Miracle-dz/UniFAR-FTUs huggingface dataset:
Is Low Heart Rate Variability Associated with Emotional Dysregulation, Psychopathological Dimensions, and Prefrontal Dysfunctions? An Integrative View

Several studies have suggested a correlation between heart rate variability (HRV), emotion regulation (ER), psychopathological conditions, and cognitive functions in the past two decades. Specifically, recent data seem to support the hypothesis that low-frequency heart rate variability (LF-HRV), an index of sympathetic cardiac control, correlates with worse executive performances, worse ER, and specific psychopathological dimensions. The present work aims to review the previous findings on these topics and integrate them from two main cornerstones of this perspective: Porges’ Polyvagal Theory and Thayer and Lane’s Neurovisceral Integration Model, which are necessary to understand these associations better. For this reason, based on these two approaches, we point out that low HRV is associated with emotional dysregulation, worse cognitive performance, and transversal psychopathological conditions. We report studies that underline the importance of considering the heart-brain relation in order to shed light on the necessity to implement psychophysiology into a broader perspective on emotions, mental health, and good cognitive functioning. This integration is beneficial not only as a theoretical ground from which to start for further research studies but as a starting point for new theoretical perspectives useful in clinical practice.
Polylactide Nanocapsules Attenuate Adverse Cardiac Cellular Effects of Lyso-7, a Pan-PPAR Agonist/Anti-Inflammatory New Thiazolidinedione

Lyso-7 is a novel synthetic thiazolidinedione, which is a receptor (pan) agonist of PPAR α,β/δ,γ with anti-inflammatory activity. We investigated the cardiotoxicity of free Lyso-7 in vitro (4.5–450 nM), and Lyso-7 loaded in polylactic acid nanocapsules (NC) in vivo (Lyso-7-NC, 1.6 mg/kg). In previous work, we characterized Lyso-7-NC. We administered intravenously Lyso-7, Lyso-7-NC, control, and blank-NC once a day for seven days in mice. We assessed cell contraction and intracellular Ca2+ transients on single mice cardiomyocytes enzymatically isolated. Lyso-7 reduced cell contraction and accelerated relaxation while lowering diastolic Ca2+ and reducing Ca2+ transient amplitude. Lyso-7 also promoted abnormal ectopic diastolic Ca2+ events, which isoproterenol dramatically enhanced. Incorporation of Lyso-7 in NC attenuated drug effects on cell contraction and prevented its impact on relaxation, diastolic Ca2+, Ca2+ transient amplitude, Ca2+ transient decay kinetics, and promotion of diastolic Ca2+ events. Acute effects of Lyso-7 on cardiomyocytes in vitro at high concentrations (450 nM) were globally similar to those observed after repeated administration in vivo. In conclusion, we show evidence for off-target effects of Lyso-7, seen during acute exposure of cardiomyocytes to high concentrations and after repeated treatment in mice. Nano-encapsulation of Lyso-7 in polymeric NC attenuated the unwanted effects, particularly ectopic Ca2+ events known to support life-threatening arrhythmias favored by stress or exercise.
Vitamin C and E Treatment Blocks Changes in Kynurenine Metabolism Triggered by Three Weeks of Sprint Interval Training in Recreationally Active Elderly Humans

The kynurenine pathway (KP) is gaining attention in several clinical fields. Recent studies show that physical exercise offers a therapeutic way to improve ratios of neurotoxic to neuroprotective KP metabolites. Antioxidant supplementation can blunt beneficial responses to physical exercise. We here studied the effects of endurance training in the form of sprint interval training (SIT; three sessions of 4–6 × 30 s cycling sprints per week for three weeks) in elderly (~65 years) men exposed to either placebo (n = 9) or the antioxidants vitamin C (1 g/day) and E (235 mg/day) (n = 11). Blood samples and muscle biopsies were taken under resting conditions in association with the first (untrained state) and last (trained state) SIT sessions. In the placebo group, the blood plasma level of the neurotoxic quinolinic acid was lower (~30%) and the neuroprotective kynurenic acid to quinolinic acid ratio was higher (~50%) in the trained than in the untrained state. Moreover, muscle biopsies showed a training-induced increase in kynurenine aminotransferase (KAT) III in the placebo group. All these training effects were absent in the vitamin-treated group. In conclusion, KP metabolism was shifted towards neuroprotection after three weeks of SIT in elderly men and this shift was blocked by antioxidant treatment.
Prognostic Impact of Genetic Variants of MECP2 and TIRAP on Clinical Outcomes of Systemic Lupus Erythematosus with and without Nephritis

