anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
In general, the dose of digoxin used should be determined on clinical grounds. However, measurement of serum digoxin concentrations can be helpful to the clinician in determining the adequacy of digoxin therapy and in assigning certain probabilities to the likelihood of digoxin intoxication.

Studies have shown diminished efficacy at serum levels < 0.5 ng/mL, while levels above 2 ng/mL are associated with increased toxicity without increased benefit. The inotropic effects of digoxin tend to appear at lower concentrations than the electrophysiological effects. Based on retrospective analysis, adverse events may be higher in the upper therapeutic range.

Perform sampling of serum concentrations just before the next scheduled dose of the drug. If this is not possible, sample at least 6 hours or later after the last dose, regardless of the route of administration or the formulation used. On a once-daily dosing schedule, the concentration of digoxin will be 10% to 25% lower when sampled at 24 versus 8 hours, depending upon the patient’s renal function. On a twice-daily dosing schedule, there will be only minor differences in serum digoxin concentrations whether sampling is done at 8 or 12 hours after a dose. The serum concentration of digoxin should always be interpreted in the overall clinical context, and an isolated measurement should not be used alone as the basis for increasing or decreasing the dose of the drug.

When decision-making is to be guided by serum digoxin levels, the clinician must consider the possibility of reported concentrations that have been falsely elevated by endogenous digoxin-like immunoreactive substances If the assay being used is sensitive to these substances, it may be prudent to obtain a baseline measurement before digoxin therapy is started, and correct later values by the reported baseline level. [see ] Drug Interactions (7.4).
A method of preparing a water-soluble or water-dispersible formulation of cannabinoids is disclosed. The formulation may comprise cannabinoids, terpenes, and flavonoids extracted from a raw cannabis biomass. The formulation can be prepared by dispersing a resinous extract containing the cannabinoids in an aqueous solution to form an emulsion. The aqueous solution can contain complexing agents, which form a complex with the cannabinoids. The aqueous solution containing solubilized cannabinoids can be separated from the emulsion by a liquid-liquid separation process. The obtained aqueous solution containing the solubilized cannabinoids can be subjected to a drying process to form a powdered cannabinoid formulation. The solids may be soluble or dispersible in aqueous-based preparations, such as beverages for consumption.
This study will use deep-chain respondent driven sampling (DC-RDS) and direct recruitment (DR) to identify and recruit HIV-infected MSM who are not virally suppressed. A subset of these men will be enrolled into one of two study arms. The intervention arm will provide a Case Manager (CM) intervention package designed to enhance linkage to care, antiretroviral treatment (ART) initiation, treatment adherence and retention in care. The control arm will provide the standard of care (SOC) for linkage to care, initiation of ART, treatment adherence and retention in care. The primary outcome of the study is viral suppression 12 months after enrollment. Phylogenetic methods will be used to evaluate the relationship between viruses in study participants. Mathematical modeling will be performed using demographic, behavioral, and clinical data generated from this study and other sources to estimate the population-level impact of the CM intervention on HIV incidence and to estimate the level of identification, linkage, ART coverage and viral suppression that would be required to achieve a substantial reduction in HIV incidence among MSM in the US settings where the study is conducted.
We conducted a self-controlled case series study to investigate the association between COVID-19 vaccination and facial palsy (FP) in South Korea. We used a large immunization registry linked with the national health information database. We included 44,564,345 patients >18 years of age who received >1 dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, or Ad.26.COV2.S) and had an FP diagnosis and corticosteroid prescription within 240 days postvaccination. We compared FP incidence in a risk window (days 1-28) with a control window (the remainder of the 240-day observation period, excluding any risk windows). We found 5,211 patients experienced FP within the risk window and 10,531 experienced FP within the control window. FP risk increased within 28 days postvaccination, primarily after first and second doses and was observed for both mRNA and viral vaccines. Clinicians should carefully assess the FP risk-benefit profile associated with the COVID-19 vaccines and monitor neurologic signs after vaccination.
