anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Cardiac fibroblasts are pivotal regulators of cardiac homeostasis and are essential in the repair of the heart after myocardial infarction (MI), but their function can also become dysregulated, leading to adverse cardiac remodelling involving both fibrosis and hypertrophy. MicroRNAs (miRNAs) are noncoding RNAs that target mRNAs to prevent their translation, with specific miRNAs showing differential expression and regulation in cardiovascular disease. Here, we show that miR-214-3p is enriched in the fibroblast fraction of the murine heart, and its levels are increased with cardiac remodelling associated with heart failure, or in the acute phase after experimental MI. Tandem mass tagging proteomics and in-silico network analyses were used to explore protein targets regulated by miR-214-3p in cultured human cardiac fibroblasts from multiple donors. Overexpression of miR-214-3p by miRNA mimics resulted in decreased expression and activity of the Piezo1 mechanosensitive cation channel, increased expression of the entire lysyl oxidase (LOX) family of collagen cross-linking enzymes, and decreased expression of an array of mitochondrial proteins, including mitofusin-2 (MFN2), resulting in mitochondrial dysfunction, as measured by citrate synthase and Seahorse mitochondrial respiration assays. Collectively, our data suggest that miR-214-3p is an important regulator of cardiac fibroblast phenotypes and functions key to cardiac remodelling, and that this miRNA represents a potential therapeutic target in cardiovascular disease.
Several international centers have used and reported on pediatric-inspired regimens to treat adolescent and adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL). However, there is a lack of prospective data from the Chinese population. We performed a prospective study with a pediatric-inspired regimen (IH-2014 regimen) to treat adolescent and adult Ph- ALL patients in our center. From 2014 to 2021, a total of 415 patients aged between 14 and 65 years (median age, 27 years) were included in this study. After a median follow-up of 40.8 months, the 5-year overall survival, disease-free survival, and event-free survival rates were 53.8%, 51.1% and 45.0%, respectively. The regimen was generally well tolerated and safe, and the overall chemotherapy-related mortality was 3.6%. Age ≥40 years and persistent detectable minimal residual disease (MRD) after induction were independent prognostic factors. Traditional risk factors for adult patients combined with post-induction MRD had predictive significance for survival and relapse, which is helpful in the selection of subsequent treatment. Patients with high-risk factors who can achieve a deep MRD response after induction do not derive benefit from allogeneic hematopoietic stem cell transplantation.
There have been no reported overdosages with Azelastine hydrochloride Nasal Spray. Acute overdosage by adults with this dosage form is unlikely to result in clinically significant adverse reactions, other than increased somnolence, since one bottle of Azelastine hydrochloride Nasal Spray contains 30 mg of azelastine hydrochloride. Clinical trials in adults with single doses of the oral formulation of azelastine hydrochloride (up to 16 mg) have not resulted in increased incidence of serious adverse reactions. General supportive measures should be employed if overdosage occurs. There is no known antidote to Azelastine hydrochloride Nasal Spray. Oral ingestion of antihistamines has the potential to cause serious adverse effects in young children. Accordingly, Azelastine hydrochloride Nasal Spray should be kept out of the reach of children.
Deposits of misfolded proteins are the cause of frequent neurological diseases such as Alzheimer's or Parkinson's disease. In Parkinson's disease, the misfolded protein alpha-synuclein is found in the olfactory mucosa of the nose, which contains nerve cells responsible for smell perception, from which the misfolded alpha-synuclein spreads further into the brain. The mechanisms that lead to this misfolding and the resulting damage to the nervous system are still unclear. One hypothesis is that inflammatory processes such as viral infections trigger the misfolding of alpha-synuclein in Parkinson's disease and can lead to its deposition. Based on this assumption and the striking involvement of the sense of smell in SARS-CoV-2 infection (COVID-19), the aim of this study is to investigate the olfactory epithelium of the nasal mucosa of COVID-19 patients for possible alpha-synuclein deposits by using nasal swabs.

