bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Feature and Prognosis of Sudden Sensorineural Hearing Loss With Rheumatoid Arthritis
Authors: Li Hui , Zhang Mingjie , Wang Mengjun , Zhang Shuhan , Ma Shiyin , Wang Xiaomin
Published: October 2020

Objectives:

Recent publications reported that patients with rheumatoid arthritis (RA) experience an increased risk of suffering sudden sensorineural hearing loss (SSNHL), however, these cases are poorly understood. This study aims to explore the clinical presentations and hearing recovery of SSNHL patients with RA.

Study Design:

Retrospective study.

Setting:

Tertiary medical center.

Patients:

Forty-seven SSNHL patients with RA (RA group) and 431 SSNHL patients without RA (non-RA group) were recruited between April 2015 and June 2019.

Interventions:

In the non-RA group, all patients were administrated with oral steroids. In the RA group, 21 patients were treated with oral steroid (OS group) and 26 patients were administrated with intratympanic steroids plus oral steroids (IS+OS group).

Main Outcome Measures:

We explored the clinical features and hearing recovery of SSNHL patients with RA in comparison with patients without RA, we also evaluated the therapeutic effect of combined steroids in SSNHL patients with RA.

Results:

RA group had higher initial hearing loss level (mean 68.5 dB), final hearing threshold (mean 52.3 dB), the rates of profound hearing loss (48.9%), and no recovery (48.9%) than non-RA group (mean 55.1 dB, mean 34.8 dB, 32.9 and 27.6%, all p < 0.05), however, had lower hearing gains (mean 16.1 dB) and the rate of partial recovery (12.8%) than non-RA group (mean 20.3 dB and 28.8%, all p < 0.05). Furthermore, IS+OS group had higher hearing gains (mean 21.1 dB) and lower rate of no recovery (30.8%) than in the OS group (mean 10.0 dB and 71.4%, all p < 0.05).

Conclusions:

SSNHL patients with RA experienced severe hearing loss and had poor hearing prognosis. IS+OS provide better hearing recovery than OS for this population.
2020 EACTS/ELSO/STS/AATS Expert Consensus on Post-cardiotomy Extracorporeal Life Support in Adult Patients
Authors: Lorusso Roberto , Whitman Glenn , Milojevic Milan , Raffa Giuseppe , McMullan David M. , Boeken Udo , Haft Jonathan , Bermudez Christian A. , Shah Ashish S. , D’Alessandro David A.
Published: October 2020

Post-cardiotomy extracorporeal life support (PC-ECLS) in adult patients has been used only rarely but recent data have shown a remarkable increase in its use, almost certainly due to improved technology, ease of management, growing familiarity with its capability and decreased costs. Trends in worldwide in-hospital survival, however, rather than improving, have shown a decline in some experiences, likely due to increased use in more complex, critically ill patients rather than to suboptimal management. Nevertheless, PC-ECLS is proving to be a valuable resource for temporary cardiocirculatory and respiratory support in patients who would otherwise most likely die. Because a comprehensive review of PC-ECLS might be of use for the practitioner, and possibly improve patient management in this setting, the authors have attempted to create a concise, comprehensive and relevant analysis of all aspects related to PC-ECLS, with a particular emphasis on indications, technique, management and avoidance of complications, appraisal of new approaches and ethics, education and training.
Loss of X Chromosome Inactivation in Androgenetic Complete Hydatidiform Moles With 46, XX Karyotype
Authors: Chen Xiaojing , Ma Yuejiang , Wang Lingfang , Zhang Xiaofei , Yu Yan , Lü Weiguo , Xie Xing , Cheng Xiaodong
Published: October 2020

Most complete hydatidiform moles (CHMs) showcase an androgenetic nature of the nuclear genome. In the normal female embryo, one of the 2 X chromosomes is inactive. However, the status of X chromosome inactivation (XCI) in androgenetic CHMs remains unknown. Seventy-one androgenetic CHM tissues with the 46, XX karyotype were collected. Seventy-four normal female villi and 74 normal male villi were collected as controls. The expression of XCI markers (XIST, TSIX, and XACT) and an X-linked gene (CDX4) was detected by real-time polymerase chain reaction. Other XCI-associated genes were also examined, including the methylation status of the human androgen receptor gene (HUMARA) by methylation-specific polymerase chain reaction), and the expression of H3K27me3, USP21, and Nanog by Western blot and immunofluorescence, respectively. In addition, 126 CHMs and 63 normal female villous samples were collected for CDX4 immunohistochemical staining. The expression of XIST RNA was significantly lower, and TSIX RNA expression was significantly higher in androgenetic CHMs than that in normal female villi (both P<0.01). The expression of CDX4 mRNA in androgenetic CHMs was elevated compared with that in normal male and normal female villous samples (both P<0.01), and CDX4 protein expression was also higher than that in normal female villous samples (P<0.01). The expression of H3K27me3 was lower in androgenetic CHMs compared with that in normal female villi(P<0.01). The methylation pattern of HUMARA was found lacking in androgenetic CHMs. The expression of Nanog and UPS21 protein in androgenetic CHMs was higher than that in normal villi (both P<0.01). Both X chromosomes are active in androgenetic CHMs with the 46, XX karyotype, and the USP21-Nanog pathway may be involved in the disruption of XCI during this process.
Single-Cell RNA-seq of Human Myeloid-Derived Suppressor Cells in Late Sepsis Reveals Multiple Subsets With Unique Transcriptional Responses: A Pilot Study
Authors: Darden Dijoia B. , Bacher Rhonda , Brusko Maigan A. , Knight Parker , Hawkins Russell B. , Cox Michael C. , Dirain Marvin L. , Ungaro Ricardo , Nacionales Dina C. , Rincon Jaimar C. , Gauthier Marie-Pierre L. , Kladde Michael , Bihorac Azra , Brusko Todd M. , Moore Frederick A. , Brakenridge Scott C. , Mohr Alicia M. , Moldawer Lyle L. , Efron Philip A.
Published: October 2020

