anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The efficacy of FOTIVDA was evaluated in TIVO-3 (NCT02627963), a randomized (1:1), open- label, multicenter trial of FOTIVDA versus sorafenib in patients with relapsed or refractory advanced RCC who received 2 or 3 prior systemic treatments including at least one VEGFR kinase inhibitor other than sorafenib or tivozanib. Patients were randomized to receive FOTIVDA 1.34 mg orally once daily for 21 days on treatment followed by 7 days off treatment for a 28-day cycle, or to receive sorafenib 400 mg orally twice a day continuously, until disease progression or unacceptable toxicity. Randomization was stratified by prior therapy [two kinase inhibitors (KIs), a KI plus an immune checkpoint inhibitor, or a KI plus other systemic agents] and by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic score. Patients were excluded if they had more than 3 prior treatments or Central Nervous System metastases. The main efficacy outcome measure was progression-free survival (PFS) assessed by a blinded independent radiology review committee. Other efficacy endpoints were objective response rate (ORR) and overall survival (OS).

The median age was 63 years (range: 30 to 90 years), 73% were male, 95% were Caucasian, ECOG performance status was 0 in 48% and 1 in 49% of patients (respectively), and 98% of patients had clear cell or clear cell component histology. Prior therapy included two KIs (45%), a KI plus an immune checkpoint inhibitor (26%), and a KI plus another systemic agent (29%). At the time of study entry, 20% of patients had favorable, 61% intermediate, and 19% poor IMDC prognoses.

Efficacy results are summarized in Table 4and Figure 1. 

Figure 1. Kaplan-Meier Plot of PFS in TIVO-3
Subjects were monitored at matched timepoints (start of study, 4-5 weeks, and 8-10 weeks) but not exposed to any intervention. Subjects were instructed to not make any dietary or lifestyle changes.
NEW MATERIAL:The compound of formulaI(the double bond between the 13- and 14- carbon atoms is trans) and its cyclodextrin clathrate compound. EXAMPLE:2-Decarboxy-2-glycoloyl-17S, 20-dimethyl-6-keto-PGE1. USE:It has gastric juice secretion suppressing and gastric ulcer suppressing activities, and useful for the prevention and/or remedy of gastric ulcer. PROCESS:The compound of formulaIis prepared by hydrolyzing the compound of formula II (the absolute configuration of the 3'-C atom is S, R or RS mixture) in the presence of an acid. The reaction is carried out in an aqueous solution of an organic acid such as acetic acid, propionic acid, oxalic acid, etc. or an inorganic acid such as HCl, in the presence of e.g. THF at room temperature -90 deg.C.
Acupuncture therapy has been proved helpful in the patients suffering from various pain problems. And it is reported to be able to reduce the intraoperative anesthetic requirement. However, so far there is few evidence from randomized controlled studies to confirm the assistant anesthetic effect of acupuncture. Electroacupuncture (EA) is a modern non-invasive technique of traditional acupuncture. Compared to traditional acupuncture, EA is more practicable, more easily to be accepted by patients and operated by physicians. Nasal sinus surgery and mammaplasty, especially breast augmentation, mostly belong to the scope of day surgeries, which demand a rapid, smooth recovery from anesthesia with minimum adverse side effects (e.g.: pain, PONV, etc).
PURPOSE: This study aimed to investigate the correlation between sarcopenia and adverse events (AEs) of postoperative imatinib therapy through computed tomography (CT) quantitative body composition for intermediate- and high-risk gastrointestinal stromal tumors (GISTs).
METHODS: The study retrospectively analyzed the clinical data of 208 patients with intermediate- and high-risk GIST treated surgically and treated with imatinib afterward at the First Affiliated Hospital of Wenzhou Medical University between October 2011 and October 2021. Images of preoperative CT scans within 1 month were used to determine the body composition of the patients. On the basis of the L3 skeletal muscle index, patients were classified into sarcopenia and nonsarcopenia groups. In 2 groups, AEs related to imatinib were analyzed.
