anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
During postnatal cardiac hypertrophy, cardiomyocytes undergo mitotic exit, relying on DNA replication-independent mechanisms of histone turnover to maintain chromatin organization and gene transcription. In other tissues, circadian oscillations in nucleosome occupancy influence clock-controlled gene expression, suggesting a role for the circadian clock in temporal control of histone turnover and coordinated cardiomyocyte gene expression. We sought to elucidate roles for the master circadian transcription factor, Bmal1, in histone turnover, chromatin organization, and myocyte-specific gene expression and cell growth in the neonatal period. Bmal1 knockdown in neonatal rat ventricular myocytes decreased myocyte size, total cellular protein synthesis, and transcription of the fetal hypertrophic gene Nppb after treatment with serum or the α-adrenergic agonist phenylephrine. Depletion of Bmal1 decreased the expression of clock-controlled genes Per2 and Tcap, as well as Sik1, a Bmal1 target upregulated in adult versus embryonic hearts. Bmal1 knockdown impaired Per2 and Sik1 promoter accessibility as measured by micrococcal nuclease-quantitative PCR and impaired histone turnover as measured by metabolic labeling of acid-soluble chromatin fractions. Sik1 knockdown in turn decreased myocyte size, while simultaneously inhibiting natriuretic peptide B transcription and activating Per2 transcription. Linking these changes to chromatin remodeling, depletion of the replication-independent histone variant H3.3a inhibited myocyte hypertrophy and prevented phenylephrine-induced changes in clock-controlled gene transcription. Bmal1 is required for neonatal myocyte growth, replication-independent histone turnover, and chromatin organization at the Sik1 promoter. Sik1 represents a novel clock-controlled gene that coordinates myocyte growth with hypertrophic and clock-controlled gene transcription. Replication-independent histone turnover is required for transcriptional remodeling of clock-controlled genes in cardiac myocytes in response to growth stimuli.
BACKGROUND: The ligaments implicated in the earliest stages of developing a progressive collapsing foot deformity are poorly understood. Commonly employed cadaveric flatfoot models are created from simultaneous transection of multiple ligaments, making it difficult to assess early changes in pressure distribution from ligaments critical for maintaining load distribution. A serial transection of ligaments may provide insight into changes in pressure distribution under the foot to identify a potential combination of ligaments that may be involved in early deformities.
METHODS: Specimens were loaded using a custom designed axial and tendon loading system. Plantar pressure data for the forefoot and hindfoot were recorded before and after six sequential ligament complex transections.
FINDINGS: Sectioning the plantar fascia (first) and short/long plantar ligaments (second) failed to generate appreciable differences in load distribution. Dividing the spring ligament (third) led to changes in hindfoot load distribution with a shift towards the lateral column indicative of hindfoot valgus angulation. All subsequent conditions resulted in similar patterns in hindfoot plantar load distribution. An anterior shift in the center of pressure only occurred after transection of all six ligament complexes.
INTERPRETATION: Loss of the plantar fascia and short/long plantar ligaments are not critical in maintaining plantar load distribution or contact area. However, the additional loss of the spring ligament caused notable changes in hindfoot load distribution, indicating the combination of these three ligament complexes is particularly critical for preventing peritalar subluxation. Minimal changes in load distribution occurred when performing additional transections to reach a complete flatfoot deformity.
This systematic review and meta-analysis aimed to assess and compare the therapeutic outcomes of cutting balloon angioplasty and high-pressure balloon angioplasty for arteriovenous fistula stenosis in hemodialysis patients. All studies indexed in PubMed, Embase, and Cochrane Library Web of Science were retrieved. The retrieval deadline was July 15, 2023. Risk of bias 2.0 was used to evaluate the quality of the included studies. Revman 5.4 software was used for data analysis. This review included three studies and 180 patients, with 90 patients in the cutting balloon angioplasty group and 90 patients in the high-pressure balloon angioplasty group. The results of the meta-analysis suggested that compared with high-pressure balloon angioplasty, cutting balloon angioplasty can improve primary lesion patency rates of internal arteriovenous fistulas at 6 months (relative risk, 1.45; 95% confidence interval, 1.08-1.96; P = 0.01). However, there were no significant differences between the technical success rate (relative risk, 0.99; 95% confidence interval, 0.93-1.05; P = 0.72) and clinical success rate (relative risk, 1.01; 95% confidence interval, 0.95-1.07; P = 0.73). Therefore, cutting balloon angioplasty is likely to increase primary lesion patency rates at 6 months. However, more high-quality, large-sample, multicenter, randomized controlled trials are needed for further validation due to the limited number of included studies.
INTRODUCTION AND HYPOTHESIS: The safety and feasibility of same-day discharge (SDD) has been consistently reported across the benign and gynecologic oncology literature. However, outcomes of SDD in the urogynecology population are sparse. The objectives of this study were to describe the success of SDD following vaginal hysterectomy and native-tissue colpopexy, and to compare the incidence of postoperative adverse events in patients discharged same-day versus postoperative day 1 (POD1). Further objectives were to compare pain, quality of recovery (QoR), and satisfaction between the groups.
METHODS: This was a single-center, prospective cohort study of patients with planned SDD. A standardized ERAS protocol was utilized. The QoR-40 questionnaire was administered at baseline, POD2, and the 6-week postoperative visit. Pain scores were captured similarly, and a satisfaction survey was administered at 6 weeks. The primary outcome was composite adverse events defined as any postoperative adverse event and/or health care utilization, excluding telephone calls, and urinary tract infection.
RESULTS: A total of 101 patients were enrolled in the study; the primary outcome was available for 99. SDD was achieved for 76 patients (77.0%); 23 patients stayed overnight (23.2%). The overall incidence of composite adverse events was 20.2% (95% CI, 13.5-29.2), and was not different between the groups (26.1% vs 18.4%, p = 0.42). Additionally, there were no differences in the QoR-40 or pain scores on POD2 and at 6 weeks. Patient satisfaction was high and similar between the groups.
CONCLUSIONS: Successful SDD was achieved in 77.0% of the patients. SDD following vaginal hysterectomy and native-tissue colpopexy appears to be safe, feasible, and associated with good QoR and a high degree of patient satisfaction.
Tacrolimus prolongs the survival of the host and transplanted graft in animal transplant models of liver, kidney, heart, bone marrow, small bowel and pancreas, lung and trachea, skin, cornea, and limb.

