bluuebunny/crossref_metadata_2025 huggingface dataset:
Individual, Social, and Environmental Correlates of Active Transportation Patterns in French Women
Authors: Perchoux Camille , Enaux Christophe , Oppert Jean-Michel , Menai Mehdi , Charreire Hélène , Salze Paul , Weber Christiane , Hercberg Serge , Feuillet Thierry , Hess Franck , Roda Célina , Simon Chantal , Nazare Julie-Anne
Published: June 2017

The objectives were (1) to define physical activity (PA) and sedentary behaviors (SB) patterns in daily life contexts (work, leisure, and transportation) in French working women from NutriNet-Santé web-cohort and (2) to identify pattern(s) of active transportation and their individual, social, and environmental correlates. 23,432 participants completed two questionnaires to evaluate PA and SB in daily life contexts and individual representations of residential neighborhood and transportation modes. Hierarchical cluster analysis was performed which identified 6 distinct movement behavior patterns: (i) active occupation, high sedentary leisure, (ii) sedentary occupation, low leisure, (iii) sedentary transportation, (iv) sedentary occupation and leisure, (v) active transportation, and (vi) active leisure. Multinomial logistic regressions were performed to identify correlates of the “active transportation” cluster. The perceived environmental characteristics positively associated with “active transportation” included “high availability of destinations around home,” “presence of bicycle paths,” and “low traffic.” A “positive image of walking/cycling,” the “individual feeling of being physically active,” and a “high use of active transport modes by relatives/friends” were positively related to “active transportation,” identified as a unique pattern regarding individual and environmental correlates. Identification of PA and SB context-specific patterns will help to understand movement behaviors’ complexity and to design interventions to promote active transportation in specific subgroups.
Daily Variation in the Occurrence of Different Subtypes of Stroke
Authors: Ripamonti Luciana , Riva Roberto , Maioli Fabiola , Zenesini Corrado , Procaccianti Gaetano
Published: June 2017

Three thousand two hundred and ninety-eight patients admitted to our Stroke Unit with hemorrhagic, large artery atherosclerosis, cardioembolic, small-vessel occlusion, and undetermined etiology-cryptogenic strokes were included in the study. The circadian variability in onset in each stroke subgroup and the associations with various risk factors were analyzed. In each subgroup, a significant minority of patients suffered from stroke during sleep. In the ischemic group, hypercholesterolemia, paroxysmal atrial fibrillation, and previous myocardial infarction facilitated the onset during waking. During waking, stroke onset was significantly higher in the morning compared to the afternoon both in the hemorrhagic and in the ischemic type. In hemorrhagic stroke, a previous stroke was associated with a lower early morning occurrence. In large artery atherosclerosis stroke, males were at higher risk of early morning occurrence (p<0.01). In small-vessel occlusion stroke, hypertension is significantly more present in the morning compared to the afternoon onset (p<0.005). Circadian patterns of stroke onset were observed both in hemorrhagic and in ischemic stroke, irrespective of the ischemic subgroup. In all groups, stroke was more likely to occur during waking than during sleep and, in the diurnal period, during morning than during afternoon. Moreover, sex and some clinical factors influence the diurnal pattern.
Genome-Wide Association Studies of Cancer in Diverse Populations
Authors: Park Sungshim L. , Cheng Iona , Haiman Christopher A.
Published: June 2017

Genome-wide association studies (GWAS) of cancer have identified more than 700 risk loci, of which approximately 80% were first discovered in European ancestry populations, approximately 15% in East Asians, 3% in multiethnic scans, and less than 1% in African and Latin American populations. These percentages closely mirror the distribution of samples included in the discovery phase of cancer GWAS to date (84% European, 11% East Asian, 4% African, and 1% Latin American ancestry). GWAS in non-European ancestry populations have provided insight into ancestry-specific variation in cancer and have pointed to regions of susceptibility that are of particular importance in certain populations. Uncovering and characterizing cancer risk loci in diverse populations is critical for understanding underlying biological mechanisms and developing future genetic risk prediction models in non-European ancestry populations. New GWAS and continued collaborations will be required to eliminate population inequalities in the number of studies, sample sizes, and variant content on GWAS arrays, and to better align genetic research in cancer to the global distribution of race/ethnicity Cancer Epidemiol Biomarkers Prev; 27(4); 405–17. ©2018 AACR.

See all articles in this CEBP Focus section, “Genome-Wide Association Studies in Cancer.”
Quantifying the Genetic Correlation between Multiple Cancer Types
Authors: Lindström Sara , Finucane Hilary , Bulik-Sullivan Brendan , Schumacher Fredrick R. , Amos Christopher I. , Hung Rayjean J. , Rand Kristin , Gruber Stephen B. , Conti David , Permuth Jennifer B. , Lin Hui-Yi , Goode Ellen L. , Sellers Thomas A. , Amundadottir Laufey T. , Stolzenberg-Solomon Rachael , Klein Alison , Petersen Gloria , Risch Harvey , Wolpin Brian , Hsu Li , Huyghe Jeroen R. , Chang-Claude Jenny , Chan Andrew , Berndt Sonja , Eeles Rosalind , Easton Douglas , Haiman Christopher A. , Hunter David J. , Neale Benjamin , Price Alkes L. , Kraft Peter
Published: June 2017

Background: Many cancers share specific genetic risk factors, including both rare high-penetrance mutations and common SNPs identified through genome-wide association studies (GWAS). However, little is known about the overall shared heritability across cancers. Quantifying the extent to which two distinct cancers share genetic origin will give insights to shared biological mechanisms underlying cancer and inform design for future genetic association studies.

