bluuebunny/crossref_metadata_2025 huggingface dataset:
YAP Orchestrates Heterotypic Endothelial Cell Communication via HGF/c-MET Signaling in Liver Tumorigenesis
Authors: Thomann Stefan , Weiler Sofia M.E. , Marquard Simone , Rose Fabian , Ball Claudia R. , Tóth Marcell , Wei Teng , Sticht Carsten , Fritzsche Sarah , Roessler Stephanie , De La Torre Carolina , Ryschich Eduard , Ermakova Olga , Mogler Carolin , Kazdal Daniel , Gretz Norbert , Glimm Hanno , Rempel Eugen , Schirmacher Peter , Breuhahn Kai
Published: October 2020

The oncogene yes-associated protein (YAP) controls liver tumor initiation and progression via cell extrinsic functions by creating a tumor-supporting environment in conjunction with cell autonomous mechanisms. However, how YAP controls organization of the microenvironment and in particular the vascular niche, which contributes to liver disease and hepatocarcinogenesis, is poorly understood. To investigate heterotypic cell communication, we dissected murine and human liver endothelial cell (EC) populations into liver sinusoidal endothelial cells (LSEC) and continuous endothelial cells (CEC) through histomorphological and molecular characterization. In YAPS127A-induced tumorigenesis, a gradual replacement of LSECs by CECs was associated with dynamic changes in the expression of genes involved in paracrine communication. The formation of new communication hubs connecting CECs and LSECs included the hepatocyte growth factor (Hgf)/c-Met signaling pathway. In hepatocytes and tumor cells, YAP/TEA domain transcription factor 4 (TEAD4)–dependent transcriptional induction of osteopontin (Opn) stimulated c-Met expression in EC with CEC phenotype, which sensitized these cells to the promigratory effects of LSEC-derived Hgf. In human hepatocellular carcinoma, the presence of a migration-associated tip-cell signature correlated with poor clinical outcome and the loss of LSEC marker gene expression. The occurrence of c-MET–expressing CECs in human liver cancer samples was confirmed at the single-cell level. In summary, YAP-dependent changes of the liver vascular niche comprise the formation of heterologous communication hubs in which tumor cell–derived factors modify the cross-talk between LSECs and CECs via the HGF/c-MET axis.

Significance:

YAP-dependent changes of the liver vascular niche comprise the formation of heterologous communication hubs in which tumor cell-derived factors modify the cross-talk between EC subpopulations.
Turning Up the Heat on MYC: Progress in Small-Molecule Inhibitors
Authors: Truica Mihai I. , Burns Michael C. , Han Huiying , Abdulkadir Sarki A.
Published: October 2020

MYC is a highly validated oncogenic transcription factor and cancer target. However, the disordered nature of this protein has made it a challenging target, with no clinical stage, direct small-molecule MYC inhibitors available. Recent work leveraging a large in silico chemical library and a rapid in vivo screen has expanded the chemotypes of direct small-molecule inhibitors (MYCi). Novel MYCi represent a class of improved MYC chemical probes that bind directly to MYC to inhibit its function and to promote its degradation by enhancing GSK3β–mediated phosphorylation. One of these compounds, MYCi975, has shown remarkable tolerability and efficacy in vivo and is associated with a selective effect on MYC target gene expression. Additional effects of MYCi on the tumor immune microenvironment including immune cell infiltration and upregulation of PD-L1 expression provide a rationale for combining MYCi with anti–PD-1/PD-L1 therapy to enhance antitumor efficacy. Our strategy for developing MYCi demonstrates an efficient way to identify selective and well-tolerated MYC inhibitors. The new MYCi provide tools for probing MYC function and serve as starting points for the development of novel anti-MYC therapeutics.
Oncolytic HSV Therapy Modulates Vesicular Trafficking Inducing Cisplatin Sensitivity and Antitumor Immunity
Authors: Hong Bangxing , Chapa Valerie , Saini Uksha , Modgil Puneet , Cohn David E. , He Guangan , Siddik Zahid H. , Sood Anil K. , Yan Yuanqing , Selvendiran Karuppaiyah , Pei Guangsheng , Zhao Zhongming , Yoo Ji Young , Kaur Balveen
Published: October 2020

Purpose:

Here we investigated the impact of oncolytic herpes simplex virus (HSV) treatment on cisplatin sensitivity of platinum-resistant ovarian cancer, and the impact of the combination on immunotherapy.

Experimental Design:

Therapeutic efficacy of the combination was assessed in platinum-resistant human and murine ovarian cancer peritoneal metastatic mouse models (n = 9–10/group). RNA sequencing along with flow cytometry of splenocytes from treated mice was employed to examine the effect of antitumor immune response (n = 3/group). Anti-PD-1 antibody was performed to evaluate impact on checkpoint inhibition in vivo.

Results:

Gene Ontology pathway analysis uncovered disruption of cellular extracellular vesicle (EV)-related pathways in infected cells (FDR = 2.97E-57). Mechanistically, we identified reduced expression of transporters expressed on EV implicated in cisplatin efflux. The increased cisplatin retention led to increased cisplatin–DNA adducts, which resulted in micronuclei and the subsequent activation of cGAS–STING pathway with a significant activation of innate immune cells and translated to an increase in antitumor immunity and efficacy. In mice bearing platinum-resistant ovarian cancer, we also observed a feedback induction of PD-L1 on tumor cells, which sensitized combination-treated mice to anti-PD-1 immune checkpoint therapy.

