bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the fit of skins with a particular focus on the biomechanics of loose skins of hagfishes
Authors: Uyeno T.A. , Clark A.J. 
Published: October 2020

There is a considerable diversity in how skins fit. Here, we review the function of both tight and loose skins and note that the latter are poorly understood. Analysis of loose skin examples suggest five functional categories: (I) freedom of movement, (II) surface area enhancement, (III) increased structural extensibility, (IV) lubrication, and (V) maladaptive examples arising through sexual or artificial selection. We investigate the skins of hagfishes as a model for understanding loose skin function by examining its structure using histology, standardized puncture resistance testing using the ASTM F1306 protocol, and the effect of internal pressure using a simple inflated balloon model. Skins of hagfishes are composed of multiple layers of cross-helically wound connective tissue fibers of a 45° angle to the longitudinal axis, resulting in a skin that functions as fabric cut “on the bias”. Hagfish skins are relatively yielding; however, skin looseness adds a “structural extensibility” that may allow hagfishes to compensate for low puncture resistance. Physical balloon models, with stiff cores that limit length changes, show that only low pressures allow short loop radii without local buckling. Hagfishes represent ideal organisms for studying loose skin function because their skins seem to fit in all functionally adaptive categories.
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

AbstractThe 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

Abstract
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

AbstractPurpose: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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.
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

Abstract
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

Abstract
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

AbstractCompartment 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

Abstract
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

Abstract
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

AbstractMyoelectric 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.