bluuebunny/crossref_metadata_2025_split huggingface dataset:
Skewed allelic expression on X chromosome associated with aberrant expression of XIST on systemic lupus erythematosus lymphocytes
Authors: Zhang Yanfeng , Li Xinrui , Gibson Andrew , Edberg Jeffrey , Kimberly Robert P , Absher Devin M 
Published: July 2020

AbstractA common feature of autoimmune diseases, including systemic lupus erythematosus (SLE), is an increased prevalence in women. However, the molecular basis for sex disparity in SLE remains poorly understood. To examine the role of X-linked transcription in SLE adaptive immune cells, we performed RNA-seq in T cell and B cell subsets from either healthy donors or patients with SLE. Analyses of allelic expression (AE) profiles identified a pattern of increased allelic imbalance across the entire X chromosome in SLE lymphocytes. X-linked genes exhibiting AE in SLE had an extensive overlap with genes known to escape X chromosome inactivation (XCI). XIST RNA was overexpressed in SLE patients. Differential XIST expression correlated with AE profiles more positively at X-linked genes than the genome-wide background. Analysis of three independent RNA-seq data verified the XIST-associated skewed AE on X chromosome in SLE. Integrative analyses of DNA methylation profiles showed an increased variability of DNA methylation levels at these AE-related X-linked genes. In cultured lymphoblastic cells, knockdown of XIST specifically altered allelic imbalance patterns between X chromosomes. Our study provides genetic evidence that upregulation of XIST accompanied with more skewed allelic expression on X chromosome is associated with the pathogenesis of SLE and may provide mechanistic insights into the increased incidence of SLE in females.
The emerging field of polygenic risk scores and perspective for use in clinical care
Authors: Yanes Tatiane , McInerney-Leo Aideen M , Law Matthew H , Cummings Shelly 
Published: July 2020

Abstract
Genetic testing is used widely for diagnostic, carrier and predictive testing in monogenic diseases. Until recently, there were no genetic testing options available for multifactorial complex diseases like heart disease, diabetes and cancer. Genome-wide association studies (GWAS) have been invaluable in identifying single-nucleotide polymorphisms (SNPs) associated with increased or decreased risk for hundreds of complex disorders. For a given disease, SNPs can be combined to generate a cumulative estimation of risk known as a polygenic risk score (PRS). After years of research, PRSs are increasingly used in clinical settings. In this article, we will review the literature on how both genome-wide and restricted PRSs are developed and the relative merit of each. The validation and evaluation of PRSs will also be discussed, including the recognition that PRS validity is intrinsically linked to the methodological and analytical approach of the foundation GWAS together with the ethnic characteristics of that cohort. Specifically, population differences may affect imputation accuracy, risk magnitude and direction. Even as PRSs are being introduced into clinical practice, there is a push to combine them with clinical and demographic risk factors to develop a holistic disease risk. The existing evidence regarding the clinical utility of PRSs is considered across four different domains: informing population screening programs, guiding therapeutic interventions, refining risk for families at high risk, and facilitating diagnosis and predicting prognostic outcomes. The evidence for clinical utility in relation to five well-studied disorders is summarized. The potential ethical, legal and social implications are also highlighted.
Pharmacogenomics for immunotherapy and immune-related cardiotoxicity
Authors: Castrillon Jessica A , Eng Charis , Cheng Feixiong 
Published: July 2020

Abstract
Immune checkpoint blockade (ICB) has become a standard of care in a subset of solid tumors. Although cancer survivorship has extended, rates of durable response of ICB remain poor; furthermore, cardiac adverse effects are emerging, which impact several mechanical aspects of the heart. Cardio-oncology programs implement a clinical assessment to curtail cardiovascular disease progression but are limited to the current clinical parameters used in cardiology. Pharmacogenomics provides the potential to unveil heritable and somatic genetic variations for guiding precision immunotherapy treatment to reduce the risk of immune-related cardiotoxicity. A better understanding of pharmacogenomics will optimize the current treatment selection and dosing of immunotherapy. Here, we summarize the recent pharmacogenomics studies in immunotherapy responsiveness and its related cardiotoxicity and highlight how patient genetics and epigenetics can facilitate researchers and clinicians in designing new approaches for precision immunotherapy. We highlight and discuss how single-cell technologies, human-induced pluripotent stem cells and systems pharmacogenomics accelerate future studies of precision cardio-oncology.
Retrovirus reactivation in CHMP2BIntron5 models of frontotemporal dementia
Authors: Fort-Aznar Laura , Ugbode Chris , Sweeney Sean T 
Published: July 2020

