bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Direct Podocalyxin–Dynamin-2 Interaction Regulates Cytoskeletal Dynamics to Promote Migration and Metastasis in Pancreatic Cancer Cells
Authors: Wong Bin Sheng , Shea Daniel J. , Mistriotis Panagiotis , Tuntithavornwat Soontorn , Law Robert A. , Bieber Jake M. , Zheng Lei , Konstantopoulos Konstantinos 
Published: April 2019

Abstract

The sialoglycoprotein podocalyxin is absent in normal pancreas but is overexpressed in pancreatic cancer and is associated with poor clinical outcome. Here, we investigate the role of podocalyxin in migration and metastasis of pancreatic adenocarcinomas using SW1990 and Pa03c as cell models. Although ezrin is regarded as a cytoplasmic binding partner of podocalyxin that regulates actin polymerization via Rac1 or RhoA, we did not detect podocalyxin–ezrin association in pancreatic cancer cells. Moreover, depletion of podocalyxin did not alter actin dynamics or modulate Rac1 and RhoA activities in pancreatic cancer cells. Using mass spectrometry, bioinformatics analysis, coimmunoprecipitation, and pull-down assays, we discovered a novel, direct binding interaction between the cytoplasmic tail of podocalyxin and the large GTPase dynamin-2 at its GTPase, middle, and pleckstrin homology domains. This podocalyxin–dynamin-2 interaction regulated microtubule growth rate, which in turn modulated focal adhesion dynamics and ultimately promoted efficient pancreatic cancer cell migration via microtubule- and Src-dependent pathways. Depletion of podocalyxin in a hemispleen mouse model of pancreatic cancer diminished liver metastasis without altering primary tumor size. Collectively, these findings reveal a novel mechanism by which podocalyxin facilitates pancreatic cancer cell migration and metastasis.

Significance:
These findings reveal that a novel interaction between podocalyxin and dynamin-2 promotes migration and metastasis of pancreatic cancer cells by regulating microtubule and focal adhesion dynamics.
Prognostic Value of Deep Learning PET/CT-Based Radiomics: Potential Role for Future Individual Induction Chemotherapy in Advanced Nasopharyngeal Carcinoma
Authors: Peng Hao , Dong Di , Fang Meng-Jie , Li Lu , Tang Ling-Long , Chen Lei , Li Wen-Fei , Mao Yan-Ping , Fan Wei , Liu Li-Zhi , Tian Li , Lin Ai-Hua , Sun Ying , Tian Jie , Ma Jun 
Published: April 2019

Abstract

Purpose:
We aimed to evaluate the value of deep learning on positron emission tomography with computed tomography (PET/CT)–based radiomics for individual induction chemotherapy (IC) in advanced nasopharyngeal carcinoma (NPC).

Experimental Design:
We constructed radiomics signatures and nomogram for predicting disease-free survival (DFS) based on the extracted features from PET and CT images in a training set (n = 470), and then validated it on a test set (n = 237). Harrell's concordance indices (C-index) and time-independent receiver operating characteristic (ROC) analysis were applied to evaluate the discriminatory ability of radiomics nomogram, and compare radiomics signatures with plasma Epstein–Barr virus (EBV) DNA.

Results:
A total of 18 features were selected to construct CT-based and PET-based signatures, which were significantly associated with DFS (P &lt; 0.001). Using these signatures, we proposed a radiomics nomogram with a C-index of 0.754 [95% confidence interval (95% CI), 0.709–0.800] in the training set and 0.722 (95% CI, 0.652–0.792) in the test set. Consequently, 206 (29.1%) patients were stratified as high-risk group and the other 501 (70.9%) as low-risk group by the radiomics nomogram, and the corresponding 5-year DFS rates were 50.1% and 87.6%, respectively (P &lt; 0.0001). High-risk patients could benefit from IC while the low-risk could not. Moreover, radiomics nomogram performed significantly better than the EBV DNA-based model (C-index: 0.754 vs. 0.675 in the training set and 0.722 vs. 0.671 in the test set) in risk stratification and guiding IC.

