bluuebunny/crossref_metadata_2025_split huggingface dataset:
From primordial gas to the medicine cabinet
Authors: Papapetropoulos Andreas , Wallace John L. , Wang Rui 
Published: November 2019

LINKED ARTICLESThis article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc
TP53 alterations in relapsed childhood acute lymphoblastic leukemia
Authors: Yu Chih‐Hsiang , Chang Wan‐Ting , Jou Shiann‐Tarng , Lin Tze‐Kang , Chang Ya‐Hsuan , Lin Chien‐Yu , Lin Kai‐Hsin , Lu Meng‐Yao , Chen Shu‐Huey , Wu Kang‐Hsi , Wang Shih‐Chung , Chang Hsiu‐Hao , Su Yi‐Ning , Hung Chia‐Cheng , Lin Dong‐Tsamn , Chen Hsuan‐Yu , Yang Yung‐Li 
Published: November 2019

AbstractTP53 alterations are frequent relapse‐acquired mutations in childhood acute lymphoblastic leukemia (ALL). The present study evaluated the clinical significance of relapsed childhood ALL in Taiwan. Diagnostic and/or relapsed bone marrow or peripheral blood was obtained from 111 children with relapsed ALL who were initially treated by using Taiwan Pediatric Oncology Group (TPOG) ALL protocols from January 1997 to May 2018. Mutations were detected by PCR and sequencing, as well as by multiplex ligation‐dependent probe amplification to detect copy number alterations. Copy number and/or sequence alterations of TP53 were detected in 29% (28 of 98) and in 46% (6 of 13) of patients with relapsed B‐cell and T‐cell ALL, respectively. This incidence was much higher than that in several similar studies conducted in Caucasian populations. Seventy percent of all TP53 alterations were gained at relapse in 67 matched samples by back‐tracking matched diagnostic samples. TP53 alterations were associated with lower 5‐year event‐free survival (EFS) and overall survival (OS) rates (P = .013 and P = .0002, respectively). Multivariate analysis confirmed the prognostic significance of TP53 alterations. Forty‐five patients received hematopoietic stem‐cell transplantations post‐relapse. Patients with TP53 alterations (14/45) had inferior 5‐year EFS and OS than patients without TP53 alterations after transplantation (P = .002 and P = .001, respectively). The significance of these TP53 alterations for patients who received transplantations was confirmed by multivariate analysis. In conclusion, TP53 alterations were enriched and useful as prognostic markers in relapsed childhood ALL.
Young Children’s Ability to Produce Valid and Relevant Counter‐Arguments
Authors: Köymen Bahar , O’Madagain Cathal , Domberg Andreas , Tomasello Michael 
Published: November 2019

In collaborative problem solving, children produce and evaluate arguments for proposals. We investigated whether 3‐ and 5‐year‐olds (N = 192) can produce and evaluate arguments against those arguments (i.e., counter‐arguments). In Study 1, each child within a peer dyad was privately given a reason to prefer one over another solution to a task. One child, however, was given further information that would refute the reasoning of their partner. Five‐year‐olds, but not 3‐year‐olds, identified and produced valid and relevant counter‐arguments. In Study 2, 3‐year‐olds were given discourse training (discourse that contrasted valid and invalid counter‐arguments) and then given the same problem‐solving tasks. After training, 3‐year‐olds could also identify and produce valid and relevant counter‐arguments. Thus, participating in discourse about reasons facilitates children’s counter‐argumentation.
Historical and new insights into pathogenesis of type 1 diabetes
Authors: Wong F S , Tree T I 
Published: November 2019

Summary
In recent years, there have been exciting new insights into pathogenesis of type 1 diabetes in a number of areas of immunology. In this edition, a collection of four review articles are presented, which encompass new findings presented at the Immunology of Diabetes Society meeting in London 2018. The articles are focused particularly in 4 related areas of investigation, which include autoantibodies in type 1 diabetes, new autoantigenic targets for CD4 T cells, trafficking of immune cells to the pancreas and islet-immune interactions in the pancreas.
Altered putamen and cerebellum connectivity among different subtypes of Parkinson's disease
Authors: Shen Bo , Pan Yang , Jiang Xu , Wu Zhuang , Zhu Jun , Dong Jingde , Zhang Wenbin , Xu Pingyi , Dai Yakang , Gao Yang , Xiao Chaoyong , Zhang Li 
Published: November 2019

