bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tranexamic acid administration is associated with an increased risk of posttraumatic venous thromboembolism
Authors: Myers Sara P. , Kutcher Matthew E. , Rosengart Matthew R. , Sperry Jason L. , Peitzman Andrew B. , Brown Joshua B. , Neal Matthew D. 
Published: September 2018

BACKGROUND
Tranexamic acid (TXA) is used as a hemostatic adjunct for hemorrhage control in the injured patient and reduces early preventable death. However, the risk of venous thromboembolism (VTE) has been incompletely explored. Previous studies investigating the effect of TXA on VTE vary in their findings. We performed a propensity matched analysis to investigate the association between TXA and VTE following trauma, hypothesizing that TXA is an independent risk factor for VTE.

METHODS
This retrospective study queried trauma patients presenting to a single Level I trauma center from 2012 to 2016. Our primary outcome was composite pulmonary embolism or deep vein thrombosis. Mortality, transfusion, intensive care unit and hospital lengths of stay were secondary outcomes. Propensity matched mixed effects multivariate logistic regression was used to determine adjusted odds ratio (aOR) and 95% confidence intervals (95% CI) of TXA on outcomes of interest, adjusting for prespecified confounders. Competing risks regression assessed subdistribution hazard ratio of VTE after accounting for mortality.

RESULTS
Of 21,931 patients, 189 pairs were well matched across propensity score variables (standardized differences <0.2). Median Injury Severity Score was 19 (interquartile range, 12–27) and 14 (interquartile range, 8–22) in TXA and non-TXA groups, respectively (p = 0.19). Tranexamic acid was associated with more than threefold increase in the odds of VTE (aOR, 3.3; 95% CI, 1.3–9.1; p = 0.02). Tranexamic acid was not significantly associated with survival (aOR, 0.86; 95% CI, 0.23–3.25; p = 0.83). Risk of VTE remained elevated in the TXA cohort despite accounting for mortality (subdistribution hazard ratio, 2.42; 95% CI, 1.11–5.29; p = 0.03).

CONCLUSION
Tranexamic acid may be an independent risk factor for VTE. Future investigation is needed to identify which patients benefit most from TXA, especially given the risks of this intervention to allow a more individualized treatment approach that maximizes benefits and mitigates potential harms.

LEVEL OF EVIDENCE
Therapeutic, level III.
Trauma and emergency general surgery patients should be extubated with an open abdomen
Authors: Taveras Luis R. , Imran Jonathan B. , Cunningham Holly B. , Madni Tarik D. , Taarea Roberto , Tompeck Allison , Clark Audra T. , Provenzale Natalie , Adeyemi Folarin M. , Minshall Christian T. , Eastman Alexander L. , Cripps Michael W. 
Published: September 2018

BACKGROUND
Open abdomen (OA) and temporary abdominal closure (TAC) are common techniques to manage several surgical problems in trauma and emergency general surgery (EGS). Patients with an OA are subjected to prolonged mechanical ventilation. This can lead to increased rates of ventilator-associated pneumonia (VAP). We hypothesized that patients who were extubated with an OA would have a decrease in ventilator hours and as a result would have a lower rate of VAP without an increase in extubation failures.

METHODS
A retrospective review was performed of all trauma and EGS patients managed at our institution with OA and TAC from January 2014 to February 2016. Patients were divided into cohorts consisting of those who were successfully extubated with an OA and those who were not. The number of extubation events and ventilator-free hours were calculated for each patient. Adverse events such as the need for reintubation with an OA and VAP were collected.

RESULTS
Fifty-two patients (20 trauma, 32 EGS) were managed with an OA and TAC during the study period. Twenty-five patients (6 trauma, 19 EGS) had at least one extubation event with an OA. Median extubation events per patient was 3 (interquartile range, 1–5). The median ventilator-free hours for patients who were extubated was 101 hours (interquartile range, 39.42–260.46). Patients that were never extubated with an OA had higher rates of VAP (30.8% vs. 3.8%, p = 0.01).

CONCLUSION
This study provides much needed data regarding the feasibility of extubation in trauma and EGS patients managed with an OA and TAC. Benefits of early extubation may include lower VAP rates in this population. Plans for reexploration hinder the decision to extubate in these patients.

