Miracle-dz/UniFAR-FTUs huggingface dataset:
CNNGRN: A Convolutional Neural Network-Based Method for Gene Regulatory Network Inference From Bulk Time-Series Expression Data

Gene regulatory networks (GRNs) participate in many biological processes, and reconstructing them plays an important role in systems biology. Although many advanced methods have been proposed for GRN reconstruction, their predictive performance is far from the ideal standard, so it is urgent to design a more effective method to reconstruct GRN. Moreover, most methods only consider the gene expression data, ignoring the network structure information contained in GRN. In this study, we propose a supervised model named CNNGRN, which infers GRN from bulk time-series expression data via convolutional neural network (CNN) model, with a more informative feature. Bulk time series gene expression data imply the intricate regulatory associations between genes, and the network structure feature of ground-truth GRN contains rich neighbor information. Hence, CNNGRN integrates the above two features as model inputs. In addition, CNN is adopted to extract intricate features of genes and infer the potential associations between regulators and target genes. Moreover, feature importance visualization experiments are implemented to seek the key features. Experimental results show that CNNGRN achieved competitive performance on benchmark datasets compared to the state-of-the-art computational methods. Finally, hub genes identified based on CNNGRN have been confirmed to be involved in biological processes through literature.
The antianginal ranolazine fails to improve glycaemia in obese liver‐specific pyruvate dehydrogenase deficient male mice

Recent studies have demonstrated that stimulating pyruvate dehydrogenase (PDH, gene Pdha1), the rate‐limiting enzyme of glucose oxidation, can reverse obesity‐induced non‐alcoholic fatty liver disease (NAFLD), which can be achieved via treatment with the antianginal ranolazine. Accordingly, our aim was to determine whether ranolazine's ability to mitigate obesity‐induced NAFLD and hyperglycaemia requires increases in hepatic PDH activity.
Metamnemonic predictions of lineup identification

ABSTRACT After a crime is committed, investigators may query witnesses about whether they believe they will be to identify the perpetrator. However, we know little about how such metacognitive judgments are related to performance on a subsequent lineup identification task. The extant research has found the strength of this relationship to be small or nonexistent, which conflicts with the large body of literature indicating a moderate relationship between predictions and performance on memory tasks. In Studies 1–3, we induce variation in encoding quality by having participants watch a mock crime video with either low, medium, or high exposure quality, and then assess their future lineup performance. Calibration analysis revealed that assessments of future lineup performance were predictive of identification accuracy. This relationship was driven primarily by poor performance following low assessments. Studies 4 and 5 showed that these predictions are not based on a witness’s evaluation of their encoding experience, nor on a contemporaneous assessment of memory strength. These results reinforce the argument that variation in memory quality is needed to obtain reliable relationships between predictions and performance. An unexpected finding is that witnesses who made a prediction shortly after encoding evinced superior memory compared to those who made a prediction later.
Double-stemmed and split structural variants of fluorescent RNA Mango aptamers

Aptamers with fluorogenic ligands are emerging as useful tools to quantify and track RNA molecules. The RNA Mango family of aptamers have a useful combination of tight ligand binding, bright fluorescence, and small size. However, the simple structure of these aptamers, with a single base-paired stem capped by a G-quadruplex, can limit the sequence and structural modifications needed for many use-inspired designs. Here we report new structural variants of RNA Mango that have two base-paired stems attached to the quadruplex. Fluorescence saturation analysis of one of the double-stemmed constructs showed a maximum fluorescence that is ∼75% brighter than the original single-stemmed Mango I. A small number of mutations to nucleotides in the tetraloop-like linker of the second stem were subsequently analyzed. The effect of these mutations on the affinity and fluorescence suggested that the nucleobases of the second linker do not directly interact with the fluorogenic ligand (TO1-biotin), but may instead induce higher fluorescence by indirectly altering the ligand properties in the bound state. The effects of the mutations in this second tetraloop-like linker indicate the potential of this second stem for rational design and reselection experiments. Additionally, we demonstrated that a bimolecular mango designed by splitting the double-stemmed Mango can function when two RNA molecules are cotranscribed from different DNA templates in a single in vitro transcription. This bimolecular Mango has potential application in detecting RNA–RNA interactions. Together, these constructs expand the designability of the Mango aptamers to facilitate future applications of RNA imaging.
Breaking the 80:20 rule in health research using large administrative data sets

