bluuebunny/crossref_metadata_2025_split huggingface dataset:
HLA Loci and Recurrence of Focal Segmental Glomerulosclerosis in Pediatric Kidney Transplantation
Authors: Shaw Brian I. , Ochoa Alejandro , Chan Cliburn , Nobuhara Chloe , Gbadegesin Rasheed , Jackson Annette M. , Chambers Eileen T. 
Published: August 2021

Background.
Recurrent focal segmental glomerulosclerosis (FSGS) after kidney transplantation accounts for the majority of allograft failures in children with primary FSGS. Although current research focuses on FSGS pathophysiology, a common etiology and mechanisms of disease recurrence remain elusive.

Methods.
We performed a retrospective review of the Scientific Registry of Transplant Recipients to determine the association of specific HLA recurrence of FSGS. Kidney transplants recipients under the age of 19 who were diagnosed with FSGS, who were transplanted after January 1, 2000, and who had complete HLA data were included in the study. We performed simple logistic regression on all HLA A, B, C, DR, and DQ represented in the dataset and FSGS recurrence and then determined those associated with recurrence using the Benjamini–Hochberg method for multiple comparisons. For those HLAs that were associated with recurrence, we further determined the effect of matching recipient and donor HLA with recurrence.

Results.
HLA DR7, DR53, DQ2, DR52, and DQ7 were associated with increased or decreased risk of recurrent disease after transplantation. We identified a risk haplotype consisting of HLA-DR7, DR53, and DQ2 that was consistently associated with an increased risk of recurrence (odds ratio 1.91; 95% confidence interval, 1.44-2.54, P < 0.001). We also found that donor/recipient concordance for HLA-DQ7 was associated with a decreased risk of recurrence (odds ratio 0.42; 95% confidence interval, 0.37-0.53, P = 0.009).

Conclusions.
HLA profiles may be used for risk stratification of recurrence of FSGS in pediatric kidney transplant recipients and deserves further study.
Predicting COVID-19 Incidences from Patients’ Viral Load using Deep-Learning
Authors: Khalil Athar , Handawi Khalil Al , Chamseddine Ibrahim , Mohsen Zeina , Nour Afif Abdel , Feghali Rita , Kokkolaras Michael 
Published: August 2021

AbstractThe transmission of the contagious COVID-19 is known to be highly dependent on individual viral dynamics. Since the cycle threshold (Ct) is the only semi-quantitative viral measurement that could reflect infectivity, we utilized Ct values to forecast COVID-19 incidences. Our COVID-19 cohort (n=9531), retrieved from a single representative cross-sectional virology test center in Lebanon, revealed that low daily mean Ct values are followed by an increase in the number of national positive COVID-19 cases. A subset of the data was used to develop a deep neural network model, tune its hyperparameters, and optimize the weights for minimal mean square error of prediction. The final model’s accuracy is reported by comparing its predictions with an unseen dataset. Our model was the first to capture the interaction of the previously reported Ct values with the upcoming number of COVID-19 cases and any temporal effects that arise from population dynamics. Our model was deployed as a publicly available and easy-to-use estimator to facilitate prospective validation. Our model has potential application in predicting COVID-19 incidences in other countries and in assessing post-vaccination policies. Aside from emphasizing patient responsibility in adopting early testing practices, this study proposed and validated viral load measurement as a rigid input that can enhance outcomes and precision of viral disease predicting models.
Global disparities in SARS-CoV-2 genomic surveillance
Authors: Brito Anderson F. , Semenova Elizaveta , Dudas Gytis , Hassler Gabriel W. , Kalinich Chaney C. , Kraemer Moritz U.G. , Ho Joses , Tegally Houriiyah , Githinji George , Agoti Charles N. , Matkin Lucy E. , Whittaker Charles ,   Danish Covid-19 Genome Consortium,   COVID-19 Impact Project,   Network for Genomic Surveillance in South Africa (NGS-SA),   GISAID core curation team, Howden Benjamin P , Sintchenko Vitali , Zuckerman Neta S. , Mor Orna , Blankenship Heather M , Oliveira Tulio de , Lin Raymond T. P. , Siqueira Marilda Mendonça , Resende Paola Cristina , Vasconcelos Ana Tereza R. , Spilki Fernando R. , Aguiar Renato Santana , Alexiev Ivailo , Ivanov Ivan N. , Philipova Ivva , Carrington Christine V. F. , Sahadeo Nikita S. D. , Gurry Céline , Maurer-Stroh Sebastian , Naidoo Dhamari , von Eije Karin J , Perkins Mark D. , Kerkhove Maria van , Hill Sarah C. , Sabino Ester C. , Pybus Oliver G. , Dye Christopher , Bhatt Samir , Flaxman Seth , Suchard Marc A. , Grubaugh Nathan D. , Baele Guy , Faria Nuno R. 
Published: August 2021

