bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infections Are Leading Cause of In-Hospital Mortality in Indian Patients With Inflammatory Myopathy
Authors: Muhammed Hafis , Gupta Latika , Zanwar Abhishek Arvind , Misra Durga P. , Lawrence Able , Agarwal Vikas , Aggarwal Amita , Misra Ramnath 
Published: December 2019

Objectives
We explored causes of in-hospital mortality in patients with inflammatory myositis at a tertiary care center in Northern India.

Methods
Records of adults and children diagnosed with dermatomyositis (DM), polymyositis, or anti-synthetase syndrome (ASSD) who died between 2000 and 2018 were reviewed, and causes of death were determined.

Results
Of the 38 patients, 20 had DM (including 2 clinically amyopathic DM), 4 juvenile DM, 12 polymyositis, whereas 2 had ASSD. Median age at death was 42.0 (interquartile range, 32.8–52.5) years. Median disease duration at death was 18.5 (interquartile range, 2.0–23.5) months. Twenty-four (63.2%) had infection as the primary cause of death. Other causes of death included pharyngeal muscle weakness and aspiration (n = 6), myocarditis (n = 2), respiratory failure (n = 2), cerebral bleed (n = 2), and pulmonary embolism (n = 1). One patient succumbed to rapidly progressive interstitial lung disease, whereas another patient with ASSD died following respiratory distress after rituximab infusion. In post hoc analysis, although thrombocytopenia appeared to be a risk factor for early mortality (odds ratio, 13.3; 95% confidence interval, 1.4–123.8; p = 0.01), this was not supported in the multivariate analysis.

Conclusions
Infections are the most common cause of in-hospital mortality in myositis patients.
Benefits of Screen-Based Postpartum Hemorrhage Simulation on Nontechnical Skills Training
Authors: Michelet Daphné , Barré Jessy , Job Anais , Truchot Jennifer , Cabon Philippe , Delgoulet Catherine , Tesnière Antoine 
Published: December 2019

Background
Postpartum hemorrhage (PPH) is the leading cause of maternal death in the world. Nontechnical skills (NTS), such as communication and teamwork, are critical for efficient management of this obstetric emergency. Specific scenarios were designed on a screen-based simulator to train NTS. This study aimed to evaluate the impact of training midwives for NTS with a PPH screen-based simulation.

Methods
A total of 24 midwives participated in the study. They were randomized in 2 groups: the NTS group (n = 12) performed 3 screen-based scenarios designed to train NTS and the control group (n = 12) performed 3 basic scenarios of the screen-based simulation without the NTS training. A structured interview followed the simulation. On the same day, each trainee underwent individually an evaluation on a PPH high-fidelity simulation scenario. Three experts, blinded to the study arm, assessed the NTS with the Anesthetists Non-Technical Skills (ANTS) score.

Results
Midwives from the NTS group achieved higher median scores in each dimension of the ANTS score: task management (4 vs. 2/4, P < 0.0001), team working (4 vs. 2/4, P < 0.0001), situation awareness (4 vs. 2.7/4, P < 0.0001), and decision-making (4 vs. 2/4, P < 0.0001). The median value of the total ANTS score was higher in the NTS group than in the control group (15.5 vs. 8/16, P < 0.0001).

Conclusions
Our study highlights that training with a NTS screen-based simulation, with specific scenarios and debriefing, leads to higher midwives' nontechnical skills performance during simulated postpartum hemorrhage.
Guidelines and Essential Elements for Prebriefing
Authors: Rutherford-Hemming Tonya , Lioce Lori , Breymier Tonya 
Published: December 2019

Summary Statement
Simulationists have reported essential elements that need to be included during prebriefing to establish best practices in simulation and support learner success in simulation. However, there is a gap in the literature; there is a need for synthesis of these reported elements.
This article reports the current established prebriefing standards and guidelines. It compiles all the elements that are recommended into one document to facilitate educator training. An infographic is included to serve as a cognitive aid and a checklist for facilitators to use in practice. Finally, this article discusses additional areas of inquiry and research that needs to be completed in relation to prebriefing.
The Prognostic Role of β-Catenin Mutations in Desmoid-type Fibromatosis Undergoing Resection Only
Authors: Timbergen Milea J. M. , Colombo Chiara , Renckens Michel , Kim Hee Sung , Rosmalen Joost van , Salas Sébastien , Mullen John T. , Colombo Piergiuseppe , Nishida Yoshihiro , Wiemer Erik A. C. , Verhoef Cornelis , Sleijfer Stefan , Gronchi Alessandro , Grünhagen Dirk J. 
Published: December 2019