Methods: In this study, we estimated the pair-wise genetic correlation between six cancer types (breast, colorectal, lung, ovarian, pancreatic, and prostate) using cancer-specific GWAS summary statistics data based on 66,958 case and 70,665 control subjects of European ancestry. We also estimated genetic correlations between cancers and 14 noncancer diseases and traits.

Results: After adjusting for 15 pair-wise genetic correlation tests between cancers, we found significant (P < 0.003) genetic correlations between pancreatic and colorectal cancer (rg = 0.55, P = 0.003), lung and colorectal cancer (rg = 0.31, P = 0.001). We also found suggestive genetic correlations between lung and breast cancer (rg = 0.27, P = 0.009), and colorectal and breast cancer (rg = 0.22, P = 0.01). In contrast, we found no evidence that prostate cancer shared an appreciable proportion of heritability with other cancers. After adjusting for 84 tests studying genetic correlations between cancer types and other traits (Bonferroni-corrected P value: 0.0006), only the genetic correlation between lung cancer and smoking remained significant (rg = 0.41, P = 1.03 × 10−6). We also observed nominally significant genetic correlations between body mass index and all cancers except ovarian cancer.

Conclusions: Our results highlight novel genetic correlations and lend support to previous observational studies that have observed links between cancers and risk factors.

Impact: This study demonstrates modest genetic correlations between cancers; in particular, breast, colorectal, and lung cancer share some degree of genetic basis. Cancer Epidemiol Biomarkers Prev; 26(9); 1427–35. ©2017 AACR.
FUS–DDIT3 Fusion Protein-Driven IGF-IR Signaling is a Therapeutic Target in Myxoid Liposarcoma
Authors: Trautmann Marcel , Menzel Jasmin , Bertling Christian , Cyra Magdalene , Isfort Ilka , Steinestel Konrad , Elges Sandra , Grünewald Inga , Altvater Bianca , Rossig Claudia , Fröhling Stefan , Hafner Susanne , Simmet Thomas , Åman Pierre , Wardelmann Eva , Huss Sebastian , Hartmann Wolfgang
Published: June 2017

Purpose: Myxoid liposarcoma is an aggressive disease with particular propensity to develop hematogenic metastases. Over 90% of myxoid liposarcoma are characterized by a reciprocal t(12;16)(q13;p11) translocation. The resulting chimeric FUS–DDIT3 fusion protein plays a crucial role in myxoid liposarcoma pathogenesis; however, its specific impact on oncogenic signaling pathways remains to be substantiated. We here investigate the functional role of FUS–DDIT3 in IGF-IR/PI3K/Akt signaling driving myxoid liposarcoma pathogenesis.

Experimental Design: Immunohistochemical evaluation of key effectors of the IGF-IR/PI3K/Akt signaling axis was performed in a comprehensive cohort of myxoid liposarcoma specimens. FUS–DDIT3 dependency and biological function of the IGF-IR/PI3K/Akt signaling cascade were analyzed using a HT1080 fibrosarcoma-based myxoid liposarcoma tumor model and multiple tumor–derived myxoid liposarcoma cell lines. An established myxoid liposarcoma avian chorioallantoic membrane model was used for in vivo confirmation of the preclinical in vitro results.

Results: A comprehensive subset of myxoid liposarcoma specimens showed elevated expression and phosphorylation levels of various IGF-IR/PI3K/Akt signaling effectors. In HT1080 fibrosarcoma cells, overexpression of FUS-DDIT3 induced aberrant IGF-IR/PI3K/Akt pathway activity, which was dependent on transcriptional induction of the IGF2 gene. Conversely, RNAi-mediated FUS–DDIT3 knockdown in myxoid liposarcoma cells led to an inactivation of IGF-IR/PI3K/Akt signaling associated with diminished IGF2 mRNA expression. Treatment of myxoid liposarcoma cell lines with several IGF-IR inhibitors resulted in significant growth inhibition in vitro and in vivo.

Conclusions: Our preclinical study substantiates the fundamental role of the IGF-IR/PI3K/Akt signaling pathway in myxoid liposarcoma pathogenesis and provides a mechanism-based rationale for molecular- targeted approaches in myxoid liposarcoma cancer therapy. Clin Cancer Res; 23(20); 6227–38. ©2017 AACR.
CD4+ T Cell and NK Cell Interplay Key to Regression of MHC Class Ilow Tumors upon TLR7/8 Agonist Therapy
Authors: Doorduijn Elien M. , Sluijter Marjolein , Salvatori Daniela C. , Silvestri Serenella , Maas Saskia , Arens Ramon , Ossendorp Ferry , van der Burg Sjoerd H. , van Hall Thorbald
Published: June 2017

