bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Clinical Features and Outcome of Pediatric Posttransplant Lymphoproliferative Disorder in Recipients of Small Bowel Allograft Versus Isolated Liver Transplantation
Authors: Chiou Fang Kuan , Beath Sue V. , Morland Bruce , Hartley Jane , van Mourik Indra , Abdel-Hady Mona , Kelly Deirdre A. , Sharif Khalid , Gupte Girish L. 
Published: October 2019

Background.
Higher incidence of posttransplant lymphoproliferative disorder (PTLD) is reported in the pediatric small bowel transplant (SBTx) population, which may be associated with more aggressive disease and poorer outcome as compared to liver transplant (LTx) recipients. We aim to compare the characteristics and outcome of PTLD in pediatric SBTx against LTx patients at a single center.

Methods.
Retrospective review of pediatric SBTx and LTx patients diagnosed with PTLD from 1989 to 2016 was conducted. Diagnosis of PTLD was biopsy-proven based on World Health Organization histologic criteria. Treatment protocol consisted of reduction of immunosuppression (RIS), rituximab (from 2000), cytotoxic T-lymphocyte (CTL) therapy (available in 1999–2004 and from 2011), and chemotherapy.

Results.
Thirty-seven PTLD patients were included following LTx (n = 23, incidence = 2.8%) and SBTx (n = 14, incidence = 14.9%). Monomorphic PTLD made up 64% of SBTx and 43% of LTx cases. RIS alone resulted in remission in 50% of LTx patients but none of the SBTx patients (P = 0.002). Poorer overall remission (57% versus 96%, P = 0.004), 2-year (46% versus 91%, P = 0.003), and 5-year survival rates (39% versus 90%, P = 0.002) were observed in the SBTx group. Risk factors associated with mortality following PTLD were SBTx (odds ratio [OR], 12.00; 95% confidence interval [CI], 2.34-61.45; P = 0.003), monomorphic histology (OR, 10.63; 95% CI, 1.88-60.25; P = 0.008), multisite involvement (OR, 6.38; 95% CI, 1.35-30.14; P = 0.019), and tumor involvement of allograft (OR, 5.33; 95% CI, 1.14-24.90; P = 0.033). Introduction of CTL therapy was associated with improved survival.

Conclusions.
Majority of PTLD following pediatric SBTx are of monomorphic subtype and associated with poorer outcome as compared to LTx patients. RIS is inadequate as a single strategy in managing PTLD in SBTx and prompt escalation to rituximab and CTL is recommended.
Bupropion Hydrochloride Sustained Release and Diurnal Enuresis: A Previously Unreported Adverse Effect
Authors: Schwitalla Theresa A. , Patel Raj A. , Catalano Glenn , Nirmalani-Gandhy Anjali 
Published: October 2019

Abstract
Bupropion hydrochloride (HCl) is an antidepressant that has many different biological targets, acting as both a norepinephrine-dopamine reuptake inhibitor as well as a nicotinic antagonist. This second-generation antidepressant is available in 3 bioequivalent formulations: immediate release, sustained release, and extended release, allowing providers to customize a patient's regimen for maximum tolerability and compliance. Although bupropion HCl's safety and tolerability have been demonstrated through several clinical trials, there are still a number of adverse effects that have been reported in the literature. These include headache, agitation, tremor, and insomnia. There is also an increased risk of developing seizures during bupropion treatment. Although urinary symptoms were noted during the clinical trials, these are relatively rare adverse effects. Here we report the case of a 61-year-old man who developed diurnal enuresis during treatment with bupropion HCl sustained release. We will review the adverse effect burden associated with the use of bupropion and discuss the neuropharmacology of urinary symptoms associated with antidepressant treatment.
Age associated microbiome modulation and its association with systemic inflammation in a Rhesus Macaque Model
Authors: Pallikkuth Suresh , Russell Kyle , Sirupangi Tirupataiah , Mendez Roberto , Kvistad Daniel , Pahwa Rajendra , Villinger Francois , Banerjee Santanu , Pahwa Savita 
Published: October 2019