We hypothesize that the invasion of olfactory neurons and subsequent inflammatory responses could trigger α-synuclein misfolding and aggregation. Therefore, we aim to investigate for the presence of α-synuclein seeding activity in the olfactory mucosa of subjects who have recovered from COVID-19 by using Real-time Quaking-Induced Conversion (RT-QuIC).
No kind of intervention has been applied to control group they awaited for therapy procedure for 6 week. They have assessed at the end of the 6 weeks.
Patients receive bevacizumab IV over 30-90 minutes on day 1 in weeks 1, 3, 5, 7, 9, and 11. Patients also receive interleukin-2 subcutaneously on days 1-5 in weeks 5-10. Treatment repeats every 12 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease then receive bevacizumab alone in weeks 1, 3, 5, 7, 9, and 11. Courses with bevacizumab alone repeat every 12 weeks in the absence of disease progression or unacceptable toxicity.
A 24-week, double-blind, placebo-controlled study of metformin hydrochloride extended-release tablets, USP, taken once daily with the evening meal, was conducted in patients with type 2 diabetes who had failed to achieve glycemic control with diet and exercise (HbA 1c 7.0-10.0%, FPG 126-270 mg/dL). Patients entering the study had a mean baseline HbA 1c of 8.0% and a mean baseline FPG of 176 mg/dL. After 12 weeks treatment, mean HbA 1c had increased from baseline by 0.1% and mean FPG decreased from baseline by 2 mg/dL in the placebo group, compared with a decrease in mean HbA 1c of 0.6% and a decrease in mean FPG of 23 mg/dL in patients treated with metformin hydrochloride extended-release tablets, USP 1000 mg once daily. Subsequently, the treatment dose was increased to 1500 mg once daily if HbA 1c was ≥ 7.0 % but <8.0% (patients with HbA 1c ≥ 8.0% were discontinued from the study). At the final visit (24-week), mean HbA 1c had increased 0.2% from baseline in placebo patients and decreased 0.6% with metformin hydrochloride extended-release tablets, USP. 

A 16-week, double-blind, placebo-controlled, dose-response study of metformin hydrochloride extended-release tablets, USP, taken once daily with the evening meal, or twice daily with meals, was conducted in patients with type 2 diabetes who had failed to achieve glycemic control with diet and exercise (HbA 1c 7.0-11.0%, FPG 126-280 mg/dL). Changes in glycemic control and body weight are shown in Table 6. 

Compared with placebo, improvement in glycemic control was seen at all dose levels of metformin hydrochloride extended-release tablets, USP and treatment was not associated with any significant change in weight (see DOSAGE AND ADMINISTRATION for dosing recommendations for metformin hydrochloride tablets, USP and metformin hydrochloride extended-release tablets, USP). 

A 24-week, double-blind, randomized study of metformin hydrochloride extended-release tablets, USP, taken once daily with the evening meal, and metformin hydrochloride tablets, USP, taken twice daily (with breakfast and evening meal), was conducted in patients with type 2 diabetes who had been treated with metformin hydrochloride tablets, USP 500 mg twice daily for at least 8 weeks prior to study entry. The metformin hydrochloride tablets, USP dose had not necessarily been titrated to achieve a specific level of glycemic control prior to study entry. Patients qualified for the study if HbA 1c was ≤ 8.5 % and FPG was ≤ 200 mg/dL. Changes in glycemic control and body weight are shown in Table 7. 

After 12 weeks of treatment, there was an increase in mean HbA 1c in all groups; in the metformin hydrochloride extended-release tablets, USP 1000 mg group, the increase from baseline of 0.23% was statistically significant (see DOSAGE AND ADMINISTRATION). 

Changes in lipid parameters in the previously described placebo-controlled dose-response study of metformin hydrochloride extended-release tablets, USP are shown in Table 8. 

