bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enteric Microbiome Markers as Early Predictors of Clinical Outcome in Allogeneic Hematopoietic Stem Cell Transplant: Results of a Prospective Study in Adult Patients
Authors: Mancini Nicasio , Greco Raffaella , Pasciuta Renée , Barbanti Maria Chiara , Pini Giacomo , Morrow Olivia Beatrice , Morelli Mara , Vago Luca , Clementi Nicola , Giglio Fabio , Lupo Stanghellini Maria Teresa , Forcina Alessandra , Infurnari Laura , Marktel Sarah , Assanelli Andrea , Carrabba Matteo , Bernardi Massimo , Corti Consuelo , Burioni Roberto , Peccatori Jacopo , Sormani Maria Pia , Banfi Giuseppe , Ciceri Fabio , Clementi Massimo 
Published: October 2017

Abstract

Background
Infections and graft-vs-host disease (GvHD) still represent major, not easily predictable complications in allogeneic hematopoietic stem cell transplant (allo-HSCT). Both conditions have been correlated to altered enteric microbiome profiles during the peritransplant period. The main objective of this study was to identify possible early microbiome-based markers useful in pretransplant risk stratification.

Methods
Stool samples were collected from 96 consecutive patients at the beginning of the pretransplant conditioning regimen (T0) and at 10 (T1) and 30 (T2) days following transplant. When significant in univariate analysis, the identified microbiome markers were used in multivariate regression analyses, together with other significant clinical variables for allo-HSCT-related risk stratification. Four main outcomes were addressed: (1) septic complications, (2) GvHD, (3) relapse of the underlying disease, and (4) mortality.

Results
The presence of &gt;5% proinflammatory Enterobacteriaceae at T0 was the only significant marker for the risk of microbiologically confirmed sepsis. Moreover, ≤10% Lachnospiraceae at T0 was the only significant factor for increased risk of overall mortality, including death from both infectious and noninfectious causes.
Finally, a low bacterial alpha-diversity (Shannon index ≤ 1.3) at T1 was the only variable significantly correlating with an increased risk of GvHD within 30 days.

Conclusions
Microbiome markers can be useful in the very early identification of patients at risk for major transplant-related complications, offering new tools for individualized preemptive or therapeutic strategies to improve allo-HSCT outcomes.
First In-Human Experience With Complete Integration of Neuromodulation Device Within a Customized Cranial Implant
Authors: Gordon Chad R , Santiago Gabriel F , Huang Judy , Bergey Gregory K , Liu Shuya , Armand Mehran , Brem Henry , Anderson William S 
Published: October 2017

Abstract

BACKGROUND
Neuromodulation devices have the potential to transform modern day treatments for patients with medicine-resistant neurological disease. For instance, the NeuroPace System (NeuroPace Inc, Mountain View, California) is a Food and Drug Administration (FDA)-approved device developed for closed-loop direct brain neurostimulation in the setting of drug-resistant focal epilepsy. However, current methods require placement either above or below the skull in nonanatomic locations. This type of positioning has several drawbacks including visible deformities and scalp pressure from underneath leading to eventual wound healing difficulties, micromotion of hardware with infection, and extrusion leading to premature explantation.

OBJECTIVE
To introduce complete integration of a neuromodulation device within a customized cranial implant for biocompatibility optimization and prevention of visible deformity.

METHODS
We report a patient with drug-resistant focal epilepsy despite previous seizure surgery and maximized medical therapy. Preoperative imaging demonstrated severe resorption of previous bone flap causing deformity and risk for injury. She underwent successful responsive neurostimulation device implantation via complete integration within a clear customized cranial implant.

RESULTS
The patient has recovered well without complication and has been followed closely for 180 d. Device interrogation with electrocorticographic data transmission has been successfully performed through the clear implant material for the first time with no evidence of any wireless transmission interference.

