bluuebunny/crossref_metadata_2025 huggingface dataset:
Linked by Ancestral Bonds: Multiple Whole-Genome Duplications and Reticulate Evolution in a Brassicaceae Tribe
Authors: Guo Xinyi , Mandáková Terezie , Trachtová Karolína , Özüdoğru Barış , Liu Jianquan , Lysak Martin A
Published: December 2020

Pervasive hybridization and whole-genome duplications (WGDs) influenced genome evolution in several eukaryotic lineages. Although frequent and recurrent hybridizations may result in reticulate phylogenies, the evolutionary events underlying these reticulations, including detailed structure of the ancestral diploid and polyploid genomes, were only rarely reconstructed. Here, we elucidate the complex genomic history of a monophyletic clade from the mustard family (Brassicaceae), showing contentious relationships to the early-diverging clades of this model plant family. Genome evolution in the crucifer tribe Biscutelleae (∼60 species, 5 genera) was dominated by pervasive hybridizations and subsequent genome duplications. Diversification of an ancestral diploid genome into several divergent but crossable genomes was followed by hybridizations between these genomes. Whereas a single genus (Megadenia) remained diploid, the four remaining genera originated by allopolyploidy (Biscutella, Lunaria, Ricotia) or autopolyploidy (Heldreichia). The contentious relationships among the Biscutelleae genera, and between the tribe and other early diverged crucifer lineages, are best explained by close genomic relatedness among the recurrently hybridizing ancestral genomes. By using complementary cytogenomics and phylogenomics approaches, we demonstrate that the origin of a monophyletic plant clade can be more complex than a parsimonious assumption of a single WGD spurring postpolyploid cladogenesis. Instead, recurrent hybridization among the same and/or closely related parental genomes may phylogenetically interlink diploid and polyploid genomes despite the incidence of multiple independent WGDs. Our results provide new insights into evolution of early-diverging Brassicaceae lineages and elucidate challenges in resolving the contentious relationships within and between land plant lineages with pervasive hybridization and WGDs.
Introduction
Authors: Ciancia Kathryn
Published: December 2020

The story of interwar Poland has traditionally been told within the historiographical framework of national minority policies in the post-1918 eastern European states. And yet, as this introductory chapter argues, it can be understood only within the context of prevailing global discussions about how notions of civilization justified claims to sovereignty. With its Polish minority, Ukrainian majority, and large Jewish population, the borderland province of Volhynia became a testing ground for various attempts to both civilize and nationalize a “backward” region. This chapter offers an introduction to Volhynia’s geography and pre-1918 history, an exploration of the second-tier actors who claimed to be importing Western civilization, and a discussion of the book’s major historiographical interventions. The case of Volhynia allows scholars to reconsider the dichotomy between civic and ethnic nationalism, to reimagine ideas of national indifference, and to trace how Poles engaged with concepts of imperialism and European nationalism.
Agents of God
Authors: Guhin Jeffrey
Published: December 2020

In Agents of God, sociologist Jeffrey Guhin describes his year and a half spent in two Sunni Muslim and two Evangelical Christian high schools in the New York City area. At first, these four schools could not seem more different, yet they are linked by much: these are all schools with conservative thoughts on gender and sexuality, with a hostility to the theory of evolution, and with a deep suspicion of secularism. And they are all also hopeful that America will be a place where their children can excel, even as they also fear the nation’s many temptations might lead their children astray. Guhin shows how these school communities use boundaries of politics, gender, and sexuality to distinguish themselves from the outside world, both in school and online. Within these boundaries, these communities have developed “external authorities” like Science, Scripture, and Prayer, each of which is felt and experienced as a real power with the ability to make commands and coerce action. For example, people can describe Science itself as showing something or the Bible itself as making a command. By offloading coercion to these external authorities, leaders in these schools are able to maintain a commitment to religious freedom while simultaneously reproducing their moral commitments in their students. Drawing on extensive classroom observation, community participation, and interviews with students, teachers, and staff, this book makes an original contribution to religious studies, sociology, and education.
The Book of Common Prayer: A Guide
Authors: Hefling Charles
Published: December 2020

This book surveys the contents and the history of the Book of Common Prayer, a sacred text which has been a foundational document of the Church of England and the other churches in the worldwide community of Anglican Christianity. The Prayer Book is primarily a liturgical text—a set of scripts for enacting events of corporate worship. As such it is at once a standard of theological doctrine and an expression of spirituality. The first part of this survey begins with an examination of one Prayer Book liturgy, known as Divine Service, in some detail. Also discussed are the rites for weddings, ordinations, and funerals and for the sacraments of Baptism and Communion. The second part considers the original version of the Book of Common Prayer in the context of the sixteenth-century Reformation, then as revised and built into the Elizabethan settlement of religion in England. Later chapters discuss the reception, revision, rejection, and restoration of the Prayer Book during its first hundred years. The establishment of the text in its classical form in 1662 was followed by a “golden age” in the eighteenth century, which included the emergence of a modified version in the United States. The narrative concludes with a chapter on the displacement of the Book of Common Prayer as a norm of Anglican identity. Two specialized chapters concentrate on the Prayer Book as a visible artifact and as a text set to music.
Gauge Field Theory in Natural Geometric Language
Authors: Canarutto Daniel
Published: December 2020

