Takshan/R1 huggingface dataset:
Impact of scheduling multiple outdoor free-play periods in childcare on child moderate-to-vigorous physical activity: a cluster randomised trial.

BACKGROUND: Increasing the frequency of periods of outdoor free-play in childcare may represent an opportunity to increase child physical activity. This study aimed to assess the efficacy of scheduling multiple periods of outdoor free-play in increasing the time children spend in moderate-to-vigorous physical activity (MVPA) while attending childcare. METHODS: The study employed a cluster randomised controlled trial design involving children aged 3 to 6 years, attending ten childcare services in the Hunter New England region of New South Wales, Australia. Five services were randomised to receive the intervention and five to a control condition. The intervention involved services scheduling three separate periods of outdoor free-play from 9 am to 3 pm per day, each at least 15 min in duration, with the total equivalent to their usual daily duration of outdoor play period. Control services implemented the usual single continuous period of outdoor free-play over this time. The primary outcome, children's moderate-to-vigorous physical activity (MVPA) while in care per day, was measured over 5 days via accelerometers at baseline and at 3 months post baseline. Secondary outcomes included percentage of time spent in MVPA while in care per day, total physical activity while in care per day and documented child injury, a hypothesised potential unintended adverse event. Childcare services and data collectors were not blind to the experimental group allocation. RESULTS: Parents of 439 (71.6%) children attending participating childcare services consented for their child to participate in the trial. Of these, 316 (72.0%) children provided valid accelerometer data at both time points. Relative to children in control services, mean daily minutes of MVPA in care was significantly greater at follow-up among children attending intervention services (adjusted difference between groups 5.21 min, 95% CI 0.59-9.83 p = 0.03). Percentage of time spent in MVPA in care per day was also greater at follow-up among children in intervention services relative to control services (adjusted difference between groups 1.57, 95% CI 0.64-2.49 p < 0.001). Total physical activity while in care per day, assessed via counts per minute approached but did not reach significance (adjusted difference between groups 14.25, 95% CI 2.26-30.76 p = 0.09). There were no differences between groups in child injury nor subgroup interactions for the primary trial outcome by child age, sex, or baseline MVPA levels. CONCLUSION: Scheduling multiple periods of outdoor free-play significantly increased the time children spent in MVPA while in attendance at childcare. This simple ecological intervention could be considered for broader dissemination as a strategy to increase child physical activity at a population level. TRIAL REGISTRATION: This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) ( ACTRN1261000347460 ). Prospectively registered 17th March 2016.
Clavicle fracture nonunion in the paediatric population: a systematic review of the literature.

Aims: Clavicle fracture nonunions are extremely rare in children. The aim of this systematic review was to assess what factors may predispose children to form clavicle fracture nonunions and evaluate the treatment methods and outcomes. Methods: We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, aiming to find papers reporting clavicle fracture nonunion in children under the age of 18 years. Data was collected on patient demographics, fracture type, mechanism of injury (MOI), surgical intervention and reported outcome. Two independent reviewers evaluated all the data. Results: A total of 13 articles reporting 21 cases of clavicle fracture nonunion were identified. The mean age at time of injury was 11.4 years (4 to 17). Falls were the most common MOI. The majority of nonunions occurred after displaced fractures on the right side. Six were refractures. Mean time of presentation following injury was 13.5 months (4 to 60). In all, 16 were treated surgically. Radiographic union was eventually achieved in 12 cases, with functional outcome satisfactory in all cases. Conclusion: Clavicle nonunion is an extremely rare but possible complication in children. The majority occur after displaced right-sided fractures or refractures and present around one year after injury. Surgical fixation provides good radiographic healing and functional outcomes. Level of evidence: IV.
Mid-term results of a physiotherapist-led Ponseti service for the management of non-idiopathic and idiopathic clubfoot.