Objective: To explore the application of online analytic processing (OLAP) to improve the efficiency of analytics using large administrative health data sets. Methods: 18 years of administrative health data (1994/95 to 2012/13) were obtained from the Alberta Ministry of Health in Canada. The data sets included hospitalization, ambulatory care and practitioner claims data. Reference files were obtained that provided information including patient demographics, resident postal code, facility, and provider details. Population counts and projections for each year, sex, age were included for rate calculations. These sources were used to develop a data cube using OLAP tools. Results: Time required for analyses was reduced to 5% of that required when comparing run-time for simple queries that did not require linkage of data sets. The data cube negated the need for many intermediary steps for data extraction and analyses for research activities. Conventional methods required over 250 GB of server space for multiple analytic subsets, compared to only 10.3 GB for the data cube. Conclusions: Cross-training in information technology and health analytics is recommended to provide capacity to better leverage OLAP tools which are available with many common applications.
Characteristics and prognostic impact of IDH mutations in AML: a COG, SWOG, and ECOG analysis

Key Points • IDH mutation did not abrogate the favorable prognostic impact of NPM1 mutation in AML for patients aged <60 years. • Patients with IDH-mutated AML without cooccurring NPM1 or triple-mutated IDH/NPM1/DNMT3A or IDH/NPM1/FLT3-ITD AML had inferior outcomes.
Biopsychosocial Model of Traumatic Stress Symptoms in Women Experiencing Homelessness: A Qualitative Descriptive Study

Abstract Trauma is nearly ubiquitous among women experiencing homelessness (WEH). WEH develop post-traumatic stress disorder (PTSD) at rates far exceeding the general population. The consequences of untreated PTSD can cascade, exacerbating existing physical, mental, and social health inequities, placing this population at risk for disproportionate biopsychosocial health adversity. Despite the outsized impact of PTSD, WEH are less likely to access or receive appropriate trauma-focused services. Understanding the unique and intersecting factors that contribute to the disproportionate PTSD toll on WEH may elucidate risk and protective factors, as well as possible intervention pathways to address the disparate trauma burden. This study employed a qualitative descriptive approach to develop understanding of the determinants of trauma risk, exposure, and outcomes among WEH. Semi-structured interviews were completed with 10 WEH, six shelter staff, four mental health professionals. Six deductively biopsychosocial model-derived themes were identified, alongside supporting categories. Themes/categories highlighted the role of biological, psychological, and socio-environmental determinants in shaping risk for and actualization of traumatic events and adverse outcomes. Trauma played an outsized role in shaping the health of WEH participants in this study, and the need for and interest in tailored trauma screening, treatment, psychoeducation options was highlighted. Recursive relationships between biopsychosocial determinants and trauma impact were identified. Participants emphasized population tailored trauma-focused interventions, specifically brief co-designed and community partner implemented interventions that address substance use behaviors, while leveraging the strengths of WEH. Addressing the marked trauma burden in WEH shows promise in promoting measurable biopsychosocial health improvements in this resilient yet overlooked population.
Made to measure: an introduction to quantifying microscopy data in the life sciences.

