bluuebunny/crossref_metadata_2025 huggingface dataset:
Disparity of Racial/Ethnic Representation in Publications Contributing to Overactive Bladder Diagnosis and Treatment Guidelines
Authors: Brown Oluwateniola , Siddique Moiuri , Mou Tsung , Boniface Emily R. , Volpe Katherine A. , Cichowski Sara ,   AUGS Disparities Special Interest Group
Published: November 2020

Objective

The aim of the study was to compare the racial/ethnic representation in studies supporting the 2019 American Urological Association/Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction overactive bladder diagnosis and treatment guideline to the racial/ethnic distribution of the U.S. population.

Methods

We analyzed the race and ethnicity of participants in the articles cited in the 2019 American Urological Association/Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction nonneurogenic overactive bladder guidelines. The primary outcome was the representation quotient, the ratio of the proportion of a racial/ethnic group in the guideline studies relative to the estimated proportion of that group in the U.S. population. Data were analyzed using descriptive statistics and Pearson χ2 test.

Results

There were 387 studies included, 35% of which reported participants’ race. Of the studies that included U.S. participants, 111 (61%) reported race and 44 (24%) reported Hispanic ethnicity. The representation quotient for White and Asian participants was 1.06 and 1.62, indicating overrepresentation relative to the U.S. population, respectively. The representation quotient for Black, Hispanic, and American Indian/Alaska Native participants was 0.85, 0.56, and 0.02, respectively, indicating underrepresentation for these groups. Evaluation of the representation quotients over time revealed no meaningful change in representation from 1990 to 2019 for any racial/ethnic group.

Conclusions

The evidence based on the overactive bladder guidelines is derived from studies that frequently failed to report race/ethnicity and is not reflective of the U.S. population. Black, Hispanic, and American Indian/Alaska Native participants that are underrepresented in U.S.-based studies, highlighting the need for more inclusive recruitment strategies in overactive bladder research.
COVID-19-related mortality by age groups in Europe: A meta-analysis
Authors: Cohen Jérémie F. , Korevaar Daniël A. , Matczak Soraya , Brice Joséphine , Chalumeau Martin , Toubiana Julie
Published: November 2020

Background and Objectives

To date, more than 1,000,000 confirmed cases and 65,000 deaths due to coronavirus disease 2019 (COVID-19) have been reported globally. Early data have indicated that older patients are at higher risk of dying from COVID-19 than younger ones, but precise international estimates of the age-breakdown of COVID-19-related deaths are lacking.

Materials and Methods

We evaluated the distribution of COVID-19-related fatalities by age groups in Europe. On April 6, 2020, we systematically reviewed COVID-19-related mortality data from 32 European countries (European Union/European Economic Area and the United Kingdom). We collated official reports provided by local Public Health or Ministry of Health websites. We included countries if they provided data regarding more than 10 COVID-19-related deaths stratified by age according to pre-specified groups (i.e., < 40, 40-69, ≥ 70 years). We used random-effects meta-analysis to estimate the proportion of age groups among all COVID-19-related fatalities.

Results

Thirteen European countries were included in the review, for a total of 31,864 COVID-19-related deaths (range: 27-14,381 per country). In the main meta-analysis (including data from Germany, Hungary, Italy, Netherlands, Portugal, Spain, Switzerland; 21,522 COVID-19-related fatalities), the summary proportions of persons < 40, 40-69, and ≥ 70 years of age among all COVID-19-related deaths were 0.1% (0.0-0.2%; I2 24%), 12.8% (10.3-15.6%; I2 94%), and 84.8% (81.3-88.1%; I2 96%), respectively.

Conclusions

People under 40 years of age represent a small fraction of the total number of COVID-19-related deaths in Europe. These results may help health authorities respond to public concerns and guide future physical distancing and mitigation strategies.
Preterm birth rates in a large tertiary Australian maternity centre during COVID-19 mitigation measures
Authors: Gallo Linda A. , Gallo Tania F. , Borg Danielle J. , Moritz Karen M. , Clifton Vicki L. , Kumar Sailesh
Published: November 2020

Objectives

To compare the prevalence of live preterm birth rates during COVID-19 restriction measures with infants born during the same weeks in 2013-2019 in Queensland, Australia.

Design, setting, participants

Deidentified obstetric and neonatal data were extracted from the Mater Mothers’ electronic healthcare records database. This is a supra-regional tertiary perinatal centre.

Main outcome measures

Logistic regressions were used to examine preterm birth rates during the beginning of COVID-19 restrictions (16 March-17 April; “early”; 6,955 births) and during the strictest part of COVID-19 restrictions (30 March-1 May; “late”; 6,953 births), according to gestational age subgroups and birth onset (planned or spontaneous). We adjusted for multiple covariates, including maternal age, body mass index, ethnicity, parity, socioeconomic status, maternal asthma, diabetes mellitus and/or hypertensive disorder. Stillbirth rates were also examined (16 March-1 May).

Results

A reduction in planned moderate/late preterm births was observed primarily during the early restriction period compared with the same calendar weeks in the previous seven years (29 versus an average of 64 per 1,000 births; adjusted odds ratio [aOR] 0.39, 95% CI 0.22-0.71). There was no effect on extremely or very preterm infants, spontaneous preterm births, or stillbirth rates. Rolling averages from January to June revealed a two-week non-significant spike in spontaneous preterm births from late-April to early-May, 2020.

