bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deletion of Lymphangiogenic and Angiogenic Growth Factor VEGF-D Leads to Severe Hyperlipidemia and Delayed Clearance of Chylomicron Remnants
Authors: Tirronen Annakaisa , Vuorio Taina , Kettunen Sanna , Hokkanen Krista , Ramms Bastian , Niskanen Henri , Laakso Hanne , Kaikkonen Minna U. , Jauhiainen Matti , Gordts Philip L.S.M. , Ylä-Herttuala Seppo 
Published: September 2018

Objective—

Dyslipidemia is one of the key factors behind coronary heart disease. Blood and lymphatic vessels play pivotal roles in both lipoprotein metabolism and development of atherosclerotic plaques. Recent studies have linked members of VEGF (vascular endothelial growth factor) family to lipid metabolism, but the function of VEGF-D has remained unexplored. Here, we investigated how the deletion of VEGF-D affects lipid and lipoprotein metabolism in atherogenic LDLR
−/−
ApoB
100/100
mice.

Approach and Results—

Deletion of VEGF-D (VEGF-D
−/−
LDLR
−/−
ApoB
100/100
) led to markedly elevated plasma cholesterol and triglyceride levels without an increase in atherogenesis. Size distribution and hepatic lipid uptake studies confirmed a delayed clearance of large chylomicron remnant particles that cannot easily penetrate through the vascular endothelium. Mechanistically, the inhibition of VEGF-D signaling significantly decreased the hepatic expression of SDC1 (syndecan 1), which is one of the main receptors for chylomicron remnant uptake when LDLR is absent. Immunohistochemical staining confirmed reduced expression of SDC1 in the sinusoidal surface of hepatocytes in VEGF-D deficient mice. Furthermore, hepatic RNA-sequencing revealed that VEGF-D is also an important regulator of genes related to lipid metabolism and inflammation. The lack of VEGF-D signaling via VEGFR3 (VEGF receptor 3) led to lowered expression of genes regulating triglyceride and cholesterol production, as well as downregulation of peroxisomal β-oxidation pathway.

Conclusions—
These results demonstrate that VEGF-D, a powerful lymphangiogenic and angiogenic growth factor, is also a major regulator of chylomicron metabolism in mice.
Vascular Bed Molecular Profiling by Differential Systemic Decellularization In Vivo
Authors: Serra Aida , Gallart-Palau Xavier , Park Jung Eun , Lim Grace Gui Yin , Lim Kah Leong , Ho Hee Hwa , Tam James P. , Sze Siu Kwan 
Published: September 2018

Objective—
Vascular endothelial dysfunction is a key component of several major human diseases, but the molecular basis of this complex disorder has been difficult to determine in vivo. Previous attempts to identify key mediators of vascular endothelial dysfunction in experimental models have been limited by the lack of suitable methods for system-wide analyses of vascular bed biology. Here, we aimed to develop a novel method for investigating vascular endothelial dysfunction pathogenesis that enables system-wide analyses of molecular interactions between endothelial glycocalyx, endothelial cells, and smooth muscle cells in murine.

Approach and Results—
We developed a new technique using whole-body differential perfusion with increasing concentrations of detergent buffer to selectively solubilize distinct layers of vascular bed tissue in rodents. When combined with proteomics techniques, our novel approach of differential systemic decellularization in vivo enabled quantitative profiling of vascular beds throughout the body. Initial perfusion with phosphate buffer was used to obtain the endothelial glycocalyx, followed by subsequent extraction of endothelial cell components, and finally by smooth muscle cell constituents with increasing concentrations of detergent. Differential systemic decellularization in vivo has also been successfully applied to characterize molecular events in the vascular bed pathology of lipopolysaccharide-challenged mice.

Conclusions—
Together, these data indicate that differential systemic decellularization in vivo permits system-wide molecular characterization of vascular bed proteomes in rodent models and can be used to advance our current understanding of vascular endothelial dysfunction pathogenesis and progression in a wide range of disease settings.
Age-Biomarkers-Clinical Risk Factors for Prediction of Cardiovascular Events in Patients With Coronary Artery Disease
Authors: Wong Yuen-Kwun , Cheung Chloe Y.Y. , Tang Clara S. , Au Ka-Wing , Hai JoJo S.H. , Lee Chi-Ho , Lau Kui-Kai , Cheung Bernard M.Y. , Sham Pak-Chung , Xu Aimin , Lam Karen S.L. , Tse Hung-Fat 
Published: September 2018

Objective—
In patients with stable coronary artery disease, conventional risk factors provide limited incremental predictive value for cardiovascular events. We sought to investigate whether a panel of cardiometabolic biomarkers alone or combined with conventional risk factors would exhibit incremental value in the prediction of cardiovascular events.

