bluuebunny/crossref_metadata_2025 huggingface dataset:
Perspectives on building sustainable newborn screening programs for sickle cell disease: Experiences from Tanzania
Authors: Bukini Daima , Nkya Siana , McCurdy Sheryl , Mbekenga Columba , Manji Karim , Parker Michael , Makani Julie
Published: October 2020

1.0

Prevalence of Sickle Cell Disease is high in Africa, with significant public health effects to the affected countries. Many of the countries with the highest prevalence of the disease also have poor health care system, high burden of infectious diseases with many other competing healthcare priorities. Though, considerable efforts have been done to implement newborn screening for Sickle Cell Disease programs in Africa but still coverage is low. Tanzania has one of the highest birth prevalence of children with Sickle Cell Disease in Africa. Also, it is one of many other African countries to implement pilot projects for Newborn Screening for Sickle Cell Disease to assess feasibility. Several efforts have been made afterwards to continue providing the screening services as well as comprehensive care for Sickle Cell Disease. Using qualitative methods, we conducted In- Depth Interviews and Focus Group Discussions with policy makers, health care providers and families to provide an analysis of their experiences and perspectives on efforts to expand and sustain Newborn Screening for Sickle Cell Disease and related comprehensive care services in the country. Findings have demonstrated both the opportunities and challenges in the implementation and sustainability of the services in low resource settings. A key area of strengthening is full integration of the services in countries’ health care systems to facilitate coverage, accessibility and affordability of the services. However, efforts at the local level to sustain the programs are encouraging and can be used as a model in other programs implemented in low resources settings.
Quantification of a Viromed Klinik Akut V 500 disinfection device to reduce the indirect risk of SARS-CoV-2 infection by aerosol particles
Authors: Kähler Christian J. , Fuchs Thomas , Hain Rainer
Published: October 2020

Indoor SARS-CoV-2 infections by droplets and aerosols are currently considered to be particularly significant. FFP2/3 respirator masks, which fit tightly and gap free, generally provide very good protection. In public transport, while shopping or in waiting rooms, they are therefore ideally suited to protect against direct and indirect infection. Unfortunately, these masks make it difficult to breathe and can be uncomfortable to wear in the long run. Therefore, these masks should be worn for a maximum of 3 × 75 minutes per day. These masks are therefore hardly suitable for schools or at work. The question therefore arises as to how people in closed rooms can be permanently protected from a SARS-CoV-2 infection. Large safety distances provide both self protection and protection of third parties, but they do not protect against indirect infection if the virus load in the room is high. Mouth and nose covers only offer protection of others against direct infection, but they do not protect the user against indirect infection. The same applies to faceshields and small protective walls. Indirect infections can be effectively prevented by free ventilation with windows or air conditioning systems that supply 100% outside air into the room, provided the air exchange rate is at minimum six times the room volume per hour. However, free ventilation by means of windows is rarely efficient enough, and in winter at the latest, it is no longer possible to open windows without wasting massive amounts of energy and endangering the health and well-being of people. The operation of air conditioning systems is also very energy-intensive during the cold season. Furthermore, most buildings do not have air conditioning systems. The question is therefore, how a largely safe protection against an indirect SARS-CoV-2 infection can be realized in closed rooms without wasting thermal energy and thus valuable resources. Technically, the problem can be solved with mobile disinfection devices or room air cleaners that separate the dangerous aerosol particles or inactivate the viruses by UV radiation or by contact with charge carriers. The potential of these devices is great and, since many German manufacturers produce these devices, they are also available. However, many of the devices offered do not provide effective protection because the volume flow is too small, the separation efficiency of the filters is too low and the performance of the UV and ionization unit is too weak. The Viromed Klinik Akut V 500 disinfection unit appears to meet the performance requirements and therefore the device is analyzed and evaluated in this study for its suitability to protect against SARS-CoV-2 infection.
The French Covid-19 contact tracing app: knowledge, attitudes, beliefs and practices of students in the health domain
Authors: Montagni Ilaria , Roussel Nicolas , Thiébaut Rodolphe , Tzourio Christophe
Published: October 2020

Background

Many countries around the world have developed mobile phone apps capable of supporting instantaneous contact tracing to control the Covid-19 pandemic. In France, a few people have downloaded and are using the StopCovid contact tracing app. Reasons for this low uptake are unexplored. Students in the health domain are especially concerned and their usage and opinions about the app can inform improvements and diffusion of StopCovid among young people.

Objective

To investigate health-related students’ knowledge, attitudes, beliefs and practices about the StopCovid app.

Methods

A field survey was conducted among 318 students at the health sciences campus of the University of Bordeaux, France, between September 25th and October 16th, 2020. Quota sampling method was used and descriptive statistics were performed.

Results

A total of 77.3% (246/318) students had heard about the app, but only 11.3% (36/318) had downloaded it and 4.7% (15/318) were still using it at the time of the survey. Main reasons for not using the app were: belief that it was not effective given its limited diffusion (17.6%, 37/210), lack of interest (17.6%, 37/210) and distrust in data security and fear to be geo-located (15.7%, 33/210). Among those who had not heard about the app, after a brief description of its functioning and confidentiality policy, 52.7% (38/72) would use it. Participants reported that the main solution for increasing the use of the app would be a better communication (71.4%, 227/318).

