bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel germline BMPR1A variant (c.72_73delGA) in a Japanese family with hereditary mixed polyposis syndrome
Authors: Miyahara Yosuke , Ishida Hideyuki , Kawabe Koichi , Eto Hiroyuki , Kasai Toyotaka , Ito Tetsuya , Kaneko Kou , Arai Motohiro , Kamae Nao , Momose Shuji , Eguchi Hidetaka , Okazaki Yasushi
Published: April 2020

Hereditary mixed polyposis syndrome (HMPS) is a rare autosomal dominant disorder characterized by a mixture of typical and/or atypical juvenile polyps, adenomas and hyperplastic polyps, resulting in an increased risk of colorectal cancer. In HMPS, four different germline BMPR1A variants from five unrelated families have been reported. This study is the first to report HMPS within a Japanese family. The proband underwent repeated colonoscopic polypectomies over a 5-year period, since the age of 67. Histological examination of these resected polyps revealed adenomas, juvenile-like polyps and hyperplastic changes. Genetic testing was conducted to identify the causative genes for hereditary gastrointestinal cancer syndromes, including BMPR1A. We detected a germline variant, c.72_73delGA, in BMPR1A. The proband’s elder brother, younger sister and nephew have also undergone repeated colonoscopic polypectomies at other clinics. His sister and nephew underwent genetic testing, and the same BMPR1A variant was identified.
Protective Effectiveness of Long-Lasting Permethrin Impregnated Clothing Against Tick Bites in an Endemic Lyme Disease Setting: A Randomized Control Trial Among Outdoor Workers
Authors: Mitchell Cedar , Dyer Megan , Lin Feng-Chang , Bowman Natalie , Mather Thomas , Meshnick Steven
Published: April 2020

Tick-borne diseases are a growing threat to public health in the United States, especially among outdoor workers who experience high occupational exposure to ticks. Long-lasting permethrin-impregnated clothing has demonstrated high initial protection against bites from blacklegged ticks, Ixodes scapularis Say (Acari: Ixodidae), in laboratory settings, and sustained protection against bites from the lone star tick, Amblyomma americanum (L.) (Acari: Ixodidae), in field tests. However, long-lasting permethrin impregnation of clothing has not been field tested among outdoor workers who are frequently exposed to blacklegged ticks. We conducted a 2-yr randomized, placebo-controlled, double-blinded trial among 82 outdoor workers in Rhode Island and southern Massachusetts. Participants in the treatment arm wore factory-impregnated permethrin clothing, and the control group wore sham-treated clothing. Outdoor working hours, tick encounters, and bites were recorded weekly to assess protective effectiveness of long-lasting permethrin-impregnated garments. Factory-impregnated clothing significantly reduced tick bites by 65% in the first study year and by 50% in the second year for a 2-yr protective effect of 58%. No significant difference in other tick bite prevention method utilization occurred between treatment and control groups, and no treatment-related adverse outcomes were reported. Factory permethrin impregnation of clothing is safe and effective for the prevention of tick bites among outdoor workers whose primary exposure is to blacklegged ticks in the northeastern United States.
X-ray variability analysis of a large series of XMM–Newton +NuSTAR observations of NGC 3227
Authors: Lobban A P , Turner T J , Reeves J N , Braito V , Miller L
Published: April 2020

We present a series of X-ray variability results from a long XMM–Newton + NuSTAR campaign on the bright, variable AGN NGC 3227. We present an analysis of the light curves, showing that the source displays typically softer-when-brighter behaviour, although also undergoes significant spectral hardening during one observation which we interpret as due to an occultation event by a cloud of absorbing gas. We spectrally decompose the data and show that the bulk of the variability is continuum-driven and, through rms variability analysis, strongly enhanced in the soft band. We show that the source largely conforms to linear rms-flux behaviour and we compute X-ray power spectra, detecting moderate evidence for a bend in the power spectrum, consistent with existing scaling relations. Additionally, we compute X-ray Fourier time lags using both the XMM–Newton and – through maximum-likelihood methods – NuSTAR data, revealing a strong low-frequency hard lag and evidence for a soft lag at higher frequencies, which we discuss in terms of reverberation models.
Molecular cross-sections for high-resolution spectroscopy of super-Earths, warm Neptunes, and hot Jupiters
Authors: Gandhi Siddharth , Brogi Matteo , Yurchenko Sergei N , Tennyson Jonathan , Coles Phillip A , Webb Rebecca K , Birkby Jayne L , Guilluy Gloria , Hawker George A , Madhusudhan Nikku , Bonomo Aldo S , Sozzetti Alessandro
Published: April 2020