CONCLUSION
Cranial contour irregularities, implant site infection, and bone flap resorption/osteomyelitis are adverse events associated with implantable neurotechnology. This method represents a novel strategy to incorporate all future neuromodulation devices within the confines of a low-profile, computer-designed cranial implant and the newfound potential to eliminate contour irregularities, improve outcomes, and optimize patient satisfaction.
Temporal relations between magnetic bright points and the solar sunspot cycle
Authors: Utz Dominik , Muller Richard , Van Doorsselaere Tom 
Published: October 2017

Abstract
The Sun shows a global magnetic field cycle traditionally best visible in the photosphere as a changing sunspot cycle featuring roughly an 11-year period. In addition we know that our host star also harbours small-scale magnetic fields often seen as strong concentrations of magnetic flux reaching kG field strengths. These features are situated in inter-granular lanes, where they show up bright as so-called magnetic bright points (MBPs). In this short paper we wish to analyse an homogenous, nearly 10-year-long synoptic Hinode image data set recorded from 2006 November up to 2016 February in the G-band to inspect the relationship between the number of MBPs at the solar disc centre and the relative sunspot number. Our findings suggest that the number of MBPs at the solar disc centre is indeed correlated to the relative sunspot number, but with the particular feature of showing two different temporal shifts between the decreasing phase of cycle 23 including the minimum and the increasing phase of cycle 24 including the maximum. While the former is shifted by about 22 months, the latter is only shifted by less than 12 months. Moreover, we introduce and discuss an analytical model to predict the number of MBPs at the solar disc centre purely depending on the evolution of the relative sunspot number as well as the temporal change of the relative sunspot number and two background parameters describing a possibly acting surface dynamo as well as the strength of the magnetic field diffusion. Finally, we are able to confirm the plausibility of the temporal shifts by a simplistic random walk model. The main conclusion to be drawn from this work is that the injection of magnetic flux, coming from active regions as represented by sunspots, happens on faster time scales than the removal of small-scale magnetic flux elements later on.
Multiethnic meta-analysis identifies new loci for pulmonary function
Authors: Wyss Annah B. , Sofer Tamar , Lee Mi Kyeong , Terzikhan Natalie , Nguyen Jennifer N. , Lahousse Lies , Latourelle Jeanne C. , Smith Albert Vernon , Bartz Traci M. , Feitosa Mary F. , Gao Wei , Ahluwalia Tarunveer S. , Tang Wenbo , Oldmeadow Christopher , Duan Qing , Jong Kim de , Wojczynski Mary K. , Wang Xin-Qun , Noordam Raymond , Hartwig Fernando Pires , Jackson Victoria E. , Wang Tianyuan , Obeidat Ma’en , Hobbs Brian D. , Huan Tianxiao , Kichaev Gleb , Jin Jianping , Graff Mariaelisa , Harris Tamara B. , Kalhan Ravi , Heckbert Susan R. , Paternoster Lavinia , Burkart Kristin M. , Liu Yongmei , Holliday Elizabeth G. , Wilson James G. , Vonk Judith M. , Sanders Jason , Barr R. Graham , Mutsert Renée de , Menezes Ana Maria Baptista , Adams Hieab H. H. , Berge Maarten van den , Joehanes Roby , Launer Lenore J. , Morrison Alanna C. , Sitlani Colleen M. , Celedón Juan C. , Kritchevsky Stephen B. , Scott Rodney J. , Christensen Kaare , Rotter Jerome I. , Bonten Tobias N. , César Wehrmeister Fernando , Bossé Yohan , Franceschini Nora , Brody Jennifer A. , Kaplan Robert C. , Lohman Kurt , McEvoy Mark , Province Michael A. , Rosendaal Frits R. , Taylor Kent D. , Nickle David C. , North Kari E. , Fornage Myriam , Psaty Bruce M. , Myers Richard H. , O’Connor George , Hansen Torben , Laurie Cathy C. , Cassano Pat , Sung Joohon , Kim Woo Jin , Attia John R. , Lange Leslie , Boezen H. Marike , Thyagarajan Bharat , Rich Stephen S. , Mook-Kanamori Dennis O. , Horta Bernardo Lessa , Uitterlinden André G , Sin Don D. , Im Hae Kyung , Cho Michael H. , Brusselle Guy G. , Gharib Sina A. , Dupuis Josée , Manichaikul Ani , London Stephanie J. 
Published: October 2017

AbstractNearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N=60,552), African (N=8,429), Asian (N=9,959), and Hispanic/Latino (N=11,775) ethnicities. We identified over 50 novel loci at genome-wide significance in ancestry-specific and/or multiethnic meta-analyses. Recent fine mapping methods incorporating functional annotation, gene expression, and/or differences in linkage disequilibrium between ethnicities identified potential causal variants and genes at known and newly identified loci. Sixteen of the novel genes encode proteins with predicted or established drug targets, includingKCNK2andCDK12.
Defining the Layers of a Sensory Cilium with STORM and Cryo-Electron Nanoscopies
Authors: Robichaux Michael A. , Potter Valencia L. , Zhang Zhixian , He Feng , Schmid Michael F. , Wensel Theodore G. 
Published: October 2017

ABSTRACTPrimary cilia are cylindrical organelles extending from the surface of most animal cells that have been implicated in a host of signaling and sensory functions. Genetic defects in their component molecules, known as “ciliopathies” give rise to devastating symptoms, ranging from defective development, to kidney disease, to progressive blindness. The detailed structures of these organelles and the true functions of proteins encoded by ciliopathy genes are poorly understood because of the small size of cilia and the limitations of conventional microscopic techniques. We describe the combination of cryo-electron tomography, enhanced by sub-tomogram averaging, with super-resolution stochastic reconstruction microscopy (STORM) to define substructures and subdomains within the light-sensing rod sensory cilium of the mammalian retina. Longitudinal and radial domains are demarcated by structural features such as the axoneme and its connections to the ciliary membrane, and are correlated with molecular markers of these compartments, including Ca2+-binding protein centrin-2 in the lumen of the axoneme, acetylated tubulin forming the axoneme, the glycocalyx extending outward from the surface of the plasma membrane, and molecular residents of the space between axoneme and ciliary membrane, including Arl13B, intraflagellar transport proteins, BBS5, and syntaxin-3. Within this framework we document that deficiencies in the ciliopathy proteins BBS2, BBS7 and BBS9 lead to inappropriate accumulation of proteins in rod outer segments while largely preserving their sub-domain localization within the connecting cilium region, but alter the distribution of syntaxin-3 clusters.
Matrix stiffness modulates infection of endothelial cells byListeria monocytogenesvia expression of cell surface vimentin
Authors: Bastounis Effie E. , Yeh Yi-Ting , Theriot Julie A. 
Published: October 2017

AbstractExtracellular matrix (ECM) stiffness is one of many mechanical forces acting on mammalian adherent cells that influence cellular function. We have addressed the open question of how ECM stiffness might alter the susceptibility of host cells to infection by bacterial pathogens. We manufactured hydrogels of varying physiologically-relevant stiffness and seeded human microvascular endothelial cells (HMEC-1) on them. We then infected HMEC-1 with the bacterial pathogenListeria monocytogenes(Lm) and found that adhesion of Lm onto host cells increases monotonically with increasing matrix stiffness, an effect that requires the activity of focal adhesion kinase (FAK). We identified cell surface vimentin as a candidate surface receptor mediating stiffness-dependent adhesion of Lm to HMEC-1, and demonstrated that bacterial infection of these host cells is decreased when surface vimentin is perturbed. Our results provide the first evidence that ECM stiffness can mediate the susceptibility of host cells to bacterial infection.
Oscillatory Networks of High-Level Mental Alignment: A Perspective-Taking MEG Study
Authors: Seymour, R.A , Wang, H. , Rippon, G. , Kessler, K. 
Published: October 2017

