bluuebunny/crossref_metadata_2025_split huggingface dataset:
LRRK2‐mediated Rab10 phosphorylation in immune cells from Parkinson's disease patients
Authors: Atashrazm Farzaneh , Hammond Deborah , Perera Gayathri , Bolliger Marc F. , Matar Elie , Halliday Glenda M. , Schüle Birgitt , Lewis Simon J.G. , Nichols R. Jeremy , Dzamko Nicolas 
Published: December 2018

AbstractBackgroundLeucine‐rich repeat kinase 2 is a potential therapeutic target for the treatment of Parkinson's disease, and clinical trials of leucine‐rich repeat kinase 2 inhibitors are in development. The objective of this study was to evaluate phosphorylation of a new leucine‐rich repeat kinase 2 substrate, Rab10, for potential use as a target engagement biomarker and/or patient enrichment biomarker for leucine‐rich repeat kinase 2 inhibitor clinical trials.MethodsPeripheral blood mononuclear cells and neutrophils were isolated from Parkinson's disease patients and matched controls, and treated ex vivo with a leucine‐rich repeat kinase 2 inhibitor. Immunoblotting was used to measure levels of leucine‐rich repeat kinase 2 and Rab10 and their phosphorylation. Plasma inflammatory cytokines were measured by multiplex enzyme‐linked immunosorbent assay.ResultsMononuclear cells and neutrophils of both controls and Parkinson's disease patients responded the same to leucine‐rich repeat kinase 2 inhibitor treatment. Leucine‐rich repeat kinase 2 levels in mononuclear cells were the same in controls and Parkinson's disease patients, whereas leucine‐rich repeat kinase 2 was significantly increased in Parkinson's disease neutrophils. Rab10 T73 phosphorylation levels were similar in controls and Parkinson's disease patients and did not correlate with leucine‐rich repeat kinase 2 levels. Immune‐cell levels of leucine‐rich repeat kinase 2 and Rab10 T73 phosphorylation were associated with plasma inflammatory cytokine levels.ConclusionsRab10 T73 phosphorylation appears to be a valid target engagement biomarker for potential use in leucine‐rich repeat kinase 2 inhibitor clinical trials. However, a lack of association between leucine‐rich repeat kinase 2 and Rab10 phosphorylation complicates the potential use of Rab10 phosphorylation as a patient enrichment biomarker. Although replication is required, increased leucine‐rich repeat kinase 2 levels in neutrophils from Parkinson's disease patients may have the potential for patient stratification. leucine‐rich repeat kinase 2 activity in peripheral immune cells may contribute to an inflammatory phenotype. © 2018 International Parkinson and Movement Disorder Society
Reproducible detection of nigral iron deposition in 2 Parkinson's disease cohorts
Authors: Langley Jason , He Naying , Huddleston Daniel E. , Chen Shengdi , Yan Fuhua , Crosson Bruce , Factor Stewart , Hu Xiaoping 
Published: December 2018

ABSTRACTBackgroundPrevious studies investigating nigral iron accumulation used T2 or T2*‐weighted contrasts to define the regions of interest (ROIs) in the substantia nigra with mixed results. Because these contrasts are not sensitive to neuromelanin, ROIs may have inadvertently missed the SNpc. An approach sensitive to neuromelanin should yield consistent results. We examine iron deposition in ROIs derived from neuromelanin‐sensitive and T2*‐weighted contrasts, respectively.MethodsT1‐weighted and multiecho gradient echo imaging data were obtained in 2 cohorts. Multiecho gradient echo imaging data were analyzed using neuromelanin‐sensitive SNpc ROIs as well as T2*‐weighted SNr ROIs.ResultsWhen compared with controls, significantly larger R2* values were seen in the SNpc of PD patients in both cohorts. Mean R2* values in the SNr of PD patients showed no consistency, with 1 cohort showing a small, statistically significant increase, whereas the other cohort exhibited no statistical difference.ConclusionMean R2* in the SNpc defined by neuromelanin‐sensitive MRI is significantly increased in PD. © 2018 International Parkinson and Movement Disorder Society
A beam scanning continuous transverse stub array antenna for Ka‐band applications
Authors: Wang Weipeng , Huang Qiulin , Liu Zhenxing , Liu Hao , Shi Xiaowei 
Published: December 2018

