bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic Opportunities for Intestinal Angioectasia‐ Targeting PPARγ and Oxidative Stress
Authors: Sarangdhar Mayur , Yacyshyn Mary B. , Gruenzel Andrew R. , Engevik Melinda A. , Harris Nathaniel L. , Aronow Bruce J. , Yacyshyn Bruce R. 
Published: October 2020

Recurrent and acute bleeding from intestinal tract angioectasia (AEC) presents a major challenge for clinical intervention. Current treatments are empiric, with frequent poor clinical outcomes. Improvements in understanding the pathophysiology of these lesions will help guide treatment. Using data from the US Food and Drug Administration (FDA)’s Adverse Event Reporting System (FAERS), we analyzed 12 million patient reports to identify drugs inversely correlated with gastrointestinal bleeding and potentially limiting AEC severity. FAERS analysis revealed that drugs used in patients with diabetes and those targeting PPARγ‐related mechanisms were associated with decreased AEC phenotypes (P < 0.0001). Electronic health records (EHRs) at University of Cincinnati Hospital were analyzed to validate FAERS analysis. EHR data showed a 5.6% decrease in risk of AEC and associated phenotypes in patients on PPARγ agonists. Murine knockout models of AEC phenotypes were used to construct a gene‐regulatory network of candidate drug targets and pathways, which revealed that wound healing, vasculature development and regulation of oxidative stress were impacted in AEC pathophysiology. Human colonic tissue was examined for expression differences across key pathway proteins, PPARγ, HIF1α, VEGF, and TGFβ1. In vitro analysis of human AEC tissues showed lower expression of PPARγ and TGFβ1 compared with controls (0.55 ± 0.07 and 0.49 ± 0.05). National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) RNA‐Seq data was analyzed to substantiate human tissue findings. This integrative discovery approach showing altered expression of key genes involved in oxidative stress and injury repair mechanisms presents novel insight into AEC etiology, which will improve targeted mechanistic studies and more optimal medical therapy for AEC.
Optimizing the Therapeutic Window of Targeted Drugs in Oncology: Potency‐Guided First‐in‐Human Studies
Authors: Goldstein Matthew J. , Peters Malte , Weber Barbara L. , Davis Charles B. 
Published: October 2020

Many targeted therapies are administered at or near the maximum tolerated dose (MTD). With the advent of precision medicine, a larger therapeutic window is expected. Therefore, dose optimization will require a new approach to early clinical trial design. We analyzed publicly available data for 21 therapies targeting six kinases, and four poly (ADP‐ribose) polymerase inhibitors, focusing on potency and exposure to gain insight into dose selection. The free average steady‐state concentration (Css) at the approved dose was compared to the in vitro cell potency (half‐maximal inhibitory concentration (IC50)). Average steady‐state area under the plasma concentration‐time curve, the fraction unbound drug in plasma, and the cell potency were taken from the US drug labels, US and European regulatory reviews, and peer‐reviewed journal articles. The Css was remarkably similar to the IC50. The median Css/IC50 value was 1.2, and 76% of the values were within 3‐fold of unity. However, three drugs (encorafenib, erlotinib, and ribociclib) had a Css/IC50 value > 25. Seven other therapies targeting the same 3 kinases had much lower Css/IC50 values ranging from 0.5 to 4. These data suggest that these kinase inhibitors have a large therapeutic window that is not fully exploited; lower doses may be similarly efficacious with improved tolerability. We propose a revised first‐in‐human trial design in which dose cohort expansion is initiated at doses less than the MTD when there is evidence of clinical activity and Css exceeds a potency threshold. This potency‐guided approach is expected to maximize the therapeutic window thereby improving patient outcomes.
A review ofCD30expression in cutaneous neoplasms
Authors: Kampa Franziska , Mitteldorf Christina 
Published: October 2020

