bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical Ventilation with Moderate Tidal Volume Exacerbates Extrapulmonary Sepsis-Induced Lung Injury via IL33-WISP1 Signaling Pathway
Authors: Liu Shuai , Deng Meihong , Pan Pinhua , Turnquist Heth R. , Pitt Bruce R. , Billiar Timothy R. , Zhang Li-Ming
Published: December 2020

IL-33 and WNT1-inducible secreted protein (WISP1) play central roles in acute lung injury (ALI) induced by mechanical ventilation with moderate tidal volume (MTV) in the setting of sepsis. Here, we sought to determine the inter-relationship between IL-33 and WISP1 and the associated signaling pathways in this process.

We used a two-hit model of cecal ligation puncture (CLP) followed by MTV ventilation (4 h 10 mL/kg) in wild-type, IL-33−/− or ST2−/− mice or wild-type mice treated with intratracheal antibodies to WISP1. Macrophages (Raw 264.7 and alveolar macrophages from wild-type or ST2-/- mice) were used to identify specific signaling components.

CLP + MTV resulted in ALI that was partially sensitive to genetic ablation of IL-33 or ST2 or antibody neutralization of WISP1. Genetic ablation of IL-33 or ST2 significantly prevented ALI after CLP + MTV and reduced levels of WISP1 in the circulation and bronchoalveolar lung fluid. rIL-33 increased WISP1 in alveolar macrophages in an ST2, PI3K/AKT, and ERK dependent manner. This WISP1 upregulation and WNT β-catenin activation were sensitive to inhibition of the β-catenin/TCF/CBP/P300 nuclear pathway.

We show that IL-33 drives WISP1 upregulation and ALI during MTV in CLP sepsis. The identification of this relationship and the associated signaling pathways reveals a number of possible therapeutic targets to prevent ALI in ventilated sepsis patients.
Impact of the COVID-19 Pandemic on Continuous EEG Utilization
Authors: Zafar Sahar F. , Khozein Rebecca J. , LaRoche Suzette M. , Westover Michael B. , Gilmore Emily J.
Published: December 2020

Purpose:

The coronavirus disease 2019 (COVID-19) has significantly impacted healthcare delivery and utilization. The aim of this article was to assess the impact of the COVID-19 pandemic on in-hospital continuous electroencephalography (cEEG) utilization and identify areas for process improvement.

Methods:

A 38-question web-based survey was distributed to site principal investigators of the Critical Care EEG Monitoring Research Consortium, and institutional contacts for the Neurodiagnostic Credentialing and Accreditation Board. The survey addressed the following aspects of cEEG utilization: (1) general center characteristics, (2) cEEG utilization and review, (3) staffing and workflow, and (4) health impact on EEG technologists.

Results:

The survey was open from June 12, 2020 to June 30, 2020 and distributed to 174 centers with 79 responses (45.4%). Forty centers were located in COVID-19 hotspots. Fifty-seven centers (72.1%) reported cEEG volume reduction. Centers in the Northeast were most likely to report cEEG volume reduction (odds ratio [OR] 7.19 [1.53–33.83]; P = 0.012). Additionally, centers reporting decrease in outside hospital transfers reported cEEG volume reduction; OR 21.67 [4.57–102.81]; P ≤ 0.0001. Twenty-six centers (32.91%) reported reduction in EEG technologist coverage. Eighteen centers had personal protective equipment shortages for EEG technologists. Technologists at these centers were more likely to quarantine for suspected or confirmed COVID-19; OR 3.14 [1.01–9.63]; P = 0.058.

Conclusions:

There has been a widespread reduction in cEEG volume during the pandemic. Given the anticipated duration of the pandemic and the importance of cEEG in managing hospitalized patients, methods to optimize use need to be prioritized to provide optimal care. Because the survey provides a cross-sectional assessment, follow-up studies can determine the long-term impact of the pandemic on cEEG utilization.
Understanding Covid-19 misinformation and vaccine hesitancy in context: Findings from a qualitative study involving citizens in Bradford, UK
Authors: Lockyer Bridget , Islam Shahid , Rahman Aamnah , Dickerson Josie , Pickett Kate , Sheldon Trevor , Wright John , McEachan Rosemary , Sheard Laura
Published: December 2020

Background

Covid-19 vaccines can offer a route out of the pandemic, yet initial research suggests that many are unwilling to be vaccinated. A rise in the spread of misinformation is thought to have played a significant role in this vaccine hesitancy. In order to maximise vaccine uptake it is important to understand why misinformation has been able to take hold at this time and why it may pose a more significant problem within certain populations and places.

Objective

To understand people’s Covid-19 beliefs, their interactions with health (mis)information during Covid-19 and attitudes towards a Covid-19 vaccine.

Design and participants

In-depth phone interviews were carried out with 20 people from different ethnic groups and areas of Bradford during Autumn 2020. Reflexive thematic analysis was conducted.

Results

Participants spoke about a wide range of emotive misinformation they had encountered regarding Covid-19, resulting in confusion, distress and mistrust. Vaccine hesitancy could be attributed to three prominent factors: safety concerns, negative stories and personal knowledge. The more confused, distressed and mistrusting participants felt about their social worlds during the pandemic, the less positive they were about a vaccine.

