bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellulomonas citrea sp. nov., isolated from paddy soil
Authors: Lee Hyo-Jin , Kim Song-Yeon , Whang Kyung-Sook
Published: September 2020

Two Gram-stain-positive, facultatively anaerobic, motile, aerobic, rod-shaped and non-spore-forming actinobacteria, strains AO-9T and AO-18, were isolated from paddy soil collected from Daejeon, Republic of Korea. Colonies were smooth, lemon-yellow and circular and 0.5–0.8×2.0–2.4 µm in diameter after 3 days of incubation at 28 °C on tryptic soy agar. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strains AO-9T and AO-18 belonged to the genus

Cellulomonas

, showing the highest sequence similarities to

Cellulomonas marina

FXJ8.089T (96.6 %),

Cellulomonas endophytica

SYSUP0004T (96.5 %),

Cellulomonas gelida

DSM 20111T (96.2 %),

Cellulomonas uda

DSM 20107T (96.1 %),

Cellulomonas rhizosphaerae

NEAU-TCZ24T (96.1 %),

Cellulomonas composti

TR7-06T (96.0 %),

Cellulomonas persica

JCM 18111T (96.0 %) and less than 96 % to other closely related species. The DNA–DNA hybridization values between strains AO-9T and AO-18 were 87 %. The average nucleotide identity and digital DNA–DNA hybridization values between strain AO-9T and type strains of related species of the genus

Cellulomonas

were 84.0–85.8 % and 20.3–20.9 %, respectively. The major cellular fatty acids are anteiso-C15:0 (49.9 %), C14:0 (12.9 %) and iso-C14:0 (12.1 %). The predominant isoprenoid quinone was MK-9 (H4). The polar lipid profile consists of diphosphatidylglycerol, phosphatidylglycerol and one unidentified lipid. The DNA G+C content was 72.9 mol%. Based on its distinctive phenotypic, phylogenetic and chemotaxonomic characteristics, the two strains are considered to represent novel species of the genus

Cellulomonas

, for which the name Cellulomonas citrea sp. nov. is proposed. The type strain is AO-9T (=KACC 19069T=NBRC 112523T).
Pseudomonas brassicae sp. nov., a pathogen causing head rot of broccoli in Japan
Authors: Sawada Hiroyuki , Fujikawa Takashi , Horita Harukuni
Published: September 2020

Phytopathogenic bacteria, MAFF 212426, MAFF 212427T, MAFF 212428 and MAFF 212429, were isolated from head rot lesions of broccoli (Brassica oleracea L. var. italica Plenck) in Hokkaido, Japan, and subjected to polyphasic taxonomic characterization. The cells were Gram-reaction-negative, aerobic, non-spore-forming, motile with one or two polar flagella, rod-shaped and formed pale yellow colonies. Results of 16S rRNA gene sequence analysis showed that they belong to the genus

Pseudomonas

with the highest similarity to ‘Pseudomonas qingdaonensis’ JJ3T (99.86 %),

Pseudomonas laurentiana

GSL-010T (99.22 %),

Pseudomonas huaxiensis

WCHPs060044T (99.01 %),

Pseudomonas japonica

NBRC 103040T (98.87 %) and

Pseudomonas alkylphenolica

KL28T (98.73 %). The genomic DNA G+C content was 63.4 mol% and the major fatty acids (>5 % of the total fatty acids) were summed feature 3 (C16 : 1 ω7c / C16 : 1 ω6c), C16 : 0, summed feature 8 (C18 : 1 ω7c / C18 : 1 ω6c) and C17 : 0 cyclo. Multilocus sequence analysis using the partial rpoD, gyrB and rpoB gene sequences and phylogenomic analyses based on the whole genome sequences demonstrated that the strains are members of the

Pseudomonas putida

group, but form a monophyletic, robust clade separated from their closest relatives. Average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values corroborated their novel species status, with 88.39 % (ANI) and 35.8 % (dDDH) as the highest scores with ‘P. qingdaonensis’ JJ3T. The strains were differentiated from their closest relatives by phenotypic characteristics, pathogenicity on broccoli, and whole-cell MALDI-TOF mass spectrometry profiles. The phenotypic, chemotaxonomic and genotypic data showed that the strains represent a novel

Pseudomonas

species, for which the name Pseudomonas brassicae sp. nov. is proposed. The type strain is MAFF 212427T (=ICMP 23635T).
Sample Pooling is a Viable Strategy for SARS-CoV-2 Detection in Low-Prevalence Settings
Authors: Chong Brian SW , Tran Thomas , Druce Julian , Ballard Susan A , Simpson Julie A , Catton Mike
Published: September 2020

BACKGROUND

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has significantly increased demand on laboratory throughput and reagents for nucleic acid extraction and polymerase chain reaction (PCR). Reagent shortages may limit the expansion of testing required to scale back isolation measures.

AIM

To investigate the viability of sample pooling as a strategy for increasing test throughput and conserving PCR reagents; to report our early experience with pooling of clinical samples.

METHODS

A pre-implementation study was performed to assess the sensitivity and theoretical efficiency of two, four, and eight-sample pools in a real-time reverse transcription PCR-based workflow. A standard operating procedure was developed and implemented in two laboratories during periods of peak demand, inclusive of over 29,000 clinical samples processed in our laboratory.

RESULTS

Sensitivity decreased (mean absolute increase in cycle threshold value of 0.6, 2.3, and 3.0 for pools of two, four, and eight samples respectively) and efficiency increased as pool size increased. Gains from pooling diminished at high disease prevalence. Our standard operating procedure was successfully implemented across two laboratories. Increased workflow complexity imparts a higher risk of errors, and requires risk mitigation strategies. Turnaround time for individual samples increased, hence urgent samples should not be pooled.

