bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compartmentalized metabolism supports midgestation mammalian development
Authors: Solmonson Ashley , Faubert Brandon , Gu Wen , Rao Aparna , Cowdin Mitzy A. , Menendez-Montes Ivan , Kelekar Sherwin , Rogers Thomas J. , Pan Chunxiao , Guevara Gerardo , Tarangelo Amy , Zacharias Lauren G. , Martin-Sandoval Misty S. , Do Duyen , Pachnis Panayotis , Dumesnil Dennis , Mathews Thomas P. , Tasdogan Alpaslan , Pham An , Cai Ling , Zhao Zhiyu , Ni Min , Cleaver Ondine , Sadek Hesham A. , Morrison Sean J. , DeBerardinis Ralph J. 
Published: April 2022

AbstractMammalian embryogenesis requires rapid growth and proper metabolic regulation1. Midgestation features increasing oxygen and nutrient availability concomitant with fetal organ development2,3. Understanding how metabolism supports development requires approaches to observe metabolism directly in model organisms in utero. Here we used isotope tracing and metabolomics to identify evolving metabolic programmes in the placenta and embryo during midgestation in mice. These tissues differ metabolically throughout midgestation, but we pinpointed gestational days (GD) 10.5–11.5 as a transition period for both placenta and embryo. Isotope tracing revealed differences in carbohydrate metabolism between the tissues and rapid glucose-dependent purine synthesis, especially in the embryo. Glucose’s contribution to the tricarboxylic acid (TCA) cycle rises throughout midgestation in the embryo but not in the placenta. By GD12.5, compartmentalized metabolic programmes are apparent within the embryo, including different nutrient contributions to the TCA cycle in different organs. To contextualize developmental anomalies associated with Mendelian metabolic defects, we analysed mice deficient in LIPT1, the enzyme that activates 2-ketoacid dehydrogenases related to the TCA cycle4,5. LIPT1 deficiency suppresses TCA cycle metabolism during the GD10.5–GD11.5 transition, perturbs brain, heart and erythrocyte development and leads to embryonic demise by GD11.5. These data document individualized metabolic programmes in developing organs in utero.
A joint NCBI and EMBL-EBI transcript set for clinical genomics and research
Authors: Morales Joannella , Pujar Shashikant , Loveland Jane E. , Astashyn Alex , Bennett Ruth , Berry Andrew , Cox Eric , Davidson Claire , Ermolaeva Olga , Farrell Catherine M. , Fatima Reham , Gil Laurent , Goldfarb Tamara , Gonzalez Jose M. , Haddad Diana , Hardy Matthew , Hunt Toby , Jackson John , Joardar Vinita S. , Kay Michael , Kodali Vamsi K. , McGarvey Kelly M. , McMahon Aoife , Mudge Jonathan M. , Murphy Daniel N. , Murphy Michael R. , Rajput Bhanu , Rangwala Sanjida H. , Riddick Lillian D. , Thibaud-Nissen Françoise , Threadgold Glen , Vatsan Anjana R. , Wallin Craig , Webb David , Flicek Paul , Birney Ewan , Pruitt Kim D. , Frankish Adam , Cunningham Fiona , Murphy Terence D. 
Published: April 2022

AbstractComprehensive genome annotation is essential to understand the impact of clinically relevant variants. However, the absence of a standard for clinical reporting and browser display complicates the process of consistent interpretation and reporting. To address these challenges, Ensembl/GENCODE1and RefSeq2launched a joint initiative, the Matched Annotation from NCBI and EMBL-EBI (MANE) collaboration, to converge on human gene and transcript annotation and to jointly define a high-value set of transcripts and corresponding proteins. Here, we describe the MANE transcript sets for use as universal standards for variant reporting and browser display. The MANE Select set identifies a representative transcript for each human protein-coding gene, whereas the MANE Plus Clinical set provides additional transcripts at loci where the Select transcripts alone are not sufficient to report all currently known clinical variants. Each MANE transcript represents an exact match between the exonic sequences of an Ensembl/GENCODE transcript and its counterpart in RefSeq such that the identifiers can be used synonymously. We have now released MANE Select transcripts for 97% of human protein-coding genes, including all American College of Medical Genetics and Genomics Secondary Findings list v3.0 (ref.3) genes. MANE transcripts are accessible from major genome browsers and key resources. Widespread adoption of these transcript sets will increase the consistency of reporting, facilitate the exchange of data regardless of the annotation source and help to streamline clinical interpretation.
Biomechanical modeling of actively controlled rectus extraocular muscle pulleys
Authors: Wei Qi , Mutawak Bassam , Demer Joseph L. 
Published: April 2022

