Miracle-dz/UniFAR-FTUs huggingface dataset:
Microbiome Multi-Omics Network Analysis: Statistical Considerations, Limitations, and Opportunities

The advent of large-scale microbiome studies affords newfound analytical opportunities to understand how these communities of microbes operate and relate to their environment. However, the analytical methodology needed to model microbiome data and integrate them with other data constructs remains nascent. This emergent analytical toolset frequently ports over techniques developed in other multi-omics investigations, especially the growing array of statistical and computational techniques for integrating and representing data through networks. While network analysis has emerged as a powerful approach to modeling microbiome data, oftentimes by integrating these data with other types of omics data to discern their functional linkages, it is not always evident if the statistical details of the approach being applied are consistent with the assumptions of microbiome data or how they impact data interpretation. In this review, we overview some of the most important network methods for integrative analysis, with an emphasis on methods that have been applied or have great potential to be applied to the analysis of multi-omics integration of microbiome data. We compare advantages and disadvantages of various statistical tools, assess their applicability to microbiome data, and discuss their biological interpretability. We also highlight on-going statistical challenges and opportunities for integrative network analysis of microbiome data.
Internalized GPCRs as Potential Therapeutic Targets for the Management of Pain

Peripheral and central neurons in the pain pathway are well equipped to detect and respond to extracellular stimuli such as pro-inflammatory mediators and neurotransmitters through the cell surface expression of receptors that can mediate rapid intracellular signaling. Following injury or infection, activation of cell surface G protein-coupled receptors (GPCRs) initiates cell signaling processes that lead to the generation of action potentials in neurons or inflammatory responses such as cytokine secretion by immune cells. However, it is now appreciated that cell surface events alone may not be sufficient for all receptors to generate their complete signaling repertoire. Following an initial wave of signaling at the cell surface, active GPCRs can engage with endocytic proteins such as the adaptor protein β-arrestin (βArr) to promote clathrin-mediated internalization. Classically, βArr-mediated internalization of GPCRs was hypothesized to terminate signaling, yet for multiple GPCRs known to contribute to pain, it has been demonstrated that endocytosis can also promote a unique “second wave” of signaling from intracellular membranes, including those of endosomes and the Golgi, that is spatiotemporally distinct from initial cell-surface events. In the context of pain, understanding the cellular and molecular mechanisms that drive spatiotemporal signaling of GPCRs is invaluable for understanding how pain occurs and persists, and how current analgesics achieve efficacy or promote side-effects. This review article discusses the importance of receptor localization for signaling outcomes of pro- and anti-nociceptive GPCRs, and new analgesic opportunities emerging through the development of “location-biased” ligands that favor binding with intracellular GPCR populations.
Using a Mindfulness-Based Intervention to Promote Subjective Well-Being, Trait Emotional Intelligence, Mental Health, and Resilience in Women With Fibromyalgia

The objective of the present study was to experimentally assess the effects of a mindfulness-based intervention (MBI) for the improvement of subjective well-being, trait emotional intelligence (TEI), mental health, and resilience in a sample of women with fibromyalgia (FM). The sample consisted of 104 women, between 29 and 77 years old (M = 47.59; SD = 5.93). The measures used were as follows: Satisfaction with Life Scale (SWLS), Positive and Negative Affection Scale (PANAS), Trait Emotional Intelligence Questionnaire Short Form (TEIQue-SF), Mental Health Questionnaire (MH-5), and Resilience Scale (ER-14). A quasi-experimental design of repeated measures with a control group (CG) was used: before and after the application of the treatment and a follow-up assessment 6 months after the completion of the intervention. In order to assess the effect of the program, the participants were randomly assigned to the experimental and control conditions. In the pretest evaluation, a multivariate analysis of variance (MANOVA) and analysis of variance (ANOVA) were carried out. In the post-test evaluation, a multivariate analysis of covariance (MANCOVA) of the study variables as a whole was performed. Then, descriptive analyses and analysis of covariance (ANCOVA) of the post-test scores (covariate pretest score) were performed. In the follow-up evaluation, a MANCOVA of the study variables as a whole was performed. Then, descriptive and ANCOVA analyses of the follow-up scores (covariate pretest score) were performed. In addition, the effect size was calculated using partial eta-squared (μ2). The post-test results confirmed statistically significant differences in satisfaction with life (SWL), positive affect (PA), mental health, and resilience. The follow-up results showed statistically significant differences in SWL, PA, TEI, mental health, and resilience. The study provides an effective intervention tool that has been validated experimentally. The general results allow the emphasis of the importance of the implementation of MBIs framed in non-pharmacological treatments in FM.
Gene Expression Value Prediction Based on XGBoost Algorithm

