bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Test Reporting and Counseling for Melanoma Risk in Minors May Improve Sun Protection Without Inducing Distress
Authors: Stump Tammy K. , Aspinwall Lisa G. , Kohlmann Wendy , Champine Marjan , Hauglid Jamie , Wu Yelena P. , Scott Emily , Cassidy Pamela , Leachman Sancy A. 
Published: January 2018

AbstractGenetic testing of minors is advised only for conditions in which benefits of early intervention outweigh potential psychological harms. This study investigated whether genetic counseling and test reporting for the CDKN2A/p16 mutation, which confers highly elevated melanoma risk, improved sun protection without inducing distress. Eighteen minors (Mage = 12.4, SD = 1.9) from melanoma‐prone families completed measures of protective behavior and distress at baseline, 1 week (distress only), 1 month, and 1 year following test disclosure. Participants and their mothers were individually interviewed on the psychological and behavioral impact of genetic testing 1 month and 1 year post‐disclosure. Carriers (n = 9) and noncarriers (n = 9) reported significantly fewer sunburns and a greater proportion reported sun protection adherence between baseline and 1 year post‐disclosure; results did not vary by mutation status. Anxiety symptoms remained low post‐disclosure, while depressive symptoms and cancer worry decreased. Child and parent interviews corroborated these findings. Mothers indicated that genetic testing was beneficial (100%) because it promoted risk awareness (90.9%) and sun protection (81.8%) without making their children scared (89.9%); several noted their child's greater independent practice of sun protection (45.4%). In this small initial study, minors undergoing CDKN2A/p16 genetic testing reported behavioral improvements and consistently low distress, suggesting such testing may be safely implemented early in life, allowing greater opportunity for risk‐reducing lifestyle changes.
The influence of obesity on operating room time and perioperative complications in cochlear implantation
Authors: Hatch Jonathan L. , Boersma Isabel M. , Weir Forest W. , Bauschard Michael J. , Holcomb Meredith A. , Lambert Paul R. , Meyer Ted A. 
Published: January 2018

ObjectiveThe rising incidence of obesity in the United States is associated with increased healthcare expenditures and resource allocation. Obesity has been associated with prolonged operating times during surgical procedures. The primary objective of this study is to compare body mass index (BMI) to length of surgery during cochlear implantation.MethodsA retrospective case control study from a tertiary academic referral center was performed. Patients included were adults who underwent primary, single‐sided cochlear implantation with documented BMI and operating room (OR) times from January 2009 to July 2015. The following data were collected: BMI, total operating room time (TORT), surgical operating room time (SORT), ASA status, perioperative and postoperative complications, age, and gender.ResultsTwo hundreds and thirty‐four patients were included and stratified into obese (BMI >30) and non‐obese (BMI < 30) categories. Statistical analysis was performed comparing TORT against the obesity category along with other variables. Independent sample t‐test demonstrated that obesity increases TORT and SORT by 16.8 min (P = 0.0002) and 9.3 min (P = 0.03), respectively, compared to the non‐obese group. Multivariate linear regression analysis demonstrated no statistically significant impact of gender, or ASA status on total operating or surgical time. Obesity was associated with increased perioperative complications (odds ratio [OR], 6.21; 95% CI, 1.18–32.80; P = 0.03) and postoperative complications (OR, 3.97; 95% CI, 1.29–12.26; P = 0.02).ConclusionsObesity leads to longer TORT and SORT during primary cochlear implant surgery. Obesity is also associated with increased perioperative and postoperative complications compared to non‐obese patients. These data have implications with utilization of operating room resources.
Respiration pattern variability and related default mode network connectivity are altered in remitted depression
Authors: Zamoscik Vera Eva , Schmidt Stephanie Nicole Lyn , Gerchen Martin Fungisai , Samsouris Christos , Timm Christina , Kuehner Christine , Kirsch Peter 
Published: January 2018

