bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Interregional Travel to Shopping Malls and Restaurants in Response to Differential COVID-19 Restrictions in the Greater Toronto Area
Authors: Soucy Jean-Paul R. , Ghasemi Amir , Sturrock Shelby L. , Berry Isha , Buchan Sarah A. , MacFadden Derek R. , Daneman Nick , Gibb Nicholas , Brown Kevin A. 
Published: April 2021

AbstractBackgroundIn the fall of 2020, the government of Ontario, Canada adopted a 5-tier, regional framework of public health measures for the COVID-19 pandemic. During the second wave of COVID-19 in Ontario, the urban core of the Greater Toronto Area (Toronto and Peel) were the first regions in the province to enter the highest restriction tier (“lockdown”) on November 23, 2020, which closed restaurants to in-person dining and limited non-essential businesses, including shopping malls, to curbside pickup. The peripheral regions of the Greater Toronto Area (York, Durham, Halton) would not enter lockdown until later the following month. In this analysis, we examine whether the implementation of differentially timed restrictions in a highly interconnected metropolitan area led to increased interregional travel, potentially driving further transmission of SARS-CoV-2.MethodsWe used anonymized smartphone data to estimate the number of visits by residents of regions in the urban core to shopping malls and restaurants in peripheral regions in the week before compared to the week after the November 23 lockdown.ResultsResidents of Toronto and Peel took fewer trips to shopping malls and restaurants in the week following lockdown. This was entirely driven by reductions in visits within the locked down regions themselves, as there was a significant increase in trips to shopping malls in peripheral regions by these residents in the same period (Toronto: +40.7%, Peel: +65.5%). Visits to restaurants in peripheral regions also increased slightly (Toronto: +6.3%, Peel: +11.8%).DiscussionHeterogeneous restrictions may undermine lockdowns in the urban core as well as driving residents from zones of higher transmission to zones of lower transmission. These concerns are likely generalizable to other major metropolitan areas, which often comprise interconnected but administratively independent regions.
Detection of SARS-CoV-2 infection by saliva and nasopharyngeal sampling in frontline healthcare workers: an observational cohort study
Authors: Walker Naomi F. , Byrne Rachel L. , Howard Ashleigh , Nikolaou Elissavet , Farrar Madlen , Glynn Sharon , Cheliotis Katerina S. , Cubas Atienzar Ana I. , Davies Kelly , Reine Jesus , Rashid-Gardner Zalina , German Esther L. , Solórzano Carla , Blandamer Tess , Hitchins Lisa , Myerscough Christopher , Gessner Brad , Biegner Elizabeth , Collins Andrea M. , Beadsworth Mike , Todd Stacy , Hill Helen , Houlihan Catherine F. , Nastouli Eleni , Adams Emily R. , Mitsi Elena , Ferreira Daniela M. 
Published: April 2021

AbstractBackgroundThe SARS-CoV-2 pandemic has caused an unprecedented strain on healthcare systems worldwide, including the UK National Health Service (NHS). During the first wave of SARS-CoV-2 transmission in UK, SARS-CoV-2 NHS diagnostic test availability was limited to self-isolating symptomatic staff. The burden of symptomatic and asymptomatic infection in healthcare workers (HCW) attending work was unknown.MethodsWe conducted an observational cohort study of SARS-CoV-2 infection in HCW working in an acute NHS Trust during the first wave of the COVID-19 pandemic, using serial self-collected saliva and nasopharyngeal (NP) samples. We also collected self-assessed symptom profiles and isolation behaviours. We retrospectively compared SARS-CoV-2 detection by RT-PCR from saliva (weekly) and NP swabs (twice weekly) from 85 individuals in this cohort and evaluated the association with symptoms.FindingsOver a 12-week period from 30th March 2020, 40% (n=34/85, CI95% 31.3-51.8%) HCWs had evidence of SARS-CoV-2 infection by surveillance NP swab and/or saliva RT-qPCR. Agreement between paired saliva and NP swabs was poor (28.6%, CI95% 13.2-48.7%) with both methods detecting symptomatic and asymptomatic infections. Symptoms were reported by 47.1% (n=40) and self-isolation by 25.9% participants (n=22). Only 41.2% (n=14/34) participants with SARS-CoV-2 infection reported any symptoms within 14 days of the infection.InterpretationHCWs are a potential source of SARS-CoV-2 transmission in hospitals and symptom screening will identify the minority of infections in HCW. Saliva is an easily accessible fluid sample for screening for SARS-CoV-2 infection and in addition to NP swab, facilitated ascertainment of symptomatic and asymptomatic cases in this setting. Combined saliva and NP testing would improve detection of SARS-CoV-2 for surveillance. Better understanding of transmissibility from asymptomatic staff using transmission-based infection precautions, is required to inform policy.
Bayesian, Universal COVID Testing
Authors: Meyer Christian T. , Kralj Joel M. 
Published: April 2021

