Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative and Evolutionary Physiology of Vasopressin/ Oxytocin-Type Neuropeptide Signaling in Invertebrates

The identification of structurally related hypothalamic hormones that regulate blood pressure and diuresis (vasopressin, VP; CYFQNCPRG-NH2) or lactation and uterine contraction (oxytocin, OT; CYIQNCPLG-NH2) was a major advance in neuroendocrinology, recognized in the award of the Nobel Prize for Chemistry in 1955. Furthermore, the discovery of central actions of VP and OT as regulators of reproductive and social behavior in humans and other mammals has broadened interest in these neuropeptides beyond physiology into psychology. VP/OT-type neuropeptides and their G-protein coupled receptors originated in a common ancestor of the Bilateria (Urbilateria), with invertebrates typically having a single VP/OT-type neuropeptide and cognate receptor. Gene/genome duplications followed by gene loss gave rise to variety in the number of VP/OT-type neuropeptides and receptors in different vertebrate lineages. Recent advances in comparative transcriptomics/genomics have enabled discovery of VP/OT-type neuropeptides in an ever-growing diversity of invertebrate taxa, providing new opportunities to gain insights into the evolution of VP/OT-type neuropeptide function in the Bilateria. Here we review the comparative physiology of VP/OT-type neuropeptides in invertebrates, with roles in regulation of reproduction, feeding, and water/salt homeostasis emerging as common themes. For example, we highlight recent reports of roles in regulation of oocyte maturation in the sea-squirt Ciona intestinalis, extraoral feeding behavior in the starfish Asterias rubens and energy status and dessication resistance in ants. Thus, VP/OT-type neuropeptides are pleiotropic regulators of physiological processes, with evolutionarily conserved roles that can be traced back to Urbilateria. To gain a deeper understanding of the evolution of VP/OT-type neuropeptide function it may be necessary to not only determine the actions of the peptides but also to characterize the transcriptomic/proteomic/metabolomic profiles of cells expressing VP/OT-type precursors and/or VP/OT-type receptors within the framework of anatomically and functionally identified neuronal networks. Furthermore, investigation of VP/OT-type neuropeptide function in a wider range of invertebrate species is now needed if we are to determine how and when this ancient signaling system was recruited to regulate diverse physiological and behavioral processes in different branches of animal phylogeny and in contrasting environmental contexts.
Genetic Variation May Have Promoted the Successful Colonization of the Invasive Gall Midge, Obolodiplosis robiniae, in China

Invasive species often cause serious economic and ecological damage. Despite decades of extensive impacts of invasives on bio-diversity and agroforestry, the mechanisms underlying the genetic adaptation and rapid evolution of invading populations remain poorly understood. The black locust gall midge, Obolodiplosis robiniae, a highly invasive species that originated in North America, spread widely throughout Asia and Europe in the past decade. Here, we used 11 microsatellite DNA markers to analyze the genetic variation of 22 O. robiniae populations in China (the introduced region) and two additional US populations (the native region). A relatively high level of genetic diversity was detected among the introduced populations, even though they exhibited lower diversity than the native US populations. Evidence for genetic differentiation among the introduced Chinese populations was also found based on the high Fst value compared to the relatively low among the native US populations. Phylogenetic trees, structure graphical output, and principal coordinate analysis plots suggested that the Chinese O. robiniae populations (separated by up to 2,540 km) cluster into two main groups independent of geographical distance. Genetic variation has been observed to increase rapidly during adaptation to a new environment, possibly contributing to population establishment and spread. Our results provide insights into the genetic mechanisms underlying successful invasion, and identify factors that have contributed to colonization by an economically important pest species in China. In addition, the findings improve our understanding of the role that genetic structure plays during invasion by O. robiniae.
Systemic Immune Modulation in Gliomas: Prognostic Value of Plasma IL-6, YKL-40, and Genetic Variation in YKL-40