Changes in lipid parameters in the previously described study of metformin hydrochloride tablets, USP and metformin hydrochloride extended-release tablets, USP are shown in Table 9.
Multiple sclerosis (MS) is a primary inflammatory demyelinating disease with different clinical courses and subtypes. The present study aimed to determine whether mitochondrial dysfunction and sirtuins 1 and 3, as metabolism and epigenetic modifying factors, might contribute to MS disease progression measured by physical disability and cognitive impairment.The volunteers (n = 20 controls, n = 59 MS) were recruited and assessed for cognitive function and disability scores; then, patients were clinically classified as relapsing-remitting (RR) in remission phase, RR in relapse phase, and secondary progressive MS. We measured sirtuin (SIRT) 1 and 3 levels, mitochondrial complex I, IV, aconitase, and α-ketoglutarate dehydrogenase (α-KGD) activity in the peripheral blood mononuclear cells (PBMCs). Furthermore, SIRT1, pyruvate, lactate, and cytochrome c (Cyt c) were determined in plasma. Finally, we performed postmortem tissue immunohistochemistry to assess the level of SIRT1 and SIRT3 in the brain lesions of patients with MS.Increased disability and cognitive impairment in patients were correlated. Plasma level of lactate showed a correlation with the disability in MS patients; moreover, a trend toward increased Cyt c plasma level was observed. Investigation of PBMCs exhibited decreased SIRT1 during the relapse phase along with a reduced complex IV activity in all MS subgroups. α-KGD activity was significantly increased in the RR-remission, and SIRT3 was elevated in RR-relapse group. This elevation correlated with disability and cognitive impairment. Finally, immunohistochemistry demonstrated increased levels of SIRT1 and 3 in the brain active lesion of patients with MS.Our data suggest that mitochondrial dysfunction and alteration in some epigenetics and metabolism modifying factors in the CNS and peripheral blood cells may contribute or correlate with MS progression.
PURPOSE: Provided is novel organic acid salt of amlodipine which has excellent physico-chemical properties. Also, provided are its manufacturing method and a pharmaceutical composition containing it as an active ingredient. CONSTITUTION: Amlodipine camphorsulfonic acid salt is represented by the formula(2). It has photostability and the crystallized form. Its manufacturing method is characterized by reacting amlodipine and camphorsulfonic acid in an inert solvent. A pharmaceutical composition for the treatment of hypertension or cardiac diseases contains amlodipine camphorsulfonic acid salt and a pharmaceutically acceptable diluent or carrier.
Obesity is a leading cause of death and disability in the United States, affecting as many as 80 million Americans. It is well-established that obesity contributes to a number of risk factors for metabolic abnormalities and cardiovascular diseases (CVD), including hypertension, diabetes, and hyperlipidemia. In addition, there is growing evidence that obesity is associated with cognitive deficits in multiple domains, even in otherwise healthy older adults. With the rapidly aging US population and the high prevalence of obesity among older adults, innovative strategies to prevent cognitive decline in this population are needed. Dietary patterns are central to the development and maintenance of obesity and evidence suggests that dietary factors also may affect cognition. Studies have shown that adherence to a Mediterranean Diet (MedDiet) is associated with less cognitive decline and reduced risk for dementia in older adults. Weight loss through caloric restriction also has been shown to improve cognitive function in obese adults. Both the MedDiet and weight loss are thought to improve cognition in obese individuals and reduce CVD/metabolic risk through beneficial changes in systemic inflammation and oxidative stress. The identification of effective lifestyle interventions for diet/weight management to improve cognition among obese older adults is a public health priority. However, no randomized controlled trials (RCTs) have examined the effect of the MedDiet with and without caloric restriction, to promote weight loss on cognitive functioning in obese older adults. The investigators propose a three-arm RCT in which 180 obese (body mass index \[BMI\] ≥ 30 and \< 50 kg/m²) older adults (55-80 years) will be randomized to: 1) an 8-month MedDiet Alone, without caloric restriction/weight loss (MedDiet-A); 2) an 8-month MedDiet lifestyle intervention with caloric restriction/weight loss (MedDiet-WL); or 3) an 8-month typical diet control (TDC) without caloric restriction/weight loss. The investigators will test the following hypotheses: 1) participants randomized to MedDiet-A and MedDiet-WL will achieve greater improvements in cognition compared to participants randomized to TDC; 2) participants randomized to MedDiet-WL will exhibit greater improvements in cognition compared to participants randomized to MedDiet-A; 3) participants randomized to MedDiet-A and MedDiet-WL will show greater improvements in CVD/metabolic risk factors, systemic inflammation, OxStress, and body weight/composition compared to participants in TDC; 4) participants randomized to MedDiet-WL will exhibit greater improvements in CVD/metabolic risk factors, systemic inflammation, OxStress, and body weight/composition compared to MedDiet-A; 5) improvements in CVD/metabolic risk factors, body composition, systemic inflammation, and OxStress will mediate the relationship between MedDiet and improved cognition. The investigators also will determine the extent to which changes in dietary habits, weight and cognitive functioning are maintained over a 6-month follow-up period.
Patients randomized to the arm A receive 6 courses the following regimen: Paclitaxel 175 mg/m²/3 hours, I.V. and carboplatin AUC 5, I.V. every 3 weeks (1 cycle = 21 days).
Attention deficit hyperactivity disorder (ADHD), characterized by inattention, hyperactivity and impulsivity, is an early onset, highly heritable, clinically heterogeneous, long-term impairing disorder with tremendous impact on individuals, families, and societies. Our research team has conducted a series of biological studies on spatial working memory deficits of ADHD, and substantial evidence has suggested spatial working memory deficits as the important neuropsychological biomarker with translational values and favorable endophenotypic properties for ADHD. Despite the abundance of molecular genetic studies on ADHD, the genetic etiologies of ADHD have been non-conclusive. Because genetic studies on endophenotypes can offer more information on genetic and brain process, endophenotypic approach can efficiently enhance the statistical power and make genome-wide association studies (GWAS) applicable in much smaller sample. To date, there has been no GWAS study on spatial working memory deficits of ADHD.

