bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exercise for Solid Organ Transplant Candidates and Recipients: A Joint Position Statement of the Canadian Society of Transplantation and CAN-RESTORE
Authors: Janaudis-Ferreira Tania , Mathur Sunita , Deliva Robin , Howes Nancy , Patterson Catherine , Räkel Agnès , So Stephanie , Wickerson Lisa , White Michel , Avitzur Yaron , Johnston Olwyn , Heywood Norine , Singh Sunita , Holdsworth Sandra 
Published: June 2019

Background.
The objectives of this position statement were to provide evidence-based and expert-informed recommendations for exercise training in adult and children solid organ transplant (SOT) candidates and recipients and on the outcomes relevant to exercise training and physical function that should be evaluated in SOT.

Methods.
We identified randomized controlled trials (RCTs) and systematic reviews of exercise interventions in adult and pediatric SOT candidates and recipients. When RCTs were not available, studies of any design were reviewed. The key recommendations were based on scientific evidence and expert-informed opinion.

Results.
We recommended that exercise training should be offered in the pre- and posttransplant phase for both adults and children. In adults, exercise training pretransplant was safe, but there was insufficient evidence to provide specific guidelines on the training characteristics. RCTs in adult SOT recipients demonstrated that exercise training improved exercise capacity, lower extremity muscle strength, and health-related quality of life. To obtain benefits, exercise training should be of moderate to vigorous-intensity level, 3–5 times a week for a minimum of 8 weeks. In pediatrics, there is an urgent need for high-quality multicenter clinical trials in the pre- and posttransplant phases. Due to limited evidence, specific recommendations regarding training characteristics could not be provided for pediatrics.

Conclusions.
The clinical relevance of this position statement is that it provides a key step toward raising awareness of the importance of exercise training in SOT patients among transplant professionals. It also identifies key areas for further research.
Characterization of Clinical and Histological Rejection of Male Genital Tissues Using a Novel Microsurgical Rat Penile Transplantation Model
Authors: Fidder Samuel A.J. , Furtmüller Georg J. , Simons Brian , Oh Byoung Chol , Chicco Maria , Etra Joanna W. , Brayton Cory , Cooney Carisa M. , Vasilic Dalibor , Kern Barbara , Lough Denver , Lee WP Andrew , Redett Richard J. , Brandacher Gerald , Cooney Damon S. 
Published: June 2019

Background.
Penis transplantation represents an exciting new avenue for restoration of male urogenitalia. However, little is known about the specific immunological features of penile transplants, limiting their application in complex urogenital reconstruction. To properly study this emerging form of transplantation, adequate preclinical models are a necessity. The purpose of this study is to establish a clinical and histological rejection classification of urogenital tissue transplants using a new rat heterotopic penile transplant model that includes preputial skin.

Methods.
Syngeneic and allogeneic heterotopic penile transplantations were performed on Lewis and Brown Norway rats using a new model designed by our group. Grafts were clinically and histologically monitored at postoperative days (POD) 3–30.

Results.
Six syngeneic and 25 allogeneic transplants were performed. All syngeneic and tacrolimus-treated grafts survived until endpoint. Allogeneic graft rejection is shown to follow a 4-stage clinical progression with all untreated allografts developing epidermal sloughing at POD7 and full rejecting between POD14 and POD16. Histological samples were used to develop a specific 4-grade rejection classification analogous to the 2007 Banff Criteria for skin-containing allografts.

Conclusions.
Graft skin and urethral lining tissue are first rejection targets followed by tunica albuginea and corpora cavernosa in a distal to proximal pattern. We established a robust and reproducible murine model to study the immunobiology of male genital tissue in the context of transplantation and developed a novel 4-grade clinical and histological rejection scale based on graft skin and urethral lining as the main targets of rejection.
BOS Is Associated With Decreased SIRT1 in Peripheral Blood Proinflammatory T, NK, and NKT-like Lymphocytes
Authors: Hodge Greg , Hodge Sandra , Liu Hong , Nguyen Phan , Holmes-Liew Chien-Li , Holmes Mark 
Published: June 2019

Background.
Immunosuppression therapy is ineffective at preventing chronic rejection of lung allografts (bronchiolitis obliterans syndrome [BOS]) and proinflammatory cytokines by steroid-resistant lymphocytes. The class III NAD-sirtuin 1 (SIRT1) is an important negative regulator of inflammation; however, SIRT1 activity following lung transplant has not been studied. We hypothesized that SIRT1 expression is decreased in proinflammatory lymphocytes following lung transplant and that treatment with SIRT1 activators (resveratrol, curcumin) and agents that prevent NAD depletion (theophylline) upregulate SIRT1 and reduce proinflammatory cytokine expression in these cells.

