anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elderly patients. Liraglutide (LRG) has high homology (97%) with natural glucagon like peptide-1, and it has been proved to be effective in some nervous system diseases. Whether LRG could regulate POCD has not been reported.
METHODS: Sevoflurane (Sev) was used to simulate postoperative cognitive dysfunction (POCD) model. Morris water maze test was performed to evaluate the memory ability and neurological function of rats. Escape latency, swim distance, crossing platform times, average velocity, and targeting quadrant time were analyzed. The cell apoptosis, mRNA and protein expression were measured through flow cytometry, PCR, and western blotting, respectively.
RESULTS: LRG significantly improved the memory ability and neurological function of Sev-treated rats, but 3-MA reversed the effects of LRG. LRG remarkably inhibited apoptosis but up-regulated autophagy related proteins both in vivo and in vitro levels. However, knocking down AMPK could markedly reverse the influence of LRG on apoptosis, autophagy, and cell apoptosis.
CONCLUSIONS: LRG induced autophagy activation can maintain cell homeostasis and promote cell survival by blocking the apoptotic pathway. LRG could improve Sev-induced POCD via activating autophagy, inhibiting apoptosis, and regulating AMPK/mTOR signaling pathway. This study provides a novel therapeutic strategy for the prevention and treatment of POCD.
BACKGROUND: Constipation is associated with the prognosis of several chronic diseases. However, the effect of constipation on the prognosis of idiopathic interstitial pneumonias (IIPs) remains unclear. This study aimed to investigate the association between constipation and the prognosis of patients with IIPs.
METHODS: In this single-center, observational study, the association between constipation and survival of patients with IIPs was retrospectively investigated using a marginal structural model (MSM) analysis with weighting of age, sex, body mass index, treatment (corticosteroids, immunosuppressants, and antifibrotic agents), and pulmonary function (percent predicted forced vital capacity and diffusing capacity of the lungs for carbon monoxide).
RESULTS: A total of 433 patients with IIPs (148 and 285 patients with idiopathic pulmonary fibrosis [IPF] and those without IPF) were included in the study. During the observation period, 238 patients developed constipation. The MSM analysis showed that constipation was significantly associated with shorter overall survival (hazard ratio [HR], 2.374; 95% confidence interval, 1.924-2.928, p < 0.001). When the use of antifibrotic agents was weighted separately as nintedanib or pirfenidone, constipation was significantly associated with shorter survival (HR, 2.427; 95% CI, 1.972-2.988, p < 0.001; and HR, 2.395; 95% CI, 1.940-2.957, p < 0.001, respectively). Furthermore, a subgroup analysis showed that constipation was associated with worse survival in patients with IPF and in those without IPF, regardless of the disease severity.
CONCLUSIONS: This study shows that constipation is an independent prognostic factor for patients with IIPs, suggesting its potential clinical utility.
Cases of anaphylaxis, serious skin reactions (e.g. Stevens Johnson syndrome), erythema multiforme, and drug rash with eosinophilia and systemic symptoms (DRESS) syndrome have been reported postmarketing with minocycline use in patients with acne. DRESS syndrome consists of cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, and one or more of the following visceral complications such as: hepatitis, pneumonitis, nephritis, myocarditis, and pericarditis. Fever and lymphadenopathy may be present. In some cases, death has been reported. If this syndrome is recognized, the drug should be discontinued immediately.
Described are regulatory sequences of the promoter of the Pax6 gene or a gene homologous to the Pax6 gene, being capable of conferring expression in pancreatic cells. Recombinant DNA molecules and vectors comprising said regulatory sequences as well as to host cells transformed therewith. Described are also pharmaceutical and diagnostic compositions comprising such regulatory sequences, recombinant DNA molecules and vectors. Furthermore, transgenic non-human animals, comprising the afore-mentioned recombinant DNA molecules or vectors stably integrated into their genome. Also provided are uses of the before described recombinant DNA molecules and vectors for the preparation of pharmaceutical compositions for treating, preventing and/or delaying a disease related to the pancreas in a subject. Furthermore, uses of the regulatory sequences, the recombinant DNA molecules and vectors of the invention for the preparation of pharmaceutical compositions for inducing a pancreatic disease in a non-human animal are provided. Additionally a method for identifying agonists/activators or antagonists/inhibitors of genes or gene products involved in pancreatic diseases employing the above mentioned regulatory sequences, recombinant DNA molecules, vectors, cells and non-human transgenic animals, to compounds identifyable by said method, to antibodies directed to said compounds as well as to pharmaceutical and diagnostic compositions comprising said agonists/activators, antagonists/inhibitors and/or antibodies.
