bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of Bone Morphogenetic Protein in Pediatric Cranioplasty With Pre- and Postoperative Radiation Therapy
Authors: Sharma Jyoti , Tuncer Fatma Betul , Gociman Barbu , Siddiqi Faizi 
Published: July 2019

Introduction:
Bone morphogenetic protein (BMP) is a signaling protein that has proven efficacy in the setting of bone repair. It has been widely used in orthopedic surgery and is being implemented more in the field of craniofacial surgery, although there is limited report on its use in pediatric patients.

Case:
A 6-year-old female with stage IV neuroblastoma with metastasis to the parietal parasagittal calvarium, which had failed to respond to multiple medical therapies, including radiation therapy. The tumor was excised and the defect was replaced with a combination of split calvarial bone graft and rhBMP-2. The patient received post-operative radiation therapy with no reports of complications of the defect site on immediate and long term follow up.

Conclusion:
The use of BMP has the potential to aid in bone generation for high-risk calvarial defects. It can be safe and efficacious to use in the pediatric population; however, future studies should be done to determine the safest and most effective dosing of BMP.
Donor Site Changes in Bone Thickness, Volume, and Density Following Split Cranial Bone Graft Harvest
Authors: B Sandeep , Sharma Ramesh K. , John Jerry R. , Khandelwal Niranjan 
Published: July 2019

Abstract
The calvarium can provide large amount of good quality corticocancellous autogenous bone graft. Although many studies have highlighted the advantages of the split cranial bone graft, there is no published work available in the literature about the fate of donor site of the split cranial bone graft. The present study was undertaken to assess the donor site as regards to the thickness, volume, and the density of the residual bone over a period of 12 months in the postoperative period. A total of 30 patients in the age group of 15 to 43 years were studied from January 2015 to January 2016. Postoperative computer tomography scans were taken at 2 weeks, 6 months, and 1 year postoperative to measure the bone thickness, volume, and density at the donor site of the split cranial bone graft harvest. The bone thickness at the donor site showed progressive increase in the thickness over the period of study and the average increase in thickness was about 12.4% at the end of 1 year. The average increase in volume at the donor site was of 2.65% after 12 months. Similarly, the average bone density increased by 3.7% at the end of 1 year. This prospective study conclusively proves that the residual bone at the donor site of the split cranial bone graft harvest site continues to grow in thickness and density over a period of 1 year.
Impact of Rural Residence on Kidney Transplant Rates Among Waitlisted Candidates in the VA Transplant Programs
Authors: O’Shea Amy M.J. , Franciscus Carrie L. , Kaboli Peter J. , Kalil Roberto S. 
Published: July 2019

Background.
Although proportionally more veterans live in rural areas compared to nonveterans, the impact of rurality status on kidney transplantation (KTP) access among veterans is unknown. Our objective was to study KTP rates among veterans listed for KTP and to compare the impact of rurality status on KTP rates among veterans and nonveterans.

Methods.
Retrospective cohort study of adult patients waitlisted per the United Network for Organ Sharing from January 2000 to December 2014. Patient characteristics were compared using Chi-square or t tests, as appropriate, by veteran status and patient rurality. Multivariable competing-risks Cox regression was performed.

Results.
The study sample included 3281 veterans receiving care in Veteran Health Administration transplant programs and 445 177 nonveterans. Veterans, compared to nonveterans, were older (57 versus 50 y; P < 0.001), more likely to be male (96% versus 60%; P < 0.001) or diabetic at waitlisting (51% versus 41%; P < 0.001), and less likely be an urban resident (79% versus 84%; P < 0.001). Among veterans, dialysis duration prior to registration was longer among urban compared to all other rurality types (810 ± 22.1 d versus 632 to 702 ± 41.6 to 77.6 d; P = 0.02). In multivariate competing risks models, there was no evidence that the hazard of transplant among veterans differs by residential rurality.