Conclusions:

To our knowledge, this is the first report to show HSV-induced cisplatin retention in infected cells. The consequential increased damaged DNA was then expelled from cells as micronuclei which resulted in induction of inflammatory responses and education of antitumor immunity. The combination therapy also created an environment that sensitized tumors to immune checkpoint therapy.
Inhibition of Lysosomal Function Mitigates Protective Mitophagy and Augments Ceramide Nanoliposome–Induced Cell Death in Head and Neck Squamous Cell Carcinoma
Authors: Shaw Jeremy J.P. , Boyer Timothy L. , Venner Emily , Beck Patrick J. , Slamowitz Tristen , Caste Tara , Hickman Alexandra , Raymond Michael H. , Costa-Pinheiro Pedro , Jameson Mark J. , Fox Todd E. , Kester Mark
Published: October 2020

Therapies for head and neck squamous cell carcinoma (HNSCC) are, at best, moderately effective, underscoring the need for new therapeutic strategies. Ceramide treatment leads to cell death as a consequence of mitochondrial damage by generating oxidative stress and causing mitochondrial permeability. However, HNSCC cells are able to resist cell death through mitochondria repair via mitophagy. Through the use of the C6-ceramide nanoliposome (CNL) to deliver therapeutic levels of bioactive ceramide, we demonstrate that the effects of CNL are mitigated in drug-resistant HNSCC via an autophagic/mitophagic response. We also demonstrate that inhibitors of lysosomal function, including chloroquine (CQ), significantly augment CNL-induced death in HNSCC cell lines. Mechanistically, the combination of CQ and CNL results in dysfunctional lysosomal processing of damaged mitochondria. We further demonstrate that exogenous addition of methyl pyruvate rescues cells from CNL + CQ–dependent cell death by restoring mitochondrial functionality via the reduction of CNL- and CQ-induced generation of reactive oxygen species and mitochondria permeability. Taken together, inhibition of late-stage protective autophagy/mitophagy augments the efficacy of CNL through preventing mitochondrial repair. Moreover, the combination of inhibitors of lysosomal function with CNL may provide an efficacious treatment modality for HNSCC.
Churches, Dignity, Gender: the Istanbul Convention as a Matter of Public Theology in Ukraine
Authors: Zorgdrager Heleen
Published: October 2020

This article is based on a case-study of the public debate in Ukraine on the so-called Istanbul Convention ‘on preventing and combating violence against women and domestic violence’. The debate polarizes churches and more liberal parts of society. The author seeks for the roots of the churches’ position not to address the structural causes of domestic violence as gender-based violence. How does this relate to embracing dignity of the human being as a core principle of the Maidan revolution and of Christian anthropology? Influential documents on moral theology play a detrimental role. The author makes suggestions to address more adequately domestic violence in public theology in Ukrainian context. The coordinates of the proposal are the need for a gender-critical dignity discourse, the need for reimagining the sacramental theology of marriage, and insights for the methodology of a public theology that wants to be both deeply engaged and truly academic.
Framing a Mosque Project as a Sunni–Shia Conflict
Authors: Pauha Teemu
Published: October 2020

In January 2015, the City of Helsinki received a proposal for the construction of ‘a grand mosque’. In December 2017, the Urban Environment committee rejected the proposal. In the interim, the proposed mosque was the subject of intense public debate. A key point of dispute was whether the mosque would increase tensions between Sunni and Shia Muslims in Finland. This article explores the ways in which the mosque project became framed as a Sunni–Shia conflict. Special focus is put on a newspaper article published in the Helsingin Sanomat in July 2015 and the framing devices used therein.
‘Welfare Does Not Know Any Borders’: Negotiations on the Transnational Assistance of Migrants before the World Wars
Authors: Althammer Beate
Published: October 2020

Today, the tensions between European conceptions of the welfare state and transnational migration are a heatedly debated issue. Little is known, however, about how the challenges of migration were addressed in the early phases of welfare state formation. Nevertheless, in the historiography the assumption is widely held that the rise of modern welfare policies around 1900 fostered the nationalist exclusion of foreigners. This article aims at qualifying this assumption by highlighting how the welfare of cross-border migrants became a topic of cross-border deliberations. It centres on the plan for an international convention on the assistance of foreigners, which was promoted by the International Congresses on Public and Private Assistance and taken up by a diplomatic conference in Paris on the eve of the First World War. On the agenda was the task of finding a formula that could guarantee migrants equal access to social services, although this proved to be a difficult goal.
Detecting Differential Item Functioning Using Multiple-Group Cognitive Diagnosis Models
Authors: Ma Wenchao , Terzi Ragip , de la Torre Jimmy
Published: October 2020

This study proposes a multiple-group cognitive diagnosis model to account for the fact that students in different groups may use distinct attributes or use the same attributes but in different manners (e.g., conjunctive, disjunctive, and compensatory) to solve problems. Based on the proposed model, this study systematically investigates the performance of the likelihood ratio (LR) test and Wald test in detecting differential item functioning (DIF). A forward anchor item search procedure was also proposed to identify a set of anchor items with invariant item parameters across groups. Results showed that the LR and Wald tests with the forward anchor item search algorithm produced better calibrated Type I error rates than the ordinary LR and Wald tests, especially when items were of low quality. A set of real data were also analyzed to illustrate the use of these DIF detection procedures.
A conjunctural account of upper- and middle-class support for Rodrigo Duterte
Authors: Garrido Marco
Published: October 2020

