bluuebunny/crossref_metadata_2025 huggingface dataset:
Working from a distance: Who can afford to stay home during COVID-19? Evidence from mobile device data
Authors: Dimke Christine , Lee Marissa , Bayham Jude
Published: July 2020

As the COVID-19 pandemic continues, local and state governments must weigh the costs and benefits of social distancing policy. However, the effectiveness of such policies depend on individuals’ willingness and ability to comply. We propose a simple method to infer sociodemographic heterogeneity in social distancing as measured by Safegraph mobile device data. We document evidence that people’s ability to work from home is a determinant of time spent at home since the beginning of the pandemic. On April 15th, census block groups that are more likely able to work from home spent 3 more hours at home compared to those who were not. We see supporting trends among block groups with differences in income and educational attainment.

JEL

J19, J69, Z00
Immunohistochemistry and Next Generation Sequencing are Complementary Tests in Identifying PTEN Abnormality in Endometrial Carcinoma Biopsies
Authors: Wang Linyuan , Piskorz Anna , Bosse Tjalling , Jimenez-Linan Mercedes , Rous Brian , Gilks C. Blake , Brenton James D. , Singh Naveena , Köbel Martin
Published: July 2020

PTEN plays a central role in the pathogenesis of endometrial carcinoma. Previous studies reported a high interobserver reproducibility for the interpretation of PTEN immunohistochemistry (IHC). However, PTEN IHC and its interpretation remain challenging during laboratory practice. The purpose of this study was to reevaluate PTEN IHC pattern in direct comparison to next generation sequencing (NGS) in identifying PTEN abnormality. IHC and tagged-amplicon NGS PTEN sequencing was performed on 182 endometrial carcinoma biopsy/curetting samples from five centers (Barts, Calgary, Cambridge, Leiden, and Vancouver). Sensitivity, specificity and accuracy of PTEN IHC to predict loss of function (LOF) PTEN mutations were calculated. Abnormalities of PTEN in association with histotype and molecular subtype were assessed. A total of five PTEN IHC patterns were recorded: absent, subclonal loss, equivocal, reduced (relative to internal control) and retained. The absence of PTEN IHC has a sensitivity of 75.4% (95% CI 62.7 – 85.5%), a specificity of 84.6% (95% CI 76.2 – 90.9%), and accuracy of 81.2% (95% CI 74.4 – 86.9%) in predicting LOF PTEN mutation. PTEN abnormality by complementary interpretation of both assays was present in 91.9% of endometrial endometrioid carcinoma, grade 1, and significantly higher in endometrial endometrioid carcinomas of all grades compared to endometrial serous carcinoma (80.0% versus 19.4%, p<0.0001). PTEN abnormalities are common across all molecular subtypes of endometrioid carcinomas. Our data support complementary testing of both IHC and sequencing of PTEN to assess the PTEN status in endometrial carcinomas.
DYNAMICS OF THE COVID-19 PANDEMICS: GLOBAL PATTERN AND BETWEEN COUNTRIES VARIATIONS
Authors: Krywyk J. , Oettgen W. , Messier M. , Mulot M. , Ugon A. , Toubiana L.
Published: July 2020

The COVID-19 pandemic affected 203 countries between December 2019 and July 2020. The early epidemic “wave” affected countries which now report a few sporadic cases, achieving a stable late phase of the epidemic. Other countries are beginning their epidemic expansion phase. The objective of our study is to characterize the dynamics of the COVID-19 spread.

Data science methods were applied to pandemic, focusing on the daily fatality in 24 countries with more than 2,000 deaths, our analysis kin the end retaining 14 countries that have completed a full cycle.

The analysis demonstrates a COVID-19 dynamic similar in these studied countries. This 3-phase dynamic is like that of common viral respiratory infections. This pattern, however, shows variability and therefore specificity which the method categorizes into clusters of “differentiated epidemic patterns”. Among the 5 detected clusters, 2 main ones regroup 11 of these countries, representing 65% of the world deaths (as of June 24, 2020).

The pattern seems common to a very large number of countries, and congruent with that of epidemics of other respiratory syndromes, opens the hypothesis that the COVID-19 pandemic would have developed its “natural history” by spreading spontaneously despite the measures taken to contain it. The diversity highlighted by the classification into “formal clusters” suggests explanations involving the notion of demographic and geographic epicenters.
Dysregulated transcriptional responses to SARS-CoV-2 in the periphery support novel diagnostic approaches
Authors: McClain Micah T. , Constantine Florica J. , Henao Ricardo , Liu Yiling , Tsalik Ephraim L. , Burke Thomas W. , Steinbrink Julie M. , Petzold Elizabeth , Nicholson Bradly P. , Rolfe Robert , Kraft Bryan D. , Kelly Matthew S. , Sempowski Gregory D. , Denny Thomas N. , Ginsburg Geoffrey S. , Woods Christopher W.
Published: July 2020