Conclusions.
Among waitlisted veterans served by Veteran Health Administration transplant programs, residential rurality status does not portend longer waiting time for KTP.
Ultrasound Molecular Imaging of Lymphocyte-endothelium Adhesion Cascade in Acute Cellular Rejection of Cardiac Allografts
Authors: Xie Yu , Chen Yihan , Zhang Li , Wu Meiying , Deng Zhiting , Yang Yali , Wang Jing , Lv Qing , Zheng Hairong , Xie Mingxing , Yan Fei 
Published: July 2019

Background.
Acute cellular rejection is one of the main reasons for graft failure after heart transplantation. A precise diagnosis at the early stage of acute cellular rejection is a big challenge for clinicians. Given the importance of the interaction between T cells and graft endothelia in initiating rejection, we developed T cell-microbubble complexes (cell-MBs) as ultrasound molecular imaging probes to monitor the lymphocyte–endothelium adhesion cascade in cardiac acute cellular rejection.

Methods.
Cell-MBs were fabricated by incubating lymphocytes with anti-CD4 antibody-conjugated MBs (MBCD4). The potential of cell-MBs as probes for detecting acute cardiac rejection was examined. Donor hearts from Brown Norway or Lewis rats were transplanted into Lewis recipients. Ultrasound molecular imaging was performed on allografts of untreated or cyclosporin A (CsA)-treated recipients, and isografts on posttransplantation day 3. Histology was used to assess rejection grades.

Results.
We detected a significantly stronger ultrasound molecular imaging signal of cell-MBs than that of MBCD4 or plain MBs in allografts of untreated and CsA-treated recipients. No signal enhancement was observed in isografts with cell-MBs. The signal of cell-MBs in allografts of the untreated group was significantly higher than that in the CsA-treated group, and the signal in the CsA-treated group was higher than that in isografts. Histology confirmed grade 3R rejection in the untreated group, grade 2R rejection in CsA-treated group, and no rejection in isografts.

Conclusions.
Our study suggests that cell-MBs can function as a promising probe to image the dynamic lymphocyte–endothelium adhesion cascade for noninvasive diagnosis of cardiac acute cellular rejection.
Improved Survival in Liver Transplant Patients Receiving Prolonged-release Tacrolimus-based Immunosuppression in the European Liver Transplant Registry (ELTR): An Extension Study
Authors: Adam René , Karam Vincent , Cailliez Valérie , Trunečka Pavel , Samuel Didier , Tisone Giuseppe , Němec Petr , Soubrane Olivier , Schneeberger Stefan , Gridelli Bruno , Bechstein Wolf O. , Risaliti Andrea , Line Pal-Dag , Vivarelli Marco , Rossi Massimo , Pirenne Jacques , Klempnauer Jurgen L. , Rummo Aleh , Di Benedetto Fabrizio , Zieniewicz Krzysztof , Troisi Roberto , Paul Andreas , Vali Toomas , Kollmar Otto , Boudjema Karim , Hoti Emir , Colledan Michele , Pratschke Johan , Lang Hauke , Popescu Irinel , Ericzon Bo-Goran , Strupas Kestutis , De Simone Paolo , Kochs Eberhard , Heyd Bruno , Gugenheim Jean , Pinna Antonio D. , Bennet William , Kazimi Mirjalal , Bachellier Philippe , Wigmore Stephen J. , Rasmussen Allan , Clavien Pierre-Alain , Hidalgo Ernest , O’Grady John G. , Zamboni Frausto , Kilic Murat , Duvoux Christophe 
Published: July 2019

Background.
We compared, through the European Liver Transplant Registry, long-term liver transplantation outcomes with prolonged-release tacrolimus (PR-T) versus immediate-release tacrolimus (IR-T)–based immunosuppression. This retrospective analysis comprises up to 8-year data collected between 2008 and 2016, in an extension of our previously published study.

Methods.
Patients with <1 month follow-up were excluded; patients were propensity score matched for baseline characteristics. Efficacy measures included: univariate/multivariate analyses of risk factors influencing graft/patient survival up to 8 years posttransplantation, and graft/patient survival up to 4 years with PR-T versus IR-T. Overall, 13 088 patients were included from 44 European centers; propensity score–matched analyses comprised 3006 patients (PR-T: n = 1002; IR-T: n = 2004).

Results.
In multivariate analyses, IR-T-based immunosuppression was associated with reduced graft survival (risk ratio, 1.49; P = 0.0038) and patient survival (risk ratio, 1.40; P = 0.0215). There was improvement with PR-T versus IR-T in graft survival (83% versus 77% at 4 y, respectively; P = 0.005) and patient survival (85% versus 80%; P = 0.017). Patients converted from IR-T to PR-T after 1 month had a higher graft survival rate than patients receiving IR-T at last follow-up (P < 0.001), or started and maintained on PR-T (P = 0.019). One graft loss in 4 years was avoided for every 14.3 patients treated with PR-T versus IR-T.