AbstractBackgroundThe surface protein CD30 is a therapeutic target of monoclonal antibody therapy. Knowledge of the frequency of CD30 expression and its prognostic relevance is therefore interesting, not only in lymphoproliferative disorders (LPD) but also in solid tumors of the skin.MethodsA review was completed in PubMed for all published reports of CD30 expression in cutaneous lymphomas, mastocytosis, epithelial tumors and sarcomas from 1982 to April 2019. Only accessible articles in English and German were considered. Entities with an expected CD30 expression, such as CD30‐positive LPD, were not evaluated.ResultsThe electronic research identified 1091 articles and a further 34 articles were obtained from manual bibliographic reference. Overall 91 articles were included that examined CD30 expression in various entities of cutaneous neoplasms and matched the inclusion criteria.ConclusionApart from cutaneous CD30‐positive LPD, the best‐studied group for CD30 expression was mycosis fungoides (MF). CD30 positivity was found in 32% of classical (patch and plaque stage) and in 59.4% cases of transformed MF. CD30 was also frequently expressed in cutaneous mastocytosis (96.5%). In solid tumors, some single reports describe CD30 expression by tumor cells, but CD30‐reactive lymphocytes were frequently observed in the tumor microenvironment (TME), especially in keratoacanthoma (KA).
Interventions for people at ultra‐high risk for psychosis: A systematic review of economic evaluations
Authors: Ologundudu Olajumoke M. , Lau Tammy , Palaniyappan Lena , Ali Shehzad , Anderson Kelly K. 
Published: October 2020

AbstractAimPsychotic disorders have long‐term negative consequences for functioning and quality of life. Ultra‐high risk (UHR) programs aim to identify and treat people during the prodromal period before their first psychotic episode. Though studies on the clinical effectiveness of treating prodromal symptoms in people at UHR for psychosis exist, no review has exclusively and comprehensively evaluated the economic impact of UHR programs. Our objective was to systematically review the literature on economic evaluations of UHR programs.MethodsWe searched the Cochrane, EMBASE, MEDLINE, and PsycInfo electronic databases, in addition to grey literature, from inception to March 2020 to identify economic evaluations of UHR programs. We included all cost and cost‐effectiveness studies of interventions for people at UHR. The data were synthesized qualitatively, and a risk of bias assessment was performed.ResultsOf the 1916 articles retrieved, six studies met our inclusion criteria. These included three cost analysis studies and three cost‐effectiveness studies. Five studies were conducted from the health system perspective and the time horizon varied between six months and ten years. Only two reported quality‐adjusted life‐years (QALYs) as their outcome. Overall, all cost‐effectiveness studies and one cost analysis suggested that UHR programs were cost‐effective and cost saving, respectively. The risk of bias assessment suggested moderate levels of bias across all studies.ConclusionEconomic evaluations of UHR programs varied in terms of outcomes and length of follow‐up; however, most studies found them to be cost‐effective. Future studies would benefit from long‐term evaluations of UHR programs and consistent valuation of outcomes.
A Cross‐Lagged Panel Model of Coparental Interaction and Father Involvement Shortly After Divorce
Authors: Petren Raymond E. , Ferraro Anthony J. , Zimmermann McKenzie L. , Anthony Michael V. , Pasley Kay 
Published: October 2020

ObjectiveTo examine (a) associations among coparental interaction (cooperation, overt conflict, covert conflict) and father involvement (engagement, in‐kind financial support), (b) associations among the three dimensions of coparental interaction, and (c) associations among the two dimensions of father involvement, shortly after divorce.BackgroundFamily relationships change shortly after divorce, yet little research has examined coparental interaction and father involvement shortly after divorce and overt and covert conflict are often not included.MethodMothers and fathers from different families in a southeastern state (N = 194) participated within 3 months after divorce (Time 1) and 3 to 6 months later (Time 2). A cross‐lagged structural equation model was used to examine reciprocal associations among dimensions of coparental interaction and father involvement.ResultsHigher father engagement and lower overt conflict (Time 1) were associated with higher cooperation (Time 2). Covert conflict was associated with later overt conflict. In‐kind support was not associated with later father engagement or coparental interaction. No reciprocal associations among variables were found.ConclusionCoparental conflict and father engagement may be salient to the development of later coparental relationships following divorce.ImplicationsPractitioners can help parents manage conflict and encourage father engagement to foster healthy coparental relationships after divorce.
CHRISTIAN ART, MASCULINE CRISIS, AND THE THREAT OF JEWISH CONVERSION IN BERTHA PAPPENHEIM'S SHORT STORIES
Authors: Davies Peter 
Published: October 2020