Systemic lupus erythematosus (SLE) is a chronic autoimmune illness with a growing prevalence in many populations. Few studies have examined genetic predisposition to SLE, so we aimed to examine the clinical impact of the genetic polymorphisms MECP2 rs2734647and TIRAP rs8177374 on the outcomes and therapeutic precision of SLE with and without nephritis. This study included 110 SLE patients—divided into 63 with lupus nephritis (LN), and 47 without nephritis—and 100 controls. Laboratory measurements including CRP, ESR, ACR, CBC, anti-ds-DNA, vitamin A, C3, and C4 were carried out, along with genotyping of MECP2 rs2734647and TIRAP rs8177374 by real-time PCR and sequencing. Treg %, vitamin A, C3, and C4 were lower, whereas Th17 % was higher, in patients vs. controls (p < 0.001). The T allele of MECP2 rs2734647 was higher in LN than in non-nephritis and control subjects. Moreover, the T allele of TIRAP rs8177374 was higher in LN than in non-nephritis and control subjects. The MECP2 and TIRAP genes could play a role in predisposition to SLE, and can also predict disease progress to nephritis, helping to personalize medicine.
Comparison of the Sustainability Effects of High-Intensity Interval Exercise and Moderate-Intensity Continuous Exercise on Cognitive Flexibility

This study examined the immediate and sustained effects of high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) on cognitive flexibility in young adults. Participants (n = 56) engaged in (1) a session of HIIE, involving 10 sets of one-minute treadmill running at an intensity targeting 90% heart rate reserve (HRR) interspersed with self-paced walking at 50% HRR; (2) a session of MICE, involving a 20 min treadmill running at an intensity of 40–59% HRR; and (3) a control session, involving 24 min of resting on separate days in a counterbalanced order. Using a more-odd shifting task, cognitive flexibility was assessed before the intervention (t0), immediately after the session (t1), and then at 30 min (t2) after the session. During the more-odd shifting task, the switch cost of response time (RT) immediately after the HIIE was significantly reduced compared to that before exercise, suggesting beneficial effects on cognitive flexibility. Additionally, the impacts of HIIE were maintained for 30 min post-exercise. However, improved cognitive flexibility was not observed until 30 min after the MICE intervention. HIIE might represent a time-efficient approach for enhancing cognitive flexibility.
Chronic Stress Detrimentally Affects In Vivo Maturation in Rat Oocytes and Oocyte Viability at All Phases of the Estrous Cycle

Simple Summary Recently, a significant relationship between stress and reproductive failure in women was reported; being one of the possible causes of infertility. The World Health Organization recognizes infertility as a global public health issue; therefore, the interest in understanding the main causes of this issue has increased over the last few decades. Thus, many studies have reported that stress can adversely alter the functionality of the hypothalamic-pituitary-gonadal axis; as well as being one of the reasons of subfertility in patients undergoing in vitro fertilization. Therefore, it can be assumed that stress is closely related to poor in vitro fertilization outcomes. In chronically stressed female rats, irregular estrous cyclicity, increased corticosterone levels, decreased oocyte viability, and increased percentage of abnormal oocytes were obtained in all estrous cycle phases, resulting in reduced oocyte maturation during proestrus. Oocyte maturation disturbed by chronic stress is a crucial factor by which chronic stress disrupts female reproduction. Abstract Background: Stress has been considered as one of the causes of decreased reproductive function in women. However, direct evidence of the effect of chronic stress on oocytes depending on estrous cycle phases is limited. Objective: The present study aimed to evaluate the impact of chronic stress on the viability, integrity, and maturation of rat oocytes depending on estrous cycle phases, specifically proestrus, estrus, and diestrus. Methods: For this purpose, adult female rats were stressed daily by cold water immersion (15 °C) for 30 consecutive days. Results: In chronically stressed female rats, irregular estrous cyclicity, increased corticosterone levels, decreased oocyte viability, and an increased percentage of abnormal oocytes were obtained in all the estrous cycle phases, resulting in reduced oocyte maturation during proestrus. Conclusion: Oocyte maturation disturbed by chronic stress is a crucial factor by which chronic stress disrupts female reproduction
Structure, Activity and Function of the Protein Arginine Methyltransferase 6

