bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of Potential and Actual Living Kidney Donors: A Single-center Experience
Authors: Cholin Liza K. , Schold Jesse D. , Arrigain Susana , Poggio Emilio D. , Sedor John R. , O’Toole John F. , Augustine Joshua J. , Wee Alvin C. , Huml Anne M. 
Published: December 2022

Background.
There are limited data and no national capture of barriers associated with initiating and completing the donation process for potential living kidney donors (LKDs).

Methods.
We performed a retrospective analysis of 3001 intake forms completed by prospective LKDs from 2016 to 2019 at a single transplant center. We analyzed data from all potential donors who completed the intake until they became ineligible or withdrew or donation was complete. We used univariate and multivariate models to evaluate independent factors associated with donation at various stages in the donation process.

Results.
The donation process was deconstructed into 5 steps: intake form, immunologic compatibility testing, clinic evaluation, selection committee review, and donation. The highest percentage of potential donors dropped out after completing the intake form, primarily because of not responding to the follow-up phone call (22.6%). Of 455 potential LKDs that completed immunologic compatibility testing, 36% were ABO or crossmatch incompatible. One-hundred eighty-eight (7.5%) of all LKD applicants reached donation, the majority of whom were White (91.0%) and female (63.8%).

Conclusions.
A minority of LKD applicants make it to donation. Our ability to track all potential LKDs from the initial touch point to the transplant center will help us develop interventions to address barriers to a successful donation.
Early Detection of Epstein-Barr Virus as a Risk Factor for Chronic High Epstein-Barr Viral Load Carriage at a Living-donor–dominant Pediatric Liver Transplantation Center
Authors: Yamada Masaki , Fukuda Akinari , Ogura Miyuki , Shimizu Seiichi , Uchida Hajime , Yanagi Yusuke , Ishikawa Yuriko , Sakamoto Seisuke , Kasahara Mureo , Imadome Ken-Ichi 
Published: December 2022

Background.
Epstein-Barr virus (EBV) infection and posttransplant lymphoproliferative disorders (PTLDs) after pediatric liver transplantation (LT) account for significant morbidity and mortality. Knowledge of EBV kinetics, epidemiology, and outcomes among pediatric living-donor LT cases is largely lacking. This study aims to provide clinical information related to EBV infection, chronic high EBV load (CHL) carriage, and PTLD at a living-donor–dominant pediatric LT center.

Methods.
A total of 5827 EBV load measurements from 394 LT recipients fulfilling inclusion criteria and their clinical data were analyzed. EBV loads >1000 copies/μg DNA (742 IU/μg DNA) were considered “high,” and CHL was defined by persistence >6 mo.

Results.
The highlighted results were as follows: (1) 94% of recipients underwent living-donor LT; (2) 80% of EBV seronegative recipients developed first EBV infection <2 y post-LT, and their EBV loads were consistently higher than those of seropositive recipients within <3 y post-LT but did not differ thereafter; (3) 61 (15%) recipients met CHL criteria, but none developed PTLD; (4) age <5 y, cytomegalovirus seronegative donors, and early development of EBV DNAemia <6 mo post-LT were independent risk factors for CHL; (5) the incidence of rejections after 1-y post-LT was comparably low among CHL carriers whose immunosuppression was minimized.

Conclusions.
Early detection of EBV following LT and CMV seronegative donors would facilitate risk stratification to prevent PTLD while titrating immunosuppression among pediatric LT recipients.
Humoral Responses in the Omicron Era Following 3-Dose SARS-CoV-2 Vaccine Series in Kidney Transplant Recipients
Authors: McEvoy Caitríona M. , Hu Queenie , Abe Kento T. , Yau Kevin , Oliver Matthew J. , Levin Adeera , Gingras Anne-Claude , Hladunewich Michelle A. , Yuen Darren A. 
Published: December 2022

Background
Kidney transplant recipients (KTRs) have a diminished response to SARS-CoV-2 vaccination compared with immunocompetent individuals. Deeper understanding of antibody responses in KTRs following third-dose vaccination would enable identification of those who remain unprotected against Omicron.

Methods
We profiled antibody responses in KTRs pre- and at 1 and 3 mo post-third-dose SARS-CoV-2 mRNA-based vaccine. Binding antibody levels were determined by ELISA. Neutralization against wild type, Beta, Delta, and Omicron (BA.1) variants was determined using a SARS-CoV-2 spike-pseudotyped lentivirus assay.

