bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient and effective control of confounding in eQTL mapping studies through joint differential expression and Mendelian randomization analyses
Authors: Fan Yue , Zhu Huanhuan , Song Yanyi , Peng Qinke , Zhou Xiang 
Published: August 2020

Abstract

Motivation
Identifying cis-acting genetic variants associated with gene expression levels—an analysis commonly referred to as expression quantitative trait loci (eQTLs) mapping—is an important first step toward understanding the genetic determinant of gene expression variation. Successful eQTL mapping requires effective control of confounding factors. A common method for confounding effects control in eQTL mapping studies is the probabilistic estimation of expression residual (PEER) analysis. PEER analysis extracts PEER factors to serve as surrogates for confounding factors, which is further included in the subsequent eQTL mapping analysis. However, it is computationally challenging to determine the optimal number of PEER factors used for eQTL mapping. In particular, the standard approach to determine the optimal number of PEER factors examines one number at a time and chooses a number that optimizes eQTLs discovery. Unfortunately, this standard approach involves multiple repetitive eQTL mapping procedures that are computationally expensive, restricting its use in large-scale eQTL mapping studies that being collected today.

Results
Here, we present a simple and computationally scalable alternative, Effect size Correlation for COnfounding determination (ECCO), to determine the optimal number of PEER factors used for eQTL mapping studies. Instead of performing repetitive eQTL mapping, ECCO jointly applies differential expression analysis and Mendelian randomization analysis, leading to substantial computational savings. In simulations and real data applications, we show that ECCO identifies a similar number of PEER factors required for eQTL mapping analysis as the standard approach but is two orders of magnitude faster. The computational scalability of ECCO allows for optimized eQTL discovery across 48 GTEx tissues for the first time, yielding an overall 5.89% power gain on the number of eQTL harboring genes (eGenes) discovered as compared to the previous GTEx recommendation that does not attempt to determine tissue-specific optimal number of PEER factors.

Availabilityand implementation
Our method is implemented in the ECCO software, which, along with its GTEx mapping results, is freely available at www.xzlab.org/software.html. All R scripts used in this study are also available at this site.

Supplementary information
Supplementary data are available at Bioinformatics online.
Zika virus in rhesus macaque semen and reproductive tract tissues: a pilot study of acute infection†
Authors: Schmidt Jenna K , Mean Katherine D , Puntney Riley C , Alexander Eric S , Sullivan Ruth , Simmons Heather A , Zeng Xiankun , Weiler Andrea M , Friedrich Thomas C , Golos Thaddeus G 
Published: August 2020

Abstract
Although sexual transmission of Zika virus (ZIKV) is well-documented, the viral reservoir(s) in the male reproductive tract remains uncertain in humans and immune-intact animal models. We evaluated the presence of ZIKV in a rhesus macaque pilot study to determine persistence in semen, assess the impact of infection on sperm functional characteristics, and define the viral reservoir in the male reproductive tract. Five adult male rhesus monkeys were inoculated with 105 PFU of Asian-lineage ZIKV isolate PRVABC59, and two males were inoculated with the same dose of African-lineage ZIKV DAKAR41524. Viremia and viral RNA (vRNA) shedding in semen were monitored, and a cohort of animals were necropsied for tissue collection to assess tissue vRNA burden and histopathology. All animals exhibited viremia for limited periods (1–11 days); duration of shedding did not differ significantly between viral isolates. There were sporadic low levels of vRNA in the semen from some, but not all animals. Viral RNA levels in reproductive tract tissues were also modest and present in the epididymis in three of five cases, one case in the vas deferens, but not detected in testis, seminal vesicles or prostate. ZIKV infection did not impact semen motility parameters as assessed by computer-assisted sperm analysis. Despite some evidence of prolonged ZIKV RNA shedding in human semen and high tropism of ZIKV for male reproductive tract tissues in mice deficient in Type 1 interferon signaling, in the rhesus macaques assessed in this pilot study, we did not consistently find ZIKV RNA in the male reproductive tract.
Brain TSPO-PET predicts later disease progression independent of relapses in multiple sclerosis
Authors: Sucksdorff Marcus , Matilainen Markus , Tuisku Jouni , Polvinen Eero , Vuorimaa Anna , Rokka Johanna , Nylund Marjo , Rissanen Eero , Airas Laura 
Published: August 2020

