bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repartnering Following Gray Divorce: The Roles of Resources and Constraints for Women and Men
Authors: Brown Susan L. , Lin I-Fen , Hammersmith Anna M. , Wright Matthew R. 
Published: January 2019

Abstract
The doubling of the gray divorce rate (i.e., divorce at age 50 or older) over the past few decades portends growth in later-life repartnering, yet little is known about the mechanisms undergirding decisions to repartner after gray divorce. Using data from the 1998–2014 Health and Retirement Study, we examined women’s and men’s likelihoods of forming a remarriage or cohabiting union following gray divorce by estimating competing risk multinomial logistic regression models using discrete-time event history data. About 22 % of women and 37 % of men repartnered within 10 years after gray divorce. Repartnering more often occurred through cohabitation than remarriage, particularly for men. Resources such as economic factors, health, and social ties were linked to repartnering, but constraints captured by the contours of the marital biography were also salient, underscoring the distinctive features of union formation in later life.
Evaluation of a virtual reality enhanced bullying prevention curriculum pilot trial
Authors: Ingram Katherine M. , Espelage Dorothy L. , Merrin Gabriel J. , Valido Alberto , Heinhorst Jennifer , Joyce Mary 
Published: January 2019

ABSTRACTIntroductionBullying is a widely prevalent public health and safety issue that can have serious long‐term consequences for youth. Given the limited efficacy of traditional bullying prevention programs, a need exists for novel, theoretically informed, prevention programming. Construal Level Theory provides a useful framework.MethodsThis study evaluated a pseudo‐randomized pilot trial of a virtual reality enhanced bullying prevention program among middle school students (N = 118) in the Midwest United States. Two models were proposed. The first predicts reductions in bullying behavior (traditional bullying, cyberbullying, relational aggression) at post‐test, mediated by changes in empathy in the virtual reality condition compared to the control condition. The second predicts increases in school belonging and willingness to intervene as an active bystander at post‐test, mediated by changes in empathy in the virtual reality condition compared to the control condition.ResultsThe virtual reality condition yielded increased empathy from pre‐to post‐intervention compared to the control condition. Through the mediating role of empathy, changes in the desirable directions were also observed for traditional bullying, sense of school belonging, and willingness to intervene as an active bystander, but not for cyberbullying or relational aggression.ConclusionsThe scope and practical limitations of the virtual reality trial prevented a larger scale and more rigorous evaluation; however, results justify an expanded examination of virtual reality as a youth violence prevention tool.
Why Moral Status Matters for Metaethics
Authors: ARRUDA CAROLINE T. 
Published: January 2019

AbstractI show that an overlooked feature of our moral life—moral status—provides a route to vindicating naturalist moral realism in much the same way that the Humean theory of motivation and judgment internalism are used to undermine it. Moral status presents two explanatory burdens for metaethical views. First, a given view must provide an ecumenical explanation of moral status, which does not depend on the truth of its metaethical claims (say, that there are mind-independent facts about moral status). Second, its explanation must be consistent with persistent normative ethical disagreement about what constitutes moral status. I conclude that naturalist moral realism succeeds, while quasi-realism fails because it cannot meet the latter requirement. This argument has three results: we have a new route for metaethical vindication more generally and for naturalist moral realism in particular; quasi-realism's plausibility is undermined by an inability to explain disagreement, but not for the familiar reasons.
The interplay between childhood trauma, cognitive biases, psychotic-like experiences and depression and their additive impact on predicting lifetime suicidal behavior in young adults
Authors: Gawęda Łukasz , Pionke Renata , Krężołek Martyna , Frydecka Dorota , Nelson Barnaby , Cechnicki Andrzej 
Published: January 2019