Objective:This meta-analysis (PROSPERO CRD42018100653) uses individual patient data (IPD) to assess the association between recurrence andCTNNB1mutation status in surgically treated adult desmoid-type fibromatosis (DTF) patients.Summary of Background Data:The majority of sporadic DTF tumors harbor aCTNNB1(ß-catenin) mutation: T41A, S45F, and S45P or are wild-type (WT). Results are conflicting regarding the recurrence risk after surgery for these mutation types.Methods:A systematic literature search was performed on June 6th, 2018. IPD from eligible studies was used to analyze differences in recurrence according toCTNNB1mutation status using Cox proportional hazards analysis. Predictive factors included: sex, age, mutation type, tumor site, tumor size, resection margin status, and cohort. The PRISMA-IPD guideline was used.Results:Seven studies, describing retrospective cohorts were included and the IPD of 329 patients were used of whom 154 (46.8%) had a T41A mutation, 66 (20.1%) a S45F mutation, and 24 (7.3%) a S45P mutation, whereas 85 (25.8%) patients had a WTCTNNB1. Eighty-three patients (25.2%) experienced recurrence. Multivariable analysis, adjusting for sex, age, and tumor site yielded aP-value of 0.011 forCTNNB1mutation. Additional adjustment for tumor size yielded aP-value of 0.082 with hazard ratio's of 0.83 [95% confidence interval (CI) 0.48–1.42), 0.37 (95% CI 0.12–1.14), and 0.44 (95% CI 0.21–0.92) for T41A, S45P and WT DTF tumors compared to S45F DTF tumors. The effect modification between tumor size and mutation type suggests that tumor size is an important mediator for recurrence.Conclusions:Primary sporadic DTFs harboring aCTNNB1S45F mutation have a higher risk of recurrence after surgery compared to T41A, S45P, and WT DTF, but this association seems to be mediated by tumor size.
Medical Malpractice Litigation in Non–Mesh-Related Pelvic Organ Prolapse Surgery: An Analysis of 91 Cases
Authors: Yao Benjamin , Slopnick Emily , Sheyn David , Chapman Graham , El-Nashar Sherif , Hijaz Adonis , Mahajan Sangeeta 
Published: December 2019

Introduction
Malpractice litigations have significant implications for patients and physicians. Studies have investigated mesh litigations in female pelvic reconstructive surgery, but none on nonmesh pelvic organ prolapse (POP) surgery. Our purpose is to determine the reasons for and outcomes of medical malpractice after nonmesh POP surgery.

Methods
Westlaw (Thompson Reuters, New York, New York) is a legal research database of US court records. We identified completed POP litigations from 1987 to 2018 using the following: “pelvic organ prolapse,” “enterocele,” “rectocele,” “cystocele,” “uterine prolapse,” and “vaginal wall prolapse.” Mesh-related cases were excluded. Outcomes included reasons for litigation, verdict, injury, and payments. Statistical analysis was performed with nonparametric tests and χ2 independence test.

Results
Ninety-one litigations were included. The median plaintiff age was 53 years (range, 36–85 years). The leading allegation was negligence of surgery (n = 59; 65%). The jury sided with the defendant physician in 67% of cases (n = 61). There was no association between case verdict and patient age (P = 0.781), geographic region (P = 0.824), or allegation (P = 0.904). The primary complications were urinary tract injury (n = 24; 26%), need for additional surgery (n = 22; 24%), and new postoperative urinary symptoms (n = 22; 24%). The median payout was $280,000 (interquartile range, $137,250–$1,300,000), with no difference between plaintiff awards or settlements (P = 0.659).

