bluuebunny/crossref_metadata_2025 huggingface dataset:
Sharing a household with children and risk of COVID-19: a study of over 300,000 adults living in healthcare worker households in Scotland
Authors: Wood Rachael , Thomson Emma C , Galbraith Robert , Gribben Ciara , Caldwell David , Bishop Jennifer , Reid Martin , Shah Anoop S V , Templeton Kate , Goldberg David , Robertson Chris , Hutchinson Sharon , Colhoun Helen , McKeigue Paul , McAllister David A
Published: September 2020

Background

Children are relatively protected from novel coronavirus infection (COVID-19). The reasons for this protection are not well understood but differences in the immune response to Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) have been implicated. If such differences are due to differential exposure to non-SARS-CoV-2 infectious agents, adults who are close contacts of children may partly share in this protection. Such a protective effect would have important implications for the lives of children, not least in terms of schooling.

Methods

Using a Scotland-wide record-linkage based occupational cohort comprising healthcare workers and members of their households, we examined whether sharing a household with young children (aged 0 to 11) attenuated the risk of hospitalisation with COVID-19, and/or testing positive for COVID-19 infection of any severity (any case of Covid-19). All healthcare workers directly employed by the National health Service (NHS) in Scotland, or contracted to provide general practice services, were included. Outcome and covariate data were obtained via linkage to Scotland-wide microbiology, drug prescribing, hospitalisation and death data.

Results

241,266 adults did not share a household with young children; 41,198, 23,783 and 3,850 shared a household with 1, 2 and 3 or more young children respectively. The risk of hospitalisation with COVID-19 was lower in those with one child and lower still in those with two or more children, adjusting for age the hazard ratio (HR) was 0.83 per child (95% CI 0.70-0.99). On additionally adjusting for sex, socioeconomic deprivation, occupation, professional role, staff/non-staff status, the number of adults and adolescents in each household, and comorbidity, the HR was 0.89 per child (95% CI 0.74-1.06). An association of the same magnitude, but more precisely estimated, was obtained for any case of COVID-19 (fully adjusted model, HR per child 0.89; 95% CI 0.84-0.95).

Conclusion

Increased household exposure to young children was associated with an attenuated risk of testing positive for SARS-CoV-2 and appeared to also be associated with an attenuated risk of COVID-19 disease severe enough to require hospitalisation.
Transcriptomic Signaling Pathways involved in a naturalistic model of Inflammation-related Depression and its remission
Authors: Moisan Marie-Pierre , Foury Aline , Dexpert Sandra , Cole Steve W , Beau Cédric , Forestier Damien , Ledaguenel Patrick , Magne Eric , Capuron Lucile
Published: September 2020

This study aimed at identifying molecular biomarkers of inflammation-related depression in order to improve diagnosis and treatment. We performed whole-genome expression profiling from peripheral blood in a naturalistic model of inflammation-associated major depressive disorder (MDD) represented by comorbid depression in obese patients. We took advantage of the marked reduction of depressive symptoms and inflammation following bariatric surgery to test the robustness of the identified biomarkers. Depression was assessed during a clinical interview using Mini-International Neuropsychiatric Interview and the 10-item, clinician administered, Montgomery-Asberg Depression Rating Scale. From a cohort of 100 massively obese patients we selected 33 of them for transcriptomic analysis. Twenty-four of them were again analyzed 4-12 months after bariatric surgery. We conducted differential gene expression analyses before and after surgery in unmedicated MDD and non-depressed obese subjects. We found that TP53 (Tumor Protein 53), GR (Glucocorticoid Receptor) and NFκB (Nuclear Factor kappa B) pathways were the most discriminating pathways associated with inflammation-related MDD. These signaling pathways were processed in composite z-scores of gene expression that were used as biomarkers in regression analyses. Results showed that these transcriptomic biomarkers highly predicted depressive symptom intensity at baseline and their remission after bariatric surgery. While inflammation was present in all patients, GR signaling overactivation was found only in depressed ones where it may further increase inflammatory and apoptosis pathways. In conclusion, using an original model of inflammation-related depression and its remission without antidepressants, we provide molecular predictors of inflammation-related MDD and new insights in the molecular pathways involved.
Estimate of the actual number of COVID-19 cases from the analysis of deaths
Authors: Etchenique Roberto , Quiroga Rodrigo
Published: September 2020

Using the calculated values for the Infection Fatality Rate (IFR) of COVID-19 it is possible to estimate the prevalence of cases of infection in the city of Buenos Aires, Argentina, throughout the pandemic. The use of confirmed cases as a metric and their replacement by more reliable parameters such as death figures are discussed. The results are analyzed according to age ranges and possible sources of error in the estimates are established.
“We can’t just wish this thing away”: Caregiver perspectives on a child’s diagnosis of 3q29 deletion
Authors: Glassford Megan R. , Purcell Ryan H. , Pass Sarah , Murphy Melissa M. ,   The Emory 3q29 Project, Bassell Gary J. , Mulle Jennifer G.
Published: September 2020

Objective

Genetic diagnoses are increasingly common in cases of intellectual disability and developmental delay. While ascertainment of a relatively common, well-studied variant may provide guidance related to treatments and developmental expectations, it is less clear how the diagnosis of a rare variant impacts caregivers, especially when the phenotype may include later onset manifestations such as psychosis. In the current study, we sought to identify caregiver concerns in the first qualitative study to assess the psychosocial impact of diagnosis on caregivers of individuals with 3q29 deletion syndrome (3q29Del), which is associated with a 40-fold increase in risk for psychosis.