Conclusions

Planned births for moderate/late preterm infants more than halved during early COVID-19 mitigation measures. Together with evidence from other nations, the COVID-19 pandemic provides a unique opportunity to identify causal and preventative factors for preterm birth.
Development of an Optical Assay to Detect SARS-CoV-2 Spike Protein Binding Interactions with ACE2 and Disruption of these Interactions Using Electric Current
Authors: Al Ahmad Mahmoud , Mustafa Farah , Panicker Neena , Rizvi Tahir A.
Published: November 2020

This study proposes a novel optical method of detecting and reducing SARS-CoV-2 transmission, the virus responsible for the COVID-19 pandemic that is sweeping the world today. SARS-CoV-2 belongs to the β-coronaviruses characterized by the crown-shaped spike protein that protrudes out of the virus particles, giving the virus a “corona” shape; hence the name coronavirus. This virus is similar to the viruses that caused SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome), the other two coronavirus epidemics that were recently contained within the last ten years. The technique being proposed uses a light source from a smart phone and a mobile spectrophotometer to enable detection of viral proteins in solution or paper as well as protein-protein interactions. The proof-of-concept is shown by detecting soluble preparations of spike protein subunits from SARS-CoV-2, followed by detection of the actual binding potential of the spike protein with its host receptor, the angiotensin-converting enzyme 2 (ACE2). The results are validated by showing that this method can detect antigen-antibody binding using two independent viral protein-antibody pairs. The binding could be detected optically both in solution and on a solid support such as nitrocellulose membrane. Finally, this technique is combined with DC bias to show that introduction of a current into the system can be used to disrupt the antigen-antibody reaction, suggesting that the proposed extended technique can be a potential means of not only detecting the virus, but also reducing virus transmission by disrupting virus-receptor interactions electrically.

Significance

The measured intensity of light can reveal information about different cellular parameters under study. When light passes through a bio-composition, the intensity is associated with its content. The nuclei size, cell shape and the refractive index variation of cells contributes to light intensity. In this work, an optical label-free real time detection method incorporating the smartphone light source and a portable mini spectrometer for SARS-CoV-2 detection was developed based on the ability of its spike protein to interact with the ACE2 receptor. The light interactions with control and viral protein solutions were capable of providing a quick decision regarding whether the sample under test was positive or negative, thus enabling SARS-CoV-2 detection in a rapid manner.
How local interactions impact the dynamics of an epidemic
Authors: Wren Lydia , Best Alex
Published: November 2020

Susceptible-Infected-Recovered (SIR) models have long formed the basis for exploring epidemiological dynamics in a range of contexts, including infectious disease spread in human populations. Classic SIR models take a mean-field assumption, such that a susceptible individual has an equal chance of catching the disease from any infected individual in the population. In reality, spatial and social structure will drive most instances of disease transmission. Here we explore the impacts of including spatial structure in a simple SIR model. We combine an approximate mathematical model (using a pair approximation) and stochastic simulations to consider the impact of increasingly local interactions on the epidemic. Our key development is to allow not just extremes of ‘local’ (neighbour-to-neighbour) or ‘global’ (random) transmission, but all points in between. We find that even medium degrees of local interactions produce epidemics highly similar to those with entirely global interactions, and only once interactions are predominantly local do epidemics become substantially lower and later. We also show how intervention strategies to impose local interactions on a population must be introduced early if significant impacts are to be seen.
Positive rates predict death rates of Covid-19 locally and worldwide 13 days ahead
Authors: Mimkes Jürgen , Janssen Rainer
Published: November 2020

In the Covid-19-pandemic, the numbers of deceased do not consistently follow the number of new infections. The CFR mortality has declined in Germany from 5 % to 0.4 %. However, if we interpret the portion of positive tests as a positive rate, we find the positive rate and the numbers of deceased to run parallel with an offset of about 13 days. This has been observed worldwide in ten other countries and locally in Germany and North Rhine-Westphalia. In Germany the IFR mortality is about 29 per one million inhabitants, in the USA about 42, in Israel about 17, in the Netherlands 23, in Austria 27, in France 33, in Spain 36, in the UK 47 and Italy about 56 per million inhabitants. In Japan and South-Korea the mortality rate is only about 3 per million inhabitants, with an offset of about 25 days.

