bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morphological and functional properties of the conducting human airways investigated by in vivo computed tomography and in vitro MRI
Authors: Van de Moortele Tristan , Wendt Christine H. , Coletti Filippo 
Published: November 2017

The accurate representation of the human airway anatomy is crucial for understanding and modeling the structure-function relationship in both healthy and diseased lungs. The present knowledge in this area is based on morphometric studies of excised lung casts, partially complemented by in vivo studies in which computed tomography (CT) was used on a small number of subjects. In the present study, we analyzed CT scans of a cohort of healthy subjects and obtained comprehensive morphometric information down to the seventh generation of bronchial branching, including airway diameter, length, branching angle, and rotation angle. Although some of the geometric parameters (such as the child-to-parent branch diameter ratio) are found to be in line with accepted values, for others (such as the branch length-to-diameter ratio) our findings challenge the common assumptions. We also evaluated several metrics of self-similarity, including the fractal dimension of the airway tree. Additionally, we used phase-contrast magnetic resonance imaging (MRI) to obtain the volumetric flow field in the three-dimensional-printed airway model of one of the subjects during steady inhalation. This is used to relate structural and functional parameters and, in particular, to close the power-law relationship between branch flow rate and diameter. The diameter exponent is found to be significantly lower than in the usually assumed Poiseuille regime, which we attribute to the strong secondary (i.e., transverse) velocity component. The strength of the secondary velocity with respect to the axial component exceeds the levels found in idealized airway models and persists within the first seven generations. NEW & NOTEWORTHY We performed a comprehensive computed tomography-based study of the conductive airway morphology in normal human subjects, including branch diameter, length, and mutual angles. We found significant departure from classic homothetic relationships. We also carried out MRI measurements of the three-dimensional inspiratory flow in an anatomy-based model and directly assessed structure-function relationships that have so far been assumed. We found that strong secondary flows (i.e., transverse velocity components) persist through the first seven generations of bronchial branching.
Chronic exposure to electronic cigarettes results in impaired cardiovascular function in mice
Authors: Olfert I. Mark , DeVallance Evan , Hoskinson Hannah , Branyan Kayla W. , Clayton Stuart , Pitzer Christopher R. , Sullivan D. Patrick , Breit Matthew J. , Wu Zhongxin , Klinkhachorn Powsiri , Mandler W. Kyle , Erdreich Brett H. , Ducatman Barbara S. , Bryner Randall W. , Dasgupta Piyali , Chantler Paul D. 
Published: November 2017

Proponents for electronic cigarettes (E-cigs) claim that they are a safe alternative to tobacco-based cigarettes; however, little is known about the long-term effects of exposure to E-cig vapor on vascular function. The purpose of this study was to determine the cardiovascular consequences of chronic E-cig exposure. Female mice (C57BL/6 background strain) were randomly assigned to chronic daily exposure to E-cig vapor, standard (3R4F reference) cigarette smoke, or filtered air ( n = 15/group). Respective whole body exposures consisted of four 1-h-exposure time blocks, separated by 30-min intervals of fresh air breaks, resulting in intermittent daily exposure for a total of 4 h/day, 5 days/wk for 8 mo. Noninvasive ultrasonography was used to assess cardiac function and aortic arterial stiffness (AS), measured as pulse wave velocity, at three times points (before, during, and after chronic exposure). Upon completion of the 8-mo exposure, ex vivo wire tension myography and force transduction were used to measure changes in thoracic aortic tension in response to vasoactive-inducing compounds. AS increased 2.5- and 2.8-fold in E-cig- and 3R4F-exposed mice, respectively, compared with air-exposed control mice ( P < 0.05). The maximal aortic relaxation to methacholine was 24% and 33% lower in E-cig- and 3R4F-exposed mice, respectively, than in controls ( P < 0.05). No differences were noted in sodium nitroprusside dilation between the groups. 3R4F exposure altered cardiac function by reducing fractional shortening and ejection fraction after 8 mo ( P < 0.05). A similar, although not statistically significant, tendency was also observed with E-cig exposure ( P < 0.10). Histological and respiratory function data support emphysema-associated changes in 3R4F-exposed, but not E-cig-exposed, mice. Chronic exposure to E-cig vapor accelerates AS, significantly impairs aortic endothelial function, and may lead to impaired cardiac function. The clinical implication from this study is that chronic use of E-cigs, even at relatively low exposure levels, induces cardiovascular dysfunction. NEW & NOTEWORTHY Electronic cigarettes (E-cigs) are marketed as safe, but there has been insufficient long-term exposure to humans to justify these claims. This is the first study to report the long-term in vivo vascular consequences of 8 mo of exposure to E-cig vapor in mice (equivalent to ~25 yr of exposure in humans). We report that E-cig exposure increases arterial stiffness and impairs normal vascular reactivity responses, similar to other risk factors, including cigarette smoking, which contribute to the development of cardiovascular disease.
Deletion of Neuropilin 1 from Microglia or Bone Marrow–Derived Macrophages Slows Glioma Progression
Authors: Miyauchi Jeremy Tetsuo , Caponegro Michael D. , Chen Danling , Choi Matthew K. , Li Melvin , Tsirka Stella E. 
Published: November 2017

