Miracle-dz/UniFAR-FTUs huggingface dataset:
Vibrio alginolyticus Survives From Ofloxacin Stress by Metabolic Adjustment

Antibiotic-resistant Vibrio alginolyticus becomes a worldwide challenge threatening both human health and food safety. The approach in managing such infection is largely absent, despite the fact that the mechanisms of antibiotic resistance have been extensively investigated. Metabolic modulation has been documented to be a novel approach in improving antibiotic efficacy. In this study, we characterize the metabolic signature of V. alginolyticus exposed to 0.3 or 0.5 μg/ml of ofloxacin (OFX). By profiling the metabolome, we find that bacteria treated by the two different concentrations of OFX generate different metabolic signatures. While a part of these metabolites was shared by both groups, the other metabolites represent their own signatures. The pathway enrichment analysis demonstrates that the pyruvate cycle is disrupted in the bacteria treated by the 0.3 μg/ml OFX as compared to those by the 0.5 μg/ml. Importantly, the disruption of pyruvate cycle confers the capability of bacteria to survive under 0.5 μg/ml of antibiotic stress. Further analysis identifies that the fatty acid biosynthesis is elevated in bacteria treated by 0.3 μg/ml OFX, and inhibition on fatty acid completely prevents the bacteria from survival even under such dose of antibiotic stress. Our study suggests that bacteria adapt to antibiotic stress by modulating the metabolic flux for survival, which could be targeted to increase antibiotic efficacy.
Novel Loss-of-Function Mutations in NPR2 Cause Acromesomelic Dysplasia, Maroteaux Type

Acromesomelic dysplasia, Maroteaux type (AMDM) is a rare skeletal dysplasia characterized by severe disproportionate short stature, short hands and feet, normal intelligence, and facial dysmorphism. Homozygous or compound heterozygous mutations in the natriuretic peptide receptor 2 (NPR2) gene produce growth-restricted phenotypes. The current study was designed to identify and characterize NPR2 loss-of-function mutations in patients with AMDM and to explore therapeutic responses to recombinant growth hormone (rhGH). NPR2 was sequenced in two Chinese patients with AMDM via next generation sequencing, and in silico structural analysis or transcript analysis of two novel variants was performed to examine putative protein changes. rhGH treatment was started for patient 1. Three NPR2 mutations were identified in two unrelated cases: two compound heterozygous mutations c.1112G>A p.(Arg371Gln) and c.2887+2T>C in patient 1 and a homozygous mutation c.329G>A p.(Arg110His) in patient 2, yielding distinct phenotypes. RNA extracted from peripheral blood cells of patient 1 showed alternatively spliced transcripts not present in control cells. Homology modeling analyses suggested that the c.1112G>A p.(Arg371Gln) mutation disrupted the binding of NPR-B homodimer to its ligand (C-type natriuretic peptide) in the extracellular domain as a result of global allosteric effects on homodimer formation. Thus, c.2887+2T>C and c.1112G>A p.(Arg371Gln) in NPR2 were loss-of-function mutations. Furthermore, rhGH therapy in patient 1 increased the patient’s height by 0.6SDS over 15 months without adversely affecting the trunk-leg proportion. The short-term growth-promoting effect was equivalent to that reported for idiopathic short stature. Overall, our findings broadened the genotypic spectrum of NPR2 mutations in individuals with AMDM and provided insights into the efficacy of rhGH in these patients.
Device Classification for Industrial Control Systems Using Predicted Traffic Features

To achieve a secure interconnected Industrial Control System (ICS) architecture, security practitioners depend on accurate identification of network host behavior. However, accurate machine learning based host identification methods depends on the availability of significant quantities of network traffic data, which can be difficult to obtain due to system constraints such as network security, data confidentiality, and physical location. In this work, we propose a network traffic feature prediction method based on a generative model, which achieves high host identification accuracy. Furthermore, we develop a joint training algorithm to improve host identification performance compared to separate training of the generative model and the classifier responsible for host identification.
Exploring the Coordination of Cardiac Ion Channels With Action Potential Clamp Technique

