bluuebunny/crossref_metadata_2025_split huggingface dataset:
BRD4 as a therapeutic target for nonfunctioning and growth hormone pituitary adenoma
Authors: Shi Chengzhang , Ye Zhao , Han Jie , Ye Xiaoqing , Lu Wenchao , Ji Chenxing , Li Zizhou , Ma Zengyi , Zhang Qilin , Zhang Yichao , He Wenqiang , Chen Zhengyuan , Cao Xiaoyun , Shou Xuefei , Zhou Xiang , Wang Yongfei , Zhang Zhaoyun , Li Yiming , Ye Hongying , He Min , Chen Hong , Cheng Haixia , Sun Jun , Cai Jianyong , Huang Chuanxin , Ye Fei , Luo Cheng , Zhou Bing , Ding Hong , Zhao Yao 
Published: April 2020

Abstract

Background
Nonfunctioning pituitary adenoma (NFPA) and growth hormone pituitary adenoma (GHPA) are major subtypes of pituitary adenomas (PAs). The primary treatment is surgical resection. However, radical excision remains challenging, and few effective medical therapies are available. It is urgent to find novel targets for the treatment. Bromodomain-containing protein 4 (BRD4) is an epigenetic regulator that leads to aberrant transcriptional activation of oncogenes. Herein, we investigated the pathological role of BRD4 and evaluated the effectiveness of BRD4 inhibitors in the treatment of NFPA and GHPA.

Methods
The expression of BRD4 was detected in NFPA, GHPA, and normal pituitary tissues. The efficacies of BRD4 inhibitors were evaluated in GH3 and MMQ cell lines, patient-derived tumor cells, and in vivo mouse xenograft models of PA. Standard western blots, real-time PCR, and flow cytometry experiments were performed to investigate the effect of BRD4 inhibitors on cell cycle progression, apoptosis, and the expression patterns of downstream genes.

Results
Immunohistochemistry studies demonstrated the overexpression of BRD4 in NFPA and GHPA. In vitro and in vivo studies showed that treatment with the BRD4 inhibitor ZBC-260 significantly inhibited the proliferation of PA cells. Further mechanistic studies revealed that ZBC-260 could downregulate the expression of c-Myc, B-cell lymphoma 2 (Bcl2), and related genes, which are vital factors in pituitary tumorigenesis.

Conclusion
In this study, we determined the overexpression of BRD4 in NFPA and GHPA and assessed the effects of BRD4 inhibitors on PA cells in vitro and in vivo. Our findings suggest that BRD4 is a promising therapeutic target for NFPA and GHPA.
Education Federalism
Authors: Robinson Kimberly Jenkins 
Published: April 2020

Abstract
Education federalism in the United States promotes state and local authority over education and a limited federal role. This approach to education federalism often serves as an influential yet underappreciated influence on education law and policy. This chapter explores how education federalism in the United States has evolved over time, its strengths and drawbacks, as well as how it has hindered efforts to advance equal educational opportunity. It argues that to achieve the nation’s education aims, education federalism must be restructured to embrace a more efficacious and efficient allocation of authority of education that embraces the policymaking strengths of each level of government while ensuring that all levels of government aim to achieve equitable access to an excellent education. The chapter proposes how to restructure education federalism to support a partnership between federal, state, and local governments to achieve equitable access to an excellent education. It also explains how this new approach to education federal could guide the United States toward a more impactful reauthorization of the Elementary and Secondary Education Act.
Climate Change Ethics and the Problem of End-State Solutions
Authors: Brooks Thom 
Published: April 2020

Abstract
How best to response to climate change is one of the most pressing challenges facing us all. Proposed solutions come in one of two approaches. The first is conservationist, seeking to minimize these effects by reducing, if not eliminating, them by bringing climate change to a stop. The second is focused specifically on adaptation mostly through technological advances to help us endure climate change by minimizing its effects. The dilemma for these proposed solutions is in their aim of being a solution to the problems that climate change brings. In short, they mistake the kind of challenge that climate change presents us. This is what I call the problem of “end-state” solutions. It is where we attempt to bring to an end a circumstance that might be influenced positively or otherwise by our activities, but beyond our full control. So to claim a so-called “solution” to such an ever-changing problem could make it better or worse without concluding it. If climate change is this kind of problem—and I will claim it is—then end-state “solutions” can be no more than a band-aid and the nature of our challenge is different, requiring an alternative future strategy. This chapter will set out how the problem of climate change is understood through attempted solutions that do not succeed. It concludes with some ideas about why this matters and the arising implications for how we should think about climate change justice beyond the false prism of end-state solutions.
The Human Right to Democracy and the Pursuit of Global Justice
Authors: Gilabert Pablo 
Published: April 2020

