Miracle-dz/UniFAR-FTUs huggingface dataset:
Deleterious alleles in the context of domestication, inbreeding, and selection

Each individual has a certain number of harmful mutations in its genome. These mutations can lower the fitness of the individual carrying them, dependent on their dominance and selection coefficient. Effective population size, selection, and admixture are known to affect the occurrence of such mutations in a population. The relative roles of demography and selection are a key in understanding the process of adaptation. These are factors that are potentially influenced and confounded in domestic animals. Here, we hypothesize that the series of events of bottlenecks, introgression, and strong artificial selection associated with domestication increased mutational load in domestic species. Yet, mutational load is hard to quantify, so there are very few studies available revealing the relevance of evolutionary processes. The precise role of artificial selection, bottlenecks, and introgression in further increasing the load of deleterious variants in animals in breeding and conservation programmes remains unclear. In this paper, we review the effects of domestication and selection on mutational load in domestic species. Moreover, we test some hypotheses on higher mutational load due to domestication and selective sweeps using sequence data from commercial pig and chicken lines. Overall, we argue that domestication by itself is not a prerequisite for genetic erosion, indicating that fitness potential does not need to decline. Rather, mutational load in domestic species can be influenced by many factors, but consistent or strong trends are not yet clear. However, methods emerging from molecular genetics allow discrimination of hypotheses about the determinants of mutational load, such as effective population size, inbreeding, and selection, in domestic systems. These findings make us rethink the effect of our current breeding schemes on fitness of populations.
The efficacy of a brief app-based mindfulness intervention on psychosocial outcomes in healthy adults: A pilot randomised controlled trial

Background Previous evidence suggests that mindfulness training may improve aspects of psychosocial well-being. Whilst mindfulness is traditionally taught in person, consumers are increasingly turning to mindfulness-based smartphone apps as an alternative delivery medium for training. Despite this growing trend, few studies have explored whether mindfulness delivered via a smartphone app can enhance psychosocial well-being within the general public. Methods The present pilot randomised controlled trial compared the impact of engaging with the self-guided mindfulness meditation (MM) app ‘Headspace’ (n = 38) for a period of 10 or 30 days, to a wait-list (WL) control (n = 36), using a cohort of adults from the general population. The Satisfaction with Life Scale, Perceived Stress Scale, and Wagnild Resilience Scale were administered online at baseline and after 10 and 30 days of the intervention. Results Twelve participants (MM n = 9, WL n = 3) were lost to follow-up for unknown reasons. Relative to the WL control, the MM app positively impacted self-reported satisfaction with life, stress, and resilience at day 10, with further improvements emerging at day 30 (Cohen’s d = 0.57, 1.42, 0.63 respectively). The rate of improvement was largest at the 10-day assessment point, dropping moderately by day 30. Participants that rated the MM app as easy to engage with experienced the largest self-reported benefits. Moreover, the MM app was able to protect against an unexpected increase in perceived stress that emerged in the control group. Conclusions This pilot randomised controlled trial shows that self-reported improvements in psychosocial outcomes can be achieved at low cost through short-term engagement with a mindfulness-based smartphone app, and should be followed up with more substantive studies. Trial registration ISRCTN ISRCTN34618894.
Correlates of psychological distress among workers in the mining industry in remote Australia: Evidence from a multi-site cross-sectional survey

The purpose of this study was to assess the prevalence of psychological distress in employees in the metalliferous mining industry in Australia, and to examine associated demographic, health, and workplace characteristics. A cross sectional survey was conducted among 1,799 participants from four metalliferous mines. Psychological distress was measured by the Kessler Psychological Distress Scale (K10), alongside other measures of personal demographics, health history, health behaviour, and workplace characteristics. Univariate and multivariate statistical methods were used to examine associations between psychological distress and personal and workplace characteristics. Levels of moderate to very high psychological distress were significantly higher in this sample (44.4%) compared to the general population (27.2%). Moderate to very high psychological distress was significantly associated with younger age; individual health factors (a prior history of depression, anxiety, or drug/alcohol problems); health behaviours (using illicit drugs in the last month); and a range of workplace factors (concern about losing their job; lower satisfaction with work; working shifts of over 12 hours duration; working in mining for financial reasons and social factors (poorer social networks). The identification of a number of social, personal and workplace factors associated with high psychological distress present useful targets to inform the development of tailored workplace interventions to reduce distress in metalliferous mine employees.
Cohort study of a specialist social worker intervention on hospital use for patients at risk of long stay