Abstract
Glioma-associated microglia and macrophages (GAM), which infiltrate high-grade gilomas, constitute a major cellular component of these lesions. GAM behavior is influenced by tumor-derived cytokines that suppress initial antitumorigenic properties, causing them to support tumor growth and to convert and suppress adaptive immune responses to the tumor. Mice that lack the transmembrane receptor neuropilin-1 (Nrp1), which modulates GAM immune polarization, exhibit a decrease in glioma volumes and neoangiogenesis and an increase in antitumorigenic GAM infiltrate. Here we show that replacing the peripheral macrophage populations of wild-type mice with Nrp1-depleted bone marrow-derived macrophages (BMDM) confers resistance to the development of glioma. This resistance occurred in a similar fashion seen in mice in which all macrophages lacked Nrp1 expression. Tumors had decreased volumes, decreased vascularity, increased CTL infiltrate, and Nrp1-depleted BMDM adopted a more antitumorigenic phenotype relative to wild-type GAMs within the tumors. Mice with Nrp1-deficient microglia and wild-type peripheral macrophages showed resistance to glioma development and had higher microglial infiltrate than mice with wild-type GAMs. Our findings show how manipulating Nrp1 in either peripheral macrophages or microglia reprograms their phenotype and their pathogenic roles in tumor neovascularization and immunosuppression.
Significance: This study highlights the proangiogenic receptor neuropilin 1 in macrophages and microglial cells in gliomas as a pivotal modifier of tumor neovascularization and immunosuppression, strengthening emerging evidence of the functional coordination of these two fundamental traits of cancer. Cancer Res; 78(3); 685–94. ©2017 AACR.
Ischemic Stroke: Histological Thrombus Composition and Pre-Interventional CT Attenuation Are Associated with Intervention Time and Rate of Secondary Embolism
Authors: Sporns Peter B. , Hanning Uta , Schwindt Wolfram , Velasco Aglae , Buerke Boris , Cnyrim Christian , Minnerup Jens , Heindel Walter , Jeibmann Astrid , Niederstadt Thomas 
Published: November 2017

