bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19: Viral-host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection
Authors: Messina Francesco , Giombini Emanuela , Agrati Chiara , Vairo Francesco , Bartoli Tommaso Ascoli , Moghazi Samir Al , Piacentini Mauro , Locatelli Franco , Kobinger Gary , Maeurer Markus , Zumla Alimuddin , Capobianchi Maria R. , Lauria Francesco Nicola , Ippolito Giuseppe ,   COVID 19 INMI Network Medicine for IDs Study Group
Published: May 2020

Background

Epidemiological, virological and pathogenetic characteristics of SARS-CoV-2 infection are under evaluation. A better understanding of the pathophysiology associated with COVID-19 is crucial to improve treatment modalities and to develop effective prevention strategies. Transcriptomic and proteomic data on the host response against SARS-CoV-2 still have anecdotic character; currently available data from other coronavirus infections are therefore a key source of information.

Methods

We investigated selected molecular aspects of three human coronavirus (HCoV) infections, namely SARS-CoV, MERS-CoV and HCoV-229E, through a network based-approach. A functional analysis of HCoV-host interactome was carried out in order to provide a theoretic host-pathogen interaction model for HCoV infections and in order to translate the results in prediction for SARS-CoV-2 pathogenesis.

The 3D model of S-glycoprotein of SARS-CoV-2 was compared to the structure of the corresponding SARS-CoV, HCoV-229E and MERS-CoV S-glycoprotein. SARS-CoV, MERS-CoV, HCoV-229E and the host interactome were inferred through published protein-protein interactions (PPI) as well as gene co-expression, triggered by HCoV S-glycoprotein in host cells.

Results

Although the amino acid sequences of the S-glycoprotein were found to be different between the various HCoV, the structures showed high similarity, but the best 3D structural overlap shared by SARS-CoV and SARS-CoV-2, consistent with the shared ACE2 predicted receptor. The host interactome, linked to the S-glycoprotein of SARS-CoV and MERS-CoV, mainly highlighted innate immunity pathway components, such as Toll Like receptors, cytokines and chemokines.

Conclusions

In this paper, we developed a network-based model with the aim to define molecular aspects of pathogenic phenotypes in HCoV infections. The resulting pattern may facilitate the process of structure-guided pharmaceutical and diagnostic research with the prospect to identify potential new biological targets.
Time-dependent discrimination advantages for harmonic sounds suggest efficient coding for memory
Authors: McPherson Malinda J. , McDermott Josh H.
Published: May 2020

Perceptual systems have finite memory resources and must store incoming signals in compressed formats. To explore whether representations of a sound’s pitch might derive from this need for compression, we compared discrimination of harmonic and inharmonic sounds across delays. In contrast to inharmonic spectra, harmonic spectra can be summarized, and thus compressed, using their fundamental frequency (f0). Participants heard two sounds and judged which was higher. Despite being comparable for sounds presented back-to-back, discrimination was better for harmonic than inharmonic stimuli when sounds were separated in time, implicating memory representations unique to harmonic sounds. Patterns of individual differences (correlations between thresholds in different conditions) indicated that listeners use different representations depending on the time delay between sounds, directly comparing the spectra of temporally adjacent sounds, but transitioning to comparing f0s across delays. The need to store sound in memory appears to determine reliance on f0-based pitch, and may explain its importance in music, in which listeners must extract relationships between notes separated in time.
Lifestyle adaptations ofRhizobiumfrom rhizosphere to symbiosis
Authors: Wheatley Rachel M. , Ford Brandon L. , Li Li , Aroney Samuel T. N. , Knights Hayley E. , Ledermann Raphael , East Alison K. , Ramachandran Vinoy K. , Poole Philip S.
Published: May 2020

By analyzing successive lifestyle stages of a modelRhizobium-legume symbiosis using mariner-based transposon insertion sequencing (INSeq), we have defined the genes required for rhizosphere growth, root colonization, bacterial infection, N2-fixing bacteroids and release from legume (pea) nodules. While only 27 genes are annotated asnifandfixinRhizobium leguminosarum, we show 603 genetic regions (593 genes, 5 tRNAs and 5 RNA features) are required for the competitive ability to nodulate pea and fix N2. Of these, 146 are common to rhizosphere growth through to bacteroids. This large number of genes, defined as rhizosphere-progressive, highlights how critical successful competition in the rhizosphere is to subsequent infection and nodulation. As expected, there is also a large group (211) specific for nodule bacteria and bacteroid function. Nodule infection and bacteroid formation require genes for motility, cell envelope restructuring, nodulation signalling, N2fixation, and metabolic adaptation. Metabolic adaptation includes urea, erythritol and aldehyde metabolism, glycogen synthesis, dicarboxylate metabolism and glutamine synthesis (GlnII). There are separate lifestyle adaptations specific to rhizosphere growth (17) and root colonization (23), distinct from infection and nodule formation. These results dramatically highlight the importance of competition at multiple stages of aRhizobium-legume symbiosis.