AbstractMentally imagining another’s perspective is a high-level social process, reliant on manipulating internal representations of the self in an embodied manner. Recently Wang et al., (1) showed that theta-band (3-7Hz) brain oscillations within the right temporo-parietal junction (rTPJ) and brain regions coding for motor/body schema contribute to the process of perspective-taking. Using a task requiring participants to engage in embodied perspective-taking, we set out to unravel the extended functional brain network and its connections in detail. We found that increasing the angle of disparity between self and other perspective was accompanied by longer reaction times and increases in theta power within rTPJ, right lateral pre-frontal cortex (PFC) and right anterior cingulate cortex (ACC). Using nonparametric Granger-causality, we showed that during later stages of perspective-taking, the lateral PFC and ACC exert top-down influences over rTPJ, indicative of executive control processes required for managing conflicts between self and other perspectives. Finally, we quantified patterns of whole-brain phase coupling (imaginary coherence) in relation to rTPJ during high-level perspective taking. Results suggest that rTPJ increases its theta-band phase synchrony with brain regions involved in mentalizing and regions coding for motor/body schema; whilst decreasing its synchrony to visual regions. Implications for neurocognitive models are discussed, and it is proposed that rTPJ acts as a ‘hub’ to route bottom-up visual information to internal representations of the self during perspective-taking, co-ordinated by theta-band oscillations. The self is then projected onto the other’s perspective via embodied motor/body schema transformations, regulated by top-down cingulo-frontal activity.Significance StatementHigh-level social processing, such as the ability to imagine another’s visuospatial experience of the world (perspective taking), is a core part of what makes us human. Building on a substantial body of converging previous evidence, our study reveals how concerted activity across the cortex in low frequencies (theta: 3-7 Hz) implements this crucial human process. We found that oscillatory power and connectivity (imaginary coherence, nonparametric Granger causality) at theta frequency linked functional sub-networks of executive control, mentalizing, and sensorimotor/body schema via a main hub located in the right temporo-parietal junction (rTPJ). Our findings inform neurocognitive models of social cognition by describing the co-ordinated changes in brain network connectivity, mediated by theta oscillations, during perspective-taking.
Oncogenic RAS-MET signal interactions are modulated by P53 status in NF1-related MPNSTs
Authors: Pridgeon Matthew G. , Tovar Elizabeth A. , Essenburg Curt J. , Madaj Zachary , Boguslawski Elissa A. , Dischinger Patrick S. , Peacock Jacqueline D. , Maina Flavio , Dono Rosanna , Winn Mary E. , Graveel Carrie R. , Steensma Matthew R. 
Published: October 2017

AbstractWe previously reported that cooperative RAS-MET signaling drives disease progression in NF1-related MPNSTs, and that MET inhibition results in downstream inhibition of RAS/MAPK in the context ofMETamplification. This study revealed that response to MET inhibition appeared to be modulated byP53gene status. It is currently unclear how P53 function affects kinome signaling and response to kinase inhibition. Here we utilized genetically engineered mouse models with variable levels ofMetandHgfamplification and differentialp53status (NF1fl/KO;lox-stop-loxMETtg/+;Plp-creERTtg/+;NF1+/KO;p53R172H;Plp-creERTtg/+; andNF1+/KO;Plp-creERTtg/+t). These NF1-MPNST models were used to assess a novel MET/MEK (i.e. RAS-MET) inhibition strategy and investigate the adaptive kinome response to MET and MEK inhibition. We demonstrate that combination MET (capmatinib) and MEK (trametinib) inhibition fully suppresses MET, RAS/MAPK, and PI3K/AKT activation in P53 wild type tumors, whereas P53-mutant tumors demonstrated sustained CRAF, BRAF, and AKT activation in the presence of combined MET and MEK inhibition. Interestingly, trametinib therapy alone strongly activates MET signaling inMETandHGF-amplified tumors regardless of P53 status, an effect that was abrogated by the addition of capmatinib. We conclude that P53 alters RAS-MET signaling interactions that drive therapy resistance in NF1-related MPNSTs.
Phylostratigraphic analysis of tumor and developmental transcriptomes reveals relationship between oncogenesis, phylogenesis and ontogenesis
Authors: Zhou Joseph X. , Cisneros Luis , Knijnenburg Theo , Trachana Kalliopi , Davies Paul , Huang Sui 
Published: October 2017

ABSTRACTThe question of the existence of cancer is inadequately answered by invoking somatic mutations or the disruptions of cellular and tissue control mechanisms. As such uniformly random events alone cannot account for the almost inevitable occurrence of an extremely complex process such as cancer. In the different epistemic realm, an ultimate explanation of cancer is that cancer is a reversion of a cell to an ancestral pre-Metazoan state, i.e. a cellular form of atavism. Several studies have suggested that genes involved in cancer have evolved at particular evolutionary time linked to the unicellular-multicellular transition. Here we used a refined phylostratigraphic analysis of evolutionary ages of the known genes/pathways associated with cancer and the genes differentially expressed between normal and cancer tissue as well as between embryonic and mature (differentiated) cells. We found that cancer-specific transcriptomes and cancer-related pathways were enriched for genes that evolved in the pre-Metazoan era and depleted of genes that evolved in the post-Metazoan era. By contrast an opposite relation was found for cell maturation: the age distribution frequency of the genes expressed in differentiated epithelial cells were enriched for post-Metazoan genes and depleted of pre-Metazoan ones. These findings support the atavism theory that cancer cells manifest the reactivation of an ancient ancestral state featuring unicellular modalities. Thus our bioinformatics analyses suggest that not only does oncogenesis recapitulate ontogenesis, and ontogenesis recapitulates phylogenesis, but also oncogenesis recapitulates phylogenesis. This more encompassing perspective may offer a natural organizing framework for genetic alterations in cancers and point to new treatment options that target the genes controlling the atavism transition.One Sentence SummaryTracing cancer gene evolutionary ages revealed that cancer reverts to a pre-existing early Metazoan state.
Gestational low-protein intake enhances the whole kidney miR-192 and miR-200 family expression and epithelial-to-mesenchymal transition in adult male offspring
Authors: Sene Letícia B , Gonçalves Rizzi Victor Hugo , Gontijo José AR , Boer Patricia A 
Published: October 2017