Philippine scholars have largely interpreted Duterte’s support among the upper and middle class as a rejection of the previous administration’s incremental reformism. They also point to the growing appeal of a politics of discipline. These explanations are insufficient. They cannot tell us why the upper and middle class supported Duterte when they did in 2016. The Aquino administration was not the first to disappoint and Duterte hardly the first avatar of discipline to appear on the political scene. In this article the author argues that we need to understand support for Duterte as having crystallized over time with respect to a series of events. Specifically, we need to account for the trajectory of democracy in the Philippines and the contingency of support for him. By placing this support in conjunctural context, we are better able to understand the upper and middle classes’ predisposition to ‘strong leaders’ and their turn to Duterte in 2016.
How Trauma, Depression, and Gender Roles Lead to Intimate Partner Violence Perpetration Among a Sample of Predominately Low-Income Black, Indigenous, Men of Color: A Mixed Methods Study
Authors: Voith Laura A. , Lee Hyunjune , Russell Katie
Published: October 2020

Despite decades of research and significant efforts by practitioners and advocates, intimate partner violence (IPV) in the United States remains a public health issue that disproportionately affects racial/ethnic minorities. The lack of mixed methods and qualitative studies, particularly with Black, Indigenous, Men of Color (BIMOC), limits the field’s ability to tease apart the complex, multifaceted aspects of IPV perpetration and minimizes diverse perspectives of how childhood trauma and key proximal factors culminate in IPV perpetration. An explanatory design, follow-up explanations model, was used with a sample of predominately low-income BIMOC in a batterer intervention program (BIP). Associations between IPV and theoretically supported factors (e.g., trauma symptoms, depression, gender roles) were examined using a cross-sectional survey ( N = 67) with ordinary least squares regression. Following up, processes explaining how these factors might lead to IPV perpetration were explored using semistructured interviews ( N = 11) with narrative analysis. Results indicate that depressive and posttraumatic stress disorder (PTSD) symptoms together predict men’s IPV perpetration. Participants’ collective narrative explains how key factors—such as adverse childhood experiences, PTSD, depression, social isolation, anger, and restricted emotionality—work together to culminate in IPV perpetration. Findings shed light on potential trajectories and antecedents that manifest in IPV perpetration, providing implications for practice techniques and program development with low-income BIMOC in BIPs.
Cooling effectiveness of matrix, pin fin array and hybrid structure: A comparative study
Authors: Yang Lianfeng , Luan Yigang , Bu Shi , Sun Haiou , Magagnato Franco
Published: October 2020

In modern gas turbines, the trailing edge of turbine blades must be cooled by compact heat transfer structures. The basic problems in the design of cooling ducts include enhancing heat transfer, reducing pressure loss and obtaining uniform temperature distribution. The purpose is to improve energy efficiency and guarantee the engine lifespan. In this work, both experiment and numerical simulation are employed to study pressure drop and heat transfer of various kinds of cooling configurations. Pin fin array, matrix and hybrid structures are investigated in a comparative study. Thermochromic liquid crystal technique is applied to obtain heat transfer distribution on the channel surface. The results show that matrix creates much stronger heat transfer than pin fin array with increased pressure loss penalty. Performances of matrix structures are quite different due to the configurations (dense or sparse). Hybrid structures are always worse than the baseline matrix in terms of average thermal performance, due to the higher pressure loss, however, heat transfer can be improved. The performance of hybrid structure depends on the arrangement and diameter of the pin fins. Pin fins in central area provide not only larger pressure loss but also stronger heat transfer than pin fins near the bend region. Cases with larger diameter result in the thermal performance degradation. Compared with sparse matrix, the hybrid structures can compensate for the lower heat transfer enhancement. As for the dense hybrid structures, the average heat transfer capacity can be improved with reasonable pin fin arrangement.
Factors associated with regular HIV testing behavior of MSM in China: a cross-sectional survey informed by theory of triadic influence
Authors: Zhao Yafang , Bromberg Daniel J , Khoshnood Kaveh , Sheng Yu
Published: October 2020

The prevalence of HIV infection among men who have sex with men (MSM) in China has increased in recent years. Regular HIV testing is a key prevention strategy for identifying HIV infections among MSM. Informed by the theory of triadic influence, we aimed to determine individual, social and environmental factors associated with regular HIV testing behavior. Regular HIV testing is defined as taking an HIV test every 3 to 6 months. Both an online survey and a face-to-face survey was administered to MSM in China. Logistic regression was used to examine associations with testing behavior. 500 MSM were surveyed, the prevalence of regular testing was 56.4%. In the final model, age of first sexual intercourse, self-efficacy, perceived risk, number of partners, orientation disclosure, knowledge of HIV testing, behavioral intention and HIV relevant behaviors (sexually transmitted infection testing history) were associated with regular HIV testing; social stream characteristics had stronger associations with regular testing than individual and environmental factors. Findings implicated that interventions aimed at improving the effective counseling service from healthcare providers and the medical environment and intrapersonal changes should be combined to encourage MSM to have their first HIV test and to keep coming back at regular intervals.
Analytical evaluation of an immunomagnetic separation PCR assay to detect pathogenic Leptospira in cattle urine samples obtained under field conditions
Authors: Tomckowiack Camilo , Henriquez Claudio , Ramirez-Reveco Alfredo , Muñoz Priscila , Collado Bernardita , Herzberg Daniel , Folch Hugo , Salgado Miguel
Published: October 2020

