bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimated incidence and number of outpatient visits for seasonal influenza in 2015–2016 in Beijing, China
Authors: WU S. , VAN ASTEN L. , WANG L. , MCDONALD S. A. , PAN Y. , DUAN W. , ZHANG L. , SUN Y. , ZHANG Y. , ZHANG X. , PILOT E. , KRAFFT T. , VAN DER HOEK W. , VAN DER SANDE M. A. B. , YANG P. , WANG Q. 
Published: November 2017

SUMMARYInformation on morbidity burden of seasonal influenza in China is limited. A multiplier model was used to estimate the incidence and number of outpatient visits for seasonal influenza by age group for the 2015–2016 season in Beijing, the capital of China, based on reported numbers of influenza-like illness consultations and proportions of positive cases from influenza surveillance systems in Beijing, general consultation rates and other parameters from previous studies, surveys and surveillance systems. An estimated total of 1 190 200 (95% confidence interval (CI) 830 400–1 549 900) cases of influenza virus infections occurred in Beijing, 2015–2016 season, with an attack rate of 5·5% (95% CI 3·9–7·2%). These infections resulted in an estimated 468 280 (95% CI 70 700–606 800) outpatient visits, with an attack rate of 2·2% (95% CI 0·3–2·8%). The attack rate of influenza virus infections was highest among children aged 0–4 years (31·9% (95% CI 21·9–41·9%)), followed by children aged 5–14 years (18·7% (95% CI 12·9–24·5%)). Our study demonstrated a substantial influenza-related morbidity in Beijing, China, especially among the preschool- and school-aged children. This suggests that development or modification of seasonal influenza targeted vaccination strategies need to recognize that incidence is highest in children.
Language difficulties and internalizing problems: Bidirectional associations from 18 months to 8 years among boys and girls
Authors: Helland Siri Saugestad , Røysamb Espen , Wang Mari Vaage , Gustavson Kristin 
Published: November 2017

AbstractStudies have shown that early language difficulties are associated with later internalizing problems. Less is known about the nature of the association: the bidirectional relationship over time, the role of different types of language difficulties, and gender differences. The present study examined bidirectional longitudinal associations between parent-rated language difficulties and internalizing problems in a four-wave cross-lagged model from 18 months to 8 years. Data from the Norwegian Mother and Child Cohort Study were used (N = 114,000). Gender-specific dichotomized language variables were created, and associations were investigated uniquely for boys and girls. Logistic regression analyses showed that all cross-lagged associations from 18 months to 5 years were significant for girls (odds ratios [ORs] = 1.48–1.94). For boys, only internalizing problems at 3 years predicted change in language difficulties (OR = 2.33). From 5 to 8 years, the cross-lagged associations between semantic language difficulties and internalizing problems were significant and strong for girls (ORs = 1.92–2.97) and nonsignificant for boys. The results suggest that the associations between language difficulties and internalizing problems are bidirectional from an early age, and that girls are especially vulnerable for developing co-occurring language difficulties and internalizing problems during the years of transition to school.
Alternative polyadenylation of ZEB1 promotes its translation during genotoxic stress in pancreatic cancer cells
Authors: Passacantilli Ilaria , Panzeri Valentina , Bielli Pamela , Farini Donatella , Pilozzi Emanuela , Fave Gianfranco Delle , Capurso Gabriele , Sette Claudio 
Published: November 2017

AbstractPancreatic ductal adenocarcinoma (PDAC) is characterized by extremely poor prognosis. The standard chemotherapeutic drug, gemcitabine, does not offer significant improvements for PDAC management due to the rapid acquisition of drug resistance by patients. Recent evidence indicates that epithelial-to-mesenchymal transition (EMT) of PDAC cells is strictly associated to early metastasization and resistance to chemotherapy. However, it is not exactly clear how EMT is related to drug resistance or how chemotherapy influences EMT. Herein, we found that ZEB1 is the only EMT-related transcription factor that clearly segregates mesenchymal and epithelial PDAC cell lines. Gemcitabine treatment caused upregulation of ZEB1 protein through post-transcriptional mechanisms in mesenchymal PDAC cells within a context of global inhibition of protein synthesis. The increase in ZEB1 protein correlates with alternative polyadenylation of the transcript, leading to shortening of the 3' untranslated region (UTR) and deletion of binding sites for repressive microRNAs. Polysome profiling indicated that shorter ZEB1 transcripts are specifically retained on the polysomes of PDAC cells during genotoxic stress, while most mRNAs, including longer ZEB1 transcripts, are depleted. Thus, our findings uncover a novel layer of ZEB1 regulation through 3'-end shortening of its transcript and selective association with polysomes under genotoxic stress, strongly suggesting that PDAC cells rely on upregulation of ZEB1 protein expression to withstand hostile environments.
Three brothers with a nonsense mutation in KAT6A caused by parental germline mosaicism
Authors: Satoh Chisei , Maekawa Ryuta , Kinoshita Akira , Mishima Hiroyuki , Doi Michiko , Miyazaki Mutsuko , Fukuda Masafumi , Takahashi Haruo , Kondoh Tatsuro , Yoshiura Koh-ichiro 
Published: November 2017