Conclusions

Covid-19 vaccine hesitancy needs to be understood in the context of the relationship between the spread of misinformation and associated emotional reactions. Vaccine programmes should provide a focused, localised and empathetic response to counter misinformation.

Patient or public contribution

A rapid community and stakeholder engagement process was undertaken to identify Covid-19 related priority topics important to both Bradford citizens and local decision makers.
X-MOL: large-scale pre-training for molecular understanding and diverse molecular analysis
Authors: Xue Dongyu , Zhang Han , Xiao Dongling , Gong Yukang , Chuai Guohui , Sun Yu , Tian Hao , Wu Hua , Li Yukun , Liu Qi
Published: December 2020

In silico modelling and analysis of small molecules substantially accelerates the process of drug development. Representing and understanding molecules is the fundamental step for various in silico molecular analysis tasks. Traditionally, these molecular analysis tasks have been investigated individually and separately. In this study, we presented X-MOL, which applies large-scale pre-training technology on 1.1 billion molecules for molecular understanding and representation, and then, carefully designed fine-tuning was performed to accommodate diverse downstream molecular analysis tasks, including molecular property prediction, chemical reaction analysis, drug-drug interaction prediction, de novo generation of molecules and molecule optimization. As a result, X-MOL was proven to achieve state-of-the-art results on all these molecular analysis tasks with good model interpretation ability. Collectively, taking advantage of super large-scale pre-training data and super-computing power, our study practically demonstrated the utility of the idea of “mass makes miracles” in molecular representation learning and downstream in silico molecular analysis, indicating the great potential of using large-scale unlabelled data with carefully designed pre-training and fine-tuning strategies to unify existing molecular analysis tasks and substantially enhance the performance of each task.
SARS-CoV-2 mutations among minks show reduced lethality and infectivity to humans
Authors: Konishi Tomokazu
Published: December 2020

SARS-CoV-2 infection in minks has become a serious problem, as the virus may mutate and reinfect humans; some countries have decided to cull minks. Here, the virus sequencing data in minks were analysed and compared to those of human-virus. Although the mink-virus maintained the characteristics of human-virus, some variants rapidly mutated, adapting to minks. Some mink-derived variants infected humans, which accounted for 40% of the total SARS-CoV-2 cases in the Netherlands. These variants appear to be less lethal and infective compared to those in humans. Variants that have mutated further among minks were not found in humans. Such mink-viruses might be suitable for vaccination for humans, such as in the case of the smallpox virus, which is less infective and toxic to humans.
Mental health, personality and lifetime psychedelic use during the COVID-19 pandemic
Authors: Cavanna Federico , Pallavicini Carla , Milano Virginia , Cuiule Juan , Di Tella Rocco , González Pablo , Tagliazucchi Enzo
Published: December 2020

Background

The COVID-19 pandemic and its consequences represent a major challenge to the mental health and well-being of the general population. Some groups may be more vulnerable than others, depending on factors such as preexisting conditions, personality, and past life experiences. Building on previous work on the potential long-term benefits of psychedelics, we hypothesized that lifetime use of these drugs could be linked to better mental health indicators in the context of the ongoing pandemic.

Methods

Two anonymous online surveys were conducted between April 2020 and June 2020, including questions about lifetime experience with psychedelics and other psychoactive drugs, and psychometric scales designed to measure personality traits, anxiety, negative and positive affect, well-being and resilience. Principal component analysis was applied to divide the sample into groups of subjects based on their drug use reports.

Results

5618 participants (29.15 ± 0.12 years, 71.97% female) completed both surveys and met the inclusion criteria, with 32.43% of the final sample reporting at least one use of a psychedelic drug. Lifetime psychedelic use was linked to increased openness and decreased conscientiousness, and with higher scores of positive affect. The reported number of past psychedelic experiences predicted higher scores of the secondary personality trait beta factor, which has been interpreted as a measure of plasticity. No significant associations between lifetime use of psychedelics and indicators of impaired mental health were observed.

Conclusion

We did not find evidence of an association between lifetime use of psychedelics and poor mental health indicators. Conversely, experience with psychedelic drugs was linked to increased positive affect and to personality traits that favor resilience and stability in the light of the ongoing crisis. Future studies should be conducted to investigate these results from a causal perspective.
Estimating Excess Mortality Following Pediatric and Adolescent Cancer in the U.S.
Authors: Williams AnnaLynn M. , Liu Qi , Bhakta Nickhill , Krull Kevin R. , Hudson Melissa M. , Robison Leslie L. , Yasui Yutaka
Published: December 2020

The increasing number of long-term survivors of childhood/adolescent cancer are at-risk for premature death resulting from cancer treatment exposures. To better understand the implications of late mortality, we estimated and characterized the magnitude and temporal patterns of annual excess deaths following childhood/adolescent cancers diagnosed in 1975-2016 in the US using SEER 9 registries. We demonstrate for several tumor types that, despite decreasing excess deaths <5.0 years from diagnosis, the total number of excess deaths is not necessarily decreasing due to the growing and aging population of survivors at risk for treatment related late effects.
Quantifying the online news media coverage of the COVID-19 pandemic
Authors: Krawczyk K. , Chelkowski T. , Mishra S. , Xifara D. , Gibert B. , Laydon D.J. , Flaxman S. , Mellan T. , Schwämmle V. , Röttger R. , Hadsund J.T. , Bhatt S.
Published: December 2020

Background

Non-pharmaceutical interventions such as lockdowns, mask wearing and social distancing have been the primary measures to effectively combat the COVID-19 pandemic. Such measures are highly effective when there is strong population wide adherence which needs to be facilitated by information on the current risks posed by the pandemic alongside a clear exposition of the rules and guidelines in place. Here we address the issue of communication on the pandemic by offering data and analysis of online news media coverage of COVID-19.

