Blame it on the injury: Trauma is a risk factor for pancreatic fistula following distal pancreatectomy compared with elective resection.

Background: Postoperative pancreatic fistula (POPF) remains a significant source of morbidity following distal pancreatectomy (DP). There is a lack of information regarding the impact of trauma on POPF rates when compared with elective resection. We hypothesize that trauma will be a significant risk factor for the development of POPF following DP.

The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens.

Background: The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function.

Results: Here, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes.

Inaccurate group meta-perceptions drive negative out-group attributions in competitive contexts.

Across seven experiments and one survey (n = 4,282), people consistently overestimated out-group negativity towards the collective behaviour of their in-group. This negativity bias in group meta-perception was present across multiple competitive (but not cooperative) intergroup contexts and appears to be yoked to group psychology more generally; we observed negativity bias for estimation of out-group, anonymized-group and even fellow in-group members' perceptions. Importantly, in the context of US politics, greater inaccuracy was associated with increased belief that the out-group is motivated by purposeful obstructionism.

Glomerular filtration rate by differing measures, albuminuria and prediction of cardiovascular disease, mortality and end-stage kidney disease.

Chronic kidney disease is common in the general population and associated with excess cardiovascular disease (CVD), but kidney function does not feature in current CVD risk-prediction models. We tested three formulae for estimated glomerular filtration rate (eGFR) to determine which was the most clinically informative for predicting CVD and mortality. Using data from 440,526 participants from UK Biobank, eGFR was calculated using serum creatinine, cystatin C (eGFRcys) and creatinine-cystatin C.

Immune exclusion by naturally acquired secretory IgA against pneumococcal pilus-1.

Successful infection by mucosal pathogens requires overcoming the mucus barrier. To better understand this key step, we performed a survey of the interactions between human respiratory mucus and the human pathogen Streptococcus pneumoniae. Pneumococcal adherence to adult human nasal fluid was seen only by isolates expressing pilus-1.

Mitochondrial Fusion by M1 Promotes Embryoid Body Cardiac Differentiation of Human Pluripotent Stem Cells.

Human induced pluripotent stem cells (iPSCs) can be differentiated into cardiomyocytes for disease modelling and personalized medicine. Mitochondrial morphology and metabolism change dramatically as iPSCs differentiate into mesodermal cardiac lineages. Inhibiting mitochondrial fission has been shown to promote cardiac differentiation of iPSCs.

Infectious pulmonary tuberculosis in a New Zealand cancer centre.

This report details the investigation of oncology and haematology patients, as well as cancer centre staff, friends and family who were exposed to an oncology patient with reactivated pulmonary tuberculosis (TB) in a New Zealand cancer centre. A total of 46 patients, seven staff members and 14 family and friends were identified as being exposed to the index case of TB (Mr K). These people were screened for TB infection by the use of a symptom questionnaire, Qiagen QuantiFeron (QFT)® Gold Plus test and, if potentially immunocompromised, a chest x-ray (CXR).

Extraction of form Factors from a Four-Dimensional Angular Analysis of B[over ¯]→D^{*}ℓ^{-}ν[over ¯]_{ℓ}.

An angular analysis of the decay B[over ¯]→D^{*}ℓ^{-}ν[over ¯]_{ℓ}, ℓ∈{e,μ}, is reported using the full e^{+}e^{-} collision data set collected by the BABAR experiment at the ϒ(4S) resonance. One B meson from the ϒ(4S)→BB[over ¯] decay is fully reconstructed in a hadronic decay mode, which constrains the kinematics and provides a determination of the neutrino momentum vector. The kinematics of the semileptonic decay is described by the dilepton mass squared, q^{2}, and three angles.

Collaborative Workshops for Community Meaning-Making and Data Analyses: How Focus Groups Strengthen Data by Enhancing Understanding and Promoting Use.

Community-based participatory research is a growing approach, but often includes higher levels of community engagement in the research design and data collection stages than in the data interpretation stage. Involving study participants in this stage could further knowledge justice, science that aligns with and supports social justice agendas. This article reports on two community-based participatory environmental health surveys conducted between 2015 and 2019 in an industrial region near Marseille, France, and focuses specifically on our approach of organizing focus groups to directly involve residents and community stakeholders in the analysis and interpretation process.

Deoxycytidine Release from Pancreatic Stellate Cells Promotes Gemcitabine Resistance.

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer deaths in the United States. The deoxynucleoside analogue gemcitabine is among the most effective therapies to treat PDAC, however, nearly all patients treated with gemcitabine either fail to respond or rapidly develop resistance. One hallmark of PDAC is a striking accumulation of stromal tissue surrounding the tumor, and this accumulation of stroma can contribute to therapy resistance.

Off-Label Medication use in Children, More Common than We Think: A Systematic Review of the Literature.

Content: Clinician prescribing of off-label medications is common due to a lack of pediatric-specific data regarding the dosing, efficacy and safety of medications regularly prescribed to children.

Objective: This systematic review summarizes the published incidence of off-label medication use in children from the past 10 years. We also performed a retrospective chart review to determine the incidence of off-label prescriptions for children seen in the OU Physicians clinics.

Genome-wide epistasis and co-selection study using mutual information.

Covariance-based discovery of polymorphisms under co-selective pressure or epistasis has received considerable recent attention in population genomics. Both statistical modeling of the population level covariation of alleles across the chromosome and model-free testing of dependencies between pairs of polymorphisms have been shown to successfully uncover patterns of selection in bacterial populations. Here we introduce a model-free method, SpydrPick, whose computational efficiency enables analysis at the scale of pan-genomes of many bacteria.

Author Correction: Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Myc targeted CDK18 promotes ATR and homologous recombination to mediate PARP inhibitor resistance in glioblastoma.