Method

Participants were recruited from the national 3q29Del registry housed at Emory University (3q29deletion.org). Fifteen participants completed a semi-structured phone interview during which they were asked about their experiences before, during, and after their child received a diagnosis of 3q29Del. Interview responses were analyzed using the general inductive approach, and overarching themes were identified.

Results

We identified the following overarching themes: difficult “diagnostic odyssey,” mixed feelings about diagnosis, frustration with degree of uncertainty, and importance of resources. Importantly, our data suggest that future risk for psychosis is often not disclosed by medical professionals, consistent with the experience of individuals with 22q11.2 deletion syndrome.

Conclusion

These results highlight potential gaps in how caregivers are informed of risk for adult-onset conditions and point to key caregiver concerns for consideration in diagnosis of 3q29Del.
Dynamic Change of COVID-19 Seroprevalence among Asymptomatic Population in Tokyo during the Second Wave
Authors: Hibino Sawako , Hayashida Kazutaka , Ahn Andrew C , Hayashida Yasutaka
Published: September 2020

Importance

Fatality rates related to COVID-19 in Japan have been low compared to Western Countries and have decreased despite the absence of lockdown. Serological tests monitored across the course of the second wave can provide insights into the population-level prevalence and dynamic patterns of COVID-19 infection.

Objective

To assess changes in COVID-19 seroprevalence among asymptomatic employees working in Tokyo during the second wave.

Design

We conducted an observational cohort study. Healthy volunteers working for a Japanese company in Tokyo were enrolled from disparate locations to determine seropositivity against COVID19 from May 26 to August 25, 2020. COVID-19 IgM and IgG antibodies were determined by a rapid COVID19 IgM/IgG test kit using fingertip blood. Across the company, tests were performed and acquired weekly. For each participant, serology tests were offered twice, separated by approximately a month, to provide self-reference of test results and to assess for seroconversion and seroreversion.

Setting

Workplace setting within a large company.

Participants

Healthy volunteers from 1877 employees of a large Japanese company were recruited to the study from 11 disparate locations across Tokyo. Participants having fever, cough, or shortness of breath at the time of testing were excluded.

Main Outcome(s) and Measure(s)

Seropositivity rate (SPR) was calculated by pooled data from each two-weeks window across the cohort. Either IgM or IgG positivity was defined as seropositive. Changes in immunological status against SARS-CoV-2 were determined by comparing results between two tests obtained from the same individual.

Results

Six hundred fifteen healthy volunteers (mean + SD 40.8 + 10.0; range 19 - 69; 45.7 % female) received at least one test. Seroprevalence increased from 5.8 % to 46.8 % over the course of the summer. The most dramatic increase in SPR occurred in late June and early July, paralleling the rise in daily confirmed cases within Tokyo, which peaked on August 4. Out of the 350 individuals (mean + SD 42.5 + 10.0; range 19 - 69; 46.0 % female) who completed both offered tests, 21.4 % of those individuals who tested seronegative became seropositive and seroreversion was found in 12.2 % of initially seropositive participants. 81.1% of IgM positive cases at first testing became IgM negative in approximately one month.

Conclusions and Relevance

COVID-19 infection may have spread widely across the general population of Tokyo despite the very low fatality rate. Given the temporal correlation between the rise in seropositivity and the decrease in reported COVID-19 cases that occurred without a shut-down, herd immunity may be implicated. Sequential testing for serological response against COVID-19 is useful for understanding the dynamics of COVID-19 infection at the population-level.
A Brief Burnout Evaluation Scale (BBES) as a potential tool to prevent collapse of the health care task force during the COVID-19 pandemic
Authors: Bastos Tamires Martins , Monteiro Gabriela Massaro Carneiro , Borges Rogério Boff , Moser Carolina Meira , Arenas Daniel Luccas , Bassols Ana Margareth , Laskoski Pricilla Braga , Hauck Simone
Published: September 2020

Introduction

In the context of the COVID-19 pandemic, where overloaded health systems seem inevitable, there is a need for reliable, conceptually adequate, and easily applied measurement tools to identify health professionals at risk.

Objective

to present the preliminary psychometric properties of a Brief Burnout Evaluation Scale (BBES) and its association with important outcomes, i.e., moderate to severe depression and suicidal ideation.

Methods

The BBES has 4 Likert-type items and was tested as part of a cross-sectional study that included 401 medical students. Reliability analysis and validity studies were performed.

Results

In the parallel analysis, two factors were extracted, explaining 84.4% of the variance. The Cronbach’s alpha was 0.78, showing high internal consistency. Considering a cut-off point of 12, the odds ratio for moderate to severe depression was 3.01 (CI 1.7-5.22; p<0.001) and for last month suicidal ideation 2.96 (CI 1.6-5.48).