AbstractBackgroundChildhood trauma, psychosis risk, cognition, and depression have been identified as important risk markers for suicidal behaviors. However, little is known about the interplay between these distal and proximal markers in influencing the risk of suicide. We aim to investigate the interplay between childhood trauma, cognitive biases, psychotic-like experiences (PLEs) and depression in predicting suicidal behaviors in a non-clinical sample of young adults.MethodsIn total, 3495 young adults were recruited to an online computer-assisted web interview. We used the Prodromal Questionnaire to assess PLEs. Childhood trauma was assessed with the Traumatic Experience Checklist (three items) and Childhood Experience of Care and Abuse Questionnaire (CECA.Q, three items). Cognitive biases were assessed with a short version of the Davos Assessment of Cognitive Biases Scale. Suicidality, psychiatric diagnoses, and substance use were screened with a self-report questionnaire.ResultsChildhood trauma, as well as PLEs, was associated with an approximately five-fold increased risk of suicidal thoughts and plans as well as suicide attempts. Participants with depression were six times more likely to endorse suicidal behaviors. Path analysis revealed that PLEs, depression and cognitive biases are significant mediators of the relationship between trauma and suicidal behaviors. The model explained 44.6% of the variance in lifetime suicidality.ConclusionsCognitive biases, PLEs, and depression partially mediate the relationship between childhood trauma and suicidal behaviors. The interplay between distal and proximal markers should be recognized and become part of clinical screening and therapeutic strategies for preventing risk of suicidality.
The Challenge of Implementing the Belt and Road Initiative in the Middle East: Connectivity Projects under Conditions of Limited Political Engagement
Authors: Evron Yoram 
Published: January 2019

AbstractSceptics query China's economic and political ability to realize its Belt and Road Initiative (BRI). Less attention has been paid to BRI's implications for one of the defining features of China's foreign policy: low engagement in areas beyond its traditional sphere of influence. The Middle East is such a case. Addressing this issue, the article explores the mutual impact of China's low political involvement in the Middle East and BRI's realization. Distinguishing cross-border connectivity projects from other BRI-associated activities, the article examines the challenges to executing BRI-related projects in Israel. It finds that realizing connectivity projects – the essence of the BRI vision – will require China to increase its regional engagement, a shift that it has so far avoided.
Spatial analyses of occurrence data of crop wild relatives (CWR) taxa as tools for selection of sites for conservation of priority CWR in Zambia
Authors: Ng'uni Dickson , Munkombwe Graybill , Mwila Godfrey , Gaisberger Hannes , Brehm Joana Magos , Maxted Nigel , Kell Shelagh , Thormann Imke 
Published: January 2019

AbstractCrop wild relatives (CWR) are valuable gene pools for crop improvement and offer unique potential and opportunity for enhancing food security and adaptation to climate change. However, current actions towards conservation of plant genetic resources in Zambia do not adequately cover CWR occurring in the country. The article describes the process leading to the development of a national strategic action plan (NSAP) for the conservation and sustainable use of priority CWR in Zambia. Based on 59 prioritized crops, a partial checklist of 459 CWR taxa was generated from the national flora checklist of 6305 taxa. The generated CWR taxa were prioritized based on the socio-economic value of the related crop, their utilization potential in crop improvement, relative distribution and threat status to produce 30 prioritized CWR taxa. Occurrence data were compiled for all CWR inventory taxa and used in spatial analyses to establish species distribution, species richness, gaps inin situconservation and genebank collections, and to identify priority sites forin situconservation andex situcollecting. Consistent with the national developmental agenda, along with the contribution of national stakeholders, spatial analyses of occurrence data of priority CWR taxa are valuable input for the development of the NSAP for the conservation and sustainable use of the priority CWR.
Eine meta-analytische Untersuchung des sozioökonomischen Status als Risikofaktor für postpartale Depression
Authors: Hehlmann Miriam I. , Schaan Violetta , Rubel Julian 
Published: January 2019

Zusammenfassung. Theoretischer Hintergrund: 13 % aller Gebärenden leiden an postpartalen Depressionen (PPD), einer Krankheit mit bedeutsamen gesundheitlichen und sozialen Konsequenzen für die Betroffenen. Zurzeit werden PPD jedoch häufig spät erkannt und behandelt. Eine Früherkennung könnte durch die Identifikation spezifischer Vulnerabilitätsfaktoren erleichtert werden. Niedriger sozioökonomischen Status (SES) wurde als potenzieller Risikofaktor für Depressionen diskutiert ( Lorant et al., 2003 ). Fragestellung: Das Ziel der vorliegenden Meta-Analyse ist die systematische Untersuchung, ob niedriger SES mit einem erhöhten Risiko für die Entwicklung einer PPD einhergeht. Methode: Um die Vergleichbarkeit der eingeschlossenen Studien zu gewährleisten, werden die internationalen Empfehlungen zur Erfassung des SES von Jöckel et al. (1998) als Inklusionskriterium herangezogen. Die identifizierten Studien werden meta-analytisch zusammengefasst. Ergebnisse: Weder Bildung mit einem relativen Risiko (RR) = 1.14 (95 % KI = 0.95, 1.45) noch Einkommen mit RR = 1.32 (95 % KI = 0.99, 1.74) waren signifikant mit der Entwicklung einer PPD assoziiert. Schlussfolgerung: Es wurde kein Zusammenhang zwischen dem erhöhten Risiko eine PPD zu entwickeln und dem Bildungsniveau oder dem Einkommen gefunden. Die vorliegende Studie macht auf die gravierenden methodischen Mängel im Bereich der Forschung von PPD und dem SES aufmerksam.
Resistin facilitates VEGF-A-dependent angiogenesis by inhibiting miR-16-5p in human chondrosarcoma cells
Authors: Chen Shiou-Sheng , Tang Chih-Hsin , Chie Meng-Ju , Tsai Chun-Hao , Fong Yi-Chin , Lu Yung-Chang , Chen Wei-Cheng , Lai Cheng-Ta , Wei Chuan-Yen , Tai Huai-Ching , Chou Wen-Yi , Wang Shih-Wei 
Published: January 2019

