bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electromechanical substrate characterization in arrhythmogenic cardiomyopathy using imaging-based patient-specific computer simulations
Authors: van Osta Nick , Kirkels Feddo , Lyon Aurore , Koopsen Tijmen , van Loon Tim , Cramer Maarten-Jan , Teske Arco J , Delhaas Tammo , Lumens Joost 
Published: December 2020

Abstract

Aims
Arrhythmogenic cardiomyopathy (AC) is an inherited cardiac disease, characterized by life-threatening ventricular arrhythmias and progressive cardiac dysfunction. The aim of this study is to use computer simulations to non-invasively estimate the individual patient’s myocardial tissue substrates underlying regional right ventricular (RV) deformation abnormalities in a cohort of AC mutation carriers.

Methods and results
In 68 AC mutation carriers and 20 control subjects, regional longitudinal deformation patterns of the RV free wall (RVfw), interventricular septum (IVS), and left ventricular free wall (LVfw) were obtained using speckle-tracking echocardiography. We developed and used a patient-specific parameter estimation protocol based on the multi-scale CircAdapt cardiovascular system model to create virtual AC subjects. Using the individual’s deformation data as model input, this protocol automatically estimated regional RVfw and global IVS and LVfw tissue properties. The computational model was able to reproduce clinically measured regional deformation patterns for all subjects, with highly reproducible parameter estimations. Simulations revealed that regional RVfw heterogeneity of both contractile function and compliance were increased in subjects with clinically advanced disease compared to mutation carriers without clinically established disease (17 ± 13% vs. 8 ± 4%, P = 0.01 and 18 ± 11% vs. 10 ± 7%, P &lt; 0.01, respectively). No significant difference in activation delay was found.

Conclusion
Regional RV deformation abnormalities in AC mutation carriers were related to reduced regional contractile function and tissue compliance. In clinically advanced disease stages, a characteristic apex-to-base heterogeneity of tissue abnormalities was present in the majority of the subjects, with most pronounced disease in the basal region of the RVfw.
Mosaic Evolution of the Phosphopantothenate Biosynthesis Pathway in Bacteria and Archaea
Authors: Thomès Luc , Lescure Alain 
Published: December 2020

Abstract
Phosphopantothenate is a precursor to synthesis of coenzyme A, a molecule essential to many metabolic pathways. Organisms of the archaeal phyla were shown to utilize a different phosphopantothenate biosynthetic pathway from the eukaryotic and bacterial one. In this study, we report that symbiotic bacteria from the group Candidatus poribacteria present enzymes of the archaeal pathway, namely pantoate kinase and phosphopantothenate synthetase, mirroring what was demonstrated for Picrophilus torridus, an archaea partially utilizing the bacterial pathway. Our results not only support the ancient origin of the coenzyme A pathway in the three domains of life but also highlight its complex and dynamic evolution. Importantly, this study helps to improve protein annotation for this pathway in the C. poribacteria group and other related organisms.
Anthropological genetics perspectives on the transatlantic slave trade
Authors: Fortes-Lima Cesar , Verdu Paul 
Published: December 2020

AbstractDuring the Trans-Atlantic Slave Trade (TAST), around twelve million Africans were enslaved and forcibly moved from Africa to the Americas and Europe, durably influencing the genetic and cultural landscape of a large part of humanity since the 15th century. Following historians, archaeologists, and anthropologists, population geneticists have, since the 1950’s mainly, extensively investigated the genetic diversity of populations on both sides of the Atlantic. These studies shed new lights into the largely unknown genetic origins of numerous enslaved-African descendant communities in the Americas, by inferring their genetic relationships with extant African, European, and Native American populations. Furthermore, exploring genome-wide data with novel statistical and bioinformatics methods, population geneticists have been increasingly able to infer the last 500 years of admixture histories of these populations. These inferences have highlighted the diversity of histories experienced by enslaved-African descendants, and the complex influences of socioeconomic, political, and historical contexts on human genetic diversity patterns during and after the slave trade. Finally, the recent advances of paleogenomics unveiled crucial aspects of the life and health of the first generation of enslaved-Africans in the Americas. Altogether, human population genetics approaches in the genomic and paleogenomic era need to be coupled with history, archaeology, anthropology, and demography in interdisciplinary research, to reconstruct the multifaceted and largely unknown history of the TAST and its influence on human biological and cultural diversities today. Here, we review anthropological genomics studies published over the past 15 years and focusing on the history of enslaved-African descendant populations in the Americas.
Tobacco smoking and mortality among Aboriginal and Torres Strait Islander adults in Australia
Authors: Thurber Katherine A , Banks Emily , Joshy Grace , Soga Kay , Marmor Alexandra , Benton Glen , White Sarah L , Eades Sandra , Maddox Raglan , Calma Tom , Lovett Raymond 
Published: December 2020