Conclusions.
PR-T-based immunosuppression might improve long-term outcomes in liver transplant recipients than IR-T-based immunosuppression.
Charcot–Marie–Tooth disease and related disorders: an evolving landscape
Authors: Laurá Matilde , Pipis Menelaos , Rossor Alexander M. , Reilly Mary M. 
Published: July 2019

Purpose of review
Charcot–Marie–Tooth (CMT) disease and related disorders are the commonest group of inherited neuromuscular diseases and represent a heterogeneous group of disorders. This review will cover recent advances in genetic diagnosis and the evolving genetic and phenotype landscape of this disease group. We will review recent evidence of the increasingly recognized phenotypic overlap with other neurodegenerative conditions including hereditary spastic paraplegia, hereditary ataxias and mitochondrial diseases and highlight the importance of deep phenotyping to inform genetic diagnosis and prognosis.

Recent findings
Through whole exome sequencing and multicentre collaboration new genes are being identified as causal for CMT expanding the genetic heterogeneity of this condition. In addition, an increasing number of variants have been identified in genes known to cause complex inherited diseases in which the peripheral neuropathy is part of the disorder and may be the presenting feature. The recent discovery of a repeat expansion in the RFC1 gene in cerebellar ataxia, neuropathy, vestibular areflexia syndrome highlights the prevalence of late-onset recessive conditions which have historically been considered to cause early-onset disease.

Summary
CMT is an evolving field with considerable phenotypic and genetic heterogeneity and deep phenotyping remains a cornerstone in contemporary CMT diagnostics.
Associations between respiratory health outcomes and coal mine fire PM2.5 smoke exposure: a cross-sectional study
Authors: Johnson Amanda L , Gao Caroline X , Dennekamp Martine , Williamson Grant J , Brown David , Carroll Matthew TC , Monaco Anthony Del , Ikin Jillian F , Abramson Michael J , Guo Yuming 
Published: July 2019

ABSTRACTRationalIn 2014, local wildfires ignited a fire in the Morwell open cut coal mine, in south-eastern Australia, which burned for six weeks. Limited research was available regarding the respiratory health effects of coal mine fire-related PM2.5 smoke exposure.ObjectiveThis study examined associations between self-reported respiratory outcomes in adults and mine fire-related PM2.5 smoke exposure.ParticipantsEligible participants were adult residents of Morwell, identified using the Victorian electoral roll.Main outcome measuresSelf-reported data were collected as part of the Hazelwood Health Study Adult Survey.Mine fire-related PM2.5 concentrations were retrospectively modelled by the Commonwealth Scientific and Industrial Research Organisation Oceans & Atmosphere Flagship. Personalised mean 24-h and peak 12-h mine fire-related PM2.5 exposures were estimated for each participant. Data were analysed by multivariate logistic regression.ResultsThere was some evidence of a dose-response relationship between respiratory outcomes and mine fire PM2.5 concentrations. Chronic cough was associated with an Odds Ratio (OR) of 1.13 (95% Confidence Interval 1.03 to 1.23; p-value 0.007) per 10 μg/m3 increment in mean PM2.5 and 1.07 (1.02 to 1.12; 0.004) per 100 μg/m3 increment in peak PM2.5. Current wheeze was associated with peak PM2.5, OR=1.06 (1.02 to 1.11; 0.004) and chronic phlegm with mean PM2.5 OR=1.10 (1.00 to 1.20; 0.052). Males, participants 18-64 years and those residing in homes constructed from non-brick/concrete materials or homes with tin/metal roofs had higher estimated ORs.ConclusionsThese findings contribute to the formation of public health policy responses in the event of future major pollution episodes.Key MessagesWhat is the key question?Was there an association between mine fire-related PM2.5 smoke exposure and self-reported respiratory health outcomes for adult residents of Morwell, approximately 2.5 years after the mine fire?What is the bottom line?There was some evidence of a dose-response relationship between respiratory outcomes and mine fire-related PM2.5 concentrations.Why read on?There is limited research regarding the health effects of coal mine fire-related PM2.5 smoke exposure and to the best of our knowledge, this is the first study to examine self-reported respiratory symptoms associated with smoke exposure from a coal mine fire.
A moment of change: shifts in myeloarchitecture characterise adolescent development of cortical gradients
Authors: Paquola C , Bethlehem RAI , Seidlitz J , Wagstyl K , Romero-Garcia R , Whitaker KJ , Vos De Wael R , Williams GB ,   NSPN Consortium, Vértes PE , Margulies DS , Bernhardt BC , Bullmore ET 
Published: July 2019