In order to elucidate novel aspects of the host response to SARS-CoV-2 we performed RNA sequencing on peripheral blood samples across 77 timepoints from 46 subjects with COVID-19 and compared them to subjects with seasonal coronavirus, influenza, bacterial pneumonia, and healthy controls. Early SARS-CoV-2 infection triggers a conserved transcriptomic response in peripheral blood that is heavily interferon-driven but also marked by indicators of early B-cell activation and antibody production. Interferon responses during SARS-CoV-2 infection demonstrate unique patterns of dysregulated expression compared to other infectious and healthy states. Heterogeneous activation of coagulation and fibrinolytic pathways are present in early COVID-19, as are IL1 and JAK/STAT signaling pathways, that persist into late disease. Classifiers based on differentially expressed genes accurately distinguished SARS-CoV-2 infection from other acute illnesses (auROC 0.95). The transcriptome in peripheral blood reveals unique aspects of the immune response in COVID-19 and provides for novel biomarker-based approaches to diagnosis.
Seroprevalence of SARS-CoV-2 IgG Antibodies in Utsunomiya City, Greater Tokyo, after first pandemic in 2020 (U-CORONA): a household- and population-based study
Authors: Nawa Nobutoshi , Kuramochi Jin , Sonoda Shiro , Yamaoka Yui , Nukui Yoko , Miyazaki Yasunari , Fujiwara Takeo
Published: July 2020

Background

The number of confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Japan are substantially lower in comparison to the US and UK, potentially due to the under-implementation of polymerase chain reaction (PCR) tests. Studies reported that more than half of the SARS-CoV-2 infections are asymptomatic, confirming the importance for conducting seroepidemiological studies. Although the seroepidemiological studies in Japan observed a reported prevalence of 0.10% in Tokyo, 0.17% in Osaka, and 0.03% in Miyagi, sampling bias was not considered. The study objective was to assess the seroprevalence of SARS-CoV-2 in a random sample of households in Utsunomiya City in Tochigi Prefecture, Greater Tokyo, Japan.

Methods

We launched the Utsunomiya COVID-19 seROprevalence Neighborhood Association (U-CORONA) Study to assess the seroprevalence of COVID-19 in Utsunomiya City. The survey was conducted between 14 June 2020 and 5 July 2020, in between the first and second wave of the pandemic. Invitations enclosed with a questionnaire were sent to 2,290 people in 1,000 households randomly selected from Utsunomiya basic resident registry. Written informed consent was obtained from all participants. The level of IgG antibodies to SARS-CoV-2 was assessed by chemiluminescence immunoassay analysis.

Results

Among 2,290 candidates, 753 returned the questionnaire and 742 received IgG tests (32.4 % participation rate). Of the 742 participants, 86.8% were 18 years or older, 52.6% were women, 71.1% were residing within 10 km from the test clinic, and 89.2% were living with another person. The age and sex distribution, distance to clinic and police district were similar with those of non-participants, while the proportion of single-person households was higher among non-participants than participants (16.2% vs. 10.8%).

We confirmed three positive cases through quantitative antibody testing. No positive cases were found among the people who live in the same household as someone with positive. All cases were afebrile. The estimated unweighted and weighted prevalence of SARS-CoV-2 infection were 0.40% (95% confidence interval: 0.08-1.18%) and 1.23% (95% confidence interval: 0.17-2.28%), respectively.

Conclusion

This study suggests the importance of detecting all cases using PCR or antigen testing, not only at a hospital, but also in areas where people assemble. Further prospective studies using this cohort are needed to monitor SARS-CoV-2 antibody levels.
A comparison of therapies using Eyetronix Flicker Glass And standard adhesive patches in children with anisometropic amblyopia: A randomized controlled trial
Authors: Min Seung Hyun , Chen Shijia , Xu Jinling , Chen Bingzhen , Chen Hui , Wang Yuwen , Zhou Jiawei , Yu Xudong
Published: July 2020

Abstract

Objective

Eyetronix Flicker Glass (EFG) has been introduced an alternative treatment for amblyopia. It is based on the premise that amblyopia can better be treated by manipulating the visual input that enter both the normal and amblyopic eye. In contrast, only the normal eye gets deprived during the traditional patching therapy. We conducted a randomized clinical trial to compare the efficacy of the therapies using the Eyetronix Flicker Glass and standard adhesive patches in children with anisometropic amblyopia.

Design

A prospective, randomized controlled trial Participants: 31 children aged 4-13 years with anisometropic amblyopia Intervention: The patients were assigned two treatment groups and were treated for 12 weeks. Those in the first group were treated with the Eyetronix Flicker Glass for one hour per day, whereas those in the latter group were treated with the standard patches for two hours per day.

Main outcome measures

Best-corrected visual acuity and contrast sensitivity of the amblyopic eye, stereopsis and fusion range were measured at both before the treatment and 3, 6 and 12 weeks after the first day of the treatment.

Results

Visual acuity of the amblyopic eye significantly improved in both groups after the treatment (p < 0.05), albeit more so in patients who had undergone the standard patching therapy. A significant improvement in contrast sensitivity of the amblyopic eye at 3, 6 and 12 cpd was also observed in patients who had undergone the standard patching therapy (p < 0.05) but not the EFG therapy (p > 0.05). However, no improvement in stereopsis and fusion range was found in patients from both treatment groups.

