anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Amyotrophic lateral sclerosis (ALS) is a universally fatal neurodegenerative condition that causes weakness leading to paralysis and death. Life expectancy is less that 5 years. The cause is generally unknown and there is no effective treatment. Patients with ALS typically exhibit a progressive paralysis due to the continued loss of motoneurons. Intraspinal injections of bone marrow mononuclear cells have been able to ameliorate the course of ALS in murine models. The purpose of this prospective, nonrandomized, open label, pilot study is to conduct the investigation of the safety and efficacy of infusion of autologous bone marrow-isolated stem/progenitor cells with different selected phenotypes into the subjects with diagnosed ALS. Especially, this clinical trial is designated to test the therapeutic (pro-regenerative and neuro-protective) functions of different stem/progenitor cell populations able to secrete bioactive neurotrophic factors. All patients enrolled will have a documented history of ALS disease prior to study enrollment. Patients diagnosed as early stage of ALS with the duration of disease less than 6 months and patients diagnosed with advanced stage of ALS disease with duration of 6-12 months will be recruited and allocated based on their disease severity to two treatment groups: Group I - patients of early ALS disease stage and Group II - patients of advanced ALS disease. Next, autologous bone marrow-isolated stem/progenitor cells administration to the cerebrospinal fluid at the site of the spinal cord will be performed. Finally, treatment safety, adverse events and exploratory parameters, including electromyographic (EMG) studies, forced vital capacity (FVC), functional rating scale (FRS) and maximum voluntary isometric contraction-arm (MVIC-arm) evaluation, to establish ALS progression rate will be recorded throughout the duration of the post-treatment follow up period.
Intervention is intake of double fortified salt with folic acid and iodine (DFS). We will ask the participants to substitute their current salt with the study saltshaker and use it when preparing food or when eating out. We estimate minimum daily intake from salt consumption by participants will be 200 micrograms (µg) of folic acid per serving. Serving is 2g of salt. Participants will be given portion suggestions: 1/2 teaspoon or 2-3 pinches or 8-10 shakes/5 times a day. Containers (125g) will be weighted at the beginning and end of 1 month. We will ask each day if woman cooked/used the salt for herself only or to list number of people each day. Participants will also agree to complete either daily paper salt log. A commercially available salt that is fortified with folic acid has been provided by AlpenJodSalz produced by Sudwestdeutsche Salzwerk. For 30 participants, we will need 30 containers.
DCC-3116 tablets in escalating dose cohorts given orally twice daily (BID) in 28-day cycles as monotherapy (single agent). If no DLT in 3 participants or 1 DLT/6 participants is observed, dose escalation may continue to the next planned dose cohort.
OBJECTIVE: To explore the clinical and genetic characteristics of five children with epilepsies due to variants of SCN8A gene.
METHODS: Clinical data of five children (four males and one female) admitted to Linyi People's Hospital due to hereditary epilepsies between August 2015 and August 2022 were collected. Whole exome sequencing was carried out for these children, and candidate variants were verified by Sanger sequencing.
RESULTS: All of the five children were found to harbor variants of the SCN8A gene. Case 1, who had benign familial infantile epilepsy, inherited a known pathogenic c.4840A>G variant from his father with similar symptoms. Cases 2 to 4 had presented with intermediate epilepsy. Among these, case 2 has harbored a de novo c.3967G>A variant which was rated as pathogenic (PS1+PS2+PM1+PM2_Supporting+PP3) based on the guidelines from the American College of Medical Genetics and Genomics. Cases 3 and 4 were found to respectively harbor a de novo c.415A>T and a c.4697C>T variant, which were both rated as likely pathogenic (PS2+PM1+PM2_Supporting+PP3). Case 5, who had early-onset infantile epileptic encephalopathy transformed into Lennox Gastaut-like syndrome, has harbored a de novo c.5615G>A variant, which was known to be pathogenic. The children had their age of onset ranging from 2 to 14 months, and all had focal seizures and generalized tonic clonic seizures. Four children (cases 1, 2, 3 and 5) had cluster seizures, four (cases 1 to 4) had become seizure-free after single or dual treatment and showed normal growth and development, whilst case 5 was drug-resistant and showed severe developmental retardation.
