anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
A method is provided for automatically identifying a disease outbreak indicative of a potential bio-terror attack. Patient records are mined from structured and unstructured clinical sources. The patient records are then analyzed by correlating selected patient data contained in the patient records with disease indicia for each of a plurality of diseases. A probability of a disease outbreak is estimated at least in part based on these correlations. Suspicion may also be indicated if anomalous disease clusters are found. If any of the estimated probabilities exceeds a threshold value, a disease outbreak alert is outputted. The disease indicia may be defined by disease progression models, which may be stored in a disease knowledge base.
PROBLEM TO BE SOLVED: To obtain the subject activator capable of stimulating metabolism, especially skin turnover by compounding Chinese gutta percha or its extract and carrot or its extract as essential components with a specifically selected component. SOLUTION: (A) Chinese gutta percha or its extract and (B) carrot or its extract as essential components are compounded with a component selected from (C) deoxyribonucleic acid, (D) chondroitin sulfate, (E) collagen or its hydrolysate and (F) an extract of adlay. When an extract of Chinese gutta percha is used as the component A, it can use the extraction solution obtained by extracting e.g. with water or an aqueous organic solvent at the room temperature or 80-100 deg.C. An example of the component C is an extract of soft roe of salmon. For instance, an extract of shark fin can be used as the component D. Further, the objective activator is preferably administered perorally in such a manner that a person can take 0.02-3g/kg of the component A and 0.005-1.5g/kg of the component B for a day.
The invention relates to a C-terminal fragment of apolipoprotein E and application thereof in inhibiting gamma secretase enzyme activity. The isolated polypeptide provided by the invention is selected from the group consisting of: (1) A fragment of the amino acid sequence shown in SEQ ID NO. 12, wherein the first amino acid residue at the N-terminal of the fragment is an amino acid residue at any one of positions 215-221 of SEQ ID NO. 12, and the last amino acid residue at the C-terminal is an amino acid residue at any one of positions 274-299 of SEQ ID NO. 12; (2) A polypeptide having at least 70% sequence identity to the fragment of (1) through substitution, deletion or addition of one or more amino acids in the amino acid sequence of the fragment of (1), while retaining the enzymatic activity of the polypeptide of (1) to inhibit gamma secretase. The invention also provides a coding sequence, a nucleic acid construct, a host cell, a pharmaceutical composition and application of the polypeptide.
The overall goal of this project is to conduct a well-powered confirmatory efficacy trial comparing a gamified, attention bias modification (ABM) mobile application and traditional ABM to sham ABM among adults with elevated symptoms of depression. The proposed R01 efficacy trial follows the NIMH intervention development sequence as it builds upon prior NIMH-funded experimental therapeutics work, specifically R21MH092430 "Attention training for Major Depressive Disorder" and R33MH109600 "Development of attention bias modification for depression". This prior work demonstrates that active ABM engages and alters negative attention bias and there is a preliminary efficacy signal that ABM reduces depression. Although traditional ABM is efficacious for the treatment of depression, "gamified" forms of ABM have the potential to be more accessible and engaging than traditional ABM. Pilot work suggests that a gamified ABM can reduce negative affect; however, its effectiveness for depression has not yet been established. Thus, investigators are proposing to conduct a well-powered, confirmatory efficacy trial to determine ABM's potential for the treatment of depression. In Aim 1, the investigators will examine the efficacy of ABM in a large sample of adults (N = 600) with elevated symptoms of depression. The investigators hypothesize that gamified and traditional ABM will lead to significantly greater reductions in self-reported and interviewer-rated depression symptoms than sham ABM. The investigators further hypothesize that traditional ABM will be non-inferior to gamified ABM (treatment superiority between the ABM conditions will also be tested). In Aim 2, the investigators will examine putative moderators and mediators of ABM. Based on ABM research with anxious populations, it is predicted that people with a strong initial attentional bias for sad stimuli will experience greater reductions in depression in response to either gamified or traditional ABM than sham ABM. In terms of mediation, compared to sham ABM, the investigators hypothesize that gamified and traditional ABM will: (1) decrease negative attentional bias measured behaviorally with reliable eye tracking methods; (2) significantly reduce depression; and (3) improve depression symptoms via their influence on negative attentional bias. Selection of the putative mediators is informed by our prior R33 ABM trial, where it was found that gaze bias away from sad stimuli mediated the effect of traditional ABM on depression symptom change. In Aim 3, an exploratory aim, the investigators will estimate the durability of ABM by collecting post-treatment symptom data 1-, 2-, 3-, and 6-months after ABM completion. Symptom change and reliable recovery across a six-month follow-up period will be estimated. Currently, the durability of ABM effects for depression is unknown, as few well-powered ABM studies for depression have obtained follow-up data. This trial would provide the most definitive data to date regarding whether ABM for depression is a promising treatment for depression.