Conclusion

Both therapies improved monocular visual functions, such as visual acuity and contrast sensitivity. However, the improvement was significantly larger after the standard patching therapy than that of the EFG therapy. However, both therapies did not improve fusion range and stereopsis. Our results indicate that although the EFG therapy deprives visual input in a binocular fashion, it does not improve binocular functions in the amblyopic population.
Low Seroprevalence of SARS-CoV-2 in Rhode Island Blood Donors Determined using Multiple Serological Assay Formats
Authors: Nesbitt Daniel J. , Jin Daniel , Hogan Joseph W. , Chan Philip A. , Simon Melissa J. , Vargas Matthew , King Ewa , Huard Richard C. , Bandy Utpala , Hillyer Christopher D. , Luchsinger Larry L.
Published: July 2020

Epidemic projections and public health policies addressing Coronavirus disease (COVID)-19 have been implemented without data reporting on the seroconversion of the population since scalable antibody testing has only recently become available. We measured the percentage of severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) seropositive individuals from 2,008 blood donors drawn in the state of Rhode Island (RI). We utilized multiple antibody testing platforms, including lateral flow immunoassays (LFAs), enzyme-linked immunosorbent assays (ELISAs) and high throughput serological assays (HTSAs). We report than an estimated seropositive rate of RI blood donors of approximately 0.6% existed in April-May of 2020. These data imply that seroconversion, and thus infection, is likely not widespread within this population. Daily new case rates peaked in RI in late April 2020. We conclude that IgG LFAs and HTSAs are suitable to conduct seroprevalence assays in random populations. More studies will be needed using validated serological tests to improve the precision and report the kinetic progression of seroprevalence estimates.
A logistic model of CoV-2 propagation
Authors: Weiss Robert F.
Published: July 2020

We describe an elemental logistic model for the propagation of CoV-2 in a community and illustrate the sensitivity of the model to key parameters such as R0, the initial rate of infections per infected person, and A0, the fraction of infected people developing neutralizing antibodies. We demonstrate the importance of the duration of immunity in the population, the development of waves of new cases of infection, and the effect of premature opening of local economies.
SIDIR: Extending SIR with Detected and Isolated Populations for Pandemic Modeling
Authors: Garman Joe , MacAvaney Sean , Yang Eugene , Frieder Ophir
Published: July 2020

Abstract

We extend the Susceptible Infected Recovered (SIR) model to include Detected (D) and Isolated (I) compartments (SIDIR). SIDIR improves COVID-19 outbreak behavior modeling by identifying infected populations as subsequently quarantined to reduce the spread of the infection (either in a hospital or self-quarantined). We present the model and provide a case study on COVID-19. The model estimates undetected cases (i.e., those infected but unconfirmed) and extrapolates when no additional undetected active (rogue) cases will remain, potentially guiding policy decisions that help control the spread of COVID-19 and future epidemics. A live demonstration of SIDIR on COVID-19 is available at:http://ir.cs.georgetown.edu/sidir.
Intravenous Immunoglobulin (IVIG) Significantly Reduces Respiratory Morbidity in COVID-19 Pneumonia: A Prospective Randomized Trial
Authors: Sakoulas George , Geriak Matthew , Kullar Ravina , Greenwood Kristina L. , Habib MacKenzie , Vyas Anuja , Ghafourian Mitra , Dintyala Venkata Naga Kiran , Haddad Fadi
Published: July 2020

Background

Interventions mitigating progression to mechanical ventilation in COVID-19 would markedly improve outcome and reduce healthcare utilization. We hypothesized that immunomodulation with IVIG would improve oxygenation and reduce length of hospital stay and progression to mechanical ventilation in COVID-19 pneumonia.

Methods

Patients with COVID-19 were randomized 1:1 to prospectively receive standard of care (SOC) plus IVIG 0.5 g/kg/day × 3 days with methylprednisolone 40 mg 30 minutes before infusion versus SOC alone.

Results

16 subjects received IVIG plus SOC and 17 SOC alone. The median age was 51 years for SOC and 58 years for IVIG. APACHE II scores and Charlson comorbidity indices were similar for IVIG and SOC (median 7.5 vs 7 and 2 for both, respectively). Seven SOC versus 2 IVIG subjects required mechanical ventilation (p=0.12, Fisher exact test). Among subjects with A-a gradient of >200 mm Hg at enrollment, the IVIG group showed i) a lower rate of progression to requiring mechanical ventilation (2/14 vs 7/12, p=0.038 Fisher exact test), ii) shorter median hospital length of stay (11 vs 19 days, p=0.01 Mann Whitney U), iii) shorter median ICU stay (2.5 vs 12.5 days, p=0.006 Mann Whitey U), and iv) greater improvement in PaO2/FiO2 at 7 days (median [range] change from time of enrollment +131 [+35 to +330] vs +44·5 [-115 to +157], p=0.01, Mann Whitney-U test) than SOC.

Conclusion

This pilot prospective randomized study comprising largely of Latino patients showed that IVIG significantly improved hypoxia and reduced hospital length of stay and progression to mechanical ventilation in COVID-19 patients with A-a gradient >200 mm Hg.
Comparative Incidence and Outcomes of COVID-19 in Kidney or Kidney-Pancreas Transplant Recipients Versus Kidney or Kidney-Pancreas Waitlisted Patients: A Pilot Study
Authors: Santos Carlos A. Q. , Rhee Yoona , Hollinger Edward F. , Olaitan Oyedolamu K. , Schadde Erik , Peev Vasil , Saltzberg Samuel N. , Hertl Martin
Published: July 2020