This monograph addresses the need to clarify basic mathematical concepts at the crossroad between gravitation and quantum physics. Selected mathematical and theoretical topics are exposed within a not-too-short, integrated approach that exploits standard and non-standard notions in natural geometric language. The role of structure groups can be regarded as secondary even in the treatment of the gauge fields themselves. Two-spinors yield a partly original ‘minimal geometric data’ approach to Einstein-Cartan-Maxwell-Dirac fields. The gravitational field is jointly represented by a spinor connection and by a soldering form (a ‘tetrad’) valued in a vector bundle naturally constructed from the assumed 2-spinor bundle. We give a presentation of electroweak theory that dispenses with group-related notions, and we introduce a non-standard, natural extension of it. Also within the 2-spinor approach we present: a non-standard view of gauge freedom; a first-order Lagrangian theory of fields with arbitrary spin; an original treatment of Lie derivatives of spinors and spinor connections. Furthermore we introduce an original formulation of Lagrangian field theories based on covariant differentials, which works in the classical and quantum field theories alike and simplifies calculations. We offer a precise mathematical approach to quantum bundles and quantum fields, including ghosts, BRST symmetry and anti-fields, treating the geometry of quantum bundles and their jet prolongations in terms Frölicher's notion of smoothness. We propose an approach to quantum particle physics based on the notion of detector, and illustrate the basic scattering computations in that context.
Democratic Rationales for Pre-Strike Ballots
Authors: Creighton Breen , Denvir Catrina , Johnstone Richard , McCrystal Shae , Orchiston Alice
Published: December 2020

Chapter 7 interrogates the central issue in the book—the extent to which pre-strike ballot requirements give effect to the democratic rights of individual workers and the public interest in ensuring that the exercise of strike action is based on democratic decision-making. It argues that pre-strike ballot requirements are imposed on trade unions in a very different context when compared with other forms of political or industrial contests. The chapter analyses unions’ democratic processes in three interrelated, but different, key decisions in the process to take strike action under the Fair Work Act 2009 (Cth): (i) the decision to apply for an order for a pre-strike ballot to be held; (ii) the decision to approve proposed industrial action in a pre-strike ballot; and (iii) the decision to take approved industrial action after such action has been approved in a pre-strike ballot. Each of these decisions occurs within the context of the legal and industrial relations framework, and the democratic processes involved are inevitably shaped by those frameworks. The evidence presented in this chapter suggests that the first and third decisions are generally conducted in a manner that allows for participatory democratic processes. However, when union members vote in a pre-strike ballot, there is little evidence of the kinds of practices that typically characterize a participatory democratic model. Instead, union engagement with members is focused on educating them about the legal requirements and the consequences of abstention or a no vote in associated bargaining, rather than on the arguments for and against the proposed industrial action.
Perspectives of policymakers and health care managers on the retention of health workers in rural and remote settings in Nigeria
Authors: Okoroafor S C , Ongom M , Mohammed B , Salihu D , Ahmat A , Osubor M , Nyoni J , Alemu W
Published: December 2020

Background

Health workers are indispensable to service delivery especially in rural and remote communities where the burden of disease is high. Nigeria faces numerous human resources for health challenges, health workers are reluctant to take up rural postings, and the government is struggling to implement planned interventions due to staff shortages. This study explored the perspectives of policymakers and primary health care (PHC) managers on factors that hinder health workers from staying in rural and remote areas and strategies for improving retention.

Methods

We interviewed purposively selected 10 policymakers and 20 PHC managers in Bauchi and Cross River States, Nigeria.

Results

Respondents identified a lack of basic social amenities, the poor state of infrastructure, poor working conditions, remuneration and the barrier to career advancement as factors that impede health workers from taking up rural postings. Strategies for improving retention include enforcing bonding; paying salaries promptly, increase in rural allowances and prioritizing health workers in rural and remote areas for capacity building.

Conclusion

The results of the study indicate the importance of applying context-specific strategies aimed at ensuring the availability of social amenities such as roads, water, electricity, telecommunication, security, the status of infrastructure, working conditions and remunerations.
Contrasting growth responses of Qilian juniper (Sabina przewalskii) and Qinghai spruce (Picea crassifolia) to CO2 fertilization despite common water-use efficiency increases at the northeastern Qinghai–Tibetan plateau
Authors: Wang Wenzhi , McDowell Nate G , Liu Xiaohong , Xu Guobao , Wu Guoju , Zeng Xiaomin , Wang Genxu
Published: December 2020

Rising atmospheric carbon dioxide (CO2) may enhance tree growth and mitigate drought impacts through CO2 fertilization. However, multiple studies globally have found that rising CO2 has not translated into greater tree growth despite increases in intrinsic water-use efficiency (iWUE). The underlying mechanism discriminating between these two general responses to CO2 fertilization remains unclear. We used two species with contrasting stomatal regulation, the relatively anisohydric Qilian juniper (Sabina przewalskii) and the relatively isohydric Qinghai spruce (Picea crassifolia), to investigate the long-term tree growth and iWUE responses to climate change and elevated CO2 using tree ring widths and the associated cellulose stable carbon isotope ratios (δ13C). We observed a contrasting growth trend of juniper and spruce with juniper growth increasing while the spruce growth declined. The iWUE of both species increased significantly and with similar amplitude throughout the trees’ lifespan, though the relatively anisohydric juniper had higher iWUE than the relatively isohydric spruce throughout the period. Additionally, with rising CO2, the anisohydric juniper became less sensitive to drought, while the relatively isohydric spruce became more sensitive to drought. We hypothesized that rising CO2 benefits relatively anisohydric species more than relatively isohydric species due to greater opportunity to acquire carbon through photosynthesis despite warming and droughts. Our findings suggest the CO2 fertilization effect depends on the isohydric degree, which could be considered in future terrestrial ecosystem models.
The Federal Reserve
Authors: Axilrod Stephen H.
Published: December 2020

