anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Previous studies have implicated rheumatoid arthritis as an independent risk factor for bone density loss. However, whether there is a causal relationship between rheumatic diseases and bone mineral density (BMD) and fractures is still controversial. We employed a bidirectional Mendelian analysis to explore the causal relationship between rheumatic diseases and BMD or fractures.
METHODS: The rheumatic diseases instrumental variables (IVs) were obtained from a large Genome-wide association study (GWAS) meta-analysis dataset of European descent. Analyses were performed for the three rheumatic diseases: ankylosing spondylitis (AS) (n = 22,647 cases, 99,962 single nucleotide polymorphisms [SNPs]), rheumatoid arthritis (RA) (n = 58,284 cases, 13,108,512 SNPs), and systemic lupus erythematosus (SLE) (n = 14,267 cases, 7,071,163 SNPs). Two-sample Mendelian randomization (MR) analyses were carried out by using R language TwoSampleMR version 0.5.7. The inverse-variance weighted (IVW), MR-Egger, and weighted median methods were used to analyze the causal relationship between rheumatic diseases and BMD or fracture.
RESULTS: The MR results revealed that there was absence of evidence for causal effect of AS on BMD or fracture. However, there is a positive causal relationship of RA with fracture of femur (95% CI = 1.0001 to 1.077, p = 0.046), and RA and fracture of forearm (95% CI = 1.015 to 1.064, p = 0.001). SLE had positive causal links for fracture of forearm (95% CI = 1.004 to 1.051, p = 0.020). Additionally, increasing in heel bone mineral density (Heel-BMD) and total bone mineral density (Total-BMD) can lead to a reduced risk of AS without heterogeneity or pleiotropic effects. The results were stable and reliable. There was absence of evidence for causal effect of fracture on RA (95% CI = 0.929 to 1.106, p = 0.759), and fracture on SLE (95% CI = 0.793 to 1.589, p = 0.516).
CONCLUSIONS: RA and SLE are risk factors for fractures. On the other hand, BMD increasing can reduce risk of AS. Our results indicate that rheumatic diseases may lead to an increased risk of fractures, while increased BMD may lead to a reduced risk of rheumatic diseases. These findings provide insight into the risk of BMD and AS, identifying a potential predictor of AS risk as a reduction in BMD.
Healthy participants will be randomized 3:1 to receive repeat doses of either GSK3965193 (Dose X) or placebo under fasted conditions. Part 2A may start while Part 1 is still ongoing. The starting dose in Part 2 will be at least 3-fold below the highest dose completed in Part 1.
The control group will undergo strengthening exercises and gait training as the usual practice in Parkinson Disease. Training will consist of individualized treatment 60 mins/day, 2 days/week, for 5 consecutive weeks (Bartolo et. al., 2010).
The present invention provides modified multifunctional thiol-ene monomers wherein one or more thiols are reacted with a Michael addition reactive double bond compound. The present invention further discloses photocurable thiol-ene formulations comprising thiol-ene monomers including the modified multifunctional thiols. The present invention further discloses photocurable thiol-ene formulations comprising thiol-ene monomers and Michael addition reactive double bond molecules and a Michael catalyst. The formulations of the present invention can be photocured to make films or coatings. In a further disclosure, the formulations, including those comprised of unmodified multifunctional thiols and multifunctional enes, are photocured to form films applied to non-flexible or flexible polymer or non-polymer substrates suitable for food packaging, electronic products, optical products and other applications and free-standing films. The present invention further discloses photocurable thiol-ene formulations comprising thiol-ene monomers and Michael addition reactive double bond molecules and a Michael catalyst. These formulations are disclosed to form free-standing films and coatings on substrates when applied to flexible substrates. Such materials are suitable for use in the packaging of food products and other products which are to be maintained in a hermetically sealed relationship to the atmosphere.
