anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
EED is a core component of polycomb repressive complex 2 (PRC2) with EZH2 and SUZ12. PRC2 has H3K27 methyltransferase activity (HMTase) that catalyzes the addition of up to three methyl groups on histone 3 at lysine residue 27 (H3K27). Germline heterozygous variants in EED, SUZ12, and EZH2 have been identified in patients with overgrowth and multiple dysmorphic features. The clinical manifestations of these syndromes significantly overlap: generalized overgrowth, intellectual disability, and scoliosis. To date, 11 unrelated patients have been published with missense variants in EED at highly conserved amino acids. We report three affected members in a family with a previously reported missense variant. All three affected members manifested very similarly, and this represents a homogenous clinical phenotype associated with EED related intellectual disability and overgrowth. This disorder is appropriately called Cohen-Gibson syndrome.
Participants are allowed to choose between a low-carbohydrate or a low-fat diet for weight loss after receiving information about these diets and their food preferences (Choice arm). Then they receive counseling on their chosen diet in a small group format. The low-carbohydrate diet limits carbohydrate intake to 20-40 grams/day initially. The low-fat diet restricts saturated fat to below 30% of daily calories and has a 500-1000 calorie deficit. Group sessions are every 2 weeks for 24 weeks then alternate with telephone calls every 2 weeks for 24 weeks. Phone calls focus on goal setting to maximize weight loss. Participants also receive counseling on behavioral techniques and physical activity. Participants in this arm have the option to switch diets at 12 weeks.
PROBLEM TO BE SOLVED: To obtain a highly active and low-toxic new compound having specific tyrosine kinase inhibitory activity and useful in treating abnormal proliferation including cancer. SOLUTION: This new compound is a compound of formula I (Y is a group of formula II or formula III; R is a group of formula IV or the like; R3 is OH; R1 is H, a 1-6C alkyl or the like; R2 is H, a halogen or the like; when Y is the group of formula II, n is 0-3, when Y is the group of formula III, n is 0-2; wherein such a condition that, for the group of formula III, only the benzene moiety is substitutable with groups R, OR1 and R2 is satisfied), pref. 2-cyano-3-(2-hydroxynaphth-1-yl)thioacrylamide or the like.  The compound of formula I is obtained by condensation reaction of a compound of formula V (e.g. 2-hydroxy-1-naphthaldehyde) with e.g. a compound of the formula NC- CH2-CSNH2 in an inert organic solvent such as ethanol in the presence of a basic catalyst such as piperidine pref. at about 0-100 deg.C followed by, as necessary, e.g. conversion to the corresponding pharmaceutically acceptable salt.
Leucine residues are commonly found in the hydrophobic face of antimicrobial peptides (AMPs) and are crucial for membrane permeabilization, leading to the cell death of invading pathogens. Melittin, which contains four leucine residues, demonstrates broad-spectrum antimicrobial properties but also significant cytotoxicity against mammalian cells. To enhance the cell selectivity of melittin, this study synthesized five analogs by replacing leucine with its structural isomer, 6-aminohexanoic acid. Among these analogs, Mel-LX3 exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria. Importantly, Mel-LX3 displayed significantly reduced hemolytic and cytotoxic effects compared to melittin. Mechanistic studies, including membrane depolarization, SYTOX green uptake, FACScan analysis, and inner/outer membrane permeation assays, demonstrated that Mel-LX3 effectively permeabilized bacterial membranes similar to melittin. Notably, Mel-LX3 showed robust antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Pseudomonas aeruginosa (MDRPA). Furthermore, Mel-LX3 effectively inhibited biofilm formation and eradicated existing biofilms of MDRPA. With its improved selective antimicrobial and antibiofilm activities, Mel-LX3 emerges as a promising candidate for the development of novel antimicrobial agents. We propose that the substitution of leucine with 6-aminohexanoic acid in AMPs represents a significant strategy for combating resistant bacteria.