AbstractBackgroundStudies with healthy participants and patients with respiratory diseases suggest a relation between respiration and mood. The aim of the present analyses was to investigate whether emotionally challenged remitted depressed participants show higher respiration pattern variability (RPV) and whether this is related to mood, clinical outcome and increased default mode network connectivity.MethodsTo challenge participants, sad mood was induced with keywords of personal negative life events in individuals with remitted depression [recurrent major depressive disorder (rMDD),n= 30] and matched healthy controls (HCs,n= 30) during functional magnetic resonance imaging. Respiration was measured by means of a built-in respiration belt. Additionally, questionnaires, a daily life assessment of mood and a 3 years follow-up were applied. For replication, we analysed RPV in an independent sample of 53 rMDD who underwent the same fMRI paradigm.ResultsDuring sad mood, rMDD compared with HC showed greater RPV, with higher variability in pause duration and respiration frequency and lower expiration to inspiration ratio. Higher RPV was related to lower daily life mood and predicted higher depression scores as well as relapses during a 3-year follow-up period. Furthermore, in rMDD compared with HC higher main respiration frequency exhibited a more positive association with connectivity of the posterior cingulate cortex and the right parahippocampal gyrus.ConclusionsThe results suggest a relation between RPV, mood and depression on the behavioural and neural level. Based on our findings, we propose interventions focusing on respiration to be a promising additional tool in the treatment of depression.
Nuclear p53-mediated repression of autophagy involves PINK1 transcriptional down-regulation
Authors: Goiran Thomas , Duplan Eric , Rouland Lila , el Manaa Wejdane , Lauritzen Inger , Dunys Julie , You Han , Checler Frédéric , Alves da Costa Cristine 
Published: January 2018

Abstract
p53 is a transcription factor that is implicated in the control of both apoptotic and autophagic cell death. This tumor suppressor elicits both pro-autophagic and anti-autophagic phenotypes depending of its intracellular localization. The ability of p53 to repress autophagy has been exclusively associated to its cytoplasmic localization. Here, we show that transcriptional activity of p53 also contributes to autophagy down-regulation. Thus, nuclear p53 controls PINK1, a key protein involved in the control of mitophagy, by repressing its promoter activity, protein and mRNA levels, ex-vivo and in vivo. We establish that deletion of an identified p53 responsive element on PINK1 promoter impacts p53-mediated PINK1 transcriptional repression and we demonstrate a p53-PINK1 physical interaction by chromatin immunoprecipitation. Accordingly, we show that only nuclear p53 accounts for its ability to repress PINK1 gene transcription. Further, we demonstrate ex-vivo and in vivo that p53 invalidation in human cells increases LC3 maturation as well as optineurin and NDP52 autophagy receptors expression and down-regulates TIM23, TOM20 and HSP60 mitophagy markers. Importantly, this phenotype is mimicked by TP53 invalidation in mice brain. Finally, by combining pharmacological and genetic approaches, we show that the p53-mediated negative regulation of autophagy is PINK1-dependent. Thus pifithrin-α-mediated blockade of p53 transcriptional activity enhances LC3 maturation and reduces p62, TIM23, TOM20 and HSP60 protein levels. This pifithrin-α-associated pro-mitophagy phenotype is fully abolished by PINK1 depletion. This data unravels a novel pathway by which nuclear p53 can repress autophagy/mitophagy that could underlie important dysfunctions in both neurodegenerative and cancer diseases.
MCL-1 is a prognostic indicator and drug target in breast cancer
Authors: Campbell Kirsteen J. , Dhayade Sandeep , Ferrari Nicola , Sims Andrew H. , Johnson Emma , Mason Susan M. , Dickson Ashley , Ryan Kevin M. , Kalna Gabriela , Edwards Joanne , Tait Stephen W. G. , Blyth Karen 
Published: January 2018

AbstractAnalysis of publicly available genomic and gene expression data demonstrates that MCL1 expression is frequently elevated in breast cancer. Distinct from other pro-survival Bcl-2 family members, the short half-life of MCL-1 protein led us to investigate MCL-1 protein expression in a breast cancer tissue microarray and correlate this with clinical data. Here, we report associations between high MCL-1 and poor prognosis in specific subtypes of breast cancer including triple-negative breast cancer, an aggressive form that lacks targeted treatment options. Deletion of MCL-1 in the mammary epithelium of genetically engineered mice revealed an absolute requirement for MCL-1 in breast tumorigenesis. The clinical applicability of these findings was tested through a combination of approaches including knock-down or inhibition of MCL-1 to show triple-negative breast cancer cell line dependence on MCL-1 in vitro and in vivo. Our data demonstrate that high MCL-1 protein expression is associated with poor outcome in breast cancer and support the therapeutic targeting of MCL-1 in this disease.
Epstein-Barr virus encoded latent membrane protein 1 suppresses necroptosis through targeting RIPK1/3 ubiquitination
Authors: Liu Xiaolan , Li Yueshuo , Peng Songling , Yu Xinfang , Li Wei , Shi Feng , Luo Xiangjian , Tang Min , Tan Zheqiong , Bode A. M. , Cao Ya 
Published: January 2018

