bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical spectrum of central nervous system myelin oligodendrocyte glycoprotein autoimmunity in adults
Authors: Cobo-Calvo Alvaro , Vukusic Sandra , Marignier Romain 
Published: March 2019

Purpose of review
The clinical interest for auto-antibodies against myelin oligodendrocyte glycoprotein (MOG) has recently reemerged, with the use of more specific detection methods. Large national cohorts have allowed characterizing a more precise clinical spectrum delineated by the presence of human MOG-antibodies.

Recent findings
In adults with MOG-antibodies, optic neuritis is the most frequent clinical presentation, with features different from multiple sclerosis (MS), including bilateral involvement and predilection for the anterior part of the optic nerve. Myelitis and brainstem syndrome are also frequent, and may clinically mimic neuromyelitis optica spectrum disorders (NMOSD). Despite the frequently severe clinical presentation, most of patients recover quickly after steroids initiation. Other less typical presentations include encephalitis with seizures, cranial nerve involvement, and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids-like. Although the majority of adult patients follow a relapsing course, long-term prognosis differs from aquaporin-4-antibodies NMOSD, with only a small proportion of patients with a poor outcome.

Summary
MOG-antibodies-associated disease is a new entity in the spectrum of inflammatory demyelinating diseases, distinct from both MS and NMOSD. There is a crucial need to identify factors associated to the risk of relapse or poor outcome, to seek patient subgroups in which immunoactive treatments could be beneficial.
Report on the spatial spread of defective interfering particles and its role in suppressing infectious particles
Authors: Ali Qasim , Ke Ruian 
Published: March 2019

AbstractDefective interfering particles (DIPs) are categorized as non-infectious viruses with large deletions in their genomic material. A cell infected by a DIP require co-infection by a wild-type virus to complete its replicative lifecycle. There is an increasing interest in developing DIP based therapies in the form of molecular parasites that steal genetic resources of infectious particles. This parasitic behavior is enhanced by constructing engineering designs of DIPs to optimize their role in suppressing the virus infection within-host. Recent experimental studies characterize viral infection as a spatial process and emphasize on its spread rate and the area populated by the infectious particles (IPs). We developed a spatio-temporal model in the framework of reaction-diffusion equations to depict the functional organization of virus particles distributed over a tissue surface. Our model investigates the scenarios and figures out the aspects that can play a vital role to suppress the infection within-host. We studied the impact of initial dose of DIPs, the efficiency of DIP production and the role of cell maturation. Our results show that an engineered DIP can substantially decrease the concentration of IPs. We assert that the decrease in the rate of spatial spread of IPs requires non-deterministic settings.
Interaction Effects of Apolipoprotein E ε 4 and Cognitive Status on the Functional Connectivity within Default Mode Network in Individuals at Risk of Cognitive Impairments
Authors: Lu Hanna , Ma Suk Ling , Chiu Wing Winnie Chu , Ho Wong Savio Wai , Lam Linda C. W. 
Published: March 2019