AbstractThe Active Pulley Hypothesis (APH) is based on modern functional anatomical descriptions of the oculomotor plant, and postulates behaviors of the orbital pulleys proposed to be positioned by the extraocular muscles (EOMs). A computational model is needed to understand this schema quantitatively. We developed and evaluated a novel biomechanical model of active horizontal rectus pulleys. The orbital (OL) and global (GL) layers of the horizontal rectus EOMs were implemented as separate musculoskeletal strands. Pulley sleeves were modeled as tube-like structures receiving the OL insertion and suspended by elastic strands. Stiffnesses and orientations of pulley suspensions were determined empirically to limit horizontal rectus EOM side-slip while allowing anteroposterior pulley travel. Independent neural drives of the OL greater than GL were assumed. The model was iteratively refined in secondary gazes to implement realistic behavior using the simplest mechanical configuration and neural control strategy. Simulated horizontal rectus EOM paths and pulley positions during secondary gazes were consistent with published MRI measurements. Estimated EOM tensions were consistent with the range of experimentally measured tensions. This model is consistent with postulated bilaminar activity of the EOMs, and the separate roles of the GL in ocular rotation, and OL in pulley positioning.
Update on prevalence of Babesia canis and Rickettsia spp. in adult and juvenile Dermacentor reticulatus ticks in the area of Poland (2016–2018)
Authors: Dwużnik-Szarek Dorota , Mierzejewska Ewa Julia , Kiewra Dorota , Czułowska Aleksandra , Robak Anna , Bajer Anna 
Published: April 2022

AbstractOrnate dog tick,Dermacentor reticulatusis an important vector ofBabesia canis,andRickettsiaspp. and other pathogens of veterinary and public health interest. The current study is the first to investigate the long-term changes in prevalence of these pathogens in expanding tick populations in Central Europe. Molecular techniques (PCR, sequencing) were applied for the detection of pathogen DNA in adult (n = 2497) and juvenile ticks (1096 larvae and 410 nymphs). DNA ofRickettsiaspp. was identified in 35% of adults and 12.6% of juvenile ticks. DNA ofB. caniswas detected in 3% of adult ticks and only in ticks from the Eastern region (regional prevalence 6%). As previously, noB. canis-positive ticks were found in Western Poland, including ticks from Wrocław area (n = 298). DNA ofB. caniswas identified in 0.33% of juvenile ticks (in 3 pools of larvae and 2 nymphs) from the Eastern region. In the current study we confirmed high occurrence ofR. raoultiiin adults ticks from all four zones and relatively high prevalence ofB. canisin the Eastern population ofD. reticulatus, corresponding well with high incidence of canine babesiosis in this area of Poland. Finally, we confirmedR. raoultiiandB. canisinfection in all life stages ofD. reticulatusticks.
Machine learning model from a Spanish cohort for prediction of SARS-COV-2 mortality risk and critical patients
Authors: Reina Reina Alejandro , Barrera José M. , Valdivieso Bernardo , Gas María-Eugenia , Maté Alejandro , Trujillo Juan C. 
Published: April 2022

AbstractPatients affected by SARS-COV-2 have collapsed healthcare systems around the world. Consequently, different challenges arise regarding the prediction of hospital needs, optimization of resources, diagnostic triage tools and patient evolution, as well as tools that allow us to analyze which are the factors that determine the severity of patients. Currently, it is widely accepted that one of the problems since the pandemic appeared was to detect (i) who patients were about to need Intensive Care Unit (ICU) and (ii) who ones were about not overcome the disease. These critical patients collapsed Hospitals to the point that many surgeries around the world had to be cancelled. Therefore, the aim of this paper is to provide a Machine Learning (ML) model that helps us to prevent when a patient is about to be critical. Although we are in the era of data, regarding the SARS-COV-2 patients, there are currently few tools and solutions that help medical professionals to predict the evolution of patients in order to improve their treatment and the needs of critical resources at hospitals. Moreover, most of these tools have been created from small populations and/or Chinese populations, which carries a high risk of bias. In this paper, we present a model, based on ML techniques, based on 5378 Spanish patients’ data from which a quality cohort of 1201 was extracted to train the model. Our model is capable of predicting the probability of death of patients with SARS-COV-2 based on age, sex and comorbidities of the patient. It also allows what-if analysis, with the inclusion of comorbidities that the patient may develop during the SARS-COV-2 infection. For the training of the model, we have followed an agnostic approach. We explored all the active comorbidities during the SARS-COV-2 infection of the patients with the objective that the model weights the effect of each comorbidity on the patient’s evolution according to the data available. The model has been validated by using stratified cross-validation with k = 5 to prevent class imbalance. We obtained robust results, presenting a high hit rate, with 84.16% accuracy, 83.33% sensitivity, and an Area Under the Curve (AUC) of 0.871. The main advantage of our model, in addition to its high success rate, is that it can be used with medical records in order to predict their diagnosis, allowing the critical population to be identified in advance. Furthermore, it uses the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD 9-CM) standard. In this sense, we should also emphasize that those hospitals using other encodings can add an intermediate layer business to business (B2B) with the aim of making transformations to the same international format.
Comparison of device-based therapy options for heart failure with preserved ejection fraction: a simulation study
Authors: Granegger Marcus , Gross Christoph , Siemer David , Escher Andreas , Sandner Sigrid , Schweiger Martin , Laufer Günther , Zimpfer Daniel 
Published: April 2022

