bluuebunny/crossref_metadata_2025 huggingface dataset:
Robust estimation for longitudinal data under outcome‐dependent visit processes
Authors: Neuhaus John M. , McCulloch Charles E.
Published: July 2020

In longitudinal data where the timing and frequency of the measurement of outcomes may be associated with the value of the outcome, significant bias can occur. Previous results depended on correct specification of the outcome process and a somewhat unrealistic visit process model. In practice, this will never exactly be the case, so it is important to understand to what degree the results hold when those assumptions are violated in order to guide practical use of the methods. This paper presents theory and the results of simulation studies to extend our previous work to more realistic visit process models, as well as Poisson outcomes. We also assess the effects of several types of model misspecification. The estimated bias in these new settings generally mirrors the theoretical and simulation results of our previous work and provides confidence in using maximum likelihood methods in practice. Even when the assumptions about the outcome process did not hold, mixed effects models fit by maximum likelihood produced at most small bias in estimated regression coefficients, illustrating the robustness of these methods. This contrasts with generalised estimating equations approaches where bias increased in the settings of this paper. The analysis of data from a study of change in neurological outcomes following microsurgery for a brain arteriovenous malformation further illustrate the results.
Modelling the travel time of transit vehicles in real‐time through a GTFS‐based road network using GPS vehicle locations
Authors: Elliott Tom , Lumley Thomas
Published: July 2020

Predicting the arrival time of a transit vehicle involves not only knowledge of its current position and schedule adherence, but also traffic conditions along the remainder of the route. Road networks are dynamic and can quickly change from free‐flowing to highly congested, which impacts the arrival time of transit vehicles, particularly buses which often share the road with other vehicles, so reliable predictions need to account for real‐time and future traffic conditions. The first step in this process is to construct a framework with which road state (traffic conditions) can be estimated using real‐time transit vehicle position data. Our proposed framework implements a vehicle model using a particle filter to estimate road travel times, which are used in a second model to estimate real‐time traffic conditions. Although development and testing took place in Auckland, New Zealand, we generalised each component to make the framework compatible with other public transport systems around the world. We demonstrate the real‐time feasibility and performance of our approach in real‐time, where a combination of R and C++ was used to obtain the necessary performance results. Future work will use these estimated traffic conditions in combination with historical data to obtain reliable arrival time predictions of transit vehicles.
Review article: prognostic significance of body composition abnormalities in patients with cirrhosis
Authors: Ebadi Maryam , Bhanji Rahima A. , Tandon Puneeta , Mazurak Vera , Baracos Vickie E. , Montano‐Loza Aldo J.
Published: July 2020

Background

Recent advances in evaluation of body composition show body mass index to be inadequate in differentiating between body compartments in cirrhosis. Given the limitations of body mass index, body composition evaluation using computed tomography has been increasingly used as a non‐invasive clinical tool with prognostic value. Another factor influencing prognosis includes sex‐specific differences in body composition that are seen in cirrhosis.

Aim

To review current knowledge regarding the frequency and clinical implications of abnormal body composition features in cirrhosis.

Methods

We searched PubMed database and limited the literature search to full‐text papers published in English. Studies using inappropriate landmarks or demarcation of body composition components on computed tomography images were eliminated.

Results

Sarcopenia is a well established factor affecting morbidity and mortality in cirrhosis. Other important body composition components that have been overlooked thus far include subcutaneous adipose tissue and visceral adipose tissue. Female patients with cirrhosis and low subcutaneous adiposity have a higher risk of mortality, whereas male patients with high visceral adiposity have a higher risk of hepatocellular carcinoma and recurrence following liver transplantation. Increased adipose tissue radiodensity has been associated with risk of decompensation and mortality.

Conclusions

Further evaluation of body composition abnormalities may help with development of targeted therapeutic strategies and improve outcome in patients with cirrhosis. Moreover, recognition of these abnormalities could improve prioritisation for liver transplantation as our current method based solely on liver function might lead to risk misclassification.
A framework for simplification of quantitative systems pharmacology models in clinical pharmacology
Authors: Derbalah Abdallah , Al‐Sallami Hesham , Hasegawa Chihiro , Gulati Abhishek , Duffull Stephen B.
Published: July 2020