Abstract
Overactivation of microglia is associated with most neurodegenerative diseases. In this study we examined whether PET-measurable innate immune cell activation predicts multiple sclerosis disease progression. Activation of microglia/macrophages was measured using the 18-kDa translocator protein (TSPO)-binding radioligand 11C-PK11195 and PET imaging in 69 patients with multiple sclerosis and 18 age- and sex-matched healthy controls. Radioligand binding was evaluated as the distribution volume ratio from dynamic PET images. Conventional MRI and disability measurements using the Expanded Disability Status Scale were performed for patients at baseline and 4.1 ± 1.9 (mean ± standard deviation) years later. Fifty-one (74%) of the patients were free of relapses during the follow-up period. Patients had increased activation of innate immune cells in the normal-appearing white matter and in the thalamus compared to the healthy control group (P = 0.033 and P = 0.003, respectively, Wilcoxon). Forward-type stepwise logistic regression was used to assess the best variables predicting disease progression. Baseline innate immune cell activation in the normal-appearing white matter was a significant predictor of later progression when the entire multiple sclerosis cohort was assessed [odds ratio (OR) = 4.26; P = 0.048]. In the patient subgroup free of relapses there was an association between macrophage/microglia activation in the perilesional normal-appearing white matter and disease progression (OR = 4.57; P = 0.013). None of the conventional MRI parameters measured at baseline associated with later progression. Our results strongly suggest that innate immune cell activation contributes to the diffuse neural damage leading to multiple sclerosis disease progression independent of relapses.
Bullying and Cyberbullying among Students with Cochlear Implants
Authors: Feijóo Sandra , Foody Mairéad , Pichel Rafael , Zamora Laia , Rial Antonio 
Published: August 2020

Abstract
Bullying is a significant problem for young people nowadays, regardless of their identity, culture, or background. Although the scientific evidence warns of a greater impact of bullying on vulnerable groups such as cochlear implant (CI) users, few specific studies have been carried out in this regard. As such, the fundamental objective of this study was to estimate the prevalence of both traditional bullying and cyberbullying among Spanish adolescents and young people with CI. Parents with children CI users were also invited to participate to explore their perspective concerning the victimization of their children. The information was collected using one survey for students aged 11–23 year (n = 102) and another for parents (n = 127). Beyond the frequency and types of bullying suffered or the methods used for coping with victimization, results also show lower rates of bullying when students were asked specifically with a single-item question than when applying multi-item questionnaires. The results are discussed in terms of the broader international bullying and victimization literature.
U-Shaped Relationship of Leukocyte Telomere Length With All-Cause and Cancer-Related Mortality in Older Men
Authors: Yeap Bu B , Hui Jennie , Knuiman Matthew W , Flicker Leon , Divitini Mark L , Arscott Gillian M , Twigg Stephen M , Almeida Osvaldo P , Hankey Graeme J , Golledge Jonathan , Norman Paul E , Beilby John P 
Published: August 2020

Abstract

Background
Telomeres are essential DNA–protein complexes whose attrition results in cellular dysfunction and senescence. Leukocyte telomere length (LTL) correlates with tissue telomere length, representing a biomarker for biological age. However, its predictive value for mortality risk, and for cardiovascular versus cancer deaths, in older adults remains uncertain.

Method
We studied 3608 community-dwelling men aged 77.0 ± 3.6 years. Leukocyte telomere length was measured using multiplex quantitative PCR, expressed as amount of telomeric DNA relative to single-copy control gene (T/S ratio). Deaths from any cause, cardiovascular disease (CVD), and cancer were ascertained using data linkage. Curve fitting used restricted cubic splines and Cox regression analyses adjusted for age, cardiometabolic risk factors, and prevalent disease.

