Miracle-dz/UniFAR-FTUs huggingface dataset:
Sex differences in oral oxycodone self‐administration and stress‐primed reinstatement in rats

The opioid epidemic has become a severe public health problem, with approximately 130 opioid‐induced deaths occurring each day in the United States. Prescription opioids are responsible for approximately 40% of these deaths. Oxycodone is one of the most commonly abused prescription opioids, but despite its prevalent misuse, the number of preclinical studies investigating oxycodone‐seeking behaviors is relatively limited. Furthermore, preclinical oxycodone studies that include female subjects are even more scarce, and it is critical that future work includes both sexes. Additionally, the oral route of administration is one of the most common routes for recreational users, especially in the early stages of drug experimentation. However, currently, only two studies have been published investigating operant oral oxycodone self‐administration in rodents. Therefore, the primary goal of the present study was to establish an oral oxycodone operant self‐administration model in adult male and female rats, as well as to examine a potential mechanism of stress‐primed reinstatement. We found that females consumed significantly more oral oxycodone than males in operant self‐administration sessions. We also found that active oxycodone self‐administration was reduced by mu opioid receptor antagonism and by substitution of water for oxycodone solution. Lastly, we induced stress‐primed reinstatement and found that this behavior was significantly attenuated by antagonism of the neurokinin‐1 receptor, consistent with our prior work examining stress‐induced reinstatement of alcohol‐ and cocaine‐seeking.
Understanding Resource Consumption in the Home, Community and Society through Behaviour and Social Practice Theories

The practices and behaviours of individuals influences resource consumption at many scales and are shaped by a multitude of psychological, social, and technical factors. This conceptual paper examines the differences between socio-psychological and social practice theories, building on the Chalk and Cheese debate in the literature. Insight is provided into their potential value in understanding resource consumption studies at different scales: the individual, the home, community, and societal. Each theory has its own qualitative and quantitative methods which allude to different conclusions and recommendations for resource consumption initiatives. We review the debate surrounding the application of both theories, adding our voice to the potential for both theories to be used at different scales and for different time periods, along with comments on the interlocking nature of practices. Design and technology changes can lead to quicker changes in behaviour and practices, whereby socio-psychological theories offer insights into changes in mind frame, values, and social norms.
Suicide among physicians and health-care workers: A systematic review and meta-analysis

Background Medical-related professions are at high suicide risk. However, data are contradictory and comparisons were not made between gender, occupation and specialties, epochs of times. Thus, we conducted a systematic review and meta-analysis on suicide risk among health-care workers. Method The PubMed, Cochrane Library, Science Direct and Embase databases were searched without language restriction on April 2019, with the following keywords: suicide* AND (« health care worker* » OR physician* OR nurse*). When possible, we stratified results by gender, countries, time, and specialties. Estimates were pooled using random-effect meta-analysis. Differences by study-level characteristics were estimated using stratified meta-analysis and meta-regression. Suicides, suicidal attempts, and suicidal ideation were retrieved from national or local specific registers or case records. In addition, suicide attempts and suicidal ideation were also retrieved from questionnaires (paper or internet). Results The overall SMR for suicide in physicians was 1.44 (95CI 1.16, 1.72) with an important heterogeneity (I2 = 93.9%, p<0.001). Female were at higher risk (SMR = 1.9; 95CI 1.49, 2.58; and ES = 0.67; 95CI 0.19, 1.14; p<0.001 compared to male). US physicians were at higher risk (ES = 1.34; 95CI 1.28, 1.55; p <0.001 vs Rest of the world). Suicide decreased over time, especially in Europe (ES = -0.18; 95CI -0.37, -0.01; p = 0.044). Some specialties might be at higher risk such as anesthesiologists, psychiatrists, general practitioners and general surgeons. There were 1.0% (95CI 1.0, 2.0; p<0.001) of suicide attempts and 17% (95CI 12, 21; p<0.001) of suicidal ideation in physicians. Insufficient data precluded meta-analysis on other health-care workers. Conclusion Physicians are an at-risk profession of suicide, with women particularly at risk. The rate of suicide in physicians decreased over time, especially in Europe. The high prevalence of physicians who committed suicide attempt as well as those with suicidal ideation should benefits for preventive strategies at the workplace. Finally, the lack of data on other health-care workers suggest to implement studies investigating those occupations.
Pre-Calibrated Visuo-Haptic Co-Location Improves Execution in Virtual Environments