Images are at the core of most modern biological experiments and are used as a major source of quantitative information. Numerous algorithms are available to process images and make them more amenable to be measured. Yet the nature of the quantitative output that is useful for a given biological experiment is uniquely dependent upon the question being investigated. Here, we discuss the 3 main types of information that can be extracted from microscopy data: intensity, morphology, and object counts or categorical labels. For each, we describe where they come from, how they can be measured, and what may affect the relevance of these measurements in downstream data analysis. Acknowledging that what makes a measurement "good" is ultimately down to the biological question being investigated, this review aims at providing readers with a toolkit to challenge how they quantify their own data and be critical of conclusions drawn from quantitative bioimage analysis experiments. This article is protected by copyright. All rights reserved.
Rates of Antidepressant, Anxiolytic, and ADHD Medication Use Among Patients Undergoing ESS

Patients with chronic rhinosinusitis (CRS) are estimated to have psychiatric comorbidity at a higher rate than the general population; however, self-report of depression diagnoses or symptoms often underestimates true prevalence in many populations. In the present study, a cohort of 2279 patients undergoing endoscopic sinus surgery (ESS) were matched to an equal number of non-CRS control subjects by age, sex, race and health status. Overall, the rate of antidepressant/anxiolytic utilization among ESS patients was 22.1%versus 11.3% for controls (P < .001, OR = 2.23, 95% CI 1.90-2.63). The rate of ADHD medication utilization among ESS patients was 3.6%versus 2.0% for controls (P = .001, OR = 1.85, 95% CI 1.28-2.68). This study suggests that patients undergoing ESS exhibit significantly higher rates of antidepressant and ADHD medication utilization relative to a matched control population.
Attitudes toward children: Distinguishing affection and stress.

BACKGROUND Adults' views and behaviors toward children can vary from being supportive to shockingly abusive, and there are significant unanswered questions about the psychological factors underpinning this variability. OBJECTIVE The present research examined the content of adults' attitudes toward children to address these questions. METHOD Ten studies (N = 4702) identified the factor structure of adults' descriptions of babies, toddlers, and school-age children and examined how the resulting factors related to a range of external variables. RESULTS Two factors emerged-affection toward children and stress elicited by them-and this factor structure was invariant across the United Kingdom, the United States, and South Africa. Affection uniquely captures emotional approach tendencies, concern for others, and broad positivity in evaluations, experiences, motivations, and donation behavior. Stress relates to emotional instability, emotional avoidance, and concern about disruptions to a self-oriented, structured life. The factors also predict distinct experiences in a challenging situation-home-parenting during COVID-19 lockdown-with affection explaining greater enjoyment and stress explaining greater perceived difficulty. Affection further predicts mentally visualizing children as pleasant and confident, whereas stress predicts mentally visualizing children as less innocent. CONCLUSIONS These findings offer fundamental new insights about social cognitive processes in adults that impact adult-child relationships and children's well-being.
Revisiting the meaning and the source of health‐related constructs and their applications in neurodisability

The aim of this review is to revisit the meaning of common concepts and frameworks promoted to capture subjective outcomes of patients, the content of their corresponding measurements, and the preferred sources of the information of interest. This is important because conceptualizations of ‘health’ and the subject evaluations thereof continue to evolve. Related but distinct concepts like quality of life (QoL), health‐related QoL (HRQoL), functional status, health status, and well‐being are often used indiscriminately to assess clinical impacts of interventions and to influence decisions about patient care and policymaking. The discussion addresses and illustrates the following issues: (1) the required features of effective and valid health‐related concepts; (2) understanding underlying factors that often create confusion about QoL and HRQoL; and (3) how these concepts provide insight into, and promote, health in the context of populations with neurodisability. The hope is to illustrate how a combination of a clear research question, a hypothesis, conceptualization of the required outcomes, and operational definitions of the domains and items of interest, including item mapping, can help to achieve robust methodology and valid findings beyond the required psychometric properties.
Cellular heterogeneity in the 16HBE14o − airway epithelial line impacts biological readouts