LEVEL OF EVIDENCE
Therapeutic study, level IV.
Effects of Exendin-4 on pancreatic islets function in treating hyperglycemia post severe scald injury in rats
Authors: Li Dawei , Shang Yuru , Shen Chuanan , Li Longzhu , Zhao Dongxu , Ma Li , Yu Yongming 
Published: September 2018

BACKGROUND
It has been established that glucagon-like peptide 1 (GLP 1) inhibits pancreatic β-cell apoptosis, increases insulin secretion, and improves glucose tolerance in scald injury. However, the effects of Exendin-4, a long-acting incretin similar to GLP 1, remained unclear in severe scald injury. Hence, this study attempted to investigate whether Exendin-4 had similar effects by protecting the histology of pancreas in severely scalded rats.

METHODS
One hundred sixty-two adult Wistar rats were equally randomized to sham burn group, burn group and burn with Exendin-4 treatment group. Rats were subjected to full skin thickness scald injuries (total body surface area: 50%) and were injected subcutaneously with Exendin-4 (4 μg/kg) twice daily. The histological changes of islets, the apoptosis of β cells, the amount of glucagon and insulin, and the concentration of plasma glucagon and insulin were observed; and the intraperitoneal glucose tolerance test was performed as well.

RESULTS
The islets and β cells were injured and the number of secretory granules decreased in the scalded rats, but less histopathological changes were seen in the rats treated with Exendin-4. The apoptosis index of treated rats was significantly lower than that of the scalded rats (p < 0.05). There was significant difference in β-cell density postinjury between the two groups (p < 0.05). More insulin and less glucagon in islets and plasma were found in the treated rats (p < 0.05), suggesting improved intraperitoneal glucose tolerance (p < 0.05) and fasting blood glucose (p < 0.05) in this group.

CONCLUSION
Based on our previous finding that GLP-1 could control hyperglycemia by increasing insulin secretion and inhibiting β-cell apoptosis in severe scald injuries, this study further confirmed that Exendin-4 could increase glycemic control following severe scald by preserving the histology of β cells in pancreatic islets and inhibiting their apoptosis.
Impact of licensed federal firearm suppliers on firearm-related mortality
Authors: Chao Stephanie D. , Kastenberg Zachary J. , Madhavan Sriraman , Staudenmayer Kristan 
Published: September 2018

BACKGROUND
Legal firearm sales occur largely through suppliers that have Federal Firearm Licensees (FFLs). Since FFL density might reflect ease-of-access to firearm purchases, we hypothesized that the number of FFL dealers would be associated with firearm-related deaths. We further hypothesized that licensee-type subsets would be associated with differential risks for gun-related deaths.

METHODS
We used data from the National Center for Health Statistics National Vital Statistics System (2008–2014) and national data on Federal Firearms Licensees for 2014. Correlation analysis and linear regression analysis were performed to determine the relationship between different licensee types and firearm-related deaths. We controlled for population, number of statewide registered firearms, and the density of other types of FFLs.

RESULTS
We identified a total of 65,297 FFLs. There was a moderate correlation (R = 0.53, ρ = 0.48) between total FFL density and firearm-related death rates. Further analysis by type of firearm-related death showed a strong correlation (R = 0.81, ρ = 0.76) between total FFL density and firearm-related suicide rates. No correlation was found between total FFL density and firearm-related homicide rate. Among individual FFL types, FFL02 (firearm dealing pawnshop) density was the only FFL-type found to be correlated with firearm-related death rates. We found a strong correlation between FFL02 density and overall firearm-related death rate (R = 0.69, ρ = 0.78) and firearm-related suicide rate (R = 0.72, ρ = 0.78). Linear regression analysis showed that even while controlling for number of registered firearms and population, the number of firearm-dealing pawnshops remained significantly associated with overall firearm-related deaths and firearm-related suicides.

CONCLUSION
Access to legally distributed firearms is associated with firearm-related death rates, particularly firearm-related suicides. Specifically, firearm-dealing pawnshops were associated with suicide-related deaths. These findings suggest that deeper exploration of legal firearm access and firearm-related injuries would benefit discussion of preventative measures.

