bluuebunny/crossref_metadata_2025_split huggingface dataset:
DCD Liver Grafts Can Safely Be Used for Recipients With Grade I–II Portal Vein Thrombosis: A Multicenter Analysis
Authors: Mercado Lydia A. , Bhangu Harpreet K. , Calderon Esteban , Mathur Amit K. , Aqel Bashar , Musto Kaitlyn R. , Watt Kymberly D. , Rosen Charles B. , Bolan Candice , LeGout Jordan D. , Taner C. Burcin , Harnois Denise M. , Croome Kristopher P. 
Published: October 2022

Background.
With donation after circulatory death (DCD) liver transplantation (LT), the goal of the recipient implantation procedure is to minimize surgical complexity to avoid a tenuous environment for an already marginal graft. The presence of portal vein thrombosis (PVT) at the time of LT adds surgical complexity, yet‚ to date, no studies have investigated the utilization of DCD liver grafts for patients with PVT.

Methods.
All DCD LT performed at Mayo Clinic-Florida, Mayo Clinic-Arizona, and Mayo Clinic-Rochester from 2006 to 2020 were reviewed (N = 771). Patients with PVT at the time of transplant were graded using Yerdel classification. A 1:3 propensity match between patients with PVT and those without PVT was performed.

Results.
A total of 91 (11.8%) patients with PVT undergoing DCD LT were identified. Grade I PVT was present in 62.6% of patients, grade II PVT in 27.5%, grade III in 8.8%, and grade 4 in 1.1%. At the time of LT, thromboendovenectomy was performed in 89 cases (97.8%). There was no difference in the rates of early allograft dysfunction (43.2% versus 52.4%; P = 0.13) or primary nonfunction (1.1% versus 1.1%; P = 0.41) between the DCD PVT and DCD without PVT groups, respectively. The rate of ischemic cholangiopathy was not significantly different between the DCD PVT (11.0%) and DCD without PVT groups (10.6%; P = 0.92). Graft (P = 0.58) and patient survival (P = 0.08) were similar between the 2 groups. Graft survival at 1-, 3-, and 5-y was 89.9%, 84.5%, and 79.3% in the DCD PVT group.

Conclusions.
In appropriately selected recipients with grades I–II PVT, DCD liver grafts can be utilized safely with excellent outcomes.
Predictors of Nonseroconversion to SARS-CoV-2 Vaccination in Kidney Transplant Recipients
Authors: Frölke Sophie C. , Bouwmans Pim , Messchendorp A. Lianne , Geerlings Suzanne E. , Hemmelder Marc H. , Gansevoort Ron T. , Hilbrands Luuk B. , Reinders Marlies E.J. , Sanders Jan-Stephan F. , Bemelman Frederike J. , Peters-Sengers Hessel ,   RECOVAC Collaborators
Published: October 2022

Background.
Kidney transplant recipients (KTRs) are still at risk of severe COVID-19 disease after SARS‑CoV‑2 vaccination, especially when they have limited antibody formation. Our aim was to understand the factors that may limit their humoral response.

Methods.
Our data are derived from KTRs who were enrolled in the Dutch Renal Patients COVID-19 Vaccination consortium, using a discovery cohort and 2 external validation cohorts. Included in the discovery (N = 1804) and first validation (N = 288) cohorts were participants who received 2 doses of the mRNA-1273 vaccine. The second validation cohort consisted of KTRs who subsequently received a third dose of any SARS-CoV-2 vaccine (N = 1401). All participants had no history of SARS-CoV-2 infection. A multivariable logistic prediction model was built using stepwise backward regression analysis with nonseroconversion as the outcome.

Results.
The discovery cohort comprised 836 (46.3%) KTRs, the first validation cohort 124 (43.1%) KTRs, and the second validation cohort 358 (25.6%) KTRs who did not seroconvert. In the final multivariable model‚ 12 factors remained predictive for nonseroconversion: use of mycophenolate mofetil/mycophenolic acid (MMF/MPA); chronic lung disease, heart failure, and diabetes; increased age; shorter time after transplantation; lower body mass index; lower kidney function; no alcohol consumption; ≥2 transplantations; and no use of mammalian target of rapamycin inhibitors or calcineurin inhibitors. The area under the curve was 0.77 (95% confidence interval [CI], 0.74-0.79) in the discovery cohort after adjustment for optimism, 0.81 (95% CI, 0.76-0.86) in the first validation cohort, and 0.67 (95% CI, 0.64-0.71) in the second validation cohort. The strongest predictor was the use of MMF/MPA, with a dose-dependent unfavorable effect, which remained after 3 vaccinations.

