bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deployment of a Clinical Pathway to Improve Postcardiac Arrest Care: A Before-After Study*
Authors: Fowler Jessica C. , Wolfe Heather A. , Xiao Rui , Kumar Sitara P. , Whitney Jane E. , Hutchins Larissa , Sutton Robert M. , Nadkarni Vinay M. , Berg Robert A. , Topjian Alexis A. 
Published: June 2020

Objectives:
Postcardiac arrest care bundles following adult cardiac arrest are associated with improved survival to discharge. We aimed to evaluate whether a clinical pathway and computerized order entry were associated with improved pediatric postcardiac arrest care and discharge outcomes.

Design:
Single-center retrospective before-after study.

Setting:
Academic PICU.

Patients:
Patients who suffered an in- or out-of-hospital cardiac arrest from January 2008 to December 2015 cared for in the PICU within 12 hours of sustained return of circulation.

Intervention:
Deployment of a postcardiac arrest clinical pathway and computerized order entry system.

Measurements and Main Results:
There were 380 patients included—163 in the pre-pathway period and 217 in the post-pathway period. Primary outcome was percent adherence to pathway clinical goals at 0–6 and 6–24 hours post-return of circulation and to diagnostics (continuous electroencephalogram monitoring, head CT for out-of-hospital cardiac arrests, echocardiogram). Secondary outcomes included survival to hospital discharge and survival with favorable neurologic outcome (Pediatric Cerebral Performance Category of 1–3 or no change from baseline). The pre-pathway and post-pathway groups differed in their baseline Pediatric Cerebral Performance Category scores and the following causes of arrest: airway obstruction, arrhythmias, and electrolyte abnormalities. Pathway adherence was not significantly different between the pre-pathway and post-pathway groups, with the exception of higher rates of continuous electroencephalogram monitoring (45% vs 64%; p < 0.001). There was no difference in survival to hospital discharge between the two groups (56% vs 67%; adjusted odds ratio, 1.68; 95% CI, 0.95–2.84; p = 0.05). Survival to discharge was higher in the post-pathway group for the in-hospital cardiac arrest cohort (55% vs 76%; adjusted odds ratio, 3.06; 95% CI, 1.44–6.51; p < 0.01). There was no difference in favorable neurologic outcome between all patients (adjusted odds ratio, 1.21; 95% CI, 0.72–2.04) or among survivors (adjusted odds ratio, 0.72; 95% CI, 0.27–1.43).

Conclusions:
After controlling for known potential confounders, the creation and deployment of a postcardiac arrest care pathway and computerized order entry set were not associated with improvement in pathway adherence or overall outcomes, but was associated with increased survival to hospital discharge for children with in-hospital cardiac arrests.
Hospital-Acquired Infection in Pediatric Subjects With Congenital Heart Disease Postcardiotomy Supported on Extracorporeal Membrane Oxygenation*
Authors: Herrup Elizabeth A. , Yuerek Mahsun , Griffis Heather M. , Connelly James T. , Thiagarajan Ravi , Rycus Peter , Blinder Joshua J. 
Published: June 2020

Objective:
To determine prevalence of and risk factors for infection in pediatric subjects with congenital heart disease status postcardiotomy supported on extracorporeal membrane oxygenation, as well as outcomes of these subjects.

Design:
Retrospective cohort from the Extracorporeal Life Support Organization.

Setting:
U.S. and international medical centers providing care to children with congenital heart disease status postcardiotomy.

Patients:
Critically ill pediatric subjects less than 8 years old admitted to medical centers between January 1, 2013, and December 31, 2015, who underwent cardiac surgery for congenital heart disease and required extracorporeal membrane oxygenation support within the first 14 postoperative days. Subjects were excluded if they underwent orthotopic heart transplantation, required preoperative extracorporeal membrane oxygenation, and had more than one postoperative extracorporeal membrane oxygenation run.

Interventions:
None.

