bluuebunny/crossref_metadata_2025_split huggingface dataset:
Airpart: interpretable statistical models for analyzing allelic imbalance in single-cell datasets
Authors: Mu Wancen , Sarkar Hirak , Srivastava Avi , Choi Kwangbom , Patro Rob , Love Michael I 
Published: April 2022

AbstractMotivationAllelic expression analysis aids in detection of cis-regulatory mechanisms of genetic variation, which produce allelic imbalance (AI) in heterozygotes. Measuring AI in bulk data lacking time or spatial resolution has the limitation that cell-type-specific (CTS), spatial- or time-dependent AI signals may be dampened or not detected.ResultsWe introduce a statistical method airpart for identifying differential CTS AI from single-cell RNA-sequencing data, or dynamics AI from other spatially or time-resolved datasets. airpart outputs discrete partitions of data, pointing to groups of genes and cells under common mechanisms of cis-genetic regulation. In order to account for low counts in single-cell data, our method uses a Generalized Fused Lasso with Binomial likelihood for partitioning groups of cells by AI signal, and a hierarchical Bayesian model for AI statistical inference. In simulation, airpart accurately detected partitions of cell types by their AI and had lower Root Mean Square Error (RMSE) of allelic ratio estimates than existing methods. In real data, airpart identified differential allelic imbalance patterns across cell states and could be used to define trends of AI signal over spatial or time axes.Availability and implementationThe airpart package is available as an R/Bioconductor package at https://bioconductor.org/packages/airpart.Supplementary informationSupplementary data are available at Bioinformatics online.
Autoimmune connective tissue diseases and aortic valve replacement outcomes: a population-based study
Authors: Gad Mohamed M. , Lichtman Devora , Saad Anas M. , Isogai Toshiaki , Bansal Agam , Abdallah Mouin S. , Roselli Eric , Chatterjee Soumya , Reed Grant W. , Kapadia Samir R. , Menon Venu , Wassif Heba 
Published: April 2022

Abstract

Aims
Patients with autoimmune connective tissue diseases (CTDs) have a high burden of valvular heart disease and are often thought of as high surgical risk patients.

Methods and results
Patients undergoing aortic valve replacement (AVR) were identified in the Nationwide Readmissions Database between January 2012 and December 2018. Patients with a history of systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, mixed C, Sjögren syndrome, polymyositis, and dermatomyositis were included in the CTD cohort. Patients undergoing coronary artery bypass grafting concomitantly with AVR were excluded. A total of 569 600 hospitalizations were included, of which16 531 (2.9%) had CTD. CTD patients were more likely to be females, with higher rates of heart failure, pulmonary hypertension, and more likely to be insured by Medicare. CTD patients had lower mortality than non-CTD patients [odds ratio (OR) 0.66; 95% confidence interval (CI): 0.59–0.74] and stroke [OR 0.87; 95% (CI): 0.79–0.97]. CTD patients undergoing SAVR had lower mortality [OR 0.69; 95% (CI): 0.60–0.80] and stroke [OR 0.86; 95% (CI): 0.75–0.98). CTD patients undergoing TAVR had lower mortality outcomes [OR 0.67; 95% (CI): 0.56–0.80]; however, they had comparable stroke outcomes [OR 0.97; 95% (CI): 0.83–1.13, P = 0.69].

Conclusions
Outcomes for patients with CTD requiring AVR are not inferior to their non-CTD counterparts. A comprehensive heart team selection of patients undergoing AVR approaches should place CTD history under consideration; however, pre-existing CTD should not be prohibitive of AVR interventions.
Progress Toward Digital Transformation in an Evolving Post-Acute Landscape
Authors: Cross Dori A , Adler-Milstein Julia 
Published: April 2022

