bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilization and Costs by Primary Care Provider Type
Authors: Smith Valerie A. , Morgan Perri A. , Edelman David , Woolson Sandra L. , Berkowitz Theodore S.Z. , Van Houtven Courtney H. , Hendrix Cristina C. , Everett Christine M. , White Brandolyn S. , Jackson George L.
Published: April 2020

Objective:

The objective of this study was to compare health care utilization and costs among diabetes patients with physician, nurse practitioner (NP), or physician assistant (PA) primary care providers (PCPs).

Research Design and Methods:

Cohort study using Veterans Affairs (VA) electronic health record data to examine the relationship between PCP type and utilization and costs over 1 year in 368,481 adult, diabetes patients. Relationship between PCP type and utilization and costs in 2013 was examined with extensive adjustment for patient and facility characteristics. Emergency department and outpatient analyses used negative binomial models; hospitalizations used logistic regression. Costs were analyzed using generalized linear models.

Results:

PCPs were physicians, NPs, and PAs for 74.9% (n=276,009), 18.2% (n=67,120), and 6.9% (n=25,352) of patients respectively. Patients of NPs and PAs have lower odds of inpatient admission [odds ratio for NP vs. physician 0.90, 95% confidence interval (CI)=0.87–0.93; PA vs. physician 0.92, 95% CI=0.87–0.97], and lower emergency department use (0.67 visits on average for physicians, 95% CI=0.65–0.68; 0.60 for NPs, 95% CI=0.58–0.63; 0.59 for PAs, 95% CI=0.56–0.63). This translates into NPs and PAs having ~$500–$700 less health care costs per patient per year (P<0.0001).

Conclusions:

Expanded use of NPs and PAs in the PCP role for some patients may be associated with notable cost savings. In our cohort, substituting care patterns and creating similar clinical situations in which they practice, NPs and PAs may have reduced costs of care by up to 150–190 million dollars in 2013.
Immunological Profiling of Paediatric Inflammatory Bowel Disease Using Unsupervised Machine Learning
Authors: Coelho Tracy , Mossotto Enrico , Gao Yifang , Haggarty Rachel , Ashton James J. , Batra Akshay , Stafford Imogen S. , Beattie Robert M. , Williams Anthony P. , Ennis Sarah
Published: April 2020

Objectives:

The current classification of inflammatory bowel disease (IBD) is based on clinical phenotypes, which is blind to the molecular basis of the disease. The aim of this study was to stratify a treatment‐naïve paediatric IBD cohort through specific innate immunity pathway profiling and application of unsupervised machine learning (UML).

Methods:

In order to test the molecular integrity of biological pathways implicated in IBD, innate immune responses were assessed at diagnosis in 22 paediatric patients and 10 age‐matched controls. Peripheral blood mononuclear cells (PBMCs) were selectively stimulated for assessing the functionality of upstream activation receptors including NOD2, toll‐like receptor (TLR) 1‐2 and TLR4, and the downstream cytokine responses (IL‐10, IL‐1β, IL‐6, and TNF‐α) using multiplex assays. Cytokine data generated were subjected to hierarchical clustering to assess for patient stratification.

Results:

Combined immune responses in patients across 12 effector responses were significantly reduced compared with controls (P = 0.003) and driven primarily by “hypofunctional” TLR responses (P values 0.045, 0.010, and 0.018 for TLR4‐mediated IL‐10, IL‐1β, and TNF‐α, respectively; 0.018 and 0.015 for TLR1‐2 ‐mediated IL‐10 and IL‐1β). Hierarchical clustering generated 3 distinct clusters of patients and a fourth group of “unclustered” individuals. No relationship was observed between the observed immune clusters and the clinical disease phenotype.

Conclusions:

Although a clinically useful outcome was not observed through hierarchical clustering, our study provides a rationale for using an UML approach to stratify patients. The study also highlights the predominance of hypo‐inflammatory innate immune responses as a key mechanism in the pathogenesis of IBD.
Diagnosis and Management of Neonatal Herpes Simplex Infection in the Emergency Department
Authors: Ramgopal Sriram , Wilson Paria M. , Florin Todd A.
Published: April 2020

Neonatal herpes simplex virus infection (HSV) is rare in neonates, with an estimated global incidence of 10 per 100,000 live births. Neonatal HSV is challenging to diagnose due to often vague signs and symptoms. Untreated, the mortality of some HSV subtypes exceeds 80%. Overtesting and overtreatment can result in prolonged hospitalizations and expose neonates to medication toxicity. In contrast, prompt evaluation and use of empiric antiviral therapy before the results of definitive testing can improve outcomes for infants with HSV. A wide degree of practice variation exists with respect to testing and treatment for neonatal HSV, and more research is required to safely risk-stratify this population. This review presents the epidemiology, risk factors, presenting features, and emergency department management of neonatal HSV infection.
Venue-Based HIV Testing at Sex Work Hotspots to Reach Adolescent Girls and Young Women Living With HIV: A Cross-sectional Study in Mombasa, Kenya
Authors: Ma Huiting , Wang Linwei , Gichangi Peter , Mochache Vernon , Manguro Griffins , Musyoki Helgar K. , Bhattacharjee Parinita , Cholette François , Sandstrom Paul , Becker Marissa L. , Mishra Sharmistha ,   on behalf of the Transitions Study Team
Published: April 2020

Background:

We estimated the potential number of newly diagnosed HIV infections among adolescent girls and young women (AGYW) using a venue-based approach to HIV testing at sex work hotspots.

