anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
This invention relates to ligand exchange proteins comprising the luminal domain of TAP-binding protein-related (TAPBPR), which functions as a MHC class I ligand-exchange catalyst when presented to mammalian cells either as a soluble extracellular protein or as a membrane bound cell surface protein. This may be useful in modulating immune responses, including for example loading immunogenic ligand onto tumors or other disease cells to induce their recognition by T cells. Ligand-exchange proteins and methods for their use are provided. The invention further relates to an approach for generating conditional peptide ligands for a range of disease-related MHC-I allotypes. The present invention relates to chicken and human TAPBPRs and tapasins as well as orthologs thereof, derivatives thereof, and any mutants thereof as well as any combinations thereof. The present invention also relates to placeholder conditional ligands for ligand-exchange reactions across multiple HLA allotypes.
High throughput assays used to identify antibodies and proteins that induce cell death are described herein. It is not necessary to identify the antigens the antibodies are reactive with prior to performing the assays. Instead, libraries of antibodies and proteins, including murine, human, humanized, single chain, and synthetic antibodies, are screened using high throughput assays to identify those antibodies and proteins which cause cell death. Standard technology is then used to screen for cell viability. Antibodies and proteins which induce apoptosis preferentially or exclusively of cancer cells are then isolated, characterized, and may be cloned. A method for cloning antibodies and proteins has been developed, which provides means for rapid identification of the antibody or protein and the gene encoding the antibody or protein, based on the presence of a “bar code” or “unique sequence.” A method for high throughput production of antibodies to human proteins has also been developed.
FIELD: vitamins. SUBSTANCE: invention relates to the unknown class of compounds showing antiinflammatory and immunomodulating effects, drugs containing these compounds, method of patients treatment and a method of synthesis of the above indicated compounds. Invention proposes compounds of the formula (I) where V is a group -(CH 2 ) n -Y-(CH 2 ) m ; n = 0, 1 or 2; m = 1 or 2; Y is oxygen or sulfur atom. 22-Methylene- or 23-methylene-group can be replaced for oxygen atom or 22- or 23-methylene-group can be replaced for a group -CH= CH-; R′ is methyl- or ethyl-group and carbon atom directly bound with C-25 atom can be substituted with one or some fluorine atoms; hydroxy-groups can be substituted by groups that can be split at in vivo conditions. Method of synthesis of compounds of the formula (I) where hydroxy-group is modified involves interaction with tert.-butylbromoacetate in the presence of a base and catalyst in a solvent followed by interaction of synthesized ester with methyl- or ethylmagnesium halide. Obtained compound is subjected for isomerization at any sequence by effect of UV-light in the presence of triplet activator and removal of silyl-groups by treatment with tetra-n-butylammonium fluoride of hydrogen fluoride and producing a compound of the formula (I) where Y and V - oxygen atom. Method of prophylaxis and treatment of patients with pathological states using D з - -vitaminotherapy involves administration of a pharmaceutical composition containing an effective dose of compound of the formula (I). EFFECT: improved method of synthesis, enhanced effectiveness of compounds synthesized. 8 cl, 2 tbl, 10 ex
Two year carcinogenicity studies were conducted in F344 rats and B6C3F1 mice. Increased transitional cell papilloma and carcinoma of the urinary bladder was observed at 24 mg/kg (25 times the MRHD on an AUC basis) and 18.75 mg/kg (12.5 times the MRHD on an AUC basis) in male rats and female mice, respectively. The urinary bladder neoplasms were secondary to calculus formation in the kidney and urinary bladder. 

Febuxostat showed a positive clastogenic response in a chromosomal aberration assay in a Chinese hamster lung fibroblast cell line with and without metabolic activation in vitro. Febuxostat was negative in the following genotoxicity assays: the in vitro Ames assay, in vitro chromosomal aberration assay in human peripheral lymphocytes, the L5178Y mouse lymphoma cell line assay, the in vivo mouse micronucleus assay, and the rat unscheduled DNA synthesis assay.