Measurements and Main Results:
A total of 1,314 extracorporeal membrane oxygenation subject encounters in the Extracorporeal Life Support Organization registry met inclusion criteria. Neonates comprised 53% (n = 696) of the cohort, whereas infants made up 33% (n = 435). Of the 994 subjects with Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery categorizable surgery, 33% (n = 325) were in Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category 4 and 23% (n = 231) in Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category 5. While on extracorporeal membrane oxygenation, 229 subjects (17%) acquired one or more extracorporeal membrane oxygenation–related infections, which represents an occurrence rate of 67 infections per 1,000 extracorporeal membrane oxygenation days. Gram-negative (62%) and Gram-positive (42%) infections occurred most commonly. Forty percent had positive blood cultures. Infants and children were at higher infection risk compared with neonatal subjects; subjects undergoing less complex surgery had higher infection rates. Unadjusted survival to hospital discharge was lower in infected subjects compared with noninfected subjects (43% vs 51%; p = 0.01). After adjusting for confounders via propensity matching, we identified no significant mortality difference between infected and noninfected subjects.

Conclusions:
Neonatal and pediatric subjects in this study have a high rate of acquired infection. Infants and children were at higher infection risk compared with neonatal subjects. There was not, however, a significant association between extracorporeal membrane oxygenation–related infection and survival to hospital discharge after propensity matching.
Accuracy of Bedside Ultrasound Femoral Vein Diameter Measurement by PICU Providers*
Authors: Good Ryan J. , Levin Melanie , Feder Susan , Loi Michele M. , Kim John S. , Branchford Brian R. , Czaja Angela S. , Carpenter Todd C. 
Published: June 2020

Objectives:
Perform a needs assessment by evaluating accuracy of PICU provider bedside ultrasound measurement of femoral vein diameter prior to utilization of the catheter-to-vein ratio for central venous catheter size selection.

Design:
Prospective observational cohort study.

Setting:
PICU within a quaternary care children’s hospital.

Patients:
PICU patients greater than 30 days and less than 6 years without a femoral central venous catheter.

Interventions:
None.

Measurements and Main Results:
Gold-standard femoral vein diameter measurements were made by a radiologist, sonographer, or bedside ultrasound expert. PICU providers then repeated the femoral vein diameter measurements, and results were compared by Bland-Altman analysis with a priori accuracy goal of limits of agreement ± 15%. Among recruited patients (n = 27), the median age was 1.1 years (interquartile range 0.5–2.3 yr), weight was 9.0 kg (interquartile range 7.0–11.5 kg), and reference femoral vein diameter was 0.36 cm (interquartile range 0.28–0.45 cm). Providers performed 148 femoral vein diameter measurements and did not meet goal accuracy when compared with the reference measurement with a bias of 4% (95% of limits of agreement –62% to 70%). A majority of patients would have a catheter-to-vein ratio greater than 0.5 using either age-based central venous catheter size selection criterion (14/27) or the provider bedside ultrasound femoral vein diameter measurement (18/27).

Conclusions:
PICU provider measurement of femoral vein diameter by bedside ultrasound is inaccurate when compared with expert reference measurement. Central venous catheter size selection based on age or PICU provider femoral vein diameter measurement can lead to a catheter-to-vein ratio greater than 0.5 and potentially increase the risk of catheter-associated venous thromboembolism. Structured bedside ultrasound training with assessment of accuracy is necessary prior to implementation of venous thromboembolism reduction efforts based on catheter-to-vein ratio recommendations.
Long-Axis In-Plane Approach Versus Short-Axis Out-of-Plane Approach for Ultrasound-Guided Central Venous Catheterization in Pediatric Patients: A Randomized Controlled Trial*
Authors: Takeshita Jun , Tachibana Kazuya , Nakajima Yasufumi , Nagai Gaku , Fujiwara Ai , Hamaba Hirofumi , Matsuura Hideki , Yamashita Tomonori , Shime Nobuaki 
Published: June 2020

Objectives:
The aim of this study was to compare the occurrence of posterior wall puncture between the long-axis in-plane and the short-axis out-of-plane approaches in a randomized controlled trial of pediatric patients who underwent cardiovascular surgery under general anesthesia.

Design:
Prospective randomized controlled trial.

Setting:
Operating room of Osaka Women’s and Children’s Hospital.

Patients:
Pediatric patients less than 5 years old who underwent cardiovascular surgery.

Interventions:
Ultrasound-guided central venous catheterization using the long-axis in-plane approach and short-axis out-of-plane approach.