Methods:

We used hotspot enumeration and cross-sectional biobehavioral survey data from the 2015 Transition Study of AGYW aged 14–24 years who frequented hotspots in Mombasa, Kenya. We described the HIV cascade among young females who sell sex (YFSS) (N = 408) versus those young females who do not sell sex (YFNS) (N = 891) and triangulated the potential (100% test acceptance and accuracy) and feasible (accounting for test acceptance and sensitivity) number of AGYW that could be newly diagnosed through hotspot-based HIV rapid testing in Mombasa. We identified the profile of AGYW with an HIV in the past year using generalized linear mixed regression models.

Results:

N = 37/365 (10.1%) YFSS and N = 30/828 (3.6%) YFNS were living with HIV, of whom 27.0% (N = 10/37) and 30.0% (N = 9/30) were diagnosed and aware (P = 0.79). Rapid test acceptance was 89.3%, and sensitivity was 80.4%. There were an estimated 15,635 (range: 12,172–19,097) AGYW at hotspots. The potential and feasible number of new diagnosis was 627 (310–1081), and 450 (223–776), respectively. Thus, hotspot-based testing could feasibly reduce the undiagnosed fraction from 71.6% to 20.2%. The profile of AGYW who recently tested was similar among YFSS and YFNS. YFSS were 2-fold more likely to report a recent HIV test after adjusting for other determinants [odds ratio (95% confidence interval): 2.2 (1.5 to 3.1)].

Conclusion:

Reaching AGYW through hotspot-based HIV testing could fill gaps left by traditional, clinic-based HIV testing services.
Into the wild and on to the table: A Western Trauma Association multicenter analysis and comparison of wilderness falls in rock climbers and nonclimbers
Authors: Bernard Matthew , Martin Matthew J. , Corsa Josh , Robinson Bryce , Zeeshan Muhammad , Joseph Bellal , Morris David , Shillinglaw William , Schurr Michael , Smith Terrie , Lara Sabino , Brown Carlos , Harrell Kevin , Maxwell Robert , Berndtson Allison E. , Curry Terry , Kaups Krista , Dirks Rachel , Rott Michael , Schroeppel Thomas , Stillman Zachery , Warriner Zachary , Inaba Kenji , Burlew Clay , Robinson Caitlin , Jackson Rebecca , Dunn Julie , Chapin Trinette , Wilson Alison , Moulton Steve , Phillips Ryan , Shahi Niti , Urban Shane , Velopulos Catherine , Davenport Daniel , C. Bernard Andrew
Published: April 2020

BACKGROUND

Wilderness activities expose outdoor enthusiasts to austere environments with injury potential, including falls from height. The majority of published data on falls while climbing or hiking are from emergency departments. We sought to more accurately describe the injury pattern of wilderness falls that lead to serious injury requiring trauma center evaluation and to further distinguish climbing as a unique pattern of injury.

METHODS

Data were collected from 17 centers in 11 states on all wilderness falls (fall from cliff: International Classification of Diseases, Ninth Revision, e884.1; International Classification of Diseases, 10th Revision, w15.xx) from 2006 to 2018 as a Western Trauma Association multicenter investigation. Demographics, injury characteristics, and care delivery were analyzed. Comparative analyses were performed for climbing versus nonclimbing mechanisms.

RESULTS

Over the 13-year study period, 1,176 wilderness fall victims were analyzed (301 climbers, 875 nonclimbers). Fall victims were male (76%), young (33 years), and moderately injured (Injury Severity Score, 12.8). Average fall height was 48 ft, and average rescue/transport time was 4 hours. Nineteen percent were intoxicated. The most common injury regions were soft tissue (57%), lower extremity (47%), head (40%), and spine (36%). Nonclimbers had a higher incidence of severe head and facial injuries despite having equivalent overall Injury Severity Score. On multivariate analysis, climbing remained independently associated with increased need for surgery but lower odds of composite intensive care unit admission/death. Contrary to studies of urban falls, height of fall in wilderness falls was not independently associated with mortality or Injury Severity Score.

CONCLUSION

Wilderness falls represent a unique population with distinct patterns of predominantly soft tissue, head, and lower extremity injury. Climbers are younger, usually male, more often discharged home, and require more surgery but less critical care.

LEVEL OF EVIDENCE

Epidemiological, Level IV.
A globally available COVID-19 – Template for clinical imaging studies
Authors: Salg G.A. , Ganten M.K. , Baumhauer M. , Heußel C.P. , Kleesiek J.
Published: April 2020

Background

The pandemic spread of COVID-19 has caused worldwide implications on societies and economies. Chest computed tomography (CT) has been found to support both, current diagnostic and disease monitoring. A joint approach to collect, analyze and share clinical and imaging information about COVID-19 in the highest quality possible is urgently needed.

Methods

An evidence-based reporting template was developed for assessing COVID-19 pneumonia using an FDA-approved medical software. The annotation of qualitative and quantitative findings including radiomics features is performed directly on primary imaging data. For data collection, secondary information from the patient history and clinical data such as symptoms and comorbidities are queried.

Results

License-royalty free, cloud-based web platform and on-premise deployments are offered. Hospitals can upload, assess, report and if pseudonymized share their COVID-19 cases. The aggregation of radiomics in correlation with rt-PCR, patient history, clinical and radiological findings, systematically documented in a single database, will lead to optimized diagnosis, risk stratification and response evaluation. A customizable analytics dashboard allows the explorative real-time data analysis of imaging features and clinical information.