The daily positive ratio, which is reported by state health authorities, allows to estimate the number of deaths (and seriously ill people) about 13 days ahead. This gives local hospitals more time for detailed planning. The daily positive rate may be interpreted as a “thermometer” of the respective country. The positive rate gives a much better picture of the state of the pandemic and should be reported by the media in addition to infection numbers. In official guidelines a 7-day-positive-rate is a much better guideline than the 7-day-incidence.
How Timing of Stay-at-home Orders and Mobility Reductions Impacted First-Wave COVID-19 Deaths in US Counties
Authors: Audirac Michelle , Tec Mauricio , Meyers Lauren Ancel , Fox Spencer , Zigler Cory
Published: November 2020

As SARS-CoV-2 transmission continues to evolve, understanding how location-specific variations in non-pharmaceutical interventions and behaviors contributed to disease transmission during the initial epidemic wave will be key for future control strategies. We offer a rigorous statistical analysis of the relative effectiveness of the timing of both official stay-at-home orders and population mobility reductions during the initial stage of the US epidemic. We use a Bayesian hierarchical regression to fit county-level mortality data from the first case on Jan 21 2020 through Apr 20 2020 and quantify associations between the timing of stay-at-home orders and population mobility with epidemic control. We find that among 882 counties with an early local epidemic, a 10-day delay in the enactment of stay-at-home orders would have been associated with 14,700 additional deaths by Apr 20 (95% credible interval: 9,100, 21,500), whereas shifting orders 10 days earlier would have been associated with nearly 15,700 fewer lives lost (95% credible interval: 11,350, 18,950). Analogous estimates are available for reductions in mobility—which typically occurred before stay-at-home orders—and are also stratified by county urbanicity, showing significant heterogeneity. Results underscore the importance of timely policy and behavioral action for early-stage epidemic control.
Prediction of evolution of the second wave of Covid-19 pandemic in Italy
Authors: Ciufolini Ignazio , Paolozzi Antonio
Published: November 2020

A relevant problem in the study of the Covid-19 pandemic is the study of its temporal evolution. Such evolution depends on a number of factors, among which the average rate of contacts between susceptible and infected individuals, the duration of infectiousness and the transmissibility, that is the probability of infection after a contact between susceptible and infected individuals. In a previous study, we analyzed the potentiality of a number of distributions to describe the evolution of the pandemic and the potentiality of each distribution to mathematically predict the evolution of the pandemic in Italy. Since the number of daily tests was changing and increasing with time, we used the ratio of the new daily cases per swab. We considered distributions of the type of Gauss (normal), Gamma, Beta, Weibull, Lognormal and in addition of the type of the Planck blackbody radiation law. The Planck law, describing the amount of energy of the electromagnetic radiation emitted by a black body at each wavelength or at each frequency, marked in 1900 the beginning of Quantum Mechanics. The result of our analysis was that, among the considered distributions, the Planck law has the best potentiality to mathematically predict the evolution of the pandemic and the best fitting capability. In this paper, we analyze the time evolution of the second wave of the Covid-19 pandemic in Italy and in particular we predict the ratio of the new daily cases per swab at Christmas 2020 using the data in the interval from 17 Oct to 21 Nov. According to Figure 4 and Figure 8, the prediction for such a ratio around Christmas is approximately within 6% and 7%. In this study there is also an attempt to account for the effects of the governmental containment measures.
The Kids Are Not Alright: A Preliminary Report of Post-COVID Syndrome in University Students
Authors: Walsh-Messinger Julie , Manis Hannah , Vrabec Alison , Sizemore Jenna , Bishof Karyn , Debidda Marcella , Malaspina Dolores , Greenspan Noah
Published: November 2020

Background

Post-COVID syndrome is increasingly recognized by the medical community but has not been studied exclusively in young adults. This preliminary report investigates the prevalence and features of protracted symptoms in non-hospitalized university students who experienced mild-to-moderate acute illness.

Methods

148 students completed an online study to earn research credit for class. Data from COVID-19 positive participants with symptoms ≥28 days (N=22) were compared to those who fully recovered (N=21) and those not diagnosed with COVID-19 (N=58).

Results

51% of participants who contracted COVID-19 (N=43) experienced symptoms ≥28 days and were classified as having post-COVID syndrome; all but one (96%) were female. During acute illness the post-COVID group, compared to those who fully recovered, experienced significantly more chest pain (64% vs 14%; P=.002), fatigue (86% vs 48%; P=.009), fever (82% vs 48%; P=.02), olfactory impairment (82% vs 52%; P=.04), headaches (32% vs 5%; P<.05), and diarrhea (32% vs 5%; P<.05). Compared to those not diagnosed with COVID-19, the post-COVID syndrome group more frequently experienced exercise intolerance (43% vs. 0%; P<.001), dyspnea (43% vs. 0%; P<.001), chest pain (31% vs 7%; P=.002), olfactory impairment (19% vs 0%; P=.004), lymphadenopathy (19% vs 0%; P=.004), gustatory impairment (14% vs 0%; P=.02), and appetite loss (36% vs 14%; P=.02).

Interpretation

Our results contradict the perception that this “yet to be defined” post-COVID syndrome predominantly affects middle-aged adults and suggest that exercise intolerance, dyspnea, chest pain, chemosensory impairment, lymphadenopathy, rhinitis, and appetite loss may differentiate post-COVID syndrome from general symptoms of pandemic, age, and academic related stress. These findings are also consistent with previous reports that females are more vulnerable to this post viral syndrome. Large-scale population-based studies are essential to discerning the magnitude and characterization of post-COVID syndrome in young adults as well as more diverse populations.
A Test-Based Strategy for Safely Shortening Quarantine for COVID-19
Authors: Lewis Dana M. , Leibrand Scott , Leibrand Howard
Published: November 2020