Conclusion
The leading allegation of malpractice litigations for nonmesh POP surgery is negligence of surgery, whereas the most common complication was urinary tract injury. A verdict in favor of the physician defendant was the most likely outcome. Plaintiff awards and settlements were not statistically different with no variation by region or time.
Cortical complexity analyses and their cognitive correlate in Alzheimer’s disease and frontotemporal dementia
Authors: Nicastro Nicolas , Malpetti Maura , Cope Thomas E. , Bevan-Jones William Richard , Mak Elijah , Passamonti Luca , Rowe James B. , O’brien John T. 
Published: December 2019

ABSTRACTThe changes of cortical structure in Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are usually described in terms of atrophy. However, neurodegenerative diseases may also affect the complexity of cortical shape, such as the fractal dimension of the brain surface. Thirty-two people with symptomatic AD-pathology (clinically probable AD, n=18, and amyloid-positive mild cognitive impairment, n=14), 24 with FTD and 28 healthy controls underwent high-resolution 3T structural brain MRI. Using surface-based morphometry, we created vertex-wise cortical thickness and fractal dimension maps for group comparisons and correlations with cognitive measures in AD and FTD. In addition to the well-established pattern of cortical thinning encompassing temporoparietal regions in AD and frontotemporal areas in FTD (FDR p< 0.05), we observed reductions of fractal dimension specifically involving precuneus and posterior cingulate for AD and orbitofrontal cortex and insula for FTD. Correlational analyses between fractal dimension and cognition showed that these regions were particularly vulnerable with regards to memory and language impairment in both AD and FTD. This study demonstrates a distinct pattern of fractal dimension impairment and correlation with cognition. Further studies are required to assess cortical complexity measures at earlier disease stages (e.g. in prodromal/ asymptomatic carriers of FTD-related gene mutations) to assess whether fractal dimension represents a sensitive imaging marker for prevention and diagnostic strategies.
Computation-guided optimization of split protein systems
Authors: Dolberg Taylor B. , Meger Anthony T. , Boucher Jonathan D. , Corcoran William K. , Schauer Elizabeth E. , Prybutok Alexis N. , Raman Srivatsan , Leonard Joshua N. 
Published: December 2019

ABSTRACTSplitting bioactive proteins, such as enzymes or fluorescent reporters, into conditionally reconstituting fragments is a powerful strategy for building tools to study and control biochemical systems. However, split proteins often exhibit a high propensity to reconstitute even in the absence of the conditional trigger, which limits their utility. Current approaches for tuning reconstitution propensity are laborious, context-specific, or often ineffective. Here, we report a computational design-driven strategy that is grounded in fundamental protein biophysics and which guides the experimental evaluation of a focused, sparse set of mutants—which vary in the degree of interfacial destabilization while preserving features such as stability and catalytic activity—to identify an optimal functional window. We validate our method by solving two distinct split protein design challenges, generating both broad insights and new technology platforms. This method will streamline the generation and use of split protein systems for diverse applications.
Modulation of T helper 1 and T helper 2 immune balance in a stress mouse model duringChlamydia muridarumgenital infection
Authors: Belay Tesfaye , Martin Elisha , Brown Gezelle , Crenshaw Raenel , Street Julia , Freeman Ashleigh , Musick Shane , Kinder Tyler 
Published: December 2019

ABSTRACTA mouse model to study the effect of cold-induced stress onChlamydia muridarumgenital infection and immune response has been developed in our laboratory. Our previous results show that cold-induced stress increases the intensity of chlamydia genital infection, but little is known about the effect of cold-induced stress on differentiations and activities of T cell subpopulations and bone marrow derived dendritic cells (BMDCs). The factors that regulate the production of T helper 1 (Th1) or T helper 2 (Th2) cytokines is not clear. The objective of this study was to examine whether cold-induced stress modulates the expression of transcription factors and hallmark cytokines of Th1 and Th2 or differentiation of BMDCs duringC. muridarumgenital infection in mice. Our results show that mRNA level of beta2-adrenergic receptor (β2-AR) compared to β1-AR and β3-AR was high in mixed population of CD4+ T cells and BMDCs. Further, decreased expression of T-bet and low level of interferon-gamma (IFN-γ) production and increased expression of GATA-3 and interleukin-4 (IL-4) production in CD4+ T of stressed mice was observed. Exposure of BMDCs to feroterol (β2-AR agonist) or ICI,118551 (β2-AR antagonist), respectively, revealed significant stimulation or inhibition of β2-AR in stressed mice. Moreover, co-culturing of mature BMDC and naïve CD4+ T cells resulted in increased production of IL-4, IL-10, and IL-17 in culture supernatants, suggesting that stimulation of β2-AR leads to the increased production of Th2 cytokines. Overall, our results show for the first time that cold-induced stress is able to modulate the pattern of Th1 and Th2 cytokine environment, suggesting that it promotes the differentiation to Th2 rather than Th1 by the overexpression of GATA-3 correlated with elevated production of IL-4, IL-10, IL-23, and IL-17 in contrast to a low expression of T-bet correlated with less IFN-γ secretion in the mouse model.
PIM Kinases Alter Mitochondrial Dynamics and Chemosensitivity in Lung Cancer
Authors: Chauhan Shailender S. , Toth Rachel K. , Jensen Corbin C. , Casillas Andrea L. , Kashatus David F. , Warfel Noel A. 
Published: December 2019