AbstractObjectiveImpairment of basal ganglia (BG)‐thalamo‐cortical circuit causes various symptoms of Parkinson's disease (PD). We investigated the functional connectivity (FC) patterns of putamen among PD subtypes and healthy control (HC) and explored their clinical significance.MethodsA total of 16 patients with tremor‐dominant (TD) PD, 23 patients with postural instability and gait difficulty‐dominant (PIGD) PD, and 31 HC that underwent functional magnetic resonance imaging were observed. Voxel‐wise FC analysis was performed by computing correlation between bilateral putamen and other voxels within the brain. Correlation analysis was performed between FC strength and clinical symptoms.ResultsCompared with PIGD group, TD group showed increased FC between left putamen and right cerebellum lobule VI and cerebellum crus I, then we compared the cerebellum FC difference among the three groups. The cerebellum lobule VI FC difference was mainly involved in motor related cortex, and the cerebellum crus I FC difference was related to cognition areas. While compared with HC, TD and PIGD groups both had significant FC difference brain areas correlated with motor and cognition symptoms. The connectively of putamen and right cerebellum lobules VI and I showed positive correlation with tremor and Montreal Cognitive Assessment degree of scores, respectively. The connectivity of putamen and sensorimotor cortex had negative correlation with PIGD scores.ConclusionsThe altered connectivity of BG‐cortical circuit in patients with PD was related to PIGD symptoms. Motor and cognitive impairments declined slower in patients with TD PD, which may be related to increased functional connectivity between putamen and cerebellum.
Immune modulation by mesenchymal stem cells
Authors: Jiang Wei , Xu Jianyong 
Published: November 2019

AbstractMesenchymal stem cells (MSCs) can be derived from various adult tissues with multipotent and self‐renewal abilities. The characteristics of presenting no major ethical concerns, having low immunogenicity and possessing immune modulation functions make MSCs promising candidates for stem cell therapies. MSCs could promote inflammation when the immune system is underactivated and restrain inflammation when the immune system is overactivated to avoid self‐overattack. These cells express many immune suppressors to switch them from a pro‐inflammatory phenotype to an anti‐inflammatory phenotype, resulting in immune effector cell suppression and immune suppressor cell activation. We would discuss the mechanisms governing the immune modulation function of these cells in this review, especially the immune‐suppressive effects of MSCs.
Spatial patterns and temporal variability of seagrass connectivity in the Mediterranean Sea
Authors: Mari Lorenzo , Melià Paco , Fraschetti Simona , Gatto Marino , Casagrandi Renato 
Published: November 2019

AbstractAimThe endemic seagrass Posidonia oceanica is a key component of the coastal seascapes of the Mediterranean Sea, where it provides crucial ecosystem services and promotes the assembly of diverse ecological communities. Although protection policies exist, P. oceanica meadows have been steadily declining in the recent past because of human activities and climate change. Here, we quantitatively analyse basin‐wide patterns of seagrass connectivity over a 30‐year‐long period and identify connectivity hotspots that may serve as priority targets for conservation actions.LocationMediterranean Sea.Time period1987–2016.Major taxa studiedThe seagrass P. oceanica.MethodsA biophysical Lagrangian approach is used to simulate dispersal of seagrass fruits operated by marine currents. Connectivity metrics (self‐retention, indegree and outdegree) are evaluated on top of Lagrangian simulations to identify the most ecologically connected areas. Time series of local connectivity scores are analysed to study temporal variability and possibly detect trends at different spatial scales.ResultsSpatio‐temporal variability is an important component of seagrass connectivity in the Mediterranean. Connectivity hotspots are unevenly distributed in all of its four main sub‐basins, and along both European and African coastlines. Although statistically significant local trends in connectivity are generally quite infrequent across the whole basin, they appear to be relatively more prevalent in connectivity hotspots. The interannual variability of average connectivity scores seems to be at least partially linked to meteorological fluctuations.Main conclusionsThe present study represents a step forward in the application of a quantitative, scalable and replicable methodological framework for the prioritization of seagrass conservation actions in the Mediterranean large marine ecosystem, a challenging environment characterized by complex socio‐economic boundary conditions and high sensitivity to the localized effects of global climate change.
CNTNAP2 is targeted to endosomes by the polarity protein PAR3
Authors: Gao Ruoqi , Pratt Christopher P. , Yoon Sehyoun , Martin‐de‐Saavedra Maria Dolores , Forrest Marc P. , Penzes Peter 
Published: November 2019