AbstractA hybrid structure continuous transverse stub (CTS) array antenna for Ka‐band is demonstrated in this article. The array comprises 16 radiating slots, the H‐plane horn antenna based on the substrate integrated waveguide (SIW) and is fed by a corporate‐feed network in parallel plate waveguide (PPW) technology. The scanning angle of the main beam of the antenna reaches ±40° through switching the horn feed. Measurement shows that the CTS antenna has an relative bandwidth of 17.2% from 26.5 to 31.5 GHz for the standards of |S11| < −10 dB. At the center frequency of 29 GHz, the antenna gain of 28 dBi is obtained, the H‐plane sidelobe level (SLL) is −28.5 dB, and the radiation efficiency reaches 90%. The measurements are in very good agreement with full‐wave simulation results. The proposed design is suitable for Satcom Ka‐band terminals in moving platforms, for example, ships and planes.
Prostate cancer classification with multiparametric MRI transfer learning model
Authors: Yuan Yixuan , Qin Wenjian , Buyyounouski Mark , Ibragimov Bulat , Hancock Steve , Han Bin , Xing Lei 
Published: December 2018

PurposeProstate cancer classification has a significant impact on the prognosis and treatment planning of patients. Currently, this classification is based on the Gleason score analysis of biopsied tissues, which is neither accurate nor risk free. This study aims to learn discriminative features in prostate images and assist physicians in classifying prostate cancer automatically.MethodsWe develop a novel multiparametric magnetic resonance transfer learning (MPTL) method to automatically stage prostate cancer. We first establish a deep convolutional neural network with three branch architectures, which transfer pretrained model to compute features from multiparametric MRI images (mp‐MRI): T2w transaxial, T2w sagittal, and apparent diffusion coefficient (ADC). The learned features are concatenated to represent information of mp‐MRI sequences. A new image similarity constraint is then proposed to enable the distribution of the features within the same category in a narrow angle region. With the joint constraints of softmax loss and image similarity loss in the fine‐tuning process, the MPTL can provide descriptive features with intraclass compactness and interclass separability.ResultsTwo cohorts: 132 cases from our institutional review board‐approved patient database and 112 cases from the PROSTATEx‐2 Challenge are utilized to evaluate the robustness and effectiveness of the proposed MPTL model. Our model achieved high accuracy of prostate cancer classification (accuracy of 86.92%). Moreover, the comparison results demonstrate that our method outperforms both hand‐crafted feature‐based methods and existing deep learning models in prostate cancer classification with higher accuracy.ConclusionThe experiment results showed that the proposed method can learn discriminative features in prostate images and classify the cancer accurately. Our MPTL model could be further applied in the clinical practice to provide valuable information for cancer treatment and precision medicine.
Decrease in Operant Responding Under Obesogenic Diet Exposure is not Related to Deficits in Incentive or Hedonic Processes
Authors: Ducrocq Fabien , Hyde Alexia , Fanet Hortense , Oummadi Asma , Walle Roman , De Smedt‐Peyrusse Véronique , Layé Sophie , Ferreira Guillaume , Trifilieff Pierre , Vancassel Sylvie 
Published: December 2018

ObjectiveA growing body of evidence suggests that obesity could result from alterations in reward processing. In rodent models, chronic exposure to an obesogenic diet leads to blunted dopamine signaling and related incentive responding. This study aimed to determine which reward‐related behavioral dimensions are actually impacted by obesogenic diet exposure.MethodsMice were chronically exposed to an obesogenic diet. Incentive and hedonic processes were tested through operant conditioning and licking microstructures, respectively. In parallel, mesolimbic dopamine transmission was assessed using microdialysis.ResultsProlonged high‐fat (HF) diet exposure led to blunted mesolimbic dopamine release, paralleled by a decrease in operant responding in all schedules tested. HF‐fed and control animals similarly decreased their operant responding in an effort‐based choice task, and HF‐fed animals displayed an overall lower calorie intake in this task. Analysis of the licking microstructures during consumption of a freely accessible reward suggested a decrease in basal hunger and a potentiation of gastrointestinal inhibition in HF‐fed animals, without changes in hedonic reactivity.ConclusionsThese results suggest that the decrease in operant responding under prolonged HF diet exposure is mainly driven by decrease in hunger as well as stronger postingestive negative feedback mechanisms, rather than by a decrease in incentive or hedonic responses.
Influence of Polypharmacy on the Effectiveness and Safety of Rivaroxaban Versus Warfarin in Patients With Nonvalvular Atrial Fibrillation
Authors: Martinez Brandon K. , Baker William L. , Sood Nitesh A. , Bunz Thomas J. , Meinecke Anna‐Katharina , Eriksson Daniel , Coleman Craig I. 
Published: December 2018

