bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying Factors Essential to the Integrity of the Esophagogastric Junction During Antireflux Procedures
Authors: Stefanova Dessislava I. , Limberg Jessica N. , Ullmann Timothy M. , Liu Mengyuan , Thiesmeyer Jessica W. , Beninato Toni , Finnerty Brendan M. , Schnoll-Sussman Felice H. , Katz Philip O. , Fahey Thomas J. , Zarnegar Rasa 
Published: July 2020

Objective:
To quantify the contribution of key steps in antireflux surgery on compliance of the EGJ.

Background:
The lower esophageal sphincter and crural diaphragm constitute the intrinsic and extrinsic sphincters of the EGJ, respectively. Interventions to treat reflux attempt to restore the integrity of the EGJ. However, there are limited data on the relative contribution of critical steps during antireflux procedures to the functional integrity of the EGJ.

Methods:
Primary antireflux surgery was performed on 100 consecutive patients with pathologic reflux. Intraoperative EGJ measurements including distensibility index (DI), cross-sectional area (CSA), and HPZ length were collected using EndoFLIP. Data was acquired pre-repair, post-diaphragmatic re-approximation with sub-diaphragmatic EGJ relocation, and post-sphincter augmentation.

Results:
Patients underwent Nissen (45%), Toupet (44%), or LINX (11%). After diaphragmatic re-approximation, DI decreased by a median 0.77 mm2/mm Hg [95%-confidence interval (CI): −0.99, −0.58; P < 0.0001], CSA decreased 16.0 mm2 (95%-CI: −20.0, −8.0; P < 0.0001), whereas HPZ length increased 0.5 cm (95%-CI: 0.5, 1.0; P < 0.0001). After sphincter augmentation, DI decreased 0.14 mm2/mm Hg (95%-CI: −0.30, −0.04; P = 0.0005) and CSA decreased 5.0 mm2 (95%-CI: −10.0, 1.0; P = 0.0.0015), whereas HPZ length increased 0.5 cm (95%-CI: 0.50, 0.54; P < 0.0001). Diaphragmatic re-approximation had a higher percent contribution to distensibility (79% vs 21%), CSA (82% vs 18%), and HPZ (60% vs 40%) than sphincter augmentation.

Conclusion:
Dynamic intraoperative monitoring demonstrates that diaphragmatic re-approximation and sub-diaphragmatic relocation has a greater effect on EGJ compliance than sphincter augmentation. As such, antireflux procedures should address both for optimal improvement of EGJ physiology.
Time to definitive fixation of pelvic and acetabular fractures
Authors: Devaney Giles L. , Bulman James , King Kate L. , Balogh Zsolt J. 
Published: July 2020

BACKGROUND
The timing of definitive surgical stabilization is a controversial topic of pelvic and acetabular fracture (PAF) management. Historically, staged care with delayed definitive fixation was recommended; however, more recently, some centers have shown early definitive fixation to be feasible in most patients. We hypothesized that time to definitive fixation of PAF decreased without adverse outcomes.

METHODS
A level 1 trauma center's prospective pelvic fracture database was retrospectively analyzed. A total of 341 of the 1,270 consecutive PAF patients had surgery between January 2009 and December 2018. Demographics, polytrauma status, hemodynamic stability, time to definitive operation, length of intensive care unit stay, hospital length of stay, mortality were recorded. Data is presented as mean ± SD, percentages. Statistical significance was determined at p < 0.05.

RESULTS
There were 34 ± 8 per year operatively treated PAF patients during the study period. The demographics (age, 44.1 ± 18 years; 74.5% males) and injury severity (Injury Severity Score, 20; interquartile range, 16–29) did not change. Time to definitive fixation on average was 85 ± 113 hours (range, 0.8–1286 hours). Linear regression analysis demonstrated a decrease in time to definitive fixation considering all patients (β = −0.186, p = 0.003). pelvic ring fractures with polytrauma (β = −1.404, p = 0.03). and hemodynamically unstable patients (β = −1.428, p = 0.037). There was no significant change in mortality, length of stay, or intensive care unit length of stay for the overall cohort or any subgroup.

CONCLUSION
Time to definitive fixation in PAF has decreased during the last decade, with the largest decrease in time to fixation occurring in the hemodynamically unstable and pelvic fracture with polytrauma cohorts. The timely definitive internal fixation is achievable without increased length of stay.

