bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of Ambulatory Heart Failure Patients Managed With an Intra-aortic Balloon Pump Before Left Ventricular Assist Device Implantation
Authors: Ternus Bradley , Behfar Atta , Schirger John , Barsness Gregory , Eleid Mackram , Patel Parag , Stulak John , Jentzer Jacob
Published: August 2020

Patients are admitted to the hospital for hemodynamic optimization before left ventricular assist device (LVAD) implantation. The aim of this study was to evaluate the clinical outcomes of hemodynamic optimization using an intra-aortic balloon pump (IABP) in ambulatory heart failure patients before LVAD placement. This retrospective single-center study included 199 noninotrope-dependent patients who underwent durable LVAD implantation between January 1, 2007 and April 10, 2017. Invasive hemodynamic as well as the primary composite end-point of stage 2 or 3 acute kidney injury, right ventricular failure, and 30-day mortality were compared between patients with and without an IABP. Median age was 64 (interquartile range [IQR], 57–71) years and 165 (82.9%) were male; 72 (36.2%) received an IABP. Patients treated with an IABP had worse baseline exercise capacity and hemodynamic parameters. Patients with an IABP had greater relative reduction in pulmonary artery mean pressure (−16% vs. −2%; p ≤ 0.001). The primary composite end-point was not different between patients who had an IABP and those who did not (20.8% vs. 20.5%; p = 0.952), as were each of the individual end-points. Despite worse baseline hemodynamic parameters and exercise capacity, ambulatory heart failure patients who received an IABP before LVAD implantation had more favorable reductions in pulmonary artery pressures without an increase in the composite end-point. These results suggest that IABP use before LVAD implantation may mitigate the risk of postoperative complications in ambulatory patients.
Is Higher Viral Load in SARS-CoV-2 Associated With Death?
Authors: Faíco-Filho Klinger Soares , Passarelli Victor Cabelho , Bellei Nancy
Published: August 2020

Background

There is no proven prognostic marker or adequate number of studies in patients hospitalized for coronavirus disease 2019 (COVID-19).

Methods

We conducted a retrospective cohort study of patients hospitalized with COVID-19 from March 14 to June 17, 2020, at São Paulo Hospital. SARS-CoV-2 viral load was assessed using the cycle threshold (Ct) values obtained from an RT-PCR assay applied to the nasopharyngeal swab samples. Disease severity and patient outcomes were compared.

Results

Among the 875 patients, 50.1% (439/875) had mild, 30.4% (266/875) moderate, and 19.5% (170/875) severe disease. A Ct value of <25 (472/875) indicated a high viral load, which was independently associated with mortality (OR: 0,34; 95% CI: 0,217–0,533; p < 0.0001).

Conclusions

Admission SARS-CoV-2 viral load is an important surrogate biomarker of infectivity and is independently associated with mortality among patients hospitalized with COVID-19.
Epstein-Barr virus and its prognostic value in a cohort of Peruvian women with cervical cancer
Authors: Castro Denisse , Vera Juana , Soto-Becerra Percy , López-Ilasaca Marco , Yabar Alejandro , Cámara Anais , Fernández Ana , Malpica Luis , Beltrán Brady
Published: August 2020

Aim

We aim to evaluate the prognostic effect of Epstein-Barr virus (EBV) infection on overall survival (OS) in Peruvian women with cervical cancer.

Methods

We conducted a retrospective cohort study. Polymerase chain reaction technique was used in paraffin-embedded tumor tissue for the detection of EBNA-1 and LMP-1. We used a multiple Cox proportional-hazard regression to estimate adjusted hazard ratios (aHR) for death and 95% confidence intervals (95% CI). In order to model continuous variables without categorization, we used a multivariable fractional polynomial approach. We performed a stability analysis using bootstrapping for internal validation.

Results

A total of 99 patients with cervical cancer were included. The prevalence of EBV in cervical cancer specimens was 22.2% (n=22). The 1-year and 5-year OS rates were 81.8% (95% CI 58.5-92.8) and 45% (95% CI 23.9-64.1) in the EBV-positive group compared to 78.8% (95% CI 67.7-86.4) and 37.8% (95% CI 25.7-49.8) in the EBV-negative group, respectively. In the multivariate analysis, positive EBV status was an independent prognostic factor for improved OS (aHR: 0.32; 95% CI 0.16 to 0.67; p=0.002) compared to negative EBV status.

Conclusions

EBV status is an independent prognostic factor for OS in cervical cancer. Evaluation of EBV status could be used as a clinical prognostic biomarker and to improve currently available prognostic models such as the FIGO system. Future prospective studies will be needed to validate these theories.
Short-term change in air pollution following the COVID-19 state of emergency: A national analysis for the United States
Authors: Tyagi Pooja , Braun Danielle , Sabath Benjamin , Henneman Lucas , Dominici Francesca
Published: August 2020

Lockdown measures taken in response to the COVID-19 pandemic produced sudden social and economic changes. We examined the extent of air pollution reduction that was attained under these extreme circumstances, whether these reductions occurred everywhere in the US, and the local factors that drove them. Employing counterfactual time series analysis based on seasonal autoregressive integrated moving average models, we found that these extreme lockdown measures led to a reduction in the weekly PM2.5 average by up to 3.4 µg m-3 and the weekly NO2 average by up to 11 ppb. These values represent a substantial fraction of the annual mean NAAQS values of 12 µg m-3 and 53 ppb, respectively. We found evidence of a statistically significant decline in NO2 concentrations following the state-level emergency declaration in almost all states. However, statistically significant declines in PM2.5 occurred mostly in the West Coast and the Northeast. Certain states experienced a decline in NO2 but an increase in PM2.5 concentrations, indicating that these two pollutants arise from dissimilar sources in these states. Finally, we found evidence that states with a higher percentage of mobile source emissions prior to the emergency measures experienced a greater decline in NO2 levels during the pandemic. Although the current social and economic restrictions are not sustainable, our results provide a benchmark to estimate the extent to which air pollution reductions can be achieved. We also identify factors that contributed to the magnitude of pollutant reductions, which can help guide future state-level policies to sustainably reduce air pollution.

