Miracle-dz/UniFAR-FTUs huggingface dataset:
STK11 (LKB1) mutations in metastatic NSCLC: Prognostic value in the real world

Background Mutations in STK11 (STK11m) and frequently co-occurring KRAS mutations (KRASm/STK11m) are associated with poor survival in metastatic NSCLC (mNSCLC) immuno-oncology trials. There are limited data regarding the prognostic significance of these mutations in a real-world setting. Methods This retrospective cohort study analyzed de-identified electronic medical records from the Flatiron Clinico-Genomic database to identify patients with mNSCLC who had initiated first-line immunotherapy (IO; alone or in combination) or chemotherapy under routine care between January 1, 2013 and June 30, 2017. The primary objectives were to assess the prevalence of STK11m and KRASm/STK11m and to determine associations of these mutations with overall and progression-free survival (OS, PFS). Results Of 2407 patients with mNSCLC, STK11m and KRASm/STK11m were present in 13.6% and 6.5% of patients, respectively. Worse OS outcomes were observed in patients with STK11m versus STK11wt mNSCLC receiving IO (first-line, HR [95% CI], 1.4 [0.9–2.3; p = 0.1]; second-line [subset of first-line cohort], HR, 1.6 [1.3–2.0; p = 0.0002]) or chemotherapy (first-line, HR, 1.4 [1.2–1.6; p < 0.0001]); PFS outcomes showed similar trends. KRASm/STK11m double mutations were associated with worse OS and PFS outcomes versus KRASwt/STK11wt with IO and chemotherapy, similar to the single mutation (STK11m vs STK11wt) findings. Conclusions This large observational genomic study among patients receiving routine care highlights the negative prognostic impact of STK11m in patients with mNSCLC treated with IO or chemotherapy. These results complement previous clinical trial data and provide further evidence in the real world of a patient population that would benefit from new treatment options.
Computational and Transcriptome Analyses Revealed Preferential Induction of Chemotaxis and Lipid Synthesis by SARS-CoV-2

The continuous and rapid emergence of new viral strains calls for a better understanding of the fundamental changes occurring within the host cell upon viral infection. In this study, we analyzed RNA-seq transcriptome data from Calu-3 human lung epithelial cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared to five other viruses namely, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East Respiratory Syndrome (SARS-MERS), influenzavirus A (FLUA), influenzavirus B (FLUB), and rhinovirus (RHINO) compared to mock-infected cells and characterized their coding and noncoding RNA transcriptional portraits. The induction of interferon, inflammatory, and immune response was a hallmark of SARS-CoV-2 infection. Comprehensive bioinformatics revealed the activation of immune response and defense response to the virus as a common feature of viral infection. Interestingly however, the degree of functional categories and signaling pathways activation varied among different viruses. Ingenuity pathways analysis highlighted altered conical and casual pathways related to TNF, IL1A, and TLR7, which are seen more predominantly during SARS-CoV-2 infection. Nonetheless, the activation of chemotaxis and lipid synthesis was prominent in SARS-CoV-2-infected cells. Despite the commonality among all viruses, our data revealed the hyperactivation of chemotaxis and immune cell trafficking as well as the enhanced fatty acid synthesis as plausible mechanisms that could explain the inflammatory cytokine storms associated with severe cases of COVID-19 and the rapid spread of the virus, respectively.
Antimicrobial constituents of Hypocrea virens, an endophyte of the mangrove-associate plant Premna serratifolia L.

