bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two-handed jaw thrust decreases postoperative sore throat in patients undergoing double-lumen endobronchial intubation
Authors: Park Jeong J. , Huh Hyub , Yoon Seung Z. , Lim Hye-Ja , Go Doo Y. , Cho Jang E. , Lee Jiwon , Park Jihoon , Kim Hyun-Chang 
Published: January 2020

BACKGROUND
Tracheal intubation using a double-lumen endobronchial tube (DLT) causes postoperative sore throat.

OBJECTIVE
To determine the effect of two-handed jaw thrust on postoperative sore throat in patients requiring insertion of a DLT.

DESIGN
A randomised study.

SETTING
A tertiary teaching hospital from December 2017 to May 2018.

PATIENTS
One-hundred and six patients undergoing one-lung anaesthesia.

INTERVENTIONS
Patients were allocated to one of two groups (n=53 each). In the jaw thrust group, the two-handed jaw thrust manoeuvre was applied at intubation and advancement of the DLT. In the control group, conventional intubation with a sham jaw thrust was performed.

MAIN OUTCOME MEASURES
Incidence of sore throat at 1, 6 and 24 h postoperatively.

RESULTS
The incidence of sore throat at 6 h postoperatively was higher in the control group than in the jaw thrust group [31 (59%) vs. 14 (26%), risk ratio (95% confidence interval) 0.45 (0.27 to 0.75), P < 0.01]. The overall incidence of sore throat was higher in the control group than in the jaw thrust group [35 (66%) vs. 18 (34%), risk ratio (95% confidence interval) 0.51 (0.34 to 0.78), P < 0.01].

CONCLUSION
The jaw thrust manoeuvre can reduce the incidence of sore throat in patients undergoing DLT insertion for one-lung ventilation.

TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT03331809.
Comparison of first trimester dating methods for gestational age estimation and their implication on preterm birth classification in a North Indian cohort
Authors: Vijayram Ramya , Damaraju Nikhita , Xavier Ashley , Desiraju Bapu Koundinya , Thiruvengadam Ramachandran , Misra Sumit , Chopra Shilpa , Khurana Ashok , Wadhwa Nitya ,   GARBH-Ini Study Group, Rengaswamy Raghunathan , Sinha Himanshu , Bhatnagar Shinjini 
Published: January 2020

AbstractBackgroundDifferent formulae have been developed globally to estimate gestational age (GA) by ultrasonography in the first trimester of pregnancy. In this study, we develop an Indian population-specific dating formula and compare its performance with published formulae. Finally, we evaluate the implications of the choice of dating method on preterm birth (PTB) rate. This study’s data was from GARBH-Ini, an ongoing pregnancy cohort of North Indian women to study PTB.MethodsComparisons between ultrasonography-Hadlock and last menstrual period (LMP) based dating methods were made by studying the distribution of their differences by Bland-Altman analysis. Using data-driven approaches, we removed data outliers more efficiently than by applying clinical parameters. We applied advanced machine learning algorithms to identify relevant features for GA estimation and developed an Indian population-specific formula (Garbhini-GA1) for the first trimester. PTB rates of Garbhini-GA1 and other formulae were compared by estimating sensitivity and accuracy.ResultsPerformance of Garbhini-GA1 formula, a non-linear function of crown-rump length (CRL), was equivalent to published formulae for estimation of first trimester GA (LoA, - 0.46,0.96 weeks). We found that CRL was the most crucial parameter in estimating GA and no other clinical or socioeconomic covariates contributed to GA estimation. The estimated PTB rate across all the formulae including LMP ranged 11.27 – 16.50% with Garbhini-GA1 estimating the least rate with highest sensitivity and accuracy. While the LMP-based method overestimated GA by three days compared to USG-Hadlock formula; at an individual level, these methods had less than 50% agreement in the classification of PTB.ConclusionsAn accurate estimation of GA is crucial for the management of PTB. Garbhini-GA1, the first such formula developed in an Indian setting, estimates PTB rates with higher accuracy, especially when compared to commonly used Hadlock formula. Our results reinforce the need to develop population-specific gestational age formulae.
Serum metabolite profiles are associated with the presence of advanced liver fibrosis in Chinese patients with chronic hepatitis B viral infection
Authors: Xie Guoxiang , Wang Xiaoning , Wei Runmin , Wang Jingye , Zhao Aihua , Chen Tianlu , Wang Yixing , Zhang Hua , Xiao Zhun , Liu Xinzhu , Deng Youping , Wong Linda , Panee Jun , Rajani Cynthia , Ni Yan , Kwee Sandi , Bian Hua , Gao Xin , Liu Ping , Jia Wei 
Published: January 2020