Methods

We collected 26 million news articles from the front pages of 172 major online news sources in 11 countries (available athttp://sciride.org). Using topic detection we identified COVID-19-related content to quantify the proportion of total coverage pandemic received in 2020. Sentiment analysis tool Vader was employed to stratify the emotional polarity of COVID-19 reporting. Further topic detection and sentiment analysis was performed on COVID-19 articles to reveal the leading themes in pandemic reporting and their respective emotional polarizations.

Findings

We find that COVID-19 coverage accounted for approximately 25% of all front-page online news articles between January and October 2020. Sentiment analysis of English-speaking sources reveals that the overall COVID-19 coverage cannot be simply classified as negative due to the disease subject matter, suggesting a wide heterogeneous reporting of the pandemic. Within this heterogenous coverage, 16% of COVID-19 news articles (or 4% of all English-speaking articles) can be classified as highly negatively polarized, citing issues such asdeath, fearorcrisis.

Interpretation

The goal of pandemic public health communication is to increase understanding of distancing rules and maximize the impact of any governmental policy. Our results suggest an information overload in COVID-19 reporting that could risk obscuring effective policy communication. We hope that our data and analysis will inform health communication strategy to minimize the risks of COVID-19 while vaccination regimes are being introduced.
Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England
Authors: Davies Nicholas G. , Abbott Sam , Barnard Rosanna C. , Jarvis Christopher I. , Kucharski Adam J. , Munday James D. , Pearson Carl A. B. , Russell Timothy W. , Tully Damien C. , Washburne Alex D. , Wenseleers Tom , Gimma Amy , Waites William , Wong Kerry L. M. , van Zandvoort Kevin , Silverman Justin D. ,   CMMID COVID-19 Working Group,   The COVID-19 Genomics UK (COG-UK) Consortium, Diaz-Ordaz Karla , Keogh Ruth , Eggo Rosalind M. , Funk Sebastian , Jit Mark , Atkins Katherine E. , Edmunds W. John
Published: December 2020

A novel SARS-CoV-2 variant, VOC 202012/01 (lineage B.1.1.7), emerged in southeast England in November 2020 and is rapidly spreading towards fixation. Using a variety of statistical and dynamic modelling approaches, we estimate that this variant has a 43–90% (range of 95% credible intervals 38–130%) higher reproduction number than preexisting variants. A fitted two-strain dynamic transmission model shows that VOC 202012/01 will lead to large resurgences of COVID-19 cases. Without stringent control measures, including limited closure of educational institutions and a greatly accelerated vaccine roll-out, COVID-19 hospitalisations and deaths across England in 2021 will exceed those in 2020. Concerningly, VOC 202012/01 has spread globally and exhibits a similar transmission increase (59–74%) in Denmark, Switzerland, and the United States.
Salivary SARS-CoV-2 antigen rapid detection: a prospective cohort study
Authors: Basso Daniela , Aita Ada , Padoan Andrea , Cosma Chiara , Navaglia Filippo , Moz Stefania , Contran Nicole , Zambon Carlo-Federico , Cattelan Anna Maria , Plebani Mario
Published: December 2020

Background

SARS-CoV-2 quick testing and reporting are now considered relevant for the containment of new pandemic waves. Antigen testing in self-collected saliva might be useful. We compared the diagnostic performance of salivary and naso-pharyngeal swab (NPS) SARS-CoV-2 antigen detection by a rapid chemiluminescent assay (CLEIA) and two different point-of-care (POC) immunochromatographic assays, with that of molecular testing.

Methods

234 patients were prospectively enrolled. Paired self-collected saliva (Salivette) and NPS were obtained to perform rRT-PCR, chemiluminescent (Lumipulse G) and POC (NPS: Fujirebio and Abbott; saliva: Fujirebio) for SARS-CoV-2 antigen detection.

Results

The overall agreement between NPS and saliva rRT-PCR was 78.7%, reaching 91.7% at the first week from symptoms onset. SARS-CoV-2 CLEIA antigen was highly accurate in distinguishing between positive and negative NPS (ROC-AUC=0.939, 95%CI:0.903-0.977), with 81.6% sensitivity and 93.8% specificity. This assay on saliva had an overall good accuracy (ROC-AUC=0.805, 95%CI:0.740-0.870), reaching the optimal value within 7 days from symptom onset (Sensitivity: 72%; Specificity: 97%). POC antigen in saliva had a very limited sensitivity (13%), performing better in NPS (Sensitivity: 48% and 66%; Specificity: 100% and 99% for Espline and Abbott respectively), depending on viral loads.

