bluuebunny/crossref_metadata_2025_split huggingface dataset:
Locally and Remotely Forced Subtropical AMOC Variability: A Matter of Time Scales
Authors: Jamet Quentin , Dewar William K. , Wienders Nicolas , Deremble Bruno , Close Sally , Penduff Thierry 
Published: April 2020

AbstractMechanisms driving the North Atlantic meridional overturning circulation (AMOC) variability at low frequency are of central interest for accurate climate predictions. Although the subpolar gyre region has been identified as a preferred place for generating climate time-scale signals, their southward propagation remains under consideration, complicating the interpretation of the observed time series provided by the Rapid Climate Change–Meridional Overturning Circulation and Heatflux Array–Western Boundary Time Series (RAPID–MOCHA–WBTS) program. In this study, we aim at disentangling the respective contribution of the local atmospheric forcing from signals of remote origin for the subtropical low-frequency AMOC variability. We analyze for this a set of four ensembles of a regional (20°S–55°N), eddy-resolving (1/12°) North Atlantic oceanic configuration, where surface forcing and open boundary conditions are alternatively permuted from fully varying (realistic) to yearly repeating signals. Their analysis reveals the predominance of local, atmospherically forced signal at interannual time scales (2–10 years), whereas signals imposed by the boundaries are responsible for the decadal (10–30 years) part of the spectrum. Due to this marked time-scale separation, we show that, although the intergyre region exhibits peculiarities, most of the subtropical AMOC variability can be understood as a linear superposition of these two signals. Finally, we find that the decadal-scale, boundary-forced AMOC variability has both northern and southern origins, although the former dominates over the latter, including at the site of the RAPID array (26.5°N).
The Moderate Alcohol and Cardiovascular Health Trial (MACH15): Design and methods for a randomized trial of moderate alcohol consumption and cardiometabolic risk
Authors: Spiegelman Donna , Lovato Laura C , Khudyakov Polyna , Wilkens Trine L , Adebamowo Clement A , Adebamowo Sally N , Appel Lawrence J , Beulens Joline WJ , Coughlin Janelle W , Dragsted Lars Ove , Edenberg Howard J , Eriksen Jane N , Estruch Ramon , Grobbee Diederick E , Gulayin Pablo E , Irazola Vilma , Krystal John H , Lazo Mariana , Murray Margaret M , Rimm Eric B , Schrieks Ilse C , Williamson Jeff D , Mukamal Kenneth J 
Published: April 2020

BackgroundObservational studies have documented lower risks of coronary heart disease and diabetes among moderate alcohol consumers relative to abstainers, but only a randomized clinical trial can provide conclusive evidence for or against these associations.AimThe purpose of this study was to describe the rationale and design of the Moderate Alcohol and Cardiovascular Health Trial, aimed to assess the cardiometabolic effects of one alcoholic drink daily over an average of six years among adults 50 years or older.MethodsThis multicenter, parallel-arm randomized trial was designed to compare the effects of one standard serving (∼11–15 g) daily of a preferred alcoholic beverage to abstention. The trial aimed to enroll 7800 people at high risk of cardiovascular disease. The primary composite endpoint comprised time to the first occurrence of non-fatal myocardial infarction, non-fatal ischemic stroke, hospitalized angina, coronary/carotid revascularization, or total mortality. The trial was designed to provide &gt;80% power to detect a 15% reduction in the risk of the primary outcome. Secondary outcomes included diabetes. Adverse effects of special interest included injuries, congestive heart failure, alcohol use disorders, and cancer.ResultsWe describe the design, governance, masking issues, and data handling. In three months of field center activity until termination by the funder, the trial randomized 32 participants, successfully screened another 70, and identified ∼400 additional interested individuals.ConclusionsWe describe a feasible design for a long-term randomized trial of moderate alcohol consumption. Such a study will provide the highest level of evidence for the effects of moderate alcohol consumption on cardiovascular disease and diabetes, and will directly inform clinical and public health guidelines.
Accuracy of whole-genome sequence imputation using hybrid peeling in large pedigreed livestock populations
Authors: Ros-Freixedes Roger , Whalen Andrew , Chen Ching-Yi , Gorjanc Gregor , Herring William O. , Mileham Alan J. , Hickey John M. 
Published: April 2020

