bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploiting deep transfer learning for the prediction of functional non-coding variants using genomic sequence
Authors: Chen Li , Wang Ye , Zhao Fengdi 
Published: April 2022

AbstractMotivationThough genome-wide association studies have identified tens of thousands of variants associated with complex traits and most of them fall within the non-coding regions, they may not be the causal ones. The development of high-throughput functional assays leads to the discovery of experimental validated non-coding functional variants. However, these validated variants are rare due to technical difficulty and financial cost. The small sample size of validated variants makes it less reliable to develop a supervised machine learning model for achieving a whole genome-wide prediction of non-coding causal variants.ResultsWe will exploit a deep transfer learning model, which is based on convolutional neural network, to improve the prediction for functional non-coding variants (NCVs). To address the challenge of small sample size, the transfer learning model leverages both large-scale generic functional NCVs to improve the learning of low-level features and context-specific functional NCVs to learn high-level features toward the context-specific prediction task. By evaluating the deep transfer learning model on three MPRA datasets and 16 GWAS datasets, we demonstrate that the proposed model outperforms deep learning models without pretraining or retraining. In addition, the deep transfer learning model outperforms 18 existing computational methods in both MPRA and GWAS datasets.Availability and implementationhttps://github.com/lichen-lab/TLVar.Supplementary informationSupplementary data are available at Bioinformatics online.
Half a century of haemodialysis: two patient journeys
Authors: Pavlovic Drasko , Salehi Tania , Piccoli Giorgina B , Coates Patrick T 
Published: April 2022

ABSTRACT
The history of renal replacement therapy (RRT) for end-stage kidney disease (ESKD) started in 1960 and has reached, in these six decades, goals initially unforeseen. This report describes two patients who commenced dialysis at the age of 17 and 27, for 53 and 45 years, respectively, whereby the modality of RRT was mostly in the form of home haemodialysis. The history of these two patients, who started RRT in distant parts of the world, Australia and Croatia, highlights not only the advances made over time, to significantly delay the onset and reduce the morbidity and mortality associated with ESKD, but also underlines the importance of empowerment and commitment, added values in home haemodialysis.
CRISPR and cardiovascular diseases
Authors: Musunuru Kiran 
Published: April 2022

AbstractCRISPR technologies have progressed by leaps and bounds over the past decade, not only having a transformative effect on biomedical research but also yielding new therapies that are poised to enter the clinic. In this review, I give an overview of (i) the various CRISPR DNA-editing technologies, including standard nuclease gene editing, base editing, prime editing, and epigenome editing, (ii) their impact on cardiovascular basic science research, including animal models, human pluripotent stem cell models, and functional screens, and (iii) emerging therapeutic applications for patients with cardiovascular diseases, focusing on the examples of hypercholesterolaemia, transthyretin amyloidosis, and Duchenne muscular dystrophy.
Cellular interplay between cardiomyocytes and non-myocytes in diabetic cardiomyopathy
Authors: Phang Ren Jie , Ritchie Rebecca H , Hausenloy Derek J , Lees Jarmon G , Lim Shiang Y 
Published: April 2022