Comparative COVID-19 epidemiologic studies between immunosuppressed and immunocompetent patients may provide insight into the impact of immunosuppressive medications on clinical outcomes. In this retrospective cohort pilot study, we determined the incidence and outcomes of COVID-19 in kidney or kidney-pancreas transplant recipients and kidney or kidney-pancreas waitlisted patients in our center. COVID-19 testing was performed in 63 of 537 kidney or kidney-pancreas transplanted patients, versus 43 of 383 kidney or kidney-pancreas waitlisted patients as of June 4, 2020 (12% versus 11%, p=0.81). COVID-19 was identified in 14 of 537 kidney or kidney-pancreas transplanted patients, versus 9 of 383 kidney or kidney-pancreas waitlisted patients (2.6% versus 2.3%, p=0.81). Hospitalization occurred in 11 of 14 transplanted patients, and 4 of 9 waitlisted patients with COVID-19 (79% versus 44%, p=0.18). Intensive care unit admission occurred in 5 of 14 transplanted patients, and 1 of 9 waitlisted patients with COVID-19 (36% versus 11%, p=0.34). Two transplanted patients with COVID-19 were mechanically ventilated and died, whereas no waitlisted patients with COVID-19 died or were mechanically ventilated. Our study provides preliminary data that can be used for power calculations to inform multicenter studies designed to validate these findings.
Evaluating temperature and humidity gradients of COVID-19 infection rates in light of Non-Pharmaceutical Interventions
Authors: Choma Joshua , Correa Fabio , Dahbi Salah-Eddine , Hayasi Kentaro , Lieberman Benjamin , Maslo Caroline , Mellado Bruce , Monnakgotla Kgomotso , Naudé Jacques , Ruan Xifeng , Stevenson Finn
Published: July 2020

We evaluate potential temperature and humidity impact on the infection rate of COVID-19 with a data up to June 10th2020, which comprises a large geographical footprint. It is critical to analyse data from different countries or regions at similar stages of the pandemic in order to avoid picking up false gradients. The degree of severity of NPIs is found to be a good gauge of the stage of the pandemic for individual countries. Data points are classified according to the stringency index of the NPIs in order to ensure that comparisons between countries are made on equal footing. We find that temperature and relative humidity gradients don’t significantly deviate from the zero-gradient hypothesis. Upper limits on the absolute value of the gradients are set. The procedure chosen here yields 6 10−3 °C−1and 3.3 10−3(%)−1upper limits on the absolute values of the temperature and relative humidity gradients, respectively, with a 95% Confidence Level. These findings do not preclude existence of seasonal effects and are indicative that these are likely to be nuanced.
Effects Of Mindfulness On Sleep Quality, Anxiety, Depression and Stress In Migraine
Authors: Burrowes Shana AB , Goloubeva Olga , Stafford Kristen , McArdle Patrick F. , Goyal Madhav , Peterlin B. Lee , Haythornthwaite Jennifer A. , Seminowicz David A.
Published: July 2020

Objective

To examine the change over time in sleep quality and psychosocial outcomes from the MRI Outcomes for Mindfulness Meditation Clinical Trial, assess how these mediated treatment response (50% reduction in headache frequency post-intervention) and examine the relationship between baseline values and treatment response.

Methods

This is a secondary analysis of a randomized placebo-controlled trial with single masking. Patients were recruited from the community, headache clinics and primary care offices in Baltimore Maryland. Eligible patients were aged 18-65 and met the International Classification of Headache Disorders criteria for episodic migraine (4-14 headache days in 28 days).The trial (primary outcomes previously reported) included 98 episodic migraine patients randomized to either enhanced (MBSR+) or stress management for headache (SMH). Follow-up visits occurred at 10, 20 and 52 weeks post baseline. Intervention groups met separately for two hours weekly for 8 weeks and then biweekly for an additional 8 weeks. MBSR+ had an additional half-day retreat held between weeks 6 and 8.

Results

There was a significant improvement in sleep quality from baseline to post-intervention (p=0.0025), in both groups. There were no significant change from baseline or between groups in anxiety, depression and stress. There was also no significant association between baseline scores and treatment response. Mediation analysis showed a significant indirect effect for sleep, anxiety, stress, and depression on treatment response, ranging from 6-8%.

Conclusions

The findings indicate that in episodic migraine, treatment response to MBSR+ compared to SMH was mediated by small, but significant improvements in sleep, anxiety, stress, and depression.
COVIDCare@Home: Lessons from a Family Medicine Led Remote Monitoring Program
Authors: Agarwal Payal , Mukerji Geetha , Laur Celia , Chandra Shivani , Pimlott Nick , Heisey Ruth , Stovel Rebecca , Goulbourne Elaine , Bhatia R. Sacha , Bhattacharyya Onil , Martin Danielle
Published: July 2020

Background

Virtual care for patients with COVID-19 allows providers to monitor COVID-19 positive patients with variable trajectories while reducing the risk of transmission to others and managing healthcare capacity in acute care facilities.

Objective

To develop and test the feasibility of a family medicine-led remote monitoring model of care (COVIDCare@Home program) to manage patients with COVID-19 in the community.

Methods

This multi-faceted, family medicine-led, interprofessional team-based remote monitoring program was developed at Women’s College Hospital in Toronto, Ontario. A cross-sectional chart review of the first cohort of patients was conducted and learnings from the implementation of CovidCare@Home are described.

Results

During the study period, April 8 to May 11, 2020, there were 97 patients (average age 48.6, 62% female) with 424 recorded virtual visits with a median virtual length of stay of 8 days (IQR 5). 5.2% required escalation to an in-person visit with no patients requiring hospitalization. 16% of patients required support with mental and social health needs.