AbstractSuccessful therapy of heart failure with preserved ejection fraction (HFpEF) remains a major unmet clinical need. Device-based treatment approaches include the interatrial shunt device (IASD), conventional assist devices pumping blood from the left ventricle (LV-VAD) or the left atrium (LA-VAD) towards the aorta, and a valveless pulsatile assist device with a single cannula operating in co-pulsation with the native heart (CoPulse). Hemodynamics of two HFpEF subgroups during rest and exercise condition were translated into a lumped parameter model of the cardiovascular system. The numerical model was applied to assess the hemodynamic effect of each of the four device-based therapies. All four therapy options show a reduction in left atrial pressure during rest and exercise and in both subgroups (> 20%). IASDs concomitantly reduce cardiac output (CO) and shift the hemodynamic overload towards the pulmonary circulation. All three mechanical assist devices increase CO while reducing sympathetic activity. LV-VADs reduce end-systolic volume, indicating a high risk for suction events. The heterogeneity of the HFpEF population requires an individualized therapy approach based on the underlying hemodynamics. Whereas phenotypes with preserved CO may benefit most from an IASD device, HFpEF patients with reduced CO may be candidates for mechanical assist devices.
Venice as a paradigm of coastal flooding under multiple compound drivers
Authors: Ferrarin Christian , Lionello Piero , Orlić Mirko , Raicich Fabio , Salvadori Gianfausto 
Published: April 2022

AbstractFull comprehension of the dynamics of hazardous sea levels is indispensable for assessing and managing coastal flood risk, especially under a changing climate. The 12 November 2019 devastating flood in the historical city of Venice (Italy) stimulated new investigations of the coastal flooding problem from different perspectives and timescales. Here Venice is used as a paradigm for coastal flood risk, due to the complexity of its flood dynamics facing those of many other locations worldwide. Spectral decomposition was applied to the long-term 1872–2019 sea-level time series in order to investigate the relative importance of different drivers of coastal flooding and their temporal changes. Moreover, a multivariate analysis via copulas provided statistical models indispensable for correctly understanding and reproducing the interactions between the variables at play. While storm surges are the main drivers of the most extreme events, tides and long-term forcings associated with planetary atmospheric waves and seasonal to inter-annual oscillations are predominant in determining recurrent nuisance flooding. The non-stationary analysis revealed a positive trend in the intensity of the non-tidal contribution to extreme sea levels in the last three decades, which, along with relative sea-level rise, contributed to an increase in the frequency of floods in Venice.
AKR1C3 expression in T acute lymphoblastic leukemia/lymphoma for clinical use as a biomarker
Authors: Reddi Deepti , Seaton Brandon W. , Woolston David , Aicher Lauri , Monroe Luke D. , Mao Zhengwei J. , Harrell Jill C. , Radich Jerald P. , Advani Anjali , Papadantonakis Nikolaos , Yeung Cecilia C. S. 
Published: April 2022