AbstractBackgroundAs the individual ages, the immune system decreases in activity while chronic systemic inflammation increases. The microbiome is also affected by age, decreasing in beneficial microbes while increasing in pathogenic, inflammation inducing microbes with corresponding changes in their metabolic profile. While aging is known to affect both, links between the two have been hard to uncover.MethodsFour young (age 3-6 years) and 12 old (age>18 years) Rhesus macaques were recruited for the study. PBMCs and plasma were collected to investigate immune cell subsets by flow cytometry and plasma cytokines by bead based multiplex cytokine analysis respectively. Stool samples were collected by ileal loop for microbiome analysis by shotgun metagenomics and serum, gut microbial lysate and microbe-free fecal extract was used to determine metabolomics by mass-spectrometry.ResultsOur aging NHP model recaptured many of the features of the age-associated immune alterations, with increased inflammation and alterations in immune cells subsets with lower number of CD4 T cells and a trend of age associated alterations in maturation subsets in older animals with lower naïve and higher central memory CD4 T cells. Older animals showed a significantly different microbiome from young animals with lower abundance of Firmicutes and higher Archaeal and Proteobacterial species. Correlation analysis showed a link between microbes in older animals with systemic inflammation. Analysis of metabolites in the serum and feces showed significant differences between specific metabolites between young and older animals that can influence age-associated morbidities.ConclusionThese data support the age associated alterations in microbiome profile and its association with persistent systemic inflammation and metabolome changes. Further mechanistic studies are needed to understand the relationship between inflammation and microbiome. Nevertheless, this NHP model recapitulates human age associated changes in immune, inflammatory and microbiome profiles and can be useful for designing future studies targeting microbiome modulations in aging.
TreeFix-TP: Phylogenetic Error-Correction for Infectious Disease Transmission Network Inference
Authors: Sledzieski Samuel , Zhang Chengchen , Mandoiu Ion , Bansal Mukul S 
Published: October 2019

AbstractBackgroundMany existing methods for estimation of infectious disease transmission networks use a phylogeny of the infecting strains as the basis for transmission network inference, and accurate network inference relies on accuracy of this underlying evolutionary history. However, phylogenetic reconstruction can be highly error prone and more sophisticated methods can fail to scale to larger outbreaks, negatively impacting downstream transmission network inference. Additionally, there are no currently available methods which are able to use within-host diversity to improve phylogenetic reconstruction.ResultsWe introduce a new method, TreeFix-TP, for accurate and scalable reconstruction of transmission phylogenies based on an error-correction framework. Our method uses intra-host strain diversity and host information to balance a parsimonious evaluation of the implied transmission network with statistical hypothesis testing on sequence data likelihood. The reconstructed tree minimizes the number of required disease transmissions while being as well supported by sequence data as the maximum likelihood phylogeny. We use a simulation framework for viral transmission and evolution to demonstrate that TreeFix-TP improves phylogenetic accuracy and downstream transmission network accuracy. We also use real data from ten HCV outbreaks and demonstrate how error-correction improves source detection.ConclusionsOur results show that using TreeFix-TP can lead to significant improvement in transmission phylogeny inference and that its performance is robust to variations in transmission and evolutionary parameters. Our experiments also demonstrate the importance of sampling multiple strain sequences from each infected host for accurate transmission network inference. TreeFix-TP is freely available open-source fromhttps://compbio.engr.uconn.edu/software/treefix-tp/.
An aphid host-responsive RNA transcript that migrates systemically in plants promotes aphid reproduction
Authors: Chen Yazhou , Singh Archana , Kaithakottill Gemy G. , Mathers Thomas C. , Gravino Matteo , Mugford Sam T. , Oosterhout Cock van , Swarbreck David , Hogenhout Saskia A. 
Published: October 2019