One of the next challenges in cancer immunotherapy is the resistance of tumors to T-cell–based treatments through loss of MHC class I. Here, we show that under these circumstances, the Toll-like receptor (TLR)-7/8 ligand imiquimod, but not the TLR3 ligand poly I:C or TLR9 ligand CpG, mediated an effective antitumor response. The rejection of these immune-escaped cancers was mediated by NK cells and CD4+ T cells, whereas activated CD8+ T cells were dispensable. Application of the innate immune stimulator at a distant site activated NK cells and thereby elicited tumor-specific T-cell responses in tumor-bearing mice. Mechanistically, imiquimod activated NK cells to kill tumor cells, resulting in release of tumor antigens and induction of tumor-specific CD4+ T cells. These T helper cells provoked a strong induction of CXCL9 and CXCL10 in the tumor environment. Simultaneously, imiquimod induced the expression of the cognate chemokine receptor CXCR3 on peripheral lymphocytes. This ignited intratumoral CD4+ T-cell infiltration and accumulation, which was critical for tumor rejection; CXCR3 blocking antibodies mitigated the clinical response. In the effector phase, NK cell recruitment to tumors and their activation depended on CD4+ T cells. Together, we have uncovered a potent immune axis of tumor-specific CD4+ T cells and NK cells that eliminates escaped MHC-Ilow tumors. Cancer Immunol Res; 5(8); 642–53. ©2017 AACR.
Monocyte-Derived Dendritic Cells with Silenced PD-1 Ligands and Transpresenting Interleukin-15 Stimulate Strong Tumor-Reactive T-cell Expansion
Authors: Van den Bergh Johan M.J. , Smits Evelien L.J.M. , Berneman Zwi N. , Hutten Tim J.A. , De Reu Hans , Van Tendeloo Viggo F.I. , Dolstra Harry , Lion Eva , Hobo Willemijn
Published: June 2017

Although allogeneic stem cell transplantation (allo-SCT) can elicit graft-versus-tumor (GVT) immunity, patients often relapse due to residual tumor cells. As essential orchestrators of the immune system, vaccination with dendritic cells (DC) is an appealing strategy to boost the GVT response. Nevertheless, durable clinical responses after DC vaccination are still limited, stressing the need to improve current DC vaccines. Aiming to empower DC potency, we engineered monocyte-derived DCs to deprive them of ligands for the immune checkpoint regulated by programmed death 1 (PD-1). We also equipped them with interleukin (IL)-15 “transpresentation” skills. Transfection with short interfering (si)RNA targeting the PD-1 ligands PD-L1 and PD-L2, in combination with IL15 and IL15Rα mRNA, preserved their mature DC profile and rendered the DCs superior in inducing T-cell proliferation and IFNγ and TNFα production. Translated into an ex vivo hematological disease setting, DCs deprived of PD-1 ligands (PD-L), equipped with IL15/IL15Rα expression, or most effectively, both, induced superior expansion of minor histocompatibility antigen–specific CD8+ T cells from transplanted cancer patients. These data support the combinatorial approach of in situ suppression of the PD-L inhibitory checkpoints with DC-mediated IL15 transpresentation to promote antigen-specific T-cell responses and, ultimately, contribute to GVT immunity. Cancer Immunol Res; 5(8); 710–5. ©2017 AACR.
Fluoride in Dental Biofilm Varies across Intra-Oral Regions
Authors: Staun Larsen Line , Baelum Vibeke , Tenuta Livia Maria Andaló , Richards Alan , Nyvad Bente
Published: June 2017

Information on differences in biofilm fluoride concentration across intra-oral regions may help explain the distribution of caries within the dentition. The aim of this cross-sectional study was to describe the fluoride concentration in saliva and in biofilm fluid and biofilm solids across 6 intra-oral regions. Unstimulated whole saliva was collected from 42 participants and biofilm harvested from the buccal sites in the 4 molar and 2 anterior regions. Samples were collected at least 1 h after use of fluoride dentifrice. No attempt was made to control the participants' food consumption or use of other topical agents. Centrifuged saliva, biofilm fluid, and biofilm solids were analysed for fluoride using a fluoride ion-selective electrode, adapted for microanalysis. Fluoride in biofilm varied across intra-oral regions. The mean biofilm fluid fluoride concentrations across the oral cavity ranged from 11.6 to 16.8 µM, being statistically significantly higher in the upper anterior region than in any other region. In all regions the fluoride concentration in biofilm fluid was higher than in saliva. For biofilm solids the fluoride concentration was highest in the lower anterior region (2,461 μmol/kg) and lowest in the lower molar regions (388 and 406 μmol/kg, respectively). Within biofilm, the solids contained most of the fluoride (81 to >99%). The biofilm fluid fluoride concentration was significantly positively associated with salivary fluoride and only marginally associated with that of biofilm solids. In conclusion, this study has shown pronounced differences in fluoride distribution across intra-oral regions and compartments. This shows that the sampling site is a crucial factor for studies of biofilm fluoride.
7-Hexagon Multifocal Electroretinography for an Objective Functional Assessment of the Macula in 14 Seconds
Authors: Schönbach Etienne M. , Chaikitmongkol Voraporn , Annam Rachel , McDonnell Emma C. , Wolfson Yulia , Fletcher Emily , Scholl Hendrik P.N.
Published: June 2017

