bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilization and Performance Benchmarking for Postoperative Imaging in Children With Complicated Appendicitis
Authors: Kashtan Mark A. , Graham Dionne A. , Rangel Shawn J. 
Published: July 2020

Objective:
The aim of this study was to characterize hospital-level variation and establish diagnostic performance benchmarks for postoperative imaging in children with complicated appendicitis.

Summary Background Data:
Wide variation in preoperative imaging in children with suspected appendicitis has been previously described. Variation in the use and accuracy of postoperative imaging to diagnose suspected organ space infection (OSI) following appendectomy has not been characterized.

Methods:
Multicenter retrospective analysis of children who underwent appendectomy for complicated appendicitis using data from the NSQIP-Pediatric Appendectomy Pilot Collaborative. Resource utilization measures included rates of postoperative imaging [ultrasound (US) and computed tomography (CT)] and imaging-associated diagnostic efficiency ratio (DER; number of OSIs diagnosed/study obtained). Radiation stewardship measures included US utilization process measures (rate of US as the initial diagnostic study and rate of CTs preceded by an attempt at US) and CT-associated DER. Hospital-level observed-to-expected ratios (O/Es) were calculated for each measure after adjusting for demographic characteristics and disease severity using multivariable regression.

Results:
A total of 1316 patients from 20 hospitals were included. Overall, 18.3% of patients underwent postoperative imaging (hospital range: 4.8%–33.3%), and O/Es varied 3.5-fold among hospitals (P < 0.01). The overall imaging-associated DER was 0.56 OSIs/study (hospital range: 0–1.00), and O/Es varied 2.7-fold among hospitals (P < 0.01). Significant variation was also observed for US as the initial diagnostic study (overall: 41.5%; O/E range: 0.40–2.01, P < 0.01), CTs preceded by US (overall: 27.3%; O/E range: 0–3.66, P < 0.01), and CT-associated DER (overall: 0.69 OSI's/CT; O/E range: 0–1.80, P < 0.01). Fifty percent of hospitals were a statistical outlier on at least 1 measure.

Conclusion:
Significant variation exists across hospitals in imaging practices to diagnose suspected OSI following appendectomy. Imaging utilization benchmarking may assist hospitals in prioritizing quality improvement efforts to optimize resource utilization and radiation stewardship.
Factors Associated With Long-Term Use of Percutaneous Tibial Nerve Stimulation for Management of Overactive Bladder Syndrome
Authors: Gordon Toya , Merchant Maqdooda , Ramm Olga , Patel Minita 
Published: July 2020

Objectives
The aims of the study were to estimate the rate of percutaneous tibial nerve stimulation maintenance therapy (PTNS-MT) among women with overactive bladder syndrome (OAB) and evaluate factors associated with long-term use of PTNS.

Methods
Patients who completed 12 weekly sessions of PTNS (PTNS-IN) for OAB between 2009 and 2016 within the Kaiser Permanente Northern California were identified using Current Procedural Terminology and International Classification of Diseases codes. Bivariate analysis was performed to compare demographic and clinical variables. A logistic regression model was used to determine factors associated with PTNS-MT compared with the use of alternative treatments following PTNS-IN.

Results
Of the 1331 patients who initiated PTNS for OAB, 347 (26%) completed PTNS-IN. Of these, 46% (n = 158) continued with long-term PTNS therapy, defined as completion of at least 8 additional PTNS sessions for a 32-week period. On bivariate analysis, those choosing PTNS-MT were more likely to be white (88%, P < 0.0001), nondiabetic (89%, P = 0.03), did not use anticholinergics before PTNS initiation (41%, P = 0.04), and had no prior surgery for stress incontinence (SUI; 84%, P = 0.01). In multivariable analysis, race was a significant factor with black, Hispanic, and Asian women less likely to continue with PTNS-MT. Women with prior use of first-line OAB therapy were 78% more likely to undergo PTNS-MT. Women with prior surgery for SUI were 53% less likely to continue PTNS-MT.

