bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-SNP mediation intersection-union test
Authors: Zhong Wujuan , Spracklen Cassandra N , Mohlke Karen L , Zheng Xiaojing , Fine Jason , Li Yun 
Published: April 2019

AbstractSummaryTens of thousands of reproducibly identified GWAS (Genome-Wide Association Studies) variants, with the vast majority falling in non-coding regions resulting in no eventual protein products, call urgently for mechanistic interpretations. Although numerous methods exist, there are few, if any methods, for simultaneously testing the mediation effects of multiple correlated SNPs via some mediator (e.g. the expression of a gene in the neighborhood) on phenotypic outcome. We propose multi-SNP mediation intersection-union test (SMUT) to fill in this methodological gap. Our extensive simulations demonstrate the validity of SMUT as well as substantial, up to 92%, power gains over alternative methods. In addition, SMUT confirmed known mediators in a real dataset of Finns for plasma adiponectin level, which were missed by many alternative methods. We believe SMUT will become a useful tool to generate mechanistic hypotheses underlying GWAS variants, facilitating functional follow-up.Availability and implementationThe R package SMUT is publicly available from CRAN at https://CRAN.R-project.org/package=SMUT.Supplementary informationSupplementary data are available at Bioinformatics online.
BDNF Controls Bidirectional Endocannabinoid Plasticity at Corticostriatal Synapses
Authors: Gangarossa Giuseppe , Perez Sylvie , Dembitskaya Yulia , Prokin Ilya , Berry Hugues , Venance Laurent 
Published: April 2019

AbstractThe dorsal striatum exhibits bidirectional corticostriatal synaptic plasticity, NMDAR and endocannabinoids (eCB) mediated, necessary for the encoding of procedural learning. Therefore, characterizing factors controlling corticostriatal plasticity is of crucial importance. Brain-derived neurotrophic factor (BDNF) and its receptor, the tropomyosine receptor kinase-B (TrkB), shape striatal functions, and their dysfunction deeply affects basal ganglia. BDNF/TrkB signaling controls NMDAR plasticity in various brain structures including the striatum. However, despite cross-talk between BDNF and eCBs, the role of BDNF in eCB plasticity remains unknown. Here, we show that BDNF/TrkB signaling promotes eCB-plasticity (LTD and LTP) induced by rate-based (low-frequency stimulation) or spike-timing–based (spike-timing–dependent plasticity, STDP) paradigm in striatum. We show that TrkB activation is required for the expression and the scaling of both eCB-LTD and eCB-LTP. Using 2-photon imaging of dendritic spines combined with patch-clamp recordings, we show that TrkB activation prolongs intracellular calcium transients, thus increasing eCB synthesis and release. We provide a mathematical model for the dynamics of the signaling pathways involved in corticostriatal plasticity. Finally, we show that TrkB activation enlarges the domain of expression of eCB-STDP. Our results reveal a novel role for BDNF/TrkB signaling in governing eCB-plasticity expression in striatum and thus the engram of procedural learning.
Quantitative MRI Analyses of Regional Brain Growth in Living Fetuses with Down Syndrome
Authors: Tarui Tomo , Im Kiho , Madan Neel , Madankumar Rajeevi , Skotko Brian G , Schwartz Allie , Sharr Christianne , Ralston Steven J , Kitano Rie , Akiyama Shizuko , Yun Hyuk Jin , Grant Ellen , Bianchi Diana W 
Published: April 2019

AbstractDown syndrome (DS) is the most common liveborn autosomal chromosomal anomaly and is a major cause of developmental disability. Atypical brain development and the resulting intellectual disability originate during the fetal period. Perinatal interventions to correct such aberrant development are on the horizon in preclinical studies. However, we lack tools to sensitively measure aberrant structural brain development in living human fetuses with DS. In this study, we aimed to develop safe and precise neuroimaging measures to monitor fetal brain development in DS. We measured growth patterns of regional brain structures in 10 fetal brains with DS (29.1 ± 4.2, weeks of gestation, mean ± SD, range 21.7~35.1) and 12 control fetuses (25.2 ± 5.0, range 18.6~33.3) using regional volumetric analysis of fetal brain MRI. All cases with DS had confirmed karyotypes. We performed non-linear regression models to compare fitted regional growth curves between DS and controls. We found decreased growth trajectories of the cortical plate (P = 0.033), the subcortical parenchyma (P = 0.010), and the cerebellar hemispheres (P &lt; 0.0001) in DS compared to controls. This study provides proof of principle that regional volumetric analysis of fetal brain MRI facilitates successful evaluation of brain development in living fetuses with DS.
Implementation of Syringe Services Programs to Prevent Rapid Human Immunodeficiency Virus Transmission in Rural Counties in the United States: A Modeling Study
Authors: Goedel William C , King Maximilian R F , Lurie Mark N , Galea Sandro , Townsend Jeffrey P , Galvani Alison P , Friedman Samuel R , Marshall Brandon D L 
Published: April 2019

