bluuebunny/crossref_metadata_2025 huggingface dataset:
Serological evidence of human infection with SARS-CoV-2: a systematic review and meta-analysis
Authors: Chen Xinhua , Chen Zhiyuan , Azman Andrew S. , Deng Xiaowei , Chen Xinghui , Lu Wanying , Zhao Zeyao , Yang Juan , Viboud Cecile , Ajelli Marco , Leung Daniel T. , Yu Hongjie
Published: September 2020

Background

A rapidly increasing number of serological surveys for anti-SARS-CoV-2 antibodies have been reported worldwide. A synthesis of this large corpus of data is needed.

Purpose

To evaluate the quality of serological studies and provide a global picture of seroprevalence across demographic and occupational groups, and to provide guidance for conducting better serosurveys.

Data sources

PubMed, Embase, Web of Science, medRxiv, bioRxiv, SSRN and Wellcome were searched for English-language papers published from December 1, 2019 to August 28, 2020.

Study selection

Serological studies that evaluated seroprevalence of SARS-CoV-2 infections in humans.

Data extraction

Two investigators independently extracted data from included studies.

Data Synthesis

Most of 178 serological studies, representing tests in >800,000 individuals, identified were of low quality. Close contacts and high-risk healthcare workers had higher seroprevalence of 22.9% (95% CI: 11.1-34.7%) and 14.9% (4.8-25.0%), compared to low-risk healthcare workers and general population of 5.5% (4.6-6.4%) and 6.3% (5.5-7.1%). Generally, young people (0-20 yrs) were less likely to be seropositive compared to the middle-aged (21-55 yrs) populations (RR, 0.8, 95% CI: 0.7-0.8). Seroprevalence correlated with clinical COVID-19 reports with 10 (range: 2 to 34) infections per confirmed COVID-19 case.

Limitations

Some heterogeneity cannot be well explained quantitatively.

Conclusions

The overall quality of seroprevalence studies examined was low. The relatively low seroprevalence among general populations suggest that in most settings, antibody-mediated herd immunity is far from being reached. Given that ratio of infections to confirmed cases is on the same order of magnitude across different locales, reported case numbers may help provide insights into the proportion of the population infected.

Primary Funding source

National Science Fund for Distinguished Young Scholars (PROSPERO: CRD42020198253).
Taste alteration in COVID-19: a rapid review with data synthesis reveals significant geographical differences
Authors: Cirillo Nicola
Published: September 2020

To facilitate a timely understanding of the differences in the prevalence of gustatory disturbances (GD) in individuals infected with SARS-CoV-2, we undertook a rapid systematic review of articles published in the repository of the National Library of Medicine (MEDLINE/PubMed) and medRxiv from their inception until September 3, 2020. The minimum requirements for completing a restricted systematic review were met. Of the 431 articles retrieved, 61 eligible studies (28,374 confirmed COVID-19 cases) from 20 countries were included in the analysis. The results show strong significant differences in the overall reported prevalence of GD between East Asia [13%, 95% CI 0.14-26.06%], Middle East [38.83%, 95% CI 27.47-50.19%], Europe [57.18%, 95% CI 52.35-62.01%], and The Americas [66.78%, 95% CI 54.77-78.79%]. There were no trends showing differences of GD prevalence in the available literature between February and August, 2020. These data show that there is a distinct geographical distribution of GD in COVID-19 patients and this may explain the differences of diagnostic criteria for COVID-19 case definition.
Factors associated with limited access to condoms and sources of condoms during the COVID-19 pandemic in South Africa
Authors: Bolarinwa Obasanjo Afolabi
Published: September 2020

Background

Evidence has shown that the prescribed lockdown and physical distancing due to the novel coronavirus disease 2019 (COVID-19) have made accessing essential health care services much more difficult in low-and middle-income countries. Access to contraception is an essential service and should not be denied, even in a global crisis, because of its associated health benefits. Therefore, it is important to maintain timely access to contraception without unnecessary barriers. Hence, this study examines the factors contributing to limited access to condoms and preferred source of condoms during the COVID-19 pandemic in South Africa.

Methods

This study used data from the National Income Dynamics Study-Coronavirus Rapid Mobile Survey (NIDS-CRAM) wave 1 survey. The NIDS-CRAM is a nationally representative survey of the National Income Dynamics Survey (NIDS), which involves a sample of South Africans from 2017 NIDS wave 5, who were then re□interviewed via telephone interview. This is the first secondary dataset on coronavirus from NIDS during the coronavirus pandemic. A total of 5,304 respondents were included in the study. Data were analysed using frequencies and percentages, chi-square test and binary logistic regression analysis.

Results

Almost one-quarter (22.40%) of South Africans could not access condoms, and every 7 in 10 South Africans preferred public source of condoms. Those who were other population groups [aOR=0.37; 95% CI=0.19-0.74] and those who were in the third wealth quintile [aOR=0.60; 95% CI=0.38-0.93] had lower odds of having access to condoms while those respondents who were aged 25-34 [aOR=0.48; 95% CI=0.27-0.83] and those with a secondary level of education and above [aOR=0.24; 95% CI=0.08-0.71] were less likely to prefer public source of condom.