Conclusions

The COVID-19-Template is based on a systematic, computer-assisted and context-guided approach to collect, analyze and share data. Epidemiological and clinical studies for therapies and vaccine candidates can be implemented in compliance with high data quality, integrity and traceability.

An additional explanation video of the COVID-19-Template video is provided via:http://cloud1.mint-medical.de/downloads/player/index.html?v=Covid19StandardizedAssessmentWeb

Highlights

Dynamic evidence-based electronic case report form (eCRF) for COVID-19 including documentation of primary imaging data, secondary clinical data and patient history including radiomics features

Computer-assisted, context-guided reporting approach based on FDA approved medical product software package available free of charge

Data quality, traceability, integrity in open-access web platform

Customizable analytics dashboard for explorative real-time data analysis of imaging features and clinical information

Human and machine-readable data export for clinical trials
Clinical and epidemiological characteristics of Coronavirus Disease 2019 (COVID-19) patients
Authors: Tan Shing Cheng
Published: April 2020

Background

Numerous groups have reported the clinical and epidemiological characteristics of Coronavirus Disease 2019 (COVID-19) cases; however, the data remained inconsistent. This paper aimed to pool the available data to provide a more complete picture of the characteristics of COVID-19 patients.

Methods

A systematic review and pooled analysis was performed. Eligible studies were identified from database and hand searches up to March 2, 2020. Data on clinical (including laboratory and radiological) and epidemiological (including demographic) characteristics of confirmed COVID-19 cases were extracted and combined by simple pooling.

Results

Of 644 studies identified, 69 studies (involving 48,926 patients) were included in the analysis. The average age of the patients was 49.16 years. A total of 51.46% of the patients were men and 52.32% were non-smokers. Hypertension (50.82%) and diabetes (20.89%) were the most frequent comorbidities observed. The most common symptoms were fever (83.21%), cough (61.74%), and myalgia or fatigue (30.22%). Altered levels of blood and biochemical parameters were observed in a proportion of the patients. Most of the patients (78.50%) had bilateral lung involvements, and 5.86% showed no CT findings indicative of viral pneumonia. Acute respiratory distress syndrome (28.36%), acute cardiac injury (7.89%) and acute kidney injury (7.60%) were the most common complications recorded.

Conclusions

Clinical and epidemiological characteristics of COVID-19 patients were mostly heterogeneous and non-specific. This is the most comprehensive report of the characteristics of COVID-19 patients to date. The information presented is important for improving our understanding of the spectrum and impact of this novel disease.
Management of rheumatic diseases in the times of COVID-19 pandemic- perspectives of rheumatology practitioners from India
Authors: Gupta Latika , Misra Durga Prasanna , Agarwal Vishwesh , Balan Suma , Agarwal Vikas
Published: April 2020

Objective

The Coronavirus disease 19 (COVID-19) pandemic has led to widespread concerns about the risk of infection in patients with rheumatic diseases (RD) receiving disease modifying ant-rheumatic drugs (DMARDs) and other immunosuppressants (IS).

Methods

A SurveyMonkey® based electronic survey was conducted amongst members of the Indian Rheumatology Association to understand the need for changes in prevailing practices.

Results

Of the 861 invitees, 221 responded. In the wake of the pandemic, 47.5% would reduce biological DMARDs (bDMARDs) while only 12.2% would reduce the use of conventional synthetic DMARDs. 64.2% were likely to defer change in IS, the reluctance being most with rituximab (58.3%) followed by cyclophosphamide (53.3%), anti-tumor necrosis factor alpha agents (52.4%) and Janus kinase inhibitors (34.39%).

Hydroxychloroquine was the preferred choice (81.9%) for the treatment of COVID-19 followed by protease inhibitors (22.1%) and intravenous immunoglobulin (8.1%). Chloroquine was less preferred (19%). More than two-thirds (70.5%) believed that COVID-19 might trigger macrophage activation syndrome. Social distancing (98.1%) and hand hygiene (74.6%) were recommended by majority. 62.8% would avoid touch for clinical examination whenever feasible.

Conclusion

Most rheumatologists perceived the need to change treatment of RDs during the COVID-19 pandemic; reduce immunosuppression and defer the usage of rituximab and bDMARDs.

Key messages

What is already known about this subject?

Patients with rheumatic diseases receiving glucocorticoids, disease modifying ant-rheumatic drugs and other immunosuppressants have increased susceptibility to infections including respiratory tract infections

What does this study add?

○

There is an urgent need to revise the management of rheumatic diseases as perceived by a large group of practicing rheumatologists in India in the times of the COVID-19 pandemic.

○

There is reluctance to initiate biological DMARDs (especially Rituximab and anti-TNF agents), tsDMARDs (JAK inhibitors) and cyclophosphamide.

○

There is an inclination to prescribe hydroxychloroquine (HCQ) even for rheumatic diseases with weak level of evidence.

How might this impact on clinical practice?