CONCLUSION: The five children had new features such as cluster seizures, occasional benign seizures in adulthood, and intermediate epilepsy which are prone to relapse after discontinuation of medication, which may be attributed to the pathogenic variants of the SCN8A gene.
There are multiple mechanisms underlying obstructive sleep apnea (OSA) development. However, how classic OSA risk factors such as body mass index (BMI) and sex portend to OSA development has not been fully described. Thus we sought to evaluate how obesity leads to OSA and assess how these mechanisms differ between men and women. The San Diego Multi-Outcome OSA Endophenotype (SNOOzzzE) cohort includes 3,319 consecutive adults who underwent a clinical in-laboratory polysomnography at the University of California, San Diego, sleep clinic between January 2017 and December 2019. Using routine polysomnography signals, we determined OSA endotypes. We then performed mediation analyses stratified by sex to determine how BMI influenced the apnea-hypopnea index (AHI) using OSA pathophysiological traits as mediators, adjusting for age, race, and ethnicity. We included 2,146 patients of whom 919 (43%) were women and 1,227 (57%) were obese [body mass index (BMI) > 30 kg/m2]. BMI was significantly associated with AHI in both women and men. In men, the adjusted effect of BMI on AHI was partially mediated by a reduction in upper airway stiffness (βstandardized = 0.124), a reduction in circulatory delay (βstandardized = 0.063), and an increase in arousal threshold (βstandardized = 0.029; Pboot-strapped,all < 0.05). In women, the adjusted effect of BMI on AHI was partially mediated by a reduction in upper airway stiffness (βstandardized = 0.05) and circulatory delay (βstandardized = 0.037; Pboot-strapped,all < 0.05). BMI-related OSA pathogenesis differs by sex. An increase in upper airway collapsibility is consistent with prior studies. A reduction in circulatory delay may lead to shorter and thus more events per hour (higher AHI), while the relationship between arousal threshold and OSA is likely complex.NEW & NOTEWORTHY Our data provide important insights into obesity-related obstructive sleep apnea (OSA) pathogenesis, thereby validating, and extending, prior research findings. This is the largest sample size study to examine the relationships between obesity and gender on OSA pathogenesis. The influence of obesity on sleep apnea severity is mediated by different mechanistic traits (endotypes).
The invention relates to temperature-sensitive type gel for preparing a non-infectious cervicitis and vaginitis animal model. A formula and a preparation technology are involved. According to the main mechanism of the preparation for preparing the model, phenol or cresol which produces irritation to mucosae is utilized as a main medicine, poloxamer 407 is used as a main material, other solubilizing or tackifying or thickening material is used as an auxiliary material, and therefore the temperature-sensitive type gel is formed. The gel is fluxible thick liquid facilitating dosage at indoor temperature; the gel rapidly and evenly adheres to the cervix opening and peripheral vaginal wall after being injected into the vagina depth portion of an animal at body temperature, and is rapidly gelled and cured, the medicine is continuously released, and therefore continuous irritation is produced. Accordingly, the model can be prepared successfully through single dosage. By using the temperature-sensitive type gel for preparing the non-infectious cervicitis and vaginitis animal model, preparation is easy, convenient, fast, efficient and good in replicability.