Quantitative systems pharmacology (QSP) is a relatively new discipline within modelling and simulation that has gained wide attention over the past few years. The application of QSP models spans drug‐target identification and validation, through all drug development phases as well as clinical applications. Due to their detailed mechanistic nature, QSP models are capable of extrapolating knowledge to predict outcomes in scenarios that have not been tested experimentally, making them an important resource in experimental and clinical pharmacology. However, these models are complicated to work with due to their size and inherent complexity. This makes many applications of QSP models for simulation, parameter estimation and trial design computationally intractable. A number of techniques have been developed to simplify QSP models into smaller models that are more amenable to further analyses while retaining their accurate predictive capabilities. Different simplification techniques have different strengths and weaknesses and hence different utilities. Understanding the utilities of different methods is essential for selection of the best method for a particular situation. In this paper, we have created an overall framework for model simplification techniques that allows a natural categorisation of methods based on their utility. We provide a brief description of the concept underpinning the different methods and example applications. A summary of the utilities of methods is intended to provide a guide to modellers in their model endeavours to simplify these complicated models.
A double‐blind, randomized, placebo‐controlled pilot trial of atorvastatin for nephrogenic diabetes insipidus in lithium users
Authors: Fotso Soh Jocelyn , Beaulieu Serge , Trepiccione Francesco , Linnaranta Outi , Torres‐Platas Gabriela , Platt Robert W. , Renaud Suzane , Su Chien‐Lin , Mucsi Istvan , D’Apolito Luciano , Mulsant Benoit H. , Levinson Andrea , Saury Sybille , Müller Daniel , Schaffer Ayal , Dols Annemiek , Low Nancy , Cervantes Pablo , Christensen Birgitte M. , Herrmann Nathan , Rajji Tarek , Rej Soham
Published: July 2020

Objective

Lithium remains an important treatment for mood disorders but is associated with kidney disease. Nephrogenic diabetes insipidus (NDI) is associated with up to 3‐fold risk of incident chronic kidney disease among lithium users. There are limited randomized controlled trials (RCT) for treatments of lithium‐induced NDI, and existing therapies can be poorly tolerated. Therefore, novel treatments are needed for lithium‐induced NDI.

Method

We conducted a 12‐week double‐blind pilot RCT to assess the feasibility and efficacy of 20 mg/d atorvastatin vs placebo in the treatment of NDI in chronic lithium users. Patients, recruited between September 2017 and October 2018, were aged 18 to 85, currently on a stable dose of lithium, and determined to have NDI.

Results

Urinary osmolality (UOsm) at 12 weeks adjusted for baseline was not statistically different between groups (+39.6 mOsm/kg [95% CI, −35.3, 114.5] in atorvastatin compared to placebo groups). Secondary outcomes of fluid intake and aquaporin‐2 excretions at 12 weeks adjusted for baseline were −0.13 L [95% CI, −0.54, 0.28] and 98.68 [95% CI, −190.34, 387.70], respectively. A moderate effect size was observed for improvements in baseline UOsm by ≥100 mOsm/kg at 12 weeks in patients who received atorvastatin compared to placebo (38.45% (10/26) vs 22.58% (7/31); Cohen's d = 0.66).

Conclusion

Among lithium users with NDI, atorvastatin 20 mg/d did not significantly improve urinary osmolality compared to placebo over a 12‐week period. Larger confirmatory trials with longer follow‐up periods may help to further assess the effects of statins on NDI, especially within patients with more severe NDI.
Rethinking counselling in prenatal screening: An ethical analysis of informed consent in the context of non‐invasive prenatal testing (NIPT)
Authors: Kater‐Kuipers Adriana , de Beaufort Inez D. , Galjaard Robert‐Jan H. , Bunnik Eline M.
Published: July 2020

Informed consent is a key condition for prenatal screening programmes to reach their aim of promoting reproductive autonomy. Reaching this aim is currently being challenged with the introduction of non‐invasive prenatal testing (NIPT) in first‐trimester prenatal screening programmes: amongst others its procedural ease—it only requires a blood draw and reaches high levels of reliability—might hinder women’s understanding that they should make a personal, informed decision about screening. We offer arguments for a renewed recognition and use of informed consent compared to informed choice, and for a focus on value‐consistent choices and personalized informational preferences. We argue for a three‐step counselling model in which three decision moments are distinguished and differently addressed: (1) professionals explore women’s values concerning whether and why they wish to know whether their baby has a genetic disorder; (2) women receive layered medical‐technical information and are asked to make a decision about screening; (3) during post‐test counselling, women are supported in decision‐making about the continuation or termination of their pregnancy. This model might also be applicable in other fields of genetic (pre‐test) counselling, where techniques for expanding genome analysis and burdensome test‐outcomes challenge counselling of patients.
Benefits of risk‐adapted and mould‐specific antifungal prophylaxis in childhood leukaemia
Authors: Meryk Andreas , Kropshofer Gabriele , Hutter Julia , Fritz Josef , Salvador Christina , Lass‐Flörl Cornelia , Crazzolara Roman
Published: July 2020

Fluconazole is one of the most commonly used drugs for antifungal prophylaxis in childhood leukaemia. However, its interaction with vincristine may induce neuropathy and the emergence of antifungal drug resistance contributes to substantial mortality caused by invasive fungal infections (IFIs). In a retrospective single‐centre study, we compared tolerability and outcome of different antifungal prophylaxis strategies in 198 children with acute leukaemia (median age 5·3 years). Until 2010, antifungal prophylaxis with fluconazole was offered to most of the patients and thereafter was replaced by liposomal amphotericin‐B (L‐AMB) and restricted to high‐risk patients only. Vincristine‐induced neurotoxicity was significantly reduced under L‐AMB, as the percentage of patients with severe constipation decreased (15·4% vs. 3·7%, before vs. after 31 December·2010, P = 0·01) and stool frequency increased by up to 38% in polyene‐treated patients (P = 0·005). Before 2011, 10 patients developed confirmed IFIs, most of them were infected with Aspergillus species. After risk adaption in 2011, IFIs were completely prevented (P = 0·007).