Background:

Increased circulating myeloid-derived suppressor cells (MDSCs) are independently associated with poor long-term clinical outcomes in sepsis. Studies implicate subsets of MDSCs having unique roles in lymphocyte suppression; however, characterization of these cells after sepsis remains incomplete. We performed a pilot study to determine the transcriptomic landscape in MDSC subsets in sepsis using single-cell RNAseq (scRNA-seq).

Methods:

A mixture of whole blood myeloid-enriched and Ficoll-enriched PBMCs from two late septic patients on post-sepsis day 21 and two control subjects underwent Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq).

Results:

We successfully identified the three MDSC subset clusters—granulocytic (G-), monocytic (M-), and early (E-) MDSCs. Sepsis was associated with a greater relative expansion of G-MDSCs versus M-MDSCs at 21 days as compared to control subjects. Genomic analysis between septic patients and control subjects revealed cell-specific and common differential expression of genes in both G-MDSC and M-MDSC subsets. Many of the common genes have previously been associated with MDSC proliferation and immunosuppressive function. Interestingly, there was no differential expression of several genes demonstrated in the literature to be vital to immunosuppression in cancer-induced MDSC.

Conclusion:

This pilot study successfully demonstrated that MDSCs maintain a transcriptomic profile that is immunosuppressive in late sepsis. Interestingly, the landscape in chronic critical illness is partially dependent on the original septic insult. Preliminary data would also indicate immunosuppressive MDSCs from late sepsis patients appear to have a somewhat unique transcriptome from cancer and/or other inflammatory diseases.
Monocyte exocytosis of mitochondrial danger-associated molecular patterns in sepsis suppresses neutrophil chemotaxis
Authors: Konecna Barbora , Park Jinbong , Kwon Woon-Yong , Vlkova Barbora , Zhang Quanzhi , Huang Wei , Kim Hyo In , Yaffe Michael B. , Otterbein Leo E. , Itagaki Kiyoshi , Hauser Carl J.
Published: October 2020

BACKGROUND

Trauma and sepsis both increase the risk for secondary infections. Injury mobilizes mitochondrial (MT) danger-associated molecular patterns (mtDAMPs) directly from cellular necrosis. It is unknown, however, whether sepsis can cause active MT release and whether mtDAMPs released by sepsis might affect innate immunity.

METHODS

Mitochondrial release from human monocytes (Mo) was studied after LPS stimulation using electron microscopy and using fluorescent video-microscopy of adherent Mo using Mito-Tracker Green (MTG) dye. Release of MTG+ microparticles was studied using flow cytometry after bacterial stimulation by size exclusion chromatography of supernatants with polymerase chain reaction (PCR) for mitochondrial DNA (mtDNA). Human neutrophil (PMN), chemotaxis, and respiratory burst were studied after PMN incubation with mtDNA.

RESULTS

LPS caused Mo to release mtDAMPs. Electron microscopy showed microparticles containing MT. mtDNA was present both in microvesicles and exosomes as shown by PCR of the relevant size exclusion chromatography bands. In functional studies, PMN incubation with mtDNA suppressed chemotaxis in a dose-dependent manner, which was reversed by chloroquine, suggesting an endosomal, toll-like receptor-9–dependent mechanism. In contrast, PMN respiratory burst was unaffected by mtDNA.

CONCLUSION

In addition to passive release of mtDAMPs by traumatic cellular disruption, inflammatory and infectious stimuli cause active mtDAMP release via microparticles. mtDNA thus released can have effects on PMN that may suppress antimicrobial function. mtDAMP-mediated “feed-forward” mechanisms may modulate immune responses and potentially be generalizable to other forms of inflammation. Where they cause immune dysfunction the effects can be mitigated if the pathways by which the mtDAMPs act are defined. In this case, the endosomal inhibitor chloroquine is benign and well tolerated. Thus, it may warrant study as a prophylactic antiinfective after injury or prior sepsis.
Traumatic brain injury induced temperature dysregulation: What is the role of β blockers?
Authors: Asmar Samer , Bible Letitia , Chehab Mohamad , Tang Andrew , Khurrum Muhammad , Castanon Lourdes , Ditillo Michael , Douglas Molly , Joseph Bellal
Published: October 2020

BACKGROUND

Traumatic brain injury (TBI) is associated with sympathetic discharge that leads to posttraumatic hyperthermia (PTH). Beta blockers (ββ) are known to counteract overactive sympathetic discharge. The aim of our study was to evaluate the effect of ββ on PTH in critically-ill TBI patients.

METHODS

We performed retrospective cohort analysis of the Medical Information Mart for Intensive Care database. We included all critically ill TBI patients with head Abbreviated Injury Scale (AIS) score of 3 or greater and other body region AIS score less than 2 who developed PTH (at least one febrile episode [T > 38.3°C] with negative microbiological cultures (blood, urine, and bronchoalveolar lavage). Patients on preinjury ββ were excluded. Patients were stratified into (ββ+) and (ββ−) groups. Propensity score matching was performed (1:1 ratio) controlling for patient demographics, injury parameters and other medications that influence temperature. Outcomes were the number of febrile episodes, maximum temperature, and the time interval between febrile episodes. Multivariate linear regression was performed.