ABSTRACTAphids are sap-feeding insects that colonize a broad range of plant species and often cause feeding damage and transmit plant pathogens, including bacteria, viruses and viroids. These insects feed from the plant vascular tissue, predominantly the phloem. However, it remains largely unknown how aphids, and other sap-feeding insects, establish intimate long-term interactions with plants. To identify aphid virulence factors, we took advantage of the ability of the green peach aphidMyzus persicaeto colonize divergent plant species. We found that aM. persicaeclone of near-identical females establishes stable colonies on nine plant species of five representative plant eudicot and monocot families that span the angiosperm phylogeny. Members of the novel aphidYafamily are differentially expressed in aphids on the nine plant species, are co-regulated and organized as tandem repeats in aphid genomes. Interestingly, aphids translocateYatranscripts into plants and some transcripts migrate systemically within several plant species. RNAi-mediated knock down ofYagenes reducesM. persicaefecundity andM. persicaeproduces more progeny on transgenic plants that heterologously produce one of the systemically migratingYatranscripts as a long non-coding (lnc)RNA. Taken together, our work led to the discovery of a new host-responsive aphid gene family that operate as virulence factors. Transcripts of this family translocate into plants, including a lncRNA that migrates systemically and promotes aphid reproduction.Significance StatementThe green peach aphidMyzus persicaecauses yield losses of a diverse range of economically important crops primarily as a vector of more than 100 different plant pathogens. We found that a single genotype ofM. persicaeis able to colonize nine plant species, including diverse dicots and maize, indicating that this aphid is truly polyphagous. Members of a new aphidYafamily undergoes coordinated expression changes inM. persicaedepending on the plant species. The aphids translocateYatranscripts into plants during feeding and these RNAs migrate to systemic leaves. Moreover, heterologousin plantaexpression ofM. persicae Ya1as a long non-coding RNA promotes aphid reproduction. Our findings indicate that cross kingdom deployment of RNA is more common than thought.
Genetic and clinical analyses of psychosis spectrum symptoms in a large multi-ethnic youth cohort reveal significant link with ADHD
Authors: Loohuis Loes Olde , Mennigen Eva , Ori Anil , Perkins Diana , Robinson Elise , Addington Jean , Cadenhead Kristin S. , Cornblatt Barbara A. , Mathalon Daniel H. , McGlashan Thomas H. , Seidman Larry J. , Keshavan Matcheri , Stone William , Tsuang Ming T. , Walker Elaine F. , Woods Scott W. , Cannon Tyrone D. , Gur Ruben C. , Gur Raquel E. , Bearden Carrie E. , Ophoff Roel A. 
Published: October 2019

AbstractObjectivePsychotic symptoms are an important feature of severe neuropsychiatric disorders, but are also common in the general population, especially in youth. The genetic etiology of psychosis symptoms in youth remains poorly understood. To characterize genetic risk for psychosis spectrum symptoms (PS), we leverage a community-based multi-ethnic sample of children and adolescents aged 8-22 years, the Philadelphia Neurodevelopmental Cohort (n = 7,225, 20% PS).MethodsUsing an elastic net regression model, we aim to classify PS status using polygenic scores (PGS) based on a range of heritable psychiatric and brain-related traits in a multi-PGS model. We also perform univariate PGS associations and evaluate age-specific effects.ResultsThe multi-PGS analyses do not improve prediction of PS status over univariate models, but reveal that the attention deficit hyperactivity disorder (ADHD) PGS is robustly and uniquely associated with PS (OR 1.12 (1.05, 1.18) P = 0.0003). This association is: i) driven by subjects of European ancestry (OR=1.23 (1.14, 1.34), P=4.15×10−7) but is not observed in African American subjects (P=0.65) and ii) independent of phenotypic overlap. We also find a significant interaction with age (P=0.01), with a stronger association in younger children. In an independent sample, we replicate an increased ADHD PGS in 328 youth at clinical high risk for psychosis, compared to 216 unaffected controls (OR 1.06, CI(1.01, 1.11), P= 0.02).ConclusionsOur findings suggest that PS in youth may reflect a different genetic etiology than psychotic symptoms in adulthood, one more akin to ADHD, and shed light on how genetic risk can be investigated across early disease trajectories.
Whole genome sequencing and the application of a SNP panel reveal primary evolutionary lineages and genomic variation in the lion (Panthera leo)
Authors: Bertola L.D. , Vermaat M. , Lesilau F. , Chege M. , Tumenta P.N. , Sogbohossou E.A. , Schaap O.D. , Bauer H. , Patterson B.D. , White P.A. , de Iongh H.H. , Laros J.F.J. , Vrieling K. 
Published: October 2019