Conclusion

Even among health students, the contact tracing app was poorly used. Findings suggest that improved communication describing its advantages and simplicity of use, and clarifying false beliefs about the app could help improving significantly its uptake.
Perceived Risk and Distress related to COVID-19: Comparing Healthcare versus non-Healthcare Workers of Pakistan
Authors: Abid Adeel , Shahzad Hania , Khan Hyder Ali , Piryani Suneel , Khan Areeba Raza , Rabbani Fauziah
Published: October 2020

Background

Healthcare workers (HCWs) find themselves susceptible to contracting COVID-19 or being the source of exposure for their family members. This puts them at a high risk of psychological distress which may compromise patient care. In this study we aim to explore the risk perceptions and psychological distress between HCWs and non-healthcare workers (NHCWs) in Pakistan.

Methods

A cross-sectional study was conducted in Pakistan using an online self-administered questionnaire. Respondents were categorized into HCWs (completed or aspiring to complete education in Medicine or allied fields) and NHCWs. HCWs were further categorized into front-line (direct patient care) and back-end HCWs.

Results

Data from 1406 respondents (507 HCWs and 899 NHCWs) was analyzed. No significant difference was observed between HCWs and NHCWs’ perception of susceptibility and severity towards COVID-19. Healthcare graduates perceived themselves (66% students vs. 80% graduates, p-value 0.011) and their family (67% students vs. 82% graduates, p-value 0.008) to be more susceptible to COVID-19 than the healthcare students. Frontline HCWs perceived themselves (83% frontline vs. 70% back-end, p-value 0.003) and their family (84% frontline vs. 72% back-end, p-value 0.006) as being more susceptible to COVID-19 than back-end healthcare professionals. Over half of the respondents were anxious (54% HCWs and 55% NHCWs). Female gender, younger age and having COVID-19 related symptoms had a significant effect on the anxiety levels of both HCWs and NHCWs.

Conclusion

Frontline HCWs, healthcare students, young people, females and individuals with lower income were at a higher risk of psychological distress due to the pandemic. Government policies should thus be directed at ensuring the mental well-being of frontline HCWs, and improving their satisfaction in order to strengthen health care delivery system.
The COVID-19 Suffolk Events Toolkit (C-SET): A structured approach to conducting COVID-secure events
Authors: Chowdhury Avirup , Zermanos Terezija , Yu Xinming , Badrinath Padmanabhan
Published: October 2020

Objectives

To develop a toolkit to provide a structured framework for assessing whether large events are COVID-secure.

Study design

Cross-sectional reporting on the development of the COVID-19 Suffolk Events Toolkit (C-SET).

Methods

The toolkit was developed through an iterative process of writing, discussion, and modification, drawing upon national UK guidance. Pilot cases and a contemporaneous consultation with experts were also undertaken, and C-SET was revised in line with the findings.

Results

C-SET offers a robust, structured approach to identifying areas of concern and potential mitigations, and collates and synthesises current national UK guidance. A flexible, modular design allows it to provide high-level input across all types of event, and allow modification to suit the needs of individual organisations. It is applicable to a variety of users, including event organisers in need of a structure, or bodies whose role is to appraise such events. It provides a semi-quantitative summary output, and in conjunction with the detailed links to guidance in the framework, allows development of clear, actionable recommendations to tangibly improve the quality of events.

Conclusions

A necessary trade-off exists between COVID-related health risks and wider risks due to economic downturn, and facilitating large events in a way that minimises COVID transmission risk may offer a way to balance these competing priorities. C-SET was developed to provide a structured approach to identifying areas of improvement across key risk domains, and suggests potential mitigations that are underpinned by national UK guidance. Use of this toolkit may aid event organisers in developing COVID-secure events, and aid regulatory bodies in suggesting actionable recommendations through generation of a summary report of areas of concern.
Detection and Segmentation of Lesion Areas in Chest CT Scans For The Prediction of COVID-19
Authors: Ter-Sarkisov Aram
Published: October 2020

In this paper we compare the models for the detection and segmentation of Ground Glass Opacity and Consolidation in chest CT scans. These lesion areas are often associated both with common pneumonia and COVID-19. We train a Mask R-CNN model to segment these areas with high accuracy using three approaches: merging masks for these lesions into one, deleting the mask for Consolidation, and using both masks separately. The best model achieves the mean average precision of 44.68% using MS COCO criterion for instance segmentation across all accuracy thresholds. The classification model, COVID-CT-Mask-Net, which learns to predict the presence of COVID-19 vs common pneumonia vs control, achieves the 93.88% COVID-19 sensitivity, 95.64% overall accuracy, 95.06% common pneumonia sensitivity and 96.91% true negative rate on the COVIDx-CT test split (21192 CT scans) using a small fraction of the training data. We also analyze the effect of Non-Maximum Suppression of overlapping object predictions, both on the segmentation and classification accuracy. The full source code, models and pretrained weights are available on https://github.com/AlexTS1980/COVID-CT-Mask-Net.
COVID -19: could green tea catechins reduce the risks?
Authors: Storozhuk Maksim
Published: October 2020

Purpose

Several lines of emerging pharmacological and epidemiological evidence imply that overall risks related to COVID-19 may be reduced by green tea catechins. Therefore, it may be expected that countries with higher per/capita green tea consumption would be less affected by COVID-19. The aim of this study was to assess this possibility.