Conclusion

The results suggest good psychometric characteristics for the BBES, thus reinforcing its utility as an assessment tool for evaluating the well-being or distress of health professionals. It carries with it the potential to implement early interventions and to prevent the descent into burnout so common today in the health care task force during the pandemic.
Temporal analysis of the clinical evolution of confirmed cases of COVID-19 in the state of Mato Grosso do Sul - Brazil
Authors: Pompeo Carolina Mariano , Ferreira Marcos Antonio , de Queiroz Cardoso Andréia Insabralde , Costa Luciana Scarlazzari , da Costa Souza Mercy , Mota Felipe Machado , Ivo Maria Lúcia
Published: September 2020

The objective was to analyze the evolution of confirmed cases of COVID-19 in the first four months of the pandemic in Mato Grosso do Sul, a state in the Center-West region of Brazil, as well as the factors related to the prevalence of deaths. This was an observational study with a cross-sectional and time series design based on data from the information system of the State Department of Health of Mato Grosso do Sul, Brazil. The microdata from the epidemiological bulletin is open and in the public domain; consultation was carried out from March to July 2020. The incidences were stratified per 100,000 inhabitants. The cross-section study was conducted to describe COVID-19 cases, and the trend analysis was performed using polynomial regression models for time series, with R-Studio software and a significance level of 5%. There was a predominance of women among the cases, and of men in terms of deaths. The presence of comorbidities was statistically related to mortality, particularly lung disease and diabetes, and the mean age of the deaths was 67.7 years. Even though the macro-region of the state capital, Campo Grande, had a higher number of cases, the most fatalities were in the macro-region of Corumbá. The trend curve demonstrated discreet growth in the incidence of cases between epidemiological weeks 11 and 19, with a significant increase in week 20 throughout the state. The trend for COVID-19 in the state of Mato Grosso do Sul was upward and regular, but there was an important and alarming exponential increase. The health authorities should adopt the necessary measures to enforce health precautions and encourage social distancing of the population so that health services will be able to care for those afflicted by the disease, especially older people, those with comorbidities, and vulnerable sectors of the population.
The effect of COVID-19 on the economy: evidence from an early adopter of localized lockdowns
Authors: Asahi Kenzo , Undurraga Eduardo A. , Valdés Rodrigo , Wagner Rodrigo
Published: September 2020

Background

Governments worldwide have implemented large-scale non-pharmaceutical interventions, such as social distancing or school closures, to prevent and control the growth of the COVID-19 pandemic. These strategies, implemented with varying stringency, have imposed substantial social and economic costs to society. As some countries begin to reopen and ease mobility restrictions, lockdowns in smaller geographic areas are increasingly being considered as an attractive policy intervention to mitigate societal costs while controlling epidemic growth. However, there is a lack of empirical evidence to support these decisions.

Methods

Drawing from a rich dataset of localized lockdowns in Chile, we used econometric methods to measure the reduction in local economic activity from lockdowns when applied to smaller or larger geographical areas. We measured economic activity by tax collection at the municipality-level.

Findings

Results show lockdowns were associated with a 10-15% drop in local economic activity, a two-fold reduction compared to municipalities not under lockdown. A three-to-four-month lockdown had a similar effect on economic activity than the year of the 2009 great recession. We found that costs are proportional to the population under lockdown, without differences when lockdowns were measured at the municipality or city-wide levels.

Conclusions

Our findings suggest that localized lockdowns have a large effect on local economic activity, but these effects are proportional to the population under lockdown. Our results suggest that epidemiological criteria should guide decisions about the optimal size of lockdown areas; the proportional effects of lockdowns on the economy seem to be unchanged by scale.

JEL codes

I10, I15, I18, H2
Design evaluation of a dental implant used in the jawbone D1 – D4 zones
Authors: Behzadian Farid , Borjali Amirhossein , Chizari Mahmoud
Published: September 2020

Many people may suffer from missing a tooth or teeth for different reasons. Dental implants are one of the primary solutions which are being used increasingly in the last few decades. In the first stage of the usual procedure, the surgeon uses a drill to create a socket into the jaw bone; then, in the next step, the implant, which is a fine metal screw most of the time, will be inserted into the pre-drilled socket.

This study investigates the biomechanical behaviors of a new dental implant which has a different performance and thread design. The strength of the new implant has been assessed under a daily loading through a series of experimental tests using dummy foam block substitute to the natural human jawbone. The feature of the new design was modified to introduce a new dental implant for brittle jawbones. The study was closely focusing on the design criteria of the implant applicable for D3-D4 zones of the jaw bone.
Reorganization of Substance Use Treatment and Harm Reduction Services during the COVID-19 Pandemic: A Global Survey
Authors: Radfar Seyed Ramin , De Jong Cornelis A J , Farhoudian Ali , Ebrahimi Mohsen , Rafei Parnian , Vahidi Mehrnoosh , Yunesian Masud , Kouimtsidis Christos , Arunogiri Shalini , Massah Omid , Deylamizadeh Abbas , Brady Kathleen T , Busse Anja
Published: September 2020

Background

The COVID-19 pandemic has impacted people with substance use disorders (SUDs) worldwide and healthcare systems have reorganized their services in response to the pandemic.