LEVEL OF EVIDENCE
Therapeutic, Level V.
Relative Yield of MEG and EEG Spikes in Simultaneous Recordings
Authors: Ebersole John S. , Wagner Michael 
Published: September 2018

Purpose:
Most clinical magnetoencephalography (MEG) centers record both MEG and EEG, but model only MEG sources. This may be related to the belief that MEG spikes are more prevalent, MEG is more sensitive, or to proprietary software limitations. Biophysics would contend, however, that EEG, being sensitive to radial and tangential source orientations, would provide complementary data for analysis.

Methods:
We recorded 306 channels of MEG and 25 channels of EEG simultaneously in 297 consecutive patients over 3 years. We inspected the MEG and EEG recordings separately, identified spikes in both, determined whether their voltage and/or magnetometer magnetic fields were dipolar and thus model-worthy, and segregated them into types based on similar and distinct field topography. We placed for each patient their spike types into categories, including those with both a recognizable MEG and EEG signal and those with only an MEG and only an EEG signal.

Results:
Eighty-three percent of patients had spikes recorded, and these patients had an average of 2.7 spike types each. Fifty-six percent of spike types were present in both MEG and EEG. However, 36% of spike types were only evident in EEG, whereas 8% were noted in MEG alone. In 49% of patients with spikes, MEG review missed at least one spike type, whereas in 17% of patients, EEG review missed at least one spike type.

Conclusions:
To obtain an optimal yield of diagnostic information, EEG should also be subjected to source analysis in any clinical MEG study. EEG and MEG data are indeed complementary.
A Waves in Diabetic Neuropathy: Pathophysiology and Neurographic Images
Authors: Rampello Liborio , Rampello Luigi , Arcidiacono Antonio 
Published: September 2018

Purpose:
To evaluate the presence of A waves in diabetic neuropathy, we designed a retrospective observational study recruiting patients with type II diabetes and chronic diabetic distal sensorimotor polyneuropathy.

Methods:
We recruited 238 patients of both sexes aged between 41 and 89 years. Neurography was undertaken on two bilateral upper (median and ulnar) and lower (peroneal and tibial) limb nerves. As controls, we considered that neurographs performed bilaterally on the same nerves of 40 healthy subjects.

Results:
In addition to neurographic changes typical of chronic distal sensorimotor neuropathy, patients had a 32.77% incidence of A waves, mostly found in the tibial (16.38%) and peroneal (8.8%) nerves. Among controls, A waves were found only in the tibial nerve of a single subject (2.5%). Chi-square test with Yates correction to compare the two percentages (32.77% of patients and 2.5% of healthy subjects): 13.98, P = 0.0002, highly significant.

Conclusions:
We postulate that demyelination may be the site of backfiring or slowing of nerve conduction velocity, explaining the appearance of A waves in their different varieties. Implementing the search for A waves in routine neurographic examination can be a useful option for the diagnosis of neuropathy and the prediction of possible latent neuropathic processes.
Reducing adverse medication events in mental health: Australian National Survey
Authors: Gadzhanova Svetla , Roughead Elizabeth , Lowy Helen , O’Connor Daniel 
Published: September 2018

Aim:To determine the extent to which evidence-based medication safety practices have been implemented in public and private mental health inpatient units across Australia.Methods:The Reducing Adverse Medication Events in Mental Health survey was piloted in Victoria, Australia, in 2015, and rolled out nationally in 2016. In total, 235 mental health inpatient units from all States and Territories in Australia were invited to participate. The survey included questions about the demographics of the mental health unit, evidence-based strategies to improve prescription writing, the administration and dispensing of medicines and pharmacy-led interventions, and also questions relating to consumer engagement in medication management and shared decision-making.Results:The response rate was 45% (N = 106 units). Overall, the survey found that 57% of the mental health units had fully or partially implemented evidence-based medication safety practices. High levels of implementation (80%) were reported for the use of standardized medication charts such as the National Inpatient Medication Chart as a way to improve medication prescription writing. Most (71%) of the units were using standardized forms for recording medication histories, and 56% were using designated forms for Medication Management Plans. However, less than one-fifth of the units had implemented electronic medication management systems, and the majority of units still relied on paper-based documentation systems.Interventions to improve medicine administration and dispensing were not highly utilized. Individual patient-based medication distribution systems were fully implemented in only 9% of the units, with a high reliance (81%) on ward stock or imprest systems. Tall Man lettering for labelling was implemented in only one-third of the units.Pharmacy services were well represented in mental health units, with 80% having access to onsite pharmacist services providing assessments of current medications and clinical review services, adverse drug reaction reporting and management services, patient and carer education and counselling, and medicines information services. However, pharmacists were involved in only half of medical reconciliations. Their involvement in post-discharge follow-up was limited to 4% of units.Conclusions:Gaps in medication safety practices included limited use of individual patient supply systems for medication distribution, a high reliance on ward stock systems and high reliance on paper-based systems for medication prescribing and administration. With regards to service provision, clinical pharmacist involvement in medical reconciliation services, therapeutic drug monitoring and interdisciplinary ward rounds should be increased. Discharge and post-discharge services were major gaps in service provision.
A nematode retrotransposon in the common shrew: horizontal transfer between parasite and host
Authors: Dunemann Sonja M. , Wasmuth James D. 
Published: September 2018