<b><i>Background and Purpose:</i></b> The introduction of stent retrievers has made the complete extraction and histological analysis of human thrombi possible. A number of large randomized trials have proven the efficacy of thrombectomy for ischemic stroke; however, thrombus composition could have an impact on the efficacy and risk of the intervention. We therefore investigated the impact of histologic thrombus features on interventional outcome and procedure-related embolisms. For a pre-interventional estimation of histologic features and outcome parameters, we assessed the pre-interventional CT attenuation of the thrombi. <b><i>Methods:</i></b> We prospectively included all consecutive patients with occlusion of the middle cerebral artery who underwent thrombectomy between December 2013 and February 2016 at our university medical center. Samples were histologically analyzed (H&amp;E, Elastica van Gieson, Prussian blue); additionally, immunohistochemistry for CD3, CD20, and CD68/KiM1P was performed. Main thrombus components (fibrin, erythrocytes, and white blood cells) were determined and compared to intervention time, frequency of secondary embolisms, as well as additional clinical and interventional parameters. Additionally, we assessed the pre-interventional CT attenuation of the thrombi in relation to the unaffected side (rHU) and their association with histologic features. <b><i>Results:</i></b> One hundred eighty patients were included; of these, in 168 patients (93.4%), complete recanalization was achieved and 27 patients (15%) showed secondary embolism in the control angiogram. We observed a significant association of high amounts of fibrin (<i>p</i> &#x3c; 0.001), low percentage of red blood cells (<i>p</i> &#x3c; 0.001), and lower rHU (<i>p</i> &#x3c; 0.001) with secondary embolism. Higher rHU values were significantly associated with higher amounts of fibrin (<i>p</i> ≤ 0.001) and low percentage of red blood cells (<i>p</i> ≤ 0.001). Additionally, high amounts of fibrin were associated with longer intervention times (<i>p</i> ≤ 0.001), whereas thrombi with high amounts of erythrocytes correlated with shorter intervention times (<i>p</i> ≤ 0.001). ROC analysis revealed reliable prediction of secondary embolisms for low rHU (AUC = 0.746; <i>p</i> ≤ 0.0001), low amounts of RBC (AUC = 0.764; <i>p</i> ≤ 0.0001), and high amounts of fibrin (AUC = 0.773; <i>p</i> ≤ 0.0001). <b><i>Conclusions:</i></b> Fibrin-rich thrombi with low erythrocyte percentage are significantly associated with longer intervention times. Embolisms in the thrombectomy process occur more often in thrombi with a small fraction of red blood cells and a low CT-density, suggesting a higher fragility of these thrombi.
Elevated Plasma Factor IXa Activity in Premenopausal Women on Hormonal Contraception
Authors: Tanratana Pansakorn , Ellery Paul , Westmark Pamela , Mast Alan E. , Sheehan John P. 
Published: November 2017

Objective—
Combined oral contraceptives induce a reversible hypercoagulable state with an enhanced risk of venous thromboembolism, but the underlying mechanism(s) remain unclear. Subjects on combined oral contraceptives also demonstrate a characteristic resistance to APC (activated protein C) in the thrombin generation assay. Here, we report the potential role of plasma factor IXa (FIXa) as a mechanism for hormone-induced systemic hypercoagulability.

Approach and Results—
A novel assay was used to determine FIXa activity in plasma samples from volunteer blood donors. Plasma from 36 premenopausal females on hormonal contraception and 35 not on hormonal contraception, 35 postmenopausal females, and 10 males were analyzed for FIXa activity, total PS (protein S), total tissue factor pathway inhibitor (TFPI), and TFPI-α antigen. Premenopausal females on hormonal contraception demonstrated significantly increased FIXa activity and decreased TFPI-α compared with the other groups. Remarkably, FIXa values were not normally distributed in the hormonal contraception group, but skewed toward the high end. Plasma FIXa activity inversely correlated with both TFPI-α and total PS antigen. Ex vivo determination of TF-dependent FIX activation in FV-deficient plasma demonstrated that inhibitory anti-TFPI antibodies enhanced FIXa generation by 2- to 3-fold, whereas addition of 75 nmol/L PS reduced FIXa generation by ≈2-fold. Further, increasing FIXa concentration enhanced APC resistance during TF-triggered plasma thrombin generation.

Conclusions—
Elevation of plasma FIXa activity in association with reductions in TFPI-α and PS is a potential mechanism for systemic hypercoagulability and resistance to APC in premenopausal females on hormonal contraception.
Sex Chromosome Complement Defines Diffuse Versus Focal Angiotensin II–Induced Aortic Pathology
Authors: Alsiraj Yasir , Thatcher Sean E. , Blalock Eric , Fleenor Bradley , Daugherty Alan , Cassis Lisa A. 
Published: November 2017

Objective—
Aortic pathologies exhibit sexual dimorphism, with aneurysms in both the thoracic and abdominal aorta (ie, abdominal aortic aneurysm [AAA]) exhibiting higher male prevalence. Women have lower prevalence of aneurysms, but when they occur, aneurysms progress rapidly. To define mechanisms for these sex differences, we determined the role of sex chromosome complement and testosterone on the location and progression of angiotensin II (AngII)–induced aortic pathologies.

