anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are rare autoimmune diseases characterized by inflammation of blood vessels. This study aimed to assess the cost-utility of avacopan in combination with rituximab (RTX) or cyclophosphamide (CYC) compared with glucocorticoids (GC) for the treatment of severe, active AAV in Spain.
METHODS: A 9-state Markov model was designed to reflect the induction of remission and sustained remission of AAV over a lifetime horizon. Clinical data and utility values were mainly obtained from the ADVOCATE trial, and costs (€ 2022) were sourced from national databases. Quality-adjusted life years (QALYs), and incremental cost-utility ratio (ICUR) were evaluated. An annual discount rate of 3% was applied. Sensitivity analyses were performed to examine the robustness of the results.
RESULTS: Avacopan yielded an increase in effectiveness (6.52 vs. 6.17 QALYs) and costs (€16,009) compared to GC, resulting in an ICUR of €45,638 per additional QALY gained. Avacopan was associated with a lower incidence of end-stage renal disease (ESRD), relapse and hospitalization-related adverse events. Sensitivity analyses suggested that the model outputs were robust and that the progression to ESRD was a driver of ICUR.
CONCLUSIONS: Avacopan is a cost-effective option for patients with severe, active AAV compared to GC in Spain.
The prevalence of cardiovascular diseases (CVDs) is increasing in the last decades, even is the main cause of death in first world countries being atherosclerosis one of the principal triggers. Therefore, there is an urgent need to decipher the underlying mechanisms involved in atherosclerosis progression. In this respect, microRNAs dysregulation is frequently involved in the progression of multiple diseases including CVDs. Our aim was to demonstrate that let-7d-5p unbalance could contribute to the pathophysiology of atherosclerosis and serve as a potential diagnostic biomarker. We evaluated let-7d-5p levels in vascular biopsies and exosome-enriched extracellular vesicles (EVs) from patients with carotid atherosclerosis and healthy donors. Moreover, we overexpressed let-7d-5p in vitro in vascular smooth muscle cells (VSMCs) to decipher the targets and the underlying mechanisms regulated by let-7d-5p in atherosclerosis. Our results demonstrate that let-7d-5p was significantly upregulated in carotid plaques from overweight patients with carotid atherosclerosis. Moreover, in EVs isolated from plasma, we found that let-7d-5p levels were increased in carotid atherosclerosis patients compared to control subjects specially in overweight patients. Receiver Operating Characteristic (ROC) analyses confirmed its utility as a diagnostic biomarker for atherosclerosis. In VSMCs, we demonstrated that increased let-7d-5p levels impairs cell proliferation and could serve as a protective mechanism against inflammation by impairing NF-κB pathway without affecting insulin resistance. In summary, our results highlight the role of let-7d-5p as a potential therapeutic target for atherosclerosis since its overexpression induce a decrease in inflammation and VSMCs proliferation, and also, as a novel non-invasive diagnostic biomarker for atherosclerosis in overweight patients.
PURPOSE:To provide a skin-beautifying agent and skin cosmetic containing a specific pyrimidopyrrole derivative as an essential component, exhibiting excellent preventing and ameliorating effect on pigmentation, having beautifying effect on the skin after ultraviolet irradiation and effective for preventing and treating spots and freckles caused by sunburn, etc. CONSTITUTION:A skin-beautifying agent composed of a pyrimidopyrrole derivative of formula (X is two H or NH) and a skin cosmetic containing the pyrimidopyrrole derivative of formula. The pyrimidopyrrole derivative of formula is produced by actinomycetes and has action to inhibit the phospholipid metabolism of cell. The compound of formula is preferably compounded to a skin cosmetic in an amount of 0.0001-5%. The skin cosmetic may be properly incorporated, in addition to the pyrimidopyrrole derivative of formula used as an essential component, with lubricant, humectant, thickener, antiseptic, emulsifier, pigment, powder, pH-modifier, drug active component, ultraviolet absorbent, antioxidant, flavor, etc. The skin cosmetic can be used in the form of cream, milky lotion, face lotion, foundation, pack, lotion, gel, solution, stick, etc.