L‐AMB prophylaxis is beneficial in childhood leukaemia patients, as it offers effective antifungal activity with improved tolerability as compared to fluconazole. The potential impact of our risk‐adapted antifungal treatment should be included in current prophylaxis guidelines for childhood leukaemia.
Mapping public health responses with attitude networks: the emergence of opinion‐based groups in the UK’s early COVID‐19 response phase
Authors: Maher Paul J. , MacCarron Pádraig , Quayle Michael
Published: July 2020

Partisan patterns of compliance with public health measures are a feature of early COVID‐19 responses. In many cases, these differences in behaviour relate to pre‐existing group identities. However, in times of rapid societal change, novel opinion‐based groups can emerge and provide a new basis for partisan identification and divergent collective behaviour. Here, we use network methods to map the emergence of opposing opinion‐based groups and assess their implications for public health behaviour. In a longitudinal study, we tracked public health attitudes and self‐reported behaviour in a sample of UK participants over four time points. Network visualisation reveal a rift in attitudinal alignment over time and the genesis of two distinct groups characterised by trust, or distrust, in science (Study 1a; N = 253). These groups also diverge in public health behaviour. In a brief follow‐up study (N = 206), we find that this opinion polarization partially reflects underlying societal divides. We discuss implications for opinion‐based group research and public health campaigns.
Neuro‐oxysterols and neuro‐sterols as ligands to nuclear receptors, GPCRs, ligand‐gated ion channels and other protein receptors
Authors: Wang Yuqin , Yutuc Eylan , Griffiths William J.
Published: July 2020

The brain is the most cholesterol rich organ in the body containing about 25% of the body's free cholesterol. Cholesterol cannot pass the blood–brain barrier and be imported or exported; instead, it is synthesised in situ and metabolised to oxysterols, oxidised forms of cholesterol, which can pass the blood–brain barrier. 24S‐Hydroxycholesterol is the dominant oxysterol in the brain after parturition, but during development, a myriad of other oxysterols are produced, which persist as minor oxysterols after birth. During both development and in later life, sterols and oxysterols interact with a variety of different receptors, including nuclear receptors, membrane bound GPCRs, the oxysterol/sterol sensing proteins INSIG and SCAP, and the ligand‐gated ion channel NMDA receptors found in nerve cells. In this review, we summarise the different oxysterols and sterols found in the CNS whose biological activity is transmitted via these different classes of protein receptors.

LINKED ARTICLES

This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc
A homozygous pathogenic variant in SHROOM3 associated with anencephaly and cleft lip and palate
Authors: Deshwar Ashish R. , Martin Nicole , Shannon Patrick , Chitayat David
Published: July 2020

Neural tube defects (NTD) are among the most common congenital anomalies, affecting about 1:1000 births. In most cases, the etiology of NTD is multifactorial and the genetic variants associated with them remain largely unknown. There is extensive evidence from animal models over the past two decades implicating SHROOM3 in neural tube formation; however, its exact role in human disease has remained elusive. In this report, we present the first case of a human fetus with a homozygous loss of function variant in SHROOM3. The fetus presents with anencephaly and cleft lip and palate, similar to previously described Shroom3 mouse mutants and is suggestive of a novel monogenic cause of NTD. Our case provides clarification on the contribution of SHROOM3 to human development after decades of model organism research.
Settlements and the Heritage Dilemma in Manila
Authors: Pante Michael D.
Published: July 2020

This essay reflects on the problematic relationship between informal settlements and built heritage in Metro Manila, Philippines. Trained as a historian with scholarly and middle‐class socio‐civic sensibilities, I am oriented toward the preservation of historically significant structures. Such a seemingly safe positionality, however, is often made problematic by the reality of informal settlers occupying heritage sites, especially in the bustling cities of Asia’s so‐called “developing economies.” This complexity goes beyond finding the right balance between preserving mementos from the past and the material needs of the present. One cannot simply take a stance privileging socioeconomic provision over historical conservation, or vice‐versa, without accounting for class positionality, competing definitions of heritage, state‐capital relations, and the varying degrees and modalities of agency exercised by informal settlers. This paper foregrounds the ongoing struggle of informal settlers in Intramuros, Manila’s centuries‐old, Spanish walled city, by historicizing its “decline” from being a colonial nerve center to an area of blight. At present, these long‐time residents, who also provide the necessary labor for the tourism industry that sustains Intramuros, find it increasingly difficult to maintain their communities, even as tourist arrivals and the revenue they generate keep growing in number. Their situation provides insights that can deepen—and even unsettle—our understanding of this brewing tension between crumbling markers of the past and the present‐day inhumane housing conditions of our cities’ marginalized people.
The Growth of Children's Semantic and Phonological Networks: Insight From 10 Languages
Authors: Fourtassi Abdellah , Bian Yuan , Frank Michael C.
Published: July 2020