A common approach to visio-haptic human-machine interfaces adopts a simpler design by shifting grounded force feedback away from the virtual scene. The alternative design favors intuitiveness by displaying visual and grounded force feedback at the same location (i.e. visuo-haptic co-location) but requires a sensibly more complex implementation and a tedious kinematic conception. The benefits of one approach over the other had not been fully investigated. Notably, (i) while users seem to better operate under co-located condition, it's not always the case. (ii) In the case of a desktop interface, the cost of a complex implementation to achieve co-location is challenged. We aim here to resolve (i) by conducting a user-centered experiment in which participants performed two generic tasks in co-located and delocated configurations, and comparing their performances. Additionally, we intend to fill the gap (ii) by testing a design without continuous head tracking, i.e., with static co-location. Participants’ performances are assessed in terms of execution time, accuracy and force variation, while their subjective experiences are collected via a survey. Findings indicate that co-located configurations lead to shorter execution times, more accurate motions, better management of forces and are largely preferred by users, even when the co-location is pre-calibrated statically.
Clinico-neuropathological features of isocitrate dehydrogenase 2 gene mutations in lower-grade gliomas

Abstract Background: Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are important for both the integrated diagnosis and the prognosis of diffuse gliomas. The p.R132H mutation of IDH1 is the most frequently observed IDH mutation, while IDH2 mutations were relatively rarely studied. The aim of the study was to determine the pathological and genetic characteristics of lower-grade gliomas that carry IDH2 mutations. Methods: Data from 238 adult patients with lower-grade gliomas were retrospectively analyzed. The status of IDH1/2 gene mutations, telomerase reverse transcriptase (TERT) promoter mutations, O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p/19q co-deletion and the expressions of IDH1 R132H, alpha-thalassemia X-linked mental retardation, and p53 were evaluated. Progression-free survival (PFS) and overall survival (OS) were calculated via Kaplan-Meier estimation using the log-rank test. Results: Totally, 71% (169/238) of patients were positive for IDH mutations, including 12 patients harboring mutations in IDH2. Among the 12 patients with IDH2 mutations, ten patients harbored the R172K mutation, one patient harbored the R172S mutation and one harbored the R172W mutation. Of these, 11 tumors occurred in the frontal lobe and showed morphology typical of oligodendroglioma. The proportion of grade II tumors was higher than that of grade III tumors in IDH2 mutant-gliomas. IDH2 mutations were frequently associated with TERT promoter mutations, 1p/19q co-deletion and MGMT promoter methylation. IDH2 mutations were associated with better outcomes compared with IDH wild-type gliomas (P < 0.05). However, the PFS and OS did not differ from that of IDH1 mutant patients (P = 0.95 and P = 0.60, respectively). Conclusions: IDH2 mutations are more frequent in oligodendrogliomas and associated with a better prognosis. IDH2 mutations may segregate in distinct clinico-pathological and genetic subtypes of gliomas, and therefore may merit routine investigation.
Effect of type of contact, counterface surface roughness, and contact area on the wear and friction of extensively cross-linked, vitamin E stabilized UHMWPE.