Conclusions

Self-collected saliva is a valid alternative to NPS for SARS-CoV-2 detection not only by molecular, but also by CLEIA antigen testing, for which the highest diagnostic accuracy was achieved in the first week from symptom onset. Saliva is not suitable for POC, although the accuracy of these tests appears satisfactory for NPS with high viral load.
Short-term forecasting of COVID-19 in Germany and Poland during the second wave – a preregistered study
Authors: Bracher J. , Wolffram D. , Deuschel J. , Görgen K. , Ketterer J.L. , Ullrich A. , Abbott S. , Barbarossa M.V. , Bertsimas D. , Bhatia S. , Bodych M. , Bosse N.I. , Burgard J.P. , Castro L. , Fairchild G. , Fuhrmann J. , Funk S. , Gogolewski K. , Gu Q. , Heyder S. , Hotz T. , Kheifetz Y. , Kirsten H. , Krueger T. , Krymova E. , Li M.L. , Meinke J.H. , Michaud I.J. , Niedzielewski K. , Ożański T. , Rakowski F. , Scholz M. , Soni S. , Srivastava A. , Zieliński J. , Zou D. , Gneiting T. , Schienle M.
Published: December 2020

We report insights from ten weeks of collaborative COVID-19 forecasting for Germany and Poland (12 October – 19 December 2020). The study period covers the onset of the second wave in both countries, with tightening non-pharmaceutical interventions (NPIs) and subsequently a decay (Poland) or plateau and renewed increase (Germany) in reported cases. Thirteen independent teams provided probabilistic real-time forecasts of COVID-19 cases and deaths. These were reported for lead times of one to four weeks, with evaluation focused on one- and two-week horizons, which are less affected by changing NPIs. Heterogeneity between forecasts was considerable both in terms of point predictions and forecast spread. Ensemble forecasts showed good relative performance, in particular in terms of coverage, but did not clearly dominate single-model predictions. The study was preregistered and will be followed up in future phases of the pandemic.
Physiology-Based Electrocardiographic Criteria for Left Bundle Branch Capture
Authors: Jastrzębski Marek , Kiełbasa Grzegorz , Curila Karol , Moskal Paweł , Bednarek Agnieszka , Rajzer Marek , Vijayaraman Pugazhendhi
Published: December 2020

Background

During left bundle branch (LBB) area pacing, it is important to confirm that the capture of the LBB is achieved, not just the capture of only the adjacent left ventricular myocardium (LV septal capture). Our aim was to establish ECG criteria for LBB capture by analyzing ECGs with confirmed LBB capture and non-capture. We hypothesized that since LBB pacing results in physiologic depolarization of the left ventricle then the native QRS can serve as a reference for the diagnosis of LBB capture in the same patient.

Methods

Only patients with direct evidence of LBB capture (output-dependent or refractoriness-dependent QRS morphology transition) were included. Several QRS characteristics were compared between the native rhythm and different types of LBB area capture. Receiver-operator characteristics analysis was performed to determine the optimal V6 R-wave peak time (RWPT) cut-off for LBB diagnosis.

Results

A total of 357 ECG tracing (124 patients) were analyzed: 118 with native rhythm, 124 with non-selective LBB capture, 69 with selective LBB capture and 46 with LV septal capture. Our hypotheses that during LBB capture the paced V6 RWPT (measured from QRS onset) equals the native V6 RWPT and that the paced V6 RWPT (measured from the stimulus) equals the LBB potential to V6 R-wave peak interval were positively validated. Criteria based on these rules had sensitivity and specificity of 98.0–88.2% and 85.7–95.4%, respectively. The optimal and 100% specific V6 RWPT values for differentiation between LBB capture and LV septal capture in patients with narrow QRS / right bundle branch block were 83 ms and 74 ms, respectively; while in patients with left bundle branch block/asystole/ventricular escape the optimal and 100% specific V6 RWPT values were 101 ms and 80 ms, respectively.

Conclusions

Novel criteria for LBB capture were developed and optimal V6 RWPT cut-offs were determined.

What this study adds

We showed that LBB pacing truly reproduce the physiological depolarization of the left ventricle since the paced V6 RWPT equals the native conduction V6 RWPT.

Individualized LBB capture criteria, that use the native QRS as a reference, were developed.

The optimal V6 RWPT values for differentiation between LBB capture and LV septal capture were determined, separately for patients with healthy and diseased LBB.
A New State-Space Epidemiological Model for Cost-Effectiveness Analysis of Non-Medical Interventions- A Study on COVID-19 in California and Florida
Authors: Deo Vishal , Grover Gurprit
Published: December 2020

In the absence of sufficient testing capacity for COVID-19, a substantial number of infecteds are expected to remain undetected, and hence, are not quarantined. This, in turn, defeats the whole purpose of non-medical containment measures, like quarantine, lockdown, travel ban, physical distancingetc., by keeping the average reproduction rate above 1. To stress upon the importance of extensive random testing for breaking the chains of transmissions, we have formulated a detailed framework for carrying out cost-effectiveness analysis (CEA) of extensive random testing in comparison to targeted testing (the existing testing policy followed by most countries). This framework can be easily extended for CEA of any other non-medical or even medical interventions for containing epidemics.

We have developed a new version of the basic susceptible-infected-removed (SIR) compartmental model, called the susceptible-infected (quarantined/ free) - recovered-deceased [SI(Q/F)RD] model, to incorporate the impact of undetected cases on the transmission dynamics of the epidemic. Further, we have presented a Dirichlet-Beta state-space formulation of the SI(Q/F)RD model for the estimation of its parameters using posterior realizations from Gibbs sampling procedure. As an application, the proposed methodology is implemented to forecast the COVID-19 transmission in California and Florida, and further carry out CEA of extensive random testing over targeted testing.