Gene expression profiling has been widely used to characterize cell status to reflect the health of the body, to diagnose genetic diseases, etc. In recent years, although the cost of genome-wide expression profiling is gradually decreasing, the cost of collecting expression profiles for thousands of genes is still very high. Considering gene expressions are usually highly correlated in humans, the expression values of the remaining target genes can be predicted by analyzing the values of 943 landmark genes. Hence, we designed an algorithm for predicting gene expression values based on XGBoost, which integrates multiple tree models and has stronger interpretability. We tested the performance of XGBoost model on the GEO dataset and RNA-seq dataset and compared the result with other existing models. Experiments showed that the XGBoost model achieved a significantly lower overall error than the existing D-GEX algorithm, linear regression, and KNN methods. In conclusion, the XGBoost algorithm outperforms existing models and will be a significant contribution to the toolbox for gene expression value prediction.
Widespread Crown Defoliation After a Drought and Heat Wave in the Forests of Tuscany (Central Italy) and Their Recovery—A Case Study From Summer 2017

An anomalous event of drought and heat occurred in central Italy during the summer of 2017. Based on the SPI (Standardized Precipitation Index) and data from the European Space Agency, this event started in November 2016 and was characterized by a strong reduction of precipitation and soil moisture, especially in lowland areas with Mediterranean climate. The aim of this case report were to describe the impact of this event on representative forest communities in central Italy, to analyze the different responses of deciduous and evergreen tree and shrub species in contrasting environmental conditions and to assess their subsequent capacity of recovery or, if not, mortality. Trees suffered severe impacts consisting of widespread crown defoliation, leaf desiccation, crown dieback and whole tree mortality. Deciduous tree species (Fagus sylvatica, Quercus pubescens, Quercus cerris) shed their leaves during the summer, but apical buds and twigs were preserved. This allowed these species to produce new shoots in the following year (2018) and to restore the canopy closure of the stands. Mediterranean evergreen broadleaves, such as Quercus ilex and Phillyrea latifolia suffered of total or partial crown desiccation with wilting leaves and branch dieback. These species partially resprouted in 2018 from axillary and latent buds. The case presented here is discussed within the wider context of the impacts of climate change on Mediterranean forests. Future research directions should include an effective forest monitoring system that combines terrestrial and remote sensing surveys, ad hoc field climate change experiments and silvicultural trials from the perspective of proactive management for the adaptation of forests to future climatic conditions.
Emerging Variants of the Integrative and Conjugant Element ICEMh1 in Livestock Pathogens: Structural Insights, Potential Host Range, and Implications for Bacterial Fitness and Antimicrobial Therapy