AbstractReports of horizontal transposon and gene transfers involving metazoan species has increased with the sequencing of their genomes. Horizontal transfer could be facilitated by the intimate relationship between a parasite and its hosts. To date, two studies have identified horizontal transfer of RTEs, a class of retrotransposable elements, involving parasites: ticks might act as vector for BovB between ruminants and squamates, and AviRTE was transferred between birds and parasitic nematodes. We wanted to know if parasitic nematodes are involved in other cases of horizontal transfer of RTEs. We searched 33 mSammalian RTEs in 81 nematode assemblies, and 10 nematode RTEs in 98 mammalian assemblies. We identified RTE1õ Sar from Sorex araneus, the common shrew, in parasitic nematodes and show that it originates from nematodes. To exclude contamination of the S. araneus assembly, we developed an approach that uses long reads and paired-end reads. With phylogenetic analysis and copy age estimation, we show that RTE1_Sar was horizontally transferred from nematodes to S. araneus. We confirm horizontal transfer of RTEs in host-parasite interactions, and we present a new method to distinguish between contamination and horizontal transfer.
Mycobacterium tuberculosisinhibits autocrine type I interferon signaling to increase intracellular survival
Authors: Banks Dallas A. , Ahlbrand Sarah E. , Keith Hughitt V. , Shah Swati , Vogel Stefanie N. , El-Sayed Najib M. , Briken Volker 
Published: September 2018

SummaryThe type I interferons (IFN-αand -β) are important for host defense against viral infections. In contrast, their role in defense against non-viral pathogens is more ambiguous. Here we report that IFN-β-signaling in macrophages has protective capacity againstMycobacterium tuberculosis(Mtb) via the increased production of nitric oxide. Furthermore, Mtb is able to inhibit IFN-α/β-receptor-mediated cell signaling and the transcription of 309 IFN-βstimulated genes which includes genes associated with innate host cell defense. The molecular mechanism of inhibition by Mtb involves reduced phosphorylation of the IFNAR-associated protein kinases JAK1 and TYK2 leading to reduced phosphorylation of the downstream targets STAT1 and STAT2. Overall, our study supports the novel concept that Mtb evolved to inhibit autocrine type I IFN signaling in order to evade host defense mechanisms.
Cancer as a tissue anomaly: classifying tumor transcriptomes based only on healthy data
Authors: Quinn Thomas P. , Nguyen Thin , Lee Samuel C. , Venkatesh Svetha 
Published: September 2018

AbstractSince the turn of the century, researchers have sought to diagnose cancer based on gene expression signatures measured from the blood or biopsy as biomarkers. This task, known as classification, is typically solved using a suite of algorithms that learn a mathematical rule capable of discriminating one group (e.g., cases) from another (e.g., controls). However, discriminatory methods can only identify cancerous samples that resemble those that the algorithm already saw during training. As such, we argue that discriminatory methods are fundamentally ill-suited for the classification of cancer: because the possibility space of cancer is definitively large, the existence of a one-of-a-kind gene expression signature becomes very likely. Instead, we propose using an established surveillance method that detects anomalous samples based on their deviation from a learned normal steady-state structure. By transferring this method to transcriptomic data, we can create an anomaly detector for tissue transcriptomes, a “tissue detector”, that is capable of identifying cancer without ever seeing a single cancer example. Using models trained on normal GTEx samples, we show that our “tissue detector” can accurately classify TCGA samples as normal or cancerous and that its performance is further improved by including more normal samples in the training set. We conclude this report by emphasizing the conceptual advantages of anomaly detection and by highlighting future directions for this field of study.
Homeolog expression quantification methods for allopolyploids
Authors: Kuo Tony , Hatakeyama Masaomi , Tameshige Toshiaki , Shimizu Kentaro K. , Sese Jun 
Published: September 2018