Members of the protein arginine methyltransferase (PRMT) family methylate the arginine residue(s) of several proteins and regulate a broad spectrum of cellular functions. Protein arginine methyltransferase 6 (PRMT6) is a type I PRMT that asymmetrically dimethylates the arginine residues of numerous substrate proteins. PRMT6 introduces asymmetric dimethylation modification in the histone 3 at arginine 2 (H3R2me2a) and facilitates epigenetic regulation of global gene expression. In addition to histones, PRMT6 methylates a wide range of cellular proteins and regulates their functions. Here, we discuss (i) the biochemical aspects of enzyme kinetics, (ii) the structural features of PRMT6 and (iii) the diverse functional outcomes of PRMT6 mediated arginine methylation. Finally, we highlight how dysregulation of PRMT6 is implicated in various types of cancers and response to viral infections.
The Cholinergic Anti-Inflammatory Pathway Attenuates the Development of Atherosclerosis in Apoe-/- Mice through Modulating Macrophage Functions

(1) Background: The cholinergic anti-inflammatory pathway (CAP) has been implicated in the regulation of various diseases, including chronic inflammatory cardiovascular disorders such as atherosclerosis (AS). This study aims to explore the underlying regulatory mechanisms of CAP activity in the progression of AS. (2) Methods: The Apoe-/- mice were subjected to sham, bilateral cervical vagotomy surgery (VGX), and VGX supplemented with Gainesville Tokushima scientists (GTS)-21 (4 mg/kg/d) and then fed with a high-fat diet for 10 weeks. Atherosclerotic lesion size and inflammation levels were investigated by histology and inflammatory cytokines analysis. The blood M1/M2 macrophages were analyzed by flow cytometry. Primary mouse bone marrow-derived macrophages (BMDM), peritoneal macrophages, and RAW264.7 cells were treated with CAP agonists acetylcholine (Ach) and GTS-21 to study their effects on macrophage functions. (3) Results: Compared with the sham group, inhibition of CAP by the VGX resulted in growing aortic lipid plaque area, deteriorated inflammatory levels, and aberrant quantity of M1/M2 macrophages in Apoe-/- mice. However, these detrimental effects of VGX were significantly ameliorated by the reactivation of CAP through GTS-21 treatment. The in vitro study using macrophages revealed that stimulation with CAP agonists suppressed M1, but promoted M2 macrophage polarization through the upregulation of TNFAIP3 and phosphorylation STAT3 levels, respectively. Moreover, the activation of CAP inhibited the formation of macrophage foam cells in the peritoneal cavity by regulating genes related to cholesterol metabolism. (4) Conclusions: This study provides novel evidence and mechanisms that the CAP plays an important role in the regulation of AS development by controlling macrophage functions, implying a potential use of CAP activation as a therapeutic strategy for AS treatment.
Degenerated, Undifferentiated, Rearranged, Lost: High Variability of Sex Chromosomes in Geometridae (Lepidoptera) Identified by Sex Chromatin

Sex chromatin is a conspicuous body that occurs in polyploid nuclei of most lepidopteran females and consists of numerous copies of the W sex chromosome. It is also a cytogenetic tool used to rapidly assess the W chromosome presence in Lepidoptera. However, certain chromosomal features could disrupt the formation of sex chromatin and lead to the false conclusion that the W chromosome is absent in the respective species. Here we tested the sex chromatin presence in 50 species of Geometridae. In eight selected species with either missing, atypical, or normal sex chromatin patterns, we performed a detailed karyotype analysis by means of comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). The results showed a high diversity of W chromosomes and clarified the reasons for atypical sex chromatin, including the absence or poor differentiation of W, rearrangements leading to the neo-W emergence, possible association with the nucleolus, and the existence of multiple W chromosomes. In two species, we detected intraspecific variability in the sex chromatin status and sex chromosome constitution. We show that the sex chromatin is not a sufficient marker of the W chromosome presence, but it may be an excellent tool to pinpoint species with atypical sex chromosomes.
The Effect of Drug Heterogeneous Distributions within Core-Sheath Nanostructures on Its Sustained Release Profiles