Emergence of multidrug-resistant pathogenic microorganisms has prompted a worldwide search for new antibiotics from various sources. Endophytic fungi from unique habitats are considered as potential sources of novel bioactive compounds. Sri Lankan mangrove ecosystem is such a distinctive and unexploited resource for the discovery of structurally diverse and biologically active metabolites including antimicrobials. Nine endophytic fungi were isolated from the leaves and twigs of Premna serratifolia L . from a mangrove habitat in the Negombo lagoon and the antimicrobial activities of their laboratory cultures were evaluated. The most promising antimicrobial activity was exhibited by the endophytic fungus Hypocrea virens . Bioassay guided fractionation of the organic extract of this fungus led to the isolation of two known metabolites; the antimicrobial epidithiodioxopiperazine, gliotoxin (1), and the closely related but less active bisdethiobis(methylthio)gliotxin (2). The chemical structures of the two compounds were determined by spectroscopy and confirmed by comparison of mass and nuclear magnetic resonance (NMR) spectral data with the reported values for these molecules. The minimum inhibitory concentration (MIC) values obtained for gliotoxin (1) in the current study are 0.13 μg mL-1 for Bacillus subtilis , 16 μg mL-1 for Staphylococcus aureus , 32 μg mL-1 for Methicillin Resistant Staphylococcus aureus (MRSA) and Escherichia coli , 64 μg mL-1 for Pseudomonas aeruginosa and Candida albicans fungus. This is the first study to report the isolation of endophytic fungi from P. serratifolia and their antimicrobial activities.
A Translational Mouse Model for NASH with Advanced Fibrosis and Atherosclerosis Expressing Key Pathways of Human Pathology

Non-alcoholic steatohepatitis (NASH) is a fast-growing liver disorder that is associated with an increased incidence of cardiovascular disease and type 2 diabetes. Animal models adequately mimicking this condition are scarce. We herein investigate whether Ldlr−/−. Leiden mice on different high-fat diets represent a suitable NASH model. Ldlr−/−. Leiden mice were fed a healthy chow diet or fed a high-fat diet (HFD) containing lard or a fast food diet (FFD) containing milk fat. Additionally, the response to treatment with obeticholic acid (OCA) was evaluated. Both high-fat diets induced obesity, hyperlipidemia, hyperinsulinemia, and increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Mice on both diets developed progressive macro- and microvesicular steatosis, hepatic inflammation, and fibrosis, along with atherosclerosis. HFD induced more severe hyperinsulinemia, while FFD induced more severe hepatic inflammation with advanced (F3) bridging fibrosis, as well as more severe atherosclerosis. OCA treatment significantly reduced hepatic inflammation and fibrosis, and it did not affect atherosclerosis. Hepatic transcriptome analysis was compared with human NASH and illustrated similarity. The present study defines a translational model of NASH with progressive liver fibrosis and simultaneous atherosclerosis development. By adaptation of the fat content of the diet, either insulin resistance (HFD) or hepatic inflammation and fibrosis (FFD) can be aggravated.
Proximate composition, mineral and total phenolic contents, and scavenging activity of breadnut fruit (Artocarpus camansi)

This study investigated the proximate composition, mineral and total phenolic contents (TPCs), and antioxidant capacity of the core, pulp and seed of breadnut Artocarpus camansi ). For proximate composition, pulp had the highest ash (1.47%) and protein contents (1.29%), and core had the highest moisture content (88.6%). The minerals present in breadnut were calcium, zinc, copper, manganese, iron and sodium. The percentage of DPPH inhibition followed the order seed > pulp > core. The TPCs of the samples were 7.88 – 22.1 mg gallic acid equivalent (GAE)/g for methanol extract and 1.69 to 5.22 mg GAE/g for water extract. Evaluation provided a strong basis for the nutritional value of A. camansi , which is an underutilised fruit. Results revealed that breadnut is an edible underutilised fruit that is cheap, contains high value of antioxidant activity and can be beneficial to the food and health industries.
Immediate effect of Kinesio taping® on deep cervical flexor endurance: A non-controlled, quasi-experimental pre-post quantitative study

ABSTRACT Objective Whether Kinesio taping® (KT) might change the endurance of the cervical deep flexor muscles. Methods Healthy university students were assessed at baseline, immediately after the KT application over the posterior cervical muscles, and at a 24-h follow-up. The clinical assessment of the endurance of the deep cervical flexor muscles using the craniocervical flexion test (CCFT) was performed. Results Sixty-two students (32 women) with a mean age of 20.4 ± 1.3 years completed the study protocol. Statistically significant pre- to post-taping differences in performance of the craniocervical flexion movement were found between baseline-immediate and baseline-24-h follow-up (p˂0.001). A statistically significant difference in the endurance of the cervical deepflexor muscles was found between baseline-immediate (for stage 2 result and cumulative endurance score), baseline-24-h follow-up (for stage 2result and cumulative endurance score), and immediate-24-h follow-up (for stage 2 result, for cumulative endurance score) p˂0.01. Conclusion Cervical KT increased endurance for the short term.
Non‐coding RNAs in aortic dissection: From biomarkers to therapeutic targets