Systems and methods for performing a simulation for an anatomical object of interest are provided. A physiological model of an anatomical object of interest of a patient is generated. Electroanatomical mapping data of the anatomical object of interest is received. The physiological model is updated based on the electroanatomical mapping data of the anatomical object of interest. A simulation for the anatomical object of interest is performed using the updated physiological model. Results of the simulation are output.
Cancer cells undergo phenotypic switching (cancer cell plasticity) in response to microenvironmental cues, including exposure to therapy/treatment. Phenotypic plasticity enables the cancer cells to acquire more mesenchymal traits promoting cancer cells' growth, survival, therapy resistance, and disease recurrence. A significant program in cancer cell plasticity is epithelial-to-mesenchymal transition (EMT), wherein a comprehensive reprogramming of gene expression occurs to facilitate the translational shift from epithelial-to-mesenchymal phenotypes resulting in increased invasiveness and metastasis. In addition, EMT plays a pivotal role in facilitating cancer cells' escape from the body's immune system using several mechanisms, such as the downregulation of major histocompatibility complex-mediated antigen presentation, upregulation of immune checkpoint molecules, and recruitment of immune-suppressive cells. Cancer cells' ability to undergo phenotypic switching and EMT-driven immune escape presents a formidable obstacle in cancer management, highlighting the need to unravel the intricate mechanisms underlying these processes and develop novel therapeutic strategies. This article discusses the role of EMT in promoting immune evasion and therapy resistance. We also discuss the ongoing research on developing therapeutic approaches targeting intrinsic and induced cell plasticity within the immune suppressive microenvironment. We believe this review article will update the current research status and equip researchers, clinicians, and other healthcare professionals with valuable insights enhancing their existing knowledge and shedding light on promising directions for future cancer research. This will facilitate the development of innovative strategies for managing therapy-resistant cancers and improving patient outcomes.
The hair lacquer contains a terpolymer of 5-30 wt. % of partially quaternised dialkylamino alkyl methacrylate (I) 20-80 wt. % N-vinyl heterocyclic monomer (II) and 10-50 wt. % of a 2-8C maleic acid ester (III). (I), (II) and (III) are copolymsd. in soln. at 60-100 degrees C in alcohol, pref. methanol, with 1% azobisisobutyro nitrile initiator followed by further addn. of initiator after polymsn. and reaction to eliminate residual monomers. The amine gps. are then quaternised with dialkyl sulphate and the solvent is replaced by water before the soln. is spray dried to a powder and washed with hexane. The lacquer is non-toxic does not attack skin or hair, does not smell, has good transparent film forming props. sets hair firmly but is tack-free, insensitive to water and humidity and compatible with aerosol propellants.
A self-ligating orthodontic bracket having an engagement base adapted for attachment to a crown of a tooth is disclosed. A body member is attached to the front surface of the base and extends forward to a front end face. The base defines a torque angle relative to a front end face of the body member. A gingival projection and an occlusal projection extend forwardly from the body member. Each protrusion has an archwire slot surface that defines an archwire slot along with a portion of the front face of the body member. The first and second channels defined in each projection are coplanar and disposed at an angle substantially equal to the torque angle with respect to the front end face of the body member. The gate is disposed in one of the first channel and the second channel. The door is movable between an open position and a closed position to selectively provide or prevent access to the archwire slot.
Part B will consist of 3 adaptive cohorts. Based on PK, pharmacodynamics, and safety results from the Part A study, participants will be administered a flat dose of dalutrafusp alfa on Day 1 of each cycle QW, Q2W and/or every 3 weeks (Q3W) until the participant meets study treatment discontinuation criteria or for up to 1 year.
BACKGROUND: Videofluoroscopy (VFS) is the gold standard in evaluating dysphagia. Water swallow tests (WST) and the Eating Assessment Tool (EAT-10) are commonly used in dysphagia screening. We aimed to determine the feasibility of WST and EAT-10 as screening tools for referral to VFS.
METHODS: Patients (n = 150, median age: 70.0 years, range: 19-92 years, 58.7% female) referred to VFS completed the WST and EAT-10 before the examination. In the WST, we evaluated both the qualitative parameters (coughing, possible change in voice) and quantitative parameters (average drinking bolus size, swallowing speed). Correlations of EAT-10 total scores and WST parameters to the VFS findings were analyzed both individually and combined.