LEVEL OF EVIDENCE
Therapeutic/care management, level IV.
The neuroprotective effect of quetiapine in critically ill traumatic brain injury patients
Authors: Asmar Samer , Lokhandwala Adil , Richards Joseph , Bible Letitia , Avila Mauricio , Castanon Lourdes , Ditillo Michael , Douglas Molly , Joseph Bellal 
Published: July 2020

INTRODUCTION
Quetiapine is an atypical antipsychotic commonly used in critical care. Cellular and animal models demonstrated its novel anti-inflammatory properties in traumatic brain injury (TBI). Our study aimed to assess the effect of quetiapine on outcomes in critically ill TBI patients. We hypothesize that quetiapine improves neurological outcomes.

METHODS
The Multiparameter Intelligent Monitoring in Intensive Care database was queried, and all adult (age, ≥18 years) isolated TBI patients (extracranial Abbreviated Injury Scale, < 2) admitted to the intensive care unit for a period of >48 hours. Patients were stratified into quetiapine (+) and no-quetiapine (−) groups. Propensity score matching was performed (1:2 ratio). Outcome measures were intensive care unit length of stay, discharge Glasgow Coma Scale (GCS), and mortality. A subanalysis was performed for patients who underwent intracranial pressure (ICP) monitoring to ascertain the effect of quetiapine dose on ICP, and cerebral perfusion pressure (CPP). Survival curves and regression analyses were performed.

RESULTS
A matched cohort of (quetiapine, 116 vs. no-quetiapine, 232) patients was obtained. Mean ± SD age was 65 ± 21 years, median head Abbreviated Injury Scale was 3 (3–4), and median GCS was 10 (9–16). The median quetiapine dose given was 50 (25–125) mg. Patients who received quetiapine had lower mortality (17.2% vs. 27.6%; p = 0.03) and a higher median GCS at discharge (12 [11–14] vs. 11 [10–13]; p < 0.04) but no difference in intensive care unit length of stay (4.1 days vs. 4.7 days; p = 0.75) or discharge to skilled nursing facility (34.5% vs. 31.9%; p = 0.63). On subanalysis of patients who received quetiapine, 40% had ICP monitoring. Higher doses of quetiapine were independently associated with progressively lower ICP (β = −0.022 mm Hg/mg of quetiapine; p = 0.01) and higher CPP (β = 0.031 mm Hg/mg quetiapine; p = 0.01).

CONCLUSION
Quetiapine may decrease mortality and improve neurological outcomes in critically ill TBI patients. It has a dose-dependent effect to decrease ICP and increase CPP. Quetiapine may be a potential therapeutic modality in critically ill TBI patients, but further studies are required to explore these mechanisms.

LEVEL OF EVIDENCE
Systematic Review, level III.
Nationwide analysis of resuscitative thoracotomy in pediatric trauma: Time to differentiate from adult guidelines?
Authors: Prieto James M. , Van Gent Jan Michael , Calvo Richard Y. , Rooney Alexandra S. , Martin Matthew J. , Sise Michael J. , Sise C. Beth , Lazar David A. , Bansal Vishal , Ignacio Romeo C. 
Published: July 2020

BACKGROUND
Emergency department thoracotomy (EDT) for pediatric patients is uncommon, and practice patterns have not been evaluated. We examined the indications and outcomes for EDT by trauma center designation using a nationwide database.

METHODS
Patients 16 years or younger who underwent EDT within 30 minutes of arrival from 2013 to 2016 were identified in the American College of Surgeons National Trauma Data Bank. Patient demographic information, indications for EDT, and outcomes were analyzed. Outcomes were compared between centers with and without pediatric trauma center designation.

RESULTS
A total of 114 patients were identified for analysis with a mean ± SD age of 10.3 ± 4.7 years. Patients were predominantly male (69%) with a median Injury Severity Score of 26 (interquartile range, 18–42). Penetrating trauma occurred in 56%. Overall, mortality was 90% and was similar in penetrating and blunt trauma (88% vs. 94%; p = 0.34). There were no survivors among the 53 patients (46%) who arrived with no signs of life. Among the 11 patients (10%) who survived, median length of stay was 26 days (interquartile range, 6–28 days). Overall, 8% of EDT was performed at free-standing pediatric trauma centers, 45% at adult centers, and 47% at combined trauma centers. Mortality rates and indications were similar among trauma centers regardless of designation status.

