bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbon flux around leaf-cytosolic glyceraldehyde-3-phosphate dehydrogenase introduces a 13C signal in plant glucose
Authors: Wieloch Thomas , Werner Roland Anton , Schleucher Jürgen
Published: July 2021

Within the plant and Earth sciences, stable isotope analysis is a versatile tool conveying information (inter alia) about plant physiological and paleoclimate variability across scales. Here, we identify a 13C signal (i.e. systematic 13C/12C variation) at tree-ring glucose C-4 and report an experimentally testable theory on its origin. We propose the signal is introduced by glyceraldehyde-3-phosphate dehydrogenases in the cytosol of leaves. It conveys two kinds of (potentially convoluted) information: (i) commitment of glyceraldehyde 3-phosphate to 3-phosphoglycerate versus fructose 1,6-bisphosphate metabolism; and (ii) the contribution of non-phosphorylating versus phosphorylating glyceraldehyde-3-phosphate dehydrogenase to catalysing the glyceraldehyde 3-phosphate to 3-phosphoglycerate forward reaction of glycolysis. The theory is supported by 13C fractionation modelling. Modelling results provide the first evidence in support of the cytosolic oxidation–reduction (COR) cycle, a carbon-neutral mechanism supplying NADPH at the expense of ATP and NADH, which may help to maintain leaf-cytosolic redox balances. In line with expectations related to COR cycling, we found a positive correlation between air vapour pressure deficit and 13C discrimination at glucose C-4. Overall, 13C-4 signal analysis may enable an improved understanding of leaf carbon and energy metabolism.
Mesophyll conductance in two cultivars of wheat grown in glacial to super-elevated CO2 concentrations
Authors: Jahan Eisrat , Thomson Peter C , Tissue David T
Published: July 2021

Mesophyll conductance (gm) is an important factor limiting photosynthesis. However, gm response to long-term growth in variable [CO2] is not well understood, particularly in crop plants. Here, we grew two cultivars of wheat (Halberd and Cranbrook), known to differ in gm under current environmental conditions, in four [CO2] treatments: glacial (206 μmol mol−1), pre-industrial (344 μmol mol−1), current ambient (489 μmol mol−1), and super-elevated (1085 μmol mol−1), and two water treatments (well-watered and moderate water limitation), to develop an evolutionary and future climate perspective on gm control of photosynthesis and water-use efficiency (WUE). In the two wheat genotypes, gm increased with rising [CO2] from glacial to ambient [CO2], but declined at super-elevated [CO2]. The responses of gm to different growth [CO2] also depend on water stress; however, the specific mechanism of gm response to [CO2] remains unclear. Although gm and gm/gsc (mesophyll conductance/stomatal conductance) were strongly associated with the variability of photosynthetic rates (A) and WUE, we found that plants with higher gm may increase A without increasing gsc, which increased WUE. These results may be useful to inform plant breeding programmes and cultivar selection for Australian wheat under future environmental conditions.
‘United through our values’? Expressing unity through value-talk after terrorism in France and Norway
Authors: Ezzati Rojan Tordhol
Published: July 2021

In the immediate aftermath of terrorism, references to ‘our values’ as a source of unity become a substantial part of public discourse. Leaders, the media, and the public emphasize ‘values’ to express that ‘we’ are united across ethnic, religious, and political differences. This article comparatively examines formulations of ‘we’, ‘us’, and ‘them’ with reference to ‘values’ (i.e. value-talk) after terror attacks in France (November 2015) and Norway (July 2011). To access speech, events, and symbols as they were unfolding, the analysis draws on the first week of national television news following these attacks. Whereas the terrorists in France were self-proclaimers of an Islamic State, the terrorist in Norway was a self-proclaimed defender of the Christian civilization. The central place of a value-based unity—regardless of the terrorists’ ethnicity and motivations—contrasts with the otherwise common idea expressed in public debate that ‘values’ embody a fundamental divide between ‘natives’ and immigrant populations. This article argues that scholarship on values, in migration studies and beyond, reifies the much-repeated assumption in public debate that there is a value-based divide between groups of people. By examining expressions of unity in contexts of conflict, the analysis untangles the dynamic and flexible ‘groupness’ articulated through value-talk. Analytical attention to this variability, I argue, better reflects the widespread attention to cultural complexities in migration studies. Through the study of value-talk in the immediate aftermath of terrorism, the article explores some of the dimensions of how and when unity is mobilized in societies marked by migration-related diversity.
High eccentricities and high masses characterize gravitational-wave captures in galactic nuclei as seen by Earth-based detectors
Authors: Gondán László , Kocsis Bence
Published: July 2021