AbstractBackgroundThe coupling of appropriate sequencing strategies and imputation methods is critical for assembling large whole-genome sequence datasets from livestock populations for research and breeding. In this paper, we describe and validate the coupling of a sequencing strategy with the imputation method hybrid peeling in real animal breeding settings.MethodsWe used data from four pig populations of different size (18,349 to 107,815 individuals) that were widely genotyped at densities between 15,000 and 75,000 markers genome-wide. Around 2% of the individuals in each population were sequenced (most of them at 1× or 2× and 37–92 individuals per population, totalling 284, at 15–30×). We imputed whole-genome sequence data with hybrid peeling. We evaluated the imputation accuracy by removing the sequence data of the 284 individuals with high coverage, using a leave-one-out design. We simulated data that mimicked the sequencing strategy used in the real populations to quantify the factors that affected the individual-wise and variant-wise imputation accuracies using regression trees.ResultsImputation accuracy was high for the majority of individuals in all four populations (median individual-wise dosage correlation: 0.97). Imputation accuracy was lower for individuals in the earliest generations of each population than for the rest, due to the lack of marker array data for themselves and their ancestors. The main factors that determined the individual-wise imputation accuracy were the genotyping status, the availability of marker array data for immediate ancestors, and the degree of connectedness to the rest of the population, but sequencing coverage of the relatives had no effect. The main factors that determined variant-wise imputation accuracy were the minor allele frequency and the number of individuals with sequencing coverage at each variant site. Results were validated with the empirical observations.ConclusionsWe demonstrate that the coupling of an appropriate sequencing strategy and hybrid peeling is a powerful strategy for generating whole-genome sequence data with high accuracy in large pedigreed populations where only a small fraction of individuals (2%) had been sequenced, mostly at low coverage. This is a critical step for the successful implementation of whole-genome sequence data for genomic prediction and fine-mapping of causal variants.
Complete genome sequence and annotation of the laboratory reference strain Shigella flexneri serotype 5a M90T and genome-wide transcriptional start site determination
Authors: Cervantes-Rivera Ramón , Tronnet Sophie , Puhar Andrea 
Published: April 2020

Abstract
Background
Shigella is a Gram-negative facultative intracellular bacterium that causes bacillary dysentery in humans. Shigella invades cells of the colonic mucosa owing to its virulence plasmid-encoded Type 3 Secretion System (T3SS), and multiplies in the target cell cytosol. Although the laboratory reference strain S. flexneri serotype 5a M90T has been extensively used to understand the molecular mechanisms of pathogenesis, its complete genome sequence is not available, thereby greatly limiting studies employing high-throughput sequencing and systems biology approaches.

Results
We have sequenced, assembled, annotated and manually curated the full genome of S. flexneri 5a M90T. This yielded two complete circular contigs, the chromosome and the virulence plasmid (pWR100). To obtain the genome sequence, we have employed long-read PacBio DNA sequencing followed by polishing with Illumina RNA-seq data. This provides a new hybrid strategy to prepare gapless, highly accurate genome sequences, which also cover AT-rich tracks or repetitive sequences that are transcribed. Furthermore, we have performed genome-wide analysis of transcriptional start sites (TSS) and determined the length of 5′ untranslated regions (5′-UTRs) at typical culture conditions for the inoculum of in vitro infection experiments. We identified 6723 primary TSS (pTSS) and 7328 secondary TSS (sTSS). The S. flexneri 5a M90T annotated genome sequence and the transcriptional start sites are integrated into RegulonDB (http://regulondb.ccg.unam.mx) and RSAT (http://embnet.ccg.unam.mx/rsat/) databases to use their analysis tools in the S. flexneri 5a M90T genome.

Conclusions
We provide the first complete genome for S. flexneri serotype 5a, specifically the laboratory reference strain M90T. Our work opens the possibility of employing S. flexneri M90T in high-quality systems biology studies such as transcriptomic and differential expression analyses or in genome evolution studies. Moreover, the catalogue of TSS that we report here can be used in molecular pathogenesis studies as a resource to know which genes are transcribed before infection of host cells. The genome sequence, together with the analysis of transcriptional start sites, is also a valuable tool for precise genetic manipulation of S. flexneri 5a M90T. Further, we present a new hybrid strategy to prepare gapless, highly accurate genome sequences. Unlike currently used hybrid strategies combining long- and short-read DNA sequencing technologies to maximize accuracy, our workflow using long-read DNA sequencing and short-read RNA sequencing provides the added value of using non-redundant technologies, which yield distinct, exploitable datasets.
Assessing graph-based read mappers against a baseline approach highlights strengths and weaknesses of current methods
Authors: Grytten Ivar , Rand Knut D. , Nederbragt Alexander J. , Sandve Geir K. 
Published: April 2020