RESULTS: In the WST, the most specific (89.7%) predictor of normal VFS findings was the absence of coughing, and the most sensitive (79.1%) parameter to predict abnormal findings was a bolus size of ≤20 mL. Using a combination of coughing and a bolus size ≤20 mL (simplified WST), the sensitivity of predicting abnormal findings increased to 83.5%. The most sensitive (84.6%) predictor of penetration/aspiration was failing any parameter in the WST. Lack of coughing indicated an absence of penetration/aspiration with an 82.5% specificity. Swallowing speed or combining the EAT-10 results with the WST results did not enhance the sensitivity or specificity of the WST for predicting the VFS results.
CONCLUSIONS: Coughing and average drinking bolus size are the most important parameters in WST when screening for referral to VFS, whereas the swallowing speed does not seem to be useful. The WST is superior to EAT-10 in predicting VFS findings.
LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1349-1355, 2024.
Participants will receive multiple doses of GDC-0134 for 28 days. To study the interactions between GDC-0134 and other drugs, some participants may receive single doses of midazolam and caffeine at various time points.
PURPOSE: Evaluate overall survival (OS), RAS, BRAF, and MSI frequencies in patients with metastatic colorectal cancer (mCRC), refractory to chemotherapy, and finally treated with cetuximab.
METHODS: A retrospective cohort study to evaluate 211 mCRC patients with wild-type KRAS treated with cetuximab. BRAF V600E, KRAS, NRAS gene mutations, and MSI status were identified using PCR techniques in a population of pre-treated patients who were refractory to fluoropyrimidines, oxaliplatin, and irinotecan. In addition, we evaluated the mutation frequency of the BRAF and NRAS genes and the MSI status of this population. Uni- and multivariate analyses were performed for independent prognostic factors of OS.
RESULTS: The median OS was 10.4 months, 6.6 months for patients with right and 11.5 months for left colon cancers (p = 0.02). The frequencies of mutations were BRAF at 3.9% (median OS of 4.9 months), NRAS at 3.38% (median OS of 6.9 months), and MSI-High status at 3.3% (median OS of 4.6 months). The OS, NRAS, and MSI frequencies were similar to those found in other studies that evaluated cetuximab in poly-treated patients and were associated with lower survival rates in univariate analyses. The frequency of BRAF mutations was lower than that found in previous studies. The only variable that remained significant for OS in the multivariate model was tumour laterality, with patients with right colon cancer presenting a worse prognosis (HR = 2.81).
CONCLUSION: Although BRAF, NRAS mutations, and MSI-High status were associated with shorter OS in univariate analyses, only tumour laterality remained an independent prognostic factor in the multivariate analysis.
TROKENDI XR can cause fetal harm when administered to a pregnant woman. Data from pregnancy registries indicate that infants exposed to topiramate in uterohave an increased risk of major congenital malformations, including but not limited to cleft lip and/or cleft palate (oral clefts), and of being small for gestational age (SGA). When multiple species of pregnant animals received topiramate at clinically relevant doses, structural malformations, including craniofacial defects, and reduced fetal weights occurred in offspring [see Use in Specific Populations (8.1)] . 

Consider the benefits and risks of TROKENDI XR ®when administering the drug in women of childbearing potential, particularly when TROKENDI XR ®is considered for a condition not usually associated with permanent injury or death [see Use in Specific Populations (8.1)] . TROKENDI XR ®should be used during pregnancy only if the potential benefit outweighs the potential risk. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential hazard to a fetus [see Use in Specific Populations (8.1)] .