PARP inhibitors (PARPis) have clinical efficacy in BRCA-deficient cancers, but not BRCA-intact tumors, including glioblastoma (GBM). We show that MYC or MYCN amplification in patient-derived glioblastoma stem-like cells (GSCs) generates sensitivity to PARPi via Myc-mediated transcriptional repression of CDK18, while most tumors without amplification are not sensitive. In response to PARPi, CDK18 facilitates ATR activation by interacting with ATR and regulating ATR-Rad9/ATR-ETAA1 interactions; thereby promoting homologous recombination (HR) and PARPi resistance.

Obesity is not associated with progression to end stage renal disease in patients with biopsy-proven glomerular diseases.

Background: Body mass index (BMI) is associated with renal disease progression in unspecified CKD. The relationship between BMI and primary glomerular disease (GN) may be more complex. We aimed to evaluate the association between BMI and renal disease progression in patients with primary glomerular disease (GN).

Proton pump inhibitor use and progression to major adverse renal events: a competing risk analysis.

Background: Proton pump inhibitors (PPIs) are associated with acute tubulointerstitial nephritis and there are reports associating their use with the development of chronic kidney disease (CKD).

Aim: To determine if PPI use is associated with major adverse renal events (MARE) in patients with CKD.

Design: Observational cohort study comprising patients with CKD attending secondary care renal clinics from 1 January 2006 until 31 December 2016.

Oxygen Regulates Human Pluripotent Stem Cell Metabolic Flux.

Metabolism has been shown to alter cell fate in human pluripotent stem cells (hPSC). However, current understanding is almost exclusively based on work performed at 20% oxygen (air), with very few studies reporting on hPSC at physiological oxygen (5%). In this study, we integrated metabolic, transcriptomic, and epigenetic data to elucidate the impact of oxygen on hPSC.

Aerosolized recombinant human butyrylcholinesterase delivered by a nebulizer provides long term protection against inhaled paraoxon in macaques.

The recent intentional use of nerve agents and pesticides in Europe and Afghanistan highlights the need for an effective countermeasure against organophosphates (OP) toxins. The most developed pretreatment candidate to date is plasma (native) human butyrylcholinesterase (HuBChE), which is limited in availability and because of its 1:1 stoichiometry with OPs, a large dose will present challenges when delivered parenterally both in terms of pharmacokinetics and manageability in the field. A tetrameric recombinant (r) form of human BChE produced in CHO-K1 cells with similar structure, in vivo stability and antidotal efficacy as the native form, has been developed to deliver rHuBChE as an aerosol (aer) to form a pulmonary bioshield capable of neutralizing inhaled OPs in situ and prevent AChE inhibition in the blood and in the brain; the latter associated with the symptoms of OP toxicity.

Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study.

Background: Invasive pneumococcal disease remains an important health priority owing to increasing disease incidence caused by pneumococci expressing non-vaccine serotypes. We previously defined 621 Global Pneumococcal Sequence Clusters (GPSCs) by analysing 20 027 pneumococcal isolates collected worldwide and from previously published genomic data. In this study, we aimed to investigate the pneumococcal lineages behind the predominant serotypes, the mechanism of serotype replacement in disease, as well as the major pneumococcal lineages contributing to invasive pneumococcal disease in the post-vaccine era and their antibiotic resistant traits.

The Impact of Heat Load on Cattle.

Heat stress and cold stress have a negative influence on cattle welfare and productivity. There have been some studies investigating the influence of cold stress on cattle, however the emphasis within this review is the influence of heat stress on cattle. The impact of hot weather on cattle is of increasing importance due to the changing global environment.

Bio-engineering a tissue flap utilizing a porous scaffold incorporating a human induced pluripotent stem cell-derived endothelial cell capillary network connected to a vascular pedicle.

Tissue flaps are used to cover large/poorly healing wounds, but involve complex surgery and donor site morbidity. In this study a tissue flap is assembled using the mammalian body as a bioreactor to functionally connect an artery and vein to a human capillary network assembled from induced pluripotent stem cell-derived endothelial cells (hiPSC ECs). In vitro: Porous NovoSorb™ scaffolds (3 mm × 1.

Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics.

Group A Streptococcus (GAS; Streptococcus pyogenes) is a bacterial pathogen for which a commercial vaccine for humans is not available. Employing the advantages of high-throughput DNA sequencing technology to vaccine design, we have analyzed 2,083 globally sampled GAS genomes. The global GAS population structure reveals extensive genomic heterogeneity driven by homologous recombination and overlaid with high levels of accessory gene plasticity.

Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis.

Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. In a genome-wide association study of human and pathogen we show that human variation explains almost half of variation in susceptibility to pneumococcal meningitis and one-third of variation in severity, identifying variants in CCDC33 associated with susceptibility.

Comparison of Drosophila melanogaster Embryo and Adult Proteome by SWATH-MS Reveals Differential Regulation of Protein Synthesis, Degradation Machinery, and Metabolism Modules.

An important area of modern biology consists of understanding the relationship between genotype and phenotype. However, to understand this relationship it is essential to investigate one of the principal links between them: the proteome. With the development of recent mass-spectrometry approaches, it is now possible to quantify entire proteomes and thus relate them to different phenotypes.

Fast hierarchical Bayesian analysis of population structure.

We present fastbaps, a fast solution to the genetic clustering problem. Fastbaps rapidly identifies an approximate fit to a Dirichlet process mixture model (DPM) for clustering multilocus genotype data. Our efficient model-based clustering approach is able to cluster datasets 10-100 times larger than the existing model-based methods, which we demonstrate by analyzing an alignment of over 110 000 sequences of HIV-1 pol genes.