bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting JNK pathway promotes human hematopoietic stem cell expansion
Authors: Xiao Xiong , Lai Weifeng , Xie Huangfan , Liu Yang , Guo Weijie , Liu Yifang , Li Yu , Li Yuanjun , Zhang Jingliang , Chen Wenhan , Shi Minhui , Shang Lijun , Yin Ming , Wang Chengyan , Deng Hongkui 
Published: January 2019

AbstractThe limited number of human hematopoietic stem cells (HSCs) has restrained their widespread clinical application. Despite great efforts in recent years, the in vitro expansion of HSCs remains a challenge due to incomplete understanding of the signaling networks underlying HSC self-renewal. Here, we show that culturing human cord blood (CB) CD34+ cells with JNK-IN-8, an inhibitor of the JNK signaling pathway, can enhance the self-renewal of HSCs with a 3.88-fold increase in cell number. These cultured CD34+ cells repopulated recipient mice for 21 weeks and can form secondary engraftment that lasted for more than 21 weeks. Knockdown of c-Jun, a major downstream target in the JNK pathway, promoted the expansion of hematopoietic stem and progenitor cells (HSPCs). Our findings demonstrate a critical role of the JNK pathway in regulating HSC expansion, provide new insights into HSC self-renewal mechanism, and may lead to improved clinical application of HSCs.
Evidence that neural information flow is reversed between object perception and object reconstruction from memory
Authors: Linde-Domingo Juan , Treder Matthias S. , Kerrén Casper , Wimber Maria 
Published: January 2019

AbstractRemembering is a reconstructive process, yet little is known about how the reconstruction of a memory unfolds in time in the human brain. Here, we used reaction times and EEG time-series decoding to test the hypothesis that the information flow is reversed when an event is reconstructed from memory, compared to when the same event is initially being perceived. Across three experiments, we found highly consistent evidence supporting such a reversed stream. When seeing an object, low-level perceptual features were discriminated faster behaviourally, and could be decoded from brain activity earlier, than high-level conceptual features. This pattern reversed during associative memory recall, with reaction times and brain activity patterns now indicating that conceptual information was reconstructed more rapidly than perceptual details. Our findings support a neurobiologically plausible model of human memory, suggesting that memory retrieval is a hierarchical, multi-layered process that prioritises semantically meaningful information over perceptual details.
Probabilistic record linkage of de-identified research datasets with discrepancies using diagnosis codes
Authors: Hejblum Boris P. , Weber Griffin M. , Liao Katherine P. , Palmer Nathan P. , Churchill Susanne , Shadick Nancy A. , Szolovits Peter , Murphy Shawn N. , Kohane Isaac S. , Cai Tianxi 
Published: January 2019

AbstractWe develop an algorithm for probabilistic linkage of de-identified research datasets at the patient level, when only diagnosis codes with discrepancies and no personal health identifiers such as name or date of birth are available. It relies on Bayesian modelling of binarized diagnosis codes, and provides a posterior probability of matching for each patient pair, while considering all the data at once. Both in our simulation study (using an administrative claims dataset for data generation) and in two real use-cases linking patient electronic health records from a large tertiary care network, our method exhibits good performance and compares favourably to the standard baseline Fellegi-Sunter algorithm. We propose a scalable, fast and efficient open-source implementation in the ludic R package available on CRAN, which also includes the anonymized diagnosis code data from our real use-case. This work suggests it is possible to link de-identified research databases stripped of any personal health identifiers using only diagnosis codes, provided sufficient information is shared between the data sources.
Histogram‐based mixed‐signal time‐to‐digital‐converter array for direct time‐of‐flight depth sensors
Authors: Seo H. , Choi J. 
Published: January 2019