Significance

Rhizobia are soil-dwelling bacteria that form symbioses with legumes and provide biologically useable nitrogen as ammonium for the host plant. High-throughput DNA sequencing has led to a rapid expansion in publication of complete genomes for numerous rhizobia, but analysis of gene function increasingly lags gene discovery. Mariner-based transposon insertion sequencing (INSeq) has allowed us to characterize the fitness contribution of bacterial genes and determine those functionally important in aRhizobium-legume symbiosis at multiple stages of development.
A chromosome-scale genome assembly for theFusarium oxysporumstrain Fo5176 to establish a modelArabidopsis-fungal pathosystem
Authors: Fokkens Like , Guo Li , Dora Susanne , Wang Bo , Ye Kai , Sánchez-Rodríguez Clara , Croll Daniel
Published: May 2020

Plant pathogens cause widespread yield losses in agriculture. Understanding the drivers of plant-pathogen interactions requires decoding the molecular dialog leading to either resistance or disease. However, progress in deciphering pathogenicity genes has been severely hampered by suitable model systems and incomplete fungal genome assemblies. Here, we report a significant improvement of the assembly and annotation of the genome of theFusarium oxysporum(Fo) strain Fo5176.Focomprises a large number of serious plant pathogens on dozens of plant species with largely unresolved pathogenicity factors. The strain Fo5176 infectsArabidopsis thalianaand, hence, constitutes a highly promising model system. We use high-coverage Pacific Biosciences Sequel long-read and Hi-C sequencing data to assemble the genome into 19 chromosomes and a total genome size of 67.98 Mb. The genome has a N50 of 4 Mb and a 99.1% complete BUSCO score. Phylogenomic analyses based on single-copy orthologs clearly place the Fo5176 strain in theFof sp.conglutinansclade as expected. We generated RNAseq data from culture medium and plant infections to train gene predictions and identified ∼18,000 genes including ten effector genes known from otherFoclades. We show that Fo5176 is able to infect cabbage and Brussel sprouts of theBrassica oleracea, expanding the usefulness of the Fo5176 model pathosystem. Finally, we performed large-scale comparative genomics analyses comparing the Fo5176 to 103 additionalFogenomes to define core and accessory genomic regions. In conjunction with the molecular tool sets available forA. thaliana, the Fo5176 genome and annotation provides a crucial step towards the establishment of a highly promising pathosystem.
The coding capacity of SARS-CoV-2
Authors: Finkel Yaara , Mizrahi Orel , Nachshon Aharon , Weingarten-Gabbay Shira , Morgenstern David , Yahalom-Ronen Yfat , Tamir Hadas , Achdout Hagit , Stein Dana , Israeli Ofir , Beth-Din Adi , Melamed Sharon , Weiss Shay , Israely Tomer , Paran Nir , Schwartz Michal , Stern-Ginossar Noam
Published: May 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing Coronavirus disease 19 (COVID-19) pandemic1,2. In order to understand SARS-CoV-2 pathogenicity and antigenic potential, and to develop diagnostic and therapeutic tools, it is essential to portray the full repertoire of its expressed proteins. The SARS-CoV-2 coding capacity map is currently based on computational predictions and relies on homology to other coronaviruses. Since coronaviruses differ in their protein array, especially in the variety of accessory proteins, it is crucial to characterize the specific collection of SARS-CoV-2 proteins in an unbiased and open-ended manner. Utilizing a suite of ribosome profiling techniques3–8, we present a high-resolution map of the SARS-CoV-2 coding regions, allowing us to accurately quantify the expression of canonical viral open reading frames (ORF)s and to identify 23 novel unannotated viral translated ORFs. These ORFs include upstream ORFs (uORFs) that are likely playing a regulatory role, several in-frame internal ORFs lying within existing ORFs, resulting in N-terminally truncated products, as well as internal out-of-frame ORFs, which generate novel polypeptides. We further show that viral mRNAs are not translated more efficiently than host mRNAs; rather, virus translation dominates host translation due to high levels of viral transcripts. Overall, our work reveals the full coding capacity of SARS-CoV-2 genome, providing a rich resource, which will form the basis of future functional studies and diagnostic efforts.
Impact of Thiol-Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin Converting Enzyme 2 Receptor
Authors: Hati Sanchita , Bhattacharyya Sudeep
Published: May 2020

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an ongoing pandemic of coronavirus disease (COVID-19), which started in 2019. This is a member of Coronaviridae family in the genus Betacoronavirus, which also includes SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). The angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV and SARS-CoV-2 to enter the host cells. In particular, the interaction of viral spike proteins with ACE2 is a critical step in the viral replication cycle. The receptor binding domain of the viral spike proteins and ACE2 have several cysteine residues. In this study, the role of thiol-disulfide balance on the interactions between SARS-CoV/CoV-2 spike proteins and ACE2 was investigated using molecular dynamic simulations. The study revealed that the binding affinity was significantly impaired when all the disulfide bonds of both ACE2 and SARS-CoV/CoV-2 spike proteins were reduced to thiol groups. The impact on the binding affinity was less severe when the disulfide bridges of only one of the binding partners were reduced to thiols. This computational finding provides a molecular basis for the severity of COVID-19 infection due to the oxidative stress.
Evolution and genetic basis of the plant-penetrating ovipositor, a key adaptation in herbivorous Drosophilidae
Authors: Peláez Julianne N. , Gloss Andrew D. , Ray Julianne F. , Charboneau Joseph L.M. , Verster Kirsten I. , Whiteman Noah K.
Published: May 2020