AbstractMutations in KAT6A, encoding a member of the MYST family of histone acetyl-transferases, were recently reported in patients with a neurodevelopmental disorder (OMIM: #616268, autosomal dominant mental retardation-32). In this report, we describe three siblings with intellectual disability (ID) or global developmental delay and a KAT6A heterozygous nonsense mutation, i.e., c.3070C>T (p.R1024*, ENST00000406337; chr8:41795056G>A on hg19). This mutation was identified by whole-exome sequencing of all three siblings but not in a healthy sibling. The mutation was not detected in the peripheral blood of their parents, suggesting the existence of parental germline mosaicism. The primary symptoms of our patients included severe to profound ID or global developmental delay, including speech delay with craniofacial dysmorphism; these symptoms are consistent with symptoms previously described for patients with KAT6A mutations. Although several features are common among patients with KAT6A mutations, the features are relatively nonspecific, making it difficult to establish a clinical entity based on clinical findings alone. To the best of our knowledge, this is the first report of cases with a KAT6A mutation in an Asian population and these cases represent the first reported instances of germline mosaicism of this disease.
Spinal arteriovenous fistula coexisting within a spinal lipoma: report of two cases
Authors: Horiuchi Yosuke , Iwanami Akio , Akiyama Takenori , Hikata Tomohiro , Watanabe Kota , Yagi Mitsuru , Fujita Nobuyuki , Okada Eijiro , Nagoshi Narihito , Tsuji Osahiko , Ishii Ken , Yoshida Kazunari , Nakamura Masaya , Matsumoto Morio 
Published: November 2017

Abstract
Introduction
Spinal lipoma and spinal arteriovenous fistula (sAVF) are different pathologies and their co-existence is extremely rare. Here we reported two cases of adult-onset sAVF occurring within a spinal lipoma and with review the literature in an attempt to identify the mechanisim of and optimal treatment of this condition.

Case presentation
Case 1 was a 51-year-old man who was treated by embolization of the feeding artery and ligation of the draining vein. Case 2 was a 53-year-old man who was treated by embolization and resection of the tumor containing the shunt zone. In both cases, symptoms improved after surgery. However, in Case 1, angiography at 1 month after the surgery revealed recurrence of the arteriovenous shunt.

Discussion
A literature search revealed only nine other similar case reports. All cases, including ours occurred in adults. In almost all cases, the shunt was located within the spinal lipoma. Pathologic examination revealed venous hypertension, but no evidence of congenital vascular malformation. Given that lipomas release angiogenic factors, the presence of a spinal lipoma may indicate its involvement in the development of acquired sAVF. Our two cases might represent a new subtype of sAVF. Based on our experiences, we recommend resection of the tumor containing the shunt for the management of sAVF.
Oscillators that sync and swarm
Authors: O’Keeffe Kevin P. , Hong Hyunsuk , Strogatz Steven H. 
Published: November 2017

AbstractSynchronization occurs in many natural and technological systems, from cardiac pacemaker cells to coupled lasers. In the synchronized state, the individual cells or lasers coordinate the timing of their oscillations, but they do not move through space. A complementary form of self-organization occurs among swarming insects, flocking birds, or schooling fish; now the individuals move through space, but without conspicuously altering their internal states. Here we explore systems in which both synchronization and swarming occur together. Specifically, we consider oscillators whose phase dynamics and spatial dynamics are coupled. We call them swarmalators, to highlight their dual character. A case study of a generalized Kuramoto model predicts five collective states as possible long-term modes of organization. These states may be observable in groups of sperm, Japanese tree frogs, colloidal suspensions of magnetic particles, and other biological and physical systems in which self-assembly and synchronization interact.
Emergent patterns of collective cell migration under tubular confinement
Authors: Xi Wang , Sonam Surabhi , Beng Saw Thuan , Ladoux Benoit , Teck Lim Chwee 
Published: November 2017