AbstractThis article discusses a number of short stories by the Austrian‐Jewish writer and feminist campaigner Bertha Pappenheim, showing how the author uses literary narratives to explore anxieties about the perceived threat of Jewish–Christian conversion at the beginning of the twentieth century. In a period of intense debate about the future of Jewish communities and identities within a rapidly modernising and secularising Christian majority culture, Pappenheim campaigned for the protection of Jewish orphans from aggressive missionaries, and for a feminist political and social practice that emerged from within Jewish traditions, rather than rejecting them. Literary narratives allowed her to explore areas of ambivalence and anxiety about this project. She chooses to do this through male protagonists, all of whom have artistic ambitions and experience moments of crisis and failure in encounters with Christian art; threats to Jewish identity are figured in terms of the aesthetic temptations of the embodied, sensual art of Christianity, which lead to decadence, isolation, and death. To set against this, Pappenheim proposes tentatively a mode of socially useful narrative, encoded as specifically Jewish, which offers the potential to preserve the tradition against the shocks of modernity.
Designing regional innovation systems in transitional economies: A creative ecosystem approach
Authors: Gasparin Marta , Quinn Martin 
Published: October 2020

AbstractRegional Innovation Systems (RIS) have become a policy panacea for states looking to develop their economies. However, much of the research on RIS is from Western developed economies, which have established infrastructures and institutional governance networks. Yet, in transitional economies, the growth rate in some parts of the economy is so rapid that policy makers and institutions are unable to record changes as they occur, including the emergence of new economic sectors, such as the creative industries. This results in knowledge gaps, leading to an inability to understand, identify or react to the needs of those nascent sectors. Our research paper, through the analysis of creative industries in Vietnam, proves that taking a creative ecosystems approach to designing RIS will bridge these knowledge gaps by providing a mechanism through which information can be collated and fed into the policy process. Our paper facilitates this process by developing a model to understand the characteristics of the creative ecosystem and as well as a flipped model of policy diffusion to allow bottom‐up development of policy in transitional economies. We then discuss how these models can be used by policy makers to design a more informed RIS to meet the needs of the sector.
The Politics of Exhaustion and the Externalization of British Border Control. An Articulation of a Strategy Designed to Deter, Control and Exclude
Authors: Welander Marta 
Published: October 2020

AbstractIn response to contemporary forms of human mobility, there has been a continued hardening of borders seeking to deter, control and exclude certain groups of people from entering nation states in Europe, North America and Australasia. Within this context, a disconcerting evolution of new and increasingly sophisticated forms of border control measures have emerged, which often play out within bilateral arrangements of “externalised” or “offshore” border controls. Drawing on extensive first‐hand field research among displaced people in Calais, Paris and Brussels in 2016–2019, this paper argues that the externalization of the British border to France is contingent upon a harmful strategy, which can be understood as the “politics of exhaustion.” This is a raft of (micro) practices and methods strategically aimed to deter, control and exclude certain groups of people on the move who have been profiled as “undesirable,” with a detrimental (un)intended impact on human lives.
Prediction of a competing endogenous RNA co‐expression network as a prognostic marker in glioblastoma
Authors: Peng Qunlong , Li Runmin , Li Ying , Xu Xiaoqian , Ni Wensi , Lin Huiran , Ning Liang 
Published: October 2020