Children tend to produce words earlier when they are connected to a variety of other words along the phonological and semantic dimensions. Though these semantic and phonological connectivity effects have been extensively documented, little is known about their underlying developmental mechanism. One possibility is that learning is driven by lexical network growth where highly connected words in the child's early lexicon enable learning of similar words. Another possibility is that learning is driven by highly connected words in the external learning environment, instead of highly connected words in the early internal lexicon. The present study tests both scenarios systematically in both the phonological and semantic domains across 10 languages. We show that phonological and semantic connectivity in the learning environment drives growth in both production‐ and comprehension‐based vocabularies, even controlling for word frequency and length. This pattern of findings suggests a word learning process where children harness their statistical learning abilities to detect and learn highly connected words in the learning environment.
Association between CYP2C19 gene polymorphisms and susceptibility to high‐altitude pulmonary edema
Authors: He Xue , Bai Mei , Guan Xiwen , Zheng Jianwen , He Yongjun , Yuan Dongya , Jin Tianbo , Wang Li
Published: July 2020

Introduction

High‐altitude pulmonary edema (HAPE) is caused by the interaction of both genetic and environmental risk factors.

Objectives

In this study, we aimed to explore whether three single nucleotide polymorphisms (SNPs) inCYP2C19gene influenced the HAPE susceptibility in the Chinese Han population.

Methods

We recruited 238 cases and 230 controls between January 2018 and October 2018 from the Affiliated Hospital of Xizang Minzu University. The relationship betweenCYP2C19gene polymorphisms and HAPE was studied by association analysis. Genotyping was performed using the Agena MassARRAY platform and the statistical analysis was performed using Chi‐squared test, independent samplettest, genetic model analysis and haplotype analysis.

Results

The main finding of our study showed that rs4494250 inCYP2C19gene was associated with an increased risk of HAPE at age >32 years in the log‐additive model (OR = 1.80, 95% CI = 1.05‐3.09,P = 0.033). Also, it was observed to be associated with a reduced risk of HAPE at age ≤2 years in the dominant model (A/G‐A/A vs G/G, OR = 0.55, 95% CI = 0.31‐0.97,P = 0.038) and in the log‐additive model (OR = 0.58, 95% CI = 0.35‐0.96,P = 0.033).

Conclusion

Our findings demonstrated thatCYP2C19genetic variants were associated with risk of developing HAPE in Han Chinese population.
A call to action: Feasible strategies to reduce the discard of transplantable kidneys in the United States
Authors: Stewart Zoe A. , Shah Shimul A. , Formica Richard N. , Kandaswamy Raja , Paramesh Anil S. , Friedman Jessica , Squires Ronald , Cooper Matthew , Axelrod David A.
Published: July 2020

Changes to the United States kidney allocation system targeted at reducing organ discard have failed to improve organ utilization. High Kidney Donor Profile Index kidneys continue to be discarded at high rates as a result of the regulatory and financial barriers to widespread utilization of these organs. However, there are potential changes to clinical practice that could improve organ utilization. Expediting the time from initial offer to final organ acceptance would reduce cold ischemic time and should improve utilization. Implementation of procurement biopsy standards to avoid biopsy of low risk organs may prevent organ discards due to inaccurate data or excessive cold ischemia time. Further, standardization of procurement biopsy pathological interpretation coupled with electronic accessibility would enable early acceptance of difficult to transplant organs. These changes to allocation practice patterns are vital given proposals to expand the geographic sharing of deceased donor kidneys. Implementation of new allocation policies must be evaluated to ensure they result in higher transplant rates and acceptable post‐transplant outcomes.
Pilomatricoma with florid osseous metaplasia: A common tumor with rare histopathological finding
Authors: Bharti Sushma , Nalwa Aasma , Rajendran Madhubala , Rao Meenakshi , Elhence Poonam Abhay
Published: July 2020

Pilomatricoma, also known as calcifying epithelioma of Malherbe, is a common benign skin adnexal tumor with differentiation toward hair cortex cells, commonly seen in head and neck region of children. It is usually solitary. Herein, we present a rare case of pilomatricoma with extensive osseous metaplasia as a thigh swelling in an adult female, considered clinically to be a sebaceous cyst. Florid osseous metaplasia is extremely rare in cases of pilomatricoma. To date, fewer than 10 cases of pilomatricoma with extensive osseous metaplasia at different sites have been reported in the English literature.
What is the role of PIWI family proteins in adult pluripotent stem cells? Insights from asexually reproducing animals, planarians
Authors: Kashima Makoto , Agata Kiyokazu , Shibata Norito
Published: July 2020

Planarians have a remarkable regenerative ability owing to their adult pluripotent stem cells (aPSCs), which are called “neoblasts.” Planarians maintain a considerable number of neoblasts throughout their adulthood to supply differentiated cells for the maintenance of tissue homeostasis and asexual reproduction (fission followed by regeneration). Thus, planarians serve as a good model to study the regulatory mechanisms of in vivo aPSCs. In asexually reproducing invertebrates, such as sponge, Hydra, and planaria, piwi family genes are the markers most commonly expressed in aPSCs. While piwi family genes are known as guardians against transposable elements in the germline cells of animals that only sexually propagate, their functions in the aPSC system have remained elusive. In this review, we introduce recent knowledge on the PIWI family proteins in the aPSC system in planarians and other organisms and discuss how PIWI family proteins contribute to the regulation of the aPSC system.
Presidential Elections, Divided Politics, and Happiness in the USA
Authors: Pinto Sergio , Bencsik Panka , Chuluun Tuugi , Graham Carol
Published: July 2020