PURPOSE:To increase the yield of a protein without containing methionine residue corresponding to a translation starting codon ATG in the N terminal, by adding a special ion source and nitrogen source to a culture medium for Escherichia coli having an expression vector having the translation starting codon ATG. CONSTITUTION:Escherichia coli having an expression vecot containing a structural gene of a protein, e.g. interleukin, on the downstream side of a translation starting codon ATG is cultivated in a culture medium prepared by adding (1) an iron ion source and/or manganese ion source and (2) a nitrogen source derived from natural products. A mineral acid salt of trivalent iron is particularly preferred for the iron ion source. A mineral acid salt of manganese is preferred for the manganese source. Such sources are preferably added in respective amounts of 2X10<-5>-5X10<-4>mol. When both are used together, the concentration ranges thereof for addition are respectively the above-mentioned values. Casamino acid, peptone, yeast extract, malt extract, etc., are preferred for the nitrogen source derived from natural products.
BACKGROUND AND OBJECTIVE: Pediatric dosing of enoxaparin was derived based on extrapolation of the adult therapeutic range to children. However, a large fraction of children do not achieve therapeutic anticoagulation with initial dosing. We aim to use real-world anti-Xa data obtained from children receiving enoxaparin per standard of care to characterize the population pharmacokinetics (PopPK).Author names: Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Also, kindly confirm the details in the metadata are correct.The author names are accurately presented and the metadata are correct.  METHODS: A PopPK analysis was performed using NONMEM, and a stepwise covariate modeling approach was applied for the covariate selection. The final PopPK model, developed with data from 1293 patients ranging in age from 1 day to 18 years, was used to simulate enoxaparin subcutaneous dosing for prophylaxis and treatment based on total body weight (0-18 years, TBW) or fat-free mass (2-18 years, FFM). Simulated exposures in children with obesity (body mass index percentile ≥95th percentile) were compared with those without obesity.
RESULTS: A linear, one-compartment PopPK model that included allometric scaling using TBW (<2 years) or FFM (≥2 years) characterized the enoxaparin pharmacokinetic data. In addition, serum creatinine was identified as a significant covariate influencing clearance. Simulations indicated that in patients aged <2 years, the recommended 1.5 mg/kg TBW-based dosing achieves therapeutic simulated concentrations. In pediatric patients aged ≥2 years, the recommended 1.0 mg/kg dose resulted in exposures more comparable in children with and without obesity when FFM weight-based dosing was applied.
CONCLUSION: Using real-world data and PopPK modeling, enoxaparin's pharmacokinetics were characterized in pediatric patients. Using FFM and twice-daily dosing might reduce the risk of overdosing, especially in children with obesity.
Renal Toxicity

Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, salt depletion, those taking diuretics and angiotensin-converting enzyme (ACE) inhibitors or ARBs, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.

TREXIMET should be discontinued if clinical signs and symptoms consistent with renal disease develop or if systemic manifestations occur.

TREXIMET is not recommended for use in patients with severe renal impairment (creatinine clearance [CrCl] <30 mL/min) unless the benefits are expected to outweigh the risk of worsening renal function [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)]. If TREXIMET is used in patients with advanced renal disease, monitor patients for signs of worsening renal function. Monitor renal function in patients with mild (CrCl = 60 to 89 mL/min) or moderate (CrCl = 30 to 59 mL/min) renal impairment, preexisting kidney disease, or dehydration.

The renal effects of TREXIMET may hasten the progression of renal dysfunction in patients with pre-existing renal disease.

Correct volume status in dehydrated or hypovolemic patients prior to initiating TREXIMET. Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during use of TREXIMET [see Drug Interactions (7)]. Avoid the use of TREXIMET in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function. If TREXIMET is used in patients with advanced renal disease, monitor patients for signs of worsening renal function.

Hyperkalemia

Increases in serum potassium concentration, including hyperkalemia, have been reported with the use of NSAIDs, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state.