Significance statement

We quantified the reduction in air pollution levels achieved under the extreme social and economic measures that were put into place as part of COVID-19 state-level emergency declarations. We found a reduction in the weekly average PM2.5 of up to 3.4 µg m-3 and the weekly average of NO2 of up to 11 ppb. These values represent a substantial fraction of the annual mean NAAQS values of 12 µg m-3 and 53 ppb, respectively. States with a larger fraction of mobile source emissions (e.g., air and road traffic) prior to the pandemic experienced larger declines in NO2 emissions, whereas PM2.5 decline was seen in areas with a higher pre-pandemic proportion of emissions from mobile, stationary (e.g., industrial) and fire sources.
Response to comment on ‘Initiation of chromosome replication controls both division and replication cycles inE. colithrough a double-adder mechanism’
Authors: Witz Guillaume , Julou Thomas , van Nimwegen Erik
Published: August 2020

Last year we published an article (Witz et al., 2019) in which we used time-lapse microscopy in combination with microfluidics to measure growth, division and replication in singleE. colicells on the one hand, and developed a new statistical analysis method to calculate the ability of different cell cycle models to capture the correlation structure observed in the data on the other hand. This led us to propose a new model of cell cycle control inE. coliwhich we called the double-adder model.

Recently Le Treut et al. published a comment (Le Treut et al., 2020) on our article which made a number of highly critical claims, including allegations that our own data support a different model than the one we proposed, and that our model cannot reproduce the ‘adder phenotype’ observed in the data. We here show that all these allegations are false and based on basic analysis errors. Although our focus is on explaining the errors in the analysis of Le Treut et al, we have attempted to make the presentation of interest to a broader scientific audience by discussing the issues in the context of what our current understanding is of the bacterial cell cycle, and to what extent recent data either support or reject various proposed models.
Action planning and affective states within the auditory peripersonal space
Authors: Bahadori Mehrdad , Barumerli Roberto , Geronazzo Michele , Cesari Paola
Published: August 2020

Fast reaction to approaching stimuli is vital for survival as for sounds entering the individual auditory Peripersonal Space (PPS). Closer sounds have found to provoke higher motor cortex activation particularly for highly arousing sounds, showing the close relationship for perceptual components of the sounds and motor preparation. Here Normal Hearing (NH) individuals and Cochlear Implanted (CI) individuals have been compared in their ability to recognize evaluate and react to affective stimuli entering the PPS. Twenty (seven females) NH and ten (three females) CI participants were asked to react to Positive (P), Negative (Ne), Neutral, (Nu) affective sounds virtually ending at five different distances from their body by performing fast arms flexion. Pre-motor Reaction Times (pm-RTs) were detected via EMG from postural muscles to measure action anticipation at different sound stopping distances; furthermore, the same sounds were evaluated for their level of valence and arousal perceived. Both groups showed the ability to localize the sound distances but only NH individuals modulated their pm-RTs based on the sound distance. Interestingly when the sound was not carrying affective components, as for Nu sounds, both NH and CI individuals triggered the promptest pre-motor reaction time (shorter pm-RT) when compared to P and N sounds. Only NH individuals modulated sound distance with the level of sound arousal, while sound’s valence was similarly perceived by both NH and CI individuals. These results underline the role of emotional states in action preparation and describe the specific perceptual components necessary to properly react to approaching sounds within peripersonal space.
Assessing ambitious nature conservation strategies within a 2 degree warmer and food-secure world
Authors: Kok Marcel T.J. , Meijer Johan R. , van Zeist Willem-Jan , Hilbers Jelle P. , Immovilli Marco , Janse Jan H. , Stehfest Elke , Bakkenes Michel , Tabeau Andrzej , Schipper Aafke M. , Alkemade Rob
Published: August 2020

Global biodiversity is projected to further decline under a wide range of future socio-economic development pathways, even in sustainability oriented scenarios. This raises the question how biodiversity can be put on a path to recovery, the core challenge for the CBD post-2020 global biodiversity framework. We designed two contrasting, ambitious global conservation strategies, ‘Half Earth’ (HE) and ‘Sharing the Planet’ (SP), and evaluated their ability to restore terrestrial and freshwater biodiversity and to provide ecosystem services while also mitigating climate change and ensuring food security. We applied the integrated assessment framework IMAGE with the GLOBIO biodiversity model, using the ‘Middle of the Road’ Shared Socio-economic Pathway (SSP2) with its projected human population growth as baseline.