Limited studies are available on vitamin B6 status in domestic cats. To this end, we evaluated glutamate-oxaloacetate transaminase (GOT) activity in hemolysates with and without pyridoxal 5'-phosphate addition in two feline populations: a cohort of 60 healthy, domestic (sexually intact and specific pathogen-free) cats maintained under strictly controlled conditions with appropriate diets housed at the Feline Nutrition and Pet Care Center, and a cohort of 57 cats randomly selected between December 2022 to January 2023 that visited the Veterinary Medicine Teaching Hospital to seek care under different circumstances. The GOT activity expressed as the ratio with and without pyridoxal 5'-phosphate addition (primary activation ratio; PAR) decreased significantly with age in the healthy cohort. The PAR values normalized to age established a cut-off for vitamin B6 deficiency in both cohorts, identifying 17 of 101 animals as vitamin B6 deficient. Using machine learning, a partition-based model (decision tree) was built to identify the most important factors that predicted vitamin B6 deficiency while using the resulting tree to make predictions for new observations. This analysis, performed with all 101 cats, revealed that the diagnosis of an infectious, chronic or acute condition (0.55) was the main contributor, followed by age (0.26), and body condition score (optimal-overweight; 0.19). Thus, our study supports that vitamin B6 supplementation may be indicated in junior to adult animals diagnosed with an infectious, chronic, or acute conditions or healthy cats with body weight ranging from optimal to overweight. In older cats, even if healthy, underweight to optimal cats appear to be at risk of vitamin B6 deficiency.
PURPOSE:To obtain a cosmetic giving excellent feeling to the skin from a water- repellent cosmetic powder produced by the double surface-treatment of powder with a specific N-mono(long chain acyl) basic amino acid and then with an oil and fat having acidic group. CONSTITUTION:The objective water-repelling cosmetic powder is produced by the double surface-treatment of powder (e.g. silicic acid, talc, sericite, mica, clay and aluminum oxide) (preferably having particle diameter of about 0.1-20mum) with (A) an N-mono(long chain acyl) basic amino acid containing one 8-22C fatty acid acyl group in one molecule (e.g. N-lauroyllysine) and then with (B) an oil and fat having acidic group (e.g. dicetyl phosphate). Cosmetic produced by using the powder has excellent water-repellency and easily spreadable on the skin to form durable make-up and give good feeling to the skin. It has especially excellent smoothness.
Quinoline-related antimalarial drugs have been associated with cardiotoxicity risk, in particular QT prolongation and QRS complex widening. In collaboration with Medicines for Malaria Venture, we discovered novel plasmepsin X (PMX) inhibitors for malaria treatment. The first lead compounds tested in anesthetized guinea pigs (GPs) induced profound QRS widening, although exhibiting weak inhibition of NaV1.5-mediated currents in standard patch clamp assays. To understand the mechanism(s) underlying QRS widening to identify further compounds devoid of such liability, we established a set of in vitro models including CaV1.2, NaV1.5 rate-dependence, and NaV1.8 patch clamp assays, human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), and Langendorff-perfused isolated GP hearts. Six compounds were tested in all models including anesthetized GP, and 8 additional compounds were tested in vitro only. All compounds tested in anesthetized GP and isolated hearts showed a similar cardiovascular profile, consisting of QRS widening, bradycardia, negative inotropy, hypotension, and for some, QT prolongation. However, a left shift of the concentration-response curves was noted from in vitro to in vivo GP data. When comparing in vitro models, there was a good consistency between decrease in sodium spike amplitude in hiPSC-CM and QRS widening in isolated hearts. Patch clamp assay results showed that the QRS widening observed with PMX inhibitors is likely multifactorial, primarily due to NaV1.8 and NaV1.5 rate-dependent sodium blockade and/or calcium channel-mediated mechanisms. In conclusion, early de-risking of QRS widening using a set of different in vitro assays allowed to identify novel PMX inhibitors with improved cardiac safety profile.