AbstractBackgroundDespite generally high smoking prevalences, stemming from colonization, the relationship of smoking to mortality has not been quantified reliably in an Indigenous population. We investigate smoking and mortality among Aboriginal and Torres Strait Islander adults in Australia, where current adult daily smoking prevalence is 40.2%.MethodsA prospective study of 1388 cardiovascular disease- and cancer-free Aboriginal adults aged ≥45 years, of the 267 153 45 and Up Study participants randomly sampled from the New South Wales general population over 2006–09. Questionnaire and mortality data were linked (through the Centre for Health Record Linkage) to mid-2019. Adjusted hazard ratios (called relative risks, RRs) for all-cause mortality—among current- and past- versus never-smokers—were estimated overall, by smoking intensity and by age at cessation. Smoking-attributable fractions and associated deaths were estimated.ResultsOver 14 586 person-years’ follow-up (median 10.6 years), 162 deaths accrued. Mortality RRs [95% confidence interval (CI)] were 3.90 (2.52–6.04) for current- and 1.95 (1.32–2.90) for past- versus never-smokers, with age heterogeneity. RRs increased with smoking intensity, to 4.29 (2.15–8.57) in current-smokers of ≥25 cigarettes/day. Compared with never-smokers, RRs were 1.48 (0.85–2.57) for those quitting at &lt;45 years of age and 2.21 (1.29–3.80) at 45–54 years. Never-smokers lived an average &gt;10 years longer than current-smokers. Around half of deaths among adults aged ≥45 years were attributable to smoking, exceeding 10 000 deaths in the past decade.ConclusionsIn this population, &gt;80% of never-smokers would survive to 75 years, versus ∼40% of current-smokers. Quitting at all ages examined had substantial benefits versus continuing smoking; those quitting before age 45 years had mortality risks similar to never-smokers. Smoking causes half of deaths in older Aboriginal and Torres Strait Islander adults; Indigenous tobacco control must receive increased priority.
Spicy food consumption and risk of gastrointestinal-tract cancers: findings from the China Kadoorie Biobank
Authors: Chan Wing Ching , Millwood Iona Y , Kartsonaki Christiana , Du Huaidong , Guo Yu , Chen Yiping , Bian Zheng , Walters Robin G , Lv Jun , He Pan , Hu Chen , Li Liming , Yang Ling , Chen Zhengming ,   for the China Kadoorie Biobank (CKB) Collaborative Group
Published: December 2020

Abstract

Background
Previous case–control studies have reported positive associations of spicy food consumption with risks of certain gastrointestinal-tract (GI) cancers. However, there is no prospective evidence on such associations, particularly from China, where there are high incidence rates of GI cancers and spicy food is widely consumed.

Methods
The prospective China Kadoorie Biobank study recruited &gt;512 000 adults aged 30–79 years from 10 areas in China during 2004–2008; 2350 oesophageal, 3350 stomach and 3061 colorectal incident cancer cases were recorded by 1 January 2017, after a median of 10.1 years of follow-up. Cox regression yielded adjusted hazard ratios (HRs) for each cancer associated with spicy food intake.