AbstractDuring the SARS-COV2 pandemic, there has been a persistent call for universal testing to better inform policy decisions. However, a little considered aspect of this call is the relationship between a test’s accuracy and the tested demographic. What are the implications of frequent, universal testing in otherwise asymptomatic demographics? By applying Bayesian statistics, it becomes clear that as the odds of having COVID decreases, there is a non-linear increase in the odds that each positive test is, in fact, a false positive. This phenomenon has precedence in the historical narrative surrounding universal mammogram screening which is no longer recommended due to the unacceptably high rate of false positives. The solution to combat the inflation of false positives is also suggested by Bayesian statistics: intelligently integrating multiple COVID diagnostic tests and symptoms via Bayes’ Theorem, an approach conceptually similar to pre-screening for mammograms. This extra information is readily available (e.g. olfactory function and fever) and will minimize the economic and emotional costs incurred by false positives while simultaneously improving the information available for policy-makers. In summary, along with the push for universal testing should be an equally rigorous approach to interpreting the test results.
Depression and Anxiety Symptoms in Young Adults Before and During the COVID-19 Pandemic: Evidence from a Canadian Population-Based Cohort
Authors: Watkins-Martin Kia , Orri Massimiliano , Pennestri Marie-Hélène , Castellanos-Ryan Natalie , Larose Simon , Gouin Jean-Philippe , Ouellet-Morin Isabelle , Chadi Nicholas , Philippe Frederick , Boivin Michel , Tremblay Richard E. , Côté Sylvana , Geoffroy Marie-Claude 
Published: April 2021

AbstractObjectivesConcerns have been raised that the COVID-19 pandemic could increase risk for adverse mental health outcomes, especially in young adults, a vulnerable age group. We investigated changes in depression and anxiety symptoms (overall and severe) from before to during the pandemic, as well as whether these changes are linked to COVID-19 related stressors and pre-existing vulnerabilities in young adults followed in the context of a population-based cohort.MethodParticipants (n=1039) from the Quebec Longitudinal Study of Child Development reported on their depression and anxiety symptoms and completed a COVID-19 questionnaire during the first wave of the COVID-19 pandemic in the summer of 2020 (age 22 years). Assessments at age 20 (2018) were used to estimate pre-pandemic depression and anxiety symptom severity.ResultsWhile overall levels of depression and anxiety symptoms did not change, there was an increase in rates of severe depression (but not severe anxiety) from before (6.1%) to during (8.2%) the pandemic. Depressive and anxiety symptoms increased from before to during the COVID-19 pandemic among young adults with the lowest levels of symptoms before the pandemic, while they decreased among those with the highest levels of pre-existing symptoms. Youth who were living alone experienced an increase in depressive symptoms. Other COVID-19 related variables (e.g., loss of education/occupation, frequent news-seeking) and pre-existing vulnerabilities (e.g., low SES, low social support) were not associated with changes in depression or anxiety symptoms.ConclusionDepression and anxiety symptoms in young adults from Québec in Summer 2020 were comparable to symptoms reported in 2018. Most COVID-19 related stressors and pre-existing vulnerabilities were not associated with changes in symptoms. However, the increased rate of severe depression and the increase in depression and anxiety symptoms among young adults with the least mental health symptoms before the COVID-19 pandemic are concerning.
Comparison of structural MRI brain measures between 1.5T and 3T: data from the Lothian Birth Cohort 1936
Authors: Buchanan Colin R. , Muñoz Maniega Susana , Valdés Hernández Maria C. , Ballerini Lucia , Barclay Gayle , Taylor Adele M. , Russ Tom C. , Tucker-Drob Elliot M. , Wardlaw Joanna M. , Deary Ian J. , Bastin Mark E. , Cox Simon R. 
Published: April 2021

