anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
PURPOSE:To obtain a suppository exhibiting excellent solidification property in cast molding process in a mold, having excellent drug stability and high releasability of a specific drug, by adding a drug to a suppository base composed of a diglyceride of a laurin-based oil or fat and a fatty acid. CONSTITUTION:The objective suppository is produced by adding a drug to a suppository base composed of 80-99wt% laurin-based oil or fat having a hydroxyl value of <=20 and composed mainly of a glyceride of a 8-18C fatty acid and 1-20wt% diglyceride of a 14-22C fatty acid. The drug is e.g. a steroid hormone (e.g. hydrocortisone acetate), local anesthetic (e.g. aspyrin), non-steriod anti-inflammatory agent (e.g. allantoin), remedy for constipation (e.g. picosulfate sodium), etc. The above suppository base has excellent drug stability and moldability as well as handleability and the suppository produced by this process has excellent drug-releasing property and absorbability.
Timothy syndrome (TS) is a severe, multisystem disorder characterized by autism, epilepsy, long-QT syndrome and other neuropsychiatric conditions1. TS type 1 (TS1) is caused by a gain-of-function variant in the alternatively spliced and developmentally enriched CACNA1C exon 8A, as opposed to its counterpart exon 8. We previously uncovered several phenotypes in neurons derived from patients with TS1, including delayed channel inactivation, prolonged depolarization-induced calcium rise, impaired interneuron migration, activity-dependent dendrite retraction and an unanticipated persistent expression of exon 8A2-6. We reasoned that switching CACNA1C exon utilization from 8A to 8 would represent a potential therapeutic strategy. Here we developed antisense oligonucleotides (ASOs) to effectively decrease the inclusion of exon 8A in human cells both in vitro and, following transplantation, in vivo. We discovered that the ASO-mediated switch from exon 8A to 8 robustly rescued defects in patient-derived cortical organoids and migration in forebrain assembloids. Leveraging a transplantation platform previously developed7, we found that a single intrathecal ASO administration rescued calcium changes and in vivo dendrite retraction of patient neurons, suggesting that suppression of CACNA1C exon 8A expression is a potential treatment for TS1. Broadly, these experiments illustrate how a multilevel, in vivo and in vitro stem cell model-based approach can identify strategies to reverse disease-relevant neural pathophysiology.
In this application, we propose an augmentation strategy intended to improve the efficacy of modafinil as a potential treatment for cocaine dependence. Recent data indicates that during chronic treatment modafinil produces substantial dopamine transporter (DAT) inhibition. Given that cocaine inhibits DA, norepenepherine (NE) and serotonin (5-HT) reuptake, it is highly likely that targeting more than one neurotransmitter system will be necessary for a medication to be effective. Assuming that this statement is true, we hypothesize that a combination pharmacotherapeutic approach that concurrently modulates multiple neurotransmitter systems will likely demonstrate a clinically significant level of efficacy above trials in which a single medication is used. The proposed approach is based on preclinical data indicating that medications that increase brain 5-HT levels reduce the effects of stimulants. We hypothesize that combining modafinil with a selective serotonin reuptake inhibitor (SSRI), which will increase synaptic levels of 5-HT, will further improve the efficacy of modafinil for reducing the effects produced by cocaine.

Specific Aims: 1) to determine the effects of treatment with oral modafinil (0 or 200 mg) plus the SSRI escitalopram (0 or 20 mg) on the subjective and reinforcing effects produced by intravenous cocaine (0 and 20 mg) in the laboratory. 2) to characterize the cocaine dependent population and the genetic basis for the rewarding effects produced by cocaine. 3) to characterize the effect of both modafinil treatment and cocaine exposure onBrain Derived Neurotrophic Factor (BDNF) in plasma. We hypothesize that both modafinil treatment and cocaine exposure will alter plasma levels of BDNF. 4 a) provide a more frequent measure of heart rate (15 sec vs. 5 minutes) and b) measure a new dependent variable, physical activity, on days with and without cocaine exposure.
Group 1:50 stressed subjects who will have a 28-day intake of dietary supplement. Of the 50 stressed subjects, 20 subjects will participate in the fMRI exam. Dietary supplement is composed of Mg (150 mg), Vitamin B6 (0.7 mg), Vitamin B9 (100µg), Vitamin B12 (1.25 µg), rhodiola (222mg), and green tea/L-théanine (125 mg).