BACKGROUND: Survival is variable in patients with glioblastoma IDH wild-type (GBM), even after comparable surgical resection of radiographically detectable disease, highlighting the limitations of radiographic assessment of infiltrative tumor anatomy. The majority of postsurgical progressive events are failures within 2 cm of the resection margin, motivating supramaximal resection strategies to improve local control. However, which patients benefit from such radical resections remains unknown.
METHODS: We developed a predictive model to identify which IDH wild-type GBMs are amenable to radiographic gross-total resection (GTR). We then investigated whether GBM survival heterogeneity following GTR is correlated with microscopic tumor burden by analyzing tumor cell content at the surgical margin with a rapid qPCR-based method for detection of TERT promoter mutation.
RESULTS: Our predictive model for achievable GTR, developed on retrospective radiographic and molecular data of GBM patients undergoing resection, had an area under the curve of 0.83, sensitivity of 62%, and specificity of 90%. Prospective analysis of this model in 44 patients found that 89% of patients were correctly predicted to achieve a residual volume (RV) < 4.9cc. Of the 44 prospective patients undergoing rapid qPCR TERT promoter mutation analysis at the surgical margin, 7 had undetectable TERT mutation, of which 5 also had a GTR (RV < 1cc). In these 5 patients at 30 months follow-up, 75% showed no progression, compared to 0% in the group with TERT mutations detected at the surgical margin (P = .02).
CONCLUSIONS: These findings identify a subset of patients with GBM that may derive local control benefits from radical resection to undetectable molecular margins.
AIM: AAnalysis of the choice of suicide method by gender and age of the deceased.
MATERIAL AND METHODS: The study presented here was based on a retrospective analysis of autopsy reports from the years 2001-2010 in the Department of Forensic Medicine of the Jagiellonian University Collegium Medicum in Kraków. The basis of the research work conducted was the collection and extensive analysis of cases of suicide deaths. Subsequently, a preference analysis of the choice of suicide method was conducted, taking into account the age and gender of the deceased. The statistical analysis performed used logistic regression in Excel's XLSTAT as an analysis tool.
RESULTS: A total of 2,073 suicide cases were collected from the time frame under discussion. The predominant method of suicide was hanging (1524 cases, 1329 men and 195 women), the second most common method was jumping from the roof or window of a high floor of a building (jumping from heights; 171 cases, 100 men, 71 women). A statistically significant correlation of suicide method with gender was found for: hanging [odds ratio (OR) male (M) vs. female (F) = 3. 4; confidence interval (CI) = 2.7-4.3; p0.001]; drowning [OR: M/F =4.1; CI = 2.6-6.4; p0.001]; jumping from heights [OR: M/F=4.1; CI=2.9-5.7; p0.001] and poisoning [OR: M/F=3.2; CI = 2.1-4.9]. Suicide with the use of firearms occurred exclusively in the case of men (40 cases). The age of the victims correlated with the method of committing suicide by jumping from heights [0R=0.98; CI=0.97-0.99; p0.001] and rail suicide [OR=0.98; CI=0.96-0.99; p0.001].
CONCLUSIONS: The study revealed that both age and gender have a significant impact on the choice of suicide method. According to available epidemiological data and the authors' predictions, a predominance of male over female sex was observed in the case of hanging, while jumping from heights was relatively more often chosen by women. The elderly were less likely to choose jumping from heights and rail suicide.