Purpose: We present the multifocal electroretinogram (mfERG) with a 7-hexagon array as an objective test of macular function that can be recorded in 14 s. We provide normal values and investigate its reproducibility and validity. Methods: Healthy participants underwent mfERG testing according to International Society for Clinical Electrophysiology of Vision (ISCEV) standards using the Espion Profile/D310 multifocal ERG system (Diagnosys, LLC, Lowell, MA, USA). One standard recording of a 61-hexagon array and 2 repeated recordings of a custom 7-hexagon array were obtained. Results: A total of 13 subjects (mean age 46.9 years) were included. The median response densities were 12.5 nV/deg2 in the center and 5.2 nV/deg2 in the periphery. Intereye correlations were strong in both the center (ρCenter = 0.821; p < 0.0001) and the periphery (ρPeriphery = 0.862; p < 0.0001). Intraeye correlations were even stronger: ρCenter = 0.904 with p < 0.0001 and ρPeriphery = 0.955 with p < 0.0001. Bland-Altman plots demonstrated an acceptable retest mean difference in both the center and periphery, and narrow limits of agreement. We found strong correlations of the center (ρCenter = 0.826; p < 0.0001) and periphery (ρPeriphery = 0.848; p < 0.0001), with recordings obtained by the 61-hexagon method. Conclusions: The 7-hexagon mfERG provides reproducible results in agreement with results obtained according to the ISCEV standard.
Trends in Endovascular Treatment of Aneurysmal Subarachnoid Hemorrhages
Authors: Mehta Tapan , Datta Neil , Patel Smit , Mehta Kathan , Hussain Mohammed , Kureshi Inaam , Ollenschleger Martin , Nouh Amre
Published: June 2017

Introduction: Aneurysmal subarachnoid hemorrhage (aSAH) accounts for 5% of all strokes; 30-day mortality is as high as 40%. We sought to evaluate outcomes of aSAH patients treated 2004-2014 by endovascular therapy (EVT), to demonstrate associated trends, and to evaluate angioplasty use for aSAH-related cerebral vasospasm. Methods: The Nationwide Inpatient Sample (NIS) database 2004-2014 was used to derive a study cohort using ICD-9 codes. Survey procedures were used to adjust for stratified cluster design of NIS. NIS trend weights were used to generate national estimates. Mortality during hospitalization and use of angioplasty for aSAH-induced cerebral vasospasm trends were evaluated with multivariate regression analysis. Results: We identified n = 10,822 (weighted n = 52,062) EVT-treated aSAH hospitalizations. Increasing years independently predicted decreased mortality (odds ratio [OR] 0.926, 95% confidence interval [CI] 0.905-0.948, p < 0.0001), decreased utilization of angioplasty (age ≥50 years [OR 0.916, 95% CI 0.867-0.968, p = 0.0019] and age <50 years [OR 0.922, 95% CI 0.879-0.967, p = 0.0009]) after controlling for increasing age, Charlson comorbidity index, and external ventricular drain placement. Angioplasty rates were higher in age <50 years compared to age ≥50 years (5 vs. 3.63%, p < 0.001). Conclusion: It is notable that EVT for aSAH management will be an integral and increasingly useful tool for initial aneurysm management. Advances in procedural techniques, operator experience, and periprocedural management could be significant contributors of decreasing mortality and reducing the need for angioplasty for cerebral vasospasm in patients admitted with aSAH.
Long-Term Follow-Up of Choroidal Neovascularization due to Angioid Streaks with pro re nata Intravitreal Anti-VEGF Treatment
Authors: Giacomelli Giovanni , Finocchio Lucia , Biagini Ilaria , Sodi Andrea , Murro Vittoria , Introini Ugo , Varano Monica , Bandello Francesco , Menchini Ugo
Published: June 2017

Purpose: To evaluate the long-term outcomes of intravitreal anti-vascular endothelial growth factor (VEGF) drugs with a pro re nata (PRN) regimen for the treatment of choroidal neovascularization (CNV) secondary to angioid streaks (AS). Methods: This is a retrospective, multicenter, noncomparative case series of consecutive AS eyes affected by treatment-naïve CNV. A complete ophthalmologic examination was performed every 30-45 days after the loading phase, including fluorescein angiography and/or optical coherence tomography. Results: In all, 52 eyes of 39 patients were treated with intravitreal bevacizumab and/or ranibizumab and followed up for a mean of 33.8 months. The best corrected visual acuity at baseline was 20/40, and it deteriorated by an average of 6.8 ETDRS letters per year (p < 0.001). We performed an average of 5.1, 6.5, and 6.8 injections at the 1-, 2-, and 3-year follow-up, respectively. Conclusions: Intravitreal anti-VEGF drugs in a PRN regimen with close monitoring appear to slow the progression of CNV in AS, but they do not prevent the affected eyes from progressive visual loss.
Esophagobronchial Fistula in a Patient with Squamous Cell Carcinoma of the Lung: A Case Report
Authors: Ozeki Taichi , Asano Michiko , Fujimoto Nobukazu , Nishimura Jun , Takada Kenji , Miyamoto Yosuke , Fuchimoto Yasuko , Wada Sae , Ozaki Shinji , Kishimoto Takumi
Published: June 2017

A 73-year-old man was referred to our hospital after a 2-week history of bloody sputum and cough. Computed tomography (CT) images of the chest showed a mass grouped with mediastinal lymph nodes, and bronchoscopy showed a projecting mass in the right main bronchus. After a transbronchial biopsy, the patient was diagnosed with squamous cell carcinoma (T4N2M0 stage IIIB). The patient was treated with systemic chemotherapy, consisting of cisplatin (40 mg/m2, days 1 and 8) and docetaxel (30 mg/m2, days 1 and 8), and concurrent thoracic irradiation at a daily dose of 2 Gy. On day 35 of treatment, the patient complained of a sore throat and cough. A CT of the chest showed punctate low-attenuation foci between the esophagus and bronchus. Gastrointestinal endoscopy and bronchoscopy demonstrated a fistula in the middle intrathoracic esophagus and the left main bronchus. The patient’s symptoms gradually improved, and the fistula was closed after the suspension of chemoradiotherapy. Radiotherapy was resumed and completed on day 82. However, on day 108, he developed a fever and cough, and a tumor with fistula was revealed in the right main bronchus. He had an esophageal stent inserted, but he later died of sudden hemoptysis.
Impact of Comorbid Irritable Bowel Syndrome on Treatment Outcome in Non-Erosive Reflux Disease on Long-Term Proton Pump Inhibitor in Japan
Authors: Funaki Yasushi , Kaneko Hiroshi , Kawamura Yurika , Yoshimine Takashi , Tamura Yasuhiro , Izawa Shinya , Ebi Masahide , Ogasawara Naotaka , Sasaki Makoto , Kasugai Kunio
Published: June 2017