Patients with inflammatory bowel disease (IBD) are at increased risk of Clostridioides difficile infection (CDI). Herein, we aimed to determine if genetic risk contributes to this observed association. We carried out a genome-wide association study (GWAS) analysis in the Michigan Genomics Initiative and the United Kingdom Biobank for CDI based on ICD codes and meta-analyzed these results with similar publicly accessible GWAS summary statistics from Finngen. Conditional and joint multi-SNP analyses were used to identify independent associations. Imputation of the human leukocyte antigen (HLA) region with fine mapping was used to try to identify causal HLA allele groups. Two-sample bidirectional Mendelian randomization (MR) was implemented to determine causal relationships between IBD and CDI. A total of 3,500 cases of CDI and 674,323 controls were meta-analyzed, revealing one genome-wide significant variant for CDI, HLA-C;LINC02571-rs3134745-C (P = 4.27E-08), which annotated to the major histocompatibility complex on chromosome 6. While fine mapping did not identify a statistically significant HLA allele group, there was a suggestive signal for HLA-B*35:01 (P = 4.74e-04). Using two-sample MR, genetically predicted IBD was associated with increased risk of CDI (MR Egger [odds ratio {OR} 1.16, 95% confidence interval {CI} 1.02-1.31]). Subset analysis revealed that risk was primarily driven by genetically predicted ulcerative colitis (MR Egger [OR 1.22, 95% CI 1.05-1.41]). These results highlight the importance of the host immune response in CDI pathogenesis, help explain the observed relationship between IBD and CDI, and open new avenues for targeted treatment of CDI in IBD.IMPORTANCEData from this paper (i) provide reproducible evidence that susceptibility CDI is genetically mediated, (ii) highlight genetic risk as a mechanism for the increased risk of CDI in patients with inflammatory bowel disease, and (iii) point toward anti-interleukin-23 therapy as a common therapeutic strategy.
This is a randomized (individuals will be assigned by chance to study treatments), double-blind (individual and investigator will not know the identity of study treatments), placebo (substance containing no active medication)-controlled, 2-arm study in patients with sputum smear-positive pulmonary infection with multi-drug resistant tuberculosis (MDR-TB) defined as tuberculosis (TB) due to infection with a strain of Mycobacterium tuberculosis (M. tuberculosis) that is resistant to both isoniazid and rifampin, or pre-extensively drug resistant (pre-XDR-TB) defined as TB due to infection with an MDR strain of M. tuberculosis that is resistant either to at least one of the injectable second-line drugs \[amikacin, kanamycin, or capreomycin\] or to any fluoroquinolone, but not both). Approximately 600 patients with sputum smear-positive pulmonary infection with MDR-TB or pre-XDR TB will receive a background regimen (BR) of MDR-TB therapy and will be randomly assigned in a 1:1 ratio to one of 2 treatment arms (Arms A \[TMC207 + BR\] and B \[placebo + BR\]). All patients will receive TMC207 or placebo in combination with a BR of MDR-TB therapy. TMC207 (or matching placebo) will be taken as oral tablets at a once daily dose of 400 mg for the first 2 weeks and 200 mg 3 times/week for the remaining period of TMC207 (or matching placebo) administration. The study will consist of a screening phase of a maximum of 3 weeks, a 36-week double-blind treatment phase, followed by a 48-week follow-up phase up to Week 84, also referred to as the treatment-free follow-up. After the treatment-free follow-up phase, there will be a safety follow-up phase of 48 weeks up to Week 132. Patients from Arms A or B who fail treatment according to prespecified criteria will be given the option to receive 24 weeks of TMC207 plus an individualized salvage regimen taken for a duration consistent with national TB guidelines. Efficacy and pharmacokinetic evaluations will be performed at time points as detailed in the protocol. Safety will be monitored throughout the study.