AbstractMulti-scanner MRI studies are reliant on understanding the apparent differences in imaging measures between different scanners. We provide a comprehensive analysis of T1-weighted and diffusion MRI (dMRI) structural brain measures between a 1.5T GE Signa Horizon HDx and a 3T Siemens Magnetom Prisma using 91 community-dwelling older participants (aged 82 years). Although we found considerable differences in absolute measurements (global tissue volumes were measured as ∼6—11% higher and fractional anisotropy was 33% higher at 3T than at 1.5T), between-scanner consistency was good to excellent for global volumetric and dMRI measures (intraclass correlation coefficient [ICC] range: 0.612—0.993) and fair to good for 68 cortical regions (FreeSurfer) and cortical surface measures (mean ICC: 0.504—0.763). Between-scanner consistency was fair for dMRI measures of 12 major white matter tracts (mean ICC: 0.475—0.564), and the general factors of these tracts provided excellent consistency (ICC ≥ 0.769). Whole-brain structural networks provided good to excellent consistency for global metrics (ICC ≥ 0.612). Although consistency was poor for individual network connections (mean ICCs: 0.275 – 0.280), this was driven by a large difference in network sparsity (0.599 versus 0.334), and consistency was improved when comparing only the connections present in every participant (mean ICCs: 0.533—0.647). Regression-based k-fold cross-validation showed that, particularly for global volumes, between-scanner differences could be largely eliminated (R2range 0.615—0.991). We conclude that low granularity measures of brain structure can be reliably matched between the scanners tested, but caution is warranted when combining high granularity information from different scanners.
A Mobile App for Prolonged Grief among Bereaved Parents: Study Protocol for a Randomized Controlled Trial
Authors: Eklund Rakel , Eisma Maarten C. , Boelen Paul A. , Arnberg Filip , Sveen Josefin 
Published: April 2021

ABSTRACTIntroductionBereaved parents have elevated risk to develop mental health problems, yet, few studies have evaluated the effect of psychosocial interventions developed for bereaved parents. Cognitive behavioral therapy (CBT), both face-to-face or digitally delivered, has shown to be an effective intervention for prolonged grief symptoms. Self-help mobile apps offer various advantages and studies show improved mental health after app interventions. No app has yet been evaluated targeting prolonged grief in bereaved parents. Therefore, the aim of this planned study is to develop and examine the effectiveness of a CBT-based mobile app, called My Grief, in reducing symptoms of prolonged grief, as well as other psychological symptoms, in bereaved parents. Another aim is to assess users’ experiences and adverse events of My Grief.Methods and analysisWe will conduct a two-armed randomized waitlist-controlled trial. Parents living in Sweden, who lost a child to cancer between one and ten years ago, with elevated symptoms of prolonged grief, will be recruited to participate in the trial. The content of My Grief covers four main domains (Learn; Self-monitoring; Exercises; Get support) and builds on principles of CBT and the proven-effective PTSD Coach app. Participants in the intervention group will fill out online questionnaires at baseline and at 3-, 6- and 12-months follow-ups, and the waitlist-controls at baseline and at 3 months. The primary outcome will be prolonged grief symptoms at the 3 months follow-up. Secondary outcomes are posttraumatic stress and depression symptoms, quality of life, and cognitive behavioral variables (i.e., avoidance, rumination, negative cognitions).Ethics and disseminationEthical approval has been received from the Swedish Ethical Review Authority (project no. 2021-00770). If the app is shown to be effective, the app will be made publicly accessible on app stores, so that it can benefit other bereaved parents.Trial registrationClinicaltrials.gov, identifier: NCT04552717.STRENGTHS AND LIMITATIONSThis is the first study to examine whether access of a self-help app can have beneficial effect on bereaved parent’s mental health, quality of lifeThis study will examine the effect of the app on cognitive-behavioral processes proposed to underlie the development of prolonged grief.Generalizability of findings from this study may be limited as parents who want to participate in such study may experience fewer barriers to talk about the loss and seek help for their grief.This study includes parents who have lost a child to cancer, hence the findings may not be generalizable to other causes.This study uses self-report questionnaires, hence we do not establish formal diagnosis of prolonged grief disorder.
Network controllability mediates the relationship between rigid structure and flexible dynamics
Authors: Gu Shi , Fotiadis Panagiotis , Parkes Linden , Xia Cedric H. , Gur Ruben C. , Gur Raquel E. , Roalf David R. , Satterthwaite Theodore D. , Bassett Danielle S. 
Published: April 2021