Clinical manifestations of leptospirosis are diverse and very similar to other febrile diseases, hence early and accurate detection of subclinical infections is a key element in disease control. We evaluated immunomagnetic separation (IMS) capture technology coupled with a standard quantitative PCR (qPCR) system for the detection of pathogenic Leptospira in urine samples from 803 cows from dairy herds with a history of clinical cases of leptospirosis. The urine samples were first processed in a purification step, then subdivided into 2 subsamples, one that continued to DNA extraction and direct qPCR, and one that was pretreated by IMS before continuing to DNA extraction and qPCR. Overall, 133 of 803 (16.6%) samples were IMS-qPCR positive, whereas only 92 of 803 (11.5%) were positive when using direct qPCR. Statistically significant differences were observed between the mean estimated Leptospira load between the IMS-qPCR and the direct qPCR positive urine samples. The IMS-qPCR technology revealed a larger number of positive results and higher bacterial loads than direct qPCR. This difference is most likely the result of the high antigen-binding capacity and capture efficiency of the IMS system. The use of polyclonal antibodies produced by the inoculation of 3 synthetic peptides, which make up the extracellular regions of the LipL32 protein, provided a high detection capacity to the IMS-qPCR technique, resulting in performance superior to direct qPCR.
Decreased swallowing function in the sarcopenic elderly without clinical dysphagia: a cross-sectional study
Authors: Chen Yen-Chih , Chen Pei-Yun , Wang Yu-Chen , Wang Tyng-Guey , Han Der-Sheng
Published: October 2020

Background

Sarcopenia and dysphagia are prevalent health issues as the elderly population continues to grow. However, whether sarcopenia, defined by either reduced handgrip strength or gait speed, would lead to pathological effects on swallowing function is still a matter of debate. Studies focusing on subclinical changes in the swallowing function in the sarcopenic elderly are lacking. This study evaluates the swallowing function in the sarcopenic elderly without dysphagia.

Methods: A cross-sectional study was conducted including subjects recruited from the community. Ninety-four individuals aged 65 and older without dysphagia were divided into two groups: sarcopenia and nonsarcopenia. The swallowing assessment included tongue pressure measurement, hyoid displacement (HD), hyoid velocity (HV) measurement with submental ultrasonography, 100-ml water-swallowing test, and the 10-item Eating Assessment Tool (EAT-10).

Results

The average tongue pressure was 47.0 ± 13.7 and 48.6 ± 11.5 kPa in the sarcopenia and nonsarcopenia groups, respectively (p = 0.55), whereas the average HD during swallowing was 15.3 ± 4.4 and 13.0 ± 4.2 mm in the sarcopenia and nonsarcopenia groups, respectively (p < 0.05). The median of HV during swallowing was 19.5 (6.41–45.86) and 15.9 (3.7–39.7) mm/s in the sarcopenia and nonsarcopenia group (p < 0.05). The median of time needed for consuming 100 ml water was 12.43 (3.56–49.34) and 5.66 (2.07–19.13) seconds in the sarcopenia and nonsarcopenia groups, respectively (p < 0.05). The median of the EAT-10 score was 0 (0–2) and 0 (0–1) in the sarcopenia and nonsarcopenia groups, respectively (p < 0.05).

Conclusions

In elderly individuals, swallowing function was significantly impaired with sarcopenia before clinical symptoms become clear. However, tongue muscles exhibited resistance to sarcopenia. We observed compensative strategies in patients with sarcopenia, such as reduced swallowing speed and increased hyoid bone movement.
Risk and protective factors for burnout among physicians from standardized residency training programs in Shanghai: a cross-sectional study
Authors: Huang Lei , Caspari Jennifer Harsh , Sun Xiaoting , Thai Jessica , Li Yaxi , Chen Fa-zhan , Zhao Xu-dong
Published: October 2020

Background

High burnout has been reported in physician populations. Although the standardized residency training (SRT) in China includes components that might put residents at a higher risk for burnout, the burnout of Chinese medical residents is unknown. This study aimed to evaluate the prevalence of burnout and the associated risk and protective factors for medical residents in the SRT program in Shanghai, China.

Methods

This study was a prospective cross-sectional design. A random sampling strategy was used to recruit 330 resident physicians from four SRT sites in Shanghai, and 318 completed questionnaires were returned. Respondents completed a self-made questionnaire including demographic and work characteristics, four burnout and wellness-specific surveys. Bivariate analyses and hierarchical multiple regression models were used to analyze factors associated with three sub-scales of burn out separately.

Results

The overall burnout rate was 71.4%. Low level rate of personal accomplishment (PA) was extremely high at 69.5%. Night shift experience, high occupational stress, and low social support were significant predictors, which explained 49.1% variance of emotional exhaustion (EE) (F = 26.528, P < 0.01). Factors that significantly predicted depersonalization (DP) included male gender, senior residents, night shift experience, high occupational stress, and low psychological empathy, which explained 51.5% variance totally (F = 29.004, P < 0.01). Senior residents, high income, low occupational stress, and high empathy were also significant predictors of decreased personal achievement (PA), which explained 18.4% variance totally (F = 12.897, P < 0.01).