High-resolution spectroscopy (HRS) has been used to detect a number of species in the atmospheres of hot Jupiters. Key to such detections is accurately and precisely modelled spectra for cross-correlation against the R ≳ 20 000 observations. There is a need for the latest generation of opacities which form the basis for high signal-to-noise detections using such spectra. In this study we present and make publicly available cross-sections for six molecular species, H2O, CO, HCN, CH4, NH3, and CO2 using the latest line lists most suitable for low- and high-resolution spectroscopy. We focus on the infrared (0.95–5 μm) and between 500 and 1500 K where these species have strong spectral signatures. We generate these cross-sections on a grid of pressures and temperatures typical for the photospheres of super-Earth, warm Neptunes, and hot Jupiters using the latest H2 and He pressure broadening. We highlight the most prominent infrared spectral features by modelling three representative exoplanets, GJ 1214 b, GJ 3470 b, and HD 189733 b, which encompass a wide range in temperature, mass, and radii. In addition, we verify the line lists for H2O, CO, and HCN with previous high-resolution observations of hot Jupiters. However, we are unable to detect CH4 with our new cross-sections from HRS observations of HD 102195 b. These high-accuracy opacities are critical for atmospheric detections with HRS and will be continually updated as new data become available.
Sustained research fund and dedicated research center to prepare for the next pandemic
Authors: Jia Hongpeng , Wu Min
Published: April 2020

The current COVID-19 pandemic caused by the SARS-CoV-2 virus is imposing a great threat to human lives and international panic the like of which has not been seen since WWII, resulting in financial crisis, disturbance to daily life, transportation shutdown, industry disruption, and country/city lockdown in every corner of the globe. The inability to effectively contain the virus indicates that our investment and attention to research, prevention, and development of treatment for this type of deadly virus are insufficient, considering that it has been 18 years since outbreak of the "brother" coronavirus, SARS-CoV. The biggest lesson learned from acrimonious past experiences is that humans quickly forget and do not continue to support related research when a pandemic has passed. This is a wake-up call for governments, industry, and private foundations to work together and to take extraordinary measures to sustain research support and establish comprehensive research centers. Only this level of response may give us hope to prepare for the future and adequately deal with the next potential pandemic caused by emerging devastating viral infections.
Mapping the Burden of COVID-19 in the United States
Authors: Miller Ian F. , Becker Alexander D. , Grenfell Bryan T. , Metcalf C. Jessica E.
Published: April 2020

As of April 5th 2020, SARS-CoV-2 has resulted in over 273,000 confirmed infections in the United States of America. Incidence continues to rise. As the epidemic threatens to overwhelm health care systems, identifying regions where the expected disease burden is likely to be high relative to the rest of the country is critical for enabling prudent and effective distribution of emergency resources. Across all global regions affected by the pandemic, an elevated risk of severe outcomes has consistently been observed in older age groups. Using age-specific mortality patterns in tandem with demographic data, we map a projection of the cumulative burden of COVID-19 and the associated cumulative burden on the healthcare system at the county-scale in the United States for a scenario in which 20% of the population of each county acquires infection. We identify regions that may be particularly impacted relative to the rest of the country, and observe a general trend that per capita disease burden and relative healthcare system demand may be highest away from major population centers.
ACE2 fragment as a decoy for novel SARS-Cov-2 virus
Authors: Renzi Fabiana , Ghersi Dario
Published: April 2020

Novel SARS-Cov-2 enters human cells via interaction between the surface spike (S) glycoprotein and the cellular membrane receptor angiotensin-converting enzyme 2 (ACE2). Using a combination of comparative structural analyses of the binding surface of the S protein to ACE2, docking experiments, and molecular dynamics simulations we computationally identified a minimal, stable fragment of ACE2. This fragment binds to the S protein, is soluble, and appears not to bind to the physiological ligand angiotensinII. These results suggest a possible use of the ACE2 fragment as a decoy that could interfere with viral binding by competition.
A streamlined approach to rapidly detect SARS-CoV-2 infection, avoiding RNA purification
Authors: Marzinotto Stefania , Mio Catia , Cifù Adriana , Verardo Roberto , Pipan Corrado , Schneider Claudio , Curcio Francesco
Published: April 2020

In the current pandemic, the presence of SARS-CoV-2 RNA in samples by nucleic acid (NA) molecular analysis is the only method available to diagnose COVID-19 disease and to assess patients’ infectiveness. Recently, the demand for laboratory reagents has greatly increased; in particular, there is a worldwide shortage of RNA extraction kits. Here, we describe a fast, simple and inexpensive method for the detection of SARS CoV-2 RNA, which includes a pretreatment with Proteinase K and a heating-cooling cycle before the amplification. This method bypasses the RNA extraction step; it leads to a higher amount of available viral RNA compared to the automated extraction methods, and generates the same profile in the subsequent amplification phase.
A modification to the Maquet Flow-i anaesthesia machine for ICU ventilation
Authors: Robinson Andrew J. , London William , Kotan Laszlo , Downing Warwick
Published: April 2020

The authors present an easily manufactured modification of Getinge Group’s Maquet Flow-i anaesthesia machine that gives it potential to be used long-term as an Intensive Care ventilator for emergency circumstances. There are some 7000 such machines in use worldwide, which could assist in increasing ICU ventilated bed capacity in a number of nations. The authors believe this modification has potential as a solution to increasing ventilator numbers for the COVID-19 pandemic, in hospitals where the Flow-i is underutilised for its designed purpose during this emergency. The technical drawing files are downloadable on the GrabCAD website and are Creative Commons (CC-BY 4.0) licensed to allow local manufacture of the modification. We welcome other Flow-i users and engineers to join us in troubleshooting this project on the associated GrabCAD discussion group during this ‘pre-print’ phase of research.
Toward respiratory support of critically ill COVID-19 patients using repurposed kidney hollow fiber membrane dialysers to oxygenate the blood
Authors: Rubin David M. , Stacey Neil , Matambo Tonderayi , Vale Claudia Do , Sussman Martin J. , Snyman Tracy , Mer Mervyn , Hildebrandt Diane
Published: April 2020