RESULTS: The proportion of AEs related to imatinib in the sarcopenia group was higher, and this disparity had a significant statistical significance (P = .013). Sarcopenia was significantly associated with hemoglobin reduction compared with nonsarcopenia (P = .015). There was a significant difference between the sarcopenia group and the nonsarcopenia group in the ratio of severe AEs (grades 3-4). Hemoglobin content (odds ratio [OR], 0.981; 95% CI, 0.963-1.000; P = .045), sex (OR, 0.416; 95% CI, 0.192-0.904; P = .027), and sarcopenia (OR, 5.631; 95% CI, 2.262-14.014; P < .001) were the influential factors of imatinib severe AEs in patients with intermediate- and high-risk GIST within 1 year after imatinib treatment.
CONCLUSION: Patients with preoperative sarcopenia have a higher incidence and severity of AEs during adjuvant imatinib therapy.
A device for the release of a substance at a defined or desired location in the alimentary tract. The device has a capsule having a separating wall therein, which forms a first chamber and a second chamber in the capsule. A hole is present in the wall of the first chamber. A compression spring, that is in a compressed state, is affixed to a body located in the second chamber. A needle is mounted on the compression spring facing the separation wall. A resonant circuit, in the second chamber, is tuned to an electromagnetic field of high frequency. The resonant circuit has a coupling coil, positioned around the body, a capacitor, connected to the other end of the coil and extending away from the first chamber, and a resistance wire, attached to the coupling coil and the capacitor. A fuse wire is connected to the compression spring, extends through the longitudinal passageway of the body and is connected to the body end facing away from the first chamber. The fuse wire contacts the resistance wire. A balloon in the expanded state is positioned in the first chamber. When the device is subjected to an external electromagnetic field having the high frequency to which the resonant circuit is tuned, the fuse wire heats up and breaks. The compressed spring is released pushing the point of the needle through the separating wall and the balloon, which bursts releasing any substance contained in the first chamber.
OBJECTIVES: Blood cultures (BCs) are commonly ordered in emergency departments (EDs), while a minority yields a relevant pathogen. Diagnostic stewardship is needed to safely reduce unnecessary BCs. We aimed to develop and validate a bacteremia prediction model for ED patients, with specific focus on the benefit of incorporating procalcitonin.
METHODS: We included adult patients with suspected bacteremia from a Dutch ED for a one-year period. We defined 23 candidate predictors for a "full model", of which nine were used for an automatable "basic model". Variations of both models with C-reactive protein and procalcitonin were constructed using LASSO regression, with bootstrapping for internal validation. External validation was done in an independent cohort of patients with confirmed infection from 71 Spanish EDs. We assessed discriminative performance using the C-statistic and calibration with calibration curves. Clinical usefulness was evaluated by sensitivity, specificity, saved BCs, and Net Benefit.
RESULTS: Among 2111 patients in the derivation cohort (mean age 63 years, 46% male), 273 (13%) had bacteremia, versus 896 (20%) in the external cohort (n = 4436). Adding procalcitonin substantially improved performance for all models. The basic model with procalcitonin showed most promise, with a C-statistic of 0.87 (0.86-0.88) upon external validation. At a 5% risk threshold, it showed a sensitivity of 99% and could have saved 29% of BCs while only missing 10 out of 896 (1.1%) bacteremia patients.
CONCLUSIONS: Procalcitonin-based bacteremia prediction models can safely reduce unnecessary BCs at the ED. Further validation is needed across a broader range of healthcare settings.
BACKGROUND: Internalized weight bias is the belief in negative, weight-based stereotypes and the application of these stereotypes to oneself. These negative stereotypes have harmful impacts on people with overweight/obesity, and weight-based discrimination is well-documented across a variety of settings. Given poor outcomes associated with internalized weight bias, particularly among individuals with obesity, it is necessary to validate measures assessing internalized weight bias among diverse samples. The present study sets out to investigate measurement invariance properties across weight status (women with vs. without overweight/obesity) and race (White vs. Asian; White vs. bi- or multi-racial) of the Modified Weight Bias Internalization Scale (WBIS-M), an 11 item self-report measure.
METHODS: Participants were 746 racially/ethnically diverse women across the weight spectrum (24.9% with overweight/obesity). Confirmatory factor analyses of the WBIS-M were initially performed among the full sample, and all sub-samples. Each model showed good to excellent descriptive model fit. Subsequent analyses examined factor loadings and item thresholds of the WBIS-M to assess metric, threshold, and scalar invariance. Invariance was determined by assessing changes in Comparative Fit Index (ΔCFI ≤ -0.010), Root Mean Square Error of Approximation (ΔRMSEA ≤ 0.015), and Standardized Root Mean Square Residuals (ΔSRMR ≤ 0.030).