Abstract

Background
Syringe services programs (SSPs) are effective venues for delivering harm-reduction services to people who inject drugs (PWID). However, SSPs often face significant barriers to implementation, particularly in the absence of known human immunodeficiency virus (HIV) outbreaks.

Methods
Using an agent-based model, we simulated HIV transmission in Scott County, Indiana, a rural county with a 1.7% prevalence of injection drug use. We compared outcomes arising in the absence of an SSP, in the presence of a pre-existing SSP, and with implementation of an SSP after the detection of an HIV outbreak among PWID over 5 years following the introduction of a single infection into the network.

Results
In the absence of an SSP, the model predicted an average of 176 infections among PWID over 5 years or an incidence rate of 12.1/100 person-years. Proactive implementation averted 154 infections and decreased incidence by 90.3%. With reactive implementation beginning operations 10 months after the first infection, an SSP would prevent 107 infections and decrease incidence by 60.8%. Reductions in incidence were also observed among people who did not inject drugs.

Conclusions
Based on model predictions, proactive implementation of an SSP in Scott County had the potential to avert more HIV infections than reactive implementation after the detection of an outbreak. The predicted impact of reactive SSP implementation was highly dependent on timely implementation after detecting the earliest infections. Consequently, there is a need for expanded proactive SSP implementation in the context of enhanced monitoring of outbreak vulnerability in Scott County and similar rural contexts.
Trends in thrombolytic treatment and outcomes of acute pulmonary embolism in Germany
Authors: Keller Karsten , Hobohm Lukas , Ebner Matthias , Kresoja Karl-Patrik , Münzel Thomas , Konstantinides Stavros V , Lankeit Mareike 
Published: April 2019

Abstract

Aims
Pulmonary embolism (PE) is the third most common cardiovascular cause of death; systemic thrombolysis is potentially lifesaving treatment in patients presenting with haemodynamic instability. We investigated trends in the use of systemic thrombolysis and the outcome of patients with acute PE.

Methods and results
We analysed data on the characteristics, comorbidities, treatment, and in-hospital outcome of 885 806 PE patients in Germany between 2005 and 2015. Incidence of acute PE was 99/100 000 population/year and increased from 85/100 000 in 2005 to 109/100 000 in 2015 [β 0.32 (0.26–0.38), P &lt; 0.001]. During the same period, in-hospital case fatality rates decreased from 20.4% to 13.9% [β −0.51 (−0.52 to −0.49), P &lt; 0.001]. The overall proportion of patients treated with systemic thrombolysis increased from 3.1% in 2005 to 4.4% in 2015 [β 0.28 (0.25–0.31), P &lt; 0.001]. Thrombolysis was associated with lower in-hospital mortality rates in patients with haemodynamic instability, both in those with shock not necessitating cardiopulmonary resuscitation (CPR) or mechanical ventilation [odds ratio (OR) 0.42 (0.37–0.48), P &lt; 0.001], and in those who underwent CPR [OR 0.92 (0.87–0.97), P = 0.002]. This association was independent from age, sex, and comorbidities. However, systemic thrombolysis was administered to only 23.1% of haemodynamically unstable patients.

