bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 vaccine confidence and hesitancy among healthcare workers: a cross-sectional survey from a MERS-CoV experienced nation
Authors: Barry Mazin , Temsah Mohamad-Hani , Alhuzaimi Abdullah , Alamro Nurah , Al-Eyadhy Ayman , Aljamaan Fadi , Saddik Basema , Alhaboob Ali , Alsohime Fahad , Alhasan Khalid , Alrabiaah Abdulkarim , Alaraj Ali , Halwani Rabih , Jamal Amr , Alsubaie Sarah , Al-Shahrani Fatimah S. , Memish Ziad A. , Al-Tawfiq Jaffar A.
Published: December 2020

Objectives

This study aimed to identify COVID-19 vaccine perception, acceptance, confidence, hesitancy, and barriers among healthcare workers (HCW).

Methods

An online national cross-sectional pilot-validated questionnaire was self-administered by HCW in Saudi Arabia, a nation with MERS-CoV experience. The main outcome variable was HCW’s acceptance of COVID-19 vaccine candidates. The associated factors of vaccination acceptance were identified through a logistic regression analysis and the level of anxiety using generalized anxiety disorder 7.

Result

Out of 1512 HCWs who completed the study questionnaire—944 (62.4%) women and 568 (37.6%) men—1058 (70%) were willing to receive COVID-19 vaccines. Logistic regression analysis revealed that male HCWs (ORa=1.551, 95% CI: 1.122–2.144), HCWs who believe in vaccine safety (ORa=2.151; 95% CI:1.708–2.708), HCWs who believe that COVID vaccines are the most likely way to stop the pandemic (ORa=1.539; 95% CI: 1.259–1.881), and HCWs who rely on Centers for Disease Control and Prevention website for COVID 19 updates (ORa=1.505, 95% CI: 1.125–2.013) were significantly associated with reporting willingness to be vaccinated. However, HCWs who believed vaccines were rushed without evidence-informed testing were found to be 60% less inclined to accept COVID-19 vaccines (ORa=0.394, 95% CI: 0.298– 0.522).

Conclusion

Most HCWs are willing to receive COVID-19 vaccines once available; yet, satisfactoriness of COVID-19 vaccination among HCWs is crucial because health professionals’ knowledge and confidence toward vaccines are important determining factors for their own vaccine acceptance and recommendation to their patients.
Investigating the origin of the Belgian second SARS-CoV-2 wave by using (pre)admission screening samples
Authors: Naesens Reinout , Heireman Laura , Vandamme Sarah , Willems Philippe , Van Herendael Bruno , Verstrepen Walter , De Schouwer Pieter , Bruynseels Peggy
Published: December 2020

The goal of this study was to estimate rates of SARS-CoV-2 carriership and viral loads in the general Antwerp population and to compare the estimated prevalences and incidences with governmental data (numbers of detected positive cases, stringency measure index) in order to evaluate the dynamics leading to the second wave. We used (pre)admission screening results from the major Antwerp hospitals for estimating community prevalences and incidences. 43.545 samples were included (April – November 2020). High SARS-CoV-2 carriership rates (mean week prevalence of 1.3%) were found in the general Antwerp population. 35.4% of positive cases carried high viral loads. Only a small proportion (15.3%) of the viral circulation was detected by the nationally implemented testing policy. In the weeks before the second Belgian wave, increasing prevalences and incidences were found, together with country-wide easing of restriction measures. In our opinion these findings have led to origin of the second viral wave.
Heartbeats entrain breathing via baroreceptor-mediated modulation of expiratory activity
Authors: Barnett William H. , Baekey David M. , Paton Julian F. R. , Dick Thomas E. , Wehrwein Erica A. , Molkov Yaroslav I.
Published: December 2020

Cardio-ventilatory coupling refers to a heartbeat (HB) occurring at a preferred latency before the onset of the next breath. We hypothesized that the pressure pulse generated by a HB activates baroreceptors that modulates brainstem expiratory neuronal activity and delays the initiation of inspiration. In supine male subjects, we recorded ventilation, electrocardiogram, and blood pressure during 20-min epochs of baseline, slow-deep breathing, and recovery. Inin siturodent preparations, we recorded brainstem activity in response to pulses of perfusion pressure. We applied a well-established respiratory network model to interpret these data. In humans, the latency between HBs and onset of inspiration was consistent across different breathing patterns. Inin situpreparations, a transient pressure pulse during expiration activated a subpopulation of expiratory neurons normally active during post-inspiration; thus, delaying the next inspiration. In the model, baroreceptor input to post-inspiratory neurons accounted for the effect. These studies are consistent with baroreflex activation modulating respiration through a pauci-synaptic circuit from baroreceptors to onset of inspiration.
Cortical resonance selects coherent input
Authors: Lewis Christopher Murphy , Ni Jianguang , Wunderle Thomas , Jendritza Patrick , Lazar Andreea , Diester Ilka , Fries Pascal
Published: December 2020