ABSTRACTBackground & AimsAccurate and noninvasive diagnosis and staging of liver fibrosis is essential for effective clinical management of chronic liver disease (CLD). We aimed to identify serum metabolite markers that reliably predict the stage of fibrosis in CLD patients.MethodsWe quantitatively profiled serum metabolites of participants in 2 independent cohorts. Based on the metabolomics data from Cohort 1 (504 HBV associated liver fibrosis patients and 502 normal controls, NC), we selected a panel of 4 predictive metabolite markers. Consequently, we constructed 3 machine learning models with the 4 metabolite markers using random forest (RF), to differentiate CLD patients from normal controls (NC), to differentiate cirrhosis patients from fibrosis patients, and to differentiate advanced fibrosis from early fibrosis, respectively.ResultsThe panel of 4 metabolite markers consisted of taurocholate, tyrosine, valine, and linoelaidic acid. The RF models of the metabolite panel demonstrated the strongest stratification ability in Cohort 1 to diagnose CLD patients from NC (area under the receiver operating characteristic curve (AUROC) = 0.997 and the precision-recall curve (AUPR) = 0.994), to differentiate fibrosis from cirrhosis (0.941, 0.870), and to stage liver fibrosis (0.918, 0.892). The diagnostic accuracy of the models was further validated in an independent Cohort 2 consisting of 300 CLD patients with chronic HBV infection and 90 NC. The AUCs of the models were consistently higher than APRI, FIB-4 and AST/ALT ratio, with both greater sensitivity and specificity.ConclusionOur study showed that this 4-metabolite panel has potential usefulness in clinical assessments of CLD progression.
The genetic architecture of left ventricular non-compaction reveals both substantial overlap with other cardiomyopathies and a distinct aetiology in a subset of cases
Authors: Mazzarotto Francesco , Hawley Megan H. , Beltrami Matteo , Beekman Leander , de Marvao Antonio , McGurk Kathryn A. , Statton Ben , Boschi Beatrice , Girolami Francesca , Roberts Angharad M. , Lodder Elisabeth M. , Allouba Mona , Romeih Soha , Aguib Yasmine , Baksi A. John , Pantazis Antonis , Prasad Sanjay K. , Cerbai Elisabetta , Yacoub Magdi H. , O’Regan Declan P. , Cook Stuart A. , Ware James S. , Funke Birgit , Olivotto Iacopo , Bezzina Connie R. , Barton Paul J.R. , Walsh Roddy 
Published: January 2020

AbstractBackgroundLeft ventricular non-compaction (LVNC) is a condition characterised by trabeculations in the myocardial wall and is the subject of considerable conjecture as to whether it represents a distinct pathology or a secondary phenotype associated with other cardiac diseases, particularly cardiomyopathies. We sought to investigate the genetic architecture of LVNC by identifying genes and variant classes robustly associated with disease and comparing these to other genetically characterised cardiomyopathies.MethodsWe performed rare variant association analysis using six different LVNC cohorts comprising 840 cases together with 125,748 gnomAD population controls and compared results to similar analyses with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) cases.ResultsWe observed substantial overlap in genes and variant classes enriched in LVNC and DCM/HCM, indicating that in many cases LVNC belongs to a spectrum of more established cardiomyopathies, with non-compaction representing a phenotypic variation in patients with DCM- or HCM-causing variants. In contrast, five variant classes were uniquely enriched in LVNC cases, of which truncating variants inMYH7, ACTN2andPRDM16may represent a distinct LVNC aetiology.MYH7truncating variants are generally considered as non-pathogenic but were detected in 2% of LVNC cases compared to 0.1% of controls, including a cluster of variants around a single splice region. Individuals withMYH7truncating variants identified in the UK Biobank and cohorts of healthy volunteers also displayed significantly greater non-compaction compared to matched controls, with 50% meeting the diagnostic criteria for LVNC. Additionally, structural variants (exon deletions) inRYR2and missense variants in the transmembrane region ofHCN4were enriched in LVNC cases, confirming prior reports regarding the association of these variant classes with combined LVNC and arrhythmia phenotypes.ConclusionsWe demonstrated that genetic association analysis can clarify the relationship between LVNC and established cardiomyopathies, highlighted substantial overlap with DCM/HCM but also identified variant classes associated with distinct LVNC and with joint LVNC/arrhythmia phenotypes. These results underline the complex genetic landscape of LVNC and inform how genetic testing in LVNC cases should be pursued and interpreted.
Optimizing immunization protocols to elicit broadly neutralizing antibodies
Authors: Sprenger Kayla G. , Louveau Joy E. , Chakraborty Arup K. 
Published: January 2020