Methods

One week after the announcement of the COVID-19 as a pandemic, in a global survey, 177 addiction medicine professionals described COVID-19-related health responses in their own 77 countries in terms of SUD treatment and harm reduction services. The health response is categorized around (1) managerial measures and systems, (2) logistics, (3) service providers and (4) vulnerable groups.

Results

Respondents from over 88% of countries reported that core medical and psychiatric care for SUDs had continued; however, only 56% of countries reported having had any business continuity plan, and, 37.5% of countries reported shortages of methadone or buprenorphine supplies. Participants of 41% of countries reported partial discontinuation of harm-reduction services such as needle and syringe programs and condom distribution. 57% of overdose prevention interventions and 81% of outreach services also having been negatively impacted.

Conclusions

Participants reported that SUD treatment and harm reduction services had been significantly impacted globally early during the COVID-19 pandemic. Based on our findings, we provide a series of recommendations to support countries to be prepared more efficiently for future waves or similar pandemics to 1) help policymakers generate business continuity plans, 2) maintain use of evidence-based interventions for people with SUDs, 3) be prepared for adequate medication supplies, 4) integrate harm reduction programs with other treatment modalities and 5) have specific considerations for vulnerable groups such as immigrants and refugees.

Highlights

COVID-19 negatively impacted services for PWSUD globally.

Addiction medicine downgraded more than other psychiatry services.

Business continuity plan for PWSUD services reported only in about half of the countries.

Refugees & migrants had more negative impact compared to other vulnerable groups.

Harm reduction services discontinued partially or totally during pandemic.
OXTR rs53576 variation with breast and nipple pain in breastfeeding women
Authors: Lucas Ruth , Zhang Yiming , Walsh Stephen J. , Starkweather Angela , Young Erin
Published: September 2020

Purpose

To evaluate associations among breast and nipple pain sensitivity and candidate pain sensitivity single-nucleotide polymorphisms [SNPs], (COMT rs6269, rs4633, rs4818, rs4680 and OXTR rs2254298, rs53576) in breastfeeding women.

Design

A secondary analysis of sixty women participating in a pilot randomized controlled trial of a pain self-management intervention.

Methods

All participants underwent standardized mechanical somatosensory testing for an assessment of pain sensitivity and provided baseline buccal swabs for genetic analysis. At 1, 2, and 6 weeks postpartum, women self-reported breast and nipple pain severity using a visual analogue scale.

Results

Women with the minor allele OXTR rs53576 reported 8.18-fold higher breast and nipple pain severity over time. For every 1-unit increase in mechanical detection threshold and windup ratio, women reported 16.51-fold and 4.82-fold higher breast and nipple pain severity respectively. Six women with the OXTR rs2254298 minor allele reported allodynia.

Discussion

The presence of OXTR alleles in women with enhanced pain sensitivity suggests a phenotype of genetic risk for ongoing breast and nipple with potential for pain-associated breastfeeding cessation. Somatosensory testing identified women who reported higher breast and nipple pain during the first weeks of breastfeeding.

Clinical Implications

Pain sensitivity testing can help to identify women at risk of intolerable and/or ongoing breastfeeding pain who may benefit from additional support to mitigate early breastfeeding cessation. Targeted interventions are needed to address breastfeeding pain, including management of infant latch, positioning, and infection as well as support for self-management of breastfeeding pain.
Mu oscillations and motor imagery performance: A reflection of success, not ability
Authors: Chen Yvonne Y , Lambert Kathryn , Madan Christopher R , Singhal Anthony
Published: September 2020

Motor imagery, or our ability to imagine movement without actually engaging in the action, has been an increasingly popular tool in rehabilitation settings. Understanding its neural underpinning is crucial for further development of new interventions. Using scalp electroencephalography (EEG), many studies have shown that mu oscillations (8-13 Hz), a variant of the alpha band recorded over the motor cortex electrodes, are involved in both the imagination and performance of movements; however, the exact relationship between mu oscillations and motor imagery is unclear. To further our understanding of the functional significance of mu oscillations and their role in both motor learning and motor performance, our study sought to investigate how suppression in mu oscillations varies during a motor imagery task according to both within subject imagery success and between subject imagery ability. We examined EEG activity while a large sample of participants performed an objective test of motor imagery ability (Test of Ability in Movement Imagery, TAMI). Results demonstrated that mu oscillatory activity significantly decreased during successful imagery trials as compared to unsuccessful ones. However, the extent of reduction in mu oscillations did not correlate with individual imagery ability. These results provide further support for the involvement of mu oscillations in motor behaviours and indicate that suppression in mu oscillations may serve as an important index for determining successful motor imagery performance within an individual. The processes that underlie this success are likely similar to those that underlie successful motor execution, given motor imagery’s proposed functional equivalence to motor imagery.
Dynamic tracking and identification of tissue-specific secretory proteins in the circulation of live mice
Authors: Kim Kwang-eun , Park Isaac , Kim Jeesoo , Kang Myeong-Gyun , Choi Won Gun , Shin Hyemi , Kim Jong-Seo , Rhee Hyun-Woo , Suh Jae Myoung
Published: September 2020

