anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Tertiary lymphoid structures (TLS), ordered structure of tumor-infiltrating immune cells in tumor immune microenvironment (TIME), play an important role in the development and anti-tumor immunity of various cancers, including liver, colon, and gastric cancers. Previous studies have demonstrated that the presence of TLS in intra-tumoral (IT), invasive margin (IM), and peri-tumoral (PT) regions of the tumors at various maturity statuses. However, the density of TLS in different regions of non-small cell lung cancer (NSCLC) has not been extensively studied.
METHODS: TLS and tumor-infiltrating immune cells were assessed using immunohistochemistry (IHC) staining in 82 NSCLC patients. Tumor samples were divided into three subregions as IT, IM and PT regions, and TLS were identified as early/primary TLS (E-TLS) or secondary/follicular TLS (F-TLS). The distribution of TLS in different maturity statuses, along with their correlation with clinicopathological characteristics and prognostic value, was assessed. Nomograms were used to predict the probability of 1-, 3-, and 5-year overall survival (OS) in patients with NSCLC.
RESULTS: The density of TLS and proportion of F-TLS in the IT region (90.2%, 0.45/mm2, and 61.0%, respectively) were significantly higher than those in the IM region (72.0%, 0.18/mm2, and 39.0%, respectively) and PT region (67.1%, 0.16/mm2, and 40.2%, respectively). A lower density of TLS, especially E-TLS in the IM region, was correlated with better prognosis in NSCLC patients. CD20+ B cells, CD3+ T cells, CD8+ cytotoxic T cells, and CD68+ macrophages were significantly overexpressed in the IM region. CD20+ B cells and CD3+ T cells in the IM region were significantly correlated with the density of E-TLS, while no statistically significant correlation was found with F-TLS. The E-TLS density in the IM region and TNM stage were independent prognostic factors for NSCLC patients. The nomogram showed good prognostic ability.
CONCLUSIONS: A higher density of E-TLS in the IM region was associated with a worse prognosis in NSCLC patients, potentially due to the inhibition of TLS maturation caused by the increased density of suppressive immune cells at the tumor invasion front.
The application takes radix tetrastigme extract as a research object, especially the research on protocatechuic acid methyl ester and isorhamnetin, and searches for a component combination with synergistic anti-inflammatory effect. Through design experiments, the synergistic anti-inflammatory effect of isorhamnetin and protocatechuic acid methyl ester is verified, and the action mechanism is related to inhibiting excessive secretion of inflammatory factors such as TNF-alpha, IL-6, IL-10 and the like, inhibiting phosphorylation of inflammatory pathway proteins such as ERK, JNK, conclusion 53p65 and the like, and promoting the expression of antioxidant related Nrf2 proteins. Experiments prove that isorhamnetin and protocatechuic acid methyl ester have synergistic anti-inflammatory effect, and the effect occurs in cell nuclei. Experiments find that 5 mu mol.L  ‑1  ‑500μmol·L  ‑1  The protocatechuic acid methyl ester in the concentration range has anti-inflammatory activity. Wherein 5. Mu. Mol.L  ‑1  Isorhamnetin +250mu mol.L  ‑1  The CI value of the protocatechuic acid methyl ester is 0.15415, and the synergistic effect is excellent.
The intervention group will have access to the web-based intervention along with telephone coaching. Participants in the intervention will receive 7 coach calls over a period of 12 weeks.
BACKGROUND: The Abbreviated Burn Severity Index and comparable scores are used to assess the probability of survival in burned patients. These scores may be useful during the initial management of the patient and in addition to the clinical evaluation. As current models do not include the influence of chronic diseases, we evaluated the impact of comorbidities on survival probability, aiming to improve the existing scoring systems and survival probability accuracy further.
METHODS: In this retrospective single-center study, patient data from a center for Severe Burn Injury were collected. Over a period of 20 years (2000-2019), a total of 1,193 patients were recorded. The influence of comorbidities (chronic kidney disease, diabetes mellitus type II, and cardiovascular diseases) on the survival probability was analyzed using regression models. These analyses were stratified for sex and period.
RESULTS: Pre-existing chronic kidney disease, as well as pre-existing cardiovascular disease, had a significant influence on the survival of patients. For chronic kidney disease, the influence was stronger in men than in women. Women were more likely to survive a burn injury with a history of chronic renal insufficiency. An improved Abbreviated Burn Severity Index model, which assigns an additional point for chronic kidney disease, best-described survival probability in our patient cohort.
CONCLUSION: Cardiovascular disease and chronic kidney disease both have an impact on the survival probability of severely burned patients, but this impact is more severe for chronic kidney disease. An additional Abbreviated Burn Severity Index point for chronic kidney disease would be a proposed adaptation to predict the outcome of burn patients better.
The participant self-administer electrical stimulation to the dorsal genital nerve (DGN) using UCon with a stimulation mode that is activated for 30 minutes once a day, at a time that is convenient for the participant. The participant uses the device at home for 14 days. Following a stimulation wash-out period (14 days), the participant then stimulates with UCon for another 14 days using the urge stimulation mode.
###  Risk Summary