Methods

Among countries with at least 3 million population (n=134), countries with relatively high (above 150 g) per/capita green tea consumption have been identified (n=21); (ii) normalized to population values of COVID-19 cases (morbidity) and deaths (mortality) for groups of countries with high and low per/capita green tea consumption were compared.

Results

Striking differences in COVID-19 morbidity and mortality between groups of countries with ‘high’ and ‘low’ green tea consumption were found. The differences were still observed after the adjustment for the onset of the disease. An analysis using multiple linear regression approach suggests that the associations are present at the level of individual countries.

Conclusion

Evidence supporting the idea that green tea constituents could reduce overall risks related to COVID-19 has been obtained. The results are promising and are in line with emerging evidence from other studies including pharmacological ones. Nevertheless, because of limitations of this study the idea still should be considered as a hypothesis requiring further assessment. Several vaccines are currently validated for COVID-19 prevention and mass vaccination has already been started in many countries. Still, it is likely that the development of an efficient drug therapy that reduces COVID-19 severity/mortality would be important for rather prolonged time. In this context, the results obtained in this study may have significant implications.
SARS-CoV-2 specific memory T lymphocytes from COVID-19 convalescent donors: identification, biobanking and large-scale production for Adoptive Cell Therapy
Authors: Ferreras C , Pascual-Miguel B , Mestre-Durán C , Navarro-Zapata A , Clares-Villa L , Martín-Cortázar C , De Paz R , Marcos A , Vicario JL , Balas A , García-Sánchez F , Eguizabal C , Solano C , Mora-Rillo M , Soria B , Pérez-Martínez A
Published: October 2020

SARS-CoV-2 is causing a second outbreak so the hope for its complete eradication is far from happening. In the absence of effective vaccines, it is mandatory to find effective treatments with low adverse effects able to treat hospitalized patients with COVID-19 disease. In this work, we determined the existence of SARS-CoV-2 specific T cells within the CD45RA−T memory cells from the blood of convalescent donors. Memory T cells can respond quickly to the infection and provide long-term immune protection to reduce the severity of the COVID-19 symptoms. Also, CD45RA−memory T cells confer protection from other pathogens the donors encountered in their life. This is vital to clear other secondary infections usually developed in hospitalized COVID-19 patients. SARS-CoV-2 specific memory T cells were found within all the CD45RA−subsets CD3+, CD4+, CD8+, and in the central memory and effector memory subpopulations. The procedure to obtain the cells is feasible, easy to implement for small scale manufacture, quick and cost-effective involving minimal manipulation, and without GMP condition requirements. This biobank of specific SARS-CoV-2 memory T cells would be immediately available ‘off-the-shelf’ to treat moderate/severe cases of COVID-19 increasing the therapeutic options available for these patients.
MEGA: Machine Learning-Enhanced Graph Analytics for Infodemic Risk Management
Authors: Hang Ching Nam , Yu Pei-Duo , Chen Siya , Tan Chee Wei , Chen Guanrong
Published: October 2020

The COVID-19 pandemic brought not only global devastation but also an unprecedented infodemic of false or misleading information that spread rapidly through online social networks. Network analysis plays a crucial role in the science of fact-checking by modeling and learning the risk of infodemics through statistical processes and computation on mega-sized graphs. This paper proposes MEGA,Machine Learning-EnhancedGraphAnalytics, a framework that combines feature engineering and graph neural networks to enhance the efficiency of learning performance involving massive graphs. Infodemic risk analysis is a unique application of the MEGA framework, which involves detecting spambots by counting triangle motifs and identifying influential spreaders by computing the distance centrality. The MEGA framework is evaluated using the COVID-19 pandemic Twitter dataset, demonstrating superior computational efficiency and classification accuracy.
Profiling of circulating chromosome 21-encoded microRNAs, miR-155 and Let-7c, in Down Syndrome People
Authors: Pérez-Villareal Jesús Manuel , Aviña-Padilla Katia , López Evangelina Beltrán , Guadrón-Llanos Alma Marlene , López-Bayghen Esther , Magaña-Gómez Javier , Meraz-Ríos Marco Antonio , Varela-Echavarría Alfredo , Angulo-Rojo Carla
Published: October 2020

Down syndrome (DS), or Trisomy 21 (Ts21), is the most common chromosomal survival aneuploidy. Nevertheless, people with DS have compromised health, and the increase in their life expectancy further heightens the risk of developing chronic degenerative diseases such as obesity, dyslipidemias and diabetes mellitus associated with higher morbidity, and mortality for cardiovascular disease from an early age. DS is also accompanied by a higher risk of neurodegeneration. The extra genetic material that characterizes DS causes an imbalance in the genetic dosage, including overexpression of miR-155 and Let-7c miRNAs, both associated with cognitive impairment and dementia in adults. The dynamics of expression of their putative target genes in the early stages of the development of DS and their clinical associations, however, remain to be ascertained. This study aimed to evaluate the relative expression of miR-155 and Let-7c in young and adult individuals with DS and its possible association with biochemical indicators of lipid metabolism. The anthropometric, clinical, biochemical, and gene expression features of miR-155 and Let-7c were analyzed in a population of 52 control and 50 DS subjects divided into groups of 20 years of age or younger and 21 years or older. Expression changes for miR-155 were not significant. Nevertheless, a negative correlation for HDL-Cholesterol concentrations and miR-155 expression was identified. Notably, Let-7c was overexpressed in DS from young and old ages. Overall, our results suggest that Let-7c is related from early stages to cognitive impairment in DS, while a similar role of miR-155 in late stages could be mediated by alterations in lipid metabolism. Further studies with both miRNAs will shed light on their potential as therapeutic targets to prevent or delay cognitive impairment in DS.
An Inexpensive Smartphone-Based Device and Predictive Models for Rapid, Non-Invasive, and Point-of-Care Monitoring of Ocular and Cardiovascular Complications Related to Diabetes
Authors: Chakravadhanula Kasyap
Published: October 2020

