Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Sense of Coherence on Work Ability: A Cross-sectional Study Among Croatian Nurses

Abstract Introduction Aimed at preparing the basis for planning evidence-based public health measures for preservation/ improvement of nurses’ work ability (WA), the objective was to assess the relationship between WA and sense of coherence (SOC). Methods A cross-sectional study was conducted in 2018 among 713 nurses in Croatia. The association between poor WA index (PWAI) and SOC score (SOCS), adjusted for possible confounders, was determined by binary logistic regression analysis. Results The results of univariate logistic regression analysis showed a statistically significant negative association between SOCS and PWAI (OR=0.977, 95% CI 0.968 – 0.986, p<0.001). The results of multivariate logistic analysis showed an even stronger statistically significant negative association between SOCS and PWAI (OR=0.966, 95% CI 0.954 – 0.977, p<0.001) when adjusted for confounders. Conclusions The present study suggested SOC as an important health promoting resource of nurses which might offer protection regarding work-related stress. Weak SOC could be an important explanatory factor of poor WA. Accordingly, improving SOC by implementing health promotion measures in nurses’ workplace could be an important way to increase the WA among nurses.
Physical activity enhances fecal lactobacilli in rats chronically drinking sweetened cola beverage

Abstract Overweight and obesity have been linked with increased intake of sugar-sweetened beverages. On the other hand, physical activity has been known to lead to weight loss. Therefore, we hypothesized that exercise might influence the Lactobacillus population in fecal microbiota as their changed abundance is often associated with shifts in the physical activity and diet. In our experiment, Wistar rats were allocated into groups with normal feed or added sugar-sweetened beverages with or without access to a running wheel. Interestingly, only a combination of physical activity and sweetened beverage intake was associated with a significant increase in fecal lactobacilli abundance, suggesting a connection between exercise and a rise in lactobacilli abundance. Moreover, physical activity has improved weight-related parameters and led to increased plasma and mRNA adiponectin levels. Ghrelin and leptin plasma levels were unaltered. Taken together, our results demonstrate that effect of physical activity on adiposity even during unhealthy feeding patterns is accompanied by increased lactobacilli abundance in the fecal microbiota population.
The ontogeny of asymmetry in echolocating whales

Extreme asymmetry of the skull is one of the most distinctive traits that characterizes toothed whales (Odontoceti, Cetacea). The origin and function of cranial asymmetry are connected to the evolution of echolocation, the ability to use high frequency sounds to navigate the surrounding environment. Although this novel phenotype must arise through changes in cranial development, the ontogeny of cetacean asymmetry has never been investigated. Here we use three-dimensional geometric morphometric to quantify the changes in degree of asymmetry and skull shape during prenatal and postnatal ontogeny for five genera spanning odontocete diversity (oceanic dolphins, porpoises, and beluga). Asymmetry in early ontogeny starts low and tracks phylogenetic relatedness of taxa. Distantly-related taxa that share aspects of their ecology overwrite these initial differences via heterochronic shifts, ultimately converging on comparable high levels of skull asymmetry. Porpoises maintain low levels of asymmetry into maturity and present a decelerated rate of growth, likely retained from the ancestral condition. Ancestral state reconstruction of allometric trajectories demonstrates that both paedomorphism and peramorphism contribute to cranial shape diversity across odontocetes. This study provides a striking example of how divergent developmental pathways can produce convergent ecological adaptations, even for some of the most unusual phenotypes exhibited among vertebrates.
KPop: Accurate, assembly-free, and scalable comparative analysis of microbial genomes