Results
Forty-four KTRs were analyzed at 1 and 3 mo (n = 26) post-third dose. At 1 mo, the proportion of participants with a robust antibody response had increased significantly from baseline, but Omicron-specific neutralizing antibodies were detected in just 45% of KTRs. Median binding antibody levels declined at 3 mo, but the proportion of KTRs with a robust antibody response was unchanged; 38.5% KTRs maintained Omicron-specific neutralization at 3 mo. No clinical variables were significantly associated with Omicron-neutralizing antibodies, but antireceptor binding domain titers appeared to identify those with Omicron-specific neutralizing capacity.

Conclusions.
Over 50% of KTRs lack Omicron-specific neutralization capacity 1 mo post-third mRNA-vaccine dose. Antibody levels of responders were well preserved at 3 mo. Anti receptor binding domain antibody titers may identify patients with a detectable Omicron-neutralizing antibody response.
Isolation and Characterization of Porcine Endocardial Endothelial Cells
Authors: Brown Kathleen N. , Phan Hong Kim T. , Jui Elysa L. , Kang Marci K. , Connell Jennifer P. , Keswani Sundeep G. , Grande-Allen K. Jane 
Published: December 2022

AbstractThe heart contains six different types of endothelial cells, each with a unique function. We sought to characterize the endocardial endothelial cells (EECs), which line the chambers of the heart. EECs are relatively understudied, yet their dysregulation can lead to various cardiac pathologies. Due to the lack of commercial availability of this cell line, we developed a protocol for isolating EECs from porcine hearts and detailed our methodology for establishing populations of EECs through cell sorting. Additionally, we compared the EEC phenotype and fundamental behaviors to a well-studied endothelial cell line, human umbilical vein endothelial cells (HUVECs). The EECs were slightly smaller than HUVECs, and they stained positively for classic endothelial phenotypic markers such as CD31, von Willebrand Factor, and vascular endothelial (VE) cadherin. The EECs proliferated more quickly than HUVECs, yet migrated more slowly to cover a scratch wound assay. Finally, the EECs maintained their robust endothelial phenotype (expression of CD31) through more than a dozen passages. In contrast, the HUVECs showed significantly reduced CD31 expression in later passages. These important phenotypic differences between EECs and HUVECs highlight the need for researchers to utilize the most relevant cell lines when studying or modeling a disease of interest.Impact statementMany researchers model cardiovascular disease via tissue engineering to determine disease etiology on the cellular and molecular level. However, researchers usually rely on commercially-available cell lines, which can result in utilizing cells that are not specific to the region of the heart being modeled and could lead to incorrect conclusions. By providing a detailed protocol for isolating and purifying endocardial endothelial cells, we are enabling other researchers to access this cell line and model cardiovascular disease states more accurately.
Cost-effective hybrid long-short read assembly delineates alternative GC-richStreptomyceschassis for natural product discovery
Authors: Heng Elena , Tan Lee Ling , Tay Dillon W. P. , Lim Yee Hwee , Yang Lay-Kien , Seow Deborah C.S. , Leong Chung Yan , Ng Veronica , Ng Siew Bee , Kanagasundaram Yoganathan , Wong Fong Tian , Koduru Lokanand 
Published: December 2022

AbstractWith the advent of rapid automatedin silicoidentification of biosynthetic gene clusters (BGCs), genomics presents vast opportunities to accelerate natural product (NP) discovery. However, prolific NP producers,Streptomyces, are exceptionally GC-rich (>80%) and highly repetitive within BGCs. These pose challenges in sequencing and high-quality genome assembly which are currently circumventedviaintensive sequencing. Here, we outline a more cost-effective workflow using multiplex Illumina and Oxford Nanopore sequencing with hybrid long-short read assembly algorithms to generate high quality genomes. Our protocol involves subjecting long read-derived assemblies to up to 4 rounds of polishing with short reads to yield accurate BGC predictions. We successfully sequenced and assembled 8 GC-richStreptomycesgenomes whose lengths range from 7.1 to 12.1 Mb at an average N50 of 5.9 Mb. Taxonomic analysis revealed previous misrepresentation among these strains and allowed us to propose a potentially new species,Streptomyces sydneybrenneri. Further comprehensive characterization of their biosynthetic, pan-genomic and antibiotic resistance features especially for molecules derived from type I polyketide synthase (PKS) BGCs reflected their potential as NP chassis. Thus, the genome assemblies and insights presented here are envisioned to serve as gateway for the scientific community to expand their avenues in NP discovery.Graphic abstractSchematic of hybrid long- and short read assembly workflow for genome sequencing of GC-richStreptomyces. Boxes shaded blue and grey correspond to experimental andin silicoworkflows, respectively.HighlightsA cost-effective genome sequencing approach for GC-richStreptomycesis presentedHybrid assembly improves BGC annotation and identificationA new species,Streptomyces sydneybrenneri, identified by taxonomic analysisGenomes of 8Streptomycesspecies are reported and analysed in this study
Embodied Latch Mechanism of the Mandible to Power at an Ultrahigh Speed in the Trap-jaw AntsOdontomachus kuroiwae
Authors: Aonuma Hitoshi , Naniwa Keisuke , Sugimoto Yasuhiro , Ohkawara Kyohsuke , Kagaya Katsushi 
Published: December 2022