Abstract
Background
Graph-based reference genomes have become popular as they allow read mapping and follow-up analyses in settings where the exact haplotypes underlying a high-throughput sequencing experiment are not precisely known. Two recent papers show that mapping to graph-based reference genomes can improve accuracy as compared to methods using linear references. Both of these methods index the sequences for most paths up to a certain length in the graph in order to enable direct mapping of reads containing common variants. However, the combinatorial explosion of possible paths through nearby variants also leads to a huge search space and an increased chance of false positive alignments to highly variable regions.

Results
We here assess three prominent graph-based read mappers against a hybrid baseline approach that combines an initial path determination with a tuned linear read mapping method. We show, using a previously proposed benchmark, that this simple approach is able to improve overall accuracy of read-mapping to graph-based reference genomes.

Conclusions
Our method is implemented in a tool Two-step Graph Mapper, which is available at https://github.com/uio-bmi/two_step_graph_mapperalong with data and scripts for reproducing the experiments. Our method highlights characteristics of the current generation of graph-based read mappers and shows potential for improvement for future graph-based read mappers.
Genome-wide analysis of Myo-inositol oxygenase gene family in tomato reveals their involvement in ascorbic acid accumulation
Authors: Munir Shoaib , Mumtaz Muhammad Ali , Ahiakpa John Kojo , Liu Genzhong , Chen Weifang , Zhou Guolin , Zheng Wei , Ye Zhibiao , Zhang Yuyang 
Published: April 2020

Abstract
Background
Ascorbic acid (Vitamin C, AsA) is an antioxidant metabolite involved in plant development and environmental stimuli. AsA biosynthesis has been well studied in plants, and MIOX is a critical enzyme in plants AsA biosynthesis pathway. However, Myo-inositol oxygenase (MIOX) gene family members and their involvement in AsA biosynthesis and response to abiotic stress remain unclear.

Results
In this study, five tomato genes encoding MIOX proteins and possessing MIOX motifs were identified. Structural analysis and distribution mapping showed that 5 MIOX genes contain different intron/exon patterns and unevenly distributed among four chromosomes. Besides, expression analyses indicated the remarkable expression of SlMIOX genes in different plant tissues. Furthermore, transgenic lines were obtained by over-expression of the MIOX4 gene in tomato. The overexpression lines showed a significant increase in total ascorbate in leaves and red fruits compared to control. Expression analysis revealed that increased accumulation of AsA in MIOX4 overexpression lines is possible as a consequence of the multiple genes involved in AsA biosynthesis. Myo inositol (MI) feeding in leaf and fruit implied that the Myo-inositol pathway improved the AsA biosynthesis in leaves and fruits. MIOX4 overexpression lines exhibited a better light response, abiotic stress tolerance, and AsA biosynthesis capacity.

Conclusions
These results showed that MIOX4 transgenic lines contribute to AsA biosynthesis, evident as better light response and improved oxidative stress tolerance. This study provides the first comprehensive analysis of the MIOX gene family and their involvement in ascorbate biosynthesis in tomato.
Novel low-nitrogen stress-responsive long non-coding RNAs (lncRNA) in barley landrace B968 (Liuzhutouzidamai) at seedling stage
Authors: Chen Zhiwei , Jiang Qi , Jiang Panpan , Zhang Wan , Huang Jianhua , Liu Chenghong , Halford Nigel G. , Lu Ruiju 
Published: April 2020

Abstract
Background
Reducing the dependence of crop production on chemical fertilizer with its associated costs, carbon footprint and other environmental problems is a challenge for agriculture. New solutions are required to solve this problem, and crop breeding for high nitrogen use efficiency or tolerance of low nitrogen availability has been widely considered to be a promising approach. However, the molecular mechanisms of high nitrogen use efficiency or low-nitrogen tolerance in crop plants are still to be elucidated, including the role of long non-coding RNAs (lncRNAs).