Results
There was a U-shaped association of LTL with all-cause mortality. Men with T/S ratio in the middle quartiles had lower mortality (quartiles, Q2 vs Q1, hazard ratio [HR] = 0.86, 95% confidence interval [CI] 0.77–0.97, p = .012; Q3 vs Q1 HR = 0.88, CI 0.79–0.99, p = .032). There was no association of LTL with CVD mortality. There was a U-shaped association of LTL with cancer mortality. Men with LTL in the middle quartiles had lower risk of cancer death (Q2 vs Q1, HR = 0.73, CI 0.59–0.90, p = .004; Q3 vs Q1, HR = 0.75, CI 0.61–0.92, p = .007).

Conclusions
In older men, both shorter and longer LTL are associated with all-cause mortality. A similar U-shaped association was seen with cancer deaths, with no association found for cardiovascular deaths. Further research is warranted to explore the prognostic utility of LTL in ageing.
Foetal virilisation caused by overproduction of non-aromatisable 11-oxygenated C19 steroids in maternal adrenal tumour
Authors: Nagasaki Keisuke , Takase Kaoru , Numakura Chikahiko , Homma Keiko , Hasegawa Tomonobu , Fukami Maki 
Published: August 2020

Abstract
It is widely believed that adrenal tumours and ovarian luteomas in pregnant women cause virilisation of female foetuses through overproduction of testosterone and/or androstenedione. However, this notion raises a fundamental question as to how these classic androgens pass through the placenta without being converted by aromatase into oestrogens. Here, we report a case of maternal adrenal tumour, in which overproduction of 11-oxygenated C19 steroids (11ox C19s), newly characterised non-aromatisable androgens in humans, caused foetal virilisation. The female proband presented with severely virilised external genitalia at birth. The mother exhibited hirsutism, hyperglycaemia and hypertension and was diagnosed as having adrenal tumour. The mother was subjected to comprehensive steroid measurement. Serum levels of 11ox C19s were markedly elevated. In contrast, testosterone and androstenedione levels remained within the normal range, and levels of most other steroids in the conventional and backdoor androgenic pathways were normal or only mildly elevated. After tumour removal, levels of 11ox C19s were markedly reduced. These results provide the first evidence that 11ox C19s can be synthesised in adrenal adenomas and, due to their non-aromatisable nature, can pass through the placental barrier to cause foetal virilisation. These findings highlight a unique pathogenic property of these newly specified androgens in humans.
Trade-offs in fishery management objectives when allowing catch limit carry-over between years
Authors: Wiedenmann John R , Holland Daniel S 
Published: August 2020

Abstract
Fisheries managed with explicit annual catch limits often have realized catches below the total allowable catch. Carry-over provisions allowing aggregate or individual carry-forward of catch underages are included in many fishery management systems, but the ramifications of these provisions on different fishery management objectives such as average catch, variability in catch, and probability and degree of overfishing are not well understood. We developed a management strategy evaluation simulation to explore performance of alternative carry-over policies assuming different life histories and under different causes of catch underages. We evaluated the impacts of the carry-overs across common management objectives to understand the trade-offs associated with different amounts of allowable carry-over. We find that carry-overs can increase yield to the fishery but can also increase the risks of overfishing, low stock biomass, low catch, and the interannual variability in catch. All of these risk measures increase with the amount of carry-over allowed in most cases, but for cases of low stock productivity or positively biased stock assessment estimates, larger carry-over allowances resulted in similar or lower yield compared to smaller allowances. The analysis suggests that some benefits of carry-over can be maintained and risks can be limited by restricting the maximum carry-over allowed.
A Non-commutative Fejér Theorem for Crossed Products, the Approximation Property, and Applications
Authors: Crann Jason , Neufang Matthias 
Published: August 2020