Results
Overall, 30% of participants reported daily spicy food consumption at baseline. Spicy food consumption was inversely associated with oesophageal cancer risk, with adjusted HRs of 1.00, 0.88, 0.76, 0.84 and 0.81 for those who never/rarely consumed (reference) and consumed monthly, 1–2 days/week, 3–5 days/week and 6–7 days/week, respectively (ptrend &lt; 0.002). The association remained similar after excluding the first 3 years of follow-up but appeared stronger in participants who did not smoke or drink alcohol regularly (ptrend &lt; 0.0001). The corresponding HRs for stomach cancer were 1.00, 0.97, 0.95, 0.92 and 0.89 (ptrend = 0.04), with the association disappearing after excluding the first 3 years of follow-up. For colorectal cancer, the HRs were 1.00, 1.00, 0.95, 0.87 and 0.90, respectively (ptrend = 0.04) and the inverse association appeared to be restricted to rectal rather than colon cancer (pheterogeneity = 0.004). The types and strength of spice used showed little additional effects on these associations.

Conclusion
In Chinese adults, higher spicy food consumption was associated with lower risks of certain GI cancers, particularly among individuals who never smoked or drank alcohol regularly.
Role of new antibiotics for KPC-producingKlebsiella pneumoniae
Authors: Theuretzbacher Ursula , Carrara Elena , Conti Michela , Tacconelli Evelina 
Published: December 2020

AbstractKlebsiella pneumoniae has accumulated a wide range of resistance determinants and has evolved into a difficult-to-treat pathogen that poses an increasing healthcare threat. KPC is an important marker for extensively drug-resistant (XDR) organisms with limited treatment options. In response to the medical need for new treatment options, several new antibiotics have been developed and registered recently. The β-lactamase inhibitor (BLI) combinations ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam, the cephalosporin–siderophore conjugate cefiderocol, the aminoglycoside derivative plazomicin and the tetracycline derivative eravacycline, focus on carbapenem-resistant Enterobacterales. These modified agents from old antibiotic classes illustrate the challenges of this requirement to address class-specific resistance mechanisms while critical gaps and some cross-resistance within a class, or to unrelated antibiotic classes, remain. The diverse molecular mechanisms and increasing diversification of carbapenem resistance among Klebsiella isolates requires improved rapid molecular diagnostic capabilities and stringent stewardship programmes to preserve the efficacy of new antibiotics for as long as possible.
Association between evidence-based training and clinician proficiency in electronic health record use
Authors: Hollister-Meadows Laura , Richesson Rachel L , Gagne Jennie De , Rawlins Neil 
Published: December 2020

Abstract

Objectives
The purpose of the study was to determine if association exists between evidence-based provider training and clinician proficiency in electronic health record (EHR) use and if so, which EHR use metrics and vendor-defined indices exhibited association.

Materials and Methods
We studied ambulatory clinicians’ EHR use data published in the Epic Systems Signal report to assess proficiency between training participants (n = 133) and nonparticipants (n = 14). Data were collected in May 2019 and November 2019 on nonsurgeon clinicians from 6 primary care, 7 urgent care, and 27 specialty care clinics. EHR use training occurred from August 5 to August 15, 2019, prior to EHR upgrade and organizational instance alignment. Analytics performed were descriptive statistics, paired t-tests, multivariate correlations, and hierarchal multiple regression.

Results
For number of appointments per 30-day reporting period, trained clinicians sustained an average increase of 16 appointments (P &lt; .05), whereas nontrained clinicians incurred a decrease of 8 appointments. Only the trained clinician group achieved postevent improvement in the vendor-defined Proficiency score with an effect size characterized as moderate to large (dCohen = 0.625)

Discussion
Controversies exist on the return of investment from formal EHR training for clinician users. Previously published literature has mostly focused on qualitative data indicators of EHR training success. The findings of our EHR use training study identified EHR use metrics and vendor-defined indices with the capacity for translation into productivity and generated revenue measurements.

Conclusions
One EHR use metric and 1 vendor-defined index indicated improved proficiency among trained clinicians.
Extensive Evaluation via Blinded Testing of an UHPLC-MS/MS Method for Quantitation of Ten Ergot Alkaloids in Rye and Wheat Grains
Authors: Tkachenko Andriy , Benson Kelly , Mostrom Michelle , Guag Jake , Reimschuessel Renate , Webb Brett 
Published: December 2020

Abstract

Background
Ergot alkaloids are mycotoxins produced by the fungus Claviceps, which can contaminate grains and pose a health risk to humans and animals. Validation of an ergot alkaloid method in collaborative projects can be challenging due to instability of analytes, a lack of reliable reference materials, and a fully validated reference method.