Conclusions:
Deep learning PET/CT-based radiomics could serve as a reliable and powerful tool for prognosis prediction and may act as a potential indicator for individual IC in advanced NPC.
Farnesoid X Receptor Constructs an Immunosuppressive Microenvironment and Sensitizes FXRhighPD-L1low NSCLC to Anti–PD-1 Immunotherapy
Authors: You Wenjie , Li Lijun , Sun Deqiao , Liu Xueqing , Xia Zongjun , Xue Shan , Chen Bi , Qin Hui , Ai Jing , Jiang Handong 
Published: April 2019

Abstract
The farnesoid X receptor (FXR) regulates inflammation and immune responses in a subset of immune-mediated diseases. We previously reported that FXR expression promotes tumor cell proliferation in non–small cell lung cancer (NSCLC). Here we study the relevance of FXR to the immune microenvironment of NSCLC. We found an inverse correlation between FXR and PD-L1 expression in a cohort of 408 NSCLC specimens; from this, we identified a subgroup of FXRhighPD-L1low patients. We showed that FXR downregulates PD-L1 via transrepression and other mechanisms in NSCLC. Cocultured with FXRhighPD-L1low NSCLC cell lines, effector function and proliferation of CD8+ T cell in vitro are repressed. We also detected downregulation of PD-L1 in FXR-overexpressing Lewis lung carcinoma (LLC) mouse syngeneic models, indicating an FXRhighPD-L1low subtype in which FXR suppresses tumor-infiltrating immune cells. Anti–PD-1 therapy was effective against FXRhighPD-L1low mouse LLC tumors. Altogether, our findings demonstrate an immunosuppressive role for FXR in the FXRhighPD-L1low NSCLC subtype and provide translational insights into therapeutic response in PD-L1low NSCLC patients treated with anti–PD-1. We recommend FXRhighPD-L1low as a biomarker to predict responsiveness to anti–PD-1 immunotherapy.
Genetic Association of Finger Photoplethysmography-Derived Arterial Stiffness Index With Blood Pressure and Coronary Artery Disease
Authors: Zekavat Seyedeh M. , Aragam Krishna , Emdin Connor , Khera Amit V. , Klarin Derek , Zhao Hongyu , Natarajan Pradeep 
Published: April 2019

Objective—
Arterial stiffness index (ASI) is independently associated with blood pressure (BP) and coronary artery disease (CAD) epidemiologically. However, it is unknown whether these associations represent causal relationships. Here, we assess whether genetic predisposition to increased ASI is associated with elevated BP and CAD risk.

Approach and Results—

We first performed a large-scale epidemiological association of finger photoplethysmography-derived ASI in the UK Biobank, finding significant associations with systolic BP (β=0.55 mm Hg; [95% CI, 0.45–0.65];
P
=5.77×10
−24
; N=137 858), diastolic BP (β=1.05 mm Hg; [95% CI, 0.99–1.11];
P
=7.27×10
−272
; N=137 862), and incident CAD (hazard ratio, 1.08; [95% CI, 1.04–1.11];
P
=1.5×10
−6
; N=3692 cases, 126 615 controls) in multivariable models. We then performed an ASI genome-wide association study analysis in 131 686 participants from the UK Biobank. Across participants not in the ASI genome-wide association study, a 6-variant ASI polygenic risk score was calculated. Each SD increase in genetic ASI was associated with systolic BP (β=4.63 mm Hg; [95% CI, 2.1–7.2];
P
=3.37×10
−4
; N=208 897), and diastolic BP (β=2.61 mm Hg; [95% CI, 1.2–4.0];
P
=2.85×10
−4
; N=208 897); however, no association was observed with incident CAD (hazard ratio, 1.12; [95% CI, 0.55–2.3];
P
=0.75; N=223 061; 7534 cases). The lack of CAD association observed was replicated among 184 305 participants (60 810 cases) from the CARDIOGRAMplusC4D (Coronary Artery Disease Genetics Consortium; odds ratio, 0.56; [95% CI, 0.26–1.24];
P
=0.15).

Conclusions—
Our data support the conclusion that finger photoplethysmography-derived ASI is an independent, genetically causal risk factor for BP, but do not support the notion that ASI is a suitable surrogate for CAD risk.
Symptomatic Carotid Plaques Demonstrate Less Leaky Plaque Microvasculature Compared With the Contralateral Side: A Dynamic Contrast‐Enhanced Magnetic Resonance Imaging Study
Authors: Crombag Geneviève A. J. C. , van Hoof Raf H. M. , Holtackers Robert J. , Schreuder Floris H. B. M. , Truijman Martine T. B. , Schreuder Tobien A. H. C. M. L. , van Orshoven Narender P. , Mess Werner H. , Hofman Paul A. M. , van Oostenbrugge Robert J. , Wildberger Joachim E. , Kooi M. Eline 
Published: April 2019

Background

Rupture of a vulnerable carotid atherosclerotic plaque is an important underlying cause of ischemic stroke. Increased leaky plaque microvasculature may contribute to plaque vulnerability. These immature microvessels may facilitate entrance of inflammatory cells into the plaque. The objective of the present study is to investigate whether there is a difference in plaque microvasculature (the volume transfer coefficient
K
trans
) between the ipsilateral symptomatic and contralateral asymptomatic carotid plaque using noninvasive dynamic contrast‐enhanced magnetic resonance imaging.