Background: Complex local and systemic immune dysfunction in glioblastoma (GBM) may affect survival. Interleukin (IL)-6 and YKL-40 are pleiotropic biomarkers present in the tumor microenvironment and involved in immune regulation. We therefore analyzed plasma IL-6, YKL-40, and genetic variation in YKL-40 and explored their ability to distinguish between glioma subtypes and predict survival in GBM. Methods: One hundred fifty-eight patients with glioma WHO grade II-IV were included in the study. Plasma collected at surgery was analyzed for IL-6 and YKL-40 (CHI3L1) by ELISA. CHI3L1 rs4950928 genotyping was analyzed on whole-blood DNA. Results: Neither plasma IL-6 nor YKL-40 corrected for age or rs4950928 genotype could differentiate GBM from lower grade gliomas. GC and GG rs4950928 genotype were associated with lower plasma YKL-40 levels (CC vs. GC, p = 0.0019; CC vs. GG, p = 0.01). Only 10 and 14 out of 94 patients with newly diagnosed GBM had elevated IL-6 or YKL-40, respectively. Most patients received corticosteroid treatment at time of blood-sampling. Higher pretreatment plasma IL-6 was associated with short overall survival (OS) [HR = 1.19 (per 2-fold change), p = 0.042] in univariate analysis. The effect disappeared in multivariate analysis. rs4950928 genotype did not associate with OS [HR = 1.30, p = 0.30]. In recurrent GBM, higher YKL-40 [HR = 2.12 (per 2-fold change), p = 0.0005] but not IL-6 [HR = 0.99 (per 2-fold change), p = 0.92] were associated with short OS in univariate analysis. Conclusion: In recurrent GBM high plasma YKL-40 may hold promise as a prognostic marker. In newly diagnosed GBM perioperative plasma IL-6, YKL-40, and genetic variation in YKL-40 did not associate with survival. Corticosteroid use may complicate interpretation of results.
Dynamics of Anthropometric Indices in a Large Paired Cohort With 10 Years of Follow-Up: Paving the Way to Sarcopenic Obesity

Introduction: Paired cohort investigations assessing the evolution of anthropometric indices are scarce. Here we assessed the 10-year evolution of BMI, total body fat, and lean body mass in 50,019 participants aged 18–90 years at the time of first assessment. Material and Methods: A retrospective cohort study using an electronic database that contains anonymized, longitudinal data from Primary Care medical records covering the 2007–2008 and 2017–2018 periods. Total body fat was estimated using the Clínica Universidad de Navarra-Body Adiposity Estimator formula, and the Hume formula was applied to estimate lean body mass. Results: The mean BMI of participants <60 years old in the 2007–2008 period increased significantly, from 27.5 to 28.3 kg/m2 (p < 0.001). However, the BMI of older subjects decreased during the next decade, from 28.9 to 28.3 kg/m2 (p < 0.001). The estimated total body fat showed a continuous progressive increase over all ages. Finally, lean body mass showed a progressive increase until the 40s, with a plateau between 40–45 years old and an uninterrupted decrease until older ages. Also, subjects who increased their BMI by 2 kg/m2 during the 10-year period were mainly women and younger at baseline, with a lower initial BMI and total body fat in comparison with those who experienced a BMI decrease of ≥2.0 kg/m2. Conclusion: The evolutions of BMI and the estimated body compositions reported here confirm that the adverse decrease in lean body mass begins in middle age. The proportion of older subjects is important when evaluating overweight and obesity prevalence in cross-sectional studies.
The Variety in the Common Theme of Translation Inhibition by Type II Toxin–Antitoxin Systems

Type II Toxin–antitoxin (TA) modules are bacterial operons that encode a toxic protein and its antidote, which form a self-regulating genetic system. Antitoxins put a halter on toxins in many ways that distinguish different types of TA modules. In type II TA modules, toxin and antitoxin are proteins that form a complex which physically sequesters the toxin, thereby preventing its toxic activity. Type II toxins inhibit various cellular processes, however, the translation process appears to be their favorite target and nearly every step of this complex process is inhibited by type II toxins. The structural features, enzymatic activities and target specificities of the different toxin families are discussed. Finally, this review emphasizes that the structural folds presented by these toxins are not restricted to type II TA toxins or to one particular cellular target, and discusses why so many of them evolved to target translation as well as the recent developments regarding the role(s) of these systems in bacterial physiology and evolution.
Employ of Citrus By-product as Fat Replacer Ingredient for Bakery Confectionery Products