Quarantine for COVID-19 is hard and could safely be made easier. Lengthy quarantine is difficult for many individuals to rigorously observe. To date, 14 days has been recommended as the quarantine period for people who are exposed to a confirmed COVID-19 case, because most infections appear by then. For household close contacts, there remains a 0.5% chance that a COVID-19 infection may appear after that time, because the COVID-19 incubation period is up to 21 days. However, the risk of transmission after 14 days is so small that public health authorities have decided that 0.5% is an acceptable risk to balance the impact of quarantine on individuals, their communities, and our economy. Therefore, this 0.5% risk of infection is a useful benchmark to consider additional strategies for reducing the burden on individuals while reducing spread of COVID-19. With appropriately timed testing and awareness of possible symptoms, a non-symptomatic individual with a negative COVID-19 test at day 7-8 would be at lower risk of being or becoming infectious than someone completing a 14-day quarantine without testing. If we implemented a test-based strategy for determining the end of quarantine, these individuals could be safely released from quarantine at an earlier date, and would be able to more rigorously quarantine themselves while potentially most infectious.
The Relationship between Weekly Periodicity and COVID-19 Progression
Authors: Li Sophia
Published: November 2020

COVID-19 is extraordinary both as once-in-a-lifetime pandemic and having abundant real-time case data, thus providing an extraordinary opportunity for timely independent analysis and novel perspectives. We investigate the weekly periodicity in the daily reported new cases and new deaths with the implied relationships to the societal and institutional responses using autocorrelation and Fourier transformation. The results show significant linear correlations between the weekly periodicity and the total cases and deaths, ranging from 50% to 84% for sizable groups of countries with population normalized deaths spanning nearly three orders of magnitude, from a few to approaching a thousand per million. In particular, the Strength Indicator of the periodicity in the new cases, defined by the autocorrelation with a 7-day lag, is positively correlated strongly to the total deaths per million in respective countries. The Persistence Indicator of the periodicity, defined as the average of three autocorrelations with 7-, 14- and 21-day lags, is an overall better indicator of the progression of the pandemic. For longer time series, Fourier transformation gives similar results. This analysis begins to fill the gap in modeling and simulation of epidemics with the inclusion of high frequency modulations, in this case most likely from human behaviors and institutional practices, and reveals that they can be highly correlated to the magnitude and duration of the pandemic. The results show that there is significant need to understand the causes and effects of the periodicity and its relationship to the progression and outcome of the pandemic, and how we could adapt our strategies and implementations to reduce the extent of the impact of COVID-19.
Exploring the Healthy Behaviors of Nigerians during the COVID-19 Pandemic
Authors: Eyisi Ifeanyichukwu Meek
Published: November 2020

Healthy behaviors remain important for staying safe during the coronavirus disease 2019 (COVID-19) pandemic. This study, therefore, explored the healthy behaviors of Nigerians during the COVID-19 pandemic and the impact of COVID-19 related news on healthy behaviors. Thirty-three (17 females and 16 males) participants from the general Nigerian population with age range of 23-64 years were recruited via social media using the snowball technique. Responses were elicited using semi-structured questions and subjected to thematic analysis. The healthy behaviors identified included; “social distancing”, “changes in nutrition”, “hand washing or sanitizing”, “exercise”, “increased vigilance from those with comorbidities”, and “use of facemask”. In another analysis, the impacts of COVID-19 related news on healthy behaviors were; “behavior modification”, “anxious impacts”, and “fake news about COVID-19 caused people to stop listening to COVID-19 related news”. Findings generated practical implications for enhancing healthy behaviors during the COVID-19 pandemic. The role of the media in strengthening healthy behaviors during the pandemic was also highlighted.
Reconstructing unseen transmission events to infer dengue dynamics from viral sequences
Authors: Salje Henrik , Wesolowski Amy , Brown Tyler , Kiang Mathew , Berry Irina Maljkovic , Lefrancq Noemie , Fernandez Stefan , Jarman Richard , Ruchusatsawat Kriangsak , Iamsirithaworn Sopon , Vandepitte Warunee P. , Suntarattiwong Piyarat , Klungthong Chonticha , Thaisomboonsuk Butsaya , Engo-Monsen Kenth , Buckee Caroline , Cauchemez Simon , Cummings Derek
Published: November 2020