AbstractRapid movements of limbs and appendages, faster than those produced by simple muscle contraction alone, are generated through mechanical networks consisting of springs and latches. The latch plays a central role in these spring-loaded mechanisms, but the structural details of the latch are not always known. The mandibles of the trapjaw antOdontomachus kuroiwaecloses the mandible extremely quickly to capture prey or to perform mandible-powered defensive jumps to avoid potential threats. The jump is mediated by a mechanical spring and latch system embodied in the mandible. An ant can strike the tip of the mandible onto the surface of an obstacle (prey, predator, or ground) in order to bounce its body away from potential threats. The angular velocity of the closing mandible was 2.3×104rad/s. Latching of the joint is a key mechanism to aid the storage of energy required to power the ballistic movements of the mandibles. We have identified the fine structure of two latch systems on the mandible forming a ‘balljoint’ using an X-ray micro-computational tomography system (X-ray micro-CT) and X-ray live imaging with a synchrotron. Here we describe the surface of the inner section of the socket and a projection on the lip of the ball. The X-ray live imaging and movements of the 3D model show that the ball with a detent ridge slipped into a socket and over the socket ridge before snapping back at the groove edge. Our results give insight into the complex spring-latch systems that underpin ultra-fast movements in biological systems.
Bi-directional Mendelian randomization and multi-phenotype GWAS show causality and shared pathophysiology between depression and type 2 diabetes
Authors: Maina Jared G , Balkhiyarova Zhanna , Nouwen Arie , Pupko Igor , Ulrich Anna , Boissel Mathilde , Bonnefond Amélie , Froguel Philippe , Khamis Amna , Prokopenko Inga , Kaakinen Marika 
Published: December 2022

AbstractOBJECTIVEDepression is a common co-morbidity of type 2 diabetes. However, the causality and underlying mechanisms remain unclear.RESEARCH DESIGN AND METHODSWe applied bi-directional Mendelian randomization (MR) to assess causality between type 2 diabetes and self-reported depression. Using the UK biobank, we performed 1) GWAS, separately, and 2) multi-phenotype GWAS (MP-GWAS) of type 2 diabetes (cases=19,344, controls=463,641) and depression, using two depression definitions–clinically diagnosed major depressive disorder (MDD, cases=5,262, controls=86,275) and self-reported depressive symptoms (PHQ-9, n=153,079). The FinnGen study was used for replication for MDD (n=23,424) and type 2 diabetes (n=32,469). Based on the results, we analyzed expression quantitative trait loci (eQTL) data from public databases to identify target genes in relevant tissues.RESULTSMR demonstrated a significant causal effect of depression on type 2 diabetes (OR=1.18[1.06-1.32], p=0.0024), but not in the reverse direction. GWAS of type 2 diabetes and depressive symptoms did not identify any shared loci between them, whereas MP-GWAS identified seven shared loci mapped toTCF7L2, CDKAL1, IGF2BP2, SPRY2, CCND2-AS1, IRS1, CDKN2B-AS1. MDD did not yield genome-wide significant loci in either GWAS or MP-GWAS. We found that most MP-GWASlocihad an eQTL, including SNPs implicating the cell cycle geneCCND2in pancreatic islets and brain, and key insulin signaling geneIRS1in adipose tissue, suggesting a multi-tissue and pleiotropic underlying mechanism.CONCLUSIONOur study reveals the complexity in the depression-diabetes relationship and our results have important implications for a more efficient prevention of type 2 diabetes from early adulthood when depressive symptoms usually occur.
Glycoprotein Acetyls and Depression: testing for directionality and potential causality using longitudinal data and Mendelian randomization analyses
Authors: Crick Daisy C P , Sanderson Eleanor , Jones Hannah , Goulding Neil , Borges Maria Carolina , Clayton Gemma , Carter Alice R , Halligan Sarah , Lawlor Deborah A , Khandaker Golam M , Fraser Abigail 
Published: December 2022

