anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
A 2-year oral carcinogenicity study in rats with doses as high as 500 mg/kg/day (about 80 times the recommended daily therapeutic dose) showed no evidence of a carcinogenic effect. There was a dose-related increase in the density of enterochromaffin-like (ECL) cells in the gastric oxyntic mucosa. In a 2-year study in mice, there was no evidence of a carcinogenic effect in male mice; although hyperplastic nodules of the liver were increased in the high-dose males as compared with placebo. Female mice given the high dose of nizatidine (2,000 mg/kg/day, about 330 times the human dose) showed marginally statistically significant increases in hepatic carcinoma and hepatic nodular hyperplasia with no numerical increase seen in any of the other dose groups. The rate of hepatic carcinoma in the high-dose animals was within the historical control limits seen for the strain of mice used. The female mice were given a dose larger than the maximum tolerated dose, as indicated by excessive (30%) weight decrement as compared with concurrent controls and evidence of mild liver injury (transaminase elevations). The occurrence of a marginal finding at high dose only in animals given an excessive and somewhat hepatotoxic dose, with no evidence of a carcinogenic effect in rats, male mice, and female mice (given up to 360 mg/kg/day, about 60 times the human dose), and a negative mutagenicity battery are not considered evidence of a carcinogenic potential for nizatidine.

Nizatidine was not mutagenic in a battery of tests performed to evaluate its potential genetic toxicity, including bacterial mutation tests, unscheduled DNA synthesis, sister chromatid exchange, mouse lymphoma assay, chromosome aberration tests, and a micronucleus test.

In a 2-generation, perinatal and postnatal fertility study in rats, doses of nizatidine up to 650 mg/kg/day produced no adverse effects on the reproductive performance of parental animals or their progeny.
Myelodysplastic syndrome (MDS) is a hematological disorder characterized by ineffective hematopoiesis. The only known curative treatment for patients with MDS is allogeneic stem cell transplantation. However, only a minority of patients are candidates for this aggressive therapy. DNA hypomethylation agents have been shown to have activity in this disorder and are postulated to work by reversing this epigenetic mechanism of gene-silencing. Recently, 5-azacitidine, administered subcutaneously for seven days, received approval by the FDA for the therapy of MDS based on a randomized trial which demonstrated a diminished risk of leukemic transformation and improved survival when compared to best supportive care.