This is a 3-year project. Our previous studies have collected blood samples and spatial working memory data of 382 patients with ADHD and 150 healthy subjects. In this 3-year project, we will recruit 232 healthy subjects, aged 7-18 years. The measures include (1) interviews for psychopathology (K-SADS-E), (2) questionnaires to measures ADHD symptoms (SNAP-IV), and (3) neuropsychological tests: Spatial Working Memory task of the CANTAB. In the first year, a case-only GWAS on spatial working memory (n = 254) will be conducted. In the second year, a control-only GWAS on spatial working memory (n = 254) will be conducted. In the third year, findings from the initial two GWAS will be replicated in a validation sample composed of 128 patients with ADHD and 128 healthy controls.

By careful calculation, a sample size of 382 ADHD subjects will provide adequate power to detect genome-wide significant genetic variations and replicate the findings in an independent validation sample. We anticipate to identify the relationship between genetic variations of ADHD and the endophenotype of spatial working memory. Our findings will significantly contribute to our understanding of the pathophysiological mechanisms of ADHD, especially the pathological pathway from genes, through endophenotype, to behavioral phenotypes.
Participants in Group 1 Immersive Virtual Reality (VR) will wear the device covering their eyes. The viewing experience will include calming nature sounds for between 15-20 minutes before their planned plain clinic procedure.
BACKGROUND: Depression is a common psychiatric disorder with limited effective treatments. Research suggests that depression involves apoptosis mechanisms. Quercetin (QUE) has been reported to have anti-apoptotic activities. In this study, we aimed to investigate the effects and mechanisms of QUE in chronic unpredictable mild stress (CUMS)-induced depression.
METHODS: After establishing mouse models of CUMS-induced depression, the mice were randomly assigned into four groups: control, CUMS, CUMS+QUE, and CUMS+Fluoxetine (FLX). The body weight of the mice was measured during the study. Then, depression-associated behaviors were evaluated using the sucrose preference test (SPT), novelty suppressed feeding test (NSFT), forced swim test (FST) and tail suspension test (TST). Apoptosis in the hippocampus and prefrontal cortex was determined using flow cytometry. Bcl-2 and Nrf2 protein expressions in the hippocampus and prefrontal cortex were also detected. Furthermore, Western blot was used to measure the protein levels of p-ERK, ERK, p-CREB, CREB, and Nrf2 in brain tissues.
RESULTS: QUE or FLX administration increased the body weight of the CUMS mice. Behavioral tests indicated that CUMS mice developed a state of depression, but QUE or FLX treatment improved their depression-associated behaviors. Meanwhile, QUE or FLX treatment decreased apoptosis in the hippocampus and prefrontal cortex. Furthermore, the decreased Nrf2 protein expression, ERK and CREB phosphorylation in CUMS group were enhanced by QUE or FLX administration.
CONCLUSION: QUE could attenuate brain apoptosis in mice with CUMS-induced depression, and the mechanism may be related to the ERK/Nrf2 pathway, indicating that QUE could be a potential treatment for depression.