AbstractCollective epithelial behaviors are essential for the development of lumens in organs. However, conventional assays of planar systems fail to replicate cell cohorts of tubular structures that advance in concerted ways on out-of-plane curved and confined surfaces, such as ductal elongation in vivo. Here, we mimic such coordinated tissue migration by forming lumens of epithelial cell sheets inside microtubes of 1–10 cell lengths in diameter. We show that these cell tubes reproduce the physiological apical–basal polarity, and have actin alignment, cell orientation, tissue organization, and migration modes that depend on the extent of tubular confinement and/or curvature. In contrast to flat constraint, the cell sheets in a highly constricted smaller microtube demonstrate slow motion with periodic relaxation, but fast overall movement in large microtubes. Altogether, our findings provide insights into the emerging migratory modes for epithelial migration and growth under tubular confinement, which are reminiscent of the in vivo scenario.
DJ-1 controls bone homeostasis through the regulation of osteoclast differentiation
Authors: Kim Hyuk Soon , Nam Seung Taek , Mun Se Hwan , Lee Sun-Kyeong , Kim Hyun Woo , Park Young Hwan , Kim Bokyung , Won Kyung-Jong , Kim Hae-Rim , Park Yeong-Min , Kim Hyung Sik , Beaven Michael A. , Kim Young Mi , Choi Wahn Soo 
Published: November 2017

AbstractReceptor activator of NF-kB ligand (RANKL) generates intracellular reactive oxygen species (ROS), which increase RANKL-mediated signaling in osteoclast (OC) precursor bone marrow macrophages (BMMs). Here we show that a ROS scavenging protein DJ-1 negatively regulates RANKL-driven OC differentiation, also called osteoclastogenesis. DJ-1 ablation in mice leads to a decreased bone volume and an increase in OC numbers. In vitro, the activation of RANK-dependent signals is enhanced in DJ-1-deficient BMMs as compared to wild-type BMMs. DJ-1 suppresses the activation of both RANK-TRAF6 and RANK-FcRγ/Syk signaling pathways because of activation of Src homology region 2 domain-containing phosphatase-1, which is inhibited by ROS. Ablation of DJ-1 in mouse models of arthritis and RANKL-induced bone disease leads to an increase in the number of OCs, and exacerbation of bone damage. Overall, our results suggest that DJ-1 plays a role in bone homeostasis in normal physiology and in bone-associated pathology by negatively regulating osteoclastogenesis.
Unique transcriptome signatures and GM-CSF expression in lymphocytes from patients with spondyloarthritis
Authors: Al-Mossawi M. H. , Chen L. , Fang H. , Ridley A. , de Wit J. , Yager N. , Hammitzsch A. , Pulyakhina I. , Fairfax B. P. , Simone D. , Yi Yao , Bandyopadhyay S. , Doig K. , Gundle R , Kendrick B. , Powrie F. , Knight J. C. , Bowness P. 
Published: November 2017

AbstractSpondyloarthritis encompasses a group of common inflammatory diseases thought to be driven by IL-17A-secreting type-17 lymphocytes. Here we show increased numbers of GM-CSF-producing CD4 and CD8 lymphocytes in the blood and joints of patients with spondyloarthritis, and increased numbers of IL-17A+GM-CSF+ double-producing CD4, CD8, γδ and NK cells. GM-CSF production in CD4 T cells occurs both independently and in combination with classical Th1 and Th17 cytokines. Type 3 innate lymphoid cells producing predominantly GM-CSF are expanded in synovial tissues from patients with spondyloarthritis. GM-CSF+CD4+ cells, isolated using a triple cytokine capture approach, have a specific transcriptional signature. Both GM-CSF+ and IL-17A+GM-CSF+ double-producing CD4 T cells express increased levels of GPR65, a proton-sensing receptor associated with spondyloarthritis in genome-wide association studies and pathogenicity in murine inflammatory disease models. Silencing GPR65 in primary CD4 T cells reduces GM-CSF production. GM-CSF and GPR65 may thus serve as targets for therapeutic intervention of spondyloarthritis.
Quantitative analysis of protein-protein interactions and post-translational modifications in rare immune populations
Authors: Avin Ayelet , Levy Maayan , Porat Ziv , Abramson Jakub 
Published: November 2017