Conclusion

This study concludes that there was limited access to condoms during the COVID-19 pandemic and that the preferred source of condoms was very skewed to public source in South Africa. Strategic interventions such as community distribution of free condoms to avert obstruction of condom access during the COVID-19 pandemic or any future pandemics should be adopted.
The major predictors of testing positive for COVID-19 among symptomatic hospitalized patients
Authors: Barasa Samson , Kiage-Mokaya Josephine , Luna Geraldine , Friedlander Michael
Published: September 2020

Introduction

Increasing corona virus disease 2019 (COVID-19) pre-test probability can minimize testing patients who are less likely to have COVID-19 and therefore reducing personal protective equipment and COVID-19 testing kit use. The aim of this study was to identify patients who were likely to test positive for COVID-19 among symptomatic patients suspected of having COVID-19 during hospitalization by comparing COVID-19 positive and negative patients.

Method

We conducted a retrospective chart review of patients who were ≥18 years old and underwent COVID-19 Polymerase chain reaction test because they presented with symptoms thought to be due to COVID-19. The Poisson regression analysis was conducted after clinical presentation, demographic, medical co-morbidities, laboratory and chest image data was retrieved from the medical records.

Results

Charts of 277 and 35 COVID-19 negative and positive patients respectively were analyzed. Dyspnea (61%) was the most common symptom among COVID-19 negative patients, while 83% and 77% COVID-19 positive patients had cough and fever respectively.

COVID-19 positive patients were more likely to present initially with cough [1.082 (1.022 - 1.145)] and fever [1.066 (1.013 - 1.122)], besides being males [1.066 (1.013 - 1.123)] and 50 to 69 years old [1.090 (1.019 - 1.166)]. Dyspnea, weakness, lymphopenia and bilateral chest image abnormality were not associated with COVID-19 positivity.

COVID-19 positive patients were less likely to have non-COVID-19 respiratory viral illness [0.934 (0.893 - 0.976)], human immunodeficiency virus [0.847 (0.763 - 0.942)] and heart failure history [0.945 (0.908 - 0.984)]. Other chronic medical problems (hypertension, diabetes mellitus, chronic obstructive pulmonary disease and coronary artery disease) were not associated with testing positive for COVID-19.

Conclusion

Cough and fever are better predictors of symptomatic COVID-19 positivity during hospitalization. Despite published studies reporting a high prevalence of lymphopenia among COVID-19 positive patients, lymphopenia is not associated with the risk of testing positive for COVID-19.
The Impact of Mask-Wearing in Mitigating the Spread of COVID-19 During the Early Phases of the Pandemic
Authors: Aravindakshan Ashwin , Boehnke Jörn , Gholami Ehsan , Nayak Ashutosh
Published: September 2020

Masks have been widely recommended as a precaution against COVID-19 transmission. Several studies have shown the efficacy of masks at reducing droplet dispersion in lab settings. However, during the early phases of the pandemic, the usage of masks varied widely across countries. Using individual response data from the Imperial College London — YouGov personal measures survey, this study investigates the effect of mask use within a country on the spread of COVID-19. The survey shows that mask-wearing exhibits substantial variations across countries and over time during the pandemic’s early phase. We use a reduced form econometric model to relate population-wide variation in mask-wearing to the growth rate of confirmed COVID-19 cases. The results indicate that mask-wearing plays an important role in mitigating the spread of COVID-19. Widespread mask-wearing within a country associates with an expected 7% (95% CI: 3.94% — 9.99%) decline in the growth rate of daily active cases of COVID-19 in the country. This daily decline equates to an expected 88.5% drop in daily active cases over a 30-day period when compared to zero percent mask-wearing, all else held equal. The decline in daily growth rate due to the combined effect of mask-wearing, reduced outdoor mobility, and non-pharmaceutical interventions averages 28.1% (95% CI: 24.2%-32%).
Machine Learning for Integrating Social Determinants in Cardiovascular Disease Prediction Models: A Systematic Review
Authors: Zhao Yuan , Wood Erica P. , Mirin Nicholas , Vedanthan Rajesh , Cook Stephanie H. , Chunara Rumi
Published: September 2020

Background

Cardiovascular disease (CVD) is the number one cause of death worldwide, and CVD burden is increasing in low-resource settings and for lower socioeconomic groups worldwide. Machine learning (ML) algorithms are rapidly being developed and incorporated into clinical practice for CVD prediction and treatment decisions. Significant opportunities for reducing death and disability from cardiovascular disease worldwide lie with addressing the social determinants of cardiovascular outcomes. We sought to review how social determinants of health (SDoH) and variables along their causal pathway are being included in ML algorithms in order to develop best practices for development of future machine learning algorithms that include social determinants.

Methods

We conducted a systematic review using five databases (PubMed, Embase, Web of Science, IEEE Xplore and ACM Digital Library). We identified English language articles published from inception to April 10, 2020, which reported on the use of machine learning for cardiovascular disease prediction, that incorporated SDoH and related variables. We included studies that used data from any source or study type. Studies were excluded if they did not include the use of any machine learning algorithm, were developed for non-humans, the outcomes were bio-markers, mediators, surgery or medication of CVD, rehabilitation or mental health outcomes after CVD or cost-effective analysis of CVD, the manuscript was non-English, or was a review or meta-analysis. We also excluded articles presented at conferences as abstracts and the full texts were not obtainable. The study was registered with PROSPERO (CRD42020175466).

Findings

Of 2870 articles identified, 96 were eligible for inclusion. Most studies that compared ML and regression showed increased performance of ML, and most studies that compared performance with or without SDoH/related variables showed increased performance with them. The most frequently included SDoH variables were race/ethnicity, income, education and marital status. Studies were largely from North America, Europe and China, limiting the diversity of included populations and variance in social determinants.