BACKGROUND: Chronic graft-versus-host disease (cGVHD) is an immune-related disorder that is the most common complication post-allogenic hematopoietic stem cell transplant. Corticosteroids with or without calcineurin inhibitors (CNIs) remain the mainstay of cGVHD treatment for first-line therapy. However, for many patients, cGVHD symptoms cannot be effectively managed and thus require second-line therapy. Currently, there is no approved treatment for second-line cGVHD treatment in China. In this study, belumosudil, a highly selective and potent rho-associated coiled-coil-containing protein kinase-2 inhibitor demonstrated to be effective for cGVHD in the United States and other Western countries, is investigated in patients with cGVHD in China for its overall benefit-risk balance.
METHODS: This multicenter, open-label phase II study evaluated the safety, efficacy, and pharmacokinetics of oral belumosudil 200 mg once daily in cGVHD patients who had been treated with at least one line of systemic therapy in China. The primary endpoint was overall response rate (ORR); each individual patient's response was assessed by the investigator using the 2014 National Institutes of Health consensus criteria. Secondary endpoints were duration of response (DOR), time to response (TTR), changes in Lee Symptom Scale (LSS) score, organ response rate, corticosteroid dose change, CNI dose change, failure-free survival, time-to-next-treatment, overall survival, and safety.
RESULTS: Thirty patients were enrolled in the study with a median follow-up time of 12.9 months. ORR was 73.3% (95% confidence interval: 54.1-87.7%) and all responders achieved partial response. Median DOR among responders was not reached and median TTR was 4.3 weeks (range: 3.9-48.1). Fifteen patients (50.0%) achieved clinically meaningful response in terms of reduction in LSS score by ≥ 7 points from baseline. Corticosteroid and CNI dose reductions were reported in 56.7% (17/30) and 35.0% (7/20) of patients, respectively. Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity, with 11 patients (36.7%) experiencing grade ≥ 3 TEAEs. The most common grade ≥ 3 TEAE was pneumonia (n = 5, 16.7%).
CONCLUSIONS: Belumosudil treatment demonstrated a favorable benefit-risk balance in treating cGVHD patients who previously have had standard corticosteroid therapy in China where approved second-line setting is absent.
TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04930562.
The invention discloses a technological method used enrichment type supercritical fluid to extract arteannuin. Its features are that using artemisia annua as material, soaking by water, microwave radiation, grinding, secondary microwave radiation, extracting, filter pressing, drying; the dried material extracting, separating enrichment, discoloration filtration, and crystallizing drying to be the finished product. Because of the extraction separation adopts supercritical CO2 extraction purification separation to remove dust and other impurities, the yield can be greatly improved. And the cheap alcohol is used as the solvent, so the cost can be greatly reduced. Compared with traditional technology, it can reduce the cost by 40%. If the arteannuin content of the material exceeds 0.35%, it will have industrial production value, which can realize resource utilization maximization. In addition, the CO2 exhaust gas can be used as antioxidant in material storage to reduce arteannuin loss caused by oxidation, which can make the processors realize season production normalization.
This study aims to investigate the effect of probiotic Lactobacillus reuteri administration on serum bilirubin levels in preterm infants. It is a randomized controlled trial conducted at the Neonatal Intensive Care Units of Dr. Wahidin Sudirohusodo Hospital, Hasanuddin University Hospital and Cahaya Medika Hospital in Makassar, South Sulawesi, Indonesia. The study population includes infants born at 32 to \<37 weeks gestational age with birth weights between 1000-2499 grams who are admitted to the NICU. Eligible infants are randomized into two groups - an intervention group receiving probiotic L. reuteri (5 drops daily for 7 days) and a control group not receiving probiotics. The primary outcome is serum bilirubin levels, measured at baseline and after 7 days of intervention. Secondary outcomes include incidence of hyperbilirubinemia requiring phototherapy and changes in bilirubin levels in those receiving phototherapy. Blood samples are collected to measure total and direct bilirubin levels. The study aims to enroll 40 infants (20 per group) to detect a clinically meaningful difference in bilirubin levels between groups. This trial will provide evidence on whether probiotic supplementation with L. reuteri can reduce the severity of hyperbilirubinemia in preterm infants. The results may inform clinical practice regarding the use of probiotics as an adjunctive therapy for neonatal jaundice in this vulnerable population.