Objective
To extensively evaluate performance of a quantitative UHPLC–MS/MS method to detect ten ergot alkaloids at concentrations between 16 and 500 ng/g in grains.

Method
The method performance was evaluated in the Blinded Method Test (BMT) exercise, which allowed organizers to successfully address the challenges. Forty completely blinded test samples were prepared in an independent laboratory and shipped to a participating laboratory to analyze on two separate days.

Results
Precision, accuracy, and HorRatr values met or exceeded the U.S. Food and Drug Administration recommendations. The design of the BMT exercise provided a high degree of confidence in data and conclusions drawn.

Conclusions
The method performed in a manner as expected, and the method can be used by the laboratory for routine testing of wheat and rye grains.

Highlights
BMT of laboratory methods facilitate validation of tests by evaluating performance in an unbiased manner.
PCBP2 Is Downregulated in Degenerating Neurons and Rarely Observed in TDP-43-Positive Inclusions in Sporadic Amyotrophic Lateral Sclerosis
Authors: Yoshimura Motoi , Honda Hiroyuki , Sasagasako Naokazu , Mori Shinichiro , Hamasaki Hideomi , Suzuki Satoshi O , Ishii Takashi , Ninomiya Toshiharu , Kira Jun-Ichi , Iwaki Toru 
Published: December 2020

Abstract
Various heterogeneous nuclear ribonucleoproteins (hnRNPs) are deposited in pathological inclusions of amyotrophic lateral sclerosis (ALS) and related diseases, such as frontotemporal lobar degeneration (FTLD). Recently, poly (rC)-binding protein 2 (PCBP2, hnRNP-E2), a member of the hnRNP family, was reported to be colocalized with transactivation-responsive DNA-binding protein 43 kDa (TDP-43)-immunopositive inclusions in cases of FTLD-TDP. Here, we used immunohistochemical methods to investigate PCBP1 and PCBP2 expression in the spinal cords of sporadic ALS patients, with special reference to TDP-43-positive inclusions. Thirty autopsy cases of sporadic ALS were examined by immunohistochemistry using antibodies against PCBP1, PCBP2, sequestosome 1 (p62), and TDP-43. In control subjects without neurological disorders, neurons predominantly expressed PCBP2, rather than PCBP1, in their cytoplasm and nuclei. Anterior horn cells of sporadic ALS patients often had various levels of PCBP2 expression, and motor neurons with skein-like inclusions often had reduced or lost cytoplasmic and nuclear PCBP2 staining. Notably, one case with FTLD-TDP subtype B pathology had marked colocalization of TDP-43 and PCBP2 in the cytoplasmic inclusions and dystrophic neurites of the cerebral cortex, hippocampus, and spinal cord. In conclusion, PCBP2 was reduced in anterior horn cells of sporadic ALS, but its occurrence in TDP-43 inclusions was a rare phenomenon.
The physical properties and evolution of the interacting system AM 1204−292
Authors: Rosa D A , Rodrigues I , Krabbe A C , Milone A C , Carvalho S 
Published: December 2020