Abstract
Frontotemporal dementia (FTD) is the second most prevalent form of pre-senile dementia after Alzheimer’s disease. Amyotrophic lateral sclerosis (ALS) can overlap genetically, pathologically and clinically with FTD indicating the two conditions are ends of a spectrum and may share common pathological mechanisms. FTD–ALS causing mutations are known to be involved in endosomal trafficking and RNA regulation. Using an unbiased genome-wide genetic screen to identify mutations affecting an FTD–ALS-related phenotype in Drosophila caused by CHMP2BIntron5 expression, we have uncovered repressors of retrovirus (RV) activity as modifiers of CHMP2BIntron5 toxicity. We report that neuronal expression of CHMP2BIntron5 causes an increase in the activity of the endogenous Drosophila RV, gypsy, in the nervous system. Genetically blocking Drosophila gypsy activation and pharmacologically inhibiting viral reverse transcriptase activity prevents degenerative phenotypes observed in fly and rat neurons. These findings directly link endosomal dysfunction to RV de-repression in an FTD–ALS model without TDP-43 pathology. These observations may contribute an understanding to previous discoveries of RV activation in ALS affected patients.
Degree of Rational Maps and Specialization
Authors: Cid-Ruiz Yairon , Simis Aron 
Published: July 2020

Abstract
One considers the behavior of the degree of a rational map under specialization of the coefficients of the defining linear system. The method rests on the classical idea of Kronecker as applied to the context of projective schemes and their specializations. For the theory to work, one is led to develop the details of rational maps and their graphs when the ground ring of coefficients is a Noetherian domain.
User reactions to COVID-19 screening chatbots from reputable providers
Authors: Dennis Alan R , Kim Antino , Rahimi Mohammad , Ayabakan Sezgin 
Published: July 2020

AbstractObjectivesThe objective was to understand how people respond to coronavirus disease 2019 (COVID-19) screening chatbots.Materials and MethodsWe conducted an online experiment with 371 participants who viewed a COVID-19 screening session between a hotline agent (chatbot or human) and a user with mild or severe symptoms.ResultsThe primary factor driving user response to screening hotlines (human or chatbot) is perceptions of the agent’s ability. When ability is the same, users view chatbots no differently or more positively than human agents. The primary factor driving perceptions of ability is the user’s trust in the hotline provider, with a slight negative bias against chatbots’ ability. Asian individuals perceived higher ability and benevolence than did White individuals.ConclusionsEnsuring that COVID-19 screening chatbots provide high-quality service is critical but not sufficient for widespread adoption. The key is to emphasize the chatbot’s ability and assure users that it delivers the same quality as human agents.
Validation of the Free Fatty Acid Test Kit for the Measurement of the Free Fatty Acid Content of Vegetable Oils, Fish Oils, Animal Fats (Tallows), Meat and Fish Meals, and Potato Chips and Grain-Based Snack Products: AOAC Performance Tested MethodSM 052004
Authors: Gordon I Virginia C , Rainey Christopher C , Studmire Willainia C 
Published: July 2020

Abstract

Background
The Official American Oil Chemists’ Society (AOCS) Ca 5a-40 method for the determination of free fatty acids is based on titration of an ethanolic solution and requires a large volume of organic solvents, large sample aliquots, and up to 18 hours extraction time for some samples. The SafTest Free Fatty Acid Test Kit is a rapid method designed to measure the free fatty acid content of vegetable oils; fish oil; animal fats (tallows); meat meal and fish meal products; and crackers, chips, and other processed grain-based snack products using micro-analytical and membrane separation principles.

Objective
The study objective was to validate the SafTest Free Fatty Acid Test in one internal study, two contracted studies, and an independent laboratory study studies.