AbstractDue to its high proliferation capacity and rapid intracranial spread, glioblastoma (GBM) has become one of the least curable malignant cancers. Recently, the competing endogenous RNAs (ceRNAs) hypothesis has become a focus in the researches of molecular biological mechanisms of cancer occurrence and progression. However, there is a lack of correlation studies on GBM, as well as a lack of comprehensive analyses of GBM molecular mechanisms based on high‐throughput sequencing and large‐scale sample sizes. We obtained RNA‐seq data from The Cancer Genome Atlas (TCGA) and Genotype‐Tissue Expression (GTEx) databases. Further, differentially expressed mRNAs were identified from normal brain tissue and GBM tissue. The similarities between the mRNA modules with clinical traits were subjected to weighted correlation network analysis (WGCNA). With the mRNAs from clinical‐related modules, a survival model was constructed by univariate and multivariate Cox proportional hazard regression analyses. Thereafter, we carried out Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, we predicted interactions between lncRNAs, miRNAs and mRNAs by TargetScan, miRDB, miRTarBase and starBase. We identified 2 lncRNAs (NORAD, XIST), 5 miRNAs (hsa‐miR‐3613, hsa‐miR‐371, hsa‐miR‐373, hsa‐miR‐32, hsa‐miR‐92) and 2 mRNAs (LYZ, PIK3AP1) for the construction of a ceRNA network, which might act as a prognostic biomarker of GBM. Combined with previous studies and our enrichment analysis results, we hypothesized that this ceRNA network affects immune activities and tumour microenvironment variations. Our research provides novel aspects to study GBM development and treatment.
Identification of a prognostic gene signature based on an immunogenomic landscape analysis of bladder cancer
Authors: Luo Yongwen , Chen Liang , Zhou Qiang , Xiong Yaoyi , Wang Gang , Liu Xuefeng , Xiao Yu , Ju Lingao , Wang Xinghuan 
Published: October 2020

AbstractCancer immune plays a critical role in cancer progression. Tumour immunology and immunotherapy are one of the exciting areas in bladder cancer research. In this study, we aimed to develop an immune‐related gene signature to improve the prognostic prediction of bladder cancer. Firstly, we identified 392 differentially expressed immune‐related genes (IRGs) based on TCGA and ImmPort databases. Functional enrichment analysis revealed that these genes were enriched in inflammatory and immune‐related pathways, including in ‘regulation of signaling receptor activity’, ‘cytokine‐cytokine receptor interaction’ and ‘GPCR ligand binding’. Then, we separated all samples in TCGA data set into the training cohort and the testing cohort in a ratio of 3:1 randomly. Data set GSE13507 was set as the validation cohort. We constructed a prognostic six‐IRG signature with LASSO Cox regression in the training cohort, including AHNAK, OAS1, APOBEC3H, SCG2, CTSE and KIR2DS4. Six IRGs reflected the microenvironment of bladder cancer, especially immune cell infiltration. The prognostic value of six‐IRG signature was further validated in the testing cohort and the validation cohort. The results of multivariable Cox regression and subgroup analysis revealed that six‐IRG signature was a clinically independent prognostic factor for bladder cancer patients. Further, we constructed a nomogram based on six‐IRG signature and other clinicopathological risk factors, and it performed well in predict patients' survival. Finally, we found six‐IRG signature showed significant difference in different molecular subtypes of bladder cancer. In conclusions, our research provided a novel immune‐related gene signature to estimate prognosis for patients' survival with bladder cancer.
Non‐financial social determinants of diabetes among public assistance recipients in Japan: A cohort study
Authors: Nishioka Daisuke , Saito Junko , Ueno Keiko , Kondo Naoki 
Published: October 2020

AbstractAims/IntroductionPoverty is an important social determinant of diabetes. Poverty is a multidimensional concept including non‐financial difficulties, such as social isolation and exclusion from communities. Many countries provide financial social assistance programs for those in need. This study aimed to explore non‐financial social determinants of diabetes among public assistance recipients in Japan, by using linkage data of two municipal public assistance databases and medical assistance claim data.Materials and MethodsWe carried out a retrospective cohort study. Public assistance is provided to households below the poverty line to ensure their income security. We extracted recipients’ sociodemographic factors of January 2016 (household number and employment status as non‐financial social determinants of diabetes) and identified the incidence of diabetes diagnosis until December 2016 as the outcome.ResultsWe included the data of 2,698 younger individuals (aged <65 years) and 3,019 older individuals (aged >65 years). A multivariable Poisson regression, with a robust standard error estimator, showed that among 2,144 younger recipients at risk, unemployment and living alone were slightly associated with 1‐year cumulative incidence of diabetes diagnosis (adjusted incidence ratio 1.20, 95% confidence interval 0.93–1.54 and adjusted incidence ratio 1.15, 95% confidence interval 0.89–1.48, respectively). Among 2,181 older recipients at risk, there was no strong association between their sociodemographic factors and incidence of diabetes diagnosis.ConclusionsUnemployment and living alone might be additional risk factors for diabetes among younger public assistance recipients. Multidimensional supports assuring financial and non‐financial securities are required to prevent diabetes among people living in poverty.
The relation between the average diameter of CNTs on Ni–Cu @ a‐C:H catalyst with the optical absorption edge and the optical dispersion parameters
Authors: GOUDARZI S. , DALOUJI V. , SOLAYMANI S. 
Published: October 2020