CONCLUSIONS

Pooling is a viable strategy for high-throughput testing of SARS-CoV-2 in low-prevalence settings.
The methodological quality of COVID-19 systematic reviews is low, except for Cochrane reviews: a meta-epidemiological study
Authors: Kataoka Yuki , Oide Shiho , Ariie Takashi , Tsujimoto Yasushi , Furukawa Toshi A.
Published: September 2020

Objectives

The objective of this study was to investigate the methodological quality of COVID-19 systematic reviews (SRs) indexed in medRxiv and PubMed, compared with Cochrane COVID Reviews.

Study Design and Setting

This is a cross-sectional meta-epidemiological study. We searched medRxiv, PubMed, and Cochrane Database of Systematic Reviews for SRs of COVID-19. We evaluated the methodological quality using A MeaSurement Tool to Assess systematic Reviews (AMSTAR) checklists. The maximum AMSTAR score is 11, and minimum is 0. Higher score means better quality.

Results

We included 9 Cochrane reviews as well as randomly selected 100 non-Cochrane reviews in medRxiv and PubMed. Compared with Cochrane reviews (mean 9.33, standard deviation 1.32), the mean AMSTAR scores of the articles in medRxiv were lower (mean difference -2.85, 95%confidence intervals (CI): -0.96 to -4.74) and those in PubMed was also lower (mean difference -3.28, 95% CI: -1.40 to -5.15), with no difference between the latter two.

Conclusions

It should be noted that AMSTAR is not a perfect tool of assessing quality SRs other than intervention. Readers should pay attention to the potentially low methodological quality of COVID-19 SRs in both PubMed and medRxiv but less so in Cochrane COVID reviews.

PROTOCOL AND REGISTRATION

We developed the protocol before conducting this study (Kataoka Y, Oide S, Ariie T, Tsujimoto Y, Furukawa TA. Quality of COVID-19 research in preprints: a meta-epidemiological study protocol. Protocols.io 2020.https://doi.org/10.17504/protocols.io.bhm8j49w.).

What is new?

Key findings

-

The methodological quality of COVID-19 systematic reviews (SRs) in medRxiv and PubMed were lower than Cochrane COVID reviews.

-

The methodological quality of reviews in medRxiv and PubMed did not differ.

What this study adds to what was known

-

Expert opinions and a preliminary review suggested the low quality of COVID-19 SRs but this hypothesis has not been examined empirically.

-

We evaluated the methodological quality of COVID-19 SRs using comprehensive search and confirmed that the quality was low except for Cochrane reviews.

What is the implication and what should change now?

Readers should pay attention to the potentially low methodological quality of COVID-19 SRs in both PubMed and medRxiv but less so in Cochrane COVID reviews.

The methodological quality of COVID-19 SRs except for Cochrane COVID reviews needed to be improved.
Delineation of the Clinical Features and Treatment Response of Oromandibular Dystonia: A Multicenter Summary of 2,057 Cases
Authors: Scorr Laura M. , Factor Stewart A. , Parra Sahyli Perez , Kaye Rachel , Paniello Randal C. , Norris Scott A. , Perlmutter Joel , Bäumer Tobias , Usnich Tatiana , Berman Brian , Mailly Marie , Roze Emmanuel , Vidailhet Marie , Jankovic Joseph , LeDoux Mark S. , Barbano Richard , Chang Florence , Fung Victor , Richardson Sarah Pirio , Blitzer Andrew , Jinnah H.A. ,   for the Dystonia Coalition Investigators
Published: September 2020

Objective

To better characterize oromandibular dystonia (OMD) to facilitate early diagnosis and test the hypothesis that botulinum toxin treatment alleviates symptoms, regardless of etiology, to provide guidance on treatment strategies.

Methods

To better characterize this condition we utilize a three-pronged approach. First, we provide a comprehensive summary of the world’s literature encompassing 1157 cases in 27 separate manuscripts. Next, we describe the clinical features of 727 OMD subjects enrolled by the Dystonia Coalition (DC), an international multicenter database. Finally, we provide details of the treatment approach and response from two expert centers where large numbers of OMD patients are followed. Cases from expert centers were utilized to analyze whether response to botulinum toxin varied by etiology of OMD.

Results

In all cohorts, typical age at onset was in the 50s and approximately 70 % of cases were female. Although the literature OMD more commonly described as a focal dystonia, analysis of the DC database revealed it more commonly appears as part of a segmental dystonia. Expert center review of 173 cases revealed botulinum toxin injections improved symptom severity by more than 50% in approximately 78% of subjects. Among the patients at expert centers, analysis revealed that treatment response did not vary by etiology.