Measurements and Main Results:
The occurrence of posterior wall puncture was compared between the long-axis in-plane and short-axis out-of-plane approaches for ultrasound-guided central venous catheterization. Patients were randomly allocated to a long-axis group or a short-axis group and underwent ultrasound-guided central venous catheterization in the internal jugular vein using either the long-axis in-plane approach (long-axis group) or the short-axis out-of-plane approach (short-axis group). After exclusion, 97 patients were allocated to the long-axis (n = 49) or short-axis (n = 48) groups. Posterior wall puncture rates were 8.2% (4/49) and 39.6% (19/48) in the long-axis and short-axis groups, respectively (relative risk, 0.21; 95% CI, 0.076–0.56; p = 0.0003). First attempt success rates were 67.3% (33/49) and 64.6% (31/48) in the long-axis and short-axis groups, respectively (relative risk, 1.04; 95% CI, 0.78–1.39; p = 0.77). Overall success rates within 20 minutes were 93.9% (46/49) and 93.8% (45/48) in the long-axis and short-axis groups, respectively (relative risk, 0.99; 95% CI, 0.90–1.11; p = 0.98).

Conclusions:
The long-axis in-plane approach for ultrasound-guided central venous catheterization is a useful technique for avoiding posterior wall puncture in pediatric patients, compared with the short-axis out-of-plane approach.
The SERCA residue Glu340 mediates inter-domain communication that guides Ca2+transport
Authors: Geurts Maxwell M. G. , Clausen Johannes D. , Arnou Bertrand , Montigny Cedric , Lenoir Guillaume , Corey Robin A. , Jaxel Christine , Møller Jesper V. , Nissen Poul , Andersen Jens Peter , le Maire Marc , Bublitz Maike 
Published: June 2020

AbstractThe sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) is a P-type ATPase that transports Ca2+from the cytosol into the SR/ER lumen, driven by ATP. This primary transport activity depends on tight coupling between movements of the transmembrane helices forming the two Ca2+binding sites and of the cytosolic headpiece mediating ATP hydrolysis. We have addressed the molecular basis for this intramolecular communication by analyzing the structure and functional properties of the SERCA mutant E340A. The mutated Glu340 residue is strictly conserved among the P-type ATPase family of membrane transporters and is located at a seemingly strategic position at the interface between the phosphorylation domain and the cytosolic ends of five out of SERCA’s ten transmembrane helices. The mutant displays a marked slowing of the Ca2+-binding kinetics, and its crystal structure in the presence of Ca2+and ATP analogue reveals a rotated headpiece, altered connectivity between the cytosolic domains and altered hydrogen bonding pattern around residue 340. Supported by molecular dynamics simulations, we conclude that the E340A mutation causes a stabilization of the Ca2+sites in a more occluded state, hence displaying slowed dynamics. This finding underpins a crucial role of Glu340 in inter-domain communication between the headpiece and the Ca2+-binding transmembrane region.
Only two out of five articles by New Zealand researchers are free-to-access: a multiple API study of access, citations, cost of Article Processing Charges (APC), and the potential to increase the proportion of open access
Authors: White Richard Kenneth Alistair , Angelo Anton , Fitchett Deborah Jane , Fraser Moira , Hayes Luqman , Howie Jess , Richardson Emma , White Bruce Duncan 
Published: June 2020

AbstractWe studied journal articles published by researchers at all eight of New Zealand universities in 2017 to determine how many were freely accessible on the web. We wrote software code to harvest data from multiple sources, code that we now share to enable others to reproduce our work on their own sample set. In May 2019, we ran our code to determine which of the 2017 articles were open at that time and by what method; where those articles would have incurred an Article Processing Charge (APC) we calculated the cost if those charges had been paid. Where articles were not freely available we determined whether the policies of publishers in each case would have allowed deposit in a non-commercial repository (Green open access). We also examined citation rates for different types of access. We found that, of our 2017 sample set, about two out of every five articles were freely accessible without payment or subscription (41%). Where research was explicitly said to be funded by New Zealand’s major research funding agencies, the proportion was slightly higher at 45%. Where open articles would have incurred an APC we estimated an average cost per article of USD1,682 (for publications where all articles require an APC, that is, Gold open access) and USD2,558 (where APC payment is optional, Hybrid open access) at a total estimated cost of USD1.45m. Of the paid options, Gold is by far more common for New Zealand researchers (82% Gold, 18% Hybrid). In terms of citations, our analysis aligned with previous studies that suggest a correlation between publications being freely accessible and, on balance, slightly higher rates of citation. This is not seen across all types of open access, however, with Diamond OA achieving the lowest rates. Where articles were not freely accessible we found that a very large majority of them (88% or 3089 publications) could have been legally deposited in an institutional repository. Similarly, only in a very small number of cases had a version deposited in the repository of a New Zealand university made the difference between the publication being freely accessible or not (125 publications). Given that most New Zealand researchers support research being open, there is clearly a large gap between belief and practice in New Zealand’s research ecosystem.
Integration of genetic, transcriptomic, and clinical data provides insight into 16p11.2 and 22q11.2 CNV genes
Authors: Vysotskiy Mikhail , Zhong Xue , Miller-Fleming Tyne W. , Zhou Dan ,   Autism Working Group of the Psychiatric Genomics Consortium,   Bipolar Disorder Working Group of the Psychiatric Genomics Consortium,   Schizophrenia Working Group of the Psychiatric Genomics Consortium, Cox Nancy J. , Weiss Lauren A 
Published: June 2020