Fertility and reproductive performance were unaffected in male or female rats that received febuxostat at oral doses up to 48 mg/kg/day (approximately 31 and 40 times the MRHD on an AUC basis in males and females respectively).
The aim of this study is to evaluate whether increased visual dependence can be identified with the help of Virtual Reality (VR). Visual dependence is normally measured using the optokinetic after nystagmus (OKAN) and the rod and disc test (RDT). In this study, these two tests are performed with the aid of Virtual Reality. The OKAN is measured by eye tracking, a key item already used daily in instruments such as video nystagmography (VNG) and video head impulse test (vHIT). Another test representative of visual dependence is the Rod and Disc test (RDT). In the RDT, patients are asked to complete a visual task so that researchers gain more knowledge about visual dependence. Until now, these tests have been performed using a large set-up and many different materials. Moreover, the exact underlying mechanism of visual dependence in PPPD patients is still unknown. The aim of this study is to investigate whether Virtual Reality can be a useful tool when performing the OKAN and RDT. In this way, a better understanding of visual dependence is sought. This study aims to determine the normative values for the OKAN and RDT performed with the aid of Virtual Reality. Therefore, a healthy group of individuals will be compared with PPPD patients as they suffer from visual dependence. To evaluate the effectiveness of the OKAN and RDT via VR, the results will be compared with the scores of the visual vertigo analogue scale (VVAS), a questionnaire to assess visual dependence.
Ratio of neutrophils to lymphocytes (NLR) is here associated with immune suppression and decreased survival times in multiple solid tumors. Based on immune cell-specific DMRs and validated cell deconvolution algorithms, the NLR in blood from glioma patients was estimated and glioma patients had elevated mdNLR scores compared to controls. The patient mdNLR scores were increased in patients with grade IV tumors compared to grade II/III. High mdNLR scores were associated with shorter survival. Candidate single (myeloid-associated) gene loci that were highly correlated with the mdNLR were identified. Single myeloid differentiation loci provide a simpler and cheaper alternative to the mdNLR, which requires complex array data. Immunomethylomics are useful and more convenient than conventional cell analysis in profiling glioma risk and survival.
PROBLEM TO BE SOLVED: To provide the subject method and its use. SOLUTION: Formation per se of volatile aldehydes from fatty acid-contg. matter and/or decomposition per se of fatty acids are inhibited by including trehalose and/or maltitol. Thereby, a method for inhibiting the formation of volatile aldehydes and/or the decomposition of fatty acids is provided by using trehalose and/or maltitol as active ingredient, and a relevant inhibitor is obtained by including trehalose and/or maltitol. Furthermore, a use of the inhibitor or the above method is provided. Owing to the above inhibitor or the method, high-quality and stable various compositions including foods and drinks, cosmetics and medicaments can be afforded.
OBJECTIVE: The goal was to identify the lifestyle risk factors associated with benign and potentially malignant oral disorders.
METHOD AND MATERIALS: The study enrolled first-time patients from the Oral Pathology Section, volunteers from Oviedo, and first-time patients from the University of Oviedo dental clinic. Patients underwent a survey that included sociodemographic information, lifestyle habits, and medical history. A comprehensive examination of the oral mucosa was conducted. Univariate and multivariate logistic regression were conducted using R software.
RESULTS: Among the 183 participants, the most prevalent lesions were varicose veins (43.20%), cheek/lip biting (34.97%), and coated tongue (33.33%). Among the oral potentially malignant disorders (16.39%) were oral lichen planus (12.64%) and leukoplakia (3.33%). Tobacco was associated with melanotic pigmentation (OR 3.87, P = .001) and coated tongue (OR 5.90, P = .001). Longer intervals since the last check-up were associated with traumatic keratosis (OR 2.95, P = .031). Age and heavy smoking were found to have higher risk of developing an oral potentially malignant disorder (OR 1.04, P = .035, and OR 7.35, P = .028, respectively).