<P>PROBLEM TO BE SOLVED: To provide a medicine which prevents the death of light receptor cells without exhibiting a significant dividing effect on the light receptor cells and is used for retinal diseases.  <P>SOLUTION: This medicine for retarding or preventing the damages to or death of retinal cells or saving the retinal cells from the damages or death contains a therapeutically effective amount of an active FGF(fibroblast growth factor)-5 polypeptide. The active FGF-5 polypeptide has at least 90% of homology based on natural sequence FGF-5 molecule. The active FGF-5 polypeptide is selected from the group consisting of sequence number: 2, sequence number: 3 and sequence number: 5. The active FGF-5 polypeptide is encoded in a nucleotide sequence which is hybridized with the nucleic acid residues 26 to 769 of the sequence number: 1 under a stringent condition.  <P>COPYRIGHT: (C)2006,JPO&NCIPI
Children diagnosed with severe tonsillar hypertrophy display discernible craniofacial features distinct from those with adenoid hypertrophy, prompting illuminating considerations regarding microbiota regulation in this non-inflammatory condition. The present study aimed to characterize the salivary microbial profile in children with tonsillar hypertrophy and explore the potential functionality therein. A total of 112 children, with a mean age of 7.79 ± 2.41 years, were enrolled and divided into the tonsillar hypertrophy (TH) group (n = 46, 8.4 ± 2.5 years old), adenoid hypertrophy (AH) group (n = 21, 7.6 ± 2.8 years old), adenotonsillar hypertrophy (ATH) group (n = 23, 7.2 ± 2.1 years old), and control group (n = 22, 8.6 ± 2.1 years old). Unstimulated saliva samples were collected, and microbial profiles were analyzed by 16S rRNA sequencing of V3-V4 regions. Diversity and composition of salivary microbiome and the correlation with parameters of overnight polysomnography and complete blood count were investigated. As a result, children with tonsillar hypertrophy had significantly higher α-diversity indices (P<0.05). β-diversity based on Bray-Curtis distance revealed that the salivary microbiome of the tonsillar hypertrophy group had a slight separation from the other three groups (P<0.05). The linear discriminant analysis effect size (LEfSe) analysis indicated that Gemella was most closely related to tonsillar hypertrophy, and higher abundance of Gemella, Parvimonas, Dialister, and Lactobacillus may reflect an active state of immune regulation. Meanwhile, children with different degrees of tonsillar hypertrophy shared similar salivary microbiome diversity. This study demonstrated that the salivary microbiome in pediatric tonsillar hypertrophy patients had different signatures, highlighting that the site of upper airway obstruction primarily influences the salivary microbiome rather than hypertrophy severity.IMPORTANCETonsillar hypertrophy is the most frequent cause of upper airway obstruction and one of the primary risk factors for pediatric obstructive sleep apnea (OSA). Studies have discovered that children with isolated tonsillar hypertrophy exhibit different craniofacial morphology features compared with those with isolated adenoid hypertrophy or adenotonsillar hypertrophy. Furthermore, characteristic salivary microbiota from children with OSA compared with healthy children has been identified in our previous research. However, few studies provided insight into the relationship between the different sites of upper airway obstruction resulting from the enlargement of pharyngeal lymphoid tissue at different sites and the alterations in the microbiome. Here, to investigate the differences in the salivary microbiome of children with tonsillar hypertrophy and/or adenoid hypertrophy, we conducted a cross-sectional study and depicted the unique microbiome profile of pediatric tonsillar hypertrophy, which was mainly characterized by a significantly higher abundance of genera belonging to phyla Firmicutes and certain bacteria involving in the immune response in tonsillar hypertrophy, offering novel perspectives for future related research.
This study aims to compare the conventional cardiopulmonary resuscitation (CPR) training program (HEROS CPR training program) with the HEROS VR (virtual reality) CPR training program to which the newly developed VR curriculum was added. The experimental group is the HEROS VR training group, and CPR training is conducted for approximately 60 minutes for 6 to 8 trainees per training. At the start and the end of the training, students are taught about cardiac arrest, recognition of emergency situations, and reporting to 119 by watching VR, and in the middle part, they practice chest compressions by watching conventional HEROS video. The control group is the existing HEROS training group. To control variables, the number of trainees per training was limited to 6 to 8, and the existing video-based CPR training was implemented. The investigators will conduct a Modified Basic Resuscitation Skills Self-Efficacy scale survey before and after training to compare the difference in the improvement of trainees' self-efficacy evaluation of CPR after CPR training in the HEROS VR curriculum and the existing HEROS curriculum.
