Miracle-dz/UniFAR-FTUs huggingface dataset:
Detecting Moments of Stress from Measurements of Wearable Physiological Sensors

There is a rich repertoire of methods for stress detection using various physiological signals and algorithms. However, there is still a gap in research efforts moving from laboratory studies to real-world settings. A small number of research has verified when a physiological response is a reaction to an extrinsic stimulus of the participant’s environment in real-world settings. Typically, physiological signals are correlated with the spatial characteristics of the physical environment, supported by video records or interviews. The present research aims to bridge the gap between laboratory settings and real-world field studies by introducing a new algorithm that leverages the capabilities of wearable physiological sensors to detect moments of stress (MOS). We propose a rule-based algorithm based on galvanic skin response and skin temperature, combing empirical findings with expert knowledge to ensure transferability between laboratory settings and real-world field studies. To verify our algorithm, we carried out a laboratory experiment to create a “gold standard” of physiological responses to stressors. We validated the algorithm in real-world field studies using a mixed-method approach by spatially correlating the participant’s perceived stress, geo-located questionnaires, and the corresponding real-world situation from the video. Results show that the algorithm detects MOS with 84% accuracy, showing high correlations between measured (by wearable sensors), reported (by questionnaires and eDiary entries), and recorded (by video) stress events. The urban stressors that were identified in the real-world studies originate from traffic congestion, dangerous driving situations, and crowded areas such as tourist attractions. The presented research can enhance stress detection in real life and may thus foster a better understanding of circumstances that bring about physiological stress in humans.
Whole genome expression microarray reveals novel roles for Kif4 in monocyte/macrophage cells.

OBJECTIVE Kinesin superfamily member 4 (Kif4), a conventional kinesin, is a microtubule-dependent molecular motor. The active movement of Kif4 participates in several cellular functions, including DNA repair, mitosis, the transport of macromolecules, survival of neurons and even tumorigenesis and progression. However, the role of Kif4 in monocyte/macrophage cells has not been reported. Our work aimed to increase understanding and further investigations of Kif4 in monocyte/macrophage cells. MATERIALS AND METHODS RAW264.7 cells were transfected with Kif4 small interfering RNA (siRNA), and whole genome expression microarray analysis was employed to analyze gene expression after cells treatment with or without Kif4 siRNA. RESULTS Our data found multiple differentially expressed genes which were enriched in the top 5 biological processes about innate immune response, immune response, response to interferon-beta, immune system process and cellular response to interferon-beta. 23 most significant pathways had been identified and enriched pathways indicated enrichment in peroxisome, lysosome, fatty acid metabolism, cell adhesion molecules and so on. CONCLUSIONS Our work may help understand the roles of Kif4 in monocyte/macrophage cells and would give useful information on basic research and the function of monocyte/macrophage cells.
Overcoming adaptive therapy resistance in AML by targeting immune response pathways

Immune stress pathways drive resistance to FLT3 inhibition in FLT3-mutant AML, but a dual inhibitor of FLT3 and IRAK1/4 overcomes this resistance. Killing two pathways with one inhibitor Acute myeloid leukemia is an aggressive cancer that can be difficult to treat because of rapidly evolving therapeutic resistance. Melgar et al. focused on a subtype of acute myeloid leukemia characterized by mutations in a gene called FLT3. Although FLT3 inhibitors can target oncogenic signaling pathways in this cancer, their effects do not last. The authors identified a pathway involved in the innate immune stress response, whose activation promoted resistance to drugs targeting the FLT3 pathway, and then developed an inhibitor that targets both pathways at once. This multikinase inhibitor showed promising results in vitro and in animals, suggesting its potential for clinical translation. Targeted inhibitors to oncogenic kinases demonstrate encouraging clinical responses early in the treatment course; however, most patients will relapse because of target-dependent mechanisms that mitigate enzyme-inhibitor binding or through target-independent mechanisms, such as alternate activation of survival and proliferation pathways, known as adaptive resistance. Here, we describe mechanisms of adaptive resistance in FMS-like receptor tyrosine kinase (FLT3)–mutant acute myeloid leukemia (AML) by examining integrative in-cell kinase and gene regulatory network responses after oncogenic signaling blockade by FLT3 inhibitors (FLT3i). We identified activation of innate immune stress response pathways after treatment of FLT3-mutant AML cells with FLT3i and showed that innate immune pathway activation via the interleukin-1 receptor–associated kinase 1 and 4 (IRAK1/4) complex contributes to adaptive resistance in FLT3-mutant AML cells. To overcome this adaptive resistance mechanism, we developed a small molecule that simultaneously inhibits FLT3 and IRAK1/4 kinases. The multikinase FLT3-IRAK1/4 inhibitor eliminated adaptively resistant FLT3-mutant AML cells in vitro and in vivo and displayed superior efficacy as compared to current targeted FLT3 therapies. These findings uncover a polypharmacologic strategy for overcoming adaptive resistance to therapy in AML by targeting immune stress response pathways.
Glycylglycine plays critical roles in the proliferation of spermatogonial stem cells