The invention provides sesquiterpene compounds, and two sesquiterpene compounds are obtained through a series of processes such as solvent distribution, chromatographic column separation, high performance liquid chromatography purification and the like. As a small molecule compound, the naturally separated active compound shows obvious NGF-like activity in an in vitro screening model PC12 cell of senile dementia. The compound is used as a guide to optimize the structure, and has important practical significance in carrying out basic research on the research and development of new drugs for preventing and treating neurodegenerative diseases such as senile dementia and the like. The sesquiterpenoids provided by the invention have obvious activity of the nerve growth factor, and can be applied to medicines and health products for preventing neurodegenerative diseases such as senile dementia and the like. The preparation method is simple and rapid, and the obtained compound has high purity. The structural formula of compound 2 is as follows: 。
The invention is extensively hydrolysed casein for use in reducing the risk of intestinal inflammation, intestinal tissue damage, or both, in a pre-term infant. Also claimed is extensively hydrolyzed casein for use in reducing expression of interleukin-1β (IL-1β), IL-8, and/or tumor necrosis factor receptor 2 (TNFR2), and a composition comprising a hydrolyzed casein. The downregulation of the cytokines may be in the intestinal epithelium of a premature baby. The casein hydrolysate may reduce the risk of necrotising enterocolitis (NEC) and/or systemic infection. The casein hydrolyzate may be in the form of a reconstituted solution comprising casein in the range of 0.01 mg/mL to 0.50 g/mL. The extensively hydrolysed casein may also be in the form of a reconstitutible powder comprising casein in the range of 10 μg/100 kcal to 15 g/100 kcal. The composition may further comprise a prebiotic, such as polydextrose or galactooligosaccharides, or milk fat globule membrane (MFGM). The composition may also be a nutritional composition, a premature infant formula, a milk fortifier, and/or a synthetic composition. Also claimed is a separate invention relating to the use of extensively hydrolysed casein for improving gut barrier function in a preterm infant by reducing intestinal permeability.
A water-in-air emulsion or suspension containing a dispensible material is formed by stabilization of small droplets (48) of aqueous liquid with an interfacial barrier of very fine, hydrophobic metal oxide particles (42) such as silane modified silica. As the droplets (48) are subjected to shear such as during passage through an orifice (28), and/or on the surface of the target, the shear forces experienced at least partially destabilize the barrier allowing the droplets to coalesce to form particles of controlled density and increased size and eventually can be totally destabilized into an elegant cream or lotion. At least 10% of the droplets may coalesce into particles after leaving the orifice. Active ingredients such as antiperspirants may be added to either the aqueous liquid phase or to the powder phase as long as they do not destabilize the suspension. A non-pressurized system comprises a container (10) suitable for dispensing the suspension having a compartment (14) receiving the suspension, a valve means (18) having an outlet orifice (28) of a dimension adapted to impart a preselected shear and destabilization to the suspension and the container being adapted to enable the suspension to be propelled through the outlet orifice. Other dispensing systems include shaker-top containers and roll-on applicators.
BACKGROUND: One of the most prevalent respiratory disorders in modern society is chronic obstructive pulmonary disease (COPD). Frequent comorbidities in patients with COPD are abnormal nutritional status and body composition variations. Malnutrition-sarcopenia syndrome, which occurs when the 2 conditions - malnutrition and sarcopenia - coexist, raises the risk of death more than either condition alone. The current study sought to determine the prevalence of malnutrition, sarcopenia, and malnutrition-sarcopenia syndrome in patients with COPD as well as the association between these diseases and the severity of COPD.
METHODS: The study was an analytical cross-sectional study conducted on hospitalized patients with COPD. The sample size of the study was calculated to be 160. A self-structured questionnaire was used to collect the data, containing sociodemographic characteristics, clinical profiles, anthropometric assessment, and bioimpedance indices. Sarcopenia was diagnosed with low muscle strength and muscle mass by the EWGSOP2 recommendations. Muscle mass is measured by BIA and muscle strength (Handgrip) was measured by a Hand Dynamometer. Assessment of the risk of malnutrition was performed using the Mini Nutritional Assessment-Short Form questionnaire and was confirmed by GLIM criteria. The COPD assessment test (CAT) tool determined the severity of the condition. For the data analysis, comparisons were made using Student's t test and Mann-Whitney test in bivariate analysis. Multivariate logistic regression analyses were performed considering the outcomes of patients with COPD by CAT scores, prolonged length of stay, and hospital readmission 6 months after discharge.