RESULTS

We analyzed 4,286 critically ill TBI patients. A matched cohort of 1,544 patients was obtained: 772 ββ + (metoprolol, 60%; propranolol, 25%; and atenolol, 15%) and 772 ββ−. Mean age was 63.4 ± 15.4 years, median head AIS score of 3 (3–4), and median Injury Severity Score of 10 (9–16). Patients in the ββ+ group had a lower number of febrile episodes (8 episodes vs. 12 episodes; p = 0.003), lower median maximum temperature (38.0°C vs. 38.5°C; p = 0.025), and a longer median time between febrile episodes (3 hours vs. 1 hour; p = 0.013). On linear regression, propranolol was found to be superior in terms of reducing the number of febrile episodes and the maximum temperature. However, there was no significant difference between the three ββ in terms of reducing the time interval between febrile episodes (p = 0.582).

CONCLUSION

Beta blockers attenuate PTH by decreasing the frequency of febrile episodes, increasing the time interval between febrile episodes, and reducing the maximum rise in temperature. ββ may be a potential therapeutic modality in PTH.

LEVEL OF EVIDENCE

Therapeutic, level IV.
Ludwig Edward Fraenkel. 28 May 1927—27 April 2019
Authors: Burton G. R. , Toland J. F.
Published: October 2020

Edward Fraenkel’s professional career began as an experimentalist at the Royal Aircraft Establishment, Farnborough, but his preoccupation with the theoretical and mathematical aspects of aerodynamics led him into academia, working initially in aerodynamics and classical applied mathematics, but later in the modern theory of nonlinear partial differential equations and its applications to fluid mechanics. He made outstanding contributions to the mathematical theories of viscous flow separation, steady vortex rings and surface waves on water.
Genomic instability in an interspecific hybrid of the genus Saccharomyces: a matter of adaptability
Authors: Morard Miguel , Ibáñez Clara , Adam Ana C. , Querol Amparo , Barrio Eladio , Toft Christina
Published: October 2020

Ancient events of polyploidy have been linked to huge evolutionary leaps in the tree of life, while increasing evidence shows that newly established polyploids have adaptive advantages in certain stress conditions compared to their relatives with a lower ploidy. The genus Saccharomyces is a good model for studying such events, as it contains an ancient whole-genome duplication event and many sequenced Saccharomyces cerevisiae are, evolutionary speaking, newly formed polyploids. Many polyploids have unstable genomes and go through large genome erosions; however, it is still unknown what mechanisms govern this reduction. Here, we sequenced and studied the natural S. cerevisiae × Saccharomyces kudriavzevii hybrid strain, VIN7, which was selected for its commercial use in the wine industry. The most singular observation is that its nuclear genome is highly unstable and drastic genomic alterations were observed in only a few generations, leading to a widening of its phenotypic landscape. To better understand what leads to the loss of certain chromosomes in the VIN7 cell population, we looked for genetic features of the genes, such as physical interactions, complex formation, epistatic interactions and stress responding genes, which could have beneficial or detrimental effects on the cell if their dosage is altered by a chromosomal copy number variation. The three chromosomes lost in our VIN7 population showed different patterns, indicating that multiple factors could explain the mechanisms behind the chromosomal loss. However, one common feature for two out of the three chromosomes is that they are among the smallest ones. We hypothesize that small chromosomes alter their copy numbers more frequently as a low number of genes is affected, meaning that it is a by-product of genome instability, which might be the chief driving force of the adaptability and genome architecture of this hybrid.
Prior cocaine exposure increases firing to immediate reward while attenuating cue and context signals related to reward value in anterior insula
Authors: Pribut Heather J. , Vázquez Daniela , Brockett Adam T. , Wei Alice D. , Tennyson Stephen S. , Roesch Matthew R.
Published: October 2020

The insula contributes to behavioral control and is disrupted by substance abuse, yet we know little about the neural signals underlying these functions or how they are disrupted after chronic drug self-administration. Here, rats self-administered either cocaine (experimental group) or sucrose (control) for twelve consecutive days. After a one-month withdrawal period, we recorded from anterior insula while rats performed a previously learned reward-guided decision-making task. Cocaine-exposed rats were more sensitive to value manipulations and were faster to respond. These behavioral changes were accompanied by elevated counts of neurons in the insula that increased firing to reward. These neurons also fired more strongly at the start of long delay trials-when a more immediate reward would be expected, and fired less strongly in anticipation of the actual delivery of delayed rewards. Although reward-related firing to immediate reward was enhanced after cocaine self-administration, reward-predicting cue and context signals were attenuated.