The emission of gravitational waves (GWs) during single–single close encounters in galactic nuclei (GNs) leads to the formation and rapid merger of highly eccentric stellar-mass black hole (BH) binaries. The distinct distribution of physical parameters makes it possible to statistically distinguish this source population from others. Previous studies determined the expected binary parameter distribution for this source population in single GNs. Here, we take into account the effects of dynamical friction, post-Newtonian corrections, and observational bias to determine the detected sources’ parameter distributions from all GNs in the Universe. We find that the total binary mass distribution of detected mergers is strongly tilted towards higher masses. The distribution of initial peak GW frequency is remarkably high between 1 and 70 Hz, $\sim \! 50{{\ \rm per\ cent}}$ of GW capture sources form above 10 Hz with e ≳ 0.95. The eccentricity when first entering the LIGO/Virgo/KAGRA band satisfies $e_{\rm 10\, Hz}\gt 0.1$ for over $92{{\ \rm per\ cent}}$ of sources and $e_{\rm 10\, Hz}\gt 0.8$ for more than half of the sources. At the point when the pericentre reaches 10GM/c2 the eccentricity satisfies e10M > 0.1 for over $\sim \! 70{{\ \rm per\ cent}}$ of the sources, making single–single GW capture events in GNs the most eccentric source population among the currently known stellar-mass binary BH merger channels in our Universe. We identify correlations between total mass, mass ratio, source detection distance, and eccentricities $e_{\rm 10\, Hz}$ and e10M. The recently measured source parameters of GW190521 lie close to the peak of the theoretical distributions and the estimated escape speed of the host environment is $\sim \! 7.5\times 10^3\!-\!1.2\times 10^4\, \rm km\, s^{-1}$, making this source a candidate for this astrophysical merger channel.
Codependency and mutual exclusivity for gene community detection from sparse single-cell transcriptome data
Authors: Nakajima Natsu , Hayashi Tomoatsu , Fujiki Katsunori , Shirahige Katsuhiko , Akiyama Tetsu , Akutsu Tatsuya , Nakato Ryuichiro
Published: July 2021

Single-cell RNA-seq (scRNA-seq) can be used to characterize cellular heterogeneity in thousands of cells. The reconstruction of a gene network based on coexpression patterns is a fundamental task in scRNA-seq analyses, and the mutual exclusivity of gene expression can be critical for understanding such heterogeneity. Here, we propose an approach for detecting communities from a genetic network constructed on the basis of coexpression properties. The community-based comparison of multiple coexpression networks enables the identification of functionally related gene clusters that cannot be fully captured through differential gene expression-based analysis. We also developed a novel metric referred to as the exclusively expressed index (EEI) that identifies mutually exclusive gene pairs from sparse scRNA-seq data. EEI quantifies and ranks the exclusive expression levels of all gene pairs from binary expression patterns while maintaining robustness against a low sequencing depth. We applied our methods to glioblastoma scRNA-seq data and found that gene communities were partially conserved after serum stimulation despite a considerable number of differentially expressed genes. We also demonstrate that the identification of mutually exclusive gene sets with EEI can improve the sensitivity of capturing cellular heterogeneity. Our methods complement existing approaches and provide new biological insights, even for a large, sparse dataset, in the single-cell analysis field.
Psychotic-like Experiences and Common Mental Disorders in Childhood and Adolescence: Bidirectional and Transdiagnostic Associations in a Longitudinal Community-based Study
Authors: Giocondo José G , Salum Giovanni A , Gadelha Ary , Argolo Felipe C , Simioni André R , Mari Jair J , Miguel Euripedes C , Bressan Rodrigo A , Rohde Luis A , Pan Pedro M
Published: July 2021

Psychotic-like Experiences (PE) in early adolescence may increase the risk for later psychotic and non-psychotic disorders. Common psychiatric disorders may also increase the risk of PE later in life. We aim to explore bidirectional associations of PE and common mental disorders among 1712 youth from a 3-year follow-up community-based study. At baseline, we evaluated 6–12 years old subjects using dimensional and categorical measures of PE by self-reports and clinician ratings. Common mental disorders were assessed by structured interviews grouped into DSM-based categories (Depressive, Anxiety, Attention Deficit Hyperactivity Disorder (ADHD) and Disruptive Behavior Disorders) and Common Adolescent Behaviors (Substance Use and Self-harm). Subjects were reassessed with the same instruments after 3 years. Our study suggests an association between PE variables over time. A total of 15.9% (n = 272) participants scored above cutoff values at baseline and an increased proportion of 20.9% (n = 358) remained positive after follow-up. We also found bidirectional associations between PE and Common Mental Disorders. Baseline PE increased the risk of Depressive Disorders, Substance Use, and Self-harm, whereas baseline ADHD was associated with later PE. Comorbidity analyses showed significant relationships in both directions, with increased risk of PE according to the number of comorbid psychiatric disorders. We showed that subthreshold psychotic symptoms predict subsequent Depressive Disorders and that, reciprocally, other comorbid psychiatric disorders, such as ADHD, can predict its future expression. These findings suggest PE might be a part of a shared psychiatric vulnerability continuum, with distinct phenotypes over development.
Decomposing Learning Inequalities in East Africa: How Much Does Sorting Matter?
Authors: Anand Paul , Behrman Jere R , Dang Hai-Anh H , Jones Sam
Published: July 2021