AbstractNecroptosis is an alternative programmed cell death pathway that is unleashed in the absence of apoptosis and mediated by signaling complexes containing receptor-interating protein kinase 1 (RIPK1) and RIPK3. This form of cell death has recently been implicated in host defense system to eliminate pathogen-infected cells. However, only a few viral species such as herpes simplex virus (HSV) and cytomegalovirus (CMV) have evolved mechanisms inhibiting necroptosis to overcome host antiviral defense, which is important for successful pathogenesis. Here, we show that the γ-herpesvirus Epstein–Barr virus (EBV) blocks necroptosis in EBV-infected human nasopharyngeal epithelial cells and nasopharyngeal carcinoma cells. Our findings indicate that EBV-encoded latent membrane protein 1 (LMP1), which lacks an RIP homotypic interaction motif (RHIM) domain, has mechanisms distinct from RHIM signaling competition to inhibit this necroptotic pathway. Intriguingly, LMP1 interacts directly with both RIPK1 and RIPK3 through its C-terminal activation region. More importantly, LMP1 can modulate the post-translational modification of the two receptor-interacting proteins. We then show that LMP1-mediated promotion of K63-polyubiquitinated RIPK1, suppression of RIPK1 protein expression and inhibition of K63-polyubiquitinated RIPK3 induced a switch in cell fate from necroptotic death to survival. These findings provide direct evidence for the suppression of necroptosis by EBV and define a mechanism of LMP1 to interrupt the initiation process of necroptosis before necrosome formation.
Culex pipiens crossing type diversity is governed by an amplified and polymorphic operon of Wolbachia
Authors: Bonneau Manon , Atyame Celestine , Beji Marwa , Justy Fabienne , Cohen-Gonsaud Martin , Sicard Mathieu , Weill Mylène 
Published: January 2018

AbstractCulex pipiens mosquitoes are infected with Wolbachia (wPip) that cause an important diversity of cytoplasmic incompatibilities (CIs). Functional transgenic studies have implicated the cidA-cidB operon from wPip and its homolog in wMel in CI between infected Drosophila males and uninfected females. However, the genetic basis of the CI diversity induced by different Wolbachia strains was unknown. We show here that the remarkable diversity of CI in the C. pipiens complex is due to the presence, in all tested wPip genomes, of several copies of the cidA-cidB operon, which undergoes diversification through recombination events. In 183 isofemale lines of C. pipiens collected worldwide, specific variations of the cidA-cidB gene repertoires are found to match crossing types. The diversification of cidA-cidB is consistent with the hypothesis of a toxin–antitoxin system in which the gene cidB co-diversifies with the gene cidA, particularly in putative domains of reciprocal interactions.
Electrically driven electron spin resonance mediated by spin–valley–orbit coupling in a silicon quantum dot
Authors: Corna Andrea , Bourdet Léo , Maurand Romain , Crippa Alessandro , Kotekar-Patil Dharmraj , Bohuslavskyi Heorhii , Laviéville Romain , Hutin Louis , Barraud Sylvain , Jehl Xavier , Vinet Maud , De Franceschi Silvano , Niquet Yann-Michel , Sanquer Marc 
Published: January 2018

AbstractThe ability to manipulate electron spins with voltage-dependent electric fields is key to the operation of quantum spintronics devices, such as spin-based semiconductor qubits. A natural approach to electrical spin control exploits the spin–orbit coupling (SOC) inherently present in all materials. So far, this approach could not be applied to electrons in silicon, due to their extremely weak SOC. Here we report an experimental realization of electrically driven electron–spin resonance in a silicon-on-insulator (SOI) nanowire quantum dot device. The underlying driving mechanism results from an interplay between SOC and the multi-valley structure of the silicon conduction band, which is enhanced in the investigated nanowire geometry. We present a simple model capturing the essential physics and use tight-binding simulations for a more quantitative analysis. We discuss the relevance of our findings to the development of compact and scalable electron–spin qubits in silicon.
Degradation routes of trafficking-defective VLDLR mutants associated with Dysequilibrium syndrome
Authors: Kizhakkedath Praseetha , John Anne , Al-Gazali Lihadh , Ali Bassam R. 
Published: January 2018