Abstract
This chapter addresses two interconnected questions about human rights and the pursuit of global justice: Is there a human right to democracy? How does the achievement of human rights, including the human right to democracy, contribute to the pursuit of global justice? The chapter answers the first question in the affirmative. It identifies three reasons for favoring democracy and explores the significance of those reasons for defending it as a human right. It answers important worries that acknowledging a human right to democracy would lead to intolerance and lack of respect for peoples’ self-determination, exaggerate the importance of democracy for securing other rights, generalize institutional arrangements that only work in some contexts, and tie human rights to specific ideas of freedom and equality that do not have the same universal appeal and urgency. Regarding the second question, the chapter distinguishes between basic and non-basic global justice and argues that democracy is significant for both. It claims that the fulfillment of human rights constitutes basic global justice, explains how a human right to democracy has significance for the legitimacy of international besides domestic institutions, and shows how forms of global democracy and the exploration of cosmopolitan and humanist commitments underlying human rights may enable and motivate the pursuit of non-basic demands of global justice (such as those concerning socioeconomic equality). The key claim in the chapter is that the fulfillment of the human right to democratic political empowerment is crucial for the pursuit of global justice.
Personal Responsibility and Global Injustice
Authors: Tan Kok-Chor 
Published: April 2020

Abstract
On what is called the “institutional approach” to justice, the primary duty that justice agents have in cases where just institutional arrangements are lacking is that of doing their part to help establish these arrangements. This special institutional focus in the context of institutional injustice can appear misdirected and insufficiently demanding. It is misdirected, according to some critics, because it wrongly fixates on means (i.e. institutional mechanisms) rather than ends (i.e. just outcomes); and it seems overly lax because it limits duties of justice to creating better institutions. With global injustice as its setting, this chapter tries to assuage these concerns.
Just Global Health
Authors: Tasioulas John , Vayena Effy 
Published: April 2020

Abstract
This chapter offers an integrated account of two strands of global health justice: health-related human rights and health-related common goods. After sketching a general understanding of the nature of human rights, it proceeds to explain both how individual human rights are to be individuated and the content of their associated obligations specified. With respect to both issues, the human right to health is taken as the primary illustration. It is argued that (1) the individuation of the right to health is fixed by reference to the subject matter of its corresponding obligations, and not by the interests it serves, and (2) the specification of the content of that right must be properly responsive to thresholds of possibility and burden. The chapter concludes by insisting that human rights cannot constitute the whole of global health justice and that, in addition, other considerations—including the promotion of health-related global public goods—should also shape such policy. Moreover, the relationship between human rights and common goods should not be conceived as mutually exclusive. On the contrary, there sometimes exists an individual right to some aspect of a common good, including a right to benefit from health-related common goods such as programs for securing herd immunity from diphtheria.
Trends in inequalities in childhood stunting in Ethiopia from 2000 to 2016: a cross sectional study
Authors: Zegeye Betregiorgis , Shibre Gebretsadik , Idriss-Wheeler Dina , Yaya Sanni 
Published: April 2020

Abstract

Background
The decrease in the magnitude of stunting over the past 20 years has been slow in Ethiopia. To date, in Ethiopia, the trends in and extent of inequality in stunting have not been investigated using methods suitably developed for disparity studies. This paper investigated both the extent and overtime dynamics of stunting inequality in Ethiopia over the last 17 years.

Methods
Using the World Health Organization’s Health Equity Assessment Toolkit software, data from the Ethiopia Demographic and Health surveys (EDHS) were analyzed between 2000 and 2016. The inequality analysis consisted of disaggregated rates of stunting using five equity stratifiers (economic status, education, residence, region and sex) and four summary measures (Difference, Population Attributable risk, Ratio and Absolute Concentration Index). A 95% uncertainty interval was constructed around point estimates to measure statistical significance.

Results
The study showed that both absolute and relative inequalities in stunting exist in all the studied years in Ethiopia. The inequality disfavors children of mothers who are poor, uneducated and living in rural areas and specific regions such as Amhara. The pro-rich (R = 1.2; 1.1, 1.3 in 2000 to R = 1.7; 1.4, 2 in 2016) and pro-educated (R = 1.6; 95%UI = 1.3, 1.9 in 2000 and R = 2.3; 95%UI = 1.5, 3 in 2011) inequalities slightly increased with time. Male children bear a disproportionately higher burden of stunting, and the disparity increased between the first and the last time points (PAR = −1.5 95%UI = −2.5, −0.6 in 2000 and PAR = −2.9 95%UI = −3.9, −1.9) based on complex measures but remained constant with simple measures (R = 1; 95%UI = 0.9, 1.1 in 2000 and R = 1.1 95%UI = 1, 1.2 in 2016). Similarly, both the sub-national regional and residence-related stunting disparities generally widened over time according to some of the inequality measures.