CONCLUSION
In a national population-based data set, the mortality after pediatric EDT is high, and many of these procedures are performed at nonpediatric trauma centers. Regardless of injury mechanism, EDT is not appropriate in children without signs of life on arrival. Pediatric guidelines are needed to increase awareness of the poor outcomes and limited indications for EDT.

LEVEL OF EVIDENCE
Therapeutic, level IV.
Comparison of postoperative complications between open and laparoscopic appendectomy: An umbrella review of systematic reviews and meta-analyses
Authors: Poprom Napaphat , Wilasrusmee Chumpon , Attia John , McEvoy Mark , Thakkinstian Ammarin , Rattanasiri Sasivimol 
Published: July 2020

BACKGROUND
Laparoscopic appendectomy (LA) has been popular for decades because of shorter hospitalization and return to routine activity. However, complications (e.g., surgical site infection [SSI] and intra-abdominal abscess [IAA]) relative to open appendectomy (OA) are still debated. We therefore conducted an umbrella review to systematically appraise meta-analyses (MAs) comparing SSI and IAA between LA and OA.

METHODS
Meta-analyses that included only randomized controlled trials were identified from MEDLINE and Scopus databases from inception until July 2018. Their findings were described, the number of overlapping studies was assessed using corrected covered area, and excess significant tests were also assessed. Finally, effect sizes of SSI and IAA were repooled.

RESULTS
Ten MAs were eligible; SSI was reported in all MAs and IAA in 8 MAs. Surgical site infection rate was 48% to 70% lower in LA than OA, but conversely, IAA rate was 1.34 to 2.20 higher in LA than OA. Overlapping included studies for SSI and IAA were 61% and 54%, respectively, indicating that less information was added across MAs. However, there was no evidence of bias from excess significant tests when pooling SSI or IAA estimates. The risk ratios (95% confidence interval) comparing LA versus OA were repooled in adults and children yielding risk ratios of 0.56 (0.47–0.67) and 0.40 (0.25–0.65) for SSI, and 1.20 (0.88–1.63) and 1.05 (0.61–1.80) for IAA.

CONCLUSION
Evidence from this umbrella review indicates that LA carries a significantly lower risk of SSI but likely a higher risk of IAA than OA.

LEVEL OF EVIDENCE
Systematic review/meta-analysis, level I.
Structural transitions in Orb2 prion-like domain relevant for functional aggregation in memory consolidation
Authors: Oroz Javier , Félix Sara S. , Cabrita Eurico J. , Laurents Douglas V. 
Published: July 2020

AbstractThe recent structural elucidation ofex vivo DrosophilaOrb2 fibrils revealed a novel amyloid formed by interdigitated Gln and His residue side chains belonging to the prion-like domain. However, atomic-level details on the conformational transitions associated with memory consolidation remain unknown. Here, we have characterized the nascent conformation and dynamics of the prion-like domain (PLD) of Orb2A using a nonconventional liquid-state NMR spectroscopy strategy based on13C detection to afford an essentially complete set of13Cα,13Cβ,1Hα and backbone13CO and15N assignments. At pH 4, where His residues are protonated, the PLD is disordered and flexible, except for a partially populated α-helix spanning residues 55-60. At pH 7, in contrast, His residues are predominantly neutral and the Q/H segments adopt minor populations of helical structure, show decreased mobility and start to self-associate. At pH 7, the His residues also bind Zn++, which promotes further association. These findings represent a remarkable case of structural plasticity, based on which an updated model for Orb2A functional amyloidogenesis is advanced.Highlights· The Orb2 prion like domain that forms the structures related to memory consolidation is studied by solution NMR.· The amyloidogenic Q/H-rich stretch is disordered and flexible at low pH.· Residues 55-60 form a partly populated α-helix at pH 4.· At pH 7, the Q/H-rich segment also adopts a low population of α-helix and rigidifies.· Zn++binding induces associative changes in the Orb2 prion-like domain.
Bootstrap aggregating improves the generalizability of Connectome Predictive Modelling
Authors: O’Connor David , Lake Evelyn M.R. , Scheinost Dustin , Constable R. Todd 
Published: July 2020