This Letter introduces a histogram‐based time‐to‐digital‐converter (TDC) array for direct time‐of‐flight depth sensors. The 12‐bit TDC array measures the time of flight (TOF) of a light pulse that is detected using an external single‐photon avalanche diode (SPAD) array. As SPADs are noisy owing to dark electrons and scattered photons, statistical measurements based on histograms are essential, but require a large memory. In this work, the authors propose a mixed‐signal TDC with an integrated histogram generation unit (HGU) that reduces memory requirement significantly as well as filters out invalid TOF readings. In addition, for application of the high‐resolution SPAD array, an area‐efficient TDC array with high uniformity was implemented by the proposed phase‐dependent latching and temporal double sampling schemes. The prototype chip was fabricated using a 180 nm CMOS process, including 8‐channel TDCs. The measurements show an integral non‐linearity (INL)/a differential nonlinearity (DNL) of 0.76/0.49 least significant bit (LSB) and high uniformity under 0.19 LSB. The HGU was designed off‐chip for prior verification, and was post‐simulated with the measured TOF from the fabricated chip. Using the histogram‐based TDC, the authors could detect an object located at a distance of 3 m accurately while reducing memory requirement by more than 128 times.
Distributed temperature sensing based on slope‐assisted Brillouin optical correlation‐domain reflectometry with over 10 km measurement range
Authors: Lee H. , Noda K. , Mizuno Y. , Nakamura K. 
Published: January 2019

The authors demonstrate distributed temperature sensing based on slope‐assisted Brillouin optical correlation‐domain reflectometry (BOCDR) with a long measurement range of >10 km. They find that to achieve such a long‐range measurement, a delay line in a reference path needs to be at least four times longer than the sensing fibre. In addition, they show that the use of such a long delay line induces forward‐propagating Brillouin‐scattered light in the reference path, which deteriorates the signal‐to‐noise ratio (SNR) of the system and should be suppressed. Finally, by exploiting a beyond‐nominal‐resolution effect of the slope‐assisted BOCDR, they detect a 3‐m‐long heated section in a 13‐km‐long silica fibre in a distributed manner; the reason for its low SNR is also discussed.
Modelling and analysis on short‐circuit failure for press‐pack IGBT devices used in VSC‐HVDC converter
Authors: Yao Ran , Li Hui , Lai Wei , Kang Shenyang , Deng Jili , Long Haiyan , Zheng Meimei , Li Jinyuan , Li Yaosheng 
Published: January 2019

Press‐pack insulated gate bipolar transistor (IGBT) device is the key component in the voltage source converter high voltage direct current (VSC‐HVDC) due the advantage of the short‐circuit failure. However, it is difficult to analyse the IGBT short‐circuit failure mode due to the complex packaging and the short failure time. This study presents a method on simulation for the short‐circuit failure mode of the press‐pack IGBT device. First, based on the structure of a single‐chip 3.3 kV/50 A press‐pack IGBT, a multi‐physical field model was presented by considering the electro–mechanical–thermal coupling effects, so that the internal weak layer was found by comparing with the different sustained pressures. Then, an equivalent method is proposed by using the different aluminium–silicon reaction osmotic hole in the chip, and the models were presented to simulate the short‐circuit failure. Furthermore, after short‐circuit failure of the device, the thermal resistance variation of each later in press‐pack IGBT device was obtained. Finally, the experiment on the steady state and the short‐circuit tests were performed, by analysing the weak layer and the short‐circuit failure position of the IGBT device, the proposed models and analysis were testified. The achievement is helpful to optimal design of the press‐pack IGBT device to improve the VSC‐HVDC converter reliability.
Combined helioseismic inversions for 3D vector flows and sound-speed perturbations
Authors: Korda David , Švanda Michal 
Published: January 2019

