anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
N6-methyladenosine (m6A) is the most prevalent modification found in eukaryotic RNA and played a significant role in various cancers. However, the mechanism by which m6A modification influences cervical cancer (CC) tumorigenesis remains unclear. Therefore, we aim to elucidate the role and mechanism of METTL3 in CC progression. In the present study, we observed a significant upregulation of METTL3 in CC tissues and cell lines. Knockdown of METTL3 resulted in reduced growth, migration, and invasion of CC cells, as well as affected apoptosis, while overexpression of METTL3 reversed these effects. Through a combined analysis of meRIP-seq and Ribo-seq data following METTL3 knockdown, NEK2 was identified as a key target of METTL3 in CC cells. Correlation analysis, MeRIP-qPCR, and luciferase reporter assay suggested that METTL3 regulates NEK2 expression through m6A modification. NEK2 synergized with METTL3 to mediate the malignant phenotype of CC cells. The METTL3-NEK2 axis promoted CC progression by activating the Wnt/β-catenin pathway and inhibiting the apoptosis pathway. In conclusion, METTL3 facilitated the malignant progression of CC and contributed to the formation of the METTL3-NEK2 regulatory axis in an m6A-dependent manner, which represented a potential target for CC therapy.
Propranolol will be administered in the form of a liquid dose via oral syringe by the participants' parent/caregiver an hour before each EIBI session. To minimize risk, the bodyweight adjusted minimum dose of propranolol used safely for test anxiety in healthy adults (10mg) will be used: participants weighing \> 30 kg will be given 4 mg, participants weighing 22.5 - 30 kg will be given 3 mg, participants weighing 15 - 22.5 kg will be given 2 mg. Participants weighing \< 15 kg will be excluded for safety reasons.
PURPOSE:To obtain a solid cosmetic having high quality and composed of a sintered inorganic pigment and a colored substance impregnated in the pore of said sintered material, by heat-treating the sintered material prior to the impregnation of the cosmetic component, thereby causing the discoloration of the material. CONSTITUTION:The objective solid cosmetic is composed of a sintered inoganic pigment such as talc, kaolin, clay kaolin, bentonite, etc., and a colored substance impregnated in the pore of said sintered material. In the production of the above cosmetic, the sintered material is subjected to a heat-treatment process prior to the impregnation of the cosmetic component in an atmosphere different from the atmosphere used in the sintering process of the material. Discoloration of the sintered material takes place by this heat-treatment to obtain a material having different color tone. A solid cosmetic having high quality can be produced by this process. EFFECT:It gives excellent feeling and color tone to the skin and has excellent shape-retainability. USE:Suitable as a thin stick such as eyeliner, eyebrow pencil, etc.
A method of targeted drug delivery and imaging using nonionic surfactant vesicles (niosomes) in combination with ultrasound is presented. Niosomes have potential applications in targeted drug delivery and imaging because of their ability to encapsulate therapeutic agents and their enhanced uptake by physiological membranes. The niosomes may be administered to the subject via catheter. Ultrasound may be used to mediate delivery non-invasively by altering the niosome membrane structure. Niosomes composed of polyoxyethylene sorbitan monostearate (Tween 61), cholesterol, and dicetyl phosphate were synthesized via a thin film hydration technique and used for encapsulation studies. Carboxyfluorescein dye (CF) was used as a drug model to demonstrate delivery. The amount of dye in the niosomes, the concentration of the vesicles, and their mean particle size after each 5 minute incremental exposure to ultrasound was monitored. It was found that ultrasound at specific frequencies can reversibly permeabilize the lipid membrane of niosomes to allow the controlled release of a compound without destroying the niosome structure.