Conclusions

There was a high burnout rate among SRT residents in Shanghai. Occupational stress and several work-related factors were significant and strong risk factors for burnout, while empathy and social support were mild protective factors. Decreased work-related demands and increased access to resources could assist residents in reducing their work stress and improving their well-being.
Timing of surgical intervention for compartment syndrome in different body region: systematic review of the literature
Authors: Coccolini Federico , Improta Mario , Picetti Edoardo , Branca Vergano Luigi , Catena Fausto , de ’Angelis Nicola , Bertolucci Andrea , Kirkpatrick Andrew W. , Sartelli Massimo , Fugazzola Paola , Tartaglia Dario , Chiarugi Massimo
Published: October 2020

Compartment syndrome can occur in many body regions and may range from homeostasis asymptomatic alterations to severe, life-threatening conditions. Surgical intervention to decompress affected organs or area of the body is often the only effective treatment, although evidences to assess the best timing of intervention are lacking. Present paper systematically reviewed the literature stratifying timings according to the compartmental syndromes which may beneficiate from immediate, early, delayed, or prophylactic surgical decompression. Timing of decompression have been stratified into four categories: (1)immediate decompressionfor those compartmental syndromes whose missed therapy would rapidly lead to patient death or extreme disability, (2)early decompressionwith the time burden of 3–12 h and in any case before clinical signs of irreversible deterioration, (3)delayed decompressionidentified with decompression performed after 12 h or after signs of clinical deterioration has occurred, and (4)prophylactic decompressionin those situations where high incidence of compartment syndrome is expected after a specific causative event.
Aging-relevant human basal forebrain cholinergic neurons as a cell model for Alzheimer’s disease
Authors: Ma Shuaipeng , Zang Tong , Liu Meng-Lu , Zhang Chun-Li
Published: October 2020

Background

Alzheimer’s disease (AD) is an adult-onset mental disorder with aging as a major risk factor. Early and progressive degeneration of basal forebrain cholinergic neurons (BFCNs) contributes substantially to cognitive impairments of AD. An aging-relevant cell model of BFCNs will critically help understand AD and identify potential therapeutics. Recent studies demonstrate that induced neurons directly reprogrammed from adult human skin fibroblasts retain aging-associated features. However, human induced BFCNs (hiBFCNs) have yet to be achieved.

Methods

We examined a reprogramming procedure for the generation of aging-relevant hiBFCNs through virus-mediated expression of fate-determining transcription factors. Skin fibroblasts were obtained from healthy young persons, healthy adults and sporadic AD patients. Properties of the induced neurons were examined by immunocytochemistry, qRT-PCR, western blotting, and electrophysiology.

Results

We established a protocol for efficient generation of hiBFCNs from adult human skin fibroblasts. They show electrophysiological properties of mature neurons and express BFCN-specific markers, such as CHAT, p75NTR, ISL1, and VACHT. As a proof-of-concept, our preliminary results further reveal that hiBFCNs from sporadic AD patients exhibit time-dependent TAU hyperphosphorylation in the soma and dysfunctional nucleocytoplasmic transport activities.

Conclusions

Aging-relevant BFCNs can be directly reprogrammed from human skin fibroblasts of healthy adults and sporadic AD patients. They show promises as an aging-relevant cell model for understanding AD pathology and may be employed for therapeutics identification for AD.
ACTION-IO as a platform to understand differences in perceptions, attitudes, and behaviors of people with obesity and physicians across countries – the Israeli experience
Authors: Dicker Dror , Kornboim Batya , Bachrach Rakefet , Shehadeh Naim , Potesman-Yona Shani , Segal-Lieberman Gabriella
Published: October 2020

Background

Obesity is a highly prevalent, complex, and chronic relapsing disease with a considerable unmet medical need. We aimed to identify perceptions, attitudes, behaviors, and barriers to effective obesity treatment among people with obesity (PwO) and physicians in Israel.

Methods

The ACTION-IO study was an online survey conducted in 11 countries, including Israel. Findings from the Israeli cohort are reported here. Israeli respondents were PwO (body mass index of ≥30 kg/m2 based on self-reported height and weight) and physicians primarily in direct patient care.

Results

In total, 750 PwO and 169 physicians completed the survey in Israel. Although most PwO (70%) and physicians (95%) perceived obesity as a chronic disease, the majority of PwO assumed full responsibility for their own weight loss (88%) compared with only 19% of physicians who placed the responsibility for weight loss on their patients with obesity. Many PwO (62%) and physicians (73%) agreed that a complete change in lifestyle would be required for PwO to lose weight and felt that treatment of obesity should be a team effort between different healthcare professionals (HCPs; 80 and 90%, respectively). Dietitians were considered by 82% of physicians to be the most effective professionals in helping PwO achieve their weight loss goals. Many PwO (69%) liked that their HCP initiated weight management discussions and 68% of those who had not previously discussed their weight would like their HCP to initiate the conversation. However, among PwO who had discussed their weight with an HCP, 59% considered the discussions to be a little helpful or not at all helpful. The beliefs that patients have little interest in or motivation for losing weight were identified by physicians as the main reasons (71 and 70%, respectively) for not initiating weight management discussions.

Conclusions

In line with the ACTION-IO international study, our Israeli dataset reveals a need to improve awareness, primarily among physicians, on the physiologic basis and clinical management of obesity, including how to approach weight and weight management discussions during patient consultations.