AbstractGenome duplication with hybridization, or allopolyploidization, occurs in animals, fungi, and plants, and is especially common in crop plants. There is increasing interest in the study of allopolyploids due to advances in polyploid genome assembly, however the high level of sequence similarity in duplicated gene copies (homeologs) pose many challenges. Here we compared standard RNA-seq expression quantification approaches used currently for diploid species against subgenome-classification approaches which maps reads to each subgenome separately. We examined mapping error using our previous and new RNA-seq data in which a subgenome is experimentally added (synthetic allotetraploid Arabidopsis kamchatica) or reduced (allohexaploid wheat Triticum aestivum versus extracted allotetraploid) as ground truth. The error rates in the two species were very similar. The standard approaches showed higher error rates (> 10% using pseudo-alignment with Kallisto) while subgenome-classification approaches showed much lower error rates (< 1% using EAGLE-RC, < 2% using HomeoRoq). Although downstream analysis may partly mitigate mapping errors, the difference in methods was substantial in hexaploid wheat, where Kallisto appeared to have systematic differences relative to other methods. Only approximately half of the differentially expressed homeologs detected using Kallisto overlapped with those by any other method. In general, disagreement in low expression genes was responsible for most of the discordance between methods, which is consistent with known biases in Kallisto. We also observed that there exist uncertainties in genome sequences and annotation which can affect each method differently. Overall, subgenome-classification approaches tend to perform better than standard approaches with EAGLE-RC having the highest precision.
Assessment of biological role and insight into druggability of the Plasmodium falciparum protease plasmepsin V
Authors: Polino Alexander J. , Nasamu Armiyaw S. , Niles Jacquin C. , Goldberg Daniel E. 
Published: September 2018

AbstractUpon infection of a red blood cell (RBC), the malaria parasite Plasmodium falciparum drastically remodels its host by exporting hundreds of proteins into the RBC cytosol. This program of protein export is essential for parasite survival, hence there is interest in export-related proteins as potential drug targets. One proposed target is plasmepsin V (PMV), an aspartic protease that cleaves export-destined proteins in the parasite ER at a motif called the Plasmodium export element (PEXEL). This cleavage is essential for effector export across the vacuolar membrane. Despite long-standing interest in PMV, functional studies have been hindered by the failure of current technologies to produce a regulatable lethal depletion of PMV. To overcome this technical barrier, we designed a facile system for stringent post-transcriptional regulation, allowing a tightly controlled, tunable knockdown of PMV. Under maximal knockdown conditions, parasite growth was arrested, validating PMV as essential for parasite survival in RBCs. We found that PMV levels had to be dramatically depleted to affect parasite growth, suggesting that the parasite maintains this enzyme in substantial excess. This has important implications for antimalarial development. Additionally, we found that PMV-depleted parasites arrest immediately after invasion of the host cell, suggesting that PMV has an unappreciated role in early development that is distinct from its previously reported role in protein export in later-stage parasites.ImportanceMalaria is endemic to large swaths of the developing world, causing nearly 500,000 deaths each year. While infection can be treated with antimalarial drugs, resistance continues to emerge to frontline antimalarials, spurring calls for new drugs and targets to feed the drug development pipeline. One proposed target is the aspartic protease plasmepsin V (PMV) that processes exported proteins, enabling the export program that remodels the host cell. This work uses facile genetic tools to produce lethal depletion of PMV, validating it as a drug target and showing that PMV is made in substantial excess in blood-stage parasites. Unexpectedly, PMV depletion leads to parasite death immediately after invasion of RBCs, distinct from other disruptions of the export pathway. This suggests that PMV inhibitors could lead to relatively rapid parasite death, and that PMV has additional unexplored role(s) during RBC infection.