Methods.
Intracellular proinflammatory cytokines and SIRT1 were measured in blood T, natural killer T-like cell (NKT-like), and natural killer (NK) cells from patients with BOS (n = 10), stable lung transplant patients (n = 11), and healthy aged-matched controls (n = 10). Blood was cultured in the presence of ±25 µM resveratrol, ±1 µM curcumin, ±5 mg/L theophylline, ±1µM prednisolone and cytokines, and SIRT1 assessed using flow cytometry.

Results.
There was a loss of SIRT1 in T, NK-like, and NK cells in BOS patients compared with stable patients and controls (%CD8+ SIRT1+ T cells: 17 ± 10; 37 ± 10; 30 ± 10) (mean ± SEM BOS, stable, control, respectively) (P < 0.05 for all). Loss of SIRT1 was associated with increased T, NKT-like, and NK cells expressing interferon (IFN)γ and tumor necrosis factor (TNF)α. SIRT1 expression by T cells significantly associated with FEV1 (R = 0.655, P = 0.006) and with time posttransplant (R = −0.552, P = 0.041). All treatments upregulated SIRT1 and inhibited IFNγ and TNFα production by T, NK, and NKT-like cells additively.

Conclusions.
BOS is associated with decreased SIRT1 in peripheral blood proinflammatory T, NK, and NKT-like lymphocytes following lung transplant. Treatment options that increase SIRT1 may improve graft survival.
Utilization of Donor Kidneys With Acute Kidney Injury in Pediatric Kidney Transplant Recipients
Authors: Solomon Sonia , Hayde Nicole 
Published: June 2019

Background.
An elevated terminal creatinine is frequently used as a reason for organ refusal in pediatric kidney transplantation. There is increasing evidence that adults who receive kidneys from donors with moderate to severe acute kidney injury (AKI) have similar outcomes to recipients who receive kidneys from donors with none to mild AKI.

Methods.
We used the Scientific Registry of Transplant Recipients to determine how many pediatric kidney transplant recipients developed delayed graft function (DGF) between 2000 and 2010.

Results.
When stratified by the donor terminal creatinine, there was no significant difference in the recipient discharge creatinine or the likelihood of developing DGF. In a logistic regression model, older donor age, male donors, and a longer cold ischemia time but not donor terminal creatinine were independent predictors of DGF. There were very few graft loss events documented in this study.

Conclusions.
Our results are in agreement with previously published data; a high donor terminal creatinine is not significantly associated with DGF in pediatric renal transplant recipients. Additional studies investigating the risk of rejection and long-term graft function are needed before adopting the practice of accepting kidneys with moderate to severe AKI in pediatric kidney transplant recipients.
Cognitive Profile, Emotional-Behavioral Features, and Parental Stress in Boys With 47,XYY Syndrome
Authors: Operto Francesca F. , Pastorino Grazia M.G. , Amadori Elisabetta , Mazza Roberta , Bernardo Pia , Campanozzi Stella , Margari Lucia , Coppola Giangennaro 
Published: June 2019

Objective:
To describe (a) the observed cognitive, emotional, and behavioral phenotype in a cohort of male children with 47,XYY syndrome and (b) stress levels in their parents.

Methods:
We conducted a cross-sectional observational study of 11 boys diagnosed with 47,XYY syndrome and compared them with 11 age-matched boys with normal karyotype (46,XY). The participants performed standardized assessments of cognitive function, emotional state, and behavioral features; the parents completed a questionnaire evaluating parental stress. All data were analyzed using parametric and nonparametric statistical methods.

Results:
All of the boys exhibited a normal cognitive profile. However, emotional-behavioral profiling revealed that internalizing and externalizing problems were more prevalent in the 47,XYY group. In addition, the stress levels of the parents of the 47,XYY group were reportedly higher than those of the parents of the 46,XY group. We also found that the time of the diagnosis had an effect on the mothers’ stress levels; that is, postnatal fetal 47,XYY diagnosis was associated with higher maternal stress, whereas prenatal fetal 47,XYY diagnosis was not.