A botulinus toxin neutralizer comprises at least one fatty acid having at least 12 carbon atoms. Such a fatty acid may be a saturated fatty acid such as lauric acid, myristic acid, palmitic acid, stearic acid, nonadecanoic acid, arachidic acid or behenic acid, or an unsaturated fatty acid such as oleic acid. The toxin neutralizer acts as if it were an antagonistic receptor for botulinus toxin and, when encountering botulinus toxin in the human body, it combines directly with the toxin and prevents the toxin from combining with the neuromuscular tissues of the human body. Hence the neutralizer prevents the outbreak of botulism. The toxin thus neutralized and affixed to the botulinus toxin is excreted from the human body. The botulinus toxin neutralizer can be manufactured easily and economically from a naturally occurring glyceride and is thus far less costly than the known antitoxin of ganglioside GTlb produced from bovine brain.
Patients receive oral placebo supplementation daily for 4 weeks. Patients undergo radical prostatectomy within 21 days after completion of placebo supplementation.
Colorectal Cancer (CRC) is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women. CRC can often be prevented through regular screening. Although colonoscopy-based screening programs result in a significant decrease in CRC incidence, the compliance rate for performing the required screening remains too low and not the desired one. Fecal Occult Blood Test (FOBT) is another widely used screening modality for CRC but have certain constraints, such as relatively low sensitivity and the need for multiple sampling (three) to reach full screening potential. The development of novel, more practical screening methods can effectively increase the screening rates for CRC through non-invasive, repeatable, cost-effective, easy-to-use, and patient-friendly procedures. This is of particular importance in different European societies and population subgroups, since an increase in the incidence of Early-Onset CRC is currently noticed, which is significantly associated with risk factors such as heredity, obesity, smoking, alcohol abuse, and hyperlipidemia.

Within this framework, ONCOSCREEN will develop a multi-tier diagnostic solution towards improved CRC screening. Furthermore, ONCOSCREEN will consider specific socio-economic determinants which increase the regional or national CRC risks, thus exploiting new solutions, particularly in younger high-risk individuals in European communities. For the validation of the developed solution, a clinical validation study (titled "ONCOSCREEN-CS") will be conducted to assess its effectiveness, sensitivity, and specificity in detecting CRC at an early stage. During the first phase of the study (ONCOSCREEN-CS-Phase A), the investigators will identify the different expression patterns of the four diagnostic solutions (ONCO-VOC, ONCO-CRISP, ONCO-NMR, ONCO-CTC) in CRC patients and healthy controls with high risk for CRC, and also initially estimate their sensitivity and specificity. During the second phase (ONCOSCREEN-CS-Phase B), the ONCOSCREEN solution will be clinically validated.
Cerebellar ataxias are a wide heterogeneous group of movement disorders. Within this broad umbrella of diseases, there are both genetics and sporadic forms. The clinical presentation of these conditions can exhibit a diverse range of symptoms across different age groups, spanning from pure cerebellar manifestations to sensory ataxia and multisystemic diseases. Over the last few decades, advancements in our understanding of genetics and molecular pathophysiology related to both dominant and recessive ataxias have propelled the field forward, paving the way for innovative therapeutic strategies aimed at preventing and arresting the progression of these diseases. Nevertheless, the rarity of certain forms of ataxia continues to pose challenges, leading to limited insights into the etiology of the disease and the identification of target pathways. Additionally, the lack of suitable models hampers efforts to comprehensively understand the molecular foundations of disease's pathophysiology and test novel therapeutic interventions. In the following review, we describe the epidemiology, symptomatology, and pathological progression of hereditary ataxia, including both the prevalent and less common forms of these diseases. Furthermore, we illustrate the diverse molecular pathways and therapeutic approaches currently undergoing investigation in both pre-clinical studies and clinical trials. Finally, we address the existing and anticipated challenges within this field, encompassing both basic research and clinical endeavors.
An insulin analogue comprises an insulin A-chain polypeptide and an insulin B-chain polypeptide. The A-chain polypeptide contains a Glu substitution at a position corresponding to position A8, and an Ala, Glu, Gln, His, Tyr, Phe or Trp substitution at a position A13, relative to wild type insulin. The B-chain polypeptide contains a cyclohexanylalanine substitution at position B24, relative to wild type insulin. The analogue may be an analogue of a mammalian insulin, such as human insulin. A nucleic acid encoding such an insulin analogue is also provided. A method of lowering the blood sugar of a patient comprises administering a physiologically effective amount of the insulin analogue or a physiologically acceptable salt thereof to a patient.