Abstract
Patients with Type 2 diabetes mellitus (T2DM) frequently exhibit a distinctive cardiac phenotype known as diabetic cardiomyopathy. Cardiac complications associated with T2DM include cardiac inflammation, hypertrophy, fibrosis, and diastolic dysfunction in the early stages of the disease, which can progress to systolic dysfunction and heart failure. Effective therapeutic options for diabetic cardiomyopathy are limited and often have conflicting results. The lack of effective treatments for diabetic cardiomyopathy is due in part, to our poor understanding of the disease development and progression, as well as a lack of robust and valid preclinical human models that can accurately recapitulate the pathophysiology of the human heart. In addition to cardiomyocytes, the heart contains a heterogeneous population of non-myocytes including fibroblasts, vascular cells, autonomic neurons, and immune cells. These cardiac non-myocytes play important roles in cardiac homeostasis and disease, yet the effect of hyperglycaemia and hyperlipidaemia on these cell types is often overlooked in preclinical models of diabetic cardiomyopathy. The advent of human-induced pluripotent stem cells provides a new paradigm in which to model diabetic cardiomyopathy as they can be differentiated into all cell types in the human heart. This review will discuss the roles of cardiac non-myocytes and their dynamic intercellular interactions in the pathogenesis of diabetic cardiomyopathy. We will also discuss the use of sodium-glucose cotransporter 2 inhibitors as a therapy for diabetic cardiomyopathy and their known impacts on non-myocytes. These developments will no doubt facilitate the discovery of novel treatment targets for preventing the onset and progression of diabetic cardiomyopathy.
The Long-Term Distributional and Welfare Effects of Covid-19 School Closures
Authors: Fuchs-Schündeln Nicola , Krueger Dirk , Ludwig Alexander , Popova Irina 
Published: April 2022

Abstract
Using a structural life-cycle model, we quantify the heterogeneous impact of school closures during the corona crisis on children affected at different ages and coming from households with different parental characteristics. In the model, public investment through schooling is combined with parental time and resource investments in the production of child human capital at different stages in the children’s development process. We quantitatively characterise the long-term consequences from a COVID-19-induced loss of schooling, and find average losses in the present discounted value of lifetime earnings of the affected children of $2.1\%$, as well as welfare losses equivalent to about $1.2\%$ of permanent consumption. Because of self-productivity in the human capital production function, younger children are hurt more by the school closures than older children. The negative impact of the crisis on children’s welfare is especially severe for those with parents with low educational attainment and low assets.
A framework for educating and empowering students by teaching about history and consequences of bias in STEM
Authors: Moreau Corrie S , Darby Andrea M , Demery Amelia-Juliette C , Arcila Hernández Lina M , Meaders Clara L 
Published: April 2022

Abstract
Racism and bias are pervasive in society—and science, technology, engineering, and mathematics (STEM) fields are not immune to these issues. It is imperative that we educate ourselves and our students about the history and consequences of this bias in STEM, investigate the research showing bias toward marginalized groups, understand how to interpret misuses of science in perpetuating bias, and identify advances and solutions to overcome racism and bias throughout our professional and personal lives. Here, we present one model for teaching a universal course for participants of all professional stages to address these issues and initiate solutions. As very few institutions require students to enroll in courses on racism and bias in STEM or even offer such courses, our curriculum could be used as a blueprint for implementation across institutions. Ultimately, institutions and academic disciplines can incorporate this important material with more region and/or discipline specific studies of bias.
Expression and structure of the Chlamydia trachomatis DksA ortholog
Authors: Mandel Cameron , Yang Hong , Buchko Garry W , Abendroth Jan , Grieshaber Nicole , Chiarelli Travis , Grieshaber Scott , Omsland Anders 
Published: April 2022

Abstract
Chlamydia trachomatis is a bacterial obligate intracellular parasite and a significant cause of human disease, including sexually transmitted infections and trachoma. The bacterial RNA polymerase-binding protein DksA is a transcription factor integral to the multicomponent bacterial stress response pathway known as the stringent response. The genome of C. trachomatis encodes a DksA ortholog (DksACt) that is maximally expressed at 15–20 h post infection, a time frame correlating with the onset of transition between the replicative reticulate body (RB) and infectious elementary body (EB) forms of the pathogen. Ectopic overexpression of DksACt in C. trachomatis prior to RB–EB transitions during infection of HeLa cells resulted in a 39.3% reduction in overall replication (yield) and a 49.6% reduction in recovered EBs. While the overall domain organization of DksACt is similar to the DksA ortholog of Escherichia coli (DksAEc), DksACt did not functionally complement DksAEc. Transcription of dksACt is regulated by tandem promoters, one of which also controls expression of nrdR, encoding a negative regulator of deoxyribonucleotide biosynthesis. The phenotype resulting from ectopic expression of DksACt and the correlation between dksACt and nrdR expression is consistent with a role for DksACt in the C. trachomatis developmental cycle.
Phosphorylation of HORMA-domain protein HTP-3 at Serine 285 is dispensable for crossover formation
Authors: Das Debabrata , Trivedi Shalini , Blazícková Jitka , Arur Swathi , Silva Nicola 
Published: April 2022