PCT No. PCT/FI95/00166 Sec. 371 Date Apr. 2, 1996 Sec. 102(e) Date Apr. 2, 1996 PCT Filed Mar. 29, 1995 PCT Pub. No. WO95/26711 PCT Pub. Date Oct. 12, 1995The present invention is directed to an ophthalmic composition in the form of a topical aqueous solution consisting essentially of an ophthalmologically active agent, an ion sensitive, hydrophilic polymer in an amount a of 0.004 to 1.5% by weight, at least one salt selected from the group of inor ganic salts and buffers in a total amount of from 0.01 to 2.0% by weight, a wetting agent in an amount of 0 to 3.0% by weight, a preservative in an amount of 0 to 0.02% by weight, water, and optionally a pH regulating agent in an amount sufficient to give a pH of 4.0 to 8.0 to the composition, the ratio between salt and polymer components being such that the solution exhibits a viscosity of less than 1000 mPas. The composition contains a sufficient amount of polymer to provide for a controlled absorption of the drug into the eye, its viscosity having been reduced to provide for better handling characteristics.
The invention discloses a composite material for artificial teeth and a selective laser sinter molding method and an application thereof. The method includes raw materials, a powder preparation method and a material molding method. The raw materials contain polymethyl methacrylate, hydroxyapatite nano-particles, an emulsifier, microcrystalline wax and paraffin. The powder preparation method comprises the following steps: firstly carrying out lipophilic modification on the hydroxyapatite nano-particles by a wax emulsification method and then preparing a polymethacrylate powder material doped with the hydroxyapatite nano-particles by hot-melting mechanical agitation and crushing ball milling. According to the molding method, a polymethacrylate powder is molded by a selective laser sintering technology. By the adoption of the artificial teeth dedicated composite material with a composite bioactivity, the problem that traditional artificial teeth have insufficient mechanical strength and poor compatibility can be solved effectively. In addition, as the selective laser sinter molding technology is provided, preparation time of artificial teeth is shortened greatly, teeth replacement cycle is minimized for patients, and requirements of doctors and patients on artificial teeth are met.
FIELD: medicine. SUBSTANCE: method involves distributing medical preparation over tissues in the radiation exposure region. Preparations containing Vitaon oil are used as the mentioned preparation administered directly before and after each irradiation treatment all over the whole course of radiation therapy. Preparations are applied several times after each treatment until radiation reaction vanishes. EFFECT: enhanced effectiveness of treatment. 2 cl
PROBLEM TO BE SOLVED: To provide an external preparation for skin which increases an enzyme activity associated with the skin condition, and improves the skin condition.SOLUTION: The invention provides an external preparation for skin containing a production acceleration component of heat shock proteins and polyethylene glycol having a weight average molecular weight of 2000-5000. The external preparation for skin of the invention can increase the enzyme activity in a horny layer, and can improve the skin condition. The external preparation for skin of the invention is preferred not to contain an oil solution substantially, and can be used as cosmetics. As a production acceleration component of heat shock proteins, specifically, extract of Curcuma longa, Paeoniae Radix, Salix alba, Glycyrrhiza, and Prunus persica can be illustrated. The root, stem, branch, leaf, seed of the plant having these production acceleration components of heat shock proteins, and a single part of the whole plant may be used, or two or more parts of the whole plant also may be used. Pulverized as it is or dried materials may be used. The extract using a polar solvent as an extracting solvent can be illustrated preferably.
The invention discloses an extraction method of a Hedyotis diffusa Willd. anti-cancer active component. The method includes: taking a Hedyotis diffusa Willd. whole plant as the raw material, extracting it 2-3 times with n-hexane, conducting pumping filtration to separate an n-hexane extraction solution and a residue, and extracting the residue 2-3 times with 85-95% ethanol so as to obtain ethanol extraction solutions; combining the ethanol extraction solutions, and carrying out concentration to obtain an extract; and re-suspending the extract in deionized water, then carrying out extraction with ether and ethyl acetate respectively, combining and concentrating the extracted substances, subjecting the mixture to silica gel column chromatography, performing gradient elution with n-hexane-dichloromethane and dichloromethane-ethyl acetate respectively, collecting the n-hexane-dichloromethane-ethyl acetate elution solution, and performing concentration and drying by evaporation, thus obtaining the Hedyotis diffusa Willd. extract. According to the invention, by means of ethanol solution extraction, liquid-liquid extraction enrichment and silica gel column chromatography purification, the method prepares the Hedyotis diffusa Willd. anti-cancer active component with increased content of free anthraquinone and total tritepenoidic acid, as well as substantially improved anticancer activity.