AbstractResistin is an adipokine that is associated with obesity, inflammation, and various cancers. Chondrosarcomas are primary malignant bone tumors that have a poor prognosis. VEGF-A is a critical angiogenic factor that is known to promote angiogenesis and metastasis in chondrosarcoma. It is unknown as to whether resistin affects human chondrosarcoma angiogenesis. In this study, we show how resistin promotes VEGF-A expression and subsequently induces angiogenesis of endothelial progenitor cells (EPCs). Resistin treatment activated the phosphatidylinositol-3-kinase (PI3K) and Akt signaling pathways, while PI3K and Akt inhibitors or siRNA diminished resistin-induced VEGF-A expression. In vitro and in vivo studies revealed the downregulation of micro RNA (miR)-16-5p in resistin-induced VEGF-A expression and EPCs angiogenesis. We also found a positive correlation between resistin and VEGF-A expression, and a negative correlation between resistin and VEGF-A with miR-16-5p in chondrosarcoma patients. These findings reveal that resistin facilitates VEGF-A expression and angiogenesis through the inhibition of miR-16-5p expression via PI3K/Akt signaling cascades. Resistin may be a promising target in chondrosarcoma angiogenesis.
CD44v6 engages in colorectal cancer progression
Authors: Ma Lixin , Dong Lihua , Chang Pengyu 
Published: January 2019

AbstractCD44 is a transmembrane glycoprotein. When the CD44 gene is expressed, its pre-messenger RNA (mRNA) can be alternatively spliced into mature mRNAs that encode several CD44 isoforms. The mRNA assembles with ten standard exons, and the sixth variant exon encodes CD44v6, which engages in a variety of biological processes, including cell growth, apoptosis, migration, and angiogenesis. Mechanistically, CD44v6 interacts with hyaluronic acid (HA) or osteopontin, or it acts as a coreceptor for various cytokines, such as epidermal growth factor, vascular endothelial growth factor, hepatocyte growth factor, and C-X-C motif chemokine 12. In this context, the receptor tyrosine kinase or G protein-coupled receptor-associated signaling pathways, including mitogen-activated protein kinase/extracellular-signal-regulated kinase and phosphoinositide-3-kinase/Akt, are activated. Using these actions, homeostasis or regeneration can be facilitated among normal tissues. However, overexpression of the mature mRNA encoding CD44v6 can induce cancer progression. For example, CD44v6 assists colorectal cancer stem cells in colonization, invasion, and metastasis. Overexpression of CD44v6 predicts poor prognosis in patients with colorectal cancer, as patients with a large number of CD44v6-positive cells in their tumors are generally diagnosed at late stages. Thus, the clinical significance of CD44v6 in colorectal cancer deserves consideration. Preclinical results have indicated satisfactory efficacies of anti-CD44 therapy among several cancers, including prostate cancer, pancreatic cancer, and gastric cancer. Moreover, clinical trials aiming to evaluate the pharmacokinetics, pharmacodynamics, efficacy, and toxicity of a commercialized anti-CD44 monoclonal antibody developed by Roche (RO5429083) have been conducted among patients with CD44-expressing malignant tumors, and a clinical trial focusing on the dose escalation of this antibody is ongoing. Thus, we are hopeful that anti-CD44 therapy will be applied in the treatment of colorectal cancer in the future.
The CHD6 chromatin remodeler is an oxidative DNA damage response factor
Authors: Moore Shaun , Berger N. Daniel , Luijsterburg Martijn S. , Piett Cortt G. , Stanley Fintan K. T. , Schräder Christoph U. , Fang Shujuan , Chan Jennifer A. , Schriemer David C. , Nagel Zachary D. , van Attikum Haico , Goodarzi Aaron A. 
Published: January 2019