Abstract
Generation of functional gametes is accomplished through a multilayered and finely orchestrated succession of events during meiotic progression. In the Caenorhabditis elegans germline, the HORMA-domain-containing protein HTP-3 plays pivotal roles for the establishment of chromosome axes and the efficient induction of programmed DNA double-strand breaks, both of which are crucial for crossover formation. Double-strand breaks allow for accurate chromosome segregation during the first meiotic division and therefore are an essential requirement for the production of healthy gametes. Phosphorylation-dependent regulation of HORMAD protein plays important roles in controlling meiotic chromosome behavior. Here, we document a phospho-site in HTP-3 at Serine 285 that is constitutively phosphorylated during meiotic prophase I. pHTP-3S285 localization overlaps with panHTP-3 except in nuclei undergoing physiological apoptosis, in which pHTP-3 is absent. Surprisingly, we observed that phosphorylation of HTP-3 at S285 is independent of the canonical kinases that control meiotic progression in nematodes. During meiosis, the htp-3(S285A) mutant displays accelerated RAD-51 turnover, but no other meiotic abnormalities. Altogether, these data indicate that the Ser285 phosphorylation is independent of canonical meiotic protein kinases and does not regulate HTP-3-dependent meiotic processes. We propose a model wherein phosphorylation of HTP-3 occurs through noncanonical or redundant meiotic kinases and/or is likely redundant with additional phospho-sites for function in vivo.
Large-scale focusing joint inversion of gravity and magnetic data with Gramian constraint
Authors: Vatankhah Saeed , Renaut Rosemary A , Huang Xingguo , Mickus Kevin , Gharloghi Mostafa 
Published: April 2022

SUMMARYA fast algorithm for the large-scale joint inversion of gravity and magnetic data is developed. The algorithm uses a non-linear Gramian constraint to impose correlation between the density and susceptibility of the reconstructed models. The global objective function is formulated in the space of the weighted parameters, but the Gramian constraint is implemented in the original space, and the non-linear constraint is imposed using two separate Lagrange parameters, one for each model domain. It is significant that this combined approach, using the two spaces provides more similarity between the reconstructed models. Moreover, it is shown theoretically that the gradient for the use of the unweighted space is not a scalar multiple of that used for the weighted space, and hence cannot be accounted for by adjusting the Lagrange parameters. It is assumed that the measured data are obtained on a uniform grid and that a consistent regular discretization of the volume domain is imposed. Then, the sensitivity matrices exhibit a block-Toeplitz-Toeplitz-block structure for each depth layer of the model domain, and both forward and transpose operations with the matrices can be implemented efficiently using two dimensional fast Fourier transforms. This makes it feasible to solve for large scale problems with respect to both computational costs and memory demands, and to solve the non-linear problem by applying iterative methods that rely only on matrix–vector multiplications. As such, the use of the regularized reweighted conjugate gradient algorithm, in conjunction with the structure of the sensitivity matrices, leads to a fast methodology for large-scale joint inversion of geophysical data sets. Numerical simulations demonstrate that it is possible to apply a non-linear joint inversion algorithm, with Lp-norm stabilisers, for the reconstruction of large model domains on a standard laptop computer. It is demonstrated, that while the p = 1 choice provides sparse reconstructed solutions with sharp boundaries, it is also possible to use p = 2 in order to provide smooth and blurred models. The methodology is used for inverting gravity and magnetic data obtained over an area in northwest of Mesoproterozoic St Francois Terrane, southeast of Missouri, USA.
Turkey implementation model for the centre of excellence in healthcare services
Authors: Gökmen Kavak Demet , Can Ceren , İbrahim Halil Kayral , Çizmeci Şenel Figen 
Published: April 2022