Interpretations

A family medicine-led, team-based remote monitoring program can safely be used to manage outpatients diagnosed with COVID-19. Attention to mental and social health needs is critical for this population. Future efforts should consider how to design programs to best support populations disproportionately impacted by COVID-19, something which primary care is well-positioned to do. Further analysis will describe the effectiveness, impact, and satisfaction with the program among patients and providers.
Covid19 2020 projection report: Germany, Israel, Italy and USA. Mid-July 2020
Authors: Meilijson Isaac
Published: July 2020

A notion of implied susceptible population size ISPS was introduced in the context of the SIR differential equations in Epidemiology, in a companion paper. It is the potential target population size for which the solution to the SIR equations would yield the current number of new affected cases. This notion is applied to the analysis and projection of Covid19 2020, illustrated on the data of Germany, Israel, Italy and USA.
The adequacy of health system measures in reducing vulnerability to COVID-19 among the health care providers working in primary health care in Rajasthan, India: A Cross-sectional Study
Authors: Das Arup Kumar , Srivastava Ambey Kumar , Ghosh Saswata , Bhargava Ruchi , Gupta Rajan , Singh Rajesh Ranjan
Published: July 2020

Background

This paper examines the role of individual, facility and system level preparedness in reducing the physiological and psychological vulnerability among primary-level health care providers (HCPs) of COVID19 pandemic in Rajasthan, India.

Method and Material

Online and telephonic interviews are conducted among 274 HCPs working in 24 PHCs (17 rural and 7 urban), across 13 districts of Rajasthan. Five dimensions of vulnerability covering awareness, exposure to infection (daily contact; contact with high-risk individuals), physical and mental health conditions, while three aspects of preparedness – at individual (personal care) and facility (provider safety; management and supervision) level – are measured by employing factor analysis. Generalized ordered logit regression model is used to measure the effect of preparedness on COVID19 related vulnerability.

Result

Among the 274 HCPs, majority of the staff are from rural PHCs (76 %), less than 35 years (87%), female (57%) and married (57 %). Almost half have high level exposure to COVID19, with mean contact rate is 90. Overall, 26% have comprehensive knowledge on COVID19, and 32% have any mental health issues. Although more than 70% of HCPs have reported more than one individual level preparedness, mental health measures adopted by the HCPs are comparably low. The facility level preparedness for enhancing safety are high such as social distance (79%) and maintaining record of each visitor (75%). However, management related measures adopted by the PHCs are perceived to be lower than the safety measures. The regression analyses suggest that safety related preparedness is significantly associated with reduction of vulnerability by 50%. The management-level preparedness has statistically no significant effect in explaining the variations in level of vulnerability.

Conclusion

The facility-level safety measures, which lowers chances of acquiring infection has a positive effect on reducing vulnerability of COVID19. However, the HCPs do not have adequate preparedness at individual, facility management (PHC) and system level to reduce COVID19 vulnerability. Findings suggest that there is a need for a non-conventional approach of monitoring and supervision, in the absence of such measures there is a chance of moral injury that will make the HCPs at the primary level vulnerable to both physiologically and psychologically.
Black bone MRI morphometry for mandibular cortical bone measurement in head and neck cancer patients: Prospective method comparison with CT
Authors:   Joint Head and Neck MRI-Radiotherapy Development Cooperative, van Dijk Lisanne V. , Ventura Juan , Wahid Kareem , Zhu Lin L. , McDonald Brigid A. , Ahmed Sara , Sanders Keith , Stieb Sonja M. , McCoy Lance , Sharafi Christina S. , Preston Kathryn , Fahim Joly , DeArmas Aubryane , Arbab Mona , Ding Yao , Wang Jihong , Rigaud Bastien , Sen Anando , Chambers Mark , Hutcheson Katherine A. , Brock Kristy K. , Lai Stephen Y. , Mohamed Abdallah S. R. , Fuller Clifton D.
Published: July 2020

Objectives

To determine the utility of low-flip angle “black bone” magnetic resonance imaging (MRI) for cortical mandibular bone assessment by comparing interdentium cortical measurements and inter-observer morphometric variability in relation to computed tomography (CT).

Methods

Quantification of cortical mandible bone width was performed as per Hamada et al. at 15 cross-sectional interdentium locations on pre-treatment black bone MRI and CT for 15 oropharyngeal cancer patients, with inter-observer analyses on a subset of 3 patients by 11 observers. Bland-Altman limits of agreement and bias estimation, Lin’s concordance correlation (LCC), and Deming orthogonal regression were used to compare CT and MRI measurements. The absolute variance and intraclass correlation coefficient (ICC) were implemented for the inter-observer error quantification.

Results

Both the Bland Altman and Deming regression analyses showed CT and black bone MRI measurements were comparable within ±0.85 mm limits of agreement, and systematically smaller for MRI. LCC (0.60[0.52;0.67]) showed moderate equivalence between modalities. The average absolute variance between the observers was similar on CT (1.13±0.06 mm) and MRI (1.15 ±0.06 mm). The ICC analyses showed that measurement consistency was significantly higher (p<0.001) for the black bone MRI (0.43[0.32;0.56]) than CT (0.22[0.13;0.35]); nonetheless, the ICC was poor for both modalities.

Conclusions

Black bone MR sequence is usable as an alternative to CT for cortical mandible bone measurements, allowing use for early detection of cortical alteration (e.g. osteonecrosis). The cortical bone measurements showed substantive but equivalent inter-observer variation on both CT and black bone MRI. (Semi)automated measurement may mitigate this in future work.
Healthcare Workers’ Mental Health and Wellbeing During the COVID-19 Pandemic in the UK: Contrasting Guidelines with Experiences in Practice
Authors: Vera San Juan Norha , Aceituno David , Djellouli Nehla , Sumray Kirsi , Regenold Nina , Syversen Aron , Symmons Sophie Mulcahy , Dowrick Anna , Mitchinson Lucy , Singleton Georgina , Vindrola-Padros Cecilia
Published: July 2020

Background

Substantial evidence has highlighted the importance of considering healthcare workers’ (HCW) mental health during the COVID-19 pandemic, and several organisations have issued guidelines with recommendations. However, the definition of wellbeing and the evidence-base behind such guidelines remains unclear.