The Federal Reserve System--the central bank of the United States, better known as The Fed--has never been more controversial. Criticism has reached such levels that Congressman Ron Paul, contender for the Republican presidential nomination in 2012, published End the Fed, with blurbs from musician Arlo Guthrie and actor Vince Vaughn. And yet, amid a slow economy and partisan gridlock, the Fed has never been more important. Stephen H. Axilrod explains this influential agency-its powers, operations, how it sets policy-in The Federal Reserve, a timely addition to Oxford's acclaimed series What Everyone Needs to Know. Of the two major governmental tools for shaping the economy, Congress controls fiscal policy-taxation and spending-and the Fed makes monetary policy-influencing how much money circulates in the economy, and how quickly. Traditionally the Fed has relied on three instruments: open-market operations (buying and selling U.S. bonds), lending to banks, and setting reserve requirements on bank deposits. It also helps to regulate the financial system. Drawing on years of experience inside the Federal Reserve System, Axilrod shows how these tools actually work, and answers a series of increasingly detailed questions in the series format. He asks, for instance, if the system of regional Fed banks needs modification for today's technological landscape; if there is corruption in the Fed's governance; what happens to profits from its operations; the impact of political pressure; the extent of Congressional oversight; and just how independent it truly is. Whether discussing the Fed's balance sheet through the financial crisis of 2008 and beyond, the federal funds rate, or the international context, Axilrod displays a mastery of his subject Coming in time for the Fed's 100th anniversary in 2013, this book deftly explains an institution that every American needs to understand.
Enhanced Recovery After Surgery Outcomes in Minimally Invasive Nonhysterectomy Gynecologic Procedures
Authors: Peters Ann , Siripong Nalyn , Wang Li , Donnellan Nicole M.
Published: December 2020

(Abstracted from Am J Obstet Gynecol 2020;223:234.e1–234.e8)

In recent years, improved perioperative patient outcomes, recovery, and satisfaction associated with enhanced recovery after surgery (ERAS) protocols have increasingly replaced traditional conventional perioperative care (CPC). Enhanced recovery after surgery protocols decrease hospital length of stay, complications, and health care cost and expedite recovery with faster return of bowel function and reduced pain and postoperative nausea and vomiting.
Coronavirus Disease 2019 During Pregnancy: A Systematic Review of Reported Cases
Authors: Gatta Anna Nunzia Della , Rizzo Roberta , Pilu Gianluigi , Simonazzi Giuliana
Published: December 2020

(Abstracted from Am J Obstet Gynecol 2020;223:36–41)

The presence of coronavirus disease 2019 (COVID-19) in pregnant patients raises concerns for adverse outcomes. The goal of this study was to collect information on mothers and neonates with COVID-19 and shed light on delivery timing and mode of delivery.
Management of Secondary Genomic Findings
Authors: Katz Alexander E. , Nussbaum Robert L. , Solomon Benjamin D. , Rehm Heidi L. , Williams Marc S. , Biesecker Leslie G.
Published: December 2020

(Abstracted from Am J Hum Genet 2020;107:3–14)

Secondary findings are defined as genomic variants that may be unrelated to the indication for testing. The American College of Medical Genetics and Genomics (ACMG) has put forth a list of 59 genes that are recommended to be considered and reported as secondary findings when genomic sequencing is performed.
Primary biliary cholangitis: pathogenic mechanisms
Authors: Prieto Jesús , Banales Jesus M. , Medina Juan F.
Published: December 2020

Purpose of review

Primary biliary cholangitis (PBC) is characterized by autoimmune damage of intrahepatic bile ducts associated with a loss of tolerance to mitochondrial antigens. PBC etiopathogenesis is intriguing because of different perplexing features, namely: a) although mitochondria are present in all cell types and tissues, the damage is mainly restricted to biliary epithelial cells (BECs); b) despite being an autoimmune disorder, it does not respond to immunosuppressive drugs but rather to ursodeoxycholic acid, a bile salt that induces HCO3
− rich choleresis; c) the overwhelming female preponderance of the disease remains unexplained. Here we present an etiopathogenic view of PBC which sheds light on these puzzling facts of the disease.

Recent findings

PBC develops in patients with genetic predisposition to autoimmunity in whom epigenetic mechanisms silence the Cl−/HCO3
− exchanger AE2 in both cholangiocytes and lymphoid cells. Defective AE2 function can produce BECs damage as a result of decreased biliary HCO3
− secretion with disruption of the protective alkaline umbrella that normally prevents the penetration of toxic apolar bile salts into cholangiocytes. AE2 dysfunction also causes increased intracellular pH (pHi) in cholangiocytes, leading to the activation of soluble adenylyl cyclase, which sensitizes BECs to bile salt-induced apoptosis. Recently, mitophagy was found to be inhibited by cytosolic alkalization and stimulated by acidification. Accordingly, we propose that AE2 deficiency may disturb mitophagy in BECs, thus, promoting the accumulation of defective mitochondria, oxidative stress and presentation of mitochondrial antigens to the immune cells. As women possess a more acidic endolysosomal milieu than men, mitophagy might be more affected in women in an AE2-defective background. Apart from affecting BECs function, AE2 downregulation in lymphocytes may also contribute to alter immunoregulation facilitating autoreactive T-cell responses.