Herbivorous insects are extraordinarily diverse, yet are found in only one-third of insect orders. This skew may result from barriers to plant colonization, coupled with phylogenetic constraint on plant-colonizing adaptations. Physical barriers have been surmounted through the evolution of key morphological innovations, such as the plant-penetrating ovipositor. Despite their significance, the evolution and genetic basis of such innovations have not been well studied. Ovipositors densely lined with hard bristles have evolved repeatedly in herbivorous lineages within the Drosophilidae. Here, we focus on the evolution of this trait in Scaptomyza, an herbivorous radiation nested in a microbe-feeding clade, sister to Hawaiian Drosophila. Our phylogenetic approach revealed that ovipositor bristle number increased as herbivory evolved. We then dissected the genomic architecture of variation in ovipositor bristle number within S. flava through a genome wide association study. Top associated variants were enriched for transcriptional repressors, and the strongest associations included genes contributing to peripheral nervous system development. Genotyping individual flies replicated the association at a variant upstream of Gαi, a neural development gene, contributing to a gain of 0.58 bristles/major allele. These results suggest that regulatory variation involving conserved developmental genes contributes to a key morphological adaptation required for plant colonization.
Disentangling selection on genetically correlated polygenic traits using whole-genome genealogies
Authors: Stern Aaron J. , Speidel Leo , Zaitlen Noah A. , Nielsen Rasmus
Published: May 2020

We present a full-likelihood method to estimate and quantify polygenic adaptation from contemporary DNA sequence data. The method combines population genetic DNA sequence data and GWAS summary statistics from up to thousands of nucleotide sites in a joint likelihood function to estimate the strength of transient directional selection acting on a polygenic trait. Through population genetic simulations of polygenic trait architectures and GWAS, we show that the method substantially improves power over current methods. We examine the robustness of the method under uncorrected GWAS stratification, uncertainty and ascertainment bias in the GWAS estimates of SNP effects, uncertainty in the identification of causal SNPs, allelic heterogeneity, negative selection, and low GWAS sample size. The method can quantify selection acting on correlated traits, fully controlling for pleiotropy even among traits with strong genetic correlation (|rg| = 80%; c.f. schizophrenia and bipolar disorder) while retaining high power to attribute selection to the causal trait. We apply the method to study 56 human polygenic traits for signs of recent adaptation. We find signals of directional selection on pigmentation (tanning, sunburn, hair,P=5.5e-15, 1.1e-11, 2.2e-6, respectively), life history traits (age at first birth, EduYears,P=2.5e-4, 2.6e-4, respectively), glycated hemoglobin (HbA1c,P=1.2e-3), bone mineral density (P=1.1e-3), and neuroticism (P=5.5e-3). We also conduct joint testing of 137 pairs of genetically correlated traits. We find evidence of widespread correlated response acting on these traits (2.6-fold enrichment over the null expectation,P=1.5e-7). We find that for several traits previously reported as adaptive, such as educational attainment and hair color, a significant proportion of the signal of selection on these traits can be attributed to correlated response,vsdirect selection (P=2.9e-6, 1.7e-4, respectively). Lastly, our joint test uncovers antagonistic selection that has acted to increase type 2 diabetes (T2D) risk and decrease HbA1c (P=1.5e-5).
Using social design to visualize outcomes of sustainable tourism planning: a multiphase, transdisciplinary approach
Authors: Arbogast Doug , Butler Peter , Faulkes Eve , Eades Daniel , Deng Jinyang , Maumbe Kudzayi , Smaldone David
Published: May 2020

Purpose

This paper aims to describe the transdisciplinary, multiphase, mixed methods, generative design research, participatory planning and social design activities developed and implemented by the West Virginia University Rural Tourism Design Team and associated outcomes.

Design/methodology/approach

The multiphase methodology included quantitative and qualitative research in initial stages of the study (key informant interviews, resident attitudes toward tourism survey, visitor preferences survey, economic impact analysis) which informed social design activities at latter stages (asset mapping, landscape design/visualization of opportunities and sites targeted for development and cultural identity design) using generative design tools facilitating co-design with the communities and helping the destination take sequential steps toward achieving their goals and objectives.

Findings

Opportunities and challenges identified through multiple methods were triangulated and pointed to the same conclusions including the need for long term planning and managed growth; protecting community values; underutilized natural, cultural and historic assets; the opportunity to develop nature-based, cultural and historical attractions; and the need for a common vision and collective identity.

Research limitations/implications

This study makes a unique contribution to literature on sustainable tourism planning by incorporating social design activities to visualize findings of more traditional planning methods and provide tangible, visible outcomes of planning activities which can guide local stakeholders in rural destinations more directly to funding for planning recommendations and project implementation.

Practical implications

The transdisciplinary and social/generative/participatory approach provided a scaffolding of outputs to the community with citizen control and active involvement throughout the planning and design process. The incorporation of social design provided tangible outcomes including site designs and a cultural identity. Generative design research gives people a language with which they can imagine and express their ideas and dreams for future experiences.