AbstractA decade of genetic studies has established contactin‐associated protein‐like 2 (CNTNAP2) as a prominent susceptibility gene associated with multiple neurodevelopmental disorders. The development and characterization of Cntnap2 knockout models in multiple species have bolstered this claim by establishing clear connections with certain endophenotypes. Despite these remarkable in vivo findings, CNTNAP2’s molecular functions are relatively unexplored, highlighting the need to identify novel protein partners. Here, we characterized an interaction between CNTNAP2 and partitioning‐defective 3 (PAR3)—a polarity molecule isolated in a yeast two‐hybrid screen with CNTNAP2’s C‐terminus. We provide evidence that the two proteins interact via PDZ domain‐mediated binding, that CNTNAP2+/PAR3+ complexes are largely associated with clathrin‐coated endocytic vesicles in heterologous cells and that PAR3 causes an enlargement of CNTNAP2 puncta size. Live imaging and fluorescence recovery after photobleaching (FRAP) reveals that PAR3 limits the mobility of CNTNAP2. Finally, overexpression of PAR3 but not a PAR3 mutant lacking all PDZ domains (PAR3∆PDZall) can cluster endogenous CNTNAP2 in primary neurons. Collectively, we conclude that PAR3 regulates CNTNAP2 spatial localization.
Online eigenvector transformation reflecting concept drift for improving network intrusion detection
Authors: Park Seongchul , Seo Sanghyun , Jeong Changhoon , Kim Juntae 
Published: November 2019

AbstractCurrently, large data streams are constantly being generated in diverse environments, and continuous storage of the data and periodic batch‐type principal component analysis (PCA) are becoming increasingly difficult. Various online PCA algorithms have been proposed to solve this problem. In this study, we propose an online PCA methodology based on online eigenvector transformation with the moving average of the data stream that can reflect concept drift. We compared the network intrusion detection performance based on online transformation of eigenvectors with that of offline methods by applying three machine learning algorithms. Both online and offline methods demonstrated excellent performance in terms of precision. However, in terms of the recall ratio, the performance of the proposed methodology with integrated online eigenvector transformation was better; thus, the F1‐measure also indicated better performance. The visualization of the principal component score shows the effectiveness of our method.
A multi‐agent affective interactive MAGDM approach and its applications
Authors: Peng Cheng , Su Chong 
Published: November 2019

AbstractTraditional multi‐attribute group decision‐making (MAGDM) methods focus on weights calculation of sub‐attributes and experts' preferences, but lack the discussion on the decision‐makers' affective interaction, and its influence on the decision preference and group consistency. To address this problem, the present study proposed a new multilayer affective computing model based on “personality–mood–emotion” pattern, under the multi‐agent decision system framework. In addition, we introduced the group trending index and affection‐preference incentive mechanism, which can help simulate MAGDM process and learn group experts' decision preferences. Further, we proposed a new multi‐agent affective interactive MAGDM (MAAI‐MAGDM) method, where we defined a novel group convergence index and an alternative decision entropy to explain the convergence process of decision and group consistency. Compared to the traditional MAGDM approaches, the proposed MAAI‐MAGDM method fully considered the affective features of each expert, reduced the dependence on aggregation operators and weight analysis, alleviated the workload of group experts, and effectively reduced the complexity of decision‐making calculation process. Finally, we verified that the proposed method can effectively assist the decision‐making processes by employing two numerical cases.
Phenological changes in North Atlantic right whale habitat use in Massachusetts Bay
Authors: Charif Russell A. , Shiu Yu , Muirhead Charles A. , Clark Christopher W. , Parks Susan E. , Rice Aaron N. 
Published: November 2019