Citrus fruits processing is one of the foremost industrial activities in Sicily and the main residual by-product consists in peels and seeds (known as “pastazzo”). Traditionally this by-product has been used for different purposes, and only most recently, it has been described as source of a wide range of healthy bioactive compounds and dietary fibers. In the present work, a debittered food grade orange fiber (DOF), extracted from orange juice by-product, was experimentally obtained and tested as fat-replacer at different percentages (30, 50, and 70%) in bakery confectionery products (brioches). The DOF showed high total fiber content, low water activity and a high water binding capacity. The obtained bakery products were characterized for nutritional, technological and microbiological parameters through storage at room temperature. Results highlighted that the addition of DOF results in final products with increased moisture content, mainly after 1 day of storage, and good textural proprieties. Furthermore, the fat-replacing strategy, at different levels of DOF, resulted in final products with, besides a constant content of carbohydrates, showed lowered fat content, increased content of dietary fiber and protein. In particular, the 50% fat replacement allowed to obtain brioches with improved technological properties and with desirable microbiological traits, mostly within the first 24 h from production and up to 5 days of storage.
2PAC

Synthesizing motions for legged characters in arbitrary environments is a long-standing problem that has recently received a lot of attention from the computer graphics community. We tackle this problem with a procedural approach that is generic, fully automatic, and independent from motion capture data. The main contribution of this article is a point-mass-model-based method to synthesize Center Of Mass trajectories. These trajectories are then used to generate the whole-body motion of the character. The use of a point mass model results in physically inconsistent motions and joint limit violations when mapped back to a full- body motion. We mitigate these issues through the use of a novel formulation of the kinematic constraints that allows us to generate a quasi-static Center Of Mass trajectory in a way that is both user-friendly and computationally efficient. We also show that the quasi-static constraint can be relaxed to generate motions usable for computer animation at the cost of a moderate violation of the dynamic constraints. Our method was integrated in our open-source contact planner and tested with different scenarios—some never addressed before—featuring legged characters performing non-gaited motions in cluttered environments. The computational efficiency of our trajectory generation algorithm (under one ms to compute one second of trajectory) enables us to synthesize motions in a few seconds, one order of magnitude faster than state-of-the-art methods. Although our method is empirically able to synthesize collision-free motions, the formal handling of environmental constraints is not part of the proposed method and left for future work.
Clinical and Genetic Heterogeneity in Six Tunisian Families With Horizontal Gaze Palsy With Progressive Scoliosis: A Retrospective Study of 13 Cases

Background: Horizontal Gaze Palsy with Progressive Scoliosis (HGPPS) is a rare autosomal recessive congenital disorder characterized by the absence of conjugate horizontal eye movements, and progressive debilitating scoliosis during childhood and adolescence. HGPPS is associated with mutations of the ROBO3 gene. In this study, the objective is to identify pathogenic variants in a cohort of Tunisian patients with HGPPS and to further define ROBO3 genotype-phenotype correlations. Methods: Thirteen Tunisian patients from six unrelated consanguineous families all manifesting HGPPS were genetically investigated. We searched for the causative variants for HGPPS using classical Sanger and whole exome sequencing. Results: Four distinct homozygous mutations were identified in ROBO3 gene. Two of these were newly identified homozygous and non-synonymous mutations, causing effectively damage to the protein by in silico analysis. The other two mutations were previously reported in Tunisian patients with HGPPS. Mutations were validated by Sanger sequencing in parents and affected individuals. Conclusion: To the best of our knowledge, this is the largest ever reported cohort on families with HGPPS in whom ROBO3 mutations were identified. These molecular findings have expanded our knowledge of the ROBO3 mutational spectrum. The relevance of our current study is two-fold; first to assist proper management of the scoliosis and second to protect families at risk.
Problem Formulation for Off-Target Effects of Externally Applied Double-Stranded RNA-Based Products for Pest Control