BACKGROUND: The Ponseti method is the preferred treatment for idiopathic clubfoot. Although popularised by orthopaedic surgeons it has expanded to physiotherapists and other health practitioners. This study reviews the results of a physiotherapist-led Ponseti service for idiopathic and non-idiopathic clubfeet and compares these results with those reported by other groups. METHOD: A prospective cohort of clubfeet (2005-2012) with a minimum 2-year follow-up after correction was reviewed. Physiotherapists treated 91 children-41 patients (69 feet) had non-idiopathic deformities and 50 children (77 feet) were idiopathic. Objective outcomes were evaluated and compared to results from other groups managing similar patient cohorts. RESULTS: The mean follow-up was 4.6 years (range 2-8.3 years) for both groups. The non-idiopathic group required a median of 7 casts to correct the clubfoot deformity with an 83 % tenotomy rate compared to a median of 5 casts for the idiopathic group with a 63 % tenotomy rate. Initial correction was achieved in 96 % of non-idiopathic feet and in 100 % of idiopathic feet. Recurrence requiring additional treatment was higher in the non-idiopathic group with 40 % of patients (36 % of feet) sustaining a relapse as opposed to 8 % (6 % feet) in the idiopathic group. Surgery was required in 26 % of relapsed non-idiopathic feet and 6 % of idiopathic. CONCLUSIONS: Although Ponseti treatment was not as successful in non-idiopathic feet as in idiopathic feet, deformity correction was achieved and maintained in the mid-term for the majority of feet. These results compare favourably to other specialist orthopaedic-based services for Ponseti management of non-idiopathic clubfeet. LEVEL OF EVIDENCE: Prognostic Level III.
Genome-centric metatranscriptomes and ecological roles of the active microbial populations during cellulosic biomass anaerobic digestion.

Background: Although anaerobic digestion for biogas production is used worldwide in treatment processes to recover energy from carbon-rich waste such as cellulosic biomass, the activities and interactions among the microbial populations that perform anaerobic digestion deserve further investigations, especially at the population genome level. To understand the cellulosic biomass-degrading potentials in two full-scale digesters, this study examined five methanogenic enrichment cultures derived from the digesters that anaerobically digested cellulose or xylan for more than 2 years under 35 or 55 °C conditions. Results: Metagenomics and metatranscriptomics were used to capture the active microbial populations in each enrichment culture and reconstruct their meta-metabolic network and ecological roles. 107 population genomes were reconstructed from the five enrichment cultures using a differential coverage binning approach, of which only a subset was highly transcribed in the metatranscriptomes. Phylogenetic and functional convergence of communities by enrichment condition and phase of fermentation was observed for the highly transcribed populations in the metatranscriptomes. In the 35 °C cultures grown on cellulose, Clostridium cellulolyticum-related and Ruminococcus-related bacteria were identified as major hydrolyzers and primary fermenters in the early growth phase, while Clostridium leptum-related bacteria were major secondary fermenters and potential fatty acid scavengers in the late growth phase. While the meta-metabolism and trophic roles of the cultures were similar, the bacterial populations performing each function were distinct between the enrichment conditions. Conclusions: Overall, a population genome-centric view of the meta-metabolism and functional roles of key active players in anaerobic digestion of cellulosic biomass was obtained. This study represents a major step forward towards understanding the microbial functions and interactions at population genome level during the microbial conversion of lignocellulosic biomass to methane. The knowledge of this study can facilitate development of potential biomarkers and rational design of the microbiome in anaerobic digesters.
Palliative resection of the primary tumor in 442 metastasized neuroendocrine tumors of the pancreas: a population-based, propensity score-matched survival analysis.

