anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
INTRODUCTION: Despite numerous antidiabetic medications available for the treatment of type 2 diabetes, a substantial percentage of patients fail to achieve optimal glycemic control. Furthermore, the escalating obesity pandemic underscores the urgent need for effective relevant pharmacotherapies. Tirzepatide, a novel dual GIP and GLP-1 receptor agonist, offers a promising therapeutic option.
AREAS COVERED: This review describes the discovery and clinical development of tirzepatide. Based on data from pivotal in vivo and in vitro studies, the authors present the pharmacodynamic profile of tirzepatide. Furthermore, they summarize data from the clinical trial programs that assessed the efficacy and safety of tirzepatide for the treatment of type 2 diabetes or obesity in a broad spectrum of patients, and discuss its therapeutic potential.
EXPERT OPINION: Tirzepatide effectively reduces glucose levels and body weight in patients with type 2 diabetes and/or obesity, with a generally safe profile. Based on data from phase 3 clinical trials, several agencies have approved its use for the treatment of type 2 diabetes and obesity. Clinicians should be aware of possible adverse events, mainly mild-to-moderate gastrointestinal side effects. Overall, tirzepatide represents a promising treatment option for the treatment of type 2 diabetes.
ETHNOPHARMACOLOGICAL RELEVANCE: Tea (Camellia sinensis) has been consumed for centuries as a traditional remedy for various metabolic diseases. The pharmacological mechanisms of many conventional medicines, including tea, often need to be clarified. Chin brick tea is a unique Chinese black tea grown in Hubei, China, rich in tea elements such as tea polyphenols and tea polysaccharides.
AIM OF THE STUDY: We focus on the effects of commercial chin brick tea on non-alcoholic fatty liver disease by altering intestinal flora and its metabolite, bile acids.
MATERIALS AND METHODS: Targeted UPLC-MS/MS was employed to quantify the tea elements in commercial chin brick tea. In this study, we performed an integrated approach of animal experiments, 16 S rDNA, and ultra-performance liquid chromatography-tandem mass spectrometry to explore the potential mechanism of action of chin brick tea in preventing non-alcoholic fatty liver disease (NAFLD).
RESULTS: After 14 weeks of administration, CBT extract could signiffcantly decrease the levels of body weight, liver weight, LDL-C, TC, ALT, IL-1β and IL-18, and slight increase HDL-C levels in NAFLD mice. The results indicated that the interventional impact of CBT with high-fat diet-induced NAFLD might depend on intestinal flora and its metabolites bile acids. Moreover, sequencing of 16 S rRNA genes demonstrated that CBT could signiffcantly improve the intestinal flora disorder of NAFLD mice. Speciffcally, CBT increased the levels of Lactobacillus, Alloprevotella, and Ruminococcaceae, while reducing the levels of Bacteroides in NAFLD mice. Then, a total of 23 bile acids were identified, 17 differential bile acids were obtained by screening, and CBT increase the primary bile acids/secondary bile acids ratio in NAFLD mice. Additionally, correlation analysis revealed that Bacteroides was negatively correlated with DCA and ωMCA, Lactobacillus was positively correlated with DCA and ωMCA, Bacteroides was positively correlated with NAFLD, Lactobacillus was negatively associated with NAFLD, and DCA and ωMCA were negatively correlated with NAFLD.
CONCLUSION: CBT extract has a good interventional impact on NAFLD mice. The mechanism by which this extract exerts its action is, at least partly, related to its regulation of intestinal flora and its metabolites bile acids.
The use of oxaziridine derivatives and their precursors (prodrugs) in the preparation of medicines for the prevention and treatment of dermatoses. <??>The use of oxaziridine derivatives and their precursors (prodrugs) having at least one functional chain of formulae (I) or (II) in the preparation of medicines for the prevention and treatment of dermatoses. <??>X and Y = H, a linear hydrocarbon residue that may contain heteroatoms, or they form a ring that may contain other heteroatoms; <??>R<1> = H, aryl or alkyl, preferably a 6 or 7 membered ring having one or more C atoms substituted by alkyl or halogen.