The patch clamp technique underwent continual advancement and developed numerous variants in cardiac electrophysiology since its introduction in the late 1970s. In the beginning, the capability of the technique was limited to recording one single current from one cell stimulated with a rectangular command pulse. Since that time, the technique has been extended to record multiple currents under various command pulses including action potential. The current review summarizes the development of the patch clamp technique in cardiac electrophysiology with special focus on the potential applications in integrative physiology.
Effects of Lifestyle Factors on Cognition in Minority Population of Older Adults: A Review

The onset of dementia and Alzheimer's disease (AD) is projected to expand over the next several decades in the United States as the population ages. However, the cognitive health burden is not equally distributed among the population, as Hispanics and African Americans are at higher risk of AD when compared with Non-Hispanic Whites. There is some evidence to indicate that cognitive decline may be associated with lifestyle factors and that interventions in these domains may prevent or delay this decline. These lifestyle factors include social engagement, physical activity, both aerobic and strength training, dietary intake, sleep and stress. This review summarizes, in general, what is known about the relationship between risk factors and cognition and, in particular what is known about this relationship in minority populations. The results show that the relationship between these risk factors and cognitive decline is stronger for some of the factors such as physical activity and dietary intake and weaker for the other factors depending on what is measured and in what populations. It does appear, however, that the studies in minority populations is limited and warrants more targeted research and interventions.
Prediction of Long-Term Recovery From Disability Using Hemoglobin-Based Models: Results From a Cohort of 1,392 Patients Undergoing Spine Surgery

Hemoglobin and its associated blood values are important laboratory biomarkers that mirror the strength of constitution of patients undergoing spine surgery. Along with the clinical determinants available during the preadmission visit, it is important to explore their potential for predicting clinical success from the patient's perspective in order to make the pre-admission visit more patient-centered. We analyzed data from 1,392 patients with spine deformity, disc disease, or spondylolisthesis enrolled between 2016 and 2019 in our institutional Spine Registry. Patient-reported outcome measure at 17 months after surgery was referred to the Oswestry disability index. High preoperative hemoglobin was found to be the strongest biochemical determinant of clinical success along with high red blood cells count, while low baseline disability, prolonged hospitalization, and long surgical times were associated with poor recovery. The neural network model of these predictors showed a fair diagnostic performance, having an area under the curve of 0.726 and a sensitivity of 86.79%. However, the specificity of the model was 15.15%, thus providing to be unreliable in forecasting poor patient-reported outcomes. In conclusion, preoperative hemoglobin may be one of the key biomarkers on which to build appropriate predictive models of long-term recovery after spine surgery, but it is necessary to include multidimensional variables in the models to increase the reliability at the patient's level.
Multi-Omics Investigations Revealed Underlying Molecular Mechanisms Associated With Tumor Stiffness and Identified Sunitinib as a Potential Therapy for Reducing Stiffness in Pituitary Adenomas