The recent explosion in the amount of available sequencing data challenges existing analysis techniques. Here we introduce KPop, a novel versatile method based on full k-mer spectra and dataset-specific transformations, through which thousands of assembled or unassembled microbial genomes can be quickly compared. Unlike minimizer-based methods that produce distances and have lower resolution, KPop is able to accurately map sequences onto a low-dimensional space. Extensive validation on simulated and real-life viral and bacterial datasets shows that KPop can correctly separate sequences at both species and sub-species levels even when the overall genomic diversity is low. KPop also rapidly identifies related sequences and systematically outperforms minimizer-based methods. KPop’s code is open-source and available on GitHub at https://github.com/PaoloRibeca/KPop.
To share or not to share? iEEG evidence for state-dependent inequity encoding in the human OFC

Social decision-making requires the integration of reward valuation and social cognition systems, both dependent on the orbitofrontal cortex (OFC). How these two OFC functions interact is largely unknown. We recorded intracranial activity from the OFC of ten patients making choices in the context of different types of inequity (disadvantageous vs. advantageous). We found that high-frequency activity (70-150 HZ) encoded the amount of self-reward, consistent with previous reports. We also observed novel evidence for encoding in human OFC of the social counterpart’s reward as well as the type of inequity being experienced. Additionally, we find social context modulates reward encoding: depending on inequity type, reward encoding was switched on and off rapidly within electrodes, across trials. These results provide direct evidence for explicit encoding of self- and other- rewards in the human OFC, and for rapid and reversible changes in encoding schemes driven by socially relevant contexts.
Is Pathways to Education an Effective Program? Proposed Program Evaluation of Ottawa-Ontario

The goal of the Pathways to Education program is to break the vicious cycle of low education and poverty that exists in Canada, through providing low-income youth with academic, social, counseling, and financial supports to encourage and facilitate their graduation from high school and enrolment into post-secondary education (PSE). The evaluation of Pathways to Education is critical from both an equity and economic perspective. From an equity perspective Pathways aims to uphold democratic ideals of equality of opportunity. From an economic perspective, one of Canada’s key concerns is being able to be a competitive player in the global marketplace. For Canada to keep up economically in the innovation, information and technology age, Canada needs more individuals to graduate from PSE institutions. An excellent solution to the problem of how to encourage Canadians to graduate from PSE is to look to youth from underrepresented groups to fill these PSE ‘graduate gaps’ (HRSDC, 2001). If the government of Canada found that Pathways to Education is efficient at increasing PSE enrollment rates of individuals from underrepresented groups, national implementation could have tremendous positive results for Canada both socially and economically (HRSDC, 2001, Olaniyan et al. 2008). Due to positive reviews and widespread support, the Pathways to Education program has received the positive attention and funding necessary to expand across Canada. It is therefore necessary to determine whether resources should be invested in the program. This paper proposes an evaluation tool that can accurately measure the direct impact of Pathways to Education to determine whether it is being effective in Ottawa. By using this tool to identify whether the program is effective in Ottawa, it is possible to determine how it is effective and in what context the program is effective.
Reconstructing the functional effect of TP53 somatic mutations on its regulon using causal signalling network modelling

The gene encoding tumor protein p53 (TP53) is the most frequently mutated gene in human cancer. Mutations in both coding and non-coding regions of TP53 can disrupt the regulatory function of the transcription factor, but the functional impact of different somatic mutations on the global TP53 regulon is complex and poorly understood. To address this, we first proceed with a machine learning (ML) approach, and then propose an integrated computational network modelling approach that reconstructs signalling networks using a comprehensive collection of experimental and predicted regulons, and compares their topology. We evaluate both these approaches in a scrutinized pan-cancer analysis of matched genomics and transcriptomics data from 1,457 cell lines (22 cancer types) and 12,531 clinical samples (54 cancer sub-types). Using a ML approach based on penalized generalized linear regression we were able to predict TP53 mutation, but failed to resolve different mutation types. Thus, to infer the impact of different TP53 mutations we compared the topological characteristics of the optimized and reconstructed (upwards of twenty thousand) gene networks and extracted gene signatures for each mutation type using network analysis. We demonstrate that by accounting for TP53 mutation characteristics such as i) mutation type (e.g. missense, nonsense), ii) deleterious consequences of the mutation, or iii) mapping to previously identified hotspots, we can infer a much richer understanding of gene expression regulation, than when simply grouping samples based on their mutation/wild type or gene expression status. Our study highlights a powerful strategy exploiting signalling networks to systematically characterize the functional impact of the full spectrum of somatic mutations. This approach can be applied in general to genetic variation, with clear implications for, but not limited to, the biomedical domain and precision medicine.
Mass Enhanced Node Embeddings for Drug Repurposing