AbstractTo investigate aldo–keto reductase 1C3 (AKR1C3) expression in T and B acute lymphoblastic leukemia/lymphoma (ALL) patients. Three commercial antibodies were evaluated for AKR1C3 immunohistochemistry (IHC) staining performance: Polyclonal Thermofisher scientific (Clone#PA523667), rabbit monoclonal Abcam [EPR16726] (ab209899) and Sigma/Millipore anti-AKR1C3 antibody, mouse monoclonal, clone NP6.G6.A6, purified from hybridoma cell culture. Initial optimization was performed on cell line controls: HCT116 (negative control); genetically modified cell line HCT116 with AKR1C3 overexpression; Nalm and TF1 cell lines. Twenty normal bone marrows from archival B and T-ALL patient samples were subsequently examined. AKR1C3 expression levels in these samples were evaluated by immunohistochemistry, Protein Wes and quantitative RT-PCR. Sigma/Millipore Anti-AKR1C3 antibody (mouse monoclonal, clone NP6.G6.A6) showed higher specificity compared to rabbit polyclonal antibody by immunohistochemistry. H-score was used to quantify percent of nuclear immunoreactivity for AKR1C3 with varying disease involvement. T-ALL samples had a higher H-score (172–190) compared to B-ALL cases (H-score, 30–160). The AKR1C3 expression in peripheral blood by Protein Wes and RT-qPCR showed concordance in relapsed/refractory and/or minimal residual T-ALL cases. Sigma/Millipore Anti-AKR1C3 antibody and mouse monoclonal, clone NP6.G6.A6 can be used to aid in AKR1C expression of T-ALL and in cases of relapsed/refractory and/or minimal residual disease.
Association between 24-h movement guidelines and cardiometabolic health in Chilean adults
Authors: Riquelme Ricardo , Rezende Leandro F. M. , Marques Adilson , Drenowatz Clemens , Ferrari Gerson 
Published: April 2022

AbstractThis study aimed to examine the association between meeting 24-h movement guidelines and cardiometabolic health in Chilean adults. We used cross-sectional data of 2618 adults from the Chilean National Health Survey 2016–2017. Meeting the 24-h movement guidelines was defined as ≥ 600 MET-min/week of physical activity; ≤ 8 h/day of sitting time; and 7 to 9 h/day of sleep duration. Cardiometabolic health indicators were body mass index, waist circumference, high triglycerides, high blood pressure, type 2 diabetes, metabolic syndrome, and risk of cardiovascular disease in a 10-year period. Meeting none out of three 24-h movement guidelines (vs all three) was associated with higher odds of overweight/obesity (OR 1.67; 95%CI 1.45 to 1.89), high waist circumference (1.65; 1.40 to 1.90), hypertension (2.88; 2.23 to 3.53), type 2 diabetes (1.60; 1.26 to 1.94), metabolic syndrome (1.97; 1.54 to 2.40) and risk of cardiovascular disease (1.50; 1.20, 1.80). Meeting one guideline (vs three) was associated with higher odds of five of out seven cardiometabolic indicators. Our study found that the composition of movement behaviors within a 24-h period may have important implications for cardiometabolic health.
Phenotypic characterization and genome analysis of a novel Salmonella Typhimurium phage having unique tail fiber genes
Authors: Sattar Sadia , Ullah Inam , Khanum Sofia , Bailie Marc , Shamsi Bushra , Ahmed Ibrar , Shah Syed Tahir Abbas , Javed Sundus , Ghafoor Aamir , Pervaiz Amna , Sohail Fakiha , Shah Naseer Ali , Imdad Kaleem , Bostan Nazish , Altermann Eric 
Published: April 2022

AbstractSalmonella enterica serovar Typhimurium is a foodborne pathogen causing occasional outbreaks of enteric infections in humans. Salmonella has one of the largest pools of temperate phages in its genome that possess evolutionary significance for pathogen. In this study, we characterized a novel temperate phage Salmonella phage BIS20 (BIS20) with unique tail fiber genes. It belongs to the subfamily Peduovirinae genus Eganvirus and infects Salmonella Typhimurium strain (SE-BS17; Acc. NO MZ503545) of poultry origin. Phage BIS20 was viable only at biological pH and temperature ranges (pH7 and 37 °C). Despite being temperate BIS20 significantly slowed down the growth of host strain for 24 h as compared to control (P < 0.009). Phage BIS20 features 29,477-base pair (bp) linear DNA genome with 53% GC content and encodes for 37 putative ORFs. These ORFs have mosaic arrangement as indicated by its ORF similarity to various phages and prophages in NCBI. Genome analysis indicates its similarity to Salmonella enterica serovar Senftenberg prophage (SEStP) sequence (Nucleotide similarity 87.7%) and Escherichia virus 186 (~ 82.4% nucleotide similarity). Capsid genes were conserved however those associated with tail fiber formation and assembly were unique to all members of genus Eganvirus. We found strong evidence of recombination hotspot in tail fiber gene. Our study identifies BIS20 as a new species of genus Eganvirus temperate phages as its maximum nucleotide similarity is 82.4% with any phage in NCBI. Our findings may contribute to understanding of origin of new temperate phages.
scTEM-seq: Single-cell analysis of transposable element methylation to link global epigenetic heterogeneity with transcriptional programs
Authors: Hunt Kooper V. , Burnard Sean M. , Roper Ellise A. , Bond Danielle R. , Dun Matthew D. , Verrills Nicole M. , Enjeti Anoop K. , Lee Heather J. 
Published: April 2022