Conclusions.
In a large sample of KTRs, we identify a selection of KTRs at high risk of nonseroconversion after SARS-CoV-2 vaccination. Modulation of MMF/MPA treatment before vaccination may help to optimize vaccine response in these KTRs. This model contributes to future considerations on alternative vaccination strategies.
Omental Flap Wrapping Around the Esophagogastric Anastomosis and Association with Anastomotic Leak in Esophagectomy for Esophageal Cancer: A Propensity Score-Matching Analysis
Authors: Yoshida Naoya , Eto Kojiro , Matsumoto Takashi , Kosumi Keisuke , Imamura Yu , Iwatsuki Masaaki , Baba Yoshifumi , Miyamoto Yuji , Watanabe Masayuki , Baba Hideo 
Published: October 2022

BACKGROUND:
Anastomotic leakage after esophagectomy remains frequent and can cause surgery-related mortality. Wrapping the esophageal conduit anastomosis with a greater omental flap is a proposed method to reduce leakage. However, the usefulness of omental wrapping (OW) has not been elucidated.

STUDY DESIGN:
This study included 338 patients with esophageal cancer who underwent McKeown esophagectomy and reconstruction using a gastric conduit between April 2005 and August 2021. The study participants were divided into 2 groups: reconstructions with and without OW. We performed propensity score matching between the reconstructions with and without OW. The propensity score was calculated according to baseline characteristics, performance and physical statuses, presence of comorbidities, and types and details of the treatment procedures undergone.

RESULTS:
We included 338 patients (169 with OW and 169 without OW) in this study. After matching, all clinical and surgical features were statistically equivalent between the groups. Reconstruction and anastomosis with OW were significantly associated with decreased leakage (p = 0.016) and surgical site infection (p = 0.041). Reconstruction and anastomosis with OW also exhibited a trend toward more frequent stricture, although this was not statistically significant (p = 0.051). Independent risk factors for leakage were reconstruction without OW (odds ratio, 2.55; 95% CI, 1.234 to 5.285; p = 0.0088) and younger age (odds ratio, 1.06; 95% CI, 1.012 to 1.102; p = 0.011).

CONCLUSIONS:
OW can reduce leakage in the esophagogastric anastomosis. OW can be performed conveniently and may be recommended to reinforce the anastomotic site, which can improve short-term outcomes after esophagectomy for esophageal cancer.
Captive rearing effects on the methylome of Atlantic salmon after oceanic migration: sex-specificity and intergenerational stability
Authors: Venney Clare J. , Bouchard Raphaël , April Julien , Normandeau Eric , Lecomte Laurie , Côté Guillaume , Bernatchez Louis 
Published: October 2022

AbstractCaptive rearing in salmon hatcheries can have considerable impacts on both fish phenotype and fitness within a single generation, even in the absence of genetic change. Evidence for hatchery-induced changes in DNA methylation is becoming abundant, though questions remain on the sex-specificity of these effects, their persistence until spawning, and potential for transmission to future generations. Here we performed whole genome methylation sequencing of fin tissue for 16 hatchery and 16 wild Atlantic salmon (Salmo salar) returning to spawn in the Rimouski River, Québec. We identified two cohorts of hatchery-reared salmon through methylation analysis, one of which was epigenetically similar to wild fish, suggesting that supplementation efforts may be able to minimize the epigenetic effects of hatchery rearing. We found considerable sex-specific effects of hatchery rearing, with few genomic regions being affected in both males and females. We also analysed the methylome of 32 F1 offspring from four groups (pure wild, pure hatchery origin, and reciprocal hybrids). We found that few epigenetic changes due to parental hatchery rearing persisted in the F1 offspring though the patterns of inheritance appear to be complex, involving nonadditive effects. Our results suggest that the epigenetic effects of hatchery rearing can be minimal in F0. There may also be minimal epigenetic inheritance and rapid loss of epigenetic changes associated with hatchery rearing. However, due to sex-specificity and nonadditive patterns of inheritance, methylation changes due to captive rearing are rather complex and the field would benefit from further research on minimizing the epigenetic effects of captive rearing in conservation efforts.
PKR activation-induced mitochondrial dysfunction in HIV-transgenic mice with nephropathy
Authors: Yoshida Teruhiko , Latt Khun Zaw , Rosenberg Avi Z. , Santo Briana A. , Myakala Komuraiah , Ishimoto Yu , Zhao Yongmei , Shrivastav Shashi , Jones Bryce A. , Yang Xiaoping , Wang Xiaoxin X. , Tutino Vincent M. , Sarder Pinaki , Levi Moshe , Okamoto Koji , Winkler Cheryl A. , Kopp Jeffrey B. 
Published: October 2022