CONCLUSIONS: These data should be considered when organizing public health programs focused on the detection and screening of heavy smokers. It is also important to strengthen the oral pathology units in universities as reference centers for students to acquire the necessary knowledge for their diagnosis and treatment, while simultaneously promoting awareness of this risk factor for oral precancer among the general population.
Untreated HCV mono and HCV/HIV coinfected women have lower degrees of liver fibrosis (LF) compared to men. Direct acting antiviral (DAA) therapy attains viral eradication in > 90% of patients with progressive LF decline in parallel. Gender-related differences in LF regression in the long term assessed by non-invasive liver fibrosis markers (NILFM) in HCV mono and HCV/HIV coinfected after DAA treatment have not been explored so far. 374 HCV-infected adult patients, 214 of them HCV/HIV coinfected, were followed-up for 24 months after starting DAA therapy. LF was assessed by NILFM: transient elastometry (TE) and several biochemical indexes (APRI, Forns, FIB-4). Men had significantly more advanced LF at baseline than women assessed by NILFM. No LF differences at baseline in age, HIV coinfection course (CD4, HIV viral load), and HCV features (HCV viral load, genotype) were detected. No significant gender differences in LF decline after comparing 24-month and baseline LF values were observed. LF changes after DAA therapy were similar in HCV mono and HCV/HIV coinfected patients and in both sexes. Gender did not influence the course of LF decline after DAA assessed by NILFM: TE (P = 0.8), APRI (P = 0.9), Forns (P = 0.4) and FIB-4 (P = 0.7) by multivariate analysis. No gender differences in the 24 month LF decline after DAA with independence of having HCV mono or HCV/HIV coinfection were found.
INTRODUCTION: Mental fatigue is an early and enduring symptom in persons with autoimmune disease particularly multiple sclerosis (MS). Neuromodulation has emerged as a potential treatment although optimal cortical targets have yet to be determined. We aimed to examine cortical hemodynamic responses within bilateral dorsolateral prefrontal cortex (dlPFC) and frontopolar areas during single and dual cognitive tasks in persons with MS-related fatigue compared to matched controls.
METHODS: We recruited persons (15 MS and 12 age- and sex-matched controls) who did not have physical or cognitive impairment and were free from depressive symptoms. Functional near infrared spectroscopy (fNIRS) registered hemodynamic responses during the tasks. We calculated oxyhemoglobin peak, time-to-peak, coherence between channels (a potential marker of neurovascular coupling) and functional connectivity (z-score).
RESULTS: In MS, dlPFC demonstrated disrupted hemodynamic coherence during both single and dual tasks, as evidenced by non-significant and negative correlations between fNIRS channels. In MS, reduced coherence occurred in left dorsolateral PFC during the single task but occurred bilaterally as the task became more challenging. Functional connectivity was lower during dual compared to single tasks in the right dorsolateral PFC in both groups. Lower z-score was related to greater feelings of fatigue. Peak and time-to-peak hemodynamic response did not differ between groups or tasks.
CONCLUSIONS: Hemodynamic responses were inconsistent and disrupted in people with MS experiencing mental fatigue, which worsened as the task became more challenging. Our findings point to dlPFC, but not frontopolar areas, as a potential target for neuromodulation to treat cognitive fatigue.
Doxycycline is stable for 48 hours in solution when diluted with Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP, to concentrations between 1 mg/mL and 0.1 mg/mL and stored at 25°C. Doxycycline in these solutions is stable under fluorescent light for 48 hours, but must be protected from direct sunlight during storage and infusion. Reconstituted solutions (1 to 0.1 mg/mL) may be stored up to 72 hours prior to start of infusion if refrigerated and protected from sunlight and artificial light. Infusion must then be completed within 12 hours. Solutions must be used within these time periods or discarded.