Pacing protocol prior to patient's extubation with 20 min. of either conventional right ventricular (RV) or biventricular (BiV) pacing, preceded and followed by 10 min. of recovery time.
Intubation ICU patients will be challenged with stepwise modifications of FiO2. The following steps will be done: 30, 40, 60, 80, 100, 80, 60, 40 and 30%.
A method and system for creating and using knowledge patterns. One or more patterns derived from one or more pharmaceutical data sources are acquired. A knowledge map is created using the one or more patterns. The knowledge map, such as a self-organizing knowledge map, includes a selected representation of a pattern space. A set of selected regions from the knowledge map are annotated. Others patterns are classified with annotated regions of the knowledge map. The knowledge ap is used for recognizing previously unseen or unkonwn patterns from large amounts of pharmaceutical data obtained by automated screening systems. The knowledge patterns may be used to select new known pharmaceutical compounds, or model new virtual pharmaceutical compounds. The method and system described herein may be used to locate and describe previously unrecognized patterns of biological or chemical activity concealed with in a selected range of drug discovery data. This may improve the identification, selection, validation and screening of new real or virtual pharmaceutical compounds. The method and system may also be used to provide new bioinformatic techniques for storing and manipulating pharmaceutical knowledge.
Various lead-in dosing strategies have been used in clinical practice for venous thromboembolism (VTE), and guidelines do not currently address if the full lead-in dosing duration is necessary after receiving parenteral anticoagulation. This study aims to identify whether full lead-in dosing duration surrounding parenteral anticoagulation affects thrombotic and bleeding outcomes. A single-center, retrospective cohort study was conducted of hospitalized patients diagnosed with VTE and treated with apixaban or rivaroxaban. Patients were grouped depending on duration of lead-in dosing, with the full lead-in dosing group considered as the appropriate duration of the direct oral anticoagulant. The primary outcome was the recurrence of VTE within the index admission to 6 months. Secondary outcomes included major bleeding, clinically relevant minor bleeding, and mortality. Ninety-three patients were prescribed full lead-in dosing, while 99 patients received reduced lead-in dosing. The primary outcome of recurrent VTE was similar between the reduced lead-in group compared to the full lead-in group (3% vs 2%; P = 1.0). Major bleeding within the index admission was significantly higher in the reduced lead-in group: 11 versus 2 (P = .02). There were no significant differences in other secondary outcomes. Full lead-in dosing compared to reduced lead-in dosing duration for VTE had similar rates of thrombotic and mortality events. The higher rate of major bleeding in the reduced lead-in dosing group likely reflects the prescribing practices in less stable patients. This study provides evidence to support reduced lead-in dosing duration in high-risk patients without compromising efficacy outcomes.
MRG-001 will be subcutaneously administered at 0.01 mL/kg 3 times per week every other day for two weeks per month (Day 0, 2, 4, 7, 9, 11). This cycle will be repeated 3 months in total.
Pharmaceutical compositions in powder form are prepared by loading drugs solubilized in supercritical fluids on cross-linked polymers.  The loading process is carried out by means of two steps.  In the first step the supercritical fluid is saturated with the drug in suitable temperature and pressure conditions.  In the second step the supercritical fluid containing the drug is contacted with the cross-linked polymer.  Owing to its particular properties the supercritical fluid penetrates into the polymer and allows the drug to impregnate the polymer itself.  After the removal of the fluid the drug remains in the polymer itself.