FIELD: organic chemistry, pharmacy. SUBSTANCE: invention discloses compounds of the formula (I)   where R 1 , R 2 , R 3 , Het and   are characterized in the description and also their oxides, pharmaceutically acceptable addition salts and stereochemically isomeric forms. Invention describes also preparing a pharmaceutical composition showing an inhibitory activity with respect to metabolism of retinoic acid and comprising therapeutically effective amount of compound of the formula (I) and a pharmaceutically acceptable carrier. Invention describes also methods of synthesis of a compound of the formula (I). EFFECT: improved method of synthesis and preparing, valuable biochemical properties. 20 cl, 8 tbl
The disclosure provides improved methods for treating or preventing a class of undesired health events including multiple related maladies, such as a disease, condition, or syndrome or the like. The improvement results from optimization of energy metabolism by administering a therapeutically effective compound selected to a) modulate mitochondrial activity to correct for deficiencies resulting from the disease, b) to boost cell energy metabolism thereby improving the original method's efficacy, and/or c) to correct for metabolic disruptions resulting from therapies or medicaments used in the method to be improved. A combination therapy may be designed based on a disease, a group and/or an individual, said combination comprising one or more energy optimization booster combined with a medicament used in an original method is an exemplary embodiment. In some circumstances optimization may involve boosting energy metabolism throughout an organism or in selected cells, tissues or subcellular structures; in some circumstances optimization may involve diminishing energy metabolism throughout an organism or in selected tissues, cells or subcellular structures. In several circumstances diminishing energy metabolism in selected cells to zero or near zero may, by essentially destroying or eliminating mitochondrial functionality of these cells to impair or destroy adverse functionality of these cells or subcellular activity, be optimal for the organism. Biochemicals, including biotherapeutics, may be delivered by any effective method or device, including, but not limited to: injection, oral dosing, nanodelivery, suppository, patches, eye drops, nasal spray, ointment, cream, synthetic gene, conjugated molecule, catheter, timed or controlled release capsule or pill, subdermal implants, diet, etc.
In the last decades, the increase in life expectancy highlights the world population aging as an irreversible process. The oxidative stress hypothesis of aging suggests that accumulation of oxidative damage during lifespan may be related to loss of cellular functions, a process normally associated with senescence. However, it has been proposed that individuals who live longer in a successful manner tend to be more adapted against aging physiological changes. Sleep is essential in maintaining health and well-being. Growing evidence suggests interrelationships between oxidative stress and sleep, while the latter is an important mechanism involved in redox balance maintenance. Therefore, the present study proposes the characterization of sleep patterns of healthy young adults, elderly individuals and individuals above 85 years old, using polysomnographic recordings, in order to clarify the importance of sleep in longevity. Furthermore, this study intends to analyze the oxidative stress-related gene expression in peripheral blood of the three studied groups, using the Superarray - RT2 Profiler" PCR Array System. After the identification of genes whose expression pattern among groups suggest a more specific role in longevity, the mechanisms of gene expression regulation, including DNA methylation patterns and microRNA expression, as well as the possible genomic sources of variation in these genes will be investigated. In addition, the oldest individual (105 years-old) will have his whole genome sequenced using next-generation sequencing technology, in order to identify rare variants associated with longevity. Subsequently, the effect of the polymorphisms and rare variants identified will be confirmed in an expanded sample constituted of individuals with various age-ranges. The study will provide a better characterization of molecular and physiological mechanisms involved in longevity, hoping to contribute to the development of more advanced clinical tools, capable to offer a better quality of life for the elderly.
A washout period of at least 10 days will occur between MK-1708 dosing in Period 1 and the first itraconazole dosing in Period 2. In Period 2, participants will receive itraconazole twice daily on Day 1 and once daily on Days 2 through Day 19. Participants will also receive a single oral dose of MK-1708 on Day 4.
Protein glutathionylation is a reversible post-translational modification that involves the attachment of glutathione to cysteine residues. It plays a role in the regulation of several cellular processes and protection against oxidative damage. Glutathionylation (GS-ylation) modulates protein function, inhibits or enhances enzymatic activity, maintains redox homeostasis, and shields several proteins from irreversible oxidative stress. Aberrant GS-ylation patterns are thus implicated in various diseases, particularly those associated with oxidative stress and inflammation, such as cardiovascular diseases, neurodegenerative disorders, cancer, and many others. Research in the recent years has highlighted the potential to manipulate protein GS-ylation for therapeutic purposes with strategies that imply both its enhancement and inhibition according to different cases. Moreover, it has become increasingly evident that monitoring the GS-ylation status of selected proteins offers diagnostic potential in different diseases. In this review, we try to summarize recent research in the field with a focus on our current understanding of the molecular mechanisms related to aberrant protein GS-ylation.