Highlights

Estimated values of excess deaths associated with COVID-19 are used to account for underreporting, and for calibrating data to obtain actual counts of cases.

A new flexible version of SIR compartmental model, called SI(Q/F)RD, is introduced to facilitate in the CEA exercise.

Dirichlet-Beta state-space formulation of the SI(Q/F)RD model is used to predict the transmission dynamics of the epidemic.

CEA is conducted in terms of outcome (reduction in infections and deaths) and total cost of tests.

Proposed methodology is applied on the data of California and Florida.
S-variant SARS-CoV-2 is associated with significantly higher viral loads in samples tested by ThermoFisher TaqPath RT-QPCR
Authors: Kidd Michael , Richter Alex , Best Angus , Mirza Jeremy , Percival Benita , Mayhew Megan , Megram Oliver , Ashford Fiona , White Thomas , Moles-Garcia Emma , Crawford Liam , Bosworth Andrew , Plant Tim , McNally Alan
Published: December 2020

Birmingham University Turnkey laboratory is part of the Lighthouse network responsible for testing clinical samples under the UK government ‘Test & Trace’ scheme. Samples are analysed for the presence of SARS-CoV-2 in respiratory samples using the Thermofisher TaqPath RT-QPCR test, which is designed to co-amplify sections of three SARS-CoV-2 viral genes.

Since more recent information became available regarding the presence of SARS-CoV-2 variants of concern (S-VoC), which can show a suboptimal profile in RT-QPCR tests such as the ThermoFisher TaqPath used at the majority of Lighthouse laboratories, we analysed recently published data for trends and significance of the S-gene ‘dropout’ variant.

Results showed that:

the population of S-gene dropout samples had significantly lower median Ct values of ORF and N-gene targets compared to samples where S-gene was detected

on a population basis, S-gene dropout samples clustered around very low Ct values for ORF and N targets

linked Ct values for individual samples showed that a low Ct for ORF and N were clearly associated with an S-dropout characteristic

when conservatively inferring relative viral load from Ct values, approximately 35% of S-dropout samples had high viral loads between 10 and 10,000-fold greater than 1 × 106, compared to 10% of S-positive samples.

This analysis suggests that patients whose samples exhibit the S-dropout profile in the TaqPath test are more likely to have high viral loads at the time of sampling. The relevance of this to epidemiological reports of fast spread of the SARS-CoV-2 in regions of the UK is discussed.
Financial Hardship and Social Assistance as Determinants of Mental Health and Food and Housing Insecurity During the COVID-19 Pandemic in the United States
Authors: Kim Daniel
Published: December 2020

Background

While social assistance through the United States (U.S.) federal Coronavirus Aid, Relief, and Economic Security (CARES) Act provided expanded unemployment insurance benefits during the coronavirus disease 2019 (COVID-19) pandemic until the summer of 2020, it is unclear whether subsequent social assistance has been or will be sufficient to meet everyday spending needs and to curb the adverse health-related sequelae of financial hardship.

Methods

This study estimated recent trends in financial hardship among working-aged Americans with job-related income loss during the pandemic. It also used multivariable logistic regression and repeated cross-sectional individual-level U.S. Household Pulse Survey data on 91,222 working-aged adults between September and December 2020 to explore the associations of financial hardship with mental health outcomes and food and housing insecurity after accounting for receipt of social assistance.

Results

Experiencing somewhat of a financial hardship (vs no hardship) was linked to 3-7 times higher odds of anxiety and depressive symptoms and a likely eviction, and 11 times higher odds of food insufficiency. Experiencing considerable financial hardship (vs no hardship) predicted 5-7 fold higher odds of anxiety and depressive symptoms, 34-fold higher odds of a likely housing eviction, and 37-fold higher odds of food insufficiency (all P values <.001). Across outcomes, these relationships were stronger at each successively higher level of financial hardship (all P values for linear trend <.001), and more than offset any corresponding benefits from social assistance.

Conclusions

Even after accounting for receipt of social assistance, working-aged adults experiencing financial hardship had markedly greater odds of anxiety and depressive symptoms, food insufficiency, and an anticipated housing eviction. These findings point to the urgent need for direct and sustained cash relief well in excess of current levels of social assistance, and provide a critical baseline assessment for evaluating the impacts of federal public policy responses to economic hardships during the pandemic. It is essential that the U.S. Congress and the new Biden administration provide adequate and needs-based social policy relief measures in order to mitigate the pandemic’s adverse impacts on the physical, mental, and social well-being of millions of Americans.
In vivo coupling of dendritic complexity with presynaptic density in primary tauopathies
Authors: Mak Elijah , Holland Negin , Jones P. Simon , Savulich George , Low Audrey , Malpetti Maura , Kaalund Sanne S , Passamonti Luca , Rittman Timothy , Romero-Garcia Rafael , Manavaki Roido , Williams Guy B. , Hong Young T. , Fryer Tim D. , Aigbirhio Franklin I. , O’Brien John T , Rowe James B
Published: December 2020

