Takshan/R1 huggingface dataset:
Improving amphibian genomic resources: a multitissue reference transcriptome of an iconic invader.

Background: Cane toads (Rhinella marina) are an iconic invasive species introduced to 4 continents and well utilized for studies of rapid evolution in introduced environments. Despite the long introduction history of this species, its profound ecological impacts, and its utility for demonstrating evolutionary principles, genetic information is sparse. Here we produce a de novo transcriptome spanning multiple tissues and life stages to enable investigation of the genetic basis of previously identified rapid phenotypic change over the introduced range. Findings: Using approximately 1.9 billion reads from developing tadpoles and 6 adult tissue-specific cDNA libraries, as well as a transcriptome assembly pipeline encompassing 100 separate de novo assemblies, we constructed 62 202 transcripts, of which we functionally annotated ∼50%. Our transcriptome assembly exhibits 90% full-length completeness of the Benchmarking Universal Single-Copy Orthologs data set. Robust assembly metrics and comparisons with several available anuran transcriptomes and genomes indicate that our cane toad assembly is one of the most complete anuran genomic resources available. Conclusions: This comprehensive anuran transcriptome will provide a valuable resource for investigation of genes under selection during invasion in cane toads, but will also greatly expand our general knowledge of anuran genomes, which are underrepresented in the literature. The data set is publically available in NCBI and GigaDB to serve as a resource for other researchers.
Genetic control of grain yield and grain physical characteristics in a bread wheat population grown under a range of environmental conditions.

KEY MESSAGE: Genetic analysis of the yield and physical quality of wheat revealed complex genetic control, including strong effects of photoperiod-sensitivity loci. Environmental conditions such as moisture deficit and high temperatures during the growing period affect the grain yield and grain characteristics of bread wheat (Triticum aestivum L.). The aim of this study was to map quantitative trait loci (QTL) for grain yield and grain quality traits using a Drysdale/Gladius bread wheat mapping population grown under a range of environmental conditions in Australia and Mexico. In general, yield and grain quality were reduced in environments exposed to drought and/or heat stress. Despite large effects of known photoperiod-sensitivity loci (Ppd-B1 and Ppd-D1) on crop development, grain yield and grain quality traits, it was possible to detect QTL elsewhere in the genome. Some of these QTL were detected consistently across environments. A locus on chromosome 6A (TaGW2) that is known to be associated with grain development was associated with grain width, thickness and roundness. The grain hardness (Ha) locus on chromosome 5D was associated with particle size index and flour extraction and a region on chromosome 3B was associated with grain width, thickness, thousand grain weight and yield. The genetic control of grain length appeared to be largely independent of the genetic control of the other grain dimensions. As expected, effects on grain yield were detected at loci that also affected yield components. Some QTL displayed QTL-by-environment interactions, with some having effects only in environments subject to water limitation and/or heat stress.
Accurate indel prediction using paired-end short reads.

BACKGROUND: One of the major open challenges in next generation sequencing (NGS) is the accurate identification of structural variants such as insertions and deletions (indels). Current methods for indel calling assign scores to different types of evidence or counter-evidence for the presence of an indel, such as the number of split read alignments spanning the boundaries of a deletion candidate or reads that map within a putative deletion. Candidates with a score above a manually defined threshold are then predicted to be true indels. As a consequence, structural variants detected in this manner contain many false positives. RESULTS: Here, we present a machine learning based method which is able to discover and distinguish true from false indel candidates in order to reduce the false positive rate. Our method identifies indel candidates using a discriminative classifier based on features of split read alignment profiles and trained on true and false indel candidates that were validated by Sanger sequencing. We demonstrate the usefulness of our method with paired-end Illumina reads from 80 genomes of the first phase of the 1001 Genomes Project ( http://www.1001genomes.org) in Arabidopsis thaliana. CONCLUSION: In this work we show that indel classification is a necessary step to reduce the number of false positive candidates. We demonstrate that missing classification may lead to spurious biological interpretations. The software is available at: http://agkb.is.tuebingen.mpg.de/Forschung/SV-M/.
DNA methylation as a predictor of fetal alcohol spectrum disorder.