AbstractResistance to chemotherapy represents a major obstacle to the successful treatment of non-small cell lung cancer (NSCLC). The goal of this study was to determine how PIM kinases impact mitochondrial dynamics, ROS production, and response to chemotherapy in lung cancer. Live cell imaging and microscopy were used to determine the effect of PIM loss or inhibition on mitochondrial phenotype and ROS. Inhibition of PIM kinases caused excessive mitochondrial fission and significant upregulation of mitochondrial superoxide, increasing intercellular ROS. Mechanistically, we define a signaling axis linking PIM1 to Drp1 and mitochondrial fission in lung cancer. PIM inhibition significantly increased the protein levels and mitochondrial localization of Drp1, causing marked fragmentation of mitochondria. An inverse correlation between PIM1 and Drp1 was confirmed in NSCLC patient samples. Inhibition of PIM sensitized NSCLC to chemotherapy and produced a synergistic anti-tumor response in vitro and in vivo. Immunohistochemistry and transmission electron microscopy verified that PIM inhibitors promote mitochondrial fission and apoptosis in vivo. These data improve our knowledge about how PIM1 regulates mitochondria and provide justification for combining PIM inhibition with chemotherapy in NSCLC.
Apparent size and morphology of bacterial microcompartments varies with technique
Authors: Kennedy Nolan W. , Hershewe Jasmine M. , Nichols Taylor M. , Roth Eric W. , Wilke Charlene D. , Jewett Michael C. , Tullman-Ercek Danielle 
Published: December 2019

AbstractBacterial microcompartments (MCPs) are protein-based organelles which encapsulate metabolic pathways. Metabolic engineers have recently sought to repurpose MCPs to encapsulate heterologous pathways to increase flux through pathways of interest. As MCP engineering becomes more common, standardized methods for analyzing changes to MCPs and interpreting results across studies will become increasingly important. In this study, we demonstrate that different imaging techniques yield variations in the apparent size of purified MCPs fromSalmonella entericaserovar Typhimurium LT2, likely due to variations in sample preparation methods. We provide guidelines for preparing samples for MCP imaging and outline expected variations in apparent size and morphology between methods. With this report we aim to establish an aid for comparing results across studies.
Local axonal conduction delays underlie precise timing of a neural sequence
Authors: Egger Robert , Tupikov Yevhen , Katlowitz Kalman A. , Benezra Sam E. , Picardo Michel A. , Moll Felix , Kornfeld Jörgen , Jin Dezhe Z. , Long Michael A. 
Published: December 2019

SUMMARYSequential activation of neurons has been observed during various behavioral and cognitive processes and is thought to play a critical role in their generation. Here, we studied a circuit in the songbird forebrain that drives the performance of adult courtship song. In this region, known as HVC, neurons are sequentially active with millisecond precision in relation to behavior. Using large-scale network models, we found that HVC sequences could only be accurately produced if sequentially active neurons were linked with long and heterogeneous axonal conduction delays. Although such latencies are often thought to be negligible in local microcircuits, we empirically determined that HVC interconnections were surprisingly slow, generating delays up to 22 ms. An analysis of anatomical reconstructions suggests that similar processes may also occur in rat neocortex, supporting the notion that axonal conduction delays can sculpt the dynamical repertoire of a range of local circuits.
Genomic Analysis of Powdery Mildew Resistance in a Hop (Humulus lupulusL.) Bi-parental Population Segregating for “R6-locus”
Authors: Padgitt-Cobb Lillian K. , Kingan Sarah B. , Henning John A. 
Published: December 2019