Approach and Results—
In the discovery cohort, we measured serum adiponectin, A-FABP (adipocyte fatty acid–binding protein), lipocalin-2, FGF (fibroblast growth factor)-19 and 21, plasminogen activator inhibitor-1, and retinol-binding protein-4 in 1166 Chinese coronary artery disease patients. After a median follow-up of 35 months, 170 patients developed new-onset major adverse cardiovascular events (MACE). In the model with age ≥65 years and conventional risk factors, area under the curve for predicting MACE was 0.68. Addition of lipocalin-2 to the age-clinical risk factor model improved predictive accuracy (area under the curve=0.73). Area under the curve further increased to 0.75 when a combination of lipocalin-2, A-FABP, and FGF-19 was added to yield age-biomarkers-clinical risk factor model. The adjusted hazard ratio on MACEs for lipocalin-2, A-FABP, and FGF-19 levels above optimal cutoffs were 2.23 (95% CI, 1.62–3.08), 1.99 (95% CI, 1.43–2.76), and 1.65 (95% CI, 1.15–2.35), respectively. In the validation cohort of 1262 coronary artery disease patients with type 2 diabetes mellitus, the age-biomarkers-clinical risk factor model was confirmed to provide good discrimination and calibration over the conventional risk factor alone for prediction of MACE.

Conclusions—
A combination of the 3 biomarkers, lipocalin-2, A-FABP, and FGF-19, with clinical risk factors to yield the age-biomarkers-clinical risk factor model provides an optimal and validated prediction of new-onset MACE in patients with stable coronary artery disease.
Tyconius’ Apocalypse Commentary, Its Reconstruction, and Its Significance for Augustine’s Doctrine of the Two Cities
Authors: van Oort Johannes 
Published: September 2018

Abstract
The present article deals with Roger Gryson’s reconstruction of Tyconius’ lost Commentary on the Apocalypse (CCL 107A), his subsequent French translation of this reconstructed Commentary (CCT 10), and the English translation Tyconius, Exposition of the Apocalypse by Francis Gumerlock, with long introduction and ample notes by David Robinson (FoC 134). After having reviewed the strenghths and weaknesses of each of these publications, the article concludes with a discussion of the significance of Tyconius’ Commentary for the question of the origin of Augustine’s two civitates doctrine.
Justin Martyr and the Authorship of the Earliest Anti-Heretical Treatise
Authors: den Dulk Matthijs 
Published: September 2018

Abstract
Justin Martyr is commonly regarded as the “inventor of heresy,” an assessment that is based to a considerable extent on his authorship of the earliest-known, now lost anti-heretical treatise mentioned in Justin’s First Apology 26. Justin’s authorship of this treatise has often been assumed, but rarely argued, and it has been contested by a number of scholars. This study evaluates the grammatical, literary, and historical aspects of this question and argues, against recent claims to the contrary, that the hypothesis that Justin was involved in the production of this important document best accommodates the available evidence.
Time Evolution of the Cloud Response to Moisture Intrusions into the Arctic during Winter
Authors: Liu Yinghui , Key Jeffrey R. , Vavrus Steve , Woods Cian 
Published: September 2018

AbstractNorthward fluxes of moisture and sensible heat into the Arctic affect the atmospheric stability, sea ice and snow cover, clouds, and surface energy budget. Intense moisture fluxes into the Arctic are called moisture intrusions; some can lead to basinwide increases in downward longwave radiation (DLR) at the surface, called downward infrared (IR) events. Using the ERA-Interim reanalysis from 1990 to 2016, this study investigated the time evolution of cloud amount and cloud properties and their impact on the surface radiation fluxes in response to Arctic moisture intrusions and downward IR events during winter for better understanding of the Arctic moisture intrusions. A composite analysis revealed several key features: moisture intrusions produce more clouds and higher cloud liquid and ice water content; positive cloud amount anomalies can persist for over 10 days over the Arctic Ocean during downward IR events; positive high-level and middle-level cloud anomalies are evident in the early stage, and positive low-level cloud anomalies are evident in the late stage. Greater clear-sky DLR and longwave cloud radiative forcing (CRF) over the Arctic Ocean accompany the greater all-sky DLR during the downward IR events. Greater clear-sky DLR can be attributed to higher air temperatures and higher total column water vapor, while greater longwave CRF is the result of larger cloud amount and cloud water content. Longwave CRF anomalies account for approximately 40% of the all-sky DLR anomalies.
Anhedonia and depression severity dissociated by dmPFC resting-state functional connectivity in adolescents
Authors: Rzepa Ewelina , McCabe Ciara 
Published: September 2018