We found that both conservation strategies result in a reduction in the loss of biodiversity and ecosystem services globally, but without additional measures to achieve effective climate mitigation they will be insufficient to restore biodiversity. The HE strategy performs better for terrestrial biodiversity protection (biodiversity intactness (MSA), Red List Index, geometric mean abundance) in currently still natural regions, reflecting global conservation priorities. The SP strategy yields more improvements for biodiversity in human-used areas, aquatic biodiversity and for regulating ecosystem services (pest control, pollination, erosion control), reflecting regional priorities. However, ‘conservation only’ scenarios show a considerable increase in food security risks (especially in Sub-Saharan Africa) compared to the baseline and limited reduction of global temperature increase. Only when conservation strategies are combined with climate change mitigation efforts and additional actions especially in the agricultural and energy system into a portfolio of ‘integrated sustainability measures’, both conservation strategies result in restoring biodiversity to current values or even some improvement, while keeping global warming below two degrees and keeping food security risks below baseline. Minimizing food wastes and reducing consumption of animal products will be crucial.
The effect of object type on building scene imagery – an MEG study
Authors: Monk Anna M. , Barnes Gareth R. , Maguire Eleanor A.
Published: August 2020

Previous studies have reported that some objects evoke a sense of local three-dimensional space (space-defining; SD), while others do not (space-ambiguous; SA), despite being imagined or viewed in isolation devoid of a background context. Moreover, people show a strong preference for SD objects when given a choice of objects with which to mentally construct scene imagery. When deconstructing scenes, people retain significantly more SD objects than SA objects. It therefore seems that SD objects might enjoy a privileged role in scene construction. In the current study, we leveraged the high temporal resolution of magnetoencephalography (MEG) to compare the neural responses to SD and SA objects while they were being used to build imagined scene representations, as this has not been examined before using neuroimaging. On each trial, participants gradually built a scene image from three successive auditorily-presented object descriptions and an imagined 3D space. We then examined the neural dynamics associated with the points during scene construction when either SD or SA objects were being imagined. We found that SD objects elicited theta changes relative to SA objects in two brain regions, the right ventromedial prefrontal cortex (vmPFC) and right superior temporal gyrus (STG). Furthermore, using dynamic causal modelling, we observed that the vmPFC drove STG activity. These findings may indicate that SD objects serve to activate schematic and conceptual knowledge in vmPFC and STG upon which scene representations are then built.
Statin-boosted cellular uptake of penetratin due to reduced membrane dipole potential
Authors: Batta Gyula , Kárpáti Levente , Henrique Gabriela Fulaneto , Tarapcsák Szabolcs , Kovács Tamás , Zákány Florina , Mándity István M. , Nagy Peter
Published: August 2020

Since cell penetrating peptides are promising tools for delivery of cargo into cells, factors limiting or facilitating their cellular uptake are intensely studied. Using labeling with pH-insensitive and pH-sensitive dyes we report that escape of penetratin from acidic endo-lysosomal compartments is retarded compared to its cellular uptake. The membrane dipole potential, known to alter transmembrane transport of charged molecules, is shown to be negatively correlated with the concentration of penetratin in the cytoplasmic compartment. Treatment of cells with therapeutically relevant concentrations of atorvastatin, an inhibitor of HMG-CoA reductase and cholesterol synthesis, significantly increased the release of penetratin from acidic endocytic compartments in two different cell types. This effect of atorvastatin correlated with its ability to decrease the membrane dipole potential. These results highlight the importance of the dipole potential in regulating cellular uptake of cell penetrating peptides and suggest a clinically relevant way of boosting this process.
Impact of COVID-19 on the Psychological Well-Being and Turnover Intentions of Frontline Nurses in the Community: A Cross-Sectional Study in the Philippines
Authors: De los Santos Janet Alexis A. , Labrague Leodoro J.
Published: August 2020

Purpose

This study aimed to assess fear of COVID-19 among nurses in a community setting.

Methods

This study employed a cross-sectional design using self-report questionnaires.

Findings

Results revealed that nurses display moderate to high fear of COVID-19 and that the female gender is correlated to fear of the virus. Moreover, the nurses’ fear influences their psychological distress and organizational and professional turnover intentions.

Conclusion

Fear of COVID-19 is universal among nurses. There is a need to assess the factors associated with the fear to better address the nurses’ psychological well-being and to avoid turnover intentions.
Benefits of local consolidative treatment in oligometastases of solid cancers: a stepwise-hierarchical pooled analysis and systematic review
Authors: Rim Chai Hong , Shin In-Soo , Park Sunmin , Lee Hye Yoon
Published: August 2020

Purpose

Any available evidence regarding the application of local consolidative therapy (LCT) for oligometastases is from phase 2 and observational studies. This study aimed to evaluate the oncologic benefits of LCT in oligometastatic setting.