This might identify areas to be addressed in a Delphi exercise to develop expert evidence to guide the management of RDs during the pandemic.
Genomic Analysis of Cardiac Surgery-Associated Mycobacterium chimaera Infections in Italy
Authors: Ghodousi Arash , Borroni Emanuele , Peracchi Marta , Palù Giorgio , Fallico Loredana , Rassu Mario , Manfrin Vinicio , Mantegani Paola , Monzillo Vincenzina , Manganelli Riccardo , Tortoli Enrico , Cirillo Daniela Maria
Published: April 2020

One hundred and twenty-two Mycobacterium chimaera strains isolated in Italy from cardiac surgery-related patients, cardiac surgery-unrelated patients and from heater-cooler units, were submitted to whole-genome sequencing and to subsequent SNP analysis. All but one strains isolated from cardiac surgery-related patients belonged to Subgroup 1.1 (19/23) or Subgroup 1.8 (3/23). Only 28 out of 79 strains isolated from heater-cooler units belonged to groupings other than 1.1 and 1.8. The strains isolated from cardiac surgery-unrelated patients were instead distributed across the phylogenetic tree. Our data, the first on isolates from Italy, are in agreement with a recent large genomic study suggesting a common source, represented by strains belonging to Subgroups 1.1 and 1.8, of cardiac surgery-related Mycobacterium chimaera infections. The strains belonging to groupings other than 1.1 and 1.8 isolated from heather-cooler units evidently resulted from contaminations at hospital level and had no share in the Mycobacterium chimaera outbreak. One Mycobacterium chimaera strain investigated in this study proved distant from every previously known Mycobacterium chimaera Groups (1, 2, 3 and 4) and we propose to assign to a novel group, named” Group 5”.
Reduction in time delay of isolation in COVID-19 cases in South Korea
Authors: Ryu Sukhyun , Jang Cheolsun , Kim Baekjin
Published: April 2020

Korean public health authorities raised the public alert to its highest level on February 23, 2020 to mitigate the 2019 novel coronavirus disease epidemic. We have identified that the mean delay from symptom onset to isolation was reduced to one day after raising the alert. Vigilance can reduce this interval.
Toilets dominate environmental detection of SARS-CoV-2 virus in a hospital
Authors: Ding Zhen , Qian Hua , Xu Bin , Huang Ying , Miao Te , Yen Hui-Ling , Xiao Shenglan , Cui Lunbiao , Wu Xiaosong , Shao Wei , Song Yan , Sha Li , Zhou Lian , Xu Yan , Zhu Baoli , Li Yuguo
Published: April 2020

Background

Respiratory and faecal aerosols play a suspected role in transmitting the SARS-CoV-2 virus. We performed extensive environmental sampling in a dedicated hospital building for Covid-19 patients in both toilet and non-toilet environments, and analysed the associated environmental factors.

Methods

We collected data of the Covid-19 patients. 107 surface samples, 46 air samples, two exhaled condensate samples, and two expired air samples were collected were collected within and beyond the four three-bed isolation rooms. We reviewed the environmental design of the building and the cleaning routines. We conducted field measurement of airflow and CO2 concentrations.

Findings

The 107 surface samples comprised 37 from toilets, 34 from other surfaces in isolation rooms (ventilated at 30-60 L/s), and 36 from other surfaces outside isolation rooms in the hospital. Four of these samples were positive, namely two ward door-handles, one bathroom toilet-seat cover and one bathroom door-handle; and three were weakly positive, namely one bathroom toilet seat, one bathroom washbasin tap lever and one bathroom ceiling-exhaust louvre. One of the 46 air samples was weakly positive, and this was a corridor air sample. The two exhaled condensate samples and the two expired air samples were negative.

Interpretation

The faecal-derived aerosols in patients’ toilets contained most of the detected SARS-CoV-2 virus in the hospital, highlighting the importance of surface and hand hygiene for intervention.

Funding

The work were partially supported by the National Natural Science Foundation of China (no 41977370), the Research Grants Council of Hong Kong’s (no 17202719) (no C7025-16G), and Scientific Research Fund of Jiangsu Provincial Department of Health (no S21017002).
A computational approach to identify interfering medications on urine drug screening assays without data from confirmatory testing
Authors: Ayala-Lopez Nadia , Aref Layla , Colby Jennifer M. , Hughey Jacob J.
Published: April 2020

Background

Urine drug screening (UDS) assays can rapidly and sensitively detect drugs of abuse, but can also produce spurious results due to interfering substances. We previously developed an approach to identify interfering medications using electronic health record (EHR) data, but the approach was limited to UDS assays for which presumptive positives were confirmed using more specific methods. Here we adapted the approach to search for medications that cause false positives on UDS assays lacking confirmation data.

Methods

From our institution’s EHR data, we used our previous dataset of 698,651 UDS and confirmation results. We also collected 211,108 UDS results for acetaminophen, ethanol, and salicylates. Both datasets included individuals’ prior medication exposures. We hypothesized that the odds of a presumptive positive would increase following exposure to an interfering ingredient independently of exposure to the assay’s target drug(s). For a given assay-ingredient pair, we quantified potential interference as an odds ratio from logistic regression. We evaluated interference of selected compounds in spiking experiments.

Results

Compared to the approach requiring confirmation data, our adapted approach showed only modestly diminished ability to detect interfering ingredients. Applying our approach to the new data, three ingredients had a higher odds ratio on the acetaminophen assay than acetaminophen itself did: levodopa, carbidopa, and entacapone. The first two, as well as related compounds methyldopa and alpha-methyldopamine, produced presumptive positives at < 40 μg/mL.