OBJECTIVE: Branchio-oto-renal syndrome (BOR, OMIM#113,650) is a rare autosomal dominant disorder that presents with a variety of symptoms, including hearing loss (sensorineural, conductive, or mixed), structural abnormalities affecting the outer, middle, and inner ear, branchial fistulas or cysts, as well as renal abnormalities.This study aims to identify the pathogenic variants by performing genetic testing on a family with Branchio-oto-renal /Branchio-otic (BO, OMIM#602,588) syndrome using whole-exome sequencing, and to explore possible pathogenic mechanisms.
METHODS: The family spans 4 generations and consists of 9 individuals, including 4 affected by the BOR/BO syndrome. Phenotypic information, including ear malformation and branchial cleft, was collected from family members. Audiological, temporal bone imaging, and renal ultrasound examinations were also performed. Whole-exome sequencing was conducted to identify candidate pathogenic variants and explore the underlying molecular etiology of BOR/BO syndrome by minigene experiments.
RESULTS: Intra-familial variability was observed in the clinical phenotypes of BOR/BO syndrome in this family. The severity and nature of hearing loss varied in family members, with mixed or sensorineural hearing loss. The proband, in particular, had profound sensorineural hearing loss on the left and moderate conductive hearing loss on the right. Additionally, the proband exhibited developmental delay, and her mother experienced renal failure during pregnancy and terminated the pregnancy prematurely. Genetic testing revealed a novel heterozygous variant NM_000503.6: c.639 + 3 A > C in the EYA1 gene in affected family members. In vitro minigene experiments demonstrated its effect on splicing. According to the American College of Medical Genetics (ACMG) guidelines, this variant was classified as likely pathogenic.
CONCLUSION: This study highlights the phenotypic heterogeneity within the same family, reports the occurrence of renal failure and adverse pregnancy outcomes in a female patient at reproductive age with BOR syndrome, and enriches the mutational spectrum of pathogenic variants in the EYA1 gene.
FIELD: food technology, medicine, biochemistry. SUBSTANCE: invention relates to cacao bean extracts, such as polyphenols, preferably polyphenols, enriched with procyanidines. Cacao extract is prepared by method involving grinding cacao beans to powder, defatting the prepared powder and extraction active compounds from this powder. Invention relates also to using cacao extracts, mainly, in antitumoral compositions, in compositions that inhibit activity of topoisomerase and as antioxidants. Invention provides the prescription of indicated compositions based on cacao extracts. EFFECT: improved preparing methods, valuable medicinal properties of extracts. 30 cl, 20 dwg, 8 tbl, 12 ex
Many RNAs cause disease, however RNA is rarely exploited as a small molecule drug target. Disclosed herein are methods for identifying privileged RNA motif-small molecule interactions to enable the rational design of compounds that modulate RNA biology starting from only sequence. A massive, library-versus-library screen was completed that probed over 50 million binding events between RNA motifs and small molecules. The resulting data provide a rich encyclopedia of small molecule-RNA recognition patterns, defining chemotypes and RNA motifs that confer selective, avid binding. The resulting interaction maps were mined against the entire viral genome of hepatitis C virus (HCV). A small molecule was identified that avidly bound RNA motifs present in the HCV3' untranslated region and inhibited viral replication while having no effect on host cells. Collectively, this investigation represents the first whole genome pattern recognition between small molecules and RNA folds.
Stage 1- Avastin 1.25 mg intravitreal injection administered at baseline (Day 0), 4 weeks and 8 weeks with prn Avastin injection at weeks 12, 16, or 20 for a total of at least 3 and up to 6 Avastin injections. Sham injections may be performed at weeks 12, 16, and 20 if prn Avastin is not required.
This study systematically evaluated and ranked the efficacy of first- and second-line antibiotics antibiotic options for the clinical management of cellulitis and erysipelas through a network meta-analysis approach. From inception to July 04, 2024, a search for relevant randomized clinical trials (RCTs) was carried out using several databases. Antibiotics including azithromycin, cefaclor, cephalexin, cloxacillin, erythromycin, cephalexin plus trimethoprim-sulfamethoxazole, cephalexin plus placebo, flucloxacillin, clindamycin, ceftriaxone, penicillin, roxithromycin, and pristinamycin were assessed regarding cure rate, the eradication of baseline pathogens, diarrhea or vomiting, and rash. In total, 10 RCTs with 1,936 cellulitis or erysipelas patients were eligible for inclusion. There were no significant differences in the cure rates for cellulitis among the antibiotics analysed, with cefaclor demonstrating the most favorable profile for curative outcomes. In terms of side effects, ceftriaxone was identified as the least likely to induce diarrhea or vomiting. For erysipelas, pristinamycin showed the most promising results in achieving cure rates. Although a comparison of the three antibiotics revealed no significant differences in rash as a side effect in erysipelas, pristinamycin was observed to carry the highest risk for rash. Our findings indicate no significant differences in cure rates among antibiotics for cellulitis. However, ceftriaxone had the fewest gastrointestinal side effects. Pristinamycin showed the highest cure rates for erysipelas but with a higher risk of rash. Future research should focus on optimizing antibiotic selection for cellulitis and erysipelas.