Conclusions

Botulinum toxin injections are an effective treatment for OMD, regardless of etiology. By providing a more comprehensive description of OMD and the therapeutic efficacy of botulinum toxin for this type of dystonia, we hope to improve clinical recognition to aid in timely diagnosis and inform treatment strategies.
Cytotoxic lymphocytes are dysregulated in multisystem inflammatory syndrome in children
Authors: Beckmann Noam D. , Comella Phillip H. , Cheng Esther , Lepow Lauren , Beckmann Aviva G. , Mouskas Konstantinos , Simons Nicole W. , Hoffman Gabriel E. , Francoeur Nancy J. , Valle Diane Marie Del , Kang Gurpawan , Moya Emily , Wilkins Lillian , Berichel Jessica Le , Chang Christie , Marvin Robert , Calorossi Sharlene , Lansky Alona , Walker Laura , Yi Nancy , Yu Alex , Hartnett Matthew , Eaton Melody , Hatem Sandra , Jamal Hajra , Akyatan Alara , Tabachnikova Alexandra , Liharska Lora E. , Cotter Liam , Fennessey Brian , Vaid Akhil , Barturen Guillermo , Tyler Scott R. , Shah Hardik , Wang Ying-chih , Sridhar Shwetha Hara , Soto Juan , Bose Swaroop , Madrid Kent , Ellis Ethan , Merzier Elyze , Vlachos Konstantinos , Fishman Nataly , Tin Manying , Smith Melissa , Xie Hui , Patel Manishkumar , Argueta Kimberly , Harris Jocelyn , Karekar Neha , Batchelor Craig , Lacunza Jose , Yishak Mahlet , Tuballes Kevin , Scott Leisha , Kumar Arvind , Jaladanki Suraj , Thompson Ryan , Clark Evan , Losic Bojan ,   The Mount Sinai COVID-19 Biobank Team, Zhu Jun , Wang Wenhui , Kasarskis Andrew , Glicksberg Benjamin S. , Nadkarni Girish , Bogunovic Dusan , Elaiho Cordelia , Gangadharan Sandeep , Ofori-Amanfo George , Alesso-Carra Kasey , Onel Kenan , Wilson Karen M. , Argmann Carmen , Alarcón-Riquelme Marta E. , Marron Thomas U. , Rahman Adeeb , Kim-Schulze Seunghee , Gnjatic Sacha , Gelb Bruce D. , Merad Miriam , Sebra Robert , Schadt Eric E. , Charney Alexander W.
Published: September 2020

Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and multiple organ involvement in individuals under 21 years following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To identify genes, pathways and cell types driving MIS-C, we sequenced the blood transcriptomes of MIS-C cases, pediatric cases of coronavirus disease 2019, and healthy controls. We define a MIS-C transcriptional signature partially shared with the transcriptional response to SARS-CoV-2 infection and with the signature of Kawasaki disease, a clinically similar condition. By projecting the MIS-C signature onto a co-expression network, we identified disease gene modules and found genes downregulated in MIS-C clustered in a module enriched for the transcriptional signatures of exhausted CD8+T-cells and CD56dimCD57+NK cells. Bayesian network analyses revealed nine key regulators of this module, includingTBX21, a central coordinator of exhausted CD8+T-cell differentiation. Together, these findings suggest dysregulated cytotoxic lymphocyte response to SARS-Cov-2 infection in MIS-C.
Estimating Unreported Deaths from Natural Causes during COVID-19
Authors: Stear Benjamin , Hernandez Kyle M. , Manian Vidya , Taylor Deanne , Conley Catharine A.
Published: September 2020

Efforts to mitigate the spread of coronavirus disease 2019 (COVID-19) in the United States require an accurate understanding of how the epidemic is progressing. The National Center for Health Statistics (NCHS) releases weekly numbers of deaths attributed to a set of ‘select causes’, including deaths from COVID-19 in the entire United States (US), by state, and cumulatively for individual counties. Comparing US and state level deaths from select causes recorded in 2020 with values from 2014-2019 identifies a number of differences that exceeded 95% confidence limits on historical mean values, including three states with deaths possibly from COVID-19 in December 2019. Comparing county-level NCHS datasets with county-level data on deaths from COVID-19 compiled by four public pandemic tracking sites suggests that a large number of COVID-19 deaths have not yet been reported to the NCHS. Dividing the numbers of COVID-19 deaths counted by the public tracking sites by the percentage of COVID-19 deaths reported to the NCHS suggests that approximately 20% of all US deaths from Natural Causes, as many as 200,000, may not yet have been reported to the NCHS. Evaluating changes in the fractions of deaths attributed to COVID-19 and other specific causes or nonspecific outcomes during the epidemic, relative to 2020 totals or historical mean values, can provide a valuable perspective on the public health consequences of COVID-19.

Significance Statement

Estimating total deaths from natural causes using the percentage of natural cause deaths from COVID-19 reported to the CDC and the number of COVID-19 deaths counted by public tracking sites suggests that up to 200,000 deaths from natural causes between 22 April and 15 August, 2020, around 20% of the total recorded as of 26 August, have not yet been reported to the CDC.
Are COVID-19 proximity tracing apps working under real-world conditions? Indicator development and assessment of drivers for app (non-)use
Authors: Wyl Viktor von , Höglinger Marc , Sieber Chloé , Kaufmann Marco , Moser André , Serra-Burriel Miquel , Ballouz Tala , Menges Dominik , Frei Anja , Puhan Milo A.
Published: September 2020

Digital proximity tracing (DPT) apps have been released to mitigate SARS-CoV-2 transmission, but it remains unclear how their effectiveness should be monitored. The aim of this study was to formalize indicators for measuring the fulfillment of assumptions for appropriate proximity tracing app functioning.

Six indicators were developed to monitor the SwissCovid app functioning and effectiveness in the Swiss population. Using official statistics and survey data, we calculated indicator values and examined socio-demographic factors associated with the SwissCovid app utilization. Indicators show that 1 in 3 adults in Switzerland have downloaded the app. However, only 15% of new cases also triggered DPT-app notifications, and indicators also reveal ignored app notifications. In the full survey sample (n=2’098), higher monthly household income or being a non-smoker were associated with higher SwissCovid app uptake; older age or having a non-Swiss nationality with a lower uptake. In a subsample including more detailed information (n=701), high trust in health authorities was associated with higher SwissCovid app uptake.

The indicators help to monitor key drivers of DPT-apps effectiveness and hint to non-compliance issues. Streamlining procedures, removing technical hurdles, and communicating the usefulness of DPT-apps are crucial to promote uptake, compliance, and ultimately effectiveness of DPT-apps for pandemic mitigation.
Sleep Duration and the Risk of Metabolic Syndrome: a Systematic Review and Meta-analysis
Authors: Hua Jianian , Jiang Hezi , Fang Qi
Published: September 2020

Objective

Epidemiologic studies have reported inconsistent findings about the association between sleep duration and metabolic syndrome. We aimed to clarify this association by method of metaanalysis.