AbstractDigitization has been a central pillar of structural investments to promote organizational capacity for transformation, and yet skilled nursing facilities (SNFs) and other post-acute providers have been excluded and/or delayed in benefitting from the past decade of substantial public and private-sector investment in information technology (IT). These settings have limited internal capacity and resources to invest in digital capabilities on their own, propagating a limited infrastructure that may only further sideline SNFs and their role in an ever-evolving health care landscape that needs to be focused on age-friendly, high-value care. Meaningful progress will require continuous refinement of supportive policy, financial investment, and scalable organizational best practices specific to the SNF context. In this essay, we lay out an action agenda to move from age-agnostic to age-friendly digital transformation. Key to the value proposition of these efforts is a focus on interoperability—the seamless exchange of electronic health information across settings that is critical for care coordination and for providers to have the information they need to make safe and appropriate care decisions. Interoperability is not synonymous with digital transformation, but a foundational building block for its potential. We characterize the current state of digitization in SNFs in the context of key health IT policy advancements over the past decade, identifying ongoing and emergent policy work where the digitization needs of SNFs and other post-acute settings can be better addressed. We also discuss accompanying implementation considerations and strategies for optimally translating policy efforts into impactful practice change across an ever-evolving post-acute landscape. Acting on these insights at the policy and practice level provides cautious optimism that nursing home care—and care for older adults across the care continuum—may benefit more equitably from the promise of future digitization.
Genetic architecture of RNA editing regulation in Alzheimer’s disease across diverse ancestral populations
Authors: Gardner Olivia K , Van Booven Derek , Wang Lily , Gu Tianjie , Hofmann Natalia K , Whitehead Patrice L , Nuytemans Karen , Hamilton-Nelson Kara L , Adams Larry D , Starks Takiyah D , Cuccaro Michael L , Martin Eden R , Vance Jeffery M , Bush William S , Byrd Goldie S , Haines Jonathan L , Beecham Gary W , Pericak-Vance Margaret A , Griswold Anthony J 
Published: April 2022

AbstractMost Alzheimer’s disease (AD)-associated genetic variants do not change protein coding sequence and thus likely exert their effects through regulatory mechanisms. RNA editing, the post-transcriptional modification of RNA bases, is a regulatory feature that is altered in AD patients that differs across ancestral backgrounds. Editing QTLs (edQTLs) are DNA variants that influence the level of RNA editing at a specific site. To study the relationship of DNA variants genome-wide, and particularly in AD-associated loci, with RNA editing, we performed edQTL analyses in self-reported individuals of African American (AF) or White (EU) race with corresponding global genetic ancestry averaging 82.2% African ancestry (AF) and 96.8% European global ancestry (EU) in the two groups, respectively. We used whole-genome genotyping array and RNA sequencing data from peripheral blood of 216 AD cases and 212 age-matched, cognitively intact controls. We identified 2144 edQTLs in AF and 3579 in EU, of which 1236 were found in both groups. Among these, edQTLs in linkage disequilibrium (r2 &gt; 0.5) with AD-associated genetic variants in the SORL1, SPI1 and HLA-DRB1 loci were associated with sites that were differentially edited between AD cases and controls. While there is some shared RNA editing regulatory architecture, most edQTLs had distinct effects on the rate of RNA editing in different ancestral populations suggesting a complex architecture of RNA editing regulation. Altered RNA editing may be one possible mechanism for the functional effect of AD-associated variants and may contribute to observed differences in the genetic etiology of AD between ancestries.
mRNA Vaccine Effectiveness Against Coronavirus Disease 2019 Hospitalization Among Solid Organ Transplant Recipients
Authors: Kwon Jennie H , Tenforde Mark W , Gaglani Manjusha , Talbot H Keipp , Ginde Adit A , McNeal Tresa , Ghamande Shekhar , Douin David J , Casey Jonathan D , Mohr Nicholas M , Zepeski Anne , Shapiro Nathan I , Gibbs Kevin W , Files D Clark , Hager David N , Shehu Arber , Prekker Matthew E , Caspers Sean D , Exline Matthew C , Botros Mena , Gong Michelle N , Li Alex , Mohamed Amira , Johnson Nicholas J , Srinivasan Vasisht , Steingrub Jay S , Peltan Ithan D , Brown Samuel M , Martin Emily T , Khan Akram , Hough Catherine L , Busse Laurence W , Duggal Abhijit , Wilson Jennifer G , Perez Cynthia , Chang Steven Y , Mallow Christopher , Rovinski Randal , Babcock Hilary M , Lauring Adam S , Felley Laura , Halasa Natasha , Chappell James D , Grijalva Carlos G , Rice Todd W , Womack Kelsey N , Lindsell Christopher J , Hart Kimberly W , Baughman Adrienne , Olson Samantha M , Schrag Stephanie , Kobayashi Miwako , Verani Jennifer R , Patel Manish M , Self Wesley H 
Published: April 2022