For most pathogens, transmission is driven by interactions between the behaviours of infectious individuals, the behaviours of the wider population, the local environment, and immunity. Phylogeographic approaches are currently unable to disentangle the relative effects of these competing factors. We develop a spatiotemporally structured phylogenetic framework that reconstructs transmission across spatial scales and apply it to geocoded dengue virus sequences from Thailand (N=726 over 18 years). We find infected individuals spend 96% of their daytime hours in their home community compared to 76% for the susceptible population (mainly children) and 42% for adults. Dynamic pockets of local immunity make transmission more likely in places with high heterotypic immunity and less likely where high homotypic immunity exists. Age-dependent mixing of individuals and vector distributions are not important in determining transmission. This approach provides previously unknown insights into one of the most complex disease systems known and will be applicable across pathogens.
Clinical and immunological benefits of convalescent plasma therapy in severe COVID-19: insights from a single center open label randomised control trial
Authors: Ray Yogiraj , Paul Shekhar Ranjan , Bandopadhyay Purbita , D’Rozario Ranit , Sarif Jafar , Lahiri Abhishake , Bhowmik Debaleena , Vasudevan Janani Srinivasa , Maurya Ranjeet , Kanakan Akshay , Sharma Sachin , Kumar Manish , Singh Praveen , Roy Rammohan , Chaudhury Kausik , Maiti Rajsekhar , Bagchi Saugata , Maiti Ayan , Perwez Md. Masoom , Mondal Abhinandan , Tewari Avinash , Mandal Samik , Roy Arpan , Saha Moumita , Biswas Durba , Maiti Chikam , Chakraborty Sayantan , Sarkar Biswanath Sharma , Haldar Anima , Saha Bibhuti , Sengupta Shantanu , Pandey Rajesh , Chatterjee Shilpak , Bhattacharya Prasun , Paul Sandip , Ganguly Dipyaman
Published: November 2020

Introduction

A single center open label phase II randomised control trial was done to assess the pathogen and host-intrinsic factors influencing clinical and immunological benefits of passive immunization using convalescent plasma therapy (CPT), in addition to standard of care (SOC) therapy in severe COVID-19 patients, as compared to patients only on SOC therapy.

Methods

Convalescent plasma was collected from patients recovered from COVID-19 following a screening protocol which also included measuring plasma anti SARS-CoV2 spike IgG content. Retrospectively, neutralizing antibody content was measured and proteome was characterized by LC-MS/MS for all convalescent plasma units that were transfused to patients. Severe COVID-19 patients with evidence for acute respiratory distress syndrome (ARDS) with PaO2/FiO2 ratio 100-300 (moderate ARDS) were recruited and randomised into two parallel arms of SOC and CPT, N=40 in each arm. Peripheral blood samples were collected on the day of enrolment (T1) followed by day3/4 (T2) and day 7 (T3). RT-PCR and sequencing was done for SARS-CoV2 RNA isolated from nasopharyngeal swabs collected at T1. A panel of cytokines and neutralizing antibody content were measured in plasma at all three timepoints. Patients were followed up for 30 days post-admission to assess the primary outcomes of all cause mortality and immunological correlates for clinical benefits.

Results

While across all age-groups no statistically significant clinical benefit was registered for patients in the CPT arm, significant immediate mitigation of hypoxia, reduction in hospital stay as well as survival benefit was recorded in severe COVID-19 patients with ARDS aged less than 67 years receiving convalescent plasma therapy. In addition to its neutralizing antibody content a prominent effect of convalescent plasma on attenuation of systemic cytokine levels possibly contributed to its benefits.

Conclusion

Precise targeting of severe COVID-19 patients is necessary for reaping the clinical benefits of convalescent plasma therapy.

Clinical trial registration

Clinical Trial Registry of India No. CTRI/2020/05/025209
Self-harm during the early period of the COVID-19 Pandemic in England: comparative trend analysis of hospital presentations
Authors: Hawton Keith , Casey Deborah , Bale Elizabeth , Brand Fiona , Ness Jennifer , Waters Keith , Kelly Sam , Geulayov Galit
Published: November 2020

Background

The COVID-19 pandemic and public health measures necessary to address it may have major effects on mental health, including on self-harm. We have used well-established monitoring systems in two hospitals in England to investigate trends in self-harm presentations to hospitals during the early period of the pandemic.

Method

Data collected in Oxford and Derby on patients aged 18 years and over who received a psychosocial assessment after presenting to the emergency departments following self-harm were used to compare trends during the three-month period following lockdown in the UK (23rd March 2020) to the period preceding lockdown and the equivalent period in 2019.

Results

During the 12 weeks following introduction of lockdown restrictions there was a large reduction in the number of self-harm presentations to hospitals by individuals aged 18 years and over compared to the pre-lockdown weeks in 2020 (mean weekly reduction of 13.5 (95% CI 5.6 - 21.4) and the equivalent period in 2019 (mean weekly reduction of 18.0 (95% CI 13.9 - 22.1). The reduction was greater in females than males, occurred in all age groups, with a larger reduction in presentations following self-poisoning than self-injury.

Conclusions

A substantial decline in hospital presentations for self-harm occurred during the three months following the introduction of lockdown restrictions. Reasons could include a reduction in self-harm at the community level and individuals avoiding presenting to hospital following self-harm. Longer-term monitoring of self-harm behaviour during the pandemic is essential, together with efforts to encourage help-seeking and the modification of care provision.
Emotion regulation in emerging adults with major depressive disorder and frequent cannabis use
Authors: Nichols Emily S. , Penner Jacob , Ford Kristen A. , Wammes Michael , Neufeld Richard W.J. , Mitchell Derek G.V. , Greening Steven G. , Théberge Jean , Williamson Peter C. , Osuch Elizabeth A.
Published: November 2020