Here we describeiSLET (in situSecretory proteinLabeling viaER-anchoredTurboID) which labels secretory pathway proteins as they transit through the ER-lumen to enable dynamic tracking of tissue-specific secreted proteomesin vivo. We expressediSLET in the mouse liver and demonstrated efficientin situlabeling of the liver-specific secreted proteome which could be tracked and identified within circulating blood plasma.iSLET is a versatile and powerful tool for studying spatiotemporal dynamics of secretory proteins, a valuable class of biomarkers and therapeutic targets.
Splitting sleep between the night and a daytime nap reduces homeostatic sleep pressure and enhances long-term memory
Authors: Cousins James N. , Leong Ruth L. F. , Jamaluddin S. Azrin , Ng Alyssa S. C. , Ong Ju Lynn , Chee Michael W.L.
Published: September 2020

Daytime naps have been linked with enhanced memory encoding and consolidation. It remains unclear how a daily napping schedule impacts learning throughout the day, and whether these effects are the same for well-rested and sleep restricted individuals. We compared memory in 112 adolescents who underwent two simulated school weeks containing 8 or 6.5 hour sleep opportunities each day. Sleep episodes were nocturnal or split between nocturnal sleep and a 90-min afternoon nap, creating four experimental groups: 8h-continuous, 8h-split, 6.5h-continuous and 6.5h-split. Declarative memory was assessed with picture encoding and an educationally realistic factual knowledge task. Splitting sleep significantly enhanced afternoon picture encoding and factual knowledge under both 6.5h and 8h durations. Splitting sleep also significantly reduced slow-wave activity during nocturnal sleep, suggesting lower homeostatic sleep pressure during the day. There was no negative impact of the split sleep schedule on morning performance, despite a reduction in nocturnal sleep duration. These findings suggest that naps could be incorporated into a daily sleep schedule that provides sufficient sleep and benefits learning.
An Advanced Framework for Time-lapse Microscopy Image Analysis
Authors: Jiang Qibing , Sudalagunta Praneeth , Meads Mark B. , Ahmed Khandakar Tanvir , Rutkowski Tara , Shain Ken , Silva Ariosto S. , Zhang Wei
Published: September 2020

Time-lapse microscopy is a powerful technique that generates large volumes of image-based information to quantify the behaviors of cell populations. This method has been applied to cancer studies to estimate the drug response for precision medicine and has great potential to address inter-patient (or intertumoral) heterogeneity. A couple of algorithms exist to analyze time-lapse microscopy images; however, most deal with very high-resolution images involving few cells (typically cell lines). There are currently no advanced and efficient computational frameworks available to process large-scale time-lapse microscopy imaging data to estimate patient-specific response to therapy based on a large population of primary cells. In this paper, we propose a robust and user-friendly pipeline to preprocess the images and track the behaviors of thousands of cancer cells simultaneously for a better drug response prediction of cancer patients.

Availability and Implementation

Source code is available at:https://github.com/CompbioLabUCF/CellTrack

ACM Reference Format

Qibing Jiang, Praneeth Sudalagunta, Mark B. Meads, Khandakar Tanvir Ahmed, Tara Rutkowski, Ken Shain, Ariosto S. Silva, and Wei Zhang. 2020. An Advanced Framework for Time-lapse Microscopy Image Analysis. InProceedings of BioKDD: 19th International Workshop on Data Mining In Bioinformatics (BioKDD).ACM, New York, NY, USA, 8 pages.https://doi.org/10.1145/nnnnnnn.nnnnnnn
A Constrained Mixture Theory Model to Study Autoregulation in the Coronary Circulation
Authors: Gharahi Hamidreza , Beard Daniel A. , Alberto Figueroa C. , Baek Seungik
Published: September 2020

Coronary autoregulation is a short-term response manifested by a relatively constant flow over a wide range of perfusion pressures for a given metabolic state. This phenomenon is thought to be facilitated through a combination of mechanisms, including myogenic, shear dependent, and metabolic controls. The study of coronary autoregulation is challenging due to the coupled nature of the mechanisms and their differential effects through the coronary tree. In this paper, we developed a novel framework to study coronary autoregulation based on the constrained mixture theory. This structurally-motivated autoregulation model required calibration of anatomical and structural parameters of coronary trees via a homeostatic optimization approach using extensive literature data. Autoregulation was then simulated for two different coronary trees: subepicardial and subendocardial. The structurally calibrated model reproduced available baseline hemodynamics and autoregulation data for each coronary tree. The autoregulation analysis showed that the diameter of the intermediate and small arterioles varies the most in response to changes in perfusion pressure. Finally, we demonstrated the utility of the model in two application examples: 1) response to drops in epicardial pressure, and 2) response to drug infusion in the coronary arteries. The proposed structurally-motivated model could be extended to study long-term growth and remodeling in the coronary circulation in response to hypertension, atherosclerosis, etc.