We examine the effects of the 2016 and 2012 US presidential election outcomes on subjective wellbeing across party identification. We use Gallup data and a regression discontinuity approach, and focus primarily on evaluative (life satisfaction) and hedonic (positive and negative affect) indicators. We find that both elections had strong negative wellbeing effects on those who identified with the losing party, with little or no increase in wellbeing for those identifying with the winning party. The negative effects for the losing side were larger in 2016 than in 2012, by a factor of three on some indicators, and were driven mainly by women and middle‐income households. As such, both elections had a net negative wellbeing effect, but more so in 2016. Local voting patterns did not have a substantial wellbeing impact, nor did congressional elections taking place the same day. In 2016, the election also changed respondents’ perceptions about the economy, their financial status, and their community. After both elections, hedonic wellbeing gaps across parties typically dissipated within two weeks, but there was more persistence in evaluative wellbeing gaps, especially in expected life satisfaction. The latter gap persisted throughout 2017.
Rapid photogrammetry of morphological traits of free‐ranging moths
Authors: Mungee Mansi , Athreya Ramana
Published: July 2020

Photogrammetric studies of free‐ranging animals are limited to mammals and birds. Recent advances in insect photogrammetry, including 3D imaging, are entirely associated with museum specimens.

We present a rapid, simple, accurate, and inexpensive morphometric method targeting thousands of free‐ranging insects attracted to light screens using images taken without collecting a specimen or even constraining the individual in any manner. A reference grid printed on the screen is used to calibrate the images for shape and size without prior knowledge of the camera‐subject configuration. The method requires only inexpensive, off‐the‐shelf, consumer equipment, and freely available programming (R statistical language) and image processing (ImageMagick) tools.

We demonstrate the efficacy of the method using a dataset of 3675 images of free‐ranging hawkmoths (Lepidoptera:Sphingidae) imaged in natural repose on a screen. We show that this method introduces no bias and has a high degree of correspondence with traditional morphometry using collected specimens. We also propose error metrics, which quantify the calibration quality and identify images with poor data.

Although this method is particularly suited for the hyperdiverse moth community, which dominates the dynamics of many terrestrial ecosystems, it can be used for other phototropic taxa identifiable on an image to (morpho)‐species. It will help in accumulating reliable trait data from hundreds of thousands of individual insects without any expenditure on specimen collection. It is particularly suited for studies which require multi‐epoch, multi‐locate sampling like investigations into ecosystem stability, climate change, and community assembly.
Effects of carrion decomposition on litter arthropod assemblages
Authors: Sawyer Samantha J. , Bloch Christopher P.
Published: July 2020

Many organisms contribute to the decomposition of carrion. For arthropods, many studies focus on the necrophagous community, those directly consuming carrion.

Necrophagous arthropods use carrion as a shelter or food source. Therefore, carrion generally increases the abundance and biodiversity of necrophagous species. However, it is unclear if carrion has similar effects on detrital communities.

This study examines changes in community structure and composition of necrophilous and detrital communities over the course of decomposition.

Five pig head carrion were placed at least 7 m apart under cages in temperate mixed forest. Leaf litter was sampled 0 m, 1.5 m, and 3 m from each carrion weekly during summer, and monthly during autumn, until the first frost. Arthropods were extracted from leaf litter by using Berlese funnels.

At the carrion site, necrophagous insects increased in abundance, species richness, and Shannon diversity during decomposition, and all decreased after dry decay.

Detritus arthropods displayed a sharp increase in abundance during advanced decay, decreasing during dry decay, and a general increase over time for species richness and diversity.

In conclusion, carrion can influence the surrounding, non‐necrophagous arthropod community, highlighting the need to investigate carrion effects beyond typical necrophagous species to have a more holistic understanding of carrion ecology.
The prognostic impact of variant allele frequency (VAF) in TP53 mutant patients with MDS: A systematic review and meta‐analysis
Authors: Deng Jili , Wu Xia , Ling Yantao , Liu Xiaoyan , Zheng Xue , Ye Wu , Gong Yuping
Published: July 2020