Aortic dissection (AD) is the rupture of the aortic intima, causing the blood in the cavity to enter the middle of the arterial wall. Without urgent and proper treatment, the mortality rate increases to 50% within 48 hours. Most patients present with acute onset of symptoms, including sudden severe pain and complex and variable clinical manifestations, which can be easily misdiagnosed. Despite this, the molecular mechanisms underlying AD are still unknown. Recently, non‐coding RNAs have emerged as novel regulators of gene expression. Previous studies have proven that ncRNAs can regulate several cardiovascular diseases; therefore, their potential as clinical biomarkers and novel therapeutic targets for AD has aroused widespread interest. To date, several studies have reported that microRNAs are crucially involved in AD progression. Additionally, several long non‐coding RNAs and circular RNAs have been found to be differentially expressed in AD samples, suggesting their potential roles in vascular physiology and disease. In this review, we discuss the functions of ncRNAs in AD pathophysiology and highlight their potential as biomarkers and therapeutic targets for AD. Meanwhile, we present the animal models previously used for AD research, as well as the specific methods for constructing mouse or rat AD models.
Making Ventilator Associated Pneumonia Rate a Meaningful Quality Marker

Introduction: Ventilator associated pneumonia (VAP) rate has been tracked as a comparable quality measure but there is significant variation between types of ICUs. We sought to understand variability and improve its utility as a marker of quality. Methods: The National Trauma Database was surveyed to identify risk factors for VAP. Logistic regression, χ2, Student’s T-test or Mann-Whitney U test were used. Results: Risk factors associated with developing VAP were: injury severity score (ISS) (OR 1.03, 95% CI 1.03 -1.04), prehospital assisted respiration (PHAR) (OR 1.10, 1.03 -1.17), thoracic injuries (OR 2.28, 1.69-3.08), diabetes (OR 1.32, 1.20 -1.46), male gender (OR 1.38, 1.28 -1.60), care at a teaching hospital (OR 1.40, 1.29 -1.47) and unplanned intubation (OR 2.76, 2.52-3.03). Discussion: ISS, PHAR, diabetes, male gender, care at a teaching hospital and unplanned intubation are risk factors for the development of VAP. These factors should be accounted for in order to make VAP an effective quality marker.
Changes in Forage Nutritive Value among Vertical Strata of a Cool‐Season Grass Canopy

An understanding of the vertical distribution of nutritive value in cool-season grasses could support decisions regarding the management of residual mass and plant height to meet nutri - tional value targets. The objective of this study was to characterize the vertical distribution of nutritive value within a grass sward and to relate it to the morphological components of the herb - age (lamina, stem + sheath, and dead matter). The research was conducted from April to o cto- ber 2009 and 2010 in a mixed cool-season grass sward consisting primarily of tall fescue ( Sche- donorus arundinaceus (Schreb.) Dumort. , nom. cons. , formerly Festuca arundinacea Schreb. ). Growing periods were initiated in April, May, June, July, and August, during which forage was allowed to accumulate for the remainder of the growing season, with weekly sampling for nutri - tive value and morphological composition. Neu - tral detergent fiber (NDF) was significantly greater in the 5- to 15-cm strata than in the 15- to 25-cm in 32% of all initiation datedays after cutting combinations across years. The NDF concentra - tion increased as the season progressed, which was associated with increasing dead matter and declining lamina content in the canopy. Differ - ences in NDF digestibility among strata were less consistent than for NDF. For the May through August initiation dates, few nutritive value dif - ferences were found among strata, which were attributed to lower nutritive value in the 10-cm strata immediately above the stubble height. Consequently, we anticipate a small decrease in nutritive value of the diet of a grazing animal as it consumes tall fescue-dominant pasture. Dep. of Horticulture and Crop Science and Dep. of Animal Science, The Ohio State Univ., Columbus, OH 43210. Salary and research sup -
Effects of the number of hospitalizations on cognitive function in Japanese patients with stable schizophrenia