Key points

Coronary autoregulation is defined as the capability of the coronary circulation to maintain the blood supply to the heart over a range of perfusion pressures. This phenomenon is facilitated through intrinsic mechanisms that control the vascular resistance by regulating the mechanical function of smooth muscle cells. Understanding the mechanisms involved in coronary autoregulation is one of the most fundamental questions in coronary physiology.

This paper presents a structurally-motivated coronary autoregulation model that uses a nonlinear continuum mechanics approach to account for the morphometry and vessel wall composition in two coronary trees in the subepicardial and subendocardial layers.

The model is calibrated against diverse experimental data from literature and is used to study heterogeneous autoregulatory response in the coronary trees. This model drastically differs from previous models, which relied on lumped parameter model formulations, and is suited to the study of long-term pathophysiological growth and remodeling phenomena in coronary vessels.
Copy-scAT: Deconvoluting single-cell chromatin accessibility of genetic subclones in cancer
Authors: Nikolic Ana , Singhal Divya , Ellestad Katrina , Johnston Michael , Gillmor Aaron , Morrissy Sorana , Chan Jennifer A , Neri Paola , Bahlis Nizar , Gallo Marco
Published: September 2020

Single-cell epigenomic assays have tremendous potential to illuminate mechanisms of transcriptional control in functionally diverse cancer cell populations. However, application of these techniques to clinical tumor specimens has been hampered by the current inability to distinguish malignant from non-malignant cells, which potently confounds data analysis and interpretation. Here we describe Copy-scAT, an R package that uses single-cell epigenomic data to infer copy number variants (CNVs) that define cancer cells. Copy-scAT enables studies of subclonal chromatin dynamics in complex tumors like glioblastoma. By deploying Copy-scAT, we uncovered potent influences of genetics on chromatin accessibility profiles in individual subclones. Consequently, some genetic subclones were predisposed to acquire stem-like or more differentiated molecular phenotypes, reminiscent of developmental paradigms. Copy-scAT is ideal for studies of the relationships between genetics and epigenetics in malignancies with high levels of intratumoral heterogeneity and to investigate how cancer cells interface with their microenvironment.
ELR is a true pattern recognition receptor that associates with elicitins from diversePhytophthoraspecies
Authors: Domazakis Emmanouil , Wouters Doret , Lochman Jan , Visser Richard G. F. , Joosten Matthieu H. A. J. , Vleeshouwers Vivianne G. A. A.
Published: September 2020

The first layer of plant immunity against pathogens is mediated by cell surface pattern recognition receptors (PRRs) that recognize pathogen molecules in the apoplast. Several pairs of PRRs and their matching extracellular ligands have been described but, in many cases, actual evidence for ligand binding by the PRR is lacking. The receptor-like protein ELR fromSolanum microdontum, which triggers cell death upon co-expression with elicitins of variousPhytophthoraspecies and enhances resistance to late blight caused byPhytophthora infestans, was previously identified as the elicitin receptor by forward genetic screenings employing the INF1 elicitin ofP. infestans. In this study, we investigated whether ELR associates with INF1 and other elicitins that are secreted by diversePhytophthoraspp. We performedin plantaandin vitroco-immunoprecipitation of ELR with several affinity-tagged elicitins, as well asin plantatransient co-expression assays. We found that ELR physically interacts with the class I elicitins INF1 and ParA1, fromP. infestansandPhytophthora parasitica, respectively, which is in line with their ability to cause cell death when co-expressed with ELR in potato. Together, we demonstrate that ELR is a genuine PRR that binds elicitins ofPhytophthoraspecies.
Perch selection of three species of kingfishers at the Pantanal wetland, Brazil
Authors: Peinado Laura C. , Ortega Zaida
Published: September 2020

Animal movement and behavior depend on the distribution of resources on the habitat. Therefore, individual animals are constantly making decisions on resource selection based on different attributes of the resource or its associated environmental variables. For fish-eating birds as kingfishers, selecting a suitable perch can report many benefits, as improving fishing success or reducing predation risk. Nowadays, not only natural structures, as branches, are available for birds to perch but also artificial ones, as electric lines. Thus, we aimed to understand which variables drive kingfishers’ perch selection, including the potential effect of its anthropic origin. We studied perch selection of three species of kingfishers inhabiting the Pantanal of Miranda of Brazil:Megaceryle torquata, Chloroceryle amazonaandChloroceryle americana. They feed in temporary ponds that are rich in trophic resources, where they have both natural and artificial potential perches. We hypothesized that artificial perches could be strongly selected, as they are more stable than natural ones and go through the ponds, providing a long surface to select optimal conditions. We assessed how kingfishers are selecting perches based on four ecologically relevant traits: (1) being artificial or natural, perch height, (3) distance to the water, and (4) plant cover. We used a resource selection function (RSF) approach to quantify the effect of these variables in the probability of presence of kingfishers. The artificial origin of a perch was independent of the probability of selection for the three species. Furthermore, birds acted randomly to the other studied variables, except for individuals ofC. amazona, which select higher perches, above 3.20 m. We discuss the implications of these results for understanding the behavioral ecology and use of space of neotropical kingfishers, and how this affects their vulnerability to human habitat alterations.