ABSTRACTBackgroundDisturbance of intrinsic brain networks is often associated with APOE ε 4 allele and cognitive dysfunction. However, little is known about the functional connectivity strength (FCS) within default mode network (DMN).ObjectiveWe aimed to examine the independent effects APOE ε 4 and cognitive status and the interaction effect on the functional connectivity within DMN.MethodsResting-state functional MRI was conducted for sixty-five senior adults who had normal cognition or cognitive decline with or without APOE ε 4. Regions within DMN include mPFC, IPL, LTC, hippocampus and PCC. The absolute values of correlation coefficient between DMN regions were employed as the measures of FCS for quantifying the functional connectivity.ResultsMain effect of APOE ε 4 was found on the FCS of bilateral PCC (F = 6.133, p = 0.016), while the main effect of cognitive status was found on the FCS of left IPL and right mPFC (F = 4.585, p = 0.036). Interaction effect was found in the FCS of right mPFC and left LTC (F = 4.698, p = 0.034), right hippocampus and left LTC (F = 7.673, p = 0.008), left PCC and left LTC (F = 6.719, p = 0.012), right IPL and right LTC (F = 4.516, p = 0.038).ConclusionsAPOE ε 4 carriers with cognitive impairment denote a preclinical status characterized by aberrant inter-hemispheric FC within DMN. The network-level connectivity may be useful in the evaluation of the individuals at risk for developing AD and affiliate network-guided brain stimulation.
Genomic profiling of childhood tumor patient-derived xenograft models to enable rational clinical trial design
Authors: Rokita Jo Lynne , Rathi Komal S. , Cardenas Maria F. , Upton Kristen A. , Jayaseelan Joy , Cross Katherine L. , Pfeil Jacob , Ritenour Laura E. , Modi Apexa , Farrel Alvin , Way Gregory P. , Kendsersky Nathan M. , Patel Khushbu , Lopez Gonzalo , Vaksman Zalman , Mayoh Chelsea , Nance Jonas , McCoy Kristyn , Haber Michelle , Evans Kathryn , McCalmont Hannah , Bendak Katerina , Böhm Julia W. , Marshall Glenn M. , Tyrrell Vanessa , Kalletla Karthik , Braun Frank K. , Qi Lin , Du Yunchen , Zhang Huiyuan , Lindsay Holly B. , Zhao Sibo , Shu Jack , Baxter Patricia , Morton Christopher , Kurmashev Dias , Zheng Siyuan , Chen Yidong , Bowen Jay , Bryan Anthony C. , Leraas Kristen M. , Coppens Sara E. , Doddapaneni HarshaVardhan , Momin Zeineen , Zhang Wendong , Sacks Gregory I. , Hart Lori S. , Krytska Kateryna , Mosse Yael P. , Gatto Gregory J. , Sanchez Yolanda , Greene Casey S. , Diskin Sharon J. , Vaske Olena Morozova , Haussler David , Gastier-Foster Julie M. , Kolb E. Anders , Gorlick Richard , Li Xiao-Nan , Reynolds C. Patrick , Kurmasheva Raushan T. , Houghton Peter J. , Smith Malcolm A. , Lock Richard B. , Raman Pichai , Wheeler David A. , Maris John M. 
Published: March 2019

SummaryAccelerating cures for children with cancer remains an immediate challenge due to extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs) from high-risk childhood cancers, many refractory to current standard-of-care treatments. Here, we genomically characterize 261 PDX models from 29 unique pediatric cancer malignancies and demonstrate faithful recapitulation of histologies, subtypes, and refine our understanding of relapsed disease. Expression and mutational signatures are used to classify tumors forTP53andNF1inactivation, as well as impaired DNA repair. We anticipate that these data will serve as a resource for pediatric oncology drug development and guide rational clinical trial design for children with cancer.HighlightsMultiplatform genomic analysis defines landscape of 261 pediatric cancer patient derived xenograft (PDX) modelsPediatric patient derived xenografts faithfully recapitulate relapsed diseaseInferredTP53pathway inactivation correlates with pediatric cancer copy number burdenSomatic mutational signatures predict impaired DNA repair across multiple histologies
Neonatal morphometric similarity mapping for predicting brain age and characterizing neuroanatomic variation associated with preterm birth
Authors: Galdi Paola , Blesa Manuel , Stoye David Q. , Sullivan Gemma , Lamb Gillian J. , Quigley Alan J. , Thrippleton Michael J. , Bastin Mark E. , Boardman James P. 
Published: March 2019

AbstractMulti-contrast MRI captures information about brain macro- and micro-structure which can be combined in an integrated model to obtain a detailed “fingerprint” of the anatomical properties of an individual’s brain. Inter-regional similarities between features derived from structural and diffusion MRI, including regional volumes, diffusion tensor metrics, neurite orientation dispersion and density imaging measures, can be modelled as morphometric similarity networks (MSNs). Here, individual MSNs were derived from 105 neonates (59 preterm and 46 term) who were scanned between 38 and 45 weeks postmenstrual age (PMA). Inter-regional similarities were used as predictors in a regression model of age at the time of scanning and in a classification model to discriminate between preterm and term infant brains. When tested on unseen data, the regression model predicted PMA at scan with a mean absolute error of 0.70±0.56 weeks, and the classification model achieved 92% accuracy. We conclude that MSNs predict chronological brain age accurately; and they provide a data-driven approach to identify networks that characterise typical maturation and those that contribute most to neuroanatomic variation associated with preterm birth.HighlightsMultiple MRI features are integrated in a single model to study brain maturation in newborns.Morphometric similarity networks (MSNs) provide a whole-brain description of the structural properties of neonatal brain.The information encoded in MSNs is predictive of chronological brain age in the perinatal period.MSNs provide a novel data-driven method for investigating neuroanatomic variation associated with preterm birth.
DUX is a non-essential synchronizer of zygotic genome activation
Authors: Iaco Alberto De , Verp Sonia , Offner Sandra , Trono Didier 
Published: March 2019