Methods

Medline, Embase, CINAHL and PsycINFO databases were searched from inception to May 2020. We collected data from 235,895 participants from 9 prospective cohort studies, and 340,492 participants from 26 cross-sectional studies. Risk ratios (RR) or odds ratios (OR) were calculated separately for cohort studies and cross-sectional studies, through meta-analysis of adjusted data from individual studies.

Results

For cohort studies, short sleep duration was associated with an increased risk of metabolic syndrome (RR, 1.15; 95% CI, 1.05-1.25). Long sleep duration was not associated with new onset metabolic syndrome (RR, 1.02, 0.85-1.18). For cross-sectional studies, both short (OR, 1.12, 95% CI, 1.08-1.18) and long (OR, 1.06, 1.01-1.11) sleep duration was associated with high prevalence of metabolic syndrome.

Conclusions

Only short sleep duration was associated with an increased risk of metabolic syndrome. Future studies should address whether the association is casual and modifiable.
Pan-cancer analysis reveals unique molecular patterns associated with age
Authors: Shah Yajas , Verma Akanksha , Marderstein Andrew , Bhinder Bhavneet , Elemento Olivier
Published: September 2020

Older age is a strong risk factor for several diseases, including cancer. In cancer, older age is also frequently associated with a more aggressive, treatment-refractory tumor phenotype. The etiology and biology of age-associated differences among cancers are poorly understood. To address this knowledge gap, we sought to delineate the differences in tumor molecular characteristics between younger and older patients across a variety of tumor types. We found that tumors in younger and older patients exhibit widespread molecular differences. First, we observed that tumors in younger individuals, unlike those in older ones, exhibit an accelerated molecular aging phenotype associated with some hallmarks of premature senescence. Second, we found that tumors from younger individuals are enriched for driver gene mutations resulting in homologous recombination defects. Third, we observed a trend towards a decrease in immune infiltration and function in older patients and found that, immunologically, young tumor tissue resembles aged healthy tissue. Taken together, we find that tumors from young individuals possess unique characteristics compared to tumors in older individuals, which can potentially be leveraged for differential therapeutic strategies.
Motor and cognitive outcomes of low birth weight neonates born in a limited resource country: a systematic review
Authors: Radaelli Graciane , Leal-Conceição Eduardo , Neto Felipe K. , Taurisano Melissa R. G. , Majolo Fernanda , Bruzzo Fernanda T. K. , Linda Booij , Nunes Magda L.
Published: September 2020

Objective

To examine the outcomes of motor and cognitive development among neonates born with low birth weight (LBW) or very low birth weight (VLBW).

Data sources

Systematic review carried out in PubMed, Cochrane Library and Web of Science using the search strategy using combinations of the following keywords and terms: preterm birth OR prematurity OR premature Infants OR premature children AND low birth weight children OR very low birth weight children AND neurodevelopment OR cognitive development OR Motor development OR follow up AND humans. Articles searched were published from inception until July, 2019, and involved children born and evaluated in Brazil. The bias risk analysis was adapted from the STROBE scale, used to evaluate the methodology of the included studies.

Data synthesis

The search identified 2,214 publications. After screening for titles and abstracts and removing duplicate entries, full texts of 38 articles were reviewed. After reading full texts, 24 articles met the inclusion criteria (articles in Portuguese and English), dated from 1998 to 2017). Endnote Version X9 software was used for data extraction. Two reviewers performed the literature search and study selection independently. Disagreements were solved by consensus or by a third reviewer.

Results

it was evidenced an inferior motor development of children with LBW when compared to the control population, the standardized mean difference of [-1.15 (95% CI - 1.56, -0.73), I2 80%], children with LBW have lower cognitive development according the standardized mean difference of [-0,71 (95% CI -0.99, -0.44) I2 67%].

Conclusion

Our review reinforces that impaired motor and cognitive outcome is a significant long-term outcome associated with LBW. The risk of impairment in those domains increases with decreasing gestational age.
Prevalence of SARS-CoV-2 Infections in a Pediatric Orthopedic Hospital
Authors: Bardai Ghalib , Ouellet Jean A. , Engelhardt Thomas , Bertolizio Gianluca , Wu Zenghui , Rauch Frank
Published: September 2020

This project assessed the prevalence of active and past infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a specialized pediatric institution that did not provide care for coronavirus disease 2019 (Covid-19). The study was performed in Montreal, the city with the highest number of Covid-19 cases in Canada during the early phase of the pandemic. Testing for SARS-CoV-2 RNA in 199 individuals (39 children, 61 accompanying persons, 99 hospital employees) did not reveal active infection in any of the study participants. However, 22 (11%) of study participants had SARSCoV-2 IgG antibodies, indicating prior infection. Ten of these participants did not report symptoms compatible with Covid-19 in the 6 months prior to the study. Thus, although no evidence for active infection was found within the institution, consideration should be given to regular staff testing to detect asymptomatic spreading of SARS-CoV-2. In addition, it could be useful to test accompanying persons in children presenting for surgical procedures.
U.S. Food and Drug Administration utilization of postmarketing requirements and postmarketing commitments, 2009-2018
Authors: Skydel Joshua J. , Zhang Audrey D. , Dhruva Sanket S. , Ross Joseph S. , Wallach Joshua D.
Published: September 2020

Background/Aims

The U.S. Food and Drug Administration (FDA) outlines clinical studies as postmarketing requirements and commitments to be fulfilled following FDA approval of new drugs and biologics (“therapeutics”). As regulators have increasingly emphasized lifecycle evaluation of approved therapeutics, postmarketing studies are intended to advance our understanding of therapeutic safety and efficacy, yet little is known about how often clinical studies are outlined or the indications they investigate. Therefore, we characterized FDA postmarketing requirements and commitments for new therapeutics approved from 2009-2018.