Interpretation

Findings show that machine learning models, as well as SDoH and related variables, improve CVD prediction model performance. The limited variety of sources and data in studies emphasize that there is opportunity to include more SDoH variables, especially environmental ones, that are known CVD risk factors in machine learning CVD prediction models. Given their flexibility, ML may provide opportunity to incorporate and model the complex nature of social determinants. Such data should be recorded in electronic databases to enable their use.

Funding

We acknowledge funding from Blue Cross Blue Shield of Louisiana. The funder had no role in the decision to publish.
Ventilation and the SARS-CoV-2 Coronavirus
Authors: Birnir Björn
Published: September 2020

In a previous paper [10] a model of the distribution of respiratory droplets and aerosols by Lagrangian turbulent air-flow was developed. It is used to show how the SARS-CoV-2 Coronavirus can be spread by the breathing of single infected person. The model shows that the concentration of viruses in the cloud, exhaled by one person, can increase to infectious levels within a certain amount of time, in a confined space where the air re-circulates. In [10] the model was used to analyze the air-flow and SARS-CoV-2 Coronavirus build-up in a restaurant in Guangzhou, China [19, 18]. In this paper, we add the analysis of two more cases, an outbreak among lay-Buddhists, on a bus [26], traveling to a ceremony in Zhejiang province, China, and an outbreak in a Call Center in Seoul, Korea [20]. The analysis and comparison of these three cases, leads to the conclusion that the SARS-CoV-2 Coronavirus attacks in two steps: The first step is a linear spread between individuals with a couple of days delay. The second step is an exponential spread effected by the air-conditioning system affecting a much larger number of people. Thus in the second step, the ventilation becomes the super-spreader.
Clinical effectiveness of drugs in hospitalized patients with COVID-19: a systematic review and meta-analysis
Authors: Zuñiga R.A. Abeldaño , Coca S.M. , Abeldaño G.F. , Villoria R.A.M. González
Published: September 2020

Objective

The aim was to assess the clinical effectiveness of drugs used in hospitalized patients with COVID-19 infection.

Method

We conducted a systematic review of randomized clinical trials assessing treatment with remdesivir, chloroquine, hydroxychloroquine, lopinavir, ritonavir, dexamethasone, and convalescent plasma, for hospitalized patients with a diagnosis of SARS-CoV-2 infection. The outcomes were mortality, clinical improvement, duration of ventilation, duration of oxygen support, duration of hospitalization), virological clearance, and severe adverse events.

Results

A total of 48 studies were retrieved from the databases. Ten articles were finally included in the data extraction and qualitative synthesis of results. The meta-analysis suggests a benefit of dexamethasone versus standard care in the reduction of risk of mortality at day 28; and the clinical improvement at days 14 and 28 in patients treated with remdesivir.

Conclusions

Dexamethasone would have a better result in hospitalized patients, especially in low-resources settings.

Significance of results

The analysis of the main treatments proposed for hospitalized patients is of vital importance to reduce mortality in low-income countries; since the COVID-19 pandemic had an economic impact worldwide with the loss of jobs and economic decline in countries with scarce resources.
Adapting Lot Quality Assurance Sampling to accommodate imperfect tests: application to COVID-19 serosurveillance in Haiti
Authors: Fulcher Isabel R. , Clisbee Mary , Lambert Wesler , Leandre Fernet Renand , Hedt-Gauthier Bethany
Published: September 2020

Background

Lot Quality Assurance Sampling (LQAS), a tool used for monitoring health indicators in low resource settings resulting in “high” or “low” classifications, assumes that determination of the trait of interest is perfect. This is often not true for diagnostic tests, with imperfect sensitivity and specificity. Here, we develop Lot Quality Assurance Sampling for Imperfect Tests (LQAS-IMP) to address this issue and apply it to a COVID-19 serosurveillance study in Haiti.

Development

As part of the standard LQAS procedure, the user specifies allowable classification errors for the system, which is defined by a sample size and decision rule. We show that when an imperfect diagnostic test is used, the classification errors are larger than specified. We derive a modified procedure, LQAS-IMP, that accounts for the sensitivity and specificity of a diagnostic test to yield correct classification errors.

Application

At Zanmi Lasante health facilities in Haiti, the goal was to assess the prior circulation of COVID-19 among healthcare workers (HCWs) using a limited number of antibody tests. As the COVID-19 antibody tests were known to have imperfect diagnostic accuracy, we used the LQAS-IMP procedure to define valid systems for sampling at eleven hospitals in Haiti.

Conclusions

The LQAS-IMP procedure accounts for imperfect sensitivity and specificity in system design; if the accuracy of a test is known, the use of LQAS-IMP extends LQAS to applications for indicators that are based on laboratory tests, such as COVID-19 antibodies.

Key Messages

It is imperative to account for the sensitivity and specificity of the diagnostic test in serosurveillance studies.

For prevalence estimation and inference, adjustments for imperfect testing properties are available to researchers. However, no adjustments currently exist for the design of Lot Quality Assurance Sampling systems, resulting in invalid classification systems when used with an imperfect diagnostic test.