Context. Time–distance helioseismology is the method of the study of the propagation of waves through the solar interior via the travel times of those waves. The travel times of wave packets contain information about the conditions in the interior integrated along the propagation path of the wave. The travel times are sensitive to perturbations of a variety of quantities. The usual task is to invert for the vector of plasma flows or the sound–speed perturbations separately. The separate inversions may be polluted by systematic bias, for instance, originating in the leakage of vector flows into the sound–speed perturbations and vice versa (called a cross-talk). Information about the cross-talk is necessary for a proper interpretation of results.
Aims. We introduce an improved methodology of the time-distance helioseismology which allows us to invert for a full 3D vector of plasma flows and the sound–speed perturbations at once. Using this methodology one can also derive the mean value of the vertical component of plasma flows and the cross-talk between the plasma flows and the sound–speed perturbations.
Methods. We used the Subtractive Optimally Localised Averaging method with a minimisation of the cross-talk as a tool for inverse modelling. In the forward model, we use Born approximation travel-time sensitivity kernels with the Model S as a background. The methodology was validated using forward-modelled travel times with both mean and difference point-to-annulus averaging geometries applied to a snapshot of fully self-consistent simulation of the convection.
Results. We tested the methodology on synthetic data. We demonstrate that we are able to recover flows and sound–speed perturbations in the near-surface layers. We have taken the advantage of the sensitivity of our methodology to entire vertical velocity, and not only to its variations as in other available methodologies. The cross-talk from both the vertical flow component and the sound–speed perturbation has only a negligible effect for inversions for the horizontal flow components. Furthermore, this cross-talk can be minimised if needed. The inversions for the vertical component of the vector flows or for the sound–speed perturbations are affected by the cross-talk from the horizontal components, which needs to be minimised in order to provide valid results. It seems that there is a nearly constant cross-talk between the vertical component of the vector flows and the sound–speed perturbations.
Anthrax toxin requires ZDHHC5-mediated palmitoylation of its surface-processing host enzymes
Authors: Sergeeva Oksana A. , van der Goot F. Gisou 
Published: January 2019

SignificanceToxins exploit numerous pathways of their host cells to gain cellular entry and promote intoxication. Therefore, studying the action of toxins allows us to better understand basic mechanisms in cell biology. In this study, we found that ZDHHC5, an enzyme that adds a lipid posttranslational modification to cysteines of proteins, is responsible for allowing anthrax toxin to enter cells. This enzyme acts on proprotein convertases that are needed to cleave these toxins to their active forms. ZDHHC5 does not affect the enzymatic activity of these proteases, but allows them to encounter the toxin by favoring their partitioning in microdomains on the cell surface, domains where the toxin has previously been shown to preferentially reside.
Bilingual education and CLIL in the Netherlands
Authors: Mearns Tessa , Graaff Rick de 
Published: January 2019

AbstractThe Netherlands is often held up an example of a ‘success story’ in terms of practices and research regarding the teaching and learning of subject content in a second language (de Graaff & van Wilgenburg, 2015;Pérez-Cañado, 2012). Nearly 30 years after its initial beginnings, bilingual secondary education in the Netherlands continues to thrive and to evolve in fitting with educational demands, as does the research associated with it. This Special Issue includes contributions addressing Content and Language Integrated Learning (CLIL) as a pedagogical approach in the context of bilingual education as a curricular paradigm, both specifically within the Dutch context. The issue contains six research articles from different perspectives, supported by discussions both from an international research standpoint and from the educational field. It is hoped that the publication of this issue will not only indicate a next stage for bilingual education policy and practice, but also give impetus to new areas for research.
How do we measure up?
Authors: Kampen Evelyn van , Mearns Tessa , Meirink Jacobiene , Admiraal Wilfried , Berry Amanda 
Published: January 2019

AbstractResearch into the pedagogies employed by CLIL teachers has been limited to date and, as such, has been identified as a key area in need of further investigation (Pérez-Cañado, 2012;Dalton-Puffer & Smit, 2013). This review uses an elaborated 4Cs Analysis Framework (adapted fromCoyle, Hood, & Marsh, 2010;Coyle, 2015a,2015b) as a basis for analysis of studies of pedagogies implemented by CLIL subject teachers internationally and in Dutch classrooms. This allows us to place the Dutch situation in an international context and to identify avenues for future research and development. The following questions guided the review: (1) What appear to be the most prominent international trends with regard to the implementation of the 4Cs in CLIL subject pedagogies?; and, (2) To what extent do Dutch CLIL subject pedagogies appear to reflect these international trends? Findings about pedagogies reported in the reviewed studies suggest that, in general, studies from the Netherlands stand out compared to international studies in several respects. Specifically, there is evidence of a relatively strong pedagogic focus in the Netherlands on developing students’ intercultural competence. The Dutch studies also stand out, however, for not addressing the role that the L1 can play in CLIL pedagogy. Furthermore, a main finding is that both the Dutch and the international studies reviewed provide little insight into aspects of CLIL pedagogy related to subject-specific culture and into ways in which content and language areintegrated.
Risk-benefit Assessment of Systematic Thoracoabdominal-pelvic Computed Tomography in Infective Endocarditis
Authors: Lecomte Raphaël , Issa Nahéma , Gaborit Benjamin , Le Turnier Paul , Deschanvres Colin , Asseray Nathalie , Le Tourneau Thierry , Michel Magali , Al Habash Ousama , Bizouarn Philippe , Camou Fabrice , Boutoille David 
Published: January 2019

Abstract

Background
In the management of infective endocarditis (IE), the presence of extracardiac complications has an influence on both diagnosis and treatment. Current guidelines suggest that systematic thoracoabdominal-pelvic computed tomography (TAP-CT) may be helpful. Our objective was to describe how systematic TAP-CT affects the diagnosis and the management of IE.