FIELD: medicine, stomatology. SUBSTANCE: composition is used at the presence of dental prosthesis and orthodontic apparatus and has sodium fluoride, calcium gluconate solution, antiseptic - preserving agent, ethyl alcohol, menthol, perfume, water, natural coniferous complex, polyvinylpyrrolidone and xylitol-sorbitol syrup. Components are taken at the definite quantitative ratio. Composition eliminates inflammatory symptoms, improves resistance of teeth and parodontium tissues. EFFECT: enhanced effectiveness of composition. 1 cl, 3 tbl, 3 ex
The purpose the research is to help determine optimal means of post-operative analgesia following hip arthroscopic procedures. Post-operative pain is a significant contributor to patient satisfaction and the side effects of narcotic pain medication are well described. The ideal intervention for achieving appropriate analgesia following hip arthroscopy has not yet been defined. Determining means of achieving acceptable post-operative pain relief while minimizing narcotic usage will help yield maximal patient outcomes.The primary research procedures entailed in this study include fascia iliaca nerve blockade with Marcaine and local field infiltration with liposomal bupivicane (Exparel). The patients in this study will include those who have both a clinical and radiographic diagnosis of femoracetabular impingement (FAI), have failed non operative treatment, and are indicated for hip arthroscopy with labral repair and femoroplasty/acetabuloplasty. The study includes the surgical procedure and the first post-operative follow up visit. The total study duration is approximately 1.5 weeks for each patient. The study will be carried out until the patients first post-operative visit which typically occurs 7-10 days after the procedure. We are to include approximately 40 patients in total for this study over a period of 4 months.
BACKGROUND: Disseminated intravascular coagulation (DIC) occurs in 30-50% of septic patients and contributes to high mortality in the intensive care unit (ICU). However, there are few proven interventions for coagulation disorder management in sepsis. Experimental and clinical data have demonstrated that sepsis could benefit from unfractionated heparin (UFH) treatment. To date, there are no large multicenter trials to determine the safety and efficacy of UFH in septic patients with suspected DIC.
METHODS: A multicenter, double-blinded, placebo-controlled randomized trial is designed to recruit 600 patients who met sepsis 3.0 criteria and suspected DIC. Participants will be randomized (1:1) to receive UFH or saline via continuous intravenous administration for 7 days within 6 h of enrolment. The primary outcome is ICU mortality. The secondary outcome includes 28-day all-cause mortality, the improvement of Sequential Organ Failure Assessment scores, and the incidence of major hemorrhage. Investigators, participants, and statisticians will be blinded to the allocation.
DISCUSSION: The HepSIC trial is to evaluate the efficacy and safety of UFH on sepsis-related DIC across different areas of China. The small dosage of UFH administration would offer a new potential approach for treating sepsis-related coagulation disorders.
ETHICS AND DISSEMINATION: Ethical approval was granted by all the ethics committees of 20 participant centers. Results will be disseminated via peer-reviewed publications and presented at conferences.
TRIAL REGISTRATION: ClinicalTrials.gov NCT02654561. Registered on 13 January 2016.
Subjects will be administered the initial dose of bosutinib, with dosage progressively increased over the course of the study. The initial dose of bosutinib is 100 mg tablet, once per day. The dose will be increased as tolerated up to 300 mg per day. The dose will be increased by 100 mg each month if the lower dose is tolerated without significant side effects. That is to say, the subject will take 100 mg/day every day for the first month, 200 mg/day every day for the second month, and 300 mg/day every day for the third month and for the remainder of the study, provided that adverse reactions do not prohibit continuation at this dosage. Stopping and dose reduction rules for reported adverse reactions have been taken from the package insert of bosutinib. The duration of treatment is 1 year.
The experimental group was informed about progressive muscle relaxation (PMR) before colonoscopy. PMR audio recordings were given to the patients. Abdominal pain and distention scores were determined after colonoscopy. PMR was applied to the patients for 30 minutes. These scores were determined again after exercise and at the 2nd, 4th, 8th, 12th, 16th, and 24th hours.
Eighty six million U.S. adults have prediabetes, and up to 75% of them will eventually develop diabetes. Landmark clinical trials have established that intensive lifestyle interventions (ILI) and metformin are safe and effective treatments to prevent or delay diabetes in adults with prediabetes and overweight/obesity. Despite being included in expert clinical guidelines, these treatments are rarely used and few studies have explored how to promote their uptake in practice. One possible approach for increasing adoption of ILI and metformin in primary care includes clinical decision support (CDS), which uses electronic systems to create tailored recommendations for evidence-based clinical care. While a large body of evidence demonstrates that CDS can improve the delivery of other recommended preventive services, this approach has not been definitively studied for ILI and metformin. The investigators plan to address this critical knowledge gap by developing and evaluating the Prevent Diabetes Mellitus Clinical Decision Support (PreDM CDS) intervention for community health center patients with prediabetes and overweight/obesity. This novel CDS engages primary care providers and clinical staff to deliver intervention components.