Novel extensively cross-linked, vitamin E stabilized polyethylene (VEXLPE) materials are expected to provide improved wear and oxidation resistance in orthopedic implants. Noncyclic, multidirectional pin-on-disk (POD) wear tests were performed for VEXLPE with flat-on-flat (FoF) and ball-on-flat (BoF) specimen configurations against CoCr counterfaces of varying surface roughness (Sa = 0.02-0.74 μm). In addition, wear tests (FoF) were performed for VEXLPE pins of varying nominal contact area (7.07-113 mm2 ) with consistent load regimen against polished CoCr disks. All specimen couples were also friction tested with a multidirectional, circularly translating POD device. In all tests, calf serum was used as the lubricant. In comparison with earlier, similar tests for conventional, gamma-sterilized ultra-high molecular weight polyethylene (UHMWPE) and for extensively cross-linked, heat treated UHMWPE (XLPE), the tribological findings for the present VEXLPE appeared promising with respect to its possible clinical use in prosthetic joints, particularly as an acetabular liner against large-diameter femoral heads, and in nonconforming contacts. Contrary to the well-known, paradoxical behavior of conventional UHMWPE, the VEXLPE wear factor decreased with increasing contact area.
Genomes of Leishmania parasites directly sequenced from patients with visceral leishmaniasis in the Indian subcontinent

Whole genome sequencing (WGS) is increasingly used for molecular diagnosis and epidemiology of infectious diseases. Current Leishmania genomic studies rely on DNA extracted from cultured parasites, which might introduce sampling and biological biases into the subsequent analyses. Up to now, direct analysis of Leishmania genome in clinical samples is hampered by high levels of human DNA and large variation in parasite load in patient samples. Here, we present a method, based on target enrichment of Leishmania donovani DNA with Agilent SureSelect technology, that allows the analysis of Leishmania genomes directly in clinical samples. We validated our protocol with a set of artificially mixed samples, followed by the analysis of 63 clinical samples (bone marrow or spleen aspirates) from visceral leishmaniasis patients in Nepal. We were able to identify genotypes using a set of diagnostic SNPs in almost all of these samples (97%) and access comprehensive genome-wide information in most (83%). This allowed us to perform phylogenomic analysis, assess chromosome copy number and identify large copy number variants (CNVs). Pairwise comparisons between the parasite genomes in clinical samples and derived in vitro cultured promastigotes showed a lower aneuploidy in amastigotes as well as genomic differences, suggesting polyclonal infections in patients. Altogether our results underline the need for sequencing parasite genomes directly in the host samples. Author summary Visceral leishmaniasis (VL) is caused by parasitic protozoa of the Leishmania donovani complex and is lethal in the absence of treatment. Whole Genome Sequencing (WGS) of L. donovani clinical isolates revealed hitherto cryptic population structure in the Indian Sub-Continent and provided insights into the epidemiology and potential mechanisms of drug resistance. However, several biases are likely introduced during the culture step. We report here the development of a method that allows determination of parasite genomes directly in clinical samples, and validate it on bone marrow and splenic aspirates of VL patients in Nepal. Our study sheds a new light on the biology of Leishmania in the human host: we found that intracellular parasites of the patients had very low levels of aneuploidy, in sharp contrast to the situation in cultivated isolates. Moreover, the observed differences in genomes between intracellular amastigotes of the patient and the derived cultured parasites suggests polyclonality of infections, with different clones dominating in clinical samples and in culture, likely due to fitness differences. We believe this method is most suitable for clinical studies and for molecular tracking in the context of elimination programs.
Malabaricone C attenuates NSAID-induced gastric ulceration by reducing oxidative/nitrative stress and inflammation and promoting angiogenic auto-healing.