Methods

The MEDLINE, EMBASE, and Cochrane library were searched. We applied stepwise analyses that enabled the evaluation of data from randomized controlled trials (RCTs), balanced studies (e.g. without significant differences regarding major prognosticators between arms), and all studies separately and in a hierarchical manner

Results

Thirty-one studies including seven randomized trials were reviewed. Pooled analyses of the effect of LCT on overall survival (OS) revealed odds ratios (ORs) of 3.04 (95% confidence interval [CI]: 2.28–4.06, p<0.001), 2.56 (95% CI: 1.79–3.66, p<0.001), and 1.41 (95% CI: 1.02–1.95, p=0.041) for all studies, balanced studies, and RCTs, respectively. The corresponding ORs for progression-free survival were 2.82 (95% CI: 1.96– 4.06, p<0.001), 2.32 (95% CI: 1.60–3.38, p<0·001), and 1.39 (95% CI: 1.09–1.80, p=0.009), respectively. The benefit of LCT was higher in non-small cell lung cancer (OR: 3.14, p<0.001; pooled 2-year OS: 65.2% vs. 37.0%) and colorectal cancer (OR: 4.11, p=0.066; pooled two-year OS: 66.2% vs. 33.2%) than in prostate (OR: 1.87, p=0.006; pooled three-year OS: 95.6% vs. 92.6%) and small cell lung cancer (OR: 1.04, p=0.942; pooled one-year OS: 60.7% vs. 42.8%). Complications were generally mild.

Conclusion

LCT provides oncologic benefits in the oligometastatic setting, although such benefits were less evident in RCTs than in data from observational studies. The appropriate LCTs should be carefully selected, considering their feasibility and disease types.
Serology assessment of antibody response to SARS-CoV-2 in patients with COVID-19 by rapid IgM/IgG antibody test
Authors: De Marinis Yang , Sunnerhagen Torgny , Bompada Pradeep , Bläckberg Anna , Yang Runtao , Svensson Joel , Ekström Ola , Eriksson Karl-Fredrik , Hansson Ola , Groop Leif , Gonçalves Isabel , Rasmussen Magnus
Published: August 2020

The coronavirus disease 2019 (COVID-19) pandemic has created a global health- and economic crisis. Lifting confinement restriction and resuming to normality depends greatly on COVID-19 immunity screening. Detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes COVID-19 by serological methods is important to diagnose a current or resolved infection. In this study, we applied a rapid COVID-19 IgM/IgG antibody test and performed serology assessment of antibody response to SARS-CoV-2. In PCR-confirmed COVID-19 patients (n=45), the total antibody detection rate is 92% in hospitalized patients and 79% in non-hospitalized patients. We also studied antibody response in relation to time after symptom onset and disease severity, and observed an increase in antibody reactivity and distinct distribution patterns of IgM and IgG following disease progression. The total IgM and IgG detection is 63% in patients with < 2 weeks from disease onset; 85% in non-hospitalized patients with > 2 weeks disease duration; and 91% in hospitalized patients with > 2 weeks disease duration. We also compared different blood sample types and suggest a potentially higher sensitivity by serum/plasma comparing with whole blood measurement. To study the specificity of the test, we used 69 sera/plasma samples collected between 2016-2018 prior to the COVID-19 pandemic, and obtained a test specificity of 97%. In summary, our study provides a comprehensive validation of the rapid COVID-19 IgM/IgG serology test, and mapped antibody detection patterns in association with disease progress and hospitalization. Our study supports that the rapid COVID-19 IgM/IgG test may be applied to assess the COVID-19 status both at the individual and at a population level.
Re-classification of archival Ovarian Carcinoma diagnostics using immunohistologic digital quantification and algorithmic prognosis
Authors: Vrabie Camelia D , Gangal Mihnea I. , Gangal Marius
Published: August 2020

Twenty years of research improved the classification of ovarian carcinoma, making the diagnostic relevant from a scientific and clinical perspective. Our research question was to find out if old studies are still pertinent under new diagnostic criteria and how we can use machine learning techniques for re-classification purposes.

The same main investigator re-classified 60 cases of ovarian carcinoma after 15 years, using 2014 WHO diagnostic criteria. Selected pathology data only (macro, micro information and immunohistochemistry images coming from a seven-stain panel) were provided for digital analysis. Biomarker images were digitalized and quantified using open source software and a validated methodology. 1080 attributes were classified using a random forest (open source) algorithm, using a supervised learning technique (the training dataset used 180 attributes). Human results were considered “ground truth” for the digital analysis.

The human analysis maintained the initial histopathologic diagnostic in 61.5% of cases. The digital prediction shows 80% accuracy and 73% precision when compared with human reclassified data. Based on results, we concluded that “recycling” of old studies is possible. Limitation of the study are the low number of cases analyzed, the total absence of clinical, treatment and prognostic data and a possible human criteria selection bias. Even if technical difficulties related to biomarker selection and histological analysis exist, digital investigation of existing, large archival registries is feasible, reliable and it can be done at a low cost.
Genomic epidemiology reveals transmission patterns and dynamics of SARS-CoV-2 in Aotearoa New Zealand
Authors: Geoghegan Jemma L , Ren Xiaoyun , Storey Matthew , Hadfield James , Jelley Lauren , Jefferies Sarah , Sherwood Jill , Paine Shevaun , Huang Sue , Douglas Jordan , Mendes Fábio K , Sporle Andrew , Baker Michael G , Murdoch David R , French Nigel , Simpson Colin R , Welch David , Drummond Alexei J , Holmes Edward C , Duchêne Sebastián , de Ligt Joep
Published: August 2020