AbstractIt is a long-standing goal of neuroimaging to produce reliable generalized models of brain behavior relationships. More recently data driven predicative models have become popular. Overfitting is a common problem with statistical models, which impedes model generalization. Cross validation (CV) is often used to give more balanced estimates of performance. However, CV does not provide guidance on how best to apply the models generated out-of-sample. As a solution, this study proposes an ensemble learning method, in this case bootstrap aggregating, or bagging, encompassing both model parameter estimation and feature selection. Here we investigate the use of bagging when generating predictive models of fluid intelligence (fIQ) using functional connectivity (FC). We take advantage of two large openly available datasets, the Human Connectome Project (HCP), and the Philadelphia Neurodevelopmental Cohort (PNC). We generate bagged and non-bagged models of fIQ in the HCP. Over various test-train splits, these models are evaluated in sample, on left out HCP data, and out-of-sample, on PNC data. We find that in sample, a non-bagged model performs best, however out-of-sample the bagged models perform best. We also find that feature selection can vary substantially within-sample. A more considered approach to feature selection, alongside data driven predictive modeling, is needed to improve cross sample performance of FC based brain behavior models.
CXCR4 inhibition in human pancreatic and colorectal cancers induces an integrated immune response
Authors: Biasci Daniele , Smoragiewicz Martin , Connell Claire M. , Wang Zhikai , Gao Ya , Thaventhiran James , Basu Bristi , Magiera Lukasz , Johnson Isaac T. , Bax Lisa , Gopinathan Aarthi , Isherwood Christopher , Gallagher Ferdia , Pawula Maria , Hudecova Irena , Gale Davina , Rosenfeld Nitzan , Barmpounakis Petros , Popa Elizabeta Cristina , Brais Rebecca , Godfrey Edmund , Mir Fraz , Richards Frances , Fearon Douglas T. , Janowitz Tobias , Jodrell Duncan 
Published: July 2020

AbstractInhibition of the chemokine receptor CXCR4 in combination with blockade of the PD-1/PD-L1 T cell checkpoint induces T cell infiltration and anti-cancer responses in murine and human pancreatic cancer. Here we elucidate the mechanism by which CXCR4 inhibition effects the tumor immune microenvironment. In human immune cell-based chemotaxis assays, we find that CXCL12-stimulated CXCR4 inhibits the directed migration mediated by CXCR1, CXCR3, CXCR5, CXCR6, and CCR2, respectively, chemokine receptors expressed by all the immune cell types that participate in an integrated immune responses. Inhibiting CXCR4 in an experimental cancer medicine study by one-week continuous infusion of the small molecule inhibitor, AMD3100 (plerixafor), induces an integrated immune response that is detected by transcriptional analysis of paired biopsies of metastases from patients with microsatellite stable colorectal and pancreatic cancer. This integrated immune response occurs in three other examples of immune-mediated damage to non-infected tissues: rejecting renal allografts, melanomas clinically responding to anti-PD1 antibody therapy, and microsatellite instable colorectal cancers. Thus, signaling by CXCR4 causes immune suppression in human PDA and CRC by impairing the function of the chemokine receptors that mediate the intratumoral accumulation of immune cells.Statement of significanceContinuous infusion of AMD3100, an antagonist of the chemokine receptor, CXCR4, induces an integrated anti-cancer immune response in metastases of patients with microsatellite stable pancreatic and colorectal cancer that is predictive of response to T cell checkpoint inhibition.
The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19
Authors: Consiglio Camila Rosat , Cotugno Nicola , Sardh Fabian , Pou Christian , Amodio Donato , Rodriguez Lucie , Tan Ziyang , Zicari Sonia , Ruggiero Alessandra , Pascucci Giuseppe Rubens , Santilli Veronica , Campbell Tessa , Bryceson Yenan , Eriksson Daniel , Wang Jun , Marchesi Alessandra , Lakshmikanth Tadepally , Campana Andrea , Villani Alberto , Rossi Paolo ,   the CACTUS study team, Landegren Nils , Palma Paolo , Brodin Petter 
Published: July 2020