Understanding the cellular underpinnings of neurodegeneration remains a challenge; loss of synapses and dendritic arborisation are characteristic and can be quantified in vivo, with [11C]UCB-J PET and MRI-based Orientation Dispersion Imaging (ODI), respectively. We aimed to assess how both measures are correlated, in 4R-tauopathies of Progressive Supranuclear Palsy (PSP-RS; n = 22) and amyloid-negative (determined by [11C]PiB PET) Corticobasal Degeneration (CBD; n =14), as neurodegenerative disease models, in this proof-of-concept study. Compared to controls (n = 27), PSP-RS and CBD patients had widespread reductions in cortical ODI, and [11C]UCB-J non-displaceable binding potential (BPND) in excess of atrophy. In PSP-RS and CBD separately, regional cortical ODI was significantly associated with [11C]UCB-J BPND in disease-associated regions (p < 0.05, FDR corrected). Our findings indicate that reductions in synaptic density and dendritic complexity in PSP-RS and CBD are more severe and extensive than atrophy. Furthermore, both measures are tightly coupled in vivo, furthering our understanding of the pathophysiology of neurodegeneration, and applicable to studies of early neurodegeneration with a safe and widely available MRI platform.
The prevalence of burnout, risk factors and job-related stressors in gastroenterologists: a systematic review
Authors: Ong John , Swift Carla , Bath Michael , Ong Sharon , Lim Wanyen , Al-Naeeb Yasseen , Shankar Arun , Dan Yock Young
Published: December 2020

Background and aims

Clinician burnout is an important occupational hazard and the scale of the problem within gastroenterology remains poorly understood. The primary objective of this study was to identify the prevalence of burnout and its symptoms in gastroenterologists. The secondary objective was to identify risk factors and job-related stressors that commonly contribute to burnout in gastroenterologists.

Methods

Systematic searches were conducted in PubMed, Scopus, Cochrane and PsycINFO by two reviewers independently for articles published to 1 September 2020. The primary outcome measure was the reported prevalence of burnout in gastroenterologists. The secondary outcome measures were (i) the prevalence of burnout symptoms (emotional exhaustion, depersonalisation and low personal accomplishment) and (ii) the frequency of risk factors and stressors reported in studies. Data were tabulated and meta-analyses were presented as Funnel and Forest plots.

Results

Data were extracted from 11 studies. 54.5% (6/11) of these studies reported the prevalence of burnout in gastroenterologists; this ranged from 18.3% to 64.4%. Similar to burnout prevalence, burnout symptoms showed geographical variation and were common in gastroenterologists (up to 63.9%). Factors associated with work volume, age, and female gender were the three most frequently reported risk factors for increased levels of anxiety, stress or burnout in 72.7% (8/11), 54.5% (6/11), and 45.5% (5/11) of studies respectively. Significant methodological and clinical heterogeneity was observed.

Conclusions

Burnout and its symptoms are common in gastroenterologists but the syndrome is understudied within the field. Further research and good quality data are needed to help address the problem.

Disclose Statement

JO is funded by the British Society of Gastroenterology to conduct burnout research in the UK, and the Journal of Gastroenterology and Hepatology Foundation (Australia) to conduct burnout research in Southeast Asia.
Comprehensive analysis and genome-wide association studies of biomass, chlorophyll, seed and salinity tolerance related traits in rice highlight genetic hotspots for crop improvement
Authors: Ul Alam Md Nafis , Azad Jewel G.M. Nurnabi , Azim Tomalika , Seraj Zeba I.
Published: December 2020

Farmland is on the decline and worldwide food security is at risk. Rice is the staple of choice for over half the Earth’s people. To sustain current demands and ascertain a food secure future, substandard farmland affected by abiotic stresses must be utilized. For rapid crop improvement, a broader understanding of polygenic traits like stress tolerance and crop yield is indispensable. To this end, the hidden diversity of resilient and neglected wild varieties must be traced back to their genetic roots. In this study, we separately assayed 15 phenotypes in a panel of 176 diverse accessions predominantly comprised of local landraces from Bangladesh. We compiled high resolution sequence data for these accessions. We collectively studied the ties between the observed phenotypic differences and the examined additive genetic effects underlying these variations. We applied a sophisticated fixed effect model to associate phenotypes with genotypes on a genomic scale. Discovered QTLs were mapped to known genes. Candidate genes were sorted by tissue specific gene expression profiles and protein level consequence of existing polymorphisms. Our explorations yielded 17 QTLs related to various traits in multiple trait classes. 12 identified QTLs were equivalent to findings from previous studies. Integrative analysis assumes novel functionality for 21 candidate genes on multiple evidence levels. These findings will usher novel avenues for the bioengineering of high yielding crops of the future fortified with genetic defenses against abiotic stressors.
Black Rice Developed Through Interspecific Hybridization (O. sativaxO. rufipogon): Origin of Black Rice Gene from Indian Wild Rice
Authors: Roy Subhas Chandra , Shil Pankaj
Published: December 2020