Externally applied dsRNA-based biocontrol products may lead to off-target degradation of messenger RNA in target and non-target organisms. For the purposes of regulatory risk assessment of such products, producing a comprehensive catalog of any off-target effects using profiling methods is unnecessary and would be ineffective in supporting decision-making. Instead, problem formulation should derive criteria that indicate acceptable risk and devise a plan to test the hypothesis that the product meets those criteria. The key to effective risk assessment of dsRNA-based biocontrols is determining whether their properties indicate acceptable or unacceptable risk, not whether they arise from on- or off-target effects of dsRNA.
ABRA

ABPA Ξ AΣ (ABRAXAS): Gnostic word of mystic meaning. We present ABRA, a suite of algorithms to compute and maintain probabilistically guaranteed high-quality approximations of the betweenness centrality of all nodes (or edges) on both static and fully dynamic graphs. Our algorithms use progressive random sampling and their analysis rely on Rademacher averages and pseudodimension, fundamental concepts from statistical learning theory. To our knowledge, ABRA is the first application of these concepts to the field of graph analysis. Our experimental results show that ABRA is much faster than exact methods, and vastly outperforms, in both runtime number of samples, and accuracy, state-of-the-art algorithms with the same quality guarantees.
Health Service Use and Treatment Choices for Pediatric Eosinophilic Esophagitis: Findings From a Cross-Sectional Survey of Australian Carers

Objectives: The incidence and the prevalence of eosinophilic esophagitis (EoE) are increasing, and healthcare utilization among children with EoE is high. This study provides novel insights into the health services and the treatments, including complementary medicines (CMs), used by carers to manage their children's EoE as well as the carers' beliefs and attitudes toward these treatments. Methods: A national cross-sectional online survey was conducted in Australia between September 2018 and February 2019. The survey included questions about health service and treatment utilization, health insurance and government support, health-related quality of life of children with EoE and their carers, views and attitudes toward CM use, and perceived efficacy of treatment. Results: The survey was completed by 181 carers (96.6% of whom were mothers) of EoE children. Most children (91.2%, n = 165) had seen a medical doctor for their EoE, and almost half had consulted with a CM practitioner (40.3%, n = 73). Pharmaceuticals (n = 156, 86.2%) were the most commonly used treatment option, followed by dietary changes (n = 142, 78.5%), CM products (n = 109, 60.2%), and CM therapies (n = 42, 23.2%). Most children received care from numerous practitioners on multiple occasions, indicating a substantial financial and treatment-related burden. Conclusions: A variety of practitioners are involved in the care of children with EoE, and a high rate of CM use warrants further attention to ensure that appropriate treatment is provided. Carer involvement and guidance, combined with individual practitioner expertise, referrals, and collaboration between providers, is essential to successfully navigate this complex disease and provide adequate care for these patients.
Borderline Personality Disorder With Depression Confers Significant Risk of Suicidal Behavior in Mood Disorder Patients—A Comparative Study