AbstractGenomic sequencing provides critical information to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments and vaccines, and guide public health responses. To investigate the spatiotemporal heterogeneity in the global SARS-CoV-2 genomic surveillance, we estimated the impact of sequencing intensity and turnaround times (TAT) on variant detection in 167 countries. Most countries submit genomes >21 days after sample collection, and 77% of low and middle income countries sequenced <0.5% of their cases. We found that sequencing at least 0.5% of the cases, with a TAT <21 days, could be a benchmark for SARS-CoV-2 genomic surveillance efforts. Socioeconomic inequalities substantially impact our ability to quickly detect SARS-CoV-2 variants, and undermine the global pandemic preparedness.One-Sentence SummarySocioeconomic inequalities impacted the SARS-CoV-2 genomic surveillance, and undermined the global pandemic preparedness.
Anti–GM-CSF autoantibodies promote a “pre-diseased” state in Crohn’s Disease
Authors: Mortha Arthur , Remark Romain , Del Valle Diane Marie , Chuang Ling-Shiang , Chai Zhi , Alves Inês , Azevedo Catarina , Gaifem Joana , Martin Jerome , Tuballes Kevin , Barcessat Vanessa , Tai Siu Ling , Huang Hsin-Hui , Laface Ilaria , Jerez Yeray Arteaga , Boschetti Gilles , Villaverde Nicole , Wang Mona D. , Korie Ujunwa M. , Murray Joseph , Choung Rok-Seon , Sato Takahiro , Laird Renee M. , Plevy Scot , Rahman Adeeb , Torres Joana , Porter Chad , Riddle Mark S. , Kenigsberg Ephraim , Pinho Salomé S. , Cho Judy H. , Merad Miriam , Colombel Jean-Frederic , Gnjatic Sacha 
Published: August 2021

AbstractBackground & AimsAnti–GM-CSF autoantibodies (aGMAb) are detected in ileal Crohn’s Disease (CD) patients. Their induction and mode of action impacting homeostasis during, or prior to disease are not well understood. We aimed to investigate the underlying mechanisms leading to the induction of aGMAb, from functional orientation to recognized epitopes, for their impact on intestinal immune homeostasis and use as predictive biomarker for complicated CD.MethodsUsing longitudinally collected sera from active component US personnel, we characterize naturally occurring aGMAb in a subset of CD patients years before disease onset. We employed biochemical, cellular, and transcriptional analysis to uncover a mechanism that governs the impaired immune balance in CD years prior to diagnosis.ResultsNeutralizing aGMAb are specific to posttranslational glycosylations on GM-CSF, detectable years prior to diagnosis, and associated with complicated CD at presentation. Glycosylation and production of GM-CSF change in CD patients, altering myeloid homeostasis and destabilizing group 3 innate lymphoid cells. Perturbations in immune homeostasis precede the inflammation and are detectable in the non-inflamed CD mucosa of patients presenting with anti-GM-CSF autoantibodies.ConclusionsAnti-GM-CSF autoantibodies predict the diagnosis of complicated CD, have unique epitopes, and impair myeloid cell homeostasis across the ILC3-GM-CSF-myeloid cell axis, altering intestinal immune homeostasis long before the diagnosis of disease.
Epidemiology of the use of inferior vena cava filters in Brazil between 2008 and 2019
Authors: Louzada Andressa Cristina Sposato , Leiderman Dafne Braga Diamante , da Silva Marcelo Fiorelli Alexandrino , Portugal Maria Fernanda Cassino , de Campos Guerra João Carlos , Teivelis Marcelo Passos , Wolosker Nelson 
Published: August 2021