Background/Aims: Irritable bowel syndrome (IBS) frequently coexists with non-erosive reflux disease (NERD). Efficacy of long-term proton pump inhibitor (PPI) treatment on NERD with or without IBS is controversial. The impact of comorbid IBS in NERD on quality of life (QOL) remains uncertain. We verified the hypothesis that NERD patients with IBS symptoms demonstrated poor responses to long-term PPI treatments, deteriorated QOL, and high frequency of psychological deviations in Japan. Methods: In all, 141 NERD patients who had been taking PPIs for more than 6 months were enrolled and analyzed. Patient profiles were assessed by GerdQ, IBS Severity Index (IBSSI-J)/Gastrointestinal Symptoms Rating Scale (GSRS)/SF-8, and Hospital Anxiety and Depression Scale (HADS). Results: IBS existed in 37 out of 141 NERD patients. Patients with IBS (the positive-IBS group) demonstrated significantly higher frequencies of extant reflux symptoms than those without IBS (64.9 vs. 40.4%). In the positive-IBS group, 40.5% were classified as middle grade by IBSSI-J. The SF-8 and GSRS scores in this group were significantly lower than those without IBS (the negative-IBS group). Prevalence of depression and anxiety by HADS in the positive-IBS group was significantly higher than that in the negative-IBS group. Conclusion: These results proved the hypothesis that considering comorbid IBS among NERD patients on long-term PPI seems recommended in Japan.
Measuring Concurrent Polydrug Use in General Populations: A Critical Assessment
Authors: Karjalainen Karoliina , Kuussaari Kristiina , Kataja Kati , Tigerstedt Christoffer , Hakkarainen Pekka
Published: June 2017

Background/Aims: Polydrug use is a complicated phenomenon that is measured in a wide variety of different ways. Using Finland as an example, we aimed to demonstrate how the prevalence and prevalence trends of concurrent polydrug use (CPU) varied in the general population based on the different measurements used. Methods: Population-based Drug Surveys conducted every 4 years during 1998-2014 were used. CPU was measured with different measurements: strict, medial and loose definition of CPU, which were based on different combinations of alcohol, illicit drugs, pharmaceutical drugs and cigarettes used during the last 12 months/30 days. Logistic regression was used to estimate the p values for assessing trends. Results: Depending on the measurements used, the prevalence of CPU in 2014 varied between 2.0 and 18.7%. Different definitions also produced contradictory trends of CPU: there was a modest increase in prevalence if it was measured with a medial (p < 0.001) or strict (p = 0.054) definition, but when measured with the loose definition (only measure that included smoking), there was a decrease in prevalence (p < 0.001). Conclusions: The prevalence of CPU varies greatly depending on the measurement used, as does the course of the prevalence trends. The concept of simultaneous polydrug use may capture the phenomenon better compared to the concept of CPU.
Astragaloside-IV Alleviates Heat-Induced Inflammation by Inhibiting Endoplasmic Reticulum Stress and Autophagy
Authors: Dong Zhiwei , Zhou Jian , Zhang Ying , Chen Yajie , Yang Zichen , Huang Guangtao , Chen Yu , Yuan Zhiqiang , Peng Yizhi , Cao Tongtong
Published: June 2017

Background: Thermal injury is the main cause of pulmonary disease in stroke after burn and can be life threatening. Heat-induced inflammation is an important factor that triggers a series of induces pathological changes. However, this mechanism underlying heat-induced inflammation in thermal inhalation injury remains unclear. Studies have revealed that astragaloside-IV (AS-IV), a natural compound extracted from Astragalus membranaceus, has protective effects in inflammatory diseases. Here, we investigated whether the protective effects of AS-IV occur because of the suppression of heat-induced endoplasmic reticulum (ER) stress and excessive autophagy Methods: AS-IV was administered to Wistar rats after thermal inhalation injury and 16HBE140-cells were treated with AS-IV. TNF-α, IL-6, and IL-8 levels were determined by ELISA and real-time PCR. ER stress and autophagy were determined by western blot. Autophagic flux was measured by recording the fluorescence emission of the fusion protein mRFP-GFP-LC3 by dynamic live-cell imaging. Results: AS-IV had protective effects against heat-induced reactive oxygen species production and attenuated ER stress. AS IV alleviated heat-induced excessive autophagy in vitro and in vivo. Excessive autophagy was attenuated by the PERK inhibitor GSK2656157 and eIF2α siRNA, suggesting that heat stress-induced autophagy can activate the PERK-eIF2α pathway. Beclin 1 and Atg5 siRNAs inhibited the upregulation of the inflammatory cytokines TNF-α, IL-6, and IL-8 after heat exposure. Conclusions: Thus, AS-IV may attenuate inflammatory responses by disrupting the crosstalk between autophagy and the PERK-eIF2α pathway and may be an ideal agent for treating inflammatory pulmonary diseases.
Study Comparing Vein Integrity and Clinical Outcomes in Open Vein Harvesting and 2 Types of Endoscopic Vein Harvesting for Coronary Artery Bypass Grafting
Authors: Krishnamoorthy Bhuvaneswari , Critchley William R. , Thompson Alexander J. , Payne Katherine , Morris Julie , Venkateswaran Rajamiyer V. , Caress Ann L. , Fildes James E. , Yonan Nizar
Published: June 2017