Methods and Results

Eighty‐eight patients with recent transient ischemic attack or ischemic stroke and ipsilateral >2 mm carotid plaque underwent 3 T
magnetic resonance imaging
to identify plaque components and to determine characteristics of plaque microvasculature. The volume transfer coefficient
K
trans
, indicative for microvascular density, flow, and permeability, was calculated for the ipsilateral and asymptomatic plaque, using a pharmacokinetic model (Patlak). Presence of a lipid‐rich necrotic core, intraplaque hemorrhage, and a thin and/or ruptured fibrous cap was assessed on multisequence
magnetic resonance imaging
. We found significantly lower
K
trans
in the symptomatic carotid plaque compared with the asymptomatic side (0.057±0.002 min
−1
versus 0.062±0.002 min
−1
;
P
=0.033). There was an increased number of slices with
intraplaque hemorrhage
(0.9±1.6 versus 0.3±0.8,
P
=0.002) and
lipid‐rich necrotic core
(1.4±1.9 versus 0.8±1.4,
P
=0.016) and a higher prevalence of plaques with a
thin and/or ruptured fibrous cap
(32% versus 17%,
P
=0.023) at the symptomatic side.

Conclusions

K
trans
was significantly lower in symptomatic carotid plaques, indicative for a decrease of plaque microvasculature in symptomatic plaques. This could be related to a larger amount of necrotic tissue in symptomatic plaques.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov.uk
. Unique identifier:
NCT
01208025.
Labor Power Plant
Authors: Schmalisch Romana , Schlicht Robert 
Published: April 2019

Abstract
In those societies in which the capitalist mode of production prevails, labour power is tradable as a commodity and, as such, not a natural good or human capacity, but rather a socially mediated and constituted relation. The project “Labour Power Plant” operates on the fictitious assumption that the everyday, all-pervasive, seemingly natural and therefore invisible micro-politics present in society do in fact not exist. In other words, that society is by itself unable to provide for the human capital on which it depends. Instead, the production of abstract workers is outsourced into a dedicated “labour power plant” – an institution that equips people with the general capacities that make them fit for the demands of the labour market. Labour Power Plant – a success story of the past, the present and the future describes the story of the institution from industrialization to today, its reaction to the labour movement, and new trends in corporate governance.
Peripartum outcomes in a large population of women with pulmonary arterial hypertension associated with congenital heart disease
Authors: Li Qiangqiang , Dimopoulos Konstantinos , Liu Tianyang , Xu Zhuoyuan , Liu Qian , Li Yanna , Zhang Jun , Gu Hong 
Published: April 2019

AimsPulmonary arterial hypertension is a severe complication in patients with congenital heart disease and poses a significant risk to women wishing to become pregnant. This study describes the clinical presentation, maternal outcomes and risk factors for the peripartum period in women with pulmonary arterial hypertension related to congenital heart disease (PAH-CHD).MethodsAll pregnant women with PAH-CHD who were admitted for delivery in a tertiary center between February 2011–September 2016 were included. Logistic regression analysis was used to identify predictors of the combined endpoint of maternal death, severe heart failure requiring treatment, or pulmonary hypertensive crisis.ResultsNinety-three women (94 pregnancies) were included. Average age was 27.5 ± 4.4 years. Thirty (31.9%) patients had Eisenmenger syndrome, 51 (54.3%) had pulmonary arterial hypertension associated with systemic-to-pulmonary shunts, and 13 (13.8%) had pulmonary arterial hypertension with corrected congenital heart disease. Twenty-three (24.5%) women required admission for delivery within two days from presentation. Elective Cesarean section was performed in 95.7% of women, with intravertebral anesthesia in 93.6%. Fifty-one (54.2%) patients received pulmonary arterial hypertension therapies during pregnancy. Six (6.4%) women died, 33 (35.1%) developed heart failure and 10 (10.6%) had a pulmonary hypertensive crisis. Patients who met the combined endpoint ( n = 34, 36.2%) were more likely to have Eisenmenger syndrome or repaired defects ( p < 0.001). Other risk factors in the multivariate model included lower arterial blood oxygen saturation, higher brain natriuretic peptide, and pericardial effusion on echocardiography.ConclusionMaternal mortality and morbidity remain high in PAH-CHD patients, who should be counseled on the risks of pregnancy and managed in a tertiary multidisciplinary environment to improve prognosis.
Dietary components and risk of cardiovascular disease and all-cause mortality: a review of evidence from meta-analyses
Authors: Kwok Chun Shing , Gulati Martha , Michos Erin D , Potts Jessica , Wu Pensee , Watson Lorraine , Loke Yoon K , Mallen Christian , Mamas Mamas A 
Published: April 2019

