bluuebunny/crossref_metadata_2025 huggingface dataset:
Nano-MOFs as targeted drug delivery agents to combat antibiotic-resistant bacterial infections
Authors: Ahmed Saleh A. , Nur Hasan Md. , Bagchi Damayanti , Altass Hatem M. , Morad Moataz , Althagafi Ismail I. , Hameed Ahmed M. , Sayqal Ali , Khder Abd El Rahman S. , Asghar Basim H. , Katouah Hanadi A. , Pal Samir Kumar
Published: December 2020

The drug resistance of bacteria is a significant threat to human civilization while the action of antibiotics against drug-resistant bacteria is severely limited owing to the hydrophobic nature of drug molecules, which unquestionably inhibit its permanency for clinical applications. The antibacterial action of nanomaterials offers major modalities to combat drug resistance of bacteria. The current work reports the use of nano–metal-organic frameworks encapsulating drug molecules to enhance its antibacterial activity against model drug-resistant bacteria and biofilm of the bacteria. We have attached rifampicin (RF), a well-documented antituberculosis drug with tremendous pharmacological significance, into the pore surface of zeolitic imidazolate framework 8 (ZIF8) by a simple synthetic procedure. The synthesized ZIF8 has been characterized using the X-ray diffraction (XRD) method before and after drug encapsulation. The electron microscopic strategies such as scanning electron microscope and transmission electron microscope methods were performed to characterize the binding between ZIF8 and RF. We have also performed picosecond-resolved fluorescence spectroscopy to validate the formation of the ZIF8-RF nanohybrids (NHs). The drug release profile experiment demonstrates that ZIF8-RF depicts pH-responsive drug delivery and is ideal for targeting bacterial disease corresponding to its inherent acidic nature. Most remarkably, ZIF8-RF gives enhanced antibacterial activity against methicillin-resistant
Staphylococcus aureus
bacteria and also prompts entire damage of structurally robust bacterial biofilms. Overall, the present study depicts a detailed physical insight for manufactured antibiotic-encapsulated NHs presenting tremendous antimicrobial activity that can be beneficial for manifold practical applications.
Large-scale spatial variabilities in the humpback whale acoustic presence in the Atlantic sector of the Southern Ocean
Authors: Schall Elena , Thomisch Karolin , Boebel Olaf , Gerlach Gabriele , Spiesecke Stefanie , Van Opzeeland Ilse
Published: December 2020

Southern Hemisphere humpback whales (Megaptera novaeangliae) inhabit a wide variety of ecosystems including both low- and high-latitude areas. Understanding the habitat selection of humpback whale populations is key for humpback whale stock management and general ecosystem management. In the Atlantic sector of the Southern Ocean (ASSO), the investigation of baleen whale distribution by sighting surveys is temporally restricted to the austral summer. The implementation of autonomous passive acoustic monitoring, in turn, allows the study of vocal baleen whales year-round. This study describes the results of analysing passive acoustic data spanning 12 recording positions throughout theASSOapplying a combination of automatic and manual analysis methods to register humpback whale acoustic activity. Humpback whales were present at nine recording positions with higher acoustic activities towards lower latitudes and the eastern and western edges of theASSO. During all months, except December (the month with the fewest recordings), humpback whale acoustic activity was registered in theASSO. The acoustic presence of humpback whales at various locations in theASSOconfirms previous observations that part of the population remains in high-latitude waters beyond austral summer, presumably to feed. The spatial and temporal extent of humpback whale presence in theASSOsuggests that this area may be used by multiple humpback whale breeding populations as a feeding ground.
Response of psychrophilic plant endosymbionts to experimental temperature increase
Authors: Seas Carolina , Chaverri Priscila
Published: December 2020

Countless uncertainties remain regarding the effects of global warming on biodiversity, including the ability of organisms to adapt and how that will affect obligate symbiotic relationships. The present study aimed to determine the consequences of temperature increase in the adaptation of plant endosymbionts (endophytes) that grow better at low temperatures (psychrophilic). We isolated fungal endophytes from a high-elevation (paramo) endemic plant,
Chusquea subtessellata
. Initial growth curves were constructed at different temperatures (4–25°C). Next, experiments were carried out in which only the psychrophilic isolates were subjected to repeated increments in temperature. After the experiments, the final growth curves showed significantly slower growth than the initial curves, and some isolates even ceased to grow. While most studies suggest that the distribution of microorganisms will expand as temperatures increase because most of these organisms grow better at 25°C, the results from our experiments demonstrate that psychrophilic fungi were negatively affected by temperature increases. These outcomes raise questions concerning the potential adaptation of beneficial endosymbiotic fungi in the already threatened high-elevation ecosystems. Assessing the consequences of global warming at all trophic levels is urgent because many species on Earth depend on their microbial symbionts for survival.
SI epidemic model applied to COVID-19 data in mainland China
Authors: Demongeot J. , Griette Q. , Magal P.
Published: December 2020

The article is devoted to the parameters identification in the SI model. We consider several methods, starting with an exponential fit to the early cumulative data of SARS-CoV2 in mainland China. The present methodology provides a way to compute the parameters at the early stage of the epidemic. Next, we establish an identifiability result. Then we use the Bernoulli–Verhulst model as a phenomenological model to fit the data and derive some results on the parameters identification. The last part of the paper is devoted to some numerical algorithms to fit a daily piecewise constant rate of transmission.
Microbacterium algeriense sp. nov., a novel actinobacterium isolated from Algerian oil production waters
Authors: Lenchi Nesrine , Anzil Adriana , Servais Pierre , Kebbouche-Gana Salima , Gana Mohamed Lamine , Llirós Marc
Published: December 2020

A non-motile, straight-rod-shaped, Gram-stain-positive and facultative anaerobic bacterium (i.e., strain G1T) was isolated from production waters from an Algerian oilfield. Growth was observed in the presence of 0.3–3.5 % (w/v) NaCl, at 20–50 °C and at pH 6.0–9.0. Results of phylogenetic analyses based on 16S rRNA gene sequences showed that strain G1T belonged to the genus

Microbacterium

. Strain G1 T was closely related to

Microbacterium oxydans

(DSM 20578T) and

Microbacterium maritypicum

(DSM 12512T) with 99.8 % sequence similarity and to

Microbacterium saperdae

(DSM 20169T) with 99.6 % sequence similarity. Strain G1 T contained MK9, MK10, MK11, MK12 and MK13 as respiratory quinones, and phosphatidylglycerol, diphosphatidylglycerol and glycolipid as the major polar lipids. The major cellular fatty acids were anteiso-C15:0, iso-C16:0 and anteiso-C17:0. The estimated DNA G+C content was 69.57 mol% based on its draft genome sequence. Genome annotation of strain G1T predicted the presence of 3511 genes, of which 3483 were protein-coding and 47 were tRNA genes. The DNA–DNA hybridization (DDH) and average nucleotide identity (ANI) values between strain G1T and

M. oxydans

(DSM 20578T) and

M. maritypicum

(DSM 12512T) were in both cases far below the respective species boundary thresholds (27.5 and 28.0 % for DDH; and 84.40 and 84.82% for ANI, respectively). Based on the data presented above, strain G1T was considered to represent a novel species for which the name Microbacterium algeriense is proposed with the type strain G1T (=DSM 109018T=LMG 31276T).
Donghicola mangrovi sp. nov., a member of the family Rhodobacteraceae isolated from mangrove forest in Thailand
Authors: Charoenyingcharoen Piyanat , Kim Ji-Sun , Theeragool Gunjana , Lee Keun-Chul , Yukphan Pattaraporn , Lee Jung-Sook
Published: December 2020

Two novel Gram-stain-negative, rod-shaped and non-motile bacterial strains, designated B5-SW-15T and C2-DW-16, were isolated from water collected in mangrove forests in Ranong Province, Thailand. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strains B5-SW-15T and C2-DW-16 belonged to the genus

Donghicola

and were most closely related to

Donghicola tyrosinivorans

DSM 100212T (98.2 and 98.1 %, respectively) and

Donghicola eburneus

DSM 29127T (97.7 and 97.6 %, respectively). The average nucleotide identity and digital DNA–DNA hybridization values between strain B5-SW-15T, strain C2-DW-16 and related species were 95.8 and 71.6 % (to strain C2-DW-16), 76.8 and 21.3 % (to

D. tyrosinivorans

DSM 100212T) and 80.3 and 24.2 % (to

D. eburneus

DSM 29127T), respectively. The predominant cellular fatty acids (>5 %) were summed feature 8 (C18 : 1
 ω6c and/or C18 : 1
 ω7c), C16 : 0 and C12 : 1 3-OH. Ubiquinone Q-10 was the sole respiratory quinone. DNA G+C contents of the isolates were 61.0 and 61.2 mol% based on whole genome sequences. Strains B5-SW-15T and C2-DW-16 contained aminolipid, phosphatidylcholine, phosphatidylethanolamine and phosphatidylglycerol as the major polar lipids. On the basis of the results from phenotypic, chemotaxonomic and phylogenetic analyses, strains B5-SW-15T and C2-DW-16 constitute a novel species of the genus

Donghicola

in the family

Rhodobacteraceae

for which the name Donghicola mangrovi sp. nov. is proposed. The type strain is B5-SW-15T (=BCC 56522T=TBRC 9562T=KCTC 72743T).
In-silico analysis of differentially expressed genes and their regulating microRNA involved in lymph node metastasis in invasive breast carcinoma
Authors: Modi Anupama , Purohit Purvi , Gadwal Ashita , Ukey Shweta , Roy Dipayan , Fernandes Sujoy , Banerjee Mithu
Published: December 2020

Introduction

Axillary nodal metastasis is related to poor prognosis in breast cancer (BC). The metastatic progression in BC is related to molecular signatures. The currently popular methods to evaluate nodal status may give false negatives or give rise to secondary complications. In this study, key candidate genes in BC lymph node metastasis have been identified from publicly available microarray datasets and their roles in BC have been explored through survival analysis and target prediction.

Methods

Gene Expression Omnibus datasets have been analyzed for differentially expressed genes (DEGs) in lymph node-positive BC patients compared to nodal-negative and healthy tissues. The functional enrichment analysis was done in database for annotation, visualization and integrated discovery (DAVID). Protein-protein interaction (PPI) network was constructed in Search Tool for the Retrieval of Interacting Genes and proteins (STRING) and visualized on Cytoscape. The candidate hub genes were identified and their expression analyzed for overall survival (OS) in Gene Expression Profiling Interactive Analysis (GEPIA). The target miRNA and transcription factors were analyzed through miRNet.

Results

A total of 102 overlapping DEGs were found. Gene Ontology revealed eleven, seventeen, and three significant terms for cellular component, biological process, and molecular function respectively. Six candidate genes, DSC3, KRT5, KRT6B, KRT17, KRT81, and SERPINB5 were significantly associated with nodal metastasis and OS in BC patients. A total of 83 targeting miRNA were identified through miRNet and hsa-miR-155-5p was found to be the most significant miRNA which was targeting five out of six hub genes.

Conclusion

In-silico survival and expression analyses revealed six candidate genes and 83 miRNAs, which may be potential diagnostic markers and therapeutic targets in BC patients and miR-155-5p shows promise as it targeted five important hub genes related to lymph-node metastasis.
Ethnicity, Household Composition and COVID-19 Mortality: A National Linked Data Study
Authors: Nafilyan Vahé , Islam Nazrul , Ayoubkhani Daniel , Gilles Clare , Katikireddi Srinivasa Vittal , Mathur Rohini , Summerfield Annabel , Tingay Karen , Asaria Miqdad , John Ann , Goldblatt Peter , Banerjee Amitava , Khunti Kamlesh
Published: December 2020

Background

Ethnic minorities have experienced disproportionate COVID-19 mortality rates. We estimated associations between household composition and COVID-19 mortality in older adults (≥ 65 years) using a newly linked census-based dataset, and investigated whether living in a multi-generational household explained some of the elevated COVID-19 mortality amongst ethnic minority groups.

Methods

Using retrospective data from the 2011 Census linked to Hospital Episode Statistics (2017-2019) and death registration data (up to 27th July 2020), we followed adults aged 65 years or over living in private households in England from 2 March 2020 until 27 July 2020 (n=10,078,568). We estimated hazard ratios (HRs) for COVID-19 death for people living in a multi-generational household compared with people living with another older adult, adjusting for geographical factors, socio-economic characteristics and pre-pandemic health. We conducted a causal mediation analysis to estimate the proportion of ethnic inequalities explained by living in a multi-generational household.

Results

Living in a multi-generational household was associated with an increased risk of COVID-19 death. After adjusting for confounding factors, the HRs for living in a multi-generational household with dependent children were 1.13 [95% confidence interval 1.01-1.27] and 1.17 [1.01-1.35] for older males and females. The HRs for living in a multi-generational household without dependent children were 1.03 [0.97 - 1.09] for older males and 1.22 [1.12 - 1.32] for older females. Living in a multi-generational household explained between 10% and 15% of the elevated risk of COVID-19 death among older females from South Asian background, but very little for South Asian males or people in other ethnic minority groups.

Conclusion

Older adults living with younger people are at increased risk of COVID-19 mortality, and this is a notable contributing factor to the excess risk experienced by older South Asian females compared to White females. Relevant public health interventions should be directed at communities where such multi-generational households are highly prevalent.

Funding

This research was funded by the Office for National Statistics.
Wearing masks and establishing COVID-19 areas reduces secondary attack risk in nursing homes
Authors: Reyné Bastien , Selinger Christian , Sofonea Mircea T , Miot Stéphanie , Pisoni Amandine , Tuaillon Edouard , Bousquet Jean , Blain Hubert , Alizon Samuel
Published: December 2020

Background

COVID-19 is spreading rapidly in nursing homes (NHs). It is urgent to evaluate the effect of infection prevention and control (IPC) measures to reduce COVID spreading.

Methods

We analysed COVID-19 outbreaks in 12 NH using rRT-PCR for SARS-CoV-2. We estimated secondary attack risks (SARs) and identified cofactors associated with the proportion of infected residents.

Results

The SAR was below 5%, suggesting a high efficiency of IPC measures. Mask-wearing or establishment of COVID-19 zones for infected residents were associated with lower SAR.

Conclusions

Wearing masks and isolating potentially infected residents appear to limit SARS-CoV-2 spread in nursing homes.
Effective post-exposure prophylaxis of Covid-19 associated with hydroxychloroquine: Prospective dataset re-analysis incorporating novel, missing data
Authors: Wiseman David M. , Kory Pierre , Saidi Samir A , Mazzucco Dan
Published: December 2020

BACKGROUND

A key trial (NCT04308668) of post-exposure prophylaxis found hydroxychloroquine-associated (HCQ) reductions of Covid-19 by 17% overall and 31% to 49% in subgroups. To understand these trends, we re-analyzed the dataset.

METHODS

Our protocol conformed to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT). We compared the incidence of Covid-19 after HCQ or placebo, stratifying by intervention lag, age, and gender.

RESULTS

Newly requested data missing from the dataset revealed that 52% and 19% of subjects received medication 1-2 days after intended and assumed overnight delivery or four-day intervention lag respectively. After re-analysis, we found reduced HCQ-associated incidence of Covid-19 with Early (up to 3 days post-exposure) (RR 0.58, 95%CI 0.35 - 0.97; p=0.044; NNT 14.5) but not Late (RR 1.22, 95%CI 0.72 - 2.04) prophylaxis.

We found a significant HCQ-associated Covid-19 reduction in subjects 18 to 45 years old with Early (RR 0.54, 95%CI 0.29-0.97; p=0.0448, NNT 11.5) but not Late (RR 1.02, 95%CI 0.55-1.89) prophylaxis, attenuated in older subjects (RR 0.75, 95%CI 0-27-2.05) and by co-morbidities. Although, we did not detect effects of gender, folate, zinc, or ascorbate, confounding effects cannot be excluded.

CONCLUSIONS

Using novel data and prospective re-analysis, hydroxychloroquine, in an age-dependent manner, was associated with reduced Covid-19 compatible illness when supplied for post-exposure prophylaxis between 1 and 3 days after high- or moderate-risk exposure, at higher loading and maintenance doses than in similar studies. The original study conclusions are controverted, and our finding warrants prospective confirmation.

Protocol registered at Open Science Framework: osf.io/fqtnw (last revised September 27, 2020,

Highlights

Missing data integrated with dataset re-analysis reversed findings of original study

Hydroxychloroquine associated reduction (42%) of Covid-19 compatible illness found

Effect in Post-exposure Prophylaxis when received 1-3 days after exposure

Risk Ratio 0.58 (95% CI 0.35-0.97, p=0.044, NNT14.5)

Findings controvert the conclusions of original study
Convalescent Plasma in COVID-19. Mortality-Safety First Results of the Prospective Multicenter FALP 001-2020 Trial
Authors: Gazitúa Raimundo , Briones José Luis , Selman Carolina , Villarroel-Espíndola Franz , Aguirre Adam , González-Steigmaier Roxana , Cereceda Karina , Mahave Mauricio , Rubio Betzabé , Ferrer-Rosende Pedro , Sapunar Jorge , Marsiglia Hugo , Morales Ricardo , Yarad Fernanda , Balcells María Elvira , Rojas Luis , Nervi Bruno , Nien Jyh Kae , Garate Javier , Prieto Carolina , Palma Sofía , Escobar Carolina , Bascuñan Josefina , Muñoz Rodrigo , Pinto Mónica , Cardemil Daniela , Navarrete Marcelo , Reyes Soledad , Espinosa Victoria , Yáñez Nicolás , Caglevic Christian
Published: December 2020

Background

The use of convalescent plasma (CP) to treat COVID-19 has shown promising results; however, its effectiveness remains uncertain. The purpose of this study was to determine the safety and mortality of CP among patients hospitalized with COVID-19.

Study Design and Methods

This multicenter, open-label, uncontrolled clinical trial is currently being conducted at nine hospitals in Chile. Patients hospitalized due to COVID-19 who were still within 14 days since symptom onset were classified into four groups: Patients with cancer and severe COVID-19. Patients with cancer and non-severe COVID-19. Patients with severe COVID-19 and patients with non-severe COVID-19 only. The intervention involved two 200-cc. CP transfusions with anti-SARS-CoV-2 IgG titers ≥ 1:320 collected from COVID-19-recovered donors.

Results

192 patients hospitalized for COVID-19 received CP transfusions. At the first transfusion, 90.6% fulfilled the criteria for severity, and 41.1% required mechanical ventilation. 11.5% of the patients had cancer. Overall 7-day and 30-day mortality since the first CP transfusion was 5.7% and 16.1% respectively. There were no differences at either time point in mortality between the four groups. Patients on mechanical ventilation when receiving CP had higher mortality rates than those who were not (22.8% vs. 11.5%; p = 0.037). Overall 30-day mortality was higher in patients over 65 than in younger patients (p = 0.019). Severe adverse events were reported in four patients (2.1%) with an overall transfusion-related lung injury rate of 1.56%. No CP-related deaths occurred.

Discussion

CP is safe when used in patients with COVID-19 even when also presenting severity criteria or risk factors. Our mortality rate is comparable to reports from larger studies. Controlled clinical trials are required to determine efficacy.

Registration

NCT04384588
Validation of a combined ELISA to detect IgG, IgA and IgM antibody responses to SARS-CoV-2 in mild or moderate non-hospitalised patients
Authors: Cook A M , Faustini S E , Williams L J , Cunningham A F , Drayson M T , Shields A M , Kay D , Taylor L , Plant T , Huissoon A , Wallis G. , Beck S , Jossi S E , Perez-Toledo M , Newby M L , Allen J D , Crispin M , Harding S , Richter A G
Published: December 2020

Background

Frequently SARS-CoV-2 results in mild or moderate disease with potentially lower concentrations of antibodies compared to those that are hospitalised. Here, we validated an ELISA using SARS-CoV-2 trimeric spike glycoprotein, with targeted detection of IgG, IgA and IgM (IgGAM) using serum and dried blood spots (DBS) from adults with mild or moderate disease.

Methods

Targeting the SARS-CoV-2 trimeric spike, a combined anti-IgG, IgA and IgM serology ELISA assay was developed using 62 PCR-confirmed non-hospitalised, mild or moderate COVID-19 samples, ≥14 days post symptom onset and 624 COVID-19 negative samples. The assay was validated using 73 PCR-confirmed non-hospitalised COVID-19 and 359 COVID-19 negative serum samples with an additional 81 DBSs, and further validated in 226 PCR-confirmed non-hospitalised COVID-19 and 426 COVID-19 negative clinical samples.

Results

A sensitivity and specificity of 98.6% (95% CI, 92.6–100.0), 98.3% (95% CI, 96.4–99.4), respectively, was observed following validation of the SARS-CoV-2 ELISA. No cross-reactivities with endemic coronaviruses or other human viruses were observed, and no change in results were recorded for interfering substances. The assay was stable at temperature extremes and components were stable for 15 days once opened. A matrix comparison showed DBS to correlate with serum results. Clinical validation of the assay reported a sensitivity of 94.7% (95% CI, 90.9-97.2%) and a specificity of 98.4% (95% CI, 96.6-99.3%).

Conclusions

The human anti-IgGAM SARS-CoV-2 ELISA provides accurate and sensitive detection of SARS-CoV-2 antibodies in non-hospitalised adults with mild or moderate disease. The use of dried blood spots makes the assay accessible to the wider community.

Supplementary Material

No
Retinal implantation of electronic vision prostheses to treat retinitis pigmentosa: A systematic review
Authors: Hallum Luke E. , Dakin Steven C.
Published: December 2020

Purpose

Retinitis pigmentosa is an hereditary disease causing photoreceptor degeneration and permanent vision loss. Retinal implantation of a stimulating electrode array is a new treatment for retinitis pigmentosa, but quantification of its efficacy is the subject of ongoing work. This review evaluates vision-related outcomes resulting from retinal implantation in participants with retinitis pigmentosa.

Methods

We searched MEDLINE and Embase for journal articles published since 1 January 2015. We selected articles describing studies of implanted participants that reported post-implantation measurement of vision. We extracted study information including design, participants’ residual vision, comparators, and assessed outcomes. To assess risk of bias, we used signalling questions and a target trial.

Results

Our search returned 425 abstracts. We reviewed the full text of 34 articles. We judged all studies to be at high risk of bias due to study design or experimental conduct. Regarding design, studies lacked the measures that typical clinical trials take to protect against bias (e.g., control groups and masking). Regarding experimental conduct, outcome measures were rarely comparable before and after implantation, and psychophysical methods were prone to bias (subjective, not forced-choice, methods). The most common comparison found was between post-implantation visual function with the device powered off versus on. This comparison is at high risk of bias.

Conclusions

There is a need for high-quality evidence of efficacy of retinal implantation to treat retinitis pigmentosa.

Translational Relevance

For patients and clinicians to make informed choices about retinitis pigmentosa treatment, visual function restored by retinal implantation must be properly quantified and reported.
Retrospective development and evaluation of prognostic models for exacerbation event prediction in patients with Chronic Obstructive Pulmonary Disease using data self-reported to a digital health application
Authors: Chmiel F. P. , Burns D. K. , Pickering J. B. , Blythin Alison , Wilkinson T. M. A. , Boniface M. J.
Published: December 2020

Background

Self-reporting digital applications provide a way of remotely monitoring and managing patients with chronic conditions in the community. Leveraging the data collected by these applications in prognostic models could provide increased personalisation of care and reduce the burden of care for people who live with chronic conditions. This study evaluated the predictive ability of prognostic models for prediction of acute exacerbation events in people with Chronic Obstructive Pulmonary Disease using data self-reported to a digital health application.

Methods

Retrospective study evaluating the use of symptom and Chronic Obstructive Pulmonary Disease assessment test data self-reported to a digital health application (myCOPD) in predicting acute exacerbation events. We include data from 2,374 patients who made a total of 68,139 self-reports. We evaluated the degree to which the different variables self-reported to the application are predictive of exacerbation events and developed both heuristic and machine-learnt models to predict whether the patient will report an exacerbation event within three days of self-reporting to the application. The model’s predictive ability was evaluated on self-reports from an independent set of patients.

Findings

Users self-reported symptoms and standard Chronic Obstructive Pulmonary Disease assessment tests display correlation with future exacerbation events. Both a baseline model (AUROC 0.655 (95 % CI: 0.689-0.676)) and a machine-learnt model (AUROC 0.727 (95 % CI: 0.720-0.735)) showed moderate ability in predicting exacerbation events occurring within three days of a given self-report. While the baseline model obtained a fixed sensitivity and specificity of 0.551 (95 % CI: 0.508-0.596) and 0.759 (95 % CI: 0.752-0.767) respectively, the sensitivity and specificity of the machine-learnt model can be tuned by dichotomizing the continuous predictions it provides with different thresholds.

Interpretation

Data self-reported to healthcare applications designed to remotely monitor patients with Chronic Obstructive Pulmonary Disease can be used to predict acute exacerbation events with moderate performance. This could increase personalisation of care by allowing pre-emptive action to be taken to mitigate the risk of future exacerbation events. It is plausible future studies could improve the accuracy of these models by either the inclusion of symptom information recorded with greater granularity or including variables not considered in our study, for example vital signs, information on activity, local environmental data, and lifestyle information.

Funding

This project was funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement No 780495 BigMedilytics.
COVID-19 RISK EVALUATION AND TESTING STRATEGIES BASED ON CONTACT TRACING NETWORK AND INFORMATION ANALYSIS
Authors: Kumar Ankush
Published: December 2020

Abstract

Contact tracing and efficient testing can have an imperative part in mitigating the COVID-19 spread, with minimal social and economic disruption. Testing serves many purposes: isolating the COVID-19 positive tested individuals, identifying the contacts at the risk, and locating the hotspots and safe zones for administrative planning. However, it is a challenging task to identify the right individuals for the test in view of the high COVID -19 spread, a large number of presymptomatic and asymptomatic cases, and limited testing capabilities. The individuals for COVID -19 are currently identified based on direct-contact, travel history, and symptoms, which are more individualized and do not explicitly include a group risk assessment, and in turn, do not preclude the transmission from the superspreaders. Policymakers need to limit testing in the shortage of test resources, and focus on gaining the most information from the tests performed. In this work, we introduce a protocol for the identification of the group of individuals to be tested for acquiring maximum risk information of a community with minimum individual tests performed. Firstly, an algorithm is proposed to determine the risk profile of all the individuals in the community by incorporating serial and parallel pathways of the infection transmission considering multiple steps of transmission. Next, we consider several potential groups that could be tested from the community, and analyze them one by one for their comparison. In a group, few individuals can be positive, and the remaining few can be negative, generating sets of several test-outcomes with unequal probabilities. The protocol involves the probability calculation and reassessment of the network’s risk profile in all the test output cases. Finally, the best group is identified in all the groups studied, in which risk profiles between post and pre-test are maximally different. The analysis shows that in general, information increases with an increase in the group size. Notably, a strategically chosen small group may provide more information from the test results, than a standard larger group. The proposed systematic strategy would help in the selection of the right individuals for the testing, and in extracting far more information from the minimum samples, to effectively aid the epidemic mitigation. The protocol is generic, and can also be applied to any other epidemic spread in the future.
Racial disparities in COVID-19 mortality across Michigan, United States
Authors: Parpia Alyssa S. , Pandey Abhishek , Martinez Isabel , El-Sayed Abdulrahman M. , Wells Chad R. , Myers Lindsey , Duncan Jeffrey , Collins Jim , Fitzpatrick Meagan C. , Galvani Alison P.
Published: December 2020

Black populations in the US are disproportionately affected by the COVID-19 pandemic, but the increased mortality burden after accounting for health and demographic characteristics is not well understood. We evaluated COVID-19 mortality in Michigan using individual-level death certificate and surveillance data from the Michigan Department of Health and Human Services from March 16 to October 26, 2020. Among the 6,065 COVID-19-related deaths, Black individuals experienced 3.6 times the mortality rate as White individuals. Black individuals under 65 years without comorbidities had a mortality rate 12.6 times that of their White counterparts. After accounting for age, sex, and comorbidities, we found that Black individuals in all strata are at higher risk of COVID-19 mortality than their White peers. We demonstrate that inequities in mortality are driven by ongoing systemic racism, as opposed to comorbidity burden or older age, and further highlight how underlying disparities across the race are compounded in crises.
The PAX1 locus at 20p11 is a modifier for bilateral cleft lip only
Authors: Curtis Sarah W. , Chang Daniel , Lee Myoung Keun , Shaffer John R. , Indencleef Karlijne , Epstein Michael P. , Cutler David J. , Murray Jeffrey C. , Feingold Eleanor , Beaty Terri H. , Claes Peter , Weinberg Seth M. , Marazita Mary L. , Carlson Jenna C. , Leslie Elizabeth J.
Published: December 2020

Nonsyndromic orofacial clefts (OFCs) are the most common craniofacial birth defect in humans and, like many complex traits, OFCs are phenotypically and etiologically heterogenous. The phenotypic heterogeneity of OFCs extends beyond the structures affected by the cleft (e.g., cleft lip (CL) and cleft lip and palate (CLP) to other features, such as the severity of the cleft. Here, we focus on bilateral and unilateral clefts as one dimension of OFC severity. Unilateral clefts are more frequent than bilateral clefts for both CL and CLP, but the genetic architecture of these subtypes is not well understood, and it is not known if genetic variants predispose for the formation of one subtype over another. Therefore, we tested for subtype-specific genetic associations in 44 bilateral CL (BCL) cases, 434 unilateral CL (UCL) cases, 530 bilateral CLP cases (BCLP), 1123 unilateral CLP (UCLP) cases, and unrelated controls (N = 1626), using the mixed-model approach implemented in GENESIS. While no novel loci were found in subtype-specific analyses comparing cases to controls, the genetic architecture of UCL was distinct compared to BCL, with 43.8% of suggestive loci (p < 1.0×10−5) having non-overlapping confidence intervals between the two subtypes. To further understand the genetic risk factors for severity differences, we then performed a genome-wide scan for modifiers using a similar mixed-model approach and found one genome-wide significant modifier locus on 20p11 (p = 7.53×10−9), 300kb downstream of PAX1, associated with higher odds of BCL compared to UCL, which also replicated in an independent cohort (p = 0.0018) and showed no effect in BCLP (p>0.05). We further found that SNPs at this locus were associated with normal human nasal shape. Taken together, these results suggest bilateral and unilateral clefts may have differences in their genetic architecture, especially between CL and CLP. Moreover, our results suggest BCL, the rarest form of OFC, may be genetically distinct from the other OFC subtypes. This expands our understanding of genetic modifiers for subtypes of OFCs and further elucidates the genetic mechanisms behind the phenotypic heterogeneity in OFCs.
Modeling the effectiveness of olfactory testing to limit SARS-CoV-2 transmission
Authors: Larremore Daniel B. , Toomre Derek , Parker Roy
Published: December 2020

A central problem in the COVID-19 pandemic is that there is not enough testing to prevent infectious spread of SARS-CoV-2, causing surges and lockdowns with human and economic toll. Molecular tests that detect viral RNAs or antigens will be unable to rise to this challenge unless testing capacity increases by at least an order of magnitude while decreasing turnaround times. Here, we evaluate an alternative strategy based on the monitoring of olfactory dysfunction, a symptom identified in 76-83% of SARS-CoV-2 infections—including those with no other symptoms—when a standardized olfaction test is used. We model how screening for olfactory dysfunction, with reflexive molecular tests, could be beneficial in reducing community spread of SARS-CoV-2 by varying testing frequency and the prevalence, duration, and onset time of olfactory dysfunction. We find that monitoring olfactory dysfunction could reduce spread via regular screening, and could reduce risk when used at point-of-entry for single-day events. In light of these estimated impacts, and because olfactory tests can be mass produced at low cost and self-administered, we suggest that screening for olfactory dysfunction could be a high impact and cost-effective method for broad COVID-19 screening and surveillance.
Rapid and accurate point-of-care testing for SARS-CoV2 antibodies
Authors: Esmail Sally , Knauer Michael J. , Abdoh Husam , Chin-Yee Benjamin , Stogios Peter , Seitova Almagul , Hutchinson Ashley , Yusifov Farhad , Skarina Tatiana , Evdokimova Elena , Ackloo Suzanne , Lowes Lori , Voss Courtney , Hedley Benjamin D. , Bhayana Vipin , Chin-Yee Ian , Li Shawn S-C.
Published: December 2020

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has grown into worst public health crisis since the 1918 influenza pandemic. As COVID-19 continues to spread around the world, there is urgent need for a rapid, yet accurate antibody test to identify infected individuals in populations to inform health decisions. We have developed a rapid, accurate and cost-effective serologic test based on antibody-dependent agglutination of antigen-coated latex particles, which uses ∼5 µl plasma and takes <5 min to complete with no instrument required. The simplicity of this test makes it ideal for point-of-care (POC) use at the community level. When validated using plasma samples that are positive or negative for SARS-CoV-2, the agglutination assay detected antibodies against the receptor-binding domain of the spike (S-RBD) or the nucleocapsid (N) protein of SARS-CoV-2 with 100% specificity and ∼98% sensitivity. Furthermore, we found that the strength of the S-RBD antibody response measured by the agglutination assay correlated with the efficiency of the plasma in blocking RBD binding to the angiotensin converting enzyme 2 (ACE2) in a surrogate neutralization assay, suggesting that the agglutination assay may be used to identify individuals with virus-neutralizing antibodies. Intriguingly, we found that >92% of patients had detectable antibodies on the day of positive viral RNA test, suggesting that seroconversion may occur earlier than previously thought and that the agglutination antibody test may complement RNA testing for POC diagnosis of SARS-CoV-2 infection.
Estimated prevalence of dental fear in adults: a systematic review and meta-analysis
Authors: Silveira Ethieli R. , Cademartori Mariana G. , Schuch Helena S. , Armfield Jason M. , Demarco Flavio F.
Published: December 2020

Objectives

To systematically review the literature on the prevalence of dental fear in adults to estimate a worldwide pooled prevalence and to investigate factors related to the heterogeneity of estimates.

Methods

Inclusion criteria were population-based studies reporting the prevalence or data that allowed the calculation of prevalence of dental fear in adults and/or elders. Five electronic databases (Embase, PubMed, Scopus, Virtual Health Library (BVS) and Web of Science) were searched. Two researchers independently performed the study selection, data extraction and quality assessment of the included studies. The prevalence pooled estimates of dental fear were calculated using fixed- and random-effect models. Subgroup analyses were performed to investigate variability between studies.

Results

The search strategy identified 4,486 studies. After removal of duplicates (1,722), title and abstract screening (2,764) and full-text reading (108), 31 publications were deemed eligible for this systematic review. A total of 72,577 individuals 18 years of age or older composed the sample of this systematic review. The global estimated prevalence of dental fear and anxiety (DFA), high DFA and severe DFA in adults were 13.8%, 11.2% and 2.6%, respectively. Subgroup analyses showed a higher prevalence of DFA, high DFA and severe DFA among women and younger adults. The instrument used to measure dental fear also affected the prevalence of the outcome.

Conclusions

Dental fear and high dental fear are prevalent in adults worldwide, being more prevalent among women.
Development and validation of automated computer aided-risk score for predicting the risk of in-hospital mortality using first electronically recorded blood test results and vital signs for COVID-19 hospital admissions: a retrospective development and validation study
Authors: Faisal Muhammad , Mohammed Mohammed A , Richardson Donald , Fiori Massimo , Beatson Kevin
Published: December 2020

Objectives

There are no established mortality risk equations specifically for unplanned emergency medical admissions which include patients with the novel coronavirus SARS-19 (COVID-19). We aim to develop and validate a computer-aided risk score (CARMc19) for predicting mortality risk by combining COVID-19 status, the first electronically recorded blood test results and latest version of the National Early Warning Score (NEWS2).

Design

Logistic regression model development and validation study using a cohort of unplanned emergency medical admissions to hospital.

Setting

York Hospital (YH) as model development dataset and Scarborough Hospital (SH) as model validation dataset.

Participants

Unplanned adult medical admissions discharged over three months (11 March 2020 to 13 June 2020) from two hospitals (YH for model development; SH for external model validation) based on admission NEWS2 electronically recorded within ±24 hours and/or blood test results within ±96 hours of admission. We used logistic regression modelling to predict the risk of in-hospital mortality using two models: 1) CARMc19_N: age + sex + NEWS2 including subcomponents + COVID19; 2) CARMc19_NB: CARMc19_N in conjunction with seven blood test results and acute kidney injury score. Model performance was evaluated according to discrimination (c-statistic), calibration (graphically), and clinical usefulness at NEWS2 thresholds of 4+, 5+, 6+.

Results

The risk of in-hospital mortality following emergency medical admission was similar in development and validation datasets (8.4% vs 8.2%). The c-statistics for predicting mortality for Model CARMc19_NB is better than CARMc19_N in the validation dataset (CARMc19_NB = 0.88 (95%CI 0.86 to 0.90) vs CARMc19_N = 0.86 (95%CI 0.83 to 0.88)). Both models had good internal and external calibration (CARMc19_NB: 1.01 (95%CI 0.88 vs 1.14) & CARMc19_N: 0.95 (95%CI 0.83 to 1.06)). At all NEWS2 thresholds (4+, 5+, 6+) model CARMc19_NB had better sensitivity and similar specificity.

Conclusions

We have developed a validated CARMc19 score with good performance characteristics for predicting the risk of in-hospital mortality following an emergency medical admission using the patient’s first, electronically recorded vital signs and blood tests results. Since the CARMc19 scores place no additional data collection burden on clinicians and is readily automated, it may now be carefully introduced and evaluated in hospitals with sufficient informatics infrastructure.
Brief Report: Sensory processing phenotypes in Phelan-McDermid Syndrome and SYNGAP1-related Intellectual Disability
Authors: Lyons-Warren Ariel M , McCormack Maria C , Holder J. Lloyd
Published: December 2020

Sensory processing differences are an established feature of both syndromic and non-syndromic Autism Spectrum Disorders (ASD). Significant work has been done to characterize and classify specific sensory profiles in non-syndromic Autism. However, it is not known if syndromic Autism disorders such as Phelan-McDermid Syndrome (PMD) or SYNGAP1-related Intellectual Disability (SYNGAP1-ID) have unique sensory phenotypes. Understanding the sensory features of these disorders is important for providing appropriate care and for understanding the underlying mechanisms of the disorders. In this manuscript we use the Short Sensory Profile-2 to characterize sensory features in 41 patients with PMD and 24 patients with SYNGAP1-ID and compare their responses to both expected results for typically developing children and published sensory profiles for non-syndromic ASD.
Early prediction of impending septic shock in children using age-adjusted Sepsis-3 criteria
Authors: Liu Ran , Greenstein Joseph L. , Fackler James C. , Bergmann Jules , Bembea Melania M. , Winslow Raimond L.
Published: December 2020

Sepsis is a syndrome which afflicts both adults and children, with many disease courses and diverse outcomes. Understanding of sepsis pathophysiology has changed over time; the Sepsis-3 criteria define sepsis in adults as organ dysfunction, quantified by SOFA score, caused by dysregulated immune response to infection. However, pediatric consensus definitions still utilize the SIRS-based Sepsis-2 criteria, though individual groups have attempted to adapt the Sepsis-3 criteria for children. We evaluate age-adjusted Sepsis-3 criteria on 2,384 pediatric patients admitted to the Johns Hopkins PICU, and apply previously-published methods for early prediction of septic shock. We obtain best early prediction performance of 0.96 AUC, 49.9% overall PPV, and a 5.8-hour median EWT using Sepsis-3 labels based on age-adjusted SOFA score. Through analyses of risk score evolution over time, we corroborate our past finding of an abrupt transition preceding onset of septic shock in children, and are able to stratify pediatric sepsis patients using their first post-threshold-crossing risk score.
Macrophage aggresome-like induced structures are flexible organizing platforms for immune signaling
Authors: Charbonneau Marie-Eve , Raghunathan Vedhika , O’Riordan Mary X.D.
Published: December 2020

Macrophages adopt a pro-inflammatory phenotype in response to environmental challenges in a process that often coincides with the formation of transient cytosolic p62/SQSTM1 inclusions containing ubiquitinated proteins in structures known as aggresome-like induced structures (ALIS). Although described as stress-induced inclusions that accumulate aggregated proteins, little direct evidence supports their hypothesized structural role in the context of immune stimulation. Here, we showed that these structures in primary macrophages are induced by multiple microbialbased ligands, including exposure to cytosolic double-stranded DNA. Rather than accumulating aggregated proteins, we observed that ubiquitinated proteins form a ring-shaped structure around the perimeter of these circular foci. We identified that different microbial stimuli induced the formation of ubiquitin-positive foci with distinct characteristics and we observed selective recruitment of context-dependent immune regulators. Our findings are consistent with a model where these ubiquitin-containing structures act as adaptable organizing centers for innate immune signaling.

Charbonneau et al. demonstrate that ubiquitin- and p62-containing cytosolic ring-shaped structures induced by bacterial infections, microbial ligands and cytosolic double-stranded DNA contain context-dependent immune regulators, revealing an important insight on the cellular architecture required to coordinate signal transduction in macrophage.
Thede novogenome of the “Spanish” slugArion vulgarisMoquin-Tandon, 1855 (Gastropoda: Panpulmonata): massive expansion of transposable elements in a major pest species
Authors: Chen Zeyuan , Doğan Özgül , Guiglielmoni Nadège , Guichard Anne , Schrödl Michael
Published: December 2020

Background

The “Spanish” slug,Arion vulgarisMoquin-Tandon, 1855, is considered to be among the 100 worst pest species in Europe. It is common and invasive to at least northern and eastern parts of Europe, probably benefitting from climate change and the modern human lifestyle. The origin and expansion of this species, the mechanisms behind its outstanding adaptive success and ability to outcompete other land slugs are worth to be explored on a genomic level. However, a high-quality chromosome-level genome is still lacking.

Findings

The final assembly ofA. vulgariswas obtained by combining short reads, linked reads, Nanopore long reads, and Hi-C data. The genome assembly size is 1.54 Gb with a contig N50 length of 8.6 Mb. We found a recent expansion of transposable elements (TEs) which results in repetitive sequences accounting for more than 75% of theA. vulgarisgenome, which is the highest among all known gastropod species. We identified 32,518 protein coding genes, and 2,763 species specific genes were functionally enriched in response to stimuli, nervous system and reproduction. With 1,237 single-copy orthologs fromA. vulgarisand other related mollusks with whole-genome data available, we reconstructed the phylogenetic relationships of gastropods and estimated the divergence time of stylommatophoran land snails (Achatina) andArionslugs at around 126 million years ago, and confirmed the whole genome duplication event shared by them.

Conclusions

To our knowledge, theA. vulgarisgenome is the first land slug genome assembly published to date. The high-quality genomic data will provide valuable genetic resources for further phylogeographic studies ofA. vulgarisorigin and expansion, invasiveness, as well as molluscan aquatic-land transition and shell formation.