Conclusions
Almost half of patients who completed PTNS-IN continued with PTNS-MT. White race, prior use of first-line OAB therapy, and no prior surgery for SUI were associated with long-term therapy.
Hepatic inflammation after burn injury is associated with necroptotic cell death signaling
Authors: Idrovo Juan-Pablo , Boe Devin M. , Kaahui Soncy , Yang Weng-Lang , Kovacs Elizabeth J. 
Published: July 2020

BACKGROUNDBurn injury still has a high attributable mortality. The elevated mortality rate of severe burns is still concerning. Hepatic inflammation and injury are common after burns and are associated with poor outcomes. Necroptosis is a programmed cell death linked with inflammation. Thus, assessing necroptotic pathways in the liver can lead to new therapeutic modalities to improve mortality after severe burns.METHODSMice underwent 15% total body surface area burn or sham injury. Three hours after burn, the mice were euthanized to collect blood and livers. Histology, injury markers, genes expression, and tissue protein levels were compared between groups.RESULTSCompared with sham, burned mice had heightened liver inflammatory cell infiltration and edema. Serum aspartate aminotransferase and alanine aminotransferase were increased by 4.9- and 3.4-fold, respectively, in burned mice relative to sham (p< 0.05). Expression of tumor necrosis factor α, interleukin-6, interleukin-1β, and CXCL1 (KC) genes were elevated in livers of burned mice by 10-, 86-, 10-, and 828-fold, respectively, compared with sham (p< 0.05). Expression of necroptotic genes, namely, receptor-interacting protein kinases 1 and 3, and mixed lineage kinase domain-like in livers of burned mice were increased by 10-, 13-, and 4.5-fold, respectively, relative to sham (p< 0.05). Receptor-interacting protein kinase 1 and phosphorylated mixed lineage kinase domain-like protein levels measured by Western-blot in livers after burn injury were elevated by 22- and 17-fold, respectively, compared with sham (p< 0.05).CONCLUSIONLiver damage occurs early after burns in mice and is associated with elevation of proinflammatory cytokines, chemokine, and proteins involved in the necroptotic pathway. This study suggests that necroptosis plays a role in the pathogenesis of liver failure secondary to burn injury.
Impact of uric acid on liver injury and intestinal permeability following resuscitated hemorrhagic shock in rats
Authors: Khazoom François , L’Écuyer Sydnée , Gilbert Kim , Gagné Marc-André , Bouchard Caroline , Rose Christopher F. , Rousseau Guy , Charbonney Emmanuel 
Published: July 2020

BACKGROUND
Multiorgan failure is a consequence of severe ischemia-reperfusion injury after traumatic hemorrhagic shock (HS), a major cause of mortality in trauma patients. Circulating uric acid (UA), released from cell lysis, is known to activate proinflammatory and proapoptotic pathways and has been associated with poor clinical outcomes among critically ill patients. Our group has recently shown a mediator role for UA in kidney and lung injury, but its role in liver and enteric damage after HS remains undefined. Therefore, the objective of this study was to evaluate the role of UA on liver and enteric injury after resuscitated HS.

METHODS
A murine model of resuscitated HS was treated during resuscitation with a recombinant uricase, a urate oxidase enzyme (rasburicase; Sanofi-Aventis, Canada Inc, Laval, Canada), to metabolize and reduce circulating UA. Biochemical analyses (liver enzymes, liver apoptotic, and inflammatory markers) were performed at 24 hours and 72 hours after HS. Physiological testing for enteric permeability and gut bacterial product translocation measurement (plasma endotoxin) were performed 72 hours after HS. In vitro, HT-29 cells were exposed to UA, and the expression of intercellular adhesion proteins (ZO-1, E-cadherin) was measured to evaluate the influence of UA on enteric permeability.

RESULTS
The addition of uricase to resuscitation significantly reduced circulating and liver UA levels after HS. It also prevented HS-induced hepatolysis and liver apoptotic/inflammatory mediators at 24 hours and 72 hours. Hemorrhagic shock–induced enteric hyperpermeability and endotoxemia were prevented with uricase.

CONCLUSIONS
After resuscitated HS, UA is an important mediator in liver and enteric injury. Uric acid represents a therapeutic target to minimize organ damage in polytrauma patients sustaining HS.
Valproic acid decreases resuscitation requirements after hemorrhage in a prolonged damage-control resuscitation model
Authors: Biesterveld Ben E. , Williams Aaron M. , Kemp Michael T. , Wakam Glenn K. , Siddiqui Ali Z. , O’Connell Rachel L. , Shamshad Alizeh , Chtraklin Kiril , Bhatti Umar F. , Li Yongqing , Alam Hasan B. 
Published: July 2020

BACKGROUND
Hemorrhage is the leading cause of preventable death in trauma. Future military conflicts are likely to be in austere environments, where prolonged damage-control resuscitation (p-DCR) may be required for 72 hours before evacuation. There is a need to demonstrate that p-DCR is feasible and to optimize its logistics. Dried plasma (DP) is a practical alternative to conventional blood products in austere settings, and valproic acid (VPA) improves survival in preclinical models of trauma and hemorrhage. We performed the current experiment to study the synergistic effects of VPA and DP and hypothesized that VPA treatment would decrease the fluid resuscitation requirements in p-DCR.