BackgroundInflammation is implicated in depression, but the issue of causality remains unclear.ObjectivesTo investigate potential causality and direction of effect between inflammation and depression.MethodsUsing data from the ALSPAC birth cohort (n=4021), we used multivariable regression to investigate bidirectional longitudinal associations of GlycA and depression symptoms score and diagnosis, assessed at ages 18y and 24y.We used two-sample Mendelian randomization (MR) to investigate potential causality and directionality. Genetic variants for GlycA were obtained from UK Biobank (UKBB) (N=115,078); for depression from the Psychiatric Genomics Consortium and UKBB (N=500,199); and for depressive symptoms (N=161,460) from the Social Science Genetic Association Consortium. In addition to the Inverse Variance Weighted (IVW) method, we used sensitivity analyses to strengthen causal inference. We conducted multivariable MR adjusting for body mass index (BMI) due to known genetic correlation between inflammation, depression and BMI.ResultsAfter adjusting for potential confounders we found no association between GlycA and depression symptoms score orvice versa. We observed an association between GlycA and depression diagnosis (OR=1.18, 95% CI: 1.03-1.36).MR suggested no causal effect of GlycA on depression, but there was evidence of a causal effect of depression on GlycA (mean difference in GlycA = 0.09; 95% CI: 0.03-0.16), which was maintained in some, but not all, sensitivity analyses.ConclusionWe found no consistent evidence for an effect of the inflammatory marker GlycA on depression. There was some evidence that depression may increase GlycA, but this may be confounded/mediated by BMI.
Large-scale benchmarking of circRNA detection tools reveals large differences in sensitivity but not in precision
Authors: Vromman Marieke , Anckaert Jasper , Bortoluzzi Stefania , Buratin Alessia , Chen Chia-Ying , Chu Qinjie , Chuang Trees-Juen , Dehghannasiri Roozbeh , Dieterich Christoph , Dong Xin , Flicek Paul , Gaffo Enrico , Gu Wanjun , He Chunjiang , Hoffmann Steve , Izuogu Osagie , Jackson Michael S. , Jakobi Tobias , Lai Eric C. , Nuytens Justine , Salzman Julia , Santibanez-Koref Mauro , Stadler Peter , Thas Olivier , Eynde Eveline Vanden , Verniers Kimberly , Wen Guoxia , Westholm Jakub , Yang Li , Ye Chu-Yu , Yigit Nurten , Yuan Guo-Hua , Zhang Jinyang , Zhao Fangqing , Vandesompele Jo , Volders Pieter-Jan 
Published: December 2022

AbstractThe detection of circular RNA molecules (circRNAs) is typically based on short-read RNA sequencing data processed by computational detection tools. During the last decade, a plethora of such tools have been developed, but a systematic comparison with orthogonal validation is missing. Here, we set up a circRNA detection tool benchmarking study, in which 16 tools were used and detected over 315,000 unique circRNAs in three deeply sequenced human cell types. Next, 1,516 predicted circRNAs were empirically validated using three orthogonal methods. Generally, tool-specific precision values are high and similar (median of 98.8%, 96.3%, and 95.5% for qPCR, RNase R, and amplicon sequencing, respectively) whereas the sensitivity and number of predicted circRNAs (ranging from 1,372 to 58,032) are the most significant tool differentiators. Furthermore, we demonstrate the complementarity of tools through the increase in detection sensitivity by considering the union of highly-precise tool combinations while keeping the number of false discoveries low. Finally, based on the benchmarking results, recommendations are put forward for circRNA detection and validation.
Distinguishing Happiness and Meaning in Life from Depressive Symptoms: a GWAS-by-subtraction study in the UK Biobank
Authors: de Vries Lianne P. , Demange Perline A. , Baselmans Bart M.L. , Vinkers Christiaan H. , Pelt Dirk H.M. , Bartels Meike 
Published: December 2022