Based on data from animal studies and its mechanism of action [see Clinical Pharmacology (12.1)], OPDIVO can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of nivolumab to cynomolgus monkeys from the onset of organogenesis through delivery resulted in increased abortion and premature infant death (see Data). Human IgG4 is known to cross the placental barrier and nivolumab is an immunoglobulin G4 (IgG4); therefore, nivolumab has the potential to be transmitted from the mother to the developing fetus. The effects of OPDIVO are likely to be greater during the second and third trimesters of pregnancy. There are no available data on OPDIVO use in pregnant women to evaluate a drug-associated risk. Advise pregnant women of the potential risk to a fetus.

The background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.

###  Data

Animal Data

A central function of the PD-1/PD-L1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to the fetus. Blockade of PD-L1 signaling has been shown in murine models of pregnancy to disrupt tolerance to the fetus and to increase fetal loss. The effects of nivolumab on prenatal and postnatal development were evaluated in monkeys that received nivolumab twice weekly from the onset of organogenesis through delivery, at exposure levels of between 9 and 42 times higher than those observed at the clinical dose of 3 mg/kg (based on AUC). Nivolumab administration resulted in a non-dose-related increase in spontaneous abortion and increased neonatal death. Based on its mechanism of action, fetal exposure to nivolumab may increase the risk of developing immune-mediated disorders or altering the normal immune response and immune-mediated disorders have been reported in PD-1 knockout mice. In surviving infants (18 of 32 compared to 11 of 16 vehicle-exposed infants) of cynomolgus monkeys treated with nivolumab, there were no apparent malformations and no effects on neurobehavioral, immunological, or clinical pathology parameters throughout the 6-month postnatal period.
Metabolism of a number of medications, including antipsychotics, antidepressants, β-blockers, and antiarrhythmics, occurs through the cytochrome P450 2D6 isoenzyme (debrisoquine hydroxylase). Approximately 10% of the Caucasian population has reduced activity of this enzyme, so-called "poor" metabolizers. Among other populations the prevalence is not known. Poor metabolizers demonstrate higher plasma concentrations of antipsychotic drugs at usual doses, which may correlate with emergence of side effects. In one study of 45 elderly patients suffering from dementia treated with perphenazine, the 5 patients who were prospectively identified as poor P450 2D6 metabolizers had reported significantly greater side effects during the first 10 days of treatment than the 40 extensive metabolizers, following which the groups tended to converge. Prospective phenotyping of elderly patients prior to antipsychotic treatment may identify those at risk for adverse events.