AbstractPurposeto study the totality of inferior vena cava filters placed in the Brazilian Public Health System, which insures more than 160 million Brazilians, trends by geographic region and in-hospital deaths after filter placements and also due to pulmonary embolism between 2008 and 2019.Patients and methodspublic and open data regarding in-hospital mortality due to pulmonary embolism and all inferior vena cava filters placed in Brazilian public hospitals between January 2008 and December 2019 were extracted from the Brazilian Public Health System’s databases.Results9108 inferior vena cava filters were placed, 98.18% of which was therapeutic. There was an overall increasing use of these devices, statistically significant for all Brazilian regions, except the North. In-hospital mortality rate in patients who received inferior vena cava filters was 6.21%, stable over time. We observed an upward trend in in-hospital mortality rate due to pulmonary embolism, statistically significant for all Brazilian regions, except the North.ConclusionWe observed a low standardized rate of inferior vena cava filter placements in Brazil between 2008 and 2019, but with a trend towards an increasing trend use. Almost all indications for filter placement were therapeutic. In hospital mortality in patients receiving inferior vena cava filters was high, 6.21%, and stable over time, whereas the trend of in-hospital mortality rate due to pulmonary embolism is increasing. Our findings were heterogeneous across Brazilian regions and contrasted to those observed in the USA, which is likely due to cultural and socioeconomic factors.
Motor Learning in Response to Different Experimental Pain Models among Healthy Individuals: A Systematic Review
Authors: Izadi Mohammad , Franklin Sae , Bellafiore Marianna , Franklin David W. 
Published: August 2021

AbstractLearning new movement patterns is a normal part of daily life, but of critical importance in both sport and rehabilitation. A major question is how different sensory signals are integrated together to give rise to motor adaptation and learning. More specifically, there is growing evidence that pain can give rise to alterations in the learning process. Despite a number of studies investigating the role of pain on the learning process, there is still no systematic review to summarize and critically assess investigations regarding this topic in the literature. Here in this systematic review, we summarize and critically evaluate studies that examined the influence of experimental pain on motor learning. Seventeen studies that exclusively assessed the effect of experimental pain models on motor learning among healthy individuals were included for this systematic review, carried out based on the PRISMA statement. The results of the review revealed there is no consensus regarding the effect of pain on the skill learning acquisition and retention. However, several studies demonstrated that participants who experienced pain continued to express a changed motor strategy to perform a motor task even one week after training under the pain condition. The results highlight a need for further studies in this area of research, and specifically to investigate whether pain has different effects on motor learning depending on the type of motor task.
L-citrulline ameliorates pathophysiology in a rat model of superimposed preeclampsia
Authors: Man Andy W. C. , Zhou Yawen , Lam Uyen D. P. , Reifenberg Gisela , Werner Anke , Habermeier Alice , Closs Ellen I. , Daiber Andreas , Münzel Thomas , Xia Ning , Li Huige 
Published: August 2021

AbstractPreeclampsia, characterized by hypertension, proteinuria, and fetal growth restriction, is one of the leading causes of maternal and perinatal mortality. By far, there is no effective pharmacological therapy for preeclampsia. The present study was conducted to investigate the effects of L-citrulline supplementation in Dahl salt-sensitive rat, a model of superimposed preeclampsia. Parental DSSR were treated with L-citrulline (2.5 g/L in drinking water) from the day of mating to the end of lactation period. Blood pressure of the rats was monitored throughout pregnancy and markers of preeclampsia were assessed. Endothelial function of the pregnant DSSR was assessed by wire myograph. L-citrulline supplementation significantly reduced gestational hypertension, proteinuria, and levels of circulating soluble fms-like tyrosine kinase 1 in DSSR. L-citrulline improved maternal endothelial function by augmenting the production of nitric oxide in the aorta and improving endothelium-derived hyperpolarizing factor-mediated vasorelaxation in resistance arteries. L-citrulline supplementation improved placental insufficiency and fetal growth, which were associated with an enhancement of angiogenesis and reduction of fibrosis and senescence in the placentas. In addition, L-citrulline downregulated genes involved in the toll-like receptor 4 and nuclear factor-κB signaling pathway. In conclusion, this study shows that L-citrulline supplementation reduces gestational hypertension, improves placentation and fetal growth in a rat model of superimposed preeclampsia. L-citrulline supplementation may represent an effective and safe therapeutic strategy for preeclampsia that benefit both the mother and the fetus.
Global network structure and local transcriptomic vulnerability shape atrophy in sporadic and genetic behavioral variant frontotemporal dementia
Authors: Shafiei Golia , Bazinet Vincent , Dadar Mahsa , Manera Ana L. , Collins D. Louis , Dagher Alain , Borroni Barbara , Sanchez-Valle Raquel , Moreno Fermin , Laforce Robert , Graff Caroline , Synofzik Matthis , Galimberti Daniela , Rowe James B. , Masellis Mario , Tartaglia Maria Carmela , Finger Elizabeth , Vandenberghe Rik , de Mendonça Alexandre , Tagliavini Fabrizio , Santana Isabel , Butler Chris , Gerhard Alex , Danek Adrian , Levin Johannes , Otto Markus , Sorbi Sandro , Jiskoot Lize C. , Seelaar Harro , van Swieten John C. , Rohrer Jonathan D. , Mišić Bratislav , Ducharme Simon ,   Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI),   GENetic Frontotemporal dementia Initiative (GENFI)
Published: August 2021