AbstractBackgroundThe study objective was to evaluate 2- and 3-dose coronavirus disease 2019 (COVID-19) mRNA vaccine effectiveness (VE) in preventing COVID-19 hospitalization among adult solid organ transplant (SOT) recipients.MethodsWe conducted a 21-site case-control analysis of 10 425 adults hospitalized in March to December 2021. Cases were hospitalized with COVID-19; controls were hospitalized for an alternative diagnosis (severe acute respiratory syndrome coronavirus 2-negative). Participants were classified as follows: SOT recipient (n = 440), other immunocompromising condition (n = 1684), or immunocompetent (n = 8301). The VE against COVID-19-associated hospitalization was calculated as 1-adjusted odds ratio of prior vaccination among cases compared with controls.ResultsAmong SOT recipients, VE was 29% (95% confidence interval [CI], −19% to 58%) for 2 doses and 77% (95% CI, 48% to 90%) for 3 doses. Among patients with other immunocompromising conditions, VE was 72% (95% CI, 64% to 79%) for 2 doses and 92% (95% CI, 85% to 95%) for 3 doses. Among immunocompetent patients, VE was 88% (95% CI, 87% to 90%) for 2 doses and 96% (95% CI, 83% to 99%) for 3 doses.ConclusionsEffectiveness of COVID-19 mRNA vaccines was lower for SOT recipients than immunocompetent adults and those with other immunocompromising conditions. Among SOT recipients, vaccination with 3 doses of an mRNA vaccine led to substantially greater protection than 2 doses.
Curating Vraca Memorial Park: Activism, Counter-Memory, and Counter-Politics
Authors: Cole Lydia C 
Published: April 2022

Abstract
In 2005, officials designated Vraca Memorial Park in Sarajevo, Bosnia–Herzegovina, as a national monument. However, official disputes over responsibility for curating stalled progress on the site's restoration. In response, activists initiated two campaigns to save and restore Vraca: “Let's Save and Restore Vraca Memorial Park” and a campaign to restore the vandalized monument Ženi borac (woman fighter). Challenging the slide toward ruination, activist curators produced the site as a lively space of politics. Contributing to international political sociology scholarship on memory and its curation, the article develops the concept of activist curatorship through sustained engagement with activist practices of clearing, cleaning, and re-curating at the site between 2005 and 2020. Activist curation is an evolving and open-ended counter-memorial practice engaged by variously situated curators, both ordinary people and museum professionals. At Vraca, activist curating is held together through an alternative mnemonic community that mobilizes the legacy of anti-fascism, while curation is central to how activist interventions endure. Activist curators create space for political commentary on the past and open space for alternative forms of political community to proliferate, those which reach beyond the fragmentation of political, social, and memorial life in post-Dayton Bosnia–Herzegovina.
CRISPR Knockouts of pmela and pmelb Engineered a Golden Tilapia by Regulating Relative Pigment Cell Abundance
Authors: Wang Chenxu , Xu Jia , Kocher Thomas D , Li Minghui , Wang Deshou 
Published: April 2022

Abstract
Premelanosome protein (pmel) is a key gene for melanogenesis. Mutations in this gene are responsible for white plumage in chicken, but its role in pigmentation of fish remains to be demonstrated. In this study, we found that most fishes have 2 pmel genes arising from the teleost-specific whole-genome duplication. Both pmela and pmelb were expressed at high levels in the eyes and skin of Nile tilapia. We mutated both genes in tilapia using CRISPR/Cas9. Homozygous mutation of pmela resulted in yellowish body color with weak vertical bars and a hypopigmented retinal pigment epithelium (RPE) due to significantly reduced number and size of melanophores. In contrast, we observed an increased number and size of xanthophores in mutants compared to wild-type fish. Homozygous mutation of pmelb resulted in a similar, but milder phenotype than pmela−/− mutants. Double mutation of pmela and pmelb resulted in loss of additional melanophores compared to the pmela−/− mutants, and also an increase in the number and size of xanthophores, producing a golden body color. The RPE pigmentation of pmela−/−;pmelb−/− was similar to pmela−/− mutants, with much less pigmentation than pmelb−/− mutants and wild-type fish. Taken together, our results indicate that, although both pmel genes are important for the formation of body color in tilapia, pmela plays a more important role than pmelb. To our knowledge, this is the first report on mutation of pmelb or both pmela;pmelb in fish. Studies on these mutants suggest new strategies for breeding golden tilapia, and also provide a new model for studies of pmel function in vertebrates.
The genetic architecture of flowering time changes in pea from wild to crop
Authors: Williams Owen , Vander Schoor Jacqueline K , Butler Jakob B , Ridge Stephen , Sussmilch Frances C , Hecht Valerie F G , Weller James L 
Published: April 2022