PURPOSE: There is an ongoing debate on whether palliative removal of the primary tumor may result in a survival benefit for patients with incurable stage IV pancreatic neuroendocrine tumors (P-NET). The objective of this study was to assess whether palliative resection of the primary tumor in patients with incurable stage IV P-NET has an impact on survival. METHODS: Patients with stage IV P-NET registered in the Surveillance, Epidemiology, and End Results database between 2004 and 2011 were identified. Those undergoing resection of metastases were excluded. Overall and cancer-specific survival of patients who did and did not undergo resection of their primary tumor were compared by means of risk-adjusted Cox proportional hazard regression analysis and propensity score-matched analysis. RESULTS: A total of 442 stage IV P-NET patients were identified, of whom 75 (17.0 %) underwent palliative primary tumor resection. The latter showed a significant benefit in both overall survival (hazard ratio [HR] of death = 0.41, 95 % confidence interval [CI] 0.25-0.66, p < 0.001) and cancer-specific survival (HR of death = 0.41, 95 % CI 0.25-0.67, p < 0.001) in unadjusted multivariate Cox regression analysis; the benefit persisted after propensity score adjustment. CONCLUSIONS: This population-based analysis of stage IV P-NET patients provides compelling evidence that palliative resection of the primary tumor is associated with significant survival benefit. Thus, the recent recommendations judging resection of the primary as inadvisable and the accompanying trend towards fewer palliative resections of the primary tumor have to be contested.
Global DNA methylation profiling reveals new insights into epigenetically deregulated protein coding and long noncoding RNAs in CLL.

BACKGROUND: Methyl-CpG-binding domain protein enriched genome-wide sequencing (MBD-Seq) is a robust and powerful method for analyzing methylated CpG-rich regions with complete genome-wide coverage. In chronic lymphocytic leukemia (CLL), the role of CpG methylated regions associated with transcribed long noncoding RNAs (lncRNA) and repetitive genomic elements are poorly understood. Based on MBD-Seq, we characterized the global methylation profile of high CpG-rich regions in different CLL prognostic subgroups based on IGHV mutational status. RESULTS: Our study identified 5800 hypermethylated and 12,570 hypomethylated CLL-specific differentially methylated genes (cllDMGs) compared to normal controls. From cllDMGs, 40 % of hypermethylated and 60 % of hypomethylated genes were mapped to noncoding RNAs. In addition, we found that the major repetitive elements such as short interspersed elements (SINE) and long interspersed elements (LINE) have a high percentage of cllDMRs (differentially methylated regions) in IGHV subgroups compared to normal controls. Finally, two novel lncRNAs (hypermethylated CRNDE and hypomethylated AC012065.7) were validated in an independent CLL sample cohort (48 samples) compared with 6 normal sorted B cell samples using quantitative pyrosequencing analysis. The methylation levels showed an inverse correlation to gene expression levels analyzed by real-time quantitative PCR. Notably, survival analysis revealed that hypermethylation of CRNDE and hypomethylation of AC012065.7 correlated with an inferior outcome. CONCLUSIONS: Thus, our comprehensive methylation analysis by MBD-Seq provided novel hyper and hypomethylated long noncoding RNAs, repetitive elements, along with protein coding genes as potential epigenetic-based CLL-signature genes involved in disease pathogenesis and prognosis.
Pediatric Vital Sign Distribution Derived From a Multi-Centered Emergency Department Database.

Background: We hypothesized that current vital sign thresholds used in pediatric emergency department (ED) screening tools do not reflect observed vital signs in this population. We analyzed a large multi-centered database to develop heart rate (HR) and respiratory rate centile rankings and z-scores that could be incorporated into electronic health record ED screening tools and we compared our derived centiles to previously published centiles and Pediatric Advanced Life Support (PALS) vital sign thresholds. Methods: Initial HR and respiratory rate data entered into the Cerner™ electronic health record at 169 participating hospitals' ED over 5 years (2009 through 2013) as part of routine care were analyzed. Analysis was restricted to non-admitted children (0 to <18 years). Centile curves and z-scores were developed using generalized additive models for location, scale, and shape. A split-sample validation using two-thirds of the sample was compared with the remaining one-third. Centile values were compared with results from previous studies and guidelines. Results: HR and RR centiles and z-scores were determined from ~1.2 million records. Empirical 95th centiles for HR and respiratory rate were higher than previously published results and both deviated from PALS guideline recommendations. Conclusion: Heart and respiratory rate centiles derived from a large real-world non-hospitalized ED pediatric population can inform the modification of electronic and paper-based screening tools to stratify children by the degree of deviation from normal for age rather than dichotomizing children into groups having "normal" versus "abnormal" vital signs. Furthermore, these centiles also may be useful in paper-based screening tools and bedside alarm limits for children in areas other than the ED and may establish improved alarm limits for bedside monitors.
Transcription factor NF-kappaB is transported to the nucleus via cytoplasmic dynein/dynactin motor complex in hippocampal neurons.