Abstract
Today, in many countries, centres of excellence that can serve as a reference are determined in order to ensure easy access and quality healthcare services for patients whose diagnosis and treatment require advanced expertise, trained health human resource, experience, and high technology. Centres of excellence provide better health outcomes and equitable and easy access for patients. In addition, they provide very important advantages such as improving the quality of health services and health outcomes at the country level by increasing the provision of effective, efficient, high-quality health care services, increasing international competitiveness and health tourism potential in the field of health, and reducing catastrophic health expenditures. In 2018, a series of studies were initiated in cooperation with the Turkey Health Services Quality and Accreditation Institute and the Republic of Turkey Ministry of Health to identify centres of excellence in Turkey. The aim of this manuscript is to share the national implementation model that is being designed for Turkey for the studies of centers of excellence in health services.
The future of quality and accreditation surveys: Digital transformation and artificial intelligence
Authors: Cayirtepe Zuhal , Senel Figen Cizmeci 
Published: April 2022

AbstractAccreditation is documented and reported by the external evaluation organization that the health facility provides services at certain standards. While on-site survey practices are being carried out by external evaluation organizations, there has been a trend toward new survey approaches using digital technologies as a result of the research carried out to ensure efficiency in surveys as well as improved effectiveness. With the emergence of the Covid-19 epidemic, external evaluation organization in all sectors has been forced to work remotely and adopt digital technology. Shared remote survey experience results reported its benefits as also some problems. The increase in the adaptation of digital technologies in quality and accreditation surveys showed that the use of technology in the survey structure will develop further in the future. Can artificial intelligence technologies be the next digital technology that will be adapted to surveys? In addition to the benefits of using artificial intelligence technologies, there are potential problems to consider and some requirements for using them. external evaluation organizations must be prepared to develop their organizational capacity to ensure that quality and accreditation surveys are responsive to changing industry needs and must make the necessary investments to make the data, which is the most important source of digital technologies, accessible and usable.Graphical Abstract
Revealing the genetic basis of eyelid pigmentation in Hereford cattle
Authors: Jara Eugenio , Peñagaricano Francisco , Armstrong Eileen , Ciappesoni Gabriel , Iriarte Andrés , Navajas Elly Ana 
Published: April 2022

Abstract
Ocular squamous cell carcinoma and infectious keratoconjunctivitis are common ocular pathologies in Hereford cattle with considerable economic impact. Both pathologies have been associated with low eyelid pigmentation, and thus, genetic selection for higher eyelid pigmentation could reduce their incidence. The objective of the present study was to reveal the genetic basis of eyelid pigmentation in Hereford cattle. The analysis included a single-step genome-wide association study (ssGWAS) and a subsequent gene-set analysis in order to identify individual genes, genetic mechanisms, and biological pathways implicated in this trait. Data consisted of eyelid pigmentation records in 1,165 Hereford bulls and steers, visually assessed in five categories between 0% and 100%. Genotypic data for 774,660 single-nucleotide polymorphism markers were available for 886 animals with pigmentation records. Pedigree information of three generations of ancestors of animals with phenotype was considered in this study, with a total of 4,929 animals. Our analyses revealed that eyelid pigmentation is a moderately heritable trait, with heritability estimates around 0.41. The ssGWAS identified at least eight regions, located on BTA1, BTA3, BTA5, BTA14, BTA16, BTA18, BTA19, and BTA24, associated with eyelid pigmentation. These regions harbor genes that are directly implicated in melanocyte biology and skin pigmentation, such as ADCY8, PLD1, KITLG, and PRKCA. The gene-set analysis revealed several functional terms closely related to melanogenesis, such as positive regulation of melanocyte differentiation and regulation of ERK1 and ERK2 cascade. Overall, our findings provide evidence that eyelid pigmentation is a heritable trait influenced by many loci. Indeed, the ssGWAS detected several candidate genes that are directly implicated in melanocyte biology, including melanogenesis. This study contributes to a better understanding of the genetic and biological basis of eyelid pigmentation and presents novel information that could aid to design breeding strategies for reducing the incidence of ocular pathologies in cattle. Additional research on the genetic link between eyelid pigmentation and ocular pathologies is needed.
An Unusual Presentation of Pulmonary Edema During an Ice Dive at Altitude
Authors: Sanou Aliye Z , Murray Robert L , Hernandez Eli , Sherrier David 
Published: April 2022