The COVID-19 pandemic has highlighted resource constraints in respiratory support. The oxygen transfer characteristics of a hollow fiber membrane dialyser were investigated with a view to repurposing the device as a low-cost, readily available blood oxygenator. Oxygen transfer in a low-flux hollow fiber dialyser with a polysulfone membrane was studied by passing first water and then blood through the dialyser in counter-current to high-purity oxygen. Oxygen transfer rates of about 15% of the nominal 250 ml(STP)/min of a typical adult oxygen consumption rate were achieved for blood flow rates of 500ml/min. Using two such dialysis devices in parallel could provide up to 30% of the nominal oxygen consumption. Specific hollow fiber dialysis devices operating with suitable pumps in a veno-venous access configuration, could provide a cost-effective and readily available supplementation of respiratory support in the face of severe resource constraints.
Early Stage Prediction of US County Vulnerability to the COVID-19 Pandemic
Authors: Mehta Mihir , Julaiti Juxihong , Griffin Paul , Kumara Soundar
Published: April 2020

Importance

The rapid spread of COVID-19 means that government and health services providers have little time to plan and design effective response policies. It is therefore important to rapidly provide accurate predictions of how vulnerable geographic regions such as counties are to the spread.

Objective

Developing county level prediction around near future disease movement for COVID-19 occurrences using publicly available data.

Design

Original Investigation; Decision Analytical Model Study for County Level COVID-19 occurrences using data from March 14-31, 2020.

Setting

Disease spread prediction for US counties.

Participants

All US county level granularity based on data fused from multiple publicly available sources inclusive of health statistics, demographics, and geographical features.

Exposure(s) (for observational studies)

Daily county level reported COVID-19 occurrences from March 14-31, 2020.

Main Outcome(s) and Measure(s)

We developed a 3-stage model to quantify, firstly the probability of COVID-19 occurrence for unaffected counties using XGBoost classifier and secondly, the number of potential occurrences of a county via XGBoost regression. Thirdly, these results are combined to compute the county level risk. This risk is then used as an estimated after-five-day-vulnerability of the county.

Results

Using data from March 14-31, 2020, the model shows a sensitivity over 71.5% and specificity over 94%.

Conclusions and Relevance

We found that population, population density, percentage of people aged 70 or greater and prevalence of comorbidities play an important role in predicting COVID-19 occurrences. We found a positive association between affected and urban counties as well as less vulnerable and rural counties. The developed model can be used for identification of vulnerable counties and potential data discrepancies. Limited testing facilities and delayed results introduces significant variation in reported cases and produces a bias in the model.

Trial Registration

Not Applicable

Key Points

Question

What are key factors that define the vulnerability of counties in the US to cases of the COVID-19 virus?

Findings

In this epidemiological study based on publicly available data, we develop a model that predicts vulnerability to COVID-19 for each US county in terms of likelihood of going from no documented cases to at least one case within five days and in terms of number of occurrences of the virus.

Meaning

Predicting county vulnerability to COVID-19 can assist health organizations to better plan for resource and workforce needs.
Noisy Pooled PCR for Virus Testing
Authors: Zhu Junan , Rivera Kristina , Baron Dror
Published: April 2020

Fast testing can help mitigate the coronavirus disease 2019 (COVID-19) pandemic. Despite their accuracy for single sample analysis, infectious diseases diagnostic tools, like RT-PCR, require substantial resources to test large populations. We develop a scalable approach for determining the viral status of pooled patient samples. Our approach converts group testing to a linear inverse problem, where false positives and negatives are interpreted as generated by a noisy communication channel, and a message passing algorithm estimates the illness status of patients. Numerical results reveal that our approach estimates patient illness using fewer pooled measurements than existing noisy group testing algorithms. Our approach can easily be extended to various applications, including where false negatives must be minimized. Finally, in a Utopian world we would have collaborated with RT-PCR experts; it is difficult to form such connections during a pandemic.We welcome new collaborators to reach out and help improve this work!
Accelerometry-assessed sleep duration and timing in late childhood and adolescence in Scottish schoolchildren: a feasibility study
Authors: Lyall Laura M. , Sangha Natasha , Wyse Cathy , Hindle Elaine , Haughton Dawn , Campbell Kate , Brown Judith , Moore Laurence , Simpson Sharon A. , Inchley Joanna C. , Smith Daniel J.
Published: April 2020