Horizontal gene transfer of integrative and conjugative elements (ICE) in bacterial pathogens of the bovine respiratory disease (BRD) complex has emerged as a significant cause of antimicrobial resistance (AMR) and therapeutic failure and mortalities in cattle. The aim of this study was to assess an AMR ICE occurring in Pasteurella multocida from a case of BRD, designated ICEMh1PM22 for its structure and host genome insertion site, and to identify consequences for host fitness and antimicrobial therapy. The modular structure of ICEMh1-like elements found in several related livestock pathogens was compared to ICEMh1PM22, and the repertoire of cargo genes in variable ICE modules was functionally categorized. AMR genes were identified as frequent additions to the variable modules of ICEMh1-like elements. Random PCR-based mapping of ICEMh1PM22-genome junctions in transconjugants provided evidence that ICEMh1PM22 integrates into the tRNA-leu for the UUG codon, and not into tRNA-leu for other codons. This was separately confirmed in the genomes of ICEMh1-like-harboring livestock pathogens. Bacterial genera harboring receptive tRNA-leuUUG were identified to establish the potential host range of ICEMh1-like elements. ICEMh1PM22-carrying transconjugants in P. multocida and Mannheimia haemolytica were less fit than isogenic strains without the ICE when grown without antimicrobial selection. This fitness cost was abrogated in the presence of subinhibitory concentrations of antimicrobials. Despite this cost, ICEMh1PM22 was retained in transconjugants in extended culture. To identify possible therapeutic efficiencies, antimicrobial combinations were screened for synergistic interactions against AMR ICEMh1PM22-carrying transconjugants. No antimicrobial combination tested exhibited synergistic interactions against AMR P. multocida or M. haemolytica harboring ICEMh1PM22. In conclusion, this study provided information on the structural variation of ICEMh1-like elements, refined the ICE insertion site and potential host range, and demonstrated the risk and consequences for AMR following horizontal transfer of ICE into BRD pathogens.
Osteoporosis in primary care

Bone health affects every generation in our communities. From the youngest to the oldest patients, their bone is constantly remodelling by resorbing old bone and forming new bone. Interestingly, we obtain a whole new skeleton every seven years. During adolescence bone formation is greater than resorption causing the trabecular like honeycomb structures within to thicken and strengthen. Many factors will influence this such as lifestyle, diet and exercise. This process plateaus in early adult life. During an adult’s third decade, bone begins to thin out
Editorial: Host Genetics in Viral Pathogenesis and Control

Viral diseases contribute to substantial morbidity and mortality and remain a major threat to global health. Although vaccines are notably successful in the prevention of many infections, effective vaccines are not available for most viruses including the pandemic human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Direct antiviral agents can efficiently inhibit the replication of certain viruses but generally do not provide sterilizing cures, with the notable exception of HCV infection. Emerging and re-emerging viruses have caused an increasing number of disease outbreaks in humans and animals. There is unmet medical need to further our understanding of viral pathogenesis to enable more effective control and prevention of viral infections. Elucidating virus–host interaction is an essential step toward this goal. Viruses generally show variation in both acquisition susceptibility and clinical presentations, suggesting that viral pathogenesis is due to complex interactions between host and viruses. This variability following viral infection has been attributed to a variety of factors, including viral strain and sequence variation as well as age, immune status and genetic background of host. This Research Topic included 21 review or original articles focused on multiple aspects of virus–host interactions, utilizing myriad cellular, genomic, and omics-based approaches to identify key genes and pathways in host defensive and virus offensive strategies.
Effects of Whole-Body Electromyostimulation on Strength-, Sprint-, and Jump Performance in Moderately Trained Young Adults: A Mini-Meta-Analysis of Five Homogenous RCTs of Our Work Group

Background: Whole-body electromyostimulation (WB-EMS) gained increasing interest in sports within recent years. However, few intervention studies have examined the effects of WB-EMS on trained subjects in comparison to conventional strength training. Objective: The aim of the present mini-meta-analysis of 5 recently conducted and published randomized controlled WB-EMS trails of our work group was to evaluate potentially favorable effects of WB-EMS in comparison to conventional strength training. Methods: We included parameter of selected leg muscle's strength and power as well as sprint and jump performance. All subjects were moderately trained athletes [>2 training sessions/week, >2 years of experience in strength training; experimental group (n = 58): 21.5 ± 3.3 y; 178 ± 8 cm; 74.0 ± 11 kg; control group (n = 54): 21.0 ± 2.3 y; 179.0 ± 9 cm; 72.6 ± 10 kg]. The following WB-EMS protocols were applied to the experimental group (EG): 2 WB-EMS sessions/week, bipolar current superimposed to dynamic exercises, 85 Hz, 350 μs, 70% of the individual pain threshold amperage. The control groups (CG) underwent the same training protocols without WB-EMS, but with external resistance. Results: Five extremely homogenous studies (all studies revealed an I2 = 0%) with 112 subjects in total were analyzed with respect to lower limb strength and power in leg curl, leg extension and leg press machines, sprint—and jump performance. Negligible effects in favor of WB-EMS were found for Fmax of leg muscle groups [SMD: 0.11 (90% CI: −0.08, 0.33), p = 0.73, I2 = 0%] and for CMJ [SMD: 0.01 (90% CI: −0.34, 0.33), p = 0.81, I2 = 0%]. Small effects, were found for linear sprint [SMD: 0.22 (90% CI: −0.15, 0.60), p = 0.77, I2 = 0%] in favor of the EMS-group compared to CON. Conclusion: We conclude that WB-EMS is a feasible complementary training stimulus for performance enhancement. However, additional effects on strength and power indices seem to be limited and sprint and jump-performance appear to be benefiting only slightly. Longer training periods and more frequent application times and a slightly larger stimulus could be investigated in larger samples to further elucidate beneficial effects of WB-EMS on performance parameters in athletes.
microRNAs in Mycobacterial Infection: Modulation of Host Immune Response and Apoptotic Pathways