GRAPHICAL ABSTRACT
The evolutionary dynamics of genetic incompatibilities introduced by duplicated genes inArabidopsis thaliana
Authors: Jiao Wen-Biao , Patel Vipul , Klasen Jonas , Liu Fang , Pecinkova Petra , Ferrand Marina , Gy Isabelle , Camilleri Christine , Effgen Sigi , Koornneef Maarten , Pecinka Ales , Loudet Olivier , Schneeberger Korbinian
Published: September 2020

Although gene duplications provide genetic backup and allow genomic changes under relaxed selection, they may potentially limit gene flow. When different copies of a duplicated gene are pseudo-functionalized in different genotypes, genetic incompatibilities can arise in their hybrid offspring. While such cases have been reported after manual crosses, it remains unclear whether they occur in nature and how they affect natural populations. Here we identified four duplicated-gene based incompatibilities including one previously not reported within an artificial Arabidopsis intercross population. Unexpectedly, however, for each of the genetic incompatibilities we also identified the incompatible alleles in natural populations based on the genomes of 1,135 Arabidopsis accessions published by the 1001 Genomes Project. Using the presence of incompatible allele combinations as phenotypes for GWAS, we mapped genomic regions which included additional gene copies which likely rescue the genetic incompatibility. Reconstructing the geographic origins and evolutionary trajectories of the individual alleles suggested that incompatible alleles frequently co-exist, even in geographically closed regions, and that their effects can be overcome by additional gene copies collectively shaping the evolutionary dynamics of duplicated genes during population history.
Optimized cultivar deployment improves the efficiency and stability of sunflower crop production at national scale
Authors: Casadebaig Pierre , Gauffreteau Arnaud , Landré Amélia , Langlade Nicolas B. , Mestries Emmanuelle , Sarron Julien , Trépos Ronan , Vincourt Patrick , Debaeke Philippe
Published: September 2020

Plant breeding programs design new crop cultivars which, while developed for distinct populations of environments, are nevertheless grown over large areas during their time in the market. Over its cultivation area, the crop is exposed to highly diverse stress patterns caused by climatic uncertainty and multiple management options, which often leads to decreased expected crop performance.

In this study, we aim is to assess how finer spatial management of genetic resources could reduce the yield variance explained by genotype × environment interactions in a set of cropping environments and ultimately improve the efficiency and stability of crop production. We used modeling and simulation to predict the crop performance resulting from the interaction between cultivar growth and development, climate and soil conditions, and management practices. We designed a computational experiment that evaluated the performance of a collection of commercial sunflower cultivars in a realistic population of cropping conditions in France, built from extensive agricultural surveys. Distinct farming locations sharing similar simulated abiotic stress patterns were clustered together to specify environment types. We then used optimization methods to search for cultivars × environments combinations leading to increased yield expectations.

Results showed that a single cultivar choice adapted to the most frequent environment-type in the population is a robust strategy. However, the relevance of cultivar recommendations to specific locations was gradually increasing with the knowledge of pedo-climatic conditions. We argue that this approach while being operational on current genetic material could act synergistically with plant breeding as more diverse material could enable access to cultivars with distinctive traits, more adapted to specific conditions.

Key message

Crop simulation helps to analyze environmental impacts on crops and provides year-independent context information. This information is of major importance when deciding which cultivar to choose at sowing time.
Characterization of Wnt Signaling Genes inDiaphorina citri, Asian Citrus Psyllid
Authors: Vosburg Chad , Reynolds Max , Noel Rita , Shippy Teresa , Hosmani Prashant S , Flores-Gonzalez Mirella , Mueller Lukas A , Hunter Wayne B , Brown Susan J , D’Elia Tom , Saha Surya
Published: September 2020

The Asian citrus psyllid,Diaphorina citri, is an insect vector that transmitsCandidatusLiberibacter asiaticus, the causal agent of the Huanglongbing (HLB) or citrus greening disease. This disease has devastated Florida’s citrus industry and threatens California’s industry as well as other citrus producing regions around the world. To find novel solutions to the disease, a better understanding of the vector is needed. TheD. citrigenome has been used to identify and characterize genes involved in Wnt signaling pathways. Wnt signaling is utilized for many important biological processes in metazoans, such as patterning and tissue generation. Curation based on RNA sequencing data and sequence homology confirm twenty four Wnt signaling genes within theD. citrigenome, including homologs for beta-catenin, Frizzled receptors, and seven Wnt-ligands. Through phylogenetic analysis, we classifyD. citriWnt-ligands asWg/Wnt1, Wnt5, Wnt6, Wnt7, Wnt10, Wnt11, andWntA. TheD. citriversion 3.0 genome with chromosomal length scaffolds reveals a conservedWnt1-Wnt6-Wnt10gene cluster with gene configuration similar to that inDrosophila melanogaster. These findings provide a greater insight into the evolutionary history ofD. citriand Wnt signaling in this important hemipteran vector. Manual annotation was essential for identifying high quality gene models. These gene models can further be used to develop molecular systems, such as CRISPR and RNAi, that target and controlD. citripopulations, to manage the spread of HLB. Manual annotation of Wnt signaling pathways was done as part of a collaborative community annotation project (https://citrusgreening.org/annotation/index).
Model guided trait-specific co-expression network estimation as a new perspective for identifying molecular interactions and pathways
Authors: Kontio Juho A. J. , Pyhäjärvi Tanja , Sillanpää Mikko J.
Published: September 2020