New Zealand, a geographically remote Pacific island with easily sealable borders, implemented a nation-wide lockdown of all non-essential services to curb the spread of COVID-19. New Zealand has now effectively eliminated the virus, with low numbers of new cases limited to new arrivals in managed quarantine facilities at the border. Here, we generated 649 SARS-CoV-2 genome sequences from infected patients in New Zealand with samples collected between 26 February and 22 May 2020, representing 56% of all confirmed cases in this time period. Despite its remoteness, the viruses imported into New Zealand represented nearly all of the genomic diversity sequenced from the global virus population. The proportion of D614G variants in the virus spike protein increased over time due to an increase in their importation frequency, rather than selection within New Zealand. These data also helped to quantify the effectiveness of public health interventions. For example, the effective reproductive number, Re, of New Zealand’s largest cluster decreased from 7 to 0.2 within the first week of lockdown. Similarly, only 19% of virus introductions into New Zealand resulted in a transmission lineage of more than one additional case. Most of the cases that resulted in a transmission lineage originated from North America, rather than from Asia where the virus first emerged or from the nearest geographical neighbour, Australia. Genomic data also helped link more infections to a major transmission cluster than through epidemiological data alone, providing probable sources of infections for cases in which the source was unclear. Overall, these results demonstrate the utility of genomic pathogen surveillance to inform public health and disease mitigation.
Repeat COVID-19 Molecular Testing: Correlation with Recovery of Infectious Virus, Molecular Assay Cycle Thresholds, and Analytical Sensitivity
Authors: Gniazdowski Victoria , Morris C. Paul , Wohl Shirlee , Mehoke Thomas , Ramakrishnan Srividya , Thielen Peter , Powell Harrison , Smith Brendan , Armstrong Derek T. , Herrera Monica , Reifsnyder Carolyn , Sevdali Maria , Carroll Karen C. , Pekosz Andrew , Mostafa Heba H.
Published: August 2020

Repeat molecular testing for SARS-CoV-2 may result in scenarios including multiple positive results, positive test results after negative tests, and repeated false negative results in symptomatic individuals. Consecutively collected specimens from a retrospective cohort of COVID-19 patients at the Johns Hopkins Hospital were assessed for RNA and infectious virus shedding. Whole genome sequencing confirmed the virus genotype in patients with prolonged viral RNA shedding and droplet digital PCR (ddPCR) was used to assess the rate of false negative standard of care PCR results. Recovery of infectious virus was associated with Ct values of 18.8 ± 3.4. Prolonged viral RNA shedding was associated with recovery of infectious virus in specimens collected up to 20 days after the first positive result in patients who were symptomatic at the time of specimen collection. The use of Ct values and clinical symptoms provides a more accurate assessment of the potential for infectious virus shedding.
Transient dynamics of SARS-CoV-2 as England exited national lockdown
Authors:   REACT Study Investigators, Riley Steven , Ainslie Kylie E. C. , Eales Oliver , Walters Caroline E. , Wang Haowei , Atchison Christina , Diggle Peter J. , Ashby Deborah , Donnelly Christl A. , Cooke Graham , Barclay Wendy , Ward Helen , Darzi Ara , Elliott Paul
Published: August 2020

Control of the COVID-19 pandemic requires a detailed understanding of prevalence of SARS-CoV-2 virus in the population. Case-based surveillance is necessarily biased towards symptomatic individuals and sensitive to varying patterns of reporting in space and time. The real-time assessment of community transmission antigen study (REACT-1) is designed to overcome these limitations by obtaining prevalence data based on a nose and throat swab RT-PCR test among a representative community-based sample in England, including asymptomatic individuals. Here, we describe results comparing rounds 1 and 2 carried out during May and mid June / early July 2020 respectively across 315 lower tier local authority areas. In round 1 we found 159 positive samples from 120,620 tested swabs while round 2 there were 123 positive samples from 159,199 tested swabs, indicating a downwards trend in prevalence from 0.13% (95% CI, 0.11%, 0.15%) to 0.077% (0.065%, 0.092%), a halving time of 38 (28, 58) days, and an R of 0.89 (0.86, 0.93). The proportion of swab-positive participants who were asymptomatic at the time of sampling increased from 69% (61%, 76%) in round 1 to 81% (73%, 87%) in round 2. Although health care and care home workers were infected far more frequently than other workers in round 1, the odds were markedly reduced in round 2. Age patterns of infection changed between rounds, with a reduction by a factor of five in prevalence in 18 to 24 year olds. Our data were suggestive of increased risk of infection in Black and Asian (mainly South Asian) ethnicities. Using regional and detailed case location data, we detected increased infection intensity in and near London. Under multiple sensitivity analyses, our results were robust to the possibility of false positives. At the end of the initial lockdown in England, we found continued decline in prevalence and a shift in the pattern of infection by age and occupation. Community-based sampling, including asymptomatic individuals, is necessary to fully understand the nature of ongoing transmission.
Recapitulation of HIV-1 Env-Antibody Coevolution in Macaques Leading to Neutralization Breadth
Authors: Roark Ryan S. , Li Hui , Williams Wilton B. , Chug Hema , Mason Rosemarie D. , Gorman Jason , Wang Shuyi , Lee Fang-Hua , Rando Juliette , Bonsignori Mattia , Hwang Kwan-Ki , Saunders Kevin O. , Wiehe Kevin , Moody M. Anthony , Hraber Peter T. , Wagh Kshitij , Giorgi Elena E. , Russell Ronnie M. , Bibollet-Ruche Frederic , Liu Weimin , Connell Jesse , Smith Andrew G. , DeVoto Julia , Murphy Alexander I. , Smith Jessica , Ding Wenge , Zhao Chengyan , Chohan Neha , Okumura Maho , Rosario Christina , Ding Yu , Lindemuth Emily , Bauer Anya M. , Bar Katharine J. , Ambrozak David , Chao Cara W. , Chuang Gwo-Yu , Geng Hui , Lin Bob C. , Louder Mark K. , Nguyen Richard , Zhang Baoshan , Lewis Mark G. , Raymond Donald , Doria-Rose Nicole A. , Schramm Chaim A. , Douek Daniel C. , Roederer Mario , Kepler Thomas B. , Kelsoe Garnett , Mascola John R. , Kwong Peter D. , Korber Bette T. , Harrison Stephen C. , Haynes Barton F. , Hahn Beatrice H. , Shaw George M.
Published: August 2020