Background Long-stay patients in acute hospitals commonly present with complex psychosocial needs and use high levels of hospital resources. Objective To determine whether a specialist social worker-led model of care was associated with a reduction in length of stay for medically stable patients with complex psychosocial needs who were at risk of long stay, and to determine the economic value of this model relative to the decision makers’ willingness to pay for bed days released. Design A prospective, matched cohort study with historical controls. Setting A large, tertiary teaching and referral hospital in metropolitan Southeast Queensland, Australia. Methods Length of hospital stay for a cohort of patients seen under the specialist social worker-led model of care was compared with a matched control group of patients admitted to the hospital prior to the introduction of the new model of care using a multistate model with the social worker model of care as an intermediate event. Costs associated with the model of care were calculated and an estimate of the ‘cost per bed day’ was produced. Results The model of care reduced mean length of stay by 33 days. This translated to 9999 bed days released over 12 months. The cost to achieve this was estimated to be $A229 000 over 12 months. The cost per bed day released was $23, which is below estimates of hospital decision makers’ willingness to pay for a bed day to be released for an alternate use. Conclusions The specialist social worker-led model of care was associated with a reduced length of stay at a relatively low cost. This is likely to represent a cost-effective use of hospital resources. The limitations of our historic control cohort selection mean that results should be interpreted with caution. Further research is needed to confirm these findings.
Discovering the mechanisms of abstraction in the performance of work teams in children to solve computational problems

El desarrollo de competencias que permitan a los ninos un desempeno satisfactorio en su proceso de formacion y, posteriormente, en su vida laboral o social, se ha convertido en un anhelo de todos los modelos educativos y de formacion que se han desarrollado. El presente articulo trata de la relacion entre el desarrollo de habilidades de pensamiento, los modelos mentales compartidos y los mecanismos de abstraccion, a partir de una revision teorica y la aplicacion con ninos de entre ocho y doce anos, de la metodologia Childprogramming , en una institucion de educacion publica en Colombia. Se presentan los resultados registrados al termino de las practicas realizadas con este grupo de estudiantes, especialmente al evaluar el uso progresivo de los mecanismos de abstraccion en el entorno de Scratch , utilizando la plataforma Dr. Scratch .
Dual Kinect v2 system can capture lower limb kinematics reasonably well in a clinical setting: concurrent validity of a dual camera markerless motion capture system in professional football players

Objectives To determine whether a dual-camera markerless motion capture system can be used for lower limb kinematic evaluation in athletes in a preseason screening setting. Design Descriptive laboratory study. Setting Laboratory setting. Participants Thirty-four (n=34) healthy athletes. Main outcome measures Three dimensional lower limb kinematics during three functional tests: Single Leg Squat (SLS), Single Leg Jump, Modified Counter-movement Jump. The tests were simultaneously recorded using both a marker-based motion capture system and two Kinect v2 cameras using iPi Mocap Studio software. Results Excellent agreement between systems for the flexion/extension range of motion of the shin during all tests and for the thigh abduction/adduction during SLS were seen. For peak angles, results showed excellent agreement for knee flexion. Poor correlation was seen for the rotation movements. Conclusions This study supports the use of dual Kinect v2 configuration with the iPi software as a valid tool for assessment of sagittal and frontal plane hip and knee kinematic parameters but not axial rotation in athletes.
Thickness of retina and choroid in the elderly population and its association with Complement Factor H polymorphism: KLoSHA Eye study