Background: Fetal alcohol spectrum disorder (FASD) is a developmental disorder that manifests through a range of cognitive, adaptive, physiological, and neurobiological deficits resulting from prenatal alcohol exposure. Although the North American prevalence is currently estimated at 2-5%, FASD has proven difficult to identify in the absence of the overt physical features characteristic of fetal alcohol syndrome. As interventions may have the greatest impact at an early age, accurate biomarkers are needed to identify children at risk for FASD. Building on our previous work identifying distinct DNA methylation patterns in children and adolescents with FASD, we have attempted to validate these associations in a different clinical cohort and to use our DNA methylation signature to develop a possible epigenetic predictor of FASD. Methods: Genome-wide DNA methylation patterns were analyzed using the Illumina HumanMethylation450 array in the buccal epithelial cells of a cohort of 48 individuals aged 3.5-18 (24 FASD cases, 24 controls). The DNA methylation predictor of FASD was built using a stochastic gradient boosting model on our previously published dataset FASD cases and controls (GSE80261). The predictor was tested on the current dataset and an independent dataset of 48 autism spectrum disorder cases and 48 controls (GSE50759). Results: We validated findings from our previous study that identified a DNA methylation signature of FASD, replicating the altered DNA methylation levels of 161/648 CpGs in this independent cohort, which may represent a robust signature of FASD in the epigenome. We also generated a predictive model of FASD using machine learning in a subset of our previously published cohort of 179 samples (83 FASD cases, 96 controls), which was tested in this novel cohort of 48 samples and resulted in a moderately accurate predictor of FASD status. Upon testing the algorithm in an independent cohort of individuals with autism spectrum disorder, we did not detect any bias towards autism, sex, age, or ethnicity. Conclusion: These findings further support the association of FASD with distinct DNA methylation patterns, while providing a possible entry point towards the development of epigenetic biomarkers of FASD.
Prenatal alcohol exposure alters steady-state and activated gene expression in the adult rat brain.

BACKGROUND: Prenatal alcohol exposure (PAE) is associated with alterations in numerous physiological systems, including the stress and immune systems. We have previously shown that PAE increases the course and severity of arthritis in an adjuvant-induced arthritis (AA) model. While the molecular mechanisms underlying these effects are not fully known, changes in neural gene expression are emerging as important factors in the etiology of PAE effects. As the prefrontal cortex (PFC) and hippocampus (HPC) play key roles in neuroimmune function, PAE-induced alterations to their transcriptome may underlie abnormal steady-state functions and responses to immune challenge. This study examined brains from adult PAE and control females from our recent AA study to determine whether PAE causes long-term alterations in gene expression and whether these mediate the altered severity and course of arthritis in PAE females. METHODS: Adult females from PAE, pair-fed (PF), and ad libitum-fed control (C) groups were injected with either saline or complete Freund's adjuvant. Animals were terminated at the peak of inflammation or during resolution (Days 16 and 39 postinjection, respectively); cohorts of saline-injected PAE, PF, and C females were terminated in parallel. Gene expression was analyzed in the PFC and HPC using whole-genome mRNA expression microarrays. RESULTS: Significant changes in gene expression in both the PFC and HPC were found in PAE compared to controls in response to ethanol exposure alone (saline-injected females), including genes involved in neurodevelopment, apoptosis, and energy metabolism. Moreover, in response to inflammation (adjuvant-injected females), PAE animals showed unique expression patterns, while failing to exhibit the activation of genes and regulators involved in the immune response observed in control and pair-fed animals. CONCLUSIONS: These results support the hypothesis that PAE affects neuroimmune function at the level of gene expression, demonstrating long-term effects of PAE on the central nervous system response under steady-state conditions and following an inflammatory insult.
Home exercise improves the quality of sleep and daytime sleepiness of elderlies: a randomized controlled trial.

Background: Aging causes physiological changes which affect the quality of sleep. Supervised physical exercise is an important therapeutic resource to improve the sleep of the elderlies, however there is a low adherence to those type of programs, so it is necessary to implement an exercise program which is feasible and effective. The study aimed to test the hypothesis that a semi-supervised home exercise program, improves sleep quality and daytime sleepiness of elderlies of the community who present poor sleep quality. Methods: This was a randomized controlled trial study, conducted from May to September 2017, in Northeastern Brazil, with elderlies of the community aging 60 years old or older, sedentary, with lower scores or equal to 5 at the Pittsburgh Sleep Quality Index (PSQI) and without cognitive decline. From one hundred ninety-one potential participants twenty-eight refused to participate, therefore, one hundred thirty-one (mean age 68 ± 7 years), and 88% female, were randomly assigned to an intervention group - IG (home exercise and sleep hygiene, n = 65) and a control group - CG (sleep hygiene only, n = 66). Sleep assessment tools were used: PSQI, Epworth sleepiness scale (ESS) and clinical questionnaire of Berlin. The level of physical activity has been assessed by means of International Physical Activity Questionnaire adapted for the elderly (IPAQ) and Mini-Mental State Examination for cognitive decline. All participants were assessed before and after the 12-week intervention period and, also, the assessors were blind. Results: The IG showed significant improvement in quality of sleep with a mean reduction of 4.9 ± 2.7 points in the overall PSQI (p < 0.01) and in all its 7 components of evaluation (p < 0.05), and improvement of secondary endpoint, daytime sleepiness, a decline of 2.8 ± 2.2 points in the ESS (p < 0.01). Conclusion: Our results suggest that semi-supervised home exercise is effective in improving the quality of sleep and self-referred daytime sleepiness of sedentary elderlies of the community who presented sleep disorders. Trial registration: Ensaiosclinicos.gov.br process number: RBR-3cqzfy.
Functional role of AKT signaling in bovine early embryonic development: potential link to embryotrophic actions of follistatin.