In animals, tacrolimus has been demonstrated to suppress some humoral immunity and, to a greater extent, cell-mediated reactions such as allograft rejection, delayed type hypersensitivity, collagen-induced arthritis, experimental allergic encephalomyelitis, and graft versus host disease.

Tacrolimus inhibits T-lymphocyte activation, although the exact mechanism of action is not known. Experimental evidence suggests that tacrolimus binds to an intracellular protein, FKBP-12. A complex of tacrolimus-FKBP-12, calcium, calmodulin, and calcineurin is then formed and the phosphatase activity of calcineurin inhibited. This effect may prevent the dephosphorylation and translocation of nuclear factor of activated T-cells (NF-AT), a nuclear component thought to initiate gene transcription for the formation of lymphokines (such as interleukin-2, gamma interferon). The net result is the inhibition of T-lymphocyte activation (i.e., immunosuppression).
ARAVA may cause fetal harm when administered to a pregnant woman. Teratogenicity and embryo-lethality occurred in animal reproduction studies with leflunomide at doses lower than the human exposure level [see Use in Specific Populations (8.1)].

ARAVA is contraindicated for use in pregnant women [see Contraindications (4)]. Exclude pregnancy before starting treatment with ARAVA in females of reproductive potential [see Dosage and Administration (2.2)]. Advise females of reproductive potential to use effective contraception during ARAVA treatment and during an accelerated drug elimination procedure after ARAVA treatment [see Use in Specific Populations (8.3)]. If a woman becomes pregnant while taking ARAVA, stop treatment with ARAVA, apprise the patient of the potential risk to a fetus, and perform an accelerated drug elimination procedure to achieve nondetectable plasma concentrations of teriflunomide, the active metabolite of leflunomide [see Warnings and Precautions (5.3)].