Tumor protein p53 (TP53) is frequently expressed in patients with myelodysplastic syndromes (MDS). Studies have already reported the poor prognostic impact of TP53 gene mutations in MDS patients. However, parts of this subgroup of patients with low‐risk MDS still have relatively better survival and longer remission times. Therefore, we performed a meta‐analysis to evaluate the prognostic difference intra‐gene of variant allele frequency (VAF). The primary endpoint was overall survival (OS), and event‐free survival (EFS) was selected as the secondary endpoint. We extracted the hazard ratio (HR) and 95% confidence interval (CI) for OS and EFS from univariate and multivariate Cox proportional hazard models. A total of 4003 MDS patients and 1278 TP53‐mutated patients from 13 cohorts of 11 studies up to February 24, 2020, were included in our meta‐analysis. Pooled HRs suggested that a high mutant VAF had an adverse impact on OS (HR = 2.11, 95% CI: 1.48‐3.01, P < .0001) but no impact on EFS (HR = 15.57, 95% CI: 0.75‐324.44, P = .003) in MDS patients. Twenty percent is a proper threshold to set (HR = 2.02, 95% CI: 1.31‐3.13, P = .001) and is a rough line between high clone burden and low clone burden, while 40% is an exact cutoff point (HR = 2.11, 95% CI: 1.26‐3.55, P < .0001) to guide diagnosis and treatment. Beyond the traditional binary classification of gene mutation, we aimed to find a way to divide mutant molecular markers more specifically by VAF to provide clinical therapeutic values. Our meta‐analysis indicates that a high VAF is an independent, adverse prognostic factor for OS in TP53 mutant MDS patients. Patients with mediate/low‐frequency parts who could be treated like wide‐type patients have relatively better survival and may choose allogeneic hematopoietic stem cell transplantation as conditions permitting. Further prospective studies are needed in the future, and a large subgroup analysis of the same cutoff point subgroups is needed to obtain a more reliable basis for the impact of other mutant gene VAFs on the prognosis of MDS.
Using accounting‐based and loan‐related information to estimate the cure probability of a defaulted company
Authors: Lohmann Christian , Ohliger Thorsten
Published: July 2020

The cure of a defaulted company has important implications for the estimation of the loss given default. In this study, we estimate the probability of a defaulted company being cured using data on a large international sample of defaulted companies. More specifically, we examine whether historic accounting information on a defaulted company and loan‐related information are associated with that company's probability of being cured. The main finding of our analysis is that both accounting‐based and loan‐related independent variables increase the validity of cure prediction models.
When, why and how tumour clonal diversity predicts survival
Authors: Noble Robert , Burley John T. , Le Sueur Cécile , Hochberg Michael E.
Published: July 2020

The utility of intratumour heterogeneity as a prognostic biomarker is the subject of ongoing clinical investigation. However, the relationship between this marker and its clinical impact is mediated by an evolutionary process that is not well understood. Here, we employ a spatial computational model of tumour evolution to assess when, why and how intratumour heterogeneity can be used to forecast tumour growth rate and progression‐free survival. We identify three conditions that can lead to a positive correlation between clonal diversity and subsequent growth rate: diversity is measured early in tumour development; selective sweeps are rare; and/or tumours vary in the rate at which they acquire driver mutations. Opposite conditions typically lead to negative correlation. In cohorts of tumours with diverse evolutionary parameters, we find that clonal diversity is a reliable predictor of both growth rate and progression‐free survival. We thus offer explanations—grounded in evolutionary theory—for empirical findings in various cancers, including survival analyses reported in the recent TRACERx Renal study of clear‐cell renal cell carcinoma. Our work informs the search for new prognostic biomarkers and contributes to the development of predictive oncology.
New insights into the mechanisms behind mechanical itch
Authors: Sakai Kent , Akiyama Tasuku
Published: July 2020

Gentle tactile stimuli, such as insects crawling on the skin, can cause itching sensation called mechanical itch. Recent studies have begun to shed light on the neural mechanisms of mechanical itch. Interestingly, the neural pathway for mechanical itch is apparently different from that for chemical itch triggered by the activation of pruriceptors with various mediators. Mechanical itch dysesthesia is frequently seen in patients with chronic itch. Mechanisms of this dysesthesia are plausibly involved in central sensitization. In this review, we summarize the current knowledge of mechanical itch under normal and pathological conditions.
The Musings of a Family Therapist in Asia When COVID‐19 Struck
Authors: Lee Wai‐Yung
Published: July 2020

In response to the COVID‐19 crisis in Asia, a family therapist in Hong Kong shares her experiences and reflections, both personally and professionally from an Eastern lens. From a state of shock and immobilization to moments of contemplation, she highlights her struggle with being caught between her Eastern roots and Western training, which has become more salient in facing COVID‐19. While the latter pulls her toward a more problem resolution stance, the former pulls her toward a more accepting position. As a result, her therapy is shaped in such a way that she tends to raise more questions instead of providing answers.
Developing a Measure of the Impact of COVID‐19 Social Distancing on Household Conflict and Cohesion
Authors: Behar‐Zusman Victoria , Chavez Jennifer V. , Gattamorta Karina
Published: July 2020