PURPOSE:To dry uniformly and completely the titled substance without causing any thermal deformation in a short time at low temps. by using CO2 in a liquid or a super critical state, and extracting a solvent contained in a difficult-to- dry substance or a heat-sensitive substance. CONSTITUTION:A material such as a difficult-to-dry or a heat-sensitive substance is packed into a drying tower 1, and CO2 in a liquid or a super critical state, which is regulated to 30-200kg/cm<2> G, preferably about 40-100kg/cm<2> G, and at -10-100 deg.C, preferably about 0-50 deg.C, by a booster 5 and a heat exchanger 6, is supplied to extract a solvent contained in said material. A CO2 phase contg. the solvent discharged from the drying tower 1 is vaporized in a heater 2 or decompressed by a reducing valve 3 to deposit the solvent which is recovered in a solvent recovery tower 4. The solvent is further recovered, if necessary, in an absorption vessel or a washing vessel 8, and the separated CO2 is again supplied into the drying tower 1 through the booster 5 and the heat exchanger 6.
Patients with impaired gag reflex or other swallowing abnormalities are at risk for regurgitation or aspiration of MoviPrep. Observe these patients during the administration of MoviPrep. Use with caution in these patients. 

Do not combine MoviPrep with starch-based thickeners [see Dosage and Administration (2.1)]. Polyethylene glycol (PEG), a component of MoviPrep, when mixed with starch-thickened liquids reduces the viscosity of the starch-thickened liquid. When a PEG-based product used for another indication was mixed in starch-based pre-thickened liquids used in patients with dysphagia, thinning of the liquid occurred and cases of choking and potential aspiration were reported.
Introduction: 5-phosphodiesterase inhibitors (PDE-5I) have been investigated as a treatment for urinary dysfunction for almost a decade. The general perception is that they play a significant role in managing lower urinary tract symptoms (LUTS), particularly those associated with benign prostatic hyperplasia (BPH). However, the specific biochemical processes by which PDE-5I repairs urinary function are still poorly understood and there is little instrumental evidence of significant improvement in urinary symptoms. Therefore, we explore the role of 5-phosphodiesterase inhibitors (PDE-5I) as complementary to the conventional treatment of symptomatic BPH; we provide the suggested biological procedures involved in the association between PDE-5 inhibitor use and improvement in LUTS; and we propose new approaches to this topic. Material and Methods: A systematic search for clinical trials, experimental studies, and systematic reviews was performed in electronic libraries (PubMed, EMBASE, Scopus) using the terms "benign prostate hypertrophy", "benign prostate hyperplasia", "lower urinary tract symptoms", "storage symptoms", "voiding symptoms", "bladder outlet obstruction" and the keywords "mechanism of action", "synergy", "PDE-5 inhibitor", "alpha1-adrenergic antagonist", "5-alpha-reductase inhibitors" in various combinations. There was no restriction on publication date. Results: To date, only a few randomized studies have been published in which the effect of the combination of a conventional drug for the treatment of symptomatic BPH and a PDE-5I was investigated. Almost all showed significant improvement in IPSS and QoL. Some studies showed significant improvements in maximum urine flow (Qmax) and postvoiding residual volume (PVR) with combination therapy compared with a single agent alone. Conclusions: PDE-5I seems effective in relieving symptoms of some BPH patients when administered as complementary to agents currently used to treat BPH. However, the mechanism of action of PDE-5 inhibitors in LUTS remains poorly understood and it is difficult to determine the specific subset of BPH patients who will benefit from the combination of PDE-5 inhibitors with the current treatment. Well-designed, sufficiently informative comparative studies focusing on specific target group profiles (age, urogenital parameters) are needed to define new therapeutic options.