Methods

We conducted a cross-sectional study of all novel therapeutics, including small molecule drugs and biologics, receiving original FDA approval from 2009-2018, using approval letters accessed through the Drug@FDA database. Outcomes included the number and characteristics of FDA postmarketing requirements and commitments for new therapeutics at original approval, including types of studies outlined, indications to be investigated, and clinical evidence to be generated.

Results

From 2009-2018, FDA approved 343 new therapeutics with 1978 postmarketing requirements and commitments. Overall, 750 (37.9%) postmarketing requirements and commitments outlined clinical studies. For 71 of 343 (20.7%) therapeutics, no postmarketing requirements nor commitments for clinical studies were outlined, while at least 1 was outlined for 272 (79.3%; median = 2 (IQR, 1-4)). Among these 272 therapeutics, the number of postmarketing requirements and commitments for clinical studies per therapeutic did not significantly change from 2009 (median 2 (IQR, 1-4)) to 2018 (median 2 (IQR, 1-3); P = .54). Among the 750 postmarketing requirements and commitments for clinical studies, 448 (59.7%) outlined new prospective cohort studies, registries, or clinical trials, while the remainder outlined retrospective studies, secondary analyses, or completion of ongoing studies. Although 455 (60.7%) clinical studies investigated only original approved therapeutic indications, 123 (16.4%) enrolled from an expansion of the approved disease population and 61 (8.1%) investigated diseases unrelated to approved indications.

Conclusions

Most therapeutics are approved by FDA with at least 1 postmarketing requirement or commitment for a clinical study, which outline investigations of safety or efficacy for both approved and unapproved indications. However, the median number of 2 clinical studies outlined has remained relatively constant over the last decade, despite increasing emphasis on lifecycle evaluation of approved therapeutics.
Pathogenic SPTBN1 variants cause a novel autosomal dominant neurodevelopmental syndrome
Authors: Cousin Margot A. , Breau Keith A. , Creighton Blake A. , Spillmann Rebecca C. , Torti Erin , Dontu Sruthi , Tripathi Swarnendu , Ajit Deepa , Harper Kathryn M. , Stankewich Michael C. , Person Richard E. , Si Yue , Normand Elizabeth A. , Blevins Amy , May Alison S. , Bier Louise , Aggarwal Vimla , Mancini Grazia M. S. , van Slegtenhorst Marjon A. , Cremer Kirsten , Becker Jessica , Engels Hartmut , Aretz Stefan , MacKenzie Jennifer J. , Brilstra Eva , van Gassen Koen L. I. , van Jaarsveld Richard H. , Oegema Renske , Parsons Gretchen M. , Mark Paul , Helbig Ingo , McKeown Sarah E. , Stratton Robert , Cogne Benjamin , Isidor Bertrand , Cacheiro Pilar , Smedley Damian , Firth Helen V. , Bierhals Tatjana , Kloth Katja , Weiss Deike , Fairley Cecilia , Shieh Joseph T. , Kritzer Amy , Jayakar Parul , Kurtz-Nelson Evangeline , Bernier Raphael , Wang Tianyun , Eichler Evan E. , van de Laar Ingrid M.B.H. , McConkie-Rosell Allyn , McDonald Marie , Kemppainen Jennifer , Lanpher Brendan C. , Schultz-Rogers Laura E. , Gunderson Lauren B. , Pichurin Pavel N. , Yoon Grace , Zech Michael , Jech Robert , Winkelmann Juliane ,   Undiagnosed Diseases Network,   Genomics England Research Consortium, Zimmermann Michael T. , Temple Brenda , Moy Sheryl S. , Klee Eric W. , Tan Queenie K.-G. , Lorenzo Damaris N.
Published: September 2020

SPTBN1 encodes βII-spectrin, the ubiquitously expressed member of the β-spectrin family that forms micrometer-scale networks associated with plasma membranes. βII-spectrin is abundantly expressed in the brain, where it is essential for neuronal development and connectivity. Mice deficient in neuronal βII-spectrin expression have defects in cortical organization, global developmental delay, dysmorphisms, and behavioral deficiencies of corresponding severity. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous variants in this gene may also present with measurable compromise of neural development and function. Here we report the identification of heterozygous SPTBN1 variants in 29 individuals who present with global developmental, language and motor delays, mild to severe intellectual disability, autistic features, seizures, behavioral and movement abnormalities, hypotonia, and variable dysmorphic facial features. We show that these SPTBN1 variants lead to loss-of-function, gain-of-function, and dominant negative effects that affect protein stability, disrupt binding to key protein partners, and disturb cytoskeleton organization and dynamics. Our studies define the genetic basis of this new neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and neural development, and underscore the critical role of βII-spectrin in the central nervous system.
Comparative performance of five commercially available serologic assays to detect antibodies to SARS-CoV-2 and identify individuals with high neutralizing titers
Authors: Patel Eshan U. , Bloch Evan M. , Clarke William , Hsieh Yu-Hsiang , Boon Denali , Eby Yolanda , Fernandez Reinaldo E. , Baker Owen R. , Keruly Morgan , Kirby Charles S. , Klock Ethan , Littlefield Kirsten , Miller Jernelle , Schmidt Haley A. , Sullivan Philip , Piwowar-Manning Estelle , Shrestha Ruchee , Redd Andrew D. , Rothman Richard E. , Sullivan David , Shoham Shmuel , Casadevall Arturo , Quinn Thomas C. , Pekosz Andrew , Tobian Aaron A.R. , Laeyendecker Oliver
Published: September 2020