Doxycycline, when diluted with Ringer's Injection, USP, or Invert Sugar, 10% in Water, or Normosol-M ®in D5-W, or Normosol- ®R in D5-W, or Plasma-Lyte ®56 in 5% Dextrose, or Plasma-Lyte ®148 in 5% Dextrose to a concentration between 1 mg/mL and 0.1 mg/mL, must be completely infused within 12 hours after reconstitution to ensure adequate stability. During infusion, the solution must be protected from direct sunlight. Reconstituted solutions (1 to 0.1 mg/mL) may be stored up to 72 hours prior to start of infusion if refrigerated and protected from sunlight and artificial light. Infusion must then be completed within 12 hours. Solutions must be used within these time periods or discarded. 

When diluted with Lactated Ringer's Injection, USP, or Dextrose 5% in Lactated Ringer's, infusion of the solution (ca. 1 mg/mL) or lower concentrations (not less than 0.1 mg/mL) must be completed within six hours after reconstitution to ensure adequate stability. During infusion, the solution must be protected from direct sunlight. Solutions must be used within this time period or discarded.

Solutions of doxycycline for injection, at a concentration of 10 mg/mL in Sterile Water for Injection, when frozen immediately after reconstitution are stable for eight weeks when stored at –20°C. If the product is warmed, care should be taken to avoid heating it after the thawing is complete. Once thawed the solution should not be refrozen.
In rats treated with cyclobenzaprine hydrochloride for up to 67 weeks at doses of approximately 5 to 40 times the maximum recommended human dose, pale, sometimes enlarged, livers were noted and there was a dose-related hepatocyte vacuolation with lipidosis. In the higher dose groups this microscopic change was seen after 26 weeks and even earlier in rats which died prior to 26 weeks; at lower doses, the change was not seen until after 26 weeks.

Cyclobenzaprine did not affect the onset, incidence or distribution of neoplasia in an 81-week study in the mouse or in a 105-week study in the rat.

At oral doses of up to 10 times the human dose, cyclobenzaprine did not adversely affect the reproductive performance or fertility of male or female rats. Cyclobenzaprine did not demonstrate mutagenic activity in the male mouse at dose levels of up to 20 times the human dose.

Pregnancy

Pregnancy Category B:Reproduction studies have been performed in rats, mice and rabbits at doses up to 20 times the human dose, and have revealed no evidence of impaired fertility or harm to the fetus due to cyclobenzaprine hydrochloride. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Narcotic analgesics, including codeine, exert their primary effects on the central nervous system and gastrointestinal tract. The analgesic effects of codeine are due to its central action; however, the precise sites of action have not been determined, and the mechanisms involved appear to be quite complex. Codeine resembles morphine both structurally and pharmacologically, but its actions at the doses of codeine used therapeutically are milder, with less sedation, respiratory depression, and gastrointestinal, urinary, and pupillary effects. Codeine produces an increase in biliary tract pressure, but less than morphine or meperidine. Codeine is less constipating than morphine.

Codeine has good antitussive activity, although less than that of morphine at equal doses. It is used in preference to morphine, because side effects are infrequent at the usual antitussive dose of codeine.

Codeine in oral therapeutic dosage does not usually exert major effects on the cardiovascular system.

Narcotic analgesics may cause nausea and vomiting by stimulating the chemoreceptor trigger zone (CTZ); however, they also depress the vomiting center, so that subsequent doses are unlikely to produce vomiting. Nausea is minimal after usual oral doses of codeine.

Narcotic analgesics cause histamine release, which appears to be responsible for wheals or urticaria sometimes seen at the site of injection on parenteral administration. Histamine release may also produce dilation of cutaneous blood vessels, with resultant flushing of the face and neck, pruritus, and sweating.

Codeine and its salts are well absorbed following both oral and parenteral administration. Codeine is about 2/3 as effective orally as parenterally. Codeine is metabolized primarily in the liver by enzymes of the endoplasmic reticulum, where it undergoes O-demethylation, N-demethylation, and partial conjugation with glucuronic acid. The drug is excreted primarily in the urine, largely as inactive metabolites and small amounts of free and conjugated morphine. Negligible amounts of codeine and its metabolites are found in the feces.

Following oral or subcutaneous administration of codeine, the onset of analgesia occurs within 15 to 30 minutes and lasts for four to six hours.