Methods
In this multicenter cohort study, between January 2013 and July 2016 we included consecutive patients who had definite or possible IE according to the Duke modified criteria, validated by endocarditis teams. We analyzed whether the Duke classification and therapeutic management were modified regarding the presence or the absence of IE-related lesion on CT and investigated the tolerance of this examination.

Results
Of the 522 patients included in this study, 217 (41.6%) had 1 or more IE-related lesions. On the basis of CT results in asymptomatic patients, diagnostic classification was upgraded from possible endocarditis to definite endocarditis for only 4 cases (0.8%). The presence of IE-related lesions on CT did not modify the duration of antibiotic treatment (P = .55), nor the decision of surgical treatment (P = .39). Specific treatment of the lesion was necessary in 42 patients (8.0%), but only 9 of these lesions (1.9%) were asymptomatic and diagnosed only on the TAP-CT. Acute kidney injury (AKI) within 5 days of CT was observed in 78 patients (14.9%).

Conclusions
The TAP-CT findings slightly affected diagnosis and treatment of IE in a very small proportion of asymptomatic patients. Furthermore, contrast media should be used with caution because of the high risk of AKI.
Impact of β-Lactam and Daptomycin Combination Therapy on Clinical Outcomes in Methicillin-susceptible Staphylococcus aureus Bacteremia: A Propensity Score–matched Analysis
Authors: Grillo Sara , Cuervo Guillermo , Carratalà Jordi , Grau Immaculada , Pallarès Natàlia , Tebé Cristian , Guillem Tió Lluisa , Murillo Oscar , Ardanuy Carmen , Domínguez M Angeles , Shaw Evelyn , Gudiol Carlota , Pujol Miquel 
Published: January 2019

AbstractBackgroundMortality rates from Staphylococcus aureus bacteremia are high and have only modestly improved in recent decades. We compared the efficacies of a β-lactam in combination with daptomycin (BL/D-C) and β-lactam monotherapy (BL-M) in improving clinical outcomes in methicillin-susceptible S. aureus (MSSA) bacteremia.MethodsA retrospective cohort study of MSSA bacteremia was performed in a tertiary hospital from January 2011 to December 2017. Patients receiving BL/D-C and BL-M were compared to assess 7-, 30-, and 90-day mortality rates. A 1:2 propensity score matching analysis was performed. Differences were assessed using Cox regression models.ResultsOf the 514 patients with MSSA bacteremia, 164 were excluded as they had received combination therapies other than BL/D-C, had pneumonia, or died within 48 hours of admission. Of the remaining 350 patients, 136 and 214 received BL/D-C and BL-M, respectively. BL/D-C patients had higher Pitt scores and persistent bacteremia more often than BL-M patients. In the raw analysis, there were no differences in mortality rates between groups. After propensity score matching, there were no significant differences between the BL/D-C (110 patients) and BL-M (168 patients) groups for all-cause mortality rates at 7 days (8.18% vs 7.74%; P = 1.000), 30 days (17.3% vs 16.1%; P = .922), and 90 days (22.7% vs 23.2%; P = 1.000), even in a subanalysis of patients with high-risk source of infection and in a subgroup excluding catheter-related bacteremia.ConclusionsBL/D-C failed to reduce mortality rates in patients with MSSA bacteremia. Treatment strategies to improve survival in MSSA bacteremia are urgently needed.
Prevalence of Congenital Cytomegalovirus Infection and Associated Risk of In Utero Human Immunodeficiency Virus (HIV) Acquisition in a High-HIV Prevalence Setting, South Africa
Authors: Pathirana Jayani , Groome Michelle , Dorfman Jeffrey , Kwatra Gaurav , Boppana Suresh , Cutland Clare , Jones Stephanie , Madhi Shabir A 
Published: January 2019