The sustained release of a water-soluble drug is always a key and important issue in pharmaceutics. In this study, using cellulose acetate (CA) as a biomacromolecular matrix, core-sheath nanofibers were developed for providing a sustained release of a model drug—metformin hydrochloride (MET). The core–sheath nanofibers were fabricated using modified tri-axial electrospinning, in which a detachable homemade spinneret was explored. A process—nanostructure–performance relationship was demonstrated through a series of characterizations. The prepared nanofibers F2 could release 95% of the loaded MET through a time period of 23.4 h and had no initial burst effect. The successful sustained release performances of MET can be attributed to the following factors: (1) the reasonable application of insoluble CA as the filament-forming carrier, which determined that the drug was released through a diffusion manner; (2) the core–sheath nanostructure provided the possibility of both encapsulating the drug completely and realizing the heterogeneous distributions of MET in the nanofibers with a higher drug load core than the sheath; (3) the thickness of the sheath sections were able to be exploited for further manipulating a better drug extended release performance. The mechanisms for manipulating the drug sustained release behaviors are proposed. The present proof-of-concept protocols can pave a new way to develop many novel biomolecule-based nanostructures for extending the release of water-soluble drugs.
A Comprehensive Insight into the Role of Exosomes in Viral Infection: Dual Faces Bearing Different Functions

Extracellular vesicles (EVs) subtype, exosome is an extracellular nano-vesicle that sheds from cells’ surface and originates as intraluminal vesicles during endocytosis. Firstly, it was thought to be a way for the cell to get rid of unwanted materials as it loaded selectively with a variety of cellular molecules, including RNAs, proteins, and lipids. However, it has been found to play a crucial role in several biological processes such as immune modulation, cellular communication, and their role as vehicles to transport biologically active molecules. The latest discoveries have revealed that many viruses export their viral elements within cellular factors using exosomes. Hijacking the exosomal pathway by viruses influences downstream processes such as viral propagation and cellular immunity and modulates the cellular microenvironment. In this manuscript, we reviewed exosomes biogenesis and their role in the immune response to viral infection. In addition, we provided a summary of how some pathogenic viruses hijacked this normal physiological process. Viral components are harbored in exosomes and the role of these exosomes in viral infection is discussed. Understanding the nature of exosomes and their role in viral infections is fundamental for future development for them to be used as a vaccine or as a non-classical therapeutic strategy to control several viral infections.
Qualitative and Quantitative Diagnosis in Head and Neck Cancer

The diagnosis is the art of determining the nature of a disease, and an accurate diagnosis is the true cornerstone on which rational treatment should be built. Within the workflow in the management of head and neck tumours, there are different types of diagnosis. The purpose of this work is to point out the differences and the aims of the different types of diagnoses and to highlight their importance in the management of patients with head and neck tumours. Qualitative diagnosis is performed by a pathologist and is essential in determining the management and can provide guidance on prognosis. The evolution of immunohistochemistry and molecular biology techniques has made it possible to obtain more precise diagnoses and to identify prognostic markers and precision factors. Quantitative diagnosis is made by the radiologist and consists of identifying a mass lesion and the estimation of the tumour volume and extent using imaging techniques, such as CT, MRI, and PET. The distinction between the two types of diagnosis is clear, as the methodology is different. The accurate establishment of both diagnoses plays an essential role in treatment planning. Getting the right diagnosis is a key aspect of health care, and it provides an explanation of a patient’s health problem and informs subsequent decision. Deep learning and radiomics approaches hold promise for improving diagnosis.
Communications between Mitochondria and Endoplasmic Reticulum in the Regulation of Metabolic Homeostasis