Purpose To analyze the associations of retinal and choroidal thickness on enhanced-depth imaging optical coherence tomography (EDI-OCT) with clinical, ophthalmic and genetic factors in the normal elderly population (aged 65 years or older). Methods In this prospective, population-based cohort study, people aged 65 years or older were enrolled in the baseline study of the Korean Longitudinal Study on Health and Aging (KLoSHA) Eye Study. All participants underwent spectral domain-OCT scan using the EDI technique. A topographic map of the retina was obtained and subfoveal choroidal thickness (SFCT) was measured manually. Blood samples from all subjects were genotyped for major age-related macular degeneration (AMD)-associated single nucleotide polymorphisms (SNPs) the major AMD-associated SNPs; CFH Y402H rs1061170, CFH I62V rs800292, ARMS2 A69S rs10490924. A statistical analysis was conducted to compare the retinal thickness, choroidal thickness, and AMD risk genotypes. Results Among the three hundred eighty people enrolled, the mean age was 76.6 years (range 65–99 years). Factors that showed correlation with either tomographic retinal parameters, retinal nerve fiber layer, or SFCT, were age and gender. Significant age-related decrease in thickness was observed in the RNFL, mean central thickness (MCT) and SFCT. Gender differences existed in central foveolar thickness (CFT) and MCT, where it was thicker in men. While chorioretinal parameters were not related with other genotypes, CFH rs1061170 risk genotype was significantly associated with thin SFCT. The group containing the AMD- risk allele (CT) had a 14.7% reduction in the SFCT compared to the non-risk TT group. Conclusions In addition to the well-known association with AMD, CFH rs1061170 is a significant genetic risk factor associated with choroidal thinning in normal eyes of the elderly population. Such findings may provide further insight into the pathogenesis of age-related macular degeneration as well as normal aging. In addition, our study provides the first normative data on retinal and choroidal thickness in population-based aged groups with a mean age over seventy-five.
A metatranscriptomic analysis of diseased social wasps (Vespula vulgaris) for pathogens, with an experimental infection of larvae and nests

Social wasps are a major pest in many countries around the world. Pathogens may influence wasp populations and could provide an option for population management via biological control. We investigated the pathology of nests of apparently healthy common wasps, Vespula vulgaris, with nests apparently suffering disease. First, next-generation sequencing and metatranscriptomic analysis were used to examine pathogen presence. The transcriptome of healthy and diseased V. vulgaris showed 27 known microbial phylotypes. Four of these were observed in diseased larvae alone (Aspergillus fumigatus, Moellerella wisconsensis, Moku virus, and the microsporidian Vavraia culicis). Kashmir Bee Virus (KBV) was found to be present in both healthy and diseased larvae. Moellerella wisconsensis is a human pathogen that was potentially misidentified in our wasps by the MEGAN analysis: it is more likely to be the related bacteria Hafnia alvei that is known to infect social insects. The closest identification to the putative pathogen identified as Vavraia culicis was likely to be another microsporidian Nosema vulgaris. PCR and subsequent Sanger sequencing using published or our own designed primers, confirmed the identity of Moellerella sp. (which may be Hafnia alvei), Aspergillus sp. , KBV, Moku virus and Nosema. Secondly, we used an infection study by homogenising diseased wasp larvae and feeding them to entire nests of larvae in the laboratory. Three nests transinfected with diseased larvae all died within 19 days. No pathogen that we monitored, however, had a significantly higher prevalence in diseased than in healthy larvae. RT-qPCR analysis indicated that pathogen infections were significantly correlated, such as between KBV and Aspergillus sp. Social wasps clearly suffer from an array of pathogens, which may lead to the collapse of nests and larval death.
New findings showing how DNA methylation influences diseases