Purpose: Pituitary adenomas (PAs) are the second most common intracranial neoplasms. Total surgical resection was extremely important for curing PAs, whereas tumor stiffness has gradually become the most critical factor affecting the resection rate in PAs. We aimed to investigate the molecular mechanisms of tumor stiffening and explore novel medications to reduce stiffness for improving surgical remission rates in PA patients. Methods: RNA sequencing, whole-genome bisulfite sequencing, and whole exome sequencing were applied to identify transcriptomic, epigenomic, and genomic underpinnings among 11 soft and 11 stiff PA samples surgically resected from patients at Peking Union Medical College Hospital (PUMCH). GH3 cell line and xenograft PA model was used to demonstrate therapeutic effect of sunitinib, and atomic force microscopy (AFM) was used to detect the stiffness of tumors. Results: Tumor microenvironment analyses and immunofluorescence staining indicated endothelial cells (ECs) and cancer-associated fibroblasts (CAFs) were more abundant in stiff PAs. Weighted gene coexpression network analysis identified the most critical stiffness-related gene (SRG) module, which was highly correlated with stiff phenotype, ECs and CAFs. Functional annotations suggested SRGs might regulate PA stiffness by regulating the development, differentiation, and apoptosis of ECs and CAFs and related molecular pathways. Aberrant DNA methylation and m6A RNA modifications were investigated to play crucial roles in regulating PA stiffness. Somatic mutation analysis revealed increased intratumoral heterogeneity and decreased response to immunotherapy in stiff tumors. Connectivity Map analysis of SRGs and pRRophetic algorithm based on drug sensitivity data of cancer cell lines finally determine sunitinib as a promising agent targeting stiff tumors. Sunitinib inhibited PA growth in vitro and in vivo, and also reduced tumor stiffness in xenograft PA models detected by AFM. Conclusion: This is the first study investigating the underlying mechanisms contributing to the stiffening of PAs, and providing novel insights into medication therapy for stiff PAs.
Evaluating Changes in Experimentation, Critical Thinking, and Sense of Wonder in Participants of Science North’s In-School Outreach Programs

The aim of this study was to evaluate and report on the impact of an in-school science outreach program on children’s self-reported science knowledge, engagement, and skills through a case study of the Science North in-school outreach program “Mission to Mars. ” A logic model method was used to outline the specific inputs, outputs, and measurable outcomes of the program. The program outcomes evaluated in this study were (1) experimentation skills, (2) critical thinking skills, and (3) sense of wonder. Results from pre-post surveys demonstrated that participants had increased program topic knowledge. Students self-reported positive emotions toward science more frequently following exposure to the program. Students’ sense of wonder toward science and toward space also increased post-program. This increase in positive emotion toward science could, in the short-term, increase student motivation toward science, which could lead to lasting interests in science in the long-term. Only a small number of students reported an increase in experimentation and critical thinking skills post-program. These skills take time to develop, and the single short-term program evaluated in this study may not have given students enough exposure to these skills for them to experience and show a noticeable change. The results of this study can provide informal science institutions like science centers with important insights into the potential learning impact of their in-school outreach programs, and can be used to improve current and future programs. Other organizations with in-school science outreach programs can benefit from using the methodology in this study to evaluate their programs, as this research includes a combination of innovative data collection methods such as concept maps to determine what students associate with the word “science,” and the use of an emoji scale to capture student emotions toward science. From a larger perspective, this study evaluating the impacts of in-school science outreach could demonstrate the potential benefits and outcomes of this unique area of informal learning, further solidifying the importance of incorporating these inquiry-based programs into classrooms.
Evaluation of Intracranial Hypertension in Patients With Hypertensive Intracerebral Hemorrhage Using Texture Analysis

Purpose Texture analysis based on clinical images had been widely used in neurological diseases. This study aimed to achieve depth information of computed tomography (CT) images by texture analysis and to establish a model for noninvasive evaluation of intracranial pressure (ICP) in patients with hypertensive intracerebral hemorrhage (HICH). Methods Forty-seven patients with HICH were selected. Related CT images and ICP value were collected. The morphological features of hematoma volume, midline shift, and ventriculocranial ratio were measured. Forty textural features were extracted from regions of interest. Four models were established to predict intracranial hypertension with morphological features, textural features of anterior horn, textural features of temporal lobe, and textural features of posterior horn. Results Model of posterior horn had the highest ability to predict intracranial hypertension (AUC = 0.90, F1 score = 0.72), followed by model of anterior horn (AUC = 0.70, F1 score = 0.53) and model of temporal lobe (AUC = 0.70, F1 score = 0.58), and model of morphological features displayed the worst performance (AUC = 0.42, F1 score = 0.38). Conclusion Texture analysis can realize interpretation of CT images in depth, which has great potential in noninvasive evaluation of intracranial hypertension.
Editorial: Multi-Disciplinary Approaches to Plant Responses to Climate Change