Our current knowledge of mycobacterial infections in humans has progressively increased over the past few decades. The infection of Mycobacterium tuberculosis causes tuberculosis (TB) disease, which has reasoned for excessive morbidity and mortality worldwide, and has become a foremost issue of health problem globally. Mycobacterium leprae, another member of the family Mycobacteriaceae, is responsible for causing a chronic disease known as leprosy that mainly affects mucosa of the upper respiratory tract, skin, peripheral nerves, and eyes. Ample amount of existing data suggests that pathogenic mycobacteria have skilled in utilizing different mechanisms to escape or offset the host immune responses. They hijack the machinery of immune cells through the modulation of microRNAs (miRs), which regulate gene expression and immune responses of the host. Evidence shows that miRs have now gained considerable attention in the research, owing to their involvement in a broad range of inflammatory processes that are further implicated in the pathogenesis of several diseases. However, the knowledge of functions of miRs during mycobacterial infections remains limited. This review summarises recent findings of differential expression of miRs, which are used to good advantage by mycobacteria in offsetting host immune responses generated against them.
Frequency and Dynamics of Non-motor Symptoms Presentation in Hispanic Patients With Parkinson Disease

The clinical phenotype of Parkinson's disease (PD) encompasses a wide range of non-motor symptoms (NMS) compromising the quality of life of affected patients. Currently, information about NMS in PD is scarce among Hispanic populations. Furthermore, few studies have reported the temporal pattern of NMS presentation. We conducted a cross-sectional study aimed to describe the frequency and time of NMS occurrence in Hispanic patients with PD using the self-completed NMS questionnaire (NMSQuest). Participants were interrogated about the time of each NMS presentation respect to the onset of motor symptoms. The frequency of NMS was described according to gender, age at disease onset, disease duration and Hoehn and Yahr (H&Y) stage. We enrolled 120 patients, 73.33% males and 26.66% females, with a mean age of 63.33 ± 8.60 years. All the participants presented at least 1 NMS. The median number of NMS per patient was 12. The most frequent NMS domains were miscellaneous, urinary tract, sleep/fatigue, and gastrointestinal tract symptoms, with no significant gender differences. The most frequent individual NMS were nocturia, urinary urgency, feeling sadness, and constipation. Any patient reported NMS before the onset of motor manifestations. The pattern of occurrence of NMS domains in our population was as follows: attention/memory, cardiovascular, gastrointestinal tract, perceptual problems/hallucinations, mood/cognition, urinary, miscellaneous, sleep/fatigue, and sexual function. Nausea/vomiting was the earliest symptom observed in all patients, whereas sexual dysfunction and changes in interest for sex were the last symptoms to occur. We found no differences in the total number and frequency of NMS between participants grouped according to their age at disease onset. Conversely, patients with a duration of disease >10 years reported a higher frequency of NMS compared to participants with a duration of disease < 10 years. The total number of NMS per patient increased as the HY stage progressed. The proportion of patients presenting symptoms of the gastrointestinal tract, urinary tract, mood/cognition, cardiovascular, and sexual function domains was higher in the HY 4–5 group. Our study provides relevant data to improve our understanding of NMS in PD, which may contribute to anticipate and plan diagnostic and therapeutic strategies among Hispanic PD patients.
The Equus Datum and the Early Radiation of Equus in China