AbstractSome of the earliest transcripts produced in fertilized human and mouse oocytes code for DUX, a double homeodomain protein that promotes embryonic genome activation (EGA). Deleting Dux by genome editing at the 1- to 2-cell stage in the mouse impairs EGA and blastocyst maturation. Here, we demonstrate that mice carrying homozygous Dux deletions display markedly reduced expression of DUX target genes and defects in both pre- and post-implantation development, with notably a disruption of the pace of the first few cell divisions and significant rates of late embryonic mortality. However, some Dux-/- embryos give raise to viable pups, indicating that DUX is important but not strictly essential for embryogenesis.Summary statementMurine DUX regulates transcription in the first embryonic cell divisions but it’s not necessary for embryogenesis
β-Caryophyllene Enhances the Transcriptional Upregulation of Cholesterol Biosynthesis in Breast Cancer Cells
Authors: Mboge Mam Y. , Ramirez-Mata Andrea , Bullock Adam , O’Donnell Riley , Mathias John V. , Davila Julie , Frost Christopher J. , Frost Susan C. 
Published: March 2019

Abstractβ-caryophyllene (BCP) exhibits anti-proliferative properties in cancer cells. Here, we examine the hypothesis that BCP induces membrane remodeling. Our data show that high concentrations of BCP increase membrane permeability of human breast cells (hBrC) causing detachment and cell death. At a sub-lethal concentration of BCP, we show that BCP induces a striking upregulation of genes involved in cholesterol biosynthesis, including the gene that encodes for HMGCoA reductase (HMGCR), the rate-determining step in cholesterol biosynthesis. In addition, stearoyl-CoA desaturase (SCD) is also upregulated which would lead to the enhanced formation of monounsaturated fatty acids, specifically oleate and palmitoleate from stearoyl CoA and palmitoyl CoA, respectively. These fatty acids are major components of membrane phospholipids and cholesterol esters. Together, these data suggest that cells respond to BCP by increasing the synthesis of components found in membranes. These responses could be viewed as a repair mechanism and/or as a mechanism to mount resistance to the cytotoxic effect of BCP. Blocking HMGCR activity enhances the cytotoxicity of BCP, suggesting that BCP may provide an additional therapeutic tool in controlling breast cancer cell growth.
Single-cell RNA-seq reveals spatially restricted multicellular fibrotic niches during lung fibrosis
Authors: Joshi Nikita , Watanabe Satoshi , Verma Rohan , Jablonski Renea P. , Chen Ching-I , Cheresh Paul , Reyfman Paul A. , McQuattie-Pimentel Alexandra C. , Sichizya Lango , Flozak Annette S. , Gottardi Cara J. , Cuda Carla M. , Perlman Harris , Jain Manu , Kamp David W. , Budinger GR Scott , Misharin Alexander V. 
Published: March 2019

AbstractOntologically distinct populations of macrophages differentially contribute to organ fibrosis through unknown mechanisms. We applied lineage tracing, spatial methods and single-cell RNA-seq to a spatially-restricted model of asbestos-induced pulmonary fibrosis. We demonstrate that while tissue-resident interstitial macrophages, tissue-resident alveolar macrophages, and monocyte-derived alveolar macrophages are present in the fibrotic niche, only monocyte-derived alveolar macrophages are causally related to fibrosis. Monocyte-derived alveolar macrophages were specifically localized to fibrotic regions in the proximity of fibroblasts where they expressed molecules known to drive fibroblast proliferation, including PDGFA. Moreover, we identified autocrine M-CSF/M-CSFR signaling in monocyte-derived alveolar macrophages as a novel mechanism promoting their self-maintenance and persistence in the fibrotic niche. Pharmacological blockade of M-CSF signaling led to disappearance of the established population of monocyte-derived alveolar macrophages. Thus, our data indicate that monocyte-derived alveolar macrophages are specifically recruited to the fibrotic niche where they are maintained by autocrine signaling and drive fibrosis by stimulating fibroblast proliferation.
FAIM opposes stress-induced loss of viability and blocks the formation of protein aggregates
Authors: Kaku Hiroaki , Rothstein Thomas L. 
Published: March 2019