BACKGROUND: TGF-β signaling pathways regulate several crucial processes in female reproduction. AKT is a non-SMAD signaling pathway regulated by TGF-β ligands essential for oocyte maturation and early embryonic development in the mouse, but its regulatory role in bovine early embryonic development is not well established. Previously, we demonstrated a stimulatory role for follistatin (a binding protein for specific members of TGF-β superfamily) in early bovine embryonic development. The objectives of the present studies were to determine the functional role of AKT signaling in bovine early embryonic development and embryotrophic actions of follistatin. METHODS: We used AKT inhibitors III and IV as pharmacological inhibitors of AKT signaling pathway during the first 72 h of in vitro embryo culture. Effects of AKT inhibition on early embryonic development and AKT phosphorylation were investigated in the presence or absence of exogenous follistatin. RESULTS: Pharmacological inhibition of AKT signaling resulted in a significant reduction in early embryo cleavage, and development to the 8- to 16-cell and blastocyst stages (d7). Treatment with exogenous follistatin increased AKT phosphorylation and rescued the inhibitory effect of AKT inhibitors III and IV on AKT phosphorylation and early embryonic development. CONCLUSIONS: Collectively, results suggest a potential requirement of AKT for bovine early embryonic development, and suggest a potential role for follistatin in regulation of AKT signaling in early bovine embryos.
Elevated Production of Nociceptive CC-chemokines and sE-selectin in Patients with Low Back Pain and the Effects of Spinal Manipulation: A Non-randomized Clinical Trial.

BACKGROUND: The involvement of inflammatory components in the pathophysiology of low back pain is poorly understood. It has been suggested that spinal manipulative therapy (SMT) may exert anti-inflammatory effects. PURPOSE: To determine the involvement of inflammation-associated chemokines (CC series) in the pathogenesis of non-specific low back pain and to evaluate the effect of SMT on that process. METHODS: Patients presenting with non-radicular, non-specific low back pain (minimum pain score 3 on 10 point visual analogue scale, VAS) were recruited according to stringent inclusion criteria. They were evaluated for appropriateness to treat using a high velocity low amplitude manipulative thrust (HVLT) in the lumbar-lumbosacral region. Blood samples were obtained at baseline and following the administration of a series of 6 HVLTs on alternate days over the period of two weeks. The in vitro levels of CC chemokines (CCL2, CCL3 and CCL4) production and plasma levels of an inflammatory biomarker, soluble E-selectin, were determined at baseline and at the termination of treatments two weeks later. RESULTS: Compared with asymptomatic controls baseline production of all chemokines was significantly elevated in acute (P=0.004 - <0.0001), and that of CCL2 and CCL4 in chronic LBP patients (P<0.0001). Furthermore, CCL4 production was significantly higher (P<0.0001) in the acute versus chronic LBP group. sE-selectin levels were significantly higher (P=0.003) in chronic but not in acute LBP patients. Following SMT, patient reported outcomes showed significant (P<0.0001) improvements in VAS and ODI scores. This was accompanied by a significant decline in CCL 3 production (P<0.0001) in both groups of patients. Change scores for CCL4 production differed significantly (P<0.0001) only for the acute LBP cohort, and no effect on the production of CCL2 or plasma sE-selectin levels was noted in either group. CONCLUSION: The production of chemotactic cytokines is significantly and protractedly elevated in LBP patients. Changes in chemokine production levels, which might be related to SMT, differ in the acute and chronic LBP patient cohorts. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0.
EthSEQ: ethnicity annotation from whole exome sequencing data.

Summary: Whole exome sequencing (WES) is widely utilized both in translational cancer genomics studies and in the setting of precision medicine. Stratification of individual's ethnicity is fundamental for the correct interpretation of personal genomic variation impact. We implemented EthSEQ to provide reliable and rapid ethnicity annotation from whole exome sequencing individual's data, validated it on 1000 Genome Project and TCGA data (2700 samples) demonstrating high precision, and finally assessed computational performances compared to other tools. EthSEQ can be integrated into any WES based processing pipeline and exploits multi-core capabilities. Availability and Implementation: R package available at github.com/aromanel/EthSEQ and CRAN repository. Contact: alessandro.romanel@unitn.it or f.demichelis@unitn.it. Supplementary information: Supplementary data are available at Bioinformatics online.
Anesthetic dreaming, anesthesia awareness and patient satisfaction after deep sedation with propofol target controlled infusion: A prospective cohort study of patients undergoing day case breast surgery.