Originality/value

This paper investigates the role of social design in a transdisciplinary, multiphase project to support sustainable tourism planning.
Exploring the relationship between entrepreneurial failure and conflict between work and family from the conservation of resources perspective
Authors: Yu Xiaoyu , Meng Xiaotong , Cao Gang , Jia Yingya
Published: May 2020

Purpose

Conflict between work and family is a significant issue for entrepreneurs. The purpose of this study is to explore the effect of entrepreneurial failure on both family–work conflict (FWC) and work–family conflict (WFC) and the moderating role of perceived control of time and organizational slack based on conservation of resources (COR) theory.

Design/methodology/approach

This study used a questionnaire to explore the relationship between entrepreneurial failure, FWC/WFC, perceived control of time and organizational slack. Data were collected from the Chinese context in 2018 and as a result received 318 valid questionnaires, obtaining a response rate of 63.6 per cent.

Findings

The study finds that entrepreneurial failure has a significant relationship with FWC but a nonsignificant relationship with WFC and that perceived control of time and organizational slack moderate the relationship between entrepreneurial failure and FWC/WFC.

Originality/value

This study aligns the field of family–work (work–family) conflict and entrepreneurial failure. It addresses a research gap in the conflict literature by introducing one form of resource loss: entrepreneurial failure as a source of conflict between work and family based on COR theory and the work–home resources model. The study also enriches the literature on the social cost of entrepreneurial failure by exploring the crossover effect of entrepreneurial failure on conflicts in the family domain. Furthermore, the study advances the understanding of managing conflict between work and family after entrepreneurial failure.
Cost of illness study for adult atopic dermatitis in Japan: A cross‐sectional Web‐based survey
Authors: Murota Hiroyuki , Inoue Sachie , Yoshida Kazufumi , Ishimoto Atsushi
Published: May 2020

Atopic dermatitis is a pruritic, eczematous dermatitis, the symptoms of which chronically fluctuate with remissions and relapses. Although a high psychosomatic and economic burden caused by atopic dermatitis is expected, few studies have been conducted estimating the cost of illness, including the self‐medication costs and productivity loss due to atopic dermatitis. The aim of this study was to conduct a cross‐sectional, Web‐based survey of the direct medical costs, self‐medication costs and productivity loss for adult atopic dermatitis patients, and estimate the burden of Japanese adult atopic dermatitis patients by disease severity. In a physician survey, the medical resource consumption related to medical treatments was surveyed by disease severity. The direct medical costs were calculated by multiplying the medical resource consumption and medical fee corresponding to each treatment. Based on the results of a patient survey, the self‐medication costs and productivity loss were estimated by sex and disease severity. Atopic dermatitis‐related productivity loss was calculated based on absenteeism, presenteeism, overall work impairment for employed workers and activity impairment for housewives. The nationwide estimations were calculated based on the estimated number of atopic dermatitis patients, employed workers with atopic dermatitis, and housewives with atopic dermatitis in their 20s–50s in Japan. Based on the surveys, all costs per patient and the scores increased with disease severity. The cost of illness for adult atopic dermatitis patients in Japan was estimated to be approximately JPY 3 trillion/year. Considering the physical and mental burdens, the burden of illness for adult atopic dermatitis was demonstrated to be vast.
Rapid decrease of serum surfactant protein‐D levels predicts the reactivity of rituximab therapy in systemic sclerosis‐associated interstitial lung disease
Authors: Ebata Satoshi , Yoshizaki Ayumi , Fukasawa Takemichi , Asano Yoshihide , Oba Koji , Sato Shinichi
Published: May 2020

Systemic sclerosis (SSc) is an autoimmune disorder characterized by vascular damage and excessive fibrosis. SSc‐associated interstitial lung disease (ILD) is a leading cause of death in SSc. Several studies have shown the efficacy of rituximab (RTX) in SSc‐ILD, but no study has examined the relation between RTX reactivity and change of serum marker levels. In this study we examined the relation between change of serum surfactant protein‐D (SP‐D) levels and change of percentage forced vital capacity (FVC) in 11 SSc‐ILD patients with anti‐topoisomerase I antibody treated by RTX. Serum SP‐D levels were significantly decreased compared with baseline at 2 weeks after first RTX infusion in good responders (P = 0.04), while not in poor responders (P = 0.77). Moreover, ΔSP‐D at 2 weeks negatively correlated with Δ%FVC at 24 weeks (P = 0.001). In conclusion, we suggested that the rapid decrease of SP‐D levels may be a predictive marker of RTX effect against SSc‐ILD.
Survival varies seasonally in a migratory bird: Linkages between breeding and non‐breeding periods
Authors: Robinson Robert A. , Meier Christoph M. , Witvliet Willem , Kéry Marc , Schaub Michael
Published: May 2020

Migratory species form an important component of biodiversity; they link ecosystems across the globe, but are increasingly threatened by global environmental change. Understanding and mitigating threats requires knowledge of how demographic processes operate throughout the annual cycle, but this can be difficult to achieve when breeding and non‐breeding grounds are widely separated.

Our goal is to quantify the importance of variability in survival during the breeding and non‐breeding seasons in determining variation in annual survival using a single population and, more broadly, the extent to which annual survival across species reflects variation in probability of surviving the migratory period.