Method
Recovery, limit of quantitation, selectivity, robustness, stability, and consistency of the SafTest Free Fatty Acid Test were evaluated.

Results
Recoveries from control solutions ranged from 97 to 106%. Repeatability (RSDr) from method developer matrix studies ranged from 1.1 to 8.1%. Biases, expressed as a percentage recovery from AOCS Ca 5a-40, averaged 96.5% for olive oils, 94.0% for animal fats, and 103.9% for meat meals. Results observed in the independent laboratory study were similar.

Conclusions
The SafTest Free Fatty Acid Test can measure free fatty acid levels in oils, fats, meal, and snack matrices with accuracy and precision comparable to AOCS Ca 5a-40.

Highlights
The SafTest Free Fatty Acid Test Kit has the advantage of using reagent volumes, instrumental analysis, and easy-to-use, standardized procedures with rapid detection times for the determination of free fatty acids.
Protection of Detainees from Sexual Violence under International Humanitarian Law
Authors: Bradley Samantha Frances 
Published: July 2020

Abstract
This article addresses the question of whether current frameworks under international humanitarian law offer adequate protection to persons detained for reasons relating to armed conflict from crimes of sexual violence. Sexual violence against detainees is a persistent issue in both international and non-international armed conflicts. Sexual violence against male detainees is also a widespread issue, with men and boys constituting the bulk of persons detained in conflict, and also facing unique barriers in reporting abuses. An evaluation of current legal frameworks under the Geneva Conventions of 1949 and the Additional Protocols of 1977 identifies key fault-lines in the law, including a widespread statutory characterisation of sexual violence as a crime principally committed against women. Case law demonstrates a resultant tendency to conceptualise sexual abuse of male detainees as torture, rather than sexual violence. Additionally, state interpretations of the law reflect this absence of gender neutrality. Compliance mechanisms are furthermore held back by the lack of clarity and specificity of prohibitions on sexual violence against detainees in international and non-international armed conflicts. Ultimately, options for strengthening the law in this area are subject to the political will of states and carry the risk of winding back existing standards of protection. The development of a non-binding but standard-setting instrument devised with the support of states and specifically prohibiting the issue of sexual violence against detainees in gender- neutral and comprehensive terms may ultimately be the most effective means of strengthening existing legal frameworks.
Outcome of tantalum rod insertion in the treatment of osteonecrosis of the femoral head with minimum follow-up of 1 year: a meta-analysis and systematic review
Authors: Onggo James Randolph , Nambiar Mithun , Onggo Jason Derry , Tay Guan , Singh Parminder J , Babazadeh Sina 
Published: July 2020

AbstractOsteonecrosis of the femoral head (ONFH) is a debilitating disease that can cause deformity and collapse of the femoral head, thus leading to the development of degenerative joint disease that can incapacitate the patient with pain and reduction in hip mobility. This study aims to determine the safety and efficacy of tantalum rod insertion in the treatment of ONFH with a minimum follow-up period of 1 year. A multi-database search was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Data from studies assessing the clinical and radiological outcomes as well as complications of tantalum rod insertion in the treatment of ONFH with a minimum follow-up period of 1 year were extracted and analyzed. Ten studies were included in this meta-analysis, consisting of 550 hips. There was a statistically significant increase in HHS (MD = 30.35, 95% CI: 20.60–40.10, P &lt; 0.001) at final follow-up versus pre-operative scores. The weighted pooled proportion (PP) of radiographic progression of ONFH was 0.221 (95% CI: 0.148–0.316), while that of progression into femoral head collapse was 0.102 (95% CI: 0.062–0.162). Conversion to total hip arthroplasty (THA) had a PP of 0.158 (95% CI: 0.107–0.227) with a mean weighted period of 32.4 months (95% CI: 24.9–39.9 months). Subgroup analysis of conversion to THA when tantalum rods were used in conjunction with bone grafting (PP = 0.150, 95% CI: 0.092–0.235) showed a marginal risk reduction than when compared with subgroup analysis of tantalum rods being used alone (PP = 0.154, 95% CI: 0.078–0.282). Tantalum rod is a safe alternative option to the current joint-preserving procedures available in the treatment of ONFH. However, more studies are needed to investigate and identify the most appropriate patients who would benefit most and the synergistic effect brought on by the use of complementary biological augmentation of bone grafting or stem cells with tantalum rods.
A Paris of Their Own: Guidebooks for Anglo-American Female Travellers and the Rewriting of Mainstream Travel Culture
Authors: Mann Paisley 
Published: July 2020