ABSTRACT
We investigate interaction effects in the stellar and gas kinematics, stellar population, and ionized gas properties of the interacting galaxy pair AM 1204−292,composed of NGC 4105 and NGC 4106. The data consist of long-slit spectra in the range 3000–7050 Å. The massive E3 galaxy NGC 4105 presents a flat stellar velocity profile, while the ionized gas is in strong rotation, suggesting an external origin. Its companion, NGC 4106, shows asymmetries in the radial velocity field, likely due to the interaction. The dynamics of the interacting pair were modelled using the P-Gadget3 treepm/sph code, from which we show that the system has just passed the first perigalacticum, which triggered an outbreak of star formation, currently at full maximum. We characterized the stellar population properties using the stellar population synthesis code starlight and, on average, both galaxies are predominantly composed of old stellar populations. NGC 4105 has a slightly negative age gradient, comparable with that of the most massive elliptical galaxies, but a steeper metallicity gradient. The SB0 galaxy NGC 4106 presents smaller radial variations in both age and metallicity in comparison with intermediate-mass early-type galaxies. These gradients have not been disturbed by interaction, since the star formation happened very recently and was not extensive in mass. Electron density estimates for the pair are systematically higher than those obtained in isolated galaxies. The central O/H abundances were obtained from photoionization models in combination with emission-line ratios, which resulted in 12 + log(O/H) = 9.03 ± 0.02 and 12 + log(O/H) = 8.69 ± 0.05 for NGC 4105 and NGC 4106, respectively.
A deep learning approach to test the small-scale galaxy morphology and its relationship with star formation activity in hydrodynamical simulations
Authors: Zanisi Lorenzo , Huertas-Company Marc , Lanusse François , Bottrell Connor , Pillepich Annalisa , Nelson Dylan , Rodriguez-Gomez Vicente , Shankar Francesco , Hernquist Lars , Dekel Avishai , Margalef-Bentabol Berta , Vogelsberger Mark , Primack Joel 
Published: December 2020

ABSTRACT
Hydrodynamical simulations of galaxy formation and evolution attempt to fully model the physics that shapes galaxies. The agreement between the morphology of simulated and real galaxies, and the way the morphological types are distributed across galaxy scaling relations are important probes of our knowledge of galaxy formation physics. Here, we propose an unsupervised deep learning approach to perform a stringent test of the fine morphological structure of galaxies coming from the Illustris and IllustrisTNG (TNG100 and TNG50) simulations against observations from a subsample of the Sloan Digital Sky Survey. Our framework is based on PixelCNN, an autoregressive model for image generation with an explicit likelihood. We adopt a strategy that combines the output of two PixelCNN networks in a metric that isolates the small-scale morphological details of galaxies from the sky background. We are able to quantitatively identify the improvements of IllustrisTNG, particularly in the high-resolution TNG50 run, over the original Illustris. However, we find that the fine details of galaxy structure are still different between observed and simulated galaxies. This difference is mostly driven by small, more spheroidal, and quenched galaxies that are globally less accurate regardless of resolution and which have experienced little improvement between the three simulations explored. We speculate that this disagreement, that is less severe for quenched discy galaxies, may stem from a still too coarse numerical resolution, which struggles to properly capture the inner, dense regions of quenched spheroidal galaxies.
Genetic risk factors for endometriosis near estrogen receptor 1 and coexpression of genes in this region in endometrium
Authors: Marla S , Mortlock S , Houshdaran S , Fung J , McKinnon B , Holdsworth-Carson S J , Girling J E , Rogers P A W , Giudice L C , Montgomery G W 
Published: December 2020

Abstract
The etiology and pathogenesis of endometriosis are complex with both genetic and environmental factors contributing to disease risk. Genome-wide association studies (GWAS) have identified multiple signals in the estrogen receptor 1 (ESR1) region associated with endometriosis and other reproductive traits and diseases. In addition, candidate gene association studies identified signals in the ESR1 region associated with endometriosis risk suggesting genetic regulation of genes in this region may be important for reproductive health. This study aimed to investigate hormonal and genetic regulation of genes in the ESR1 region in human endometrium. Changes in serum oestradiol and progesterone concentrations and expression of hormone receptors ESR1 and progesterone receptor (PGR) were assessed in endometrial samples from 135 women collected at various stages of the menstrual cycle. Correlation between hormone concentrations, receptor expression and expression of genes in the ESR1 locus was investigated. The effect of endometriosis risk variants on expression of genes in the region was analyzed to identify gene targets. Hormone concentrations and receptor expression varied significantly across the menstrual cycle. Expression of genes in the ESR1 region correlated with progesterone concentration; however, they were more strongly correlated with expression of ESR1 and PGR suggesting coregulation of genes. There was no evidence that endometriosis risk variants directly regulated expression of genes in the region. Limited sample size and cellular heterogeneity in endometrial tissue may impact the ability to detect significant genetic effects on gene expression. Effects of these variants should be validated in a larger dataset and in relevant individual cell types.