When sensitivity and specificity of a diagnostic test is known, Lot Quality Assurance Sampling for Imperfect Tests should be used to determine the sample size and decision rule for a system as it will result in valid classification errors.
Deciphering the evolution of the transcriptional and regulatory landscape in human placenta
Authors: Sun Ming-an , Wolf Gernot , Wang Yejun , Ralls Sherry , Senft Anna D. , Jin Jinpu , Dunn-Fletcher Caitlin E. , Muglia Louis J. , Macfarlan Todd S.
Published: September 2020

In mammals, the placenta mediates maternal-fetal nutrient and waste exchange and provides immunomodulatory actions that facilitate maternal-fetal tolerance. The placenta is highly diversified among mammalian species, yet the molecular mechanisms that distinguish the placenta of human from other mammals are not fully understood. Using an interspecies transcriptomic comparison of human, macaque, and mouse term placentae, we identified hundreds of genes with lineage-specific expression – including dozens that are placentally-enriched and potentially related to pregnancy. We further annotated the enhancers for different human tissues using epigenomic data and demonstrate that the placenta and chorion are unique in that their enhancers display the least conservation. We identified numerous lineage-specific human placental enhancers, and found they are highly overlapped with specific families of endogenous retroviruses (ERVs), including MER21A, MER4A/B and MER39B that were previously linked to immune response and placental function. Among these ERV families, we further demonstrate that MER41 insertions create dozens of lineage-specific Serum Response Factor (SRF) binding loci in human, including one adjacent toFBN2, a placenta-specific gene with increased expression in humans that produces the peptide hormone placensin to stimulate glucose secretion and trophoblast invasion. Our results demonstrate the prevalence of lineage-specific human placental enhancers which are frequently associated with ERV insertions and likely facilitated the lineage-specific evolution of the mammalian placenta.
Integration of Biodynamic Imaging and RNA-seq classifies chemotherapy response in canine diffuse large B-cell lymphoma
Authors: Fine Jonathan , Utturkar Sagar , Dhawan Deepika , Miguel Phillip San , Chopra Gaurav , Turek John , Nolte David , Childress Michael O. , Lanman Nadia A.
Published: September 2020

Diffuse large B-cell lymphoma (DLBCL) is a common, aggressive cancer of notorious genotypic and phenotypic heterogeneity. A major challenge is predicting response to drug treatment, which has typically been done using genomic tools alone with little success. A novel method that incorporates phenotypic profiling for predicting the effectiveness of therapy for individual patients is desperately needed. BioDynamic Imaging (BDI) is a technique for measuring time-dependent fluctuations in back-scattered light through living tumor tissues to identify critical changes in intracellular dynamics that are associated with phenotypic response to drugs. In this study, BDI and RNA sequencing (RNA-seq) data were collected on tumor samples from dogs with naturally occurring DLBCL, an animal model of increasingly recognized relevance to the human disease. BDI and RNA-seq data were combined to identify correlations between gene co-expression modules and linear combinations of biomarkers to provide biological mechanistic interpretations of BDI biomarkers. Using regularized multivariate logistic regression, we combined RNA-seq and BDI data to develop a novel model to accurately classify the clinical response of canine DLBCL to combination chemotherapy (i.e. CHOP). Our model incorporates data on the expression of 4 genes and 3 BDI-derived phenotypic biomarkers, capturing changes in transcription, microtubule related processes, and apoptosis. This pilot study suggests that the combination of multi-scale transcriptomic and phenotypic data can identify patients that respond to a given treatmenta prioriin a disease that has been difficult to treat. Our work provides an important framework for future development of strategies and treatments in precision cancer medicine.
Free ammonia pretreatment for anaerobic sludge digestion reduces the spread of antibiotic resistance
Authors: Zhang Zehao , Liu Huan , Wang Qilin
Published: September 2020

Sludge from the wastewater treatment plants (WWTPs) has been recognized as a reservoir of antibiotic resistance genes (ARGs). Free ammonia (FA, i.e. NH3-N) pretreatment has been demonstrated to be able to enhance anaerobic digestion, which is a widely used method for sludge treatment. However, the effect of combined FA pretreatment and anaerobic digestion on the fate of ARGs is still unknown. This study demonstrated for the first time that combined FA pretreatment (420 mg NH3-N/L for 24 h) and anaerobic digestion could reduce the abundances of the tested ARGs by 0.06 log10gene copies/g TS (total solids) compared with the anaerobic digestion alone. Specifically, the experimental results showed that combined FA pretreatment and anaerobic digestion reduced the abundances ofaac(6’)-Ib-cr, blaTEM, sul2, tetA,tetBandtetXby 0.07, 0.37, 0.09, 0.32, 0.24 and 0.59 log10gene copies/g TS compared with anaerobic digestion alone. In contrast, combined FA pretreatment and anaerobic digestion slightly increased the abundance oftetGby 0.05 log10gene copies/g TS compared with anaerobic digestion alone. In addition, FA pretreatment did not significantly affect the abundance ofsul1 and tetMduring anaerobic digestion. This study revealed that FA pretreatment for anaerobic digestion could potentially reduce the spread of antibiotic resistance from the sludge to soil (while agriculture reuse is used as the sludge disposal method), thereby protecting the environment and human health.
CUB and Sushi Multiple Domains 1 (CSMD1) opposes the complement cascade in neural tissues
Authors: Baum Matthew L. , Wilton Daniel K. , Muthukumar Allie , Fox Rachel G. , Carey Alanna , Crotty William , Scott-Hewitt Nicole , Bien Elizabeth , Sabatini David A. , Lanser Toby , Frouin Arnaud , Gergits Frederick , Håvik Bjarte , Gialeli Chrysostomi , Nacu Eugene , Blom Anna M. , Eggan Kevin , Johnson Matthew B. , McCarroll Steven A. , Stevens Beth
Published: September 2020