Abstract
We prove that a locally compact group has the approximation property (AP), introduced by Haagerup–Kraus [ 21], if and only if a non-commutative Fejér theorem holds for its associated $C^*$- or von Neumann crossed products. As applications, we answer three open problems in the literature. Specifically, we show that any locally compact group with the AP is exact. This generalizes a result by Haagerup–Kraus [ 21] and answers a problem raised by Li [ 27]. We also answer a question of Bédos–Conti [ 4] on the Fejér property of discrete $C^*$-dynamical systems, as well as a question by Anoussis–Katavolos–Todorov [ 3] for all locally compact groups with the AP. In our approach, we develop a notion of Fubini crossed product for locally compact groups and a dynamical version of the slice map property.
Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis
Authors: Stepniewska Kasia , Humphreys Georgina S , Gonçalves Bronner P , Craig Elaine , Gosling Roly , Guerin Philippe J , Price Ric N , Barnes Karen I , Raman Jaishree , Smit Menno R , D’Alessandro Umberto , Stone Will J R , Bjorkman Anders , Samuels Aaron M , Arroyo-Arroyo Maria I , Bastiaens Guido J H , Brown Joelle M , Dicko Alassane , El-Sayed Badria B , Elzaki Salah-Eldin G , Eziefula Alice C , Kariuki Simon , Kwambai Titus K , Maestre Amanda E , Martensson Andreas , Mosha Dominic , Mwaiswelo Richard O , Ngasala Billy E , Okebe Joseph , Roh Michelle E , Sawa Patrick , Tiono Alfred B , Chen Ingrid , Drakeley Chris J , Bousema Teun 
Published: August 2020

Abstract

Background
Since the World Health Organization recommended single low-dose (0.25 mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant Plasmodium falciparum, several single-site studies have been conducted to assess efficacy.

Methods
An individual patient meta-analysis to assess gametocytocidal and transmission-blocking efficacy of PQ in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (1) gametocyte carriage in the first 2 weeks post treatment; and (2) the probability of infecting at least 1 mosquito or of a mosquito becoming infected.

Results
In 2574 participants from 14 studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytemia on day 0 (odds ratio [OR], 0.22; 95% confidence interval [CI], .17–.28 and OR, 0.12; 95% CI, .08–.16, respectively). Rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (P = .010 for day 7). Addition of 0.25 mg/kg PQ was associated with near complete prevention of transmission to mosquitoes.

Conclusions
Transmission blocking is achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP.
Childhood detention during COVID-19 in Italy: building momentum for a comprehensive child protection agenda
Authors: Logar Silvia , Leese Maggie 
Published: August 2020

Abstract
Childhood detention represents an integral part of the public health response to the COVID-19 emergency. Prison conditions in Italy put detained minors at grave risk of contracting sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To date (29 April 2020), the Italian penitentiary system is housing 161 minors (147 males), most of them in pre-trial custody, as well as 50 children &lt;3 y of age residing with their mothers in detention. Furthermore, the government reported 5265 unaccompanied minor migrants, mainly from Gambia and Egypt. The fundamental approach to be followed in childhood detention during COVID-19 is prevention of the introduction of infectious agents into detention facilities, limiting the spread within the prison and reducing the possibility of spread from the prison to the outside community. This appears challenging in countries like Italy with intense SARS-CoV-2 transmission. The current COVID-19 pandemic shows the need to provide a comprehensive childhood protection agenda, as the provision of healthcare for people in prisons and other places of detention is a state responsibility.
Dispute by Design? Legalization, Backlash, and the Drafting of Investment Agreements
Authors: Berge Tarald Laudal 
Published: August 2020