We use a 25‐year dataset in which individuals of a long‐distance migratory bird, the alpine swift Tachymarptis melba, were captured towards the beginning and end of each breeding season to estimate age‐ and season‐specific survival probabilities and incorporate explicit estimation of the correlations in survival between age‐classes and seasons.

Monthly survival was higher during the breeding period than during the rest of the year and strongly affected by conditions in the breeding season; effects that remained apparent in the following non‐breeding season, but not subsequently. Recruitment of juveniles was dependent on the timing of breeding, being higher if egg‐laying commenced before the median date, and substantially lower if not.

Across migratory bird species, variation in annual survival largely reflects variation in the probability of surviving the migratory period. Using a double‐capture approach, even within a single season, provides valuable insights into the demography of migratory species, which will help understand the extent and impacts of the threats they face in a changing world.
Glacial microbiota are hydrologically connected and temporally variable
Authors: Cameron Karen A. , Müller Oliver , Stibal Marek , Edwards Arwyn , Jacobsen Carsten Suhr
Published: May 2020

Glaciers are melting rapidly. The concurrent export of microbial assemblages alongside glacial meltwater is expected to impact the ecology of adjoining ecosystems. Currently, the source of exported assemblages is poorly understood, yet this information may be critical for understanding how current and future glacial melt seasons may influence downstream environments. We report on the connectivity and temporal variability of microbiota sampled from supraglacial, subglacial and periglacial habitats and water bodies within a glacial catchment. Sampled assemblages showed evidence of being biologically connected through hydrological flowpaths, leading to a meltwater system that accumulates prokaryotic biota as it travels downstream. Temporal changes in the connected assemblages were similarly observed. Snow assemblages changed markedly throughout the sample period, likely reflecting changes in the surrounding environment. Changes in supraglacial meltwater assemblages reflected the transition of the glacial surface from snow‐covered to bare‐ice. Marked snowmelt across the surrounding periglacial environment resulted in the flushing of soil assemblages into the riverine system. In contrast, surface ice within the ablation zone and subglacial meltwaters remained relatively stable throughout the sample period. Our results are indicative that changes in snow and ice melt across glacial environments will influence the abundance and diversity of microbial assemblages transported downstream.
Phage biocontrol to combat Pseudomonas syringae pathogens causing disease in cherry
Authors: Rabiey Mojgan , Roy Shyamali R. , Holtappels Dominique , Franceschetti Linda , Quilty Billy J. , Creeth Ryan , Sundin George W. , Wagemans Jeroen , Lavigne Rob , Jackson Robert W.
Published: May 2020

Bacterial canker is a major disease of Prunus species, such as cherry (Prunus avium). It is caused by Pseudomonas syringae pathovars, including P. syringae pv. syringae (Pss) and P. syringae pv. morsprunorum race 1 (Psm1) and race 2 (Psm2). Concerns over the environmental impact of, and the development of bacterial resistance to, traditional copper controls calls for new approaches to disease management. Bacteriophage‐based biocontrol could provide a sustainable and natural alternative approach to combat bacterial pathogens. Therefore, seventy phages were isolated from soil, leaf and bark of cherry trees in six locations in the south east of England. Subsequently, their host range was assessed against strains of Pss, Psm1 and Psm2. While these phages lysed different Pss, Psm and some other P. syringae pathovar isolates, they did not infect beneficial bacteria such as Pseudomonas fluorescens. A subset of thirteen phages were further characterized by genome sequencing, revealing five distinct clades in which the phages could be clustered. No known toxins or lysogeny‐associated genes could be identified. Using bioassays, selected phages could effectively reduce disease progression in vivo, both individually and in cocktails, reinforcing their potential as biocontrol agents in agriculture.
Species delimitation and geography
Authors: Hausdorf Bernhard , Hennig Christian
Published: May 2020

Abstract

Despite the importance of the geographical arrangement of populations for the inference of species boundaries, only a few approaches that integrate spatial information into species delimitation have thus far been developed. Persistent differentiation of sympatric groups of individuals is the best criterion for species status. Species delimitation becomes more prone to error if allopatric metapopulations are considered because it is often difficult to assess whether observed differences between allopatric metapopulations would be sufficient to prevent the fusion of these metapopulations upon contact. We propose a novel approach for testing the hypothesis that the multilocus genetic distances between individuals or populations belonging to two different candidate species are not larger than expected based on their geographical distances and the relationship of genetic and geographical distances within the candidate species. A rejection of this null hypothesis is an argument for classifying the two studied candidate species as distinct species. Case studies show that the proposed tests are suitable to distinguish between intra‐ and interspecific differentiation. The regression approach proposed here is more appropriate for testing species hypotheses with regard to isolation by distance than (partial) Mantel tests. Our tests assume a linear relationship between genetic and (transformed) geographical distances. This assumption can be compromised by a high genetic variability within populations as found in a case study with microsatellite markers.
Surgical outcomes of 215 patients with thymic epithelial tumors: A single‐center experience
Authors: Tian Wenxin , Sun Yaoguang , Wu Qingjun , Jiao Peng , Ma Chao , Yu Hanbo , Huang Chuan , Tong Hongfeng
Published: May 2020

Objectives

To evaluate the oncological prognosis and neurological outcomes for patients with thymic epithelial tumors (TETs) after thymectomy.