Children and adolescents commonly suffer from sleep and circadian rhythm disturbances, which may contribute to poorer mental health and wellbeing during this critical developmental phase. Many studies however rely on self-reported sleep measures. This study assessed whether accelerometry data collection was feasible within the school setting as a method for investigating the extent of sleep and circadian disruption, and associations with subjective wellbeing, in Scotland. Fourteen days of wrist-worn accelerometry data were collected from 69 pupils, aged 10-14 years. Objective measures of sleep timing, sleep duration and circadian rest-activity patterns were derived. Questionnaires assessed subjective sleep timing, depressive symptoms, and experiences of wearing the accelerometer. Pupils slept on average less than 8 hours per night, failing to meet standard age-specific recommendations. Sleep timing was later and duration longer on weekends compared to weekdays (B = 0.87, 95% confidence interval (CI) 0.70, 1.04; B = 0.49, 95% CI 0.29, 0.69), indicating social jetlag. Lower daytime activity was correlated with higher depressive symptoms (r = -0.84, p = 0.008). Compared to primary school pupils, secondary pupils had shorter sleep window duration and lower circadian relative amplitude. Over half of participants reported some discomfort/inconvenience wearing the accelerometer. These data highlight that inadequate sleep is prevalent in this sample of schoolchildren. Future, larger scale investigations will examine in more detail the associations between sleep, circadian function and physical activity with mental health and wellbeing.
Identification and Estimation of Undetected COVID-19 Cases Using Testing Data from Iceland
Authors: Aspelund Karl M. , Droste Michael , Stock James H. , Walker Christopher D.
Published: April 2020

In the early stages of the COVID-19 pandemic, international testing efforts tended to target individuals whose symptoms and/or jobs placed them at a high presumed risk of infection. Testing regimes of this sort potentially result in a high proportion of cases going undetected. Quantifying this parameter, which we refer to as the undetected rate, is an important contribution to the analysis of the spread of the SARS-CoV-2 virus. We show that partial identification techniques can credibly deal with the data problems that common COVID-19 testing programs induce (i.e. excluding quarantined individuals from testing and low participation in random screening programs). We use public data from two Icelandic testing regimes during the first month of the outbreak and estimate an identified interval for the undetected rate. Our main approach estimates that the undetected rate was between 89% and 93% before the medical system broadened its eligibility criteria and between 80% and 90% after.
Association Between BCG Policy is Significantly Confounded by Age and is Unlikely to Alter Infection or Mortality Rates
Authors: Kirov Stefan
Published: April 2020

Recently a number of publications looked at the association between COVID-19 morbidity and mortality on one hand and countries’ policies with respect to BCG vaccination on the other. This connection arises from differences in the rates of infection in countries where BCG vaccination is mandatory compared to countries where mandatory vaccination no longer exists or was never implemented in the first place. In at least 2 preprint publications the authors expressed the view that the “known immunological benefits” of BCG vaccination may be behind the biological mechanism of such observation.

One study accounted for different income levels in different groups. Another study did not attempted to do so, instead exploring the differences between countries where a booster shot is given vs others where no such practice exists (finding no connection).

Both of these studies did not explore other potential confounding factors. Meanwhile the press has focused on these headlines and pushed the narrative that BCG vaccination is causally linked to infection and mortality rates. This poses a serious challenge, demonstrated by the recently initiated clinical trials on BCG vaccination within the COVID19 context.

This study shows that population age is a very significant confounding factor that explains the rates of infections much better and has a solid biology mechanism which explains this correlation. It suggests that BCG vaccination may have little or no causal link to infection rates and advises that any follow up studies should control for several confounding factors, such as population age, ethnicity, rates of certain chronic diseases, time from community spread start date, major public policy decisions and income levels.
Association of County-Level Socioeconomic and Political Characteristics with Engagement in Social Distancing for COVID-19
Authors: Kavanagh Nolan M. , Goel Rishi R. , Venkataramani Atheendar S.
Published: April 2020

The U.S. is the epicenter of the coronavirus disease 2019 (COVID-19) pandemic. In response, governments have implemented measures to slow transmission through “social distancing.” However, the practice of social distancing may depend on prevailing socioeconomic conditions and beliefs. Using 15–17 million anonymized cell phone records, we find that lower per capita income and greater Republican orientation were associated with significantly reduced social distancing among U.S. counties. These associations persisted after adjusting for county-level sociodemographic and labor market characteristics as well as state fixed effects. These results may help policymakers and health professionals identify communities that are most vulnerable to transmission and direct resources and communications accordingly.
Gaussian Statistics and Data-Assimilated Model of Mortality due to COVID-19: China, USA, Italy, Spain, UK, Iran, and the World Total
Authors: Lee T.-W. , Park J.E. , Hung David
Published: April 2020

Covid-19 is characterized by rapid transmission and severe symptoms, leading to deaths in some cases (ranging from 1.5 to 12% of the affected, depending on the country). We identify the Gaussian nature of mortality due to covid-19, as shown in China where it appears to have run its course (during the first sweep of the pandemic at least) and other coutnries, and also in Imperial College modeling. Gaussian distribution involves three parameters, the height, peak location and the width, and the streaming data can be used to infer function value, slope and inflection location as a minimum set of constraints to estimate the subsequent trajectories. Thus, we apply the Gaussian function template as the basis for a data-assimilated model of covid-19 trajectories, first to USA, United Kingdom (UK), Iran and the world total in this study. As more data become available, the Gaussian trajectories are updated, for other nations and also for state-by-state projections in USA.
Motion Sifnos: A randomized, double-blind, placebo-controlled study demonstrating the effectiveness of tradipitant in the treatment of motion sickness
Authors: Polymeropoulos Vasilios M. , É. Czeisler Mark , Gibson Mary M. , Anderson Austin A. , Miglo Jane , Wang Jingyuan , Xiao Changfu , Polymeropoulos Christos M. , Birznieks Gunther , Polymeropoulos Mihael H.
Published: April 2020

Background

Novel therapies are needed for the treatment of motion sickness given the inadequate relief, and bothersome and dangerous adverse effects of currently approved therapies. Neurokinin-1 (NK1) receptor antagonists have the potential to be effective in improving the symptoms of motion sickness, given the involvement of Substance P in nauseogenic and emetic pathways and the expression of NK1 receptors in the gastrointestinal system. Here, we evaluated the efficacy of tradipitant, a novel NK1 receptor antagonist, in preventing motion sickness in variable sea conditions.