Synchronization has been implicated in neuronal communication, but causal evidence remains indirect. We used optogenetics to generate depolarizing currents in pyramidal neurons of cat visual cortex, emulating excitatory synaptic inputs under precise temporal control, while measuring spike output. Cortex transformed constant excitation into strong gamma-band synchronization, revealing the well-known cortical resonance. Increasing excitation with ramps increased the strength and frequency of synchronization. Slow, symmetric excitation profiles revealed hysteresis of power and frequency. Crucially, white-noise input sequences enabled causal analysis of network transmission, establishing that cortical resonance selectively transmits coherent input components. Models composed of recurrently coupled excitatory and inhibitory units uncovered a crucial role of feedback inhibition and suggest that hysteresis can arise through spike-frequency adaptation. The presented approach provides a powerful means to investigate the resonance properties of local circuits and probe how these properties transform input and shape transmission.
In Vivo CRISPR Screens Identify E3 Ligase Cop1 as a Modulator of Macrophage Infiltration and Cancer Immunotherapy Target
Authors: Wang Xiaoqing , Tokheim Collin , Wang Binbin , Gu Shengqing Stan , Tang Qin , Li Yihao , Traugh Nicole , Zhang Yi , Li Ziyi , Zhang Boning , Fu Jingxin , Xiao Tengfei , Li Wei , Meyer Clifford A. , Chu Jun , Jiang Peng , Cejas Paloma , Lim Klothilda , Long Henry , Brown Myles , Liu X. Shirley
Published: December 2020

Despite remarkable clinical efficacies of immune checkpoint blockade (ICB) in cancer treatment, ICB benefits in triple-negative breast cancer (TNBC) remain limited. Through pooled in vivo CRISPR knockout (KO) screens in syngeneic TNBC mouse models, we found that inhibition of the E3 ubiquitin ligase Cop1 in cancer cells decreases the secretion of macrophage-associated chemokines, reduces tumor macrophage infiltration, and shows synergy in anti-tumor immunity with ICB. Transcriptomics, epigenomics, and proteomics analyses revealed Cop1 functions through proteasomal degradation of the C/ebpδ protein. Cop1 substrate Trib2 functions as a scaffold linking Cop1 and C/ebpδ, which leads to polyubiquitination of C/ebpδ. Cop1 inhibition stabilizes C/ebpδ to suppress the expression of macrophage chemoattractant genes. Our integrated approach implicates Cop1 as a target for improving cancer immunotherapy efficacy by regulating chemokine secretion and macrophage levels in the TNBC tumor microenvironment.

Highlights

Large-scale in vivo CRISPR screens identify new immune targets regulating the tumor microenvironment

Cop1 knockout in cancer cells enhances anti-tumor immunity

Cop1 modulates chemokine secretion and macrophage infiltration into tumors

Cop1 targets C/ebpδ degradation via Trib2 and influences ICB response
Duck, duck, goose: Benchmark bird surveys help quantify counting errors and bias in a citizen-science database
Authors: Robinson W. Douglas , Hallman Tyler A. , Hutchinson Rebecca A.
Published: December 2020

The growth of biodiversity data sets generated by citizen scientists continues to accelerate. The availability of such data has greatly expanded the scale of questions researchers can address. Yet, error, bias, and noise continue to be serious concerns for analysts, particularly when data being contributed to these giant online data sets are difficult to verify. Counts of birds contributed to eBird, the world’s largest biodiversity online database, present a potentially useful resource for tracking trends over time and space in species’ abundances. We quantified counting errors in a sample of 1406 eBird checklists by comparing numbers contributed by birders (N=246) who visited a popular birding location in Oregon, USA, with numbers generated by a professional ornithologist engaged in a long-term study creating benchmark (reference) measurements of daily waterbird counts. We focused on waterbirds, which are easily visible at this site. We evaluated potential predictors of count differences, including characteristics of contributed checklists, of each species, and of time of day and year. Count differences were biased toward undercounts, with more than 75% of counts being below the daily benchmark value. When only checklists that actually reported a species known to be present were included, median count errors were −29.1% (range: 0 to −42.8 %; N=20 species). Model sets revealed an important influence of each species’ reference count, which varied seasonally as waterbird numbers fluctuated, and of percent of species known to be present each day that were included on each checklist. That is, checklists indicating a more thorough survey of the species richness at the site also had, on average, lower counting errors. However, even on checklists with the most thorough species lists, counts were biased low and exceptionally variable in their accuracy. To improve utility of such bird count data, we suggest three strategies to pursue in the future. One is to assess additional options for analytically determining how to select checklists that have the highest probability of including less biased count data, as well as exploring options for correcting bias during the analysis stage. Another is to add options for users to provide additional information that helps analysts choose checklists, such as an option for users to tag checklists where they focused on obtaining accurate counts. We also recommend exploration of opportunities to effectively calibrate citizen-science bird count data by establishing a formalized network of marquis sites where dedicated observers regularly contribute carefully collected benchmark data.
Analysis of Intermolt and Postmolt Transcriptomes Provides Insight into Molecular Mechanisms of the Red Swamp Crayfish,Procambarus ClarkiiMolting
Authors: Su Shengyan , Munganga Brian Pelekelo , Tian Can , Li JianLin , Yu Fan , Li Hongxia , Wang Meiyao , He Xinjin , Tang Yongkai
Published: December 2020