AbstractA number of proteinopathies are associated with accumulation of misfolded proteins, which form pathological insoluble deposits. It is hypothesized that molecules capable of blocking formation of such protein aggregates might avert disease onset or delay disease progression. Here we report that Fas Apoptosis Inhibitory Molecule (FAIM) counteracts stress-induced loss of viability. We found that levels of ubiquitinated protein aggregates produced by cellular stress are much greater in FAIM-deficient cells and tissues. Moreover, in an in vitro cell-free system, FAIM specifically and directly prevents pathological protein aggregates without participation by other cellular elements, in particular the proteasomal and autophagic systems. Although this activity is similar to the function of heat shock proteins (HSPs), FAIM, which is highly conserved throughout evolution, bears no homology to any other protein, including HSPs. These results identify a new actor that protects cells against stress-induced loss of viability by preventing protein aggregates.
Anti-tubercular activity of novel 4-anilinoquinolines and 4-anilinoquinazolines
Authors: Asquith Christopher R. M. , Fleck Neil , Torrice Chad D. , Crona Daniel J. , Grundner Christoph , Zuercher William J. 
Published: March 2019

ABSTRACTWe screened a series of 4-anilinoquinolines and 4-anilinoquinazolines and identified novel inhibitors of Mycobacterium tuberculosis (Mtb). The focused 4-anilinoquinoline/quinazoline scaffold arrays yielded compounds with high potency and the identification of 6,7-dimethoxy-N-(4-((4-methylbenzyl)oxy)phenyl)quinolin-4-amine (34) with an MIC90 value of 0.63-1.25 μM. We also defined a series of key structural features, including the benzyloxy aniline and the 6,7-dimethoxy quinoline ring, that are important for Mtb inhibition. Importantly the compounds showed very limited toxicity and scope for further improvement by iterative medicinal chemistry.
A unified method for rare variant analysis of gene-environment interactions
Authors: Lim Elise , Chen Han , Dupuis Josée , Liu Ching-Ti 
Published: March 2019

AbstractAdvanced technology in whole-genome sequencing has offered the opportunity to comprehensively investigate the genetic contribution, particularly rare variants, to complex traits. Many rare variants analysis methods have been developed to jointly model the marginal effect but methods to detect gene-environment (GE) interactions are underdeveloped. Identifying the modification effects of environmental factors on genetic risk poses a considerable challenge. To tackle this challenge, we develop a unified method to detect GE interactions of a set of rare variants using generalized linear mixed effect model. The proposed method can accommodate both binary and continuous traits in related or unrelated samples. Under this model, genetic main effects, sample relatedness and GE interactions are modeled as random effects. We adopt a kernel-based method to leverage the joint information across rare variants and implement variance component score tests to reduce the computational burden. Our simulation study shows that the proposed method maintains correct type I error rates and high power under various scenarios, such as differing the direction of main genotype and GE interaction effects and the proportion of causal variants in the model for both continuous and binary traits. We illustrate our method to test gene-based interaction with smoking on body mass index or overweight status in the Framingham Heart Study and replicate theCHRNB4gene association reported in previous large consortium meta-analysis of single nucleotide polymorphism (SNP)-smoking interaction. Our proposed set-based GE test is computationally efficient and is applicable to both binary and continuous phenotypes, while appropriately accounting for familial or cryptic relatedness.
Extracellular vesicle-mediated RNA release inHistoplasma capsulatum
Authors: Alves Lysangela R. , da Silva Roberta Peres , Sanchez David A. , Zamith-Miranda Daniel , Rodrigues Marcio L. , Goldenberg Samuel , Puccia Rosana , Nosanchuk Joshua D. 
Published: March 2019

