anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
INTRODUCTION: Significant health inequalities in major adverse limb events exist. Ethnically minoritized groups are more prone to have a major adverse event following peripheral vascular interventions. This systematic review and meta-analysis aimed to describe the postoperative implications of racial and ethnic status on clinical outcomes following vascular interventions for claudication and chronic limb-threatening ischemia.
METHODS: Searches were conducted across seven databases from inception to June 2021 and were updated in October 2022 to identify studies reporting claudication or chronic limb-threatening ischemia in patients who underwent open, endovascular, or hybrid procedures. Studies with documented racial and ethnic status and associated clinical outcomes were selected. Extracted data included demographic and clinical characteristics, vascular interventions, and measured outcomes associated with race or ethnicity. Meta-analyses were performed using random-effect models to report pooled odds ratios (ORs) with 95% confidence intervals (CIs).
RESULTS: Seventeen studies evaluating the impact of Black versus White patients undergoing amputation as a primary intervention were combined in a meta-analysis, revealing that Black patients had a higher incidence of amputations as a primary intervention than White patients (OR: 1.91, 95% CI: 1.61-2.27). Another meta-analysis demonstrated that Black patients had significantly higher rates of amputation after revascularization (OR: 1.56, 95% CI: 1.28-1.89). Furthermore, multiple trends were demonstrated in the secondary outcomes evaluated.
CONCLUSIONS: Our findings suggest that Black patients undergo primary major amputation at a significantly higher rate than White patients, with similar trends seen among Hispanic and First Nations patients. Black patients are also significantly more likely to be subjected to amputation following attempts at revascularization when compared to White patients.
The development of successful therapeutics for dementias requires an understanding of their shared and distinct molecular features in the human brain. We performed single-nuclear RNA-seq and ATAC-seq in Alzheimer's disease (AD), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP), analyzing 41 participants and ∼1 million cells (RNA + ATAC) from three brain regions varying in vulnerability and pathological burden. We identify 32 shared, disease-associated cell types and 14 that are disease specific. Disease-specific cell states represent glial-immune mechanisms and selective neuronal vulnerability impacting layer 5 intratelencephalic neurons in AD, layer 2/3 intratelencephalic neurons in FTD, and layer 5/6 near-projection neurons in PSP. We identify disease-associated gene regulatory networks and cells impacted by causal genetic risk, which differ by disorder. These data illustrate the heterogeneous spectrum of glial and neuronal compositional and gene expression alterations in different dementias and identify therapeutic targets by revealing shared and disease-specific cell states.
Therapeutic interventions to treat alcohol use disorders (AUD) still need to be improved. A novel alcohol-specific inhibition-training seems to be a promising new intervention. In this study, recently abstinent patients with AUD attending an inpatient treatment program will be randomly assigned to one of two alcohol-specific inhibition-training groups (varying in Go/NoGo-ratio) or to a control condition. Besides the effects on drinking behavior, inhibition and implicit attitudes, the investigators expect the training to influence neurophysiological reactivity to alcohol related stimuli. A subgroup of patients will therefore additionally undergo EEG recording so that the neurophysiological effects of the training can be assessed and related to clinical outcome. Furthermore, since training effects rely on learning processes, the influence of endogenous cortisol level (a consolidation-enhancer which peaks in the morning) on training outcome will be examined by the variation of daytime of the training. All patients' inhibitory control and implicit associations towards alcohol will be measured before and after training. The training effects will be examined on proximal outcome variables (e.g. implicit associations, inhibitory control, abstinence related self-efficacy, craving) and on distal outcome variables at 3-, 6- and 12- months follow-up (e.g. percent abstinent days (primary outcome)).
This arm will only provide the measurements at the different time points (waves 0,1, and 2) over 12 months. After the follow-up planned in the study, feedback as well as recommendations concerning parenting will be provided.
Drug: Olmesartan medoxomil tablets(Daiichi Sankyo Inc, Japan). The initial dose is 20mg once daily. If blood pressure requiring further reduction after two weeks, olmesartan medoxomil may be increased to 40mg once daily.
Safety during long-term use for more than two years at the doses required for parkinsonism has not been established.