NEW MATERIAL:An anti-inflammatory polysaccharide obtained from barks of Melia azadirachta. Description: white or slightly brown powder; solubility: soluble in water, insoluble in organic solvents such as methanol, benzene or ethyl acetate; saccharide composition: consisting of glucose and arabinose at a ratio of 2:1; molecular weight: about 8,400; specific ratory power: [alpha]D<22>=-64 deg. (c=0.5 in H2O); infrared absorption spectrum: shown in the figure; ultraviolet absorption sepctrum: showing no absorption maximum but terminal absorption, when its aqueous solution is measured. USE:Anti-inflammatory: it shows strong inhibition against carragheenin edemas and granulation propagation with extremely lowered toxicity. PREPARATION:An extract from Melia azadirachta barks with hot water is treated with molecular sieve to collect compounds of about 8,400 molecular weight. For example, the extract is treated with a molecular sieve with a fractional molecular weight of 1X10<3>-2X10<5> to obtain 3 fractions. Then, the second fraction is treated with molecular sieves with a fraction weight of 500-10,000 or 500-50,000 to effect purification.
Decitabine 3.5mg/m2，ivdrip，qd x 3d, every four weeks for one cycle. It will be given three cycles.
Compounds and methods are provided for inhibiting a PI4-kinase Methods of treating a pathogen infection and methods of treating cancer are also provided. The PI4-kinase inhibitor can be a compound that is a 5-aryl or heteroaryl-thiazole, e.g., as described herein. In certain embodiments, the PI4-kinase inhibitor is a substituted 2-amino-5-phenylthiazole or substituted 2-amino-5-pyridylthiazole compound. In some embodiments, the compounds have broad spectrum anti-infective activity against a variety of infective diseases, where the diseases are caused by pathogens containing a basic amino acid PIP-2 pincer (BAAPP) domain that interacts with phosphatidylinositol 4,5-bisphosphate (PIP-2) to mediate pathogen replication. Also provided are methods of treating a subject for cancer using a PI4-kinase inhibitor. Aspects of the methods include inhibiting PI4-kinase in a cancer cell to reduce cellular proliferation.
The invention discloses an anti-bacterial anti-allergy composition for oral care products. The anti-bacterial anti-allergy composition comprises an anti-allergy agent and probiotics, wherein the anti-allergy agent comprises at least one of potassium salt and/or strontium salt. The invention further discloses an application of the anti-bacterial anti-allergy composition to toothpaste, liquid toothpaste, mouth wash, tooth powder, tooth gel or chewing gum. The invention further discloses anti-bacterial anti-allergy toothpaste and a preparation method thereof. The toothpaste comprises a moisturizer, a friction agent, a thickening agent, a surfactant, a sweetening agent, essence, water and the anti-bacterial anti-allergy composition. The preparation method comprises the following steps: adding the moisturizer into a container firstly, adding the thickening agent, and rapidly stirring uniformly; adding the friction agent, the surfactant, the sweetening agent and the potassium salt and/or strontium salt in sequence, adding the probiotics, and uniformly stirring; performing vacuum pumping, adding the essence lastly, stirring, homogenizing and degassing to obtain the anti-bacterial anti-allergy composition. By adopting the anti-bacterial anti-allergy composition, symptoms such as gingival bleeding, halitosis, gomphiasis, tooth sensitivity and the like of a user can be eliminated.