Conclusion
Although the proportion of PE patients treated with systemic thrombolysis increased slightly in Germany between 2005 and 2015, only the minority of haemodynamically unstable patients currently receive this treatment. In the nationwide inpatient cohort, thrombolytic therapy was associated with reduced in-hospital mortality rates in PE patients with shock, and also in those who underwent CPR.
Stereotactic radiosurgery for ablation of ventricular tachycardia
Authors: Neuwirth Radek , Cvek Jakub , Knybel Lukas , Jiravsky Otakar , Molenda Lukas , Kodaj Michal , Fiala Martin , Peichl Petr , Feltl David , Januška Jaroslav , Hecko Jan , Kautzner Josef 
Published: April 2019

Aims
Stereotactic body radiotherapy (SBRT) for ventricular tachycardias (VTs) could be an option after failed catheter ablation. In this study, we analysed the long-term efficacy and toxicity of SBRT applied as a bail-out procedure.

Methods and results
Patients with structural heart disease and unsuccessful catheter ablations for VTs underwent SBRT. The planning target volume (PTV) was accurately delineated using exported 3D electroanatomical maps with the delineated critical part of re-entry circuits. This was defined by detailed electroanatomic mapping and by pacing manoeuvres during the procedure. Using the implantable cardioverter-defibrillator lead as a surrogate contrast marker for respiratory movement compensation, 25 Gy was delivered to the PTV using CyberKnife. We evaluated occurrences of sustained VT, electrical storm, antitachycardia pacing, and shock; time to death; and radiation-induced events. From 2014 until March 2017, 10 patients underwent radiosurgical ablation (mean PTV, 22.15 mL; treatment duration, 68 min). After radiosurgery, four patients experienced nausea and one patient presented gradual progression of mitral regurgitation. During the follow-up (median 28 months), VT burden was reduced by 87.5% compared with baseline (P = 0.012) and three patients suffered non-arrhythmic deaths. After the blanking period, VT recurred in eight of 10 patients. The mean time to first antitachycardia pacing and shock were 6.5 and 21 months, respectively.

Conclusion
Stereotactic body radiotherapy appears to show long-term safety and effectiveness for VT ablation in structural heart disease inaccessible to catheter ablation. We report one possible radiation-related toxicity and promising overall survival, warranting evaluation in a prospective multicentre clinical trial.
Predicted highly derived class 1 CRISPR-Cas system in Haloarchaea containing diverged Cas5 and Cas7 homologs but no CRISPR array
Authors: Makarova Kira S , Karamycheva Svetlana , Shah Shiraz A , Vestergaard Gisle , Garrett Roger A , Koonin Eugene V 
Published: April 2019

ABSTRACT
Screening of genomic and metagenomic databases for new variants of CRISPR-Cas systems increasingly results in the discovery of derived variants that do not seem to possess the interference capacity and are implicated in functions distinct from adaptive immunity. We describe an extremely derived putative class 1 CRISPR-Cas system that is present in many Halobacteria and consists of distant homologs of the Cas5 and Cas7 protein along with an uncharacterized conserved protein and various nucleases. We hypothesize that, although this system lacks typical CRISPR effectors or a CRISPR array, it functions as a RNA-dependent defense mechanism that, unlike other derived CRISPR-Cas, utilizes alternative nucleases to cleave invader genomes.
The Impact of Retirement on Cardiovascular Disease and Its Risk Factors: A Systematic Review of Longitudinal Studies
Authors: Xue Baowen , Head Jenny , McMunn Anne 
Published: April 2019

AbstractBackground and ObjectivesPeople are now spending longer in retirement than ever before and retirement has been found to influence health. This study systematically reviewed the impact of retirement on cardiovascular disease (CVD) and its risk factors (metabolic risk factors, blood biomarkers, physical activity, smoking, drinking, and diet).Research Design and MethodsLongitudinal studies published in Medline, Embase, Social Science Citation Index, PsycINFO, and Social Policy and Practice were searched. No language restrictions were applied if there was an English abstract. Eighty-two longitudinal studies were included after critical appraisals.ResultsStudies in the United States often found no significant effect of retirement on CVD, while studies in European countries, except France, showed a detrimental effect of retirement on CVD. Results from the United States and several European countries consistently show that retirement increase adiposity measures among those retired from physically demanding jobs. For diabetes and hypertension, five out of nine studies suggest no effect of retirement. Retirement has been repeatedly linked to increasing leisure-time physical activity but may reduce work- and transport-related physical activity in turn. Most studies showed that retirement either decreased smoking or had no effect on smoking. The evidence did not show a clear conclusion on drinking. Only a few studies have assessed the impact on diet and blood biomarkers.Discussion and ImplicationsEffect of retirement varies according to the health outcomes studied and country of the study population. Policy concerning extending the retirement age needs to focus on ensuring they are suited to the individual.
Making space for Aboriginal and Torres Strait Islander community health workers in health promotion
Authors: Conte Kathleen P , Gwynn Josephine , Turner Nicole , Koller Claudia , Gillham Karen E 
Published: April 2019