Abstract
Change in phenology has been an important component in crop evolution, and selection for earlier flowering through a reduction in environmental sensitivity has helped broaden adaptation in many species. Natural variation for flowering in domesticated pea (Pisum sativum L.) has been noted and studied for decades, but there has been no clear account of change relative to its wild progenitor. Here we examined the genetic control of differences in flowering time between wild P. sativum ssp. humile and a typical late-flowering photoperiodic P. s. sativum accession in a recombinant inbred population under long and short photoperiods. Our results confirm the importance of the major photoperiod sensitivity locus Hr/PsELF3a and identify two other loci on chromosomes 1 (DTF1) and 3 (DTF3) that contribute to earlier flowering in the domesticated line under both photoperiods. The domesticated allele at a fourth locus on chromosome 6 (DTF6) delays flowering under long days only. Map positions, inheritance patterns, and expression analyses in near-isogenic comparisons imply that DTF1, DTF3, and DTF6 represent gain-of-function alleles of the florigen/antiflorigen genes FTa3, FTa1, and TFL1c/LF, respectively. This echoes similar variation in chickpea and lentil, and suggests a conserved route to reduced photoperiod sensitivity and early phenology in temperate pulses.
Fructan oligosaccharide priming alters apoplastic sugar dynamics and improves resistance againstBotrytis cinereain chicory
Authors: Versluys Maxime , Toksoy Öner Ebru , Van den Ende Wim 
Published: April 2022

AbstractCarbohydrates such as fructans can be involved in priming or defence stimulation, and hence potentially provide new strategies for crop protection against biotic stress. Chicory (Cichorium intybus) is a model plant for fructan research and is a crop with many known health benefits. Using the chicory–Botrytis cinerea pathosystem, we tested the effectiveness of fructan-induced immunity, focussing on different plant and microbial fructans. Sugar dynamics were followed after priming and subsequent pathogen infection. Our results indicated that many higher plants might detect extracellular levan oligosaccharides (LOS) of microbial origin, while chicory also detects extracellular small inulin-type fructooligosaccharides (FOS) of endogenous origin, thus differing from the findings of previous fructan priming studies. No clear positive effects were observed for inulin or mixed-type fructans. An elicitor-specific burst of reactive oxygen species was observed for sulfated LOS, while FOS and LOS both behaved as genuine priming agents. In addition, a direct antifungal effect was observed for sulfated LOS. Intriguingly, LOS priming led to a temporary increase in apoplastic sugar concentrations, mainly glucose, which could trigger downstream responses. Total sugar and starch contents in total extracts of LOS-primed leaves were higher after leaf detachment, indicating they could maintain their metabolic activity. Our results indicate the importance of balancing intra- and extracellular sugar levels (osmotic balance) in the context of ‘sweet immunity’ pathways.
Phenological optimization of late reproductive phase for raising wheat yield potential in irrigated mega-environments
Authors: Hu Pengcheng , Chapman Scott C , Sukumaran Sivakumar , Reynolds Matthew , Zheng Bangyou 
Published: April 2022

Abstract
Increasing grain number through fine-tuning duration of the late reproductive phase (LRP; terminal spikelet to anthesis) without altering anthesis time has been proposed as a genetic strategy to increase yield potential (YP) of wheat. Here we conducted a modelling analysis to evaluate the potential of fine-tuning LRP in raising YP in irrigated mega-environments. Using the known optimal anthesis and sowing date of current elite benchmark genotypes, we applied a gene-based phenology model for long-term simulations of phenological stages and yield-related variables of all potential germplasm with the same duration to anthesis as the benchmark genotypes. These diverse genotypes had the same duration to anthesis but varying LRP duration. Lengthening LRP increased YP and harvest index by increasing grain number to some extent and an excessively long LRP reduced YP due to reduced time for canopy construction for high biomass production of pre-anthesis phase. The current elite genotypes could have their LRP extended for higher YP in most sites. Genotypes with a ratio of the duration of LRP to pre-anthesis phase of about 0.42 ensured high yields (≥95% of YP) with their optimal sowing and anthesis dates. Optimization of intermediate growth stages could be further evaluated in breeding programmes to improve YP.
Effects of high temperature and nitrogen availability on the growth and composition of the marine diatomChaetoceros pseudocurvisetus
Authors: Flanjak Lana , Vrana Ivna , Cvitešić Kušan Ana , Godrijan Jelena , Novak Tihana , Penezić Abra , Gašparović Blaženka 
Published: April 2022