The subcutaneous route of administration can present challenges to implementing this therapy. In the CALGB studies 8921 and 9221, approximately 23% of patients had significant injection site pain. Moreover, 35 % of patients had injection site bruising which can be extensive in thrombocytopenic patients. Due to limitations on drug concentration and administration volumes for subcutaneous dosing, patients often need to have two or three injections at separate sites each day to meet target dosing. In addition, the schedule of administration is inconvenient in an outpatient setting secondary to the need to schedule administrations over weekends. Therefore, there is great interest in pursuing an abbreviated intravenous route for administration of the drug.
INTRODUCTION: There is increased focus on the negative impact of the overprescribing of medication, specifically psychotropic medication, including anti-seizure medications (ASM), in people with Intellectual Disability (ID). This is particularly important for the older adult population, where multi-morbidity and polypharmacy are more common. ASMs are associated with psychiatric and behavioral adverse effects. Furthermore, there is growing awareness of the anticholinergic burden for older adults with epilepsy and ID and the relationship with behaviors that challenge (BtC).
AREAS COVERED: This review defines the older adult population and outlines the relationship between epilepsy and ID. BtC is outlined in the context of the population and the relationship with ASMs. The evidence base to guide prescribing and de-prescribing for newer ASMs is also presented, including pragmatic data.
EXPERT OPINION: Polypharmacy, particularly psychotropics, are a mortality risk factor for older adults with epilepsy and ID. Therefore, any BtC requires a holistic assessment with a multi-disciplinary approach. This includes specific consideration of all prescribed medicines in the context of polypharmacy. There should be routine reviews, at least annually, for those aged 40 years and over particularly focused on anticholinergic burden and/or polypharmacy.
PURPOSE:To obtain a lipid membranous structure for oral administration capable of efficiently conveying a held medicine to Peyer's patches in digestive tracts after administration and improving the absorbability of medicines which have been poor in absorbability in the oral administration. CONSTITUTION:A lipid membranous structure for oral administration is obtained by adding at least one selected from phosphatidylserine (preferably hydrogenated phosphatidylserine, dipalmitoylphosphatidylserine or distearoylphosphatidylserine), mannose derivatives and mannan derivatives as a membrane ingredient in an amount of >=1%, preferably 5-50% molar fraction based on the total lipid membranous ingredient to a lipid membranous structure such as a liposome, an emulsion or a micelle. This lipid membranous structure has the above-mentioned effects. Furthermore, medicines capable of being held with the aforementioned lipid membranous structure vary with the kind of the lipid membranous structure, but are not especially limited in the case of, e.g. the liposome. Fat-soluble medicines and sparingly water-soluble medicines can be cited as the medicines capable of being held with the lipid membranous structure.
Participants in the time-restricted feeding (TRF) group will consume all calories within an 8-hour period of time each day. Participants in this group will receive placebo capsules. Participants in all groups will follow an identical resistance training program and be provided with whey protein supplements.
INTRODUCTION: Riboflavin Transporter Deficiency (RTD) is a rare neurological disorder characterized by pontobulbar palsy, hearing loss, and motor cranial nerve involvement. SLC52A3 and SLC52A2 mutations are causes of RTD. SLC52A2 mutations are usually found in childhood onset cases. Fifteen Iranian RTD diagnosed patients without SLC52A2 mutations have been previously described. We aimed to identify causative mutations in two childhood cases.
METHODS: We recruited patients with diagnosis of BVVL. Comprehensive clinical evaluations were performed on the patients. SLC52A3 and SLC52A2 genes were PCR-amplified and Sanger sequenced. Candidate disease causing variations were screened for segregation with disease status in the respective families and control individuals.
RESULTS: A novel homozygous SLC52A3 mutation (p.Met1Val) and a heterozygous SLC52A2 mutation (p.Ala288Val) were both observed in one proband with typical RTD presentations. The aggregate of presentations in the early stages of disease in the second patient that included weakness in the lower extremities, absence of bulbar or hearing defects, prominent sensory polyneuropathy as evidenced in electrodiagnostic studies, and absence of sensory symptoms including sensory ataxia did not prompt immediate RTD diagnosis. Dysarthria and decreased hearing manifested later in the disease course. A novel homozygous SLC52A2 (p.Val314Met) mutation was identified.
CONCLUSION: A literature search found recent reports of other atypical RTD presentations. These include MRI findings, speech understanding difficulties accompanied by normal hearing, anemia, and left ventricular non-compaction. Knowledge of unusual presentations lessens the chance of misdiagnosis or delayed RTD diagnosis which, in light of favorable effects of riboflavin supplementation, is of immense importance.
NEW MATERIAL:Peptides having amino acid sequence expressed by formula I-formula XII, etc. and consisting of 15-26 amino acids having phospholipase A2 inhibiting activity. USE:An antiphlogistics. PREPARATION:For example, a peptide chain is synthesized on a carrier resin by repeatedly carrying out operations packing the carrier resin into a reaction vessel of peptide automatic synthesizer and reacting the carrier resin with an amino acid having protected alpha-amino group and side chain functional group from C-end side in a solvent such as methylene chloride solution according to amino acid sequence, then treating the reaction product with methylene chloride solution, etc., containing trifluoroacetic acid in order to remove a protecting group of alpha-amino group and cleaning the carrier resin having the deprotected amino acid with methylene chloride, etc. Then the peptide chain synthesized on the carrier resin is subjected to elimination from the resin of peptide and removal to total protecting groups by treating the peptide resin with hydrogen fluoride and purified with a column chromatography, etc. to provide the peptide expressed by the formula.
Individualize dosing and use the lowest dose of VAFSEO sufficient to reduce the need for red blood cell transfusions. Do not target a hemoglobin level higher than 11 g/dL.

VAFSEO can be taken with or without food.

VAFSEO should be swallowed whole. Tablets should not be cut, crushed, or chewed.

VAFSEO can be administered without regard to the timing or type of dialysis [see Clinical Pharmacology (12.3)].