METHODS
Female swine were subjected to 50% hemorrhage (associated with 20% survival using non–plasma-based p-DCR) and left unresuscitated for 1 hour to simulate medic response time. They were then randomized to receive VPA (150 mg/kg + DP 250 mL; DP-VPA group; n = 5) or DP alone (DP group; n = 6). All animals were resuscitated to a systolic blood pressure of 80 mm Hg with lactated Ringer according to the Tactical Combat Casualty Care Guidelines for 72 hours, after which packed red blood cells were transfused to simulate evacuation to higher levels of care.

RESULTS
The DP-VPA group needed significantly (p = 0.002) less volume of lactated Ringer to reach and maintain the target systolic blood pressure. This would translate to a 4.3 L volume sparing effect for a 70-kg person.

CONCLUSION
Addition of a single dose of VPA significantly decreases the volume of resuscitation required in a p-DCR model.
Biologic mesh implantation is associated with serious abdominal wall complications in patients undergoing emergency abdominal surgery: A randomized-controlled clinical trial
Authors: Jakob Manuel O. , Haltmeier Tobias , Candinas Daniel , Beldi Guido 
Published: July 2020

BACKGROUND
Open, emergency abdominal surgery is associated with a high incidence of fascial dehiscence and incisional hernia. Implantation of biologic meshes potentially reinforces the abdominal wall and therefore decreases such complications. The aim of this prospective randomized study was to compare the outcome after prophylactic intraperitoneal implantation of a biologic Strattice mesh (Allergan, Dublin, Ireland) with standard abdominal closure in patients undergoing emergency abdominal surgery.

METHODS
A two-arm randomized clinical trial was performed in patients undergoing emergency abdominal surgery at Bern University Hospital, University of Bern, Switzerland, from April 2016 to March 2019. Patients were randomly assigned to prophylactic implantation of a biological intraperitoneal mesh using Strattice, Allergan (mesh group), or standard abdominal closure using a single, continuous running suture (no-mesh group). Because of safety concerns, patient enrollment was closed prematurely.

RESULTS
Eligibility for inclusion was assessed in 61 patients. A total of 48 patients were randomized (21 in the mesh group, 28 in the no-mesh group). No differences in baseline characteristics were found. Abdominal wall complications requiring reoperations were more frequent in the mesh group compared to the no-mesh group (5 [83.3%] of 13 vs. 1 [14.3%] of 13 patients, p = 0.026). Mesh-associated abdominal wall complications included nonintegration of the mesh into the abdominal wall, dissolution of the mesh, and mesh-related infections.

CONCLUSION
In patients undergoing emergency abdominal surgery, intraperitoneal biologic Strattice mesh implantation is associated with significantly more frequent abdominal wall complications requiring reoperation. Therefore, the use of such meshes cannot be recommended in the contaminated environment of emergency abdominal surgery.

LEVEL OF EVIDENCE
Therapeutic, level I.
MoBPSweb: A web-based framework to simulate and compare breeding programs
Authors: Pook T. , Büttgen L. , Ganesan A. , Ha N.T. , Simianer H. 
Published: July 2020

ABSTRACTSelective breeding is a continued element of both crop and livestock breeding since early prehistory. In this work, we are proposing a new web-based simulation framework (“MoBPSweb”) that is combining a unified language to describe breeding programs with the simulation software MoBPS, standing for ‘Modular Breeding Program Simulator’. Thereby, MoBPSweb is providing a flexible environment to enter, simulate, evaluate and compare breeding programs. Inputs can be provided via modules ranging from a Vis.js-based flash environment for “drawing” the breeding program to a variety of modules to provide phenotype information, economic parameters and other relevant information. Similarly, results of the simulation study can be extracted and compared to other scenarios via output modules (e.g. observed phenotypes, accuracy of breeding value estimation, inbreeding rates). Usability of the framework is showcased along a toy example of a dairy cattle breeding program on farm level, with comparing scenarios differing in implemented breeding value estimation, selection index and selection intensity being considered. Comparisons are made considering both short and long-term effects of the different scenarios in terms of genomic gains, rates of inbreeding and the accuracy of the breeding value estimation. Lastly, general applicability of the MoBPSweb framework and the general potential for simulation studies for genetics and in particular in breeding are discussed.
A role for protease activated receptor type 3 (PAR3) in nociception demonstrated through development of a novel peptide agonist
Authors: Mwirigi Juliet , Kume Moeno , Hassler Shayne N , Ahmad Ayesha , Ray Pradipta R. , Jiang Changyu , Chamessian Alexander , Mseeh Nakleh , Ludwig Breya P , Rivera Benjamin D. , Nieman Marvin T , Van de Ven Thomas , Ji Ru-Rong , Dussor Gregory , Boitano Scott , Vagner Josef , Price Theodore J 
Published: July 2020

