bluuebunny/crossref_metadata_2025_split huggingface dataset:
“The Low Principles of Jurisprudence”: Legal Indeterminacy in Edmund Burke's Impeachment of Warren Hastings
Authors: Goodman Rob 
Published: June 2020

AbstractEdmund Burke's impeachment of Warren Hastings for his conduct as governor-general in India represented the era's most serious internal challenge to British imperialism. But the impeachment's legal and institutional implications have been neglected. The central points of contention were the nature of impeachment in Britain and the nature of law in India. Burke insisted that impeachment must override the “low” and “mean” standards of the common law, yet he celebrated India for its dense judicial institutions. Hastings took the opposite position, demanding that the impeachment adhere strictly to the common law, yet defending his conduct in India by appeal to its political expediency, rather than its lawfulness. Each found himself in a “rhetorical contradiction,” alternately arguing in praise of, and in critique of, legal reasoning and procedures. While Hastings attempted to surmount the contradiction through the discourse of realism, Burke turned to the discourse of natural law—a language of lawfulness without legalism.
Scoping review of Paleolithic dietary patterns: a definition proposal
Authors: de la O Víctor , Zazpe Itziar , Martínez J. Alfredo , Santiago Susana , Carlos Silvia , Zulet M. Ángeles , Ruiz-Canela Miguel 
Published: June 2020

AbstractThe Paleolithic diet (PaleoDiet) is an allegedly healthy dietary pattern inspired by the consumption of wild foods and animals assumed to be consumed in the Paleolithic era. Despite gaining popularity in the media, different operational definitions of this Paleolithic nutritional intake have been used in research. Our hypothesis is that specific components used to define the PaleoDiet may modulate the association of this diet with several health outcomes. We comprehensively reviewed currently applied PaleoDiet scores and suggested a new score based on the food composition of current PaleoDiet definitions and the theoretical food content of a staple dietary pattern in the Paleolithic age. In a PubMed search up to December 2019, fourteen different PaleoDiet definitions were found. We observed some common components of the PaleoDiet among these definitions although we also found high heterogeneity in the list of specific foods that should be encouraged or banned within the PaleoDiet. Most studies suggest that the PaleoDiet may have beneficial effects in the prevention of cardiometabolic diseases (type 2 diabetes, overweight/obesity, CVD and hyperlipidaemias) but the level of evidence is still weak because of the limited number of studies with a large sample size, hard outcomes instead of surrogate outcomes and long-term follow-up. Finally, we propose a new PaleoDiet score composed of eleven food items, based on a high consumption of fruits, nuts, vegetables, fish, eggs and unprocessed meats (lean meats); and a minimum content of dairy products, grains and cereals, and legumes and practical absence of processed (or ultra-processed) foods or culinary ingredients.
Tainted Largess: A Moral Framework For Medical School Donations
Authors: SANKY CHARLES , APPEL JACOB M. 
Published: June 2020

AbstractRather than being a neutral phenomenon, the authors propose that medical school donations should be viewed as a social good for advancing education and improving healthcare. Seen in this light, they aim to offer a framework for analysis that will be useful to medical institutions and their stakeholders in addressing proposed donations from contentious or divisive sources, and in managing those donations that subsequently appear controversial.
Avoiding Gender Exploitation and Ethics Dumping in Research with Women
Authors: COOK JULIE 
Published: June 2020

AbstractThere is a long history of women being underrepresented in biomedical and health research. Specific women’s health needs have been, and in some cases still are, comparatively neglected areas of study. Concerns about the health and social impacts of such bias and exclusion have resulted in inclusion policies from governments, research funders, and the scientific establishment since the 1990s. Contemporary understandings of foregrounding sex and gender issues within biomedical research range from women’s rights to inclusion, to links between human rights, women’s health and sustainable development, and the increasing scientific and funding expectation for studies to consider the sex (biological) and gender (cultural) implications of research design, results and impact. However, there are also exploitation issues to consider when foregrounding the inclusion of women as research participants, especially for research ethics committees and institutional review boards. A hidden risk is that exploitative research designs and practices may be missed, particularly by reviewers who may not have a nuanced understanding of gender-based harm. Utilizing contemporary case studies of ethics dumping, this paper highlights some of the concerns, and makes recommendations for IRBs/research ethics reviewers to help ensure that essential research is undertaken to the highest ethical standards.
‘Removing the Barriers’: Mary Midgley on Concern for Animals
Authors: Cooper David E. 
Published: June 2020