Diabetes is a massive global problem, with growth especially rapid in developing regions, which can lead to several damaging complications. Among the most impactful of these are diabetic retinopathy, the leading cause of blindness among working class adults, and cardiovascular disease, the leading cause of death worldwide. However, diagnosis is often too late to prevent irreversible damage caused by these linked conditions. This study describes the development of an integrated test, automated and not requiring laboratory blood analysis, for screening of these conditions. First, a random forest model was developed by retrospectively analyzing the influence of various risk factors (obtained quickly and non-invasively) on cardiovascular risk. Next, a deep-learning model was developed for prediction of diabetic retinopathy from retinal fundus images by a modified and re-trained InceptionV3 image classification model. The input was simplified by automatically segmenting the blood vessels in the retinal image. The technique of transfer learning enables the model to capitalize on existing infrastructure on the target device, meaning more versatile deployment, especially helpful in low-resource settings. The models were integrated into a smartphone-based device, combined with an inexpensive 3D-printed retinal imaging attachment. Accuracy scores, as well as the receiver operating characteristic curve, the learning curve, and other gauges, were promising. This test is much cheaper and faster, enabling continuous monitoring for two damaging complications of diabetes. It has the potential to replace the manual methods of diagnosing both diabetic retinopathy and cardiovascular risk, which are time consuming and costly processes only done by medical professionals away from the point of care, and to prevent irreversible blindness and heart-related complications through faster, cheaper, and safer monitoring of diabetic complications. As well, tracking of cardiovascular and ocular complications of diabetes can enable improved detection of other diabetic complications, leading to earlier and more efficient treatment on a global scale.
Clinical evaluation of a fully automated, lab developed multiplex RT-PCR assay integrating dual-target SARS-CoV-2 and Influenza–A/B detection on a high-throughput platform
Authors: Nörz Dominik , Hoffmann Armin , Aepfelbacher Martin , Pfefferle Susanne , Lütgehetmann Marc
Published: October 2020

1

Background

Laboratories worldwide face high demands for molecular testing during the SARS-CoV-2 pandemic that might be further aggravated with the upcoming influenza season in the northern hemisphere. Considering that symptoms of influenza are largely undistinguishable from COVID-19, both SARS-CoV-2 and the Influenza viruses require concurrent testing by RT-PCR in patients presenting with symptoms of respiratory tract infection. In this study, we adapted and evaluated a laboratory developed multiplex RT-PCR assay for simultaneous detection of SARS-CoV-2 (dual-target), Influenza-A and Influenza-B (SC2/InflA/InflB-UCT) on a fully automated high-throughput system (cobas6800).

Methods

Analytical performance was assessed by serial dilution of quantified reference material and cell culture stocks in transport medium, including pre-treatment for chemical inactivation. For clinical evaluation, residual portions of 164 predetermined patient samples containing SARS-CoV-2 (n=52), Influenza-A (n=43) or Influenza-B (n=19), as well as a set of negative samples was subjected to the novel multiplex assay.

Results

The assay demonstrated analytical performance comparable to currently available commercial tests, with limits of detection of 94.9 cp/ml for SARS-CoV-2, 14.6 cp/ml for Influenza-A and 422.3 cp/ml for Influenza-B. Clinical evaluation showed excellent agreement with the comparator assays (sensitivity 98.1%, 97.7% and 100% for Sars-CoV-2, Influenza-A and -B respectively).

Conclusion

The SC2/InflA/InflB-UCT allows for efficient high-throughput testing for all three pathogens and thus provides streamlined diagnostics while conserving resources during the Influenza-season.

Highlights

Simultaneous detection of highly pathogenic respiratory viruses Influenza-A/B and SARS-CoV-2

Including a dual-target assay for SARS-CoV-2 detection

Full automation on the cobas6800 high-throughput platform
Estimating the Case Fatality Ratio for COVID-19 using a Time-Shifted Distribution Analysis
Authors: Thomas B. S. , Marks N. A.
Published: October 2020