Accurate serological assays to detect antibodies to SARS-CoV-2 are needed to characterize the epidemiology of SARS-CoV-2 infection and identify potential candidates for COVID-19 convalescent plasma (CCP) donation. This study compared the performance of commercial enzyme immunoassays (EIAs) to detect IgG or total antibodies to SARS-CoV-2 and neutralizing antibodies (nAb). The diagnostic accuracy of five commercially available EIAs (Abbott, Euroimmun, EDI, ImmunoDiagnostics, and Roche) to detect IgG or total antibodies to SARS-CoV-2 was evaluated from cross-sectional samples of potential CCP donors that had prior molecular confirmation of SARS-CoV-2 infection for sensitivity (n=214) and pre-pandemic emergency department patients for specificity (n=1,102). Of the 214 potential CCP donors, all were sampled >14 days since symptom onset and only a minority had been hospitalized due to COVID-19 (n=16 [7.5%]); 140 potential CCP donors were tested by all five EIAs and a microneutralization assay. When performed according to the manufacturers’ protocol to detect IgG or total antibodies to SARS-CoV-2, the sensitivity of each EIA ranged from 76.4% to 93.9%, and the specificity of each EIA ranged from 87.0% to 99.6%. Using a nAb titer cutoff of ≥160 as the reference positive test (n=140 CCP donors), the empirical area under receiver operating curve of each EIA ranged from 0.66 (Roche) to 0.90 (Euroimmun). Commercial EIAs with high diagnostic accuracy to detect SARS-CoV-2 antibodies did not necessarily have high diagnostic accuracy to detect high nAbs. Some but not all commercial EIAs may be useful in the identification of individuals with high nAbs in convalescent individuals.
A comprehensive analysis of recovered COVID-19 patients and dynamic trend in antibodies over 3 months using ELISA and CLIA methods
Authors: Dehgani-Mobaraki Puya , Zaidi Asiya Kamber , Floridi Alessandro , Lepri Alessandro , Floridi Emanuela , Gherardi Alessia , Bernini-Carri Enrico , D’urzo Eleonora , Dehgani-Mobaraki Massoud
Published: September 2020

Background

Since the Coronavirus disease-2019 outbreak, most studies have focused on etiopathogenic aspects and treatment strategies. Acquired immunity still remains a dilemma. The aim of our study included a comprehensive analysis of patient characteristics, evaluation of antibody response, and its trend over a period of three months in recovered patients.

Methods

Monocentric investigator-initiated pilot longitudinal observational study conducted by the Association Naso Sano, on a cohort of 30 COVID recovered patients based in the Umbria region, followed up from April to June 2020 for baseline blood counts, IgM and IgG trends using two different serological assays-ELISA and CLIA. The demographics, blood group, co-morbidities and treatment modalities were recorded from each patient along with an analysis of clinical profile, dates concerning symptom onset, first positive and two consecutive negative swabs using an online questionnaire followed by serological testing. Descriptive and Bivariate (Pearson correlation coefficient) statistics were conducted to detect statistically significant correlations.

Findings

The study involved 30 patients with a M:F ratio of 0.57 and a distribution of mild (67%), moderate (30%) and critical (3%). Majority of the patients were healthcare workers (40%) and the mean viral shedding duration was 20.13 ± 6.17 days. The IgG levels offered long-standing protection as long as 3 months in some cases. A statistically significant, directly proportional correlation (Pearson) exists between ELISA and CLIA values for IgM. Some patients also expressed titers lower than the detection threshold and therefore a positive RT-PCR test does not necessarily guarantee a high IgG response in the recovery period.

Interpretation

The data presented in our study provides a relative long-term analysis and possible explanation regarding the protection developed by patients recovered from COVID-19.
Risk Factors for ICU Admission, Mechanical Ventilation and Mortality in Hospitalized Patients with COVID-19 in Hubei, China
Authors: Ren Hong Gang , Guo Xingyi , Blighe Kevin , Zhu Fang , Martin Janet , Safdar Luqman Bin , Yang Pengcheng , Wang Dao Wen , Hu Qinyong , Huo Nan , Stebbing Justin , Cheng Davy
Published: September 2020

Purpose

To examine the risk factors for Intensive Care Unit (ICU) admission, mechanical ventilation and mortality in hospitalized patients with COVID-19.

Methods

This was a retrospective cohort study including 432 patients with laboratory-confirmed COVID-19 who were admitted to three medical centers in Hubei province from January 1st to April 10th 2020. Primary outcomes included ICU admission, mechanical ventilation and death occurring while hospitalized or within 30 days.

Results

Of the 432 confirmed patients, 9.5% were admitted to the ICU, 27.3% required mechanical ventilation, and 33.1% died. Total leukocyte count was higher in survivors compared with those who died (8.9 vs 4.8 × 109/l), but lymphocyte counts were lower (0.6 vs 1.0 × 109/l). D-dimer was significantly higher in patients who died compared to survivors (6.0ug/l vs 1.0ug/l, p<0.0001. This was also seen when comparing mechanically versus non-mechanically-ventilated patients. Other significant differences were seen in AST, ALT, LDH, total bilirubin and creating kinase. The following were associated with increased odds of death: age > 65 years (adjusted hazard ratio (HR 2.09, 95% CI 1.02-4.05), severe disease at baseline (5.02, 2.05-12.29), current smoker (1.67, 1.37-2.02), temperature >39° C at baseline (2.68, 1.88-4.23), more than one comorbidity (2.12, 1.62-3.09), bilateral patchy shadowing on chest CT or X-ray (3.74, 1.78-9.62) and organ failure (6.47, 1.97-26.23). The following interventions were associated with higher CFR: glucocorticoids (1.60, 1.04-2.30), ICU admission (4.92, 1.37-17.64) and mechanical ventilation (2.35, 1.14-4.82).

Conclusion

Demographics, including age over 65 years, current smoker, diabetes, hypertension, and cerebrovascular disease, were associated with increased risk of mortality. Mortality was also associated with glucocorticoid use, mechanical ventilation and ICU admission.