Objective We investigated risk factors for suicidal ideation and behavior among currently depressed patients with major depressive disorder (MDD), major depressive episode (MDE) in bipolar disorder (BD), or MDE with comorbid borderline personality disorder (MDE/BPD). We compared current and lifetime prevalence of suicidal ideation and behavior, and investigated dimensional measures of BPD or mixed affective features of the MDE as indicators of risk. Methods Based on screening of 1,655 referrals, we recruited 124 psychiatric secondary care outpatients with MDE and stratified them into three subcohorts (MDD, BD, and MDE/BPD) using the Structured Clinical Interview for DSM-IV I and II. We examined suicidal ideation and behavior with the Columbia Suicide Severity Rating Scale (CSSRS). In addition, we quantified the severity of BPD symptoms and BD mixed features both categorically/diagnostically and dimensionally (using instruments such as the Borderline Personality Disorder Severity Index) in two time frames. Results There were highly significant differences between the lifetime prevalences of suicide attempts between the subcohorts, with attempts reported by 16% of the MDD, 30% of the BD, and 60% of the BPD subcohort. Remarkably, the lifetime prevalence of suicide attempts in patients with comorbid BD and BPD exceeded 90%. The severity of BPD features was independently associated with risk of suicide attempts both lifetime and during the current MDE. It also associated in a dose-dependent manner with recent severity of ideation in both BPD and non-BPD patients. In multinominal logistic regression models, hopelessness was the most consistent independent risk factor for severe suicidal ideation in both time frames, whereas younger age and more severe BPD features were most consistently associated with suicide attempts. Conclusions Among patients with major depressive episodes, diagnosis of bipolar disorder, or presence of comorbid borderline personality features both imply remarkably high risk of suicide attempts. Risk factors for suicidal ideation and suicidal acts overlap, but may not be identical. The estimated severity of borderline personality features seems to associate with history of suicidal behavior and current severity of suicidal ideation in dose-dependent fashion among all mood disorder patients. Therefore, reliable assessment of borderline features may advance the evaluation of suicide risk.
Childhood Adversity and Dimensional Variations in Adult Sustained Attention

Background and Objective Sustained attention is a transdiagnostic phenotype linked with most forms of psychopathology. We sought to understand factors that influence the development of sustained attention, by looking at the relationship between childhood adversity and adult sustained attention. Participants, Setting, and Methods Participants were 5,973 TestMyBrain.org visitors from English-speaking countries who completed a continuous performance task (gradCPT) of sustained attention and a childhood adversity questionnaire. We analyzed gradCPT performance using a signal detection approach. Results Discrimination ability (the main metric of performance on the gradCPT) was associated with total childhood adversity load, even when controlling for covariates related to age, gender, parental education, race, country of origin, and relative socioeconomic status (β = −0.079, b = −0.032). Conclusion Our results demonstrate that attention differences related to childhood adversity exposure can (1) be measured using brief, performance-based measures of sustained attention, (2) persist into adulthood, and (3) be detected at the population level. These results, paired with the well-documented associations between sustained attention and psychopathology, indicate that sustained attention may be an important mechanism for understanding early influences on mental health.
Integrated Analysis of Summary Statistics to Identify Pleiotropic Genes and Pathways for the Comorbidity of Schizophrenia and Cardiometabolic Disease

Genome-wide association studies (GWAS) have identified abundant risk loci associated with schizophrenia (SCZ), cardiometabolic disease (CMD) including body mass index, coronary artery diseases, type 2 diabetes, low- and high-density lipoprotein, total cholesterol, and triglycerides. Although recent studies have suggested that genetic risk shared between these disorders, the pleiotropic genes and biological pathways shared between them are still vague. Here we integrated comprehensive multi-dimensional data from GWAS, expression quantitative trait loci (eQTL), and gene set database to systematically identify potential pleiotropic genes and biological pathways shared between SCZ and CMD. By integrating the results from different approaches including FUMA, Sherlock, SMR, UTMOST, FOCUS, and DEPICT, we revealed 21 pleiotropic genes that are likely to be shared between SCZ and CMD. These genes include VRK2, SLC39A8, NT5C2, AMBRA1, ARL6IP4, OGFOD2, PITPNM2, CDK2AP1, C12orf65, ABCB9, SETD8, MPHOSPH9, FES, FURIN, INO80E, YPEL3, MAPK3, SREBF1, TOM1L2, GATAD2A, and TM6SF2. In addition, we also performed the gene-set enrichment analysis using the software of GSA-SNP2 and MAGMA with GWAS summary statistics and identified three biological pathways (MAPK-TRK signaling, growth hormone signaling, and regulation of insulin secretion signaling) shared between them. Our study provides insights into the pleiotropic genes and biological pathways underlying mechanisms for the comorbidity of SCZ and CMD. However, further genetic and functional studies are required to validate the role of these potential pleiotropic genes and pathways in the etiology of the comorbidity of SCZ and CMD, which should provide potential targets for future diagnostics and therapeutics.