In people with mental health issues, approximately 20% have co-occurring substance use, often involving cannabis. Although emotion regulation can be affected both by major depressive disorder (MDD) and by cannabis use, the relationship among all three factors is unknown. In this study, we used fMRI to evaluate the effect that cannabis use and MDD have on brain activation during an emotion regulation task. Differences were assessed in 74 emerging adults aged 16-23 with and without MDD who either used or did not use cannabis. Severity of depressive symptoms, emotion regulation style, and age of cannabis use onset were also measured. Both MDD and cannabis use interacted with the emotion regulation task in the left temporal lobe, however the location of the interaction differed for each factor. Specifically, MDD showed an interaction with emotion regulation in the middle temporal gyrus, whereas cannabis use showed an interaction in the superior temporal gyrus. Emotion regulation style predicted activity in the right superior frontal gyrus, however, this did not interact with MDD or cannabis use. Severity of depressive symptoms interacted with the emotion regulation task in the left middle temporal gyrus. The results highlight the influence of cannabis use and MDD on emotion regulation processing, suggesting that both may have a broader impact on the brain than previously thought.
The Interaction of Child Abuse and rs1360780 of the FKBP5 Gene is Associated with Amygdala Resting-State Functional Connectivity in Young Adults
Authors: Wesarg Christiane , Veer Ilya M. , Oei Nicole Y. L. , Daedelow Laura S. , Lett Tristram A. , Banaschewski Tobias , Barker Gareth J. , Bokde Arun L.W. , Quinlan Erin Burke , Desrivières Sylvane , Flor Herta , Grigis Antoine , Garavan Hugh , Brühl Rüdiger , Martinot Jean-Luc , Artiges Eric , Nees Frauke , Orfanos Dimitri Papadopoulos , Poustka Luise , Hohmann Sarah , Fröhner Juliane H. , Smolka Michael N. , Whelan Robert , Schumann Gunter , Heinz Andreas , Walter Henrik ,   IMAGEN Consortium
Published: November 2020

Extensive research has demonstrated that rs1360780, a common single nucleotide polymorphism within the FKBP5 gene, interacts with early-life stress in predicting psychopathology. Previous results suggest that carriers of the TT genotype of rs1360780 who were exposed to child abuse show differences in structure and functional activation of emotion-processing brain areas belonging to the salience network. Extending these findings on intermediate phenotypes of psychopathology, we examined if the interaction between rs1360780 and child abuse predicts resting-state functional connectivity (rsFC) between the amygdala and other areas of the salience network. We analyzed data of young European adults from the general population (N = 774; mean age = 18.76 years) who took part in the IMAGEN study. In the absence of main effects of genotype and abuse, a significant interaction effect was observed for rsFC between the right centromedial amygdala and right posterior insula (p < .025, FWE-corrected), which was driven by stronger rsFC in TT allele carriers with a history of abuse. Our results suggest that the TT genotype of rs1360780 may render individuals with a history of abuse more vulnerable to functional changes in communication between brain areas processing emotions and bodily sensations, which could underlie or increase risk for psychopathology.
Airway antibodies emerge according to COVID-19 severity and wane rapidly but reappear after SARS-CoV-2 vaccination
Authors: Cagigi Alberto , Yu Meng , Österberg Björn , Svensson Julia , Falck-Jones Sara , Vangeti Sindhu , Åhlberg Eric , Azizmohammadi Lida , Warnqvist Anna , Falck-Jones Ryan , Gubisch Pia C , Ödemis Mert , Ghafoor Farangies , Eisele Mona , Lenart Klara , Bell Max , Johansson Niclas , Albert Jan , Sälde Jörgen , Pettie Deleah , Murphy Michael , Carter Lauren , King Neil P , Ols Sebastian , Normark Johan , Ahlm Clas , Forsell Mattias , Färnert Anna , Loré Karin , Smed-Sörensen Anna
Published: November 2020

Understanding the presence and durability of antibodies against SARS-CoV-2 in the airways is required to provide insights on the ability of individuals to neutralize the virus locally and prevent viral spread. Here, we longitudinally assessed both systemic and airway immune responses upon SARS-CoV-2 infection in a clinically well-characterized cohort of 147 infected individuals representing the full spectrum of COVID-19 severity; from asymptomatic infection to fatal disease. In addition, we evaluated how SARS-CoV-2 vaccination influenced the antibody responses in a subset of these individuals during convalescence as compared to naïve individuals. Not only systemic but also airway antibody responses correlated with the degree of COVID-19 disease severity. However, while systemic IgG levels were durable for up to 8 months, airway IgG and IgA had declined significantly within 3 months. After vaccination, there was an increase in both systemic and airway antibodies, in particular IgG, often exceeding the levels found during acute disease. In contrast, naïve individuals showed low airway antibodies after vaccination. In the former COVID-19 patients, airway antibody levels were significantly elevated after the boost vaccination, highlighting the importance of prime and boost vaccination also for previously infected individuals to obtain optimal mucosal protection.
Social responsibility is the crucial factor in adopting early vaccination plans
Authors: Georgiou Harris V.
Published: November 2020

Early vaccination of the general population is a very crucial aspect in the successful mitigation of highly infectious diseases, as it is the case of the SARS-CoV-2 pandemic. The perception of possible side-effects from early batches of vaccines, presumably under-tested, is often a hindering factor for people not in high-risk categories to optin for early vaccination. In this work, early vaccination is formulated under a game-theoretic view with preference ranking and expectation maximization, in order to explore the constraints and conditions under which individuals are keen to opt-in for getting vaccinated. Although simple preference ranking leads to purely non-cooperative / non-altruistic Nash equilibrium, stable cooperative strategies can emerge under simple constraints on the payoffs, specifically the individual cost from possible side-effects versus the collective gain for the community (‘herd’) when endorsing vaccination by default.