Methods

Consecutive patients with TETs who underwent thymectomy at Beijing Hospital from January 2011 to December 2018 were retrospectively enrolled into the study. Clinical, pathological, and perioperative data was collected. Patients were followed‐up by telephone interview and outpatient records. Statistical analyses were performed using SPSS version 19.0.

Results

A total of 215 patients (115 men and 100 women) were included in this study of which 133 patients (61.9%) had TETs associated with myasthenia gravis (MG), and 82 patients (38.1%) had thymic tumors without MG. A total of 194 (90.2%) patients were successfully followed‐up. The median follow‐up period was 42 months. The five‐year overall survival (OS) rate was 88.6%. MG was the first cause of death for patients with MG (6/10). Prognosis in MG patients was similar to those without MG. Multivariate Cox regression analysis demonstrated that TNM stage III + IV was an independent risk factor for OS. Incomplete resection and younger age were risk factors for tumor recurrence. For patients with MG, the cumulative complete stable remission (CSR) rate increased with the postoperative follow‐up period, and the five‐year CSR rate was 44.7%. Univariate Cox analysis indicated that age, preoperative MG duration and preoperative medication might correlate with CSR. Multivariate Cox analysis only indicated older age as a negative factor of achieving CSR.

Conclusions

MG had little influence on OS and tumor recurrence of thymic tumors. The new TNM staging system was an independent prognostic factor. Incomplete resection and younger age were risk factors for tumor recurrence. Older age was a negative factor of achieving CSR for thymoma patients with MG after extended thymectomy.

Key points

Significant findings of the study

MG was not a prognostic factor for thymic tumors. The new TNM staging system was useful for prediction of prognosis. Incomplete resection and younger age were risk factors for tumor recurrence. Older age led to a lower probability of achieving CSR for thymomatous MG.

What this study adds

This study had a relatively large sample size of patients with thymic epithelial tumors in a single center. We evaluated not only the oncological prognosis, but also neurological outcomes after thymectomy, which was a more comprehensive assessment of surgical effect for thymic epithelial tumors.
Targeting eradication of introduced watersnakes using integral projection models
Authors: Rose Jonathan P. , Todd Brian D.
Published: May 2020

Projection models are frequently used to identify and evaluate management actions to control or eradicate non‐native species. Integral projection models (IPMs) are an appealing option for many taxa because IPMs can model vital rates as a function of continuous variables, like size, without discretizing into a few classes. Despite their strengths, IPMs have yet to see widespread use in invasive species management. Here, we used an IPM to evaluate management actions for an introduced population of common watersnakes (Nerodia sipedon) recently established in California, USA, where they pose a threat to many highly imperiled native fauna. We developed the IPM using data on the survival, growth and fecundity of native and non‐native populations of N. sipedon to identify management targets that would facilitate its eradication. Population growth of N. sipedon was most sensitive to the growth and survival of snakes during their first year, when they grow from approximately 180 mm snout–vent length (SVL) to 350 mm, providing a clear target for eradication efforts. The IPM also provided finer resolution life‐history information for targeting eradication than a simple size class‐based matrix model. Simulated eradication effort showed funnel trapping, which targets all but the smallest and largest snakes, was more effective at decreasing population growth than hand capture focused on snakes >400 mm SVL. Our study highlights the value of IPMs for targeting eradication of introduced or invasive species, and we argue for wider adoption of these models for evaluating management actions.
Does translocation affect short‐term survival in a long‐lived species, the Spanish imperial eagle?
Authors: Muriel R. , Balbontín J. , Calabuig C. P. , Morlanes V. , Ferrer M.
Published: May 2020

In long‐lived species, usually with deferred maturity and low release numbers, the success of conservation translocations is especially sensitive to survival and site fidelity during the prolonged establishment phase. Concurrent management actions usually implemented in threatened populations may also influence translocation‐related responses. Therefore, the specific performance of translocations should be ideally assessed on vital rates of comparable management groups while accounting for other conservation actions. In this study, we analysed the impact of translocation on the short‐term survival and the relative contribution of electrocution on power pylons by comparing translocated and wild‐reared radio‐tracked juvenile Spanish imperial eagles Aquila adalberti before and after the implementation of further long‐term conservation actions of the species and other generic measures in southern Spain. A multi‐event multi‐state capture–recapture approach accounting for tag retention was applied on a long‐term dataset of resightings and dead recoveries throughout the first 2 years after fledging. Survival probability was similar in translocated and contemporary non‐translocated eagles, but higher than in wild‐reared birds before the generalization of multi‐action plans from the 1980s. It was also higher during early dispersal than in the post‐fledging dependence period. Although mortality due to electrocution decreased in absolute terms after implementing anti‐electrocution measures, its relative contribution as the main mortality source did not differ between translocated and wild‐reared birds or between periods (65%). Our results show that when translocations are properly implemented, observed vital rates of released animals can be comparable to those of wild‐reared individuals subjected to similar generic management addressing mortality sources. As for any management action, post‐release monitoring should play a key role in translocation programmes, with emphasis on comparative studies analysing potential factors affecting survival under active management contexts.
Pseudoglucagonoma syndrome: Description of an ‘Idiopatic’ case
Authors: Ferrara Gerardo , Ingordo Irene , Ingordo Vito
Published: May 2020