Neutralizing antibodies elicited by HIV-1 coevolve with viral Envs in distinctive patterns, in some cases acquiring substantial breadth. Here we show that primary HIV-1 Envs, when expressed by simian-human immunodeficiency viruses in rhesus macaques, elicited patterns of Env-antibody coevolution strikingly similar to those in humans. This included conserved immunogenetic, structural and chemical solutions to epitope recognition and precise Env-amino acid substitutions, insertions and deletions leading to virus persistence. The structure of one rhesus antibody, capable of neutralizing 49% of a 208-strain panel, revealed a V2-apex mode of recognition like that of human bNAbs PGT145/PCT64-35M. Another rhesus antibody bound the CD4-binding site by CD4 mimicry mirroring human bNAbs 8ANC131/CH235/VRC01. Virus-antibody coevolution in macaques can thus recapitulate developmental features of human bNAbs, thereby guiding HIV-1 immunogen design.

One sentence summary

Virus-antibody coevolution in rhesus macaques recapitulates developmental features of human antibodies.
Clump sequencing exposes the spatial expression programs of intestinal secretory cells
Authors: Manco Rita , Averbukh Inna , Porat Ziv , Halpern Keren Bahar , Amit Ido , Itzkovitz Shalev
Published: August 2020

Single-cell RNA sequencing combined with spatial information on landmark genes enables reconstruction of spatially-resolved tissue cell atlases. However, such approaches are challenging for rare cell types, since their mRNA contents are diluted in the spatial transcriptomics bulk measurements used for landmark gene detection. In the small intestine, enterocytes, the most common cell type, exhibit zonated expression programs along the crypt-villus axis, but zonation patterns of rare cell types such as goblet and tuft cells remain uncharacterized. Here, we present ClumpSeq, an approach for sequencing small clumps of attached cells. By inferring the crypt-villus location of each clump from enterocyte landmark genes, we establish spatial atlases for all epithelial cell types in the small intestine. We uncover immune-modulatory programs in villus tip goblet and tuft cells and heterogeneous migration patterns of enteroendocrine cells. ClumpSeq can be applied for reconstructing spatial atlases of rare cell types in other tissues and tumors.
miR760 regulates ATXN1 levels via interaction with its 5′ untranslated region
Authors: Nitschke Larissa , Tewari Ambika , Coffin Stephanie L. , Xhako Eder , Pang Kaifang , Gennarino Vincenzo A. , Johnson Jennifer L. , Blanco Francisco A. , Liu Zhandong , Zoghbi Huda Y.
Published: August 2020

Identifying modifiers of dosage-sensitive genes involved in neurodegenerative disorders is imperative to discover novel genetic risk factors and potential therapeutic entry points. In this study, we focus on Ataxin-1 (ATXN1), a dosage-sensitive gene involved in the neurodegenerative disease spinocerebellar ataxia type 1 (SCA1). While the precise maintenance of ATXN1 levels is essential to prevent disease, the mechanisms that regulate ATXN1 expression remain largely unknown. We demonstrate that ATXN1’s unusually long 5′ untranslated region (5′ UTR) negatively regulates its expression via posttranscriptional mechanisms. Based on recent reports that microRNAs (miRNAs) can interact with both 3′ and 5′ UTRs to regulate their target genes, we identify miR760 as a negative regulator that binds to a conserved site in ATXN1’s 5′ UTR to induce RNA degradation and translational inhibition. We found that delivery of Adeno-associated virus (AAV)-expressing miR760 in the cerebellum reduces ATXN1 levels in vivo and mitigates motor coordination deficits in a mouse model of SCA1. These findings provide new insights into the regulation of ATXN1 levels, present additional evidence for miRNA-mediated gene regulation via 5′ UTR binding, and raise the possibility that noncoding mutations in the ATXN1 locus may act as risk factors for yet to be discovered progressive ataxias.
Pressure effects on the EXAFS Debye–Waller factor of iron
Authors: Hieu Ho Khac , Duc Nguyen Ba , Hung Nguyen Van , Hanh Pham Thi Minh , Hai Tran Thi
Published: August 2020

The pressure effects on atomic mean-square relative displacement characterizing the extended X-ray absorption fine structure (EXAFS) Debye–Waller factor of iron metal have been investigated based on the Debye model. The analytical expressions of the Debye frequency and EXAFS Debye–Waller factor have been derived as functions of crystal volume compressibility. Based on the well established equation-of-state including the contributions of the anharmonic and electronic thermal pressures, numerical calculations have been performed for iron up to a pressure of 220 GPa and compared with experimental data when possible. These results show that the Debye frequency increases rapidly with compression, and beyond 150 GPa it behaves as a linear function of pressure. Meanwhile the mean-square relative displacement curve drops robustly with pressure, especially at pressures smaller than 100 GPa. This phenomenon causes the enhancement of EXAFS signals at high pressure. Reversely, the increasing of temperature will reduce the amplitude of EXAFS spectra.
CFD simulation of empty fuel tanks separation from a trainer jet
Authors: Olejnik Aleksander , Dziubiński Adam , Kiszkowiak Łukasz
Published: August 2020

Purpose

This study aims to create 6-degree of freedom (SDOF) for computational fluid dynamics (CFD) simulations of body movement, and to validate using the experimental data for empty tank separation from I-22 Iryda jet trainer. The procedure has an ability to be modified or extended, to simulate, for example, a sequential release from the joints.