Introduction: Given the heterogeneity within depression, in this study we aim to examine how resting-state functional connectivity (RSFC) in adolescents is related to anhedonia and depression severity on a continuum in line with the research domain criteria (RDoC) approach. Methods: We examined how RSFC in the dorsal medial prefrontal cortex (dmPFC), nucleus accumbens (NAcc) and pregenual anterior cingulate cortex (pgACC) was related to anhedonia and depression severity in 86 adolescents (13–21 years). Results: We found both anhedonia and depression severity related to decreased dmPFC RSFC with the precuneus, a part of the default mode network. However we also found that increased dmPFC connectivity with the ACC/paracingulate gyrus related to anhedonia whereas increased RSFC with the frontal pole related to depression severity. Discussion: This work extends the view that the dmPFC is a potential therapeutic target for depression in two ways: 1. We report dmPFC connectivity in adolescents; and 2. We show different dmPFC RSFC specific to anhedonia and depression severity, providing neural targets for intervention in young people at risk of depression.
Cannabidiol treatment reduces the motivation to self-administer methamphetamine and methamphetamine-primed relapse in rats
Authors: Hay Gracie L , Baracz Sarah J , Everett Nicholas A , Roberts Jessica , Costa Priscila A , Arnold Jonathon C , McGregor Iain S , Cornish Jennifer L 
Published: September 2018

Background: Methamphetamine is an addictive stimulant that can cause many adverse physical, psychological and psychosocial effects. Preliminary evidence shows cannabidiol, a non-intoxicating constituent of the cannabis plant, may have efficacy in treating opioid and nicotine dependence. However, no study has yet examined whether cannabidiol treatment might impact on methamphetamine addiction. Aims: The current study investigated whether cannabidiol administration reduces the motivation to self-administer methamphetamine and relapse to methamphetamine-seeking behavior following abstinence. Methods: Thirty-two male Sprague Dawley rats with implanted jugular vein catheters were initially trained to self-administer methamphetamine via lever press during two-hour sessions on a fixed ratio 1 schedule of reinforcement. Rats in experiment 1 ( n=16) then advanced to a progressive ratio reinforcement schedule to examine the effects of cannabidiol (0, 20, 40, and 80 mg/kg intraperitoneal) on motivation to self-administer methamphetamine. Rats in experiment 2 ( n=16) were tested for cannabidiol effects on methamphetamine-primed reinstatement following extinction. Results: Cannabidiol (80 mg/kg, but not 40 mg/kg, or 20 mg/kg) reduced the motivation to self-administer methamphetamine and attenuated methamphetamine-primed relapse to methamphetamine-seeking behavior after extinction. Conclusion: This is the first demonstration that cannabidiol can reduce the motivation to seek and consume methamphetamine, and suggests that cannabidiol might be worth trialing as a novel pharmacotherapy for methamphetamine dependence.
Sex Differences in the Association Between Cannabis Use and Suicidal Ideation and Attempts, Depression, and Psychological Distress Among Canadians
Authors: Halladay Jillian E. , Boyle Michael H. , Munn Catharine , Jack Susan M. , Georgiades Katholiki 
Published: September 2018

Background: Depression, anxiety, and substance use disorders are leading causes of morbidity worldwide. The most commonly used illicit substance is cannabis and there is some evidence that the association between cannabis use and poor mental health is more pronounced among females compared with males. This analysis examines sex differences in the association between cannabis use and major depressive episode (MDE), suicidal thoughts and attempts, and psychological distress. Methods: This study uses data from the 2002 and 2012 Canadian Community Health Survey’s Mental Health Component, repeated cross-sectional surveys of nationally representative samples of Canadians 15 years of age and older ( n = 43,466). Linear and binary logistic regressions were performed, applying weighting and bootstrapping. Results: There were significant sex differences in the strength of the association between cannabis use and suicidal thoughts and attempts and psychological distress, but not MDE. Females who reported using cannabis occasionally (defined as 1 to 4 times a month) reported higher levels of psychological distress than their male counterparts. Females who reported using regularly (defined as more than once per week) reported higher levels of psychological distress and were more likely to report suicidal thoughts and attempts. Conclusions: Future research is needed to further our understanding of the nature of these sex differences. Public health messaging should incorporate being female as a potential risk factor for the co-occurrence of cannabis use and emotional problems, particularly at higher frequencies of use. Clinicians should also be aware of this association to better inform integrated mental health and substance use screening, discussions, and care, particularly for female patients.
Treatment with low‐dose tacrolimus inhibits bleeding complications in a patient with hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension
Authors: Sommer N , Droege F , Gamen KE , Geisthoff U , Gall H , Tello K , Richter MJ , Deubner LM , Schmiedel R , Hecker M , Spiekerkoetter E , Wirsching K , Seeger W , Ghofrani HA , Pullamsetti S 
Published: September 2018