Abstract
Despite a clear need, ‘closing the gap’ in health disparities for Aboriginal and Torres Strait Islander communities (hereafter, respectfully referred to as Aboriginal) continues to be challenging for western health care systems. Globally, community health workers (CHWs) have proven effective in empowering communities and improving culturally appropriate health services. The global literature on CHWs reflects a lack of differentiation between the types of roles these workers carry out. This in turn impedes evidence syntheses informing how different roles contribute to improving health outcomes. Indigenous CHW roles in Australia are largely operationalized by Aboriginal Health Workers (AHWs)—a role situated primarily within the clinical health system. In this commentary, we consider whether the focus on creating professional AHW roles, although important, has taken attention away from the benefits of other types of CHW roles particularly in community-based health promotion. We draw on the global literature to illustrate the need for an Aboriginal CHW role in health promotion; one that is distinct from, but complementary to, that of AHWs in clinical settings. We provide examples of barriers encountered in developing such a role based on our experiences of employing Aboriginal health promoters to deliver evidence-based programmes in rural and remote communities. We aim to draw attention to the systemic and institutional barriers that persist in denying innovative employment and engagement opportunities for Aboriginal people in health.
Identifying key elements to inform HIV-testing interventions for primary care in Belgium
Authors: Apers Hanne , Nöstlinger Christiana , Van Beckhoven Dominique , Deblonde Jessika , Apers Ludwig , Verheyen Katleen , Loos Jasna ,   HERMETIC Study Group, Kaupe Ruta , Kïvïte Anda , Lemsalu Liis , Marty Lise , Michels David , Supervie Virginie , Castr Daniela Rojas , Upmace Inga 
Published: April 2019

Abstract
General practitioners (GPs) play a key role in reducing the hidden HIV-epidemic, but many diagnostic opportunities are missed in primary care. This study aimed at informing the development of an HIV-testing intervention for GPs in Flanders (Belgium) using formative research with a participatory approach. Through the active involvement of an advisory board and 16 group discussions with 122 Flemish GPs, GPs’ current HIV-testing practices and perceived practical relevance of 2 distinct HIV-testing strategies (i.e. provider-initiated testing of key populations and indicator condition-based testing) were explored in terms of their relevance and feasibility in routine primary care. Self-reported HIV-testing practices revealed that most tests performed were patient-initiated, pretest counseling was rarely done, and post-test counseling was offered mainly for patients with an HIV-diagnosis. GPs reported multiple barriers to provider-initiated HIV-testing, i.e. personal discomfort, fear of offending their patient, limited knowledge of benefits of early HIV-diagnosis, misconceptions about HIV-risks, lack of guidelines and time. Difficulties to identify patient’s sexual orientation or ethical concerns were mentioned as barriers for target group-based HIV testing. GPs assessed the current list of 64 indicator conditions as too difficult to integrate in routine care, deeming a reduced list of GP-relevant conditions as more feasible. Combined strategies (i.e. target group- and indicator-based testing) supported by official screening recommendations were perceived as successful strategies for provider-initiated HIV-testing in primary care. This formative research delivered qualitative evidence for the development of an HIV-testing intervention for primary care settings.
Quantum Teleportation and Super-Dense Coding in Operator Algebras
Authors: Gao Li , Harris Samuel J , Junge Marius 
Published: April 2019