The concomitant administration of other drugs that inhibit the activity of P450 2D6 may acutely increase plasma concentrations of antipsychotics. Among these are tricyclic antidepressants and selective serotonin reuptake inhibitors, e.g. fluoxetine, sertraline and paroxetine. When prescribing these drugs to patients already receiving antipsychotic therapy, close monitoring is essential and dose reduction may become necessary to avoid toxicity. Lower doses than usually prescribed for either the antipsychotic or the other drug may be required.
The objective of the study is to test whether social incentives that encourage physical activity with another person are more effective than incentives for individual exercise. Physical inactivity and social isolation are growing epidemics linked to increased morbidity and mortality particularly among aging Americans. This research aims to address both problems by encouraging co-productive physical activities among college students. Co-productive physical activity mean anything involving physical activity that two people can do together, e.g., walking their dogs or shopping together. Additionally, in light of the COVID-19 pandemic, walking together in this study means either walking while communicating digitally or over the phone, or by physically walking together while wearing a mask, staying 6 feet apart, and following the recommendations from health professionals. A small randomized controlled trial will test the effectiveness of social incentives relative to traditional incentives in promoting walking behavior. Participants who are rewarded for walking together will be compared to those who are rewarded for walking even when alone. The results will indicate whether social incentives are more motivating than traditional incentives for walking behavior.
PART A The SAD treatment group is comprised of 3 cohorts where subjects will be randomized to either PTI-428 or placebo. Following the conclusion of at least 3 SAD treatment groups, a set of adult subjects diagnosed with CF will participate in an assigned MAD treatment group. The MAD treatment group is comprised of 3 cohorts. MAD Cohort 1 will enroll adult subjects with CF currently on stable ORKAMBI® background therapy for a minimum of 3 months at the time of randomization. MAD Cohorts 2 and 3 will enroll adult subjects with CF who are not currently on any background therapies. Subjects in all MAD cohorts will be randomized to either PTI-428 or placebo. Each dose will be administered once daily (QD) for a total of 7 Days.

PART B Following the conclusion of MAD Cohort 1, a set of adult subjects diagnosed with CF currently on stable ORKAMBI® background therapy for a minimum of 3 months will participate in Part B. The Part B Phase II treatment group is comprised of 2 cohorts where subjects will be randomized to either PTI-428 or placebo. Each dose will be administered QD for a total of 28 days.

PART C Following the conclusion of Part B Phase II, a set of adult subjects diagnosed with CF will participate in Part C. The Part C Phase II treatment group is comprised of 3 cohorts. Part C Cohort 1 will enroll adult subjects with CF who are eligible to take, but not currently taking, ORKAMBI® in accordance with the approved label. Part C Cohort 2 will enroll adult subjects with CF currently on stable KALYDECO® background therapy for a minimum of 3 months at the time of randomization. Part C Cohort 3 will enroll adult subjects with CF who are not currently on any background therapies and are pancreatic sufficient. Each PTI-428 or placebo dose will be administered QD for a total of 28 days.
Activity in vitro and ex vivo

In vitro methodologies employing various broth or solid media with and without additional nutrients have been utilized to determine ciclopirox minimum inhibitory concentration (MIC) values for the dermatophytic molds. (1-2) As a consequence, a broad range of MIC values, 1-20 mcg/mL were obtained for Trichophyton rubrum and Trichophyton mentagrophytes species. Correlation between in vitro MIC results and clinical outcome has yet to be established for ciclopirox. 

One ex vivo study was conducted evaluating 8% ciclopirox against new andestablished Trichophyton rubrum and Trichophyton mentagrophytes infections in ovine hoof material. (3) After 10 days of treatment the growth of T. rubrum and T. mentagrophytes in the established infection model was very minimally affected. Elimination of the molds from hoof material was not achieved in either the new or established infection models.
Disclosed is a film for biological adhesion, which contains regenerated cellulose and has high adhesion to biological tissues. The disclosed film (10) for biological adhesion contains regenerated cellulose and an adhesive component. The binding component adheres to the regenerated cellulose. The film (10) for biological adhesion is a self-supporting film having a thickness of 20 to 6500 nm. The adhesive component contains a polyamino acid. The biological adhesion membrane (10) can maintain the form of the membrane without a support.
Three prospective, randomized, controlled clinical studies (North American, Eastern European, and Nordic) were conducted to evaluate the efficacy of toremifene citrate for the treatment of breast cancer in postmenopausal women. The patients were randomized to parallel groups receiving toremifene citrate 60 mg (FAR60) or tamoxifen 20 mg (TAM20) in the North American Study or tamoxifen 40 mg (TAM40) in the Eastern European and Nordic studies. The North American and Eastern European studies also included high-dose toremifene arms of 200 and 240 mg daily, respectively. The studies included postmenopausal patients with estrogen-receptor (ER) positive or estrogen-receptor (ER) unknown metastatic breast cancer. The patients had at least one measurable or evaluable lesion. The primary efficacy variables were response rate (RR) and time to progression (TTP). Survival (S) was also determined. Ninety-five percent confidence intervals (95% CI) were calculated for the difference in RR between FAR60 and TAM groups and the hazard ratio (relative risk for an unfavorable event, such as disease progression or death) between TAM and FAR60 for TTP and S.  
Two of the 3 studies showed similar results for all effectiveness endpoints. However, the Nordic Study showed a longer time to progression for tamoxifen (see table).   
Clinical Studies