PBC can be considered as a disorder of Cl−/HCO3
− exchange in individuals with genetic predisposition to autoimmunity.
The Safety and Feasibility of Gynecologic Cancer Surgery Combined With Surgery for Pelvic Floor Dysfunction
Authors: McConnell Nicole J. , Stewart J. Ryan , Martin Alexandra , Gaskins Jeremy T. , Medlin Erin E.
Published: December 2020

(Abstracted from Female Pelvic Med Reconstr Surg 2020;26:563–569)

There is a high prevalence of pelvic floor disorders (PFDs) in women with gynecologic cancer. These disorders have a negative impact in these women on their quality of life, which is an important determinant of both progression-free survival and overall survival in gynecologic cancer patients.
Self-harm presentations to Emergency Departments and Place of Safety during the ‘first wave’ of the UK COVID-19 pandemic: South London and Maudsley data on service use from February to June 2020
Authors: Nuzum Eleanor , Martin Evangelia , Morgan Gemma , Dutta Rina , Mueller Christoph , Polling Catherine , Pritchard Megan , Velupillai Sumithra , Stewart Robert
Published: December 2020

The lockdown and social distancing policy imposed due to the COVID-19 pandemic has had a substantial impact on both mental health service delivery, and the ways in which people are accessing these services. Previous reports from the South London and Maudsley NHS Trust (SLaM; a large mental health service provider for around 1.2m residents in South London) have highlighted increased use of virtual contacts by mental health teams, with dropping numbers of face-to-face contacts over the first wave of the pandemic. There has been concern that the impact of the COVID-19 pandemic would lead to higher mental health emergencies, particularly instances of self-harm. However, with people advised to stay at home during the ‘first wave’ lockdown, it is as yet unclear whether this impacted mental health service presentations. Taking advantage of SLaM’s Clinical Records Interactive Search (CRIS) data resource with daily updates of information from its electronic mental health records, this paper describes overall presentations to Emergency Department (ED) mental health liaison teams, and those with self-harm. The paper focussed on three periods: i) a pre-lockdown period 1st February to 15th March, ii) a lockdown period 16th March to 10th May and iii) a post-lockdown period 11th May to 28th June. In summary, all attendances to EDs for mental health support decreased during the lockdown period, including those with self-harm. All types of self-harm decreased during lockdown, with self-poisoning remaining the most common. Attendances to EDs for mental health support increased post-lockdown, although were only just approaching pre-lockdown levels by the end of June 2020.
An Evidence-based Assessment of Genes in Dilated Cardiomyopathy
Authors: Jordan Elizabeth , Peterson Laiken , Ai Tomohiko , Asatryan Babken , Bronicki Lucas , Brown Emily , Celeghin Rudy , Edwards Matthew , Fan Judy , Ingles Jodie , James Cynthia A , Jarinova Olga , Johnson Renee , Judge Daniel P , Lahrouchi Najim , Deprez Ronald Lekanne , Lumbers R Thomas , Mazzarotto Francesco , Domingo Argelia Medeiros , Miller Rebecca , Morales Ana , Murray Brittney , Peters Stacey , Pilichou Kalliopi , Protonotarios Alexandros , Semsarian Christopher , Shah Palak , Syrris Petros , Thaxton Courtney , van Tintelen J Peter , Walsh Roddy , Wang Jessica , Ware James , Hershberger Ray E
Published: December 2020

Background: The cardiomyopathies are classically categorized as hypertrophic (HCM), dilated (DCM), and arrhythmogenic right ventricular (ARVC), and each have a signature genetic theme. HCM and ARVC are largely understood as genetic diseases of sarcomere or desmosome proteins, respectively. In contrast, >250 genes spanning more than 10 gene ontologies have been implicated in DCM, representing a complex and diverse genetic architecture. To clarify this, a systematic curation of evidence to establish the relationship of genes with DCM was conducted.
Methods: An international Panel with clinical and scientific expertise in DCM genetics was assembled to evaluate evidence supporting monogenic relationships of genes with idiopathic DCM. The Panel utilized the ClinGen semi-quantitative gene-disease clinical validity classification framework.
Results: Fifty-one genes with human genetic evidence were curated. Twelve genes (23%) from eight gene ontologies were classified as having definitive (BAG3, DES, FLNC, LMNA, MYH7, PLN, RBM20, SCN5A, TNNC1, TNNT2, TTN) or strong (DSP) evidence. Seven genes (14%) (ACTC1, ACTN2, JPH2, NEXN, TNNI3, TPM1, VCL) including two additional ontologies were classified as moderate evidence; these genes are likely to emerge as strong or definitive with additional evidence. Of the 19 genes classified as definitive, strong or moderate, six were similarly classified for HCM and three for ARVC. Of the remaining 32 genes (63%), 25 (49%) had limited evidence, 4 (8%) were disputed, 2 (4%) had no disease relationship, and 1 (2%) was supported by animal model data only. Of 16 commercially available genetic testing panels evaluated, most definitive genes were included, but panels also included numerous genes with minimal human evidence.
Conclusions: In a systematic curation of published evidence for genes considered relevant for monogenic DCM, 12 were classified as definitive or strong and seven as moderate evidence spanning 10 gene ontologies. Notably, these 19 genes only explain a minority of DCM cases, leaving the remainder of DCM genetic architecture incompletely addressed. While clinical genetic testing panels include most high evidence genes, genes lacking robust evidence are also commonly included. Until the genetic architecture of DCM is more fully defined, care should be taken in the interpretation of variable evidence DCM genes in clinical practice.
A Framework for Automated Gene Selection in Genomic Screening
Authors: Lazo de la Vega Lorena , Yu Wanfeng , Machini Kalotina , Austin-Tse Christina , Hao Limin , Blout Zawatsky Carrie L , Mason-Suares Heather , Green Robert C , Rehm Heidi L , Lebo Matthew S
Published: December 2020