Upon discontinuing ARAVA, it is recommended that all females of reproductive potential undergo an accelerated drug elimination procedure. Women receiving ARAVA treatment who wish to become pregnant must discontinue ARAVA and undergo an accelerated drug elimination procedure, which includes verification that plasma concentrations of the active metabolite of leflunomide, teriflunomide, are less than 0.02 mg/L (0.02 mcg/mL). Based on animal data, human plasma concentrations of teriflunomide of less than 0.02 mg/L (0.02 mcg/mL) are expected to have minimal embryo-fetal risk [see Contraindications (4), Warnings and Precautions (5.3), and Use in Specific Populations (8.1)].
No intervention for 15 weeks but the same registrations, diaries and forms as the intervention group. The control group will however be omitted from muscle strength testing.
The present invention relates to novel uses for ubiquitin conjugating enzyme E2-EPF5. In particular, inhibition of E2-EPF5 activity is shown to reduce the production VEGF, as well as other proteins regulated the transcription factor HIF-1, in response to hypoxia. Based on these findings the present invention provides therapeutic methods and pharmaceutical compositions useful for the treatment of diseases related VEGF induced angiogenesis. In addition, E2-EPF5 is provided as target for the development of therapeutics. Accordingly, the invention provides screening methods for identifying candidate compounds that inhibit E2-EPF5 activity and may therefore be used to treat VEGF induced angiogenesis such as tumor related angiogenesis. Finally, the invention also provides methods for the inhibition of VEGF and other HIF-1 regulated proteins.
For subjects assigned to the maraviroc group, subjects will receive maraviroc at 300mg by mouth twice daily for 24 weeks in addition to taking their current anti-HIV medication. For subjects on ritonavir, the dose of maraviroc will be 150mg by mouth twice daily.
Risperidone contains risperidone, an atypical antipsychotic belonging to the chemical class of benzisoxazole derivatives. The chemical designation is 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one. Its molecular formula is C23H27FN4O2 and its molecular weight is 410.49. The structural formula is:

Risperidone, USP is a white to slightly beige powder. It is practically insoluble in water, freely soluble in methylene chloride, and soluble in methanol and 0.1 N HCl. 

Each risperidone orally disintegrating tablet intended for oral administration contains 0.5 mg or 1 mg or 2 mg of risperidone. In addition, each tablet also contains the following inactive ingredients: aspartame, basic butylated methacrylate copolymer, calcium stearate, crospovidone, flavor firmenich powder peppermint, mannitol and sodium lauryl sulfate.
AIMS: A multi-stakeholder consensus has proposed MASLD (metabolic dysfunction-associated steatotic liver disease). We aimed to investigate the pathological findings related to the mid-term mortality of patients with biopsy-proven MASLD in Japan.
METHODS: We enrolled 1349 patients with biopsy-proven MASLD. The observational period was 8010 person years. We evaluated independent factors associated with mortality in patients with MASLD by Cox regression analysis. We also investigated pathological profiles related to mortality in patients with MASLD using data-mining analysis.
RESULTS: The prevalence of MASH and stage 3/4 fibrosis was observed in 65.6% and 17.4%, respectively. Forty-five patients with MASLD died. Of these, liver-related events were the most common cause at 40% (n = 18), followed by extrahepatic malignancies at 26.7% (n = 12). Grade 2/3 lobular inflammation and stage 3/4 fibrosis had a 1.9-fold and 1.8-fold risk of mortality, respectively. In the decision-tree analysis, the profiles with the worst prognosis were characterised by Grade 2/3 hepatic inflammation, along with advanced ballooning (grade 1/2) and fibrosis (stage 3/4). This profile showed a mortality at 8.3%. Furthermore, the random forest analysis identified that hepatic fibrosis and inflammation were the first and second responsible factors for the mid-term prognosis of patients with MASLD.
CONCLUSIONS: In patients with biopsy-proven MASLD, the prevalence of MASH and advanced fibrosis was approximately 65% and 20%, respectively. The leading cause of mortality was liver-related events. Hepatic inflammation and fibrosis were significant factors influencing mid-term mortality. These findings highlight the importance of targeting inflammation and fibrosis in the management of patients with MASLD.
Autologous blood transfusion is a major problem in a wide range of competitive sports. Methods with increased sensitivity, specificity, and feasibility are needed to identify athletes who cheat in this manner and compromise their health and the integrity of their sports in general. Complete blood counts (CBC) offer routine high-resolution assessment of the current hematologic status of individuals, providing estimates of a number of blood characteristics, such as the total hemoglobin concentration in the blood (HGB) and the volume fraction of cells in the blood (HCT). These CBC components are homeostatically controlled by the carefully regulated dynamic processes of red blood cell (RBC) production in and release from the bone marrow, RBC maturation in the peripheral circulation over the course of the \~100-day RBC lifespan, and clearance and recycling of senescent cells. Any significant perturbation to the circulating population of RBCs, like autologous transfusion, will immediately trigger compensatory modulation of one or more of these dynamic processes. The investigators believe quantification of these underlying dynamic processes will enable us to detect autologous transfusion. These dynamic RBC processes cannot currently be measured directly, but novel mathematical modeling enables their inference from routine complete blood and reticulocyte counts. The investigators propose to test the ability of modeled RBC dynamics to identify instances of autologous blood transfusion.
Each mL of Oral Solution for oral administration contains:

Furosemide is a diuretic which is an anthranilic acid derivative. Chemically, it is 4-chloro-N-furfuryl-5-sulfamoylanthranilic acid. Furosemide is a white to slightly yellow, crystalline powder. It is practically insoluble in water; freely soluble in acetone, dimethylformamide and in solutions of alkali hydroxides; soluble in methanol; sparingly soluble in alcohol; slightly soluble in ether; very slightly soluble in chloroform. The CAS Registry Number is 54-31-9.

The structural formula is as follows:

C12H11ClN2O5S M.W. 330.75

Furosemide Oral Solution USP is also available for oral administration containing either 10 mg per mL or 40 mg per 5 mL. The oral solution contains the following inactive ingredients: D and C Yellow No. 10, FD and C Yellow No. 6, flavors, potassium carbonate 1½ hydrate, propylene glycol, purified water and sorbitol solution. The 10 mg/mL solution is orange flavored and contains prosweet liquid and saccharin sodium. The 40 mg/5 mL solution is pineapple-peach flavored and contains sweet tone.
In this observational cross-sectional study, cone beam computed tomography scans will be recruited that are with the required complement of teeth and in the age range between 20 and 60 years then, correlation between chronological age versus cone beam computed tomography age through pulp space analysis will be done by two methods which are linear measurements and volumetric measurements of pulp and tooth size. First, linear measurements will be done according to kvaal's et al approach, measurements from mandibular lateral incisors, canines and first premolars and maxillary central and lateral incisors and second premolars were most strongly correlated with age, so these teeth will be selected for the investigation. A paired t-test on these measurements showed that there were no significant differences between teeth from the left and the right side of the jaw. Consequently, teeth from either the left or the right side will be chosen, whichever will be best suited for measurement. Not knowing the age and gender of the individual, the following measurements will be carried out on the radiographs of all six types of teeth: the maximum tooth length (T), pulp length and root length (R) on the mesial surface from the enamel-cementum junction (ECJ) to the root apex, the root and pulp width both at the ECJ (level A) and at the midroot level, i.e. halfway between the ECJ and the apex of the root (level C), as well as at the midpoint between the ECJ and midroot level (level B). Second, volumetric Measurements will be done to calculate pulp/ tooth volume ratio.
PURPOSE: An antibacterial composition against helicobacter, containing Zanthoxylum schinifolium extract and bergapten or lupeol is provided to prevent and treat various gastric and duodenal diseases without irritation. CONSTITUTION: An antibacterial composition against helicobacter contains Zanthoxylum schinifolium extract as an active ingredient. The extract is prepared using alcohol of 1-4 carbon atoms or mixture solvent thereof. The helicobacteria include Helicobacter pylori, Helicobacter canis, Helicobacter cinaed, Helicobacter heilmannii, Helicobacter felis, Helicobacter mustelae, Helicobacter fenelliae, Helicobacter rappini, Helicobacter hepaticus, Helicobacter bilis, or Helicobacter pullorum. The antibacterial composition contains bergapten or lupeol as an active ingredient. The compounds are obtained from Helicobacter Zanthoxylum schinifolium. A pharmaceutical composition for preventing and treating gastric and duodenal diseases contains the extract. The pharmaceutical composition also contains bergapten or lupeol as an active ingredient.
Mitochondrial Ca2+ overload can mediate mitochondria-dependent cell death, a major contributor to several human diseases. Indeed, Duchenne muscular dystrophy (MD) is driven by dysfunctional Ca2+ influx across the sarcolemma that causes mitochondrial Ca2+ overload, organelle rupture, and muscle necrosis. The mitochondrial Ca2+ uniporter (MCU) complex is the primary characterized mechanism for acute mitochondrial Ca2+ uptake. One strategy for preventing mitochondrial Ca2+ overload is deletion of the Mcu gene, the pore forming subunit of the MCU-complex. Conversely, enhanced MCU-complex Ca2+ uptake is achieved by deleting the inhibitory Mcub gene. Here we show that myofiber-specific Mcu deletion was not protective in a mouse model of Duchenne MD. Specifically, Mcu gene deletion did not reduce muscle histopathology, did not improve muscle function, and did not prevent mitochondrial Ca2+ overload. Moreover, myofiber specific Mcub gene deletion did not augment Duchenne MD muscle pathology. Interestingly, we observed MCU-independent Ca2+ uptake in dystrophic mitochondria that was sufficient to drive mitochondrial permeability transition pore (MPTP) activation and skeletal muscle necrosis, and this same type of activity was observed in heart, liver, and brain mitochondria. These results demonstrate that mitochondria possess an uncharacterized MCU-independent Ca2+ uptake mechanism that is sufficient to drive MPTP-dependent necrosis in MD in vivo.
The purpose of this study is to measure the mucosal immunological effects and peripheral blood effects of the oral IL-12/23 inhibitor, STA-5326 mesylate, in subjects with active Crohn's disease (CD). Crohn's disease is a chronic, relapsing inflammatory condition of the small and large bowel associated with excessive Th1 cytokine production. Since IL-12 is a key cytokine driving the Th1 response, novel therapies targeting IL-12 have been successful in treating CD in animal models and in humans. Data from humans and from animal models further suggest that both IL-12 and IL-23 may have a role in this active gut inflammation. STA-5326 mesylate is an oral drug that suppresses IL-12p40 production (a subunit shared by IL-12 and IL-23) in vitro and has apparent safety and clinical activity in a recent open-label trial of treatment for CD.