597940 Disclosed herein is a method the manufacture of 3alpha-hydroxy, 3beta-methyl-5alpha-pregnan-20-one (ganaxolone) comprising: reacting 5alpha-pregnane-3,20-dione (Dione 2) with an organometallic methylating agent in an inert solvent and thereby obtaining ganaxolone, wherein the organometallic methylating agent contains iron, titanium or a combination thereof. The method additionally comprising heating the obtained ganaxolone in an organic solvent, such as ethyl acetate, to obtain purified ganaxolone. The method additionally comprising generating the organometallic methylating agent by adding about 2 to about 4 equivalents of methyl magnesium halide or methyl lithium to a solution of anhydrous ferric halide or anhydrous ferrous halide in the inert solvent and thereby forming the organometallic methylating agent(s). The method additionally comprising adding lithium chloride to iron halide in the inert solvent prior to generating the organometallic methylating agent, wherein the amount of lithium chloride added is about 0.1 to about 4 equivalents of lithium chloride to equivalent of iron halide. The method wherein the organometallic methylating agent is dimethyl iron (Me2Fe), methyl triethoxy titanium, methylchloro diethoxy titanium ((CH3)Cl(CH3CH2O)2Ti), methyl trichlorotitanium (CH3Cl3Ti), tetramethyltitanium ((CH3)4Ti), dimethyl dichloro titanium ((CH3)2Cl2Ti), trimethyl chlorotitanium ((CH3)3ClTi) or methyl iron chloride (CH3FeCl). The method wherein the organometallic methylating agent is an ate complex containing a (Me)3Fe- anion and either lithium or MgX as a cation, wherein X is a halide.
PROBLEM TO BE SOLVED: To obtain a cosmetic material having an excellent preserving effect without blending a preserving agent. SOLUTION: This cosmetic material is obtained by blending a fatty acid salt and a polyvalent alcohol. As the fatty acid salt, it may preferably be the one produced by blending a fatty acid and a base as components in the preparation of the cosmetic material. Otherwise, the fatty acid salt may be directly blended in the preparation of the cosmetic material. The blending amounts are 0.1-40wt.% 6-22C fatty acid (e.g. stearic acid), 0.01-35wt.% base (e.g. L- arginine) and 1-30wt.% polyvalent alcohol (e.g. 1,3-butanediol). A soap, a shampoo, a cosmetic for the hair of a head, a hair dye, a cream, a milky lotion, a toilet lotion, a bath soap, etc., are prepared by blending the other commonly used components.  This composition exhibits safe and potent antimicrobial effects and demonstrates an excellent preserving effect to the secondary contamination with bacteria without using a common preserving agent. It is possible to resolve the trouble of a skin irritation caused by the preserving agent.
Sleep disturbance is a recognized risk factor for Alzheimer's disease (AD), but the underlying micro-pathological evidence remains limited. To bridge this gap, we established an amyloid-β oligomers (AβO)-induced rat model of AD and subjected it to intermittent sleep deprivation (SD). Diffusion tensor imaging (DTI) and transmission electron microscopy were employed to assess white matter (WM) integrity and ultrastructural changes in myelin sheaths. Our findings demonstrated that SD exacerbated AβO-induced cognitive decline. Furthermore, we found SD aggravated AβO-induced asymmetrical impairments in WM, presenting with reductions in tract integrity observed in commissural fibers and association fasciculi, particularly the right anterior commissure, right corpus callosum, and left cingulum. Ultrastructural changes in myelin sheaths within the hippocampus and corpus callosum further confirmed a lateralized effect. Moreover, SD worsened AβO-induced lateralized disruption of the brain structural network, with impairments in critical nodes of the left hemisphere strongly correlated with cognitive dysfunction. This work represents the first identification of a lateralized impact of SD on the mesoscopic network and cognitive deficits in an AD rat model. These findings could deepen our understanding of the complex interplay between sleep disturbance and AD pathology, providing valuable insights into the early progression of the disease, as well as the development of neuroimaging biomarkers for screening early AD patients with self-reported sleep disturbances. Enhanced understanding of these mechanisms may pave the way for targeted interventions to alleviate cognitive decline and improve the quality of life for individuals at risk of or affected by AD.
BACKGROUND: Healthcare-associated infections are among the most common complications during hospitalization. These infections increase morbidity and mortality and they increase length of hospital stay and the cost of healthcare. The aims of our study were to monitor hand hygiene (HH) compliance, HH technique quality and factors related to HH practice among health professionals in a COVID-19 Intensive Care Unit (ICU).