Inequalities in learning opportunities arise from both household- and school-related factors. Although these factors are unlikely to be independent, few studies have considered the extent to which sorting between schools and households might aggravate educational inequalities. To fill this gap, this article presents a novel variance decomposition, which is then applied to data from over one million children from East Africa. Results indicate that sorting accounts for around 8 percent of the test-score variance, similar in magnitude to the contribution of differences in school quality. Empirical simulations of steady-state educational inequalities reveal that policies to mitigate sorting could substantially reduce educational inequalities over the long run.
Awareness and perceptions among members of a Japanese cancer patient advocacy group concerning the financial relationships between the pharmaceutical industry and physicians: a mixed-methods analysis of survey data
Authors: Murayama Anju , Senoo Yuki , Harada Kayo , Kotera Yasuhiro , Saito Hiroaki , Sawano Toyoaki , Suzuki Yosuke , Tanimoto Tetsuya , Ozaki Akihiko
Published: July 2021

Objectives

Financial conflicts of interest (FCOI) between pharmaceutical companies (Pharma) and healthcare domains may unduly influence physician-led clinical practice and patient-centered care. However, the extent of awareness and perceptions of FCOI among Japanese cancer patients remains unclear. This study aimed to assess these factors and their impacts on physician trustworthiness among Japanese cancer patients.

Methods

A cross-sectional study using self-administered surveys was conducted on a Japanese cancer patient advocacy group with 800 registered members from January to February 2019. Main outcome measures included awareness and perceptions of physician-Pharma interactions, their impact on physician trustworthiness, and attitudes towards FCOI among professions. We also performed thematic analyses on additional comments responders provided in the surveys.

Results

Among the 524 invited members, 96 (18.3%) completed the questionnaire. Of these, 69 (77.5%) were cancer patients. The proportion of participants aware of such interactions ranged from 2.1% to 65.3%, depending on the interaction type. Participants were generally neutral on how the interactions would affect physician trustworthiness. A large proportion of participants agreed that these interactions were unethical, could influence physicians’ prescribing behavior leading to unnecessary prescriptions, and negatively affect physician trustworthiness. Qualitative responses (n=56) indicated that patients expected physicians to use sound ethical judgment and avoid accepting incentives. Participants were also concerned about their treatment and the undue influence of FCOI on physicians.

Conclusion

Most participants were aware of at least one FCOI between Pharma and physicians and perceived them negatively. Further efforts to regulate FCOI appear necessary to protect patient-centered care.
The Emergence of SARS-CoV-2 Variant Lambda (C.37) in South America
Authors: Romero Pedro E. , Dávila-Barclay Alejandra , Salvatierra Guillermo , González Luis , Cuicapuza Diego , Solis Luis , Marcos-Carbajal Pool , Huancachoque Janet , Maturrano Lenin , Tsukayama Pablo
Published: July 2021

We report the emergence of a novel lineage of SARS-CoV-2 in South America, termed C.37. It presents seven nonsynonymous mutations in the Spike gene (Δ247-253, G75V, T76I, L452Q, F490S, T859N) and a deletion in the ORF1a gene (Δ3675-3677) also found in variants of concern (VOCs) Alpha, Beta, and Gamma. Initially reported in Lima, Peru, in late December 2020, it now accounts for 97% of Peruvian public genomes in April 2021. It is expanding in Chile and Argentina, and there is evidence of onward transmission in Colombia, Ecuador, Mexico, the USA, Germany, and Israel. On June 15, 2021, the World Health Organization designated C.37 as Variant of Interest (VOI) Lambda.
Examining spousal and family support as predictors of long-term weight loss and remission of type 2 diabetes following bariatric surgery
Authors: Tan Edina YQ , Lee Phong Ching , Tham Kwang Wei , Ganguly Sonali , Lim Chin Hong , Liu Jean CJ
Published: July 2021

Background

Postoperative outcomes vary considerably across bariatric patients and may be related to psychosocial factors. In this study, we examined whether a patient’s family support predicts weight loss and the remission of type 2 diabetes (T2DM) up to 5 years following surgery.

Methods

Between 2008 to 2018, 359 patients completed a pre-surgical questionnaire before undergoing gastric bypass or sleeve gastrectomy. As part of the questionnaire, patients described their family support in terms of structure (marital status, number of family members in the household) and function (marriage satisfaction, family emotional support, family practical support). These were applied as predictors to percent total weight loss (%TWL) and T2DM remission at 1, 2, 3, 4, and 5 years following surgery.

Results

Marital satisfaction was found to be a significant predictor of post-surgical weight trajectories. Namely, patients who reported higher marital satisfaction were more likely to sustain weight loss than patients who reported lower marital satisfaction (β = 0.92, SE = 0.37,p= 0.02).

Conclusions

Given the link between marital support and long-term weight outcomes, providers could consider asking patients about their spousal relationships during pre-surgical counselling.