A case of pseudoglucagonoma syndrome, that is necrolytic migratory erythema, in a patient with no coexistent glucagonoma, is described. The patient was a 59‐year‐old man with waxing and waning dermatitis of the buttocks, characterised by arciform erythematous papulo‐squamous lesions with micro‐pustulation. Histopathology was characteristic for necrolytic migratory erythema, but no other underlying disease was detected. Other cases of pseudoglucagonoma syndrome described in literature are briefly reviewed.
Transperineal ultrasound predicts endoscopic and histological healing in ulcerative colitis
Authors: Sagami Shintaro , Kobayashi Taku , Aihara Kanako , Umeda Misaki , Morikubo Hiromu , Matsubayashi Mao , Kiyohara Hiroki , Nakano Masaru , Ohbu Makoto , Hibi Toshifumi
Published: May 2020

Background

Transabdominal ultrasound is useful to assess inflammation in patients with ulcerative colitis (UC); however, the assessment of the rectum is challenging and a barrier for its widespread use.

Aim

To evaluate if transperineal ultrasound is useful for predicting endoscopic and histological findings of the rectum in UC.

Methods

Fifty‐three consecutive adults with UC who required colonoscopy were included and transperineal ultrasound was performed in combination with transabdominal ultrasound within a week before or after colonoscopy with rectal biopsy. Mayo endoscopic subscore (MES) ≤1 was defined as endoscopic healing and Geboes score <2.1, Robarts histopathology index ≤6, and Nancy index ≤1 were defined as histological healing. Limberg score and bowel wall thickness were recorded with transperineal ultrasound. Faecal calprotectin was also measured.

Results

Excellent correlation was confirmed between colonoscopy and transabdominal ultrasound in all segments except for the rectum. Rectal bowel wall thickness and Limberg score in transperineal ultrasound well correlated with rectal MES and histological indices. Bowel wall thickness ≤4 mm predicted endoscopic (Area under the curve [AUC] = 0.90) and histological (AUC = 0.87‐0.89) healing. In multivariable logistic regression analysis, only bowel wall thickness in transperineal ultrasound was a significant independent predictor for rectal endoscopic and histologic healing (P < 0.05) and the predictability was better than faecal calprotectin.

Conclusions

Transperineal ultrasound predicts endoscopic and histological healing of the rectum. The combination of transperineal ultrasound with transabdominal ultrasound visualises the entire colorectum and is an ideal modality for the treat‐to‐target strategy.

Clinical Trials Registry number UMIN000033611 (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000038323).
Reciprocity Game
Authors: Chen Linfeng
Published: May 2020

This paper shows that reciprocity comes from the desire to cooperate in finitely repeated prisoner's dilemma game. Before playing the finitely repeated prisoner's dilemma game, players choose the reciprocity level and commit to it, and the reciprocity level is public information. There are T equilibria if the prisoner's dilemma game is repeated for T periods, and each equilibrium is associated with different levels of cooperation. Further, if players choose their reciprocity levels sequentially, then the most cooperative equilibrium will be the unique equilibrium. However, reciprocity does not matter for the one‐period game and the infinitely repeated game.
Pre‐planning and its effects on repeated dishonest behavior: An experiment
Authors: Chowdhury Subhasish M. , Kim Chulyoung , Kim Sang‐Hyun
Published: May 2020

We investigate experimentally the effects of the opportunity to pre‐plan one's action on dynamic (im)moral decision makings in two stages. In the experiment we either provided the subjects at the outset with the information that they might be able to tell lies to improve their payoff repeatedly (hence they could pre‐plan accordingly), or provided such information at the beginning of each stage (and hence they could not pre‐plan). Furthermore, we controlled whether they had the incentive to resort to telling a lie in the first stage or not. Our two main findings are: (i) when subjects were not informed about the second opportunity to lie at the outset, those who had an opportunity to lie in the first stage lied more often in the second stage compared to those who did not have such an opportunity; and (ii) pre‐planning induced subjects to lie more often in the first stage. We conjecture that pre‐planning invited a compensatory, instead of consistent, action, and thus induced more dishonest responses in the beginning and fewer later. We also discuss the extent of ‘partial lying’, i.e., lying in only one stage, across the treatments and its effect on the overall rate of lying.
Serum sCD40L levels are increased in patients with psoriatic arthritis and are associated with clinical response to apremilast
Authors: Venerito V , Natuzzi D , Bizzoca R , Lacarpia N , Cacciapaglia F , Lopalco G , Iannone F
Published: May 2020