PURPOSE:To obtain an external preparation capable of releasing most of medicine within prescribed time, having large water-absorbing ability of tacky agent and good adhesion to skin by laminating a high polymer tacky agent containing eperisone to eperisone-impermeable supporter. CONSTITUTION:The aimed external preparation for improving myotonia and circulation obtained by laminating a high polymer tacky agent containing 4'- ethyl-2-methyl-3-piperidinopropiophenone (eperisone) expressed by the formula and/or salt thereof to a supporter inert and impermeable to the above-mentioned medicine. when eperisone and salt thereof are used at a mixed ratio of 200-0.1, especially 20-5, plasticization of the tacky agent is suppressed and preparation having higher stability is obtained. A copolymer consisting of 40-75 pts.wt. 2-ethylhexyl acrylate, 20-55 pts.wt. methoxyethyl acrylate and 5-40 pts.wt. vinyl acetate is preferably used as the above-mentioned tacky agent.
Diagnosis based on clinical symptomatology and skin test positive for allergen and negative for other drugs and substances. Skin tests are performed 6 weeks after allergic reaction.
Disclosed are a PROTAC compound with cyclophilin A degradation activity, a preparation method therefor, and use thereof. The structural formula of the PROTAC compound is represented by formula (I). The compound represented by formula (I) provided by the present invention can be used for preventing and/or treating CypA-mediated diseases, such as CypA-mediated inflammation, autoimmune diseases, and/or tumors. The present invention also provides a pharmaceutical composition comprising the compound represented by formula I as an active ingredient and at least one pharmaceutically acceptable carrier, excipient, and/or diluent. The PROTAC compound provided by the present invention can degrade CypA protein in a targeted manner, so that the PROTAC compound can be used for preparing medicaments for treating inflammation, autoimmune diseases, tumors, and other related diseases. The compound represented by formula I in the present invention has a significant inhibitory function on virus-induced pneumonia, rheumatoid arthritis, and lung cancer cell migration and infiltration.
BACKGROUND: Morphometric analysis of the psoas major muscle has shown utility in predicting postoperative morbidity in various surgical fields, but its usefulness in predicting complications in elderly patients undergoing multilevel lumbar fusion surgery has not been studied. The study aimed to investigate if psoas major parameters are independent risk factors of early postoperative complication among elderly patients.
METHODS: Patients who underwent multilevel lumbar fusion for degenerative lumbar spinal stenosis (DLSS) were included. The psoas major was measured at the lumbar 3/4 intervertebral disc level in three ways on computed tomography image: psoas muscle mass index, mean muscle attenuation, and morphologic change of the psoas major. Early complications were graded using the Clavien-Dindo classification system and the Comprehensive complication index (CCI). A CCI ≥ 26.2 indicated severe complications. Logistic regression was performed to identify independent risk factors.
RESULTS: This retrospective study reviewed 108 patients (mean age 70.9 years, female to male ratio 1.8:1). Complications were observed in 72.2% of patients, with allogeneic blood transfusion being the most frequent (66.7%), followed by wound infection, acute heart failure (2.8% each). Severe complications occurred in 13.9% of patients. After multivariable regression analysis, those in the lowest psoas muscle attenuation tertile had higher odds of experiencing early postoperative complications (OR: 3.327, 95% CI 1.134-9.763, p = 0.029) and severe complications (OR: 6.964, 95% CI 1.928-25.160, p = 0.003).
CONCLUSION: The psoas muscle attenuation can be used as a predictor of early postoperative complications in elderly patients undergoing multilevel lumbar fusion surgery for DLSS.