Conclusions
Stunting appeared to be highly prevalent among certain sub-groups (i.e. poor, uneducated and living in rural regions). The subpopulations experiencing excessively high stunting prevalence should be the focus of policy makers’ attention as they work to achieve the WHO 40% reduction in stunting target by 2025 and the UN Agenda 2030 for Sustainable Development Goals.
Increased expression of the transforming growth factor β–inducible gene HIC-5 in systemic sclerosis skin and fibroblasts: a novel antifibrotic therapeutic target
Authors: Piera-Velazquez Sonsoles , Fertala Jolanta , Huaman-Vargas Gonzalo , Louneva Natalia , Jiménez Sergio A 
Published: April 2020

AbstractObjectiveSSc is a systemic fibrotic disease affecting skin, numerous internal organs and the microvasculature. The molecular pathogenesis of SSc tissue fibrosis has not been fully elucidated, although TGF-β1 plays a crucial role. The Hic-5 protein encoded by the TGF-β1-inducible HIC-5 gene participates in numerous TGF-β-mediated pathways, however, the role of Hic-5 in SSc fibrosis has not been investigated. The aim of this study was to examine HIC-5 involvement in SSc tissue fibrosis.MethodsAffected skin from three patients with diffuse SSc and dermal fibroblasts cultured from affected and non-affected SSc skin were examined for HIC-5 and COL1A1 gene expression. Real-time PCR, IF microscopy, western blotting and small interfering RNA–mediated HIC-5 were performed.ResultsHIC-5 and COL1A1 transcripts and Hic-5, type 1 collagen (COL1) and α-smooth muscle actin (α-SMA) protein levels were increased in clinically affected SSc skin compared with normal skin and in cultured dermal fibroblasts from affected SSc skin compared with non-affected skin fibroblasts from the same patients. HIC-5 knockdown caused a marked reduction of COL1 production in SSc dermal fibroblasts.ConclusionHIC-5 expression is increased in affected SSc skin compared with skin from normal individuals. Affected SSc skin fibroblasts display increased HIC-5 and COL1A1 expression compared with non-affected skin fibroblasts from the same patients. Hic-5 protein was significantly increased in cultured SSc dermal fibroblasts. HIC-5 mRNA knockdown in SSc fibroblasts caused &gt;50% reduction of COL1 production. Although these are preliminary results owing to the small number of skin samples studied, they indicate that Hic-5 plays a role in the profibrotic activation of SSc dermal fibroblasts and may represent a novel molecular target for antifibrotic therapy in SSc.
Identifying 5 Common Psychiatric Disorders Associated Chemicals Through Integrative Analysis of Genome-Wide Association Study and Chemical-Gene Interaction Datasets
Authors: Cheng Shiqiang , Wen Yan , Ma Mei , Zhang Lu , Liu Li , Qi Xin , Cheng Bolun , Liang Chujun , Li Ping , Kafle Om Prakash , Zhang Feng 
Published: April 2020

AbstractPsychiatric disorders are a group of complex psychological syndromes whose etiology remains unknown. Previous study suggested that various chemicals contributed to the development of psychiatric diseases through affecting gene expression. This study aims to systematically explore the potential relationships between 5 major psychiatric disorders and more than 11 000 chemicals. The genome-wide association studies (GWAS) datasets of attention deficiency/hyperactive disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depression disorder (MDD), and schizophrenia (SCZ) were driven from the Psychiatric GWAS Consortium and iPSYCH website. The chemicals related gene sets were obtained from the comparative toxicogenomics database (CTD). First, transcriptome-wide association studies (TWAS) were performed by FUSION to calculate the expression association testing statistics utilizing GWAS summary statistics of the 5 common psychiatric disorders. Chemical-related gene set enrichment analysis (GSEA) was then conducted to explore the relationships between chemicals and each of the psychiatric diseases. We observed several significant correlations between chemicals and each of the psychiatric disorders. We also detected common chemicals between every 4 of the 5 major psychiatric disorders, such as androgen antagonists for ADHD (P value = .0098), ASD (P value = .0330), BD (P value = .0238), and SCZ (P value = .0062), and imipramine for ADHD (P value = .0054), ASD (P value = .0386), MDD (P value = .0438), and SCZ (P value = .0008). Our study results provide new clues for revealing the roles of environmental chemicals in the development of psychiatric disorders.
State-Level Immigration Policy Context and Health: How Are Latinx Immigrant Parents Faring?
Authors: Ayón Cecilia 
Published: April 2020