SummaryIn this study, the average diameter of the grown CNTs on Ni–Cu NPs @ a‐C:H substrates were increased by increasing of Cu content. The obtained results indicated that by increase of Cu content, all films exhibited high‐absorption spectra; therefore, we were facing an increase in the energy gap of films. The values of dT/dλ and dR/dλ measurements for grown CNTs with 75% Cu shown that maximum values of optical band gap correspond to with values of 2.48 eV and 2.90 eV, respectively. It can be seen that with increase of average diameter of the grown CNTs, the values of Urbach energy of films were increased. The RBS and EDAX measurements were confirmed presence of Ni and Cu atoms into films. The films deposited with 75% Cu were more smooth. Films deposited with 75% Cu have more disordered. Films deposited with 75% Cu atoms have maximum values of the oscillator strength f and the dispersion energy Ed about of 0.108 eV2 and 0.0543 eV, respectively.
Hepatitis B surface antibody titres and hepatitis B reactivation with direct‐acting antiviral therapy for hepatitis C
Authors: Poola Shiva , Sanaka Sirish , Sewell Kerry , Tillmann Hans L. 
Published: October 2020

AbstractHBV reactivation can occur while undergoing direct‐acting antiviral (DAA) therapy for hepatitis C virus (HCV). The role of hepatitis B surface antibody (HBsAb) has not been systematically explored. Therefore, the purpose of this systematic review was to explore the role of the presence of HBsAb on the risk of HBV reactivation related to DAA therapy. We reviewed MEDLINE, CINAHL, EMBASE and Cochrane Central for studies on DAA therapy and data on HBsAb in patients with resolved hepatitis B (hepatitis B surface antigen–negative and hepatitis B core antibody–positive). We identified twenty‐nine reports: thirteen case reports with HBV reactivation (10 HBsAb‐negative and 3 HBsAb‐positive patients) and sixteen cohort studies totalling 2528 patients with resolved HBV infection (1429 HBsAb negative, 1099 HBsAb positive). Reactivation was found in 12 (0.8%) HBsAb‐negative and 7 (0.6%) HBsAb‐positive individuals of cohort studies. All but two HBV reactivation occurred in patients with HBsAb titre <30 iU/L. The presence of HBsAb showed a trend towards delayed reactivation (median 12 weeks vs 9.5 weeks; P = .07). Importantly, with the exception of a patient with escape variant and an HIV‐infected individual, no HBsAb‐positive individual demonstrated clinical reactivation. HBsAb presence seems to protect from clinical HBV reactivation related to DAA therapy. The most pronounced prevention for reactivation may require titres greater than 30 iU/L.
Mean–field moral hazard for optimal energy demand response management
Authors: Élie Romuald , Hubert Emma , Mastrolia Thibaut , Possamaï Dylan 
Published: October 2020

AbstractWe study the problem of demand response contracts in electricity markets by quantifying the impact of considering a continuum of consumers with mean–field interaction, whose consumption is impacted by a common noise. We formulate the problem as a Principal–Agent problem with moral hazard in which the Principal—she—is an electricity producer who observes continuously the consumption of a continuum of risk‐averse consumers, and designs contracts in order to reduce her production costs. More precisely, the producer incentivizes each consumer to reduce the average and the volatility of his consumption in different usages, without observing the efforts he makes. We prove that the producer can benefit from considering the continuum of consumers by indexing contracts on the consumption of one Agent and aggregate consumption statistics from the distribution of the entire population of consumers. In the case of linear energy valuation, we provide closed‐form expression for this new type of optimal contracts that maximizes the utility of the producer. In most cases, we show that this new type of contracts allows the Principal to choose the risks she wants to bear, and to reduce the problem at hand to an uncorrelated one.