AbstractThe investment treaty regime is currently going through extensive reform. Driven by a raft of investor–state dispute settlement cases, states are asking: How should we draft future investment agreements? This article presents the first empirical analysis of what drives risk in investment agreements. Drawing on states’ own reform narratives, and on unique data on the content of over two thousand investment agreements, I analyze how legalization in investment agreements is associated with the risk of attracting investor–state dispute settlement claims. I find that the only legalization dimension that robustly predicts investor–state dispute settlement claims in investment agreements is substantive obligation, and that this risk is not significantly affected by introducing more flexibility or precision. These findings have important implications for states engaged in reform of their international investment policies. Most prominently, they suggest that states should focus more on what substantive clauses they include in their investment agreements, rather than on how these clauses are written.
Predicting Human Operator’s Decisions Based on Prospect Theory
Authors: de Souza Paulo E U , Chanel Caroline P C , Mailliez Melody , Dehais Frédéric 
Published: August 2020

AbstractThe aim of this work is to predict human operator’s (HO) decisions in a specific operational context, such as a cooperative human-robot mission, by approximating his/her utility function based on prospect theory (PT). To this aim, a within-subject experiment was designed in which the HO has to decide with limited time and incomplete information. This experiment also involved a framing effect paradigm, a typical cognitive bias causing people to react differently depending on the context. Such an experiment allowed to acquire data concerning the HO’s decisions in two different mission scenarios: search and rescue and Mars rock sampling. The framing was manipulated (e.g. positive vs. negative) and the probability of the outcomes causing people to react differently depending on the context. Statistical results observed for this experiment supported the hypothesis that the way the problem was presented (positively or negatively framed) and the emotional commitment affected the HO’s decisions. Thus, based on the collected data, the present work is willed to propose: (i) a formal approximation of the HO’s utility function founded on the prospect theory and (ii) a model used to predict the HO’s decisions based on the economics approach of multi-dimensional consumption bundle and PT. The obtained results, in terms of utility function fit and prediction accuracy, are promising and show that similar modeling and prediction method should be taken into account when an intelligent cybernetic system drives human–robot interaction. The advantage of predicting the HO’s decision, in this operational context, is to anticipate his/her decision, given the way a question is framed to the HO. Such a predictor lays the foundation for the development of a decision-making system capable of choosing how to present the information to the operator while expecting to align his/her decision with the given operational guideline.
Management of posaconazole-induced pseudohyperaldosteronism
Authors: Davis Matthew R , Nguyen Minh-Vu H , Gintjee Thomas J , Odermatt Alex , Young Brian Y , Thompson George R 
Published: August 2020

Abstract

Background
Posaconazole-induced pseudohyperaldosteronism (PIPH) has been associated with elevated posaconazole serum concentrations. Clinicians are faced with the difficult task of managing patients with PIPH while maintaining the efficacy of antifungal therapy. Commonly, modifications to posaconazole therapy are utilized in managing PIPH, including dosage reduction of posaconazole or switch to an alternative antifungal.

Objectives
To characterize the management of patients diagnosed with PIPH and their response to various therapeutic interventions.

Methods
We retrospectively reviewed 20 consecutive adult patients diagnosed with PIPH. Patient data collected included blood pressure, electrolytes, endocrine laboratory values and posaconazole serum concentrations collected before and after therapeutic intervention.

Results
Of 20 patients included, 17 patients (85%) underwent therapeutic modification, with posaconazole dose reduction (n = 11) as the most common change. Other modifications included discontinuation (n = 3), switch to an alternative antifungal (n = 2) and addition of spironolactone (n = 1). Clinical improvement (decrease in systolic blood pressure and increase in serum potassium) was observed in 9 of 17 patients (52.9%). An average decrease in systolic blood pressure of 7.1 mmHg and increase in serum potassium of 0.22 mmol/L was observed following therapeutic modification.

Conclusions
We report our experience with PIPH management, for which there is no universally effective strategy. We utilized a stepwise approach for management, starting with posaconazole dose reduction and repeat assessment of clinical and laboratory parameters. If resolution of PIPH is not achieved, an alternative triazole antifungal or the addition of an aldosterone antagonist are additional potential interventions. It is possible for PIPH to persist after therapeutic modification despite these interventions. Thus, early diagnosis and continuous monitoring is warranted.