AbstractThe assimilation of inorganic nutrients by phytoplankton strongly depends on environmental conditions such as the availability of nitrogen and temperature, especially warming. The acclimation or adaptation of different species to such changes remains poorly understood. Here, we used a multimethod approach to study the viability and physiological and biochemical responses of the marine diatom Chaetoceros pseudocurvisetus to different temperatures (15, 25, and 30 °C) and different N:P ratios. Nitrogen limitation had a greater effect than high temperature on cell growth and reproduction, leading to a marked elongation of setae, decreased phosphorus assimilation, increased lipid accumulation, and decreased protein synthesis. The elongation of setae observed under these conditions may serve to increase the surface area available for the uptake of inorganic and/or organic nitrogen. In contrast, high temperatures (30 °C) had a stronger effect than nitrogen deficiency on cell death, nitrogen assimilation, chlorophyll a accumulation, the cessation of setae formation, and cell lipid remodelling. Significant changes in thylakoid lipids were observed in cells maintained at 30 °C, with increased levels of digalactosyldiacylglycerol and sulfoquinovosyldiacylglycerol. These changes may be explained by the role of galactolipids in thylakoid membrane stabilization during heat stress.
Down-regulation of PvSAMS impairs S-adenosyl-L-methionine and lignin biosynthesis, and improves cell wall digestibility in switchgrass
Authors: Li Yu , Xiong Wangdan , He Feng , Qi Tianxiong , Sun Zhen , Liu Yuchen , Bai Shiqie , Wang Honglun , Wu Zhenying , Fu Chunxiang 
Published: April 2022

Abstract
S-adenosyl- l-methionine (SAM) is the methyl donor involved in the biosynthesis of guaiacyl (G) and syringyl (S) lignins in vascular plants. SAM is synthesized from methionine through the catalysis of the enzyme S-adenosylmethionine synthase (SAMS). However, the detailed function of SAMS in lignin biosynthesis has not been widely investigated in plants, particularly in monocot species. In this study, we identified PvSAMS genes from switchgrass (Panicum virgatum L.), an important dual-purpose fodder and biofuel crop, and generated numerous transgenic switchgrass lines through PvSAMS RNA interference technology. Down-regulation of PvSAMS reduced the contents of SAM, G-lignins, and S-lignins in the transgenic switchgrass. The methionine and glucoside derivatives of caffeoyl alcohol were found to accumulate in the transgenic plants. Moreover, down-regulation of PvSAMS in switchgrass resulted in brownish stems associated with reduced lignin content and improved cell wall digestibility. Furthermore, transcriptomic analysis revealed that most sulfur deficiency-responsive genes were differentially expressed in the transgenic switchgrass, leading to a significant increase in total sulfur content; thus implying an important role of SAMS in the methionine cycle, lignin biosynthesis, and sulfur assimilation. Taken together, our results suggest that SAMS is a valuable target in lignin manipulation, and that manipulation of PvSAMS can simultaneously regulate the biosynthesis of SAM and methylated monolignols in switchgrass.
Effect of AGN on the morphological properties of their host galaxies in the local Universe
Authors: Getachew-Woreta Tilahun , Pović Mirjana , Masegosa Josefa , Perea Jaime , Beyoro-Amado Zeleke , Márquez Isabel 
Published: April 2022

ABSTRACT
The morphological classification of active galaxies may be affected by the presence of active galactic nuclei (AGNs). In this paper, we provide the most detailed analysis on how different AGN contributions, from 5 per cent to 75 per cent, to the total optical light may affect six commonly used morphological parameters and the final classification of AGN host galaxies at z ∼ 0. We used a local sample of &gt; 2000 visually classified non-active galaxies, to quantify how the contribution of a bright nuclear point source of different intensity could affect morphological parameters such as: asymmetry, Abraham concentration index, Gini, M20 moment of light, smoothness, and Conselice-Bershady concentration index. We found that most of the morphological parameters are affected by AGN contributions above 25 per cent, with late-type galaxies being more affected than early-types. We found that Gini, Abraham concentration index, and asymmetry are the most stable parameters even for AGN contributions above 25 per cent, in comparison to Conselice-Bershady concentration index and M20 moment of light. Smoothness parameter shall be avoided when classifying AGN host galaxies, or at least it shall be used simultaneously in combination with several other parameters.