In the present study, we explored expression changes in the transcriptomes of two molting stages (post-molt (M) and Intermolt (NM)) of the red swamp crayfish. A total of 307608398 clean reads, with an average length of 145bp were obtained. Further clustering and assembly of the transcripts generated 139100 unigenes. The results were searched against the NCBI, NR, KEGG, Swissprot, and KOG databases, in order to annotate gene descriptions, associate them with gene ontology terms, and assign them to pathways. Several genes and other factors involved in a number of molecular events critical for molting, such as energy requirements, hormonal regulation, immune response, and exoskeleton formation were identified, evaluated, and characterized. The information presented here provides a basic understanding of the molecular mechanisms underlying the crayfish molting process, with respect to energy requirements, hormonal regulation, immune response, and skeletal related activities during post-molt stage and the intermolt stage.
MRI- and histologically derived neuroanatomical atlas of theAmbystoma mexicanum(axolotl)
Authors: Lazcano Iván , Cisneros-Mejorado Abraham , Concha Luis , Ortíz Retana Juan José , Garza-Villarreal Eduardo A. , Orozco Aurea
Published: December 2020

Amphibians are an important vertebrate model system to understand anatomy, genetics and physiology. Importantly, the brain and spinal cord of adult urodels (salamanders) have an incredible regeneration capacity, contrary to anurans (frogs) and the rest of adult vertebrates. Among these amphibians, the axolotl (Ambystoma mexicanum) has gained most attention because of the surge in the understanding of CNS regeneration and the recent sequencing of its whole genome. However, a complete comprehension of the brain anatomy is not available. In the present study we created a magnetic resonance imaging atlas of thein vivoneuroanatomy of the juvenile axolotl brain. This is the first MRI atlas for this species and includes 3 levels: 1) 80 regions of interest (ROIs); 2) a division of the brain according to the embryological origin of the neural tube, and 3) left and right hemispheres. Additionally, we localized the myelin rich regions of the juvenile brain. The atlas, the template that the atlas was derived from, and a masking file, can be found on Zenodo at DOI: 10.5281/zenodo.4311937. This MRI brain atlas aims to be an important tool for future research of the axolotl brain and that of other amphibians.
Expanding the range of editable targets in the wheat genome using the variants of the Cas12a and Cas9 nucleases
Authors: Wang Wei , Tian Bin , Pan Qianli , Chen Yueying , He Fei , Bai Guihua , Akhunova Alina , Trick Harold N. , Akhunov Eduard
Published: December 2020

The development of CRISPR-based editors having different protospacer adjacent motif (PAM) recognition specificities, or guide RNA length/structure requirements broadens the range of possible genome editing applications. Here, we evaluated the natural and engineered variants of Cas12a (FnCas12a fromFrancisella novicidaand LbCas12a fromLachnospiraceae bacterium) and Cas9 for wheat genome editing efficiency and ability to induce heritable mutations in endogenous genes controlling important agronomic traits in wheat. Unlike FnCas12a, LbCas12a was able to induce mutations in the wheat genome in the current study, even though with a lower rate than that reported for SpCas9. The eight-fold improvement in the gene editing efficiency was achieved for LbCas12a by using the guide RNAs flanked by ribozymes and driven by the RNA polymerase II promoter from switchgrass. The efficiency of multiplexed genome editing (MGE) using LbCas12a was mostly similar to that obtained using the simplex RNA guides. A LbCas12a-MGE construct was successfully applied for generating heritable mutations in a gene controlling grain size and weight in wheat. We show that the range of editable loci in the wheat genome could be expanded by using the engineered variants of Cas12a (LbCas12a-RVR) and Cas9 (Cas9-NG and xCas9) that recognize the TATV and NG PAMs, respectively, with the Cas9-NG showing higher editing efficiency on the targets with atypical PAMs compared to xCas9. In conclusion, our study reports the set of validated natural and engineered variants of Cas12a and Cas9 editors for targeting loci in the wheat genome not amenable to Cas9-based modification.
Directed differentiation of Dental Pulp Pluripotent-like Stem Cells into Hepatocyte-like Cells
Authors: Gil-Recio Carlos , Montori Sheyla , Cámara Vallejo M , Demour Saddam Al , Ferrés-Padró Eduard , Barajas Miguel , Martin Carles , Madhoun Ashraf Al , Atari Maher
Published: December 2020

Liver diseases are a major cause of morbidity and mortality. Dental pulp pluripotent-like stem cells (DPPSC) are a considerable promise in tissue engineering and regenerative medicine as a source of tissue-specific cells, therefore this study aims to demonstrate their ability to generate functional hepatocyte-like cellsin vitro. Cells were differentiated on a collagen scaffolds in serum free media supplemented with growth factors and cytokines to recapitulate liver development. At day 5, the differentiated DPPSC cells expressed the endodermal markers FOXA1 and FOXA2. Then, the cells were derived into the hepatic lineage generating hepatocyte-like cells. In addition to the associated morphological changes, the cells expressed the hepatic genes HNF6, AFP. The terminally differentiated hepatocyte-like cells expressed the liver functional proteins albumin and CYP3A4. In this study, we report an efficient serum-free protocol to differentiate DPPSCs into functional hepatocyte-like cells. Our approach promotes the use of DPPSCs as a new source of adult stem cells for prospective use in liver regenerative medicine.
Causes of Outcome Learning: A causal inference-inspired machine learning approach to disentangling common combinations of potential causes of a health outcome
Authors: Rieckmann A , Dworzynski P , Arras L , Lapuschkin S , Samek W , Arah OA , Rod NH , Ekstrøm CT
Published: December 2020