In 1975, Holliday and Pugh as well as Riggs independently hypothesized that DNA methylation in eukaryotes could act as a hereditary regulation mechanism that influences gene expression and cell differentiation. Interest in the study of epigenetic processes has been inspired by their reversibility as well as their potentially preventable or treatable consequences. Recently, we have begun to understand that the features of DNA methylation are not the same for all cells. Major differences have been found between differentiated cells and stem cells. Methylation influences various pathologies, and it is very important to improve the understanding of the pathogenic mechanisms. Epigenetic modifications may take place throughout life and have been related to cancer, brain aging, memory disturbances, changes in synaptic plasticity, and neurodegenerative diseases, such as Parkinson’s disease and Huntington’s disease. DNA methylation also has a very important role in tumor biology. Many oncogenes are activated by mutations in carcinogenesis. However, many genes with tumor-suppressor functions are “silenced” by the methylation of CpG sites in some of their regions. Moreover, the role of epigenetic alterations has been demonstrated in neurological diseases. In neuronal precursors, many genes associated with development and differentiation are silenced by CpG methylation. In addition, recent studies show that DNA methylation can also influence diseases that do not appear to be related to the environment, such as IgA nephropathy, thus affecting the expression of some genes involved in the T-cell receptor signaling. In conclusion, DNA methylation provides a whole series of fundamental information for the cell to regulate gene expression, including how and when the genes are read, and it does not depend on the DNA sequence.
Albumin-Bilirubin Grade as a Novel Predictor of Survival in Advanced Extrahepatic Cholangiocarcinoma

Aim Child-Pugh (CP) grade has been used to assess liver function and postoperative outcomes in biliary tract neoplasms. The aim of this study was to preliminarily explore the prognostic significance of an alternative model of liver function, called albumin-bilirubin (ALBI) grade, in patients with extrahepatic cholangiocarcinoma (EHC). Methods A total of 109 advanced EHC patients, who received percutaneous transhepatic biliary stenting combined with iodine-125 seed implantation from January 2012 to April 2017 in our department, were enrolled. Preoperative clinical data were collected to calculate the CP and ALBI grades. The performance of ALBI score in predicting postoperative death was compared with that of CP score by using the receiver operating characteristic (ROC) curve. Kaplan-Meier analysis and Cox regression model were performed for overall survival (OS) analysis. Results The median survival time of our cohort was 12 months, and the 1-year and 2-year survival rates were 56.9% and 12.8%, respectively. The area under the ROC curve of ALBI score for predicting death was significantly greater than the CP score (0.751, 95% CI: 0.641–0.861, P < 0.001 vs. 0.688, 95% CI: 0.567–0.809, P < 0.001). The univariate analysis revealed that the factors related to overall survival of EHC were carbohydrate antigen 19-9, total bilirubin, albumin, ALBI grade, and CP score. In multivariate analysis, ALBI grade (HR = 1.65, 95% CI: 1.04–2.61, P = 0.032), but not CP score, was identified as an independent prognostic model. Conclusion We demonstrated that the ALBI grade could be used as a predictor of survival in unresectable EHC patients.
Correlations between CD34 Immunolabelled Blood Vessels and CD34 mRNA Expression in Colorectal Cancer

Purpose: This study aims to determine the correlation between microvessel density of CD34 immunolabelled blood vessels and CD34 mRNA gene expression in colorectal cancer tissue. Material/Methods: Standard immunohistochemistry and gene expression was perform on samples collected from 76 patients with colorectal cancer in order to determinate the number of CD34 immunolabelled blood vessels and the relative quantity of CD34 mRNA. Results: For the study group, the mean CD34 immunolabelled microvascular density (MVD) was of 307/mm2, and the mean CD34 gene expression value for colon cancer was 2.303. The low p value (<0.001) of the Spearman correlation test showed a significant direct correlation between CD34 MVD and CD34 gene expression for the entire study group. Conclusions: CD34 gene`s expression can be looked at as a prognostic factor in colorectal cancer.
Discontinuing cotrimoxazole preventive therapy in HIV-infected adults who are stable on antiretroviral treatment in Uganda (COSTOP): A randomised placebo controlled trial