AbstractIn spite of recent advances in proteomics, quantitative analyses of protein–protein interactions (PPIs) or post-translational modifications (PTMs) in rare cell populations remain challenging. This is in particular true for analyses of rare immune and/or stem cell populations that are directly isolated from humans or animal models, and which are often characterized by multiple surface markers. To overcome these limitations, here we have developed proximity ligation imaging cytometry (PLIC), a protocol for proteomic analysis of rare cells. Specifically, by employing PLIC on medullary thymic epithelial cells (mTECs), which serve as a paradigm for a rare immune population, we demonstrate that PLIC overcomes the inherent limitations of conventional proteomic approaches and enables a high-resolution detection and quantification of PPIs and PTMs at a single cell level.
Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus
Authors: Schulz Herbert , Ruppert Ann-Kathrin , Herms Stefan , Wolf Christiane , Mirza-Schreiber Nazanin , Stegle Oliver , Czamara Darina , Forstner Andreas J. , Sivalingam Sugirthan , Schoch Susanne , Moebus Susanne , Pütz Benno , Hillmer Axel , Fricker Nadine , Vatter Hartmut , Müller-Myhsok Bertram , Nöthen Markus M. , Becker Albert J. , Hoffmann Per , Sander Thomas , Cichon Sven 
Published: November 2017

AbstractEmerging evidence emphasizes the strong impact of regulatory genomic elements in neurodevelopmental processes and the complex pathways of brain disorders. The present genome-wide quantitative trait loci analyses explore the cis-regulatory effects of single-nucleotide polymorphisms (SNPs) on DNA methylation (meQTL) and gene expression (eQTL) in 110 human hippocampal biopsies. We identify cis-meQTLs at 14,118 CpG methylation sites and cis-eQTLs for 302 3′-mRNA transcripts of 288 genes. Hippocampal cis-meQTL-CpGs are enriched in flanking regions of active promoters, CpG island shores, binding sites of the transcription factor CTCF and brain eQTLs. Cis-acting SNPs of hippocampal meQTLs and eQTLs significantly overlap schizophrenia-associated SNPs. Correlations of CpG methylation and RNA expression are found for 34 genes. Our comprehensive maps of cis-acting hippocampal meQTLs and eQTLs provide a link between disease-associated SNPs and the regulatory genome that will improve the functional interpretation of non-coding genetic variants in the molecular genetic dissection of brain disorders.
Millisecond dynamics of BTK reveal kinome-wide conformational plasticity within the apo kinase domain
Authors: Sultan Mohammad M. , Denny Rajiah Aldrin , Unwalla Ray , Lovering Frank , Pande Vijay S. 
Published: November 2017

AbstractBruton tyrosine kinase (BTK) is a key enzyme in B-cell development whose improper regulation causes severe immunodeficiency diseases. Design of selective BTK therapeutics would benefit from improved, in-silico structural modeling of the kinase’s solution ensemble. However, this remains challenging due to the immense computational cost of sampling events on biological timescales. In this work, we combine multi-millisecond molecular dynamics (MD) simulations with Markov state models (MSMs) to report on the thermodynamics, kinetics, and accessible states of BTK’s kinase domain. Our conformational landscape links the active state to several inactive states, connected via a structurally diverse intermediate. Our calculations predict a kinome-wide conformational plasticity, and indicate the presence of several new potentially druggable BTK states. We further find that the population of these states and the kinetics of their inter-conversion are modulated by protonation of an aspartate residue, establishing the power of MD & MSMs in predicting effects of chemical perturbations.
Biogenic selenium and its hepatoprotective activity
Authors: Li Baozhen , Li Dan , Jing Weixin , Fan Jinhua , Dahms Hans-Uwe , Lee Shao-Chin , Wang Lan 
Published: November 2017