AbstractBackgroundPrevious phylogeographic studies of the lion (Panthera leo) have improved our insight into the distribution of genetic variation, as well as a revised taxonomy which now recognizes a northern (Panthera leo leo) and a southern (Panthera leo melanochaita) subspecies. However, existing whole range phylogeographic studies on lions either consist of very limited numbers of samples, or are focused on mitochondrial DNA and/or a limited set of microsatellites. The geographic extent of genetic lineages and their phylogenetic relationships remain uncertain, clouded by massive sampling gaps, sex-biased dispersal and incomplete lineage sorting.ResultsIn this study we present results of low depth whole genome sequencing and subsequent variant calling in ten lions sampled throughout the geographic range, resulting in the discovery of >150,000 Single Nucleotide Polymorphisms (SNPs). Phylogenetic analyses revealed the same basal split between northern and southern populations as well as four population clusters on a more local scale. Further, we designed a SNP panel, including 125 autosomal and 14 mitochondrial SNPs, which was tested on >200 lions from across their range. Results allow us to assign individuals to one of these four major clades (West & Central Africa, India, East Africa, or Southern Africa) and delineate these clades in more detail.ConclusionsThe results presented here, particularly the validated SNP panel, have important applications, not only for studying populations on a local geographic scale, but also for tracing samples of unknown origin for forensic purposes, and for guiding conservation management ofex situpopulations. Thus, these genomic resources not only contribute to our understanding of the evolutionary history of the lion, but may also play a crucial role in conservation efforts aimed at protecting the species in its full diversity.
Phenotypic clustering reveals distinct subtypes of polycystic ovary syndrome with novel genetic associations
Authors: Dapas Matthew , Lin Frederick T. J. , Nadkarni Girish N. , Sisk Ryan , Legro Richard S. , Urbanek Margrit , Hayes M. Geoffrey , Dunaif Andrea 
Published: October 2019

AbstractBackgroundPolycystic ovary syndrome (PCOS) is a common, complex genetic disorder affecting up to 15% of reproductive age women worldwide, depending on the diagnostic criteria applied. These diagnostic criteria are based on expert opinion and have been the subject of considerable controversy. The phenotypic variation observed in PCOS is suggestive of an underlying genetic heterogeneity, but a recent meta-analysis of European ancestry PCOS cases found that the genetic architecture of PCOS defined by different diagnostic criteria was generally similar, suggesting that the criteria do not identify biologically distinct disease subtypes. We performed this study to test the hypothesis that there are biologically relevant subtypes of PCOS.Methods and FindingsUnsupervised hierarchical cluster analysis was performed on quantitative anthropometric, reproductive, and metabolic traits in a genotyped discovery cohort of 893 PCOS cases and an ungenotyped validation cohort of 263 PCOS cases. We identified two PCOS subtypes: a “reproductive” group (21-23%) characterized by higher luteinizing hormone (LH) and sex hormone binding globulin (SHBG) levels with relatively low body mass index (BMI) and insulin levels; and a “metabolic” group (37-39%), characterized by higher BMI, glucose, and insulin levels with lower SHBG and LH levels. We performed a GWAS on the genotyped cohort, limiting the cases to either the reproductive or metabolic subtypes. We identified alleles in four novel loci that were associated with the reproductive subtype at genome-wide significance (PRDM2/KAZN1, P=2.2×10-10;IQCA1, P=2.8×10-9;BMPR1B/UNC5C, P=9.7×10-9;CDH10,P=1.2×10-8) and one locus that was significantly associated with the metabolic subtype (KCNH7/FIGN, P=1.0×10-8). We have previously reported that rare variants inDENND1A, a gene regulating androgen biosynthesis, were associated with PCOS quantitative traits in a family-based whole genome sequencing analysis. We classified the reproductive and metabolic subtypes in this family-based PCOS cohort and found that the subtypes tended to cluster in families and that carriers of rareDENND1Avariants were significantly more likely to have the reproductive subtype of PCOS. Limitations of our study were that only PCOS cases of European ancestry diagnosed by NIH criteria were included, the sample sizes for the subtype GWAS were small, and the GWAS findings were not replicated.ConclusionsIn conclusion, we have found stable reproductive and metabolic subtypes of PCOS. Further, these subtypes were associated with novel susceptibility loci. Our results suggest that these subtypes are biologically relevant since they have distinct genetic architectures. This study demonstrates how precise phenotypic delineation can be more powerful than increases in sample size for genetic association studies.
Shape coding in occipito-temporal cortex relies on object silhouette, curvature and medial-axis
Authors: Papale Paolo , Leo Andrea , Handjaras Giacomo , Cecchetti Luca , Pietrini Pietro , Ricciardi Emiliano 
Published: October 2019