Background Cotrimoxazole (CTX) preventive therapy (CPT) reduces opportunistic infections and malaria in HIV-infected patients. In Africa, policies on sustained CPT during antiretroviral therapy (ART) differ between countries. We assessed the safety of discontinuing CPT in stable patients on ART in Uganda. Methods COSTOP was a double-blind placebo-controlled trial. Patients aged ≥18 years, on CPT, and stable on ART (CD4 counts ≥250 cells/μL); were randomised to daily oral placebo (PLC group) or cotrimoxazole 960 mg/tablet (CTX group). Co-primary outcomes were: (i) time to first cotrimoxazole-preventable infection, with non- inferiority of PLC defined as the upper one-sided 95% confidence limit of the adjusted hazard ratio(aHR) ≤1.25; and (ii) time to first grade 3/4 haematological adverse event. Findings 2180 subjects (1091 PLC; 1089 CTX) were enrolled. 932 PLC and 943 CTX completed the trial after 12 months minimum follow up. Ninety-eight participants (59 PLC; 39 CTX) experienced 120 cotrimoxazole- preventable events, mainly bacterial pneumonia (72 events, 4 deaths PLC); (48 events, 2 deaths CTX). The aHR for time to first event was 1.57 (upper one-sided 95% confidence limit 2.21) in per protocol population (similar results in ITT population). 551 participants (318 CTX; 233 PLC) experienced 1043 haematological adverse events (616 CTX; 427 PLC). Time to the first adverse event, mainly neutropenia, was shorter in the CTX group (aHR 0.70 95%CI 0.59–0.82; log-rank χ2 = 18.08; P<0.0001). 362 (276 PLC, 86 CTX) participants experienced at least one episode of confirmed clinical malaria (P<0.0001). Interpretation In ART stable patients with CD4 counts ≥250 cells/μL, continued CPT significantly reduces risk of severe bacterial infections and protects against malaria, while discontinuing CPT reduces haematological adverse events.
The behavior of adult Drosophila in the wild

Little is known about how Drosophila adults behave in the wild, including mating, allocation of food and space, and escape from predators. This lack of information has negative implications for our ability to understand the capabilities of the nervous system to integrate sensory cues necessary for the adaptation of organisms in natural conditions. We characterized a set of behavioral routines of D. melanogaster and D. simulans adults in three ecologically different orchards: grape, apple and prickly pear. We also investigated how the flies identify conspecifics and aliens in the wild to better understand relationships between group formation and adaptation of Drosophila to breeding sites. We characterized the locations by recording in each orchard humidity, temperature, illumination conditions, pH of fruits, the presence/absence of other Drosophila species and the predator ant Linepithema humile. Our findings suggest that the home range of these species of Drosophila includes decaying fruits and, principally, a variety of microhabitats that surround the fruits. The ecological heterogeneity of the orchards and odors emitted by adult D. melanogaster and D. simulans influence perch preferences, cluster formation, court and mating, egg-laying site selection, and use of space. This is one of the first large examinations of the association between changing, complex environments and a set of adult behaviors of Drosophila. Therefore, our results have implications for understanding the genetic differentiation and evolution of populations of species in the genus Drosophila.
Limited detection of human polyomaviruses in Fanconi anemia related squamous cell carcinoma

Fanconi anemia is a rare genome instability disorder with extreme susceptibility to squamous cell carcinoma of the head and neck and anogenital tract. In patients with this inherited disorder, the risk of head and neck cancer is 800-fold higher than in the general population, a finding which might suggest a viral etiology. Here, we analyzed the possible contribution of human polyomaviruses to FA-associated head and neck squamous cell carcinoma (HNSCC) by a pan-polyomavirus immunohistochemistry test which detects the T antigens of all known human polyomaviruses. We observed weak reactivity in 17% of the HNSCC samples suggesting that based on classical criteria, human polyomaviruses are not causally related to squamous cell carcinomas analyzed in this study.