Schizophrenia risk is associated with increased gene copy number and brain expression ofcomplement component 4(C4). Because the complement system facilitates synaptic pruning, theC4association has renewed interest in a hypothesis that excessive pruning contributes to schizophrenia pathogenesis. However, little is known about complement regulation in neural tissues or whether such regulation could be relevant to psychiatric illness. Intriguingly, common variation withinCSMD1, which encodes a putative complement inhibitor, has consistently associated with schizophrenia at genome-wide significance. We found that Csmd1 is predominantly expressed in the brain by neurons, and is enriched at synapses; that human stem cell-derived neurons lacking CSMD1 are more vulnerable to complement deposition; and that mice lacking Csmd1 have increased brain complement activity, fewer synapses, aberrant complement-dependent development of a neural circuit, and synaptic elements that are preferentially engulfed by cultured microglia. These data suggest that CSMD1 opposes the complement cascade in neural tissues.

Graphic Abstract.

Our findings support a model in which CSMD1 opposes actions of the complement cascade in neural tissues (top left). We investigated two models in which Csmd1 was genetically ablated: human cortical neurons derived from embryonic stem cells, and a back-crossed C57bl6-Tac mouse line (top right). Csmd1 is normally expressed by neurons and present at synapses where it can protect them from complement (bottom left); in the absence of Csmd1 (bottom right), we find more deposition of complement (on cultured human cortical neurons and in the mouse visual system), reduced numbers of synapses (in the mouse visual system), and synaptic fractions that are more readily engulfed by microglia (ex vivo). Created withBioRender.com.
An autism-associated calcium channel variant causes defects in neuronal polarity and axon termination in the ALM neuron ofC. elegans
Authors: Buddell Tyler , Quinn Christopher C.
Published: September 2020

Variants of theCACNA1C voltage-gated calcium channelgene have been associated with autism and other neurodevelopmental disorders including bipolar disorder, schizophrenia, and ADHD. The Timothy syndrome mutation is a rarede novogain-of-function variant inCACNA1Cthat causes autism with high penetrance, providing a powerful avenue into investigating the role ofCACNA1Cvariants in neurodevelopmental disorders. In our previous work, we demonstrated that anegl-19(gof)mutation, that is equivalent to the Timothy syndrome mutation in the human homologCACNA1C,can disrupt termination of the PLM axon inC. elegans. Here, we find that theegl-19(gof)mutation disrupts the polarity of process outgrowth in the ALM neuron ofC. elegans. We also find that theegl-19(gof)mutation can disrupt termination of the ALM axon. These results suggest that the Timothy syndrome mutation can disrupt multiple steps of axon development. Further work exploring the molecular mechanisms that underlie these perturbations in neuronal polarity and axon termination will give us better understanding to how variants inCACNA1Ccontribute to the axonal defects that underlie autism.
Telomere-to-telomere assembly of the genome of an individualOikopleura dioicafrom Okinawa using Nanopore-based sequencing
Authors: Bliznina Aleksandra , Masunaga Aki , Mansfield Michael J. , Tan Yongkai , Liu Andrew W. , West Charlotte , Rustagi Tanmay , Chien Hsiao-Chiao , Kumar Saurabh , Pichon Julien , Plessy Charles , Luscombe Nicholas M.
Published: September 2020

Background

The larvaceanOikopleura dioicais an abundant tunicate plankton with the smallest (65-70 Mbp) non-parasitic, non-extremophile animal genome identified to date. Currently, there are two genomes available for the Bergen (OdB3) and Osaka (OSKA2016)O. dioicalaboratory strains. Both assemblies have full genome coverage and high sequence accuracy. However, a chromosome-scale assembly has not yet been achieved.

Results

Here, we present a chromosome-scale genome assembly (OKI2018_I69) of the OkinawanO. dioicaproduced using long-read Nanopore and short-read Illumina sequencing data from a single male, combined with Hi-C chromosomal conformation capture data for scaffolding. The OKI2018_I69 assembly has a total length of 64.3 Mbp distributed among 19 scaffolds. 99% of the assembly is in five megabase-scale scaffolds. We found telomeres on both ends of the two largest scaffolds, which represent assemblies of two fully contiguous autosomal chromosomes. Each of the other three large scaffolds have telomeres at one end only and we propose that they correspond to sex chromosomes split into a pseudo-autosomal region and X-specific or Y-specific regions. Indeed, these five scaffolds mostly correspond to equivalent linkage groups of OdB3, suggesting overall agreement in chromosomal organization between the two populations. At a more detailed level, the OKI2018_I69 assembly possesses similar genomic features in gene content and repetitive elements reported for OdB3. The Hi-C map suggests few reciprocal interactions between chromosome arms. At the sequence level, multiple genomic features such as GC content and repetitive elements are distributed differently along the short and long arms of the same chromosome.