Nearly all diseases can be caused by different combinations of exposures. Yet, most epidemiological studies focus on the causal effect of a single exposure on an outcome. We present the Causes of Outcome Learning (CoOL) approach, which seeks to identify combinations of exposures (which can be interpreted causally if all causal assumptions are met) that could be responsible for an increased risk of a health outcome in population sub-groups. The approach allows for exposures acting alone and in synergy with others. It involves (a) a pre-computational phase that proposes a causal model; (b) a computational phase with three steps, namely (i) analytically fitting a non-negative additive model, (ii) decomposing risk contributions, and (iii) clustering individuals based on the risk contributions into sub-groups based on the predefined causal model; and (c) a post-computational phase on hypothesis development and validation by triangulation on new data before eventually updating the causal model. The computational phase uses a tailored neural network for the non-negative additive model and Layer-wise Relevance Propagation for the risk decomposition through this model. We demonstrate the approach on simulated and real-life data using the R package ‘CoOL’. The presentation is focused on binary exposures and outcomes but can be extended to other measurement types. This approach encourages and enables epidemiologists to identify combinations of pre-outcome exposures as potential causes of the health outcome of interest. Expanding our ability to discover complex causes could eventually result in more effective, targeted, and informed interventions prioritized for their public health impact.
HEALTH OUTCOMES IN COPD SMOKERS USING HEATED TOBACCO PRODUCTS: A 3-YEAR FOLLOW-UP
Authors: Polosa R , Morjaria JB , Prosperini U , Busà B , Pennisi A , Gussoni G , Rust S , Maglia M , Caponnetto P
Published: December 2020

Background

Given that many patients with chronic obstructive pulmonary disease (COPD) smoke despite their symptoms, it is important to understand the long term health impact of cigarette substitution with heated tobacco products (HTPs). We monitored health parameters for 3-years in COPD patients who substantially attenuated or ceased cigarette consumption after switching to HTPs.

Methods

Changes in daily cigarette smoking, annualized disease exacerbations, lung function indices, patients reported outcomes (CAT scores) and 6-minute walk distance (6MWD) from baseline were measured in COPD patients using HTPs at 12, 24 and 36 months. These were compared to a group of age- and sex-matched COPD patients who continued smoking.

Results

Complete data sets were available for 38 patients (19 in each group). Subjects using HTPs had a substantial decrease in annualized COPD exacerbations within the group mean (±SD) from 2.1 (±0.9) at baseline to 1.4 (±0.8), 1.2 (±0.8) and 1.3 (±0.8) at 12-, 24- and 36-month follow-up (p<0.05 for all visits). In addition, substantial and clinically significant improvements in CAT scores and 6MWD were identified at all 3 time points in the HTP cohort. No significant changes were observed in COPD patients who continued smoking.

Conclusions

This study is the first to describe the long-term health effects of HTP use in COPD patients. Consistent improvements in respiratory symptoms, exercise tolerance, quality of life, and rate of disease exacerbations were observed in patients with COPD who abstained from smoking or substantially reduced their cigarette consumption by switching to HTP use.
Projecting the impact of a two-dose COVID-19 vaccination campaign in Ontario, Canada
Authors: Vilches Thomas N. , Zhang Kevin , Van Exan Robert , Langley Joanne M. , Moghadas Seyed M.
Published: December 2020

Background

A number of highly effective COVID-19 vaccines have been developed and approved for mass vaccination. We evaluated the impact of vaccination on COVID-19 outbreak and disease outcomes in Ontario, Canada.

Methods

We used an agent-based transmission model and parameterized it with COVID-19 characteristics, demographics of Ontario, and age-specific clinical outcomes. We implemented a two-dose vaccination program according to tested schedules in clinical trials for Pfizer-BioNTech and Moderna vaccines, prioritizing healthcare workers, individuals with comorbidities, and those aged 65 and older. Daily vaccination rate was parameterized based on vaccine administration data. Using estimates of vaccine efficacy, we projected the impact of vaccination on the overall attack rate, hospitalizations, and deaths. We further investigated the effect of increased daily contacts at different stages during vaccination campaigns on outbreak control.

Results

Maintaining non-pharmaceutical interventions (NPIs) with an average of 74% reduction in daily contacts, vaccination with Pfizer-BioNTech and Moderna vaccines was projected to reduce hospitalizations by 27.3% (95% CrI: 22.3% - 32.4%) and 27.0% (95% CrI: 21.9% - 32.6%), respectively, over a one-year time horizon. The largest benefits of vaccination were observed in preventing deaths with reductions of 31.5% (95% CrI: 22.5% - 39.7%) and 31.9% (95% CrI: 22.0% - 41.4%) for Pfizer-BioNTech and Moderna vaccines, respectively, compared to no vaccination. We found that an increase of only 10% in daily contacts at the end of lockdown, when vaccination coverage with only one dose was 6%, would trigger a surge in the outbreak. Early relaxation of population-wide measures could lead to a substantial increase in the number of infections, potentially reaching levels observed during the peak of the second wave in Ontario.

Conclusions

Vaccination can substantially mitigate ongoing COVID-19 outbreaks. Sustaining population-wide NPIs, to allow for a sufficient increase in population-level immunity through vaccination, is essential to prevent future outbreaks.
Common variants near the bradykinin receptor B2gene are associated with angioedema induced by angiotensin-converting-enzyme inhibitor treatment - a genome wide association study
Authors: Ghouse Jonas , Ahlberg Gustav , Andreasen Laura , Banasik Karina , Brunak Søren , Schwinn Michael , Larsen Ina Holst , Petersen Oscar , Sørensen Erik , Ullum Henrik , Rasmussen Eva Rye , Eriksson Niclas , Hallberg Pär , Wadelius Mia , Bundgaard Henning , Olesen Morten S.
Published: December 2020

Objective

Angioedema is a rare, but potentially life-threatening adverse reaction, associated with angiotensin-converting-enzyme inhibitors (ACEi). Identification of potential genetic factors related to this adverse event may help identify at-risk patients.