PURPOSE:To obtain an external agent for the remedy of burn caused by hydrofluoric acid, containing calcium gluconate and a local anesthetic as active components, effective in alleviating pain and enabling long-term massage treatment. CONSTITUTION:The objective drug preparation is produced by compounding 0.1-5wt.% of calcium gluconate, 0.5-5wt.% of a local anesthetic and, as necessary, 1.0-30wt.% of a polyhydric alcohol (e.g. propylene glycol), 0.1-10wt.% of a nonionic surfactant (e.g. polyoxyethylene fatty acid ester), 0.1-10wt.% of a gelling agent (e.g. xanthan gum) and 1-20wt.% of a higher fatty acid (e.g. stearic acid) glycerol ester and optionally conventional additives and converting the mixture in the form of a drug preparation by conventional method. The local anesthetic is preferably cocaine chloride, lidocaine hydrochloride or ethyl aminobenzoate.
All patients randomized to receive the stepped care management procedures will meet with the trauma support specialist (TSS) prior to discharge from the hospital, who will provide coaching on use of mobile technology for mental health concerns. The TSS will complete follow-up correspondence across the 3-6 month time period to assess mental health functioning and use of information technology that addresses medical concerns. Patients who report barriers to mHealth technologies and request additional therapeutic services for mental health concerns assistance will receive evidence-based motivational interviewing and cognitive behavioral intervention procedures that can span up to 3-6 months.
PURPOSE OF REVIEW: Trigeminal postherpetic neuralgia (TG-PHN) is a neuropathic pain condition complicating herpes zoster (HZ) attributed to the trigeminal nerve. It poses significant challenges due to its persistent and debilitating nature. This review explores the clinical characteristics of TG-PHN, analyzes its pathophysiological underpinnings, and addresses existent and potential therapies.
RECENT FINDINGS: TG-PHN is one of the most common and complex PHN locations. It has distinguishing clinical and pathophysiological characteristics, starting with viral triggered injuries to the trigeminal ganglion (TG) and peripheral tissue and involving the ascending and descending brain modulation pathways. Current therapies include vaccines, oral and topical medications, and interventional approaches, like nerve blocks and neurostimulation. This review covers TG-PHN's clinical and physiological components, treatment options, and potential future targets for improved management. By exploring the complexities of this condition, we aim to contribute to developing more effective and targeted therapies for patients suffering from trigeminal PHN.
PURPOSE: The compounds of formula 1 or their pharmaceutically acceptable derivatives relate to indole derivatives and pharmaceutical reagents containing the compounds which are useful in the treatment of diseases such as relapsed stenosis, renal failure and pulmonary hypertension. CONSTITUTION: The compounds of the invention may contain 1 or more chiral center and thus exist as multiple stereoisomer type. All stereoisomer type and their mixtures are included in the scope of the invention. The compounds are useful because of having pharmacological activities in animals including human. The treatment of relapsed stenosis, renal failure and pulmonary hypertension have especial interest. The compounds of the invention can be administered singly or as a part of combination treatment.