Provided is a method for producing an extract of  Momordica charantia var. pavel , said extract containing less than 5 ppm of quinine. The method for producing an extract of  M. charantia var. pavel  comprises a cultivation step, a harvesting step, a drying step, a grinding step, a classification step and an extraction step. In the cultivation step,  M. charantia var. pavel  is cultivated while picking growing flowers or buds. In the harvesting step,  M. charantia var. pavel  leaves and/or stems obtained in the cultivation step are harvested as a starting material. In the drying step, the starting material is warm-air dried at 60-80 o C inclusive to give a dry product. In the grinding step, the dry product is ground to give a ground product. In the classification step, the ground product is classified to give a classified product with a grain size of 50-200 mesh inclusive. In the extraction step, the classified product is extracted with ethanol to give an extract. Also provided is a  M. charantia var. pavel  extract that contains less than 5 ppm of quinine.
The purpose of this study is to validate the Disease Severity Index (DSI) from the HepQuant SHUNT Liver Diagnostic Kit (Test) for likelihood of large esophageal varices. Our HALT-C Training dataset demonstrated that the DSI 18.3 had sensitivity 95%, specificity 54%, PPV 19%, NPV \>99%, negative likelihood ratio (NLR) 0.09, and positive likelihood ratio (PLR) 2.09 for large varices. To validate DSI 18.3 as a cutoff for large varices, we will enroll 420 subjects with chronic liver disease (CLD) of mixed etiologies from 15 to 25 US clinical centers (CLD Validation dataset). The target prevalence of large varices is ≥20%. Each subject will have been scheduled for an esophago-gastro-duodenoscopy (EGD) as part of their standard of care for either variceal or non-variceal indications. Enrolled subjects will undergo standard clinical assessment, laboratory tests, and the HepQuant SHUNT Test. The EGD will be performed within 6 weeks following the HepQuant SHUNT Test. The relationship of DSI to large varices will be analyzed by univariate and multivariate logistic regression analyses, AUROC, and linear and nonlinear regression and correlation coefficients. Diagnostic performance of the DSI cutoff will be defined in the CLD Validation dataset and validated for likelihood of large esophageal varices. The validated DSI cutoff will identify subjects who are either unlikely or likely to have large esophageal varices.
Diverse individuals age at different rates and display variable susceptibilities to tissue aging, functional decline and aging-related diseases. Centenarians, exemplifying extreme longevity, serve as models for healthy aging. The field of human aging and longevity research is rapidly advancing, garnering significant attention and accumulating substantial data in recent years. Omics technologies, encompassing phenomics, genomics, transcriptomics, proteomics, metabolomics and microbiomics, have provided multidimensional insights and revolutionized cohort-based investigations into human aging and longevity. Accumulated data, covering diverse cells, tissues and cohorts across the lifespan necessitates the establishment of an open and integrated database. Addressing this, we established the Human Aging and Longevity Landscape (HALL), a comprehensive multi-omics repository encompassing a diverse spectrum of human cohorts, spanning from young adults to centenarians. The core objective of HALL is to foster healthy aging by offering an extensive repository of information on biomarkers that gauge the trajectory of human aging. Moreover, the database facilitates the development of diagnostic tools for aging-related conditions and empowers targeted interventions to enhance longevity. HALL is publicly available at https://ngdc.cncb.ac.cn/hall/index.
<P>PROBLEM TO BE SOLVED: To obtain a sustained-release medicine composition in physiologically active protein.  <P>SOLUTION: The sustained-release preparation is obtained by mixing interleukin 11 with hyaluronic acid. The sustained-release preparation is obtained by mixing interleukin 11 with two kinds of a cationic polymer and an anionic polymer having different charges. The continuous blood concentration transition of interleukin 11 and enhancement of pharmacological action followed by the concentration transition are attained. Avoidance of frequent administration, alleviation of adverse effect and enhancement of treating effect of interleukin 11 are expected.  <P>COPYRIGHT: (C)2006,JPO&NCIPI