PURPOSE:A beverage that is prepared by using at least fruit of Chinese water melon and improved in teste and flavor like a tea, thus increasing health by drinking it everyday. CONSTITUTION:The plant of TOOGAN (Chineses water melon), all parts above the ground other than fruits and seeds are dried, cut into pieces and the pieces are steamed at 98-100 deg.C. Then, they are rolled variously in suitable temperature as tea leaves and prepared, to give TOOGAN tea leaves. They may be combined with other herbal tea such as AMACHAZURU. The resultant tea leaves of TOOGAN are mixed with dried and crushed of the fruit of the plant or its extract to give the objective health tea. EFFECT:Saponins in the fruits are extracted in tea water to show effects of activation of cells and increase of blood circulation, when it is drunk as a tea.f.
Cardiac fibrosis is a prevalent pathological process observed in the progression of numerous cardiovascular diseases and is associated with an increased risk of sudden cardiac death. Although the BRD4 inhibitor JQ1 has powerful antifibrosis properties, its clinical application is extremely limited due to its side effects. There remains an unmet need for effective, safe, and low-cost treatments. Here, we present a multifunctional biomimetic nanoparticle drug delivery system (PM&EM nanoparticles) assembled by platelet membranes and erythrocyte membranes for targeted JQ1 delivery in treating cardiac fibrosis. The platelet membrane endows PM&EM nanoparticles with the ability to target cardiac myofibroblasts and collagen, while the participation of the erythrocyte membrane enhances the long-term circulation ability of the formulated nanoparticles. In addition, PM&EM nanoparticles can deliver sufficient JQ1 with controllable release, achieving excellent antifibrosis effects. Based on these advantages, it is demonstrated in both pressures overloaded induced mouse cardiac fibrosis model and MI-induced mouse cardiac fibrosis that injection of the fusion membrane biomimetic nanodrug carrier system effectively reduced fibroblast activation, collagen secretion, and improved cardiac fibrosis. Moreover, it significantly mitigated the toxic and side effects of long-term JQ1 treatment on the liver, kidney, and intestinal tract. Mechanically, bioinformatics prediction and experimental validation revealed that PM&EM/JQ1 NPs reduced liver and kidney damage via alleviated oxidative stress and mitigated cardiac fibrosis via the activation of oxidative phosphorylation activation. These results highlight the potential value of integrating native platelet and erythrocyte membranes as a multifunctional biomimetic drug delivery system for treating cardiac fibrosis and preventing drug side effects.
Patients receive androgen deprivation therapy and EBRT as in Arm I. Within 4-6 weeks after completion of radiation therapy, patients receive docetaxel IV over 1 hour on day 1 of every 21 days for 6 cycless in the absence of disease progression or unexpected toxicity.
Antigenic cell fragments, pathogen-associated molecular patterns, and other immunostimulants in bacterial lysates or extracts may induce local and systemic immune responses in specific and nonspecific paradigms. Based on current knowledge, this review aimed to determine whether bacterial lysate has comparable functions in infectious diseases and cancer treatment. In infectious diseases, including respiratory and urinary tract infections, immune system activation by bacterial lysate can identify and combat pathogens. Commercially available bacterial lysates, including OM-85, Ismigen, Lantigen B, and LW 50020, were effective in children and adults in treating respiratory tract infections, chronic obstructive pulmonary disease, rhinitis, and rhinosinusitis with varying degrees of success. Moreover, OM-89, Uromune, Urovac, Urivac, and ExPEC4V showed therapeutic benefits in controlling urinary tract infections in adults, especially women. Bacterial lysate-based therapeutics are safe, well-tolerated, and have few side effects, making them a good alternative for infectious disease management. Furthermore, a nonspecific immunomodulation by bacterial lysates may stimulate innate immunity, benefiting cancer treatment. "Coley's vaccine" has been used to treat sarcomas, carcinomas, lymphomas, melanomas, and myelomas with varying outcomes. Later, several similar bacterial lysate-based therapeutics have been developed to treat cancers, including bladder cancer, non-small cell lung cancer, and myeloma; among them, BCG for in situ bladder cancer is well-known. Proinflammatory cytokines, including IL-1, IL-6, IL-12, and TNF-α, may activate bacterial antigen-specific adaptive responses that could restore tumor antigen recognition and response by tumor-specific type 1 helper cells and cytotoxic T cells; therefore, bacterial lysates are worth investigating as a vaccination adjuvants or add-on therapies for several cancers.