AbstractBackgroundHedonic (e.g., happiness) and eudaimonic (e.g., meaning in life) well-being are negatively related to depressive symptoms. Genetic variants play a role in this association, reflected in substantial genetic correlations. We investigated the (genetic) overlap and differences between well-being and depressive symptoms.MethodsWe used results of Genome-Wide Association studies (GWAS) and applied GWAS-by-subtraction in the UK Biobank sample. Analyses were pre-registered.ResultsSubtracting GWAS summary statistics of depressive symptoms from those of happiness and meaning in life, we obtained GWASs of respectively ‘pure’ happiness (neffective= 216,497) and ‘pure’ meaning” (neffective=102,300). For both, we identified one genome-wide significant SNP (rs1078141 and rs79520962, respectively). After the subtraction, SNP heritability reduced from 6.3% to 3.3% for pure happiness and from 6.2% to 4.2% for pure meaning. The genetic correlation between the well-being measures reduced from .78 to .65, indicating that only a part of the genetic overlap between happiness and meaning in life is due to overlap with depressive symptoms. Pure happiness and pure meaning became genetically unrelated to traits strongly associated with depressive symptoms, including tiredness, loneliness, and psychiatric disorders. For several other traits, including ADHD, income, educational attainment, smoking, and drinking alcohol, the genetic correlations of well-being versus pure well-being changed substantially.ConclusionsGWAS-by-subtraction allowed us to investigate the genetic variance of well-being unrelated to depressive symptoms. Genetic correlations with different traits led to new insights about this unique part of well-being. The findings can have implications for interventions to increase well-being and/or decrease depressive symptoms.
Morphogenesis and development of human telencephalic organoids in the absence and presence of exogenous ECM
Authors: Martins-Costa Catarina , Pham Vincent , Sidhaye Jaydeep , Novatchkova Maria , Peer Angela , Möseneder Paul , Corsini Nina S. , Knoblich Jürgen A. 
Published: December 2022

AbstractEstablishment and maintenance of apical-basal polarity is a fundamental step in brain development, instructing the organization of neural progenitor cells (NPCs) and the developing cerebral cortex. Particularly, basally located extracellular matrix (ECM) is crucial for this process. In vitro, epithelial polarization can be achieved via endogenous ECM production, or exogenous ECM supplementation. While neuroepithelial development is recapitulated in cerebral organoids, the effects of different ECM sources in tissue morphogenesis remain unexplored. Here, we show that exposure to exogenous ECM at early neuroepithelial stages causes rapid tissue polarization and complete rearrangement of neuroepithelial architecture within 3 days. In unexposed cultures, endogenous ECM production by NPCs results in gradual polarity acquisition over an extended time. After the onset of neurogenesis, tissue architecture and neuronal differentiation are largely independent of the initial ECM source. These results advance the knowledge on neuroepithelial biology in vitro, with a focus on mechanisms of exogenously- and endogenously-guided morphogenesis. They demonstrate the self-sustainability of neuroepithelial cultures by endogenous processes, prompting an urgent reassessment of indiscriminate use of exogenous ECM in these model systems.
Phase separation-mediated actin bundling by the postsynaptic density condensates
Authors: Chen Xudong , Jia Bowen , Zhu Shihan , Zhang Mingjie 
Published: December 2022

AbstractThe volume and the electric strength of an excitatory synapse is near linearly correlated with the area of its postsynaptic density (PSD). Extensive research in the past have revealed that the PSD assembly directly communicates with actin cytoskeleton in the spine to coordinate activity-induced spine volume enlargement as well as long-term stable spine structure maintenance. However, the molecular mechanism underlying the communication between the PSD assembly and spine actin cytoskeleton is poorly understood. In this study, we discover thatin vitroreconstituted PSD condensates can promote actin polymerization and filamentous actin bundling without help of any actin regulatory proteins. The Homer scaffold within the PSD condensates and a positively charged actin binding surface of the Homer EVH1 domain are essential for the PSD condensate-induced actin bundle formationin vitroand for spine growth in neurons. Homer-induced actin bundling can only occur when Homer forms condensates with other PSD scaffold proteins such as Shank and SAPAP. The PSD-induced actin bundle formation is sensitively regulated by CaMKII or by the product of the immediate early geneHomer1a. Thus, the communication between PSD and spine cytoskeleton may be modulated by targeting the phase separation of the PSD condensates.