Molecular chaperones are protective in neurodegenerative diseases by preventing protein misfolding and aggregation, such as extracellular amyloid plaques and intracellular tau neurofibrillary tangles in Alzheimer's disease (AD). In addition, AD is characterized by an increase in astrocyte reactivity. The chaperone HSPB1 has been proposed as a marker for reactive astrocytes; however, its astrocytic functions in neurodegeneration remain to be elucidated. Here, we identify that HSPB1 is secreted from astrocytes to exert non-cell-autonomous protective functions. We show that in human AD brain, HSPB1 levels increase in astrocytes that cluster around amyloid plaques, as well as in the adjacent extracellular space. Moreover, in conditions that mimic an inflammatory reactive response, astrocytes increase HSPB1 secretion. Concomitantly, astrocytes and neurons can uptake astrocyte-secreted HSPB1, which is accompanied by an attenuation of the inflammatory response in reactive astrocytes and reduced pathological tau inclusions. Our findings highlight a protective mechanism in disease conditions that encompasses the secretion of a chaperone typically regarded as intracellular.
A wet wipe, non-woven wipe or folded, packaged wipe comprises a flexible sheet 1 with a perimeter pocket 2. The pocket has an opening which faces towards the main body of the sheet whereby the pocket can serve as a finger socket to enable a user to insert at least one finger in the pocket and thereby manipulate the sheet over surfaces to be cleaned. A fold of the sheet can form the pocket. Alternatively, the pocket can be formed by a small panel or tab, of the same or different sheet material, that is stitched, adhered or otherwise fastened to the sheet. Preferably, the sheet has a brushing means (3, Fig. 2), or an abrasive or roughened surface, wherein the brushing means may comprise protrusions, bristles or brush hairs for brushing away dirt.
They will be educated and motivated by an intensive program consisting of verbal instructions, Power Point lectures, posters and live demonstrations about oral hygiene instructions and teaching the proper way to brush the teeth. These will be reinforced by the investigator at intervals of 1 week, 1 month, 3 months, 6 months and 1 year.
PURPOSE:To prepare a pharmaceutical adhesive plaster having suppressed decomposition of the drug component and improved stability, by compounding a hydrated organic solvent extract of rosemary, delta-tocopherol and ascorbyl stearate to a plaster base composed of a rubber-based adhesive substance. CONSTITUTION:The objective plaster is obtained by compounding a plaster base composed of a rubber-based adhesive substance (e.g. natural rubber) with a hydrated organic solvent extract of rosemary (e.g. ethanol extract of rosemary), delta-tocopherol and ascorbyl stearate. The application of a drug component to the skin is carried out usually by the use of a pharmaceutical adhesive plaster obtained e.g. by compounding the drug component to a plaster composed of an adhesive substance. When a pharmaceutical preparation obtained by compounding a drug, especially a compound containing phenolic OH-group or an amine compound to a plaster composed of a rubber-based adhesive substance is stored for a long period, the remedying effect is remarkably decreased by the decomposition and dissipation of the drug component. The decomposition of the drug can be suppressed by compounding the above extract, etc. to the plaster.
PREHAB exercises will be determined during the physical therapy visit (1x/week) and completed daily with varying frequency for three weeks. Subjects will undergo microsurgical resection of VS.
Viruses of the influenza group, e.g. Myxovirus influencae-A, -B or -C are concentrated and purified by dialysing an aqueous suspension of the virus against water to an extent such that the virus forms a precipitate and separating the precipitated virus fraction from the supernatant solution. The concentration of bivalent metallic cations (e.g. Ca, Mg, Ba and/or Co) in the dialysis water is preferably adjusted to a value from 0.003 to 0.012 M. During dialysis, the conductivity of the suspension is reduced to below 3 x 103Á mho/cm. and the chloride content is reduced to 1.3 mg./ ml. or less. The virus suspension may be an allantoic fluid, obtained from embryonated infected hen's eggs, which has 'been clarified by low speed centrifugation before .the dialysis, which may be carried out in a kidney machine. The separated precipitate may be washed with a solution containing 0.1 M bivalent metallic cations, e.g. Ca the separated or washed precipitate may be resuspended in a buffer containing triammonium citrate. Influenza vaccines may be obtained by inactivating the viruses, e.g. with formaldehyde, before or after dialysis or using an attenuated strain of virus and presenting the concentrated virus suspensions in a pharmaceutically acceptable vehicle.