This report introduces the COVID‐19 Family Environment Scale (CHES), which aims to measure the impact of social distancing due to COVID‐19 on household conflict and cohesion. Existing measures do not capture household experiences relevant to the pandemic, in which families are largely confined to their homes while sharing a life‐threatening situation. Using best practice guidelines, we developed a pool of items and revised them with review by a panel of experts, and cognitive interviewing with community respondents. We administered the CHES by online survey to 3,965 adults. The CHES consists of 15 items for each of two subscales, household conflict (α = .847) and household cohesion (α = .887). Exploratory factor analysis yielded two factors, corresponding to the intended conflict and cohesion items, which accounted for 29% of variance. Confirmatory factor analysis partially supported the 2‐factor model (RMSEA = .057; CFI = .729, TLI = .708, and SRMR = .098). The CHES also contains 25 optional items to describe respondent and household characteristics, and household‐level COVID‐19 exposure. The CHES, publicly available athttps://elcentro.sonhs.miami.edu/research/measures-library/covid-19/index.html, provides a tool for measuring the impact of the COVID‐19 pandemic on important determinants of resilience in the face of major stressful events. Further work is needed to address the factor structure and establish validity of the CHES.
The colorful versatility of adipocytes: white‐to‐brown transdifferentiation and its therapeutic potential in humans
Authors: Maurer Stefanie , Harms Matthew , Boucher Jeremie
Published: July 2020

Brown and brite adipocytes contribute to energy expenditure through nonshivering thermogenesis. Though these cell types are thought to arise primarily from the de novo differentiation of precursor cells, their abundance is also controlled through the transdifferentiation of mature white adipocytes. Here, we review recent advances in our understanding of the regulation of white‐to‐brown transdifferentiation, as well as the conversion of brown and brite adipocytes to dormant, white‐like fat cells. Converting mature white adipocytes into brite cells or reactivating dormant brown and brite adipocytes has emerged as a strategy to ameliorate human metabolic disorders. We analyze the evidence of learning from mice and how they translate to humans to ultimately scrutinize the relevance of this concept. Moreover, we estimate that converting a small percentage of existing white fat mass in obese subjects into active brite adipocytes could be sufficient to achieve meaningful benefits in metabolism. In conclusion, novel browning agents have to be identified before adipocyte transdifferentiation can be realized as a safe and efficacious therapy.
The structure of a novel membrane‐associated 6‐phosphogluconate dehydrogenase fromGluconacetobacter diazotrophicus(Gd6PGD) reveals a subfamily of short‐chain 6PGDs
Authors: Sarmiento‐Pavía Pedro D. , Rodríguez‐Hernández Annia , Rodríguez‐Romero Adela , Sosa‐Torres Martha E.
Published: July 2020

The enzyme 6‐phosphogluconate dehydrogenase catalyzes the conversion of 6‐phosphogluconate to ribulose‐5‐phosphate. It represents an important reaction in the oxidative pentose phosphate pathway, producing a ribose precursor essential for nucleotide and nucleic acid synthesis. We succeeded, for the first time, to determine the three‐dimensional structure of this enzyme from an acetic acid bacterium,Gluconacetobacter diazotrophicus(Gd6PGD). ActiveGd6PGD, a homodimer (70 kDa), was present in both the soluble and the membrane fractions of the nitrogen‐fixing microorganism. TheGd6PGD belongs to the newly described subfamily of short‐chain (333 AA) 6PGDs, compared to the long‐chain subfamily (480 AA; e.g.,Ovis aries, Homo sapiens). The shorter amino acid sequence inGd6PGD induces the exposition of hydrophobic residues in the C‐terminal domain. This distinct structural feature is key for the protein to associate with the membrane. Furthermore, in terms of function, the short‐chain 6PGD seems to prefer NAD+over NADP+, delivering NADH to the membrane‐bound NADH dehydrogenase of the microorganisms required by the terminal oxidases to reduce dioxygen to water for energy conservation.

Enzyme

ECnonbreakingspace1.1.1.343.

Database

Structural data are available in PDB database under the accession number6VPB.
Retail and Place Attractiveness: The Effects of Big‐Box Entry on Property Values
Authors: Daunfeldt Sven‐Olov , Mihaescu Oana , Öner Özge , Rudholm Niklas
Published: July 2020

The opponents of big‐box entry argue that large retail establishments generate a variety of negative externalities. The advocates, on the contrary, argue that access to a large retail market not only delivers direct economic benefits, but also a variety of positive spill‐over effects, and therefore, can be considered a consumer amenity that increases the attractiveness of the entry location. To test the validity of these competing arguments, we use the entry of IKEA in Sweden as a quasi‐experiment and investigate if increased access to retail is associated with place attractiveness, where attractiveness is proxied by residential property values. We find that entry by IKEA increases prices of the properties sold in the entry cities by, on average, 4.2% or 62,980 SEK (approximately 6,600 USD), but such an effect is statistically insignificant for the properties in the immediate vicinity of the new IKEA retail trade area. We also observe an attenuation of the effect with distance from the new IKEA store, where the properties located 10 km away experience a 2% price increase. Our results indicate that large retailers have the potential to increase place attractiveness, but perhaps not in the immediate vicinity of the new establishment.
Evaluation of visual pedagogy in improving plaque control and gingival inflammation among preschool children with autism spectrum disorder: An interventional study
Authors: Du Rennan Yanlin , Lam Phoebe Pui Ying , Yiu Cynthia Kar Yung , McGrath Colman Patrick
Published: July 2020

Background

Visual pedagogy (VP) is a behavioural intervention used to facilitate learning among autistic children. Limited studies have evaluated VP when applied to dentistry.