If a dose of VAFSEO is missed, it should be taken as soon as possible, unless it is the same day as the next dose. In this case, the missed dose should be skipped, and the next dose taken at the usual time. Double doses should not be taken to make-up for a missed dose.
Arteriovenous fistulas (AVFs) for hemodialysis often fail to become usable due to failure to mature (FTM). The most common cause is stenosis of the artery or vein. Another potential cause is the presence of collateral or side branch veins that steal blood flow from the main fistula channel. The utility of ligating these veins to improve maturation of those failing AVFs is controversial. To evaluate this, 35 patients presenting for fistulograms for evaluation of AVFs with FTM, found to have side branch veins will be prospectively enrolled. After management of stenoses (if present), they will be randomly assigned to ligation of the venous side branches or not. Maturation rates for each group will be prospectively assessed. For patients assigned to the control group who have persistent failure to mature, a cross-over intervention will be performed and side branch ligation will be offered.
The research project will be conducted at a free clinic that serves a primarily Spanish-speaking Latinx patient population in the Inland Southern California region. Patients in this study will be randomized to one of two intervention arms: Arm 1: PN model delivered by CHWs/promotoras and Arm 2: PN model delivered by clinic staff. CHWs who live in the region and work at the free clinic will deliver the PN model for Arm 1 participants. CHWs have a detailed knowledge of local health resources, as well as lived experience of the barriers patients in their community face when accessing healthcare services. Medical students who are volunteer clinic staff will deliver the PN model for Arm 2 participants. Medical students are the doctors in training who provide primary care services to patients at the CVFC under the supervision of well-established physicians. Baseline data and follow-up data at 12 weeks will be collected along with qualitative interviews with patients in both arms of the study.
The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) is debated. We investigated whether the administration of ICS could lower the mortality risk in patients with COPD. We utilized the Korean National Health Insurance Service-National Sample Cohort database from 2002 to 2019. We included patients who had claim codes for COPD and inhalation respiratory medicine at least twice a year. A time-dependent Cox regression model was employed to estimate the association between ICS usage and survival. The cumulative dose of ICS was classified into three groups, and the mortality risk was compared among these groups. Of 16,463 included patients, there were 4395 (26.7%) deaths during the mean follow-up period of 5.0 years. The time-dependent Cox regression model demonstrated that ICS users had a significantly lower mortality risk compared to non-users (adjusted hazard ratio, 0.89; 95% CI, 0.83-0.94; p < 0.001), particularly among individuals aged ≥ 55 years, women, never smokers, and those with history of asthma or coronary heart disease. Higher cumulative dose groups were associated with a lower mortality risk compared to the lowest cumulative dose group. In conclusion, the administration of ICS seemed to be associated with a lower mortality risk in patients with COPD.
PURPOSE: To provide a medicinal compsn. which contains the fragments of hormone and immunological carrier or adjuvant and has the effect of intensifying the hormone activity in vertebrate animals. CONSTITUTION: The fragments of the hormone and/or the immunological carrier and/or adjuvant are incorporated as the effective components and further, a carrier permissible as a medicine are incorporated into the compsn. The epitope specificness of antibodies is adequately selected, by which the effect at the time of administration of the growth hormone, insulin, thyroid stimulating hormone and interferon is intensified or the effects analogous therewith are exhibited. For example, the growth period of domestic animals including cattle, swine and poultry is shorted and the growth with a smaller amt. of feed is made possible. The lactogenic period or quantity of the vertebrate animals is increased. The ratio of the red meat and fats of the meat of the livestock animals is increased. The growth of the surface products of the animals, such as the hair of goat and fur, is increased.  The effects of inducing normal growth by treating a child of infantilism lacking in the growth hormone, etc., are exhibited.
PURPOSE:To provide the bad smell-removing agent containing the extract of Asparagus.lineales as an active ingredient and capable of rapidly improving body smells and the bad smells of excreta, etc., without being affected with beverages, foods, etc. CONSTITUTION:The agent contains the extract of Asparagus.lineales belonging to the family Leguminosae as an active ingredient. The extraction is performed by a method comprising extracting the leaves or stems of the Asparagus.lineales with water and/or an organic solvent, by a method comprising grinding the leaves or stems of the Asparagus.lineales, etc. The agent is used in forms such as granules, powder, capsules, coating agents, syrups. suppositories, injections, solutions, powdery granules. tablets. emulsions, jellies, etc., or its mixtures with other beverages or foods. The administration amount of the agent is 100-2000 ml/day as a solution of 1-5g dry leaves/1 when the agent is commonly used by a man, 2-30 ml/kg body weight when used for animals, and 1-10 g/day when used as a lyophilized granular powder.
Multi-organ hypersensitivity reactions occurring days to weeks or months after initiating treatment have been reported in rare cases. Signs or symptoms may include, but are not limited to fever, skin rashes, vasculitis, lymphadenopathy, disorders mimicking lymphoma, arthralgia, leukopenia, eosinophilia, hepato-splenomegaly and abnormal liver function tests. These signs and symptoms may occur in various combinations and not necessarily concurrently. Signs and symptoms may initially be mild. Various organs, including but not limited to, liver, skin, immune system, lungs, kidneys, pancreas, myocardium, and colon may be affected (see PRECAUTIONS, General and PRECAUTIONS, Information for Patients).