Magnesium sulfate 30 mg/kg with 100 ml saline will apply in 10 min before induction of general anesthesia (maximum magnesium dose 2g) (Group M) . When the magnesium infusion completed, general anesthesia induction will start.
Following successful completion of a screening visit, participants will attend the laboratory to complete 3 experimental visits during which they will undertake a 45-minute bout of moderate intensity continuous exercise on a bicycle ergometer at \~60% of the individualised VȮ2max. Prior to commencing exercise, participants will consume a standardised low-glycaemic index, carbohydrate-based meal (equating to 0.75g.CHO.kg.bm-1) with, or without, a 25% reduction in their meal-time insulin dose as well as with carbohydrates before or during exercise (according to the randomisation). Venous blood glucose sampling will be taken in 15-minute intervals leading into and after exercise with 5-minute intervals performed during exercise. Samples will be used to retrospectively cross-compare the metabolic, hormonal, and physiological responses between visits. Visits 1 \& 2 will be separated by ≥14 days to ensure adequate familiarisation with the AHCL system whilst visits 2 \& 3 will be separated by ≥3days. Each participant will undertake 1 screening and 3 experimental visits equating to a total of 80 study visits.
Endoscopic resection of small polyps is performed routinely through conventional outpatient colonoscopy. Larger polyps or incipient tumors can be excised with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). These minimally invasive procedures have been shown to be viable alternatives to conventional surgical resections with less risk of complications, shorter hospital stay and lower costs.

Both flexible endoscopic and open/laparoscopic surgical approaches have procedural limitations that can have considerable impact on patient care. Traditional endoscopic tools have technical inadequacies that may inhibit the physician's ability to complete more complex tasks consistent with a surgical technique. Conversely, a traditional open or laparoscopic surgical approach involves increased risk of complications (such as surgical site infection), increased pain and blood loss, longer recovery, and surgical scars. The objective of this clinical study is to assess the safety and efficacy of the ColubrisMX Endoluminal Surgical (ELS) System, a new robotic technology designed to assist the physician with precision, flexibility, and control during endoluminal removal of colorectal lesions.
Pregnant women in this group will perform treadmill exercise during 20 minutes. The intensity of exercise will be maintained between 60% and 80% of maximum heart rate by Karvonen formula, in addition to the subjective perception of exertion on the modified Borg scale (moderate intensity).
Hypersensitivity/infusion reactions, including but not limited to flushing, chest pain, dyspnea, hypotension, apnea, loss of consciousness, hypersensitivity and anaphylaxis, have been associated with the administration of temsirolimus. These reactions can occur very early in the first infusion, but may also occur with subsequent infusions. Patients should be monitored throughout the infusion and appropriate supportive care should be available. Temsirolimus infusion should be interrupted in all patients with severe infusion reactions and appropriate medical therapy administered. 

Temsirolimus injection should be used with caution in persons with known hypersensitivity to temsirolimus or its metabolites (including sirolimus), polysorbate 80, or to any other component (including the excipients) of Temsirolimus injection. 

An H1 antihistamine should be administered to patients before the start of the intravenous temsirolimus infusion. Temsirolimus injection should be used with caution in patients with known hypersensitivity to an antihistamine, or patients who cannot receive an antihistamine for other medical reasons. 

If a patient develops a hypersensitivity reaction during the Temsirolimus injection infusion, the infusion should be stopped and the patient should be observed for at least 30 to 60 minutes (depending on the severity of the reaction). At the discretion of the physician, treatment may be resumed with the administration of an H1-receptor antagonist (such as diphenhydramine), if not previously administered [see Dosage and Administration (2.2)], and/or an H2-receptor antagonist (such as intravenous famotidine 20 mg or intravenous ranitidine 50 mg) approximately 30 minutes before restarting the Temsirolimus injection infusion. The infusion may then be resumed at a slower rate (up to 60 minutes). 

A benefit-risk assessment should be done prior to the continuation of temsirolimus therapy in patients with severe or life-threatening reactions.