Key Points

⍰

Psychosocial factors may influence postoperative outcomes

⍰

Family support was examined as a predictor of weight loss and type 2 diabetes

⍰

Marital satisfaction significantly predicted post-surgical weight trajectories
Modeling robust COVID-19 intensive care unit occupancy thresholds for imposing mitigation to prevent exceeding capacities
Authors: Runge Manuela , Richardson Reese A.K. , Clay Patrick , Eagan Arielle , Holden Tobias M. , Singam Manisha , Tsuboyama Natsumi , Arevalo Philip , Fornoff Jane , Patrick Sarah , Ezike Ngozi O. , Gerardin Jaline
Published: July 2021

In managing COVID-19 with non-pharmaceutical interventions, occupancy of intensive care units (ICU) is often used as an indicator to inform when to intensify mitigation and thus reduce SARS-CoV-2 transmission, strain on ICUs, and deaths. However, ICU occupancy thresholds at which action should be taken are often selected arbitrarily. We propose a quantitative approach using mathematical modeling to identify ICU occupancy thresholds at which mitigation should be triggered to avoid exceeding the ICU capacity available for COVID-19 patients. We used a stochastic compartmental model to simulate SARS-CoV-2 transmission and disease progression, including critical cases that would require intensive care. We calibrated the model for the United States city of Chicago using daily COVID-19 ICU and hospital census data between March and August 2020. We projected ICU occupancies from September to May 2021 under two possible levels of transmission increase. The effect of combined mitigation measures was modeled as a decrease in the transmission rate that took effect when projected ICU occupancy reached a specified threshold. We found that mitigation did not immediately eliminate the risk of exceeding ICU capacity. Delaying action by 7 days increased the probability of exceeding ICU capacity by 10-60% and this increase could not be counteracted by stronger mitigation. Even under modest transmission increase, a threshold occupancy no higher than 60% was required when mitigation reduced the reproductive number Rt to just below 1. At higher transmission increase, a threshold of at most 40% was required with mitigation that reduced Rt below 0.75 within the first two weeks after mitigation. Our analysis demonstrates a quantitative approach for the selection of ICU occupancy thresholds that considers parameter uncertainty and compares relevant mitigation and transmission scenarios. An appropriate threshold will depend on the location, number of ICU beds available for COVID-19, available mitigation options, feasible mitigation strengths, and tolerated durations of intensified mitigation.
RT-LAMP has high accuracy for detecting SARS-CoV-2 in saliva and naso/oropharyngeal swabs from asymptomatic and symptomatic individuals
Authors: Kidd Stephen P. , Burns Daniel , Armson Bryony , Beggs Andrew D. , Howson Emma L. A. , Williams Anthony , Snell Gemma , Wise Emma L. , Goring Alice , Vincent-Mistiaen Zoe , Grippon Seden , Sawyer Jason , Cassar Claire , Cross David , Lewis Thomas , Reid Scott M. , Rivers Samantha , James Joe , Skinner Paul , Banyard Ashley , Davies Kerrie , Ptasinska Anetta , Whalley Celina , Ferguson Jack , Bryer Claire , Poxon Charlie , Bosworth Andrew , Kidd Michael , Richter Alex , Burton Jane , Love Hannah , Fouch Sarah , Tillyer Claire , Sowood Amy , Patrick Helen , Moore Nathan , Andreou Michael , Morant Nick , Houghton Rebecca , Parker Joe , Slater-Jefferies Joanne , Brown Ian , Gretton Cosima , Deans Zandra , Porter Deborah , Cortes Nicholas J. , Douglas Angela , Hill Sue L. , Godfrey Keith M. , Fowler Veronica L.
Published: July 2021

Previous studies have described RT-LAMP methodology for the rapid detection of SARS-CoV-2 in nasopharyngeal (NP) and oropharyngeal (OP) swab and saliva samples. This study describes the validation of an improved sample preparation method for extraction free RT-LAMP and defines the clinical performance of four different RT-LAMP assay formats for detection of SARS-CoV-2 within a multisite clinical evaluation. Direct RT-LAMP was performed on 559 swabs and 86,760 saliva samples and RNA RT-LAMP on extracted RNA from 12,619 swabs and 12,521 saliva from asymptomatic and symptomatic individuals across healthcare and community settings. For Direct RT-LAMP, overall diagnostic sensitivity (DSe) of 70.35% (95% CI 63.48-76.60%) on swabs and 84.62% (79.50-88.88%) on saliva was observed, with diagnostic specificity (DSp) of 100% (98.98-100.00%) on swabs and 100% (99.72-100.00%) on saliva when compared to RT-qPCR; analysing samples with RT-qPCR ORF1ab CT values of ≤25 and ≤33, DSe of 100% (96.34-100%) and 77.78% (70.99-83.62%) for swabs were observed, and 99.01% (94.61-99.97%) and 87.61% (82.69-91.54%) for saliva, respectively. For RNA RT-LAMP, overall DSe and DSp were 96.06% (92.88-98.12%) and 99.99% (99.95-100%) for swabs, and 80.65% (73.54-86.54%) and 99.99% (99.95-100%) for saliva, respectively. These findings demonstrate that RT-LAMP is applicable to a variety of use-cases, including frequent, interval-based testing of saliva with Direct RT-LAMP from asymptomatic individuals that may otherwise be missed using symptomatic testing alone.
Predictors of Depression and Anxiety Symptoms in Brazil during COVID-19
Authors: Zhang Stephen X. , Huang Hao , Li Jizhen , Antonelli-Ponti Mayra , Farias de Paiva Scheila , Aparecido da Silva José
Published: July 2021