AbstractHIV disease remains prevalent in the USA and chronic kidney disease remains a major cause of morbidity in HIV-1-positive patients. Host double-stranded RNA (dsRNA)-activated protein kinase (PKR) is a sensor for viral dsRNA, including HIV-1. We show that PKR inhibition by compound C16 ameliorates the HIV-associated nephropathy (HIVAN) kidney phenotype in the Tg26 transgenic mouse model, with reversal of mitochondrial dysfunction. Combined analysis of single-nucleus RNA-seq and bulk RNA-seq data revealed that oxidative phosphorylation was one of the most downregulated pathways and identified signal transducer and activator of transcription (STAT3) as a potential mediating factor. We identified in Tg26 mice a novel proximal tubular cell cluster enriched in mitochondrial transcripts. Podocytes showed high levels of HIV-1 gene expression and dysregulation of cytoskeleton-related genes; and these cells dedifferentiated. In injured proximal tubules, cell-cell interaction analysis indicated activation of the profibrogenic PKR-STAT3-platelet derived growth factor (PDGF)-D pathway. These findings suggest that PKR inhibition and mitochondrial rescue are potential novel therapeutic approaches for HIVAN.Translational StatementThis work identified mitochondrial dysfunction in transgenic mice manifesting HIV-associated nephropathy mice kidney, using combination of single-nuclear and bulk RNA-seq analysis. Kidney damage was ameliorated by the PKR inhibitor C16, and mitochondrial rescue was shown by transcriptomic profiling and functional assay. These findings suggest that PKR inhibition and mitochondrial rescue are potential therapeutic approaches for HIV-associated nephropathy.
Environmental filtering of life-history trait diversity in urban populations ofArabidopsis thaliana
Authors: Schmitz Gregor , Linstädter Anja , Frank Anke S. K. , Dittberner Hannes , Thome Jessica , Schrader Andrea , Linne von Berg Karl-Heinz , Fulgione Andrea , Coupland George , de Meaux Juliette 
Published: October 2022

AbstractThe challenges to which plants are exposed in urban environments represent, in miniature, the challenges plants face as a result of global environmental change. Hence, urban habitats provide a unique opportunity to assess whether processes of local adaptation are taking place despite the short temporal and geographical scales that characterize the Anthropocene.We quantified the ecological diversity of urban habitats hostingA. thalianapopulations. Using plant community indicators, we show that these patches differ in their levels of soil nutrient content and disturbance. Accordingly, plants in each patch displayed a range of flowering time, size and fitness.Using a deep sampling approach coupled with reduced genome-sequencing, we demonstrate that most individuals can be assigned to a limited set of clonal lineages; the genetic diversity of these lineages is a sample of the diversity observed in western European populations of the species, indicating that established urban populations originate from a broad regional pool of lineages.We assessed the genetic and phenotypic diversity of these lineages in a set of common garden experiments. We report marked genetic differences in life-history traits, including time of primary and secondary dormancy as well as of flowering. These genetic differences in life-history traits are not randomly distributed but sorted out by ecological differences among sites of origin.Synthesis:Our study shows that the genetically diverse phenology of a regionalA. thalianagene pool is not randomly distributed but filtered by heterogeneity in the urban environment. To out knowledge, this report is the first to show a pattern indicative of environmental filtering enhancing local genetic adaptation within urban environments. We conclude that environmental filtering helps maintain functional diversity within species.
Inferring time of infection from field data using dynamic models of antibody decay
Authors: Borremans Benny , Mummah Riley O , Guglielmino Angela H , Galloway Renee L , Hens Niel , Prager K C , Lloyd-Smith James O 
Published: October 2022