The significance of protein S-palmitoylation in angiogenesis has been largely overlooked, leaving various aspects unexplored. Recent identification of Gpx1 as a palmitoylated protein has generated interest in exploring its potential involvement in novel pathological mechanisms related to angiogenesis. In this study, we demonstrate that Gpx1 undergoes palmitoylation at cysteine-76 and -113, with PPT1 playing a crucial role in modulating the depalmitoylation of Gpx1. Furthermore, we find that PPT1-regulated depalmitoylation negatively impacts Gpx1 protein stability. Interestingly, inhibiting Gpx1 palmitoylation, either through expression of a non-palmitoylated Gpx1 mutant or by expressing PPT1, significantly enhances neovascular angiogenesis. Conversely, in PPT1-deficient mice, angiogenesis is notably attenuated compared to wild-type mice in an Oxygen-Induced Retinopathy (OIR) model, which mimics pathological angiogenesis. Physiologically, under hypoxic conditions, Gpx1 palmitoylation levels are drastically reduced, suggesting that increasing Gpx1 palmitoylation may have beneficial effects. Indeed, enhancing Gpx1 palmitoylation by inhibiting PPT1 with DC661 effectively suppresses retinal angiogenesis in the OIR disease model. Overall, our findings highlight the pivotal role of protein palmitoylation in angiogenesis and propose a novel mechanism whereby the PPT1-Gpx1 axis modulates angiogenesis, thereby providing a potential therapeutic strategy for targeting PPT1 to combat angiogenesis.
The invention provides a composition containing epinephrine and prodrug thereof, and relates to the technical field of pharmaceutical preparations. Sublingual and nasal routes of administration are non-invasive and are preferred over injectable administration. Due to the high vascularization of the mucosa, the drug can be rapidly absorbed through the mucosa and directly enter the systemic circulation, thereby avoiding longer gastrointestinal transit times and gastrointestinal and hepatic first pass effects due to metabolism. The two administration routes can meet the requirement of quick effect of the medicine required by anaphylactic reaction. Absorption of the drug through the sublingual or nasal cavity requires penetration of the drug into mucosal tissue. The composition containing epinephrine and the prodrug thereof provided by the invention can quickly increase the epinephrine concentration to a proper effective treatment concentration through a permeation enhancement technology, and maintain the concentration for a period of time, so that adverse reactions caused by the ultra-high peak concentration are avoided, and more convenient and effective treatment selection is brought to allergic patients.
Normal saline injections were used for placebo injections. Injections were based on treatment plan determined in clinical setting by study PI and physical therapist. 25 cc syringe was used and amount of saline injected was unit based on muscles to be injected according to the treatment plan.
Monitor vital signs (blood pressure, heart rate) before infusion starts, periodically during infusion, and post-infusion in a healthcare setting [see Dosage and Administration (2.6)]. Upon completion of the infusion, clinically assess the patient status. Continued observation may be necessary if clinically indicated.

Perform electrocardiogram (ECG) monitoring during infusion in patients with a history of bradycardia, conduction disorder, or with structural heart disease, as some patients with CLN2 disease may develop conduction disorders or heart disease. In patients without cardiac abnormalities, regular 12-lead ECG evaluations should be performed every 6 months.

In clinical Trial 1 and Trial 2 to 96 weeks, hypotension was reported in 2 of 24 (8%) patients, which occurred during or up to eight hours after BRINEURA infusion. Patients did not require alteration in treatment, and reactions resolved spontaneously or after intravenous fluid administration [see Adverse Reactions (6.1)].
BACKGROUND: The complement inhibitor CSMD1 acts as a tumor suppressor in various types of solid cancers. Despite its high level of expression in the brain, its function in gliomas, malignant brain tumors originating from glial cells, has not been investigated.
METHODS: Three cohorts of glioma patients comprising 1500 patients were analyzed in our study along with their clinical data. H4, U-118 and U-87 cell lines were used to investigate the tumor suppressor function of CSMD1 in gliomas. PDGFB-induced brain tumor model was utilized for the validation of in vitro data.