Conclusions

We show that a hybrid approach of integrating multiple sequencing technologies with chromosome conformation information results in an accuratede novochromosome-scale assembly ofO. dioica’s highly polymorphic genome. This assembly will be a useful resource for genome-wide comparative studies betweenO. dioicaand other species, as well as studies of chromosomal evolution in this lineage.
Distinct mechanisms for TMPRSS2 expression explain organ-specific inhibition of SARS-CoV-2 infection by enzalutamide
Authors: Li Fei , Han Ming , Dai Pengfei , Xu Wei , He Juan , Tao Xiaoting , Wu Yang , Tong Xinyuan , Xia Xinyi , Guo Wangxin , Zhou Yunjiao , Li Yunguang , Zhu Yiqin , Zhang Xiaoyu , Liu Zhuang , Aji Rebiguli , Cai Xia , Li Yutang , Qu Di , Chen Yu , Jiang Shibo , Wang Qiao , Ji Hongbin , Xie Youhua , Sun Yihua , Lu Lu , Gao Dong
Published: September 2020

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a global public health threat due to the lack of effective drugs or vaccines against SARS-CoV-2. The efficacy of several repurposed drugs has been evaluated in clinical trials. Among these drugs, a relatively new antiandrogen agent, enzalutamide, was proposed because it reduces the expression of transmembrane serine protease 2 (TMPRSS2), a key component mediating SARS-CoV-2-driven entry into host cells, in prostate cancer cells. However, definitive evidence for the therapeutic efficacy of enzalutamide in COVID-19 is lacking. Here, we evaluated the antiviral efficacy of enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and SARS-CoV-2-infected Ad-ACE2-transduced Tmprss2 knockout (Tmprss2-KO) and wild-type (WT) mice. TMPRSS2 knockout significantly inhibited SARS-CoV-2 infectionin vivo. Enzalutamide effectively inhibited SARS-CoV-2 infection in human prostate cancer cells (LNCaP) but not in human lung cancer cells or patient-derived lung organoids. Although Tmprss2 knockout effectively blocked SARS-CoV-2 infection in ACE2-transduced mice, enzalutamide showed no antiviral activity due to the AR independence of TMPRSS2 expression in mouse and human lung epithelial cells. Moreover, we observed distinct AR binding patterns between prostate cells and lung cells and a lack of direct binding of AR to TMPRSS2 in human lung cells. Thus, our findings do not support the postulated protective role of enzalutamide in treating COVID-19.
Ab-initio determination of the shape of membrane proteins in a nanodisc
Authors: Orioli Simone , Hansen Carl G. Henning , Arleth Lise
Published: September 2020

We introduce a new software, calledMarbles, that employs SAXS intensities to predict the shape of membrane proteins embedded into membrane nanodiscs. To gain computational speed and efficient convergence, the strategy is based on a hybrid approach that allows one to account for the nanodisc contribution to the SAXS intensity through a semi-analytical model, while the embedded membrane protein is treated as set of beads, similarly to well known ab-initio methods. The code, implemented in C++ with a Python user interface, provides a good performance and includes the possibility to systematically treat unstructured domains. We prove the reliability and flexibility of our approach by benchmarking the code on a toy model and two proteins of very different geometry and size.
Vulnerability of Elevation-Restricted Endemic Birds of the Cordillera de Talamanca (Costa Rica and Panama) to Climate Change
Authors: Liu Zhen , Sandoval Luis , Sherman Lauren , Wilson Andrew
Published: September 2020

Animals endemic to tropical mountains are known to be especially vulnerable to climate change. The Cordillera de Talamanca (Costa Rica and Panama) is a geographically isolated mountain chain and global biodiversity hotspot, home to more than 50 endemic bird species. We used eBird community science observations to predict the distributions of a suite of 48 of these endemic birds in 2006-2015, and in 2070, under four climate change scenarios. Species distributions were predicted using program Maxent, incorporating elevation, satellite derived habitat data, and WorldClim climate variables. Model fit, as assessed by Area under the Receiver Operator Curve (AUC) was very high for most species, ranging from 0.877 to 0.992 (mean of 0.94). We found that most species are predicted to undergo range contractions by 2070, with a mean of 15% under modest climate change (RCP 2.6) up to a mean of 40% under more severe climate change (RCP 8.5). Most of the current ranges of these species are within existing protected areas (average of 59% in 2006-2015), and with prospective range contractions, the importance of these protected areas is forecast to increase. We suggest that these predicted range declines should elevate conservation concerns for this suite of species, and vigilance, in the form of better population monitoring, is urgently needed.
The KCNQ4-mediated M-current regulates the circadian rhythm in mesopontine cholinergic neurons
Authors: Bayasgalan T. , Stupniki S. , Kovács A. , Csemer A. , Szentesi P. , Pocsai K. , Dionisio L. , Spitzmaul G. , B. Pál
Published: September 2020