Background:

Current consensus statements maintain that endoscopic vein harvesting (EVH) should be standard care in coronary artery bypass graft surgery, but vein quality and clinical outcomes have been questioned. The VICO trial (Vein Integrity and Clinical Outcomes) was designed to assess the impact of different vein harvesting methods on vessel damage and whether this contributes to clinical outcomes after coronary artery bypass grafting.

Methods:

In this single-center, randomized clinical trial, patients undergoing coronary artery bypass grafting with an internal mammary artery and with 1 to 4 vein grafts were recruited. All veins were harvested by a single experienced practitioner. We randomly allocated 300 patients into closed tunnel CO
2
EVH (n=100), open tunnel CO
2
EVH (n=100), and traditional open vein harvesting (n=100) groups. The primary end point was endothelial integrity and muscular damage of the harvested vein. Secondary end points included clinical outcomes (major adverse cardiac events), use of healthcare resources, and impact on health status (quality-adjusted life-years).

Results:

The open vein harvesting group demonstrated marginally better endothelial integrity in random samples (85% versus 88% versus 93% for closed tunnel EVH, open tunnel EVH, and open vein harvesting;
P
<0.001). Closed tunnel EVH displayed the lowest longitudinal hypertrophy (1% versus 13.5% versus 3%;
P
=0.001). However, no differences in endothelial stretching were observed between groups (37% versus 37% versus 31%;
P
=0.62). Secondary clinical outcomes demonstrated no significant differences in composite major adverse cardiac event scores at each time point up to 48 months. The quality-adjusted life-year gain per patient was 0.11 (
P
<0.001) for closed tunnel EVH and 0.07 (
P
=0.003) for open tunnel EVH compared with open vein harvesting. The likelihood of being cost-effective, at a predefined threshold of £20 000 per quality-adjusted life-year gained, was 75% for closed tunnel EVH, 19% for open tunnel EVH, and 6% for open vein harvesting.

Conclusions:

Our study demonstrates that harvesting techniques affect the integrity of different vein layers, albeit only slightly. Secondary outcomes suggest that histological findings do not directly contribute to major adverse cardiac event outcomes. Gains in health status were observed, and cost-effectiveness was better with closed tunnel EVH. High-level experience with endoscopic harvesting performed by a dedicated specialist practitioner gives optimal results comparable to those of open vein harvesting.

Clinical Trial Registration:

URL:
https://www.isrctn.com
. International Standard Randomised Controlled Trial Registry Number: 91485426.
The Beginnings of Pashto Narrative Prose
Authors: Pelevin Mikhail
Published: June 2017

The article argues that the first specimens of Pashto original narratives in free prose are to be found in the historiographical compilation Tārīkh-i muraṣṣaʿ (1724) among the texts of the chronicles, diaries, and memoirs written by the Khaṯak tribal rulers Khūshḥāl Khān (d. 1689) and Afżal Khān (d. circa 1740/41). Over thirty fragments from these texts may be qualified as short stories for, being focused on particular events and episodes, they are distinguished by strikingly realistic manner of narration and well developed elements of detailing, descriptiveness and emotiveness. Richly illustrated with translations of selected excerpts from original Pashto texts the article summarises the stories’ subject-matters by grouping them into three main categories (wars, incidents, everyday life events) and discusses various aspects of the authors’ narration techniques, such as compression of time and space in kea moments of action, accentuated portrayal of characters, extensive use of direct speech with a range of stylistic timbres. The article proves that the stories of the Khaṯak chiefs may be viewed also as unique documents on the realities of the Pashtun tribal life in pre-modern times.
Sex-Slavery: One Aspect of the Yezidi Genocide
Authors: Nicolaus Peter , Yuce Serkan
Published: June 2017

Even though almost three years have passed since the black banners of the terror organisation, calling themselves the “Islamic State of Iraq and Syria” (ISIS) were first hoisted throughout the Yezidi heartland of Sinjar, the Yezidi community continues to be targeted by ISIS, militias. 300,000 vegetate in camps as Internally Displaced Persons (IDP) in Iraqi Kurdistan; thousands of others have been killed, are missing, or remain in captivity where they are subjected to unspeakable sexual and physical abuse. With deference for these victims of violence, and without detracting from the collective suffering and trauma of the entire Yezidi community of Sinjar (families, women, men, and children alike), the authors have chosen to focus the present article on the plight and misery of the females; who were, and still are, facing despicable sexual abuses, unfathomable atrocities, and unfettered human rights violations. In doing so, they highlight the views of the fundamentalist Islam practiced by ISIS that encourages sex-slavery, while elaborating on the complacent acceptance of ISIS terror tactics by the local Sunni population of the territories they control. The work goes on to describe how survivors escaped, as well as how they are received and treated by the Yezidi community and state authorities. This discussion includes an overview of the national and international mechanisms available for prosecuting ISIS members for their crimes of genocide against the Yezidi people. The authors further stress that the genocide has contributed to, and even accelerated the process of the Yezidi selfidentification as a unique ethno-religious entity; which, in turn, has produced changes to their religious traditions. These changes will be briefly covered by examining a new approach to the institution of the Kerāfat.
Unraveling the white-clothed Diestostemma Amyot & Serville: a taxonomic revision of the American sharpshooters of the D. bituberculatum complex (Hemiptera: Cicadellidae)
Authors: PINTO ÂNGELO PARISE , MEJDALANI GABRIEL , TAKIYA DANIELA MAEDA
Published: June 2017