Approach and Results—

We used transgenic male mice expressing
Sry
(sex-determining region Y) on an autosome to create
Ldlr
(low-density lipoprotein receptor)–deficient male mice with an XY or XX sex chromosome complement. Transcriptional profiling was performed on abdominal aortas from XY or XX males, demonstrating 1746 genes influenced by sex chromosomes or sex hormones. Males (XY or XX) were either sham-operated or orchiectomized before AngII infusions. Diffuse aortic aneurysm pathology developed in XY AngII-infused males, whereas XX males developed focal AAAs. Castration reduced all AngII-induced aortic pathologies in XY and XX males. Thoracic aortas from AngII-infused XY males exhibited adventitial thickening that was not present in XX males. We infused male XY and XX mice with either saline or AngII and quantified mRNA abundance of key genes in both thoracic and abdominal aortas. Regional differences in mRNA abundance existed before AngII infusions, which were differentially influenced by AngII between genotypes. Prolonged AngII infusions resulted in aortic wall thickening of AAAs from XY males, whereas XX males had dilated focal AAAs.

Conclusions—
An XY sex chromosome complement mediates diffuse aortic pathology, whereas an XX sex chromosome complement contributes to focal AngII-induced AAAs.
Genetic and Functional Profiling of CD16-Dependent Natural Killer Activation Identifies Patients at Higher Risk of Cardiac Allograft Vasculopathy
Authors: Paul Pascale , Picard Christophe , Sampol Emmanuelle , Lyonnet Luc , Di Cristofaro Julie , Paul-Delvaux Louise , Lano Guillaume , Nicolino-Brunet Corinne , Ravis Eleonore , Collart Frederic , Dignat-George Francoise , Dussol Bertrand , Sabatier Florence , Mouly-Bandini Annick 
Published: November 2017

Background:
Cardiac transplantation is an effective therapy for end-stage heart failure. Because cardiac allograft vasculopathy (CAV) is the major cause of late mortality after heart transplant (HT), there is a need to identify markers that reflect inflammatory or cytotoxic immune mechanisms contributing to its onset. Noninvasive and early stratification of patients at risk remains a challenge for adapting individualized therapy. The CD16 (Fc-gamma receptor 3A [FCGR3A]) receptor was recently identified as a major determinant of antibody-mediated natural killer (NK) cell activation in HT biopsies; however, little is known about the role of CD16 in promoting allograft vasculopathy. This study aimed to investigate whether markers that reflect CD16-dependent circulating NK cell activation may identify patients at higher risk of developing CAV after HT.

Methods:
Blood samples were collected from 103 patients undergoing routine coronarography angiography for CAV diagnosis (median 5 years since HT). Genomic and phenotypic analyses of FCGR3A/CD16 Fc-receptor profiles were compared in CAV-positive (n=52) and CAV-free patients (n=51). The levels of CD16 expression and rituximab-dependent cell cytotoxic activity of peripheral NK cells in HT recipients were evaluated using a noninvasive NK-cellular humoral activation test.

Results:

Enhanced levels of CD16 expression and antibody-dependent NK cell cytotoxic function of HT recipients were associated with the FCGR3A-VV genotype. The frequency of the FCGR3A-VV genotype was significantly higher in the CAV
+
group (odds ratio, 3.9;
P
=0.0317) than in the CAV
-
group. The FCGR3A-VV genotype was identified as an independent marker correlated with the presence of CAV at the time of coronary angiography by using multivariate logistic regression models. The FCGR3A-VV genotype was also identified as a baseline-independent predictor of CAV risk (odds ratio, 4.7;
P
=0.023).

Conclusions:
This study unravels a prominent role for the CD16-dependent NK cell activation pathway in the complex array of factors that favor the progression of transplant arteriosclerosis. It highlights the clinical potential of a noninvasive evaluation of FCGR3A/CD16 in the early stratification of CAV risk. The recognition of CD16 as a major checkpoint that controls immune surveillance may promote the design of individualized NK cell–targeted therapies to limit vascular damage in highly responsive sensitized patients.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01569334.
Treatment and Outcome of Hemorrhagic Transformation After Intravenous Alteplase in Acute Ischemic Stroke: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association
Authors: Yaghi Shadi , Willey Joshua Z. , Cucchiara Brett , Goldstein Joshua N. , Gonzales Nicole R. , Khatri Pooja , Kim Louis J. , Mayer Stephan A. , Sheth Kevin N. , Schwamm Lee H. 
Published: November 2017

Purpose—
Symptomatic intracranial hemorrhage (sICH) is the most feared complication of intravenous thrombolytic therapy in acute ischemic stroke. Treatment of sICH is based on expert opinion and small case series, with the efficacy of such treatments not well established. This document aims to provide an overview of sICH with a focus on pathophysiology and treatment.