AbstractStudies of infectious disease ecology often rely heavily on knowing when individuals were infected, but estimating this time of infection can be challenging, especially in wildlife. Time of infection can be estimated from various types of data, with antibody level data being one of the most promising sources of information. The use of antibody levels to back-calculate infection time requires the development of a host-pathogen system-specific model of antibody dynamics, and a leading challenge in such quantitative serology approaches is how to model antibody dynamics in the absence of experimental infection data. Here, we present a way to do this in a Bayesian framework that facilitates the incorporation of all available information about potential infection times. We apply the model to estimate infection times of Channel Island foxes infected withLeptospira interrogans, leading to reductions of 51-92% in the window of possible infection times. Using simulated data, we show that the approach works well across a broad range of parameter settings and can lead to major improvements of infection time estimates that depend on system characteristics such as antibody decay rate and variation in peak antibody levels after exposure. The method substantially simplifies the challenge of modeling antibody dynamics in the absence of individuals with known infection times, opens up new opportunities in wildlife disease ecology, and can even be applied to cross-sectional data once the model is trained.
Improved RNA homology detection and alignment by automatic iterative search in an expanded database
Authors: Singh Jaswinder , Paliwal Kuldip , Singh Jaspreet , Litfin Thomas , Zhou Yaoqi 
Published: October 2022

AbstractUnlike 20-letter-coded proteins, RNA homologous sequences are notoriously difficult to detect because their 4-letter-coded sequences can quickly lose their sequence identity. As a result, employing secondary structures has been found necessary to improve the sensitivity and the accuracy of homolog search. However, exact secondary structures often are not known. As a result, Rfam, the de facto gold-standard of RNA homologous families, has to rely on manual curation and experimental secondary structure if available. Here, we showed that using a combination of BLAST and iterative INFERNAL searches along with an expanded sequence database leads multiple sequence alignments (MSA) that are comparable to those provided by Rfam MSAs, according to secondary structure extracted from mutational coupling analysis and alignment accuracy when compared to structure alignment. The fully automatic tool (RNAcmap2) allows making homolog search, multiple sequence alignment, and mutational coupling analysis for any non-Rfam RNA sequences with Rfam-like performance.
EGIDExpress: An Interactive Shiny Web App to Visualize and Share Large Biological Datasets
Authors: Besse John A. , Osswald Garrett A. , Ballaban Adina Y. , Caldwell Julie M. , Rothenberg Marc E. 
Published: October 2022

AbstractBiomedical research on rare diseases faces challenges such as low availability of biological specimens to study and limited funding. Eosinophilic gastrointestinal diseases (EGIDs) are rare conditions associated with inappropriate inflammation and the accumulation of eosinophils in various segments of the gastrointestinal tract. We aimed to build a repository of large datasets related to EGIDs that would be easily browsable, interpretable, and accessible in order to facilitate data sharing and hypothesis generation. Using the R-code based package Shiny, we built a website that allows visualization of multiple types of datasets including microarray, RNAseq, protein array, single-cell RNAseq, and ChIPseq. Users can access EGIDExpress (https://egidexpress.research.cchmc.org/) to browse data on a per-gene basis and to generate graphic representation of the data. Additionally, users can download the processed data to initiate their own analyses. Within 34 months of launching EGIDExpress, over 2400 users from 37 countries and 37 states within the United States accessed the site. Overall, EGIDExpress is accelerating research on EGIDs and provides a prototypic platform for broad research data sharing.
Engineering human spinal microphysiological systems to model opioid-induced tolerance
Authors: Cai Hongwei , Ao Zheng , Tian Chunhui , Wu Zhuhao , Kaurich Connor , Chen Zi , Gu Mingxia , Hohmann Andrea G. , Mackie Ken , Guo Feng 
Published: October 2022

AbstractOpioids are commonly used for treating chronic pain. However, with continued use, they may induce tolerance and/or hyperalgesia, which limits therapeutic efficacy. The human mechanisms of opioid-induced hyperalgesia are significantly understudied, in part, because current models cannot fully recapitulate human pathology. Here, we engineered novel human spinal microphysiological systems (MPSs) integrated with plug-and-play neural activity sensing for modeling human nociception and opioid-induced tolerance. Each spinal MPS consists of a flattened human spinal cord organoid derived from human stem cells and a 3D printed organoid holder device for plug-and-play neural activity measurement. We found that the flattened organoid design of MPSs not only reduces hypoxia and necrosis in the organoids, but also promotes their neuron maturation, neural activity, and functional development. We further demonstrated that prolonged opioid exposure resulted in neurochemical correlates of opioid tolerance and hyperalgesia, as measured by altered neural activity, reduced densities of glutamate transporter levels and downregulation of μ-opioid receptor expression of human spinal MPSs. The MPSs are scalable, cost-effective, easy-to-use, and compatible with commonly-used well-plates, thus allowing plug-and-play measurements of neural activity. We believe the MPSs hold a promising translational potential for studying human pain etiology, screening new treatments, and validating novel therapeutics for human pain medicine.
The complete genome sequence of Pseudomonas syringae pv. actinidifoliorum ICMP 18803
Authors: Templeton Matthew D. , Arshed Saadiah , Andersen Mark T. , Jayaraman Jay 
Published: October 2022