An efficient framework to identify disease-causing genes is needed to evaluate genomic data for both individuals with an unknown disease etiology and those undergoing genomic screening. Here, we propose a framework for gene selection used in genomic analyses, including screening applications limited to genes with strong or established evidence levels and diagnostic applications that includes genes with less or emerging evidence of disease association. We extracted genes with evidence for gene-disease association from the Human Gene Mutation Database, Online Mendelian Inheritance in Man, and ClinVar to build a diagnostic gene list of 5,973 genes. Next, we applied stringent filters in conjunction with computationally curated evidence (DisGeNET) to create a list limited to 3,600 genes with stronger levels of evidence for disease association. When compared to manual gene curation efforts, including the Clinical Genome Resource, genes with strong or definitive disease associations are included in both gene lists at high percentages, while genes with limited evidence are largely removed. We further confirmed the utility of this approach in the screening of 45 ostensibly healthy genomes. Our approach efficiently creates highly sensitive gene lists for genomic applications, while remaining dynamic and updatable, enabling time savings in gene curation and review.
Current forecast of COVID-19: a Bayesian and Machine Learning approaches
Authors: Prieto Kernel
Published: December 2020

We address the estimation of the effective reproductive numberRtbased on serological data using Bayesian inference. We also explore the Bayesian learning paradigm to estimateRt. We calculateRtfor the top five most affected principal regions of Mexico. We present a forecast of the spread of coronavirus in Mexico based on a contact tracing model using Bayesian inference inspired in a data-driven approach. We investigate the health profile of individuals diagnosed with coronavirus in order to predict their type of patient care (inpatient or outpatient) and survival. Specifically, we analyze the comorbidity associated with coronavirus using Machine Learning. We implemented two classifiers, the first one, to predict the type of care procedure a diagnosed person with coronavirus presenting chronic diseases will obtain: outpatient or hospitalized. Second one, a classifier for the survival of the patient: survived or deceased. We present two techniques to deal with these kinds of unbalanced dataset related with outpatient/hospitalized and survived/deceased cases, occurring in general for these type coronavirus datasets in the world, in order obtain to a better performance for the classification.
Unique predictors of intended uptake of a COVID-19 vaccine
Authors: Lennon Robert P. , Small Meg L. , Smith Rachel A. , Van Scoy Lauren J. , Myrick Jessica G. , Martin Molly A. ,   Data4Action Research Group
Published: December 2020

Introduction

An effective vaccine for COVID-19 is only of value if the public has confidence in taking it. There is little data on COVID-19-specific vaccine confidence or its determinants in the United States. The objective of this study was to determine public confidence in a COVID-19 vaccine.

Methods

A cross-sectional survey of Pennsylvanian adults, August-October, 2020, to identify their likelihood of taking an approved, no-cost coronavirus vaccine, general vaccine acceptance, and sociodemographic traits to identify predictors of vaccine acceptance.

Results

Of the 950 respondents, 55% were “very likely”, 20% “somewhat likely”, 14% “unsure”, 4% “somewhat unlikely”, and 7% “very unlikely” to take a coronavirus vaccine, even though 70% had taken the flu vaccine since September 2019. The strongest predictors of vaccine acceptance were trust in the system evaluating vaccines and perceptions of local COVID-19 vaccination norms. The strongest predictors of negative vaccine intentions were worries about unknown side-effects and positive attitudes toward natural infection. Sociodemographic factors, political views, and religiosity did not predict vaccine intentions.

Conclusions

Fewer adults intend to take a coronavirus vaccine than currently take the flu vaccine. To overcome coronavirus vaccine hesitancy, information campaigns to reinforce positive predictors and overcome negative predictors are indicated.
COVID-19 in persons affected by Hansen’s disease in Brazil
Authors: Deps Patrícia D. , Repsold Taynah A. R. , Salgado Claudio G. , de Carvalho Bouth Raquel , Cerqueira Selma Regina Penha Silva , Brezinscki Marisa Simon , Peixoto Rebeca Ruppert Galarda Baptista , Barreto Jaison Antonio , Fonseca Andrea M. A. , Peixoto Marlene L. S. , Mendes Seyna Ueno R. , Mendes Rafael Pereira Rabelo , dos Santos Oliveira Pedro Paulo , Gomes Ciro Martins
Published: December 2020

Background

Hansen’s disease (HD) is endemic in Brazil, a country with the third highest number of COVID-19 cases in the world and the second highest number of COVID-19 deaths. COVID-19 in persons affected by HD has not been described at population level in this country.