Isolated cases of a lupus erythematosus-like syndrome have been reported. There have been occasional reports of elevated levels of cholesterol, HDL cholesterol, and triglycerides in patients taking anticonvulsants. 

A case of aseptic meningitis, accompanied by myoclonus and peripheral eosinophilia, has been reported in a patient taking carbamazepine in combination with other medications. The patient was successfully dechallenged, and the meningitis reappeared upon rechallenge with carbamazepine.
The search for novel tumor biomarkers and targets is of significant importance for the early clinical diagnosis and treatment of Hepatocellular Carcinoma (HCC). The mechanisms by which ATP citrate lyase (ACLY) promotes HCC progression remain unclear, and the connection between ACLY and REGγ has not been reported in the literature. In vitro, we will perform overexpression/knockdown of ACLY or overexpression/knockdown of REGγ to investigate the impact of ACLY on HCC cells and its underlying mechanisms. In vivo, we will establish mouse tumor models with overexpression/knockdown of ACLY or overexpression/knockdown of REGγ to study the effect of ACLY on mouse tumors and its mechanisms. Firstly, ACLY overexpression upregulated REGγ expression and activated the REGγ-proteasome pathway, leading to changes in the expression of downstream signaling pathway proteins. This promoted HCC cell proliferation, invasion, and migration in vitro, as well as tumor growth and metastasis in vivo. Secondly, ACLY overexpression increased acetyl-CoA production, upregulated the acetylation level of the REGγ promoter region histone H3K27ac, and subsequently induced REGγ expression. Lastly, enhanced acetylation of the REGγ promoter region histone H3K27ac resulted in upregulated REGγ expression, activation of the REGγ-proteasome pathway, changes in downstream signaling pathway protein expression, and promotion of HCC cell proliferation, invasion, and migration in vitro, as well as tumor growth and metastasis in vivo. Conversely, REGγ knockdown reversed these effects. ACLY and REGγ may serve as potential biomarkers and clinical therapeutic targets for HCC.
PURPOSE: A two-layered lotion having a polar oil on an aqueous phase is provided to improve skin safety and to enhance skin penetration and moisturizing. CONSTITUTION: A two-layered lotion contains an aqueous phase and an oil phase. The oil phase contains aqueous polymers and polar oil. The polar oil is dispersed in a particle in case of shaking the lotion. The aqueous polymer is sodium carbomer, carboxyvinyl polymer, acryl polymers, xanthan gum, gellan gum, hyaluronic acid, guar gum, locust bean gum, Arabia gum, pectin, mannan, starch, or sodium carboxy methylcellulose. The aqueous phase contains a moisturizing agent.
PURPOSE:To obtain a remedy for hyperammonemia useful for treating hepatic encephalopathia capable of reducing ammonia catalyst in blood with an extremely low dose, comprising valiolamine derivative or a salt thereof as an active ingredient. CONSTITUTION:A valiolamine derivative shown by the formula (A is OH< phenoxy, thienyl, furyl, pyridyl, cyclohexyl, 1-10C hydrocarbon which may contain replaceable phenyl, OH, etc.) or a salt thereof is blended with an ordinary medical carrier and pharmaceutically manufactured by a conventional procedure to give the aimed substance. The amount of the compound shown by the formula blended is 0.0001-100wt.%. The substance can be processed into a dosage from such as tablet, capsule or suppository. A dose is 0.01-100mg/day. N- Benzylvaliolamine may be cited as the compound shown by the formula.
BACKGROUND: Skin fibrosis is the typical pathological manifestation of systemic sclerosis (SSc) and localized scleroderma (LS); it has an unclear aetiology and few effective treatments. Although excessive collagen secretion by fibroblasts is the primary cause of skin fibrosis, evidence has suggested that vascular damage is the initiating event and that various cell types, including fibroblasts, work together to contribute to the pathogenesis of skin fibrosis.