Background: Anesthetic dreaming and anesthesia awareness are well distinct phenomena. Although the incidence of intraoperative awareness is more common among patients who reported a dream after surgery, the exact correlation between the two phenomena remains an unsolved rebus. The main purpose of this study was to investigate anesthetic dreaming, anesthesia awareness and psychological consequences eventually occurred under deep sedation. Intraoperative dreaming experiences were correlated with dream features in natural sleep. Methods: Fifty-one patients, undergoing surgical excision of fibroadenomas under a Bispectral index-guided deep sedation anesthesia with propofol target controlled infusion, were enrolled into this prospective study. Psychological assessment was performed through the State Trait Anxiety Inventory. A questionnaire was adopted to register dreaming and anesthesia awareness. Data were collected after emergence (t0), 24 hours (t1), 1 month (t2), 6 months (t3). Results: Six patients (12%) reported anesthetic dreaming at t0 confirming the response at each subsequent evaluation. One patient (2%) confirmed dreaming during anesthesia in all, but denied it at t0. There was a high correlation between the intraoperative dream contents and the features of dreams in natural sleep. No cases of anesthesia awareness were detected. A similar level of satisfaction was observed in dreaming and no-dreaming patients. Conclusions: Anesthetic dreaming does not seem to influence satisfaction of patients undergoing deep sedation with propofol target controlled infusion. A psychological assessment would seem to improve the evaluation of possible psychological consequences in dreamer patient.
CCR7(+) selected gene-modified T cells maintain a central memory phenotype and display enhanced persistence in peripheral blood in vivo.

BACKGROUND: Adoptive T cell immunotherapy (ATCT) for cancer entails infusing patients with T cells that recognise and destroy tumour cells. Efficient engraftment of T cells and persistence in the circulation correlate with favourable clinical outcomes. T cells of early differentiation possess an increased capacity for proliferation and therefore persistence, using these cells for ATCT could therefore lead to improved clinical outcomes. METHOD: We describe a method to enrich T cells of early differentiation status using paramagnetic beads and antibodies targeting cells expressing C-C motif chemokine receptor 7 (CCR7). RESULTS: Selection of cells expressing CCR7 enriches T cells of bearing markers of early differentiation status. This was validated through analysis of an array of surface markers and an observed reduction in effector cell functions ex vivo. CCR7 selection resulted in dramatic 83.6 and 137 fold increases in circulating levels of CD4 and CD8 T cells respectively compared to non-sorted T cells 3 weeks after adoptive transfer to NSG mice. We observed no significant difference in the engraftment levels of CCR7 or CD62L selected cells in the NSG mouse model. Comparison of cells ex vivo, however, suggests CCR7 selection is superior to CD62L selection in enriching T cells of early differentiation status. CONCLUSIONS: CCR7 selection offers a means to enrich T cells of early differentiation status for ACTC. Together our data suggests that these T cells are likely to display enhanced engraftment and persistence in patients in vivo and could therefore improve therapeutic efficacy of ACTC.
Gastrointestinal safety of etoricoxib in osteoarthritis and rheumatoid arthritis: A meta-analysis.

OBJECTIVE: To ascertain if etoricoxib increases the risk of gastrointestinal adverse events (GAEs) compared with placebo, diclofenac, and naproxen in the treatment of patients with osteoarthritis (OA) or rheumatoid arthritis (RA). METHODS: Studies were searched in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials from inception to August 2017. Randomized Clinical Trials (RCTs) that compared etoricoxib with placebo and other active drug for patients with OA or RA and reported data on gastrointestinal safety (which is of interest to patients and clinicians) were included. The follow-up time window for GAEs was defined as within 28 days subsequent to the last dose of study medication. A meta-analysis was conducted using a fixed-effect model. Risk ratios (RRs) and 95% confidence intervals (CIs) were measured. RESULTS: We found nine randomized clinical trials (RCTs) that included information on gastrointestinal safety during follow-up time. Among them, five RCTs compared etoricoxib with placebo, four RCTs compared etoricoxib with diclofenac, and three RCTs compared etoricoxib with naproxen. Etoricoxib did not increase the risk of GAEs compared with placebo. Compared with diclofenac and naproxen, etoricoxib reduced the GAE risk (RR, 0.67; 95% CI, 0.59-0.76; p < 0.00001; 0.59; 0.48-0.72; < 0.00001) during follow-up time. CONCLUSIONS: In patients with OA or RA, etoricoxib did not increase the GAE risk compared with placebo, but reduced the GAE risk effectively compared with diclofenac and naproxen during follow-up time.