Conclusions

Our approach can reveal interfering medications using EHR data from institutions at which UDS results are not routinely confirmed.
Injection Molded Autoclavable, Scalable, Conformable (iMASC) system for aerosol-based protection
Authors: Byrne James D. , Wentworth Adam J. , Chai Peter R. , Huang Hen-Wei , Babaee Sahab , Li Canchen , Becker Sarah L. , Tov Caitlynn , Min Soekkee , Traverso Giovanni
Published: April 2020

There is a dire need for personal protective equipment (PPE) within healthcare settings during the COVID-19 pandemic. In particular, single use disposable N95 face masks have been limited in supply. We have developed an Injection Molded Autoclavable, Scalable, Conformable (iMASC) system for aerosol-based protection. The iMASC system was designed as a reusable liquid silicone rubber mask with disposable N95 filter cartridges that can fit most face sizes and shapes. This system reduced the amount of N95 filter while preserving breathability and fit. Using finite element analysis, we demonstrated mask deformation and reaction forces from facial scans of twenty different wearers. In addition, we validated these findings by successful fit testing in twenty participants in a prospective clinical trial. The iMASC system has the potential to protect our healthcare workers with a reusable N95-comparable face mask that is rapidly scalable.
State-specific Projection of COVID-19 Infection in the United States and Evaluation of Three Major Control Measures
Authors: Chen Shi , Li Qin , Gao Song , Kang Yuhao , Shi Xun
Published: April 2020

Most models of the COVID-19 pandemic in the United States do not consider geographic variation and spatial interaction. In this research, we developed a travel-network-based susceptible-exposed-infectious-removed (SEIR) mathematical compartmental model system that characterizes infections by state and incorporates inflows and outflows of interstate travelers. Modeling reveals that curbing interstate travel when the disease is already widespread will make little difference. Meanwhile, increased testing capacity (facilitating early identification of infected people and quick isolation) and strict social-distancing and self-quarantine rules are most effective in abating the outbreak. The modeling has also produced state-specific information. For example, for New York and Michigan, isolation of persons exposed to the virus needs to be imposed within 2 days to prevent a broad outbreak, whereas for other states this period can be 3.6 days. This model could be used to determine resources needed before safely lifting state policies on social distancing.
Susceptible supply limits the role of climate in the COVID-19 pandemic
Authors: Baker Rachel E. , Yang Wenchang , Vecchi Gabriel A. , Metcalf C. Jessica E. , Grenfell Bryan T.
Published: April 2020

Preliminary evidence suggests that climate may modulate the transmission of SARS-CoV-2. Yet it remains unclear whether seasonal and geographic variations in climate can substantially alter the pandemic trajectory, given high susceptibility is a core driver. Here, we use a climate-dependent epidemic model to simulate the SARS-CoV-2 pandemic probing different scenarios of climate-dependence based on known coronavirus biology. We find that while variations in humidity may be important for endemic infections, during the pandemic stage of an emerging pathogen such as SARS-CoV-2 climate may drive only modest changes to pandemic size and duration. Our results suggest that, in the absence of effective control measures, significant cases in the coming months are likely to occur in more humid (warmer) climates, irrespective of the climate-dependence of transmission and that summer temperatures will not substantially limit pandemic growth.
Portable and accurate diagnostics for COVID-19: Combined use of the miniPCR thermocycler and a well-plate reader for SARS-CoV-2 virus detection
Authors: González-González Everardo , Santiago Grissel Trujillo-de , Mayorga Itzel Montserrat Lara- , Martínez-Chapa Sergio Omar , Moisés Alvarez Mario
Published: April 2020

The coronavirus disease 2019 (COVID-19) pandemic has crudely demonstrated the need for massive and rapid diagnostics. By the first week of July, more than 10,000,000 positive cases of COVID-19 have been reported worldwide, although this number could be greatly underestimated. In the case of an epidemic emergency, the first line of response should be based on commercially available and validated resources. Here, we demonstrate the use of the miniPCR, a commercial compact and portable PCR device recently available on the market, in combination with a commercial well-plate reader as a diagnostic system for detecting genetic material of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of COVID-19. We used the miniPCR to detect and amplify SARS-CoV-2 DNA sequences using the sets of initiators recommended by the World Health Organization (WHO) for targeting three different regions that encode for the N protein. Prior to amplification, samples were combined with a DNA intercalating reagent (i.e., EvaGreen Dye). Sample fluorescence after amplification was then read using a commercial 96-well plate reader. This straightforward method allows the detection and amplification of SARS-CoV-2 nucleic acids in the range of ∼625 to 2×105 DNA copies. The accuracy and simplicity of this diagnostics strategy may provide a cost-efficient and reliable alternative for COVID-19 pandemic testing, particularly in underdeveloped regions where RT-QPCR instrument availability may be limited. The portability, ease of use, and reproducibility of the miniPCR makes it a reliable alternative for deployment in point-of-care SARS-CoV-2 detection efforts during pandemics.
COVID-19 pandemic: Impact of lockdown, contact and non-contact transmissions on infection dynamics
Authors: Roy Shovonlal
Published: April 2020