Abstract
Both E. M. Forster’s A Room with a View (1908) and Charles Dickens’s Little Dorrit (1855–1857) satirize British guidebook users, depicting them as mindless followers rather than as individual explorers of foreign landscapes. Series by John Murray and Baedeker dominated the landscape of Victorian travel, and scholars have pointed out that while mainstream guidebooks made foreign tourism more accessible for the middle class, they also presented travel as a heavily prescriptive and systematic endeavour, one that often sheltered British travellers from an encounter with foreignness. This article extends our understanding of the Victorian guidebook’s legacy by examining three Anglo-American guidebooks for women travelling to Paris – Mary Abbot’s A Woman’s Paris (1900), Elizabeth Otis Williams’ Sojourning, Shopping, and Studying in Paris (1907), and Alice M. Ivimy’s A Woman’s Guide to Paris (1909). It suggests that these fin-de-siècle women’s guidebooks emerged as a critique both of mainstream guidebooks’ prescriptive approach to foreign travel and of the narrow interests to which they catered. This article shows how, in actively resisting the genre’s emphasis on uniformity and expediency, guidebooks for women instead privileged spontaneous discovery, personal interest, and an encounter with the Parisian culture and landscape. In doing so, it seeks to reformulate our understanding of women’s travel narratives and of the cultural legacy of Victorian guidebooks.
The Exclusive Economic Zone is in reality a sovereign right of a State? The dispute over the Southeastern Mediterranean natural gas fields
Authors: Koulouris Nikolaos 
Published: July 2020

Abstract
The notion of Exclusive Economic Zone (EEZ) is a relatively new one. Its gestation during the second half of the 20th century was slow and arduous. But, after its birth, it gained a very important and crucial place within the sector of International Law and especially the branch of the Law of the Sea. Furthermore, it implicates strong and unprecedented geopolitical issues, emerged between a lot of neighbouring states. Pursuant to the rule establishing its notion, the EEZ confers upon a State a sovereign right, subject to a number of restrictions, which do not, nevertheless, affect the core of its integrity. But, in real international life this integrity is seriously jeopardized. International Law, because of its particularity, cannot be equipped by and enjoy the means of forced execution, which are inherent to the national legal system of every sovereign State. The EEZ, as it is provided by the International Law and especially the United Nations Convention on the Law Of the Sea, is not in reality a sovereign right of a State. It depends on the consensus of the State with adjacent coast and overlapping EEZ, which is a ‘prerequisite’ legally not existing.
The ferroxidase LPR5 functions in the maintenance of phosphate homeostasis and is required for normal growth and development of rice
Authors: Ai Hao , Cao Yue , Jain Ajay , Wang Xiaowen , Hu Zhi , Zhao Gengmao , Hu Siwen , Shen Xing , Yan Yan , Liu Xiuli , Sun Yafei , Lan Xiaoxia , Xu Guohua , Sun Shubin 
Published: July 2020

Abstract
Members of the Low Phosphate Root (LPR) family have been identified in rice (Oryza sativa) and expression analyses have been conducted. Here, we investigated the functions of one of the five members in rice, LPR5. qRT-PCR and promoter–GUS reporter analyses indicated that under Pi-sufficient conditions OsLPR5 was highly expressed in the roots, and specific expression occurred in the leaf collars and nodes, and its expression was increased under Pi-deficient conditions. In vitro analysis of the purified OsLPR5 protein showed that it exhibited ferroxidase activity. Overexpression of OsLPR5 triggered higher ferroxidase activity, and elevated concentrations of Fe(III) in the xylem sap and of total Fe in the roots and shoots. Transient expression of OsLPR5 in Nicotiana benthamiana provided evidence of its subcellular localization to the cell wall and endoplasmic reticulum. Knockout mutation in OsLPR5 by means of CRISPR-Cas9 resulted in adverse effects on Pi translocation, on the relative expression of Cis-NATOsPHO1;2, and on several morphological traits, including root development and yield potential. Our results indicate that ferroxidase-dependent OsLPR5 has both a broad-spectrum influence on growth and development in rice as well as affecting a subset of physiological and molecular traits that govern Pi homeostasis.
Generating and characterizing single- and multigene mutants of the Rubisco small subunit family in Arabidopsis
Authors: Khumsupan Panupon , Kozlowska Marta A , Orr Douglas J , Andreou Andreas I , Nakayama Naomi , Patron Nicola , Carmo-Silva Elizabete , McCormick Alistair J 
Published: July 2020