Rice (Oryza sativaL.) is a most important staple food grain consumed by more than half of the world’s population. Wild rice (O. rufipogonGriff.) is considered as the immediate ancestral progenitor of cultivated riceO. sativa, evolved through the process of domestication. Most of the cultivated rice produced grains with white pericarp, but can also produce grains with brown, red and black (or purple rice) pericarp. Red rice pericarp accumulates proanthocyanidin whereas black rice contains anthocyanin, both have antioxidant activity and health benefits. Black pericarp is predicted to be regulated by alleles of three genetic loci- Kala1, Kala3, and Kala4. Recombinational and insertional genetic rearrangement in the promoter region of Kala4 is crucial for the development of black pericarp in rice grain. In the present study, we report first time in the breeding history that aromatic black rice lines were developed through interspecific hybridization and introgression in the genetic background ofO. sativacv.Badshabhog, Chenga and Ranjit. Badshabhog and Ranjit is white grain rice but Chenga is red rice category. Common Asian wild riceO. rufipogonis used as donor parent (red grain) and source of black rice gene. Several possible genetic explanations have come up for the creation of black rice pericarp in the progeny lines. Possible reason may be the rearrangement and insertion of LINE1 in the promoter region of Kala4 allele through recombination mechanism leading to ectopic expression of Kala4 gene for the accumulation of anthocyanin and resulted in black rice formation. Other genes and regulatory factors may be induced and become functional to produce black pericarp. Black pericarp colour appeared in F2 populations in the wide crosses (Badshabhog xO. rufipogonand Chenga xO. rufipogon) but not in the cross with (Ranjit xO. rufipogon). Black pericarp trait inherited in F4 and F5 population with segregation phenotypes.

This is a first report in the history of rice genetics and pre-breeding research, that black rice has been created through wide crossing and introgression by combining wild riceO. rufipogonin the genetic background ofO. sativa. Present experimental evidence provides a new model of black rice origin. Thus, black rice (indica type) of Indian subcontinent originated independently through natural out crossing and artificial selection in the course of domestication.
Disruption of nasal bacteria enhances protective immune responses to influenza A virus and SARS-CoV-2 infection in mice
Authors: Nagai Minami , Moriyama Miyu , Ichinohe Takeshi
Published: December 2020

Gut microbiota plays a critical role in the induction of adaptive immune responses to influenza virus infection. However, the role of nasal bacteria in the induction of the virus-specific adaptive immunity is less clear. Here we demonstrate that while intranasal administration of influenza virus hemagglutinin vaccine alone was insufficient to induce the vaccine-specific antibody responses, disruption of nasal bacteria by lysozyme or addition of culturable oral bacteria from a healthy human volunteer rescued inability of the nasal bacteria to generate antibody responses to intranasally administered the split-virus vaccine. Myd88-depdnent signaling in the hematopoietic compartment was required for adjuvant activity of intranasally administered oral bacteria. In addition, we found that the oral bacteria-combined intranasal vaccine induced protective antibody response to influenza virus and SARS-CoV-2 infection. Our findings here have identified a previously unappreciated role for nasal bacteria in the induction of the virus-specific adaptive immune responses.
Reconstructing Great Basin Butterfly-Pollen Interaction Networks over the Past Century
Authors: Balmaki Behnaz , Christensen Tara , Dyer Lee A.
Published: December 2020

Aims

Insects and the plants they interact with dominate terrestrial biomes and constitute over half of the earth’s macro-organismal diversity. Their abundance in museum collections can provide a wealth of natural history data if they are collected as part of careful ecological studies or conservation programs. Here, we summarize pollen-insect quantitative networks gleaned from adult lepidopteran museum specimens to characterize these interactions and to examine how richness and frequency of butterfly-pollen associations have changed over a 100-year time series in Nevada and California. Pollen collected from well-curated butterfly specimens can provide insight into spatial and temporal variation in pollen-butterfly interactions and provide a complement to other approaches to studying pollination, such as pollinator observation networks.

Location

Great Basin and Sierra Nevada: California, Nevada

Time period

The last 100 years

Major Taxon studied

Butterflies

Methods

We estimated butterfly-pollen network parameters based on pollen collected from butterfly specimens from the Great Basin and Sierra Nevada. Additionally, we pooled interaction networks associated with specimens captured before and after 2000 to compare pollen-pollinator interaction variation under drought periods in California and Nevada in the last two decades versus previous years in the time series.

Results

Butterfly-pollen networks indicated that most pollen-butterfly species interactions are specialized and appear to be different from observational networks. Interaction networks associated with specimens captured before and after 2000 revealed that compared to previous decades, butterfly-pollen networks over the past 20 years had higher nestedness and connectance, with high pollen richness and low pollen abundance.

Main conclusions

These findings represent another unique approach to understanding more about pollination biology, and how butterfly-pollen interactions are impacted by climate variation and ecosystem alteration.
Neuronal cascades shape whole-brain functional dynamics at rest
Authors: Rabuffo Giovanni , Fousek Jan , Bernard Christophe , Jirsa Viktor
Published: December 2020

At rest, mammalian brains display remarkable spatiotemporal complexity, evolving through recurrent brain states on a slow timescale of the order of tens of seconds. While the phenomenology of the resting state dynamics is valuable in distinguishing healthy and pathological brains, little is known about its underlying mechanisms. Here, we identify neuronal cascades as a potential mechanism. Using full-brain network modeling, we show that neuronal populations, coupled via a detailed structural connectome, give rise to large-scale cascades of firing rate fluctuations evolving at the same time scale of resting-state networks. The ignition and subsequent propagation of cascades depend upon the brain state and connectivity of each region. The largest cascades produce bursts of Blood-Oxygen-Level-Dependent (BOLD) co-fluctuations at pairs of regions across the brain, which shape the simulated resting-state network dynamics.We experimentally confirm these theoretical predictions. We demonstrate the existence and stability of intermittent epochs of functional connectivity comprising BOLD co-activation bursts in mice and human fMRI. We then provide evidence for the existence and leading role of the neuronal cascades in humans with simultaneous EEG/fMRI recordings. These results show that neuronal cascades are a major determinant of spontaneous fluctuations in brain dynamics at rest.