Design, Setting and Participants

A genome-wide association study (GWAS) involving patients of European descent, all taking ACEi was conducted in a discovery cohort (Copenhagen Hospital Biobank), and associations were confirmed in a replication cohort (Swedegene). Cases were defined as persons with an angioedema event and a filled prescription for an ACEi 180 days prior to the event. Controls were defined as persons with continuous treatment with ACEi without any history of angioedema. Odds ratios (ORs) and 95 % confidence intervals (95 % CI) were computed for angioedema risk by logistic mixed model regression analysis. Summary statistics from the discovery and the replication cohorts were analyzed with a fixed effects meta-analysis model.

Exposure

Single-nucleotide polymorphisms associated with ACEi-associated angioedema.

Main outcome

Hospital record of angioedema.

Results

The discovery cohort consisted of 462 cases and 53,391 ACEi-treated controls. The replication cohort consisted of 144 cases and 1,345 ACEi-treated controls. In the discovery cohort, we identified one locus, residing at chromosome 14q32.2, that was associated with angioedema at the genome-wide significance level ofP <5 × 10−8. The lead variant at this locus, rs34485356, is an intergenic variant located 60 kb upstream ofBDKRB2(OR 1.62; 95 % CI 1.38 to 1.90;P= 4.3 × 10−9). This variant was validated in our replication cohort with similar direction and effect size (OR 1.60; 95 % CI 1.13 to 2.25;P= 7.2 × 10−3). We found that carriers of the risk allele had significantly lower systolic (−0.46 mmHg per T allele; 95 % CI −0.83 to −0.10;P= 0.013) and diastolic blood pressure (−0.26 mmHg per T allele; 95 % CI −0.46 to −0.05;P= 0.013).

Conclusion

In this GWAS, involving individuals treated with ACEi, we found that common variants located in close proximity to the bradykinin receptor B2gene were associated with ACEi-related angioedema.BDKRB2genotype-directed therapy may aid in improving safety in evidence-based clinical decision-making.
QT Interval Prolongation in Patients Treated for COVID-19
Authors: Habibzadeh Parham , Sarami Abdollah , Yadollahie Mahboobeh , Hashemiasl Kourosh , Salahi Arezoo , Habibzadeh Farrokh
Published: December 2020

Background

Many of the drugs commonly used for the treatment of COVID-19 cause QT interval prolongation and increase the risk of life-threatening cardiac arrhythmias. It has been shown that maintaining serum potassium and magnesium levels above 4 and 3 mg/dL, respectively, would prevent the QTc prolongation.

Objective

To determine if keeping only the serum magnesium level above 3 mg/dL could be considered an effective measure to prevent QTc prolongation in patients with COVID-19 receiving these drugs.

Methods

In a retrograde observational study, QTc interval was measured in 14 patients diagnosed with COVID-19 before and 3 days after initiation of treatment with either hydroxychloroquine or lopinavir-ritonavir, while their serum magnesium levels were kept ≥3 mg/dL.

Results

The baseline QTc interval of 412 (SD 36) ms significantly increased by an average of 34 (95% CI 13 to 55) ms after 3 days of treatment. 5 patients, mostly those with lower serum potassium levels, had QTc prolongation ≥60 ms.

Conclusion

Although it seems that the risk of fatal cardiac arrhythmias in this setting is not high, it is prudent to monitor the serum electrolytes, particularly potassium, in patients with COVID-19 who are treated with either hydroxychloroquine or lopinavir-ritonavir.
Kinetics of SARS-CoV-2 antibody responses pre- and post- COVID-19 convalescent plasma transfusion in patients with severe respiratory failure: an observational case-control study
Authors: Klein Matthew N. , Wang Elizabeth Wenqian , Zimand Paul , Beauchamp Heather , Donis Caitlin , Ward Matthew D. , Martinez-Hernandez Aidaelis , Tabatabai Ali , Baddley John W. , Bloch Evan M. , Mullins Kristin E. , Fontaine Magali J.
Published: December 2020

OBJECTIVES

To investigate if COVID-19 convalescent plasma (CCP) transfusion in patients with severe respiratory failure will increase plasma levels of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody titers while improving survival and clinical outcomes.

DESIGN

Observational, retrospective, control study of anti-Receptor binding domain (RBD) of SARS-CoV-2 IgG and IgM titers from serial plasma samples drawn before and after CCP administration. Clinical improvement in CCP recipients is assessed and compared to COVID-19 control patients.

SETTING

Patients hospitalized with severe COVID19, United States, between April 17 and July 19, 2020

PARTICIPANTS

34 patients hospitalized with severe or life threatening COVID-19 and who consented and received a CCP transfusion, 95 control patients with COVID-19 not transfused with CCP. 34 out the 95 control patients were matched for age, sex, and the level of respiratory support required. Patients less than 18 years old were excluded.