AbstractThe North Atlantic right whale (Eubalaena glacialis) is one of the world's most highly endangered baleen whales, with approximately 400–450 individuals remaining. Massachusetts Bay (MB) and Cape Cod Bay (CCB) together comprise one of seven areas in the Gulf of Maine where right whales seasonally congregate. Here, we report on acoustically detected presence of right whales in MB over a nearly 6 year period, July 2007–April 2013, a time of both rapid ocean warming throughout the Gulf of Maine and apparent changes in right whale migratory dynamics. We applied an automated detection algorithm to assess hourly presence of right whale “up‐calls” in recordings from a 19‐channel acoustic array covering approximately 4,000 km2 in MB. Over the survey, up‐calls were detected in 95% of 8 day periods. In each year, as expected, we observed a “peak season” of elevated up‐call detections in late winter and early spring corresponding to the season when right whales congregate to feed in CCB. However, we also saw an increase in right whale occurrence during time periods thought to be part of the “off‐season.” With the exception of 2009–2010, when acoustic presence was unusually low, the mean percent of hours in which up‐calls were detected increased every year, both during the peak season (from 38% in 2008 to 70% in 2012), and during the summer–fall season (from 2% in 2007 to 13% in 2012). Over the entire study, the peak season start date varied between 17 January and 26 February. Changes in right whale phenology in MB likely reflect broadscale changes in habitat use in other areas within the species range. This study demonstrates the value of continuous long‐term survey datasets to detect and quantify shifts in cetacean habitat use as environmental conditions change and the long‐term continued survival of right whales remains uncertain.
Science and Technology Studies (STS), modern Middle East History, and the infrastructural turn
Authors: Shafiee Katayoun 
Published: November 2019

AbstractThis article critically surveys the field of Science and Technology Studies (STS) and modern Middle East History. Scholarship in STS has helped transform the writing of history by developing new ways of thinking about what the political and the technical are and how they work. Historians of the modern Middle East have expanded on these microstudies to think about the larger, more extended effects beyond the laboratory, and to reconfigure the role of nature and technology in the reassembly of questions of agency, knowledge production, governance, political community and nation, and possibilities for democracy in the region. The discussion tracks the turn to thematerialortechnicalin modern Middle East History by placing the nonhuman at the center of the analysis of power. Making extensive use of industry and company archives, recent scholarship has drawn on STS to introduce new puzzles to the field of Middle East History concerning the political economy of the countryside, large‐scale infrastructures, energy and democracy, and the political agency of the multinational corporation.
HIV testing strategies employed in health care settings in the European Union/European Economic Area (EU/EEA): evidence from a systematic review
Authors: Desai S , Tavoschi L , Sullivan AK , Combs L , Raben D , Delpech V , Jakobsen SF , Amato‐Gauci AJ , Croxford S 
Published: November 2019

ObjectivesDespite the availability of HIV testing guidelines to facilitate prompt diagnosis, late HIV diagnosis remains high across Europe. The study synthesizes recent evidence on HIV testing strategies adopted in health care settings in the European Union/European Economic Area (EU/EEA).MethodsPreferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines were followed and systematic searches were run in five databases (2010–2017) to identify studies describing HIV testing interventions in health care settings in the EU/EEA. The grey literature was searched for unpublished studies (2014–2017). Two reviewers independently performed study selection, data extraction and critical appraisal.ResultsOne hundred and thirty intervention and/or feasibility studies on HIV testing in health care settings were identified. Interventions included testing provision (n = 94), campaigns (n = 14) and education and training for staff and patients (n = 20). HIV test coverage achieved through testing provision varied: 2.9–94% in primary care compared to 3.9–66% in emergency departments. HIV test positivity was lower in emergency departments (0–1.3%) and antenatal services (0–0.05%) than in other hospital departments (e.g. inpatients: 0–5.3%). Indicator condition testing programmes increased HIV test coverage from 3.9–72% before to 12–85% after their implementation, with most studies reporting a 10–20% increase. There were 51 feasibility and/or acceptability studies that demonstrated that HIV testing interventions were generally acceptable to patients and providers in health care settings (e.g. general practitioner testing acceptable: 77–93%).ConclusionsThis review has identified several strategies that could be adopted to achieve high HIV testing coverage across a variety of health care settings and populations in the EU/EEA. Very few studies compared the intervention under investigation to a baseline, but, where this was assessed, data suggested increases in testing.
For showing only, or for selling? The optimal physical store mode selection decision for e‐tailers under competition
Authors: Fan Xiaojun , Wang Junbin , Zhang Ting 
Published: November 2019