ABSTRACTThe protease activated receptor (PAR) family is a group of G-protein coupled receptors (GPCRs) activated by proteolytic cleavage of the extracellular domain. PARs are expressed in a variety of cell types with crucial roles in hemostasis, immune responses, inflammation, and pain. PAR3 is the least researched of the four PARs, with little known about its expression and function. We sought to better understand its potential function in the peripheral sensory nervous system. Mouse single-cell RNA sequencing data demonstrates that PAR3 is widely expressed in dorsal root ganglion (DRG) neurons. Co-expression of PAR3 mRNA with other PARs was identified in various DRG neuron subpopulations, consistent with its proposed role as a coreceptor of other PARs. We developed a lipid tethered PAR3 agonist, C660, that selectively activates PAR3 by eliciting a Ca2+response in DRG and trigeminal (TG) neurons.In vivo, C660 induces mechanical hypersensitivity and facial grimacing in WT but not PAR3-/-mice. We characterized other nociceptive phenotypes in PAR3-/-mice and found a loss of hyperalgesic priming in response to IL-6, carrageenan, and a PAR2 agonist, suggesting that PAR3 contributes to long-lasting nociceptor plasticity in some contexts. To examine a potential role of PAR3 in regulating activity of other PARs in sensory neurons, we administered PAR1, PAR2, and PAR4 agonists and assessed mechanical and affective pain behaviors in WT and PAR3-/-mice. We observed that the nociceptive effects of PAR1 agonists were potentiated in the absence of PAR3. Our findings suggest a complex role of PAR3 in the physiology and plasticity of nociceptors.
D614G Spike Variant Does Not Alter IgG, IgM, or IgA Spike Seroassay Performance
Authors: Klumpp-Thomas Carleen , Kalish Heather , Hicks Jennifer , Mehalko Jennifer , Drew Matthew , Memoli Matthew J , Hall Matthew D , Esposito Dominic , Sadtler Kaitlyn 
Published: July 2020

ABSTRACTEmergence of a new variant of spike protein (D614G) with increased infectivity and transmissibility has prompted many to analyze the potential role of this variant in the SARS-CoV-2 pandemic. When a new variant emerges, there is a concern regarding whether an individual exposed to one variant of a virus will have cross-reactive immune memory to the second variant. Accordingly, we analyzed the serologic reactivity of D614 (original) and G614 variant spike proteins. We found that antibodies from a high-incidence population in New York City reacted both toward the original D614 spike and the G614 spike variant. These data suggest that patients who have been exposed to either SARS-CoV-2 variant have humoral immunity that can respond against both variants. This is an important finding both for SARS-CoV-2 disease biology and for potential antibody-based therapeutics.
A case-control and cohort study to determine the relationship between ethnic background and severe COVID-19
Authors: Zakeri Rosita , Bendayan Rebecca , Ashworth Mark , Bean Daniel M , Dodhia Hiten , Durbaba Stevo , O’Gallagher Kevin , Palmer Claire , Curcin Vasa , Aitken Elizabeth , Bernal William , Barker Richard D , Norton Sam , Gulliford Martin , Teo James TH , Galloway James , Dobson Richard JB , Shah Ajay M 
Published: July 2020