  


1CR = complete response; 2PR = partial response; 3RR = response rate; 4CI = confidence interval  
The high-dose groups, toremifene 200 mg daily in the North American Study and 240 mg daily in the Eastern European Study, were not superior to the lower toremifene dose groups, with response rates of 22.6% and 28.7%, median times to progression of 5.6 and 6.1 months, and median survivals of 30.1 and 23.8 months, respectively. The median treatment duration in the three pivotal studies was 5 months (range 4.2-6.3 months).
INTRODUCTION: To determine whether differences exist in the measured range of motion (ROM) by the goniometer, equinometer, and 3-dimensional (3D) gait analysis in different settings (under general anesthesia (GA) or in the clinic) among patients with cerebral palsy.
METHODS: A prospective comparative cohort study was conducted at our orthopaedics center, where 15 patients with diplegic cerebral palsy (30 limbs) were evaluated, all of whom had Gross Motor Function Classification System (GMFCS) level I and II. ROM was measured by (1) goniometer under GA (benchmark), (2) goniometer analysis during clinical examination, (3) equinometer under GA, (4) equinometer in the clinic, and (5) 3D gait analysis. ROM was measured during both knee flexion and extension. Subgroup analysis based on the GMFCS level was performed.
RESULTS: Nine patients were male with GMFCS level I and a mean age of 14.3 (SD=7.2) years. Statistically significant differences were noted between all studied measurement techniques in terms of ROM, dorsiflexion, and plantarflexion during both knee flexion and extension. The GMFCS level was an effect modifier of ROM measurements.
DISCUSSION: The ROM parameters during both knee flexion and extension differed from one measurement device/technique to another. The GMFCS level played a notable effect-modifying role on the ROM parameters.
Asthma is a chronic inflammatory disease of the airways characterized by reversible airflow obstruction and a bronchial hyperreactivity in response to a variety of stimuli. In most patients, the onset of asthma symptoms may be controlled. However, many of them may manifest asthma attacks or crises of breathing called exacerbations, which occur with breathing problems, wheezing, coughing or tightness of chest, and may threaten their life. Such exacerbations are caused by a combination of environmental and genetic factors. However, since studies so far have been limited, a reduced number of genes associated with the predisposition to these complications have been identified. In addition, some studies have used next-generation DNA sequencing techniques to characterize the microbiome (i.e., microbial community) of the airways, finding changes related to asthma. The main hypothesis of the Genomics and Metagenomics of Asthma Severity (GEMAS) study is that exacerbations of asthma are caused by a combination of the intrinsic genetic factors of the individual, changes in the respiratory microbiome and the interaction between both factors. The objectives of this project are: 1) to identify genetic variants that are associated with asthma exacerbations; 2) to examine the changes occurring in the microbial communities of the oral cavity and respiratory tract in individuals with exacerbations; 3) to analyze the association of the host genetic variants and the microbiome changes related to exacerbations.