As with any chronic therapy, periodic evaluation of hepatic, hematopoietic, cardiovascular, and renal function is recommended. Symptomatic hypotension can occur and, therefore, caution should be exercised when treating patients receiving antihypertensive drugs.

High doses of bromocriptine mesylate may be associated with confusion and mental disturbances. Since parkinsonian patients may manifest mild degrees of dementia, caution should be used when treating such patients. 

Bromocriptine mesylate administered alone or concomitantly with levodopa may cause hallucinations (visual or auditory). Hallucinations usually resolve with dosage reduction; occasionally, discontinuation of bromocriptine mesylate is required. Rarely, after high doses, hallucinations have persisted for several weeks following discontinuation of bromocriptine mesylate.

As with levodopa, caution should be exercised when administering bromocriptine mesylate to patients with a history of myocardial infarction who have a residual atrial, nodal, or ventricular arrhythmia.

Retroperitoneal fibrosis has been reported in a few patients receiving long-term therapy (2 to 10 years) with bromocriptine mesylate in doses ranging from 30 to 140 mg daily. 

Epidemiological studies have shown that patients with Parkinson’s disease have a higher risk (2- approximately 6-fold higher) of developing melanoma than the general population. Whether the increased risk observed was due to Parkinson’s disease or other factors, such as drugs used to treat Parkinson’s disease, is unclear. For the reasons stated above, patients and providers are advised to monitor for melanomas frequently and on a regular basis when using bromocriptine mesylate for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists). 

Discontinuation of bromocriptine mesylate should be undertaken gradually whenever possible, even if the patient is to remain on levodopa. A symptom complex resembling the neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction, withdrawal of, or changes in antiparkinsonian therapy.

Symptoms including apathy, anxiety, depression, fatigue, insomnia, sweating, and pain have been reported during taper or after discontinuation of dopamine agonists, including bromocriptine mesylate. These symptoms generally do not respond to levodopa. Prior to discontinuation of bromocriptine mesylate, patients should be informed about potential withdrawal symptoms, and closely monitored during and after discontinuation of bromocriptine mesylate. In case of severe withdrawal symptoms, re-administration of a dopamine agonist at the lowest effective dose may be considered.
Peri-ulcer injection of Umbilical cord MSC (1.0 million cells/cm2 of the ulcer) will be administered at multiple sites (maximum of 30 sites) with intervals of 3 cm x 3 cm around the ulcer with total volume of 0.1 to 0.2 ml per injection. Whatever IMP is drawn into the syringe for administration to the wound must be completely dispensed and nothing should be left in the syringe. Number of injections and volume of each injection can be as per Investigator's discretion. The same to be recorded in the source notes and CRF.The injection will be done approximately using a 24G needle and 1 ml/3ml syringe approximately within 0.75 cm from the edge of the ulcer. The needle should enter the base of the ulcer from the edge. After injection, patients must be in a lying down position for at least one hour in daycare center at the site and monitoring of oxygen saturation will be done up to 2 hours ± 10 minutes after the administration of the product.
Peanut allergy is a common problem with no current treatment. Recent studies have shown some success with oral or sublingual immunotherapy for the treatment of food allergy. Oral treatment, which requires very high doses, is associated with a small but appreciable risk of systemic reactions. Sublingual immunotherapy, which utilizes much smaller doses, is safer but constraints inherent in the available methods of sublingual administration have limited the utility of this method. Typically sublingual immunotherapy for food allergy has used either fresh foods or a simple liquid extract. These methods are not optimized for practicality or dwell duration in the mouth, and, thus far, dosing has been limited by the ability to make concentrated extracts and by the volume of extract that can be applied to the sublingual space. This study is being conducted to determine if a dissolving peanut extract film, will improve efficacy for immunotherapy for peanut allergy.
The postnatal period is a critical phase involving important physiological, psychological and social changes. In 2013, WHO recommends at least three postnatal contacts on day 3, between days 7 and 14, and six weeks after birth. Despite these recommendations, pediatric emergency department (PED) visits for newborns are constantly increasing. Some studies have shown that most of these visits were related to nonserious diseases, mainly due to a lack of knowledge and information. At the same time, some high-risk newborns have been identified as likely to be admitted to PED and subsequently hospitalized. All these findings highlight the great need for education and parental support by health staff from the time of maternity discharged, particularly when certain high-risk conditions are identified.