For comprehensive recognition on Equus Datum, we review all the stenonid species in China and discuss the phylogenetic relationship of early Equus. The conclusion indicates at least two dispersal waves of Equus into the Old World from North America, and the second wave led to a radiation of genus Equus in China. In China, the ages of the lower boundaries of the fossiliferous layers in classical Early Pleistocene faunal localities are all around 2.5 Ma (close to the age of lower boundary of the Quaternary) according to magnetostratigraphic and biostratigraphic analyses. All of the geochronological results reveal a status of China as an evolutionary center of Equus in Eurasia. In late Neogene, the dominant equid lineage in China was Hipparion. Even in Pliocene, when Hipparion was not as widespread as before, there were still 5 genera and 7 species. In Early Pleistocene, the genus Hipparion included only 2 genera and 3 species. In the meantime Equus dispersed into China depended on the connections of Bering land bridge (BLB) caused by lowered sea level under global cooling and Arctic ice-sheet forming. The rise of Equus was accompanied by the recession of Hipparion. The dispersal and radiation of Equus in China were not a coincidence, but a complicated process of adaption and competition, and a comprehensive outcome of significant climatic, tectonic and biotic events.
The Importance of Cl− Exclusion and Vacuolar Cl− Sequestration: Revisiting the Role of Cl− Transport in Plant Salt Tolerance

Salinity threatens agricultural production systems across the globe. While the major focus of plant researchers working in the field of salinity stress tolerance has always been on sodium and potassium, the transport patterns and physiological roles of Cl− in plant salt stress responses are studied much less. In recent years, the role of Cl− in plant salinity stress tolerance has been revisited and has received more attention. This review attempts to address the gap in knowledge of the role of Cl− transport in plant salinity stress tolerance. Cl− transport, Cl− exclusion, vacuolar Cl− sequestration, the specificity of mechanisms employed in different plant species to control shoot Cl− accumulation, and the identity of channels and transporters involved in Cl− transport in salt stressed plants are discussed. The importance of the electrochemical gradient across the tonoplast, for vacuolar Cl− sequestration, is highlighted. The toxicity of Cl− from CaCl2 is briefly reviewed separately to that of Cl− from NaCl.
Autonomic dysfunction in multiple sclerosis and optic neuritis

Multiple sclerosis (MS) is one of the major causes of disability in the young, mostly affecting people between 20–45 years of age. MS is considered as an autoimmune disorder, characterized by discrete areas of central nervous system inflammation, demyelination and axonal injury. Symptoms related to alterations of the autonomic nervous system are frequent in patients with MS. Bladder dysfunction or impairment of sexual performance is highly distressing for most MS patients, whereas the clinical relevance of other autonomic symptoms is less clear. The present study was designed to clarify the involvement of cardiovascular and sudomotor dysfunctions in patients with MS, to study the sudomotor functions in patients with optic neuritis (optic neuritis being a frequent initial manifestation of MS), and to assess the extent of demyelinative lesions in the CNS by using magnetic resonance imaging and by correlating the findings thus obtained with autonomic nervous system responses. The study showed cardiovascular autonomic regulation failure in MS patients manifesting itself both in the heart rate responses to deep breathing and in the heart rate and blood pressure responses in the tilt table test. In particular, midbrain lesions were found to be associated with cardiovascular dysfunction. MS patients also showed abnormal sympathetic skin responses indicating sudomotor failure. Focal MS lesions in the temporal lobe, in the pons and in the cerebellum were also associated with abnormal sympathetic skin responses. MS patients were also found to have an impairment in thermoregulatory sweating, which seemed to be related to disease severity and to total lesion volume in the brain. Sympathetic skin responses were also abnormal in optic neuritis patients, suggesting sudomotor autonomic failure. Patients with optic neuritis showed no thermoregulatory dysfunction.