AbstractThe biological processes underpinning adolescent brain maturation remain elusive. Expanding on previous work showing age-related changes in cortical morphology, we studied an accelerated longitudinal cohort of adolescents and young adults (n=223, two time points) to investigate dynamic reconfigurations in myeloarchitecture. Intracortical profiles were generated using magnetization transfer (MT) data, a myelin-sensitive magnetic resonance imaging contrast. Mixed-effect models of depth specific intracortical profiles demonstrated two separate processes i) related to overall increases in MT, and ii) showing a flattening of the MT profile related to enhanced signal in mid-to-deeper layers, especially in heteromodal and unimodal association cortices. This development was independent of morphological changes, and enhanced MT in mid-to-deeper layers was found to spatially co-localise specifically with gene expression markers of oligodendrocytes. Covariance analysis between all pairs of intracortical profiles revealed that these intracortical changes contributed to a gradual and dynamic differentiation from higher-order to lower-order systems. Depth-dependent trajectories of intracortical myeloarchitectural development contribute to the maturation of structural hierarchies in the human neocortex, providing a model for adolescent development that bridges microstructural and macroscopic scales of brain organization.eLife digestIntracortical myelin imposes a spatial structure on cortico-cortical connections, yet little is known about how myeloarchitecture develops throughout youth. We formulated a novel approach to study cortical myeloarchitecture in individual humans and leveraged an accelerated longitudinal design to track age-related changes from 14-27 years. We discovered two unique processes: one involving increasing mean myelin and another characterised by the preferential accumulation of myelin in mid-to-deeper cortical layers. Both processes contributed to an increasing segregation of lower-order from higher-order systems along the macroscale cortical hierarchy. These findings illustrate how layer specific microstructural changes contribute to the maturation of cortical organization and suggest adolescent fine tuning of hierarchical gradients of cortical networks.
Passive diffusion through nuclear pore complexes regulates levels of the yeast SAGA and SLIK coactivators complexes
Authors: Makio Tadashi , Wozniak Richard W. 
Published: July 2019

AbstractNuclear pore complexes (NPCs) control gene expression by regulating the bi-directional exchange of proteins and RNAs between nuclear and cytoplasmic compartments, including access of transcriptional regulators to the nucleoplasm. Here we show that the yeast nucleoporin Nup170, in addition to binding and silencing subtelomeric genes, supports transcription of genes regulated by the SAGA transcriptional activator. Specifically, we show that less SAGA complex is bound to target genes in the absence Nup170. Consistent with this observation, levels of the SAGA complex are decreased in cells lacking Nup170, while SAGA-related SLIK complexes are increased. This change in the ratio of SAGA to SLIK complexes is due to increased nuclear activity of Pep4, a protease responsible for production of the SLIK complex. Further analyses of various nucleoporin mutants revealed that the increased nuclear entry of Pep4 observed in thenup170Δ mutant likely occurs as consequence of an increase in the sieving limits of the NPC diffusion channel. On the basis of these results, we propose that changes in passive diffusion rates represents a mechanism for regulating SAGA/SLIK complex-mediated transcriptional events.
TNFRSF14 (HVEM) is a novel immune checkpoint for cancer immunotherapy in humanized mice
Authors: Aubert Nicolas , Brunel Simon , Olive Daniel , Marodon Gilles 
Published: July 2019