The COVID-19 pandemic in Brazil is extremely severe, and Brazil has the third-highest number of cases in the world. The goal of the study is to identify the prevalence rates and several predictors of depression and anxiety in Brazil during the initial outbreak of COVID-19. We surveyed 482 adults in 23 Brazilian states online on 9–22 May 2020, and found 70.3% of the adults (N=339) had depressive symptoms and 67.2% (N=320) had anxiety symptoms. The results of multi-class logistic regression models revealed that females, younger adults and those with fewer children had a higher likelihood of depression and anxiety symptoms; adults who worked as employees were more likely to have anxiety symptoms than those who were self-employed or unemployed; adults who spent more time browsing COVID-19 information online were more likely to have depression and anxiety symptoms. Our results provide preliminary evidence and early warning for psychiatrists and healthcare organizations to better identify and focus on the more vulnerable sub-populations in Brazil during the ongoing COVID-19 pandemic.
Effectiveness of mRNA and ChAdOx1 COVID-19 vaccines against symptomatic SARS-CoV-2 infection and severe outcomes with variants of concern in Ontario
Authors: Nasreen Sharifa , Chung Hannah , He Siyi , Brown Kevin A. , Gubbay Jonathan B. , Buchan Sarah A. , Fell Deshayne B. , Austin Peter C. , Schwartz Kevin L. , Sundaram Maria E. , Calzavara Andrew , Chen Branson , Tadrous Mina , Wilson Kumanan , Wilson Sarah E. , Kwong Jeffrey C.
Published: July 2021

SARS-CoV-2 variants of concern (VOC) are more transmissible and have the potential for increased disease severity and decreased vaccine effectiveness. We estimated the effectiveness of BNT162b2 (Pfizer-BioNTech Comirnaty), mRNA-1273 (Moderna Spikevax), and ChAdOx1 (AstraZeneca Vaxzevria) vaccines against symptomatic SARS-CoV-2 infection and COVID-19 hospitalization or death caused by the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) VOCs in Ontario, Canada using a test-negative design study. Effectiveness against symptomatic infection ≥7 days after two doses was 89–92% against Alpha, 87% against Beta, 88% against Gamma, 82–89% against Beta/Gamma, and 87–95% against Delta across vaccine products. The corresponding estimates ≥14 days after one dose were lower. Effectiveness estimates against hospitalization or death were similar to, or higher than, against symptomatic infection. Effectiveness against symptomatic infection is generally lower for older adults (≥60 years) compared to younger adults (<60 years) for most of the VOC-vaccine combinations.
A prospective study of time-dependent childhood adversity and DNA methylation across childhood and adolescence
Authors: Lussier Alexandre A. , Zhu Yiwen , Smith Brooke J. , Cerutti Janine , Simpkin Andrew J. , Smith Andrew D.A.C. , Suderman Matthew J. , Walton Esther , Relton Caroline L , Ressler Kerry J. , Dunn Erin C.
Published: July 2021

Background

Children exposed to adversity often have epigenetic profiles, including DNA methylation (DNAm) signatures, that differ from children without adversity histories. These signatures may be more common among children exposed during sensitive periods in development. However, it remains unclear if adversity has persistent (versus transient) effects on the epigenome across childhood and adolescence. Thus, we examined the relationship between time-varying adversity and genome-wide DNAm, measured three times from birth to adolescence using prospective data from the Avon Longitudinal Study of Parents and Children.

Methods

We first investigated the timing of exposure to seven types of adversity (measured 5-8 times between ages 0-11) and DNAm at age 15 using a structured life course modeling approach (SLCMA). We also assessed the persistence of adversity-DNAm associations identified from age 7 DNAm into adolescence and the influence of adversity on DNAm trajectories from ages 0-15.

Results

Adversity exposure was associated with differences in age 15 DNAm at 41 loci (R2≥0.035; p<1×10−5; 22 at FDR<0.05). Most loci were associated with adversities (i.e., physical, sexual, or emotional abuse; one-adult households) occurring between ages 3-5. DNAm differences present at age 7 resolved by adolescence; age 15 differences were not apparent in childhood. We also identified six distinct DNAm trajectories that highlighted both immediate and latent effects of adversity. Associations were robust in internal validation analyses using nonparametric bootstrapping.