A total of 300 Spanish subjects with asthma with and without a history of asthma exacerbations in the past 12 months will be recruited. Saliva, nasal and pharyngeal samples will be collected to study the oral cavity and the upper respiratory tract microbiome through next-generation sequencing technologies. Sequencing of the 16S ribosomal RNA (16S rRNA) gene will allow to characterize the bacterial diversity and abundance, as well as to infer the functionality of the microbiome in each sample. These parameters will be used to establish correlations between the microbiome and the presence of asthma exacerbations. Finally, the association between the genetic variation associated with exacerbations in genomic studies and the measurements of abundance, diversity and functions related to exacerbations will be jointly examined.
The purpose of this study is to predict and explain on the basis of brain function and structure the behavioral and brain effects of an evidence-based intervention for adults with high-functioning autism, Virtual Reality-Social Cognition Training (Kandalaft et al., 2012; Journal of Autism and Developmental Disorders). Adults with autism will be randomly assigned to receive either (a) two hours per week of intervention services for five weeks, or (b) a treatment as usual control. The intervention will focus on enhancing social skills, social cognition, and social functioning. Outcome measures will evaluate changes in these social skills, cognition, and functioning using standardized assessments. We will perform structural and functional magnetic resonance imaging (MRI) scans at three time points-before the treatment, after the treatment, and a 3-month follow-up (i.e., Time Point #1, 2, and 3).

All the recruitment will be taking place at Yale Child Study Center (YCSC), while the intervention will be delivered online by therapists located at the Center for BrainHealth at the University of Texas at Dallas (UTD). The intervention is called Virtual Reality-Social Cognition Training (VR-SCT) and has been approved by the IRB at UTD (approval number #06-54).
BACKGROUNDS: Carotid atherosclerosis is prone to rupture and cause ischemic stroke in advanced stages of development. Our research aims to provide markers for the progression of atherosclerosis and potential targets for its treatment.
METHODS: We performed a thorough analysis using various techniques including DEGs, GO/KEGG, xCell, WGCNA, GSEA, and other methods. The gene expression omnibus datasets GSE28829 and GSE43292 were utilized for this comprehensive analysis. The validation datasets employed in this study consisted of GSE41571 and GSE120521 datasets. Finally, we validated PLEK by immunohistochemistry staining in clinical samples.
RESULTS: Using the WGCNA technique, we discovered 636 differentially expressed genes (DEGs) and obtained 12 co-expression modules. Additionally, we discovered two modules that were specifically associated with atherosclerotic plaque. A total of 330 genes that were both present in DEGs and WGCNA results were used to create a protein-protein network in Cytoscape. We used four different algorithms to get the top 10 genes and finally got 6 overlapped genes (TYROBP, ITGB2, ITGAM, PLEK, LCP2, CD86), which are identified by GSE41571 and GSE120521 datasets. Interestingly, the area under curves (AUC) of PLEK is 0.833. Besides, we found PLEK is strongly positively correlated with most lymphocytes and myeloid cells, especially monocytes and macrophages, and negatively correlated with most stromal cells (e.g, neurons, myocytes, and fibroblasts). The expression of PLEK were consistent with the immunohistochemistry results.
CONCLUSIONS: Six genes (TYROBP, ITGB2, ITGAM, PLEK, LCP2, CD86) were found to be connected with carotid atherosclerotic plaques and PLEK may be an important biomarker and a potential therapeutic target.
This article investigates discomfort development for forces exerted repetitively and for extended durations through a rigid cuff. Three force patterns, chosen to mimic exoskeleton use, were applied to the thigh of 15 healthy participants for 30 min. Changes in perceived comfort and skin effects were recorded. Discomfort was detected at normal forces ranging from 40 to >230 N. Repetitive force application triggered discomfort after a median of 4.1 min (normal force only) and 5.4 min (normal and shear force) respectively. Discomfort increased over time but the repetitive force applications did generally not result in pain and there were no significant differences between repetitive loading patterns. Exoskeleton design and use should be informed by comfort thresholds specific to prolonged repetitive loading. Large interindividual differences in perception of discomfort limit the possibilities for generally applicable comfort thresholds. Further research is needed to investigate how patient groups perceive such repetitive loading.
A detailed 90 minute clinical assessment was conducted before and after treatment administration for each visit. Flumazenil 1mg in 10cc normal saline was given intravenously (iv) over 5-10 minutes on the first visit as treatment. 10 cc of normal saline placebo was given intravenously (iv) over 5-10 minutes on the second visit as treatment.