AbstractGlobal changes in DNA methylation are observed in development and disease, and single-cell analyses are highlighting the heterogeneous regulation of these processes. However, technical challenges associated with single-cell analysis of DNA methylation limit these studies. We present single-cell transposable element methylation sequencing (scTEM-seq) for cost-effective estimation of average DNA methylation levels. By targeting high-copy SINE Alu elements, we achieve amplicon bisulphite sequencing with thousands of loci covered in each scTEM-seq library. Parallel transcriptome analysis is also performed to link global DNA methylation estimates with gene expression. We apply scTEM-seq to KG1a acute myeloid leukaemia (AML) cells, and primary AML cells. Our method reveals global DNA methylation heterogeneity induced by decitabine treatment of KG1a cells associated with altered expression of immune process genes. We also compare global DNA methylation estimates to expression of transposable elements and find a predominance of negative correlations. Finally, we observe co-ordinated upregulation of many transposable elements in a sub-set of decitabine treated cells. By linking global DNA methylation heterogeneity with transcription, scTEM-seq will refine our understanding of epigenetic regulation in cancer and beyond.
Chronic myocardial and coronary arterial effects of intracoronary supersaturated oxygen therapy in swine with normal and ischemic-reperfused myocardium
Authors: Kaluza Grzegorz L. , Creech Jeffrey L. , Furer Ariel , Afari Maxwell E. , Milewski Krzysztof , Yi Geng-Hua , Cheng Yanping , Conditt Gerard B. , McGregor Jenn C. , Blum Donald , Rousselle Serge D. , Granada Juan F. , Burkhoff Daniel 
Published: April 2022

AbstractThe study assessed chronic myocardial, coronary and systemic effects of intracoronary supersaturated oxygen (SSO2) therapy. Left anterior descending coronary arteries of 40 swine were stented and randomized to 90-min selective intracoronary infusion of SSO2 (pO2 760–1000 mmHg) or normoxemic saline. In 20 out of 40 animals, SSO2 delivery followed a 60-min balloon occlusion to induce myocardial infarction (MI). In both normal and MI models, intracoronary treatment with hyperoxemic SSO2 therapy showed no evidence of coronary thrombosis. There were no biologically relevant differences between treatments at either time point in regard to coronary intervention site healing and neointimal growth. No signs of any myocardial or systemic toxicity were observed after 7 or 30 days. A trend was observed toward reduced incidence of microscopic MI scars and reduced infarct size in histopathology, as well as toward better recovery of echocardiographically evaluated global and regional contractility at 30 days. No treatment related infarcts or thromboemboli were observed in the downstream organs.
Dominican amber net-winged beetles suggest stable paleoenvironment as a driver for conserved morphology in a paedomorphic lineage
Authors: Ferreira Vinicius S. , Solodovnikov Alexey , Ivie Michael A. , Kundrata Robin 
Published: April 2022

AbstractPaedomorphosis is a heterochronic syndrome in which adult individuals display features of their immature forms. In beetles, this phenomenon occurs widely in the superfamily Elateroidea, including the net-winged beetles (Lycidae), and, due to the usual flightlessness of paedomorphic females, it is hypothesized to cause speciation rates higher than in non-paedomorphic lineages. However, some fossils of paedomorphic lycids do not support this with palaeobiological data. Discovery of new Lycidae fossils attributed to the West Indian extant paedomorphic genus Cessator Kazantsev in the Dominican amber also suggests morphological stasis within this genus in the Greater Antilles. We describe Cessator anachronicus Ferreira and Ivie, sp. nov. based on adult males, as well as the first ever recorded fossil net-winged beetle larva of the same genus. We propose that the relatively young age of the studied fossils combined with the stable conditions in the forest floor of the Greater Antilles through the last tens of million years could explain the exceptionally conserved morphology in the net-winged beetles affected by the paedomorphic syndrome.