Aims The optimal diet for cardiovascular health is controversial. The aim of this review is to summarize the highest level of evidence and rank the risk associated with each individual component of diet within its food group. Methods and results A systematic search of PudMed was performed to identify the highest level of evidence available from systematic reviews or meta-analyses that evaluated different dietary components and their associated risk of all-cause mortality and cardiovascular disease. A total of 16 reviews were included for dietary food item and all-cause mortality and 17 reviews for cardiovascular disease. Carbohydrates were associated with a reduced risk of all-cause mortality (whole grain bread: relative risk (RR) 0.85, 95% confidence interval (CI) 0.82–0.89; breakfast cereal: RR 0.88, 95% CI 0.83–0.92; oats/oatmeal: RR 0.88, 95% CI 0.83–0.92). Fish consumption was associated with a small benefit (RR 0.98, 95% CI 0.97–1.00) and processed meat appeared to be harmful (RR 1.25, 95% CI 1.07–1.45). Root vegetables (RR 0.76, 95% CI 0.66–0.88), green leafy vegetables/salad (RR 0.78, 95% CI 0.71–0.86), cooked vegetables (RR 0.89, 95% CI 0.80–0.99) and cruciferous vegetables (RR 0.90, 95% CI 0.85–0.95) were associated with reductions in all-cause mortality. Increased mortality was associated with the consumption of tinned fruit (RR 1.14, 95% CI 1.07–1.21). Nuts were associated with a reduced risk of mortality in a dose–response relationship (all nuts: RR 0.78, 95% CI 0.72–0.84; tree nuts: RR 0.82, 95% CI 0.75–0.90; and peanuts: RR 0.77, 95% CI 0.69–0.86). For cardiovascular disease, similar associations for benefit were observed for carbohydrates, nuts and fish, but red meat and processed meat were associated with harm. Conclusions Many dietary components appear to be beneficial for cardiovascular disease and mortality, including grains, fish, nuts and vegetables, but processed meat and tinned fruit appear to be harmful.
Primer on Hereditary Cancer Predisposition Genes Included Within Somatic Next-Generation Sequencing Panels
Authors: Akras Zade , Bungo Brandon , Leach Brandie H. , Marquard Jessica , Ahluwalia Manmeet , Carraway Hetty , Grivas Petros , Sohal Davendra P.S. , Funchain Pauline 
Published: April 2019

PURPOSE It has been estimated that 5% to 10% of cancers are due to hereditary causes. Recent data sets indicate that the incidence of hereditary cancer may be as high as 17.5% in patients with cancer, and a notable subset is missed if screening is solely by family history and current syndrome-based testing guidelines. Identification of germline variants has implications for both patients and their families. There is currently no comprehensive overview of cancer susceptibility genes or inclusion of these genes in commercially available somatic testing. We aimed to summarize genes linked to hereditary cancer and the somatic and germline panels that include such genes. METHODS Germline predisposition genes were chosen if commercially available for testing. Penetrance was defined as low, moderate, or high according to whether the gene conferred a 0% to 20%, 20% to 50%, or 50% to 100% lifetime risk of developing the cancer or, when percentages were not available, was estimated on the basis of existing literature descriptions. RESULTS We identified a total of 89 genes linked to hereditary cancer predisposition, and we summarized these genes alphabetically and by organ system. We considered four germline and six somatic commercially available panel tests and quantified the coverage of germline genes across them. Comparison between the number of genes that had germline importance and the number of genes included in somatic testing showed that many but not all germline genes are tested by frequently used somatic panels. CONCLUSION The inclusion of cancer-predisposing genes in somatic variant testing panels makes incidental germline findings likely. Although somatic testing can be used to screen for germline variants, this strategy is inadequate for comprehensive screening. Access to genetic counseling is essential for interpretation of germline implications of somatic testing and implementation of appropriate screening and follow-up.
CT Fat Density Accurately Reflects Histologic Fat Quality in Adults With HIV On and Off Antiretroviral Therapy
Authors: Lake Jordan E , Moser Carlee , Johnston Liz , Magyar Clara , Nelson Scott D , Erlandson Kristine M , Brown Todd T , McComsey Grace A 
Published: April 2019