ABSTRACTPrecisely how the anatomical structure of the brain supports a wide range of complex functions remains a question of marked importance in both basic and clinical neuroscience. Progress has been hampered by the lack of theoretical frameworks explaining how a structural network of relatively rigid inter-areal connections can produce a diverse repertoire of functional neural dynamics. Here, we address this gap by positing that the brain’s structural network architecture determines the set of accessible functional connectivity patterns according to predictions of network control theory. In a large developmental cohort of 823 youths aged 8 to 23 years, we found that the flexibility of a brain region’s functional connectivity was positively correlated with the proportion of its structural links extending to different cognitive systems. Notably, this relationship was mediated by nodes’ boundary controllability, suggesting that a region’s strategic location on the boundaries of modules may underpin the capacity to integrate information across different cognitive processes. Broadly, our study provides a mechanistic framework that illustrates how temporal flexibility observed in functional networks may be mediated by the controllability of the underlying structural connectivity.AUTHOR SUMMARYPrecisely how the relatively rigid white matter wiring of the human brain gives rise to a diverse repertoire of functional neural dynamics is not well understood. In this work, we combined tools from network science and control theory to address this question. Capitalizing on a large developmental cohort, we demonstrated that the ability of a brain region to flexibly change its functional module allegiance over time (i.e., its modular flexibility), was positively correlated with its proportion of anatomical edges projecting to multiple cognitive networks (i.e., its structural participation coefficient). Moreover, this relationship was strongly mediated by the region’s boundary controllability, a metric capturing its capacity to integrate information across multiple cognitive domains.
Binding mechanism of neutralizing Nanobodies targeting SARS-CoV-2 Spike Glycoprotein
Authors: Golcuk Mert , Hacisuleyman Aysima , Erman Burak , Yildiz Ahmet , Gur Mert 
Published: April 2021

ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters human cells upon binding of its spike (S) glycoproteins to ACE2 receptors. Several nanobodies neutralize SARS-CoV-2 infection by binding to the receptor-binding domain (RBD) of S protein, but the underlying mechanism is not well understood. Here, we identified an extended network of pairwise interactions between RBD and nanobodies H11-H4, H11-D4, and Ty1 by performing all-atom molecular dynamics (MD) simulations. Simulations of the nanobody-RBD-ACE2 complex revealed that H11-H4 more strongly binds to RBD without overlapping with ACE2 and triggers dissociation of ACE2 due to electrostatic repulsion. In comparison, Ty1 binding results in dissociation of ACE2 from RBD due to an overlap with the ACE2 binding site, whereas H11-D4 binding does not trigger ACE2 dissociation. Mutations in SARS-CoV-2 501Y.V1 and 501.V2 variants resulted in a negligible effect on RBD-ACE2 binding. However, the 501.V2 variant weakened H11-H4 and H11-D4 binding while strengthening Ty1 binding to RBD. Our simulations indicate that all three nanobodies can neutralize 501Y.V1 while Ty1 is more effective against the 501.V2 variant.
Broad cross-reactivity across sarbecoviruses exhibited by a subset of COVID-19 donor-derived neutralizing antibodies
Authors: Jette Claudia A. , Cohen Alexander A. , Gnanapragasam Priyanthi N.P. , Muecksch Frauke , Lee Yu E. , Huey-Tubman Kathryn E. , Schmidt Fabian , Hatziioannou Theodora , Bieniasz Paul D. , Nussenzweig Michel C. , West Anthony P. , Keeffe Jennifer R. , Bjorkman Pamela J. , Barnes Christopher O. 
Published: April 2021