Methods

A total of 126 adults participated in the Motion Sifnos Study. Groups of participants were assigned to one of seven boat trips lasting approximately four hours on the Pacific Ocean. Participants were randomized 1:1 to tradipitant 170 mg or placebo and completed the Motion Sickness Severity Scale (MSSS) every 30 minutes, in addition to other assessments. Severity of motion sickness was assessed with the incidence of vomiting and the MSSS.

Results

Participants on tradipitant had a significantly lower incidence of vomiting as compared to those on placebo across all boat trips (tradipitant=17.5%, placebo=39.7%, p=0.0039). For trips exposed to rough sea conditions, the difference in the incidence of vomiting between the groups was more dramatic (tradipitant=15.79%, placebo=72.22%, p=0.0009). Across these trips, motion sickness symptoms were significantly lower in the tradipitant group compared to the placebo group (tradipitant=3.19, placebo=4.57, p=0.0235).

Discussion

Tradipitant has the potential to be an effective therapy for the prevention of vomiting and treatment of nausea in people with motion sickness.
Covid-19 predictions using a Gauss model, based on data from April 2
Authors: Schüttler Janik , Schlickeiser Reinhard , Schlickeiser Frank , Kröger Martin
Published: April 2020

We propose a Gauss model (GM), a map from time to the bell-shaped Gauss function to model the deaths per day and country, as a quick and simple model to make predictions on the coronavirus epidemic. Justified by the sigmoidal nature of a pandemic, i.e. initial exponential spread to eventual saturation, we apply the GM to existing data, as of April 2, 2020, from 25 countries during first corona pandemic wave and study the model’s predictions. We find that logarithmic daily fatalities caused by Covid-19 are well described by a quadratic function in time. By fitting the data to second order polynomials from a statistical χ2-fit with 95% confidence, we are able to obtain the characteristic parameters of the GM, i.e. a width, peak height and time of peak, for each country separately, with which we extrapolate to future times to make predictions. We provide evidence that this supposedly oversimplifying model might still have predictive power and use it to forecast the further course of the fatalities caused by Covid-19 per country, including peak number of deaths per day, date of peak, and duration within most deaths occur. While our main goal is to present the general idea of the simple modeling process using GMs, we also describe possible estimates for the number of required respiratory machines and the duration left until the number of infected will be significantly reduced.
Rate and synchrony at the level of the auditory nerve are not sufficient to account for behaviorally estimated cochlear compression - a modeling study
Authors: Encina-Llamas Gerard , Lindahl Jens Thuren , Epp Bastian
Published: April 2020

Methods based on psychoacoustical forward masking have been proposed to estimate the local compressive growth of the basilar membrane (BM). This results from normal outer hair cells function, which leads to level-dependent amplification of BM vibration. Psychoacoustical methods assume that cochlear processing can be isolated from the response of the overall system, that sensitivity is dominated by the tonotopic location of the probe and that the effect of forward masking is different for on- and off-characteristic frequency (CF) maskers. In the present study, a computational model of the auditory nerve (AN) in combination with signal detection theory was used to test these assumptions. The underlying idea was that, for the BM compression to be estimated using psychoacoustics, enough information should be preserved at the level of the AN, because this forms an information bottleneck in the ascending auditory pathway. The simulated AN responses were quantified in terms of rate and synchrony for different types of AN fibers and CFs. The results show that, when using a low-intensity probe, local activity at the tonotopic location of the probe frequency is the dominant contributor to sensitivity in the healthy auditory system. However, on- and off-CF maskers produced similar forward masking onto the probe, which was mainly encoded by high- and to little extent by medium-spontaneous rate fibers. The simulation results suggested that the estimate of compression based on the behavioral experiments cannot be derived from sensitivity at the level of the AN but may require additional contributions, supporting previous physiological studies.
ESTIMATING COVID-19 INFECTIONS IN HOSPITAL WORKERS IN THE UNITED STATES
Authors: Razzak Junaid A. , Bhatti Junaid A. , Tahir Ramzan , Pasha-Razzak Omrana
Published: April 2020

Objective

We estimated that how many hospital workers in the United States (US) might get infected or die in the COVID-19 pandemic. We also estimated the impact of personal protective equipment (PPE) and age restrictions on these estimates.

Methods

Our secondary analyses estimated hospital worker infections in the US based on health worker infection and death rates per 100 deaths from COVID-19 in Hubei and Italy. We used Monte Carlo simulations to compute point estimates with 95% confidence intervals for hospital worker infections in the US based on the two scenarios. We computed potential decrease in infections if the PPE were available only to those involved in direct care of COVID-19 patients (∼ 30%) and if workers aged ≥ 60 years are restricted from patient care. Estimates were adjusted for hospital workers per bed in the US compared to China and Italy.