AbstractCell survival after oxidative DNA damage requires signaling, repair and transcriptional events often enabled by nucleosome displacement, exchange or removal by chromatin remodeling enzymes. Here, we show that Chromodomain Helicase DNA-binding protein 6 (CHD6), distinct to other CHD enzymes, is stabilized during oxidative stress via reduced degradation. CHD6 relocates rapidly to DNA damage in a manner dependent upon oxidative lesions and a conserved N-terminal poly(ADP-ribose)-dependent recruitment motif, with later retention requiring the double chromodomain and central core. CHD6 ablation increases reactive oxygen species persistence and impairs anti-oxidant transcriptional responses, leading to elevated DNA breakage and poly(ADP-ribose) induction that cannot be rescued by catalytic or double chromodomain mutants. Despite no overt epigenetic or DNA repair abnormalities, CHD6 loss leads to impaired cell survival after chronic oxidative stress, abnormal chromatin relaxation, amplified DNA damage signaling and checkpoint hypersensitivity. We suggest that CHD6 is a key regulator of the oxidative DNA damage response.
Neuroinflammation-induced lymphangiogenesis near the cribriform plate contributes to drainage of CNS-derived antigens and immune cells
Authors: Hsu Martin , Rayasam Aditya , Kijak Julie A. , Choi Yun Hwa , Harding Jeffrey S. , Marcus Sarah A. , Karpus William J. , Sandor Matyas , Fabry Zsuzsanna 
Published: January 2019

AbstractThere are no conventional lymphatic vessels within the CNS parenchyma, although it has been hypothesized that lymphatics near the cribriform plate or dura maintain fluid homeostasis and immune surveillance during steady-state conditions. However, the role of these lymphatic vessels during neuroinflammation is not well understood. We report that lymphatic vessels near the cribriform plate undergo lymphangiogenesis in a VEGFC – VEGFR3 dependent manner during experimental autoimmune encephalomyelitis (EAE) and drain both CSF and cells that were once in the CNS parenchyma. Lymphangiogenesis also contributes to the drainage of CNS derived antigens that leads to antigen specific T cell proliferation in the draining lymph nodes during EAE. In contrast, meningeal lymphatics do not undergo lymphangiogenesis during EAE, suggesting heterogeneity in CNS lymphatics. We conclude that increased lymphangiogenesis near the cribriform plate can contribute to the management of neuroinflammation-induced fluid accumulation and immune surveillance.
Controlling the shape of 3D microstructures by temperature and light
Authors: Hippler Marc , Blasco Eva , Qu Jingyuan , Tanaka Motomu , Barner-Kowollik Christopher , Wegener Martin , Bastmeyer Martin 
Published: January 2019

AbstractStimuli-responsive microstructures are critical to create adaptable systems in soft robotics and biosciences. For such applications, the materials must be compatible with aqueous environments and enable the manufacturing of three-dimensional structures. Poly(N-isopropylacrylamide) (pNIPAM) is a well-established polymer, exhibiting a substantial response to changes in temperature close to its lower critical solution temperature. To create complex actuation patterns, materials that react differently with respect to a stimulus are required. Here, we introduce functional three-dimensional hetero-microstructures based on pNIPAM. By variation of the local exposure dose in three-dimensional laser lithography, we demonstrate that the material parameters can be altered on demand in a single resist formulation. We explore this concept for sophisticated three-dimensional architectures with large-amplitude and complex responses. The experimental results are consistent with numerical calculations, able to predict the actuation response. Furthermore, a spatially controlled response is achieved by inducing a local temperature increase by two-photon absorption of focused light.
Kinetic analysis of multistep USP7 mechanism shows critical role for target protein in activity
Authors: Kim Robbert Q. , Geurink Paul P. , Mulder Monique P. C. , Fish Alexander , Ekkebus Reggy , El Oualid Farid , van Dijk Willem J. , van Dalen Duco , Ovaa Huib , van Ingen Hugo , Sixma Titia K. 
Published: January 2019