In France, guidelines on maternity discharge after childbirth include pediatric nurses as professionals involved in postnatal follow-up. Pediatric nurses could be a crucial actor in the follow-up of at-risk newborn, in collaboration with other health professionals and contribute to a reduction in PED visits and/or hospitalization in first weeks of life.
The present invention relates to bifunctional fusion molecules comprising a mutated polypeptide ligand (e.g., mutated IFN-a) having reduced biological activity attached to a disease tissue targeting biologic or a tumor associated antigen (TAA)-targeting biologic (e.g., anti-PD-L1 antibody), wherein the targeting biologic or TAA-targeting biologic directs the mutated ligands to cells that express on their surfaces the antigens to which said targeting biologic binds, as well as receptors for said ligands. Importantly, because the mutated polypeptide ligands have reduced biological activity, the resultant fusion molecule have reduced off-target activity/toxicity. More importantly, the targeting of the mutated ligand by the targeting biologic restores the activity of the mutated ligand, with the degree of activity restoration apparently correlated with the level of targeting biologic on the cells. As such, the fusion molecules of the present invention advance the state of art by providing bifunctional fusion molecules having a greater therapeutic window than those previously described. The invention further relates to methods of treating cancer in a patient and in particular, patients with refractory and/or recurrent cancers involving the use of these bifunctional fusion molecules. The invention also relates to methods of treating infectious disease, including but not limited to chronic hepatitis B and C infections in a patient involving the use of these bifunctional fusion molecules.
BACKGROUND: Breast tumorigenesis is a complex and multistep process accompanied by both genetic and epigenetic dysregulation. In contrast to the extensive studies on DNA epigenetic modifications 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) in malignant breast tumors, their roles in the early phases of breast tumorigenesis remain ambiguous.
RESULTS: DNA 5hmC and 5mC exhibited a consistent and significant decrease from usual ductal hyperplasia to atypical ductal hyperplasia and subsequently to ductal carcinoma in situ (DCIS). However, 5hmC showed a modest increase in invasive ductal breast cancer compared to DCIS. Genomic analyses showed that the changes in 5hmC and 5mC levels occurred around the transcription start sites (TSSs), and the modification levels were strongly correlated with gene expression levels. Meanwhile, it was found that differentially hydroxymethylated regions (DhMRs) and differentially methylated regions (DMRs) were overlapped in the early phases and accompanied by the enrichment of active histone marks. In addition, TET2-related DNA demethylation was found to be involved in breast tumorigenesis, and four transcription factor binding sites (TFs: ESR1, FOXA1, GATA3, FOS) were enriched in TET2-related DhMRs/DMRs. Intriguingly, we also identified a certain number of common DhMRs between tumor samples and cell-free DNA (cfDNA).
CONCLUSIONS: Our study reveals that dynamic changes in DNA 5hmC and 5mC play a vital role in propelling breast tumorigenesis. Both TFs and active histone marks are involved in TET2-related DNA demethylation. Concurrent changes in 5hmC signals in primary breast tumors and cfDNA may play a promising role in breast cancer screening.
INTRODUCTION: Rare diseases (RDs) collectively impact over 30 million people in Europe. Most individual conditions have a low prevalence which has resulted in a lack of research and expertise in this field, especially regarding genetic newborn screening (gNBS). There is increasing recognition of the importance of incorporating patients' needs and general public perspectives into the shared decision-making process regarding gNBS. This study is part of the Innovative Medicine Initiative project Screen4Care which aims at shortening the diagnostic journey for RDs by accelerating diagnosis for patients living with RDs through gNBS and the use of digital technologies, such as artificial intelligence and machine learning. Our objective will be to assess expecting parent's perspectives, attitudes and preferences regarding gNBS for RDs in Italy and Germany.