Graph representation learning has recently emerged as a promising approach to solve pharmacological tasks by modeling biological networks. Among the different tasks, drug repurposing, the task of identifying new uses for approved or investigational drugs, has attracted a lot of attention recently. In this work, we propose a node embedding algorithm for the problem of drug repurposing. The proposed algorithm learns node representations that capture the influence of nodes in the biological network by learning a mass term for each node along with its embedding. We apply the proposed algorithm to a multiscale interactome network and embed its nodes (i. e., proteins, drugs, diseases and biological functions) into a low-dimensional space. We evaluate the generated embeddings in the drug repurposing task. Our experiments show that the proposed approach outperforms the baselines and offers an improvement of 53.33% in average precision over typical walk-based embedding approaches.
The Vacc-SeqQC project: Benchmarking RNA-Seq for clinical vaccine studies

Over the last decade, the field of systems vaccinology has emerged, in which high throughput transcriptomics and other omics assays are used to probe changes of the innate and adaptive immune system in response to vaccination. RNA-Seq technology has matured in recent years and is now widely deployed for transcriptional analysis of clinical specimens. The goal of this study was to benchmark technical parameters of RNA-Seq in the context of a multi-site, double-blind randomized clinical trial using primary patient samples. We collected longitudinal peripheral blood mononuclear cell (PBMC) samples from 10 subjects after vaccination with a live attenuated Francisella tularensis vaccine and performed RNA-Seq at two different sites using aliquots from the same sample to generate two large-scale replicate datasets. We evaluated the impact of: (i) filtering lowly-expressed genes, (ii) using external RNA controls, (iii) fold change and false discovery rate (FDR) filtering, (iv) read length, and (v) sequencing depth on differential expressed genes (DEGs) concordance between replicate datasets. Using synthetic mRNA spike-ins, we developed a method for empirically establishing minimal read-count thresholds for maintaining fold change accuracy on a per-experiment basis. We defined a reference PBMC transcriptome by pooling sequence data, and established the impact of read depth and gene filtering on transcript representation. Lastly, we modeled statistical power to detect DE genes for a range of sample sizes, effect sizes, and coverage depths. The results from this study provide RNA sequencing benchmarks and guidelines for planning future similar vaccine studies.
Acute inhibition of the STA3 signaling pathway during epileptogenesis prevent GABAergic cells’ loss and imprinting of epileptic state: an in-vitro proof

Epilepsy, the condition of recurrent unprovoked seizures resulting from a wide variety of causes, is one of the world’s most prominent brain syndrome. Seizures which are an expression of neuronal network dysfunction occur in a positive feedback loop of concomitant factors where seizures generate more seizures, including also neuro-inflammatory responses. Among other pathways involved in inflammatory responses, the JAK/STAT signaling pathway has been proposed to prevent epilepsy. In this work we tested on a model of temporal lobe epilepsy in-vitro, the hypothesis that acute inhibition of STAT3-phosphorylation - during epileptogenesis, can prevent structural damages in the hippocampal circuits, and the imprinting both of neural epileptic activity and inflammatory glial states. We performed calcium imaging of spontaneous circuits’ dynamics in organotypic hippocampal slices previously exposed to hyper-excitable conditions through the blockage of GABAergic synaptic transmission. Epileptogenic conditions lead to imprinted epileptic dynamics in the circuits in terms of higher frequency of neuronal firing and circuits’ synchronizations, higher correlated activity in neuronal pairs and decreased complexity in synchronization patterns. Acute inhibition of the STAT3-phosphorylation during epileptogenesis, prevented the imprinting of epileptic activity patterns, general cell loss, GABAergic cells’ loss and the persistence of inflammatory reactive glial states. This work provides further evidence that inhibiting the STAT3 signaling pathway under epileptogenesis can prevent patho-topological reorganization of neuro-glial circuits.
CHI3L1 enhances melanoma lung metastasis via regulation of T cell co-stimulators and CTLA-4/B7 axis