BACKGROUND: Long-term changes in synaptic plasticity require gene transcription, indicating that signals generated at the synapse must be transported to the nucleus. Synaptic activation of hippocampal neurons is known to trigger retrograde transport of transcription factor NF-kappaB. Transcription factors of the NF-kappaB family are widely expressed in the nervous system and regulate expression of several genes involved in neuroplasticity, cell survival, learning and memory. PRINCIPAL FINDINGS: In this study, we examine the role of the dynein/dynactin motor complex in the cellular mechanism targeting and transporting activated NF-kappaB to the nucleus in response to synaptic stimulation. We demonstrate that overexpression of dynamitin, which is known to dissociate dynein from microtubules, and treatment with microtubule-disrupting drugs inhibits nuclear accumulation of NF-kappaB p65 and reduces NF-kappaB-dependent transcription activity. In this line, we show that p65 is associated with components of the dynein/dynactin complex in vivo and in vitro and that the nuclear localization sequence (NLS) within NF-kappaB p65 is essential for this binding. CONCLUSION: This study shows the molecular mechanism for the retrograde transport of activated NF-kappaB from distant synaptic sites towards the nucleus.
BRONCO: Biomedical entity Relation ONcology COrpus for extracting gene-variant-disease-drug relations.

Comprehensive knowledge of genomic variants in a biological context is key for precision medicine. As next-generation sequencing technologies improve, the amount of literature containing genomic variant data, such as new functions or related phenotypes, rapidly increases. Because numerous articles are published every day, it is almost impossible to manually curate all the variant information from the literature. Many researchers focus on creating an improved automated biomedical natural language processing (BioNLP) method that extracts useful variants and their functional information from the literature. However, there is no gold-standard data set that contains texts annotated with variants and their related functions. To overcome these limitations, we introduce a Biomedical entity Relation ONcology COrpus (BRONCO) that contains more than 400 variants and their relations with genes, diseases, drugs and cell lines in the context of cancer and anti-tumor drug screening research. The variants and their relations were manually extracted from 108 full-text articles. BRONCO can be utilized to evaluate and train new methods used for extracting biomedical entity relations from full-text publications, and thus be a valuable resource to the biomedical text mining research community. Using BRONCO, we quantitatively and qualitatively evaluated the performance of three state-of-the-art BioNLP methods. We also identified their shortcomings, and suggested remedies for each method. We implemented post-processing modules for the three BioNLP methods, which improved their performance. Database URL:http://infos.korea.ac.kr/bronco.
Reducing risk of type 2 diabetes after gestational diabetes: a qualitative study to explore the potential of technology in primary care.

BACKGROUND: Despite the seven-fold increased risk of type 2 diabetes mellitus (T2DM) among females previously diagnosed with gestational diabetes (GD), annual rates of follow-up in primary care are low. There is a need to consider how to reduce the incidence of progression to T2DM among this high-risk group. AIM: To examine the views of females diagnosed with GD to ascertain how to improve primary care support postnatally, and the potential role of technology in reducing the risk of progression to T2DM. DESIGN AND SETTING: A qualitative study of a purposive sample of 27 postnatal females leaving secondary care with a recent diagnosis of GD. METHOD: Semi-structured interviews were conducted with 27 females, who had been previously diagnosed with GD, at around 6-12 weeks postnatally. Interviews were audiotaped, transcribed, and analysed thematically. RESULTS: Facilitators and barriers to engaging in a healthy postnatal lifestyle were identified, the most dominant being competing demands on time. Although females were generally satisfied with the secondary care they received antenatally, they felt abandoned postnatally and were uncertain what to expect from their GP in terms of follow-up and support. Females felt postnatal care could be improved by greater clarity regarding this, and enhanced by peer support, multidisciplinary input, and subsidised facilities. Technology was seen as a potential adjunct by providing information, enabling flexible and personalised self-management, and facilitating social support. CONCLUSION: A more tailored approach for females previously diagnosed with GD may help reduce the risk of progression to T2DM. A need for future research to test the efficacy of using technology as an adjunct to current care was identified.
A case of anti-Rd causing fetal anemia.