The airway epithelial cell line, 16HBE14o−, is an important cell model for studying airway disease. 16HBE14o− cells were originally generated from primary human bronchial epithelial cells by SV40‐mediated immortalization, a process that is associated with genomic instability through long‐term culture. Here, we explore the heterogeneity of these cells, with respect to expression of the cystic fibrosis transmembrane conductance regulator (CFTR) transcript and protein. We isolate clones of 16HBE14o− with stably higher and lower levels of CFTR in comparison to bulk 16HBE14o−, designated CFTRhigh and CFTRlow. Detailed characterization of the CFTR locus in these clones by ATAC‐seq and 4C‐seq showed open chromatin profiles and higher order chromatin structure that correlate with CFTR expression levels. Transcriptomic profiling of CFTRhigh and CFTRlow cells showed that the CFTRhigh cells had an elevated inflammatory/innate immune response phenotype. These results encourage caution in interpreting functional data from clonal lines of 16HBE14o− cells, generated after genomic or other manipulations.
Recent progress of organ-on-a-chip towards cardiovascular diseases: advanced design, fabrication, and applications

Cardiovascular diseases (CVDs) are a major cause of death worldwide, leading to increased medical care costs. To turn the scale, it is essential to acquire a more in-depth and comprehensive understanding of CVDs and thus formulate more efficient and reliable treatments. Over the last decade, tremendous effort has been made to develop microfluidic systems to recapitulate native cardiovascular environments because of their unique advantages over conventional 2D culture systems and animal models such as high reproductivity, physiological relevance, and good controllability. These novel microfluidic systems could be extensively adopted for natural organ simulation, disease modeling, drug screening, disease diagnosis and therapy. Here, a brief review of the innovative designs of microfluidic devices for CVDs research is presented, with specific discussions on material selection, critical physiological and physical considerations. In addition, we elaborate on various biomedical applications of these microfluidic systems such as blood-vessel-on-a-chip and heart-on-a-chip, which are conducive to the investigation of the underlying mechanisms of CVDs. This review also provides systematic guidance on the construction of next-generation microfluidic systems for the diagnosis and treatment of CVDs. Finally, the challenges and future directions in this field are highlighted and discussed.
High frequency of Voltage-gated sodium channel (VGSC) gene mutations in Aedes albopictus (Diptera: Culicidae) suggest rapid insecticide resistance evolution in Shanghai, China

Background Dengue fever is an infectious disease that is imported into Shanghai, China and requires prevention and control measures. Controlling the vector Aedes albopictus through insecticide use is a key approach to dengue control. However, the rapid evolution of insecticide resistance in Ae. albopictus has raised concerns about the failure of dengue control efforts. Knockdown resistance (kdr) caused by point mutations in the voltage-gated sodium channel (VGSC) gene is a primary mechanism of pyrethroid resistance. In this study, we investigated the kdr mutations of Ae. albopictus in Shanghai and evaluated the trend in its evolution. Methodology/principal findings We collected 17 populations of Ae. albopictus from 15 districts in Shanghai in 2020, extracted genomic DNA from individual mosquitoes, and amplified Domain II, III, and IV in VGSC using PCR. Following sequencing, we obtained 658 VGSC sequences. We detected the nonsynonymous mutations V1016G, I1532T, and F1534S/C/I, among which V1016G and F1534C/I were reported in Shanghai for the first time and F1534I was a novel mutant allele in Ae. albopictus. The overall mutation frequency was 84.65%, with individual mutation frequencies ranging from 46.81% to 100%, excluding the Fengxian District population, which had a frequency of 0%. The V1016G and I1532T mutation types accounted for 7.14% and 3.42%, respectively. The mutant allele at codon 1534 accounted for 63.98% of all mutations, including TCC/S (62.77%), TGC/C (1.06%), and ATC/I (0.15%). We identified and classified five intron types in Domain III by length, including A (83 bp, 12.07%), B (68 bp, 87.30%), C (80 bp, 0.16%), D (72 bp, 0.16%), and E (70 bp, 0.31%). Individuals with intron B had a significant mutation tendency at codon 1534 relative to intron A (chi-square test, p < 0.0001). We found no correlation between mutation frequency and the amount of pyrethroid used (Pearson correlation, p = 0.4755). Conclusions/significance In recent years, kdr mutations in the Ae. albopictus population in Shanghai have rapidly evolved, as evidenced by an increase in mutation types and significantly increased mutation frequency. The F1534I/ATC mutant allele was found to be a novel mutation, F1534C/TGC was reported for the first time in Shanghai, and intron B in Domain III was significantly associated with mutation frequency at codon 1534. Continuous monitoring of resistance changes and strict regulation of insecticide use are required.
The Dual Control Model of Sexual Response: A Scoping Review, 2009–2022