SummaryMany anti-SARS-CoV-2 neutralizing antibodies target the ACE2-binding site on viral spike receptor-binding domains (RBDs). The most potent antibodies recognize exposed variable epitopes, often rendering them ineffective against other sarbecoviruses and SARS-CoV-2 variants. Class 4 anti-RBD antibodies against a less-exposed, but more-conserved, cryptic epitope could recognize newly-emergent zoonotic sarbecoviruses and variants, but usually show only weak neutralization potencies. We characterized two class 4 anti-RBD antibodies derived from COVID-19 donors that exhibited broad recognition and potent neutralization of zoonotic coronavirus and SARS-CoV-2 variants. C118-RBD and C022-RBD structures revealed CDRH3 mainchain H-bond interactions that extended an RBD β-sheet, thus reducing sensitivity to RBD sidechain changes, and epitopes that extended from the cryptic epitope to occlude ACE2 binding. A C118-spike trimer structure revealed rotated RBDs to allow cryptic epitope access and the potential for intra-spike crosslinking to increase avidity. These studies facilitate vaccine design and illustrate potential advantages of class 4 RBD-binding antibody therapeutics.
Geospatial characterizing of Under-Five Mortality in Alexandria, Egypt
Authors: Hassan Mahmoud Adel , Ramadan Ahmed , Tahoun Mohamed Mostafa , Omran Abdel Rahman , Ebrahim Ali Shaimaa Gad EL Karim , Khedr Esmail Ola Fahmy , Adel Elrewany Ehab Mohamed , Ahmed El-Meligy Passent Ehab El-din , Elzayat Amira Mahmoud , el Malawany Dina Hussein , Mahboob Amira Saad , Eldewiki Mohamed Kamal , Abdellatif Hammouda Esraa Abdellatif Mohamed , Ghazy Ramy Mohamed 
Published: April 2021

AbstractThis study aimed to identify geo-spatial pattern of under-five mortality (U5M) in Alexandria and its key determinants. We analyzed the geospatial distribution of 3064 deaths registered at 24 health offices reported from January 2018 to June 2019. The localities of Alexandria city were clustered into high and low incidence areas. Neonates represented 58.7% of U5M, while post-neonates and children were 31.1%, 10.2% respectively. Male deaths were significantly higher (P=0.036). The main leading causes of U5M were prematurity (28.32%), pneumonia (11.01%), cardiac arrest (10.57%), congenital malformation (9.95%), and childhood cardiovascular diseases (9.20%). Spatial distribution of U5M (including the most common three causes) tend to be clustered in western parts of Alexandria (El Hawaria, Bahig, Hamlis and Ketaa Maryiut). Another 9 clusters are at risk of being hotspots. Illiteracy, divorce, and poor locality characteristics (household size, population density, and access to water supply and sanitation), were statistically significant predictors of U5M.
Bedside formulation of a personalized multi-neoantigen vaccine against mammary carcinoma
Authors: Mohsen Mona O. , Speiser Daniel E. , Michaux Justine , Pak HuiSong , Stevenson Brian J. , Vogel Monique , Inchakalody Varghese P. , de Brot Simone , Coukos George , Dermime Said , Bassani-Sternberg Michal , Bachmann Martin F. 
Published: April 2021

AbstractAbstract FigureGraphical abstractIndividualized neoantigen vaccination against mammary carcinomaBackgroundHarnessing the immune system to purposely recognize and destroy tumours represents a significant breakthrough in clinical oncology. Nonsynonymous mutations (neoantigenic peptides) were identified as powerful cancer targets. This knowledge can be exploited for further improvements of active immunotherapies, including cancer vaccines as T cells specific for neoantigens are not attenuated by immune tolerance mechanism and do not harm healthy tissues. The current study aimed at developing an optimized multi-target vaccine using short or long neoantigenic peptides utilizing virus-like particles (VLPs) as an efficient vaccine platform.MethodsHere we identified mutations of murine mammary carcinoma cells by integrating mass spectrometry-based immunopeptidomics and whole exome sequencing. Neoantigenic peptides were synthesized and covalently linked to virus-like nanoparticles using a Cu-free click-chemistry method for easy preparation of vaccines against mouse mammary carcinoma.ResultsAs compared to short peptides, vaccination with long peptides was superior in the generation of neoantigen-specific CD4+and CD8+T cells which readily produced IFN-γ and TNF-α. The resulting anti-tumour effect was associated with favourable immune re-polarization in the tumour microenvironment through reduction of myeloid-derived suppressor cells. Vaccination with long neoantigenic peptides also decreased post-surgical tumour recurrence and metastases, and prolonged mouse survival, despite the tumour’s low mutational burden.ConclusionIntegrating mass spectrometry-based immunopeptidomics and whole exome-sequencing is an efficient technique for identifying neoantigenic peptides. A multi-target VLP-based vaccine shows a promising anti-tumour results in an aggressive murine mammary carcinoma cell line. Future clinical application using this strategy is readily feasible and practical, as click-chemistry coupling of personalized synthetic peptides to the nanoparticles can be done at the bedside directly before injection.