METHODS AND ANALYSIS: A mixed method approach will assess perspectives, attitudes and preferences of (1) expecting parents seeking genetic consultation and (2) 'healthy' expecting parents from the general population in two countries (Germany and Italy). Focus groups and interviews using the nominal group technique and ranking exercises will be performed (qualitative phase). The results will inform the treatment of attributes to be assessed via a survey and a discrete choice experiment (DCE). The total recruitment sample will be 2084 participants (approximatively 1000 participants in each country for the online survey). A combination of thematic qualitative and logit-based quantitative approaches will be used to analyse the results of the study.
ETHICS AND DISSEMINATION: This study has been approved by the Erlangen University Ethics Committee (22-246_1-B), the Freiburg University Ethics Committee (23-1005 S1-AV) and clinical centres in Italy (University of FerraraCE: 357/2023/Oss/AOUFe and Hospedale Bambino Gesu: No.2997 of 2 November 2023, Prot. No. _902) and approved for data storage and handling at the Uppsala University (2022-05806-01). The dissemination of the results will be ensured via scientific journal publication (open access).
The invention provides N-substituted phenyl-4-one derivatives and salts thereof. The N-substituted phenyl-4-one derivatives are synthesized through condensation of o-hydroxypyrone derivatives and aminophenol, alkylation, amine condensation and hydrogenation deprotection. A series of the N-substituted phenyl-4-one derivatives are designed and synthesized in the invention, and pharmacological activity screening tests show that like compounds have a substantial histamine H3 acceptor antagonist activity and an anti-Abeta-aggregation activity. The invention also provides an application of the N-substituted phenyl-4-one derivatives, salts thereof, and intermediates generated in the preparation process in the preparation of Alzheimer-related treatment medicines, especially a use of the derivatives, the salts thereof and the intermediates in the preparation of medicines for treating histamine H3 acceptor and Abeta-aggregation related diseases as a histamine H3 acceptor antagonist and a amyloid peptide (Abeta) aggregation inhibitor. A synthesis method of the compounds has the advantages of easily-available required raw materials, reasonable route design, mild reaction conditions, high yield of each step, simple operation and low production cost. A structural general formula of the derivatives is shown in the specification.
Obesity is becoming a major global public health issue. Calorie restriction (CR) is the most important treatment for weighting loss. In recent years, two novel types of intermittent fasting recently have gained more attention: the 5:2 diet and time-restricted eating (TRE). TRE requires individuals to eat in a specified number of hours per day (typically 4 to 10 hours) without energy intake restriction. The 5:2 diet involves 5 feast days and 2 fast days per week; participants eat ad libitum without restriction on feast days while 25% of energy needs (approximately 500-800 kcal per day) are consumed on fast days. However, the effects of dietary strategy of intermittent fasting plus time-restricted eating (modified time-restricted eating: TRE 5 days and fasting 2days per week) on weight loss and cardiometabolic risk factors in obese adults have not been proved. This randomized controlled trial aimed to evaluate the effect of modified time-restricted eating (mTRE) and CR on weight loss and cardiometabolic risk factors in obese adults compared to usual health care over 12 months.
New medicaments for dissolving or partially dissolving gallstones contain plant extracts of ivy as therapeutically active ingredients, together with usual adjufants and carrier materials. yThe extract is produced by extn. of ivy with an organic solvent, with or without the addn. of water. In an example coarsely powdered ivy leaves (Hera hederae) are extd. with 60% ethanol and the oily part of the extract is sepd. off. 0.7 g. of oily extract are dissolved in 100 g. olive oil to give a pharmaceutical formulation.
The invention belongs to the technical field of pharmaceutical preparation and discloses a cyclosporine soft capsule for immunosuppression and a preparation method of the cyclosporine soft capsule. The preparation comprises a capsule shell and capsule content. The capsule content comprises cyclosporine, poloxamer, polyethylene glycol and single linoleic acid glyceride. Compared with the prior art, organic solvents such as ethanol and propylene glycol do not need to be added, and drug stability is enhanced. Polyoxyethylene castor oil does not need to be added as surfactants, and toxicity of an existing preparation is reduced. The preparation method is simple, and industrial mass production can be achieved easily.