Results
In this study, we identified 498 lncRNAs in barley (Hordeum vulgare) landrace B968 (Liuzhutouzidamai), of which 487 were novel, and characterised 56 that were responsive to low-nitrogen stress. For functional analysis of differentially-expressed lncRNAs, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment of co-expressed and co-located protein-coding genes were analyzed, and interactions with annotated co-expressed protein coding genes or micro RNAs (miRNAs) were further predicted. Target mimicry prediction between differentially-expressed lncRNAs and miRNAs identified 40 putative target mimics of lncRNAs and 58 target miRNAs. Six differentially-expressed lncRNAs were further validated by qPCR, and one in particular showed consistent differential expression using both techniques. Expression levels of most of the lncRNAs were found to be very low, and this may be the reason for the apparent inconsistency between RNA-seq and qPCR data.

Conclusions
The analysis of lncRNAs that are differentially-expressed under low-nitrogen stress, as well as their co-expressed or co-located protein coding genes and target mimics, could elucidate complex and hitherto uncharacterised mechanisms involved in the adaptation to low-nitrogen stress in barley and other crop plants.
Endoscopic decompression of acute intestinal distension is associated with reduced mortality in critically ill patients
Authors: Book Thorsten , Kirstein Martha M. , Schneider Andrea , Manns Michael P. , Voigtländer Torsten 
Published: April 2020

Abstract
Background
Endoscopic placement of intestinal decompression tubes is a feasible technique for treatment of acute intestinal dilation. Given the heterogeneity of the underlying diseases leading to intestinal obstruction data on the significance of endoscopic procedures for treatment of these conditions are sparse.

Methods
In the study period from 2008 to 2019 all patients receiving a decompression tube were identified by retrospective chart review and analyzed.

Results
A total of 59 decompression tubes were placed in 50 patients. Technical success was achieved in 98% (58/59 tubes). As major complication one small bowel perforation occurred (1/59; 1.7%). Causes for impaired intestinal transit comprised tumor stenoses 22% (11/50), infections 18% (9/50), post-operative paralysis 14% (7/50), neurological diseases 8% (4/50), trauma 2% (1/50) and others 36% (18/50). Most patients (74%; 37/50) were critically ill and treated on intensive care unit. Treatment response after tube insertion was documented in 76% of patients (38/50) whereas 24% (12/50) did not fulfill response criteria. Patients with treatment response showed a significantly better outcome compared to non-responders. Responders had a median survival of 113 days (95% CI 41–186) compared to 15 days (95% CI 6–24) in non-responders (p = 0.002). Analysis of laboratory parameters after stratification in responders and non-responders to endoscopic therapy showed that non-responders had significantly higher levels of CRP and lower platelet count at baseline (CRP 262 mg/L (IQR 101–307) vs. 94 mg/L (IQR 26–153): p = 0.027; platelets 69 thsd/μL (IQR 33–161) vs. 199 thsd/μL (IQR 138–289): p = 0.009).

Conclusions
Endoscopic decompression is a safe procedure for acute management of impaired intestinal transit even in critically ill patients. Response to therapy is associated with improved outcome and markers of inflammation and organ function such as CRP, platelet count and serum lactate have to be taken into account for therapy monitoring and evaluation of prognosis.
The epidemiologic characteristics and associated risk factors of preterm birth from 2004 to 2013 in Taiwan
Authors: Chang Yu-Kang , Tseng Yuan-Tsung , Chen Kow-Tong 
Published: April 2020

Abstract
Background
The rate of preterm birth has been increasing worldwide. Most preterm babies are at an increased risk of central nervous system impairments as well as respiratory and gastrointestinal complications. The aim of this study was to investigate the epidemiologic characteristics of and associated factors contributing to preterm birth in Taiwan.

Methods
Information on obstetric antecedents and risk factors for preterm birth in pregnant women was obtained from the National Health Insurance Research (NHIR) database provided by the Taiwan National Health Research Institute. All live births from 2004 to 2013 in Taiwan were included in this study.

Results
A total of 130,362 live births from 2004 to 2013 were included in this study. Overall, the average annual rate of preterm births increased by 5.3% (from 3.33% in 2004 to 5.11% in 2013). Multiple logistic regression analyses showed that nulliparous women, multifetal pregnancies, advanced mother age, history of preterm birth, history of maternal drug abuse/dependence, and maternal medical complications were positively associated with an increased risk of preterm birth (all p-values< 0.05).