Design/methodology/approach

A set of CFD simulations are calculated. Both the SDOF procedure and the CFD simulation settings are validated using the wind tunnel data available for the aircraft.

Findings

The simulation using designed procedure gives predictable results, but offers availability to be modified to represent external forces, i.e. from body interaction or control system without necessity to model the control surfaces.

Practical implications

The procedure could be used to model the separation of external stores and design the deployment of anti-radar chaff, flares or ejection seats.

Originality/value

The work presents original work, caused by insufficient abilities of original SDOF procedure in ANSYS code. Additional value is the ability of the procedure to be easily modified.
China’s AI Strike Force on COVID-19
Authors: Wong Wilson Kia Onn
Published: August 2020

Purpose

This paper examines the methodical and highly efficacious manner in which China deployed its comprehensive AI (artificial intelligence) strategy to significantly stymie the spread of COVID-19 across the country.

Design/methodology/approach

This study deploys a case-study approach, supported by the literature on existing and emerging AI and related technologies.

Findings

The onset of the COVID-19 pandemic has revealed to the world the remarkable progress China has made in AI and its accompanying ecosystem. More importantly, this outlier event demonstrates the surgical, hybridised manner in which China has utilised these emerging technologies in containing its spread (i.e. “AI Epidemiological Targeting”) and set itself on the path to unleashing their full potential (i.e. “AI Symbiosis Paradigm”). Nonetheless, China still needs to harness its rapidly advancing AI prowess in identifying COVID-19's pathogenesis and developing a proven vaccine.

Originality/value

This study presents a pioneering effort to analyse the deployment of AI and its ecosystem in the “war” against COVID-19.
Dynamic stress analysis on nonlinear vibration of a stiffened plate with initial stresses and geometric imperfections considering different resonance conditions
Authors: Ma Niu-Jing , Gu Li-Xiong , Piao Long , Zhang Xing-Zhi
Published: August 2020

Purpose

Stiffened plates have been widely used in civil, marine, aerospace engineering. As a kind of thin-walled structure operating in complex environment, stiffened plates mostly undergo a variety of dynamic loads, which may sometimes result in large-amplitude vibration. Additionally, initial stresses and geometric imperfections are widespread in this type of structure. Furthermore, it is universally known that initial stresses and geometric imperfections may affect mechanical behavior of structures severely, particularly in dynamic analysis. Thus, the purpose of this paper is to study the stress variation rule of a stiffened plate during large-amplitude vibration considering initial stresses and geometric imperfections.

Design/methodology/approach

The initial stresses are represented in the form of initial bending moments applying to the stiffened plate, while the initial geometric imperfections are considered by means of trigonometric series, and they are assumed existing in the plate along the z-direction exclusively. Then, the dynamic equilibrium equations of the stiffened plate are established using Lagrange’s equation as well as aforementioned conditions. The nonlinear differential equations of motion are simplified as a two-degree-of-freedom system by considering 1:2 and 1:3 internal resonances, respectively, and the multiscale method is applied to solve the equations.

Findings

The influence of initial stresses on the plate, stresses during internal resonance is remarkable, while that is moderate for initial geometric imperfections. (Upon considering the existence of initial stresses or geometric imperfections, the stresses of motivated modes are less than the primary mode for both and internal resonances). The influence of bidirectional initial stresses on the plate’s stresses during internal resonance is more remarkable than that of unidirectional initial stresses. The coupled vibration in 1%3A2 internal resonance is fiercer than that in internal resonance.

Originality/value

Stiffened plates are widely used in engineering structures. However, as a type of thin-walled structure, stiffened plates vibrate with large amplitude in most cases owning to their complicated operation circumstance. In addition, stiffened plates usually contain initial stresses and geometric imperfections, which may result in the variation of their mechanical behavior, especially dynamical behavior. Based on the above consideration, this paper studies the nonlinear dynamical behavior of stiffened plates with initial stresses and geometrical imperfections under different internal resonances, which is the originality of this work. Furthermore, the research findings can provide references for engineering design and application.
A robust numerical method for a coupled system of singularly perturbed parabolic delay problems
Authors: Kumar Mukesh , Singh Joginder , Kumar Sunil , Aakansha Aakansha
Published: August 2020

Purpose

The purpose of this paper is to design and analyze a robust numerical method for a coupled system of singularly perturbed parabolic delay partial differential equations (PDEs).

Design/methodology/approach

Some a priori bounds on the regular and layer parts of the solution and their derivatives are derived. Based on these a priori bounds, appropriate layer adapted meshes of Shishkin and generalized Shishkin types are defined in the spatial direction. After that, the problem is discretized using an implicit Euler scheme on a uniform mesh in the time direction and the central difference scheme on layer adapted meshes of Shishkin and generalized Shishkin types in the spatial direction.