AbstractNatural infections and vaccination with a pathogen typically stimulates the production of potent antibodies specific for the pathogen through a Darwinian evolutionary process known as affinity maturation. Such antibodies provide protection against reinfection by the same strain of a pathogen. A highly mutable virus, like HIV or influenza, evades recognition by these strain-specific antibodies via the emergence of new mutant strains. A vaccine that elicits antibodies that can bind to many diverse strains of the virus – known as broadly neutralizing antibodies (bnAbs) – could protect against highly mutable pathogens. Despite much work, the mechanisms by which bnAbs emerge remain uncertain. Using a computational model of affinity maturation, we studied a wide variety of vaccination strategies. Our results suggest that an effective strategy to maximize bnAb evolution is through a sequential immunization protocol, wherein each new immunization optimally increases the pressure on the immune system to target conserved antigenic sites, thus conferring breadth. We describe the mechanisms underlying why sequentially driving the immune system increasingly further from equilibrium, in an optimal fashion, is effective. The optimal protocol allows many evolving B cells to become bnAbs via diverse evolutionary paths.Significance StatementThe global health burden could be substantially alleviated by the creation of universal vaccines against highly mutable pathogens like HIV and influenza. Broadly-neutralizing antibodies (bnAbs) are encouraging targets for such vaccines, because they can bind to diverse strains of highly mutable pathogens. BnAbs typically develop only rarely upon natural infection, after the immune system has been exposed to many mutated versions of a pathogen. Thus, sequentially administering multiple different pathogen-like proteins (antigens) is a promising strategy to elicit bnAbs through vaccination. However, it remains unclear how best to design and administer these antigens. We explore this matter using physics-based simulations, and provide new mechanistic insights into antibody evolution that could guide the creation of universal vaccines against highly mutable pathogens.
Executable Simulation Model of the Liver
Authors: König Matthias 
Published: January 2020

AbstractTo address the issue of reproducibility in computational modeling we developed the concept of an executable simulation model (EXSIMO). An EXSIMO combines model, data and code with the execution environment to run the computational analysis in an automated manner using tools from software engineering. Key components are i) models, data and code for the computational analysis; ii) tests for models, data and code; and iii) an automation layer to run tests and execute the analysis. An EXSIMO combines version control, model, data, units, annotations, analysis, reports, execution environment, testing, continuous integration and release. We applied the concept to perform a replication study of a computational analysis of hepatic glucose metabolism in the liver. The corresponding EXSIMO is available fromhttps://github.com/matthiaskoenig/exsimo.
Genome-wide Functional Characterization of Escherichia coli Promoters and Sequence Elements Encoding Their Regulation
Authors: Urtecho Guillaume , Insigne Kimberly D. , Tripp Arielle D. , Brinck Marcia S. , Lubock Nathan B. , Acree Christopher , Kim Hwangbeom , Chan Tracey , Kosuri Sriram 
Published: January 2020