Aim

To evaluate the effectiveness of VP in improving oral hygiene and gingival health status of autistic children.

Design

The interventional study was conducted among 122 autistic preschool children and their parents in Hong Kong. Toothbrushing visual pedagogy (TBVP) was provided to parents for supervising their children with toothbrushing at home. The children's sociodemographic background, developmental profile, and clinical parameters were obtained via parental questionnaire, standardised assessment form, and clinical examination, respectively. The change in plaque and gingival indices over time and potential confounding factors were evaluated with Friedman's two‐way analysis of variance and logistic regressions, respectively.

Results

Significantly lower level of plaque and gingival inflammation was found at 3 months and 6 months than baseline. The oral health status of children with poorer baseline oral hygiene status and gingival health was more likely to improve with TBVP. Other developmental and socio‐economic backgrounds had insignificant associations on the improvement of these clinical parameters.

Conclusion

The findings suggest TBVP is effective in promoting oral hygiene maintenance and improving the periodontal conditions among individuals diagnosed with ASD.
Labour‐Based Justifications of Intellectual Property and the Problem of Disruptive Innovations
Authors: Duncan Samuel
Published: July 2020

Justifying intellectual property on the basis of labour is an understandably popular strategy, but there is a tension in basing some intellectual property claims on labour that has gone largely unnoticed in treatments of the subject: many forms of innovation cause people to lose their jobs, which seriously hampers the ability of those who lose work to productively use their own labour. This article shows that even under Lockean and other labour‐based justifications of intellectual property rights those who claim property rights to innovations of this type have special obligations to compensate those who lose work because of their inventions. By examining the problem that such innovations create, I hope to contribute to larger debates about automation and the job losses it often brings. Lockean and other labour‐based theories of intellectual property are generally taken to secure strong, noninstrumental rights to intellectual property if they are successful. So, if even these theories imply that those who profit from the innovations driving automation have special obligations to those left jobless by it, that is strong evidence that they do in fact have such obligations.
Update on high‐power short‐duration ablation for pulmonary vein isolation
Authors: Qiu Jie , Wang Yan , Wang Dao Wen , Hu Mei , Chen Guangzhi
Published: July 2020

Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. However, this procedure remains complex and time‐consuming, and the recurrence of AF after PVI is still unsatisfactory. Current technologies have improved our knowledge of the association between radiofrequency lesion creation and ablation parameters (power and duration), which triggered the development of high‐power short‐duration (HPSD). During the past decade, several preclinical and clinical studies have been conducted to confirm the feasibility, safety, and outcome of PVI ablation with HPSD or very high‐power short‐duration (vHPSD) settings, which increased electrophysiologists' interests in the utility of HPSD strategies. This paper describes the theoretical basis and recent research findings of HPSD or vHPSD ablation and summarizes the state‐of‐the‐art evidence behind the role of this strategy in PVI.
Morphometric characteristics of myocardial sleeves of the pulmonary veins
Authors: Szczepanek Elżbieta , Bolechała Filip , Koziej Mateusz , Jasińska Katarzyna A. , Hołda Mateusz K.
Published: July 2020

Background

The pulmonary veins are covered by a myocardial layer, which is often an electrical substrate for atrial fibrillation. The aim of this study was to study the morphologic characteristics of the myocardial sleeves of pulmonary veins by examining a large group of freshly autopsied human material.

Methods and Results

The study macroscopically examined a total of 498 pulmonary veins draining the left atrium (120 unpreserved human hearts). In 75.0% of specimens, a classical pulmonary venous pattern was observed. The remainder of specimens either had an additional middle right pulmonary vein (20.0% of cases) or a common left pulmonary vein (5.0% of cases). Among all the veins seen in the classical pulmonary venous drainage type, the left superior pulmonary vein had the longest myocardial sleeves (9.4 ± 4.6 mm; coverage = 60.1 ± 19.4%), followed by the left inferior pulmonary vein (6.6 ± 3.5 mm; coverage = 47.6 ± 18.3%), the right superior pulmonary vein (6.0 ± 2.7 mm; coverage = 50.5 ± 13.9%) and then the right inferior pulmonary vein (5.0 ± 2.8 mm; coverage = 45.6 ± 16.2%; analysis of variance p < .001). In hearts with an additional right pulmonary vein, this vessel had the shortest myocardial sleeves (2.7 ± 1.1 mm; coverage = 36.0 ± 11.6%). In hearts with a common left pulmonary vein, the myocardial sleeves had the longest course for the common vein (13.7 ± 4.4 mm; coverage = 79.7 ± 4.9%).

Conclusions

Myocardial sleeves of the pulmonary veins were seen in each examined specimen, however, their length varied significantly. In hearts with a classical venous drainage pattern, the left superior pulmonary vein had the longest sleeves. When present, an additional middle right pulmonary vein had the shortest myocardial sleeves, while the left common pulmonary vein had the longest sleeves.