Abstract Background The present study aimed to determine whether the number of hospitalizations in schizophrenia patients is associated with reduced cognitive performance, which may in turn imply that recurrences indirectly lead to a worsening in the disorder’s progression. Methods Cognitive performance in stable schizophrenia patients was assessed using the Brief Assessment of Cognition in Schizophrenia, Japanese-language version, on 30 patients who had not experienced any hospitalizations (G0), 57 patients who had experienced only one hospitalization (G1), 47 patients with two hospitalizations (G2), and 59 patients with three or more hospitalizations (G3). Results Significant differences in motor function and attention and processing speed were found between patients with G0 and those with G1. Significant differences in working memory and verbal fluency were found between patients with G1 and those with G2. Patients with G3 performed even more poorly in comparison with those with G1, showing deficits in verbal memory, working memory, executive function, and composite score. The patients with G3 displayed a greater range of impairment and demonstrated deficits in executive function compared with patients with G2. Finally, G2 and G3 performed more poorly than G0, with deficits in the various cognitive areas. Conclusion The number of hospitalizations predicted cognitive performance, which suggests that relapse or recurrence may have a long-term neuropsychological impact. Prospective follow-up studies must be completed to explore this effect further because better treatment adherence may have a protective effect on neurocognitive function.
Cardiac Arrhythmia Prevention in Ischemia and Reperfusion by Low-Dose Dietary Fish Oil Supplementation in Rats.

BACKGROUND Supplementing animal diets with fish oil increases myocardial omega-3 polyunsaturated fatty acids [ω-3 (n-3) PUFA], lowers heart rate, and prevents malignant cardiac arrhythmias. In contrast to epidemiological reports, results of some human clinical trials and of unphysiologically high doses employed in animal studies call into question the application of dietary ω-3 PUFA for cardioprotection. OBJECTIVE This study tested the hypothesis that low ω-3 PUFA dietary thresholds for myocardial incorporation in rats, equivalent in dose to what humans derive from eating fish, can reduce heart rate and arrhythmia vulnerability. METHODS Male Sprague-Dawley rats (12-15 wk old) were fed isoenergetic diets containing 10% fat for 4-5 wk. The control diet (CON) contained 5.5% beef tallow, 2.5% sunflower seed oil, and 2% olive oil. Fish oil diets contained high-DHA tuna oil, exchanged for olive oil: 0.31% [fish oil group 1 (FO1)] (human equivalent EPA + DHA 570 mg/d); 1.25% [fish oil group 2 (FO2)] (equivalent EPA + DHA 2.3 g/d). Anaesthetized rats (pentobarbital, 60 mg/kg intraperitoneally) were subjected in vivo to 15-min cardiac ischemia by left coronary artery occlusion and then reperfusion, with arrhythmias detected by electrocardiogram. RESULTS Fish oil dose dependently modulated myocardial membrane fatty acids (DHA mean ± SEM: CON, 5.0 ± 0.2%; FO1, 13.1 ± 0.9%; FO2, 18.3 ± 0.4%; n = 4-5; P-trend < 0.001 ANOVA); resting heart rate (CON, 453 ± 6; FO1, 432 ± 4; FO2, 422 ± 5 bpm; n = 15-18; P-trend < 0.001); reduced ventricular fibrillation (VF) (CON, 89%; FO1, 60%; P = 0.052; FO2, 50%; n = 15-18; P = 0.013 chi square); and total arrhythmia severity (arrhythmia score: CON, 6.1 ± 0.4; FO1, 4.6 ± 0.5; FO2, 3.1 ± 0.7; n = 15-18; P-trend < 0.01) during ischemia and reperfusion (VF: Con, 86%; FO1, 22% P = 0.011; FO2, 8% P = 0.001; n = 7-12); (arrhythmia score: CON, 4.6 ± 0.3; FO1, 3.1 ± 0.3; FO2, 1.3 ± 0.3; n = 7-12; P-trend < 0.001). CONCLUSIONS Ventricular arrhythmias were prevented and heart rate was slowed by lower ω-3 PUFA intake in rats than previously reported, equivalent to human fish consumption and associated with increased myocardial DHA. The efficacy of low-dose fish oil demonstrates biological plausibility for nutritional ω-3 fatty acid-mediated cardioprotection and suggests that effectiveness in human clinical trials may be obscured by failure to exclude fish eaters.
Clinical Characteristics and Outcomes of Patients with Severe COVID-19 and Chronic Obstructive Pulmonary Disease (COPD)