Glial cell line-derived neurotrophic factor (GDNF) is critical for the proliferation of spermatogonial stem cells (SSCs), but the underlying mechanisms remain poorly understood. In this study, an unbiased metabolomic analysis was performed to examine the metabolic modifications in SSCs following GDNF deprivation, and 11 metabolites were observed to decrease while three increased. Of the 11 decreased metabolites identified, glycylglycine was observed to significantly rescue the proliferation of the impaired SSCs, while no such effect was observed by adding sorbitol. However, the expression of self-renewal genes, including B-cell CLL/lymphoma 6 member B, ETS variant 5, GDNF family receptor α1 and early growth response protein 4 remained unaltered following glycylglycine treatment. This finding suggests that although glycylglycine serves an important role in the proliferation of SSCs, it is not required for the self-renewal of SSCs.
Development of a physical employment standard for a branch of the UK military

Abstract A Physical Employment Standard (PES) was developed for the British Royal Air Force Regiment (RAF Regt). Twenty-nine RAF Regt personnel completed eight critical tasks wearing Combat Equipment Fighting Order (31.5 kg) while being monitored for physical and perceptual effort. A PES was developed using task simulations, measured on 61 incumbents. The resultant PES consists of: 1) a battlefield test involving task simulations: single lift and point-of-entry (psss/fail); timed elements (react to effective enemy fire and crawl) set at 95th performance percentile; casualty evacuation (CASEVAC) casualty drag and CASEVAC simulated stretcher carry completed without stopping. 2) a Multi Stage Fitness Test level 9.10 to assess aerobic fitness to complete a tactical advance to battle. The task-based PES should ensure RAF Regt personnel have a baseline level of fitness to perform and withstand the physical demands of critical tasks to at least a minimum acceptable standard. Practitioner summary: A Physical Employment Standard (PES) was developed for the British RAF Regiment by measuring the physiological demands of critical tasks on a representative cohort of incumbent personnel. A task-based PES should ensure that only those candidates, irrespective of gender, race or disability, with the necessary physical attributes to succeed in training and beyond, are selected.
The Mechanisms Involved in Morphine Addiction: An Overview

Opioid use disorder is classified as a chronic recurrent disease of the central nervous system (CNS) which leads to personality disorders, co-morbidities and premature death. It develops as a result of long-term administration of various abused substances, along with morphine. The pharmacological action of morphine is associated with its stimulation of opioid receptors. Opioid receptors are a group of G protein-coupled receptors and activation of these receptors by ligands induces significant molecular changes inside the cell, such as an inhibition of adenylate cyclase activity, activation of potassium channels and reductions of calcium conductance. Recent data indicate that other signalling pathways also may be involved in morphine activity. Among these are phospholipase C, mitogen-activated kinases (MAP kinases) or β-arrestin. The present review focuses on major mechanisms which currently are considered as essential in morphine activity and dependence and may be important for further studies.
First Insights into the Intrapuparial Development of Bactrocera dorsalis (Hendel): Application in Predicting Emergence Time for Tephritid Fly Control