ABSTRACT
Military diving operations occur in a wide range of austere environments, including high-altitude environments and cold weather environments; however, rarely do both conditions combine. Ice diving at altitude combines the physiologic risks of diving, a hypothermic environment, and a high-altitude environment all in one. Careful planning and consideration of the potential injuries and disease processes affiliated with the aforementioned physiologic risks must be considered. In this case report, we describe a Navy diver who became obtunded secondary to hypoxia during an ice dive at 2,987 m (9,800 ft) elevation and was subsequently diagnosed with high-altitude pulmonary edema. Further consideration of the environment, activities, and history does not make this a clear case, and swimming-induced pulmonary edema which physiologically possesses many overlaps with high-altitude pulmonary edema may have contributed or been the ultimate causal factor for the diver’s acute response.
Helium line emissivities for nebular astrophysics
Authors: Del Zanna G , Storey P J 
Published: April 2022

ABSTRACT
We present the results of several collisional-radiative models describing optically thin emissivities of the main lines in neutral helium formed by recombination, for a grid of electron temperatures and densities, typical of H ii regions and planetary nebulae. Accurate emissivities are required for example to measure the helium abundance in nebulae and as a consequence its primordial value. We compare our results with those obtained by previous models, finding significant differences, well above the target accuracy of 1 per cent. We discuss in some detail our chosen set of atomic rates and the differences with those adopted by previous models. The main differences lie in the treatment of electron and proton collision rates and we discuss which transitions are least sensitive to the choice of these rates and therefore best suited to high-precision abundance determinations. We have focused our comparisons on the case B approximation where only He and He+ are considered, but also present results of full models including the bare nuclei, photoexcitation, and photoionization, and either black-body or observed illuminating spectrum in the case of the Orion nebula, to indicate which spectral lines are affected by opacity. For those transitions, accurate radiative transfer calculations should be performed. We provide tables of emissivities for all transitions within n ≤ 5 and all those between the n ≤ 5 and n′ ≤ 25 states, in the log Te (K) = 103.0(0.1)4.6 and log Ne (cm−3) = 102(0.5)6 ranges, and a fortran code to interpolate to any Te, Ne within these ranges.
Atmosphere loss in oblique Super-Earth collisions
Authors: Denman Thomas R , Leinhardt Zoë M , Carter Philip J 
Published: April 2022

ABSTRACT
Using smoothed particle hydrodynamics we model giant impacts of Super-Earth mass rocky planets between an atmosphere-less projectile and an atmosphere-rich target. In this work, we present results from head-on to grazing collisions. The results of the simulations fall into two broad categories: (1) one main post-collision remnant containing material from target and projectile; (2) two main post-collision remnants resulting from ‘erosive hit-and-run’ collisions. All collisions removed at least some of the target atmosphere, in contrast to the idealized hit-and-run definition in which the target mass is unchanged. We find that the boundary between ‘hit-and-run’ collisions and collisions that result in the projectile and target accreting/merging to be strongly correlated with the mutual escape velocity at the predicted point of closest approach. Our work shows that it is very unlikely for a single giant impact to remove all of the atmosphere. For all the atmosphere to be removed, head-on impacts require roughly the energy of catastrophic disruption (i.e. permanent ejection of half the total system mass) and result in significant erosion of the mantle. We show that higher impact angle collisions, which are more common, are less efficient at atmosphere removal than head-on collisions. Therefore, single collisions that remove all the atmosphere without substantially disrupting the planet are not expected during planet formation.