COVID-19 coronavirus pandemic has virtually locked down the entire world of human population, and through its rapid and unstoppable spread COVID-19 has essentially compartmentalised the population merely into susceptible, exposed, infected and recovered classes. Adapting the classical epidemic modelling framework, two distinct routes of COVID-19 transmission are incorporated into a model: (a) direct person-to-person contact transmission, and (b) indirect airborne and fomites-driven transmission. The indirect non-contact transmission route needs to explored in models of COVID-19 spread, because evidences show that this route of transmission is entirely viable with hugely uncertain level of relative contribution. This theoretical study based on model simulations demonstrates the following: (1) Not incorporating indirect transmission route in the model leads to underestimation of the basic reproduction number, and hence will impact on the COVID-19 mitigation decisions; (2) Lockdown measures can suppress the primary infection peak, but will lead to a secondary peak whose relative strength and time of occurrence depend on the success and duration of the lockdown measures; (3) To make lockdown effective, a considerable level of reduction in both contact and non-contact transmission rates over a long period is required; (4) To bring down the infection cases below any hypothetical health-care capacity, reduction of non-contact transmission rate is key, and hence active measures should be taken to reduce non-contact transmission (e.g., extensive uses of areal and aerosol disinfectant in public spaces to improve contaminated surfaces and air); (5) Any premature withdrawal of lockdown following the sign of a brief retracement in the infection cases can backfire, and can lead to a quicker, sharper and higher secondary peak, due to reactivation of the two transmission routes. Based on these results, this study recommends that any exit policy from lockdown, should take into account the level of transmission reduction in both routes, the absolute scale of which will vary among countries depending on their health-service capacity, but should be computed using accurate time-series data on infection cases and transmission rates.
Modelling the impact of interventions on the progress of the COVID-19 outbreak including age segregation
Authors: Rodriguez Jorge , Paton Mauricio , Uratani Joao M , Acuna Juan M
Published: April 2020

Infectious diseases can be devastating, especially when new and highly contagious, producing epidemic outbreaks that can become pandemics. Such is the case of COVID-19, the worst pandemic the world has seen in more than 100 years. Predicting the course and outcomes of such a pandemic in relation to possible interventions is crucial for societal and healthcare planning and forecasting of resource needs. In this work a deterministic model was developed, using elements from the SIR-type models, that describes individuals in a population in compartments by infection stage and age group. The model assumes a close well-mixed community with no migrations. Infection rates and clinical and epidemiological information govern the transitions between stages of the disease. The present model provides a platform to build upon and its current low complexity retains accessibility to both experts and non-experts as well as policy makers to comprehend the variables and phenomena at play.
The impact of several possible interventions that have been or may be applied to slow the spread of the COVID-19 outbreak is evaluated. Key findings in our model simulation results indicate that (i) universal social isolation measures may be effective in reducing total fatalities only if they are strict and the average number of daily social interactions is reduced to very low numbers; (ii) selective isolation of only the age groups most vulnerable to the disease (i.e. older than 60) appears almost as effective in reducing total fatalities but at a much lower economic damage; (iii) the use of protective equipment (PPE) appears capable of very significantly reducing total fatalities if implemented extensively and to a high degree; (iv) extensive random testing of the population leading to infection recognition and subsequent immediate (self) isolation of the infected individuals, appears to be an ineffective intervention due to the required (unreachable with existing test sensitivities) high percentage of infection detections and the incapability to be sustained over time; (v) an increase in the number of critical care beds to directly save significant numbers of lives with a direct reduction in total final fatalities per each extra available critical care bed unit.
Control Strategies to Curtail Transmission of COVID-19
Authors: Shah Nita H. , Suthar Ankush H. , Jayswal Ekta N.
Published: April 2020

Recently the World Health Organization has declared the outbreak of a severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) as a pandemic, and declared it as Public Health Emergency of International Concern. More than 683,536 positive cases and 32,139 deaths caused by novel corona virus 2019 (COVID-19) has affected 199 countries and territories. This pandemic can transform into an extremely destructive form if we still do not take it seriously. In the present study, we propose a generalized SEIR model of COVID-19 to study the behaviour of its transmission under different control strategies. In the model, all possible cases of human to human transmission are taken care and its reproduction number is formulated to analyse accurate transmission dynamics of the coronavirus outbreak. Optimal control theory is applied in the model to pretend the impact of various intervention strategies, including voluntary quarantine, isolation of infected individuals, improving an individual’s immunity and hospitalisation. Also, effect of the control strategies on model is analysed graphically by simulating the model numerically.
Cyclic exit strategies to suppress COVID-19 and allow economic activity
Authors: Karin Omer , Bar-On Yinon M. , Milo Tomer , Katzir Itay , Mayo Avi , Korem Yael , Dudovich Boaz , Yashiv Eran , Zehavi Amos J. , Davidovitch Nadav , Milo Ron , Alon Uri
Published: April 2020

Many countries have applied lockdown that helped suppress COVID-19, but with devastating economic consequences. Here we propose exit strategies from lockdown that provide sustainable, albeit reduced, economic activity. We use mathematical models to show that a cyclic schedule of 4-day work and 10-day lockdown, or similar variants, can prevent resurgence of the epidemic while providing part-time employment. The cycle pushes the reproduction number R below one by reduced exposure time and by exploiting the virus latent period: those infected during work days reach peak infectiousness during lockdown days. The number of work days can be adapted in response to observations. Throughout, full epidemiological measures need to continue including hygiene, physical distancing, compartmentalization, testing and contact tracing. This conceptual framework, when combined with other interventions to control the epidemic, can offer the beginnings of predictability to many economic sectors.
Plasma Metabolomic and Lipidomic Alterations Associated with COVID-19
Authors: Wu Di , Shu Ting , Yang Xiaobo , Song Jian-Xin , Zhang Mingliang , Yao Chengye , Liu Wen , Huang Muhan , Yu Yuan , Yang Qingyu , Zhu Tingju , Xu Jiqian , Mu Jingfang , Wang Yaxin , Wang Hong , Tang Tang , Ren Yujie , Wu Yongran , Lin Shu-Hai , Qiu Yang , Zhang Ding-Yu , Shang You , Zhou Xi
Published: April 2020