ICOS/ICOSL and CD28/B7-1/B7-2 are T cell co-stimulators and CTLA-4 is an immune checkpoint inhibitor that play critical roles in the pathogenesis of neoplasia. Chitinase 3-like-1 (CHI3L1) is induced in many cancers where it portends a poor prognosis and contributes to tumor metastasis. Here we demonstrate that CHI3L1 inhibits the expression of ICOS, ICOSL and CD28 while stimulating CTLA-4 and the B7 moieties in melanoma lung metastasis. We also demonstrate that RIG-like helicase innate immune activation augments T cell co-stimulation, inhibits CTLA-4 and suppresses pulmonary metastasis. At least additive antitumor responses were seen in melanoma lung metastasis treated with anti-CTLA-4 and anti-CHI3L1 antibodies in combination. Synergistic cytotoxic T cell-induced tumor cell death and the heightened induction of the tumor suppressor PTEN were seen in co-cultures of T and tumor cells treated with bispecific antibodies that target both CHI3L1 and CTLA-4. Thus, CHI3L1 contributes to pulmonary metastasis by inhibiting T cell co-stimulation and stimulating CTLA-4. The simultaneous targeting of CHI3L1 and the CTLA-4 axis with individual and, more powerfully with bispecific antibodies, represent promising therapeutic strategies for pulmonary metastasis.
A potential marker for problematic mother-infant bonding revealed by magnetoencephalography study of first-time mothers listening to infant cries

Studies using magnetoencephalography (MEG) have identified the orbitofrontal cortex (OFC) to be an important early hub for a ‘parental instinct’ in the brain. This complements the finding from functional magnetic resonance imaging (fMRI) studies linking reward, emotion regulation, empathy and mentalisation networks to the ‘parental brain’. Here, we used MEG in 43 first-time mothers listening to infant and adult cry vocalisations to investigate the link with mother-infant postpartum bonding scores and their level of sleep deprivation (assessed using both actigraphy and sleep logs). We found significant differences 800-1000ms after onset of infant compared to adult cries in source-reconstructed brain activity in areas previously linked to the parental brain. Importantly, mothers with weaker bonding scores showed decreased brain responses to infant cries in the auditory cortex, middle and superior temporal gyrus, OFC, hippocampal areas, supramarginal gyrus and inferior frontal gyrus at around 100-200ms after stimulus onset. In contrast, we did not find correlations with sleep deprivation scores. The significant changes in brain processing of an infant’s distress signals could be a novel marker of weaker infant bonding in new mothers and should be investigated in vulnerable populations.
An action-observation network in the common marmoset identified by ultra-high field fMRI

Thirty years have passed since the first description of neurons in Old World macaque monkeys that fire both during the execution and observation of goal-directed actions. Since then, these so-called “mirror neurons” have been shown to play important roles in understanding the actions of others, learning by imitation, and social cognition in macaques and humans. In contrast to Old World primates, an action-observation network has not yet been identified in New World primates. Here we used ultra-high field fMRI at 9.4T in awake common marmosets (Callithrix jacchus) while they watched videos depicting the upper-limb of marmosets performing goal-directed (grasping food) or non-goal-directed actions. We found that the observation of goal-directed actions, compared to non-goal directed ones, activated a frontotemporoparietal network, including areas 6 and 45 in premotor and prefrontal cortices, and areas PGa-IPa, FST, and the TE complex in temporoparietal regions. These results demonstrate the existence of an evolutionarily conserved action observation network in primates that likely predates the separation of Old and New World monkeys.
Binge alcohol drinking alters the differential control of cholinergic interneurons over nucleus accumbens D1 and D2 medium spiny neurons