AbstractEukaryotic cells, including fungi, release extracellular vesicles (EVs). These lipid bilayered compartments play essential roles in cellular communication and pathogenesis. EV composition is complex and includes proteins, glycans, pigments, and RNA. RNA classes with putative roles in pathogenesis have been described in EVs produced by fungi. Here we describe the RNA content in EVs produced by the G186AR and G217B strains ofHistoplasma capsulatum, an important human fungal pathogen. A total of 124 mRNA were identified in both strains. In this set of RNA classes, 93 transcripts were enriched in EVs from the G217B strain, while 31 enriched in EVs produced by the G186AR strain. This result suggests that there are important strain-specific properties in the mRNA composition of fungal EVs. We also identified short fragments (25-40 long) that were strain-specific, with a greater number of them identified in EVs produced by the G217B strain. Remarkably, the most enriched processes were stress responses and translation. Half of these fragments aligned to the reverse strand of the transcript, suggesting the occurrence of miRNA-like molecules in fungal EVs. We also compared the transcriptome profiles ofH. capsulatumwith the RNA composition of EVs and no correlation was observed. Altogether, our study provided information about the RNA molecules present inH. capsulatumEVs, and the differences in composition between the G186AR and G217B strains. In addition, we showed that the correlation between the most expressed transcripts in the cell and their presence in the EVs, reinforcing the idea that the RNAs were directed to the EVs by a regulated mechanism.ImportanceExtracellular vesicles (EVs) play important roles in cellular communication and pathogenesis. The RNA molecules in EVs have been implicated in a variety of processes. In pathogenic fungi, EV-associated RNA classes have recently been described; however, only a few studies describing the RNA in fungal EVs are available. An improved knowledge on EV-associated RNA will contribute to the understanding of their role during infection. In this study, we described the RNA content in EVs produced by two isolates ofHistoplasma capsulatum. Our results add this important pathogen to the current short list of fungal species with the ability to use EVs for the extracellular release of RNA.
Measurement error correlation within blocks of indicators in consistent partial least squares
Authors: Rademaker Manuel E. , Schuberth Florian , Dijkstra Theo K. 
Published: March 2019

Purpose
The purpose of this paper is to enhance consistent partial least squares (PLSc) to yield consistent parameter estimates for population models whose indicator blocks contain a subset of correlated measurement errors.

Design/methodology/approach
Correction for attenuation as originally applied by PLSc is modified to include a priori assumptions on the structure of the measurement error correlations within blocks of indicators. To assess the efficacy of the modification, a Monte Carlo simulation is conducted.

Findings
In the presence of population measurement error correlation, estimated parameter bias is generally small for original and modified PLSc, with the latter outperforming the former for large sample sizes. In terms of the root mean squared error, the results are virtually identical for both original and modified PLSc. Only for relatively large sample sizes, high population measurement error correlation, and low population composite reliability are the increased standard errors associated with the modification outweighed by a smaller bias. These findings are regarded as initial evidence that original PLSc is comparatively robust with respect to misspecification of the structure of measurement error correlations within blocks of indicators.

Originality/value
Introducing and investigating a new approach to address measurement error correlation within blocks of indicators in PLSc, this paper contributes to the ongoing development and assessment of recent advancements in partial least squares path modeling.
Identifying the resource integration processes of green service
Authors: Guyader Hugo , Ottosson Mikael , Frankelius Per , Witell Lars 
Published: March 2019

Purpose
The purpose of this paper is to improve the understanding of green service. In particular, the focus is on identifying homopathic and heteropathic resource integration processes that preserve or increase the resourceness of the natural ecosystem.

Design/methodology/approach
Through an extensive multiple case study involving ten service providers from diverse sectors based on a substantial number of interviews, detailed accounts of green service are provided.

Findings
Six resource integration processes were identified: reducing, recirculating, recycling, redistributing, reframing and renewing. While four of these processes are based on homopathic resource integration, both reframing and renewing are based on heteropathic resource integration. While homopathic processes historically constitute a green service by mitigating the impact of consumption on the environment, heteropathic resource integration increases the resourceness of the natural ecosystem through emergent processes and the (re)creation of natural resources.

Research limitations/implications
The present study breaks away from the paradigm that “green service” is about reducing the negative environmental impact of existing services, toward providing a green service that expands biological diversity and other natural resources.

Originality/value
Transformative service research on environmental sustainability is still in its infancy. The present study contributes through conceptualizing green service, redefining existing resource integration processes (reducing, recirculating, recycling) and identifying new resource integration processes (redistributing, reframing, renewing).