Conclusions

These findings highlight the immediate and latent effects of childhood adversity on DNAm, providing a potential biological mechanism linking adversity to physical and mental health outcomes across development.
Clinicogenomic analysis of breakthrough infections by SARS CoV2 variants after ChAdOx1 nCoV- 19 vaccination in healthcare workers
Authors: Kale Pratibha , Gupta Ekta , Bihari Chhagan , Patel Niharika , Rooge Sheetalnath , Pandey Amit , Bajpai Meenu , Khillan Vikas , Chattopadhyay Partha , Devi Priti , Maurya Ranjeet , Jha Neha , Mehta Priyanka , Kumar Manish , Sharma Pooja , Saifi Sheeba , S Aparna , Alam Sarfaraz , Uppili Bharathram , Faruq Mohammed , Agrawal Anurag , Pandey Rajesh , Sarin Shiv Kumar
Published: July 2021

Background

India saw a massive surge and emergence of SARS CoV2 variants. We elucidated clinical and humoral immune response and genomic analysis of vaccine breakthrough (VBT) infections after ChAdOx1 nCoV-19 vaccine in healthcare workers (HCWs).

Methods

The study was conducted on 1858 HCWs receiving two doses of ChAdOx1 nCoV-19 vaccine. Serial blood samples were collected to measure SARS CoV2 IgG and neutralizing antibodies. 46 RT-PCR positive samples from VBT infections were subjected to whole genome sequencing (WGS).

Results

Infection was confirmed in 219 (11.79%) HCWs of which 21.46% (47/219) were non-vaccinated, significantly more (p <0.001) than 9.52% (156/1639) vaccinated group. VBT infections were significantly higher in doctors and nurses compared to other hospital staff (p <0.001). Unvaccinated individuals had 1.57 times higher risk of infection compared to partially vaccinated (p 0.02) and 2.49 times than fully vaccinated (<0.001). Partially vaccinated were at higher risk of infection than fully vaccinated (RR 1.58,p 0.01). There were 3 (1.36%) severe cases and 1 death in unvaccinated group compared to none in the vaccinated. Non-response after 14 days of second dose was seen in 6.5% (3/46) and low antibody levels (1-4.62 S/CO) in 8.69% (4/46). Delta variant (B.1.617.2) was dominant (69.5%) and reinfection was documented in 4 (0.06%) HCWs.

Conclusions

Nearly one in ten vaccinated HCWs can get infected, more so with only single dose (13.65%) than two doses (8.62%). Fully vaccinated are better protected with higher humoral immune response. Genomic analysis revealed an alarming rise of Delta variant (B.1.617.2) in VBT infections.
LeMeDISCO: A computational method for large-scale prediction & molecular interpretation of disease comorbidity
Authors: Astore Courtney , Zhou Hongyi , Skolnick Jeffrey
Published: July 2021

Often different diseases tend to co-occur (i.e., they are comorbid), which yields the question: what is the molecular basis of their coincidence? Perhaps, common proteins are comorbid disease drivers. To understand the origin of disease comorbidity and to identify the essential proteins and pathways underlying comorbid diseases, we developed LeMeDISCO (Large-Scale Molecular Interpretation of Disease Comorbidity), an algorithm that predicts disease comorbidities from shared mode of action (MOA) proteins predicted by the AI-based MEDICASCY algorithm. LeMeDISCO was applied to predict the general occurrence of comorbid diseases for 3608 distinct diseases. To illustrate LeMeDISCO’s power, we elucidate the possible etiology of coronary artery disease and ovarian cancer by determining the comorbidity enriched MOA proteins and pathways and suggest hypotheses for subsequent scientific investigation. The LeMeDISCO web server is available for academic users at: http://sites.gatech.edu/cssb/LeMeDISCO.
PERFORMANCE AND UTILITY OF AN ORAL FLUID-BASED RAPID POINT-OF-CARE TEST FOR SARS-COV-2 ANTIBODY RESPONSE FOLLOWING COVID-19 INFECTION OR VACCINATION
Authors: Rao Paturi V. , Nair-Shaef Dhanalakshmi , Chen Siting , Kazmierczak Steven C. , Roberts Charles T. , Nagalla Srinivasa R.
Published: July 2021

Analysis of anti-SARS-CoV-2 antibodies can identify recent-onset or prior COVID-19 infection or vaccine-induced humoral immunity. We have developed a rapid point-of-care test for IgG, M, or A-class immunoglobulins that recognize the S1 domain of the SARS-CoV-2 spike protein (CovAb™). The test employs a lateral-flow strip design with a recombinant SARS-CoV-2 spike protein S1 domain capture antigen to detect anti-SARS-CoV-2 antibodies in oral fluid samples. Oral fluid samples are collected with a swab that captures the gingival crevicular fluid component of oral fluid that represents a plasma transudate and that is the primary source of oral fluid monomeric antibodies. The sensitivity of the CovAb™ test is 97.29% and the specificity is 98.13%, and the results obtained are similar to those obtained using matched fingerstick whole blood samples and in an EUA-approved commercial serology test. Oral fluid SARS-CoV-2 antibodies could be detected in subjects more than 7 months post-symptom onset. We also demonstrate the utility of the CovAb™ test in characterizing adaptive immune responses to vaccination in COVID-19-naïve and exposed populations after first and second vaccine doses and show that significant heterogeneity in magnitude of antibody titers achieved is seen after both doses and that prior COVID-19 exposure increases the adaptive immune response to vaccination.
Dermatophytic Diseases: A Review of Tinea Pedis
Authors: Julien Gyamfi Agyemang , Adiyaga Wezena Cletus , Saaka Rahmat Alela-Emoma , Sunyazi Samuel Sunwiale , Batuiamu Abraham Titigah , Abugri Daniel , Abugri James
Published: July 2021