AbstractBackgroundThere is a paucity of data on the burden of congenital cytomegalovirus (cCMV) infections in low- and middle-income countries, including their association with maternal human immunodeficiency virus (HIV) infections. We investigated the prevalence of cCMV in a patient population with a high rate of HIV and antiretroviral therapy (ART) use during pregnancy in Soweto, Johannesburg.MethodsSaliva from neonates were screened for cytomegalovirus (CMV) infection by polymerase chain reaction (PCR) at birth. Additional saliva and urine samples were tested within 3 weeks of birth to confirm positive saliva results. HIV PCR testing was done on the whole blood of HIV-exposed neonates. Maternal and neonatal data were extracted from clinical records.ResultsOf 2685 neonates screened for cCMV, 828 (31%) were born to HIV-infected women, 95% of whom (790/828) were on ART at delivery. The overall prevalence of cCMV was 2.5% (95% confidence interval [CI] 1.9–3.2), with significantly higher cCMV prevalence in HIV-exposed neonates (5.2%, 95% CI 3.8–6.9) than HIV-unexposed neonates (1.4%, 95% CI 0.9–2.0). The risk of in utero HIV infection was 20-fold greater (odds ratio 20.1, 95% CI 6.09–66.46) in HIV-exposed, cCMV-infected neonates, and this increased risk was not associated with the maternal CD4+ T-cell count or the maternal duration of ART.ConclusionsThe prevalence of cCMV in our setting is substantially higher than the global estimate of 0.64%, partly due to the increased susceptibility for cCMV in HIV-exposed neonates. The significantly increased risk of in utero HIV infection in neonates with cCMV indicates that CMV coinfection plays a major role in the residual burden of in utero HIV transmission, even in the era of ART.
Integration or Separation? Malcolm X’s College Debates, Free Speech, and the Challenge to Racial Liberalism on Campus
Authors: Felber Garrett 
Published: January 2019

Abstract
Malcolm X participated in over thirty speaking engagements at prominent colleges and universities between 1960 and 1963. His popularity on campuses coincided with a new epoch of civil rights struggle as students became involved in Freedom Rides and sit-in campaigns to desegregate lunch counters and interstate travel. Most invitations were debates on the topic “Integration or Separation?” which pitted Malcolm against an integrationist opponent. The insertion of racial separatism into a discourse that took integration as an unquestioned aim of the movement pushed students to question and defend their own understandings of racial liberalism. Nearly a dozen invitations were extended by NAACP student chapters that had been revitalized amid the new flurry of student involvement. Years before the founding of the first Black Student Union (BSU) at San Francisco State, these chapters were far more ideologically diverse and active than their forbearers, and often invited Malcolm X to speak out of a commitment to students’ rights to free speech and academic freedom. When administrations blocked and cancelled his visits, students became politicized around issues of academic liberties, thereby situating the Nation of Islam and Malcolm X at the nexus of early debates within the student free speech movement. These became part of the early challenge to university paternalism. While these debates and lectures have often been discussed individually, this essay looks at their cumulative effect by situating them during the emergence of student radicalism on campus and the growth of youth participation in the civil rights movement.
Choosing medications wisely: Is it time to address paediatric polypharmacy?
Authors: Bogler Orly , Roth Daniel , Feinstein James , Strzelecki Marina , Seto Winnie , Cohen Eyal 
Published: January 2019

Abstract
There is a growing focus in the medical community on de-escalating medical treatments where appropriate; however, specific efforts to reduce medication burden in patients with polypharmacy has largely been targeted toward adult populations. Polypharmacy increases the risk of adverse drug reactions in children, and that risk may be further increased by the use of off-label drugs. The paediatric prescribing community should explore pharmacovigilance strategies and deprescription initiatives that prioritize patients with polypharmacy. Currently, best practices may be extrapolated from the adult literature, including medication review algorithms and patient education tools. Enhancing access to nonpharmacological modalities to address child and youth mental health may mitigate psychotropic polypharmacy. The aim of these initiatives should be to improve patient outcomes and experiences by avoiding adverse drug events and drug–drug interactions.