Conclusions:
Generally, 47,XYY syndrome is associated with certain cognitive, emotional, and behavioral features. High stress levels have been reported by the mothers of 47,XYY boys who had been diagnosed postnatally because of unexpected developmental delay and/or learning difficulties. The present study highlights the need to better define the neuropsychiatric phenotype of 47,XYY children; namely, the effect of the chromosomal abnormality on their cognitive function and emotional-behavioral (internalizing and externalizing) features. This study could improve prenatal counseling and pediatric surveillance.
Community Engagement during outbreak response: standards, approaches, and lessons from the 2014-2016 Ebola outbreak in Sierra Leone
Authors: Bedson Jamie , Jalloh Mohamed F. , Pedi Danielle , Bah Saiku M. , Owen Katharine , Oniba Allan , Sangarie Musa , Fofanah James , Jalloh Mohamed B. , Sengeh Paul , Skrip Laura A. , Althouse Benjamin M , Hébert-Dufresne Laurent 
Published: June 2019

Summary pointsThe Social Mobilization Action Consortium (SMAC) was Sierra Leone’s largest coordinated community engagement initiative during the 2014 - 2016 Ebola outbreak. It worked in all 14 districts in Sierra Leone across >12,000 communities (approximately 70% of all communities), through 2,466 trained Community Mobilizers, a network of 2,000 mosques and churches, and 42 local radio stations.We describe SMAC’s Theory of Change and utilization of the Community-Led Ebola Action (CLEA) approach. We present an extensive dataset of community engagement and monitoring with a focus on over 50,000 SMAC weekly reports collected by Community Mobilizers between December 2014 and September 2015.Community engagement and real-time data collection at scale is achievable in the context of a health emergency if adequately structured, managed, coordinated and resourced.We describe a correlation between systemic community engagement, community action planning and Ebola-safe behaviors at community-level.The SMAC integrated approach demonstrates the scope of data – including surveillance data - that can be generated directly by communities through structured community engagement interventions implemented at scale during an Ebola outbreak.We highlight important insights gleaned over time on how to informally integrate social mobilization into community-based surveillance of sick people and deaths.
Ultraviolet radiation exposure and melanoma: evidence for gene-environment interaction in a large prospective cohort
Authors: Olsen Catherine M. , Pandeya Nirmala , Law Matthew H. , MacGregor Stuart , Iles Mark M. , Thompson Bridie S. , Green Adele C. , Neale Rachel E. , Whiteman David C. ,   for the QSkin Study
Published: June 2019

ABSTRACTMelanoma develops as the result of complex interactions between sun exposure and genetic factors. Data on the relationship between sunlight and melanoma from prospective studies are scant, and the combination of ultraviolet exposure data collected before melanoma diagnosis and genetic information is rarer still. We aimed to quantify the association between ambient and personal UV exposure in relation to risk of incident melanoma (invasive; invasive+in situ) in a large population-based prospective study of men and women (n=38,833) residing in a high ambient UV setting, and to examine potential gene-environment interactions. During a median follow-up time of 4.4 years, 782 (1.5%) participants developed cutaneous melanoma (316 invasive, 466 in situ). Country of birth, age at migration and sunburns during all periods of life were significantly associated with melanoma risk. Histories of keratinocyte cancer and of other actinic lesions were both strongly associated with melanoma risk. An interaction with polygenic risk is possible; among people at low risk, markers of cumulative sun exposure were associated with melanoma. In contrast, among people at high polygenic risk, markers of high-level early life ambient exposure were associated with melanoma. Polygenic risk scores can assist in identifying individuals for whom sunlight exposure is most relevant.
The Non-random Location of Autosomal Genes that Participate in X Inactivation
Authors: Migeon Barbara R. 
Published: June 2019

ABSTRACTBy transcribing XIST RNA, the human inactive X chromosome has a prime role in X-dosage compensation. Yet, the autosomes also play an important role in the process. In fact, multiple genes on human chromosome 1 interact with XIST RNA to silence the inactive Xs, no matter how many there are. And it is likely that multiple genes on human chromosome 19 prevent the silencing of thesingleactive X, which is a highly dosage sensitive process. Previous studies of the organization of chromosomes in the nucleus and their genomic interactions indicate that most contacts are intra-chromosomal. Coordinate transcription or dosage regulation could explain the clustered organization of these autosomal genes on these two chromosomes that are critical for X dosage compensation in human cells. Unlike those on chromosome 1, the genes within the critical eight MB region of chromosome 19, have remained together in all mammals assayed, except rodents, indicating that their proximity in non-rodent mammals is evolutionarily conserved.
Two distinct functional axes of positive feedback-enforced PRC2 recruitment in mouse embryonic stem cells
Authors: Perino Matteo , van Mierlo Guido , Wardle Sandra M.T. , Marks Hendrik , Veenstra Gert Jan C. 
Published: June 2019

AbstractPolycomb Repressive Complex 2 (PRC2) plays an essential role in development by catalysing trimethylation of histone H3 lysine 27 (H3K27me3), resulting in gene repression. PRC2 consists of two sub-complexes, PRC2.1 and PRC2.2, in which the PRC2 core associates with distinct ancillary subunits such as MTF2 and JARID2, respectively. Both MTF2, present in PRC2.1, and JARID2, present in PRC2.2, play a role in core PRC2 recruitment to target genes in mouse embryonic stem cells (mESCs). However, it remains unclear how these distinct sub-complexes cooperate to establish Polycomb domains. Here, we combine a range of Polycomb mutant mESCs with chemical inhibition of PRC2 catalytic activity, to systematically dissect their relative contributions to PRC2 binding to target loci. We find that PRC2.1 and PRC2.2 mediate two distinct paths for recruitment, with mutually reinforced binding. Part of the cross-talk between PRC2.1 and PRC2.2 occurs via their catalytic product H3K27me3, which is bound by the PRC2 core-subunit EED, thereby mediating a positive feedback. Strikingly, removal of either JARID2 or H3K27me3 only has a minor effect on PRC2 recruitment, whereas their combined ablation largely attenuates PRC2 recruitment. This strongly suggests an unexpected redundancy between JARID2 and EED-H3K27me3-mediated recruitment of PRC2. Furthermore, we demonstrate that all core PRC2 recruitment occurs through the combined action of MTF2-mediated recruitment of PRC2.1 to DNA and PRC1-mediated recruitment of JARID2-containing PRC2.2. Both axes of binding are supported by EED-H3K27me3 positive feedback, but to a different degree. Finally, we provide evidence that PRC1 and PRC2 mutually reinforce reciprocal binding. Together, these data disentangle the interdependent and cooperative interactions between Polycomb complexes that are important to establish Polycomb repression at target sites.HighlightsSystematic analysis of Polycomb complex binding to target loci in mESCs using null mutations and chemical inhibition.PRC1, PRC2.1 and PRC2.2 are all mutually dependent for binding to chromatin, mediated in part by H3K27me3.PRC2.1 recruitment is dependent on MTF2PRC2.2 recruitment by JARID2 is dependent on PRC1 and largely redundant with recruitment by H3K27me3
Targeting of the dosage-compensated male X-chromosome during earlyDrosophiladevelopment
Authors: Rieder LE , Jordan WT , Larschan EN 
Published: June 2019

ABSTRACTThe essential process of dosage compensation, which corrects for the imbalance in X-linked gene expression between XX females and XY males, represents a key model for how genes are targeted for coordinated regulation. However, the mechanism by which dosage compensation complexes identify the X-chromosome during early development remained unknown because of the difficulty of sexing embryos prior to zygotic transcription. We used meiotic drive to sexDrosophilaembryos prior to zygotic transcription and ChIP-seq to measure dynamics of dosage compensation factor targeting. TheDrosophilaMale-Specific Lethal dosage compensation complex (MSLc) requires the ubiquitous zinc-finger protein Chromatin-Linked Adaptor for MSL Proteins (CLAMP) to identify the X-chromosome. We observe a multi-stage process in which MSLc first identifies CLAMP binding sites throughout the genome followed by concentration at the strongest X-linked MSLc sites. We provide insight into the dynamic mechanism by which a large transcription complex identifies its binding sites during early development.
Strategies for Integrating Single-Cell RNA Sequencing Results With Multiple Species
Authors: Hart Ronald P. 
Published: June 2019

Single-cell RNA sequencing (scRNAseq) is a robust technology for parsing gene expression in individual cells from a tissue or other complex source. One application involves experiments where cells from multiple species are recovered from a single sample, such as when human cells are transplanted into an animal model. We transplanted microglial precursor cells into newborn mouse brain and then recovered unenriched cortical tissue six months later. Dissociated cells were assessed by scRNAseq. The default method for analyzing these results begins by aligning sequencing reads with a mixture of both mouse and human reference genomes. While this clearly identifies the human cells as a distinct cluster, the clustering is artificially driven by expression from non-comparable gene identifiers from different species. We devised a method for translating expression counts from human to mouse and evaluated four algorithms for parsing mixed-species scRNAseq data. Our optimal approach split raw sequencing reads according to the best alignment score in each genome, and then re-aligned reads only with the appropriate genome. After gene symbol translation, pooled results indicate that cell types are more appropriately clustered and that differential expression analysis identifies species-specific patterns. This method should be applicable to any mixed-species scRNAseq experiment.Summary of optimal strategyMixed-species scRNAseq data are aligned with mixture of mouse and human reference genomesThe BAM file is scanned to find the best alignment score for each sequencing read identifier; these are used to split the paired FASTQ files into two sets of filesEach set of species-specific, paired FASTQ files is re-aligned with only the appropriate reference genomeRaw counts imported into SeuratThe human counts table is translated to mouse gene symbols using a custom HomoloGene translation tableResults are merged and analyzed
Central Nervous System Delivery and Biodistribution Analysis of an Antibody-Enzyme Fusion for the Treatment of Lafora Disease
Authors: Austin Grant L. , Simmons Zoe R. , Klier Jack E. , Hodges Brad L. , Shaffer Robert , McKnight Tracy R. , Pauly James R. , Armstrong Dustin , Kooi Craig W. Vander , Gentry Matthew S. 
Published: June 2019

AbstractLafora disease is a fatal juvenile epilepsy, characterized by the malignant accumulation of aberrant glucan inclusions called Lafora Bodies (LBs). Cerebral delivery of protein-based therapeutics for the clearance of Lafora Bodies remain a unique challenge in the field. Recently, a humanized antigen-binding fragment (hFab) derived from a murine systemic lupus erythematosus DNA autoantibody (3E10) has been shown to mediate cell penetration and been proposed as a broadly applicable carrier to mediate cellular targeting and uptake. We report studies on cerebral delivery of VAL-0417, an antibody-enzyme fusion composed of the 3E10 hFab and human pancreatic α-amylase for the clearance of LBs in a mouse model of lafora disease. Herein, we report development of an enzyme-linked immunosorbant-based bioassay to detect VAL-0417 post treatment as a measure of delivery efficacy. We demonstrate the robust and sensitive detection of the fusion protein in multiple tissue types. Using our method, we measured biodistribution in different methods of delivery. We found intracerebroventricular administration provided the most robust delivery, while intrathecal administration only showed modest biodistribution. These data define critical steps in the translational pipeline of VAL-0417for the treatment of Lafora disease.
Viral satellites exploit phage proteins to escape degradation of the bacterial host chromosome
Authors: McKitterick Amelia C. , Hays Stephanie G. , Alam Munirul , Seed Kimberley D. 
Published: June 2019

SummaryPhage defense systems are often found on mobile genetic elements (MGEs), where they constitutively defend against invaders or are induced to respond to new assaults. Some MGEs, the phage satellites, exploit phages for their own transmission after induction, reducing phage production and protecting their hosts in the process. One such satellite inVibrio cholerae, PLE, is triggered by the lytic phage ICP1 to excise from the chromosome, replicate, and transduce to neighboring cells, completely sabotaging phage production. Here, we found that ICP1 has evolved to possess one of two syntenic loci encoding an SF1B-type helicase, either of which PLE can exploit to directly drive PLE replication. Further, loss of PLE mobilization limits anti-phage activity due to phage-mediated degradation of the bacterial genome. Our work provides insight into the unique challenges imposed on the parasites of lytic phages and underscores the adaptions of these satellites to their ever-evolving target phage.