Abstract
We show for any $d,m\ge 2$ with $(d,m)\neq (2,2)$, the matrix-valued generalization of the (tensor product) quantum correlation set of $d$ inputs and $m$ outputs is not closed. Our argument uses a reformulation of super-dense coding and teleportation in terms of $C^*$-algebra isomorphisms. Namely, we prove that for certain actions of cyclic group ${{\mathbb{Z}}}_d$, $$\begin{equation*}M_d(C^*({{\mathbb{F}}}_{d^2}))\cong{{\mathcal{B}}}_d\rtimes{{\mathbb{Z}}}_d\rtimes{{\mathbb{Z}}}_d , M_d({{\mathcal{B}}}_d)\cong C^*({{\mathbb{F}}}_{d^2})\rtimes{{\mathbb{Z}}}_d\rtimes{{\mathbb{Z}}}_d,\end{equation*}$$where ${{\mathcal{B}}}_d$ is the universal unital $C^*$-algebra generated by the elements $u_{jk}, \, 0 \le i, j \le d-1$, satisfying the relations that $[u_{j,k}]$ is a unitary operator, and $C^*({{\mathbb{F}}}_{d^2})$ is the universal $C^*$-algebra of $d^2$ unitaries. These isomorphisms provide a nice connection between the embezzlement of entanglement and the non-closedness of quantum correlation sets.
Guidance for Studies Evaluating the Accuracy of Rapid Tuberculosis Drug-Susceptibility Tests
Authors: Georghiou Sophia B , Schumacher Samuel G , Rodwell Timothy C , Colman Rebecca E , Miotto Paolo , Gilpin Christopher , Ismail Nazir , Rodrigues Camilla , Warren Rob , Weyer Karin , Zignol Matteo , Arafah Sonia , Cirillo Daniela Maria , Denkinger Claudia M 
Published: April 2019

Abstract
The development and implementation of rapid molecular diagnostics for tuberculosis (TB) drug-susceptibility testing is critical to inform treatment of patients and to prevent the emergence and spread of resistance. Optimal trial planning for existing tests and those in development will be critical to rapidly gather the evidence necessary to inform World Health Organization review and to support potential policy recommendations. The evidence necessary includes an assessment of the performance for TB and resistance detection as well as an assessment of the operational characteristics of these platforms. The performance assessment should include analytical studies to confirm the limit of detection and assay ability to detect mutations conferring resistance across globally representative strains. The analytical evaluation is typically followed by multisite clinical evaluation studies to confirm diagnostic performance in sites and populations of intended use. This paper summarizes the considerations for the design of these analytical and clinical studies.
A modal extension of Jaśkowski’s discussive logic $\textbf{D}_\textbf{2}$
Authors: Mruczek-Nasieniewska Krystyna , Nasieniewski Marek , Pietruszczak Andrzej 
Published: April 2019

Abstract
In Jaśkowski’s model of discussion, discussive connectives represent certain interactions that can hold between debaters. However, it is not possible within the model for participants to use explicit modal operators. In the paper we present a modal extension of the discussive logic $\textbf{D}_{\textbf{2}}$ that formally corresponds to an extended version of Jaśkowski’s model of discussion that permits such a use. This logic is denoted by $\textbf{m}\textbf{D}_{\textbf{2}}$. We present philosophical motivations for the formulation of this logic. We also give syntactic characterizations of the logic and propose a comparison with certain other modal systems. In particular, we prove that $\textbf{m}\textbf{D}_{\textbf{2}}$ is neither normal nor regular. On the basis of the axiomatization of $\textbf{D}_{\textbf{2}}$, we give an axiomatization of $\textbf{m}\textbf{D}_{\textbf{2}}$. We also give another axiomatization which is not based on the axiomatization of $\textbf{D}_{\textbf{2}}$. Furthermore, we give a natural Kripke-style semantics for $\textbf{m}\textbf{D}_{\textbf{2}}$ and prove the respective adequacy theorems.
Exact Inference in Long-Horizon Predictive Quantile Regressions with an Application to Stock Returns
Authors: Gungor Sermin , Luger Richard 
Published: April 2019

AbstractWe develop an exact and distribution-free procedure to test for quantile predictability at several prediction horizons and quantile levels jointly, while allowing for an endogenous predictive regressor with any degree of persistence. The approach proceeds by combining together the quantile regression t-statistics from each considered prediction horizon and quantile level, and uses Monte-Carlo resampling techniques to control the familywise error rate in finite samples. A simulation study confirms that the proposed inference procedure is indeed level-correct and that testing several quantile levels jointly can deliver more power to detect predictability. In an empirical application to excess stock returns, we find that the default yield spread predicts the right tail while the short-term interest rate predicts the center of the return distribution. This predictability evidence is stronger at shorter rather than longer horizons.