Take-Home Message

COVID-19 patients with risk factors were more likely to be admitted into ICU and more likely to require mechanical ventilation.
Time in blood glucose range 70 to 180 mg/dL and survival rate in critically ill patients: A retrospective observational study
Authors: Naraba Hiromu , Goto Tadahiro , Shirakawa Toru , Sonoo Tomohiro , Kanda Naoki , Nakano Hidehiko , Takahashi Yuji , Hashimoto Hideki , Nakamura Kensuke
Published: September 2020

Objective

Time in targeted blood glucose range (TIR) 70-140 mg/dL has been associated with an increased risk of mortality in critically ill patients. Nevertheless, it remains unclear whether TIR is associated with 28-day mortality in critically ill patients under glycemic control with a less tight target glucose range of 70-180 mg/dL. We aimed to assess whether TIR 70-180 mg/dL was associated with 28-day mortality and to identify the optimal TIR.

Design

A retrospective observational study.

Setting

Data from a tertiary care centre in Japan, from 1 January 2016 through 31 October 2019.

Participants

1,230 adult patients admitted to the intensive care unit for more than three days.

Outcome measure

The primary outcome was 28-day mortality.

Results

Of 1,230 patients, patients with HbA1c ≥6.5% had a higher 28-day mortality than those with <6.5% (32.0% vs. 22.7%; p=0.003). In the multivariate logistic regression, TIR <80% was associated with an increased risk of 28-day mortality in patients with HbA1c <6.5% with an adjusted odds ratio (OR) of 1.88 (95% confidence interval [CI]: 1.36-2.61). When using 10% incremental TIR as a categorical variable, lower TIR was associated with worse 28-day mortality compared to TIR ≥90% in patients with HbA1c <6.5% (e.g., adjusted OR of TIR <60%, 3.62 [95%CI 2.36-5.53]). Similar associations were found in the analyses using the COX proportional hazards model. In addition, sensitivity analyses using TIR of the first three days showed that the overall associations were consistent with primary analyses.

Conclusions

Our study demonstrated that lower TIR 70-180 mg/dL was associated with higher 28-day mortality in nondiabetic critically ill patients.

Article Summary

Strengths and limitations of this study

This is the first study to evaluate the association between less tight TIR (70-180 mg/dl) and mortality in critically ill patients.

We found consistent results in the analyses using logistic regression model and Cox proportional hazard model.

The primary findings were also observed in the analysis using TIR in the first three days.

We did not use a continuous glucose monitoring device to calculate TIR.

Due to the nature of the single-centre study design, the generalizability of the findings might be limited.
Asymptomatic cases and limited transmission of SARS-CoV-2 in residents and healthcare workers in three Dutch nursing homes
Authors: van Buul Laura W. , van den Besselaar Judith H. , Koene Fleur M.H.P.H. , Buurman Bianca M. , Hertogh Cees M.P.M. ,   the COVID-19 NH-STUDY GROUP
Published: September 2020

Purpose

Many nursing homes worldwide have been hit by outbreaks of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to assess the contribution of a- and presymptomatic residents and healthcare workers in transmission of SARS-CoV-2 in three nursing homes.

Methods

Two serial point-prevalence surveys, 1 week apart, among residents and healthcare workers of three Dutch nursing homes with recent SARS-CoV-2 introduction. Nasopharyngeal and oropharyngeal testing for SARS-CoV-2, including reverse-transcriptase polymerase chain reaction (rRT-PCR) was presymptomatic or asymptomatic with standardized symptom assessment.

Results

In total, 297 residents and 542 healthcare workers participated in the study. At the first point-prevalence survey, 15 residents tested positive of which one was presymptomatic (Ct value>35) and three remained asymptomatic (Ct value of 23, 30 and 32). At the second point-prevalence survey one resident and one healthcare worker tested SARS-CoV-2 positive (Ct value >35 and 24, respectively) and both remained asymptomatic.

Conclusion

This study confirms a-and presymptomatic occurrence of Covid-19 among residents and health care workers. Ct values below 25 suggested that these cases have the potential to contribute to viral spread. However, very limited transmission impeded the ability to answer the research question. We describe factors that may contribute to the prevention of transmission and argue that the necessity of large-scale preemptive testing in nursing homes may be dependent of the local situation regarding prevalence of cases in the surrounding community and infection control opportunities.

KEY SUMMARY POINTS

Aim

To assess the contribution of a- and presymptomatic residents and healthcare workers in transmission of SARS-CoV-2 in three nursing homes by facility wide preemptive testing.

Findings

Occurrence of a-and presymptomatic residents and healthcare workers with Ct values below 25 was confirmed. However, evaluation of contribution to transmission of the virus was not possible because of limited positive cases in the follow-up.

Message

Necessity of large-scale preemptive testing for a- and presymptomatic SARS-CoV-2 cases in nursing homes may be dependent on prevalence of cases in the surrounding community and infection control opportunities.
Accelerated aging in the brain, epigenetic aging in blood, and polygenic risk for schizophrenia
Authors: Teeuw Jalmar , Ori Anil , Brouwer Rachel M. , de Zwarte Sonja M.C. , Schnack Hugo G. , Pol Hilleke E. Hulshoff , Ophoff Roel A.
Published: September 2020

Abstract

Schizophrenia patients show signs of accelerated aging in cognitive and physiological domains. Both schizophrenia and accelerated aging, as measured by MRI brain images and epigenetic clocks, are correlated with increased mortality. However, the association between these aging measures have not yet been studied in schizophrenia patients.

In schizophrenia patients and healthy subjects, accelerated aging was assessed in brain tissue using a longitudinal MRI (N=715 scans; mean scan interval 3.4 year) and in blood using two epigenetic age clocks (N=172). Differences (‘gaps’) between estimated ages and chronological ages were calculated, as well as the acceleration rate of brain aging. The correlations between these aging measures as well as with polygenic risk scores for schizophrenia (PRS; N=394) were investigated.