AbstractThis paper focuses on Mary Midgley's influential discussions, over more than thirty years, of the relationship between human beings and animals, in particular on her concern to ‘remove the barriers’ that stand in the way of proper understanding and treatment of animals. These barriers, she demonstrates, have been erected by animal science, epistemology and mainstream moral philosophy alike. In each case, she argues, our attitudes to animals are warped by approaches that are at once excessively abstract, over-theoretical and guilty of a collective hubris on the part of humankind. In keeping with Midgley's own position, it is argued in this paper that, to remove these barriers, what is required is not yet another theory of how and why animals matter, but attention to actual engagements with animals and to the moral failings or vices that distort people's relationships with them.
Distribution characteristics of circulating homocysteine and folate and related factors in agriculture, stock-raising and urban populations: a cross-sectional survey
Authors: Pan Fengyu , Heizhati Mulalibieke , Wang Lin , Zhou Ling , Hong Jing , Zhang Delian , Chang Guijuan , Luo Qin , Sun Le , Yue Na , Li Nanfang 
Published: June 2020

AbstractObjective:To investigate homocysteine (Hcy) and folate levels, prevalence of hyperhomocysteinaemia (HHcy) and folate deficiency, which are affected by lifestyles in urban, agricultural and stock-raising populations.Design:This is a cross-sectional study.Setting:Urban, agricultural and stock-raising regions in Emin, China.Participants:Totally 1926 subjects – 885 (45·9 %) from urban, 861 (44·7 %) from agricultural and 180 (9·4 %) from stock-raising regions – were obtained using multistage stratified random sampling. Inclusion criteria encompassed inhabitants aged ≥15 years who resided at the current address for ≥6 months and agreed to participate in the study. Surveys on health behaviour questionnaires and physical examinations were conducted and blood samples collected.Results:The folate level of subjects from the stock-raising region was the lowest, followed by those from the agricultural region, and the highest in those from the urban region (3·48 v. 6·50 v. 7·12 ng/ml, P < 0·001), whereas mean Hcy showed no significant difference across regions. The OR for HHcy in stock-raising regions was 1·90 (95 % CI 1·11, 3·27) compared with the urban region after adjusting for all possible covariates. The OR for folate deficiency in stock-raising and agriculture regions was 11·51 (95 % CI 7·09, 18·67) and 1·91 (95 % CI 1·30, 2·82), respectively, compared with the urban region after adjusting for all possible covariates.Conclusions:HHcy and folate deficiency are highly prevalent in stock-raisers, which is of important reference for HHcy control in Xinjiang, with a possibility of extension to others with approximate lifestyles.
Factors associated with the onset of major depressive disorder in adults with type 2 diabetes living in 12 different countries: results from the INTERPRET-DD prospective study
Authors: Lloyd C. E. , Sartorius N. , Ahmed H. U. , Alvarez A. , Bahendeka S. , Bobrov A. E. , Burti L. , Chaturvedi S. K. , Gaebel W. , de Girolamo G. , Gondek T. M. , Guinzbourg M. , Heinze M. G. , Khan A. , Kiejna A. , Kokoszka A. , Kamala T. , Lalic N. M. , Lecic-Tosevski D. , Mannucci E. , Mankovsky B. , Müssig K. , Mutiso V. , Ndetei D. , Nouwen A. , Rabbani G. , Srikanta S. S. , Starostina E. G. , Shevchuk M. , Taj R. , Valentini U. , van Dam K. , Vukovic O. , Wölwer W. 
Published: June 2020

Abstract

Aims
To examine the factors that are associated with changes in depression in people with type 2 diabetes living in 12 different countries.