Investigators retrospectively reviewed HF patients discharged from acute HF hospitalizations between March 2015 and May 2021 at the heart failure center, Kaohsiung Chang Gung Memorial Hospital. Cognitive function was assessed with the Luria-Nebraska Neuropsychological Battery-Screening test (LNNB-S) Chinese version by an experienced psychologist. Participants may have cognitive impairment when their LNNB-S \>=10. A heart failure disease management program was delivered to all patients before discharge, including an HF specialist nurse education program, dietitian consultation, physiatrist consultation, and psychologist consultation and assessment. Participants were advised to receive phase II cardiac rehabilitation (CR) after the cardiopulmonary exercise test (CPET) within one month. Moderate continuous aerobic exercise training was prescribed individually according to the CPET result. Participants who received at least one exercise session of phase II CR were considered as receiving CR. Other participants were considered non-receiving CR. Kaplan-Meier curves and log-rank test were constructed to compare the composite endpoint and all-causes mortality in four groups (Group a: Candidates without cognitive impairment and receiving CR. Group b: Candidates without cognitive impairment and not-receiving CR. Group c: Candidates with cognitive impairment and receiving CR. Group d: Candidates with cognitive impairment and not-receiving CR.)
148,203. Strubell, A. April 2, 1914, [Convention date]. Vaccines and immunizing and like serums.- Relates to a process for obtaining cow's milk having the property of conferring immunity to tuberculosis. A cow is treated for a period of months prior to and after calving with relatively large and increasing doses of a vaccine containing killed human fatty tubercle bacilli or, preferably, disintegrated or opened-up preparations thereof containing the whole of the partial antigens, both soluble and insoluble. The bacilli employed are preferably cultivated in the manner described in Specification 148,202. The milk of such an animal is stated to contain free partial anti-bodies, and to confer immunity on a person consuming it. Tables are given showing the doses of vaccine employed and the results of tests of the blood serum and milk serum of the cows and of the blood serum and reactions of the calf. The Specification describes also a known process for obtaining an immunizing-milk in which the cow is treated with a vaccine containing only the water-soluble partial antigens of the disintegrated bacilli and the toxin thereof. The method of obtaining such vaccine from the bacilli and from the culture medium by cold processes and by processes involving heating are described in detail, and a table of the doses employed is given. The Specification as open to inspection under Sect. 91 of the Act refers also to a still more prolonged treatment of the animal whereby milk containing free antigens in addition to the antibodies is stated to be obtained and to be capable of conferring active immunity on the consumer. This subject-matter does not occur in the Specification as accepted.
Omeprazole can prolong the elimination of diazepam, warfarin and phenytoin, drugs that are metabolized by oxidation in the liver. There have been reports of increased INR and prothrombin time in patients receiving proton pump inhibitors, including omeprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and warfarin may need to be monitored for increases in INR and prothrombin time. Although in normal subjects no interaction with theophylline or propranolol was found, there have been clinical reports of interaction with other drugs metabolized via the cytochrome P-450 system (eg, cyclosporine, disulfiram, benzodiazepines). Patients should be monitored to determine if it is necessary to adjust the dosage of these drugs when taken concomitantly with ZEGERID.

Because of its profound and long-lasting inhibition of gastric acid secretion, it is theoretically possible that omeprazole may interfere with absorption of drugs where gastric pH is an important determinant of their bioavailability (eg, ketoconazole, ampicillin esters, and iron salts). In the clinical efficacy trials antacids were used concomitantly with the administration of omeprazole.

Concomitant administration of omeprazole and atazanavir has been reported to reduce the plasma levels of atazanavir.

Concomitant administration of omeprazole and tacrolimus may increase the serum levels of tacrolimus.

Co-administration of omeprazole and clarithromycin have resulted in increases of plasma levels of omeprazole, clarithromycin, and 14-hydroxy-clarithromycin (see also CLINICAL PHARMACOLOGY, Pharmacokinetics).