The taxonomy of the Proconiini genus Diestostemma Amyot & Serville is revisited and the D. bituberculatum species complex is proposed to include D. bituberculatum (Signoret), D. rubriventris (Schmidt), and four new species. A revision of this species complex includes a new geographical record for D. rubriventris and description and illustration of three Ecuadorian and one Brazilian new species based on males and females: D. albinoi sp. nov. (Ecuador: Orellana Province), D. cavichiolii sp. nov. (Brazil: Mato Grosso State), D. gervasioi sp. nov. (Ecuador: Orellana Province), and D. olivia sp. nov. (Ecuador: Orellana Province). These species, all named as homages to the treehopper specialist Dr. Albino Morimasa Sakakibara and his former students, are very similar to D. bituberculatum in general appearance, differing mainly by the shape of the male and female terminalia, but also by slight aspects of the external morphology. The status of the name-bearing specimen of D. rubriventris is modified from lectotype to holotype. The study shows that the species diversity of Diestostemma is far from being entirely known. However, several old available names should be evaluated in a full revision context before description of other new species.
Examining Differences in Bias Homicide Across Victim Groups
Authors: Gruenewald Jeff , Allison Kayla
Published: June 2017

Little is known about how situations of bias homicide might vary dependent upon who is targeted. Drawing from doing difference theory, we comparatively examine several event-level variables for bias homicide involving three different target groups. Data on bias homicide occurring in the United States come from the U.S. Extremist Crime Database (ECDB). Our findings reveal significant differences across bias victim groups, specifically regarding weapon use, location of incidents, victim–offender relationships, and victim and offender demographics. The results of this study have important implications for the theoretical and methodological advancement of empirical research on bias crime and for law enforcement responsible for identifying and investigating bias crimes.
Perspectives of Urban School Principals From Nontraditional Contexts: A Study of Urban Public Charter and Private School Leaders
Authors: Robey Philip V. , Helfenbein Robert J.
Published: June 2017

Principals from 76 urban public charter and private (Catholic) schools located in three midsized cities participated in a sequential explanatory investigation measuring perceptions of key elements related to school administration. Topics include students, selves, and elements related to the job of principal. Findings indicate that most principals view few administrative tasks as very challenging yet regard experience and skills as very important. Principals also perceive high level of authority over areas related to instruction. Comparisons by school type indicate close alignment of perspectives.
The Effects of the Great Recession on the School Mobility of Youth
Authors: Mordechay Kfir
Published: June 2017

Residential stability matters to a young person’s educational success, and the housing crisis spurred by the Great Recession (2007-2009) has disrupted the residential stability of many families. Using data from a large high school district in San Bernardino County, California, as a case study, this study utilizes a multilevel model to examine the extent to which the housing crisis affected student mobility rates in an area considered an epicenter of the recession. Results show that race was a much stronger predictor of student mobility than socioeconomic status during the crisis. In 2008, mobility rates were especially high for Black students, controlling for a variety of background characteristics. Research and policies that could be helpful in reducing mobility are discussed.
Large Sample Confidence Intervals for Item Response Theory Reliability Coefficients
Authors: Andersson Björn , Xin Tao
Published: June 2017

In applications of item response theory (IRT), an estimate of the reliability of the ability estimates or sum scores is often reported. However, analytical expressions for the standard errors of the estimators of the reliability coefficients are not available in the literature and therefore the variability associated with the estimated reliability is typically not reported. In this study, the asymptotic variances of the IRT marginal and test reliability coefficient estimators are derived for dichotomous and polytomous IRT models assuming an underlying asymptotically normally distributed item parameter estimator. The results are used to construct confidence intervals for the reliability coefficients. Simulations are presented which show that the confidence intervals for the test reliability coefficient have good coverage properties in finite samples under a variety of settings with the generalized partial credit model and the three-parameter logistic model. Meanwhile, it is shown that the estimator of the marginal reliability coefficient has finite sample bias resulting in confidence intervals that do not attain the nominal level for small sample sizes but that the bias tends to zero as the sample size increases.
Estimation of an IRT Model by Mplus for Dichotomously Scored Responses Under Different Estimation Methods
Authors: Paek Insu , Cui Mengyao , Öztürk Gübeş Neşe , Yang Yanyun
Published: June 2017