RESULTS: The downregulation of CSMD1 expression correlated with reduced overall and disease-free survival, elevated tumor grade, wild-type IDH genotype, and intact 1p/19q status. Moreover, enhanced activity was noted in the neuroinflammation pathway. Importantly, ectopic expression of CSMD1 in glioma cell lines led to decreased aggressiveness in vitro. Mechanically, CSMD1 obstructed the TNF-induced NF-kB and STAT3 signaling pathways, effectively suppressing the secretion of IL-6 and IL-8. There was also reduced survival in PDGFB-induced brain tumors in mice when Csmd1 was downregulated.
CONCLUSIONS: Our study has identified CSMD1 as a tumor suppressor in gliomas and elucidated its role in TNF-induced neuroinflammation, contributing to a deeper understanding of glioma pathogenesis.
Cytotoxic treatment of patients with colorectal cancer (CRC) includes most various different drugs but 5-fluorouracil (5-FU) is the cornerstone in most regimens. Leucovorin (LV) is frequently used as a part of a standard treatment regime for advanced CRC in combination with 5-FU. In numerous randomized clinical trials the addition of LV to 5-FU has been shown to significantly improve the antitumor activity and to prolong the survival of patients receiving adjuvant chemotherapy or treatment for advanced disease as to compared to treatment with 5-FU as single drug therapy.

In most European countries 5-FU is given as an infusion during 46 hours in combination with a two hour infusion of LV. This regime is called the deGramont schedule. In the Nordic countries, 5-FU and LV are often given as bolus injections according to the regime called Nordic FLV. Leucovorin is a prodrug which has to be metabolized to methylenetetrahydrofolate (mTHF) in order to increase inhibition of the target enzyme thymidylate synthase (TS). Due to the low concentrations of the reduced folate forms intracellular there is a lack of knowledge of the pharmacodynamics of LV when used as an infusion. When the 5-FU/LV used today was introduced it was technically not possible to measure the different metabolites of the reduced folates in blood and tissue. In the literature there is only one published reference measuring the blood concentration after a two hour infusion of LV. However, it has recently been possible to separate and quantitate the different folates using sensitive Liquid Chromatography/Masspectrometry (LC/MS) methods. Furthermore it has been stated that differences in enzyme activity for genes involved in the transport and metabolism of folates may be responsible for the large inter individual differences in folate tissue concentrations.

This study is designed to gain an understanding of how a single intravenous infusion of LV affects the folate concentration in blood, tumor and adjacent mucosa tissue. By using the LC/MS method which was recently developed and it is now possible to quantitate the different metabolites of LV in small tissue samples as well as in blood. It is further now possible to measure by quantitative Polymerase Chain Reaction techniques (PCR) the most important genes involved in the folate transport and metabolism ((SHMT1), SerineHydroxyMethylTransferase1 and (ABCC3) ATP-binding cassette, sub-family C, (CFTR/MRP), member 3)).
BACKGROUND: Although health insurance (HI) has effectively mitigated healthcare financial burdens, its contribution to healthy lifestyle choices and the presence of non-communicable diseases (NCDs) is not well established. We aimed to systematically review the existing evidence on the effect of HI on healthy lifestyle choices and NCDs.
METHODS: A systematic review was conducted across PubMed, Medline, Embase, Cochrane Library and CINAHLComplet@EBSCOhost from inception until 30 September 2022, capturing studies that reported the effect of HI on healthy lifestyle and NCDs. A narrative synthesis of the studies was done. The review concluded both longitudinal and cross-sectional studies. A critical appraisal checklist for survey-based studies and the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies were used for the quality assessment.
RESULT: Twenty-four studies met the inclusion criteria. HI was associated with the propensity to engage in physical activities (6/11 studies), consume healthy diets (4/7 studies), not to smoke (5/11 studies) or take alcohol (5/10 studies). Six (of nine) studies showed that HI coverage was associated with a lowered prevalence of NCDs.
CONCLUSION: This evidence suggests that HI is beneficial. More reports showed that it propitiated a healthy lifestyle and was associated with a reduced prevalence of NCDs.