AbstractElemental selenium nanoparticles (SeNPs) have multiple biological activities. In this study, we investigated the protective effects of biogenic SeNPs (BioSeNPs) on CCl4-induced liver damage in mice. The results showed that: (i) when compared to sodium selenite (SS), BioSeNPs has a similar tissue distribution after intragastrical administration to mice; (ii) BioSeNPs and SS showed comparable efficacy in increasing the activities of glutathione peroxidase and thioredoxin reductase in liver cell lines, mice blood and liver; (iii) pretreatment with BioSeNPs inhibiting the elevation of activities of various enzymes significantly which included aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase and liver lipid peroxide (p < 0.05 or p < 0.01) in CCl4-treated mice; (iv) activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) were significantly increased (p < 0.05 or p < 0.01) after a pretreatment with BioSeNPs in CCl4-treated mice; (v) histopathological damages in the liver from CCl4-treated mice were ameliorated by a pretreatment with BioSeNPs. In conclusion, these results have shown that BioSeNPs is able to protect the liver from CCl4-induced hepatic damage via increasing the antioxidant capacity and inhibiting oxidative damage. BioSeNPs may have the potential to be used as a trace element food supplement inducing antioxidant bioactivities.
People with higher interoceptive sensitivity are more altruistic, but improving interoception does not increase altruism
Authors: Piech Richard M. , Strelchuk Daniela , Knights Jake , Hjälmheden Jonathan V. , Olofsson Jonas K. , Aspell Jane E. 
Published: November 2017

AbstractPeople consistently show preferences and behaviors that benefit others at a cost to themselves, a phenomenon termed altruism. We investigated if perception of one’s body signals – interoception - may be underlying such behaviors. We tested if participants’ sensitivity to their own heartbeat predicted their decision on a choice between self-interest and altruism, and if improving this sensitivity through training would make participants more altruistic. Across these two experiments, interoceptive sensitivity predicted altruism measured through monetary generosity. Improving interoceptive sensitivity did, however, not lead to more altruistic behaviour. We conclude that there is a unique link between interoception and altruistic behaviour, likely established over an individual’s history of altruistic acts, and the body responses they elicit. The findings suggest that humans might literally ‘listen to their heart’ to guide their altruistic behavior.
Human ATG3 binding to lipid bilayers: role of lipid geometry, and electric charge
Authors: Hervás Javier H. , Landajuela Ane , Antón Zuriñe , Shnyrova Anna V. , Goñi Felix M. , Alonso Alicia 
Published: November 2017

AbstractSpecific protein-lipid interactions lead to a gradual recruitment of AuTophaGy-related (ATG) proteins to the nascent membrane during autophagosome (AP) formation. ATG3, a key protein in the movement of LC3 towards the isolation membrane, has been proposed to facilitate LC3/GABARAP lipidation in highly curved membranes. In this work we have performed a biophysical study of human ATG3 interaction with membranes containing phosphatidylethanolamine, phosphatidylcholine and anionic phospholipids. We have found that ATG3 interacts more strongly with negatively-charged phospholipid vesicles or nanotubes than with electrically neutral model membranes, cone-shaped anionic phospholipids (cardiolipin and phosphatidic acid) being particularly active in promoting binding. Moreover, an increase in membrane curvature facilitates ATG3 recruitment to membranes although addition of anionic lipid molecules makes the curvature factor relatively less important. The predicted N-terminus amphipathic α-helix of ATG3 would be responsible for membrane curvature detection, the positive residues Lys 9 and 11 being essential in the recognition of phospholipid negative moieties. We have also observed membrane aggregation induced by ATG3 in vitro, which could point to a more complex function of this protein in AP biogenesis. Moreover, in vitro GABARAP lipidation assays suggest that ATG3-membrane interaction could facilitate the lipidation of ATG8 homologues.
In vivo characterization of the electrophysiological and astrocytic responses to a silicon neuroprobe implanted in the mouse neocortex
Authors: Mols Katrien , Musa Silke , Nuttin Bart , Lagae Liesbet , Bonin Vincent 
Published: November 2017

AbstractSilicon neuroprobes hold great potential for studies of large-scale neural activity and brain computer interfaces, but data on brain response in chronic implants is limited. Here we explored with in vivo cellular imaging the response to multisite silicon probes for neural recordings. We tested a chronic implant for mice consisting of a CMOS-compatible silicon probe rigidly implanted in the cortex under a cranial imaging window. Multiunit recordings of cortical neurons with the implant showed no degradation of electrophysiological signals weeks after implantation (mean spike and noise amplitudes of 186 ± 42 µVpp and 16 ± 3.2 µVrms, respectively, n = 5 mice). Two-photon imaging through the cranial window allowed longitudinal monitoring of fluorescently-labeled astrocytes from the second week post implantation for 8 weeks (n = 3 mice). The imaging showed a local increase in astrocyte-related fluorescence that remained stable from the second to the tenth week post implantation. These results demonstrate that, in a standard electrophysiology protocol in mice, rigidly implanted silicon probes can provide good short to medium term chronic recording performance with a limited astrocyte inflammatory response. The precise factors influencing the response to silicon probe implants remain to be elucidated.