Sleep is a fundamental process essential for reparatory and restorative mechanisms in all organisms. Recent research has linked sleep to various pathological conditions, including cancer and neurodegeneration, which are associated with various molecular changes in different cellular environments. Despite the potential significance of various molecules, the HSPA1A or Hsp70 protein, which has possible connections with sleep and different neuropsychological and pathological disorders, has been explored the least. This paper explores the potential for manipulating and discovering drugs related to the Hsp70 protein to alleviate sleep problems and improve the prognosis for various other health issues. This paper discusses the critical role of Hsp70 in cancer, neurodegeneration, apoptosis, sleep, and its regulation at the structural level through allosteric mechanisms and different substrates. The significant impact of Hsp70's connection to various conditions suggests that existing sleep medicine could be used to improve such conditions, leading to improved outcomes, minimized research costs, and a new direction for current research. Overall, this paper highlights the potential of Hsp70 protein as a key therapeutic target for developing new drugs for the treatment of sleep disorders, cancer, neurodegeneration, and other related pathological conditions. Further research into the molecular mechanisms of Hsp70 regulation and its interactions with other cellular pathways is necessary to develop targeted treatments for these conditions.Communicated by Ramaswamy H. Sarma.
Fifty participants will take part in the 12 week CBTw program. All participants will receive standard SE services during the study. The longitudinal design will consist of assessments of competitive employment outcomes, important psychosocial outcomes, and background and demographic variables at baseline and at two follow-up periods' immediately following the conclusion of the CBTw program and six months after the conclusion of the program.
For each of the diseases being evaluated (WG, MPA, CSS, PAN, GCA, TAK), patients with the other 5 diseases will be the control group. Within these groups, 1st half of these patients will be assigned to the development cohort and the second half to the validation cohort. Classification criteria.
BACKGROUND: Cholesterol crystals (CCs) are recognized as a risk factor for vulnerable atherosclerotic plaque rupture (PR) and major adverse cardiovascular events. However, their predictive factors and association with plaque vulnerability in patients with acute myocardial infarction (AMI) remain insufficiently explored. Therefore, This study aims to investigate the association between CCs and plaque vulnerability in culprit lesions of AMI patients, identify the factors influencing CCs formation, and develop a predictive model for CCs.
METHODS: A total of 431 culprit lesions from AMI patients who underwent pre-intervention optical coherence tomography (OCT) imaging were analyzed. Patients were divided into groups based on the presence or absence of CCs and PR. The relationship between CCs and plaque vulnerability was evaluated. A risk nomogram for predicting CCs was developed using the least absolute shrinkage and selection operator and logistic regression analysis.
RESULTS: CCs were identified in 64.5 % of patients with AMI. The presence of CCs was associated with a higher prevalence of vulnerable plaque features, such as thin-cap fibroatheroma (TCFA), PR, macrophage infiltration, neovascularization, calcification, and thrombus, compared to patients without CCs. The CCs model demonstrated an area under the curve (AUC) of 0.676 for predicting PR. Incorporating CCs into the TCFA model (AUC = 0.656) significantly enhanced predictive accuracy, with a net reclassification improvement index of 0.462 (95 % confidence interval [CI]: 0.263-0.661, p < 0.001) and an integrated discrimination improvement index of 0.031 (95 % CI: 0.013-0.048, p = 0.001). Multivariate regression analysis identified the atherogenic index of plasma (odds ratio [OR] = 2.417), TCFA (OR = 1.759), macrophage infiltration (OR = 3.863), neovascularization (OR = 2.697), calcification (OR = 1.860), and thrombus (OR = 2.430) as independent risk factors for CCs formation. The comprehensive model incorporating these factors exhibited reasonable discriminatory ability, with an AUC of 0.766 (95 % CI: 0.717-0.815) in the training set and 0.753 (95 % CI: 0.704-0.802) in the internal validation set, reflecting good calibration. Decision curve analysis suggested that the model has potential clinical utility within a threshold probability range of approximately 18 % to 85 %.
CONCLUSIONS: CCs were associated with plaque vulnerability in the culprit lesions of AMI patients. Additionally, this study identified key factors influencing CCs formation and developed a predictive model with potential clinical applicability.