AbstractUSP7 is a highly abundant deubiquitinating enzyme (DUB), involved in cellular processes including DNA damage response and apoptosis. USP7 has an unusual catalytic mechanism, where the low intrinsic activity of the catalytic domain (CD) increases when the C-terminal Ubl domains (Ubl45) fold onto the CD, allowing binding of the activating C-terminal tail near the catalytic site. Here we delineate how the target protein promotes the activation of USP7. Using NMR analysis and biochemistry we describe the order of activation steps, showing that ubiquitin binding is an instrumental step in USP7 activation. Using chemically synthesised p53-peptides we also demonstrate how the correct ubiquitinated substrate increases catalytic activity. We then used transient reaction kinetic modelling to define how the USP7 multistep mechanism is driven by target recognition. Our data show how this pleiotropic DUB can gain specificity for its cellular targets.
Anti-breast Cancer Activity of SPG-56 from Sweet Potato in MCF-7 Bearing Mice in Situ through Promoting Apoptosis and Inhibiting Metastasis
Authors: Li Zhaoxing , Yu Yang , Wang Meimei , Xu Heshan , Han Bing , Jiang Pu , Ma Hang , Li Yuanfeng , Tian Cheng , Zhou Deqi , Li Xuegang , Ye Xiaoli 
Published: January 2019

AbstractSPG-56 is a newly isolated glycoprotein from sweet potatoes (Zhongshu NO. 1), but its value for suppressing breast cancer progression remains unknown. This study was designed to investigate the potential anti-cancer effects of SPG-56, which consists of 2.9% sugar and 97.1% protein. The effects of SPG-56 on the proliferation and apoptosis of breast cancer cells were determined using CCK-8 and Hoechst 33342 assays and flow cytometry, after staining with Annexin V and PI respectively. The activities of SPG-56 against breast cancer were examined using female BALB/c nude mice orthotopically implanted with human breast carcinoma cells of the types MCF-7 and 4T1-Luc. The cellular experiments showed that SPG-56 inhibited proliferation and promoted apoptosis of MCF-7 cells dose- and time-dependently. Oral administration of SPG-56 significantly suppressed the development of MCF-7 tumor cells (P < 0.01) as compared with an untreated group. The serum tumor markers CEA, CA125 and CA153 in a 240 mg/kg/d SPG-56 decreased by 54.8%, 91.8%, and 90.3%, respectively. The experiments further demonstrated that SPG-56 inhibited the metastasis of breast cancer in MCF-7 and 4T1-bearing mice by altering the expression of MMP2, MMP9, VEGF, Occludin and Claudin. It is concluded that SPG-56 may have potential as a novel anti-tumor candidate for breast cancer.
Stigmasterol accumulation causes cardiac injury and promotes mortality
Authors: Tao Caroline , Shkumatov Artem A. , Alexander Shawn T. , Ason Brandon L. , Zhou Mingyue 
Published: January 2019

AbstractCardiovascular disease is expected to remain the leading cause of death worldwide despite the introduction of proprotein convertase subtilisin/kexin type 9 inhibitors that effectively control cholesterol. Identifying residual risk factors for cardiovascular disease remains an important step for preventing and clinically managing the disease. Here we report cardiac injury and increased mortality occurring despite a 50% reduction in plasma cholesterol in a mouse model of phytosterolemia, a disease characterized by elevated levels of dietary plant sterols in the blood. Our studies show accumulation of stigmasterol, one of phytosterol species, leads to left ventricle dysfunction, cardiac interstitial fibrosis and macrophage infiltration without atherosclerosis, and increased mortality. A pharmacological inhibitor of sterol absorption prevents cardiac fibrogenesis. We propose that the pathological mechanism linking clinical sitosterolemia to the cardiovascular outcomes primarily involves phytosterols-induced cardiac fibrosis rather than cholesterol-driven atherosclerosis. Our studies suggest stigmasterol is a potent and independent risk factor for cardiovascular disease.
Perspective: The promises of a holistic view of proteins—impact on antibody engineering and drug discovery
Authors: Phua Ser-Xian , Chan Kwok-Fong , Su Chinh Tran-To , Poh Jun-Jie , Gan Samuel Ken-En 
Published: January 2019

AbstractThe reductionist approach is prevalent in biomedical science. However, increasing evidence now shows that biological systems cannot be simply considered as the sum of its parts. With experimental, technological, and computational advances, we can now do more than view parts in isolation, thus we propose that an increasing holistic view (where a protein is investigated as much as a whole as possible) is now timely. To further advocate this, we review and discuss several studies and applications involving allostery, where distant protein regions can cross-talk to influence functionality. Therefore, we believe that an increasing big picture approach holds great promise, particularly in the areas of antibody engineering and drug discovery in rational drug design.