Estimating the case fatality ratio (CFR) for COVID-19 is an important aspect of public health. However, calculating CFR accurately is problematic early in a novel disease outbreak, due to uncertainties regarding the time course of disease and difficulties in diagnosis and reporting of cases. In this work, we present a simple method for calculating the case fatality ratio using only public case and death data over time by exploiting the correspondence between the time distributions of cases and deaths. The time-shifted distribution (TSD) analysis generates two parameters of interest: the delay time between reporting of cases and deaths and the case fatality ratio. These parameters converge reliably over time once the exponential growth phase has finished. Analysis is performed for early COVID-19 outbreaks in many countries, and we discuss corrections to CFR values using excess-death and seroprevalence data to estimate the infection fatality ratio (IFR). While CFR values range from 0.2-20% in different countries, estimates for IFR are mostly around 0.5-0.8% for countries that experienced moderate outbreaks and 1-3% for severe outbreaks. The simplicity and transparency of TSD analysis enhance its usefulness in characterizing a new disease as well as the state of the health and reporting systems.
Ct threshold values, a proxy for viral load in community SARS-CoV-2 cases, demonstrate wide variation across populations and over time
Authors: Walker A. Sarah , Pritchard Emma , House Thomas , Robotham Julie V , Birrell Paul J , Bell Iain , Bell John I , Newton John N , Farrar Jeremy , Diamond Ian , Studley Ruth , Hay Jodie , Vihta Karina-Doris , Peto Tim , Stoesser Nicole , Matthews Philippa C. , Eyre David W. , Pouwels Koen B. ,   the COVID-19 Infection Survey team
Published: October 2020

Information on SARS-CoV-2 in representative community surveillance is limited, particularly cycle threshold (Ct) values (a proxy for viral load). Of 3,312,159 nose and throat swabs taken 26-April-2020 to 13-March-2021 in the UK’s national COVID-19 Infection Survey, 27,902(0.83%) were RT-PCR-positive, 10,317(37%), 11,012(40%) and 6,550(23%) for 3, 2 or 1 of the N, S and ORF1ab genes respectively, with median Ct=29.2 (∼215 copies/ml; IQR Ct=21.9-32.8, 14-56,400 copies/ml). Independent predictors of lower Cts (i.e. higher viral load) included self-reported symptoms and more genes detected, with at most small effects of sex, ethnicity and age. Single-gene positives almost invariably had Ct>30, but Cts varied widely in triple-gene positives, including without symptoms. Population-level Cts changed over time, with declining Ct preceding increasing SARS-CoV-2 positivity. Of 6,189 participants with IgG S-antibody tests post-first RT-PCR-positive, 4,808(78%) were ever antibody-positive; Cts were significantly higher in those remaining antibody-negative. Community SARS-CoV-2 Ct values could be a useful epidemiological early-warning indicator.

IMPACT STATEMENT

Ct values from SARS-CoV-2 RT-PCR tests vary widely and over calendar time. They have the potential to be used more broadly in public testing programmes as an “early-warning” system for shifts in infectious load and hence transmission.
Saliva is a promising alternative specimen for the detection of SARS-CoV-2 in children and adults
Authors: Yee Rebecca , Truong Thao , Pannaraj Pia S. , Eubanks Natalie , Gai Emily , Jumarang Jaycee , Turner Lauren , Peralta Ariana , Lee Yesun , Bard Jennifer Dien
Published: October 2020

Testing efforts for SARS-CoV-2 have been burdened by the scarcity of testing materials and personal protective equipment for healthcare workers. The simple and painless process of saliva collection allows for widespread testing, but enthusiasm is hampered by variable performance compared to nasopharyngeal swab (NPS) samples. We prospectively collected paired NPS and saliva samples from a total of 300 unique adult and pediatric patients. SARS-CoV-2 RNA was detected in 32.2% (97/300) of the individuals using the TaqPath COVID-19 Combo Kit (Thermo Fisher). Performance of saliva and NPS were compared against the total number of positives regardless of specimen type. The overall concordance for saliva and NPS was 91.0% (273/300) and 94.7% (284/300), respectively. The positive percent agreement (PPA) for saliva and NPS was 81.4% (79/97) and 89.7% (87/97), respectively. Saliva detected 10 positive cases that were negative by NPS. In symptomatic and asymptomatic pediatric patients not previously diagnosed with COVID-19, the performances of saliva and NPS were comparable (PPA: 82.4% vs 85.3%). The overall PPA for adults were 83.3% and 90.7% for saliva and NPS, respectively, with saliva detecting 4 cases less than NPS. However, saliva performance in symptomatic adults was identical to NPS (PPA of 93.8%). With lower cost and self-collection capabilities, saliva can be an appropriate alternative sample choice to NPS for detection of SARS-CoV-2 in children and adults.

Saliva is an acceptable alternative specimen compared to nasopharyngeal swabs for detection of SARS-CoV-2. Specifically, saliva demonstrated comparable performance to nasopharyngeal swabs in symptomatic and asymptomatic pediatric patients and in symptomatic adults.
Stay-at-home and face mask policies intentions inconsistent with incidence and fatality during US COVID-19 pandemic
Authors: Wu Samuel X. , Wu Xin
Published: October 2020

In addition to the United States CDC recommendations, many states imposed stay-at-home (SAH) and mandatory face mask (MFM) orders during COVID-19 pandemic. The purpose of this study was to characterize the relationship between SAH and MFM approaches with the incidence and fatality during the pandemic period until the 2020-08-23 (about 171 days). States with SAH orders showed potential decreases of infection and fatality during SAH period (about 45 days). However, many results in this study were inconsistent with the intent of public health strategies of SAH and MFM. There were similar incidence rates among SAH + MFM, SAH + no-MFM and no-SAH + no-MFM states. After normalized to population density, there were no significant differences in total positive cases, average daily new cases and average daily fatality among the 3 groups during the pandemic period. This study suggested that SAH and MFM orders in the general public alone, probably have limited effects in lowering transmission and fatality. From the policy-making level, if we cannot strictly isolate contagious patients with effective contact tracing, we presume that following the CDC recommendations could be appropriate in helping mitigate the COVID-19 disaster and limiting collateral social-economic damage with close monitoring of healthcare capacity.
Incidence and risk factors of pulmonary hypertension after venous thromboembolism: An analysis of a large healthcare database
Authors: Lutsey Pamela L. , Prins Kurt W. , Evensen Line H. , Walker Rob F. , Farley Joel F. , MacLehose Richard F. , Alonso Alvaro , Zakai Neil A. , Thenappan Thenappan
Published: October 2020

Background

Pulmonary hypertension (PH) is a devastating potential complication of pulmonary embolism (PE), a manifestation of venous thromboembolism (VTE). The incidence of and risk factors for PH in those with prior VTE is poorly characterized.

Methods

ICD codes from inpatient and outpatient medical claims from MarketScan administrative databases for years 2011-2018 were used were used to identify cases of VTE, comorbidities prior to the VTE event, and PH occurring subsequent to the VTE event. Cumulative incidence and hazard ratios (HR), and their 95% confidence intervals (CI), were calculated.

Results

The 170,021 VTE cases included in the analysis were on average (± SD) 57.5 ± 15.8 years old and 50.5% were female. A total of 5,946 PH cases accrued over an average follow-up of 1.94 years. Two years after incident VTE the cumulative incidence (95% CI) of PH was 3.5% (3.4%, 3.7%) overall. It was higher among women [3.9% (3.8%-4.1%)] than men [3.2% (3.0%-3.3%)], and among patients presenting with PE [6.2% (6.0%-6.5%)] than those presenting with deep vein thrombosis-only [1.1% (1.0%-1.2%)]. Adjusting for age and sex, risk of PH was higher among VTE patients with underlying comorbidities. The strongest associations were observed with concomitant heart failure [HR: 2.17 (1.04-2.31)], chronic pulmonary disease [2.01 (1.90-2.14)], and myocardial infarction [1.53 (1.40-1.67)].

Conclusions

In this large real-world population of insured people with VTE, 3.5% developed PH in the 2 years following their initial VTE event. Risk was higher among women, with increasing age, and in those with additional comorbidities at the time of the VTE event. These data provide insights into the burden of PH and risk factors for PH among VTE patients.
Efficacy of Convalescent Plasma Therapy compared to Fresh Frozen Plasma in Severely ill COVID-19 Patients: A Pilot Randomized Controlled Trial
Authors: Bajpai Meenu , Kumar Suresh , Maheshwari Ashish , Chhabra Karan , kale Pratibha , Gupta Amita , Narayanan Ashad , Gupta Ekta , Trehanpati Nirupama , Bihari Chhagan , Agarwal Reshu , Gupta Kamini , Gupta Upendra kumar , Bhardwaj Ankit , Kumar Guresh , Islam Mojahidul , Singh Ravinder , Yadav Pushpa , Maiwall Rakhi , Sarin Shiv Kumar
Published: October 2020

Background

The role of convalescent plasma (COPLA) for the treatment of severely ill Corona Virus Disease-2019 is under investigation. We compared the efficacy and safety of convalescent plasma with fresh frozen plasma (FFP) in severe COVID-19 patients.

Methods and findings

This was an open-label, single-centre phase II RCT on 29 patients with severe COVID-19 from India. One group received COPLA with standard medical care (SMC) (n=14), and another group received FFP with SMC (n=15). A total of 29 patients were randomized in the two treatment groups. Eleven out of 14 (78.5%) patients remained free of ventilation at day seven in the intervention arm while the proportion was 14 out of 15 (93.3 %) in the control arm (p= 0.258). The median reductions in RR per min at 48-hours in COPLA-group and FFP group were -6.5 and -3 respectively [p=0.004] and at day seven were -14.5 and -10 respectively (p=0.008). The median improvements in percentage O2 saturation at 48-hours were 6.5 and 2 respectively [p=0.001] and at day seven were 10 and 7.5 respectively (p=0.026). In the COPLA-group, the median improvement in PaO2/FiO2 was significantly superior to FFP at 48-hours [41.94 and 231.15, p=0.009], and also at day-7 [5.55 and 77.01 p<0.001]. We did not find significant differences in hospitalization duration between the groups (0.08).

Conclusion

COPLA therapy resulted in rapid improvement in respiratory parameters and shortened time to clinical recovery, although no significant reduction in mortality was observed in this pilot trial. We need larger trials to draw conclusive evidence on the use of Convalescent plasma in COVID-19. This trial is registered with ClinicalTrial.gov (identifier: NCT04346446).
The Genetics and Evolution of Eye Color in Domestic Pigeons (Columba livia)
Authors: Si Si , Xu Xiao , Zhuang Yan , Gao Xiaodong , Zhang Honghai , Zou Zhengting , Luo Shu-Jin
Published: October 2020

The avian eye color, generally referred to the color of the iris, results from both pigments and structural coloration. Avian iris colors exhibit striking interspecific and, in some domestic species, intraspecific variations, suggesting unique evolutionary and ecological histories. Here we tackled the genetic basis of the pearl (white) iris color in domestic pigeons (Columba livia), to elucidate the largely unknown genetic mechanism underlying the evolution of avian iris coloration. Using a genome-wide association study (GWAS) in 92 pigeons, we mapped the pearl iris trait to a 9 kb region and a facilitative glucose transporter geneSLC2A11B. A nonsense mutation W49X leading to a premature stop codon in SLC2A11B was identified as the causal variant. Transcriptome analysis suggested that SLC2A11B loss-of-function may downregulate the xanthophore-differentiation geneCSF1R, and a key geneGCH1involved in biosynthesis of pteridine, whose absence results in pearl iris. Coalescence and phylogenetic analyses indicated the mutation originated about 5,400 years ago coinciding with the onset of pigeon domestication, while positive selection was detected likely associated with artificial breeding. Within Aves, potentially impaired SLC2A11B was found in 10 species from six distinct lineages correlated to their signature brown or blue eyes. Analysis of vertebrate SLC2A11B orthologs revealed relaxed selection in the avian clade, consistent with the scenario that, during and after avian divergence from reptile ancestor, the SLC2A11B-involved development of dermal chromatophores likely degenerated due to feather coverage. Our findings provide new insight into the mechanism of avian iris color variations and the evolution of pigmentation in vertebrates.
Reelin haploinsufficiency affects skilled motor performance associated with suppression of training-induced gene enrichment, synaptic function and activity-dependent cortical plasticity in mice
Authors: Nishibe Mariko , Toyoda Hiroki , Katsuyama Yu
Published: October 2020

RELN (Reelin) is one of the genes implicated in neurodevelopmental psychiatric vulnerability. Patients with neurodevelopmental disorders can experience impairments in fine motor skills. While Reelin modulates synaptic function, whether Reelin haploinsufficiency affects activity-dependent cortical plasticity which supports development of skilled movement is unclear. Here, heterozygousReelermutant (HRM) andDab1floxed/ +;Emx1-Cremice both displayed learning improvements measured by the reach-to-grasp task, but their performance levels of the forelimb motor skill were lower, compared with controls. The level of skilled motor performance was correlated with the area of cortical representations of the trained forelimb, examined after 10 days of training. Furthermore, we hypothesized that the genetic haploinsufficiency also alters changes that occur during the early phase of the training. Examined on day 3, the training induced synaptic modifications of the layer III cortical neurons in (wild-type) WT mice, which were contributed by synaptic potentiation and increase in spontaneous action-potential driven glutamatergic-transmission. On the other hand, the basal excitatory and inhibitory synaptic function were depressed, affected both by presynaptic and postsynaptic synaptic impairments in naive HRM; and thus, no further training-induced synaptic plasticity occurred in HRM. Lastly, examined after 3 days of training, the gene enrichment observed in trained WT mice was absent in trained HRM mice. The finding suggests the Reelin haploinsufficiency alters the skilled motor function; and we propose the suppression of gene enrichment, and synaptic abnormality led by the genetic insufficiency may contribute to impede the occurrence of activity-dependent cortical plasticity.

Significance Statement

Impairments in fine motor skills occur in subjects with neurodevelopmental disorders. We report a mutation relevant to the neurodevelopmental disorders can impact the cortical plasticity associated with skilled motor function. In wild-type mice, the motor training induced extensive activity-dependent cortical map plasticity, synaptic modifications through synaptic potentiation and excitatory-transmission increase, as well as enrichments in certain gene expressions. On the other hand, mice with Reelin haploinsufficiency (presumed mouse model of neurodevelopmental disorders) exhibited lower level of skilled motor performance, and the underlying correlates shown in wild-type mice were found suppressed. We conclude the suppression of gene enrichment, and synaptic abnormality due to Reelin haploinsufficiency may underlie the limited development of activity-dependent cortical plasticity, contributing to impairments in motor skills.
Spontaneous emergence of behaviorally relevant motifs in human motor cortex
Authors: Livne Tomer , Kim DoHyun , Metcalf Nicholas V. , Shulman Gordon L. , Corbetta Maurizio
Published: October 2020

Spontaneous neural activity has been shown to preserve the inter-regional structure of cortical activity evoked by a task. It is unclear, however, whether patterns of spontaneous activity within a cortical region comprise representations associated with specific behaviors or mental states. The current study investigated the hypothesis that spontaneous neural activity in human motor cortex represents motor responses that commonly occur in daily life. To test this hypothesis 15 healthy participants were scanned in a 3T fMRI scanner while performing four simple hand movements differing by their daily life relevance, and while not performing any specific task (resting-state scans). Using the task data, we identified cortical patterns in a motor ROI corresponding to the different hand movements. These task-defined patterns were compared to spontaneous cortical activity patterns in the same motor ROI. The results indicated a higher similarity of the spontaneous patterns to the most common hand movement than to the least common hand movement. This finding provides the first evidence that spontaneous activity in human cortex forms fine-scale, patterned representations associated with behaviors that frequently occur in daily life.
Diversity of ACE2 and its interaction with SARS-CoV-2 receptor binding domain
Authors: Low-Gan Jessie , Huang Ruiqi , Warner Gabrielle , Kelley Abigail , McGregor Duncan , Smider Vaughn
Published: October 2020