The pandemic of the coronavirus disease 2019 (COVID-19) has become a global public health crisis. The symptoms of COVID-19 range from mild to severe conditions. However, the physiological changes associated with COVID-19 are barely understood. In this study, we performed targeted metabolomic and lipidomic analyses of plasma from a cohort of COVID-19 patients who had experienced different symptoms. We found the metabolite and lipid alterations exhibit apparent correlation with the course of disease in these COVID-19 patients, indicating that the development of COVID-19 affected whole-body metabolism of the patients. In particular, malic acid of the TCA cycle and carbamoyl phosphate of urea cycle reveal the altered energy metabolism and hepatic dysfunction, respectively. It should be noted that carbamoyl phosphate is profoundly down-regulated in fatal patients compared with mild patients. And more importantly, guanosine monophosphate (GMP), which is mediated by not only GMP synthase but also CD39 and CD73, is significant changed between healthy subjects and COVID-19 patients, as well as between the mild and fatal groups. In addition, the dyslipidaemia was observed in COVID-19 patients. Overall, the disturbed metabolic patterns have been found to align with the progress and severity of COVID-19. This work provides valuable knowledge about plasma biomarkers associated with COVID-19 and potential therapeutic targets, as well as important resource for further studies of COVID-19 pathogenesis.
A hybrid multi-scale model of COVID-19 transmission dynamics to assess the potential of non-pharmaceutical interventions
Authors: Bouchnita Anass , Jebrane Aissam
Published: April 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that emerged in Wuhan, China in December 2019. It has caused a global outbreak which represents a major threat to global health. Public health resorted to non-pharmaceutical interventions such as social distancing and lockdown to slow down the spread of the pandemic. However, the effect of each of these measures remains hard to quantify. We design a multi-scale model that simulates the transmission dynamics of COVID-19. We describe the motion of individual agents using a social force model. Each agent can be either susceptible, infected, quarantined, immunized or deceased. The model considers both mechanisms of direct and indirect transmission. We parameterize the model to reproduce the early dynamics of disease spread in Italy. We show that panic situations increase the risk of infection transmission in crowds despite social distancing measures. Next, we reveal that pre-symptomatic transmission accelerates the onset of the exponential growth of cases. After that, we demonstrate that the persistence of SARS-CoV-2 on hard surfaces determines the number of cases reached during the peak of the epidemic. Then, we show that the restricted movement of the individuals flattens the epidemic curve. Finally, model predictions suggest that measures stricter than social distancing and lockdown were used to control the epidemic in Wuhan, China.
Primate phageomes are structured by superhost phylogeny and environment
Authors: Gogarten Jan F. , Rühlemann Malte , Archie Elizabeth , Tung Jenny , Akoua-Koffi Chantal , Bang Corinna , Deschner Tobias , Muyembe-Tamfun Jean-Jacques , Robbins Martha M. , Schubert Grit , Surbeck Martin , Wittig Roman M. , Zuberbühler Klaus , Baines John F. , Franke Andre , Leendertz Fabian H. , Calvignac-Spencer Sébastien
Published: April 2020

The evolutionary origins of human-associated bacteriophage communities are poorly understood. To address this question, we examined fecal phageomes of 23 wild non-human primate taxa, including multiple representatives of all the major primate radiations, and find relatives of the majority of human-associated phages. Primate taxa have distinct phageome compositions that exhibit a clear phylosymbiotic signal, and phage-superhost co-divergence is detected for 44 individual phages. Within species, neighboring social groups harbor evolutionarily and compositionally distinct phageomes, structured by superhost social behavior. However, captive non-human primate phageomes are more similar to humans than their wild counterparts, revealing replacement of wild-associated phages with human-associated ones. Together, our results suggest that potentially labile primate-phage associations persisted across millions of years of evolution, potentially facilitated by transmission between groupmates.

One Sentence Summary

Relatives of human-associated phages in wild primates reveal ancient but dynamic superhost-phage associations shaped by social transmission.
Single cell plasticity and population coding stability in auditory thalamus upon associative learning
Authors: Taylor James Alexander , Hasegawa Masashi , Benoit Chloé Maëlle , Freire Joana Amorim , Theodore Marine , Ganea Dan Alin , Lu Tingjia , Gründemann Jan
Published: April 2020

Cortical and limbic brain areas are regarded as centres for learning. However, how thalamic sensory relays participate in plasticity upon associative learning, yet support stable long-term sensory coding remains unknown. Using a miniature microscope imaging approach, we monitor the activity of populations of auditory thalamus (MGB) neurons in freely moving mice upon fear conditioning. We find that single cells exhibit mixed selectivity and heterogeneous plasticity patterns to auditory and aversive stimuli upon learning, which is conserved in amygdala-projecting MGB neurons. In contrast to individual cells, population level encoding of auditory stimuli remained stable across days. Our data identifies MGB as a site for complex neuronal plasticity in fear learning upstream of the amygdala that is in an ideal position to drive plasticity in cortical and limbic brain areas. These findings suggest that MGB’s role goes beyond a sole relay function by balancing experience-dependent, diverse single cell plasticity with consistent ensemble level representations of the sensory environment to support stable auditory perception with minimal affective bias.
MiR-203 inhibits the proliferation, invasion, and migration of pancreatic cancer cells by down-regulating fibroblast growth factor 2
Authors: Fu Xi-Feng , Zhao Hai-Chao , Chen Chang-Zhou , Wang Kang , Gao Fei , Tian Yang-Zhang , Li Hui-Yu , Zhao Hao-Liang
Published: April 2020