Intrapuparial development is a special pattern of metamorphosis in cyclorrhaphous flies, in which the pupa forms in an opaque, barrel-like puparium. This has been well studied in forensic insects for age estimations. In this study, the intrapuparial development of a quarantine agricultural pest, Bactrocera dorsalis (Hendel), was studied under a constant temperature of 27 ± 1 °C and 70 ± 5% relative humidity. Results showed that intrapuparial development could be divided into five stages: Larval-pupal apolysis, cryptocephalic pupa, phanerocephalic pupa, pharate adult, and emergent adult. It lays a morphology-based foundation for molecular mechanism studies and enhances the understanding of the physiological basis for changes in intrapuparial development. More importantly, the chronology of intrapuparial development can be used to predict the emergence time of tephritid flies, indicating when to spray insecticides to control these phytophagous agricultural pests. This may be an effective approach to reduce the use of insecticides and slow down the evolution of insecticidal resistance.
Examining the distinctiveness of body image concerns in patients with anorexia nervosa and bulimia nervosa.

OBJECTIVE This study examined the distinctiveness of specific constructs of body-image disturbance in patients with anorexia nervosa (AN) and bulimia nervosa (BN). We compared weight/shape dissatisfaction, weight/shape overvaluation, weight/shape preoccupation, and fear of weight gain in patients with AN and BN and examined how each specific body-image construct relates to clinical measures within and between AN and BN. METHOD A clinical sample of 490 treatment-seeking patients diagnosed with DSM-5 AN (N = 310) or BN (N = 180) by clinicians using structured interviews in Portugal completed the Eating Disorder Examination-Questionnaire to assess body image and eating-disorder (ED) psychopathology. RESULTS Both within and between AN and BN, the four body-image constructs varied in their strengths of association among themselves, with ED psychopathology, and body mass index (BMI). Analyses revealed considerable variability in variance accounted for in clinical measures by body-image constructs. Body-image constructs predicted significant, albeit small, variance in BMI within BN (dissatisfaction, preoccupation significant) but not within AN. Body-image constructs predicted significant, albeit small, variance in the frequencies of binge eating and purging in AN (with preoccupation significant for both and fear for purging) but not within BN. Body-image constructs predicted significant variance in ED psychopathology (large amounts of variance for Eating Concern and Restraint) within both AN and BN (with overvaluation, preoccupation, and fear significant). CONCLUSION Clinical manifestations of body-image disturbances are complex and show important differences across AN and BN. Understanding distinctions and differential salience of different body-image constructs across different EDs can inform refinement of specific case conceptualization.
The effect of plantain syrup on heavy menstrual bleeding: A randomized triple blind clinical trial

Given the importance of heavy menstrual bleeding (HMB), we investigated the effect of plantain syrup on HMB. This randomized clinical trial was performed on 68 women with HMB who were referred to the traditional medicine clinics of Mashhad University of Medical Sciences. The intervention group received placebo capsule and plantain syrup, whereas the control group received mefenamic acid capsule and placebo syrup in the first 5 days of menstruation for three menstruation cycles. Patients were asked to complete pictorial blood assessment chart one cycle before the intervention and three intervention cycles. Hemoglobin was measured at the beginning and at the end of the study. The results showed that the bleeding duration and severity diminished in both groups. No significant difference was observed between two groups in severity of bleeding after intervention (Cohen's d = .24), but duration of bleeding in mefenamic acid group was reduced significantly in comparison with plantain group (Cohen's d = .57). Although mean hemoglobin alterations in mefenamic acid group had a significant difference before and after the intervention, there was no significant difference between the two groups in mean hemoglobin alterations postintervention. Plantain syrup could be suggested as a complementary treatment for HMB, but further studies are required.
A Prospective Analysis of Genetic Variants Associated with Human Lifespan