Methods

We collated numbers of COVID-19 cases and deaths among patients who were receiving routine treatment for HD at six centres across Brazil (Belém, Bauru, Brasília, Vitória, Petrolina, Palmas) between 1st March and 10th December 2020.

Results

Of 1,333 HD patients receiving treatment, 70 (5.2%) reported having had COVID-19. Almost all patients (97% (1,296/1,333)) including all but one of the COVID-19 cases were receiving MDT comprising rifampicin (600mg once per month), dapsone (100mg daily), and clofazimine (50 mg daily plus 300 mg once per month). Four patients died, including a patient in their 30’s on MDT who had a severe type 2 HD reaction (erythema nodosum leprosum) and who was taking clofazimine 100mg daily.

Conclusions

We cannot determine from these preliminary data whether persons affected by Hansen’s disease have a higher or lower risk of COVID-19 and related mortality compared with the general population. We will continue to monitor the effects of COVID-19 in persons affected by and treated for HD and extend this to monitor SARS-CoV-2 vaccine effectiveness in this group of patients.
Clinical and Virological Characteristics of Hospitalized COVID-19 Patients in a German Tertiary Care Center during the First Wave of the SARS-CoV-2 Pandemic
Authors: Thibeault Charlotte , Mühlemann Barbara , Helbig Elisa T. , Mittermaier Mirja , Lingscheid Tilman , Tober-Lau Pinkus , Meyer-Arndt Lil A. , Meiners Leonie , Stubbemann Paula , Haenel Sascha S. , de Jarcy Laure Bosquillon , Lippert Lena , Pfeiffer Moritz , Stegemann Miriam S. , Roehle Robert , Wiebach Janine , Hippenstiel Stefan , Zoller Thomas , Müller-Redetzky Holger , Uhrig Alexander , Balzer Felix , von Kalle Christof , Suttorp Norbert , Jones Terry C. , Drosten Christian , Witzenrath Martin , Sander Leif E. ,   Pa-COVID Study Group, Corman Victor M. , Kurth Florian
Published: December 2020

Background

Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories.

Methods

A cohort of 168 hospitalized adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care center was analyzed.

Results

Forty-four percent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95%CI 1.10-1.37, p<0.01), age 60-69 as compared to 18-59 years (aOR 4.33, 95%CI 1.07-20.10, p=0.04), and history of hypertension (aOR 5.55, 95%CI 2.00-16.82, p<0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p<0.01). Median duration of hospitalization was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV-patients.

Conclusion

Our results indicate a short duration of symptoms before admission as a risk factor for severe disease and different viral load kinetics in severely affected patients.
Decay of Fc-dependent antibody functions after mild to moderate COVID-19
Authors: Lee Wen Shi , Selva Kevin John , Davis Samantha K. , Wines Bruce D. , Reynaldi Arnold , Esterbauer Robyn , Kelly Hannah G. , Haycroft Ebene R. , Tan Hyon-Xhi , Juno Jennifer A. , Wheatley Adam K. , Hogarth P. Mark , Cromer Deborah , Davenport Miles P. , Chung Amy W. , Kent Stephen J.
Published: December 2020

The capacity of antibodies to engage with innate and adaptive immune cells via the Fc region is important in preventing and controlling many infectious diseases, and is likely critical in SARS-CoV-2 infection. The evolution of such antibodies during convalescence from COVID-19 is largely unknown. We developed novel assays to measure Fc-dependent antibody functions against SARS-CoV-2 spike (S)-expressing cells in serial samples from a cohort of 53 subjects primarily with mild-moderate COVID-19, out to a maximum of 149 days post-infection. We found that S-specific antibodies capable of engaging dimeric FcγRIIa and FcγRIIIa decayed linearly over time. S-specific antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent phagocytosis (ADP) activity within plasma declined linearly as well, in line with the decay of S-specific IgG. Although there was significant decay in S-specific plasma ADCC and ADP activity, they remained readily detectable by all assays in 94% of our cohort at the last timepoint studied, in contrast with neutralisation activity which was only detectable in 70% of our cohort by the last timepoint. Our results suggest that Fc effector functions such as ADCC and ADP could contribute to the durability of SARS-CoV-2 immunity, particularly late in convalescence when neutralising antibodies have waned. Understanding the protective potential of antibody Fc effector functions is critical for defining the durability of immunity generated by infection or vaccination.
Catechol-Containing Compounds are a Broad Class of Protein Aggregation Inhibitors: II. Rosmarinic Acid Potently Detoxifies Amylin Amyloid and Ameliorates Diabetic Pathology in HIP Rats
Authors: Wu Ling , Velander Paul , Brown Anne M. , Wang Yao , Liu Dongmin , Bevan David R. , Zhang Shijun , Xu Bin
Published: December 2020