RESULTS: Based on these previously established statistical cutoffs, the WBIS-M showed invariance across weight status and racial groups in the present sample. The current results lend support for use of the WBIS-M to measure internalized weight bias in women who do and do not have overweight/obesity, and among White, Asian, and bi- or multi-racial women.
CONCLUSION: This may inform future studies that wish to utilize the WBIS-M, such as investigations of mean level differences in internalized weight bias. These findings may have clinical applications in the treatment and prevention of obesity, given the heightened levels of internalized weight bias and weight-based discrimination faced by individuals with higher body weights.
Lycopene, a carotenoid mainly found in tomato-based food products, has strong antioxidant properties relative to other carotenoids and has been postulated to play a role in the prevention of coronary heart disease through a variety of mechanisms. Lycopene cooked and consumed in oil mediums is optimal for not only its efficient absorption, but also its potential clinical effectiveness. Studies have also linked serum lycopene with the early stages of atherosclerosis, as measured by carotid artery intima-media thickness (IMT), a noninvasive ultrasound examination of the carotid arteries and potential surrogate endpoint for subsequent cardiovascular morbidity and mortality used in previous clinical trials of vitamin supplements. Short-term intervention studies of lycopene supplements are limited, having explored mechanisms through which lycopene or its readily absorbable food sources may increase plasma lycopene or induce changes in other relevant biochemical markers impacting the subsequent risk of coronary heart disease. Ateronon is a lycopene supplement developed with the understanding that the potential clinical effectiveness of lycopene is impacted by its bioavailability. A single daily 7 mg tablet of Ateronon provides more bioavailable lycopene than diet alone, is absorbed efficiently, and completely inhibits the atherogenic lipid oxidation processes in subjects. Clinical studies suggest that short-term treatment with Ateronon among those with coronary heart disease leads to favorable reductions in lipid levels, lipoprotein oxidation, blood pressure, and Rose-Blackburn scores. Therefore, we will conduct a randomized, double-blind, placebo-controlled clinical trial of 7 mg Ateronon taken daily for 1 year among 200 patients aged ≥50 years with stable coronary heart disease. This clinical trial is a collaborative effort between the Division of Preventive Medicine and the Vascular Medicine Program in the Division of Cardiology. Our primary aim is whether taking Ateronon for 1 year is associated with favorable changes in carotid IMT. Secondary aims expand to whether Ateronon leads to favorable 1-year changes in coronary biomarkers related to oxidative stress and endothelial dysfunction; blood pressure; plasma carotenoids; AtheroAbzyme levels; and other traditional coronary biomarkers. This clinical trial of Ateronon seeks to improve our understanding of various mechanisms through which Ateronon, a concentrated and highly bioavailable form of lycopene, may reduce the risk of developing coronary heart disease.
Cancer continues to pose a significant global health challenge, as evidenced by the increasing incidence rates and high mortality rates, despite the advancements made in chemotherapy. The emergence of chemoresistance further complicates the effectiveness of treatment. However, there is growing interest in the potential of metformin, a commonly prescribed drug for type 2 diabetes mellitus (T2DM), as an adjuvant chemotherapy agent in cancer treatment. Although the precise mechanism of action of metformin in cancer therapy is not fully understood, it has been found to have pleiotropic effects, including the modulation of metabolic pathways, reduction in inflammation, and the regulation of cellular proliferation. This comprehensive review examines the anticancer properties of metformin, drawing insights from various studies conducted in vitro and in vivo, as well as from clinical trials and observational research. This review discusses the mechanisms of action involving both insulin-dependent and independent pathways, shedding light on the potential of metformin as a therapeutic agent for different types of cancer. Despite promising findings, there are challenges that need to be addressed, such as conflicting outcomes in clinical trials, considerations regarding dosing, and the development of resistance. These challenges highlight the importance of further research to fully harness the therapeutic potential of metformin in cancer treatment. The aims of this review are to provide a contemporary understanding of the role of metformin in cancer therapy and identify areas for future exploration in the pursuit of effective anticancer strategies.