Significance Statement

The insula plays a clear role in drug-addiction and drug-induced impairments of decision-making, yet there is little understanding of its underlying neural signals. We found that chronic cocaine self-administration reduces cue and context-encoding in insula, while enhancing signals related to immediate reward. These changes in neural activity likely contribute to impaired decision-making and impulsivity observed after drug use.
Design Of A Rapid And Reversible Fluorescence Assay To Detect Covid-19 And Other Pathogens
Authors: Yerramilli V. Siddartha , Scarlata Suzanne
Published: October 2020

We describe a rapid and reusable biophysical method to assay COVID-19 and other pathogens. The method uses fluorescent sensors (i.e. molecular beacons) designed to detect COVID-19 RNA or any RNA of interest, concurrent with an internal control without the need for amplification. The molecular beacons are stem-loop structures in which a ∼10 nucleotide loop region has the complementary sequence of a region of the target RNA, and a fluorophore and quencher are placed on the 5’ and 3’ ends of the stem. The energy of hybridization of the loop with its target is designed to be greater than the hybridization energy of the energy of the stem so that when the beacon encounters its target RNA, the structure opens resulting in dequenching of the fluorophore. Here, we designed a COVID-19 beacon that is completely quenched in its native form and undergoes a 50-fold increase in fluorescence when exposed to nanomolar amounts of synthetic viral oligonucleotide. No changes in intensity are seen when control RNA is added. A control beacon to a human GAPDH RNA, chosen for its high levels in saliva, behaved similar to the COVID-19 beacon. This increase in fluorescence with beacon opening can be completely reversed upon addition of single stranded DNA complementary to COVID-19 beacon loop region. Beacons can be attached to an insert matrix allowing their use in concentrated form and can be made from morphilino oligonucleotides that are resistant to RNases. We present an analysis of the parameters that will allow the development of test strips to detect virus in aerosol, body fluids and community waste.

Statement of significance

A platform for reusable and rapid detection of COVID-19 RNA and other pathogenic RNAs without the need for amplification or sophisticated instrumentation in a complex environment is described.
Extremely preterm infant admissions within the SafeBoosC-III consortium during the COVID-19 lockdown
Authors: Rasmussen Marie Isabel , Lühr Hansen Mathias , Pichler Gerhard , Dempsey Eugene , Pellicer Adelina , EL-Khuffash Afif , Shashidhar A , Piris-Borregas Salvador , Alsina Miguel , Cetinkaya Merih , Chalak Lina , Ozkan Hilal , Baserga Mariana , Sirc Jan , Fuchs Hans , Ergenekon Ebru , Arruza Luis , Mathur Amit , Stocker Martin , Vaccarello Olalla Otero , Szczapa Tomasz , Sarafidis Kosmas , Krolak-Olejnik Barbara , Memisoglu Asli , Reigstad Hallvard , Rafińska-Ważny Elżbieta , Hatzidaki Eleftheria , Peng Zhang , Gkentzi Despoina , Viellevoye Renaud , De Buyst Julie , Mastretta Emmanuele , Wang Ping , Hahn Gitte Holst , Bender Lars , Cornette Luc , Tkaczyk Jakub , Rio Ruth del , Fumagalli Monica , Papathoma Evangelina , Wilinska Maria , Naulers Gunnar , Sadowska-Krawczenko Iwona , Lecart Chantal , Couce María Luz , Fredly Siv , Heuchan Anne Marie , Karen Tanja , Greisen Gorm
Published: October 2020

Objective

To evaluate if the number of admitted extremely preterm (EP) infants (born before 28 weeks of gestational age) has changed in the neonatal intensive care units (NICUs) of the SafeBoosC-III consortium during the global lockdown when compared to the corresponding time period in 2019.

Design

This is a retrospective, observational study. Forty-six out of 79 NICUs (58%) from 17 countries participated. Principal investigators were asked to report the following information: 1) Total number of EP infant admissions to their NICU in the three months where the lockdown restrictions were most rigorous during the first phase of the COVID-19 pandemic, 2) Similar EP infant admissions in the corresponding three months of 2019, 3) the level of local restrictions during the lockdown period and 4) the local impact of the COVID-19 lockdown on the everyday life of a pregnant woman.

Results

There was no significant difference between the number of EP infant admissions during the three most rigorous lockdown months of the COVID-19 pandemic compared to the corresponding three months in 2019 (n=428 versus n=457 respectively, p=0.33). There were no significant changes within individual geographic regions and no significant association between the level of lockdown restrictions and change in the number of EP infant admissions (p=0.334).

Conclusion

This largerad hocstudy did not confirm previous studies’ report of a major reduction in the number of extremely preterm births during the first phase of the COVID-19 pandemic.
Assessment of Learning Organization Practice and Disciplines in Case of Sire District Public Health Office, Arsi Zone, Oromia Region, Ethiopia, 2018:Qualitative Case Study
Authors: Hailu Biniam Worku
Published: October 2020

Learning Organizations are organizations where people continually expand their capacity to create the results they truly desire, where new and expansive patterns of thinking are nurtured, where collective aspirations are set free and where people are continually learning how to learn together. The aim of this study was to assess Learning organization practice and disciplines in case of Sire District Public health office. Learning organization if implemented in the health institutions it enables ignition of newly created more another’s learning organization units moreover, learning organization concept if implemented in the organization it can enables organization to achieve their goal systematically besides this, it also enhance employees their job commitment whereas, the organization not implemented learning organization concept might be opposite of this or vice versa. The study employed qualitative case-study design in sire District public health office. Document review, in depth interview and Focus group discussion with flexible probing techniques were employed to collect the data from 3 key informants and 2 FGD from January 1, 2018 to January 11, 2018. A semi structured interview guide was prepared to explore key informants’ idea about current situation and efforts made to enable organization to be a learning organization and also thematic analyses were used to analyze the findings of the study. The study result revealed that the organization assessed in both parameter of learning organization (five disciplines Peter Senge and Pedler et al criteria of practice of learning organization) the organization was practiced preponderance of learning organization concept was practiced within five disciplines of learning organizations there were implemented in their office. The finding of the study revealed that sire district public health office was practiced learning organization and disciplines in there organization that was exercised as good and the organization also participate entire employees and stakeholders to carry out organizational plan that were align with national strategies of the country moreover, the organization had created enabling learning opportunities to enhance a learning organization among themselves and others.
A national study of self-reported COVID symptoms during the first viral wave in Canada
Authors: Tang Xuyang , Gelband Hellen , Lam Teresa , Nagelkerke Nico , Reid Angus , Jha Prabhat ,   for the Action to beat Coronavirus (Ab-C) Study Investigators
Published: October 2020

Importance

Accurate understanding of COVID pandemic during the first viral wave in Canada could help prepare for future epidemic waves.