AbstractThe primary CO2-fixing enzyme Rubisco limits the productivity of plants. The small subunit of Rubisco (SSU) can influence overall Rubisco levels and catalytic efficiency, and is now receiving increasing attention as a potential engineering target to improve the performance of Rubisco. However, SSUs are encoded by a family of nuclear rbcS genes in plants, which makes them challenging to engineer and study. Here we have used CRISPR/Cas9 [clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9] and T-DNA insertion lines to generate a suite of single and multiple gene knockout mutants for the four members of the rbcS family in Arabidopsis, including two novel mutants 2b3b and 1a2b3b. 1a2b3b contained very low levels of Rubisco (~3% relative to the wild-type) and is the first example of a mutant with a homogenous Rubisco pool consisting of a single SSU isoform (1B). Growth under near-outdoor levels of light demonstrated Rubisco-limited growth phenotypes for several SSU mutants and the importance of the 1A and 3B isoforms. We also identified 1a1b as a likely lethal mutation, suggesting a key contributory role for the least expressed 1B isoform during early development. The successful use of CRISPR/Cas here suggests that this is a viable approach for exploring the functional roles of SSU isoforms in plants.
Marriage: A Get Out of Jail Free Card?
Authors: Richardson Siane 
Published: July 2020

Abstract
Marital rape is a particularly heinous form of sexual violence that occurs within intimate relationships. However, throughout much of the world, the marriage contract affords legal immunity to marital partners who would otherwise be convicted as sexual offenders. By reviewing the laws of the Commonwealth jurisdictions, this research highlights the necessity for reform in many jurisdictions that continue to allow for marital exemptions to sexual offending. This review identified three main forms of marital exemption, that is the general marital exemption to the primary sexual offence, the creation of spousal-specific sexual offences, and the use of marital exemptions to remove or reduce liability for sexual offences involving minors. The operation of these marital exemptions is then considered in the context of international human rights law and its prohibition on sexual violence within intimate relationships. An analysis of the jurisprudence surrounding Article 2 of CEDAW, Article 19 of the CRC and the prohibition of torture informs the argument that international human rights law requires the prohibition of marital exemptions to sexual offending throughout the Commonwealth nations. Marital exemptions continue to afford sexual offending with impunity across many Commonwealth jurisdictions in breach of the international human rights obligations of those nations and reform should occur in order to uphold the rights of sexual violence survivors.
A search for fast-radio-burst-like emission from Fermi gamma-ray bursts
Authors: Bouwhuis Mieke , Bannister Keith W , Macquart Jean-Pierre , Shannon R M , Kaplan David L , Bunton John D , Koribalski Bärbel S , Whiting M T 
Published: July 2020

ABSTRACT
We report the results of the rapid follow-up observations of gamma-ray bursts (GRBs) detected by the Fermi satellite to search for associated fast radio bursts. The observations were conducted with the Australian Square Kilometre Array Pathfinder at frequencies from 1.2 to 1.4 GHz. A set of 20 bursts, of which four were short GRBs, were followed up with a typical latency of about 1 min, for a duration of up to 11 h after the burst. The data were searched using 4096 dispersion measure trials up to a maximum dispersion measure of 3763 pc cm−3, and for pulse widths w over a range of duration from 1.256 to 40.48 ms. No associated pulsed radio emission was observed above $26 \, {\rm Jy\, ms}\, (w/1\, {\rm ms})^{-1/2}$ for any of the 20 GRBs.