection, the cell membrane fluorescence signal in the delivery system was significantly greater (5.65510±8.2268) p/s/cm²/sr than that in the other groups (p=0.043). Ischemic mice treated with BMSCs in the delivery system presented an improved limb salvage rate (0.926±0.12)% compared with that of ischemic mice treated with BMSCs in PBS (0.841±0.029)% at the 5th week after ischemia establishment (p=0.0033).
CONCLUSION: Our findings suggest that the survival time of BMSCs is prolonged in this innovative delivery system. The combination of nanospheres and hydrogels effectively restored vascular blood perfusion while exerting minimal toxicity on BMSCs. This novel approach combining oxygen-releasing nanospheres and self-healing hydrogels as a delivery system represents an advancement in enhancing the functionality of BMSCs to treat CLTI.
The invention discloses an externally applied drug for treating lymphatic diseases. The externally applied drug comprises a guide drug, a treatment drug and a consolidation drug. The guide drug is prepared from seed of Cannabis sativa L., linseed oil, badger oil, white sugar, buckwheat flour, water and loess. The treatment drug is prepared from pangolin, saffron crocus, red date, radix ranunculi ternati paste, radix euphorbiae lantu paste, castor seed, soya bean, apricot kernel or peach seed, rheum officinale, tobacco, cuttlefish bone, toothpaste, badger oil, badger bone powder, badger skin paste, loess, saliva and water. The consolidation drug is prepared from rapeseed, Wuli cold-dispelling powder, egg white, loess, buckwheat flour and water. The externally applied drug is a Chinese herbal medicine composition for treating scrofula, and can effectively treat scrofula caused by lung qi deficiency and liver qi stagnation. An experiment proves that the Chinese herbal medicine composition is safe, has no side effect and short treatment time, produces effects fast, has substantial treatment effects and a low treatment cost and realizes simultaneous treatment of principal and subordinate symptoms.
Obesity is associated with chronic inflammation that affects various organs in the body, including the reproductive system, which is a key factor in male infertility. 1-Deoxynojirimycin (1-DNJ) is a natural alkaloid in mulberry leaves, which has anti-inflammatory capabilities, yet, it's effects on obesity-induced inflammation-related male infertility remain unclear. Therefore, this research investigates the underlying mechanism by which 1-DNJ may mitigate fertility impairment in male mice caused by obesity-related inflammation. Male mice with high-fat diet (HFD)-induced obesity were treated with 1-DNJ or metformin for 8 weeks. Metabolic profiles were evaluated by enzyme method. Reproductive capacity was assessed by sperm viability, motility and counts, immunohistochemistry was performed to evaluate the testicular damage caused by obesity and inflammation. The inflammation was assessed by measuring the levels of tumor necrosis factor α (TNFα), interleukin 1β (IL-1β), and interleukin 6 (IL-6). The activation of IκB kinase β (IKKβ) and nuclear factor κB (NF-κB) was examined using western blot and immunohistochemistry. HFD induced obesity in mice with obvious lipid metabolism disorder. The obese male mice had a decreased testosterone level, impaired sperm motility, and increased inflammatory factors. 1-DNJ treatment improved the testosterone level in the obese mice, ameliorated the testicular structure damage and improve sperm viability. In addition, 1-DNJ treatment inhibited IKKβ/NF-kB signaling pathway and reduced inflammation in obese mice. 1-DNJ can improve the fertility of obese men by reducing obesity as well as obesity-induced inflammation. These findings provide new insights for 1-DNJ to alleviate inflammation caused by obesity and provide future possibilities for treating male infertility.
The primary objective of this study is to assess the internal and external responsiveness of the ESM-PROM in examining changes in symptom scores between baseline and post-treatment. Secondary objectives are to identify differences in characteristics between responders and non-responders to linaclotide and to assess for side effects of linaclotide treatment, using the ESM-PROM. This is a prospective, observational, single-group, open-label study, initiated and performed in Maastricht University Medical Center (MUMC+). The study population will conclude 30 IBS-C subjects that are newly prescribed with linaclotide by their treating physician at the outpatient department of gastroenterology and hepatology in the Maastricht UMC+. Primary study outcomes are the weekly average of the mean and maximum abdominal pain scores per day on the ESM-PROM per period (i.e. baseline, after 4 weeks and after 12 weeks). The ESM-PROM is completed during 7 consecutive days at each period and therefore, the measurements start one week before linaclotide treatment (baseline) and end one week after finishing linaclotide treatment (after 12 weeks). Further endpoints are the change scores of abdominal pain between pre- and post-treatment, measured using the ESM-PROM. Additionally, the proportion of overall responders to linaclotide treatment after 4 and 12 weeks assessed using the conventional end-of-day diary will be used to evaluate external responsiveness. Further endpoints are symptom scores as reported using the ESM-PROM, concerning abdominal pain, bloating, abdominal fullness, fecal urgency, stool consistency, straining, CSBM frequency and SBM frequency. Secondary outcomes are other factors measured using the ESM-PROM, i.e. non-GI physical symptoms, psychological status at the moment of symptom assessment, contextual information regarding the moment of symptom assessment as well as information on food and substance intake.
Guanfacine is a once-daily, extended-release formulation of guanfacine hydrochloride, USP in a matrix tablet formulation for oral administration only. The chemical designation is N-amidino-2-(2,6-dichlorophenyl) acetamide monohydrochloride. The molecular formula is C9H9Cl2 N3O·HCl corresponding to a molecular weight of 282.55. The chemical structure is:

  


Guanfacine hydrochloride, USP is a white to off-white crystalline powder, sparingly soluble in water (approximately 1 mg/mL) and alcohol and slightly soluble in acetone. The only organic solvent in which it has relatively high solubility is methanol (>30 mg/mL). Each tablet contains guanfacine hydrochloride, USP equivalent to 1 mg, 2 mg, 3 mg, or 4 mg of guanfacine base. The tablets also contain methacrylic acid and ethyl acrylate copolymer, hypromellose, glyceryl dibehenate, microcrystalline cellulose, lactose monohydrate, fumaric acid, talc, silicon dioxide and magnesium stearate. In addition, the 3 mg and 4 mg tablets also contain FD&C Blue #2 Aluminum Lake and iron oxide yellow.

FDA approved dissolution test specifications differ from USP.
In this comprehensive state-of-the-art review, we provide an evidence-based analysis of current drug therapies for patients with heart failure with preserved ejection fraction (HFpEF) in the acute and chronic phases with concurrent hypertension. Additionally, we explore the latest developments and emerging evidence on the efficacy, safety, and clinical outcomes of common and novel drug treatments in the management of HFpEF with concurrent hypertension. During the acute phase of HFpEF, intravenous diuretics, mineralocorticoid receptor antagonists (MRAs), and vasodilators are pivotal, while in the chronic phase, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have proven effective in enhancing clinical outcomes. However, the use of calcium channel blockers in HFpEF with hypertension should be approached with caution, owing to their potential negative inotropic effects. We also explored emerging drug therapies for HFpEF, such as sodium-glucose co-transporter 2 (SGLT2) inhibitors, angiotensin receptor-neprilysin inhibitor (ARNI), soluble guanylate cyclase (sGC) stimulators, novel MRAs, and ivabradine. Notably, SGLT2 inhibitors have shown promise in reducing heart failure hospitalizations and cardiovascular mortality in patients with HFpEF, regardless of their diabetic status. Additionally, ARNI and sGC stimulators have demonstrated potential in improving symptoms, functional capacity, and quality of life. Nonetheless, additional research is necessary to pinpoint optimal treatment strategies for HFpEF with concurrent hypertension. Furthermore, long-term studies are essential to assess the durability and sustained benefits of emerging drug therapies. Identification of novel targets and mechanisms underlying HFpEF pathophysiology will pave the way for innovative drug development approaches in the management of HFpEF with concurrent hypertension.
The following proteins (a) to (c), DNAs encoding these proteins, etc. are provided. (a) A protein having an amino acid sequence represented by any of SEQ ID NOS:1 to 3. (b) A protein having an amino acid sequence showing an identity of 90% or more with an amino acid sequence represented by any of SEQ ID NOS:1 to 3 and having a transcriptional regulation ability. (c) a protein having an amino acid sequence encoded by a DNA, which is hybridizable under stringent conditions with a DNA comprising the base sequence represented by base nos. 102 to 2507 in the base sequence represented by SEQ ID NO:4, a DNA comprising the base sequence represented by base nos. 51 to 2456 in the base sequence represented by SEQ ID NO:5 or a DNA comprising the base sequence represented by base nos. 35 to 2440 in the base sequence represented by SEQ ID NO:6, and having a transcriptional regulation ability.
PROBLEM TO BE SOLVED: To produce an anticoagulant, capable of being a substitute for a heparin anticoagulant and having excellent safety with relatively high productivity at a low cost by sulfonating a silkworm product. SOLUTION: This anticoagulant comprises a sulfonated silkworm product, preferably a sulfonated fibroin or a sulfonated sericin. The product is preferably obtained by adding concentrated sulfuric acid at 10-90wt.% concentration in an amount of 0.5-500 pts.wt. based on 1 pt.wt. extracted substance to the substance extracted from, e.g. silk yarn or contents of a silk gland of a silkworm such as fibroin or sericin and carrying out the sulfonation treatment at a temperature within the range of 20-100 deg.C for about several tens of minutes to several hours.
Women or people with a uterus are vulnerable to both normal and abnormal bleeding. During the reproductive years, the uterus is prepared physiologically to accept an embryo and support its growth and development during pregnancy, or in the absence of implantation of an embryo, recycle through the process of menstruation and accept an embryo a month or so later. If fertilization takes place and an embryo or embryos implant in the uterus, the fetal trophoblast, or outer cell layer of the embryo, invades and dilates the maternal spiral arteries and forms the placenta. No matter when in gestation a pregnancy ends, at the conclusion of pregnancy, the placenta should separate from the wall of the uterus and be expelled. Abnormal bleeding occurs during pregnancy or after delivery when the normal uteroplacental interface has not been established or is interrupted; during miscarriage; during ectopic pregnancy; during premature separation of the placenta; or during postpartum hemorrhage. Heavy menstrual bleeding, a subset of abnormal menstrual bleeding, can be quantitatively defined as >80 mL of blood loss per cycle. Unlike postpartum hemorrhage, heavy menstrual bleeding is significantly associated with an underlying bleeding disorder. While there is other reproductive tract bleeding in women, notably bleeding at the time of ovulation or with a life-threatening ruptured ectopic pregnancy, the unique bleeding that women experience is predominantly uterine in origin. Many of the unique aspects of uterine hemostasis, however, remain unknown.
This study aims to compare the efficacy of single-indicator models versus comprehensive models in predicting cardiac deterioration events in patients with acute heart failure (AHF), providing a more precise predictive tool for clinical practice. This retrospective cohort study included 484 patients with AHF treated at our hospital between June 2018 and January 2023. Patients were categorized into a deterioration group and a non-deterioration group based on the occurrence of cardiac deterioration events within 1 year, defined as cardiogenic shock, cardiac arrest, or the need for mechanical circulatory support. We collected clinical data, laboratory markers, and imaging indicators for analysis. Both single-indicator models and comprehensive models (clinical data + indicators) were constructed and evaluated using the area under the receiver operating characteristic (ROC) curve (AUC) to assess their predictive performance. Among the 484 AHF patients, 121 were in the deterioration group and 363 were in the non-deterioration group. Among the single indicators, WBC had the highest AUC of 0.683. The indicator model (WBC, NOMO, Cr, BUN, Troponin, NT-proBNP, D-Dimer, LVEF, and RVFAC) achieved an AUC of 0.886 in the training set and 0.876 in the validation set. The comprehensive model (age, time from onset to admission, heart failure type, WBC, NOMO, Cr, BUN, troponin, NT-proBNP, LA, D-dimer, fibrinogen, and RVFAC) had an AUC of 0.940 in the training set and 0.925 in the validation set. In the training set, the comprehensive model had a significantly higher AUC than the indicator model (P < .05), while no significant difference was observed between the 2 in the validation set (P > .05). Furthermore, decision curve analysis (DCA) and calibration curve analysis indicated that the comprehensive model provided greater clinical benefits and better predictive accuracy in clinical applications. The comprehensive model demonstrates superior predictive capability for cardiac deterioration events in AHF patients, significantly outperforming both single-indicator and indicator models. This suggests that a comprehensive assessment can more accurately identify high-risk patients, offering a more reliable basis for clinical decision-making.