Background The rapid worldwide spread of the coronavirus disease 2019 (COVID-19) epidemic has placed patients with pre-existing conditions at risk of severe morbidity and mortality. The present study investigated the clinical characteristics and outcomes of patients with severe COVID-19 and chronic obstructive pulmonary disease (COPD). Material/Methods This study enrolled 336 consecutive patients with confirmed severe COVID-19, including 28 diagnosed with COPD, from January 20, 2020, to April 1, 2020. Demographic data, symptoms, laboratory values, comorbidities, and clinical results were measured and compared in survivors and non-survivors. Results Patients with severe COVID-19 and COPD were older than those without COPD. The proportions of men, of patients admitted to the intensive care unit (ICU) and of those requiring invasive ventilation were significantly higher in patients with than without COPD. Leukocyte and neutrophil counts, as well as the concentrations of NT-proBNP, hemoglobin, D-dimer, hsCRP, ferritin, IL-2R, TNF-α and procalcitonin were higher, whereas lymphocyte and monocyte counts were lower, in patients with than without COPD. Of the 28 patients with COPD, 22 (78.6%) died, a rate significantly higher than in patients without COPD (36.0%). A comparison of surviving and non-surviving patients with severe COVID-19 and COPD showed that those who died had a longer history of COPD, more fatigue, and a higher ICU occupancy rate, but a shorter average hospital stay, than those who survived. Conclusions COPD increases the risks of death and negative outcomes in patients with severe COVID-19.
Temperature-Dependent Functional Response of Harmonia axyridis (Coleoptera: Coccinellidae) on the Eggs of Spodoptera litura (Lepidoptera: Noctuidae) in Laboratory

Simple Summary Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae) is a notorious and polyphagous pest of several economically important agricultural crops. It is worldwide in distribution and primarily managed through typical dependence on insecticides, which resulted in health and the environmental challenges and selected for resistance development in S. litura field populations. Resistance caused chemical control failures and S. litura outbreaks around the world. This necessitated development of eco-friendly alternative approaches such as biological control. With this view, current study investigated the functional response of Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae) at various growth stages (i.e., 1st, 2nd, 3rd and 4th instars, and male and female stages) and temperatures (i.e., 15, 20, 25, 30 and 35 °C) against S. litura eggs to enable the recognition of efficient biocontrol stages that could be utilized to suppress S. litura populations. In our findings, egg consumption depended on the growth stage of the predator as well as temperature. All stages consumed S. litura eggs, but more promising stages with active egg consumption were the 4th instar and adults (male and female) typically at higher temperatures (25–35 °C). We conclude that these stages may be exploited to suppress S. litura populations in fields and greenhouses. Abstract Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae) is a major pest of several economically important crops with worldwide distribution. Use of insecticides is the principal strategy for its management, which has subsequently led to insecticide resistance and control failures. Functional response of Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae) at larval and adult stages was evaluated in this study, using S. litura eggs as the prey at various temperatures varying between 15 and 35 °C. Based on logistic model findings, linear parameters of various predatory stages of H. axyridis at various temperatures were significantly negative, which indicate a type II functional response. The theoretical maximum number (T/Th) of eggs consumed increased with increasing temperature across all predatory stages. According to the random predator equation, the coefficients of attack rate increased and that of handling time decreased as the temperature increased. The 4th instar and adult stages were superior candidates for biocontrol of the target prey, typically at higher temperatures. The maximum attack rate (0.546 ± 0.058 h−1) and lowest handling time (0.189 ± 0.004 h) were exhibited by the females at 30 and 35 °C, respectively, whereas these parameters were inferior for early instars. These findings clearly depict that the 4th instar and adult predators are efficient egg consumers and can serve as potential suppressors of S. litura field populations. The limitations of the predictions formulated by functional response trials are also discussed.