Results

The hospital worker infections per 100 deaths were 108.2 in Hubei and 94.1 in Italy. Based on Hubei scenario, we estimated that about 53,640 US hospital workers (95% CI: 43,160 to 62,251) might get infected from COVID-19. The Italian scenario suggested 53,097 US hospital worker (95% CI: 37,133 to 69,003) might get infected during the pandemic. Availability of PPE to high-risk workers could reduce counts to 28,100 (95% CI: 23,048 to 33,242) considering Hubei and to 28,354 (95% CI: 19,829 to 36,848) considering Italy. Restricting hospital workers aged ≥ 60 years from direct patient care reduced counts to 1,985 (95% CI: 1,627 to 2,347) considering Hubei and to 2,002 (95% CI: 1,400 to 2,602) considering the Italian scenario.

Conclusion

We estimated significant burden of illness due to COVID-19 if no strategies are adopted. Making PPE available to all hospital workers and reducing exposure of hospital workers above the age of 60 could have significant reductions in hospital worker infections.

VISUAL ABSTRACT

Figure 1.

Estimated number of COVID-19 related infections among healthcare workers in the United States based on Hubei and Italian scenarios
INFEKTA: A General Agent-based Model for Transmission of Infectious Diseases: Studying the COVID-19 Propagation in Bogotá - Colombia
Authors: Gomez Jonatan , Prieto Jeisson , Leon Elizabeth , Rodríguez Arles
Published: April 2020

The transmission dynamics of the coronavirus - COVID-19-have challenged humankind at almost every level. Currently, research groups around the globe are trying to figure out such transmission dynamics using different scientific and technological approaches. One of those is by using mathematical and computational models like the compartmental model or the agent-based models. In this paper, a general agent-based model, called INFEKTA, that combines the transmission dynamics of an infectious disease with agents (individuals) that can move on a complex network of accessible places defined over a Euclidean space representing a real town or city is proposed. The applicability of INFEKTA is shown by modeling the transmission dynamics of the COVID-19 in Bogotá city, the capital of Colombia.
Prediction of the clinical outcome of COVID-19 patients using T lymphocyte subsets with 340 cases from Wuhan, China: a retrospective cohort study and a web visualization tool
Authors: Liu Qibin , Fang Xuemin , Tokuno Shinichi , Chung Ungil , Chen Xianxiang , Dai Xiyong , Liu Xiaoyu , Xu Feng , Wang Bing , Peng Peng
Published: April 2020

Background

Wuhan, China was the epicenter of the 2019 coronavirus outbreak. As a designated hospital, Wuhan Pulmonary Hospital has received over 700 COVID-19 patients. With the COVID-19 becoming a pandemic all over the world, we aim to share our epidemiological and clinical findings with the global community.

Methods

In this retrospective cohort study, we studied 340 confirmed COVID-19 patients from Wuhan Pulmonary Hospital, including 310 discharged cases and 30 death cases. We analyzed their demographic, epidemiological, clinical and laboratory data and implemented our findings into an interactive, free access web application.

Findings

Baseline T lymphocyte Subsets differed significantly between the discharged cases and the death cases in two-sample t-tests: Total T cells (p < 2·2e-16), Helper T cells (p < 2·2e-16), Suppressor T cells (p = 1·8-14), and TH/TS (Helper/Suppressor ratio, p = 0·0066). Multivariate logistic regression model with death or discharge as the outcome resulted in the following significant predictors: age (OR 1·05, p 0·04), underlying disease status (OR 3·42, p 0·02), Helper T cells on the log scale (OR 0·22, p 0·00), and TH/TS on the log scale (OR 4·80, p 0·00). The McFadden pseudo R-squared for the logistic regression model is 0·35, suggesting the model has a fair predictive power.

Interpretation

While age and underlying diseases are known risk factors for poor prognosis, patients with a less damaged immune system at the time of hospitalization had higher chance of recovery. Close monitoring of the T lymphocyte subsets might provide valuable information of the patient’s condition change during the treatment process. Our web visualization application can be used as a supplementary tool for the evaluation.

Funding

The authors report no funding.
A Highly Scalable and Rapidly Deployable RNA Extraction-Free COVID-19 Assay by Quantitative Sanger Sequencing
Authors: Chandler-Brown Devon , Bueno Anna M. , Atay Oguzhan , Tsao David S.
Published: April 2020

There is currently an urgent unmet need to increase coronavirus disease 2019 (COVID-19) testing capability to effectively respond to the COVID-19 pandemic. However, the current shortage in RNA extraction reagents as well as limitations in qPCR protocols have resulted in bottlenecks in testing capacity. Herein, we describe a novel molecular diagnostic for COVID-19 based on Sanger sequencing. This assay uses the addition of a frame-shifted spike-in, a modified PCR master mix, and custom Sanger sequencing data analysis to detect and quantify SARS-CoV-2 RNA at a limit of detection comparable to existing qPCR-based assays, at 10-20 genome copy equivalents. Crucially, our assay was able to detect SARS-CoV-2 RNA from viral particles suspended in transport media that was directly added to the PCR master mix, suggesting that RNA extraction can be skipped entirely without any degradation of test performance. Since Sanger sequencing instruments are widespread in clinical laboratories and commonly have built-in liquid handling automation to support up to 3840 samples per instrument per day, the widespread adoption of qSanger COVID-19 diagnostics can unlock more than 1,000,000 tests per day in the US.
Role of RNA Guanine Quadruplexes in Favoring the Dimerization of SARS Unique Domain in Coronaviruses
Authors: Hognon Cécilia , Miclot Tom , Iriepa Cristina Garcia , Francés-Monerris Antonio , Grandemange Stephanie , Terenzi Alessio , Marazzi Marco , Barone Giampaolo , Monari Antonio
Published: April 2020