This protocol will enroll and randomize 12 subjects with moderate to severe active CD (CD Activity Index \[CDAI\] 220 to 450, inclusive) for 4 weeks of daily study drug treatment (9 subjects will receive 100 mg STA-5326 mesylate and 3 will receive placebo). Subjects will be evaluated for safety that will include monitoring of adverse events and concomitant medications, clinical laboratory testing, electrocardiogram (ECG) tracings, and physical examinations including vital signs. Efficacy assessments will include the CDAI, the Simple Endoscopic Score for CD (SES-CD), results from the Inflammatory Bowel Disease Questionnaire (IBDQ), and changes from Baseline for plasma C reactive protein (CRP) (measured by high sensitivity assay). In addition, immunologic effects (lymphocyte phenotyping cytokine secretion from peripheral blood and lamina propria mononuclear cells \[LPMCs\]) will be assessed. Descriptive statistics (n, mean, median, standard deviation, minimum and maximum range) will be used to summarize data for each treatment group.
Based on previous clinical studies and our preliminary preclinical data, we want to test the hypotheses that plasma and intracellular coenzyme Q10 levels are decreased after burn injury and that coenzyme Q10 (ubiquinol) supplementation reverses or ameliorates insulin resistance, metabolic derangements, mitochondrial dysfunction, and increased circulating DAMPs in burn patients. The aforementioned previous studies and preliminary data warrant a small-scale clinical study to evaluate coenzyme Q10 status, and bioavailability and efficacy of coenzyme Q10 (ubiquinol) supplementation in burn patients. Coenzyme Q10 (ubiquinol) supplementation could represent a novel, safe and low-cost strategy to improve the clinical outcome of burn patients. We are conducting a randomized, double-blind, placebo-controlled intervention study with anticipated enrollment of 50 subjects. Adult burn patients with 5% or greater of total body surface area (TBSA) burn at the Massachusetts General Hospital (MGH) Burn Center will be approached to consider study participation. All enrolled patients will be randomized to receive coenzyme Q10 (ubiquinol) supplementation or placebo. Blood samples will be used for evaluation of coenzyme Q10 concentration, mitochondrial DNA copy number, non-mitochondrial DAMPs (e.g., cell-free total DNA), and defective neutrophil migration.