BACKGROUND: Rd (SC4) is a low-frequency antigen of the Scianna blood group system. Only very few reports on anti-Rd in pregnancy exist. Mild to moderate hemolytic disease of the newborn caused by anti-Rd has been reported. This report may add further information on the clinical significance of anti-Rd for the fetus. CASE REPORT: In a case of severe fetal anemia (hemoglobin concentration, 3.0 g/dL) repeated intrauterine transfusions were required. The strongly positive direct antiglobulin test (DAT) of the fetal red blood cells led to the diagnosis of hemolytic disease. The routine antibody screen was negative, extended testing revealed a maternal anti-Rd with a titer of 256. Both the newborn and her father were confirmed to carry the SC*01.04 allele. CONCLUSION: Anti-Rd can cause fetal anemia. Low-frequency antigens including Rd are normally not present on screening cells. Antibodies directed against low-frequency antigens will usually not be detected by routine antibody screening in pregnancy. Thus, in cases of fetal anemia the DAT should always be included in the diagnostic workup.
IMPACT: a whole-exome sequencing analysis pipeline for integrating molecular profiles with actionable therapeutics in clinical samples.

OBJECTIVE: Currently, there is a disconnect between finding a patient's relevant molecular profile and predicting actionable therapeutics. Here we develop and implement the Integrating Molecular Profiles with Actionable Therapeutics (IMPACT) analysis pipeline, linking variants detected from whole-exome sequencing (WES) to actionable therapeutics. METHODS AND MATERIALS: The IMPACT pipeline contains 4 analytical modules: detecting somatic variants, calling copy number alterations, predicting drugs against deleterious variants, and analyzing tumor heterogeneity. We tested the IMPACT pipeline on whole-exome sequencing data in The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples with known EGFR mutations. We also used IMPACT to analyze melanoma patient tumor samples before treatment, after BRAF-inhibitor treatment, and after BRAF- and MEK-inhibitor treatment. RESULTS: IMPACT Food and Drug Administration (FDA) correctly identified known EGFR mutations in the TCGA lung adenocarcinoma samples. IMPACT linked these EGFR mutations to the appropriate FDA-approved EGFR inhibitors. For the melanoma patient samples, we identified NRAS p.Q61K as an acquired resistance mutation to BRAF-inhibitor treatment. We also identified CDKN2A deletion as a novel acquired resistance mutation to BRAFi/MEKi inhibition. The IMPACT analysis pipeline predicts these somatic variants to actionable therapeutics. We observed the clonal dynamic in the tumor samples after various treatments. We showed that IMPACT not only helped in successful prioritization of clinically relevant variants but also linked these variations to possible targeted therapies. CONCLUSION: IMPACT provides a new bioinformatics strategy to delineate candidate somatic variants and actionable therapies. This approach can be applied to other patient tumor samples to discover effective drug targets for personalized medicine. IMPACT is publicly available at http://tanlab.ucdenver.edu/IMPACT.
HiPub: translating PubMed and PMC texts to networks for knowledge discovery.

UNLABELLED: We introduce HiPub, a seamless Chrome browser plug-in that automatically recognizes, annotates and translates biomedical entities from texts into networks for knowledge discovery. Using a combination of two different named-entity recognition resources, HiPub can recognize genes, proteins, diseases, drugs, mutations and cell lines in texts, and achieve high precision and recall. HiPub extracts biomedical entity-relationships from texts to construct context-specific networks, and integrates existing network data from external databases for knowledge discovery. It allows users to add additional entities from related articles, as well as user-defined entities for discovering new and unexpected entity-relationships. HiPub provides functional enrichment analysis on the biomedical entity network, and link-outs to external resources to assist users in learning new entities and relations. AVAILABILITY AND IMPLEMENTATION: HiPub and detailed user guide are available at http://hipub.korea.ac.kr CONTACT: kangj@korea.ac.kr, aikchoon.tan@ucdenver.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.