Objectives

Assessing the applicability of wellbeing guidelines in practice; identifying unaddressed HCWs’ needs; and providing recommendations for supporting frontline staff during the current and future pandemics.

Methods and Design

This paper discusses the findings of a qualitative study based on interviews with frontline healthcare staff in the UK and examines them in relation to a rapid review of wellbeing guidelines developed in response to the COVID-19 pandemic.

Results

14 guidelines were included in the rapid review and 33 interviews with HCWs were conducted in the qualitative study. As a whole, the guidelines placed greater emphasis on wellbeing at an individual level, while HCWs placed greater emphasis on structural conditions at work, such as understaffing and the invaluable support of the community. This in turn had implications for the focus of wellbeing intervention strategies; staff reported an increased availability of formal mental health support, however, understaffing or clashing schedules prevented them from participating in these activities.

Conclusion

HCWs expressed wellbeing needs which align with social-ecological conceptualisations of wellbeing related to quality of life. This approach to wellbeing has been highlighted in literature about HCWs support in previous health emergencies, yet it has not been monitored during this pandemic. Wellbeing guidelines should explore staff’s needs and contextual characteristics affecting the implementation of recommendations.
High stability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA under minimal storage conditions for detection by Real-Time PCR
Authors: Summer Sabrina , Schmidt Ralf , Herdina Anna Nele , Krickl Isabella , Madner Julia , Greiner Georg , Mayer Florian J. , Perkmann-Nagele Nicole , Strassl Robert
Published: July 2020

Reliable diagnosis, executed by Real-Time PCR (RT-PCR), builds the current basis in SARS-CoV-2 containment. Transport and storage conditions are the main indicators determining the quality of respiratory specimens. According to shortages in commercially available viral transport media, the primary aim of this study was to explore the reliability of minimal transport media including saline and CDC Viral Transport Media (HBSS VTM) composition for SARS-CoV-2 diagnosis by Real-time PCR compared to recommended commercially available standard Universal Transport Media (UTM). This study also implicated the stability of other respiratory viruses, including influenza A, respiratory syncytial virus, adenovirus, rhinovirus and human metapneumovirus, providing further evidence for future recommendations on transport and storage of respiratory viruses. Both viral transport media (self-made HBSS VTM and UTM) and saline (0.9% NaCl) allow adequate detection of SARS- CoV-2 and other respiratory viruses, regardless of an increase in storage temperature (up to 28 °C) and time (over 28 days). Treatment of SARS-CoV-2 specimens with varying chlorine concentrations, commonly used in swimming pools, resulted in a significant decrease of viral RNA.

Importance

Detection of respiratory viruses including SARS-CoV-2 depends on the quality of respiratory specimens, predominantly determined by transport and storage conditions. Our study revealed the high resilience of SARS-CoV-2 and other respiratory viruses enabling proper detection in clinical specimens even after long- time storage at high temperatures. This study provides evidence for future recommendations for transport and storage of respiratory viruses, including SARS- CoV-2.

Treatment of SARS-CoV-2-positive respiratory specimens with chlorine indicates an early degradation of the virus after the addition of the oxidant, proposing sufficient inactivation of the virus in swimming pool water.
Threshold analyses on combinations of testing, population size, and vaccine coverage for COVID-19 control in a university setting
Authors: Zhao Xinmeng , Tatapudi Hanisha , Corey George , Gopalappa Chaitra
Published: July 2020

We simulated epidemic projections of a potential COVID-19 outbreak in a residential university population in the United States under varying combinations of asymptomatic tests (5% to 33% per day), transmission rates (2.5% to 14%), and contact rates (1 to 25), to identify the contact rate threshold that, if exceeded, would lead to exponential growth in infections. Using this, we extracted contact rate thresholds among non-essential workers, population size thresholds in the absence of vaccines, and vaccine coverage thresholds. We further stream-lined our analyses to transmission rates of 5 to 8%, to correspond to the reported levels of face-mask-use/physical-distancing during the 2020 pandemic.

Our results suggest that, in the absence of vaccines, testing alone without reducing population size would not be sufficient to control an outbreak. If the population size is lowered to 34% (or 44%) of the actual population size to maintain contact rates at 4 (or 7) among non-essential workers, mass tests at 25% (or 33%) per day would help control an outbreak. With the availability of vaccines, the campus can be kept at full population provided at least 95% are vaccinated. If vaccines are partially available such that the coverage is lower than 95%, keeping at full population would require asymptomatic testing, either mass tests at 25% per day if vaccine coverage is at 63-79%, or mass tests at 33% per day if vaccine coverage is at 53-68%. If vaccine coverage is below 53%, to control an outbreak, in addition to mass tests at 33% per day, it would also require lowering the population size to 90%, 75%, and 60%, if vaccine coverage is at 38-53%, 23-38%, and below 23%, respectively.