This study tests the potential for CDS to promote diabetes prevention and weight loss efforts in primary care. The current study objectives were to: 1) interview providers about their preferences for CDS focused on prediabetes; 2) develop a novel CDS tool, the Prediabetes CDS (PreDM CDS), promoting evidence-based care for prediabetes; and 3) conduct a pilot evaluation of the novel CDS tool using electronic health record data. Study investigators hypothesize that the proposed PreDM CDS will increase patient's adoption of ILI and metformin, producing modest weight loss and improvements in other cardiometabolic markers.
Lung cancer (LC) is the leading cause of cancer-associated deaths worldwide, among which non-small-cell lung cancer (NSCLC) accounts for 80%. Stromal cell-derived factor-1 (SDF-1) inhibition results in a significant depletion of NSCLC metastasis. Additionally, SDF-1 is the only natural chemokine known to bind and activate the receptor CXCR4. Thus, we attempted to clarify the molecular mechanism of SDF-1 underlying NSCLC progression. Transwell migration, adhesion, and G-LISA assays were used to assess megakaryocytic chemotaxis in vitro and in vivo in terms of megakaryocytic migration, adherence, and RhoA activation, respectively. Western blotting was used to assess PI3K/Akt-associated protein abundances in MEG-01 cells and primary megakaryocytes under the indicated treatment. A hematology analyzer and flow cytometry were used to assess platelet counts in peripheral blood and newly formed platelet counts in Lewis LC mice under different treatments. Immunochemistry and flow cytometry were used to measure CD41+ megakaryocyte numbers in Lewis LC mouse tissue under different treatments. ELISA was used to measure serum TPO levels, and H&E staining was used to detect NSCLC metastasis.SDF-1 receptor knockdown suppressed megakaryocytic chemotaxis in Lewis LC mice. SDF-1 receptor inhibition suppressed megakaryocytic chemotaxis via the PI3K/Akt pathway. SDF-1 receptor knockdown suppressed CD41+ megakaryocyte numbers in vivo through PI3K/Akt signaling. SDF-1 receptor inhibition suppressed CD41+ megakaryocytes to hinder NSCLC metastasis. SDF-1 facilitates NSCLC metastasis by enhancing the chemoattraction of megakaryocytes via the PI3K/Akt signaling pathway, which may provide a potential new direction for seeking therapeutic plans for NSCLC.
PURPOSE:To decrease the melting temperature, and to suppress the decomposition of the physiologically active substance and the lowering of titer, etc. with heat, in the preparation of a slow-releasing composite obtained by the inclusion of the physiologically active substance in molten polypeptide, by heating the polypeptide under specific pressurized condition. CONSTITUTION:One or more polypeptides, e.g. poly-gamma-methyl-L-glutamate are mixed with one or more physiologically active substances such as anti-malignant tumor agent (e.g. 5-fluorouracil), a hormone preparation, etc., and the mixture is heated under 2-20,000kg/cm<2> to melt the polypeptides. The molten mixture is formed to a desired form, and preferably irradiated with light or ionizing radiation at room temperature --100 deg.C to obtain the slow-releasing composite including the physiologically active substances.
This invention pertains to a multi-layered tablet for a triple combination release of active agents to an environment of use. More particularly, the invention pertains to a multi-layered tablet (1) comprising two external drug-containing layers (2 and 3) in stacked arrangement with respect to and on opposite sides of an oral dosage form (4) that provides a triple combination release of at least one active agent. In one embodiment of the invention the dosage form is an osmotic device. In another embodiment of the invention the dosage form is a gastro-resistant coated core. In yet another embodiment of the invention the dosage form is a matrix tablet. In a different embodiment the dosage form is a hard capsule.