AbstractLow density lipoprotein receptor (LDLR) family members are involved in signaling in the developing brain. Previously we have reported that missense mutations in the Very Low Density Lipoprotein Receptor gene (VLDLR), causing Dysequilibrium syndrome (DES), disrupt ligand-binding, due to endoplasmic reticulum (ER) retention of the mutants. We explored the degradation routes of these VLDLR mutants in cultured cells. Our results indicate that VLDLR mutants are retained in the ER for prolonged periods which could be facilitated by association with the ER-resident chaperone calnexin. The mutants were prone to aggregation and capable of eliciting ER stress. The VLDLR mutants were found to be degraded predominantly by the proteasomal pathway, since ubiquitinated VLDLR was found to accumulate in response to proteasomal inhibition. Further, the mutants were found to interact with the ER degradation adaptor protein SEL1L. The degradation of VLDLR wild type and mutant were delayed in CRISPR/Cas9 edited SEL1L knock-out cells which was reversed by exogenous expression of SEL1L. In summary, ER retention of pathogenic VLDLR mutants involves binding to calnexin, elevated ER stress, and delayed degradation which is dependent on SEL1L. Since core LDLR family members share common structural domains, common mechanisms may be involved in their ER processing.
Decentralized dynamic understanding of hidden relations in complex networks
Authors: Mocanu Decebal Constantin , Exarchakos Georgios , Liotta Antonio 
Published: January 2018

AbstractAlmost all the natural or human made systems can be understood and controlled using complex networks. This is a difficult problem due to the very large number of elements in such networks, on the order of billions and higher, which makes it impossible to use conventional network analysis methods. Herein, we employ artificial intelligence (specifically swarm computing), to compute centrality metrics in a completely decentralized fashion. More exactly, we show that by overlaying a homogeneous artificial system (inspired by swarm intelligence) over a complex network (which is a heterogeneous system), and playing a game in the fused system, the changes in the homogeneous system will reflect perfectly the complex network properties. Our method, dubbed Game of Thieves (GOT), computes the importance of all network elements (both nodes and edges) in polylogarithmic time with respect to the total number of nodes. Contrary, the state-of-the-art methods need at least a quadratic time. Moreover, the excellent capabilities of our proposed approach, it terms of speed, accuracy, and functionality, open the path for better ways of understanding and controlling complex networks.
Pretreatment of wheat straw leads to structural changes and improved enzymatic hydrolysis
Authors: Zheng Qi , Zhou Tiantian , Wang Yibin , Cao Xiaohua , Wu Songqing , Zhao Meili , Wang Haoyuan , Xu Ming , Zheng Baodong , Zheng Jingui , Guan Xiong 
Published: January 2018

AbstractWheat straw (WS) is a potential biomass for production of monomeric sugars. However, the enzymatic hydrolysis ratio of cellulose in WS is relatively low due to the presence of lignin and hemicellulose. To enhance the enzymatic conversion of WS, we tested the impact of three different pretreatments, e.g. sulfuric acid (H2SO4), sodium hydroxide (NaOH), and hot water pretreatments to the enzymatic digestions. Among the three pretreatments, the highest cellulose conversion rate was obtained with the 4% NaOH pretreatment at 121 °C (87.2%). In addition, NaOH pretreatment was mainly effective in removing lignin, whereas the H2SO4 pretreatment efficiently removed hemicellulose. To investigate results of pretreated process for enhancement of enzyme-hydolysis to the WS, we used scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy to analyze structural changes of raw and treated materials. The structural analysis indicated that after H2SO4 and NaOH pretreatments, most of the amorphous cellulose and partial crystalline cellulose were hydrolyzed during enzymatic hydrolysis. The findings of the present study indicate that WS could be ideal materials for production of monomeric sugars with proper pretreatments and effective enzymatic base hydrolysis.
CCR5/CCL5 axis interaction promotes migratory and invasiveness of pancreatic cancer cells
Authors: Singh Santosh Kumar , Mishra Manoj K. , Eltoum Isam-Eldin A. , Bae Sejong , Lillard James W. , Singh Rajesh 
Published: January 2018