Methods
People with type 2 diabetes treated in out-patient settings aged 18–65 years underwent a psychiatric assessment to diagnose major depressive disorder (MDD) at baseline and follow-up. At both time points, participants completed the Patient Health Questionnaire (PHQ-9), the WHO five-item Well-being scale (WHO-5) and the Problem Areas in Diabetes (PAID) scale which measures diabetes-related distress. A composite stress score (CSS) (the occurrence of stressful life events and their reported degree of ‘upset’) between baseline and follow-up was calculated. Demographic data and medical record information were collected. Separate regression analyses were conducted with MDD and PHQ-9 scores as the dependent variables.

Results
In total, there were 7.4% (120) incident cases of MDD with 81.5% (1317) continuing to remain free of a diagnosis of MDD. Univariate analyses demonstrated that those with MDD were more likely to be female, less likely to be physically active, more likely to have diabetes complications at baseline and have higher CSS. Mean scores for the WHO-5, PAID and PHQ-9 were poorer in those with incident MDD compared with those who had never had a diagnosis of MDD. Regression analyses demonstrated that higher PHQ-9, lower WHO-5 scores and greater CSS were significant predictors of incident MDD. Significant predictors of PHQ-9 were baseline PHQ-9 score, WHO-5, PAID and CSS.

Conclusion
This study demonstrates the importance of psychosocial factors in addition to physiological variables in the development of depressive symptoms and incident MDD in people with type 2 diabetes. Stressful life events, depressive symptoms and diabetes-related distress all play a significant role which has implications for practice. A more holistic approach to care, which recognises the interplay of these psychosocial factors, may help to mitigate their impact on diabetes self-management as well as MDD, thus early screening and treatment for symptoms is recommended.
The Genetics of Reading and Language
Authors: Luciano Michelle , Bates Timothy C. 
Published: June 2020

AbstractRecounts how our collaboration with Nick Martin was shaped over two decades, leading to the first studies of predictions from the ‘Dual Route Cascaded’ computational model of reading in twins, and extending into the molecular work, first linkage, fine mapping of genes identified in pedigree studies, into now the genomewide association study era and the first polygenic risk scores for reading and their potential in early clarifying causality and validating interventions, as well as for future global collaborations in improving these predictors and identifying causal variants. We highlight Nick’s warm, future-focused optimism, support and inclusive approach without which none of this would have been possible. The circle of Nick asking, over half a century ago, ‘What genes do you think make some kids get better grades?’ has built a diverse scientific legacy involving thousands of papers and collaborations. The (heritable) traits of curiosity, boldness, warmth, interest in societally important questions, openness to new methods, ambition and collaborative skill to bring into being the infrastructure and samples needed for this research are rare, and we are grateful.
The relationships between systemic cytokine profiles and inflammatory markers in colorectal cancer and the prognostic significance of these parameters
Authors: Park Ji Won , Chang Hee Jin , Yeo Hyun Yang , Han Nayoung , Kim Byung Chang , Kong Sun-Young , Kim Jeongseon , Oh Jae Hwan 
Published: June 2020

Abstract
Background
Immunomodulatory cytokines and systemic inflammatory markers are important during cancer development and progression. This study investigated the association and prognostic impact of systemic cytokine profiles and inflammatory markers in colorectal cancer (CRC).

Methods
Interleukin (IL)-1β, IL-6, IL-8, IL-9, IL-10, tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) serum levels were measured using multiplex bead assays in CRC patients. Data on systemic inflammatory markers, such as the modified Glasgow prognostic score (mGPS), the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI) and fibrinogen, were collected. Survival analysis was performed to identify factors associated with progression-free survival (PFS) and overall survival (OS).

Results
There were moderate-to-strong correlations within serum cytokines, as well as within systemic inflammatory markers, whereas the associations between serum cytokines and systemic inflammatory markers were generally weak. IL-8 and the LMR were independent significant prognostic factors for PFS and OS. The low IL-8 and high LMR group had the best survival (both PFS and OS) of all groups.