Threshold estimates from this study, interpolated over the range of transmission rates, can collectively help inform campus level preparedness plans for adoption of face mask/physical-distancing, testing, remote instructions, and personnel scheduling, during non-availability or partial-availability of vaccines, in the event of SARS-Cov2-type disease outbreaks.
Huntingtin lowering reduces somatic instability at CAG-expanded loci
Authors: Coffey Sydney R. , Andrew Marissa , Ging Heather , Hamilton Joseph , Flower Michael , Kovalenko Marina , Bragg Robert M. , Cantle Jeffrey P. , McHugh Cassandra A. , Carrillo José M. , Rodier Julie-Anne , Marchionini Deanna M. , Wilkinson Hilary A. , Kwak Seung , Howland David S. , Bennett C. Frank , Pinto Ricardo Mouro , Auburger Georg , Zeitlin Scott O. , Kordasiewicz Holly B. , Tabrizi Sarah J. , Wheeler Vanessa C. , Carroll Jeffrey B.
Published: July 2020

Expanded trinucleotide repeats cause many human diseases, including Huntington’s disease (HD). Recent studies indicate that somatic instability of these repeats contributes to pathogenesis in several expansion disorders. We find that lowering huntingtin protein (HTT) levels reduces somatic instability of both theHttandAtxn2CAG tracts in knockin mouse models, and theHTTCAG tract in human iPSC-derived neurons, revealing an unexpected role for HTT in regulating somatic instability.
Calcium binding protein Ncs1 is calcineurin-regulated inCryptococcus neoformansand essential for cell division and virulence
Authors: Squizani Eamim Daidrê , Reuwsaat Júlia Catarina Vieira , Lev Sophie , Motta Heryk , Sperotto Julia , Kaufman-Francis Keren , Desmarini Desmarini , Vainstein Marilene Henning , Staats Charley Christian , Djordjevic Julianne T. , Kmetzsch Lívia
Published: July 2020

Intracellular calcium (Ca2+) is crucial for signal transduction inCryptococcus neoformans, the major cause of fatal fungal meningitis. The calcineurin pathway is the only Ca2+-requiring signalling cascade implicated in cryptococcal stress adaptation and virulence, with Ca2+-binding mediated by the EF-hand domains of the Ca2+sensor protein calmodulin. In this study, we identified the cryptococcal ortholog of neuronal calcium sensor-1 (Ncs1) as a member of the EF-hand superfamily. We demonstrated that Ncs1 has a role in Ca2+homeostasis under stress and non-stress conditions, as thencs1Δmutant is sensitive to a high Ca2+concentration and has an elevated basal Ca2+level that correlates with increased expression of the Ca2+transporter genes,CCH1andMID1. Furthermore,NCS1expression is induced by Ca2+, with the Ncs1 protein adopting a punctate subcellular distribution. We also demonstrate that, in contrast toSaccharomyces cerevisiae,NCS1expression inC. neoformansis regulated by the calcineurin pathway via the transcription factor Crz1, asNCS1expression is reduced by FK506 treatment andCRZ1deletion. Moreover, thencs1Δmutant shares a high temperature and high Ca2+sensitivity phenotype with the calcineurin and calmodulin mutants (cna1Δ andcam1Δ) and theNCS1promoter contains two calcineurin/Crz1-dependent response elements (CDRE1). Ncs1-deficency coincided with reduced growth, characterized by delayed bud emergence and aberrant cell division, and hypovirulence in a mouse infection model. In summary, our data shows that Ncs1 plays distinct roles in Ca2+sensing inC. neoformansdespite widespread functional conservation of Ncs1 and other regulators of Ca2+homeostasis.

Importance

Cryptococcus neoformansis the major cause of fungal meningitis in HIV infected patients. Several studies have highlighted the important contribution of Ca2+signalling and homeostasis to the virulence ofC. neoformans. Here, we identify the cryptococcal ortholog of neuronal calcium sensor-1 (Ncs1) and demonstrate its role in Ca2+homeostasis, bud emergence, cell cycle progression and virulence. We also show that Ncs1 function is regulated by the calcineurin/Crz1 signalling cascade. Our work provides evidence of a link between Ca2+homeostasis and cell cycle progression inC. neoformans.
Four-dimensional characterization of theBabesia divergensasexual life cycle: from the trophozoite to the multiparasite stage
Authors: Conesa José Javier , Sevilla Elena , Terrón María C. , González Luis Miguel , Gray Jeremy , Pérez-Berná Ana J. , Carrascosa José L. , Pereiro Eva , Chichón Francisco Javier , Luque Daniel , Montero Estrella
Published: July 2020

Babesiais an apicomplexan parasite of significance that causes the disease known as babesiosis in domestic and wild animals and in humans worldwide.Babesiainfects vertebrate hosts and reproduces asexually by a form of binary fission within erythrocytes/red blood cells (RBCs), yielding a complex pleomorphic population of intraerythrocytic parasites. Seven of them, clearly visible in human RBCs infected withBabesia divergens, are considered the main forms and named single, double and quadruple trophozoites, paired and double paired-pyriforms, tetrad or Maltese Cross, and multiparasite stage. However, these main intraerythrocytic forms coexist with RBCs infected with transient parasite combinations of unclear origin and development. In fact, little is understood about howBabesiabuilds this complex population during its asexual life cycle. By combining the emerging technique cryo soft X-ray tomography and video microscopy, main and transitory parasites were characterized in a native whole cellular context and at nanometric resolution. As a result, the architecture and kinetic of the parasite population has been elucidated. Importantly, the process of multiplication by binary fission, involving budding, was visualized in live parasites for the first time, revealing that fundamental changes in cell shape and continuous rounds of multiplication occur as the parasites go through their asexual multiplication cycle. Based on these observations, a four-dimensional (4D) asexual life cycle model has been designed highlighting the origin of the tetrad, double paired-pyriform and multiparasite stages and the transient morphological forms that, surprisingly, intersperse in a chronological order between one main stage and the next along the cycle.