AbstractPancreatic cancer (PC) is one of the deadliest cancers and remains a major challenge due to its invasive and metastatic nature. Increased levels of CCR5 and CCL5 have established indicators for disease status in various cancers, including PC. However, their role in invasion and metastasis of PC is not known. Here we conducted immunohistochemistry of PC tissues and found elevated epithelial staining for CCR5 and CCL5 in metastatic PC tissues compared to non-neoplastic. In vitro experiments, such as flow cytometry, immunofluorescence and western blotting with human PC cell lines (AsPc-1, BxPc-3 and MIA PaCa-2), showed higher expression levels of CCR5. The CCL5 activation of PC cells expressing CCR5 increased their invasive potential, while treatment with CCR5 inhibitor maraviroc inhibited the CCL5 activation. CCL5 induced proliferation of PC cells was mediated through F-actin polymerization, while there was marked reduction when the cells were treated with maraviroc. The direct interaction of CCR5 with CCL5 was verified using a calcium mobilization assay. Taken together, our results demonstrate that CCR5 and CCL5 are potential markers for metastatic PC cancer, and their interaction leads to the increased PC cell invasion. Thus, blocking CCR5/CCL5 axis might prove beneficial to prevent metastasis and provide a more therapeutic strategy to control PC progression.
Intra-retinal Arterial Cannulation using a Microneedle for Central Retinal Artery Occlusion
Authors: Kadonosono Kazuaki , Yamane Shin , Inoue Maiko , Yamakawa Tadashi , Uchio Eiichi 
Published: January 2018

AbstractCentral retinal artery occlusion (CRAO) is a severe disease, often causing blindness. We evaluated the efficacy and safety of a surgical procedure for the treatment of acute CRAO in which retinal arterial cannulation with tissue plasminogen activator (tPA) is performed. The surgical procedure consisted of vitrectomy followed by cannulation of the central retinal artery and injection of tPA (200 μg) using a 47-gauge microneedle. Thirteen CRAO patients were treated within 48 hours of the onset of symptoms. The central retinal artery of all 13 eyes was successfully cannulated. The mean interval between the onset of symptoms and surgery was 38.7 hours. The results for all 13 eyes treated showed a statistically significant improvement in mean visual acuity between before and one month after treatment (−1.60 vs. −0.82 logarithmic values for minimum angle resolution (LogMAR), p = 0.0021). Fluorescein angiography showed complete reperfusion and incomplete reperfusion in 10 eyes and 3 eyes, respectively. Recently developed surgical instruments have made retinal-arterial cannulation feasible. Intra-retinal-arterial cannulation has potential as a method of improving visual function and microcirculation in eyes affected by CRAO.
Moderate acute alcohol intoxication increases visual motion repulsion
Authors: Wang Zhengchun , Wang Huan , Tzvetanov Tzvetomir , Zhou Yifeng 
Published: January 2018

AbstractAmong the serious consequences of alcohol abuse is the reduced ability to process visual information. Diminished vision from excessive consumption of alcohol has been implicated in industrial, home, and automobile accidents. Alcohol is also generally recognized as an inhibitor in the brain by potentiating GABA-ergic transmission. In this study, we focused on visual motion processing and explored whether moderate alcohol intoxication induced changes in inhibitory mediated motion repulsion in a center-surround configuration. We conducted a double-blind, placebo-controlled, within-subjects study on the effect of alcohol on visual motion repulsion. Each subject underwent three experimental conditions (no alcohol, placebo and moderate alcohol) on separate days. The order of the placebo and moderate alcohol conditions was counterbalanced. The results showed that the effects of the surround context on the perception of the center motion direction were similar in both the sober (no alcohol) and placebo conditions. However, contextual modulations were significantly stronger during intoxication compared to both the sober and placebo conditions. These results demonstrate that moderate alcohol consumption is associated with altered neural function in visual cortical areas and that motion repulsion deficits might reflect the inhibitory effects of alcohol on the central nervous system.