The cough-depressing action, in animal studies, was observed to occur 15 minutes after oral administration of codeine, peak action at 45 to 60 minutes after ingestion. The duration of action, which is dose-dependent, usually did not exceed 3 hours.
BACKGROUND: The aim of this study was to investigate the patterns of recurrence and their associated risk factors in patients who underwent resection for pancreatic carcinoma.
METHODS: This retrospective study included 272 patients, who underwent Ro/R1-resection of PDAC from 2005 to 2020 at the University Hospital Erlangen. Risk factors for different recurrence patterns and the prognostic value of recurrence pattern on the overall survival after recurrence were evaluated.
RESULTS: 61 % of the patients experienced recurrence, mostly within the first 12 postoperative months (62 %) and in the form of metastases (87 %). The median overall survival from recurrence was 9.2 months. The preoperative absence of diabetes and the presence of lymph node metastasis were independent risk factors for recurrence and a preoperative CA19-9 exceeding 97 U/ml for early recurrence. Additionally, lymph node metastases were associated with a higher risk of metastatic recurrence. Early recurrence, but not the site of recurrence, was identified as an independent prognostic factor for worse overall survival from recurrence.
CONCLUSION: The occurrence of recurrence and especially of early and metastatic recurrence are associated with a worse overall survival. Patients lacking preoperative diabetes, having high preoperative CA19-9 values and lymph node metastases are particularly at risk for (early) recurrence.
OBJECTIVES: The relationship between long-term exposure to occupational noise and hearing loss has been extensively documented. We aimed to assess spatial and temporal changes in the burden of occupational noise-induced hearing loss (ONIHL) in 204 countries and territories with varying socio-demographic indexes (SDI) from 1990 to 2019.
DESIGN: Temporal and spatial trends in age-standardized disability-adjusted life year rates (ASDR) for ONIHL were estimated by sex, age, SDI level, country, and geographic region from 1990 to 2019. We used the Joinpoint model to calculate annual average percentage changes to assess such trends and projected trends in ASDR for ONIHL globally and across different income regions from 2020 to 2044 using an age-period-cohort model. We fitted the relationship between ASDR and SDI, ASDR and healthcare access and quality index, respectively.
RESULTS: Overall, the global burden of ONIHL has decreased since 1990, especially in middle and lower SDI regions. In 2019, the global ASDR for ONIHL was 84.23 (95% confidence interval: 57.46 to 120.52) per 100,000 population. From 1990 to 2019, the global ASDR for ONIHL decreased by 1.72% (annual average percentage change = -0.05, 95% confidence interval: -0.07 to -0.03). Our projections showed a decreasing trend in the global ONIHL burden until 2044. ASDR and SDI ( R = -0.8, p < 0.05), ASDR and healthcare access and quality index ( R = -0.75, p < 0.05) showed significant negative correlations.
CONCLUSIONS: The global ONIHL burden has decreased over the past three decades, especially in regions with middle and lower SDI levels. However, the global ONIHL burden still remained severe in 2019, notably among males, the middle-aged and elderly, and regions with lower SDI levels.
Approximately 275 patients will be randomized to receive benralizumab 30 mg SC or matching placebo. After enrolment, eligible patients will enter a 6-week screening/run in period. Patients who meet eligibility criteria will be randomised 1:1 at Week 0 (Day 0) to receive either placebo or benralizumab 30 mg SC every 4 weeks for the first 3 doses (Weeks 0, 4 and 8) and every 8 weeks thereafter (Weeks 16, 24, 32, 40 and 48). An end of treatment visit will be conducted at Week 56.All patients who complete the 56-week DB treatment period on investigational product (IP) may be eligible to continue into around one year OLE, during which all patients will receive 8 doses of benralizumab 30 mg. Patients in Benra arm during DB period will receive one dummy dose. The last study visit will occur at 8 weeks after the last dose of IP (Week 112/FU). Patients who do not enter OLE, will have their last study visit at Week 56 (EoDB) for follow-up and without administration of IP.
INTRODUCTION: Management of secondary hyperparathyroidism (SHPT) is a challenging endeavor with several factors contruibuting to treatment failure. Calcimimetic therapy has revolutionized the management of SHPT, leading to changes in indications and appropriate timing of parathyroidectomy (PTX) around the world.
METHODS: We compared response rates to clinical vs. surgical approaches to SHPT in patients on maintenance dialysis (CKD 5D) and in kidney transplant patients (Ktx). A retrospective analysis of the one-year follow-up findings was carried out. CKD 5D patients were divided into 3 groups according to treatment strategy: parathyroidectomy, clinical management without cinacalcet (named standard - STD) and with cinacalcet (STD + CIN). Ktx patients were divided into 3 groups: PTX, CIN (cinacalcet use), and observation (OBS).
RESULTS: In CKD 5D we found a significant parathormone (PTH) decrease in all groups. Despite all groups had a higher PTH at baseline, we identified a more pronounced reduction in the PTX group. Regarding severe SHPT, the difference among groups was evidently wider: 31%, 14% and 80% of STD, STD + CIN, and PTX groups reached adequate PTH levels, respectively (p<0.0001). Concerning the Ktx population, although the difference was not so impressive, a higher rate of success in the PTX group was also observed.
CONCLUSION: PTX still seems to be the best treatment choice for SHPT, especially in patients with prolonged diseases in unresourceful scenarios.