AbstractBackgroundPeople of minority ethnic background may be disproportionately affected by severe COVID-19 for reasons that are unclear. We sought to examine the relationship between ethnic background and (1) hospital admission for severe COVID-19; (2) in-hospital mortality.MethodsWe conducted a case-control study of 872 inner city adult residents admitted to hospital with confirmed COVID-19 (cases) and 3,488 matched controls randomly sampled from a primary healthcare database comprising 344,083 people resident in the same region. To examine in-hospital mortality, we conducted a cohort study of 1827 adults consecutively admitted with COVID-19. Data collected included hospital admission for COVID-19, demographics, comorbidities, in-hospital mortality. The primary exposure variable was self-defined ethnicity.ResultsThe 872 cases comprised 48.1% Black, 33.7% White, 12.6% Mixed/Other and 5.6% Asian patients. In conditional logistic regression analyses, Black and Mixed/Other ethnicity were associated with higher admission risk than white (OR 3.12 [95% CI 2.63-3.71] and 2.97 [2.30-3.85] respectively). Adjustment for comorbidities and deprivation modestly attenuated the association (OR 2.28 [1.87-2.79] for Black, 2.66 [2.01-3.52] for Mixed/Other). Asian ethnicity was not associated with higher admission risk (OR 1.20 [0.86-1.66]). In the cohort study of 1827 patients, 455 (28.9%) died over a median (IQR) of 8 (4-16) days. Age and male sex, but not Black (adjusted HR 0.84 [0.63-1.11]) or Mixed/Other ethnicity (adjusted HR 0.69 [0.43-1.10]), were associated with in-hospital mortality. Asian ethnicity was associated with higher in-hospital mortality (adjusted HR 1.54 [0.98-2.41]).ConclusionsBlack and Mixed ethnicity are independently associated with greater admission risk with COVID-19 and may be risk factors for development of severe disease. Comorbidities and socioeconomic factors only partly account for this and additional ethnicity-related factors may play a large role. The impact of COVID-19 may be different in Asians.Funding sourcesBritish Heart Foundation (CH/1999001/11735 and RE/18/2/34213 to AMS); the National Institute for Health Research Biomedical Research Centre (NIHR BRC) at Guy’s & St Thomas’ NHS Foundation Trust and King’s College London (IS-BRC-1215-20006); and the NIHR BRC at South London and Maudsley NHS Foundation Trust and King’s College London (IS-BRC-1215-20018).
Defining the transcriptional landscape of infiltrating immune cells in human and mouse bladder cancer
Authors: Yu Haocheng , Sfakianos John P. , Wang Li , Daza Jorge , Galsky Matthew D. , Bhardwaj Nina , Elemento Olivier , Faltas Bishoy M. , Zhu Jun , Mulholland David J. 
Published: July 2020

SummaryThe tumor immune cell landscape is composed of infiltrating myeloid cells (TIMs) and lymphocytes (TILs) that are important for regulating tumor progression and response to immune therapies. Since at least 70% of bladder cancer patients are poorly responsive to immune checkpoint blockade, there is a need for in depth analysis of the immune landscape both within individual tumor samples and between patients. To facilitate this, we have conducted single cell RNA sequencing (scRNA-seq) to map and transcriptionally define immune cells from 10 human bladder tumors. While all human tumors showed the of presence of major immune cell types, significant differences were observed in the relative numbers of these populations. To determine the translational utility of these findings we also performed scRNA-seq of TIMs-TILs isolated from mouse bladder tumors that were induced by the BBN carcinogen. In human and mouse comparison, we identified significant cross-species conservation in gene expression programs for NK, T, dendritic cells, monocytes and macrophages immune cell populations. Our data identified the conserved expression of key immunotherapy targets between human and mouse tumors including coordinately high gene expression ofPD-1,CTLAandIDO1while also noting species divergent expression ofTIM3,LAG3andCD274(PDL-1). To identify predictive immune cell-tumor interactions we computed conserved ligand-receptor (cell-cell) interaction scores between immune cell subsets and the epithelial tumor compartment. Together, this study defines the transcriptional status of bladder cancer immune cells and provides the rationale for future studies related to treatment response and therapeutic resistance.
2-LocusCleave and Rescueselfish elements harness a recombination rate-dependent generational clock for self limiting gene drive
Authors: Oberhofer Georg , Ivy Tobin , Hay Bruce A 
Published: July 2020

AbstractSelf-limiting gene drive allows control over the spread and fate of linked traits.Cleave and Rescue(ClvR) elements create self-sustaining drive and comprise a DNA sequence-modifying enzyme (Cas9-gRNAs,Cleaver) that disrupts an essential gene, and a tightly linked, uncleavable version of the essential gene (Rescue).ClvRspreads by creating conditions in which those without it die because they lack essential gene function. We show that whenClvRis implemented in a 2-locus format, with key elements –Rescue(and Cargo), and Cas9 and/or gRNAs – located at different genomic positions, spread of theRescueis self-limiting. Drive strength and duration are determined by a recombination rate-dependent generational clock, providing an important point of control for different ecological and regulatory contexts. We implement 2-locusClvRinDrosophila. Rescuespreads to high frequency in a Cas9-dependent manner, while the frequency of Cas9 decreases, demonstrating transient drive and loss of future drive potential.