Objective

To track the early course of the pandemic by examining self-reported COVID symptoms over time before testing became widely available.

Design

Adults from the nationally representative Angus Reid Forum were randomly invited to complete an online survey in May/June 2020. The study is a part of the Action to Beat Coronavirus antibody testing study.

Setting

A 20-item internet survey.

Participants

14,408 adults age 18 years of age.

Exposures

The months that respondents and any household members first experienced various respiratory, neurological, sleep, skin or gastric symptoms.

Main Outcomes and Measure

“COVID symptom-positive,” defined as fever (or fever with hallucinations) plus at least one of difficulty breathing, a dry severe cough, loss of smell or “COVID toe.”

Results

In total, 14,408 panel members (48% male and 52% female) completed the survey. Despite overrepresentation of higher levels of education, the prevalence of obesity, smoking, diabetes and hypertension were similar to national census and health surveys. A total of 811 (5.6%) were COVID symptom-positive; highest rates were at ages 18-44 years (8.3% among), declining at older ages. Females had higher odds of reporting COVID symptoms (OR = 1.32, 95%CI 1.11 – 1.56) as did visible minorities (OR = 1.74, 1.29 – 2.35). COVID symptom positivity for respondents and their household members peaked in March (OR = 1.93, 95% CI = 1.59 – 2.34 compared to earlier months).

Conclusions and Relevance

This study enhances our current understanding of the progression of the COVID epidemic in Canada, with few laboratory-confirmed cases in January and February, peaking in April. The results suggest substantial viral transmission in March, before widespread testing began, and a gradual decline in cases since May.
Trait Anxiety Effects on Late Phase Threatening Speech Processing: Evidence from Electroencephalography
Authors: Busch-Moreno Simon , Tuomainen Jyrki , Vinson David
Published: October 2020

The effects of threatening stimuli, including threatening language, on trait anxiety have been widely studied. However, whether anxiety levels have a direct effect on language processing has not been so consistently explored. The present study focuses on eventrelated potential (ERP) patterns resulting from electroencephalographic (EEG) measurement of participants’ (n = 36) brain activity while they perform a dichotic listening task. Participants’ anxiety level was measured via a behavioural inhibition system scale (BIS). Later, participants listened to dichotically paired sentences, one neutral and the other threatening, and indicated at which ear they heard the threatening stimulus. Threatening sentences expressed threat semantically-only, prosodically-only, or both combined (congruent threat). ERPs showed a late positivity, interpreted as a late positive complex (LPC). Results from Bayesian hierarchical models provided strong support for an association between LPC and BIS score. This was interpreted as an effect of trait anxiety on deliberation processes. We discuss two possible interpretations. On the one hand, verbal repetitive thinking, as associated with anxious rumination and worry, can be the mechanism disrupting late phase deliberation processes. Instantiated by inner speech, verbal repetitive thinking might be the vehicle of anxiety-related reappraisal and/or rehearsal. On the other hand, increased BIS could be simply affecting an extended evaluation stage as proposed by multistep models, maybe due to over-engagement with threat or to task-related effects.

Graphical Abstract
Regional differences in vaccine uptake and serological responses to vaccine and circulating strains of H1N1 viruses among patients with confirmed influenza
Authors: Fink Ashley L. , Liu Hsuan , Shaw-Saliba Kathryn , Mehoke Thomas , Evans Jared , Liu Zhen-Ying , Lewis Mitra , Sauer Lauren , Thielen Peter , Chen Kuan-Fu , Rothman Richard , Klein Sabra L. , Pekosz Andrew
Published: October 2020

Background

Seasonal epidemics of influenza are often characterized through national or international surveillance efforts to determine vaccine efficacy and vaccine strain selection, but they do not provide detailed information about local variations in factors that can influence influenza cases and disease severity.

Methods

Surveillance for influenza like illness was performed in Emergency Medicine Departments in Taipei, Taiwan and Baltimore, Maryland during the winter of 2015-16. Detailed demographic and clinical data were obtained. Nasal swabs or washes were collected for influenza virus diagnosis, sequencing and isolation. Serum was collected to determine neutralizing antibody levels.

Results

H1N1 viruses dominated both sites, but more influenza cases occurred in Taipei compared to Baltimore. H1 HA clade diversity was greater in Taipei. Vaccination rates were lower in Taipei than Baltimore, but vaccination was associated with an increase in serum neutralizing antibodies to recent H1N1 strains in Taipei, but not Baltimore. There was a higher level of preexisting immunity to circulating H1N1 strains in Baltimore.