AIMS Non-steroidal anti-inflammatory drugs (NSAIDs), amongst the most commonly used drugs worldwide, are associated with gastrointestinal complications that severely limit the clinical utility of this essential class of pain medications. Here, we mechanistically dissect the protective impact of a natural product, malabaricone C, on NSAID-induced gastropathy. RESULTS Malabaricone C dose dependently diminished erosion of the stomach lining and inflammation in mice treated with NSAIDs with the protective impact translating to improvement in survival. By decreasing oxidative and nitrative stress, malabaricone C treatment prevented NSAID-induced mitochondrial dysfunction and cell death; NF-κB induction, release of pro-inflammatory cytokines and neutrophil infiltration; and disruptions in the vascular endothelial growth factor/endostatin balance that contributes to mucosal auto-healing. Importantly, malabaricone C failed to impact the therapeutic anti-inflammatory properties of multiple NSAIDs in a model of acute inflammation. In all assays tested, malabaricone C proved as or more efficacious than the current first line therapy for NSAID-dependent GI complications, the proton pump inhibitor omeprazole. Innovation and Conclusion: Given that omeprazole-mediated prophylaxis is, itself, associated with a shift in NSAID-driven GI complications from the upper GI to the lower GI system, there is a clear and present need for novel therapeutics aimed at ameliorating NSAID-induced gastropathy. Malabaricone C provided significant protection against NSAID-induced gastric ulcerations impacting multiple critical signaling cascades contributing to inflammation, cell loss, extracellular matrix degradation, and angiogenic auto-healing. Thus, malabaricone C represents a viable lead compound for the development of novel gastroprotective agents.
Is Destiny Worth the Distance? On Private Equity in Emerging Markets

We study the performance determinants of private equity investing in emerging markets (EM) compared to developed markets (DM) using a novel dataset. Using a multilevel linear model specification, our results suggest that performance in emerging markets in highly dependent on geographical and cultural proximity. The effect is significantly higher for GPs investing in both markets compared to pure DM- and EM-players respectively. Cross-cultural and geographical effects are enhanced when the GP investment teams are also culturally close using different measures. Our results also show that the realized returns are highly dependent on the investment period, the investment style and the GP’s experience on each market.
Immunologic alterations in the pancreatic cancer microenvironment of patients treated with neoadjuvant chemo- and radiotherapy.

Pancreatic ductal adenocarcinoma (PDAC) has dismal five-year survival (<9%). We hypothesize that exposure of tumors to conventional therapies may preferentially modulate immune biomarkers in the tumor microenvironment in PDAC. PDAC patients who underwent upfront surgical resection or who received neoadjuvant FOLFIRINOX with or without neoadjuvant radiotherapy followed by surgical resection were selected for study. Total expression of immunologically relevant transcripts and spatially resolved expression of immunologically relevant proteins was quantitated using multiplexed methods (Nanostring nCounter and GeoMX platforms). This analysis identified numerous differentially expressed transcripts associated with the type of neoadjuvant therapy received. Moreover, we identified significant alterations in the expression and/or spatial distribution of immunologically relevant proteins in different regions (tumor cell rich, immune cell rich, stromal cell rich) of the TME. These data provide insight into the immunological effects of clinically relevant neoadjuvant therapy for resectable/borderline-resectable PDAC, by describing significant differences in the expression of key immunologic biomarkers within the PDAC microenvironment that were associated with the type of treatment patients received prior to surgical resection. This represents a comprehensive analysis of numerous biomarkers conducted on the PDAC microenvironment. This work may guide strategic new combination therapies for pancreatic cancer.
Childhood anxiety sensitivity, fear downregulation, and anxious behaviors: Vagal suppression as a moderator of risk.