The invention belongs to the technical field of medical care, and particularly relates to a medical pillow for treating middle-aged chronic bronchitis. The medical pillow for treating middle-aged chronic bronchitis comprises a pillow body, and the upper surface of the pillow body is provided with conical protrusions corresponding to acupuncture points of the head. A medicine bag is arranged in the pillow body, and the medicine bag extends into the conical protrusions. The medicine bag is filled with medicine liquid. The medicine liquid comprises, by weight, the following raw materials: ephedra herb, ternate pinellia, flos lonicerae, radix glycyrrhizae, pericarpium citri reticulatae, folium eriobotryae, common coltsfoot flower, inula flower, semen armeniacae amarum, herba asari and crude radix astragali. A heating wire is arranged in the medicine bag, and a temperature control switch is arranged on the outer side of the pillow body. The medicine liquid in the medical pillow is mild in medicine property, has no side effect, and does not cause harm to the body of a middle-aged person. When a patient sleeps, chronic bronchitis can be treated, and the patient does not need to waste time and energy. In addition, radical cure for chronic bronchitis can be achieved by using the medical pillow for treating middle-aged chronic bronchitis for a long time.
Drug delivery systems that can deliver therapeutic and/or diagnostic agents to the colon are disclosed. The systems include pectin beads crosslinked with zinc or any divalent cation of interest, which beads are then coated with Eudragit®-type polymers. The drug delivery systems are orally administrable, but can deliver the active agents to the colon. In some embodiments, they can administer the agents to various positions in the gastro-intestinal tract, including the colon. The agent can be a small molecule, peptide, protein, nucleic acid, or complex structures of natural, recombinant or synthetic origin. In still other embodiments, the agent is a diagnostic agent. The agents can be used to diagnose, treat or investigate humans and animals for a variety of conditions, including infectious diseases, inflammatory diseases, cancers and the like. Colon-specific delivery is obtained by formulating a prophylactic, therapeutic, and/or diagnostic agent with specific polymers that degrade in the colon, such as pectin. The pectin is gelled/crosslinked with a cation such as a zinc cation. The formulation, typically in the form of ionically crosslinked pectin beads, is subsequently coated with a specific polymer such as a Eudragit® polymer. Processes for obtaining such beads are also disclosed.
PURPOSE:To obtain a gel-like silicone composition which is dry to the touch and has long-term stability by mixing a silicone oil with a specified polyorganosiloxane containing polyoxyalkylene groups and water. CONSTITUTION:The composition is produced by homogeneously mixing a silicone oil with a polyoxyalkylene-containing organopolysiloxane of formula I (wherein R is methyl or phenyl; A is methyl, phenyl or a group of formula II; R' is H, acyl or 1-4C alkyl: a and b and each 5-50; m is 50-1000; and n is 1-40) and water on, e.g. a homomixer. This composition can desirably be used for, e.g. sunscreen gels or liquid foundations. Examples of the organopolysiloxane of formula I include compounds of formulas III and IV.
Barley net form net blotch (NFNB) is a destructive foliar disease caused by Pyrenophora teres f. teres. Barley line CIho5791, which harbors the broadly effective chromosome 6H resistance gene Rpt5, displays dominant resistance to P. teres f. teres. To genetically characterize P. teres f. teres avirulence/virulence on the barley line CIho5791, we generated a P. teres f. teres mapping population using a cross between the Moroccan CIho5791-virulent isolate MorSM40-3 and the avirulent reference isolate 0-1. Full genome sequences were generated for 103 progenies. Saturated chromosome-level genetic maps were generated, and quantitative trait locus (QTL) mapping identified two major QTL associated with P. teres f. teres avirulence/virulence on CIho5791. The most significant QTL mapped to chromosome (Ch) 1, where the virulent allele was contributed by MorSM40-3. A second QTL mapped to Ch8; however, this virulent allele was contributed by the avirulent parent 0-1. The Ch1 and Ch8 loci accounted for 27 and 15% of the disease variation, respectively, and the avirulent allele at the Ch1 locus was epistatic over the virulent allele at the Ch8 locus. As a validation, we used a natural P. teres f. teres population in a genome-wide association study that identified the same Ch1 and Ch8 loci. We then generated a new reference quality genome assembly of parental isolate MorSM40-3 with annotation supported by deep transcriptome sequencing of infection time points. The annotation identified candidate genes predicted to encode small, secreted proteins, one or more of which are likely responsible for overcoming the CIho5791 resistance. [Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 "No Rights Reserved" license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2024.