Trial registration

Registered at ClinicalTrials.gov, NCT03584191. Data first posted on ClinicalTrials.gov: 12 July 2018 - ‘Retrospectively registered’.
A muscle synergies-based movements detection approach for recognition of the wrist movements
Authors: Masoumdoost Aida , Saadatyar Reza , Kobravi Hamid Reza
Published: October 2020

Myoelectric signals are regarded as the control signal for prosthetic limbs. But, the main research challenge is reliable and repeatable movement detection using electromyography. In this study, the analysis of the muscle synergy pattern has been considered as a key idea to cope with this main challenge. The main objective of this research was to provide an analytical tool to recognize six wrist movements through electromyography (EMG) based on analysis of the muscle synergy patterns. In order to design such a system‚ the synergy patterns of the wrist muscles have been extracted and utilized to identify wrist movements. Also, different decision fusion algorithms were used to increase the reliability of the synergy pattern classification. The classification performance was evaluated while no data subject was enrolled. In terms of the achieved performance, using a multi-layer perceptron (MLP) neural network as the fusion algorithm turned out to be the best combination. The classification average accuracy, obtained in an offline manner, was about 99.78 ± 0.45%. While the classification average cross-validation accuracy, obtained in an offline manner, using Bayesian fusion, and Bayesian fuzzy clustering (BFC) fusion algorithm were 99.33 ± 0.80% and 96.43 ± 1.08%, respectively.
Pathogenicity of severe fever with thrombocytopenia syndrome virus in mice regulated in type I interferon signaling
Authors: Park Seok-Chan , Park Jun Young , Choi Jin Young , Lee Sung-Geun , Eo Seong Kug , Oem Jae-Ku , Tark Dong-Seob , You Myungjo , Yu Do-Hyeon , Chae Joon-Seok , Kim Bumseok
Published: October 2020

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonotic disease, which causes high fever, thrombocytopenia, and death in humans and animals in East Asian countries. The pathogenicity of SFTS virus (SFTSV) remains unclear. We intraperitoneally infected three groups of mice: wild-type (WT), mice treated with blocking anti-type I interferon (IFN)-α receptor antibody (IFNAR Ab), and IFNAR knockout (IFNAR−/−) mice, with four doses of SFTSV (KH1, 5 × 105 to 5 × 102 FAID50). The WT mice survived all SFTSV infective doses. The IFNAR Ab mice died within 7 days post-infection (dpi) with all doses of SFTSV except that the mice were infected with 5 × 102 FAID50 SFTSV. The IFNAR−/− mice died after infection with all doses of SFTSV within four dpi. No SFTSV infection caused hyperthermia in any mice, whereas all the dead mice showed hypothermia and weight loss. In the WT mice, SFTSV RNA was detected in the eyes, oral swabs, urine, and feces at 5 dpi. Similar patterns were observed in the IFNAR Ab and IFNAR−/− mice after 3 dpi, but not in feces. The IFNAR Ab mice showed viral shedding until 7 dpi. The SFTSV RNA loads were higher in organs of the IFNAR−/− mice compared to the other groups. Histopathologically, coagulation necrosis and mononuclear inflammatory cell infiltration in the liver and white pulp atrophy in the spleen were seen as the main lesions in the IFN signaling lacking mice. Immunohistochemically, SFTSV antigens were mainly detected in the marginal zone of the white pulp of the spleen in all groups of mice, but more viral antigens were observed in the spleen of the IFNAR−/− mice. Collectively, the IFN signaling-deficient mice were highly susceptible to SFTSV and more viral burden could be demonstrated in various excreta and organs of the mice when IFN signaling was inhibited.
Octreotide (somatostatin analog) attenuates cardiac ischemia/reperfusion injury via activating nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway in rat model of hyperthyroidism
Authors: Gomaa Randa Salah , Mahmoud Nevertyty Mohamed , Mohammed Nourelhuda Abdelaziz
Published: October 2020

Background

Hyperthyroidism is known to increase the risk of ischemic heart diseases. Octreotide has been reported to attenuate ischemia/reperfusion (I/R) injury. Whether it is useful when ischemic heart disease is accompanied with co-morbidities like hyperthyroidism needs more clarifying. So, this study aimed to explore the effect of octreotide on cardiac I/R injury in hyperthyroid rats and to clarify if Nrf2 activation is involved in this effect. Forty adult female Wistar rats were subdivided into control (euthyroid) (n= 10) and hyperthyroid (n= 30) groups. Rats in hyperthyroid group receivedl-thyroxine (12 mg/L) in drinking water for 35 days, then were randomly divided into three equal subgroups (n= 10): hyperthyroid control positive group, hyperthyroid octreotide treated group, and hyperthyroid octreotide + Nrf2 inhibitor (brusatol) treated group. Isolated hearts were submitted to I/R and evaluated for cardiac hemodynamics and infarct size. Serum T3 and T4, coronary efflux lactate dehydrogenase (LDH) and creatine kinase-myoglobin binding (CK-MB) and cardiac tissue malondialdehyde (MDA) were estimated. Nrf2- regulated gene expressions of HO-1, SOD, GPx, and catalase were assessed.

Results

Octreotide administration to hyperthyroid rats improved baseline and post-ischemic recovery of cardiac hemodynamics, decreased the high coronary efflux LDH and CK-MB and tissue MDA, reduced infarction size, and upregulated the decreased antioxidative enzymes HO-1, SOD, GPx, and catalase mRNA expressions in the hyperthyroid I/R rat hearts. The Nrf2 inhibitor brusatol reversed the cardioprotective effect of octreotide in hyperthyroid I/R rat hearts.