Background Ventral striatal cholinergic interneurons (ChIs) play a central role in basal ganglia function by regulating associative learning and reward processing. In the nucleus accumbens (NAc), ChIs regulate glutamatergic, dopaminergic, and GABAergic neurotransmission. However, it is unclear how ChIs orchestrate the control of these neurotransmitters to determine the excitability of medium spiny neurons (MSNs) expressing either dopamine D1 or D2 receptors. Additionally, the effects of binge alcohol drinking on ChIs-mediated modulation of glutamatergic synaptic transmission in NAc MSNs are also undefined. Methods We optogenetically stimulated ChIs while recording evoked and spontaneous excitatory postsynaptic currents (sEPSCs) in D1- and D2-MSN of ChAT.ChR2. eYFPxDrd1.tdtomato mice. To determine the effect of ChIs on mouse behavior and alcohol consumption, we implanted ChAT.ChR2. eYFP mice with fiber optic cannulas and stimulated ChIs while mice were allowed to drink 20% alcohol using the binge alcohol drinking- in-the-dark (DID) paradigm. Results We demonstrated that NAc ChIs decrease the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in both D1- and D2-MSNs,. While inhibition of D1-MSNs glutamate release by ChIs depends on dopamine release, that of D2-MSNs results from a direct interactions between ChIs and glutamatergic terminals. Interestingly, after two weeks of binge alcohol drinking, the effect of ChIs stimulation on glutamate release was reversed in D1-MSNs, while its effect on D2-MSNs remained unchanged. Finally, in vivo optogenetic stimulation of NAc ChIs significantly increased alcohol consumption. Conclusions These results identify ChIs as a key target for the regulation of NAc circuitry and as a potential treatment of alcohol addiction.
The Effect of Breaking Up Sedentary Time with Calisthenics on Neuromuscular Function: A Preliminary Study

Prolonged sedentary behaviour has a detrimental effect on neuromuscular function and is associated with decreased muscle strength and force control, and a decreased ability to maintain balance. Breaking up sedentary time with regular bouts of physical activity has numerous health benefits, though the effects on neuromuscular function are unknown. This study aimed to investigate the effect of breaking up sedentary time with calisthenic exercise on neuromuscular function. To that end, 17 healthy adults, who spent ≥6 hours a day sitting, were randomly assigned to a four-week calisthenics intervention (n = 8) or a control group (n = 9). The calisthenics intervention involved performing up to eight sets of exercises during the working day (09:00-17:00); with one set consisting of eight repetitions of five different exercises (including squats and lunges). Before and immediately after the intervention, measures of knee extensor maximal voluntary contraction (MVC; right leg only) and submaximal force control (measures of the magnitude and complexity of force fluctuations; right leg only), and dynamic balance (Y balance test; both legs) were taken. The calisthenics intervention resulted in a significant increase in knee extensor MVC (P = 0.036), significant decreases in the standard deviation (P 0.031) and coefficient of variation (P = 0.016) of knee extensor force fluctuations during contractions at 40% MVC, and a significant increase in Y balance test posterolateral reach with left leg stance (P = 0.046). These results suggest that breaking up sedentary time with calisthenics may be effective at increasing muscle strength, force steadiness and dynamic balance. New findings What is the central question of this study? This study sought to determine whether breaking up sedentary time with a (4-week) calisthenics exercise intervention could improve neuromuscular function. What is the main finding and its importance? A 4-week calisthenic exercise intervention increased knee extensor maximal strength, knee extensor force steadiness during submaximal contractions, and aspects of dynamic balance. These results indicate the regularly breaking up sedentary time with calisthenics can mitigate against the negative effects of prolonged sedentary time.