METHODS: An observational, prospective study. Between September and December 2021, we observed 69 healthcare professionals in an eight-bed ICU for patients with COVID-19 in midwestern Brazil. We used the WHO observation form to collect data. The dependent variable was HH compliance and independent variables were professional category, sex, HH quality (3-step technique for at least 15 s), number of HH opportunities observed, observation shift and inappropriate glove use.
RESULTS: We observed 1185 HH opportunities. The overall compliance rate was 26.4%, but only 6.5% were performed with the correct 3-step technique for the minimum time. HH compliance was considerably lower for moments "before" tasks (6.7%; 95% CI 4.8%, 9.2%) compared with moments "after" tasks (43.8%; 95% CI 39.9%, 47.8%). The logistic model found that inappropriate glove use, night shift and physicians (p < 0.001) were associated with low HH compliance. The infrastructure analysis found that the unit had an insufficient number of alcohol-based handrub (ABHR) dispensers at the point of care and that the mechanism for activating them was poorly designed.
CONCLUSIONS: HH compliance was very low. Inappropriate glove use was associated with low compliance and the unit's infrastructure did not support good HH practice. The fact that healthcare professionals were more likely to do HH after tasks, suggests that they use HH to protect themselves rather than the patients. Adequate infrastructure and ongoing health education with a focus on HH while caring for patients in contact precautions are essential for improving HH compliance and patient safety.
Observational prospective cohort: The primary objective of the study is to determine if variation of YKL-40 concentration (in blood or sputum) over 24 months will correlate with the biological or clinical condition of the patients. For this study, only patients (FEV1 \> 30%) positive for Pseudomonas in the past year will be included, while B Cepacia positive patients will be excluded. There are presently 200 patients meeting these inclusion criteria. The investigators choose to limit the study population to patients with Pseudomonas since they are more likely to have FEV1 changes or clinical evolution during the observation period. The investigators expect a high participation rate since the only obligation for the patients is to provide samples at each visit. A blood (for serum and DNA) and sputum samples will be taken at each regular clinic visit (3-4/year-no evidence of exacerbation in the past two weeks) as well as at the beginning and at the end of an exacerbation treated with IV antibiotics. This will also allow the investigators to determine if there is a change in YKL-40 during an exacerbation. The patients will be followed for a period of 24 months. In parallel to the measurement of YKL-40 in blood and airway secretions, other biological parameters will be monitored (see list below) as well as the BMI, lung function (FEV1/FVC), oxygen saturation and heart rate. The investigators will also monitor the glucose metabolism status of the patient (IGT, CFRD) and the number of exacerbations per year as well as any significant changes in the microbiology status of the patients. A pulmonary exacerbation will be defined as an acute exacerbation of pulmonary symptoms that in the opinion of the CF physician is severe enough to require intravenous antibiotics. The proposed sample size, was shown by power calculation, to be sufficient to demonstrate a meaningful changes in YKL-40 (initial-final) given plausible values of the standard deviation of this difference between patients.
This open-label, single dose, randomized, two-period, two-treatment, two-sequence, crossover study was conducted to investigate the bioequivalence of two formulations of balsalazide disodium 750 mg capsules under non-fasting conditions. The study was conducted with 60 (60 completing) healthy adults in accordance with Protocol No. BALS-06128 (Version 22 December 2006). In each study period, a single, oral 2250 mg dose (3 x 750 mg capsules) was administered to all subjects following an overnight fast of at least 10 hours. The test formulation was Mylan Pharmaceuticals Inc.'s Balsalazide Disodium Capsules, 750 mg and the reference formulation was Colazal® 750 mg capsules (manufactured for Salix Pharmaceuticals, Inc.). The subjects received the test product in one study period and the reference product in the other study period. Drug administration occurred according to the dosing randomization schedule (see Appendix 16.1.7). There was a 7-day washout interval between treatments.
BACKGROUND: Despite numerous studies that have explored the association between individual antioxidants or specific combinations and the risk of hearing loss, there is lack of information regarding the relationship between dietary total antioxidant capacity (dTAC) and hearing loss. The conflicting results on this association further highlight the need for more research in this area. This study aims to investigate the association between overall dietary antioxidant intake and the risk of hearing loss among Iranian adults.