Anxiety sensitivity-the fear that anxiety-related sensations will result in catastrophic physical, social, or psychological consequences-is a robust risk factor for clinical anxiety. However, less is known about how anxiety sensitivity may interact with physiological modulation of arousal to predict anxious children's fear responses. The present investigation examined vagal withdrawal as a moderator of the association between anxiety sensitivity and anxious children's ability to downregulate subjective feelings of fear in response to an anxiety-provoking speech task. Observer ratings of anxious behaviors and performance during the task were also examined. It was hypothesized that children's anxiety sensitivity levels would interact with respiratory sinus arrhythmia (RSA) suppression to explain unique variance in subjective fear downregulation, anxious behaviors, and task performance. Participants were 105 children with anxiety disorders (N = 105; M = 10.07 years, SD = 1.22; 57% female) who completed diagnostic interviews, questionnaires, a speech about their family, and an RSA assessment in baseline and speech conditions. Interactions between RSA suppression and anxiety sensitivity predicted unique variance in subjective fear downregulation. Specifically, the greatest difficulties downregulating subjective fear responses were exhibited by children with high anxiety sensitivity and low RSA suppression. Interactions between RSA suppression and anxiety sensitivity did not predict variance in observer ratings of anxious behaviors or task performance. However, higher baseline RSA and speech RSA were significantly associated with fewer anxious behaviors during the speech. Higher baseline RSA was also significantly associated with better speech performance. These findings highlight the importance of vagal withdrawal and its interaction with anxiety sensitivity in predicting downregulation of subjective fear among clinically anxious children. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Η επίδραση της επεξεργασίας οπτικών συστημάτων στην ανάπτυξη της ικανότητας γι ακατανόηση και παραγωγή διαφορετικών ειδών κειμένων από μαθητές της Δευτεροβάθμιας Εκπαίδευσης

The purposes of the present research are: a) The designing of a learning environment based on the processing of authentic texts in which the message is transmitted through the combination of verbal and visual modes, b) The investigation of the influence of this learning environment on the develop¬ment of school age children's ability to produce different kinds of multi-modal texts. In the research participated 25 7th grade students who attended a private school in a suburb of East Attica. The data used in the research were the diagrams and (lie texts that the students produced during the instructional intervention which lasted six months. Results of the research showed that the participation of the children in a learning environment which gave them the opportunity to read a diagram and transform it in sentences that constitute a certain text type helped them cm the one hand to produce texts that are characterized by systematic use of functional characteristics that differentiate different text types and on the other hand to become aware of the met cognitive skills and strategies that are involved in the writing process of multi-modal texts.
Infective valve endocarditis after transcatheter aortic valve implantation-a dangerous liaison.

Infective endocarditis (IE) is a rare disease in the general population (1), but the annual incidence is markedly increased in patients with previous cardiac valve surgery, which impacts 4,000–6,000 cases per million patients (2). Due to the recent development of transcatheter aortic valve implantation (TAVI), our knowledge about TAVI-IE is still limited, in particular, in comparison to IE developing after surgical aortic valve replacement (SAVR-IE). Initial data on TAVI-IE are concerning, since it is difficult to diagnose and prognosis is dismal. This Editorial will summarize our current knowledge concerning diagnosis, treatment and prevention of TAVI-IE.
Emotional intelligence predicts academic performance: A meta-analysis.

Schools and universities devote considerable time and resources to developing students' social and emotional skills, such as emotional intelligence (EI). The goals of such programs are partly for personal development but partly to increase academic performance. The current meta-analysis examines the degree to which student EI is associated with academic performance. We found an overall effect of ρ = . 20 using robust variance estimation (N = 42,529, k = 1,246 from 158 citations). The association is significantly stronger for ability EI (ρ = .24, k = 50) compared with self-rated (ρ = .12, k = 33) or mixed EI (ρ = .19, k = 90). Ability, self-rated, and mixed EI explained an additional 1.7%, 0.7%, and 2.3% of the variance, respectively, after controlling for intelligence and big five personality. Understanding and management branches of ability EI explained an additional 3.9% and 3.6%, respectively. Relative importance analysis suggests that EI is the third most important predictor for all three streams, after intelligence and conscientiousness. Moderators of the effect differed across the three EI streams. Ability EI was a stronger predictor of performance in humanities than science. Self-rated EI was a stronger predictor of grades than standardized test scores. We propose that three mechanisms underlie the EI/academic performance link: (a) regulating academic emotions, (b) building social relationships at school, and (c) academic content overlap with EI. Different streams of EI may affect performance through different mechanisms. We note some limitations, including the lack of evidence for a causal direction. (PsycINFO Database Record (c) 2019 APA, all rights reserved).