Protein aggregation is associated with a large number of human protein misfolding diseases, yet FDA-approved drugs are currently not available. Amylin amyloid and plaque depositions in the pancreas are hallmark features of type 2 diabetes. Moreover, these amyloid deposits are implicated in the pathogenesis of diabetic complications such as neurodegeneration. We recently discovered that catechols and redox-related quinones/ anthraquinones represent a broad class of protein aggregation inhibitors. Further screening of a targeted library of natural compounds in complementary medicine that were enriched with catechol-containing compounds identified rosmarinic acid as a potent inhibitor of amylin aggregation (estimated inhibitory concentration IC50= 200-300 nM). Structure-function relationship analysis of rosmarinic acid showed the additive effects of two catechol-containing components of the RA molecule. We further showed that RA does not reverse fibrillation back to monomeric amylin, but lead to non-toxic, remodeled protein aggregates. Rosmarinic acid has significantex vivoefficacy in reducing human amylin oligomer levels in HIP rat sera as well as in sera from diabetic patients.In vivoefficacy studies of rosmarinic acid treatment with the diabetic HIP rat model demonstrated significant reduction in amyloid islet deposition and strong mitigation of diabetic pathology. Our work provides newin vitromolecular mechanisms andin vivoefficacy insights for a model nutraceutical agent against type 2 diabetes and other aging-related protein misfolding diseases.
Rapid, point-of-care molecular diagnostics with Cas13
Authors: Agrawal Shreeya , Fanton Alison , Chandrasekaran Sita S. , Charrez Bérénice , Escajeda Arturo M. , Son Sungmin , Mcintosh Roger , Bhuiya Abdul , de León Derby María Díaz , Switz Neil A. , Armstrong Maxim , Harris Andrew R. , Prywes Noam , Lukarska Maria , Biering Scott B. , Smock Dylan C. J. , Mok Amanda , Knott Gavin J. , Dang Qi , Van Dis Erik , Dugan Eli , Kim Shin , Liu Tina Y. ,   IGI Testing Consortium, Harris Eva , Stanley Sarah A. , Lareau Liana F. , Tan Ming X. , Fletcher Daniel A. , Doudna Jennifer A. , Savage David F. , Hsu Patrick D.
Published: December 2020

Rapid nucleic acid testing is a critical component of a robust infrastructure for increased disease surveillance. Here, we report a microfluidic platform for point-of-care, CRISPR-based molecular diagnostics. We first developed a nucleic acid test which pairs distinct mechanisms of DNA and RNA amplification optimized for high sensitivity and rapid kinetics, linked to Cas13 detection for specificity. We combined this workflow with an extraction-free sample lysis protocol using shelf-stable reagents that are widely available at low cost, and a multiplexed human gene control for calling negative test results. As a proof-of-concept, we demonstrate sensitivity down to 40 copies/μL of SARS-CoV-2 in unextracted saliva within 35 minutes, and validated the test on total RNA extracted from patient nasal swabs with a range of qPCR Ct values from 13-35. To enable sample-to-answer testing, we integrated this diagnostic reaction with a single-use, gravity-driven microfluidic cartridge followed by real-time fluorescent detection in a compact companion instrument. We envision this approach for Diagnostics with Coronavirus Enzymatic Reporting (DISCoVER) will incentivize frequent, fast, and easy testing.
Direct Molecular Analysis of In Vivo and Freshly Excised Tissues in Human Surgeries with the MasSpec Pen Technology
Authors: Zhang Jialing , Sans Marta , DeHoog Rachel J. , Garza Kyana Y. , King Mary E. , Feider Clara L. , Bensussan Alena , Keating Michael F. , Lin John Q. , Povilaitis Sydney , Katta Nitesh , Milner Thomas E. , Yu Wendong , Nagi Chandandeep , Dhingra Sadhna , Pirko Christopher , Brahmbhatt Kirtan A. , Van Buren George , Carter Stacey , Fisher William E. , Thompson Alastair , Grogan Raymon H. , Suliburk James , Schiavinato Eberlin Livia
Published: December 2020

Intraoperative tissue analysis is critical to guide surgical procedures and improve patient outcomes. Here, we describe the clinical translation and intraoperative use of the MasSpec Pen technology for direct molecular analysis of in vivo and freshly excised tissues in the operating room. In this study, the MasSpec Pen was used by surgeons and surgical staff during 100 surgeries over a 12-month period, allowing rapid detection of rich mass spectral profiles from 715 in vivo and ex vivo analyses performed on thyroid, parathyroid, lymph node, breast, pancreatic, and bile duct tissues during parathyroidectomies, thyroidectomies, breast, and pancreatic neoplasia surgeries. The MasSpec Pen enabled gentle extraction and sensitive detection of various molecular species including small metabolites and lipids using a droplet of sterile water without causing apparent tissue damage. Notably, effective molecular analysis was achieved while no limitations to sequential histologic tissue analysis were identified and no device-related complications were reported for any of the patients. Collectively, this study shows that the MasSpec Pen system can be successfully incorporated into the operating room, allowing direct detection of rich molecular profiles from tissues with a seconds-long turnaround time that could be inform surgical and clinical decisions without disrupting tissue analysis workflows.
NOTCH3 variants are common in the general population and associated with stroke and vascular dementia: an analysis of 200,000 participants
Authors: Cho Bernard PH , Nannoni Stefania , Harshfield Eric L , Tozer Daniel J , Gräf Stefan , Bell Steven , Markus Hugh S
Published: December 2020

Background

Cysteine-altering NOTCH3 variants identical to those causing the rare monogenic form of stroke, CADASIL, have been reported more common than expected in the general population, but their clinical significance and contribution to stroke and dementia risk in the community remains unclear.