RESULTS: The mean age of the participants was 48 ± 5 years. Approximately 61.9% were found to be sarcopenic. Approximately 45.6% of participants had malnutrition. Malnutrition sarcopenia syndrome was diagnosed in 32.5% of patients. The study analysis revealed that patients with COPD with malnutrition-sarcopenia syndrome had more than twice the odds of prolonged hospital stay, re-admission within 6 months, and higher CAT scores.
CONCLUSION: The study revealed a high prevalence of sarcopenia, malnutrition, and malnutrition sarcopenia syndrome in patients with COPD. These conditions were found to be statistically significant with prolonged length of stay, re-admission within 6 months, and CAT scores. The findings highlight the importance of addressing these conditions as part of the management of the patients.
Neuroblastoma is the most common tumour of childhood after brain tumours. Approximately half of cases are high risk and despite extensive treatments outcome is very poor. More than 60% of high risk patients suffer relapse or further spread of their disease and long-term survival is below 10%. Existing imaging techniques are not sensitive enough to accurately assess the level of risk which is critical in determining the best choice of treatment. This study will compare a new type of imaging against the existing imaging techniques. The new scans use a new tracer called \[124I\]mIBG which is taken up by the cancer tissue much more than by normal tissues. This tracer can be used with a 3D imaging technique called PET/CT to pinpoint where the disease has spread and quantify the amount of disease. Patients will be those scheduled to have an \[123I\]mIBG scan for routine care during a planned break in treatment.
Like other topical corticosteroids, CLOBEX® (clobetasol propionate) Lotion, 0.05% has anti-inflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids in general is unclear. However, corticosteroids are thought to act by induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.

Pharmacokinetics

The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle, the integrity of the epidermal barrier and occlusion. For example, occlusive dressing with hydrocortisone for up to 24 hours has not been demonstrated to increase penetration; however, occlusion of hydrocortisone for 96 hours markedly enhances penetration. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and other disease processes in the skin may increase percutaneous absorption.

There are no human data regarding the distribution of corticosteroids to body organs following topical application. Nevertheless, once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systematically administered corticosteroids. Due to the fact that circulating levels are usually below the level of detection, the use of pharmacodynamic endpoints for assessing the systemic exposure of topical corticosteroids is necessary. They are metabolized, primarily in the liver, and are then excreted by the kidneys. In addition, some corticosteroids and their metabolites are also excreted in the bile.

CLOBEX® (clobetasol propionate) Lotion, 0.05% is in the super-high range of potency as compared with other topical corticosteroids in vasoconstrictor studies.

In studies evaluating the potential for hypothalamic-pituitary-adrenal (HPA) axis suppression, CLOBEX® Lotion, 0.05% demonstrated rates of suppression that were numerically higher than those of a clobetasol propionate 0.05% cream (Temovate E® Emollient, 0.05%), (See PRECAUTIONS).
Thoracic mobility exercises were given to the participants. Exercises has to be performed with combination of breathing which involve holding time 10 seconds 5 repetition per set, 3 sets Each exercise has to perform 5 days in a week for 2 weeks two times a day.
Pioglitazone is a Pioglitazone hydrochloride, and white circle-shaped tablet. It is administered once-daily with 15mg, with or without meals. The once-daily administration begins with 15mg, and if need increase, researchers can increase up to 30mg at week 12.