We present a massive investigation into the genetic basis of human lifespan. Beginning with a genome-wide association (GWA) study using a de-identified snapshot of the unique AncestryDNA database – more than 300,000 genotyped individuals linked to pedigrees of over 400,000,000 people – we mapped six genome-wide significant loci associated with parental lifespan. We compared these results to a GWA analysis of the traditional lifespan proxy trait, age, and found only one locus, APOE, to be associated with both age and lifespan. By combining the AncestryDNA results with those of an independent UK Biobank dataset, we conducted a meta-analysis of more than 650,000 individuals and identified fifteen parental lifespan-associated loci. Beyond just those significant loci, our genome-wide set of polymorphisms accounts for up to 8% of the variance in human lifespan; this value represents a large fraction of the heritability estimated from phenotypic correlations between relatives.
The Fish Pathogen Vibrio ordalii Under Iron Deprivation Produces the Siderophore Piscibactin

Vibrio ordalii is the causative agent of vibriosis, mainly in salmonid fishes, and its virulence mechanisms are still not completely understood. In previous works we demonstrated that V. ordalii possess several iron uptake mechanisms based on heme utilization and siderophore production. The aim of the present work was to confirm the production and utilization of piscibactin as a siderophore by V. ordalii. Using genetic analysis, identification by peptide mass fingerprinting (PMF) of iron-regulated membrane proteins and chemical identification by LC-HRMS, we were able to clearly demonstrate that V. ordalii produces piscibactin under iron limitation. The synthesis and transport of this siderophore is encoded by a chromosomal gene cluster homologous to another one described in V. anguillarum, which also encodes the synthesis of piscibactin. Using β-galactosidase assays we were able to show that two potential promoters regulated by iron control the transcription of this gene cluster in V. ordalii. Moreover, biosynthetic and transport proteins corresponding to piscibactin synthesis and uptake could be identified in membrane fractions of V. ordalii cells grown under iron limitation. The synthesis of piscibactin was previously reported in other fish pathogens like Photobacterium damselae subsp. piscicida and V. anguillarum, which highlights the importance of this siderophore as a key virulence factor in Vibrionaceae bacteria infecting poikilothermic animals.
Effects of Prevalent and Incident Atrial Fibrillation on Renal Outcome, Cardiovascular Events, and Mortality in Patients with Chronic Kidney Disease

Background: Little is known about how incident atrial fibrillation (AF) affects the clinical outcomes in chronic kidney disease (CKD) patients and whether there is a different influence between pre-existing and incident AF. Methods: Incident CKD patients from 2000 to 2013 were retrieved from the National Health Insurance Research Database (NHIRD) of Taiwan and they were classified as non-AF (n = 15,251), prevalent AF (n = 612), and incident AF (n = 588). The outcomes of interest were end-stage renal disease (ESRD) requiring dialysis, all-cause mortality, cardiovascular (CV) mortality, acute myocardial infarction (AMI), stroke or systemic thromboembolism. Results: Compared with CKD patients without AF, those with prevalent or incident AF were associated with higher adjusted rates of ESRD (hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.32–1.48; HR, 2.91; 95% CI, 2.74–3.09, respectively), stroke or systemic thromboembolism (HR, 1.89; 95% CI, 1.77–2.03; HR, 1.67; 95% CI, 1.54–1.81, respectively), AMI (HR, 1.24; 95% CI, 1.09–1.41; HR, 1.99; 95% CI, 1.75–2.27, respectively), all-cause mortality (HR, 1.64; 95% CI, 1.56–1.72; HR, 2.17; 95% CI, 2.06–2.29, respectively), and CV mortality (HR, 2.95; 95% CI, 2.62–3.32; HR, 4.61; 95% CI, 4.09–5.20, respectively). Intriguingly, CKD patients with prevalent AF were associated with lower adjusted rates of ESRD, AMI, all-cause mortality, and CV mortality compared with those with incident AF. Conclusion: Both incident and prevalent AF were independently associated with greater risks of AMI, all-cause mortality, CV mortality, ESRD, and stroke or systemic thromboembolism. Our findings are novel in that, compared with prevalent AF, incident AF possessed an even higher risk of some clinical consequences, including ESRD, all-cause mortality, CV mortality, and AMI.
The ZT Biopolymer: A Self-Assembling Protein Scaffold for Stem Cell Applications