A wide variety of parametric approaches and co-expression networks have been developed for finding gene-by-gene interactions underlying complex traits from expression data. However, a little is known about the practical correspondence and synergistic potential of these different schemes. We provide a framework for parallel consideration of parametric interaction models with quantitative traits and co-expression networks based on a previously uncharacterized link between them. Resulting trait-specific co-expression network estimation method 1) serves to enhance the interpretation of biological networks in a more parametric sense and 2) exploits the underlying parametric model itself in the estimation process. It is tailored for simultaneous identification and classification of molecular interactions and pathways regulating complex traits by accounting for common characteristics of genetic architectures due to which the mainstream methods often lack efficiency. A remarkable advance over the state-of-art methods is illustrated theoretically and through comprehensive simulated scenarios. In particular, prognostically important novel findings in acute myeloid leukemia analysis demonstrate the method’s immediate practical relevance.

Author summary

Here we built up a mathematically justified bridge between parametric approaches and co-expression networks that have become prevalent for identifying molecular interactions underlying complex traits. We first shared our concern that methodological improvements around these schemes adjusting only their power and scalability are bounded by more fundamental scheme-specific limitations. Subsequently, our theoretical results were exploited to overcome these limitations to find gene-by-gene interactions neither of which can capture alone. We also aimed to illustrate theoretically and empirically how this framework enables the interpretation of co-expression networks in a more parametric sense to achieve systematic insights into complex biological processes more reliably. The main procedure was fit for various types of biological applications and high-dimensional data to cover the area of systems biology as broadly as possible. In particular, we chose to illustrate the method’s applicability for gene-profile based risk-stratification in cancer research using public acute myeloid leukemia datasets.
Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine
Authors: Liu Qiang , Hu Juan , Wang Jin , Wei Xin , Ping Conghui , Gao Yue , Xie Chang , Yu Ye , Li Dongdong , Yao Jing
Published: September 2020

The multimodal sensory channel transient receptor potential vanilloid-3 (TRPV3) is expressed in epidermal keratinocytes and implicated in chronic pruritus, allergy, and inflammation-related skin disorders. Gain-of-function mutations of TRPV3 cause hair growth disorders in mice and Olmsted Syndrome in human. Nevertheless, whether and how TRPV3 could be therapeutically targeted remains to be elucidated. We here report that mouse and human TRPV3 channel is selectively targeted by the clinical medication dyclonine that exerts a potent inhibitory effect. Accordingly, dyclonine rescued cell death caused by gain-of-function TRPV3 mutations and suppressed pruritus symptoms in vivo in mouse model. At the single-channel level, dyclonine inhibited TRPV3 open probability but not the unitary conductance. By molecular docking and mutagenesis, we further uncovered single residues in TRPV3 pore region that could toggle the inhibitory efficiency of dyclonine. The functional and mechanistic insights obtained on dyclonine-TRPV3 interaction will help to conceive updated therapeutics for skin inflammation.
Diverse myeloid cells are recruited to the developing and inflamed mammary gland
Authors: Wilson Gillian J , Fukuoka Ayumi , Vidler Francesca , Graham Gerard J
Published: September 2020

The immune system plays fundamental roles in the mammary gland, shaping developmental processes and controlling inflammation during infection and cancer. Here we reveal unanticipated heterogeneity in the myeloid cell compartment during development of virgin, pregnant and involuting mouse mammary glands, and in milk. We investigate the functional consequences of individual and compound chemokine receptor deficiency on cell recruitment. Diverse myeloid cell recruitment was also shown in models of sterile inflammation and bacterial infection. Strikingly, we have shown that inflammation and infection can alter the abundance of terminal end buds, a key developmental structure, within the pubertal mammary gland. This previously unknown effect of inflammatory burden during puberty could have important implications for understanding the control of pubertal timing.
Environmental influences and individual characteristics that affect learner-centered teaching practices
Authors: Emery Nathan , Maher Jessica Middlemis , Ebert-May Diane
Published: September 2020

Research-based teaching practices can improve student learning outcomes in a variety of complex educational environments. The implementation of learner-centered teaching practices in STEM can both benefit or be constrained by different factors related to individual instructors and the teaching environment. However, we know little of how the instructional climate varies across institutions and how this climate affects teaching practices. Our study sought to describe the relative importance of environmental influences and individual characteristics on learner- centered teaching practices across institutions. We also assessed departmental climate for 35 US higher education institutions. We found that self-efficacy in teaching and professional development exert a strong influence on faculty teaching practices. While departmental climate did not emerge as a significant predictor of teaching practices, there was consistently low support for teaching, and institution size was negatively correlated with leadership and evaluation of effective teaching. We also found that professional development may prepare instructors to teach learner-centered courses in different collegial teaching climates. Our results suggest that through cultivating self-efficacy and participating in iterative professional development, instructors can implement effective teaching practices across institutional environments.