ABSTRACTDeletions and duplications of the multigenic 16p11.2 and 22q11.2 copy number variants (CNVs) are associated with brain-related disorders including schizophrenia, intellectual disability, obesity, bipolar disorder, and autism spectrum disorder (ASD). The contribution of individual CNV genes to each of these phenotypes is unknown, as is the contribution of CNV genes to subtler health impacts. Hypothesizing that DNA copy number acts via RNA expression, we attempted a novelin silicofine-mapping approach in non-carriers using both GWAS and biobank data. We first asked whether expression level of a CNV gene impacts risk for a known brain-related phenotype(s). Using transcriptomic imputation, we tested for association within GWAS for schizophrenia, IQ, BMI, bipolar disorder, and ASD. We found individual genes in 16p11.2 associated with schizophrenia, BMI, and IQ (SPN), using conditional analysis to identifyINO80Eas the driver of schizophrenia, andSPNandINO80Eas drivers of BMI. Second, we used a biobank containing electronic health data to compare the medical phenome of CNV carriers to controls within 700,000 individuals to investigate a spectrum of health effects, identifying novel and previously observed traits. Third, we used genotypes for over 48,000 biobank individuals to perform phenome-wide association studies between imputed expressions of 16p11.2 and 22q11.2 genes and over 1,500 health traits, finding seventeen significant gene-trait pairs, including psychosis (NPIPB11, SLX1B) and mood disorders (SCARF2), and overall enrichment of mental traits. Our results demonstrate how integration of genetic and clinical data aids in understanding CNV gene function, and implicate pleiotropy and multigenicity in CNV biology.
N-glycosylation network construction and analysis to modify glycans on the spike S glycoprotein of SARS-CoV-2
Authors: Krishnan Sridevi , Krishnan Giri P 
Published: June 2020

AbstractBackgroundThe spike S-protein of SARS-CoV-2 is N-glycosylated. The N-glycan structure and composition of this glycoprotein influence how the virus interacts with host cells.ObjectiveTo identify a putative N-glycan biosynthesis pathway of SARS-CoV-2 (HEK293 cell recombinant) from previously published mass spectrometric studies, and to identify what effect blocking some enzymes has on the overall glycoprotein profile. Finally, our goal was to provide the biosynthesis network, and glycans in easy-to-use format for further glycoinformatics work.MethodsWe reconstructed the glycosylation network based on previously published empirical data using GNAT, a glycosylation network analysis tool. Our compilation of the network tool had 23 glycosyltransferase and glucosidase enzymes, and could infer the pathway of glycosylation machinery based on glycans identified in the virus spike protein. Once the glycan biosynthesis pathway was generated, we simulated the effect of blocking specific enzymes - Mannosidase-II and alpha-1,6-fucosyltransferase to see how they would affect the biosynthesis network.ResultsOf the 23 enzymes, a total of 12 were involved in glycosylation of SARS-CoV-2 - Man-Ia, MGAT1, MGAT2, MGAT4, MGAT5, B4GalT, B4GalT, Man II, SiaT, ST3GalI, ST3GalVI and FucT8. Blocking enzymes resulted in a substantially modified glycan profile of the protein.ConclusionsA network analysis of N-glycan biosynthesis of SARS-CoV-2 spike protein shows an elaborate enzymatic pathway with several intermediate glycans, along with the ones identified by mass spectrometric studies. Variations in the final N-glycan profile of the virus, given its site-specific microheterogeneity, could be a factor in the host response to the infection and response to antibodies. Here we provide all the resources generated - the glycans derived from mass spectrometry and intermediate glycans in glycoCT xml format, and the biosynthesis network for future drug and vaccine development work.
A classification-based approach to estimate the number of resting fMRI dynamic functional connectivity states
Authors: Saha Debbrata K. , Damaraju Eswar , Rashid Barnaly , Abrol Anees , Plis Sergey M. , Calhoun Vince D. 
Published: June 2020