Study ObjectivePatients with nonvalvular atrial fibrillation (NVAF) often have multiple comorbidities requiring concomitant medications in addition to their oral anticoagulant (OAC). The objective of this study was to evaluate the impact of polypharmacy on the effectiveness and safety of rivaroxaban versus warfarin in patients with NVAF managed in routine clinical practice.DesignRetrospective claims analysis.Data SourceUnited States Truven MarketScan database (November 2012–March 2017).PatientsAdults who were OAC naïve during the 12 months before the day of the first qualifying rivaroxaban or warfarin dispensing (index date); had at least two International Classification of Diseases, Ninth or Tenth Revision diagnosis codes for atrial fibrillation without codes suggesting valvular heart disease; had at least 12 months of continuous insurance coverage prior to the qualifying OAC dispensing; and were experiencing polypharmacy (concomitant prescription claims for five or more unique chronic medication claims) were included. Patients who had concomitant prescription claims for ≥ 10 unique chronic medication claims constituted the substantial polypharmacy cohort used in the secondary analysis. Patients receiving rivaroxaban were propensity‐score matched in a 1:1 ratio to patients receiving warfarin (13,981 patients in each polypharmacy OAC group, and 1765 patients in each substantial polypharmacy OAC group).Measurements and Main ResultsPatients were followed until occurrence of an event (stroke or systemic embolism [SSE] combined [primary effectiveness outcome] or major bleeding [primary safety outcome]), OAC discontinuation or switch (30‐day permissible gap), insurance disenrollment, or end of follow‐up period. Rates of SSE, ischemic stroke, and major bleeding were compared by using Cox regression, reported as hazard ratios (HRs) and 95% confidence intervals (CIs). In patients with NVAF taking five or more chronic medications, rivaroxaban was associated with a 34% (95% CI 12–50) and 40% (95% CI 16–57) hazard reduction of SSE and ischemic stroke, respectively. Occurrence of major bleeding was similar between OAC cohorts (HR 1.08, 95% CI 0.92–1.28). A secondary analysis in patients with NVAF with substantial polypharmacy (taking ≥ 10 chronic medications) was also performed. Similar trends in SSE (HR 0.44), ischemic stroke alone (HR 0.62), and major bleeding (HR 1.07) were observed in patients with NVAF who had substantial polypharmacy, although 95% CIs crossed 1.0 for each outcome in this smaller study cohort.ConclusionThis real‐world study suggests that in the setting of polypharmacy and NVAF, rivaroxaban is an effective and safe alternative to warfarin.
Why are the early elementary race/ethnicity test score gaps in science larger than those in reading or mathematics? National evidence on the importance of language and immigration context in explaining the gap‐in‐gaps
Authors: Curran F. Chris , Kitchin James 
Published: December 2018

AbstractRecent work examining science test performance in the earliest grades of school has demonstrated that science test score gaps by race/ethnicity are apparent as early as kindergarten and that, in a number of cases, the racial/ethnic test score gaps in science are significantly larger than the corresponding gaps in reading or mathematics. This study explores the factors that explain the differences in the magnitudes of racial/ethnic disparities in performance on science standardized tests as compared to those in reading/mathematics. Drawing on nationally representative data from over 10,000 kindergartners in the 2010–2011 school year, this study employs regression models that examine the explanatory power of nine conceptual domains for explaining the “gap‐in‐gaps” or test score gap differences in science relative to mathematics or reading. Results indicate that the gap‐in‐gaps is relatively unchanged by the inclusion of many conceptual domains but that students' language and immigration contexts do explain substantial portions of the gap‐in‐gaps for Hispanic and Asian students. Implications for policy and practice are discussed.
Policy Recommendations for Africa
Authors: Park Jong-Dae 
Published: December 2018