Studies in skin diseases, particularly Tinea pedis are very rare in Ghana leading to low investment in dermatological services in the country and the African continent. Globally, Tinea pedis affects about 15% of the world’s population. Importantly, it is a major public health problem and socioeconomic issue. Currently, the most recommended treatment for Tinea pedis infection are polyenes, azoles, allylamines, and fluorocytosines. Although these drugs are effective, they do have adverse side effects and are limited in the clinical settings in developing countries especially Ghana.

Method

Research papers were collected from Pubmed, Google scholar, chemical abstracts, and journal websites, reporting both in vitro and in vivo information on Tinea pedis. General information on Tinea pedis, the methods of infection, transfer, treatment options, and resistance were obtained after screening the articles. Many agents are involved in cases of Tinea pedis but are predominantly caused by Trichophyton rubrum which feeds on the keratinous layer of the topmost skin of the foot causing skin discoloration, itching, and maceration. The disease is influenced by individual lifestyle, environmental conditions, and individual factors such as age, sex, and host immunity and is prevented by the maintenance of good personal hygiene.

Tinea pedis like other tinea infections are treated with both topical and systemic agents. The classes of medications used in the treatment of Tinea pedis are polyenes, azoles, allylamines, and fluorocytosines. Tinea pedis antifungal resistance development could be partly associated with incomplete medication and misuse of antifungal medications. Additionally, patients with serious underlying health conditions such as compromised immune systems like HIV/AIDS, diabetes, radiotherapy for cancer, and transplantation could complicate resistance.

Conclusion

Although, fungal diseases do not cause epidemics the increasing rate of fungal infections and therefore Tinea pedis has to be checked and prevented. High budgets are made in the development of medications which mostly lose their effectiveness over time due to resistance development. Good personal hygiene is very effective but the available medications must be used appropriately for effective treatment and resistance avoidance. Infection prevention and control, tracking and data sharing, good and easily accessible antifungals, vaccines, and maintenance of personal and environmental hygiene are the topmost preventive measures against resistance development.
Infection spread simulation technology in a mixed state of multi variant viruses
Authors: Koizumi Makoto , Utamura Motoaki , Kirikami Seiichi
Published: July 2021

ATLM was extended to simulate the spread of infection in a mixed state of mutant virus and conventional virus. It is applied to the 4th wave of infection spread in Tokyo, and (1) the 4th wave bottoms out near the end of the state of emergency, and the number of infected people increases again. (2) The rate of increase will be mainly by L452R virus, while the increase by N501Y virus will be suppressed. (3) It is anticipated that the infection will spread during the Olympic Games. (4) When mutant virus competes, the infection of highly infectious virus rises sharply while the infection by weakly infectious ones has converged. (5) It is effective as an infection control measure to find an infected person early and shorten the period from infection to quarantine by PCR test or antigen test as a measure other than vaccine.
Convalescent plasma for hospitalized patients with COVID-19 and the effect of plasma antibodies: a randomized controlled, open-label trial
Authors:   The CONCOR-1 Study Group,   CONCOR-1 writing committee, Bégin Philippe , Callum Jeannie , Jamula Erin , Cook Richard , Heddle Nancy M. , Tinmouth Alan , Zeller Michelle P. , Beaudoin-Bussières Guillaume , Amorim Luiz , Bazin Renée , Loftsgard Kent Cadogan , Carl Richard , Chassé Michaël , Cushing Melissa M. , Daneman Nick , Devine Dana V. , Dumaresq Jeannot , Fergusson Dean A. , Gabe Caroline , Glesby Marshall J. , Li Na , Liu Yang , McGeer Allison , Robitaille Nancy , Sachais Bruce S. , Scales Damon C. , Schwartz Lisa , Shehata Nadine , Turgeon Alexis F. , Wood Heidi , Zarychanski Ryan , Finzi Andrés , Arnold Donald M. ,   for The CONCOR-1 Study Group
Published: July 2021

The efficacy of convalescent plasma for COVID-19 is unclear. While most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content may influence patient outcomes.

We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 days of respiratory symptom onset. Patients were allocated 2:1 to 500 mL of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 days. The effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression.

The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. 940 patients were randomized and 921 patients were included in the intent-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) in the convalescent plasma arm and 86/307 (28.0%) in the standard of care arm; relative risk (RR) 1.16 (95% confidence interval (CI) 0.94-1.43; p=0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% vs. 26.4%; RR=1.27, 95% CI 1.02-1.57, p=0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standard log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (OR=0.74; 0.57-0.95 and OR=0.66; 0.50-0.87, respectively), while IgG against the full transmembrane Spike protein increased it (OR=1.53, 95% CI 1.14-2.05).