SummaryDespite decades of intense genetic, biochemical, and evolutionary characterizations of bacterial promoters, we lack the ability to identify or predict transcriptional activities of promoters using primary sequence. Even in simple, well-characterized organisms such asE. colithere is little agreement on the number, location, and strength of promoters. We use a genomically-encoded massively parallel reporter assay to perform the first full characterization of autonomous promoter activity across theE. coligenome. We measure promoter activity of >300,000 sequences spanning the entire genome and map 2,228 promoters active in rich media. Surprisingly, 944 of these promoters were found within intragenic sequences and are associated with conciliatory sequence adaptations by both the protein-coding regions and overlapping RNAP binding sites. Furthermore, we perform a scanning mutagenesis of 2,057 promoters to uncover sequence elements regulating promoter activity, revealing 3,317 novel regulatory elements. Finally, we show that despite these large datasets and modern machine learning algorithms, predicting endogenous promoter activity from primary sequence is still challenging.
CRISPR-based bioengineering of the Transferrin Receptor revealed a role for Rab7 in the biosynthetic secretory pathway
Authors: Deffieu Maika S. , Cesonyte Ieva , Delalande François , Boncompain Gaelle , Dorobantu Cristina , Song Eli , Lucansky Vincent , Hirschler Aurélie , Cianferani Sarah , Xu Tao , Perez Franck , Carapito Christine , Gaudin Raphael 
Published: January 2020

AbstractThe regulated secretory trafficking of neosynthesized transmembrane receptors is particularly challenging to investigate as it is under-represented at steady state compared to the abundance of the other trafficking routes. Here, we combined the retention using selective hook (RUSH) system to a CRISPR/Cas9 gene editing approach (eRUSH) to identify molecular players involved in the trafficking of neosynthesized Transferrin Receptor (TfR)en routeto the plasma membrane (PM). TfR-eRUSH monoclonal cells expressing endogenous, ER-retainable and fluorescent TfR were engineered and characterized. Spatiotemporal quantitative proteomics of TfR-eRUSH cells allowed the identification of molecular partners associated with TfR-containing membranes and provided a comprehensive list of potential regulators, co-trafficking cargos, and enriched pathways. Furthermore, we chose to focus our attention on the Rab GTPase family members for their function as vesicle trafficking regulators and performed a Rab-targeted siRNA screen that we correlated to our proteomics data. Unexpectedly, we identified Rab7-harboring vesicles as an intermediate compartment of the Golgi-to-PM transport of the neosynthetic TfR. These vesicles did not exhibit degradative properties and were not associated to Rab6A-harboring vesicles, also involved in Golgi-to-PM transport. However, Rab6A-TfR vesicles delivered TfR directly to the PM, while in contrast, Rab7A was transiently associated to neosynthetic TfR-containing post-Golgi vesicles but dissociated before PM vesicle fusion. Together, our study proposes the eRUSH as a powerful tool to further study the secretory pathway and reveals an unforeseen role for Rab7 in the neosynthetic transport of the TfR, highlighting the diversity of the secretory vesicles’ nature for a given cargo.
Dense cellular segmentation for EM using 2D-3D neural network ensembles
Authors: Guay Matthew D. , Emam Zeyad A.S. , Anderson Adam B. , Aronova Maria A. , Storrie Brian , Pokrovskaya Irina D. , Leapman Richard D. 
Published: January 2020

ABSTRACTCell biologists can now build 3D models from segmentations of electron microscopy (EM) images, but accurate manual segmentation of densely-packed organelles across gigavoxel image volumes is infeasible. Here, we introduce 2D-3D neural network ensembles that produce dense cellular segmentations at scale, with accuracy levels that outperform baseline methods and approach those of human annotators.
Alignment of single-cell RNA-seq samples without over-correction using kernel density matching
Authors: Chen Mengjie , Zhan Qi , Mu Zepeng , Wang Lili , Zheng Zhaohui , Miao Jinlin , Zhu Ping , Li Yang I 
Published: January 2020