Abstract

Context
Microscopic measurement of adipocyte size is the gold standard for determining adipose tissue (AT) quality. AT density on CT may also reflect adipocyte quality (lower density = poorer quality).

Objective
We used abdominal subcutaneous AT (SAT) specimens and CT scans to validate CT SAT density as a marker of SAT quality in adults living with HIV.

Setting and Design
Secondary data analysis from completed trial of antiretroviral therapy (ART) initiation (ACTG A5224s). CT abdominal SAT density was measured in HU. SAT specimens were digitally scanned for calculation of mean adipocyte area.

Participants
Participants had SAT biopsy and CT data at baseline (n = 54) and HIV-1 RNA <50 copies per milliliter on ART and biopsy or CT data at week 96 (n = 30).

Outcome Measures
Spearman correlations and linear regression models adjusting for participant characteristics examined associations between SAT density and adipocyte area.

Results
Baseline median age was 40 years, CD4+ T lymphocyte count 219 cells per cubic millimeter, and body mass index 26.0 kg/m2; 89% were male and 67% white. Median SAT area and density were 199 cm2 and −100 HU. Over 96 weeks, SAT area increased (+18%) and SAT density decreased (−3%). Mean SAT adipocyte area correlated with SAT density (P < 0.01) off and on ART after adjustment for SAT area, age, race, sex, CD4+ T lymphocyte count, and HIV-1 RNA.

Conclusions
CT SAT density correlates with biopsy-quantified SAT adipocyte size in adults with HIV on and off ART, suggesting that CT is a useful tool for noninvasive assessment of SAT quality.
Interval Walking Improves Glycemic Control and Body Composition After Cancer Treatment: A Randomized Controlled Trial
Authors: Christensen Jesper F , Sundberg Anna , Osterkamp Jens , Thorsen-Streit Sarah , Nielsen Anette B , Olsen Cecilie K , Djurhuus Sissal S , Simonsen Casper , Schauer Tim , Ellingsgaard Helga , Østerlind Kell , Krarup Peter-Martin , Mosgaard Camilla , Vistisen Kirsten , Tolver Anders , Pedersen Bente K , Hojman Pernille 
Published: April 2019

Abstract

Context
Patients with colorectal cancer have increased risk of metabolic diseases including diabetes. Exercise training may counteract metabolic dysregulation, but the impact of exercise training on glycemic control, including postprandial glycemia, has never been explored in patients with colorectal cancer.

Objective
To examine the effects of home-based interval walking on aerobic and metabolic fitness and quality of life in patients with colorectal cancer.

Design
Randomized controlled trial.

Setting
Clinical research center.

Participants
Thirty-nine sedentary (<150 minutes moderate-intensity exercise per week) patients with stage I to III colorectal cancer who had completed primary treatment.

Intervention
Home-based interval walking 150 min/wk or usual care for 12 weeks.

Main Outcome Measures
Changes from baseline to week 12 in maximum oxygen uptake (VO2peak) by cardiopulmonary exercise test, glycemic control by oral glucose tolerance test (OGTT), body composition by dual-energy x-ray absorptiometry scan, blood biochemistry, and quality of life.

Results
Compared with control, interval walking had no effect on VO2peak [mean between-group difference: −0.32 mL O2 · kg−1 · min−1 (−2.09 to 1.45); P = 0.721] but significantly improved postprandial glycemic control with lower glucose OGTT area under the curve [−126 mM · min (−219 to −33); P = 0.009], 2-hour glucose concentration [−1.1 mM (−2.2 to 0.0); P = 0.056], and improved Matsuda index [1.94 (0.34; 3.54); P = 0.01]. Also, interval walking counteracted an increase in fat mass in the control group [−1.47 kg (−2.74 to −0.19); P = 0.025].

Conclusion
A home-based interval-walking program led to substantial improvements in postprandial glycemic control and counteracted fat gain in posttreatment patients with colorectal cancer, possibly providing an effective strategy for prevention of secondary metabolic diseases.