The pathogenesis of psoriatic arthritis (PsA) involves several pathways, including the CD40/CD40L signaling which promotes the release of multiple cytokines. Transmembrane CD40L is also released in soluble form (sCD40L) and phosphodiesterase 4 (PDE4) seems to be involved in its cleavage. We aimed to investigate whether apremilast, a PDE4 inhibitor, could modify circulating levels of sCD40L in PsA patients, and the possible associations of these changes with clinical response. Consecutive PsA patients starting apremilast in routine clinical practice were prospectively observed. Disease Activity of Psoriatic Arthritis (DAPSA), Psoriasis Area Severity Index (PASI), Leeds Enthesitis Score (LEI) and serum samples were collected at baseline and at 6 months. Samples were run in a Bio-Plex ProTM plate for sCD40L. To investigate the association of sCD40L level with DAPSA based minor response, low disease activity (LDA) and/or remission at 6 months of treatment, multivariate logistic regression models with backward selection (P < 0·05) were built. We studied 27 patients (16 of 27 women, 59·6%) with PsA and mean age [± standard deviation (s.d.)] of 58·4 ± 10 years. A significant reduction of the mean values of DAPSA, LEI and PASI was detected at 6 months. Mean serum levels of sCD40L decreased from baseline 5364 ± 2025 pg/ml to 4412 ± 2629 at 6 months (P = 0·01). Baseline DAPSA [odds ratio (OR) = 0·80, 95% confidence interval (CI) = 0·65–0·98] and sCD40L (OR = 1·001, 95% CI = 1·0001–1·0027) were independently associated with DAPSA LDA/remission at 6 months. In PsA patients, sCD40L levels decrease upon apremilast treatment and might predict short-term clinical response to apremilast.
Changes in real‐world treatment patterns for diabetic macular oedema from 2009 to 2019 and 5‐year outcomes: Data from the Fight Retinal Blindness! Registry
Authors: Biechl Anne C. , Bhandari Sanjeeb , Nguyen Vuong , Arnold Jennifer J. , Young Stephanie , Fraser‐Bell Samantha , Mehta Hemal , Gillies Mark , Barthelmes Daniel
Published: May 2020

Importance

Evaluating the treatment outcomes of diabetic macular oedema (DMO) in routine clinical practice provides data for comparison with those of clinical trials.

Background

Phase 3 clinical trials of vascular endothelial growth factor (VEGF) inhibitors for DMO have reported significant improvements in visual acuity (VA) not previously reported with laser and steroid treatments.

Design

Retrospective analysis of observational data from routine clinical practice.

Participants

Eyes receiving treatments for DMO tracked in the Fight Retinal Blindness! Registry.

Methods

We analysed 510 eyes (347 patients) that started DMO treatment between 2009 and 2014.

Main Outcome Measures

Changes in DMO treatment patterns and mean change in VA (letters logMAR) and central subfield thickness (CST) 5 years after starting treatment.

Results

Treatment choice for DMO changed to predominantly VEGF inhibitors from 2009 to 2014. A total of 238 eyes (47%) were followed for at least 5 years. The mean VA at the start of treatment improved from 2009 (58 letters) to 2014 (68 letters) while mean VA change at 5 years were + 4.5 and + 5.3 letters for eyes starting treatment in 2009 and 2014, respectively. The mean CST dropped from 401 μm at baseline to 314 μm at 5 years. Eyes received a median of four injections in the first, two in the second, third and fourth and three in the fifth years.

Conclusions and Relevance

Changing the treatment of DMO from macular laser and intravitreal triamcinolone to VEGF inhibitors from 2011 onwards was associated with better VA outcomes, part of which were due to better VA at the start of treatment. The outcomes of treatment in eyes in real‐world practice were, however, worse than those reported by clinical trials, likely because they were undertreated.
Factors associated with use of immunohistochemical markers in the histopathological diagnosis of cutaneous melanocytic lesions
Authors: May Caitlin J. , Piepkorn Michael W. , Knezevich Stevan R. , Elder David E. , Barnhill Raymond L. , Lee Annie C. , Flores Martiniano J. , Kerr Kathleen F. , Reisch Lisa M. , Elmore Joann G.
Published: May 2020

Background

Melanocytic tumors are often challenging and constitute almost one in four skin biopsies. Immunohistochemical (IHC) studies may assist diagnosis; however, indications for their use are not standardized.

Methods

A test set of 240 skin biopsies of melanocytic tumors was examined by 187 pathologists from 10 US states, interpreting 48 cases in Phase I and either 36 or 48 cases in Phase II. Participant and diagnosis characteristics were compared between those who reported they would have ordered, or who would have not ordered IHC on individual cases. Intraobserver analysis examined consistency in the intent to order when pathologists interpreted the same cases on two occasions.

Results

Of 187 participants interpreting 48 cases each, 21 (11%) did not request IHC tests for any case, 85 (45%) requested testing for 1 to 6 cases, and 81 (43%) requested testing for ≥6 cases. Of 240 cases, 229 had at least one participant requesting testing. Only 2 out of 240 cases had more than 50% of participants requesting testing. Increased utilization of testing was associated with younger age of pathologist, board‐certification in dermatopathology, low confidence in diagnosis, and lesions in intermediate MPATH‐Dx classes 2 to 4. The median intraobserver concordance for requesting tests among 72 participants interpreting the same 48 cases in Phases I and II was 81% (IQR 73%‐90%) and the median Kappa statistic was 0.20 (IQR 0.00, 0.39).

Conclusion

Substantial variability exists among pathologists in utilizing IHC.