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand, 2 Integrative Computational Bioscience Center, Mahidol University, Bangkok, Thailand, 3 Systems Biology of Diseases Research Unit, Faculty of Science, Mahidol University, Bangkok, Thailand, UMR5004 Biochimie et Physiologie Moléculaire des Plantes, Montpellier, France, Department of Mathematical Sciences, University of Liverpool, Liverpool, United Kingdom, 6 School of Biology and
A Year Through the COVID-19 Pandemic: Deleterious Impact of Hormonal Contraception on Psychological Distress in Women

Background Women are more at risk than men of suffering from psychological distress during disease outbreaks. Interestingly, no biological factors have been studied to explain this disparity in such contexts. Sex hormone variations induced by hormonal contraceptives (HC) have been associated with mental health vulnerabilities. However, most studies have examined current effects of HC without considering whether a chronic modulation of sex hormone levels could induce long-lasting effects that persist after HC cessation. Objectives To date, the role of HC on psychological health in women during a disease outbreak is still unknown. We aimed to investigate both current and long-term effects of HC on psychological distress throughout the COVID-19 pandemic. Method At four time points during the COVID-19 pandemic (June 2020, September 2020, December 2020, March 2021), we collected self-reported data on psychological distress, assessing symptoms of post-traumatic stress [via the Impact of Event Scale-Revised (IES-R)], symptoms of depression, anxiety, and stress [via the Depression Anxiety Stress Scales (DASS-21)]. Linear mixed models were first used to compare men (n = 49), naturally cycling women (n = 73), and women using HC (n = 32) across time. To examine long-lasting effects of HC, exploratory analyses were restricted to women, comparing current HC users (n = 32), past users (n = 56), and never users (n = 17). Results The first model revealed that women taking HC reported stable post-traumatic stress symptoms across time, compared to naturally cycling women and men who showed a significant decrease from T1 to T2. HC users also reported greater DASS-21 total scores over time. Moreover, HC users reported higher stress and anxiety symptoms than men. In the second model, results showed that past HC users had similar anxiety levels as current HC users. These two groups reported significantly more anxiety symptoms than never users. Conclusion HC users report increased distress during the pandemic relative to naturally cycling women and men. Our results also suggest a long-lasting effect of HC intake, highlighting the importance of considering both the current use of HC and its history. This could provide some insight into potential avenues for explaining why some women are prone to higher psychological distress than men.
Exploring the Change of Host and Microorganism in Chronic Obstructive Pulmonary Disease Patients Based on Metagenomic and Metatranscriptomic Sequencing

Background Chronic obstructive pulmonary disease (COPD) is a universal respiratory disease resulting from the complex interactions between genes and environmental conditions. The process of COPD is deteriorated by repeated episodes of exacerbations, which are the primary reason for COPD-related morbidity and mortality. Bacterial pathogens are commonly identified in patients’ respiratory tracts both in the stable state and during acute exacerbations, with significant changes in the prevalence of airway bacteria occurring during acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Therefore, the changes in microbial composition and host inflammatory responses will be necessary to investigate the mechanistic link between the airway microbiome and chronic pulmonary inflammation in COPD patients. Methods We performed metatranscriptomic and metagenomic sequencing on sputum samples for twelve AECOPD patients before treatment and for four of them stable COPD (stabilization of AECOPD patients after treatment). Sequencing reads were classified by Kraken2, and the host gene expression was analyzed by Hisat2 and HTseq. The correlation between genes was obtained by the Spearman correlation coefficient. Mann–Whitney U-test was applied to identify microbes that exhibit significantly different distribution in two groups. Results At the phyla level, the top 5 dominant phyla were Firmicutes, Actinobacteria, Proteobacteria, Bacteroidetes, and Fusobacteria. The proportion of dominant gates in metagenomic data was similar in metatranscriptomic data. There were significant differences in the abundance of specific microorganisms at the class level between the two methods. No significant difference between AECOPD and stable COPD was found. However, the different expression levels of 5 host genes were significantly increased in stable COPD and were involved in immune response and inflammatory pathways, which were associated with macrophages. Conclusion Our study may provide a clue to investigate the mechanism of COPD and potential biomarkers in clinical diagnosis and treatment.
Association of Organochlorine Pesticides With Genetic Markers of Endoplasmic Reticulum Stress in Type 2 Diabetes Mellitus: A Case–Control Study Among the North-Indian Population