Pulmonary arterial hypertension (PAH) can be found in patients suffering from a loss‐of‐function mutation of the gene encoding for the activin receptor‐like kinase 1 (ALK‐1), a bone morphogenetic protein (BMP) type 1 receptor. Interestingly, ALK‐1 mutations also lead to hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant disease characterized by arteriovenous malformations (AVMs) leading to potentially life‐threatening bleeding complications such as epistaxis. Current therapeutic options for both diseases are limited and often only temporary or accompanied by severe side effects. Here, we report of a patient with a mutation of the ALK‐1 gene suffering from both HHT and PAH. Recently, it was shown that tacrolimus increased ALK‐1 signaling and had beneficial effects in selected end‐stage PAH patients. We thus hypothesized that treatment with tacrolimus may prevent disease progression in this patient. Surprisingly, treatment with low‐dose tacrolimus dramatically improved his HHT‐associated epistaxis but did not attenuate progression of PAH.
Anti-tumour effect of low molecular weight heparin in localised lung cancer: a phase III clinical trial
Authors: Meyer Guy , Besse Benjamin , Doubre Hélène , Charles-Nelson Anaïs , Aquilanti Sandro , Izadifar Armine , Azarian Reza , Monnet Isabelle , Lamour Corinne , Descourt Renaud , Oliviero Gérard , Taillade Laurent , Chouaid Christos , Giraud Frederique , Falcoz Pierre-Emmanuel , Revel Marie-Pierre , Westeel Virginie , Dixmier Adrien , Tredaniel Jean , Dehette Stéphanie , Decroisette Chantal , Prevost Alain , Pichon Eric , Fabre Elizabeth , Soria Jean-Charles , Friard Sylvie , Stern Jean-Baptiste , Jabot Laurence , Dennewald Georges , Pavy Gérard , Petitpretz Patrick , Tourani Jean-Marc , Alifano Marco , Chatellier Gilles , Girard Philippe 
Published: September 2018

The anti-tumour and anti-metastatic properties of heparins have not been tested in patients with early stage cancer. Whether adjuvant low molecular weight heparin (LMWH) tinzaparin impacts the survival of patients with resected non-small cell lung cancer (NSCLC) was investigated.Patients with completely resected stage I, II or IIIA NSCLC were randomly allocated to receive subcutaneous tinzaparin 100 IU·kg−1once a day for 12 weeks or no treatment in addition to standard of care. The trial was open-label with blinded central adjudication of study outcomes. The primary outcome was overall survival.In 549 patients randomised to tinzaparin (n=269) or control (n=280), mean±sdage was 61.6±8.9 years, 190 (34.6%) patients had stage II−III disease, and 220 (40.1%) patients received adjuvant chemotherapy. Median follow-up was 5.7 years. There was no significant difference in overall survival between groups (hazard ratio (HR) 1.24, 95% CI 0.92–1.68; p=0.17). There was no difference in the cumulative incidence of recurrence between groups (subdistribution HR 0.94, 95% CI 0.68–1.30; p=0.70).Adjuvant tinzaparin had no detectable impact on overall and recurrence-free survival of patients with completely resected stage I−IIIA NSCLC. These results do not support further clinical evaluation of LMWHs as anti-tumour agents.
Pedestrian detection with motion features via two-stream ConvNets
Authors: Yoshihashi Ryota , Trinh Tu Tuan , Kawakami Rei , You Shaodi , Iida Makoto , Naemura Takeshi 
Published: September 2018