Refractory Coronary Artery Disease is a significant cause of mortality and decreased quality of life. Intracoronary infusion of CD133+ progenitor cells is a viable treatment option for patients with this condition. After clinical and laboratory evaluation, 50-100 ml of bone marrow will be obtained by bone marrow aspiration from the posterior iliac crest under local anesthesia. From this sample, CD133+ endothelial progenitor cells will be isolated, purified and packed within the next 12 hours of extraction, and resuspended in 30 ml saline solution. The patient will undergo coronary catheterization for selection of the target obstructed artery for cell infusion, which will be performed using a balloon catheter under hemodynamic monitoring. Once concluded, the patient will be transferred to intermediate care unit for post-interventional observation for approximately 24 hours before being released. Ambulatory follow-up will be performed at specific intervals to determine efficacy and safety of this intervention by clinical and laboratory examination, including imaging and cardiac function studies.
PROBLEM TO BE SOLVED: To prepare a gummy preparation easily takable without using water, effective for masking the bitter taste and disagreeable smell of medicine and capable of improving compliance. SOLUTION: A carbohydrate is heated together with water and mixed with a gelling agent composed mainly of gelatin. A medicine is added to the mixed liquid and optionally an acidulant, a colorant, a flavor, etc., are added to the mixture to obtain a gummy preparation base. The objective gummy preparation is prepared by cooling and solidifying the base. The obtained gummy preparation is usually coated with edible oil and fat or granulated sugar to prevent the agglomeration of the gummy preparation. The gummy composition is a gelatinous candy composition composed of 65-87-wt.% of a carbohydrate, 3-10wt.% of a gelling agent composed mainly of gelatin and 10-25wt.% of water, having Aw (water activity at 20 deg.C) of <=0.7, free from the problem of the proliferation of microorganisms and preservable over a long period.  It can be used as various pharmaceuticals such as antianxiety agent, antiepiletic agent, antipyretic analgesic agent, agent for psychoneurosis, antispasmodic agent, cardiotonic agent, antiarrhythmic agent, diuretic agent, hypotensor, hypolipidemic agent, etc.
Neoadjuvant tyrosine kinase inhibitor (TKI) therapy is an important treatment option for advanced renal cell carcinoma (RCC). Many RCC patients may fail to respond or be resistant to TKI therapy. We aimed to explore the key mechanisms of neoadjuvant therapy résistance. We obtained tumor samples from matched pre-treatment biopsy and post-treatment surgical samples and performed single-cell RNA sequencing. Sunitinib-resistant ccRCC cell lines were established. Ferroptosis was detected by ferrous ion and lipid peroxidation levels. Tumor growth and resistance to Sunitinib was validated in vitro and vivo. Immunohistochemistry was used to validate the levels key genes and lipid peroxidation. Multi-center cohorts were included, including TCGA, ICGC, Checkmate-025 and IMmotion151 clinical trial. Survival analysis was performed to identify the associated clinical and genomic variables. Intratumoral heterogeneity was first described in the whole neoadjuvant management. The signature of endothelial cells was correlated with drug sensitivity and progression-free survival. Ferroptosis was shown to be the key biological program in malignant cell resistance. We observed tissue lipid peroxidation was negatively correlated with IL6 and tumor response. TKI-resistant cell line was established. SLC7A11 knockdown promoted cell growth and lipid peroxidation, increased the ferroptosis level, and suppressed the growth of tumor xenografts significantly (P < 0.01). IL6 could reverse the ferroptosis and malignant behavior caused by SLC7A11 (-) via JAK2/STAT3 pathway, which was rescued by the ferroptosis inducer Erastin. Our data indicate that ferroptosis is a novel strategy for advanced RCC treatment, which activated by IL6, providing a new idea for resistance to TKIs.