The development of cell culture systems for the naturalistic propagation, self-renewal and differentiation of cells ex vivo is a high goal of molecular engineering. Despite significant success in recent years, the high cost of up-scaling cultures, the need for xeno-free culture conditions, and the degree of mimicry of the natural extracellular matrix attainable in vitro using designer substrates continue to pose obstacles to the translation of cell-based technologies. In this regard, the ZT biopolymer is a protein-based, stable, scalable, and economical cell substrate of high promise. ZT is based on the naturally occurring assembly of two human proteins: titin-Z1Z2 and telethonin. These protein building blocks are robust scaffolds that can be conveniently functionalized with full-length proteins and bioactive peptidic motifs by genetic manipulation, prior to self-assembly. The polymer is, thereby, fully encodable. Functionalized versions of the ZT polymer have been shown to successfully sustain the long-term culturing of human embryonic stem cells (hESCs), human induced pluripotent stem cells (hiPSCs), and murine mesenchymal stromal cells (mMSCs). Pluripotency of hESCs and hiPSCs was retained for the longest period assayed (4 months). Results point to the large potential of the ZT system for the creation of a modular, pluri-functional biomaterial for cell-based applications.
An Elite Gene Guided Reproduction Operator for Many-Objective Optimization

Traditional reproduction operators in many-objective evolutionary algorithms (MaOEAs) seem to not be so effective to tackle many-objective optimization problems (MaOPs). This is mainly because the population size cannot be set to an arbitrarily large value if the computational efficiency is of concern. In such a case, the distance between the parents becomes remarkably large and, consequently, it is not easy to reproduce a superior offspring in high-dimensional objective space. To alleviate this problem, an elite gene-guided (EGG) reproduction operator is proposed to tackle MaOPs in this article. In this operator, an elite gene pool is built by collecting the knee points from the current population. Then, the offspring is produced by exchanging the genes with this elite gene pool under an exchange rate, aiming to reserve more promising genes into the next generation. In order to provide new genes for the population, other genes will be disturbed under a disturbance rate. The settings and functional analysis of the exchange rate and disturbance rate are studied using several experiments. The proposed EGG operator is easy to implement and can be embedded to any MaOEA. As examples, we show the embedding of the proposed EGG operator into four competitive MaOEAs, that is, MOEA/D, NSGA-III, $\theta $ -DEA, and SPEA2-SDE provide some advantages over simulated binary crossover, differential evolution, and an evolutionary path-based reproduction operator on solving a number of benchmark problems with 3 to 15 objectives.
DeepVolume: Brain Structure and Spatial Connection-Aware Network for Brain MRI Super-Resolution

Thin-section magnetic resonance imaging (MRI) can provide higher resolution anatomical structures and more precise clinical information than thick-section images. However, thin-section MRI is not always available due to the imaging cost issue. In multicenter retrospective studies, a large number of data are often in thick-section manner with different section thickness. The lack of thin-section data and the difference in section thickness bring considerable difficulties in the study based on the image big data. In this article, we introduce DeepVolume, a two-step deep learning architecture to address the challenge of accurate thin-section MR image reconstruction. The first stage is the brain structure-aware network, in which the thick-section MR images in axial and sagittal planes are fused by a multitask 3-D U-net with prior knowledge of brain volume segmentation, which encourages the reconstruction result to have correct brain structure. The second stage is the spatial connection-aware network, in which the preliminary reconstruction results are adjusted slice-by-slice by a recurrent convolutional network embedding convolutional long short-term memory (LSTM) block, which enhances the precision of the reconstruction by utilizing the previously unassessed sagittal information. We used 305 paired brain MRI samples with thickness of 1.0 mm and 6.5 mm in this article. Extensive experiments illustrate that DeepVolume can produce the state-of-the-art reconstruction results by embedding more anatomical knowledge. Furthermore, considering DeepVolume as an intermediate step, the practical and clinical value of our method is validated by applying the brain volume estimation and voxel-based morphometry. The results show that DeepVolume can provide much more reliable brain volume estimation in the normalized space based on the thick-section MR images compared with the traditional solutions.