The present invention provides, inter alia, compounds having the structures of formulas described herein; pharmaceutically acceptable salts, solvates, hydrates, tautomers, and isotopic forms thereof; and compositions ( e.g. , pharmaceutical compositions and kits) containing one or more of the foregoing. Also provided are methods of administering and uses involving the compounds and/or pharmaceutical compositions for treating or preventing disease. The disease can be a proliferative disease, such as a cancer ( e.g. , a blood cancer ( e.g. , a leukemia or lymphoma), a brain cancer, a breast cancer, melanoma, multiple myeloma, or an ovarian cancer) a benign neoplasm, pathologic angiogenesis, or a fibrotic disease. While no aspect of the invention is limited by the biological events that may transpire, administering a compound or other composition described herein may selectively inhibit the aberrant expression or activity of cyclin-dependent kinase 7 (CDK7) and, thereby, induce cellular apoptosis and/or inhibit the transcription of disease-related genes in the patient (or in a biological sample).
Developments in the field of technology, patient density in polyclinic services, limited number of nurses specialized in the field and the desire to carry out effective workforce planning bring different education methods to the agenda in the field of nursing. Creating the metaverse universe, which has been used in many technological fields in recent years, is among the newest of these technological developments. When the content created in Metaverse-based training is presented to the user, the user has the opportunity to enter the universe, choose the avatar the participant wants, and navigate and gain information by entering the desired module among the training modules created for participant. At the same time, since it offers an interactive training module to the participant, there are no limitations such as time, place or subject as in other training models. When the literature was examined, no study was found in which metaverse-based education was used in the field of epilepsy. In this context, our research aimed to examine the usability of metaverse-based epilepsy education and its effect on parents' epilepsy knowledge level.
Both cyclosporine doses and the target range for whole blood trough concentrations should be reduced, when given in a regimen with everolimus, in order to minimize the risk of nephrotoxicity [See Warnings and Precautions (5.6), Drug Interactions (7.2), Clinical Pharmacology (12.8)].

The recommended cyclosporine therapeutic ranges when administered with everolimus are 100 to 200 ng/mL through Month 1 posttransplant, 75 to 150 ng/mL at Months 2 and 3 posttransplant, 50 to 100 ng/mL at Month 4 posttransplant, and 25 to 50 ng/mL from Month 6 through Month 12 posttransplant. The median trough concentrations observed in the clinical trial ranged between 161 to 185 ng/mL through Month 1 posttransplant and between 111 to 140 ng/mL at Months 2 and 3 posttransplant. The median trough concentration was 99 ng/mL at Month 4 posttransplant and ranged between 46 to 75 ng/mL from Months 6 through Month 12 posttransplant [See Clinical Pharmacology (12.8), Clinical Studies (14.1)].

Cyclosporine, USP Modified is to be administered as oral capsules twice daily unless cyclosporine oral solution or intravenous administration of cyclosporine cannot be avoided. Cyclosporine, USP Modified should be initiated as soon as possible, and no later than 48 hours after reperfusion of the graft and dose adjusted to target concentrations from Day 5 onwards.

If impairment of renal function is progressive, the treatment regimen should be adjusted. In renal transplant patients, the cyclosporine dose should be based on cyclosporine whole blood trough concentrations [See Clinical Pharmacology (12.8)].

In renal transplantation, there are limited data regarding dosing everolimus with reduced cyclosporine trough concentrations of 25 to 50 ng/mL after 12 months. Everolimus has not been evaluated in clinical trials with other formulations of cyclosporine. Prior to dose reduction of cyclosporine, it should be ascertained that steady-state everolimus whole blood trough concentration is at least 3 ng/mL. There is an interaction of cyclosporine on everolimus, and consequently, everolimus concentrations may decrease if cyclosporine exposure is reduced [See Drug Interactions (7.2)].