MAIN OUTCOME MEASURES

Serial trends of anti-RBD of SARS-CoV-2 IgG and IgM titers in CCP recipients are compared to those in control patients. The primary outcome is survival at 30 days, and the secondary outcomes are length of ventilatory and/or extracorporeal membrane oxygenation (ECMO) support, length of stay (LOS) in the hospital, and LOS in the ICU.

RESULTS

CCP transfusion occurred in 34 patients at a median of 12 days following COVID-19 symptom onset. Immediately prior to CCP transfusion, patients median anti-RBD SARS-CoV-2 IgG and IgM titers were 1:3200 (IQR, 1:50 to 1:9600) and 1:320 (IQR, 1:40 to 1:640) respectively. Following a Loess regression analysis, the kinetics and distribution of anti-RBD of SARS-CoV-2 IgG and IgM in plasma from CCP recipients were comparable to those from a control group of 68 patients who did not receive CCP. CCP recipients presented with similar survival, similar duration on ventilatory and/or ECMO support, as well as ICU and hospital LOS, compared to a matched control group of 34 patients.

CONCLUSION

In the present study, hospitalized COVID-19 patients with severe respiratory failure transfused with CCP presented with high titers of SARS-CoV-2 IgG antibodies before transfusion and did not show improved survival at 30 days.
Understanding Suicide in Our Community Through the Lens of the Pediatric ICU: An Epidemiological Review (2011-2017) of One Midwestern City in the US
Authors: Kampfschulte Andrew , Oram Matthew , Escobar Vasco Alejandra M. , Essenmacher Brittany , Herbig Amy , Behere Aniruddh , Leimanis-Laurens Mara L. , Rajasekaran Surender
Published: December 2020

Suicide frequency has tripled for some pediatric age groups over the last decade, of which, serious attempts result in pediatric intensive care unit (PICU) admissions. We paired clinical, aggregate geospatial, and temporal demographics to understand local community variables to determine if epidemiological patterns emerge that associate with risk for PICU admission. Data was extracted at an urban, high-volume, quaternary care facility from January 2011 to December 2017 via ICD 10 codes associated with suicide. Clinical, socioeconomic, geographical, and temporal variables were reviewed. 1,036 patients over age 9 were included, of which n=161 were PICU admissions. Females represented higher proportions of all suicide-related hospital admissions (67.9%). Looking at race/ethnicity, PICU admissions were largely Caucasian (83.2%); Blacks and Hispanics had lower odds of PICU admissions (OR: 0.49; 0.17, respectively). PICU-admitted patients were older (16.0 vs. 15.5; p=0.0001), with lower basal metabolic index (23.0 vs. 22.0; p=0.0013), and presented in summer months (OR: 1.51, p = 0.044). Time-series decomposition showed seasonal peaks in June and August. Local regions outside city limits identified higher numbers of PICU admissions. PICUs serve discrete geographical regions and are a source of information, when paired with clinical-geospatial/seasonal analyses, highlighting clinical and societal risk factors associated with PICU admissions.
Mathematical modelling projections versus the actual course of the COVID-19 epidemic following the nationwide lockdown in Kyrgyzstan
Authors: Moldokmatova Ainura , Estebesova Aida , Dooronbekova Aizhan , Zhumalieva Chynar , Mukambetov Aibek , Abdyldaev Talant , Kubatova Aisuluu , Ibragimov Shamil , Usenbaev Nurbolot , Kutmanova Ainura , White Lisa J
Published: December 2020

Kyrgyzstan was placed under a two-month, nationwide lockdown due to the COVID-19 epidemic, starting on March 25, 2020. Given the highly disruptive effects of the lockdown on the national economy and people’s lives, the government decided not to extend lockdown beyond the initially planned date of May 10, 2020. The strategy chosen by the government was close to the input parameters of our model’s baseline scenario, ‘full lockdown release’, which we presented to policymakers in April 2020, along with various other hypothetical scenarios with managed lockdown release options. To explore whether our model could accurately predict the actual course of the epidemic following the release of lockdown, we compared the outputs of the baseline scenario, such as new cases, deaths, and demand for and occupancy of hospital beds, with actual official reports. Our analysis revealed that the model could accurately predict the timing of the epidemic peak, with a difference of just two weeks, although the magnitude of the peak was overestimated compared with the official statistics. However, it is important to note that the accuracy of the official reports remains debatable, so outputs relating to the size of the epidemic and related pressures on the health system will need to be updated if new evidence becomes available.
Signal and noise in circRNA translation
Authors: Hansen TB
Published: December 2020

Within recent years, circular RNAs (circRNAs) have been an attractive new field of research in RNA biology and disease. Consequently, numerous studies have been published towards the disclosure of circRNA biogenesis and function. Initially, circRNAs were described as a subclass of cytoplasmic non-coding RNA, however, a few recent observations have proposed that circRNAs may instead be templates for protein production. The extent to which this is the case is currently debated, and therefore using rigorous data analysis and proper experimental setups is instrumental to settle the current controversies. Here, the conventional experiments used for detecting circRNA translation are outlined, and guidelines to distinguish signal from the inherent noise are discussed. While these guidelines are specific for circRNA translation, most also apply to all other aspects of non-canonical translation.
Metabolic potential for reductive acetogenesis and a novel energy-converting [NiFe] hydrogenase inBathyarchaeiafrom termite guts – a genome-centric analysis
Authors: Loh Hui Qi , Hervé Vincent , Brune Andreas
Published: December 2020