ABSTRACTBackgroundStudies have been showed that maternal protein-restricted adult offspring, present pronounced reduction of nephron number associated with decreased fractional urinary sodium excretion and arterial hypertension. Also, recent advances in our understanding of the molecular pathways that govern the association of gestational nutritional restriction, intrauterine growth retardation inflammation with impaired nephrogenesis, nephron underdosing and kidney fibrosis point to the epithelial to mesenchymal transition (EMT) as the common.MethodIn the current study, the protein and sodium urinary excretion rates were evaluated and immunohistochemistry and western blot techniques were used to characterize the whole kidney structure changes in 16-wk old male LP offspring compared with age-matched controls. We also verify the expression of miRNAs, mRNAs and proteins markers of fibrosis and epithelial-to-mesenchymal transition in entire kidney prepared from LP offspring.ResultsIn the current study, we may assume that arterial hypertension and long-term hyperfiltration process manifests, itself by proteinuria was accompanied by increased whole kidney mRNA expression of TGF-β1, ZEB1, type I collagen and, fibronectin in parallel to decreased expression of E-cadherin in 16-wk old LP offspring. Surprisingly, the renal tissue miR-129, miR-141, miR-200c and miR-429 were significantly upregulated in LP offspring compared to age-matched NP rats.ConclusionConsidering that the overload in remaining nephrons, we may state that hypertension and proteinuria development following maternal protein restriction, may be a preponderant factor for the development of EMT and fibrous process and altered kidney ultrastructure in rat offspring. However, further studies are required to assess the contribution of miRNAs on renal injury progression in gestational protein-restricted model of fetal programming.
Computational model of brainstem circuit for state-dependent control of hypoglossal motoneurons
Authors: Naji Mohsen , Komarov Maxim , Krishnan Giri P. , Malhotra Atul , Powell Frank , Rukhadze Irma , Fenik Victor B. , Bazhenov Maxim 
Published: October 2017

AbstractIn patients with obstructive sleep apnea (OSA) the pharyngeal muscles become relaxed during sleep, which leads to a partial or complete closure of upper airway. Empirical studies suggest that withdrawal of noradrenergic and serotonergic drives importantly contribute to depression of hypoglossal motoneurons during rapid eye-movement (REM) sleep and, therefore, may contribute to OSA pathophysiology; however, specific cellular and synaptic mechanisms remain unknown. It was recently suggested that, in order to explain experimental observations, the neuronal network for monoaminergic control of excitability of hypoglossal motoneurons has to include excitatory and inhibitory perihypoglossal interneurons that would mediate noradrenergic and serotonergic drives to the motoneurons. In this study, we applied a biophysical network model to validate the rationality of the proposed circuit and to investigate the dynamics of its neuronal populations during REM sleep-induced withdrawal of noradrenergic and serotonergic drives. The state-dependent activity of the model hypoglossal motoneurons during simulated REM sleep with or without a virtual application of noradrenergic and serotonergic drugs was in qualitative agreement with in vivo data. The study predicts the dynamics of the perihypoglossal interneurons during these conditions and corroborates the hypothesis that the excitatory interneurons may integrate both noradrenergic and serotonergic drives. The latter drive has to be mediated by the inhibitory interneurons. The study suggests that perihypoglossal interneurons may serve as novel potential targets for pharmacological treatment of OSA.