ABSTRACTGenetic response in hop to fungal pathogen infection has been evaluated at the chromosomal level through QTL analyses but very little information exists on the expression of genes during infection periods. Raw GBS reads and phenotypic data from a previously published QTL analysis along with a newly assembled PacBio-derived hop reference genome were used to re-evaluate resistance to races v4/v6 of powdery mildew (PM;Podosphaera humuli). QTL analyses revealed two tightly linked regions of association on a single linkage group. The three SNP markers most tightly linked to PM resistance (found on contig 000559F) were observed downstream from a putative R-gene locus for powdery mildew resistance. This 230 kb region contained a series of seven putative R-genes surrounded by seven putative peroxidase-3 genes downstream and seven putative glucan endo-1,3-beta-glucosidase upstream and an expressed F-box domain protein. RNAseq data showed all putative R-genes along with all putative glucan endo-1,3-beta-glucosidase genes were expressed under diseased conditions, while none of the peroxidase genes were expressed. The second region contained three SNPs found on contig 002916F next to two putative R-genes. RNAseq data showed complex expression of exons contained in putative isoforms of R-genes. This preliminary information will prove valuable information for development of precise markers located either within or next to genes responsible for race v4/v6 PM resistance.
Reduced axonal caliber and white matter changes in a rat model of Fragile X syndrome with a deletion of a K Homology domain of Fmr1
Authors: Golden Carla E. M. , Yee Yohan , Wang Victoria X. , Harony-Nicolas Hala , Hof Patrick R. , Lerch Jason P. , Buxbaum Joseph D. 
Published: December 2019

AbstractFragile X syndrome (FXS) is a neurodevelopmental disorder that is caused by mutations in the FMR1 gene that are known to cause neuroanatomical alterations. The morphological underpinnings of these alterations have not been elucidated. Furthermore, while alterations have been identified in both male and female individuals, neuroanatomy in female rodent models has not been assessed. We identified structural differences in regions that are also altered in FXS in male and female rat models, including the splenium of the corpus callosum. Interestingly, different sets of regions were disrupted in male and female rat models and, remarkably, male rats had higher brain-wide diffusion than female rats overall. We found reduced axonal caliber in the splenium, offering a mechanism for its structural changes. Our results provide insight into which brain regions are vulnerable to a loss of Fmr1 expression and suggest a potential mechanism for how its loss causes white matter dysfunction in FXS.
Metagenomic shotgun analyses reveal complex patterns of intra- and interspecific variation in the intestinal microbiomes of codfishes
Authors: Riiser Even Sannes , Haverkamp Thomas H.A. , Varadharajan Srinidhi , Borgan Ørnulf , Jakobsen Kjetill S. , Jentoft Sissel , Star Bastiaan 
Published: December 2019

AbstractThe relative importance of host-specific selection or environmental factors in determining the composition of the intestinal microbiome in wild vertebrates remains poorly understood. Here, we use metagenomic shotgun sequencing of individual specimens to compare the intra- and interspecific variation of intestinal microbiome communities in two ecotypes (NEAC and NCC) of Atlantic cod (Gadus morhua) – that have distinct behavior and habitats– and threeGadidaespecies that occupy a range of ecological niches. Interestingly, we find significantly diverged microbiomes amongst the two Atlantic cod ecotypes. Interspecific patterns of variation are more variable, with significantly diverged communities for most species’ comparisons, apart from the comparison between coastal cod (NCC) and Norway pout (Trisopterus esmarkii), whose community compositions are not significantly diverged. The absence of consistent species-specific microbiomes suggests that external environmental factors, such as temperature, diet or a combination there-off comprise major drivers of the intestinal community composition of codfishes.ImportanceThe composition of the intestinal microbial community associated with teleost fish is influenced by a diversity of factors, ranging from internal factors (such as host-specific selection) to external factors (such as niche occupation). These factors are often difficult to separate, as differences in niche occupation (e.g. diet, temperature or salinity) may correlate with distinct evolutionary trajectories. Here, we investigate four gadoid species with contrasting levels of evolutionary separation and niche occupation. Using metagenomic shotgun sequencing, we observe distinct microbiomes amongst two Atlantic cod (Gadus morhua) ecotypes (NEAC and NCC) with distinct behavior and habitats. In contrast, interspecific patterns of variation are more variable. For instance, we do not observe interspecific differentiation between the microbiomes of coastal cod (NCC) and Norway pout (Trisopterus esmarkii) whose lineages have evolutionary separated over 20 million years ago. The observed pattern of microbiome variation in these gadoid species is therefore most parsimoniously explained by differences in niche occupation.