The invention relates to a medicine used for treating intestinal diseases, in particular to a reagent warmly invigorating spleen and stomach. The medicine has katsumade galangal seed 30 to 50g, officinal magnolia bark 10 to 20g, pilose asiabell root 10 to 20g, south dodder seed 10 to 30g, common ginger 10 to 15g, costus root 10 to 15g, kudzuvine root 5 to 20g, white peony root 5 to 15g, divaricate saposhnikovia root 5 to 10g, dahuricae angelica root 5 to 10g and bitter orange 10 to 20g by weight. The invention mainly adopts dampness resolving, assisted by warming, clearing and yin nourishing,which breaks through the limitation of classic warmly invigorating spleen and kidney, and embodies the theory of strengthening spleen by dryness ascending. Avoiding disadvantages of warm and dry things injuring yin and generating heat, the invention has fast and lasting curative effects with no toxicity or side effects. The reagent of the invention is characterized in that materials are easy to obtain, the preparation is relatively simple and the cost is low. With cure rate reaching 87 to 96 percent in clinical observation, the invention is an ideal reagent for treating spleen and stomach.
The targeted cycling exercise dosage will consist of 1.) a session duration=30mins, 2.) frequency=3times/wk and 3.) Intensity= (60-84% heart rate reserve (HHR).4.) overall program duration=3months.
Hypoxia is the key pathobiological trigger of tubular oxidative stress and cell death that drives the transition of acute kidney injury (AKI) to chronic kidney disease (CKD). The mitochondrial-rich proximal tubular epithelial cells (PTEC) are uniquely sensitive to hypoxia and thus, are pivotal in propagating the sustained tubular loss of AKI-to-CKD transition. Here, we examined the role of PTEC-derived small extracellular vesicles (sEV) in propagating the 'wave of tubular death'. Ex vivo patient-derived PTEC were cultured under normoxia (21 % O2) and hypoxia (1 % O2) on Transwell inserts for isolation and analysis of sEV secreted from apical versus basolateral PTEC surfaces. Increased numbers of sEV were secreted from the apical surface of hypoxic PTEC compared with normoxic PTEC. No differences in basolateral sEV numbers were observed between culture conditions. Biological pathway analysis of hypoxic-apical sEV cargo identified distinct miRNAs linked with cellular injury pathways. In functional assays, hypoxic-apical sEV selectively induced ferroptotic cell death (↓glutathione peroxidase-4, ↑lipid peroxidation) in autologous PTEC compared with normoxic-apical sEV. The addition of ferroptosis inhibitors, ferrostatin-1 and baicalein, attenuated PTEC ferroptosis. RNAse A pretreatment of hypoxic-apical sEV also abrogated PTEC ferroptosis, demonstrating a role for sEV RNA in ferroptotic 'wave of death' signalling. In line with these in vitro findings, in situ immunolabelling of diagnostic kidney biopsies from AKI patients with clinical progression to CKD (AKI-to-CKD transition) showed evidence of ferroptosis propagation (increased numbers of ACSL4+ PTEC), while urine-derived sEV (usEV) from these 'AKI-to-CKD transition' patients triggered PTEC ferroptosis (↑lipid peroxidation) in functional studies. Our data establish PTEC-derived apical sEV and their intravesicular RNA as mediators of tubular lipid peroxidation and ferroptosis in hypoxic kidney injury. This concept of how tubular pathology is propagated from the initiating insult into a 'wave of death' provides novel therapeutic check-points for targeting AKI-to-CKD transition.
The invention relates to a preparation method of modified zein peptide and belongs to the technical field of utilization of zein. According to the preparation method of the modified zein peptide, market zein flakes serve as raw materials. The the preparation method of the modified zein peptide includes the following steps of preparing a zein emulsion, conducting single enzyme hydrolysis and an acylation reaction, drying, and obtaining the modified zein peptide. A plurality of byproducts are obtained through separation and concentration. The preparation method of the modified zein peptide has the advantages of being simple in technology, easy to operate, simple in production equipment, safe in production, high in comprehensive utilization efficiency of resources, free from discharge of waste gas, waste water and industrial residue, beneficial to environmental protection, low in production cost, convenient to popularize and apply, strong in water-solubility of the prepared product and the like. In addition, the preparation method of the modified zein peptide can be widely applied to modification production of the zein flakes. The product and the byproducts prepared through the preparation method of the modified zein peptide can be widely applied to industries such as textile, medicicine, food and chemistry.
Improved aerodynamically light particles for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the aerodynamically light particles are made of biodegradable material and have a tap density of less than 0.4 g/cm 3  and a mass mean diameter between 5 μm and 30 μm. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear α-hydroxy-acid polyester backbone having at least one amino acid group incorporated therein and at least one poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, aerodynamically light particles having a large mean diameter, for example greater than 5 μm, can be used for enhanced delivery of a therapeutic agent to the alveolar region of the lung. The aerodynamically light particles incorporating a therapeutic agent may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide variety of therapeutic agents.
Patients receive ribociclib PO QD on days 1-21, tucatinib PO BID on days 1-28, and trastuzumab IV over 30-90 minutes every 7 days. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
Participants received a placebo intravenous (IV) infusion on day 1 then 12 mg subcutaneous sumatriptan on day 2 (Part 1). After a 2-day washout participants received another placebo IV infusion on day 4 followed by 12 mg subcutaneous sumatriptan on day 5 (Part 2).
A method of clustering or grouping subjects that are similar to one another. A dataset contains, for each subject, a set of quantitative values which each represent a respective clinical or pathological feature of that subject. A principle component analysis, PCA, is performed on the dataset. Loadings of one of the first two principle components identified by the PCA are used to generate a respective dataset of weighting values. These weighting values are used to weigh or modify each set of quantitative values in the dataset. A clustering algorithm is performed on the weighted sets of subject data. The process may be iterated until user-defined stopping conditions are satisfied.
For the Pharmacist-Administered HPV Vaccine Series Completion group (intervention group), primary care providers will refer patients who have received the initial HPV vaccine to receive the additional doses at patients' community retail pharmacies. Patients between ages 9-14 will need to receive one additional HPV vaccine dose with their community pharmacist 6-12 months after receiving Dose 1. Patients aged 15 and older will need to receive the 2nd dose 1-2 months after receiving the first HPV vaccine dose and the 3rd dose 6-months after receiving the initial dose.
AIMS: A reduction in both dystrophin and neuronal nitric oxide synthase (NOS1) secondary to microRNA-31 (miR-31) up-regulation contributes to the atrial electrical remodelling that underpins human and experimental atrial fibrillation (AF). In contrast, patients with Duchenne muscular dystrophy (DMD), who lack dystrophin and NOS1 and, at least in the skeletal muscle, have raised miR-31 expression, do not have increase susceptibility to AF in the absence of left ventricular (LV) dysfunction. Here, we investigated whether dystrophin deficiency is also associated with atrial up-regulation of miR-31, loss of NOS1 protein, and increased AF susceptibility in young mdx mice.
METHODS AND RESULTS: Echocardiography showed normal cardiac structure and function in 12-13 weeks mdx mice, with no indication by assay of hydroxyproline that atrial fibrosis had developed. The absence of dystrophin in mdx mice was accompanied by an overall reduction in syntrophin and a lower NOS1 protein content in the skeletal muscle and in the left atrial and ventricular myocardium, with the latter occurring alongside reduced Nos1 transcript levels (exons 1-2 by quantitative polymerase chain reaction) and an increase in NOS1 polyubiquitination [assessed using tandem polyubiquitination pulldowns; P < 0.05 vs. wild type (WT)]. Neither the up-regulation of miR-31 nor the substantial reduction in NOS activity observed in the skeletal muscle was present in the atrial tissue of mdx mice. At difference with the skeletal muscle, the mdx atrial myocardium showed a reduction in the constitutive NOS inhibitor, caveolin-1, coupled with an increase in NOS3 serine1177 phosphorylation, in the absence of differences in the protein content of other NOS isoforms or in the relative expression NOS1 splice variants. In line with these findings, transoesophageal atrial burst pacing revealed no difference in AF susceptibility between mdx mice and their WT littermates.
CONCLUSION: Dystrophin depletion is not associated with atrial miR-31 up-regulation, reduced NOS activity, or increased AF susceptibility in the mdx mouse. Compared with the skeletal muscle, the milder atrial biochemical phenotype may explain why patients with DMD do not exhibit a higher prevalence of atrial arrhythmias despite a reduction in NOS1 content.