Coronaviruses may produce severe acute respiratory syndrome (SARS). As a matter of fact, a new SARS-type virus, SARS-CoV-2, is responsible of a global pandemic in 2020 with unprecedented sanitary and economic consequences for most countries. In the present contribution we study, by all-atom equilibrium and enhanced sampling molecular dynamics simulations, the interaction between the SARS Unique Domain and RNA guanine quadruplexes, a process involved in eluding the defensive response of the host thus favoring viral infection of human cells. Our results evidence two stable binding modes involving an interaction site spanning either the protein dimer interface or only one monomer. The free energy profile unequivocally points to the dimer mode as the thermodynamically favored one. The effect of these binding modes in stabilizing the protein dimer was also assessed, being related to its biological role in assisting SARS viruses to bypass the host protective response. This work also constitutes a first step of the possible rational design of efficient therapeutic agents aiming at perturbing the interaction between SARS Unique Domain and guanine quadruplexes, hence enhancing the host defenses against the virus.

TOC GRAPHICS
Clinical evaluation of a SARS-CoV-2 RT-PCR assay on a fully automated system for rapid on-demand testing in the hospital setting
Authors: Nörz Dominik , Fischer Nicole , Schultze Alexander , Kluge Stefan , Mayer-Runge Ulrich , Aepfelbacher Martin , Pfefferle Susanne , Lütgehetmann Marc
Published: April 2020

1

Background

The ongoing SARS-CoV-2 pandemic presents a unique challenge for diagnostic laboratories around the world. Automation of workflows in molecular diagnostics are instrumental for coping with the large number of tests ordered by clinicians, as well as providing fast-tracked rapid testing for highly urgent cases. In this study we evaluated a SARS-CoV-2 LDT for the NeuMoDx 96 system, a fully automated device performing extraction and real-time PCR.

Methods

A publicly available SARS-CoV-2 RT-PCR assay was adapted for the automated system. Analytical performance was evaluated using in-vitro transcribed RNA and clinical performance was compared to the cobas 6800-based reference assay within the lab.

Results

The NeuMoDx-sarbeco-LDT displayed good analytical performance with an LoD of 95.55 cp/ml and no false positives during evaluation of cross-reactivity. A total of 176 patient samples were tested with both the Sarbeco-LDT and the reference assay. Positive and negative agreement were 100% and 99.2% respectively. Invalid-rate was 6.3%.

Conclusion

The NeuMoDx-sarbeco-LDT showed analytical and clinical performance comparable to the cobas6800-based reference assay. Due to its random-access workflow concept and rapid time-to-result of about 80 minutes, the device is very well suited for providing fast-tracked SARS-CoV-2 diagnostics for urgent clinical samples in the hospital setting.

Highlights

A publicly available SARS-CoV-2 RT-PCR assay was adapted and evaluated on the open mode of the NeuMoDx 96 system (Qiagen)

The assay showed comparable analytical and clinical performance to the reference assay

Fast turn-around times (80 minutes) and random-access workflow of the system makes the assay well suited for urgent clinical samples.
New Epidemiological Model Suggestions Revealing Size of Epidemics Based on the COVID-19 Pandemic Example: Wavelength Models
Authors: Bulut Tevfik
Published: April 2020

The main purpose of the study is to introduce the wavelength models developed to measure the size of outbreaks based on the COVID-19 example. In this way, the wavelengths of the outbreaks can be calculated, ensuring that the outbreaks are valid, reliable and easy to follow at the national and international level. Wavelength models consist of approved case, death, recovered case and net wavelength models. Thus, the size of the outbreak can be measured both individually and as a whole. COVID-19 cases of 181 countries were used to demonstrate the application of the models. The prominent findings in the applied wavelength models are as follows: the countries with the highest case wavelength are USA, Italy, Spain and Germany, respectively. However, Italy ranks first in the death wavelength, followed by Spain, the USA and France. On the other hand, China has taken the first place in the recovered case wavelength. This country was followed by Spain and Germany and Italy, respectively. Based on all these wavelength models mentioned, net wavelength lengths are calculated. According to the findings of net wavelengths obtained, Canada ranked first, followed by United Kingdom, USA and Italy, respectively.
Efficient network immunization under limited knowledge
Authors: Liu Yangyang , Sanhedrai Hillel , Dong GaoGao , Shekhtman Louis M. , Wang Fan , Buldyrev Sergey V. , Havlin Shlomo
Published: April 2020