Participants received enzalutamide 160 mg, administered as four 40-mg capsules, once per day by mouth. Study drug treatment continued until disease progression, unacceptable toxicity, or withdrawal.
Participants assigned to the SMART 2.0 with technology and personal health coaching treatment group (i.e., treatment one) will receive the following: 1) consumer-level wearable and scale with a corresponding app, 2) daily text messages related to physical activity, diet, sleep and weight loss/maintenance, 3) access to SMART 2.0 social media pages and content through an online group with 6 to 12 participants total, and 4) technology-mediated, real-time individual health coaching. Participants will receive 1 to 2 text messages on a daily basis; be asked to use their wearable on a daily basis and self-weigh using the scale at least once per week; be asked to interact with their online group via social media as frequently as possible; and speak with their health coach at a predetermined session schedule.
Compounds binding to the bromodomains of bromodomain and extra-terminal (BET) family proteins, particularly BRD4, are promising anticancer agents. Nevertheless, side effects and drug resistance pose significant obstacles in BET-based therapeutics development. Using high-throughput screening of a 200,000-compound library, we identified small molecules targeting a phosphorylated intrinsically disordered region (IDR) of BRD4 that inhibit phospho-BRD4 (pBRD4)-dependent human papillomavirus (HPV) genome replication in HPV-containing keratinocytes. Proteomic profiling identified two DNA damage response factors-53BP1 and BARD1-crucial for differentiation-associated HPV genome amplification. pBRD4-mediated recruitment of 53BP1 and BARD1 to the HPV origin of replication occurs in a spatiotemporal and BRD4 long (BRD4-L) and short (BRD4-S) isoform-specific manner. This recruitment is disrupted by phospho-IDR-targeting compounds with little perturbation of the global transcriptome and BRD4 chromatin landscape. The discovery of these protein-protein interaction inhibitors (PPIi) not only demonstrates the feasibility of developing PPIi against phospho-IDRs but also uncovers antiviral agents targeting an epigenetic regulator essential for virus-host interaction and cancer development.
The present invention is directed to detectable compositions and methods for making and using such compositions. Detectable compositions comprise detectable constructs comprising a detectable agent. Due to the actions of a specific bioactivity in vivo or in vitro, the detectable construct is altered in some manner so that the detectable agent is detected. The present invention provides diagnostic imaging agents such as for MRI and optical imaging, which are used for sensitive detection of a specific bioactivity within a tissue. The present invention comprises methods and compositions for biocleavable or biodegradable compositions for carrying and releasing active agents for therapeutic or other medical uses. The methods and compositions of the present invention further comprise micelle compositions. The active agents of the present invention may comprise drugs, vaccines, and imaging agents.
Type 2 diabetes mellitus (T2DM) is associated with obesity and, therefore, it is important to target both overweight and hyperglycaemia. Glucagon plays important roles in glucose, amino acid and fat metabolism and may also regulate appetite and energy expenditure. These physiological properties are currently being exploited therapeutically in several compounds, most often in combination with glucagon-like peptide-1 (GLP-1) agonism in the form of dual agonists. With this combination, increases in hepatic glucose production and hyperglycaemia, which would be counterproductive, are largely avoided. In multiple randomized trials, the co-agonists have been demonstrated to lead to significant weight loss and, in participants with T2DM, even improved glycated haemoglobin (HbA1c) levels. In addition, significant reductions in hepatic fat content have been observed. Here, we review and discuss the studies so far available. Twenty-six randomized trials of seven different GLP-1 receptor (GLP-1R)/glucagon receptor (GCGR) co-agonists were identified and reviewed. GLP-1R/GCGR co-agonists generally provided significant weight loss, reductions in hepatic fat content, improved lipid profiles, insulin secretion and sensitivity, and in some cases, improved HbA1c levels. A higher incidence of adverse effects was present with GLP-1R/GCGR co-agonist treatment than with GLP-1 agonist monotherapy or placebo. Possible additional risks associated with glucagon agonism are also discussed. A delicate balance between GLP-1 and glucagon agonism seems to be of particular importance. Further studies exploring the optimal ratio of GLP-1 and glucagon receptor activation and dosage and titration regimens are needed to ensure a sufficient safety profile while providing clinical benefits.