Background

Aberrant fibroblast growth factor 2 (FGF2) expression is a major cause of poor prognosis in pancreatic cancer. MiR-203 is a newly discovered microRNA (miRNA) that can affect the biological behavior of tumors. This study investigated whether miR-203 can regulate FGF2 expression and its role in pancreatic cancer cell proliferation, apoptosis, invasion, and migration.

Methods

MiR-203 expression in different cell lines was examined by qRT-PCR, followed by the establishment of knockdown and overexpression cell models. We used the CCK-8 assay to examine cell proliferation and the annexin V-APC/7-AAD double-staining method to detect apoptosis. In addition, we used wound healing and transwell assays to investigate the effects of miR-203 on the migration and invasion of pancreatic cancer cells. The effects of miR-203 knockdown and overexpression on FGF2 mRNA expression were detected by qRT-PCR. We also overexpressed FGF2 and examined the effects of FGF2 overexpression on the proliferation, apoptosis, invasion, and migration of pancreatic cancer cells. The binding of miR-203 to FGF2 was assessed by a luciferase reporter assay.

Results

We found that the miR-203 expression level was significantly down-regulated in pancreatic cancer cells compared to normal pancreatic cells. Functionally, the knockdown of miR-203 inhibited cell proliferation and increased apoptosis. Equally important, miR-203 reduced the migration and invasion of pancreatic cancer cells. In addition, we found that miR-203 overexpression inhibited FGF2 expression in pancreatic cancer cells by qRT-PCR. FGF2 overexpression significantly affected the proliferation, invasion, and metastasis of pancreatic cancer cells. Mechanistically, miR-203 base-paired with the FGF2 mRNA, resulting in the knockdown of the FGF2 mRNA and the down-regulation of the FGF2 protein.

Conclusions

MiR-203 inhibits FGF2 expression, regulates the proliferation of pancreatic cancer cells, and inhibits the invasion and metastasis of pancreatic cancer cells.
Knowledge Beacons: Web Service Workflow for FAIR Data Harvesting of Distributed Biomedical Knowledge
Authors: Hannestad Lance M. , Dančík Vlado , Godden Meera , Suen Imelda W. , Huellas-Bruskiewicz Kenneth C. , Good Benjamin M. , Mungall Christopher J. , Bruskiewich Richard M.
Published: April 2020

The continually expanding distributed global compendium of biomedical knowledge is diffuse, heterogeneous and huge, posing a serious challenge for biomedical researchers in knowledge harvesting: accessing, compiling, integrating and interpreting data, information and knowledge. In order to accelerate research towards effective medical treatments and optimizing health, it is critical that efficient and automated tools for identifying key research concepts and their experimentally discovered interrelationships are developed.

As an activity within the feasibility phase of a project called “Translator”(https://ncats.nih.gov/translator) funded by the National Center for Advancing Translational Sciences (NCATS) to develop a biomedical science knowledge management platform, we designed a Representational State Transfer (REST) web services Application Programming Interface (API) specification, which we call a Knowledge Beacon. Knowledge Beacons provide a standardized basic workflow for the discovery of concepts, their relationships and associated supporting evidence from distributed online repositories of biomedical knowledge. This specification also enforces the annotation of knowledge concepts and statements to the NCATS endorsed the Biolink Model data model and semantic encoding standards (https://biolink.github.io/biolink-model/). Implementation of this API on top of diverse knowledge sources potentially enables their uniform integration behind client software which will facilitate research access and integration of biomedical knowledge.

Availability

The API and associated software is open source and currently available for access athttps://github.com/NCATS-Tangerine/translator-knowledge-beacon.
A rare variant in ANP32B impairs influenza virus replication in human cells
Authors: Staller Ecco , Baillon Laury , Frise Rebecca , Peacock Thomas P. , Sheppard Carol M. , Sancho-Shimizu Vanessa , Barclay Wendy
Published: April 2020

Viruses require host factors to support their replication, and genetic variation in such factors can affect susceptibility to infectious disease. Influenza virus replication in human cells relies on ANP32 proteins, which are involved in assembly of replication-competent dimeric influenza virus polymerase (FluPol) complexes. Here, we investigate naturally occurring single nucleotide variants (SNV) in the humanAnp32AandAnp32Bgenes. We note that variant rs182096718 inAnp32Bis found at a higher frequency than other variants in either gene. This SNV results in a D130A substitution in ANP32B, which is less able to support FluPol activity than wildtype ANP32B and binds FluPol with lower affinity. Interestingly, ANP32B-D130A exerts a dominant negative effect over wildtype ANP32B and interferes with the functionally redundant paralogue ANP32A. FluPol activity and virus replication are attenuated in CRISPR-edited cells expressing wildtype ANP32A and mutant ANP32B-D130A. We propose a model in which the D130A mutation impairs FluPol dimer formation, thus resulting in compromised replication. We suggest that both homozygous and heterozygous carriers of rs182096718 may have some genetic protection against influenza viruses.