Methods—
A literature review was performed for randomized trials, prospective and retrospective studies, opinion papers, case series, and case reports on the definitions, epidemiology, risk factors, pathophysiology, treatment, and outcome of sICH. The document sections were divided among writing group members who performed the literature review, summarized the literature, and provided suggestions on the diagnosis and treatment of patients with sICH caused by systemic thrombolysis with alteplase. Several drafts were circulated among writing group members until a consensus was achieved.

Results—
sICH is an uncommon but severe complication of systemic thrombolysis in acute ischemic stroke. Prompt diagnosis and early correction of the coagulopathy after alteplase have remained the mainstay of treatment. Further research is required to establish treatments aimed at maintaining integrity of the blood-brain barrier in acute ischemic stroke based on inhibition of the underlying biochemical processes.
Mechanism of Daytime Strong Winds on the Northern Slopes of Himalayas, near Mount Everest: Observation and Simulation
Authors: Sun Fanglin , Ma Yaoming , Hu Zeyong , Li Maoshan , Tartari Gianni , Salerno Franco , Gerken Tobias , Bonasoni Paolo , Cristofanelli Paolo , Vuillermoz Elisa 
Published: November 2017

AbstractThe seasonal variability of strong afternoon winds in a northern Himalayan valley and their relationship with the synoptic circulation were examined using in situ meteorological data from March 2006 to February 2007 and numerical simulations. Meteorological observations were focused on the lower Rongbuk valley, on the north side of the Himalayas (4270 m MSL), where a wind profile radar was available. In the monsoon season (21 May–4 October), the strong afternoon wind was southeasterly, whereas it was southwesterly in the nonmonsoon season. Numerical simulations were performed using the Weather Research and Forecasting Model to investigate the mechanism causing these afternoon strong winds. The study found that during the nonmonsoon season the strong winds are produced by downward momentum transport from the westerly winds aloft, whereas those during the monsoon season are driven by the inflow into the Arun Valley east of Mount Everest. The air in the Arun Valley was found to be colder than that of the surroundings during the daytime, and there was a horizontal pressure gradient from the Arun Valley to Qomolangma Station (QOMS), China Academy of Sciences, at the 5200-m level. This explains the formation of the strong afternoon southeasterly wind over QOMS in the monsoon season. In the nonmonsoon season, the colder air from Arun Valley is confined below the ridge by westerly winds associated with the subtropical jet.
Evaluation of a Fast-Track Postgraduate Social Work Program in England Using Simulated Practice
Authors: Scourfield Jonathan , Maxwell Nina , Zhang Meng Le , de Villiers Teresa , Pithouse Andrew , Kinnersley Paul , Metcalf Elizabeth , Tayyaba Sadia 
Published: November 2017

Objective: Using data from our evaluation of the Frontline fast-track social work training program, introduced by the Government in England, we compare the performance of the first cohort of Frontline trainees with students from regular social work programs using simulated practice. Method: Forty-nine Frontline trainees were compared with 36 postgraduate students in high-tariff universities and 30 students from a range of other regular programs. Kruskal–Wallis tests were used to compare the performance of the three groups in interviews and written reflections. Results: Frontline trainees were rated significantly higher than comparison groups for the quality of their interviewing and written reflection. Despite these higher ratings for practice quality, the Frontline trainees’ rating of their own confidence in their abilities was lower than their counterparts on regular programs. Conclusions: The practice quality of Frontline graduates is promising. Longitudinal research is needed in real practice settings.
Computational and mathematical methods in brain atlasing
Authors: Nowinski Wieslaw L 
Published: November 2017

Brain atlases have a wide range of use from education to research to clinical applications. Mathematical methods as well as computational methods and tools play a major role in the process of brain atlas building and developing atlas-based applications. Computational methods and tools cover three areas: dedicated editors for brain model creation, brain navigators supporting multiple platforms, and atlas-assisted specific applications. Mathematical methods in atlas building and developing atlas-aided applications deal with problems in image segmentation, geometric body modelling, physical modelling, atlas-to-scan registration, visualisation, interaction and virtual reality. Here I overview computational and mathematical methods in atlas building and developing atlas-assisted applications, and share my contribution to and experience in this field.