CD19-directed chimeric antigen receptor (CAR) T cells can induce durable remissions in relapsed/refractory large B-cell lymphomas (R/R LBCLs), but 60% of patients do not respond or relapse. Biological mechanisms explaining lack of response are emerging, but they are largely unsuccessful in predicting disease response at the patient level. Additionally, to maximize the cost-effectiveness of CAR T-cell therapy, biomarkers able to predict response and survival before CAR T-cell manufacturing would be desirable. We performed transcriptomic and functional evaluations of leukapheresis products in 95 patients with R/R LBCL enrolled in a prospective observational study, to identify correlates of response and survival to tisagenlecleucel and axicabtagene ciloleucel. A signature composed of 4 myeloid genes expressed by T cells isolated from leukapheresis products is able to identify patients with a very short progression-free survival (PFS), highlighting the impact of monocytes in CAR T-cell therapy response. Accordingly, response and PFS were also negatively influenced by high circulating absolute monocyte counts at the time of leukapheresis. The combined evaluation of peripheral blood monocytes at the time of leukapheresis and the 4-gene signature represents a novel tool to identify patients with R/R LBCL at very high risk of progression after CAR T-cell therapy and could be used to plan trials evaluating CAR T cells vs other novel treatments or allogeneic CAR T cells. However, it also highlights the need to incorporate monocyte depletion strategies for better CAR T production.
With Institutional ethics board and Health Canada approval and parental consent and child assent, pediatric patients (ages 3-12) undergoing tonsillectomy or adenotonsillectomy (under standardized anesthesia) will be randomized to receive dextromethorphan hydrobromide (1mg/kg orally) 30 min preoperatively and again 8 hours postoperatively OR placebo (syrup identical in taste, appearance and volume) at the same time points. The primary outcome is an integrated assessment of perioperative pain scores and opioid use for 24 hours postoperatively. Pain scores were collected preoperatively at rest and then at 1,2,3,8,9,10 and 24 hours postoperatively using the validated Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). Secondary outcomes include nausea, vomiting, respiratory depression, and bleeding recorded by blinded observers for 24 hours postoperatively.

Our hypothesis is that dextromethorphan will decrease the incidence/severity of post-tonsillectomy pain. The improved pain control will be apparent through reduced opioid consumption and integrated pain scores. This will result in a reduced incidence of opioid-related side effects and adverse events.
Investigators plan a prospective clinical trial. Participants with SCI were included to study if times from injury were at least one year. Participants had an AIS grades of A-D with spasticity. We evaluated that participants with AIS A and B SCI were motor complete group, AIS C and D SCI were motor incomplete group. Spasticity was assessed with Modified Ashworth Scale (MAS) and spasms were assessed with Penn Spasm Frequency Scale (PSFS). Hip adductor and extensor spasticity, knee extensor and flexor spasticity and ankle plantar flexor spasticity were assessed by using MAS. Body composition was measured by dual-energy x-ray absorptiometry. All participants underwent a 75 gram (g) oral glucose tolerance test (OGTT). Insulin sensitivity was assessed by calculating Matsuda index and HOMA-IR. Investigators assessed the effects of spasticity on glucose metabolism and body composition in participants with SCI.
Based on the above and on the remarkable properties of the 2′-O,4′-C-methylene bridged LNA monomers it was decided to synthesise oligonucleotides comprising one or more 2′-O,4′-C-methylene-β-D-xylofuranosyl nucleotide monomer(s) as the first stereoisomer of LNA modified oligonucleotides. Modelling clearly indicated the xylo-LNA monomers to be locked in an N-type furanose conformation. Whereas the parent 2′-deoxy-β-D-xylofuranosyl nucleosides were shown to adopt mainly an N-type furanose conformation, the furanose ring of the 2′-deoxy-β-D-xylofuranosyl monomers present in xylo-DNA were shown by conformational analysis and computer modelling to prefer an S-type conformation thereby minimising steric repulsion between the nucleobase and the 3′-O-phopshate group (Seela, F.; Wömer, Rosemeyer, H.  Helv. Chem. Acta  1994, 77, 883). As no report on the hybridisation properties and binding mode of xylo-configurated oligonucleotides in an RNA context was believed to exist, it was the aim to synthesise 2′-O,4′-C-methylene-β-D-xylofuranosyl nucleotide monomer and to study the thermal stability of oligonucleotides comprising this monomer. The results showed that fully modified or almost fully modified Xylo-LNA is useful for high-affinity targeting of complementary nucleic acids. When taking into consideration the inverted stereochemistry at C-3′ this is a surprising fact. It is likely that Xylo-LNA monomers, in a sequence context of Xylo-DNA monomers, should have an affinity-increasing effect.