Conclusions
Systemic cytokine profiles and inflammatory markers have relatively weak intergroup correlations. A composite classification of systemic cytokine profiles and inflammatory markers has an enhanced prognostic value in CRC.
FMRP(1–297)-tat restores ion channel and synaptic function in a model of Fragile X syndrome
Authors: Zhan Xiaoqin , Asmara Hadhimulya , Cheng Ning , Sahu Giriraj , Sanchez Eduardo , Zhang Fang-Xiong , Zamponi Gerald W. , Rho Jong M. , Turner Ray W. 
Published: June 2020

AbstractFragile X Syndrome results from a loss of Fragile X Mental Retardation Protein (FMRP). We now show that FMRP is a member of a Cav3-Kv4 ion channel complex that is known to regulate A-type potassium current in cerebellar granule cells to produce mossy fiber LTP. Mossy fiber LTP is absent in Fmr1 knockout (KO) mice but is restored by FMRP(1-297)-tat peptide. This peptide further rapidly permeates the blood-brain barrier to enter cells across the cerebellar-cortical axis that restores the balance of protein translation for at least 24 h and transiently reduces elevated levels of activity of adult Fmr1 KO mice in the Open Field Test. These data reveal that FMRP(1-297)-tat can improve function from the levels of protein translation to synaptic efficacy and behaviour in a model of Fragile X syndrome, identifying a potential therapeutic strategy for this genetic disorder.
The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture
Authors: Di Blasio S. , van Wigcheren G. F. , Becker A. , van Duffelen A. , Gorris M. , Verrijp K. , Stefanini I. , Bakker G. J. , Bloemendal M. , Halilovic A. , Vasaturo A. , Bakdash G. , Hato S. V. , de Wilt J. H. W. , Schalkwijk J. , de Vries I. J. M. , Textor J. C. , van den Bogaard E. H. , Tazzari M. , Figdor C. G. 
Published: June 2020

AbstractThe tumour microenvironment (TME) forms a major obstacle in effective cancer treatment and for clinical success of immunotherapy. Conventional co-cultures have shed light onto multiple aspects of cancer immunobiology, but they are limited by the lack of physiological complexity. We develop a human organotypic skin melanoma culture (OMC) that allows real-time study of host-malignant cell interactions within a multicellular tissue architecture. By co-culturing decellularized dermis with keratinocytes, fibroblasts and immune cells in the presence of melanoma cells, we generate a reconstructed TME that closely resembles tumour growth as observed in human lesions and supports cell survival and function. We demonstrate that the OMC is suitable and outperforms conventional 2D co-cultures for the study of TME-imprinting mechanisms. Within the OMC, we observe the tumour-driven conversion of cDC2s into CD14+ DCs, characterized by an immunosuppressive phenotype. The OMC provides a valuable approach to study how a TME affects the immune system.
Development of an exon skipping therapy for X-linked Alport syndrome with truncating variants in COL4A5
Authors: Yamamura Tomohiko , Horinouchi Tomoko , Adachi Tomomi , Terakawa Maki , Takaoka Yutaka , Omachi Kohei , Takasato Minoru , Takaishi Kiyosumi , Shoji Takao , Onishi Yoshiyuki , Kanazawa Yoshito , Koizumi Makoto , Tomono Yasuko , Sugano Aki , Shono Akemi , Minamikawa Shogo , Nagano China , Sakakibara Nana , Ishiko Shinya , Aoto Yuya , Kamura Misato , Harita Yutaka , Miura Kenichiro , Kanda Shoichiro , Morisada Naoya , Rossanti Rini , Ye Ming Juan , Nozu Yoshimi , Matsuo Masafumi , Kai Hirofumi , Iijima Kazumoto , Nozu Kandai 
Published: June 2020

AbstractCurrently, there are no treatments for Alport syndrome, which is the second most commonly inherited kidney disease. Here we report the development of an exon-skipping therapy using an antisense-oligonucleotide (ASO) for severe male X-linked Alport syndrome (XLAS). We targeted truncating variants in exon 21 of the COL4A5 gene and conducted a type IV collagen α3/α4/α5 chain triple helix formation assay, and in vitro and in vivo treatment efficacy evaluation. We show that exon skipping enabled trimer formation, leading to remarkable clinical and pathological improvements including expression of the α5 chain on glomerular and the tubular basement membrane. In addition, the survival period was clearly prolonged in the ASO treated mice group. This data suggests that exon skipping may represent a promising therapeutic approach for treating severe male XLAS cases.
Anion order in oxysulfide perovskites: origins and implications
Authors: Pilania Ghanshyam , Ghosh Ayana , Hartman Steven T. , Mishra Rohan , Stanek Christopher R. , Uberuaga Blas P. 
Published: June 2020