AbstractBackgroundTNFRSF14 (herpes virus entry mediator (HVEM) delivers a negative signal to T cells through the B and T Lymphocyte Attenuator (BTLA) molecule and has been associated with a worse prognosis in numerous malignancies. A formal demonstration that the HVEM/BTLA axis can be targeted for cancer immunotherapy is however still lacking.MethodsWe used immunodeficient NOD.SCID.gc-null mice reconstituted with human PBMC and grafted with human tumor cell lines subcutaneously. Tumor growth was compared using linear and non linear regression statistical modeling. The phenotype of tumor-infiltrating leukocytes was determined by flow cytometry. Statistical testing between groups was performed by a non-parametric t test. Quantification of mRNA in the tumor was performed using NanoString pre-designed panels. Bioinformatics analyses were performed using Metascape, Gene Set Enrichment Analysis and Ingenuity Pathways Analysis with embedded statistical testing.ResultsWe showed that a murine monoclonal antibody to human HVEM significantly impacted the growth of various HVEM-positive cancer cell lines in humanized NSG mice. Using CRISPR/cas9 mediated deletion of HVEM, we showed that HVEM expression by the tumor was necessary and sufficient to observe the therapeutic effect. Tumor cell killing by the mAb was dependent on innate immune cells still present in NSG mice, as indicated byin vivoandin vitroassays. Mechanistically, tumor control by human T cells by the mAb was dependent on CD8 T cells and was associated with an increase in the proliferation and number of tumor-infiltrating leukocytes. Accordingly, the expression of genes belonging to T cell activation pathways, such as JAK/STAT and NFKB were enriched in anti-HVEM-treated mice, whereas genes associated with immuno-suppressive pathways were decreased. Finally, we developed a simplein vivoassay to directly demonstrate that HVEM/BTLA is an immune checkpoint for T-cell mediated tumor control.ConclusionsOur results show that targeting HVEM is a promising strategy for cancer immunotherapy.
Exploring the infection dynamics of a bacterial pathogen on a remote oceanic island reveals annual epizootics impacting an albatross population
Authors: Jaeger Audrey , Gamble Amandine , Lagadec Erwan , Lebarbenchon Camille , Bourret Vincent , Tornos Jérémy , Barbraud Christophe , Lemberger Karin , Delord Karine , Weimerskirch Henri , Thiebot Jean-Baptiste , Boulinier Thierry , Tortosa Pablo 
Published: July 2019

AbstractOceanic islands with reduced species richness provide an opportunity to investigate the emergence, maintenance and transmission of infectious diseases threatening wildlife. On Amsterdam Island, in the southern Indian Ocean, massive and recurrent mortality of the nestlings of Indian yellow-nosed albatross (Thalassarche carteri) has been attributed to avian cholera caused byPasteurella multocida, a bacterial pathogen of likely human introduction. To understand the annual dynamics of pathogen prevalence, we measured the shedding of bacterial DNA by the albatrosses during four successive breeding seasons. The screening of 583 bird swabs by Real-Time PCR revealed an intense circulation ofP. multocidaduring each study year, with a steady increase of infection prevalence across the breeding season. In the three years of highest pathogen prevalence, the epizootics were associated with massive die-offs of nestlings, inducing low annual fledging success (< 20%). These findings and developed PCR protocol have crucial applications for refining wildlife conservation plans aiming at controlling this disease.
The wild species genome ancestry of domestic chickens
Authors: Lawal Raman Akinyanju , Martin Simon H. , Vanmechelen Koen , Vereijken Addie , Silva Pradeepa , Al-Atiyat Raed Mahmoud , Aljumaah Riyadh Salah , Mwacharo Joram M. , Wu Dong-Dong , Zhang Ya-Ping , Hocking Paul M. , Smith Jacqueline , Wragg David , Hanotte Olivier 
Published: July 2019

AbstractHybridization and/or introgression play a key role in the evolutionary history of animal species. It is commonly observed in several orders in wild birds. The domestic chickenGallus gallus domesticusis the commonest livestock species exploited for the benefit of mankind. The origin of its diversity remains unsettled. Here, we report a genome-wide analyses for signatures of introgression within domestic village chicken. We first established the genome-wide phylogeny and divergence time across the genusGallus, showing the sister relationships between Grey junglefowlG. sonneratiiand Ceylon junglefowlG. lafayettiiand that the Green junglefowl is the first diverging lineage within the genusGallus. Then, by analysing the whole-genome sequences of geographically diverse chicken populations, we reveal extensive bidirectional introgression between Grey junglefowl and domestic chicken and to a much less extent with Ceylon junglefowl. A single case of Green junglefowlG. variusintrogression was identified. These introgressed regions include biological functions related to the control of gene expression. Our results show that while the Red junglefowl is the main ancestral species, introgressive hybridization episodes have impacted the genome and contributed to the diversity of domestic chicken, although likely at different level across its geographic range.