The invention discloses a mycobacterium tuberculosis multi-immunogen antigen, mRNA encoding the same and application thereof, belonging to the technical field of biological medicine. The mycobacterium tuberculosis multi-immunogen antigen of the present invention comprises immunogen I and at least one of the following immunogens: immunogen II, immunogen III; the immunogen I is Ag85B protein or an antigenic fragment thereof, the immunogen II is ESAT6 protein or an antigenic fragment thereof, and the immunogen III is Rv2660c protein or an antigenic fragment thereof. The invention discloses polynucleotide mRNA encoding the antigen. The invention also discloses application of the mycobacterium tuberculosis multi-immunogen antigen or polynucleotide mRNA. The multi-immunogen antigen of the mycobacterium tuberculosis can be used for preparing mRNA vaccine. Experimental results show that the mRNA vaccine provided by the invention can excite specific immune response against mycobacterium tuberculosis.
FIELD: medicine, pharmaceutics. ^ SUBSTANCE: present invention refers to organic chemistry, namely new compounds of formula , wherein A represents residues of formulae ^ , , , X represents O; X1-X4 represents N, CH, CR1 or C-, X9-X12 represents N, CH, CR4 or C-, X13-X16 represents N, CH, CR or C-, wherein C represents an attachment point of the group A to a residue of the structure of formula (I); R' represents H or alkyl; R represents alkoxy, or Het; R1 represents F, CI, Br, I, OH, CN, carboxy, CONR6R7, NR2COR8, NR2COOR8, alkoxy, fluorinated alkoxy, Ar, Het or OHet; or R1 represents one of the following formulas: wherein n is equal to 2 and m is equal to 3; R2 represents H, alkyl, fluorinated alkyl, cycloalkyl, Het or Het-NH-CO-; R4 represents F, Cl, Br, I, OH, alkoxy, cycloalkoxy, Het or OHet; or R4 represents one of the following formulae: , wherein n is equal to 2 and t is equal to 3; each R6 and R7 independently represents alkyl, or cycloalkyl, or R6 and R7 together represent alkylene group containing 5-6 carbon atoms which forms a cycle with N atoms; R8 represent alkyl, or cycloalkylalkyl; R9 represents alkyl; Ar represents aryl group; Het represents heterocyclic group which is completely saturated, particularly saturated or completely unsaturated containing 5 to 10 ring atoms in which at least 1 ring atom represents N, O or S atom which is unsubstituted or substituted once or several times by the substituted specified in cl. 1; and their pharmaceutically acceptable salts or solvates or N-oxides, or solvates of their pharmaceutically acceptable salts, or solvates of N-oxides of their pharmaceutically acceptable salts wherein said compound can be presented in the form of a polymorph, wherein if said compound shows chirality, it can be presented in the form of a mixture of enanthiomers or a mixture of diastereoisomers, or can be presented in the form of single enanthiomer or single diastereoisomer; and wherein at least one of the groups R, R1 or R4 represents Het or OHet, wherein the group Het is specified in each case in substituted or unsubstituted azabicyclooctyl, oxaazabicycloheptyl, diazabicycloheptyl, diazabicyclononyl, diazabicyclooctyl, pyrazolyl, dihydroimidazolyl, 1,4-diazepanyl, hezahydropyrrolopyrazinyl and octahydropyrrolopyridinyl. Also the invention refers to other compounds of formula (I), to specific compounds, to a pharmaceutical composition based on the compound of formula (I), to a method of selective activation/stimulation of -7 nicotinic receptors, to application of the compound of formula (I) for making the drug. ^ EFFECT: there are produced new compounds showing effective biological properties. ^ 53 cl, 1 tbl
Single-arm, dose-escalation starting at 1,000 IU or 2,000 IU of vitamin D3 daily for a 6 month period, followed by a conditional titration up to 4,000 IU daily for at least 6 months thereafter. No placebo.