Conclusion
The overall proportion of preterm births increased from 2004 to 2013 in Taiwan. Babies born preterm had a higher risk of developing morbidities and mortalities. The development of a comprehensive program to identify the high-risk group is needed for effective interventions to prevent premature birth.
Final results from IMPROVE: a randomized, controlled, open-label, two-arm, cross-over phase IV study to determine patients’ preference for everolimus in combination with exemestane or capecitabine in combination with bevacizumab in advanced HR-positive, HER2-negative breast cancer
Authors: Decker Thomas , Söling Ulrike , Hahn Antje , Maintz Christoph , Kurbacher Christian Martin , Vehling-Kaiser Ursula , Sent Dagmar , Klare Peter , Hagen Volker , Chiabudini Marco , Falkenstein Julia , Indorf Martin , Runkel Eva , Potthoff Karin 
Published: April 2020

Abstract
Background
The objective of the IMPROVE study was patients’ preference for either endocrine-based therapy or combined chemo- and anti-angiogenic therapy in advanced HR-positive/HER2-negative breast cancer.

Methods
In this randomized, cross-over phase IV study, 77 patients were recruited in 26 sites in Germany. Patients were randomized 1:1 to receive either capecitabine plus bevacizumab (Cap+Bev) as first-line therapy followed by cross-over to everolimus plus exemestane (Eve+Exe) as second-line therapy (Arm A) or the reverse sequence (Arm B). The primary endpoint was patients’ preference for either regimen, assessed by the Patient Preference Questionnaire 12 weeks after cross-over. Key secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and quality of life (QoL).

Results
61.5% of patients preferred Cap+Bev (p = 0.1653), whereas 15.4% preferred Eve+Exe and 23.1% were indecisive. Physicians showed a similar tendency towards Cap+Bev (58.1%) as the preferred regimen versus Eve+Exe (32.3%). Median first-line PFS was longer for Cap+Bev than for Eve+Exe (11.1 months versus 3.5 months). Median second-line PFS was similar between Cap+Bev and Eve+Exe (3.6 months versus 3.7 months). Median OS was comparable between Arm A (28.8 months) and Arm B (24.7 months). 73.0% and 52.6% (first−/second-line, Cap+Bev) and 54.1% and 52.9% (first−/second-line, Eve+Exe) of patients experienced grade 3/4 TEAEs. No treatment-related deaths occurred. QoL and treatment satisfaction were not significantly different between arms or treatment lines.

Conclusions
Patients tended to favor Cap+Bev over Eve+Exe, which was in line with physicians’ preference. Cap+Bev showed superior first-line PFS, while QoL was similar in both arms. No new safety signals were reported.

Trial registration
EudraCT No: 2013–005329-22. Registered on 19 August 20
Trends in the epidemiology of young-onset colorectal cancer: a worldwide systematic review
Authors: Saad El Din Khalid , Loree Jonathan M. , Sayre Eric C. , Gill Sharlene , Brown Carl J. , Dau Hallie , De Vera Mary A. 
Published: April 2020

Abstract
Background
Recent data suggest that the risk of young-onset colorectal cancer (yCRC), in adults less than 50 years of age, is increasing. To confirm findings and identify contemporary trends worldwide, we conducted a systematic review of studies examining population-level trends in yCRC epidemiology.

Methods
We searched MEDLINE (1946–2018), EMBASE (1974–2018), CINAHL (1982–2018), and Cochrane Database of Systematic Reviews (2005–2018) for studies that used an epidemiologic design, assessed trends in yCRC incidence or prevalence, and published in English. Extracted information included country, age cut-off for yCRC, and reported trends in incidence or prevalence (e.g. annual percent change [APC]). We pooled similarly reported trend estimates using random effects models.

Results
Our search yielded 8695 articles and after applying our inclusion criteria, we identified 40 studies from 12 countries across five continents. One study assessed yCRC prevalence trends reporting an APCp of + 2.6 and + 1.8 among 20–39 and 40–49 year olds, respectively. 39 studies assessed trends in yCRC incidence but with substantial variability in reporting. Meta-analysis of the most commonly reported trend estimate yielded a pooled overall APCi of + 1.33 (95% CI, 0.97 to 1.68; p < 0.0001) that is largely driven by findings from North America and Australia. Also contributing to these trends is the increasing risk of rectal cancer as among 14 studies assessing cancer site, nine showed an increased risk of rectal cancer in adults less than 50 years with APCi up to + 4.03 (p < 0.001).

Conclusions
Our systematic review highlights increasing yCRC risk in North America and Australia driven by rising rectal cancers in younger adults over the past two decades.