Conclusions

Regional differences in preexisting immunity and H1N1 strain circulation may have contributed to the vastly different 2015-16 influenza seasons in Taipei and Baltimore and suggest immune responses to vaccination can be affected by the degree of preexisting immunity in the population.
Assessing the feasibility and effectiveness of household-pooled universal testing to control COVID-19 epidemics
Authors: Libin Pieter , Willem Lander , Verstraeten Timothy , Torneri Andrea , Vanderlocht Joris , Hens Niel
Published: October 2020

Current outbreaks of SARS-CoV-2 are threatening the health care systems of several countries around the world. The control of SARS-CoV-2 epidemics currently relies on non-pharmaceutical interventions, such as social distancing, teleworking, mouth masks and contact tracing. However, as pre-symptomatic transmission remains an important driver of the epidemic, contact tracing efforts struggle to fully control SARS-CoV-2 epidemics. Therefore, in this work, we investigate to what extent the use of universal testing, i.e., an approach in which we screen the entire population, can be utilized to mitigate this epidemic. To this end, we rely on PCR test pooling of individuals that belong to the same households, to allow for a universal testing procedure that is feasible with the current testing capacity. We evaluate two isolation strategies: on the one handpool isolation, where we isolate all individuals that belong to a positive PCR test pool, and on the other handindividual isolation, where we determine which of the individuals that belong to the positive PCR pool are positive, through an additional testing step. We evaluate this universal testing approach in the STRIDE individual-based epidemiological model in the context of the Belgian COVID-19 epidemic. As the organisation of universal testing will be challenging, we discuss the different aspects related to sample extraction and PCR testing, to demonstrate the feasibility of universal testing when a decentralized testing approach is used. We show through simulation, that weekly universal testing is able to control the epidemic, even when many of the contact reductions are relieved. Finally, our model shows that the use of universal testing in combination with stringent contact reductions could be considered as a strategy to eradicate the virus.
An Agent-Based Model to assess COVID-19 spread and health systems burden in Telangana state, India
Authors: M S Narassima , Jammy Guru Rajesh , A Sankarshana , Pant Rashmi , S P Anbuudayasankar , Choudhury Lincoln , Yeldandi Vijay , Singh Shubham , John Denny
Published: October 2020

Objectives

To assess the transmission dynamics and the health systems’ burden of COVID-19 using an Agent Based Modeling (ABM) approach using a synthetic population.

Study design

The study used a synthetic population with 31,738,240 agents representing 90.67 percent of the overall population of Telangana state, India as per 2011 Census of India. Lockdown phases as per Indian scenario considering the effects of post-lockdown, use of control measures and immunity on secondary infections were studied.

Methods

The counts of people in different health states were measured separately for each district of Telangana. The model was run for 365 days and six scenarios with varying proportions of people using control measures (100%, 75% and 50%) and varying immunity periods (90 and 180 days). Sensitivity Analysis has been done for two districts to compare the change in transmission dynamics when incubation period and asymptomatic proportion are changed.

Results

Results indicate that the peak values were attained soon after the lockdown was lifted. The risk estimates indicate that protection factor values are higher when more proportion of people adopt control measures.

Conclusions

ABM approach helps to analyze grassroot details compared to compartmental models. Risk estimates allow the policymakers to determine the protection offered, its strength and percentage of population shielded by use of control measures.
Development and comparison of a novel multiple cross displacement amplification (MCDA) assay with other nucleic acid amplification methods for SARS-CoV-2 detection
Authors: Wai Luu Laurence Don , Payne Michael , Zhang Xiaomei , Luo Lijuan , Lan Ruiting
Published: October 2020

The development of alternative isothermal amplification assays including multiple cross displacement amplification (MCDA) may address speed and portability limitations of real-time PCR (rt-PCR) methods for SARS-CoV-2 detection. We developed a novel SARS-CoV-2 MCDA assay and compared its speed and sensitivity to loop-mediated isothermal amplification (LAMP) and rt-PCR. Two MCDA assays targeting SARS-CoV-2 N gene and ORF1ab was designed. The fastest time to detection and sensitivity of MCDA was compared to LAMP and rt-PCR using DNA standards and transcribed RNA. For N gene, MCDA was faster than LAMP and rt-PCR by 10 and 20 minutes, respectively with fastest time to detection at 5.2 minutes. rt-PCR had highest sensitivity with limit of detection at 10 copies/µl compared with MCDA (100 copies/µl) and LAMP (500 copies/µl). For ORF1ab, MCDA and LAMP had similar speed with fastest time to detection at 9.7 and 8.4 minutes, respectively. LAMP was more sensitive for ORF1ab detection with 50 copies/µl compared to MCDA (500 copies/µl). In conclusion, different nucleic acid amplification methods provide different advantages. MCDA is the fastest nucleic acid amplification method for SARS-CoV-2 while rt-PCR is the most sensitive. These advantages should be considered when determining the most suitable nucleic acid amplification methods for different applications.
The excess insulin requirement in severe COVID-19 compared to non-COVID-19 viral pneumonitis is related to the severity of respiratory failure and pre-existing diabetes
Authors: Lockhart Sam M. , Griffiths Harry , Petrisor Bogdan , Usman Ammara , Calvo-Latorre Julia , Heales Laura , Bansiya Vishakha , Mahroof Razeen , Morris Andrew Conway
Published: October 2020

Objective

Severe COVID-19 has been anecdotally associated with high insulin requirements. It has been proposed that this may be driven by a direct diabetogenic effect of the virus that is unique to SARS-CoV-2, but evidence to support this is limited. To explore this, we compared insulin requirements in patients with severe COVID-19 and non-COVID-19 viral pneumonitis.

Research Design

Retrospective cohort study of patients with severe COVID-19 admitted to our intensive care unit between March and June 2020. A historical control cohort of non-COVID-19 viral pneumonitis patients was identified from routinely collected audit data.

Results

Insulin requirements were similar in patients with COVID-19 and non-COVID-19 viral pneumonitis after adjustment for pre-existing diabetes and severity of respiratory failure.