AbstractThe complete genome of Pseudomonas syringae pv. actinidifoliorum ICMP18803 (Pfm) was sequenced using the Oxford Nanopore minION platform to an average read depth of 123. The genome assembled into a single chromosome of 6,353,853 bp after error-correction with Illumina short reads using Pilon. The complement of effector genes from a P. syringae pathovar plays the predominant role in defining its pathogenicity. Automatic gene annotation pipelines often poorly identify and name effector genes, however. Despite Pfm being a relatively weak pathogen of kiwifruit, a set of 31 effectors, 26 of which were full length, was identified by mapping the comprehensive effector library generated by Dillon et al. (2019). The Pfm genome with the effector complement, correctly named and annotated was resubmitted to Genbank (CP081457).
Dysregulated Expression of Circadian Genes in Lymphoblastoid Cells of Patients with ASD
Authors: Ding Hui , Kuang Shuzhen , Chen Chin-Fu 
Published: October 2022

AbstractPatients with Autism Spectrum Disorder (ASD) often exhibit disturbances in sleep, metabolism, and immune system. The molecular mechanisms for these clinical features in ASD are currently unknown. We demonstrated that circadian genes in the cells of patients with ASD often are dysregulated compared to controls. The dysregulation of circadian genes was reflected in two different ways: (1) abnormal levels of expression; and (2) a change of gene-gene association pattern in the co-expression network. We also observed a link between abnormal expression of circadian genes in lymphoblastoid cells with sleep phenotypes in patients with ASD. Our results suggest that circadian genes and circadian rhythms might play critical roles in the pathogenesis of ASD.
Experimental validation of the free-energy principle with in vitro neural networks
Authors: Isomura Takuya , Kotani Kiyoshi , Jimbo Yasuhiko , Friston Karl J. 
Published: October 2022

AbstractEmpirical applications of the free-energy principle are not straightforward because they entail a commitment to a particular process theory, especially at the cellular and synaptic levels. Using a recently established reverse engineering technique, we confirm the quantitative predictions of the free-energy principle using in vitro networks of rat cortical neurons that perform causal inference. Upon receiving electrical stimuli—generated by mixing two hidden sources—neurons self-organised to selectively encode the two sources. Pharmacological up- and downregulation of network excitability disrupted the ensuing inference, consistent with changes in prior beliefs about hidden sources. As predicted, changes in effective synaptic connectivity reduced variational free energy, where the connection strengths encoded parameters of the generative model. In short, we show that variational free energy minimisation can quantitatively predict the self-organisation of neuronal networks, in terms of their responses and plasticity. These results demonstrate the applicability of the free-energy principle to in vitro neural networks and establish its predictive validity in this setting.
An in-silico approach for novel molecular glue design by rationalizing known molecular glue mediated ternary complex formation
Authors: Geoffrey A S Ben , Kulkarni Nagaraj M , Agrawal Deepak , Bharti Nivedita , Vetrivel Rajappan , Gurram Kishan 
Published: October 2022

AbstractProtein function modulation using small molecule binding is an important therapeutic strategy for many diseases. However, many proteins remain undruggable due to lack of suitable binding pockets for small molecule binding. Proximity induced protein degradation using molecular glues has recently been identified as in important strategy to target the undruggable proteins. Molecular glues were discovered serendipitously and as such currently lack an established approach for in-silico design rationale. In this work, we attempt to establish the rationale for a known case and having inferred the rationale, we discuss how the rationale can be applied in-silico to design novel molecular glue through AI powered techniques. We believe the establishing of in-silico rationale for molecular glue design would be a valuable and welcome addition to the literature to further accelerate the discovery of molecular glues to drug undruggable targets.