The M-current is a voltage gated potassium current inhibited by muscarinic activation and affected by several other G-protein coupled receptors. Its channels are formed by KCNQ subunits, from which KCNQ4 is restricted to certain brainstem structures. We sought evidence for the function of the M-current in the pedunculopontine nucleus (PPN) and the contribution of KCNQ4 subunits to the M-current and aimed to find its functional significance in the PPN. We found that cholinergic inputs of the PPN can effectively inhibit M-current. This current is capable of synchronizing neighboring neurons and inhibition of the M-current decreases neuronal synchronization. We showed that only a subpopulation of cholinergic neurons has KCNQ4-dependent M-current. The KCNQ4 subunit expression potentially regulates the presence of other KCNQ subunits. Deletion of KCNQ4 leads to alterations in adaptation of activity to light-darkness cycles, thus representing the potential role of KCNQ4 in regulation of sleep-wakefulness cycles. The presence of this protein restricted to certain brainstem nuclei raises the possibility that it might be a potential target for selective therapeutic interventions affecting the reticular activating system.
Exploratory neuroimmune profiling identifies CNS-specific alterations in COVID-19 patients with neurological involvement
Authors: Song Eric , Bartley Christopher M. , Chow Ryan D. , Ngo Thomas T. , Jiang Ruoyi , Zamecnik Colin R. , Dandekar Ravi , Loudermilk Rita P. , Dai Yile , Liu Feimei , Hawes Isobel A. , Alvarenga Bonny D. , Huynh Trung , McAlpine Lindsay , Rahman Nur-Taz , Geng Bertie , Chiarella Jennifer , Goldman-Israelow Benjamin , Vogels Chantal B.F. , Grubaugh Nathan D. , Casanovas-Massana Arnau , Phinney Brett S. , Salemi Michelle , Alexander Jessa , Gallego Juan A. , Lencz Todd , Walsh Hannah , Lucas Carolina , Klein Jon , Mao Tianyang , Oh Jieun , Ring Aaron , Spudich Serena , Ko Albert I. , Kleinstein Steven H. , DeRisi Joseph L. , Iwasaki Akiko , Pleasure Samuel J. , Wilson Michael R. , Farhadian Shelli F.
Published: September 2020

One third of COVID-19 patients develop significant neurological symptoms, yet SARS-CoV-2 is rarely detected in central nervous system (CNS) tissue, suggesting a potential role for parainfectious processes, including neuroimmune responses. We therefore examined immune parameters in cerebrospinal fluid (CSF) and blood samples from a cohort of patients with COVID-19 and significant neurological complications. We found divergent immunological responses in the CNS compartment, including increased levels of IL-12 and IL-12-associated innate and adaptive immune cell activation. Moreover, we found increased proportions of B cells in the CSF relative to the periphery and evidence of clonal expansion of CSF B cells, suggesting a divergent intrathecal humoral response to SARS-CoV-2. Indeed, all COVID-19 cases examined had anti-SARS-CoV-2 IgG antibodies in the CSF whose target epitopes diverged from serum antibodies. We directly examined whether CSF resident antibodies target self-antigens and found a significant burden of CNS autoimmunity, with the CSF from most patients recognizing neural self-antigens. Finally, we produced a panel of monoclonal antibodies from patients’ CSF and show that these target both anti-viral and anti-neural antigens—including one mAb specific for the spike protein that also recognizes neural tissue. This exploratory immune survey reveals evidence of a compartmentalized and self-reactive immune response in the CNS meriting a more systematic evaluation of neurologically impaired COVID-19 patients.

One Sentence Summary

A subset of COVID-19 patients with neurologic impairment show cerebrospinal fluid-specific immune alterations that point to both neuroinvasion and anti-neural autoimmunity as potential causes of impairment.
Secondhand homes: Woodpecker cavity location and structure influences secondary nester’s success
Authors: Hardin Faith O. , Leivers Samantha , Grace Jacquelyn K. , Cairns David M. , Campbell Tyler , Pierce Brian , Morrison Michael L.
Published: September 2020

Understanding how ecosystem engineers influence other organisms has long been a goal of ecologists. Woodpeckers select nesting sites with high food availability and will excavate and then abandon multiple cavities through their lifetime. These cavities are crucial to secondary cavity nesting birds (SCB) that are otherwise limited by the availability of naturally occurring cavities.

Our study examined the role food resources have on the nest site location and home range size of woodpeckers, and the respective influence woodpeckers and the construction of cavities have on the nesting success of SCB.

Using five years of avian point count data to locate golden-fronted woodpeckers (GFWO:Melanerpes aurifrons), we correlated insect availability with GFWO home range size and determined differences in insect availability between GFWO occupied and unoccupied sites, while recording nesting success (success: ≥ 1 fledgling) for the GFWO and common SCB in south Texas: Black-crested Titmouse (Baeolophus atricristatus), Ash-throated Flycatcher (Myiarchus cinerascens), Brown-crested Flycatcher (Myiarchus tyrannulus), and Bewick’s Wren (Thryomanes bewickii). We used model averaging to fit species-specific logistic regression models to predict nest success based on cavity metrics across all species.

Sites occupied by GFWO had a higher biomass of insects in orders Coleoptera, Hymenoptera, and Orthoptera than unoccupied sites, and there was a negative correlation between the availability of these insect orders and home-range size. GFWO had increased nest success in trees with increased vegetation cover and lower levels of decay, while

SCB had higher levels of nesting success in abandoned GFWO cavities opposed to naturally occurring ones, and in trees with low decay.