Significance Statement

If the collective gain from community-scale vaccination is deemed even marginally greater than each individual’s cost of possible side-effects, then the best strategy is to ‘cooperate’, i.e., every individual to opt-in for getting vaccinated.

This condition is independent from the probabilities of getting infected, with or without vaccination, and it is sufficient to lead to a stable cooperative Nash equilibrium.

In any lethal infectious disease like SARS-CoV-2 and less-than-lethal possible side-effects from the vaccine, for anyone that is susceptible plus one more in his/her own close environment, vaccination is the optimal strategy for all.
The Epidemiologic Transition Theory and Evidence for Cancer Transitions in the US, Select European Nations, and Japan
Authors: Gersten Omer , Barbieri Magali
Published: November 2020

Despite cancer being a leading cause of death worldwide, scant research has been carried out on the existence of “cancer transitions,” the idea that as nations develop, they move from a situation where infectious related cancers are prominent, to one where non-infectious related cancers dominate. We use annual cause-of-death data to produce death rates for common types of cancer in select high-income countries. We find that cancer mortality patterns parallel the epidemiologic transition, which states that as countries advance, they move from a regime where infectious diseases are most common to one where non-infectious disease are most common. An implication is that the epidemiologic transition theory as originally formulated continues to be relevant despite some researchers arguing that we need additional stages beyond the original three.
ExaminingFouquieria splendensin an environmental and ecological context: Effect of topography and interspecific neighbors on ocotillo morphology and distribution
Authors: Bernat Anastasia , So Tang Acacia Tsz , Steenson Allegra , Larsen Eric
Published: November 2020

Fouquieria splendensis a stem-succulent native to the Chihuahuan, Mojave, and Sonoran Deserts that spans Mexico and the American Southwest. It is well-known for its variable morphology, the underlying reason for which remains incompletely understood. Here, we attempt to quantify the effect of topographic and interspecific factors onF. splendensmorphology and distribution. To this end, we measured 27 ocotillos located in the Organ Pipe Cactus National Monument within the Sonoran Desert during June of 2019. We also quantified the spatial distribution of interspecific neighbors relative toF. splendenswithin two topographically different sites: a bajada gradient and a plain. Using ocotillo morphology, the distances to the nearest neighbors of ocotillos, and hydrographic data extracted from the National Hydrography Dataset, we demonstrate 1) the effect of major interspecific neighbors, i.e. shrubs and cacti, on ocotillo morphology; 2) the effect of elevation on intraspecific spacing as individuals compete for limited space; and 3) a trade-off between height and number of branches. This placesF. splendensmorphology in its larger environmental and ecological context, highlighting the importance of individual traits and associated trade-offs among traits affected by topography and interspecific neighbors. By examining the ocotillo in a multi-species community and diverse landscape, this study provides empirical insight into a wider range of factors contributing to the variation inF. splendensmorphology and spacing.
Cryptic promoter activation occurs by at least two different mechanisms in theArabidopsisgenome
Authors: Kudo Hisayuki , Matsuo Mitsuhiro , Satoh Soichirou , Hachisu Rei , Nakamura Masayuki , Yamamoto Yoshiharu Y , Hata Takayuki , Kimura Hiroshi , Matsui Minami , Obokata Junichi
Published: November 2020

In gene-trap screening of plant genomes, promoterless reporter constructs are often expressed without trapping of annotated gene promoters. The molecular basis of this phenomenon, which has been interpreted as the trapping of cryptic promoters, is poorly understood. In this study, usingArabidopsisgene-trap lines in which a firefly luciferase (LUC) open reading frame (ORF) was expressed from intergenic regions, we found that cryptic promoter activation occurs by at least two different mechanisms: one is the capturing of pre-existing promoter-like chromatin marked by H3K4me3 and H2A.Z, and the other is the entirely new formation of promoter chromatin near the 5’ end of the insertedLUCORF. To discriminate between these, we denoted the former mechanism as “cryptic promoter capturing”, and the latter one as “promoterde novoorigination”. The latter finding raises a question as to how insertedLUCORF sequence is involved in this phenomenon. To examine this, we performed a model experiment with chimericLUCgenes in transgenic plants. UsingArabidopsis psaH1promoter–LUCconstructs, we found that the functional core promoter region, where transcription start sites (TSS) occur, cannot simply be determined by the upstream nor core promoter sequences; rather, its positioning proximal to the insertedLUCORF sequence was more critical. This result suggests that the insertion of theLUCORF sequence alters the local distribution of the TSS in the plant genome. The possible impact of the two types of cryptic promoter activation mechanisms on plant genome evolution and endosymbiotic gene transfer is discussed.
Streamlined Magnetic Resonance Fingerprinting: Fast Whole-brain Coverage with Deep-learning Based Parameter Estimation
Authors: Khajehim Mahdi , Christen Thomas , Tam Fred , Graham Simon J.
Published: November 2020