Symbiotic digestion of lignocellulose in the hindgut of higher termites is mediated by a diverse assemblage of bacteria and archaea. During a large-scale metagenomic study, we reconstructed 15 metagenome-assembled genomes (MAGs) ofBathyarchaeiathat represent two distinct lineages in subgroup 6 (formerly MCG-6) unique to termite guts. One lineage (TB2;CandidatusTermitimicrobium) encodes all enzymes required for reductive acetogenesis from H2and CO2via an archaeal variant of the Wood–Ljungdahl pathway. This includes a novel 11-subunit hydrogenase, which possesses the genomic architecture of the respiratory Fpo-complex of other archaea but whose catalytic subunit is phylogenetically related to and shares the conserved [NiFe] cofactor-binding motif with [NiFe] hydrogenases of subgroup 4g. We propose that this novel Fpo-like hydrogenase provides the reduced ferredoxin required for CO2reduction and is driven by the electrochemical membrane potential generated from the ATP conserved by substrate-level phosphorylation. Members of the other lineage (TB1;CandidatusTermiticorpusculum) are not capable of lithotrophic acetogenesis because they consistently lack hydrogenases and/or methylene-tetrahydromethanopterin reductase, a key enzyme of the pathway. Both lineages have the genomic capacity to reduce ferredoxin by oxidizing amino acids and might conduct methylotrophic acetogenesis using unidentified methylated compound(s). Our results indicate thatBathyarchaeiaof subgroup 6 contribute to acetate formation in the guts of higher termites and substantiate the genomic evidence for reductive acetogenesis from organic substrates, including methylated compounds, in other uncultured representatives of the phylum.
Multi-omics insights into host-viral response and pathogenesis in Crimean-Congo Hemorrhagic Fever Viruses for novel therapeutic target
Authors: Neogi Ujjwal , Elaldi Nazif , Appelberg Sofia , Ambikan Anoop T. , Kennedy Emma , Dowall Stuart , Bagci Binnur K. , Gupta Soham , Rodriguez Jimmy E. , Svensson-Akusjärvi Sara , Monteil Vanessa M. , Végvári Ákos , Benfeitas Rui , Banerjea Akhil C. , Weber Friedemann , Hewson Roger , Mirazimi Ali
Published: December 2020

The pathogenesis and host-viral interactions of the Crimean–Congo hemorrhagic fever orthonairovirus (CCHFV) are convoluted and not well evaluated. Application of the multi-omics system biology approaches including biological network analysis in elucidating the complex host-viral response, allow for interrogating the viral pathogenesis. The present study aimed to fingerprint the system-level alterations during acute CCHFV-infection and the cellular immune responses during productive CCHFV-replicationin vitro. We used system-wide network-based system biology analysis of peripheral blood mononuclear cells (PBMCs) from a longitudinal cohort of CCHF patients during the acute phase of infection and after one year of recovery (convalescent phase) and untargeted quantitative proteomics analysis of the most permissive CCHFV-infected Huh7 and SW13 cells. In the RNAseq analysis of the PBMCs, comparing the acute and convalescent-phase, we observed system-level host’s metabolic reprogramming towards central carbon and energy metabolism (CCEM) with distinct upregulation of oxidative phosphorylation (OXPHOS) during CCHFV-infection. Upon application of network-based system biology methods, negative coordination of the biological signaling systems like FOXO/Notch axis and Akt/mTOR/HIF-1 signaling with metabolic pathways during CCHFV-infection were observed. The temporal quantitative proteomics in Huh7 showed a dynamic change in the CCEM over time and was in agreement with the cross-sectional proteomics in SW13 cells. By blocking the two key CCEM pathways, glycolysis and glutaminolysis, viral replication was inhibitedin vitro. Activation of key interferon stimulating genes during infection suggested the role of type I and II interferon-mediated antiviral mechanisms both at system-level and during progressive replication.

Significance Statement

A combination of multi-modal systems-wide host-immune response andin vitrotemporal analysis identified molecular re-arrangement in CCEM and fingerprinting the interferon-mediated antiviral mechanism during CCHFV-infection. Using the newly gained insights, we then modulated the key pathways of CCEM by drugs and inhibited the productive CCHFV-replication inin vitroinfection models. Our study thus provides a comprehensive, system-level picture of the regulation of cellular and metabolic pathways during productive CCHFV-infection for the first time that aids in identifying novel therapeutic targets and treatment strategies.
Understanding patterns of adherence to COVID-19 mitigation measures: A qualitative interview study
Authors: Denford Sarah , Morton Kate S , Lambert Helen , Zhang Juan , Smith Louise E , Rubin G James , Cai Shenghan , Zhang Tingting , Robin Charlotte , Lasseter Gemma , Hickman Mathew , Oliver Isabel , Yardley Lucy
Published: December 2020

In an effort to reduce the spread of COVID-19, the UK government has introduced a series of mitigation measures. The success of these measures in preventing transmission is dependent on adherence, which is currently considered to be low. Evidence highlights the disproportionate impact of mitigation measures on individuals from Black, Asian and minority ethnic (BAME) communities, as well as among those on a low income, and an understanding of barriers to adherence in these populations is needed. In this qualitative study we examined patterns of adherence to mitigation measures and reasons underpinning these behaviors among people on low income and those from BAME communities.