Our results suggest that SCB may be drawn to nest in abandoned woodpecker cavities where they have higher rates of nest success compared to natural cavities. Additionally, the prevalence for GFWO to excavate cavities in trees with lower levels of decay contradicts previous literature and may indicate a novel temperature trade-off, with live trees requiring more energy to excavate, but providing more protection from high breeding season temperatures in arid and semi-arid areas.
Robust Tobacco Smoking Self-Report in two Cohorts of Vulnerable Pregnant Women and Adults
Authors: Saberi Sara , Smith Marie-Soleil R. , Ajaykumar Abhinav , Zhu Mayanne M. T. , Gadawski Izabelle , Sattha Beheroze , Maan Evelyn J. , Van Schalkwyk Julie , Elwood Chelsea , Boucoiran Isabelle , Money Deborah M. , Côté Hélène C.F. ,   CIHR Team in Cellular Aging and HIV Comorbidities in Women and Children (CARMA)
Published: September 2020

Background

Stigma associated with tobacco smoking, especially during pregnancy, may lead to underreporting and possible bias in studies relying on self-reported smoking data. Cotinine, a nicotine metabolite with a ∼20h half-life in blood, is often used as a biomarker of smoking. The objective of this study was to examine the concordance between self-reported smoking and plasma cotinine concentration among participants enrolled in two related cohorts of vulnerable individuals: human immunodeficiency virus (HIV)-positive and HIV-negative pregnant women enrolled in the CARMA-PREG cohort and HIV-positive and HIV-negative non-pregnant women and men enrolled in the CARMA-CORE cohort.

Methods

For HIV-positive (n=76) and negative (n=24) pregnant women, plasma cotinine was measured by ELISA in specimens collected during the third trimester, between 28 and 38 weeks of gestation. Plasma cotinine was also measured in HIV-positive (n=43) and negative (n=57) women and men enrolled in the CARMA-CORE cohort.

Results

Self-reported smokers were more likely to have low income (p<0.001) in both cohorts, and to deliver preterm (p=0.007) in CARMA-PREG. In the CARMA-PREG cohort, concordance between plasma cotinine was 95% for self-reported smoking, and 89% for self-reported non-smoking. In the CARMA-CORE cohort we observed similarly high concordances of 96% and 92% for self-reported smoking and non-smoking, respectively. In this sample, the odds of discordance between self-reported smoking status and cotinine levels were not significantly different between self-reported smokers and non-smokers, nor between pregnant women and others. Taken together, the overall concordance between plasma cotinine and self-reported data was 94% with a Cohen’s kappa coefficient of 0.860 among all participants.

Conclusions

Given the high proportion of vulnerable people in the CARMA-PREG and CARMA-CORE cohorts, our results may not be fully generalizable to the general population. However, they demonstrate that participant surveying in a non-judgemental context can lead to accurate and robust self-report data.

Implications

Reliable self-reported smoking data is necessary to account for smoking status in subsequent studies. Our results suggest that future studies should ensure that study participants feel sale to speak candidly to non-judgemental research staff to obtain reliable self-report data.
Recoveries of Ringed Red-Footed Falcons (Falco vespertinus) in Germany - An update documentation
Authors: Kunze Dietmar , Nennstiel Lisa
Published: September 2020

Bird ringing is used for a long time for scientific investigation of migration routes and to better understand breeding events as well as population ecological aspects. It is applied as an inexpensive method although the well-known and major disadvantage of bird ringing is the usually low response rate. In the case of rarer species such as the Red-Footed Falcon (RFF), however, this quota could be higher due to the exclusivity and greater attention of observers. Motivated by own field observations of color-ringed RFF south of Brunswick, Germany in 2019 and no clear and comprehensive publication of verified additional recoveries and ringings, we did further research regarding this issue by following methods: 1) Contacting European Bird Ringing Centers and associated projects, 2) Query and comparison of files with the three national German Bird Ringing Stations, 3) Expanded literature research, 4) Evaluating reports in the citizen science platform ornitho.de, 5) Checking websites of ringing projects (in particular satellite tracking programs) and 6) Own observations.

Surprisingly, this study revealed 18 recovered RFF ringed in foreign countries (14 Hungary, 3 Italy, 1 Romania (GPS tracked bird)) during migration or post-nuptial pre-migration time. Additionally, 1 RFF that was caught and ringed in Germany was recovered abroad.

This result updates and increases the number of recoveries of RFF in Germany compared to the actual published state on the order of 18 (so far none) and on the order of 6 concerning ID-encoded RFF (GPS-bird excluded) compared to documentation state of the three Bird Ringing Centers in Germany (so far 3 at Beringungszentrale [BZ] Hiddensee, 1 at Institut für Vogelforschung [IfV] Heligoland). Our research and evaluation of raw data succeeded to a 100% identification rate of the bird’s origin countries (n=18) while the rate of ID-encoded RFF by color ring codes revealed 58.8% (n=10, GPS-bird excluded). The reported-by-observer response rate was 41.2%. Interesting data of about the phenology, age and origin of the RFF recovered in Germany are presented. Questions and considerations about the recent reporting system of ringed birds and the increased numbers of RFF during the last years in Germany are discussed.
Convergent evolution of increased urine concentrating ability in desert mammals
Authors: Rocha Joana L. , Brito José C. , Nielsen Rasmus , Godinho Raquel
Published: September 2020

One of the most celebrated textbook examples of physiological adaptations to desert environments is the unique ability that desert mammals have to produce hyperosmotic urine. Commonly perceived as an adaptation mainly observed in small rodents, the extent to which urine concentrating ability has independently evolved in distinct lineages, including medium-sized and large desert mammals, has not previously been assessed using modern phylogenetic approaches. Here, we explicitly test the general hypothesis that desert-dwelling mammals have evolved increased ability to concentrate urine compared to non-desert species, controlling for body mass and other covariates. Phylogenetic generalized least-squares models show that the mean aridity index of a species distribution range largely predicts its urine concentrating ability, even when accounting for body mass differences and phylogenetic correlations. In contrast, we find much weaker correlations between mass-adjusted basal metabolic rate and environmental variables.