AbstractMore and more e‐tailers are launching physical stores, in addition to their online presence. Whether and when it is best for the physical channel to be a pure showroom or a selling store remains unanswered. To address this issue, we develop a game‐theoretical model wherein two competitive e‐tailers decide to launch physical stores for showing only (as a showroom) or for actual transactions (as a selling store). By deriving the equilibrium, we obtain three major findings. First, building a pure showroom or a pure selling store is not always optimal. Interestingly, when the proportion of the store consumer segment is not too high, and the strength of the consumers’ brand preference is intermediate, an asymmetric channel configuration occurs in equilibrium, that is, one e‐tailer launches a showroom and the other launches the selling store. Second, if the strength of the consumers’ brand preference is high relative to the proportion of the store consumer segment, a “prisoner's dilemma” emerges, that is, both e‐tailers are worse off in the pure showroom channel configuration. Third, the total consumer surplus reaches the highest level if a symmetric showroom or an asymmetric channel equilibrium occurs. Otherwise, the equilibrium channel configurations are always suboptimal for consumers.
circFBXL5 promotes breast cancer progression by sponging miR‐660
Authors: Zhou Huamao , Tang Guohui , Zhao Mi , Xie Liming , Xie Yuanjie , Zhang Zhiwei , He Xiusheng 
Published: November 2019

AbstractIncreasing studies have revealed that circular RNAs (circRNAs) play important roles in cancer progression. However, the potential involvement of circRNAs in breast cancer metastasis to lung is not clear so far. In this study, we conducted circular RNA microarrays of primary breast cancer tissues and lung metastatic tissues. The results revealed that circFBXL5 (hsa_circ_0125597) up‐regulated the most in lung metastatic tissues. Survival analysis revealed that high levels of circFBXL5 correlated with worse outcome of breast cancer. Further experiments showed that knockdown of circFBXL5 inhibited breast cancer cell proliferation and migration to lung. Mechanism study showed that circFBXL5 acted as a sponge for miR‐660 and compete binding to miR‐660 with SRSF6, leading to increased expression of SRSF6. Collectively, our study highlighted the regulatory function of the circFBXL5/miR‐660/SRSF6 pathway in breast cancer progression, which could be potential therapeutic targets for breast cancer.
Pan‐cancer RNA‐seq data stratifies tumours by some hallmarks of cancer
Authors: Frost F. Graeme , Cherukuri Praveen F. , Milanovich Samuel , Boerkoel Cornelius F. 
Published: November 2019

AbstractNumerous genetic and epigenetic alterations cause functional changes in cell biology underlying cancer. These hallmark functional changes constitute potentially tissue‐independent anticancer therapeutic targets. We hypothesized that RNA‐Seq identifies gene expression changes that underly those hallmarks, and thereby defines relevant therapeutic targets. To test this hypothesis, we analysed the publicly available TCGA‐TARGET‐GTEx gene expression data set from the University of California Santa CruzToil recompute project using WGCNA to delineate co‐correlated ‘modules’ from tumour gene expression profiles and functional enrichment of these modules to hierarchically cluster tumours. This stratified tumours according to T cell activation, NK‐cell activation, complement cascade, ATM, Rb, angiogenic, MAPK, ECM receptor and histone modification signalling. These correspond to the cancer hallmarks of avoiding immune destruction, tumour‐promoting inflammation, evading growth suppressors, inducing angiogenesis, sustained proliferative signalling, activating invasion and metastasis, and genome instability and mutation. This approach did not detect pathways corresponding to the cancer enabling replicative immortality, resisting cell death or deregulating cellular energetics hallmarks. We conclude that RNA‐Seq stratifies tumours along some, but not all, hallmarks of cancer and, therefore, could be used in conjunction with other analyses collectively to inform precision therapy.