BACKGROUND: The concept of positive health (PH) supports an integrated approach for patients by taking into account six dimensions of health. This approach is especially relevant for patients with chronic disorders. Chronic gastrointestinal and hepato-pancreatico-biliary (GI-HPB) disorders are among the top-6 of the most prevalent chronically affected organ systems. The impact of chronic GI-HPB disorders on individuals may be disproportionally high because: (1) The affected organ system frequently contributes to a malnourished state; and (2) persons with chronic GI-HPB disorders are often younger than persons with chronic diseases in other organ systems.
AIM: To describe and quantify the dimensions of PH in patients with chronic GI-HPB disorders.
METHODS: Prospective, observational questionnaire study performed between 2019 and 2021 in 235 patients with a chronic GI-HPB disorder attending the Outpatient Department of the Maastricht University Medical Center. Validated questionnaires and data from patient files were used to quantify the six dimensions of PH. Internal consistency was tested with McDonald's Omega. Zero-order Pearson correlations and t-tests were used to assess associations and differences. A P value < 0.05 was considered significant.
RESULTS: The GI-HPB patients scored significantly worse in all dimensions of PH compared to control data or norm scores from the general population. Regarding quality of life, participation and daily functioning, GI-HPB patients scored in the same range as patients with chronic disorders in other organ systems, but depressive symptoms (in 35%) and malnutrition (in 45%) were more frequent in patients with chronic GI-HPB disorders. Intercorrelation scores between the six dimensions were only very weak to weak, forcing us to quantify each domain separately.
CONCLUSION: All six dimensions of PH are impaired in the GI-HPB patients. Malnutrition and depressive symptoms are more prevalent compared to patients with chronic disorders in other organ systems.
Specified dosage for Morphine was 0.1 mg/kg. so based on the patient's weight(averagely 70 kg), about 7 mg Morphine was used.
Abatacept (3 mg/kg) was administered as iv infusion over approximately 30 minutes on Days 1, 15, and 29 and every 28 days thereafter up to and including Day 141. The dose was calculated based on screening visit weight of participants.
Patients receive gemcitabine hydrochloride IV, nab-paclitaxel IV, and selinexor PO on days 1, 8, and 15. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Patients will follow intermittent fasting for 16 hours with time restricted eating during an 8 hour window. The subjects are also advised to minimize sugar intake to \<15g per serving.
The NICOTROL Inhaler provides the smoker with adequate amounts of nicotine to reduce the urge to smoke, and may provide some degree of comfort by providing a hand-to-mouth ritual similar to smoking, although the importance of such an effect in smoking cessation is, as yet, unknown.

The success or failure of smoking cessation is influenced by the quality, intensity and frequency of supportive care. Patients are more likely to quit smoking if they are seen frequently and participate in formal smoking cessation programs.

The goal of NICOTROL Inhaler therapy is complete abstinence. If a patient is unable to stop smoking by the fourth week of therapy, treatment should probably be discontinued.

Patients who fail to quit on any attempt may benefit from interventions to improve their chances for success on subsequent attempts. Patients who were unsuccessful should be counseled and should then probably be given a therapeutic holiday before the next attempt. A new quit attempt should be encouraged when conditions are more favorable.

Based on the clinical trials, a reasonable approach to assisting patients in their attempt to quit smoking is to begin initial treatment, using the recommended dosage (See DOSAGE AND ADMINISTRATION). Dosage can then be adjusted in those patients with signs or symptoms of nicotine withdrawal or excess. Patients who are successfully abstinent on NICOTROL Inhaler should be treated at the selected dosage for up to 12 weeks, after which use of the Inhaler should be gradually reduced over the next 6 to 12 weeks. Some patients may not require gradual reduction of dosage and may abruptly stop treatment successfully. The safe use of this product for longer than 6 months has not been established.