SUMMARYSARS-CoV-2 infection is typically very mild and often asymptomatic in children. A complication is the rare Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever, organ dysfunction and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2 and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T-cell subsets, IL-17A and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests multiple autoantibodies that could be involved in the pathogenesis of MIS-C.HIGHLIGHTSHyperinflammation in MIS-C differs from that of acute COVID-19T-cell subsets discriminate Kawasaki disease patients from MIS-CIL-17A drives Kawasaki, but not MIS-C hyperinflammation.Global autoantibodies profiling indicate possibly pathogenic autoantibodies
Comorbidity of self-harm and disordered eating in young people: Evidence from a UK population-based cohort
Authors: Warne Naomi , Heron Jon , Mars Becky , Moran Paul , Stewart Anne , Munafò Marcus , Biddle Lucy , Skinner Andy , Gunnell David , Bould Helen 
Published: July 2020

AbstractSelf-harm and eating disorders are often comorbid in clinical samples but their co-occurrence in the general population is unclear. We assessed the co-occurrence of self-harm and disordered eating behaviours at age 16 and 24 years in 3384 females and 2326 males from a UK population-based cohort. There was substantial overlap at both time points: almost two-thirds of 16-year-old females, and two-in-five 24-year old males who self-harmed also reported disordered eating. Among young people, self-harm may signal the occurrence of disordered eating and vice versa. It is important to screen for both sets of difficulties to provide appropriate treatment.
Determinants of disease prevalence and antibiotic consumption for children under five in Nepal: analysis and modelling of Demographic Health Survey data from 2006 to 2016
Authors: Zheng Charlotte , Karkey Abilasha , Wang Tianyi , van Doorn H. Rogier , Lewycka Sonia 
Published: July 2020

AbstractObjectivesOur aims were to examine the geographic, socio-economic and behavioural factors associated with disease and antibiotic consumption in Nepal between 2006 and 2016 and to explore healthcare seeking patterns and the source of antibiotics.MethodsCross-sectional data from children under five in households in Nepal was extracted from the 2006, 2011 and 2016 Demographic Health Surveys (DHS). Univariate and multivariate analyses were carried out to assess the association of disease prevalence and antibiotic use with age, sex, ecological zone, urban/rural location, wealth index, maternal smoking, use of clean fuel, sanitation, nutrition, access to healthcare and vaccinations.ResultsPrevalence of fever, acute respiratory infection (ARI) and diarrhoea decreased between 2006 and 2016, while the proportion using antibiotics increased. Wealth, use of clean fuel, improved toilet sanitation, nutrition and access to healthcare were associated with reduced rates of disease. Those in the highest wealth index use less antibiotics and antibiotic consumption in rural areas surpassed urban regions over time. Health-seeking from the private sector has overtaken government facilities since 2006 with antibiotics mainly originating from pharmacies and private hospitals. Adherence to WHO recommended antibiotics has reduced over time.ConclusionsWith rising wealth, there has been a decline in disease prevalence but an increase in antibiotic use with more access to unregulated sources. Understanding antibiotic use and identifying associated behavioural and socio-economic factors may help to inform interventions to reduce inappropriate antibiotic use whilst ensuring access to those who need them.
The molecular architecture of CenH3-deficient holocentromeres in Lepidoptera is dependent on transcriptional and chromatin dynamics
Authors: Senaratne Aruni P. , Muller Héloïse , Fryer Kelsey A. , Drinnenberg Ines A. 
Published: July 2020

AbstractDespite their essentiality for chromosome segregation, centromeres are diverse among eukaryotes and embody two main configurations: mono- and holocentromeres, referring respectively to a localized or unrestricted distribution of centromeric activity. Previous studies revealed that holocentricity in many insects coincides with the loss of the otherwise essential centromere component CenH3 (CENP-A), suggesting a molecular link between the two events. In this study, we leveraged recently-identified centromere components to map and characterize the centromeres of Bombyx mori. This uncovered a robust correlation between centromere profiles and regions of low chromatin dynamics. Transcriptional perturbation experiments showed that low chromatin activity is crucial for centromere formation inB. mori. Our study points to a novel mechanism of centromere formation that occurs in a manner recessive to the chromosome-wide chromatin landscape. Based on similar profiles in additional Lepidoptera, we propose an evolutionarily conserved mechanism that underlies the establishment of holocentromeres through loss of centromere specificity.