AbstractThis section presents comprehensive policy recommendations for Africa. The overarching theme is ‘the need for drastic turnaround’. An important question asked here is: ‘What induces people to act?’ The mechanism of incentives and sanctions, and how they should be framed to make societies developmental, are elaborated upon. The chapter assesses the present structure of economic development in Africa and points out the essential principles or elements that are lacking. Out of this, a new development formula for Africa is deduced. The author also touches upon government reform and economic policies. In closing, he stresses the need for education in ethics and mindset change.
Review of Conventional Explanations
Authors: Park Jong-Dae 
Published: December 2018

AbstractThis chapter is aimed at objectively assessing various possible reasons for Africa’s poverty and underdevelopment. It reviews the conventional or popular explanations for Africa’s prolonged predicament, as well as other factors possibly negatively impacting Africa. The topics addressed are colonial legacies, ethnicism and neo-patrimonialism; institutions, governance and democracy, the role of government; natural conditions like climate and geography, and other factors including corruption and globalization. The author sizes up the existing views or discourses from critical perspective and, in the process, sheds new lights on what are commonly misunderstood.
Finding the Missing Links
Authors: Park Jong-Dae 
Published: December 2018

AbstractThis chapter takes a step further in the methodical ‘building-block’ approach aimed at deriving ultimate solutions for Sub-Saharan African countries’ development. At the outset, the nature of Africa’s underperformance, especially in comparison to Asian countries, is characterized as the question regarding ‘intent’ and ‘internalization’ of development. Then, the ‘missing links’ of Africa’s development, the basic but crucial elements for development that are generally weak or deficient in the Sub-Saharan African countries are introduced: a sense of nation or national identity; ‘development-mindedness’; and the strong role of the state. A key analytical concept highlighted and detailed here is ‘development-mindedness’ or ‘KPOP’, which stands for ‘knowledge’, ‘practising’, ‘owning’ and ‘passion’.
Korea’s Path of Development in Retrospect
Authors: Park Jong-Dae 
Published: December 2018

AbstractHere, the case of Korea’s development is examined applying the same ‘building-block’ approach. This chapter scrutinizes Korea’s evolution in a time-linear and multi-dimensional fashion, taking us through its historical background, liberation and state-building, and its ‘economic miracle’ period and beyond. The author then recaps the overall achievements of South Korea and presents the ‘schematic itinerary of Korea’s development’ which epitomizes Korea’s path of economic and socio-political transformation. A key feature of Korea’s development is described in terms of compressed development both in the economic and socio-political realms.
Applicability of the Korean Development Model for Africa
Authors: Park Jong-Dae 
Published: December 2018

AbstractThis chapter and the ensuing chapters constitute a crucial part of this work where the Korean model of development is applied to Sub-Saharan Africa. The ideas discussed here form the integral part of the ‘building-bridge’ approach, which aims at linking Africa to Korea’s development model. At the outset, the lessons of the fundamentals of economics and industrialization are cited. This is followed by reflections on Korea’s past circumstances and Africa’s current situation. It concludes with an assessment on the relevance of the Korean developmental model for Sub-Saharan African nations.
A qualitative investigation of expected versus actual initial sexual experiences before age 16
Authors: Garceau Camille , Ronis Scott T. 
Published: December 2018