Conclusion

Octreotide can reduce oxidative stress to effectively alleviate I/R injury in the hyperthyroid rat hearts through upregulation of Nrf2-dependent antioxidative signaling pathways.
The Effect of EU Integration on Health Care in Central and Eastern Europe
Authors: Sokol Tomislav
Published: October 2020

The effect of EU policy and its legal framework on health care in CEE member states has been complex. In relation to health care access and financial sustainability, it has been detrimental in certain parts of CEE. This has primarily been the result of economic/fiscal governance instruments of the EU and free-movement rules facilitating outflows of health care professionals. Although there has been a general improvement in access to health care since accession to the EU, the instruments the EU has used to handle the economic crisis have somewhat offset this improvement. Additionally, outflow of health care professionals has resulted in retention strategies such as salary increases and investments in medical infrastructure in some CEE member states, increasing the standard of health care. Still, differences between East and West in terms of important health indicators continue to exist, and EU instruments aimed at compensating this generally lack power to provide meaningful solutions. It seems more solidarity between member states is the only way to increase legitimacy of the European integration in CEE member states and thus prevent them from feeling as outsiders within the EU. Without such a development, CEE countries will continue to lag behind other parts of the Union.
Activation of the Keap1-Nrf2 pathway by specioside and the n-butanol extract from the inner bark of Tabebuia rosea (Bertol) DC
Authors: Garzón-Castaño Sandra Catalina , Jiménez-González Francisco Javier , Veloza Luz Angela , Sepúlveda-Arias Juan Carlos
Published: October 2020

Background: A large number of chemical compounds exert their antioxidant effects by activation of key transcriptional regulatory mechanisms, such as the transcription factor Nrf2. The aim of this study was to evaluate the activation of the Keap1-Nrf2 pathway by both the n-butanol extract obtained from the inner bark of Tabebuia rosea (Bertol) DC and specioside isolated from this extract.

Methods: The antioxidant activity of the extract and specioside isolated from the inner bark of T. rosea were evaluated using the oxygen radical absorbance capacity (ORAC) and the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (DPPH) techniques, whereas their effects on the viability of HepG2 cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The effects of the compound and the extract on activating the Keap1-Nrf2 pathway were evaluated using a Nrf2 Transcription Factor Assay kit. Induction of the Nrf2-mediated antioxidant response genes HMOX-1 and NQO1 was evaluated by real-time PCR. The protective effects against H2O2-induced oxidative stress in HepG2 cells was determined as the percent protection using the MTT method.

Results: Both the n-butanol extract and specioside exhibited activity at low concentrations without affecting cellular viability, since the cell viability was greater than 80% after 24 hours of exposure at each tested concentration. In addition, Nrf2 dissociated from Keap1 after treatment with the n-butanol extract at a concentration of 0.25 µg/mL after 4 hours of exposure. An increase in the Nrf2 level in the cytoplasm after 4 hours of exposure to 2 μM specioside was observed. Nrf2 levels stabilized in the nucleus 12 hours after stimulation with both specioside and the extract. After 6 hours of stimulation, both the extract and specioside induced the expression of HMOX-1 and NQO1.

Conclusion: The n-butanol extract from the inner bark of T. rosea and specioside produced protective effects against H2O2-induced oxidative stress in HepG2 cells.
Formation of Urban Agglomerations As a Factor in Ensuring the "Connectivity" of the Economic Space of Russia
Authors: Mel'nikova D. , Mariyen L.
Published: October 2020

The work is devoted to the modern development of urban agglomerations as one of the potential mechanisms for rational use of the territory and the best form of settlement. A study of the spatial development of three agglomerations in Russia was conducted: Volgograd, Novosibirsk, and Vladivostok regions, selected based on the comparability of the average distance from the core to the agglomeration border and representing different Federal districts, using the comparative analysis method. The study allowed us to determine at what stage of formation the selected agglomerations are located in order to further strengthen the competitive advantages of a particular territory in order to preserve or improve the quality of life of the population. It is assumed that the insufficient number of economic growth centers in Russian agglomerations and their lagging behind in key socio-economic criteria is due to the lack of a developed transport network, social infrastructure facilities and insufficient level of comfort of the urban environment outside the agglomeration core.
Improvement of Museum Exhibition Planning Processes Based on Project Management Methods
Authors: Hodzhayan E.
Published: October 2020

The urgency of development management to ensure competitiveness of culture institutions in conditions of transition to market conditions of managing. The basic principles of integration mechanism of project management in traditional management system of culture institution are analyzed. The ideas about the art project are generalized. The possibilities of a harmonious combination of process and project approaches to the management of culture institution are analyzed. In article using methods of network planning on the example of managing exhibition activity of the museum is considered. This allowed to design effective organization of works on exhibition design.
ADyC. Arte, Diseño y Comunicación (2018)
Authors: Mancera Martínez Manuel Fernando
Published: October 2020

En ADyC 2018 podemos encontrar un conjunto de realidades marcadas por el infinito, ese infinito cargado de motivo envolvente que se fusiona en la linde que distingue, a cada uno de sus diseños, como una miscelánea red gráfica que pretende germinar y formalizar futuras propuestas creativas. Cada uno de los diseñadores / ilustradores que conforman esta colección, aportan su visión personal a la reproducción creativa: geometrizaciones, personajes fantásticos, objetos animados, arquitecturas imposibles, extravagantes composiciones...
Keeping it simple
Authors: White Hilary
Published: October 2020