The purpose of this article is twofold. The first is to provide evaluative information on the recovery of model parameters and their standard errors for the two-parameter item response theory (IRT) model using different estimation methods by Mplus. The second is to provide easily accessible information for practitioners, instructors, and students about the relationships between IRT and item factor analysis (FA) parameterizations. Specifically, this is done using the “Theta” and “Delta” parameterizations in Mplus for unidimensional and multidimensional modeling with dichotomous and polytomous responses with and without the scaling constant D. The first objective aims at investigating differences that may occur when using different estimation methods in Mplus for binary response modeling. The second objective was motivated by practical interest observed among graduate students and applied researchers. The relations between IRT and Mplus FA “Theta” and “Delta” parameterizations are described using expressions without the use of matrices, which can be understood efficiently by applied researchers and students.
Strength adaptations of the tibia bone for prescribed sets of isometric forces and joint angles
Authors: Florio CS
Published: June 2017

The isometric exercise induced tibial bone strength adaptations due to various prescribed net resultant forces generated by a leg arranged with specified hip, knee, and ankle joint angles were examined using a computationally based bone shape adaptation model. With the leg straight, or the knee flexed at 90°, and the hip either neutral or flexed by 45°, a force was repeatedly generated at the toe either anteriorly, posteriorly, superiorly, or inferiorly, in paired sequences of these directions, or in a clockwise pattern of all four directions. Model-predicted individual muscle forces, amounts of cortical bone surface accretion or resorption, and the resulting changes in bone stress distributions were compared. Similarities between adaptations to specific combinations of joint angles and net resultant force directions were found to follow similarities in the bone stress distributions rather than in muscle activity. The ratio of standard deviation to the surface-averaged measure of local stress was a good predictor of potential improvement in overall stress state uniformity. With flexed knee and neutral hip, greater adaptive improvements in tibial surface stress uniformity were found than with both joints flexed. Flexed configurations caused greater changes and overall strength improvements than exercises performed with a straight leg. Regions of local tibial cortical thickening were identified for specific joint angles and single-load resultant force directions. Sequential series of loads were also identified to enhance these effects and mitigate concurrent thinning in other regions. The presented information can aid in the design and analysis of targeted muscle and bone strengthening exercises.
Toys that squeak: Toy type impacts quality and quantity of parent–child interactions
Authors: Miller Jennifer L. , Lossia Amanda , Suarez-Rivera Catalina , Gros-Louis Julie
Published: June 2017

Given the dependent nature of parent–infant interactions necessary for language development, it is important to understand how context may influence these interactions. This study examines how contextual variables influence communicative, cognitive and social measures of parent–infant interactions. Specifically, how do feedback toys and traditional toys associate with important parent and child measures necessary for learning and development? Here we report evidence that toy type is associated with quality and quantity of parent–child interactions. Condition 1 examined parent–child interactions during two separate play sessions; one contained feedback toys and the other contained traditional toys. Condition 2 combined the toys so dyads had access to both types at the same time. Infants produced higher levels of directed vocalizations and directed gestures, but had shorter durations of sustained attention, when interacting with traditional toys compared to feedback toys. Parents responded more to infants’ vocalizations and gestures when interacting with traditional toys. In general, these results suggest that toy properties can play a significant role in parent–infant interactions.
Increasing Quiet Compliance by Detained Male Adolescents
Authors: Brogan Kristen M. , Rapp John T. , Niedfeld Amanda M. , Coon Jodi C. , Everhart Newman Jan L. , Burkhart Barry R.
Published: June 2017

Some adjudicated adolescents receive treatment for their offenses in residential facilities. Detained adolescents’ engagement in either low levels of compliant behavior or excess behavior (e.g., swearing, gestures) while following commands from residential personnel may result in decreased opportunities for those youth to access preferred activities. The current study employed nonconcurrent multiple baseline across participants designs to evaluate the effects of a procedure to increase seven detained adolescents’ quiet compliance with academic and vocational demands. Results show that problem behavior decreased to zero or near-zero levels for each participant during simulated conditions and suggest that self-control, alone or in combination with a differential reinforcement of low rate behavior for omitting problem behavior, may have been responsible for the behavior changes. We discuss some clinical implications of the findings.
Irregular migration struggles and active subjects of trans-border politics: New research strategies for interrogating the agency of the marginalised
Authors: Strange Michael , Squire Vicki , Lundberg Anna
Published: June 2017

The politics of migration has become increasingly prominent as a site of struggle. However, the active subjecthood of people on the move in precarious situations is often overlooked. Irregular migration struggles raise questions about how to understand the agency of people who are marginalised. What does it mean to engage people produced as ‘irregular’ as active subjects of trans-border politics? And what new research strategies can we employ to this end? The articles presented in this Special Issue of Politics each differently explore how actions by or on behalf of irregular/ised migrants involve processes of subjectivity formation that imply a form of agency. Collectively we explore how irregular migration struggles feature as a site marked by active subjects of trans-border politics. We propose a research agenda based on tracing those processes – both regulatory, activist, and everyday – that negotiate and contest how an individual is positioned as an ‘irregular migrant’. The ethos behind such research is to explore how the most marginalised individuals reclaim or reconfigure subjecthood in ambiguous terms.
Identifying Computer-Generated Portraits: The Importance of Training and Incentives
Authors: Mader Brandon , Banks Martin S. , Farid Hany
Published: June 2017

The past two decades have seen remarkable advances in photo-realistic rendering of everything from inanimate objects to landscapes, animals, and humans. We previously showed that despite these tremendous advances, human observers remain fairly good at distinguishing computer-generated from photographic images. Building on these results, we describe a series of follow-up experiments that reveal how to improve observer performance. Of general interest to anyone performing psychophysical studies on Mechanical Turk or similar platforms, we find that observer performance can be significantly improved with the proper incentives.