Brain aging and epigenetic aging were not significantly correlated. Polygenic risk for schizophrenia was significantly correlated with brain age gap, brain age acceleration rate, and negatively correlated with DNAmAge gap, but not with PhenoAge gap. However, after controlling for disease status and multiple comparisons correction, these effects were no longer significant. Our results imply that the (accelerated) aging observed in the brain and blood reflect distinct biological processes. Our findings will require replication in a larger cohort.
COVID-19 Myocardial Pathology Evaluated Through scrEening Cardiac Magnetic Resonance (COMPETE CMR)
Authors: Clark Daniel E. , Parikh Amar , Dendy Jeffrey M. , Diamond Alex B. , George-Durrett Kristen , Fish Frank A. , Fitch Warne , Hughes Sean G. , Soslow Jonathan H.
Published: September 2020

Background

Myocarditis is a leading cause of sudden cardiac death among competitive athletes and may occur without antecedent symptoms. COVID-19-associated myocarditis has been well-described, but the prevalence of myocardial inflammation and fibrosis in young athletes after COVID-19 infection is unknown.

Objectives

This study sought to evaluate the prevalence and extent of cardiovascular involvement in collegiate athletes that had recently recovered from COVID-19.

Methods

We conducted a retrospective cohort analysis of collegiate varsity athletes with prior COVID-19 infection, all of whom underwent cardiac magnetic resonance (CMR) prior to resumption of competitive sports in August 2020.

Results

Twenty-two collegiate athletes with prior COVID-19 infection underwent CMR. The median time from SARS-CoV-2 infection to CMR was 52 days. The mean age was 20.2 years. Athletes represented 8 different varsity sports. This cohort was compared to 22 healthy controls and 22 tactical athlete controls. Most athletes experienced mild illness (N=17, 77%), while the remainder (23%) were asymptomatic. No athletes had abnormal troponin I, electrocardiograms, or LVEF < 50% on echocardiography. Late gadolinium enhancement was found in 9% of collegiate athletes and one athlete (5%) met formal criteria for myocarditis.

Conclusions

Our study suggests that the prevalence of myocardial inflammation or fibrosis after an asymptomatic or mild course of ambulatory COVID-19 among competitive athletes is modest (9%), but would be missed by ECG, Ti, and strain echocardiography. Future investigation is necessary to further phenotype cardiovascular manifestations of COVID-19 in order to better counsel athletes on return to sports participation.

Condensed Abstract

COVID-19-associated myocarditis has been well-described, but the prevalence of myocardial inflammation and fibrosis in athletes after COVID-19 is unknown. We conducted a retrospective cohort analysis of 22 collegiate athletes with prior COVID-19 infection who underwent electrocardiography, troponin I, echocardiography with strain, and CMR. The median time from SARS-CoV-2 infection to CMR was 52 days. All athletes experienced mild illness or were asymptomatic. Late gadolinium enhancement was found in 9%. This suggests the prevalence of myocardial inflammation or fibrosis after an asymptomatic or mild course of COVID-19 among competitive athletes is modest, but would be missed without CMR screening.
PREDICTIVE VALUE OF SMELL AND TASTE TEST VS PCR-RT SARS-COV-2 AND RAPID DIAGNOSTIC TESTS IN THE DIAGNOSIS OF INFECTION BY COVID-19. A PROSPECTIVE MULTI-CENTRIC STUDY
Authors: Rosalinda Pieruzzini , Carlos Ayala-Grosso , José de Jesús Navas , Carolina Rodríguez Wilneg , Nathalia Parra , Emily Luque , Aida Sánchez Gago , Scarleth González , Alexandra Hagobian , Angeline Grullón , Karen Díaz , Mariano Morales , Melanie De Jesús , Sonia Peña , Luis Rodríguez , Lenin Peña Luis , Ana Asaro , Magda Magris
Published: September 2020

There is a relationship between smell and taste disturbances and coronavirus infection. These symptoms have been considered the best predictor of coronavirus infection, for this reason, it was decided to evaluate the predictive value of the smell and taste test and its association with the results of SARS-CoV-2 PCR-RT and rapid diagnostic tests. in the diagnosis of pathology. Methodology: 248 patients divided into 3 groups: asymptomatic, symptomatic without chemosensory disorders, and chemosensory disorders alone. All of them underwent SARS-CoV-2 PCR-RT, a rapid diagnostic test and a test of Venezuelan smell and basic taste at the beginning. Weekly follow-up with smell and taste test and SARS-CoV-2 PCR-RT until recovery. Results: 20.56% of patients had smell and taste disorders to a variable degree and were positive by SARS-CoV-PCR-RT. 2.15.3% of patients with chemosensory disorders were negative for COVID-19. The positive predictive value of the smell and taste test was 57.3; Sensitivity 41.13% and specificity 69.35%. There were no statistically significant differences by age, sex and chemosensory disorders. The predominant chemosensory disorder was the combination of mild hyposmia and hypogeusia and appeared in the company of other symptoms. Recovery occurred in an average of 8.5 days, asynchronously with the SARS-CoV-2 RT-PCR negativization, which occurred up to more than 15 days after the senses recovered. Maximum time of negativization of the RT-PCR of 34 days. Conclusion: chemosensory disorders are a symptom and / or sign of coronavirus disease but cannot be considered as predictors of said disease in this population studied. The gold standard remains the SARS-CoV-2 PCR-RT test. Rapid diagnostic tests should be used for follow-up. Recommendations: it is necessary to expand the sample, include routine psychophysical smell and taste tests to screen cases and take race and virus mutations into consideration to explain behavior in certain populations.