ABSTRACTIntroductionIndividuals often develop expectations prior to their initial sexual experiences based on external messages from peers and the broader culture. According to sexual script theory (Simon & Gagnon, 1986), these expectations form schemas about how an initial sexual experience should occur. When reality deviates from these schemas, dissatisfaction can occur (McCormick, 1987). The current study examines the contrast between expectations and reported initial sexual experiences before age 16.MethodsForty young adult participants were recruited from four local Atlantic Canadian universities (77.5% women; M age = 20.20, SD = 1.31; 75% heterosexual; 77.5% Caucasian). Semi‐structured qualitative interviews on participants' actual initial sexual experiences, expectations of initial sexual experiences, and perceived consequences of initial sexual experiences were conducted. Thematic analysis of the interviews was conducted using a grounded theory framework.ResultsFindings indicated that respondents’ expectations were influenced by sources such as various media, peers, family, and religion. Initial sexual experiences reportedly met, surpassed, or failed to meet participants' expectations. The presence or absence of a discrepancy between expected and actual sexual experiences was perceived to shape subsequent sexual encounters. A theoretical model of development and adaptations of sexual experience expectations was developed in accordance with these results.ConclusionsComparisons between expected and actual initial sexual experiences can be perceived by youth as having consequences on their personal and interpersonal well‐being. Honest communication between parents, educators, and youth should therefore be prioritized in order to establish more realistic expectations of initial sexual experiences.
Scope and extent of healthcare-associated Middle East respiratory syndrome coronavirus transmission during two contemporaneous outbreaks in Riyadh, Saudi Arabia, 2017
Authors: Alanazi Khalid H. , Killerby Marie E. , Biggs Holly M. , Abedi Glen R. , Jokhdar Hani , Alsharef Ali A. , Mohammed Mutaz , Abdalla Osman , Almari Aref , Bereagesh Samar , Tawfik Sameh , Alresheedi Husain , Alhakeem Raafat F. , Hakawi Ahmed , Alfalah Haitham , Amer Hala , Thornburg Natalie J. , Tamin Azaibi , Trivedi Suvang , Tong Suxiang , Lu Xiaoyan , Queen Krista , Li Yan , Sakthivel Senthilkumar K. , Tao Ying , Zhang Jing , Paden Clinton R. , Al-Abdely Hail M. , Assiri Abdullah M. , Gerber Susan I. , Watson John T. 
Published: December 2018

AbstractObjectiveTo investigate a Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak event involving multiple healthcare facilities in Riyadh, Saudi Arabia; to characterize transmission; and to explore infection control implications.DesignOutbreak investigation.SettingCases presented in 4 healthcare facilities in Riyadh, Saudi Arabia: a tertiary-care hospital, a specialty pulmonary hospital, an outpatient clinic, and an outpatient dialysis unit.MethodsContact tracing and testing were performed following reports of cases at 2 hospitals. Laboratory results were confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) and/or genome sequencing. We assessed exposures and determined seropositivity among available healthcare personnel (HCP) cases and HCP contacts of cases.ResultsIn total, 48 cases were identified, involving patients, HCP, and family members across 2 hospitals, an outpatient clinic, and a dialysis clinic. At each hospital, transmission was linked to a unique index case. Moreover, 4 cases were associated with superspreading events (any interaction where a case patient transmitted to ≥5 subsequent case patients). All 4 of these patients were severely ill, were initially not recognized as MERS-CoV cases, and subsequently died. Genomic sequences clustered separately, suggesting 2 distinct outbreaks. Overall, 4 (24%) of 17 HCP cases and 3 (3%) of 114 HCP contacts of cases were seropositive.ConclusionsWe describe 2 distinct healthcare-associated outbreaks, each initiated by a unique index case and characterized by multiple superspreading events. Delays in recognition and in subsequent implementation of control measures contributed to secondary transmission. Prompt contact tracing, repeated testing, HCP furloughing, and implementation of recommended transmission-based precautions for suspected cases ultimately halted transmission.
How Accurately Should We Model Ice Shelf Melt Rates?
Authors: Goldberg D. N. , Gourmelen N. , Kimura S. , Millan R. , Snow K. 
Published: December 2018

AbstractAssessment of ocean‐forced ice sheet loss requires that ocean models be able to represent sub‐ice shelf melt rates. However, spatial accuracy of modeled melt is not well investigated, and neither is the level of accuracy required to assess ice sheet loss. Focusing on a fast‐thinning region of West Antarctica, we calculate spatially resolved ice‐shelf melt from satellite altimetry and compare against results from an ocean model with varying representations of cavity geometry and ocean physics. Then, we use an ice‐flow model to assess the impact of the results on grounded ice. We find that a number of factors influence model‐data agreement of melt rates, with bathymetry being the leading factor; but this agreement is only important in isolated regions under the ice shelves, such as shear margins and grounding lines. To improve ice sheet forecasts, both modeling and observations of ice‐ocean interactions must be improved in these critical regions.