Semi-structured interviews were conducted with 20 participants from BAME and low-income White backgrounds. The topic guide was designed to explore how individuals are adhering to social distancing and self-isolation measures during the COVID-19 pandemic, and to explore in detail the reasons underpinning this behavior. Data were analyzed using ‘thematic analysis following which charts were used to help compare concepts within and between participants and develop an understanding of patterns of adherence.

Participants were confused by the constantly changing and seemingly contradictory rules and guidance. As a result, decisions were made about how best to protect themselves and their household from COVID-19, and from the detrimental impact of lockdown restrictions. This was not always in line with government advice. We identified three categories of adherence to lockdown measures 1) caution motivated super-adherence 2) risk-adapted partial-adherence and 3) necessity-driven partial-adherence. Decisions about adherence considered potential for exposure to the virus, ability to reduce risk through use of protective measures, and perceived importance of/need for the behavior.

This research highlights a need for a more nuanced understanding of adherence to lockdown measures. Provision of practical and financial support could reduce the number of people who have to engage in necessity-driven partial-adherence. Information about viral transmission could help people assess the risk associated with partial-adherence more accurately. More evidence is required on population level risks of people adopting risk-adapted partial-adherence.
Did the elderly suffer more from housing deprivation? Evidence from Poland
Authors: Matel Anna , Marcinkiewicz Jacek
Published: December 2020

Purpose

The elderly seem to be more subject to housing problems due to lower income, older age of the housing stock and lower mobility. Nonetheless, housing deprivation (HD) is commonly analysed amongst the general population. Less is known about the differences between age clusters, which seems to be a crucial issue in countries like Poland due to population ageing. What is more, the current literature usually analyses only the occurrence of HD, while also an accumulation of its indicators seems to be substantial. The aim of this article is to identify the differences in HD (its occurrence and accumulation) amongst elderly and non-elderly households and to diagnose the risk factors behind those phenomena.

Design/methodology/approach

The HD index was calculated and compared. Next, the multinomial logit models were used to assess risk factors of HD.

Findings

The study showed that, surprisingly, HD in Poland occurs more frequently amongst non-elderly households. The elderly ones suffered more from housing cost overburden, while non-elderly from the overpopulation. In large part, analysed risk factors had a stronger influence on housing conditions of the elderly than non-elderly households.

Social implications

Social policy tools should focus on the situation of single elderly households, especially living in houses, often in villages. This group is particularly affected by problems with the quality of the dwelling and housing cost overburden.

Originality/value

In the paper, the occurrence and accumulation of HD indicators were analysed. The authors applied a methodological framework that is applicable to other European Union (EU) member states based on the EU Survey on Income and Living Conditions (EU-SILC) data. It is possible to continue the research study and compare different economies.
Wavelet-based analysis of guar futures in India: did we kill the golden goose?
Authors: Bandyopadhyay Arunava , Bhowmik Souvik , Rajib Prabina
Published: December 2020

Purpose

Guar Gum (GG) is used in Shale oil exploration. Excessive price increase in the Guar futures market had a spillover impact on Guar spot prices and affected Guar export from India as Shale oil producers started exploring alternate sources. In this paper, the role of excessive speculation in the futures market, and its adverse impact on the guar-based agri-business ecosystem have been empirically explored.

Design/methodology/approach

Volatility spillover dynamics between WTI crude oil and Guar futures have been explored using bivariate-Granger Causality, BEKK–GARCH models with Wavelet multi-resolution analysis. The wavelet-based models capture the multi-scale features of mean and volatility spillover to identify the effect of heterogenous investment behavior in the time and frequency domain.

Findings

The results provide evidence that excessive speculation in futures markets increases spot market volatility. The results also suggest that the excess presence of short-term investors can destabilize the futures market.

Research limitations/implications

The purpose of the commodity futures market is to support price discovery and risk management. However, speculative practices can destabilize these purposes leading to the failure of the business ecosystem.

Originality/value

The novelty of this paper is twofold. First, it explores the economic linkages between the spot and futures market and tests whether the presence of heterogeneous traders affects the economic linkages. Second, it models the impact of short-term speculative investment on the destabilization of the spot market.
“Snitches get stitches”: researching both sides of illegal markets
Authors: Potter Lisa , Potter Gary R.
Published: December 2020

Purpose

The question of “taking sides” has received a lot of attention within qualitative criminology. Much of this has focused on the moral-philosophical or value-laden aspects of taking sides, following Becker's 1967 essay “whose side are we on”. However, the question of taking sides also has methodological implications, especially for qualitative researchers who wish to study multiple sides of a criminological problem, such as the perspectives of offenders and law enforcement around a particular illegal activity.

Design/methodology/approach

This paper considers some of the practical, ethical and analytical challenges of studying illegal markets from opposing sides – the market participants' perspective on one side and law enforcement on the other. It outlines the advantages of researching both sides: the improved validity and reliability that comes with exploring and trying to reconcile different perspectives and the potential this has for developing theory and policy. It then explores the challenges researchers may face when trying to engage with opposing sides in qualitative fieldwork.

Findings

The paper pays particular attention to some practical and ethical questions researchers may face in this situation: who to research first, whether to be open about researching both sides and whether researchers should ever share information they have received from one side with their participants from the other side.

Originality/value

The authors do not offer absolute answers to these questions. Rather, the authors aim to outline some of the factors researchers may need to consider when juggling qualitative research involving participants on both sides of the law.