Magnetic resonance fingerprinting (MRF) is a novel quantitative MRI (qMRI) framework that provides simultaneous estimates of multiple relaxation parameters as well as metrics of field inhomogeneity in a single acquisition. However, current bottlenecks exist in the forms of (1) scan time; (2) need for custom image reconstruction; (3) large dictionary sizes; (4) long dictionary-matching time. The aim of this study is to introduce a novel streamlined magnetic-resonance fingerprinting (sMRF) framework that is based on a single-shot echo-planar imaging (EPI) sequence to simultaneously estimate tissue T1, T2, and T2* with integrated B1+correction. Encouraged by recent work on EPI-based MRF, we developed a method that combines spin-echo EPI with gradient-echo EPI to achieve T2 in addition to T1 and T2* quantification. To this design, we add simultaneous multi-slice (SMS) acceleration to enable full-brain coverage in a few minutes. Moreover, in the parameter-estimation step, we use deep learning to train a deep neural network (DNN) to accelerate the estimation process by orders of magnitude. Notably, due to the high image quality of the EPI scans, the training process can rely simply on Bloch-simulated data. The DNN also removes the need for storing large dictionaries. Phantom scans along with in-vivo multi-slice scans from seven healthy volunteers were acquired with resolutions of 1.1×1.1×3 mm3and 1.7×1.7×3 mm3, and the results were validated against ground truth measurements. Excellent correspondence was found between our T1, T2, and T2* estimates and results obtained from standard approaches. In the phantom scan, a strong linear relationship (R=1-1.04, R2>0.96) was found for all parameter estimates, with a particularly high agreement for T2 estimation (R2>0.99). Similar findings are reported for the in-vivo human data for all of our parameter estimates. Incorporation of DNN results in a reduction of parameter estimation time on the order of 1000 x and a reduction in storage requirements on the order of 2500 x while achieving highly similar results as conventional dictionary matching (%differences of 7.4±0.4%, 3.6±0.3% and 6.0±0.4% error in T1, T2, and T2* estimation). Thus, sMRF has the potential to be the method of choice for future MRF studies by providing ease of implementation, fast whole-brain coverage, and ultra-fast T1/T2/T2* estimation.
Translesion DNA synthesis-driven mutagenesis in very early embryogenesis of fast cleaving embryos
Authors: Furno Elena Lo , Busseau Isabelle , Lorenzi Claudio , Saghira Cima , Danzi Matt C , Zuchner Stephan , Maiorano Domenico
Published: November 2020

In early embryogenesis of fast cleaving embryos DNA synthesis is short and surveillance mechanisms preserving genome integrity are inefficient implying the possible generation of mutations. We have analyzed mutagenesis inXenopus laevisandDrosophila melanogasterearly embryos. We report the occurrence of a high mutation rate inXenopusand show that it is dependent upon the translesion DNA synthesis (TLS) master regulator Rad18. Unexpectedly, we observed a homology-directed repair contribution of Rad18 in reducing the mutation load. Genetic invalidation of TLS in the pre-blastodermDrosophilaembryo resulted in reduction of both the hatching rate and Single Nucleotide Variations on specific chromosome regions in adult flies. Altogether, these findings indicate that during very earlyXenopusandDrosophilaembryos TLS strongly contributes to the high mutation rate. This may constitute a previously unforeseen source of genetic diversity contributing to the polymorphisms of each individual with implications for genome evolution and species adaptation.
Plant genome response to incoming coding sequences: stochastic transcriptional activation independent of integration loci
Authors: Satoh Soichirou , Hata Takayuki , Takada Naoto , Tachikawa Makoto , Matsuo Mitsuhiro , Kushnir Sergei , Obokata Junichi
Published: November 2020

Horizontal gene transfer can occur between phylogenetically distant organisms, such as prokaryotes and eukaryotes. In these cases, how do the translocated genes acquire transcriptional competency in the alien eukaryotic genome? According to the conventional view, specific loci of the eukaryotic genome are thought to provide transcriptional competency to the incoming coding sequences. To examine this possibility, we randomly introduced the promoterless luciferase (LUC)-coding sequences into the genome ofArabidopsis thalianacultured cells and performed a genome-wide “transgene location vs. expression” scan. We mapped 4,504 promoterlessLUCinserts on theA. thalianachromosomes, and found that about 30% of them were transcribed. Only a small portion of them were explained by the conventional transcriptional fusions with the annotated genes, and the remainder occurred in a quite different manner; (1) they occurred all over the chromosomal regions, (2) independently of the insertion sites relative to the annotated gene loci, inherent transcribed regions, or heterochromatic regions, and (3) with one magnitude lower transcriptional level than the conventional transcriptional fusions. This type of transcriptional activation occurred at about 30% of the inserts, raising a question as to what this 30% means. We tested two hypotheses: the activation occurred at 30% of the entire chromosomal regions, or stochastically at 30% of each insertion event. Our experimental analysis indicates that the latter model could explain this transcriptional activation, a new type of plant genome response to the incoming coding sequences. We discuss the possible mechanisms and evolutionary roles of this phenomenon in the plant genome.