With its focus on simplicity, nature and the beauty to be found in the old and imperfect, how might the wisdom of wabi sabi inform the environment we create for children in our setting?
Deep and Meaningful
Authors: Watson Nicola
Published: October 2020

This second in a four-part series focuses on the Specific areas of learning, flagging up new points for reflection and providing a practical guide to support every day best practice in your setting.
Valuing experience
Authors: Trevor argue Georgina , Ince Amanda , Ang Lynn
Published: October 2020

If learning has been mapped backwards from intended outcomes in the revised EYFS, there is a danger that it loses meaningful context, argue Georgina Trevor, Amanda Ince and Lynn Ang.
Recruiting Creatively
Authors: Edmunds Imogen
Published: October 2020

Early years employers who have needed to recruit during the pandemic have had to adapt to new approaches, which in the longer term could prove a better way of doing things, says Imogen Edwards.
When Less is More
Authors: Garnett Steve
Published: October 2020

Understanding the role that working memory – and its limitations – play in children's learning is vital when it comes to developing effective teaching strategies, says Steve Garnett.
Between the covers
Authors: Rawstrone Annette
Published: October 2020

It is important not to be stuck in a rut when you and your child choose books to read together. Annette Rawstrone suggests casting the net wide and being open to a variety of titles to get your child started on the path to literacy.
Create a story map
Authors: Hart Karen
Published: October 2020

Laying the foundations for reading is about more than helping children to begin to match and recognise letters. It's all about showing that books are fun, are for sharing and are full of ways to make play more exciting.
Influence of Particle Shape and Contact Parameters on DEM-Simulated Bulk Density of Wheat
Authors: Petingco Marvin C. , Casada Mark E. , Maghirang Ronaldo G. , Fasina Oladiran O. , Chen Zhengpu , Ambrose R. P. Kingsly
Published: October 2020

Highlights

Decreasing aspect ratio and improved geometrical smoothness of particles increased DEM-predicted bulk density of wheat.

Among the three particle models, the 5-sphere ellipsoidal particle was the best option to represent wheat particles, as indicated by the simulated bulk densities that best agreed with the experiments.

Among the contact parameters, the wheat-to-wheat coefficient of static friction and wheat-surface coefficient of rolling friction had the greatest influence on simulated bulk density.

Abstract. The discrete element method (DEM) has been shown to be an effective tool for simulating the behavior of granular material. The accuracy of simulations depends highly on the contact models, particle physical parameters, and contact parameters used. The objectives of this study were to determine the influence of particle shape and contact parameters on simulated wheat bulk density and to develop an effective wheat particle model for DEM simulation of filling a container using EDEM software. Grain characteristics, including single-kernel weight, kernel density, kernel dimensions, aspect ratio, and bulk density, were determined for three size fractions of wheat used in the experiments. Three categories of particle models (5-sphere pseudo-ellipsoidal, 7-sphere pseudo-ellipsoidal, and ASG-generated) with varying aspect ratios and geometrical smoothness were tested in the simulations. Results showed that DEM-simulated bulk density of wheat increased with lower aspect ratio and greater geometrical smoothness of pseudo-ellipsoidal particles (7-sphere versus 5-sphere). Increasing the number of spheres to approximately 30 for better representation of wheat kernel shape, using ASG-generated particles, did not reproduce the trend of greater simulated bulk density seen in the experiments. Among the six contact parameters, the wheat-wheat coefficient of static friction and wheat-surface coefficient of rolling friction had the most significant effect on the simulated bulk density. Among the different sets of particle models, the 5-sphere pseudo-ellipsoidal particles, having aspect ratios close to that of wheat kernels in each size fraction, were found to be the most practical and appropriate particle model for use in DEM simulation of wheat bulk density. This study contributes to better understanding of the influence of particle shape and contact parameters on DEM-simulated bulk density and provides a calibrated particle model for use in simulating container filling operations. Keywords: Bulk density, Contact parameters, DEM, Particle shape, Wheat.
Application of Monoclinic Bismuth Vanadate in Photooxidation of Arsenic-Polluted Water
Authors: Chen Miaomiao , Li Yi , Pan Hong , Teng Jiuwei , Bora Ganesh , Wang Ying , Zhu Yi
Published: October 2020

Highlights

Photooxidation of trivalent arsenic to pentavalent arsenic was catalyzed by s-m BiVO4 under visible light irradiation.

The roles of catalyst, light, and oxygen were investigated.

The photooxidation mechanism was studied, and a possible reaction route is proposed.

Abstract. Oxidation is a necessary step for inorganic arsenic removal. In this study, monoclinic bismuth vanadate (BiVO4) was synthesized to photooxidize trivalent arsenic to pentavalent arsenic in water in the presence of light and oxygen. Light irradiation initiates photooxidation after physical absorption of arsenite on BiVO4. Addition of oxygen slightly improved the photooxidation efficiency. Photooxidation parameters were optimized; 2.6 mM of BiVO4 synthesized at pH 2 was effective to photooxidize 0.1 M of arsenite in alkaline solution, and 99.8% removal of trivalent arsenic was achieved with a photooxidation efficiency of 85.5%. Photooxidation by BiVO4 might be initiated by hydroxyl radicals resulting from irradiation by visible light. Appropriate BiVO4 morphology and alkalinity of the reaction mixture facilitated photooxidation. Keywords: Arsenic, BiVO4, Photooxidation, Speciation.