Methods

Cysteine-altering NOTCH3 variants were identified in UK Biobank whole-exome sequencing data (N=200,632). Frequency of stroke, dementia and other clinical features of CADASIL, and MRI white matter hyperintensity volume were compared between variant carriers and non-carriers. MRIs from those with variants were visually rated, each matched with three controls.

Results

Of 200,632 participants with exome sequencing data available, 443 (∼1 in 450) carried 67 different cysteine-altering NOTCH3 variants. After adjusting for age, sex, and ancestry principal components, NOTCH3 variant carriers had increased risk of stroke (OR: 2.33, p=0.0003), and vascular dementia (OR: 5.03, p=0.007), and increased WMH volume (standardised difference: 0.52, p<0.001), and white matter ultrastructural damage on DTI-PSMD (standardised difference: 0.71, p<0.001). On visual analysis of MRIs from 47 carriers and 148 matched controls, variants were associated with presence of lacunes (OR: 4.83, p<0.001) and cerebral microbleeds (OR: 3.61, p<0.001). WMH prevalence was most increased in the anterior temporal lobes (OR: 6.92, p<0.001) and external capsule (OR: 12.44, p<0.001).

Conclusions

Cysteine-changing NOTCH3 variants are common in the general population and are risk factors for apparently “sporadic” stroke and vascular dementia. They are associated with MRI changes of SVD, in a distribution similar to that seen in CADASIL.
Excess mortality during the first ten months of COVID-19 epidemic at Jakarta, Indonesia
Authors: Elyazar Iqbal RF , Surendra Henry , Ekawati Lenny L , Djaafara Bimandra A. , Nurhasim Ahmad , Arif Ahmad , Hidayana Irma , Widyastuti  , Oktavia Dwi , Adrian Verry , Salama Ngabila , Hamdi Imam , Andrianto Adhi , Lina Rosa N , Lestari Karin D , Shankar Anuraj H , Hamers Raph L , Thwaites Guy , Baird J. Kevin
Published: December 2020

Excess mortality during the COVID-19 epidemic is an important measure of health impacts. We examined mortality records from January 2015 to October 2020 from government sources at Jakarta, Indonesia: 1) burials in public cemeteries; 2) civil death registration; and 3) health authority death registration. During 2015-2019, an average of 26,342 burials occurred each year from January to October. During the same period of 2020, there were 42,460 burials, an excess of 61%. Burial activities began surging in early January 2020, two months before the first official laboratory confirmation of SARS-CoV-2 infection in Indonesia in March 2020. Analysis of civil death registrations or health authority death registration showed insensitive trends during 2020. Burial records indicated substantially increased mortality associated with the onset of and ongoing COVID-19 epidemic in Jakarta and suggest that SARS-CoV-2 transmission may have been initiated and progressing at least two months prior to official detection.

Article summary line

Analysis of civil records of burials in Jakarta, Indonesia showed a 61% increase during 2020 compared to the previous five years, a trend that began two months prior to first official confirmation of SARS-CoV-2 transmission in the city.
Are commercial antibody assays substantially underestimating SARS-CoV-2 ever infection? An analysis on a population-based sample in a high exposure setting
Authors: Nasrallah Gheyath K. , Dargham Soha R. , Shurrab Farah , Al-Sadeq Duaa W. , Al-Jighefee Hadeel , Chemaitelly Hiam , Kanaani Zaina Al , Khal Abdullatif Al , Kuwari Einas Al , Coyle Peter , Jeremijenko Andrew , Kaleeckal Anvar Hassan , Latif Ali Nizar , Shaik Riyazuddin Mohammad , Abdul Rahim Hanan F. , Yassine Hadi M. , Al Kuwari Mohamed G. , Qotba Hamda , Romaihi Hamad Eid Al , Tang Patrick , Bertollini Roberto , Al-Thani Mohamed , Althani Asmaa A. , Abu-Raddad Laith J.
Published: December 2020

Background

Performance of three automated commercial serological IgG-based assays was investigated for assessing SARS-CoV-2 ever (past or current) infection in a population-based sample in a high exposure setting.

Methods

PCR and serological testing was performed on 394 individuals.

Results

SARS-CoV-2-IgG seroprevalence was 42.9% (95% CI 38.1%-47.8%), 40.6% (95% CI 35.9%-45.5%), and 42.4% (95% CI 37.6%-47.3%) using the CL-900i, VidasIII, and Elecsys assays, respectively. Between the three assays, overall, positive, and negative percent agreements ranged between 93.2%-95.7%, 89.3%-92.8%, and 93.8%-97.8%, respectively; Cohen kappa statistic ranged from 0.86-0.91; and 35 specimens (8.9%) showed discordant results. Among all individuals, 12.5% (95% CI 9.6%-16.1%) had current infection, as assessed by PCR. Of these, only 34.7% (95% CI 22.9%-48.7%) were seropositive by at least one assay. A total of 216 individuals (54.8%; 95% CI 49.9%-59.7%) had evidence of ever infection using antibody testing and/or PCR during or prior to this study. Of these, only 78.2%, 74.1%, and 77.3% were seropositive in the CL-900i, VidasIII, and Elecsys assays, respectively.

Conclusions

All three assays had comparable performance and excellent agreement, but missed at least 20% of individuals with past or current infection. Commercial antibody assays can substantially underestimate ever infection, more so when infection rates are high.