Conclusions

In this single center study, we could not find evidence of a unique diabetogenic effect of COVID-19. We suggest that high insulin requirements in this disease relate to its propensity to cause severe respiratory failure in patients with pre-existing metabolic disease.
Renin Angiotensin System Inhibition and Susceptibility and Outcomes from COVID-19: A Systematic Review and Meta-analysis of 69,200 COVID-19 Patients
Authors: Zhang Yi , Yu Shikai , Xu Yawei , Williams Bryan
Published: October 2020

Background

Early observational studies suggested that the use of the renin angiotensin system (RAS) inhibitors, specifically angiotensin converting enzyme inhibitors or angiotensin receptor blockers, may increase the risk of infection with SARS-CoV-2 and adversely affect the prognosis or survival of infected patients. To explore the impact of RAS inhibitor use on the risk of SARS-CoV-2 infection and the prognosis of SARS-CoV-2 infected patients, from all published studies.

Methods and Findings

A systematic review and meta-analysis of the use of RAS inhibitors in relation to infection with SARS-CoV-2 and/or the severity and mortality associated with COVID-19 was conducted. English language bibliographic databases PubMed, Web of Science, OVID Embase, Scopus, MedRxiv, BioRxiv, searched from Jan 1st, 2020 to July 20th, 2020. 58 observational studies (69,200 COVID-19 patients and 3,103,335 controls) were included. There was no difference in the susceptibility to SARS-CoV-2 infection between RAS inhibitor users and non-users (unadjusted OR 1.05, 95% CI 0.90 to 1.21), (adjusted OR 0.93, 95% CI 0.85 to 1.02), (adjusted HR 1.07, 95% CI 0.87 to 1.31). There was no significant difference in the severe Covid-19 case rate between RAS inhibitor users and non-users (unadjusted OR 1.05, 95% CI 0.81 to 1.36), (adjusted OR 0.76, 95% CI 0.52 to 1.12), or in mortality due to COVID-19 between RAS inhibitor users and non-users (unadjusted OR 1.12, 95% CI 0.88 to 1.44), (adjusted OR 0.97, 95% CI 0.77 to 1.23), (adjusted HR 0.62, 95% CI 0.34 to 1.14).

Conclusions

In the most comprehensive analysis of all available data to date, treatment with RAS inhibitors was not associated with increased risk of infection, severity of disease, or mortality due to COVID-19. The best available evidence suggests that these treatments should not be discontinued on the basis of concern about risk associated with COVID-19.
Dilution-based Evaluation of Airborne Infection Risk - Thorough Expansion of Wells-Riley Model
Authors: Zhang Sheng , Lin Zhang
Published: October 2020

Evaluation of airborne infection risk with spatial and temporal resolutions is indispensable for the design of proper interventions fighting infectious respiratory diseases (e.g., COVID-19), because the distribution of aerosol contagions is both spatially and temporally non-uniform. However, the well-recognized Wells-Riley model and modified Wells-Riley model (i.e., the rebreathed-fraction model) are limited to the well-mixed condition and unable to evaluate airborne infection risk spatially and temporally, which could result in overestimation or underestimation of airborne infection risk. This study proposes a dilution-based evaluation method for airborne infection risk. The method proposed is benchmarked by the Wells-Riley model and modified Wells-Riley model, which indicates that the method proposed is a thorough expansion of the Wells-Riley model for evaluation of airborne infection risk with both spatial and temporal resolutions. Experiments in a mock hospital ward also demonstrate that the method proposed effectively evaluates the airborne infection risk both spatially and temporally.
The relationship between neighborhood poverty and COVID-19 mortality within racial/ethnic groups (Cook County, Illinois)
Authors: Feldman Justin M. , Bassett Mary T.
Published: October 2020

Abstract

Background

Prior research has identified higher rates of COVID-19 mortality among people of color (relative to non-Hispanic whites) and populations in high-poverty neighborhoods (relative to wealthier neighborhoods). It is unclear, however, whether non-Hispanic whites in high-poverty neighborhoods experience elevated mortality, or whether people of color living in wealthy areas are relatively protected. Exploring socioeconomic position in combination with race/ethnicity can lead to a more detailed understanding of the specific processes that result in COVID-19 inequities.

Methods and Findings

We used census and individual-level mortality data for the non-Hispanic white, non-Hispanic Black, and Hispanic/Latinx populations of Cook County, Illinois, USA. We excluded deaths related to nursing homes and other institutions. We calculated age and gender-adjusted mortality rates by race/ethnicity, census tract poverty quartile, and age group (0-64 and ≥65 years).

Within all racial/ethnic groups, COVID-19 mortality rates were greatest in the highest-poverty quartile and lowest in the lowest-poverty quartile. The mortality rate for younger non-Hispanic whites in the highest-poverty quartile was 13.5 times that of younger non-Hispanic whites in the lowest-poverty quartile (95% CI: 8.5, 21.4). For young people in the highest-poverty quartile, the non-Hispanic white and Black mortality rates were similar. Among younger people in the lowest-poverty quartile, non-Hispanic Black and Hispanic/Latinx people had mortality rates nearly three times that of non-Hispanic whites. For the older population, the mortality rate among non-Hispanic whites in the highest-poverty quartile was less than that of lowest-poverty non-Hispanic Black and Hispanic/Latinx populations.