IMPORTANCE

Babesiosis is a disease caused by intraerythrocytic Babesia parasites, which possess many clinical features that are similar to those of malaria. This worldwide disease, is increasing in frequency and geographical range, and has a significant impact on human and animal health.Babesia divergensis one of the species responsible for human and cattle babesiosis causing death unless treated promptly. WhenB. divergensinfects its vertebrate hosts it reproduces asexually within red blood cells. During its asexual life cycle,B. divergensbuilds a population of numerous intraerythrocytic (IE) parasites of difficult interpretation. This complex population is largely unexplored, and we have therefore combined three and four dimensional (3D and 4D) imaging techniques to elucidate the origin, architecture, and kinetic of IE parasites. Unveil the nature of these parasites have provided a vision of theB. divergensasexual cycle in unprecedented detail and a key step to develop control strategies against babesiosis
Artificial Intelligence Predicts and Explains West Nile Virus Risks Across Europe: Extraordinary Outbreaks Determined by Climate and Local Factors
Authors: Gayle Albert A
Published: July 2020

Year-to-year emergence of West Nile virus has been sporadic and notoriously hard to predict. In Europe, 2018 saw a dramatic increase in the number of cases and locations affected. In this work, we demonstrate a novel method for predicting outbreaks and understanding what drives them. This method creates a simple model for each region that directly explains how each variable affects risk. Behind the scenes, each local explanation model is produced by a state-of-the-art AI engine. This engine unpacks and restructures output from an XGBoost machine learning ensemble. XGBoost, well-known for its predictive accuracy, has always been considered a “black box” system. Not any more. With only minimal data curation and no “tuning”, our model predicted where the 2018 outbreak would occur with an AUC of 97%. This model was trained using data from 2010-2016 that reflected many domains of knowledge. Climate, sociodemographic, economic, and biodiversity data were all included. Our model furthermore explained the specific drivers of the 2018 outbreak for each affected region. These effect predictions were found to be consistent with the research literature in terms of priority, direction, magnitude, and size of effect. Aggregation and statistical analysis of local effects revealed strong cross-scale interactions. From this, we concluded that the 2018 outbreak was driven by large-scale climatic anomalies enhancing the local effect of mosquito vectors. We also identified substantial areas across Europe at risk for sudden outbreak, similar to that experienced in 2018. Taken as a whole, these findings highlight the role of climate in the emergence and transmission of West Nile virus. Furthermore, they demonstrate the crucial role that the emerging “eXplainable AI” (XAI) paradigm will have in predicting and controlling disease.

Highlights

This study shows that the extraordinary 2018 West Nile virus outbreak in Europe was likely due to cross-scale effects between large climatic systems and local mosquito vector populations

We found that large areas in Europe are similarly vulnerable to large and sudden outbreaks

These findings were powered by a novel AI-driven engine for deriving locally precise models; this explanatory engine was supported by a high-performance XGBoost model (97% AUC).

AI-driven local models allow for high-power statistical analyses, including: hypothesis testing,, standardized effect size calculation, multivariate clustering, and tertiary inferential modeling
Systematic evaluation and external validation of 22 prognostic models among hospitalised adults with COVID-19: An observational cohort study
Authors: Gupta Rishi K. , Marks Michael , Samuels Thomas H. A. , Luintel Akish , Rampling Tommy , Chowdhury Humayra , Quartagno Matteo , Nair Arjun , Lipman Marc , Abubakar Ibrahim , Smeden Maarten van , Wong Wai Keong , Williams Bryan , Noursadeghi Mahdad
Published: July 2020

Background

The number of proposed prognostic models for COVID-19, which aim to predict disease outcomes, is growing rapidly. It is not known whether any are suitable for widespread clinical implementation. We addressed this question by independent and systematic evaluation of their performance among hospitalised COVID-19 cases.

Methods

We conducted an observational cohort study to assess candidate prognostic models, identified through a living systematic review. We included consecutive adults admitted to a secondary care hospital with PCR-confirmed or clinically diagnosed community-acquired COVID-19 (1stFebruary to 30thApril 2020). We reconstructed candidate models as per their original descriptions and evaluated performance for their original intended outcomes (clinical deterioration or mortality) and time horizons. We assessed discrimination using the area under the receiver operating characteristic curve (AUROC), and calibration using calibration plots, slopes and calibration-in-the-large. We calculated net benefit compared to the default strategies of treating all and no patients, and against the most discriminating predictor in univariable analyses, based on a limited subset ofa prioricandidates.

Results

We tested 22 candidate prognostic models among a cohort of 411 participants, of whom 180 (43.8%) and 115 (28.0%) met the endpoints of clinical deterioration and mortality, respectively. The highest AUROCs were achieved by the NEWS2 score for prediction of deterioration over 24 hours (0.78; 95% CI 0.73-0.83), and a novel model for prediction of deterioration <14 days from admission (0.78; 0.74-0.82). Calibration appeared generally poor for models that used probability outcomes. In univariable analyses, admission oxygen saturation on room air was the strongest predictor of in-hospital deterioration (AUROC 0.76; 0.71-0.81), while age was the strongest predictor of in-hospital mortality (AUROC 0.76; 0.71-0.81). No prognostic model demonstrated consistently higher net benefit than using the most discriminating univariable predictors to stratify treatment, across a range of threshold probabilities.

Conclusions

Oxygen saturation on room air and patient age are strong predictors of deterioration and mortality among hospitalised adults with COVID-19, respectively. None of the prognostic models evaluated offer incremental value for patient stratification to these univariable predictors.