Background Organochlorine pesticides (OCPs) have been long linked to type 2 diabetes mellitus (T2DM); however, this relation at the molecular level has not been explored yet. Endoplasmic reticulum (ER) stress and pro-inflammatory pathways are considered vital ones in the pathogenesis of T2DM. We aimed to investigate the existence of any association between OCPs, ER stress, and pro-inflammatory pathways in subjects with known T2DM. Methods Seventy subjects each with T2DM and normal glucose tolerance were recruited from the surgery department. Their visceral adipose tissue was collected intraoperatively. OCP concentration, ER stress, and pro-inflammatory markers were analyzed and compared between two study groups. Results We found 18 OCPs and their metabolites in visceral adipose tissue samples of study participants. The levels of δ-HCH, heptachlor, endrin, and p,p′DDT were significantly higher in the T2DM group and were also positively correlated with fasting and postprandial plasma glucose levels (p < 0.01). We observed a positive association of δ-HCH (p < 0.01), heptachlor (p < 0.05), and endrin (p < 0.05) with central adiposity and ER stress markers. However, we failed to establish the correlation of OCPs with any of the pro-inflammatory markers. Conclusion The existence and simultaneous complex correlation of OCPs with ER stress may explain their role in the pathogenesis of T2DM, revealing the persistence of the gene–environment interaction in the etiology of T2DM.
Mediation Effects of IL-1β and IL-18 on the Association Between Vitamin D Levels and Mild Cognitive Impairment Among Chinese Older Adults: A Case–Control Study in Taiyuan, China

Objective Mild cognitive impairment (MCI) is a common, chronic, and complex disease in the elderly, which is often influenced by a variety of factors that include nutrition and inflammation. This study was undertaken to evaluate the mediation effects of inflammation on the association between vitamin D levels and MCI. Methods We explored the associations of inflammation and cognitive impairment related to 25(OH)D3 deficiency among 360 older people from the communities in China. Demographic characteristics, lifestyle, and health status were investigated by questionnaire, cognitive function was detected by MoCA, and plasma 25(OH)D3, interleukin-1β (IL-1β), and interleukin-18 (IL-18) were measured by ELISA. Spearman’s correlation analysis and logistic regression analysis were used to analyze the relationship among 25(OH)D3, IL-1β, and IL-18 in the MCI group and the control group and further to analyze the relationship between 25(OH)D3 and inflammatory factors in the MCI group. Finally, mediation analysis was performed to evaluate whether inflammation mediated the effect of 25(OH)D3 deficiency on cognitive impairment. Results There were lower plasma 25(OH)D3 concentration and higher IL-1β and IL-18 levels in the MCI group compared with the controls. The levels of 25(OH)D3 were positively correlated with the MoCA scores and scores of different domains; the levels of IL-1β and IL-18 were negatively correlated with them (p < 0.05). In multivariate logistic analysis, there were significant associations among 25(OH)D3, IL-1β, IL-18, and MCI after adjusted. Further analysis revealed the significant association between the subjects with VD deficiency and the highest quartile of IL-18 in MCI (OR = 4.066), not with IL-1β after adjusting the confounding variables in MCI group. Ultimately, mediation analysis suggested that IL-1β and IL-18 could explain 25.4 and 17.5% of effect of the risk of cognitive impairment related to 25(OH)D3 deficiency. Conclusion Our findings suggested that 25(OH)D3 deficiency could increase the risk of cognitive impairment by a mechanism partly involving inflammation. Therefore, vitamin D supplementation may improve or delay the decline in cognitive function caused by inflammation in the elderly.