Targeted immunization or attacks of large-scale networks has attracted significant attention by the scientific community. However, in real-world scenarios, knowledge and observations of the network may be limited thereby precluding a full assessment of the optimal nodes to immunize (or remove) in order to avoid epidemic spreading such as that of current COVID-19 epidemic. Here, we study a novel immunization strategy where only n nodes are observed at a time and the most central between these n nodes is immunized (or attacked). This process is continued repeatedly until 1 − p fraction of nodes are immunized (or attacked). We develop an analytical framework for this approach and determine the critical percolation threshold pc and the size of the giant component P∞; for networks with arbitrary degree distributions P(k). In the limit of n → ∞ we recover prior work on targeted attack, whereas for n = 1 we recover the known case of random failure. Between these two extremes, we observe that as n increases, pc increases quickly towards its optimal value under targeted immunization (attack) with complete information. In particular, we find a new scaling relationship between |pc(∞) − pc(n) | and n as |pc(∞) − pc(n)| ~ n−1 exp(−αn). For Scale-free (SF) networks, where P(k) ~ k−γ, 2 < γ < 3, we find that pc has a transition from zero to non-zero when n increases from n = 1 to order of logN (N is the size of network). Thus, for SF networks, knowledge of order of logN nodes and immunizing them can reduce dramatically an epidemics.
Effectiveness of “Reducing Disability in Alzheimer’s Disease” among dyads with moderate dementia
Authors: Perales-Puchalt Jaime , Barton Kelli , Ptomey Lauren T , Niedens C. Michelle , Yeager Amy , Gilman Laura , Seymour Pam , George Amanda , Sprague Susan C. , Neira Antonio Mirás , Van Dyke Rik , Teri Linda , Vidoni Eric D
Published: April 2020

Interventions such as Reducing Disability in Alzheimer’s Disease (RDAD) improve the health of care receiver-caregiver dyads but plans to implement it locally in regional community agencies yielded three changes: 1) reduced reliance on licensed clinicians, 2) centralized exercise interventionists and 3) more flexible delivery. We aimed to assess the effectiveness of the Kansas City RDAD implementation (RDAD-KC) among a non-probabilistic sample of dyads with moderate dementia, which addressed these changes. We hypothesized that dyads’ health would improve from baseline to the end-of-treatment. Outcomes improved (p<0.01) from pre to post-intervention: Behavioral symptom severity (range 0-36) decreased from 11.3 to 8.6, physical activity increased from 125.0 to 190.0 minutes/week, caregiver unmet needs (range 0-34) decreased from 10.6 to 5.6, caregiver behavioral symptom distress (0-60) decreased from 15.5 to 10.4 and caregiver strain (0-26) decreased from 11.1 to 9.7. This adapted implementation of RDAD leads to clinically meaningful improvements and might inform scaling-up.
Applying the unified models of ecology to forecast epidemics, with application to Covid-19
Authors: Loberg Shelby W , Lehman Clarence
Published: April 2020

During a burgeoning outbreak of a novel disease, public attention will ordinarily expand as the severity of the outbreak expands--as infections multiply and news reports accumulate. Such public attention will in turn reinforce tactics to control the outbreak. In classical epidemiological models, effects of such tactics can be incorporated in standard parameters of transmission, recovery, and mortality. Unfortunately, early in an outbreak those individual parameters may be poorly known, hence corresponding models can get lost in uncertainty. This makes it difficult to determine whether the disease is spreading exponentially or logistically, or along another path. Examining cases over time is also problematic, as a logistically growing infection that is leveling off appears exponential in early phases. Here we report on the most basic mechanistic, ecological model we can imagine, which can help distinguish growth that is and is not under control. This approach did a satisfactory job predicting the final outcome of the Ebola outbreak of 2014-15. The model's two parameters were computable in real time, well before the outcome was actually known. The first parameter is an intrinsic rate of increase in cumulative deaths or reported cases. The second parameter is related to the human social system and represents all tactics that combine to control the outbreak. That parameter is coupled to the number of cumulative deaths or cases. We examine the basic mechanisms operating in this model and show the predictions made during the Ebola outbreak. We also consider how this basic model is performing for the Covid-19 pandemic and highlight ecological models that align with popularly discussed concepts such as flatten-the-curve, exponential growth, and inflection points of curves.
Chest CT Scan of Hospitalized Patients with COVID-19: A Case-Control Study
Authors: Wu Lianpin , Jin Qike , Chen Jie , He Jiawei , Dong Jianghu (James)
Published: April 2020

Introduction

This paper sought to investigate the clinical characteristic differences between suspected and confirmed patients with COVID-19 from CT scan to prevent and treat this infectious disease, since the coronavirus outbreak in the world has seriously affected the quality of life.

Methods

We proposed to use a retrospective case-control study to give a comparison between suspected patients and confirmed patients in the clinical characteristics.

Results

(56%) patients were confirmed for COVID-19 from suspected 167 patients. We find that elder people were more likely to be infected by COVID-19. Among the confirmed 94 patients, 2 (2%) patients were admitted to an intensive care unit, and 0 (0%) patients died during the study period. We find that images of CT scan of patients with a COVID-19 are significantly different from patients without a COVID-19.

Conclusions

To our best knowledge, it is the first time to use the case-control design to study the coronavirus disease, since it is particularly appropriate for investigating infectious disease outbreaks. The clinical treatment experience in this study can supply a guideline for treating COVID-19 as the number of the infected patients is increasing in the world. Compared with other studies, we find that the mortality rate and the intensive care unit rate can be reduced if patients can be treated timely in the right identification and detection with nucleic acid testing and chest CT scan. Therefore, we recommend nucleic acid testing and chest CT scan for the clinical treatment practice from this successful clinical treatment study.