ABSTRACT The Dual Control Model proposes that sexual arousal and related processes are dependent on the balance between sexual excitation and sexual inhibition, and that individuals vary in their propensity for these processes. This scoping review provides an overview and discussion of the questionnaires used to measure the propensities for sexual excitation and inhibition, their translation and validation in other languages, and their application in empirical research on topics ranging from sexual desire and arousal, sexual (dys)function, sexual risk taking, asexuality, hypersexuality, and sexual aggression. A total of 152 papers, published between 2009 and 2022 and identified using online databases, were included in this review. The findings, consistent with those reviewed by Bancroft et al. (2009), suggest that sexual excitation is particularly relevant to sexual desire and responsivity and predictive of asexuality and hypersexuality. Sexual inhibition plays a role in sexual dysfunction. sexual risk taking, and sexual aggression, although often in interaction with sexual excitation. Suggestions for the further development of the model and for future studies are discussed.
Feasibility, Client Engagement, and Person-Centeredness of Telehealth Goal Setting and Goal Management Intervention

Telehealth-delivered goal setting and goal management may guide occupational therapists (OTs) to form a strong foundation of active client engagement and personally meaningful goals on which to base effective telehealth intervention. The objective was to determine the feasibility of a goal setting and goal management system, called MyGoals, delivered through telehealth and hybrid formats for adults with chronic conditions. This was a mixed-method feasibility study. The Credibility and Expectancy Questionnaire and Client Satisfaction Questionnaire–8 measured credibility, expectancy, and satisfaction. The Goals and Participation subscales of the Client-Centredness of Goal Setting Scale measured engagement and person-centeredness. Targeted self-ratings measured change objective achievement. Individuals’ perspectives on MyGoals’ feasibility were further explored in semi-structured interviews. In telehealth (N = 8) and hybrid (N = 9) groups, MyGoals had good credibility (M = 25.5, SD = 1.9), expectancy (M = 23.4, SD = 3.3), satisfaction (M = 31.3, SD = 0.9), client engagement (M = 29.4, SD = 1.5), person-centeredness (M = 19.5, SD = 1.2), and change objective achievement (M = 9.6, SD = 0.2). The interview data suggested improvements for MyGoals. In conclusion, telehealth delivery of MyGoals is feasible to support goal setting and goal management for adults with chronic conditions.
CRISPR-based assays for point of need detection and subtyping of influenza

The high disease burden of influenza virus poses a significant threat to human health and requires better methods to rapidly detect its many circulating species, subtypes, and variants. No current diagnostic technology meets the combined critical needs for a rapid, sensitive, specific, and cost-effective method for point-of-need (PON) influenza detection and discrimination with minimal equipment requirements. Here, we introduce such a method using SHINE (Streamlined Highlighting of Infections to Navigate Epidemics), a CRISPR-based RNA detection platform. We develop and validate four SHINE assays for the detection and differentiation of clinically relevant influenza species (A and B) and subtypes (H1N1 and H3N2). These optimized assays achieve 100% concordance with reverse-transcriptase real-time polymerase chain reaction (RT-qPCR) when tested on clinical samples. We also created duplex Cas12/Cas13 SHINE assays to simultaneously detect two targets and demonstrate its use in discriminating two alleles of an oseltamivir resistance (H275Y) mutation as well as to detect influenza A and human RNAse P, as a built-in internal control. Our assays have the potential to expand influenza detection outside of clinical laboratories in order to enhance influenza diagnosis and surveillance.