Mitochondria associated membranes (MAM), which are the contact sites between endoplasmic reticulum (ER) and mitochondria, have emerged as an important hub for signaling molecules to integrate the cellular and organelle homeostasis, thus facilitating the adaptation of energy metabolism to nutrient status. This review explores the dynamic structural and functional features of the MAM and summarizes the various abnormalities leading to the impaired insulin sensitivity and metabolic diseases.
A Cost-Effective CNN-LSTM-Based Solution for Predicting Faulty Remote Water Meter Reading Devices in AMI Systems

Automatic meter infrastructure (AMI) systems using remote metering are being widely used to utilize water resources efficiently and minimize non-revenue water. We propose a convolutional neural network-long short-term memory network (CNN-LSTM)-based solution that can predict faulty remote water meter reading (RWMR) devices by analyzing approximately 2,850,000 AMI data collected from 2762 customers over 360 days in a small-sized city in South Korea. The AMI data used in this study is a challenging, highly unbalanced real-world dataset with limited features. First, we perform extensive preprocessing steps and extract meaningful features for handling this challenging dataset with limited features. Next, we select important features that have a higher influence on the classifier using a recursive feature elimination method. Finally, we apply the CNN-LSTM model for predicting faulty RWMR devices. We also propose an efficient training method for ML models to learn the unbalanced real-world AMI dataset. A cost-effective threshold for evaluating the performance of ML models is proposed by considering the mispredictions of ML models as well as the cost. Our experimental results show that an F-measure of 0.82 and MCC of 0.83 are obtained when the CNN-LSTM model is used for prediction.
Parental Quality of Life and Involvement in Intervention for Children or Adolescents with Autism Spectrum Disorders: A Systematic Review

Previous research has examined several parental, child-related, and contextual factors associated with parental quality of life (QoL) among parents with a child or an adolescent with autism spectrum disorders (ASD); however, no systematic review has examined the relationship between parental QoL and parental involvement in intervention. To fill this gap, a systematic review was conducted using four electronic databases and checked reference lists of retrieved studies. Records were included in the systematic review if they presented original data, assessed parental QoL, and involvement in intervention for children or adolescents with ASD, were published in peer-reviewed journals between 2000 and 2020, and were written in English. Among the 96 screened full-texts, 17 articles met the eligibility criteria. The selected studies included over 2000 parents of children or adolescents with ASD. Three categories of parental involvement (i.e., none, indirect, direct) were identified, which varied across studies, although most had direct parental involvement. The results from this review show that increased parental involvement in the intervention for children or adolescents with ASD may be one way to promote their QoL. However, further research specifically focused on parental involvement during the intervention for children and adolescents with ASD is warranted.
A Set of 17 microRNAs Common for Brain and Cerebrospinal Fluid Differentiates Primary Central Nervous System Lymphoma from Non-Malignant Brain Tumors

The diagnosis of primary central nervous system (CNS) lymphoma, which is predominantly of the diffuse large B-cell lymphoma type (CNS DLBCL), is challenging. MicroRNAs (miRs) are gene expression-regulating non-coding RNAs that are potential biomarkers. We aimed to distinguish miR expression patterns differentiating CNS DLBCL and non-malignant CNS diseases with tumor presentation (n-ML). Next generation sequencing-based miR profiling of cerebrospinal fluids (CSFs) and brain tumors was performed. Sample source-specific (CSF vs. brain tumor) miR patterns were revealed. Even so, a set of 17 miRs differentiating CNS DLBCL from n-ML, no matter if assessed in CSF or in a tumor, was identified. Along with the results of pathway analyses, this suggests their pathogenic role in CNS DLBCL. A combination of just four of those miRs (miR-16-5p, miR-21-5p, miR-92a-3p, and miR-423-5p), assessed in CSFs, discriminated CNS DLBCL from n-ML samples with 100% specificity and 67.0% sensitivity. Analyses of paired CSF-tumor samples from patients with CNS DLBCL showed significantly lower CSF levels of miR-26a, and higher CSF levels of miR-15a-5p, miR-15b-5p, miR-19a-3p, miR-106b-3p, miR-221-3p, and miR-423-5p. Noteworthy, the same miRs belonged to the abovementioned set differentiating CNS DLBCL from non-malignant CNS diseases. Our results not only add to the basic knowledge, but also hold significant translational potential.