METHODS: This cross-sectional study recruited 3443 adult participants aged between 19 and 67 years (with an average age of 41.4 years ± 8.8) who were employed at Tehran University of Medical Sciences in Iran. Participants underwent dietary assessment using a validated Food Frequency Questionnaire (FFQ). The hearing status of each participant was evaluated by a licensed audiologist in a soundproof room, using diagnostic audiometry that adhered to American National Standards specifications and followed standard audiometric clinical procedures. The dietary total antioxidant capacity (dTAC) was calculated using the Ferric Reducing-Antioxidant Power (FRAP) values.
RESULTS: 43.6% of male participants had hearing loss, while 26.8% among female participants. After accounting for various confounding factors, no significant association was observed between higher levels of dTAC and reduced odds of hearing loss in the overall population. However, among men under the age of 40, higher levels of dTAC were associated with decreased odds of hearing loss, even after adjusting for several covariates (OR: 0.56, 95% CI: 0.31-1.02, Ptrend = 0.02). This relationship was not evident in men over 40 years of age or among women.
CONCLUSION: The study found an inverse relationship between higher antioxidant intake in the diet and lower odds of hearing loss, specifically among men who were 40 years old or younger. However, this relationship was not observed in the overall population or among women. Additional prospective studies are necessary to validate these results.
Chronic kidney disease is increasing at an alarming rate and correlates with the increase in diabetes, obesity, and hypertension that disproportionately impact socioeconomically disadvantaged communities. Iron plays essential roles in many biological processes including oxygen transport, mitochondrial function, cell proliferation, and regeneration. However, excess iron induces the generation and propagation of reactive oxygen species, which lead to oxidative stress, cellular damage, and ferroptosis. Iron homeostasis is regulated in part by the kidney through iron resorption from the glomerular filtrate and exports into the plasma by ferroportin (FPN). Yet, the impact of iron overload in the kidney has not been addressed. To test more directly whether excess iron accumulation is toxic to kidneys, we generated a kidney proximal tubule-specific knockout of FPN. Despite significant intracellular iron accumulation in FPN mutant tubules, basal kidney function was not measurably different from wild type kidneys. However, upon induction of acute kidney injury (AKI), FPN mutant kidneys exhibited significantly more damage and failed recovery, evidence for ferroptosis, and increased fibrosis. Thus, disruption of iron export in proximal tubules, leading to iron overload, can significantly impair recovery from AKI and can contribute to progressive renal damage indicative of chronic kidney disease. Understanding the mechanisms that regulate iron homeostasis in the kidney may provide new therapeutic strategies for progressive kidney disease and other ferroptosis-associated disorders.NEW & NOTEWORTHY Physiological iron homeostasis depends in part on renal resorption and export into the plasma. We show that specific deletion of iron exporters in the proximal tubules sensitizes cells to injury and inhibits recovery. This can promote a chronic kidney disease phenotype. Our paper demonstrates the need for iron balance in the proximal tubules to maintain and promote healthy recovery after acute kidney injury.
Those randomized to the ONBOARD group will receive 12 weeks of CGM supplies and provide hemoglobin A1c values, data downloads, and survey responses during various time points in the study. They will also receive the intervention which consists of four 60-minute sessions with study interventionist, held 2 weeks apart.
PURPOSE OF REVIEW: Endometriosis (EM) is a chronic gynecological disease that affects about 10% of women worldwide. It is characterized by the implantation of endometrial cells at ectopic sites. The most common symptom of EM is painful menstruation, which can often lead to chronic pelvic pain that significantly worsens the quality of life. Because some disease-related processes, such as inflammation, hormonal activity, menstrual cycle, or prostaglandin metabolism, can be modified by diet, nutrition may have a significant impact on development and treatment of EM. The purpose of this article was to overview the current knowledge regarding the dietary management of endometriosis.
