anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
There are few reports on soluble epoxide hydrolase (sEH) structure-activity relationship studies using natural product-based scaffolds. In this study, we discovered that C-30 urea derivatives of glycyrrhetinic acid such as 33, rather than C-20/C-3 urea derivatives, possess in vitro sEH inhibitory capabilities. Furthermore, we explored the impact of stereoconfigurations at C-3 and C-18 positions, and glycosidic bonds at the 3-OH on the compound's activity. Consequently, a glycoside of 33, specifically 49Cα containing alpha-oriented mannose, exhibited promising in vivo efficacy in alleviating carrageenan-induced paw edema and acetic acid-induced writhing. Meanwhile, 49Cα demonstrated potential in mitigating acute pancreatitis by modulating the ratios of anti-inflammatory epoxyeicosatrienoic acids (EETs) to pro-inflammatory dihydroxyeicosatrienoic acids (DHETs). The co-crystal structure of sEH in complex with 49Cα revealed that the N-tetrahydropyranylmethylene urea hydrogen bonded with the residues within the sEH tunnel, contrasting with the mannose component that extended beyond the tunnel's confines. Our findings highlight 49Cα (coded LQ-38) as a promising candidate for anti-inflammatory and analgesic effects, and pave the way for the future rational design of triterpenoid-based sEH inhibitors.
OBJECTIVE: The economic burden of autism spectrum disorder (ASD) on individuals, their families and society as a whole is poorly understood. Accurate figures are crucial for economic estimates and service planning.
METHODS: The total lifetime individual costs and annual societal costs of ASD in China were estimated with a prevalence-based, gross cost of illness approach and data from multiple sources. The direct medical costs in outpatient and inpatient settings from the electronic health records (EHRs) of hospitals, and direct nonmedical costs from a national survey were included. The indirect costs were from both the national survey and the estimation using human capital methods. Age-specific lifetime incremental societal costs were measured. Comorbidity-related and unrelated costs were analyzed separately.
RESULTS: The discounted lifetime cost for an individual with ASD in China was $2.65 million (at 2020 prices, $) for those without intellectual disability (ID) and $4.61 million (at 2020 prices, $) for those with ID. The total cost of ASD amounted to $41.8 billion in 2020. Productivity loss were major cost drivers for ASD individuals without ID. Direct nonmedical costs (rehabilitation or adult care costs etc.) were major drivers for ASD individuals with ID. In a lifetime course, the total annual costs for middle aged and elderly (>42 years) were highest, followed by transitional adults (18-29 years) and preschoolers, both for individuals with or without ID. The distribution of costs over the lifespan varied by the cost category.
CONCLUSIONS: ASD imposes a substantial economic burden on families and health care systems. Sectors and services coordination should be given policy considerations.
A process is described for the enzyme catalyzed synthesis of polymeric microspheres from monomers such as ethylphenol, naphthols and hydroxypyrenes in reverse micelles in the presence of a detergent. Polymeric microspheres synthesized are porous with nonuniform densities. Polymers prepared from naphthols and hydroxypyrenes are fluorescent with electroluminescent properties. A number of materials such as enzymes, drugs and inorganic materials such as iron oxide and cadmium sulfide are encapsulated in the hollow polymeric microspheres synthesized. These encapsulations are carried out during or after the syntheses of the polymeric microspheres. Functional properties of the encapsulated materials such as enzyme, magnetic and nonlinear optical properties are demonstrated in the polymeric composites.
BACKGROUND: Classical anticoagulants and antiplatelets are associated with high frequencies of bleeding complications or treatment failure when used as single agents. Thrombin plays an important role in the blood coagulation system. GP IIb/IIIa is the central receptor of platelets, which can recognize the Arg-Gly-Asp (RGD) sequence and activate platelets.
MATERIAL AND METHODS: Molecular simulation and homology modeling were performed to design a novel dual-target anticoagulant short peptide (PTIP ). The activities of PTIP on coagulation and platelet in vitro were analyzed. The antithrombotic activity of PTIP was determined by pulmonary thromboembolism model, ferric chloride injury model and arteriovenous bypass thrombosis model. Bleeding effect and toxicity of PTIP were evaluated.