OBJECTIVES: To explore the relationship between vascular endothelial cell lesions and immune cell infiltration, along with the interactions between various cell types within the fibrotic skin ecosystem.
METHODS: Single-cell RNA sequencing was performed on skin biopsies from three healthy donors and seven patients with SSc. Additional data from three patients with localized scleroderma available in the Gene Expression Omnibus (GSE160536) were integrated by Harmony. CellChat (version 1.5.0) was used to analyse the cell communication network. A Transwell® assay and a bleomycin (BLM) mouse model were used to explore the role of atypical chemokine receptor 1 (ACKR1; 'Duffy antigen') in immune cell infiltration. Milo single-cell Western blot was used to show fibroblast subcluster activation.
RESULTS: A total of 62 295 cells were obtained and subpopulations of stromal and immune cells identified. Interaction network analysis found that multiple chemokines secreted by macrophages, pericytes and proinflammatory fibroblasts could bind with ACKR1, which was highly expressed by endothelial cells in lesional skin. The Transwell® assay revealed that overexpression of ACKR1 in human umbilical vein endothelial cells facilitated leucocyte infiltration following treatment with interleukin-8. BLM mice showed enhanced ACKR1 expression, massive immune cell infiltration and skin fibrosis that was attenuated by ACKR1 inhibition. Furthermore, infiltrated macrophages expressing high levels of transforming growth factor (TGF)-β1 or platelet-derived growth factor B (PDGFB) could activate secreted frizzled-related protein 2 (SFRP2)/asporin (ASPN)+ fibroblasts to contribute to the excessive accumulation of extracellular matrix. It was also found that the SOX4-ASPN axis plays an important role in the TGF-β signalling cascade and the aetiology of skin fibrosis.
CONCLUSIONS: Our results reveal that high expression of ACKR1 by endothelial cells in fibrotic skin tissue promotes immune cell infiltration and that SFRP2/ASPN+ fibroblasts synergize to exacerbate skin fibrosis.
To estimate the overall responder rate after 4 weeks of Proton Pump Inhibitor empirical treatment This will be a multicenter prospective observational study carried out in China. Investigator will collect data in a pre-specified Case Report Form from the outpatient. Informed consents will be needed. Investigator will provide patient diary card to each patient for them to note down the symptom frequency every day. Main data from each outpatient will include demographics, Gerd Q, symptom frequency and Proton Pump Inhibitor empirical treatment. Data from each outpatient will be collected on the screening day, 2 weeks and 4 weeks.
Fulphila is administered subcutaneously via a single-dose prefilled syringe for manual use. 

Prior to use‚ remove the carton from the refrigerator and allow the Fulphila prefilled syringe to reach room temperature for a minimum of 30 minutes. Discard any prefilled syringe left at room temperature for greater than 72 hours. 

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer Fulphila if discoloration or particulates are observed. 

###  Pediatric Patients weighing less than 45 kg

The Fulphila prefilled syringe is not designed to allow for direct administration of doses less than 0.6 mL (6 mg). The syringe does not bear graduation marks, which are necessary to accurately measure doses of Fulphila less than 0.6 mL (6 mg) for direct administration to patients. Thus, the direct administration to patients requiring dosing of less than 0.6 mL (6 mg) is not recommended due to the potential for dosing errors. Refer to Table 1.