Abstract
This study examined associations between perceived immigration policy effects and stress among Latinx immigrant parents living in Maricopa County, Arizona, which implemented a series of restrictive immigration policies. Three hundred Latinx immigrant parents participated in the study. A hierarchical regression model was used to examine the relationship between perceived immigration policy effects (that is, subscales include Discrimination, Social Exclusion, Threat to Family, and Children’s Vulnerability) on parents’ stress levels while controlling for demographics. The model also included protective factors (that is, familismo, social support, self-efficacy) and immigrant-specific indicators of health (that is, length of time in the United States and deportation of a family member). Findings revealed that threat to family and children’s vulnerability were associated with heightened stress levels among parents. There were no differences in stress levels by length of time in the United States or deportation of a family member, and protective factors were not associated with reduced stress levels. At a practice level, findings stress the need to work with families to address their fears of family separation and parents’ concerns for how the immigration policy context affects their children. At a policy level, advocacy is needed to secure access to care for immigrants and maintain families together.
Gender Support Disparities in a Majority-Female Profession
Authors: Radey Melissa , Schelbe Lisa 
Published: April 2020

AbstractTheory and empirical evidence establish gender disparities in work pay and promotion trajectories, particularly in majority-male workplaces. Workplace support’s role, particularly in majority-female workplaces, in facilitating gendered occupational trajectories is less clear. Authors used a statewide sample of child welfare workers (N = 1,501) to examine gender differences in support and analyzed qualitative interviews with a subsample of participants (n = 37) to explore the role of gender in support perceptions. Analyses indicated that men perceived more supervisory and organizational support, whereas gender was not related to coworker support. The qualitative analysis indicated that receiving support required initiative. Men took initiative because they felt entitled. Many women expressed reservations, often warranted from experience, about initiating support to avoid bothering others and to honor workplace hierarchy. Men’s initiative allowed them access to support, thus increasing propensity toward job success. This study indicates that gender differences in workplace support may contribute to producing a self-perpetuating system of structural inequality.
FINSA/FINIA—new regulation for foreign trustees in Switzerland
Authors: Blumenfeld Marc 
Published: April 2020

Abstract
In the light of the international trends to regulate and supervise financial services and their providers (Markets in Financial Instruments Directive (MiFID) II, Prospectus Directive, Packaged Retail and Insurance-based Investment Products (PRIIPs)), the Financial Services Act (FINSA) and the Financial Institutions Act (FINIA) entered into force in Switzerland on 1 January 2020. The new Swiss regulation introduces prudential supervision for asset managers and trustees who have only been subject to Anti-Money Laundering (AML) regulation in Switzerland until now. Foreign trustees will also be affected by the FINSA/FINIA if they engage in activities in Switzerland. This article provides a high-level outline of the new regulatory playing field for foreign trustees in Switzerland.
Intrinsically disordered regions are abundant in simplexvirus proteomes and display signatures of positive selection
Authors: Mozzi Alessandra , Forni Diego , Cagliani Rachele , Clerici Mario , Pozzoli Uberto , Sironi Manuela 
Published: April 2020

Abstract
Whereas the majority of herpesviruses co-speciated with their mammalian hosts, human herpes simplex virus 2 (HSV-2, genus Simplexvirus) most likely originated from the cross-species transmission of chimpanzee herpesvirus 1 to an ancestor of modern humans. We exploited the peculiar evolutionary history of HSV-2 to investigate the selective events that drove herpesvirus adaptation to a new host. We show that HSV-2 intrinsically disordered regions (IDRs)—that is, protein domains that do not adopt compact three-dimensional structures—are strongly enriched in positive selection signals. Analysis of viral proteomes indicated that a significantly higher portion of simplexvirus proteins is disordered compared with the proteins of other human herpesviruses. IDR abundance in simplexvirus proteomes was not a consequence of the base composition of their genomes (high G + C content). Conversely, protein function determines the IDR fraction, which is significantly higher in viral proteins that interact with human factors. We also found that the average extent of disorder in herpesvirus proteins tends to parallel that of their human interactors. These data suggest that viruses that interact with fast-evolving, disordered human proteins, in turn, evolve disordered viral interactors poised for innovation. We propose that the high IDR fraction present in simplexvirus proteomes contributes to their wider host range compared with other herpesviruses.
Ecological Assembly Processes of the Bacterial and Fungal Microbiota of Wild and Domesticated Wheat Species
Authors: Hassani M. Amine , Özkurt Ezgi , Franzenburg Sören , Stukenbrock Eva H. 
Published: April 2020

Domestication has led to substantial changes in plant physiology. How this anthropogenic intervention has contributed in altering the wheat microbiota is not well understood. Here, we investigated the role of ecological selection, drift, and dispersal in shaping the bacterial and fungal communities associated with domesticated wheat Triticum aestivum and two wild relatives, T. boeoticum and T. urartu. Our study shows that the bacterial and fungal microbiota of wild and domesticated wheat species follow distinct community assembly patterns. Further, we revealed a more prominent role of neutral processes in the assembly of the microbiota of domesticated wheat and propose that domestication has relaxed selective processes in the assembly of the wheat microbiota. [Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .