bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in healthcare workers’ knowledge, attitudes, practices, and stress during the COVID-19 pandemic
Authors: Temsah Mohamad-Hani , Al Huzaimi Abdullah , Alrabiaah Abdulkarim , Alamro Nurah , Al-Sohime Fahad , Al-Eyadhy Ayman , Alhasan Khalid , Kari Jameela A. , Alhaboob Ali , Alsalmi Amro , AlMuhanna Wejdan , Almaghlouth Ibrahim , Aljamaan Fadi , Halwani Rabih , Saddik Basema , Barry Mazin , Al-Zamil Fahad , AlHadi Ahmad N. , Al-Subaie Sarah , Jamal Amr , Somily Ali Mohammed
Published: May 2021

Coronavirus disease 2019 (COVID-19) has caused an unprecedented health crisis around the world, not least because of its heterogeneous clinical presentation and course. The new information on the pandemic emerging daily has made it challenging for healthcare workers (HCWs) to stay current with the latest knowledge, which could influence their attitudes and practices during patient care.

This study is a follow-up evaluation of changes in HCWs’ knowledge, attitudes, and practices as well as anxiety levels regarding COVID-19 since the beginning of the pandemic. Data were collected through an anonymous, predesigned, self-administered questionnaire that was sent online to HCWs in Saudi Arabia.

The questionnaire was sent to 1500 HCWs, with a 63.8% response rate (N = 957). The majority of respondents were female (83%), and the most common age group was 31 to 40 years (52.2%). Nurses constituted 86.3% of the respondents. HCWs reported higher anxiety during the COVID-19 pandemic which increased from 4.91 ± 2.84 to 8.6 ± 2.27 on an 11-point Likert scale compared to other viral outbreaks. HCWs believed that their own preparedness as well as that of their hospital's intensive care unit or emergency room was higher during the COVID-19 pandemic than during the Middle East respiratory syndrome coronavirus pandemic (2012–2015). About 58% of HCWs attended one or more simulations concerning the management of COVID-19 patients in their intensive care unit/emergency room, and nearly all had undergone N95 mask fit testing. The mean score of HCWs’ knowledge of COVID-19 was 9.89/12. For most respondents (94.6%), the perception of being at increased risk of infection was the main cause of anxiety related to COVID-19; the mean score of anxiety over COVID-19 increased from 4.91 ± 2.84 before to 8.6 ± 2.27 during the pandemic in Saudi Arabia.

HCWs’ anxiety levels regarding COVID-19 have increased since a pandemic was declared. It is vital that healthcare facilities provide more emotional and psychological support for all HCWs.
Assessment of basic reproductive number for COVID-19 at global level
Authors: Yu Cheng-Jun , Wang Zi-Xiao , Xu Yue , Hu Ming-Xia , Chen Kai , Qin Gang
Published: May 2021

Background:

There are large knowledge gaps regarding how transmission of 2019 novel coronavirus disease (COVID-19) occurred in different settings across the world. This study aims to summarize basic reproduction number (R0) data and provide clues for designing prevention and control measures.

Methods:

Several databases and preprint platforms were retrieved for literature reporting R0 values of COVID-19. The analysis was stratified by the prespecified modeling method to make the R0 values comparable, and by country/region to explore whether R0 estimates differed across the world. The average R0 values were pooled using a random-effects model.

Results:

We identified 185 unique articles, yielding 43 articles for analysis. The selected studies covered 5 countries from Asia, 5 countries from Europe, 12 countries from Africa, and 1 from North America, South America, and Australia each. Exponential growth rate model was most favored by researchers. The pooled global R0 was 4.08 (95% CI, 3.09–5.39). The R0 estimates for new and shifting epicenters were comparable or even higher than that for the original epicenter Wuhan, China.

Conclusions:

The high R0 values suggest that an extraordinary combination of control measures is needed for halting COVID-19.
Association between diuretic administration before diagnosis and incidence of acute kidney injury in patients with minimal change disease
Authors: Shimamura Yoshinosuke , Abe Koki , Maeda Takuto , Ogawa Yayoi , Takizawa Hideki , Ishigami Junichi , Matsushita Kunihiro
Published: May 2021

We examined the association between diuretic administration before the diagnosis of minimal change disease and the incidence of acute kidney injury. Moreover, we examined whether the use of diuretics affected the time to complete remission in adults with such disease.

The present study was a single-center, retrospective, observational cohort study. We included 107 patients with biopsy-proven minimal change disease who were treated at a tertiary referral center in Japan between January 1, 2000 and March 31, 2019. All biopsy specimens were examined by a board-certified renal pathologist. The patients were considered to have minimal change disease when the kidney biopsy specimen had no glomerular lesions or only mild focal mesangial prominence (not exceeding 3 or 4 cells per segment) by light microscopy and/or foot process effacement by electron microscopy. Logistic regression and Kaplan–Meier curve analyses were performed, comparing the data of patients who received diuretics or not.

The median age was 47 (28–66) years, 52% of patients were women, and the median proteinuria dosage was 8.3 (5.3–11.2) g/d. When minimal change disease was diagnosed, 27% of patients were taking diuretics. Within 30 days after the diagnosis, acute kidney injury occurred in 27% of patients. On multivariable logistic regression analysis, the use of diuretics was significantly associated with a higher risk of acute kidney injury. The use of diuretics was also associated with a longer time to complete remission.

Diuretic administration can be associated with an elevated acute kidney injury risk and longer remission time in adult patients with newly diagnosed minimal change disease.
Mortality and Neurologic Sequelae in Influenza-Associated Encephalopathy: Retrospective Multicenter PICU Cohort in France
Authors: Cleuziou Pierre , Renaldo Florence , Renolleau Sylvain , Javouhey Etienne , Tissieres Pierre , Léger Pierre-Louis , Bergounioux Jean , Desguerre Isabelle , Dauger Stéphane , Levy Michaël ,   Groupe Francophone de Réanimation et Urgences Pédiatriques (GFRUP)
Published: May 2021

OBJECTIVES:

To describe and estimate the mortality rate of severe influenza-associated encephalopathy/encephalitis among children admitted to PICUs.

DESIGN:

Multicenter retrospective study.

SETTING:

Twelve French PICUs.

PATIENTS:

All children admitted for influenza-associated encephalopathy/encephalitis between 2010 and 2018 with no severe preexisting chronic neurologic disorders and no coinfection potentially responsible for the disease.

INTERVENTION:

None.

MEASUREMENTS AND MAIN RESULTS:

We collected the clinical presentation; laboratory, electroencephalographic, and MRI findings; and treatments used in the PICU. The primary outcome was mortality. The secondary outcomes included sequelae at discharge and last follow-up. We included 41 patients with a median (interquartile range) age of 4.7 years (2.5–8.2 yr). The main reasons for admission were altered consciousness (59%) and status epilepticus (34%); 48% of patients had meningitis, and one third had acute necrotizing encephalopathy on MRI. Mechanical ventilation was required in 73% of patients and hemodynamic support in 24%. The use of specific treatments was variable; steroids were given to 49% of patients. Seven patients (17%) died in the PICU. Median (interquartile range) PICU stay length was 7 days (2–13 d), and total hospital length of stay was 23 days (7–33 d). On hospital discharge, 49% (n = 20) had neurologic sequelae, with 27% (n = 11) having severe disabilities defined by modified Rankin Score greater than or equal to 4.

CONCLUSIONS:

Children requiring PICU admission for influenza-associated encephalopathy/encephalitis have high mortality and morbidity rates. The management remains highly variable due to the lack of guidelines.
Massilia horti sp. nov. and Noviherbaspirillum arenae sp. nov., two novel soil bacteria of the Oxalobacteraceae
Authors: Peta Vincent , Raths Rachel , Bücking Heike
Published: May 2021

We isolated two new soil bacteria: ONC3T(from garden soil in NC, USA; LMG 31738T=NRRL B-65553T) and M1T(from farmed soil in MI, USA; NRRL B-65551T=ATCC TSD-197T=LMG 31739T) and characterized their metabolic phenotype based on Biolog, MALDI-TOF MS and fatty acid analyses, and compared 16S rRNA and whole genome sequences to other members of theOxalobacteraceaeafter sequencing on an Illumina Nextera platform. Based on the results of 16S rRNA sequence analysis, ONC3Tshows the highest sequence similarity toMassilia solisilvaeJ18T(97.8 %),Massilia terraeJ11T(97.7 %) andMassilia agilisJ9T(97.3 %). Strain M1Tis most closely related toNoviherbaspirillum denitrificansTSA40T,Noviherbaspirillum agriK-1-15TandNoviherbaspirillum autotrophicumTSA66T(sequence identity of 98.2, 98.0 and 97.8 %, respectively). The whole genome of ONC3Thas an assembled size of 5.62 Mbp, a G+C content of 63.8 mol% and contains 5104 protein-coding sequences, 56 tRNA genes and two rRNA operons. The genome of M1Thas a length of 4.71 MBp, a G+C content of 63.81 mol% and includes 4967 protein-coding genes, two rRNA operons and 44 tRNA genes. Whole genome comparisons identifiedMassiliasp. WG5 with a 79.3 % average nucleotide identity (ANI) and 22.6 % digital DNA–DNA hybridization (dDDH), andMassiliasp. UBA11196 with 78.2 % average amino acid identity (AAI) as the most closely related species to ONC3T. M1Tis most closely related toN. autotrophicumTSA66Twith an ANI of 80.27 %, orN. denitrificansTSA40Twith a dDDH of 22.3 %. The application of community-accepted standards such as <98.7 % in 16S sequence similarity and <95–96 % ANI or 70 % DDH support the classification ofMassilia hortiONC3TandNoviherbaspirillum arenaeM1Tas novel species within theOxalobacteraceae.
Sphingobacterium phlebotomi sp. nov., a new member of family Sphingobacteriaceae isolated from sand fly rearing substrate
Authors: Kakumanu Madhavi L. , Marayati Bahjat Fadi , Wada-Katsumata Ayako , Wasserberg Gideon , Schal Coby , Apperson Charles S. , Ponnusamy Loganathan
Published: May 2021

A Gram-stain-negative, rod-shaped, non-motile, non-spore-forming, aerobic bacterium, designated type strain SSI9T, was isolated from sand fly (Phlebotomus papatasi Scopoli; Diptera: Psychodidae) rearing substrate and subjected to polyphasic taxonomic analysis. Strain SSI9T contained phosphatidylethanolamine as a major polar lipid, MK-7 as the predominant quinone, and C16 : 1ω6c/C16 : 1ω7c, iso-C15 : 0, iso-C17 : 0 3-OH and C16 : 0 as the major cellular fatty acids. Phylogenetic analysis based on 16S rRNA gene sequences revealed that SSI9T represents a member of the genus

Sphingobacterium

, of the family Sphingobacteriaceae sharing 96.5–88.0 % sequence similarity with other species of the genus

Sphingobacterium

. The results of multilocus sequence analysis using the concatenated sequences of the housekeeping genes recA, rplC and groL indicated that SSI9T formed a separate branch in the genus

Sphingobacterium

. The genome of SSI9T is 5 197 142 bp with a DNA G+C content of 41.8 mol% and encodes 4395 predicted coding sequences, 49 tRNAs, and three complete rRNAs and two partial rRNAs. SSI9T could be distinguished from other species of the genus

Sphingobacterium

with validly published names by several phenotypic, chemotaxonomic and genomic characteristics. On the basis of the results of this polyphasic taxonomic analysis, the bacterial isolate represents a novel species within the genus

Sphingobacterium

, for which the name Sphingobacterium phlebotomi sp. nov. is proposed. The type strain is SSI9T (=ATCC TSD-210T=LMG 31664T=NRRL B-65603T).
SARS-CoV-2 replicon for high-throughput antiviral screening
Authors: Zhang Qiu-Yan , Deng Cheng-Lin , Liu Jing , Li Jia-Qi , Zhang Hong-Qing , Li Na , Zhang Ya-Nan , Li Xiao-Dan , Zhang Bo , Xu Yi , Ye Han-Qing
Published: May 2021

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus, which is highly pathogenic and classified as a biosafety level 3 (BSL-3) agent, has greatly threatened global health and efficacious antivirals are urgently needed. The high requirement of facilities to manipulate the live virus has limited the development of antiviral study. Here, we constructed a reporter replicon of SARS-CoV-2, which can be handled in a BSL-2 laboratory. The Renilla luciferase activity effectively reflected the transcription and replication levels of the replicon genome. We identified the suitability of the replicon in antiviral screening using the known inhibitors, and thus established the replicon-based high-throughput screening (HTS) assay for SARS-CoV-2. The application of the HTS assay was further validated using a few hit natural compounds, which were screened out in a SARS-CoV-2 induced cytopathic-effect-based HTS assay in our previous study. This replicon-based HTS assay will be a safe platform for SARS-CoV-2 antiviral screening in a BSL-2 laboratory without the live virus.
Impact of different SARS-CoV-2 assays on laboratory turnaround time
Authors: Marquis Bastian , Opota Onya , Jaton Katia , Greub Gilbert
Published: May 2021

Introduction. Clinical microbiology laboratories have had to cope with an increase in the volume of tests due to the emergence of the SARS-CoV-2 virus. Short turnaround times (TATs) are important for case tracing and to help clinicians in patient management. In such a context, high-throughput systems are essential to process the bulk of the tests. Rapid tests are also required to ensure shorter TATs for urgent situations. In our laboratory, SARS-CoV-2 assays were initially implemented on our custom platform using a previously published method. The commercial cobas 6800 (Roche diagnostics) assay and the GeneXpert Xpress (Cepheid) SARS-CoV-2 assay were implemented on 24 March and 8 April 2020, respectively, as soon as available.

Hypothesis/Gap Statement. Despite the abundant literature on SARS-CoV-2 assays, the articles focus mainly on the diagnostic performances. This is to our knowledge the first article that specifically studies the TAT of different assays.

Aim. We aimed to describe the impact of various SARS-CoV-2 assays on the TAT at the beginning of the outbreak.

Methodology. In this study, we retrospectively analysed the TAT of all SARS-CoV-2 assays performed in our centre between 24 February and 9 June, 2020.

Results. We retrieved 33 900 analyses, with a median TAT of 6.25 h. TATs were highest (6.9 h) when only our custom platform was used (24 February to 24 March, 2020). They were reduced to 6.1 h when the cobas system was introduced (24 March to 8 April, 2020). The implementation of the GeneXpert further reduced the median TAT to 4.8 h (8 April to 9 June, 2020). The GeneXpert system had the shortest median TAT (1.9 h), followed by the cobas (5.5 h) and by our custom platform (6.9 h).

Conclusion. This work shows that the combination of high-throughput systems and rapid tests allows the efficient processing of a large number of tests with a short TAT. In addition, the use of a custom platform allowed the quick implementation of an in-house test when commercial assays were not yet available.
A longitudinal study of antibody responses to selected host antigens in rheumatic fever and rheumatic heart disease
Authors: Surve Nuzhat Z. , Kerkar Prafulla G. , Deshmukh Chandrahas T. , Nadkar Milind Y. , Mehta Preeti R. , Ketheesan Natkunam , Sriprakash Kadaba S. , Karmarkar Mohan G.
Published: May 2021

Introduction.Group A streptococci can trigger autoimmune responses that lead to acute rheumatic fever (ARF) and rheumatic heart disease (RHD).

Gap Statement.Some autoantibodies generated in ARF/RHD target antigens in the S2 subfragment region of cardiac myosin. However, little is known about the kinetics of these antibodies during the disease process.

Aim.To determine the antibody responses over time in patients and healthy controls against host tissue proteins - cardiac myosin and peptides from its S2 subfragment, tropomyosin, laminin and keratin.

Methodology.We used enzyme-linked immunosorbent assays (ELISA) to determine antibody responses in: (1) healthy controls; (2) patients with streptococcal pharyngitis; (3) patients with ARF with carditis and (4) patients with RHD on penicillin prophylaxis.

Results.We observed significantly higher antibody responses against extracellular proteins - laminin and keratin in pharyngitis group, patients with ARF and patients with RHD when compared to healthy controls. The antibody responses against intracellular proteins - cardiac myosin and tropomyosin were elevated only in the group of patients with ARF with active carditis. While the reactivity to S2 peptides S2-1-3, 8–11, 14, 16–18, 21–22 and 32 was higher in patients with ARF, the reactivity in the RHD group was high only against S2-1, 9, 11, 12 when compared to healthy controls. The reactivity against S2 peptides reduced as the disease condition stabilized in the ARF group whereas the reactivity remained unaltered in the RHD group. By contrast antibodies against laminin and keratin persisted in patients with RHD.

Conclusion.Our findings of antibody responses against host proteins support the multistep hypothesis in the development of rheumatic carditis. The differential kinetics of serum antibody responses against S2 peptides may have potential use as markers of ongoing cardiac damage that can be used to monitor patients with ARF/RHD.
Modelling upper respiratory viral load dynamics of SARS-CoV-2
Authors: Challenger Joseph D. , Foo Cher Y. , Wu Yue , Yan Ada W. C. , Marjaneh Mahdi Moradi , Liew Felicity , Thwaites Ryan S. , Okell Lucy C. , Cunnington Aubrey J.
Published: May 2021

Relationships between viral load, severity of illness, and transmissibility of virus, are fundamental to understanding pathogenesis and devising better therapeutic and prevention strategies for COVID-19. Here we present within-host modelling of viral load dynamics observed in the upper respiratory tract (URT), drawing upon 2172 serial measurements from 605 subjects, collected from 17 different studies. We developed a mechanistic model to describe viral load dynamics and host response, and contrast this with simpler mixed-effects regression analysis of peak viral load and its subsequent decline. We observed wide variation in URT viral load between individuals, over 5 orders of magnitude, at any given point in time since symptom onset. This variation was not explained by age, sex, or severity of illness, and these variables were not associated with the modelled early or late phases of immune-mediated control of viral load. We explored the application of the mechanistic model to identify measured immune responses associated with control of viral load. Neutralizing antibody correlated strongly with modelled immune-mediated control of viral load amongst subjects who produced neutralizing antibody. Our models can be used to identify host and viral factors which control URT viral load dynamics, informing future treatment and transmission blocking interventions.
Latin American Registry of renal involvement in COVID-19 disease. The relevance of assessing proteinuria throughout the clinical course
Authors: Lombardi Raúl , Ferreiro Alejandro , Ponce Daniela , Claure-Del Granado Rolando , Aroca Gustavo , Venegas Yanissa , Pereira Mariana , Chavez-Iñiguez Jonathan , Rojas Nelson , Villa Ana , Colombo Marcos , Carlino Cristina , Guimarâes Caio , Younes-Ibrahim Mauricio , Rizo Lilia Maria , Guzmán Gisselle , Varela Carlos , Rosa-Diez Guillermo , Janiques Diego , Ayala Roger , Coronel Galo , Roessler Eric , Amor Serena , Osorio Washington , Rivas Natalia , Pereira Benedito , de Azevedo Caroline , Flores Adriana , Ubillo José , Raño Julieta , Yu Luis , Burdmann Emmanuel A. , Rodríguez Luis , Galagarza-Gutiérrez Gianny , Curitomay-Cruz Jesús
Published: May 2021

The Latin American Society of Nephrology and Hypertension carried out a cohort prospective, multinational registry of patients with kidney impairment associated to COVID-19 in Latin America through open invitation in order to describe the characteristics of the disease in the region. A population of 870 patients from 12 countries were included. Median age was 63 years (54-74), most of patients were male (68.4%) and had comorbidities (87.2%). Acute kidney injury (AKI) was hospital-acquired in 64.7% and non-oliguric in 59.9%. Multiorgan dysfunction syndrome (MODS) due to COVID-19 and volume depletion were the main causes of AKI (59.2% and 35.7% respectively). Kidney replacement therapy was started in 46.2%. Non-recovery of renal function was observed in 65.3%. 71.5% of patients were admitted to ICU and 72.2% underwent mechanical ventilation. Proteinuria at admission was present in 62.4% of patients and proteinuria during hospital-stay occurred in 37.5%. Those patients with proteinuria at admission had higher burden of comorbidities, higher baseline sCr, higher mortality and MODS was severe. On the other hand, patients with de novo proteinuria had lower burden of comorbidities and near normal sCr at admission, but showed adverse course of disease and higher in-mortality. COVID-19 MODS was the main cause of AKI in both groups. All-cause mortality was 57.4%, and it was associated to age, chronic cardiac disease, fluid depletion, COVID-19 MODS, non-recovery of renal function, ICU admission, vasopressors, in-hospital complications and hospital stay. In conclusion, our study contributes to a better knowledge of this condition and highlights the relevance of the detection of proteinuria throughout the clinical course.
The Effect of Combined Respiratory Muscle Training (cRMT) on dysarthric speech following single CVA: A retrospective pilot study
Authors: Arnold Robert J. , Bausek Nina , Gaskill Christopher S. , Midani Tarek
Published: May 2021

Background

Dysarthria frequently occurs as a result of stroke and adversely impacts speech sound production, making it more difficult for the listener to understand what the person with dysarthria is attempting to communicate. This in turn may lead to social isolation, depression, and increased cost of care. Some studies have underscored the importance of respiratory muscle strengthening as it relates to improvement of speech intelligibility, However, the benefits of respiratory muscle training on dysarthric speech following stroke have not been explored. This retrospective investigation examined the effects of a combined Respiratory Muscle Training (cRMT) protocol upon speech intelligibility in persons post single cerebrovascular accident (CVA).

Methods

The clinical data of 10 patients who requested speech therapy at a pro bono outpatient clinic for the diagnosis and treatment of dysarthria following a single stroke was utilized for this study. The intervention group was treated with three 5-minute sessions with cRMT each day for 28 consecutive days. The control group received no cRMT and no other therapeutic exercise intervention during the time period. Respiratory function and speech intelligibility were assessed pre- and post-intervention in terms of peak expiratory flow, subject self-perception of intelligibility, and word level intelligibility.

Results

After 28 days of cRMT, the intervention group exhibited significant gains compared to the control group in peak expiratory flow (PEF) (IG: 73.12% vs CG: 4.66%), Self-Perception of Intelligibility (IG: 72.38% vs CG: 0.83%), and the word task of the Assessment of Intelligibility of Dysarthric Speech (AIDS) (IG: 43.92% vs. CG: 0%).

Conclusion

These retrospective data demonstrate cRMT is a feasible and effective treatment for improving breath support and speech intelligibility in persons with dysarthric speech after single stroke.
The Physiologic Response to COVID-19 Vaccination
Authors: Quer Giorgio , Gadaleta Matteo , Radin Jennifer M. , Andersen Kristian G. , Baca-Motes Katie , Ramos Edward , Topol Eric J. , Steinhubl Steven R.
Published: May 2021

Two mRNA vaccines and one adenovirus-based vaccine against SARS CoV-2 are currently being distributed at scale in the United States. Objective evidence of a specific individual’s physiologic response to that vaccine are not routinely tracked but may offer insights into the acute immune response and personal and/or vaccine characteristics associated with that. We explored this possibility using a smartphone app-based research platform developed early in the pandemic that enabled volunteers (38,911 individuals between 25 March 2020 and 4 April 2021) to share their smartwatch and activity tracker data, as well as self-report, when appropriate, any symptoms, COVID-19 test results and vaccination dates and type. Of 4,110 individuals who reported at least one mRNA vaccination dose, 3,312 provided adequate resting heart rate data from the peri-vaccine period for analysis. We found changes in resting heart rate with respect to an individual baseline increased the days after vaccination, peaked on day 2, and returned to normal on day 6, with a much stronger effect after second dose with respect to first dose (average changes 1.6 versus 0.5 beats per minute). The changes were more pronounced for individuals who received the Moderna vaccine (on both doses), those who previously tested positive to COVID-19 (on dose 1), and for individuals aged <40 years, after adjusting for possible confounding factors. Taking advantage of continuous passive data from personal sensors could potentially enable the identification of a digital fingerprint of inflammation, which might prove useful as a surrogate for vaccine-induced immune response.
A Call For Better Methodological Quality Of Reviews On Using Artificial Intelligence For COVID-19 Detection In Medical Imaging – An Umbrella Systematic Review
Authors: Jemioło Paweł , Storman Dawid , Orzechowski Patryk
Published: May 2021

Objective

In this umbrella systematic review, we screen existing reviews on using artificial intelligence (AI) techniques to diagnose COVID-19 in patients of any age and sex (both hospitalised and ambulatory) using medical images and assess their methodological quality.

Methods

We searched seven databases (MEDLINE, EMBASE, Web of Science, Scopus, dblp, Cochrane Library, IEEE Xplore) and two preprint services (arXiv, OSF Preprints) up to September 1, 2020. Eligible studies were identified as reviews or surveys where any metric of classification of detection of COVID-19 using AI was provided. Two independent reviewers did all steps of identification of records (titles and abstracts screening, full texts assessment, essential data extraction, and quality assessment). Any discrepancies were resolved by discussion. We qualitatively analyse methodological credibility of the reviews using AMSTAR 2 and evaluate reporting using PRISMA-DTA tools, leaving quantitative analysis for further publications.

Results

We included 22 reviews out of 725 records covering 165 primary studies. This review covers 416,254 participants in total, including 50,022 diagnosed with COVID-19. The methodological quality of all eligible studies was rated as critically low. 91% of papers had significant flaws in reporting quality. More than half of the reviews did not comment on the results of previously published reviews at all. Almost three fourth of the studies included less than 10% of available studies.

Discussion

In this umbrella review, we focus on the descriptive summary of included papers. Much wasting time and resources could be avoided if referring to previous reviews and following methodological guidelines. Due to the low credibility of evidence and flawed reporting, any recommendation about automated COVID-19 clinical diagnosis from medical images using AI at this point cannot be provided.

Funding

PO was supported by NIH grant AI116794 (the funding body had no role in the design, in any stage of the review, or in writing the manuscript); PJ and DS did not receive any funding.

Registration

The protocol of this review was registered on the OSF platform [1].
Obstructive sleep apnea is highly prevalent in COVID19 moderate to severe ARDS survivors: Findings of level I Polysomnography in a tertiary care hospital
Authors: Goyal Abhishek , Saxena Khushboo , Kar Avishek , Khurana Alkesh , Bhagtana Parneet Kaur , Rupa Sridevi Chinta Siva Koti , Pakhare Abhijit
Published: May 2021

Study Objectives

Studies have found Obstructive Sleep Apnea (OSA) as a risk factor for increased risk for COVID19 Acute respiratory Distress Syndrome (ARDS); but most of the studies were done in already known patients of OSA. This study was done to find prevalence of OSA in patients with COVID-19 related acute respiratory distress syndrome.

Methodology

A hospital based longitudinal study was conducted among COVID 19 Intensive Care Unit (ICU) survivors. All consecutive COVID19 with moderate to severe ARDS were evaluated for OSA by Level I Polysomnography (PSG) after 4-6 weeks of discharge. Prevalence of OSA and PSG variables {Total sleep time, Sleep efficiency, sleep stage percentage, Apnea Hypopnea Index (AHI), T90, nadir oxygen} was estimated.

Results

Out of 103 patients discharged from ICU during study period (October 2020 to 15 December 2020), 67 underwent Level I PSG. Mean Age was 52.6±10.9 years and mean Body Mass Index was 27.5 ± 6.2 Kg/m2. Total sleep time was 343.2 ± 86 minutes, sleep efficiency was 75.9±14.2%. OSA (AHI ≥5) was seen in 65/67 patients and 49 patients had moderate to severe OSA (i.e. AHI ≥ 15).

Conclusion

Moderate-severe OSA was highly prevalent (73%) in COVID19 moderate to severe ARDS survivors. Role of OSA in pathophysiology of COVID19 ARDS needs further evaluation.

Highlights

This study was done to find prevalence of OSA in patients with COVID-19 related Acute respiratory distress syndrome

Moderate-severe OSA is highly prevalent (73%) in COVID19 ARDS survivors.

To the best of our knowledge, it is first study in which level I PSG was done in COVID19 survivors.
Development and validation protocol for an instrument to measure women’s empowerment in urban sanitation across countries: The Agency, Resources, and Institutional Structures for Sanitation-related Empowerment (ARISE) Scales
Authors: Sinharoy Sheela S. , Conrad Amelia , Patrick Madeleine , McManus Shauna , Caruso Bethany A.
Published: May 2021

Introduction

Despite an increasing emphasis on gender and empowerment in water, sanitation, and hygiene (WaSH) programs, no rigorously validated survey instruments exist for measuring empowerment within the WaSH sector. Our objective is to develop and validate quantitative survey instruments to measure women’s empowerment in relation to sanitation in urban areas of low-and middle-income countries.

Methods and analysis

We are developing the Agency, Resources, and Institutional Structures for Sanitation-related Empowerment (ARISE) scales through a process that involves three phases: item development; scale development and initial validation; and scale evaluation and further validation. The first phase includes domain specification, item generation, face validity and content validity assessment, and item refinement. The second phase involves a second round of face validity and content validity assessment, followed by survey implementation in two cities (Tiruchirappalli, India and Kampala, Uganda) and data analysis involving factor analysis and item response theory approaches, as well as reliability and validity testing. The third phase involves a final round of face validity and content validity assessment, followed by survey implementation in three additional cities (Narsapur and Warangal, India; and Lusaka, Zambia) and statistical analysis using similar approaches as in Phase 2 for further validation.

Ethics and dissemination

Ethics approvals have been received from ethics boards in all study locations. The study team will share findings with key stakeholders to inform programming activities and will publish results in peer-reviewed journals.

Article Summary

Strengths and limitations of this study

We employ rigorous methods to develop survey instruments, including testing and validating 15 scales, to assess domains of women’s empowerment related to sanitation.

Phased data collection is being carried out across five urban locations in South Asia and Africa to ensure that the survey instruments are valid and comparable across contexts.

Our survey instruments are specific to women in urban settings; adaptation and further validity testing is needed to develop instruments that can be administered in other settings (e.g. rural, peri-urban) and with men.

The survey instruments are focused on empowerment at the individual, household, and community levels; they do not assess empowerment in markets (e.g. across the sanitation value chain) or in relation to policies and formal governance.
Engineering a customizable antibacterial T6SS-based platform inVibrio natriegens
Authors: Jana Biswanath , Keppel Kinga , Salomon Dor
Published: May 2021

Bacterial pathogens are a major risk to human, animal, and plant health. To counteract the spread of antibiotic resistance, alternative antibacterial strategies are urgently needed. Here, we constructed a proof-of-concept customizable, modular, and inducible antibacterial toxin delivery platform. By engineering a type VI secretion system (T6SS) that is controlled by an externally induced on/off switch, we transformed the safe bacterium,Vibrio natriegens, into an effective antibacterial weapon. Furthermore, we demonstrated that the delivered effector repertoire, and thus the toxicity range of this platform, can be easily manipulated and tested. We believe that this platform can serve as a foundation for novel antibacterial bio-treatments, as well as a unique tool to study antibacterial toxins.
Emerging genetic diversity of SARS-CoV-2 RNA dependent RNA polymerase (RdRp) alters its B-cell epitopes
Authors: Kumar Sushant , Azad Gajendra Kumar
Published: May 2021

The RNA dependent RNA polymerase (RdRp) plays crucial role in virus life cycle by replicating the viral RNA genome. The SARS-CoV-2 is an RNA virus that rapidly spread worldwide and during this process acquired mutations. This study was carried out to identify mutations in RdRp as the SARS-CoV-2 spread in India. We compared the 668 RdRp sequences reported from India with the first reported RdRp sequence from Wuhan, China. Our data revealed that RdRp have acquired sixty mutations among Indian isolates. Our protein modelling study also revealed that several mutants including D833Y, A699S, Y149C and C464F can potentially alter stability and flexibility of RdRp. We also predicted the potential B cell epitopes contributed by RdRp and identified thirty-six linear continuous and twenty-five discontinuous epitopes. Among sixty RdRp mutants identified in this study, 40% of them localises in the B cell epitopes region. Altogether, this study highlights the need to identify and characterize the variations in RdRp to understand the impact of these mutations on SARS-CoV-2.
SARS-CoV-2 cell-to-cell infection is resistant to neutralizing antibodies
Authors: Kruglova Natalia , Siniavin Andrei , Gushchin Vladimir , Mazurov Dmitriy
Published: May 2021

The COVID-19 pandemic caused by SARS-CoV-2 has posed a global threat to human lives and economics. One of the best ways to determine protection against the infection is to quantify the neutralizing activity of serum antibodies. Multiple assays have been developed to validate SARS-CoV-2 neutralization; most of them utilized lentiviral or vesicular stomatitis virus-based particles pseudotyped with the spike (S) protein, making them safe and acceptable to work with in many labs. However, these systems are only capable of measuring infection with purified particles. This study has developed a pseudoviral assay with replication-dependent reporter vectors that can accurately quantify the level of infection directly from the virus producing cell to the permissive target cell. Comparative analysis of cell-free and cell-to-cell infection revealed that the neutralizing activity of convalescent sera was more than tenfold lower in cell cocultures than in the cell-free mode of infection. As the pseudoviral system could not properly model the mechanisms of SARS-CoV-2 transmission, similar experiments were performed with replication-competent coronavirus, which detected nearly complete SARS-CoV-2 cell-to-cell infection resistance to neutralization by convalescent sera. Based on available studies, this is the first attempt to quantitatively measure SARS-CoV-2 cell-to-cell infection, for which the mechanisms are largely unknown. The findings suggest that this route of SARS-CoV-2 transmission could be of great importance for treatment and prevention of COVID-19.

Importance

Immune surveillance of viral or bacterial infections is largely mediated by neutralizing antibodies. Antibodies against the SARS-CoV-2 spike protein are produced after vaccination or infection, but their titers only partly reflect the degree of protection against infection. To identify protective antibodies, a neutralization test with replicating viruses or pseudoviruses (PVs) is required. This study developed lentiviral-based PV neutralization assays that, unlike similar systems reported earlier, enable quantitative measurement of SARS-CoV-2 neutralization in cell cocultures. Using both PVs and replication-competent virus, it was demonstrated that SARS-CoV-2 cell-to-cell infection is considerably more resistant to serum neutralization than infection with purified viral particles. The tests are easy to set up in many labs, and are believed to be more informative for monitoring SARS-CoV-2 collective immunity or entry inhibitor screening.
Preliminary Analysis of Safety and Immunogenicity of a SARS-CoV-2 Variant Vaccine Booster
Authors: Wu Kai , Choi Angela , Koch Matthew , Ma LingZhi , Hill Anna , Nunna Naveen , Huang Wenmei , Oestreicher Judy , Colpitts Tonya , Bennett Hamilton , Legault Holly , Paila Yamuna , Nestorova Biliana , Ding Baoyu , Pajon Rolando , Miller Jacqueline M , Leav Brett , Carfi Andrea , McPhee Roderick , Edwards Darin K
Published: May 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic of coronavirus disease 2019 (COVID-19) that has led to more than 3 million deaths worldwide. Safe and effective vaccines are now available, including the mRNA-1273 prototype vaccine, which encodes for the Wuhan SARS-CoV-2 spike (S) protein stabilized in the prefusion conformation by 2 proline substitutions. This vaccine showed 94% efficacy in prevention of symptomatic COVID-19 disease in a phase 3 clinical study. Recently, SARS-CoV-2 variants have emerged, some of which have shown decreased susceptibility to neutralization by vaccine-induced antibody, most notably the B.1.351 variant, although the overall impact on vaccine efficacy remains to be determined. In addition, recent evidence of waning antibody levels after infection or vaccination point to the need for periodic boosting of immunity. Here we present the preliminary evaluation of a clinical study on the use of the prototype mRNA-1273 or modified COVID-19 mRNA vaccines, designed to target emerging SARS-CoV-2 variants as booster vaccines in participants previously vaccinated approximately 6 months earlier with two doses of the prototype vaccine, mRNA-1273. The modified vaccines include a monovalent mRNA-1273.351 encoding for the S protein found in the B.1.351 variant and multivalent mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. As single 50 µg booster vaccinations, both mRNA-1273 and mRNA-1273.351 had acceptable safety profiles and were immunogenic. Antibody neutralization titers against B.1.351 and P.1 variants measured by SARS-CoV-2 pseudovirus neutralization (PsVN) assays before the booster vaccinations, approximately 6 to 8 months after the primary series, were low or below the assay limit of quantification, although geometric mean titers versus the wild-type strain remained above levels likely to be protective. Two weeks after the booster vaccinations, titers against the wild-type original strain, B.1.351, and P.1 variants increased to levels similar to or higher than peak titers after the primary series vaccinations. Although both mRNA-1273 and mRNA-1273.351 boosted neutralization of the wild-type original strain, and B.1.351 and P.1 variants, mRNA-1273.351 appeared to be more effective at increasing neutralization of the B.1.351 virus versus a boost with mRNA-1273. The vaccine trial is ongoing and boosting of clinical trial participants with the multivalent mRNA-1273.211 is currently being evaluated.
Rossmann-toolbox: a deep learning-based protocol for the prediction and design of cofactor specificity in Rossmann-fold proteins
Authors: Kaminski Kamil , Ludwiczak Jan , Jasinski Maciej , Bukala Adriana , Madaj Rafal , Szczepaniak Krzysztof , Dunin-Horkawicz Stanislaw
Published: May 2021

The Rossmann fold enzymes are involved in essential biochemical pathways such as nucleotide and amino acid metabolism. Their functioning relies on interaction with cofactors, small nucleoside-based compounds specifically recognized by a conserved βαβ motif shared by all Rossmann fold proteins. While Rossmann methyltransferases recognize only a single cofactor type, the S-Adenosylmethionine (SAM), the oxidoreductases, depending on the family, bind nicotinamide (NAD, NADP) or flavin-based (FAD) cofactors. In this study, we show that despite its short length, the βαβ motif unambiguously defines the specificity towards the cofactor. Following this observation, we trained two complementary deep learning models for the prediction of the cofactor specificity based on the sequence and structural features of the βαβ motif. A benchmark on two independent test sets, one containing βαβ motifs bearing no resemblance to those of the training set, and the other comprising 38 experimentally confirmed cases of rational design of the cofactor specificity, revealed the nearly perfect performance of the two methods. The Rossmann-toolbox protocols can be accessed via the webserver athttps://lbs.cent.uw.edu.pl/rossmann-toolboxand are available as a Python package athttps://github.com/labstructbioinf/rossmann-toolbox.

Key points

The Rossmann fold encompasses a multitude of diverse enzymes involved in most of the essential cellular pathways

Proteins belonging to the Rossmann fold co-evolved with their nucleoside-based cofactors and require them for the functioning

Manipulating the cofactor specificity is an important step in the process of enzyme engineering

We developed an end-to-end pipeline for the prediction and design of the cofactor specificity of the Rossmann fold proteins

Owing to the utilization of deep learning approaches the pipeline achieved nearly perfect accuracy
Neural Representations of Food-Related Attributes in the Human Orbitofrontal Cortex During Choice Deliberation in Anorexia Nervosa
Authors: Xue Alice M. , Foerde Karin , Timothy Walsh B. , Steinglass Joanna E. , Shohamy Daphna , Bakkour Akram
Published: May 2021

Decisions about what to eat recruit the orbitofrontal cortex (OFC) and involve the evaluation of food-related attributes, such as taste and health. These attributes are utilized differently by healthy individuals and patients with disordered eating behavior, but it is unclear whether these attributes are decodable from activity in the OFC in both groups and whether neural representations of these attributes are differentially related to decisions about food. We used fMRI combined with behavioral tasks to investigate the representation of taste and health attributes in the human OFC and the role of these representations in food choices in healthy individuals and patients with anorexia nervosa (AN). We found that subjective ratings of tastiness and healthiness could be decoded from patterns of activity in the OFC in both groups. However, health-related patterns of activity in the OFC were more related to the magnitude of choice preferences among patients with AN than healthy individuals. These findings suggest that maladaptive decision-making in AN is associated with more consideration of health information represented by the OFC during deliberation about what to eat.

Significance Statement

An open question about the orbitofrontal cortex (OFC) is whether it supports the evaluation of food-related attributes during deliberation about what to eat. We found that healthiness and tastiness information were decodable from patterns of neural activity in the OFC in both patients with anorexia nervosa (AN) and healthy controls. Critically, neural representations of health were more strongly related to choices in patients with AN, suggesting that maladaptive overconsideration of healthiness during deliberation about what to eat is related to activity in the OFC. More broadly, these results show that activity in the human OFC is associated with the evaluation of relevant attributes during value-based decision-making. These findings may also guide future research into the development of treatments for AN.
Cell Types of Origin in the Cell Free Transcriptome in Human Health and Disease
Authors: Vorperian Sevahn K. , Moufarrej Mira N. ,   Tabula Sapiens Consortium, Quake Stephen R.
Published: May 2021

Cell-free RNA (cfRNA) can be used to noninvasively measure dynamic and longitudinal physiological changes throughout the body. While there is considerable effort in the liquid biopsy field to determine disease tissue-of-origin, pathophysiology occurs at the cellular level. Here, we describe two approaches to identify cell type contributions to cfRNA. First we usedTabula Sapiens, a transcriptomic cell atlas of the human body to computationally deconvolve the cell-free transcriptome into a sum of cell type specific transcriptomes, thus revealing the spectrum of cell types readily detectable in the blood. Second, we used individual tissue transcriptomic cell atlases in combination with the Human Protein Atlas RNA consensus dataset to create cell type signature scores which can be used to infer the implicated cell types from cfRNA for a variety of diseases. Taken together, these results demonstrate that cfRNA reflects cellular contributions in health and disease from diverse cell types, potentially enabling determination of pathophysiological changes of many cell types from a single blood test.
Unbiased integration of single cell transcriptome replicates
Authors: Lopez Martin Loza , Teraguchi Shunsuke , Standley Daron M. , Diez Diego
Published: May 2021

Single cell transcriptomic approaches are becoming mainstream, with replicate experiments commonly performed with the same single cell technology. Methods that enable integration of these datasets by removing batch effects while preserving biological information are required for unbiased data interpretation. Here we introduce Canek for this purpose. Canek leverages information from mutual nearest neighbor to combine local linear corrections with cell-specific non-linear corrections within a fuzzy logic framework. Using a combination of real and synthetic datasets, we show that Canek corrects batch effects while introducing the least amount of bias compared with competing methods. Canek is computationally efficient and can easily integrate thousands of single-cell transcriptomes from replicated experiments.