Conclusions

Our findings suggest racial/ethnic inequalities in COVID-19 mortality are partly, but not entirely, attributable to the higher average socioeconomic position of non-Hispanic whites relative to the non-Hispanic Black and Hispanic/Latinx populations. Future research on health equity in COVID-19 outcomes should collect and analyze individual-level data on the potential mechanisms driving population distributions of exposure, severe illness, and death.
Rapid SARS-CoV-2 antigen detection by immunofluorescence – a new tool to detect infectivity
Authors: Porte Lorena , Legarraga Paulette , Iruretagoyena Mirentxu , Vollrath Valeska , Pizarro Gabriel , Munita José M. , Araos Rafael , Weitzel Thomas
Published: October 2020

The evaluated SARS-CoV-2 antigen rapid fluorescence immunoassays reliably identified patients within the first 5 days of symptom onset, when respiratory secretions carried high viral loads. This high performance suggests that these tests might play an important role for future PCR-independent strategies to detect early or infective cases.
Another Feature of Silicon Nanowire Field Effect Transistor Biosensor: Dynamic Detection
Authors: Chen Hang , Deng Lijuan , Li Hang , Huang Longchang , Zhu Xiaoping , Jiang Yanfeng , Wang Tong
Published: October 2020

Silicon nanowire field effect transistor (SiNW-FET) biosensors are capable of label-free, real-time and biological detection with high sensitivity and specificity. However, direct observation on protein-protein interaction in blood or serum is still very difficult because of the complex physiological environment and Debye-screening effect. In order to overcome the detection obstacles, we used dialysis desalination method to purify the detection fluid and overcome Debye-screening effect. In our research, a top-down approach was proposed to fabricate the SiNW-FET, APTES-Glu chemical chain was used to link antibody to the SiNWs. And after verified the detection ability of silicon nanometer biosensors, the dynamic detection process of HbA1c was successfully realized. This could be helpful for accurate diagnosis of diabetes for clinical application. And it makes it possible to dynamic research of small biomolecules without markers.
Markers Of Coagulation And Hemostatic Activation Identify COVID-19 Patients At High Risk For Thrombotic Events, ICU Admission and Intubation
Authors: Alabyad Darwish , Rangaraju Srikant , Liu Michael , Imran Rajeel , Kempton Christine L. , Sharifpour Milad , Auld Sara C. , Gaddh Manila , Sniecinski Roman , Maier Cheryl L. , Guarner Jeannette , Duncan Alexander , Nahab Fadi
Published: October 2020

Background

Coronavirus disease 2019 (COVID-19) has been associated with a coagulopathy giving rise to venous and arterial thrombotic events. The objective of our study was to determine whether markers of coagulation and hemostatic activation (MOCHA) on admission could identify COVID-19 patients at risk for thrombotic events and other complications.

Methods

COVID-19 patients admitted to a tertiary academic healthcare system from April 3, 2020 to July 31, 2020 underwent standardized admission testing of MOCHA profile parameters (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer) with abnormal MOCHA defined as ≥ 2 markers above the reference. Prespecified thrombotic endpoints included deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, and access line thrombosis; other complications included ICU admission, intubation and mortality. We excluded patients on anticoagulation therapy prior to admission and those who were pregnant.

Results

Of 276 patients (mean age 59 ± 6.4 years, 47% female, 62% African American race) who met study criteria, 45 (16%) had a thrombotic event. Each coagulation marker on admission was independently associated with a vascular endpoint (p<0.05). Admission MOCHA with ≥ 2 abnormalities (n=203, 74%) was associated with in-hospital vascular endpoints (OR 3.3, 95% CI 1.2-8.8), as were admission D-dimer ≥ 2000 ng/mL (OR 3.1, 95% CI 1.5-6.6), and admission D-dimer ≥ 3000 ng/mL (OR 3.6, 95% CI 1.6-7.9). However, only admission MOCHA with ≥ 2 abnormalities was associated with ICU admission (OR 3.0, 95% CI 1.7-5.2) and intubation (OR 3.2, 95% CI 1.6-6.4), while admission D-dimer ≥2000 ng/mL and admission D-dimer ≥ 3000 ng/mL were not associated. MOCHA and D-dimer cutoffs were not associated with mortality. Admission MOCHA with <2 abnormalities (26% of the cohort) had a sensitivity of 88% and negative predictive value of 93% for a vascular endpoint.

Conclusions

Admission MOCHA with ≥ 2 abnormalities identified COVID-19 patients at increased risk of ICU admission and intubation during hospitalization more effectively than isolated admission D-dimer measurement. Admission MOCHA with <2 abnormalities identified a subgroup of patients at low risk for vascular events. Our results suggest that an admission MOCHA profile can be useful to risk-stratify COVID-19 patients.
Repetitive and Brief Occlusion of the Majority of the Vena Cava Flow Attenuates Pulmonary Arterial Hypertension and ImprovesIK+of the Pulmonary Arterial Smooth Muscle Cells in Rat Models: a novel potential therapeutic strategy for PAH
Authors: Liu Nan , Xing Ying , Wang Lv , Wang Chen
Published: October 2020

By now, there are limited therapeutic approaches satisfactory for pulmonary arterial hypertension (PAH) treatment. In the present study, we established a novel rat model, repetitive and brief occlusion (RBO) of the majority of the right atrium venous blood flow in the conscious rats. Using this model, we found that the RBO treatment significantly improved the pulmonary hemodynamics with a lower pulmonary vascular resistance observed. The IK+and big-conductance Ca2+-activated K+(BK) channels were involved in the mechanism of the RBO treatment for PAH. Although the results are limited, the conclusion are solid and we believe this manuscript is valuable for all the researchers and clinical doctors who are interested in PAH.