Abstract
Motion information can be important for detecting objects, but it has been used less for pedestrian detection, particularly with deep-learning-based methods. We propose a method that uses deep motion features as well as deep still-image features, following the success of two-stream convolutional networks, each of which are trained separately for spatial and temporal streams. To extract motion clues for detection differentiated from other background motions, the temporal stream takes as input the difference in frames that are weakly stabilized by optical flow. To make the networks applicable to bounding-box-level detection, the mid-level features are concatenated and combined with a sliding-window detector. We also introduce transfer learning from multiple sources in the two-stream networks, which can transfer still image and motion features from ImageNet and an action recognition dataset respectively, to overcome the insufficiency of training data for convolutional neural networks in pedestrian datasets. We conducted an evaluation on two popular large-scale pedestrian benchmarks, namely the Caltech Pedestrian Detection Benchmark and Daimler Mono Pedestrian Detection Benchmark. We observed 10% improvement compared to the same method but without motion features.
Meaningful and Accurate Disclosure of Conflict of Interest at the ASTRO National Meeting: A Need for Reassessment of Current Policies
Authors: Ahmed Awad A. , Yoo Stella K. , Mehta Shahil , Holliday Emma B. , Deville Curtiland , Vapiwala Neha , Wilson Lynn D. , Jagsi Reshma , Prasad Vinay , Thomas Charles R. 
Published: September 2018

Purpose: Conflict of interest (COI) disclosure is essential to research integrity. The average reading comprehension in English is 3.8 words per second (wps). This study examines presenters at the American Society for Radiation Oncology (ASTRO) national meeting over a recent 3-year period to determine whether disclosure is presented accurately and in a manner that allows the audience to comprehend the content. Methods: We examined videos of presentations as well as slides from 2014 to 2016 from the ASTRO virtual meeting, noting whether a COI slide was presented, the duration the slide was visible, and the number of disclosures. Disclosures were cross-referenced for discrepancies with the publicly reported Centers for Medicare and Medicaid Services Open Payments database. Using a cutoff of 4 wps, we noted how many presentations were presented at speeds of ≤ 4 wps and > 4 wps. Results: The final data set consisted of 401 presentations delivered by 364 presenters. Using a threshold of 4 wps, 34.0% of presenters had COI slides shown too fast for the average audience to comprehend. Moreover, 16.3% of US physicians incorrectly underreported industry funding received. Of these presentations with discrepancies, 32.6% did not have a COI slide, 39.5% failed to disclose any COI, 27.9% partially disclosed COIs, and 11.6% contained multiple discrepancies. The number of wps were correlated with having a discrepancy on multivariable regression ( P = .046; odds ratio, 1.08; 95% CI, 1.01 to 1.19). Conclusion: A substantial minority of presentations at ASTRO lack meaningful disclosure, and a surprising number incorrectly reported COIs. Additional guidance may be needed to promote more meaningful and accurate disclosure of COIs at major national meetings in oncology.
Proposed classification for interproximal contacts of primary molars using CBCT: a pilot study
Authors: Kirthiga M. , Muthu M. S. , Kayalvizhi G. , Krithika C. 
Published: September 2018

Background: Interproximal contact areas in primary teeth are known to be broader, flatter, and situated more gingivally than in permanent teeth. The objective of the present study was to evaluate the different types of intact interproximal contact areas in primary teeth using cone beam computed tomography (CBCT) among children. Methods: A cross-sectional study was designed with 74 contacts from 28 existing CBCT images of children aged between 3 and 14 years, obtained from the Indian Dental Education Academy, Chennai, India. The shape of the contact area was observed at three levels, the coronal, middle, and apical thirds, in three different sections of CBCT. Prevalence of the types of contact areas was expressed in the form of numbers and percentages. Results: The weighted Cohen’s kappa values for inter-examiner reliability was 0.893 at baseline. Results exhibited four different types of contact areas between the primary molars, namely, O type, X type, I type, and S type, based on the shapes observed; hence, the proposed classification is referred to as OXIS. The most common pattern seen was I (66.2%), followed by X (21.6%), O (9.4%) and the least common was S (2.7%). Conclusion: The three-dimensional evaluation of intact interproximal contact areas between primary molars are of four types, O,X, I and S.
Gagging – bringing up an old problem part 2: management of the condition
Authors: Murchie Bryan Daniel 
Published: September 2018

Abstract: This is the second-part of a two-part series on gagging patients. The first paper discussed the aetiology of gagging and diagnosing the severity of the condition. This paper will investigate the different management approaches which can be considered for patients who suffer from an exaggerated gag reflex. CPD/Clinical Relevance: Once the gagging patient has been successfully diagnosed, it is important to consider the most appropriate treatment options. No two cases are alike, therefore, the clinician must carefully tailor the treatment plan for each patient, as with any other form of dental treatment.