AbstractConnections among brain regions allow pathological perturbations to spread from a single source region to multiple regions. Patterns of neurodegeneration in multiple diseases, including behavioral variant of frontotemporal dementia (bvFTD), resemble the large-scale functional systems, but how bvFTD-related atrophy patterns relate to structural network organization remains unknown. Here we investigate whether neurodegeneration patterns in sporadic and genetic bvFTD are conditioned by connectome architecture. Regional atrophy patterns were estimated in both genetic bvFTD (75 patients, 247 controls) and sporadic bvFTD (70 patients, 123 controls). We first identify distributed atrophy patterns in bvFTD, mainly targeting areas associated with the limbic intrinsic network and insular cytoarchitectonic class. Regional atrophy was significantly correlated with atrophy of structurally- and functionally-connected neighbors, demonstrating that network structure shapes atrophy patterns. The anterior insula was identified as the predominant group epicenter of brain atrophy using data-driven and simulation-based methods, with some secondary regions in frontal ventromedial and anteromedial temporal areas. Finally, we find that FTD-related genes, namely C9orf72 and TARDBP, confer local transcriptomic vulnerability to the disease, effectively modulating the propagation of pathology through the connectome. Collectively, our results demonstrate that atrophy patterns in sporadic and genetic bvFTD are jointly shaped by global connectome architecture and local transcriptomic vulnerability.
High temporal resolution RNA-seq time course data reveals mammalian lncRNA activation mirrors neighbouring protein-coding genes
Authors: Muskovic Walter , Slavich Eve , Maslen Ben , Kaczorowski Dominik C. , Cursons Joseph , Crampin Edmund , Kavallaris Maria 
Published: August 2021

ABSTRACTBackgroundThe advent of next-generation sequencing revealed extensive transcription beyond protein-coding genes, identifying tens of thousands of long non-coding RNAs (lncRNAs). Selected functional examples raised the possibility that lncRNAs, as a class, may maintain broad regulatory roles. Compellingly, lncRNA expression is strongly linked with adjacent protein-coding gene expression, suggesting a potential cis-regulatory function. Evidence for these regulatory roles may be obtained through careful examination of the precise timing of lncRNA expression relative to adjacent protein-coding genes.ResultsWhere causal cis-regulatory relationships exist, lncRNA activation is expected to precede changes in adjacent target gene expression. Using an RNA-seq time course of uniquely high temporal resolution, we profiled the expression dynamics of several thousand lncRNAs and protein-coding genes in synchronized, transitioning human cells. Our findings reveal lncRNAs are expressed synchronously with adjacent protein-coding genes. Analysis of lipopolysaccharide-activated mouse dendritic cells revealed the same temporal relationship observed in transitioning human cells.ConclusionOur findings suggest broad-scale cis-regulatory roles for lncRNAs are not common. The strong association between lncRNAs and adjacent genes may instead indicate an origin as transcriptional by-products from active protein-coding gene promoters and enhancers.
Elys deficiency constrains Kras-driven tumour burden by amplifying oncogenic stress
Authors: Morgan Kimberly J , Doggett Karen , Geng Fan-Suo , Whitehead Lachlan , Smith Kelly A , Hogan Benjamin M , Simons Cas , Baillie Gregory J , Molania Ramyar , Papenfuss Anthony T , Hall Thomas E , Ober Elke A , Stainier Didier Y R , Gong Zhiyuan , Heath Joan K 
Published: August 2021