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Significance Statement

Functional connectivity and its dynamics are widely used as a proxy of brain function and dysfunction. Their neuronal underpinnings remain unclear. Using connectome-based modeling, we link the fast microscopic neuronal scale to the slow emergent whole-brain dynamics. We show that cascades of neuronal activations spontaneously propagate in resting state-like conditions. The largest neuronal cascades result in the co-fluctuation of Blood-Oxygen-Level-Dependent signals at pairs of brain regions, which in turn translate to stable brain states. Thus, we provide a theoretical framework for the emergence and the dynamics of resting-state networks. We verify these predictions in empirical mouse fMRI and human EEG/fMRI datasets measured in resting states conditions. Our work sheds light on the multiscale mechanisms of brain function.
Pairs of mutually compensatory frameshifting mutations contribute to protein evolution in vertebrates and insects
Authors: Biba Dmitry , Klink Galya , Bazykin Georgii
Published: December 2020

Insertions and deletions of lengths not divisible by 3 in protein-coding sequences cause frameshifts that usually induce premature stop codons and may carry a high fitness cost. However, this cost can be partially offset by a second compensatory indel restoring the reading frame. The role of such pairs of compensatory frameshifting mutations (pCFMs) in evolution has not been studied systematically. Here, we use whole-genome alignments of protein coding genes of 100 vertebrate species, and of 122 insect species, studying the prevalence of pCFMs in their divergence. We detect a total of 619 candidate pCFM-genes; 11 of them pass stringent quality filtering, including three human genes:RAB36, ARHGAP6andNCR3LG1. In some instances, amino acid substitutions closely predating or following pCFMs restored the biochemical similarity of the frameshifted segment to the ancestral amino acid sequence, possibly reducing or negating the fitness cost of the pCFM. Typically, however, the resulting sequence bore no biochemical similarity to the ancestral one, indicating that pCFMs can uncover radically novel regions of protein space. In total, pCFMs represent an appreciable and previously overlooked source of novel variation in amino acid sequences.
Landscape configuration of an Amazonian island-like ecosystem drives population structure and genetic diversity of a habitat-specialist bird
Authors: Ritter Camila D. , Ribas Camila C. , Menger Juliana , Borges Sergio H. , Bacon Christine D. , Metzger Jean P. , Bates John , Cornelius Cintia
Published: December 2020

Context

Amazonian white-sand ecosystems(campinas)are open vegetation patches which form a natural island-like system in a matrix of tropical rainforest. Due to their clear distinction from the surrounding matrix, the spatial characteristics ofcampinapatches may affect the genetic diversity and composition of their specialized organisms such as the small and endemic passerineElaenia ruficeps.

Objectives

Here, we estimate the relative contribution of the current extension, configuration and geographical context ofcampinapatches to the patterns of genetic diversity and population structure ofE. ruficeps.

Methods

We sampled individuals ofE. ruficepsfrom three landscapes in Central Amazonia with contrastingcampinaspatial distribution, from landscapes with large and connected patches to landscapes with small and isolated patches. We estimate population structure, genetic diversity, and contemporary and historical migration within and among the three landscapes and used landscape metrics as predictor variables. Furthermore, we estimate genetic isolation by distance and resistance among individuals sampled within landscapes.

Results

We identified three genetically distinct populations with asymmetrical gene flow among landscapes and a decreasing migration rate with distance. Within each landscape, we found low genetic differentiation without genetic isolation by distance nor by resistance. In contrast, we found differentiation and spatial correlation between landscapes.

Conclusions

Our results uncover population dynamics ofE. ruficepsthrough time. Together with previous studies, this suggests that both regional context and landscape structure shape the connectivity among populations ofcampinaspecialist birds, and that Amazonian landscapes, together with their associated biota, have responded to recent climatic changes.
A benchmark of structural variation detection by long reads through a realistic simulated model
Authors: Dierckxsens Nicolas , Li Tong , Vermeesch Joris R. , Xie Zhi
Published: December 2020

Despite the rapid evolution of new sequencing technologies, structural variation detection remains poorly ascertained. The high discrepancy between the results of structural variant analysis programs makes it difficult to assess their performance on real datasets. Accurate simulations of structural variation distributions and sequencing data of the human genome are crucial for the development and benchmarking of new tools. In order to gain a better insight into the detection of structural variation with long sequencing reads, we created a realistic simulated model to thoroughly compare SV detection methods and the impact of the chosen sequencing technology and sequencing depth. To achieve this, we developed Sim-it, a straightforward tool for the simulation of both structural variation and long-read data. These simulations from Sim-it revealed the strengths and weaknesses for current available structural variation callers and long read sequencing platforms. Our findings were also supported by the latest structural variation benchmark set developed by the GIAB Consortium. With these findings, we developed a new method (combiSV) that can combine the results from five different SV callers into a superior call set with increased recall and precision. Both Sim-it and combiSV are open source and can be downloaded at https://github.com/ndierckx/.