COVID-19, the clinical syndrome caused by the SARS-CoV-2 virus, has rapidly spread globally causing tens of millions of infections and over a million deaths. The potential animal reservoirs for SARS-CoV-2 are currently unknown, however sequence analysis has provided plausible potential candidate species. SARS-CoV-2 binds to the angiotensin I converting enzyme 2 (ACE2) to enable its entry into host cells and establish infection. We analyzed the binding surface of ACE2 from several important animal species to begin to understand the parameters for the ACE2 recognition by the SARS-CoV-2 spike protein receptor binding domain (RBD). We employed Shannon entropy analysis to determine the variability of ACE2 across its sequence and particularly in its RBD interacting region, and assessed differences between various species’ ACE2 and human ACE2. As cattle are a known reservoir for coronaviruses with previous human zoonotic transfer, and has a relatively divergent ACE2 sequence, we compared the binding kinetics of bovine and human ACE2 to SARS-CoV-2 RBD. This revealed a nanomolar binding affinity for bovine ACE2 but an approximate ten-fold reduction of binding compared to human ACE2. Since cows have been experimentally infected by SARS-CoV-2, this lower affinity sets a threshold for sequences with lower homology to human ACE2 to be able to serve as a productive viral receptor for SARS-CoV-2.
Biotransformation of lindane (γ-hexachlorocyclohexane) to non-toxic end products by sequential treatment with three mixed anaerobic microbial cultures
Authors: Puentes Jácome Luz A. , Lomheim Line , Gaspard Sarra , Edwards Elizabeth A.
Published: October 2020

The γ isomer of hexachlorocyclohexane (HCH), also known as lindane, is a carcinogenic persistent organic pollutant. Lindane was used worldwide as an agricultural insecticide. Legacy soil and groundwater contamination with lindane and other HCH isomers is still a big concern. The biotic reductive dechlorination of HCH to non-desirable and toxic lower chlorinated compounds such as monochlorobenzene (MCB) and benzene, among others, has been broadly documented. Here, we demonstrate for the first time that complete biotransformation of lindane to non-toxic end products is attainable using a sequential treatment approach with three mixed anaerobic microbial cultures referred to as culture I, II, and III. Biaugmentation with culture I achieved dechlorination of lindane to MCB and benzene. Culture II was able to dechlorinate MCB to benzene, and finally, culture III carried out methanogenic benzene degradation. DistinctDehalobacterpopulations, corresponding to different 16S rRNA amplicon sequence variants in culture I and culture II, were responsible for lindane and MCB dechlorination, respectively. This study continues to highlight key roles ofDehalobacterspp. as chlorobenzene- and HCH-organohalide-respiring bacteria and demonstrates that sequential treatment with specialized anaerobic cultures may be explored at field sites in order to address legacy soil and groundwater contamination with HCH.
Assessment of ANG variants in Parkinson’s disease
Authors: Grenn Francis P. , Moore Anni , Bandres-Ciga Sara , Krohn Lynne , Blauwendraat Cornelis
Published: October 2020

Genetic risk factors are occasionally shared between different neurodegenerative diseases. Previous studies have linked ANG, a gene encoding angiogenin, to both Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). Functional studies suggest ANG plays a neuroprotective role in both PD and ALS by reducing cell death. We further explored the genetic association between ANG and PD by analyzing genotype data from the International Parkinson’s Disease Genomics Consortium (IPDGC) (14,671 cases and 17,667 controls) and whole genome sequencing (WGS) data from the Accelerating Medicines Partnership - Parkinson’s disease initiative (AMP-PD, https://amp-pd.org/) (1,647 cases and 1,050 controls). Our analysis did not replicate the findings of previous studies and found no significant association between ANG variants and PD risk.
Long-term monitoring of SARS-CoV-2 in wastewater of the Frankfurt metropolitan area in Southern Germany
Authors: Agrawal Shelesh , Orschler Laura , Lackner Susanne
Published: October 2020

Wastewater-based epidemiology (WBE) is a great approach that enables us to comprehensively monitor the community to determine the scale and dynamics of infections in a city, particularly in metropolitan cities with a high population density. Therefore, we monitored the time course of the SARS-CoV-2 RNA concentration in raw sewage in the Frankfurt metropolitan area, the European financial center. To determine the SARS-CoV-2 concentration in sewage, we continuously collected samples from two wastewater treatment plant (WWTP) influents (Niederrad and Sindlingen) serving the Frankfurt metropolitan area and performed RT-qPCR analysis targeting three genes (N gene, S gene, and ORF1ab gene). In August, a resurgence in the SARS-CoV-2 RNA load was observed, reaching 3 x 1013 copies/day, which represents similar levels compared to April with approx. 2 x 1014 copies/day. This corresponds to an also continuous increase again in COVID-19 cases in Frankfurt since August, with an average of 28.6 incidences, compared to 28.7 incidences in April. Different temporal dynamics were observed between different sampling points, indicating local dynamics in COVID-19 cases within the Frankfurt metropolitan area. The SARS-CoV-2 load to the WWTP Niederrad ranged from approx. 4 x 1011 to 1 x 1015 copies/day, the load to the WWTP Sindlingen from approx. 1 x 1011 to 2 x 1014 copies/day, which resulted in a preceding increase in these loading in July ahead of the weekly averaged incidences. The study shows that WBE has the potential as early warning system for SARS-CoV-2 infections and as monitoring system to identify global hotspots of COVID-19.