Laser irradiation will be applied in two doses for patients in this group, but only on one side of the jaw. The second dose will be given after 24 hour of the first one. The other side of the jaw will receive a placebo procedure (i.e. a red light beam will be emitted on the gingival tissues as if they are irradiated by a laser beam).
A pre- and post- study design will be utilized to assess the impact of implementing the Pathway Platform in the primary care setting. The Pathway Platform consists of a mobile app for patients and a care team interface that can be accessed through Epic (electronic medical record system). Up to 20 primary care sites will be identified to participate in the study. Care team members involved in depression management will receive education on evidence-based clinical practices for depression care, such as measurement-based care practices and shared- decision making. Clinics with behavioral resources will also receive additional education on behavioral health integration. Training on how to onboard patients to use the Pathway Platform and utilize electronic medical records to view data collected in the Pathway Platform will also be provided. Study outcomes identified in this protocol will be assessed among 200 patients who will be enrolled in the Pathway Platform (post-implementation cohort). Outcomes will also be assessed in another 200 patients from the same participating clinics prior to study implantation (pre-implantation cohort). Implementation success will be evaluated by comparing study outcomes among the two cohorts with a total sample size of 400 patients (of which 200 will receive the intervention and 200 will not). The primary outcome is PHQ-9 utilization over six months and will be compared between the pre- and post- implementation cohorts. Additional process measures will be compared, including shared-decision making, medication adjustments, referrals to behavioral health, primary care follow-up post hospitalizations, and remission and response. Data collected in the Pathway Platform will also be evaluated to explore pre-defined patient outcomes.
All students to be included in the study will be pre-tested through Google Form's. After the pre-test, the students in the experimental group will be sent images created by the researchers via text message for 4 weeks (22 days) and consisting of the information given in the Basic Principles and Practices in Midwifery Course. Each visual will contain one piece of information. The researchers will send 6 visuals to the students in the experimental group via text message every day for 4 weeks, except Saturdays and Sundays. The post-test will be applied immediately after the end of the implementation process. The messages will be short and contain a single piece of information.
The objective of this study is to evaluate the 24-month clinical performance of three different bulk-fill restorative resin materials in Class II restorations. Forty patients with at least three approximal lesions in premolar and molar teeth will be participated in the study. A total of 120 Class II cavities will be restored using Tetric EvoCeram Bulk Fill (n=40), SureFil SDR flow + Ceram X mono (n=40), and everX Posterior + G-aenial Posterior (n=40) with their respective adhesives according to the manufacturers' instructions. All restorations will be placed by one operator. The restorations will be evaluated at baseline and at 6, 12, 18, and 24 months using modified USPHS criteria by one examiner. The restoration groups for each category will be compared using Pearson's chi-square test, while Cochran's Q test will be used to compare the changes across different time points within each restorative material (p\<0.05).
Interventional group: All patients included in this group will receive a continuous heated and humidified high-flow (30 to 60 l/min) oxygenation with a nasal cannula for 48 hours. Initially, flow rate will be started at 50 l/min with a FiO2 at 50%. According to the protocol, flow rate and FiO2 will be titrated on SpO2 and respiratory tolerance. Weaning and failure of high-flow oxygenation are described in detail in the study protocol.