AbstractRecent work has focused on the study of dynamic (vs static) brain connectivity in resting fMRI data. In this work, we focus on temporal correlation between time courses extracted from coherent networks or components called functional network connectivity (FNC). Dynamic functional network connectivity (dFNC) is most commonly estimated using a sliding window-based approach to capture short periods of FNC change. These data are then clustered to estimate transient connectivity patterns or states. Determining the number of states is a challenging problem. The elbow criterion is a widely used approach to determine the optimal number of states. In our work, we present an alternative approach that evaluates classification (e.g. healthy controls versus patients) as a measure to select the optimal number of states (clusters). We apply different classification strategies to perform classification between healthy controls (HC) and patients with schizophrenia (SZ) for different numbers of states (i.e. varying the model order in the clustering algorithm). We compute cross-validated accuracy for different model orders to evaluate the classification performance. Our results are consistent with our earlier work which shows that overall accuracy improves when dynamic connectivity measures are used separately or in combination with static connectivity measures. Results also show that the optimal model order for classification is different from that using the standard k-means model selection method and that such optimization improves resulting in cross-validated accuracy. The optimal model order obtained from the proposed approach also gives significantly improved classification performance over the traditional model selection method. In sum, the observed results suggest that if one’s goal is to perform classification, using the proposed approach as a criterion for selecting the optimal number of states in dynamic connectivity analysis leads to improved accuracy in hold-out data.
CoronaHiT: High throughput sequencing of SARS-CoV-2 genomes
Authors: Baker Dave J. , Aydin Alp , Le-Viet Thanh , Kay Gemma L. , Rudder Steven , Martins Leonardo de Oliveira , Tedim Ana P. , Kolyva Anastasia , Diaz Maria , Alikhan Nabil-Fareed , Meadows Lizzie , Bell Andrew , Gutierrez Ana Victoria , Trotter Alexander J. , Thomson Nicholas M. , Gilroy Rachel , Griffith Luke , Adriaenssens Evelien M. , Stanley Rachael , Charles Ian G. , Elumogo Ngozi , Wain John , Prakash Reenesh , Meader Emma , Mather Alison E. , Webber Mark A. , Dervisevic Samir , Page Andrew J. , O’Grady Justin 
Published: June 2020

AbstractThe COVID-19 pandemic has spread to almost every country in the world since it started in China in late 2019. Controlling the pandemic requires a multifaceted approach including whole genome sequencing to support public health interventions at local and national levels. One of the most widely used methods for sequencing is the ARTIC protocol, a tiling PCR approach followed by Oxford Nanopore sequencing (ONT) of up to 96 samples at a time. There is a need, however, for a flexible, platform agnostic, method that can provide multiple throughput options depending on changing requirements as the pandemic peaks and troughs. Here we present CoronaHiT, a method capable of multiplexing up to 96 small genomes on a single MinION flowcell or >384 genomes on Illumina NextSeq, using transposase mediated addition of adapters and PCR based addition of barcodes to ARTIC PCR products. We demonstrate the method by sequencing 95 and 59 SARS-CoV-2 genomes for routine and rapid outbreak response runs, respectively, on Nanopore and Illumina platforms and compare to the standard ARTIC LoCost nanopore method. Of the 154 samples sequenced using the three approaches, genomes with ≥ 90% coverage (GISAID criteria) were generated for 64.3% of samples for ARTIC LoCost, 71.4% for CoronaHiT-ONT, and 76.6% for CoronaHiT-Illumina and have almost identical clustering on a maximum likelihood tree. In conclusion, we demonstrate that CoronaHiT can multiplex up to 96 SARS-CoV-2 genomes per MinION flowcell and that Illumina sequencing can be performed on the same libraries, which will allow significantly higher throughput. CoronaHiT provides increased coverage for higher Ct samples, thereby increasing the number of high quality genomes that pass the GISAID QC threshold. This protocol will aid the rapid expansion of SARS-CoV-2 genome sequencing globally, to help control the pandemic.