ABSTRACTThe nucleoporin ELYS, encoded by AHCTF1, is a large multifunctional protein with essential roles in nuclear pore assembly and mitosis. Using a zebrafish model of hepatocellular carcinoma, in which the expression of an inducible mutant kras transgene (krasG12V) drives hepatocyte-specific hyperplasia and liver enlargement, we show that reducing ahctf1 gene dosage by 50% markedly shrinks tumour burden, while non-hyperplastic tissues are unaffected. We demonstrate that ahctf1 heterozygosity impairs nuclear pore formation, mitotic spindle assembly and chromosome segregation, leading to DNA damage and activation of TP53-dependent and independent mechanisms of cell death and cell cycle arrest. This selective vulnerability of cancer cells to mild disruption of Elys function uncovers a novel synthetic lethal interaction between ahctf1 and kras mutations that could be exploited therapeutically. Heterozygous expression of both ahctf1 and ranbp2, or treatment of heterozygous ahctf1 larvae with the nucleocytoplasmic transport inhibitor, Selinexor, completely blocked krasG12V-driven hepatocyte hyperplasia, revealing promising avenues for combinatorial treatments.
An intranasal OMV-based vaccine induces high mucosal and systemic protecting immunity against a SARS-CoV-2 infection
Authors: van der Ley Peter A. , Zariri Afshin , van Riet Elly , Oosterhoff Dinja , Kruiswijk Corine P. 
Published: August 2021

ABSTRACTThe development of more effective, accessible and easy to administer COVID-19 vaccines next to the currently marketed mRNA, viral vector and whole inactivated virus vaccines, is essential to curtain the SARS-CoV-2 pandemic. A major concern is reduced vaccine-induced immune protection to emerging variants, and therefore booster vaccinations to broaden and strengthen the immune response might be required. Currently, all registered COVID-19 vaccines and the majority of COVID-19 vaccines in development are intramuscularly administered, targeting the induction of systemic immunity. Intranasal vaccines have the capacity to induce local mucosal immunity as well, thereby targeting the primary route of viral entry of SARS-CoV-2 with the potential of blocking transmission. Furthermore, intranasal vaccines offer greater practicality in terms of cost and ease of administration. Currently, only eight out of 112 vaccines in clinical development are administered intranasally. We developed an intranasal COVID-19 subunit vaccine, based on a recombinant, six proline stabilized, D614G spike protein (mC-Spike) of SARS-CoV-2 linked via the LPS-binding peptide sequence mCramp (mC) to Outer Membrane Vesicles (OMVs) from Neisseria meningitidis. The spike protein was produced in CHO cells and after linking to the OMVs, the OMV-mC-Spike vaccine was administered to mice and Syrian hamsters via intranasal or intramuscular prime-boost vaccinations. In all animals that received OMV-mC-Spike, serum neutralizing antibodies were induced upon vaccination. Importantly, high levels of spike-binding immunoglobulin G (IgG) and A (IgA) antibodies in the nose and lungs were only detected in intranasally vaccinated animals, whereas intramuscular vaccination only induced an IgG response in the serum. Two weeks after their second vaccination hamsters challenged with SARS-CoV-2 were protected from weight loss and viral replication in the lungs compared to the control groups vaccinated with OMV or spike alone. Histopathology showed no lesions in lungs seven days after challenge in OMV-mC-Spike vaccinated hamsters, whereas the control groups did show pathological lesions in the lung. The OMV-mC-Spike candidate vaccine data are very promising and support further development of this novel non-replicating, needle-free, subunit vaccine concept for clinical testing.
Genomic drivers of large B-cell lymphoma resistance to CD19 CAR-T therapy
Authors: Jain Michael D. , Ziccheddu Bachisio , Coughlin Caroline A. , Faramand Rawan , Griswold Anthony J. , Reid Kayla M , Landgren Ola , Locke Frederick L. , Maura Francesco , Davila Marco L. , Schatz Jonathan H. 
Published: August 2021

ABSTRACTChimeric antigen receptor-reprogrammed autologous T cells directed to CD19 are breakthrough immunotherapies for heavily pretreated patients with aggressive B-cell lymphomas but still fail to cure most patients. Host inflammatory and tumor microenvironmental factors associate with CAR-19 resistance, but the tumor-intrinsic factors underlying these phenomena remain undefined. To characterize genomic drivers of resistance, we interrogated whole genome sequencing of 30 tumor samples from 28 uniformly CAR-19-treated large-cell lymphoma patients. We reveal that patterns of genomic complexity (i.e., chromothripsis and APOBEC mutational activity), and distinct genomic alterations (deletions of RB1 or RHOA) associate with more exhausted immune microenvironments and poor outcome after CAR-19 therapy. Strikingly, pretreatment reduced expression or sub-clonal mutation of CD19 did not affect responses, suggesting CAR-19 therapy successes are due not only to direct antigen-dependent cytotoxicity but require surmounting immune exhaustion in tumor microenvironments to permit broader host responses that eliminate tumors.