Findings

The method is proved to be robust convergent of almost second-order in space and first-order in time. Numerical results are presented to support the theoretical error bounds.

Originality/value

A coupled system of singularly perturbed parabolic delay PDEs is considered and some a priori bounds are derived. A numerical method is developed for the problem, where appropriate layer adapted Shishkin and generalized Shishkin meshes are considered. Error analysis of the method is given for both Shishkin and generalized Shishkin meshes.
The creative minds of extraordinary pastry chefs: an integrated theory of aesthetic expressions – a portraiture study
Authors: Lee Kai-Sean , Blum Denise , Miao Li , Tomas Stacy R.
Published: August 2020

Purpose

This paper aims to demystify the creative experiences of an extraordinary group of pastry chefs – The Malaysian World Pastry Team, champions of the 2019 World Pastry Cup. The authors adopted an expressionist theoretical lens informed by two aesthetic philosophers – John Dewey and Wassily Kandinsky.

Design/methodology/approach

A two-year portraiture was conducted – a qualitative methodology that draws features from phenomenology and narrative inquiry, rendering artistically and empirically written “portraits” that reflect themes and patterns of participants’ experiences. In-depth interviews, observations and material artifacts were collected amid a journey alongside nine extraordinary Malaysian pastry chefs.

Findings

Presented in story structures, the authors offer three “portraits” of culinary creativity, each representing a core essence of the creative phenomenon: creative harmony in the form of sensorial and symbolic poetry; imaginative episodes as a hypnotic state of inspiration and incubation; and the creative duality of scientific rationalism and artistic fashion. The authors delineated the intricacies of each theme by presenting them as individual narratives.

Research limitations/implications

The portraits indicated that culinary creativity reflects an organic and emancipating aesthetic experience that is unbounded by formative structures or sequential processes. This provides a novel theoretical view that moves beyond conventional studies’ capitalistic frameworks, and toward the intimate viewpoints of the chef-creators. Specific contributions are discussed.

Originality/value

Through a unique qualitative approach and an aesthetic theoretical framework, this study provided a novel perspective on the culinary creative process. The aesthetic view captures culinary creativity through the eyes of the creator, a viewpoint less considered, yet imperative to the culinary profession.
International reserves: self-insurance and monetary policy in crisis
Authors: Silva Junior Antonio Francisco de Almeida da
Published: August 2020

Purpose

This work presents a model of a two-period economy to discuss the link between the precautionary motivation for holding international reserves and the country's monetary policy concerns due to a crisis.

Design/methodology/approach

There are two possible states of nature in the second period of the economy: a normal state and a crisis state. These states of nature represent uncertainty to the policy maker and he can insure against a crisis. The household has a constant-elasticity-of-substitution (CES) utility function, where utility depends on consumption and money.

Findings

By allowing money in the utility function and in the household financial constraint and considering that the objective of the central bank is to smooth inflation, it is concluded that monetary policy plays a role in the precautionary motivation of holding international reserves.

Practical implications

The model can be used to calculate optimal reserves holdings in its complete or even in its simplified version. Furthermore, it is possible to evaluate the impact of the intra-temporal substitution elasticity between consumption and real money in the decision of accumulating international reserves.

Originality/value

Higher intra-temporal substitution elasticities implies in more insurance via international reserves, and this discussion is not found in the existent literature on international reserves.
Relational flexibility norms and relationship-building capabilities as a mediating mechanism in export performance: insights from exporting SMEs in an emerging economy, Peru
Authors: Malca Oscar , Bolaños Jean Pierre , Acedo Francisco J. , Rubio Donet Jorge Luis , Peña-Vinces Jesus
Published: August 2020

Purpose

The purpose of this study is to analyse the mediating and moderating effects of relational flexibility norms on relationship building capacities and export performance.

Design/methodology/approach

The study followed a quantitative and cross-sectional approach. The analysis was applied to 95 Peruvian Exporting SMEs which were examined through structural equation modelling (SEM) using AMOS 24.0 statistical package. The responses were gathered through telephone and personal interviews which were tested using the Mann–WhitneyUtest, finding no statistically significant differences.

Findings

The main finding of the study is to demonstrate the indirect effect of relational flexibility norms on the export performance of SMEs through relationship-building capabilities. In this way, these capabilities become very important variables in the export management of SMEs, since they directly affect the relationship of the Exporter–Importer dyad.

Research limitations/implications

One of the limitations is the cross-sectional type study that applies to the short-term effects of relational norms. Organizational characteristics and other factors that may affect export performance should also be considered in future research, as well as longitudinal studies should be developed.

Practical implications

The study allows SMEs to focus management efforts on strengthening the relationship – building capabilities, which are very important given SMEs' resource constraints. Therefore, an adequate management of relations with importers can contribute to the reduction of control and coordination costs; and have a positive impact on export performance. Similarly, the study contributes to the management of export promotion by suggesting that one area to be prioritized is the strengthening of the relationship capacities of exporting SMEs.

Originality/value

The study provides the analysis of the mediating effect of the relationship-building capability between relational flexibility and export performance. In this way, it enriches the theoretical analysis and contributes with the empirical evidence of an emerging country like the case of Peru.