RECENT FINDINGS: The attention of researchers has so far concentrated mainly on the role of nutrition in the risk of developing EM, while less attention has been paid to examining the use of diet in the treatment of the disease. Current studies focus primarily on various dietary components that have antiproliferative, anti-inflammatory, antioxidant, analgesic, and estrogen-lowering properties. Exploring different ways of coping with endometriosis can make a significant contribution to improving the quality of life of women at risk or diagnosed with EM.
Subjects will receive food supplements in the form of 200ml juice drinks, containing either the active component, 1000mg of eicosapentaenoic acid and 1000mg docosahexaenoic acid, or matching placebo for a duration of six months. Neither the active nor the placebo food supplements taste of fish, so the subject will be blind to whether he/she is receiving the active intervention or placebo.
It has been demonstrated previously that human leukocyte antigen class I (HLA-I) and class II (HLA-II) alleles may modulate JAK2 V617F and CALR mutation (CALRmut)-associated oncogenesis in myeloproliferative neoplasms (MPNs). However, the role of immunogenetic factors in MPNs remains underexplored. We aimed to investigate the potential involvement of HLA genes in CALRmut+ MPNs. High-resolution genotyping of HLA-I and -II loci was conducted in 42 CALRmut+ and 158 JAK2 V617F+ MPN patients and 1,083 healthy controls. A global analysis of the diversity of HLA-I genotypes revealed no significant differences between CALRmut+ patients and controls. However, one HLA-I allele (C*06:02) showed an inverse correlation with presence of CALR mutation. A meta-analysis across independent cohorts and healthy individuals from the 1000 Genomes Project confirmed an inverse correlation between the presentation capabilities of the HLA-I loci for JAK2 V617F and CALRmut-derived peptides in both patients and healthy individuals. scRNA-Seq analysis revealed low expression of TAP1 and CIITA genes in CALRmut+ hematopoietic stem and progenitor cells. In conclusion, the HLA-I genotype differentially restricts JAK2 V617F and CALRmut-driven oncogenesis potentially explaining the mutual exclusivity of the two mutations and differences in their presentation latency. These findings have practical implications for the development of neoantigen-based vaccines in MPNs.
Various embodiments of the present disclosure pertain to methods of optimizing a treatment efficacy of a biological system by tuning a property of the biological system through the addition of an optimizing agent to the biological system. The tuning can include: (a) determining a property parameter of the biological system; (b) selecting an optimizing agent to be added to the biological system based on the determined property parameter; and (c) adding the optimizing agent to the biological system. The optimizing agent can include a kosmotropic material. The biological system can include a tissue, such as a tumor. The methods of the present disclosure can be utilized to enhance the efficacy of various treatments, such as the heat treatment of a biological system exposed to a radiofrequency field. The methods of the present disclosure can also include a step of treating the biological system.
BACKGROUND: The midline incision during total knee arthroplasty (TKA) is known to damage the infrapatellar branch of the saphenous nerve (IPBSN), leading to lateral flap numbness. The aim was to evaluate the rate of persistent skin numbness (RSN) and area of skin numbness (AON) after a lateral-based skin incision compared with the standard midline incision in bilateral TKA patients.
METHODS: Thirty-six patients undergoing bilateral TKA were included and randomly assigned to receive the lateral skin incision (lateral side of the tibial tubercle) on one knee and the standard midline incision on the contralateral. All other surgical steps were identical. Primary outcomes were the RSN at 1 year and the AON at 6 weeks, 3, 6, and 12 months postoperatively. Kneeling ability test (KAT), operative time, and length of incision were also recorded.
RESULTS: The lateral incision had half the RSN at 12 months compared to the midline incision (25% vs 53%; p = 0.01). The median AON at 1-year after surgery was 0 [0-0.5] cm2 in lateral incision vs 4 [0-7.5] cm2 in midline group (p < 0.001). KAT was minimally better in the lateral group at 110° of kneeling between 6-month to 1-year. Operative time and length of incision were similar between both groups.
CONCLUSION: The lateral skin incision reduced RSN by approximately 50% compared with the midline incision. The AON in lateral incision was 4 cm2 smaller than midline at 1-year after surgery. Moving a skin incision more lateral may be considered to minimize the numbness after TKA.