AbstractObject recognition relies on different transformations of the retinal input, carried out by the visual system, that range from local contrast to object shape and category. While some of those transformations are thought to occur at specific stages of the visual hierarchy, the features they represent are correlated (e.g., object shape and identity) and selectivity for the same feature overlaps in many brain regions. This may be explained either by collinearity across representations, or may instead reflect the coding of multiple dimensions by the same cortical population. Moreover, orthogonal and shared components may differently impact on distinctive stages of the visual hierarchy. We recorded functional MRI (fMRI) activity while participants passively attended to object images and employed a statistical approach that partitioned orthogonal and shared object representations to reveal their relative impact on brain processing. Orthogonal shape representations (silhouette, curvature and medial-axis) independently explained distinct and overlapping clusters of selectivity in occitotemporal (OTC) and parietal cortex. Moreover, we show that the relevance of shared representations linearly increases moving from posterior to anterior regions. These results indicate that the visual cortex encodes shared relations between different features in a topographic fashion and that object shape is encoded along different dimensions, each representing orthogonal features.New & NoteworthyThere are several possible ways of characterizing the shape of an object. Which shape description better describes our brain responses while we passively perceive objects? Here, we employed three competing shape models to explain brain representations when viewing real objects. We found that object shape is encoded in a multi-dimensional fashion and thus defined by the interaction of multiple features.
Exploiting the GTEx resources to decipher the mechanisms at GWAS loci
Authors: Barbeira Alvaro N , Bonazzola Rodrigo , Gamazon Eric R , Liang Yanyu , Park YoSon , Kim-Hellmuth Sarah , Wang Gao , Jiang Zhuoxun , Zhou Dan , Hormozdiari Farhad , Liu Boxiang , Rao Abhiram , Hamel Andrew R , Pividori Milton D , Aguet François ,   GTEx GWAS Working Group, Bastarache Lisa , Jordan Daniel M , Verbanck Marie , Do Ron ,   GTEx Consortium, Stephens Matthew , Ardlie Kristin , McCarthy Mark , Montgomery Stephen B , Segrè Ayellet V , Brown Christopher D. , Lappalainen Tuuli , Wen Xiaoquan , Im Hae Kyung 
Published: October 2019

AbstractThe resources generated by the GTEx consortium offer unprecedented opportunities to advance our understanding of the biology of human diseases. Here, we present an in-depth examination of the phenotypic consequences of transcriptome regulation and a blueprint for the functional interpretation of genome-wide association study-discovered loci. Across a broad set of complex traits and diseases, we demonstrate widespread dose-dependent effects of RNA expression and splicing. We develop a data-driven framework to benchmark methods that prioritize causal genes and find no single approach outperforms the combination of multiple approaches. Using colocalization and association approaches that take into account the observed allelic heterogeneity of gene expression, we propose potential target genes for 47% (2,519 out of 5,385) of the GWAS loci examined. Our results demonstrate the translational relevance of the GTEx resources and highlight the need to increase their resolution and breadth to further our understanding of the genotype-phenotype link.
Up-regulation of autophagy by low concentration of salicylic acid delays methyl jasmonate-induced leaf senescence
Authors: Yin Runzhu , Yu Jingfang , Ji Yingbin , Liu Jian , Cheng Lixin , Zhou Jun 
Published: October 2019

ABSTRACTCrosstalk between salicylic acid (SA) and jasmonic acid (JA) signaling plays an important role in molecular regulation of plant senescence. Our previous works found that SA could delay methyl jasmonate (MeJA)-induced leaf senescence in a concentration-dependent manner. Here, the effect of low concentration of SA (LCSA) application on MeJA-induced leaf senescence was further assessed. High-throughput sequencing (RNA-Seq) results showed that LCSA did not have dominant effects on the genetic regulatory pathways of basal metabolism like nitrogen metabolism, photosynthesis and glycolysis. The ClusterONE was applied to identify discrete gene modules based on protein-protein interaction (PPI) network. Interestingly, an autophagy-related (ATG) module was identified in the differentially expressed genes (DEGs) that exclusively induced by MeJA together with LCSA. RT-qPCR confirmed that the expression of most of the determined ATG genes were upregulated by LCSA. Remarkably, in contrast to wild type (Col-0), LCSA cannot alleviate the leaf yellowing phenotype in autophagy defective mutants (atg5-1 and atg7-2) upon MeJA treatment. Confocal and western blot results showed that LCSA increased the number of autophagic bodies and autophagic flux during MeJA-induced leaf senescence. Collectively, our work revealed up-regulation of autophagy by LCSA as a key regulator to alleviate MeJA-induced leaf senescence.