The symptoms of nicotine withdrawal overlap those of nicotine excess (See Pharmacodynamics and ADVERSE REACTIONS sections). Since patients using NICOTROL Inhaler may also smoke intermittently, it is sometimes difficult to determine if they are experiencing nicotine withdrawal or nicotine excess. Controlled clinical trials of nicotine products suggest that palpitations, nausea and sweating are more often symptoms of nicotine excess, whereas anxiety, nervousness and irritability are more often symptoms of nicotine withdrawal.
Sciatica (leg pain referred from the lower back) is a common problem that causes significant pain and disability. Many patients experience lasting symptoms that do not respond to pain relief or physiotherapy. This group of patients are commonly managed by Spinal Specialists who help determine the best treatment approach and consider if investigations are required. In the United Kingdom (UK), clinical guidelines suggest that imaging for Sciatica is only appropriate for patients who are considered likely to need surgery or when the cause is suspected to be serious such as cancer or infection. Patients who do not meet the criteria for investigations express frustration when clinical tests and opinion alone are used to diagnose and treat Sciatica. Some patients are unable to accept that investigations are not required and loose confidence in treatment. If Sciatica is to be managed effectively, the treatment offered must be acceptable to and successfully negotiated with patients.

Little research is currently available regarding patients' expectations or experiences of undergoing investigations for Sciatica. The aim of this study is to explore the experience of patients who have undergone investigations for Sciatica, to gain an understanding of how patients experience investigations as part of their overall management of Sciatica.This study specifically explores the experiences of patients whose Sciatica is likely to be caused by nerve root involvement.

This study will be exploratory, based on an Interpretative Phenomenological Approach (IPA). Up to 15 patients who have undergone investigations for Sciatica will be interviewed using a semi-structured format. Patients will be recruited from one National Health Service (NHS) Trust on the South Coast of England. Interviews will be audio-recorded, transcribed verbatim and analysed thematically, based on an IPA approach. The end product of analysis will be a detailed account of patient's experience of investigations, supported by direct quotes. The intention is that this account will help health-care providers to understand patients' experiences and to plan and provide Sciatica care that is effective, evidence based and acceptable to patients.
The invention relates to a method for treating mitochondrial genetic diseases. The inventors have worked with primary fibroblasts from patients and control individuals and collected protein lysates for western blotting. Importantly, they observed that the genetic mitochondrial disorders, show a significant increase in phosphorylation of ribosomal protein S6 (pS6) compared to control fibroblasts, indicative of hyperactivated mTOR signaling. Patients with mitochondrial disorders and controls cells were treated for 48 hours with DMSO or BYL719. All lines from patients with mitochondrial diseases show reduced membrane potential, determined by TMRE staining intensity, and abnormal morphology, fragmentation and the presence of depolarized (low TMRE staining) mitochondria. Treatment with BYL719 attenuated these phenotypes in all MELAS fibroblasts while having no overt impact on the control cells. Similar experiments using flow cytometry confirmed membrane potential (TMRE) rescue by BYL719 treatment in MELAS fibroblasts.
Hydrogel adhesion materials are widely reported for tissue engineering repair applications, however, wet tissue surface moisture can reduce the wet-adhesion properties and mechanical strength of hydrogels limiting their application. Here, anti-hydration gelatin-acrylic acid-ethylene dimethacrylate (GAE) hydrogels with hydrophobic cross-linked chains are constructed. The prepared GAE hydrogel is soaked in PBS (3 days) with a volume change of 0.6 times of the original and the adhesive strength, Young's modulus, toughness, and burst pressure are maintained by ≈70% of the original. A simple and universal method is used to introduce hydrophobic chains as cross-linking points to prepare hydrogels with anti-hydration, toughness, and high wet state adhesion. The hydrophobic cross-linked chains not only restrict the movement of molecular chains but also hinder the intrusion of water molecules. Antihydration GAE hydrogels exhibit good biocompatibility, slow drug release, and dynamic oral wet-state tissue repair properties. Therefore, the anti-hydration hydrogel has excellent toughness, wet tissue adhesion properties, and good prospects for biological applications.