AbstractHeteroanionic oxysulfide perovskite compounds represent an emerging class of new materials allowing for a wide range of tunability in the electronic structure that could lead to a diverse spectrum of novel and improved functionalities. Unlike cation ordered double perovskites—where the origins and design rules of various experimentally observed cation orderings are well known and understood—anion ordering in heteroanionic perovskites remains a largely uncharted territory. In this contribution, we present and discuss insights that have emerged from our first-principles-based electronic structure analysis of a prototypical anion-ordered SrHf(O0.5S0.5)3 oxysulfide chemistry, studied in all possible anion configurations allowed within a finite size supercell. We demonstrate that the preferred anion ordering is always an all-cis arrangement of anions around an HfO3S3 octahedron. As a general finding beyond the specific chemistry, the origins of this ordering tendency are traced back to a combined stabilization effect stemming from electronic, elastic, and electrostatic contributions. These qualitative notions are also quantified using state-of-the-art machine learning models. We further study the relative stability of the identified ordering as a function of A (Ca, Sr, Ba) and B (Ti, Zr, Hf) site chemistries and probe chemistry-dependent trends in the electronic structure and functionality of the material. Most remarkably, we find that the identified ground-state anion ordering breaks the inversion symmetry to create a family of oxysulfide ferroelectrics with a macroscopic polarization >30 μC/cm2, exhibiting a significant promise for electronic materials applications.
Stratification and prediction of drug synergy based on target functional similarity
Authors: Yang Mi , Jaaks Patricia , Dry Jonathan , Garnett Mathew , Menden Michael P. , Saez-Rodriguez Julio 
Published: June 2020

AbstractDrug combinations can expand therapeutic options and address cancer’s resistance. However, the combinatorial space is enormous precluding its systematic exploration. Therefore, synergy prediction strategies are essential. We here present an approach to prioritise drug combinations in high-throughput screens and to stratify synergistic responses. At the core of our approach is the observation that the likelihood of synergy increases when targeting proteins with either strong functional similarity or dissimilarity. We estimate the similarity applying a multitask machine learning approach to basal gene expression and response to single drugs. We tested 7 protein target pairs (representing 29 combinations) and predicted their synergies in 33 breast cancer cell lines. In addition, we experimentally validated predicted synergy of the BRAF/insulin receptor combination (Dabrafenib/BMS-754807) in 48 colorectal cancer cell lines. We anticipate that our approaches can be used for prioritization of drug combinations in large scale screenings, and to maximize the efficacy of drugs already known to induce synergy, ultimately enabling patient stratification.
Effects of Laser-Beam Defocus on Microstructural Features of Compositionally Graded WC/Co-Alloy Composites Additively Manufactured by Multi-Beam Laser Directed Energy Deposition
Authors: Kunimine Takahiro , Miyazaki Ryusei , Yamashita Yorihiro , Funada Yoshinori 
Published: June 2020

AbstractEstablishing processing routes for obtaining metal-matrix composites (MMCs) with uniformly-dispersed reinforcements is one of the main subjects in additively manufactured composite materials to achieve designed microstructures and mechanical properties. Here we report on the microstructural features of compositionally graded WC/Co-alloy composites additively manufactured by multi-beam laser directed energy deposition (multi-beam LDED). For tailoring microstructures of compositionally graded WC/Co-alloy composites with uniformly-dispersed reinforcements, the combinational method: the laser-beam defocus function in the multi-beam LDED system and granulated powder was attempted. By laser defocusing in the multi-beam LDED system, composites with uniformly-dispersed WC particles in Co alloy matrix was successfully obtained due to melting of Co bond in WC-12 wt.%Co granulated particles. It was found that the laser defocusing of multi-beam lasers affects temperature increase of flying powder during the laser focusing area, resulting in change of processing mode from melt-pool mode to thermal spray mode. The preferable property gradients in the WC/Co-alloy composites could be obtained by controlling the feeding rate of the powders and laser-beam defocus. These experimental results demonstrated the effectiveness of the laser-beam-defocus function in the multi-beam LDED system as a key factor for tailoring microstructures of additively-manufactured functionally graded MMCs with uniformly-dispersed reinforcements.