RESULTS: We have constructed a novel dual-target peptide (PTIP) based on the direct thrombin inhibitor peptide (DTIP). PTIP was expressed at high levels in Pichia pastoris. PTIP interfered with thrombin-mediated coagulation and ADP-induced platelet aggregation in vitro. When injected intravenously or subcutaneously, PTIP showed potent and dose-dependent extension of aPTT and PT which were similar to DTIP; but only PTIP was capable of inhibiting platelet aggregation. PTIP (1.0 mg/kg) decelerated thrombosis formation in venous and arterial vessels induced by FeCl3 injury. PTIP (1.0 mg/kg) also prevented deep venous thrombosis and increased the survival rate associated with pulmonary thromboembolism. And PTIP effectively reduced thrombus length in arteriovenous bypass thrombosis model. Moreover, the antithrombotic dose of PTIP could not induce bleeding.
CONCLUSION: These data establish that PTIP represents a novel antithrombotic agent whose effects involve both inhibition of platelet activation and reduction of fibrin generation. And PTIP not only can be used in venous thrombosis and arterial thrombosis, it can also replace the combined treatment of antiplatelet and anticoagulant drugs in thrombotic diseases.
INTRODUCTION: Previous consensus-based long COVID research has focused on establishing research priorities, developing clinical definitions, core outcomes and a list of recommendations of patient-reported outcome measures that can be used to assess and characterise long COVID. Complementing and extending this work, the proposed study will bring together diverse knowledge users to prioritise concepts of care, quality of life and symptoms to inform a national patient registry on long COVID.
METHODS AND ANALYSIS: We will conduct a Delphi process involving Canadians with lived experiences and/or professional expertise with long COVID (including clinicians, policymakers, caregivers and community leaders). A pool of long COVID survey questions has been established through an environmental scan; these questions were coded by topic and will be presented via a series of online, anonymous survey questionnaires to a diverse cohort of 100 participants. Over the course of three Delphi rounds, participants will prioritise and recommend topics related to care, quality of life and symptoms. We will use the prioritised topics to develop a list of core questions as a minimum data set to standardise data collection and inform a national patient registry on long COVID in Canada.
ETHICS AND DISSEMINATION: This study has been approved by the University of Saskatchewan Behavioural Research Ethics Board (BEH #4296). Findings will be shared at national conferences and will be published in an open-access peer-reviewed journal. In addition, the minimum data set will be shared with key knowledge users as recommendations to inform a national long COVID patient registry.
The invention discloses a medicine for treating acne. The medicine is prepared from the following traditional Chinese medicines as raw materials in parts by weight: 2.5-3.5 parts of calomel, 2.5-3.5 parts of scutellaria baicalensis, 2.5-3.5 parts of radix angelicae, 2.5-3.5 parts of rhizoma typhonii and 2.5-3.5 parts of divaricate saposhnikovia roots. The raw materials in parts by weight are grinded into powder, and then the powder is mixed with honey in a proportion of 1:2 to prepare a paste. After the affected part is cleaned everyday, the medicine is wiped at the affected part in the morning and evening twice a day. The medicine disclosed by the invention is fast in effect, good in effect and basically free from side effects. After being taken for 3 days, the medicine has a remarkable curative effect. The medicine promotes balance of internal secretion, inhibits increase of secretion of the sebaceous gland, promotes blood circulation to remove blood stasis, regulates qi and blood, improves the blood circulation of skin and promotes the rapid growth of skin cells, and has a good curative effect on acne.
Wounds that occur in adults form scars due to fibrosis, whereas those in embryos regenerate. If wound healing in embryos is mimicked in adults, scarring can be reduced. We found that mouse fetuses could regenerate tissues up to embryonic day (E) 13, but visible scars remained thereafter. This regeneration pattern requires actin cable formation at the epithelial wound margin via activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). Here, we investigated whether the AMPK-activating effect of salicylate, an anti-inflammatory drug, promotes regenerative wound healing. Salicylate administration resulted in actin cable formation and complete wound regeneration in E14 fetuses, in which scarring should have normally occurred, and promoted contraction of the panniculus carnosus muscle, resulting in complete wound regeneration. In vitro, salicylate further induced actin remodeling in mouse epidermal keratinocytes in a manner dependent on cell and substrate target-specific AMPK activation and subsequent regulation of Rac1 signaling. Furthermore, salicylate promoted epithelialization, enhanced panniculus carnosus muscle contraction, and inhibited scar formation in adult mice. Administration of salicylates to wounds immediately after injury may be a novel method for preventing scarring by promoting a wound healing pattern similar to that of embryonic wounds.
This study is an open-label, randomized, controlled trial. A total of 240 patients who are recruited in 2 quarantine hospitals (15th of May hospital, Cairo, and Al Rajhi hospital, Assiut), will be randomly assigned in a 1:1:1 ratio (80 patient in each treatment arm), to receive either the fixed combination of Sofosbuvir/Ledipasvir (400 mg and 90 mg, orally) once daily for 14 days, plus the standard care treatment regimen (SCT) for COVID-19 patients according to the Egyptian Ministry of Health (MOH) protocol (Group 1), or nitazoxanide (500 mg, orally) four times per day for 14 days, plus STC (Group 2), or SCT alone (Group 3). All treatment groups will be followed up by laboratory investigations and PCR for SARS-CoV-2 virus at the time of enrollment, days 5, 8, 11, and 14. Supportive care comprised, as necessary, supplemental oxygen, noninvasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, and extracorporeal membrane oxygenation (ECMO). To ensure a balanced distribution of case severities in all study groups, randomization will be stratified based on the case severity index issued by WHO (https://www.who.int/docs/default-source/coronaviruse/clinical-management-of-novel-cov.pdf).

Written informed consent will be obtained from all patients or the patient's legal representative if the patient is too unwell to provide consent. The trial will be conducted in accordance with the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines of the International Conference on Harmonisation. The authors are responsible for designing the trial and for compiling and analyzing the data. The authors vouch for data completeness and accuracy and adherence to the trial protocol.
Materials with the consistency of a self supporting paste are shaped by filling an expanded shell profile mould using pressure and then removing most of the mould to leave a collar at the mouth of the mould as an integral support for the moulded stick of paste. The mould may be filled by an injection or extrusion process via an elongated nozzle which is progressively withdrawn from within the mould as filling proceeds. Alt. the mould may be gravity filled with a paste compsn. predispersed in micro capsules which are subsequently burst by compression to create a cohesive paste within the mould. The mould pref. is a fibrous plastic or paper based structure which is porous to air and is supported in a mould holder via which the cavity can be evacuated through the mould walls during filling. The collar may be a conventional plastic mount for a lipstick holder etc. For shaping and mounting paste sticks for cosmetic commercial or office aids, or for medications such as styptic or chiropody crayons.
Obesity is a major risk factor for obstructive sleep apnea (OSA), a condition characterized by repetitive respiratory disturbances, intermittent hypoxia, sleep fragmentation by frequent microarousals and low amounts of deep slow wave sleep (SWS). Today, more than 10 million American women suffer from OSA. OSA has been identified as an independent risk factor for the metabolic syndrome. Because OSA is more prevalent in men than in women, a disproportionate number of studies of OSA and its consequences have been conducted in men. Thus, OSA has been characterized as a disorder associated with gender-based health care inequity. Recent evidence, including data from our group, suggests that reduced amounts and intensity of SWS (i.e. slow-wave activity \[SWA\]) may play a pivotal role in the development of metabolic and cardiovascular disturbances in obese men and women, particularly those with OSA. This project will focus on sex differences in SWA and their relationship with daytime sleepiness and metabolic vulnerability in obese men and women with and without OSA. We propose to simultaneously characterize: 1. sleep-wake regulation; 2. measures of diabetes risk; 3. measures of cardiovascular risk; and 4. profiles of sex steroids, cortisol and adipokines in a. obese men without OSA, b. obese men with OSA before and after treatment with continuous positive airway pressure (CPAP), c. obese pre-menopausal women without OSA, and d. obese pre-menopausal women with OSA before and after CPAP treatment. The completion of these interdisciplinary studies will provide a unique data set contrasting in obese women versus obese men the relationships between sleep and the metabolic syndrome, OSA and the metabolic syndrome and the impact of CPAP treatment on the metabolic syndrome. This work will provide important insights regarding the pathophysiology of OSA and its adverse consequences in obese men and women, and the basis for the development of effective sex-specific prevention and treatment strategies.
BACKGROUND: The kidney and eyes share common pathways and are thought to be closely connected. Chronic kidney disease and major eye diseases, such as cataract and glaucoma, are strongly associated with age. However, further investigation is needed to understand the joint impact of age and kidney diseases on eye diseases. In this study, we assessed the risk of eye diseases in relation to age and kidney failure in Taiwanese adults.
METHODS: Our study included 127,561 cancer-free volunteers aged 30 to 70 years who participated in the Taiwan Biobank (TWB) project from 2008 to 2020. Information on the main exposures (kidney failure and age) and the outcome (eye diseases, including glaucoma, cataract, xerophthalmia, and retinal detachment) was collected through questionnaires.
RESULTS: In general, kidney failure and older age were independently associated with a higher risk of eye, particularly cataract and retinal detachment: prevalence odds ratio (POR); 95% confidence interval (CI) = 2.480; 1.635-3.761 for cataract and 3.885; 1.968-7.666 for retinal detachment. A significant interaction between kidney failure and age on cataract was observed (p-value = 0.0002). Age-stratified analysis revealed a higher risk of cataract among patients with kidney failure aged below 50 (POR = 6.534; 95% CI = 2.493-17.124) and between 50 and 60 years (POR = 3.957; 95%CI = 1.986-7.881). Combining kidney failure and age (reference: no kidney failure and age < 50 years), kidney failure in all age groups was associated with a higher risk of cataract. The PORs; 95% CIs were 10.725; 4.227-27.211 for patients below 50 years, 28.487; 14.270-56.866 for those aged 50-60 years, and 43.183; 24.434-72.824 for those > 60 years. Combining cataract and age (reference: no cataract and age < 50 years), patients below 50 years had the highest risk of kidney failure (POR; 95% CI = 9.510; 3.722-24.297).
CONCLUSIONS: Our study suggests that age and kidney failure may jointly contribute to eye diseases, particularly cataract. The association between cataract and kidney failure could be bidirectional, especially in individuals below 50 years. This significant bidirectional relationship underscores the need for screening patients with cataract for kidney failure and vice versa, particularly in younger adults.
There are very few cases of overdose with levodopa reported in the published literature. Based on the available information, the acute symptoms of levodopa and dopa decarboxylase inhibitor overdose can be expected to arise from dopaminergic overstimulation. Doses of a few grams may result in CNS disturbances, with an increasing likelihood of cardiovascular disturbance (e.g., hypotension, tachycardia) and more severe psychiatric problems at higher doses. An isolated report of rhabdomyolysis and another of transient renal insufficiency suggest that levodopa overdose may give rise to systemic complications, secondary to dopaminergic overstimulation. 

  


COMT inhibition by entacapone treatment is dose-dependent. A massive overdose of entacapone may theoretically produce a 100% inhibition of the COMT enzyme in people, thereby preventing the O-methylation of endogenous and exogenous catechols. 

  


In clinical trials, the highest single dose of entacapone administered to humans was 800 mg, resulting in a plasma concentration of 14.1 mcg per mL. The highest daily dose given to humans was 2,400 mg, administered in one study as 400 mg six times daily with carbidopa/levodopa for 14 days in 15 Parkinson’s disease patients, and in another study as 800 mg three times daily for 7 days in 8 healthy volunteers. At this daily dose, the peak plasma concentrations of entacapone averaged 2.0 mcg per mL (at 45 min, compared to 1.0 mcg per mL and 1.2 mcg per mL with 200 mg entacapone at 45 min.). Abdominal pain and loose stools were the most commonly observed adverse events during this study. Daily doses as high as 2,000 mg entacapone have been administered as 200 mg 10 times daily with carbidopa/levodopa or benserazide/levodopa for at least 1 year in 10 patients, for at least 2 years in 8 patients and for at least 3 years in 7 patients. Overall, however, clinical experience with daily doses above 1,600 mg is limited.
An exercise program has been prepared for patients for use in mirror therapy. In this exercise program, firstly, joint movements of the hand and fingers (opening and closing the fingers one by one, making a fist, moving the hand to the right and left, turning the wrist) are shown. Then, activities with some small objects used in daily life (squeezing ball, putting clothespins, collecting paper clips from the table, using tongs, turning cards, turning pages) is shown. The patient will repeat the movement for 3 minutes. The patient will hold the affected extremity behind the mirror with the healthy extremity, the patient will look towards the affected side from the mirror and try to do the movements with the affected extremity. . The treatment period will be 20 sessions, 5 days a week, for 4 weeks.The exercises will take 1 hour, including half an hour of mirror therapy and half an hour of conventional exercises.
LADA is actually a form of type 1 diabetes, which is caused by autoimmune damage of islet β cells and triggered by environmental factors based on genetic susceptibility. LADA shows some characteristics of type 2 diabetes at its onset, which develops slowly and latent, and easily be misdiagnosed as type 2 diabetes due to slowly β cell function deterioration. This is a multi-center, open- label, 1:1:1 randomized controlled trial to investigate the protective effects of saxagliptin and vitamin D3 in LADA patients. The study comprises the 0-6weeks of screening period and the 104-week intervention period. After obtaining the informed consent，the screening will find out the eligible patients according to the inclusion/exclusion criteria, then the patients will be randomized to the 104-week intervention period. Subjects will be randomized into one of the three groups(arms) through central dynamic randomization: metformin (and insulin), metformin(and insulin) +saxagliptin, metformin(and insulin) +saxagliptin+vitamin D3. Our previous randomized- controlled pilot study showed that dipeptidyl peptidase 4 (DPP-4) inhibitors could significantly improve islet β-cell function in patients with LADA. The main purpose of this study: To evaluate whether saxagliptin (and vitamin D3) with metformin (and insulin) therapy can better protect islet β cell function than metformin (and insulin).
One-hundred-and-ninety-two weanling pigs (6.7 kg body weight) were used to evaluate the impact of a carbohydrases-protease enzyme complex (CPEC) on growth performance, nutrient digestibility, and gut microbiome. Pigs were assigned to one of the four dietary treatments for 42 d according to a 2 × 2 factorial arrangement of diet type (low fiber [LF] or high fiber [HF]) and CPEC supplementation (0 or 170 mg/kg diet). The LF diet was prepared as corn-wheat-based diet while the HF diet was wheat-barley-based and contained wheat middlings and canola meal. Each dietary treatment consisted of 12 replicate pens (six replicates per gender) and four pigs per replicate pen. Over the 42-d period, there was no interaction between diet type and CPEC supplementation on growth performance indices of pigs. Dietary addition of CPEC improved (P < 0.05) the body weight of pigs at days 28 and 42 and the gain-to-feed ratio of pigs from days 0 to 14. During the entire experimental period, dietary CPEC supplementation improved (P < 0.05) the average daily gain and gain-to-feed ratio of pigs. There were interactions between diet type and CPEC supplementation on apparent total tract digestibility (ATTD) of dry matter (DM; P < 0.01), gross energy (GE; P < 0.01), and neutral detergent fiber (NDF; P < 0.05) at d 42. Dietary CPEC addition improved (P < 0.05) ATTD of DM, GE, and NDF in the HF diets. At day 43, dietary CPEC addition resulted in improved (P < 0.05) apparent ileal digestibility (AID) of NDF and interactions (P < 0.05) between diet type and CPEC supplementation on AID of DM and crude fiber. Alpha diversity indices including phylogenetic diversity and observed amplicon sequence variants of fecal microbiome increased (P < 0.05) by the addition of CPEC to the HF diets on day 42. An interaction (P < 0.05) between diet type and CPEC addition on Bray-Curtis dissimilarity index and Unweighted UniFrac distances was observed on day 42. In conclusion, CPEC improved weanling pig performance and feed efficiency, especially in wheat-barley diets, while dietary fiber composition had a more significant impact on fecal microbial communities than CPEC administration. The results of this study underscores carbohydrase's potential to boost pig performance without major microbiome changes.
Up to three escalation cohorts in phase 1 followed by one expansion cohort in phase 2. Subjects have AML and bone marrow blast count \<5%, administered by IV infusion following lymphodepleting chemotherapy.