AbstractSingle-cell RNA sequencing (scRNA-seq) technology is poised to replace bulk cell RNA sequencing for most biological and medical applications as it allows users to measure gene expression levels in a cell-type-specific manner. However, data produced by scRNA-seq often exhibit batch effects that can be specific to a cell-type, to a sample, or to an experiment, which prevent integration or comparisons across multiple experiments. Here, we presentDmatch, a method that leverages an external expression atlas of human primary cells and kernel density matching to align multiple scRNA-seq experiments for downstream biological analysis.Dmatchfacilitates alignment of scRNA-seq datasets with cell-types that may overlap only partially, and thus allows integration of multiple distinct scRNA-seq experiments to extract biological insights. In simulation,Dmatchcompares favorably to other alignment methods, both in terms of reducing sample-specific clustering, and in terms of avoiding over-correction. When applied to scRNA-seq data collected from clinical samples in a healthy individual and five autoimmune disease patients,Dmatchenabled cell-type-specific differential gene expression comparisons across biopsy sites and disease conditions, and uncovered a shared population of pro-inflammatory monocytes across biopsy sites in RA patients. We further show thatDmatchincreases the number of eQTLs mapped from population scRNA-seq data.Dmatchis fast, scalable, and improves the utility of scRNA-seq for several important applications.Dmatchis freely available online (https://qzhan321.github.io/dmatch/).
Low-Dimensional Spatio-Temporal Dynamics Underlie Cortex-Wide Neural Activity
Authors: MacDowell Camden J. , Buschman Timothy J. 
Published: January 2020

AbstractCognition arises from the dynamic flow of neural activity through the brain. To capture these dynamics, we used mesoscale calcium imaging to record neural activity across the dorsal cortex of awake mice. We found that the large majority of variance in cortex-wide activity (∼75%) could be explained by a limited set of ∼14 ‘motifs’ of neural activity. Each motif captured a unique spatio-temporal pattern of neural activity across the cortex. These motifs generalized across animals and were seen in multiple behavioral environments. Motif expression differed across behavioral states and specific motifs were engaged by sensory processing, suggesting the motifs reflect core cortical computations. Together, our results show that cortex-wide neural activity is highly dynamic, but that these dynamics are restricted to a low-dimensional set of motifs, potentially to allow for efficient control of behavior.
Postglacial migration across a large dispersal barrier outpaces regional expansion from glacial refugia: evidence from two conifers in the Pacific Northwest
Authors: Fernandez MC , Hu FS , Gavin DG , deLafontaine G , Heath KD 
Published: January 2020

AbstractUnderstanding how climate refugia and migration over great distances have facilitated species survival during periods of past climate change is crucial for evaluating contemporary threats to biodiversity. In addition to tracking a changing climate, extant species must face complex, anthropogenically fragmented landscapes. The dominant conifer species in the mesic temperate forests of the Pacific Northwest are split by the arid rain-shadow of the Cascade Range into coastal and interior distributions, with continued debate over the origins of the interior populations. If the Last Glacial Maximum extirpated populations in the interior then postglacial migration across the arid divide would have been necessary to create the current distribution, whereas interior refugial persistence could have locally repopulated the disjunction. These alternative scenarios have significant implications for the postglacial development of the Pacific Northwest mesic forests and the impact of dispersal barriers during periods of climate change. Here we use genotyping-by-sequencing (ddRADseq) and phylogeographical modeling to show that the postglacial expansion of both mountain hemlock and western redcedar consisted largely of long-distance spread inland in the direction of dominant winds, with limited expansion from an interior redcedar refugium. Our results for these two key mesic conifers, along with fossil pollen data, address the longstanding question on the development of the Pacific Northwest mesic forests and contrast with many recent studies emphasizing the role of cryptic refugia in colonizing modern species ranges.Statement of SignificanceUnderstanding whether habitat fragmentation hinders range shifts as species track a changing climate presents a pressing challenge for biologists. Species with disjunct distributions provide a natural laboratory for studying the effects of fragmentation during past periods of climate change. We find that dispersal across a 50-200-km inhospitable barrier characterized the expansion of two conifer species since the last ice age. The importance of migration, and minimal contribution of more local glacial refugia, contrasts with many recent studies emphasizing the role of microrefugia in populating modern species distributions. Our results address a longstanding question on the development of the disjunct mesic conifer forests of the Pacific Northwest and offer new insights into the spatiotemporal patterns of refugial populations and postglacial vegetation development previously unresolved despite decades of paleoecological studies.