Convalescent plasma did not reduce the risk of intubation or death at 30 days among hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavourable antibody profiles may be associated with worse clinical outcomes compared to standard care.

Trial registration

CONvalescent Plasma for Hospitalized Adults With COVID-19 Respiratory Illness (CONCOR-1); NCT04348656; https://www.clinicaltrials.gov/ct2/show/NCT04348656
The development and usability testing of digital knowledge translation tools for parents of children with acute otitis media
Authors: Le Anne , Hartling Lisa , Scott Shannon D.
Published: July 2021

Acute otitis media (AOM) is the most common bacterial ear infection affecting up to 80% of children before the age of three. Despite the common occurrence of the illness and the wide range of material available at clinics and online, parents are not always aware of these resources and they are often difficult to understand. We worked with parents to develop and assess the usability of a whiteboard animation video and interactive infographic for AOM in children. Parents rated the tools highly across all usability items, suggesting that creative tools developed using multi-method development processes can be useful, relevant, understandable, and will be used by the intended audience.

Following the completion of the English-language products, our team culturally adapted the tools for the Pakistan context and evaluated the usability of these adapted tools. During usability testing, parents indicated that they felt the tools were useful, demonstrating that culturally adapted version of knowledge translations tools are effective in ensuring that parents could understand complex health information.
Current therapeutic trends for tinnitus cure and control – a scoping review
Authors: Chhaya Vatsal A , Patel Divya G , Mehta Shamik P , Rajvir Jignesh P , Jhinjhuwadia Vinodkumar J , Sehgal Pranshuta , Khambholja Kapil M
Published: July 2021

Introduction

Chronic tinnitus treatment has been an enigma due to a lack of practice insights. To date, there has been limited evidence-based research on tinnitus therapies available. Our objective for this scoping was to assess the latest knowledge update in the field of tinnitus treatment and/or management and inform the clinical fraternity with evidence-based knowledge.

Materials and Methods

We retrieved randomized and non-randomized controlled trials, systematic reviews, meta-analyses, and observational studies from 2014 to 2021(starting from 1 Apr 2021) on chronic tinnitus patients within the context of evidence-based guidelines available on tinnitus therapies. We considered free, full-text, English language articles from PubMed, Cochrane, and Google using an AI-powered evidence synthesis tool named VOODY. We excluded studies on epidemiology, technical objectives assessing other than efficacy/safety outcomes, or review articles. Charted data from selected sources of evidence (related to study characteristics, intervention, sample size, efficacy and safety data, and quality of life-related outcomes as applicable) were presented in the form of graphs, tables, and other visual representations.

Results

We retrieved two evidence-based clinical practice guidelines (US and EU regions). Of total 3923 results, 119 underwent screening based on eligibility criteria and 52 were included for the final charting. Out of these 52 articles, three major treatment trends emerged: 1. Acoustic therapies 2. Stimulation Therapies and 3. Herbal, Complementary and Alternative Medicine and Nutrition Therapies. However, none of these were recommended to practice as per the latest EU guideline in 2019 due to no to limited strength of evidence. Other therapies included drugs, cognitive/habituation therapies, and digital interventions.

Conclusion

Although tinnitus guidelines did not recommend stimulation therapies, tinnitus research is seen focusing on stimulation. Therefore, it is highly recommended to consider existing clinical practice guidelines and orient tinnitus research focus on digital interventions and multidisciplinary therapies over the standalone therapies for better outcomes.
The drop in reported invasive pneumococcal disease among adults during the first COVID-19 wave in the Netherlands explained
Authors: Dirkx Kirsten , Mulder Bert , Post Annelies , Rutten Martijn , Swanink Caroline , Wertheim Heiman , Cremers Amelieke
Published: July 2021

Streptococcus pneumoniae is the main bacterial pathogen causing respiratory infections. Since the COVID-19 pandemic emerged, less pneumococcal disease was identified by surveillance systems around the world. Measures to prevent transmission of SARS-CoV-2 also reduce transmission of pneumococci, but this would gradually lead to lower disease rates. Here, we explore additional factors that have contributed to the instant drop in pneumococcal disease cases captured in surveillance. Our observations on referral practices and other impediments to diagnostic testing indicate that residual IPD has likely occurred but remained undetected by conventional hospital-based surveillance. Depending on setting, we discuss alternative monitoring strategies that could improve sight on pneumococcal disease dynamics.
SARS-CoV-2 vaccine breakthrough infections with the alpha variant are asymptomatic or mildly symptomatic among health care workers
Authors: Rovida Francesca , Cassaniti Irene , Paolucci Stefania , Percivalle Elena , Sarasini Antonella , Piralla Antonio , Giardina Federica , Sammartino Jose Camilla , Ferrari Alessandro , Bergami Federica , Muzzi Alba , Novelli Viola , Meloni Alessandro , Cutti Sara , Grugnetti Anna Maria , Grugnetti Giuseppina , Rona Claudia , Daglio Marinella , Marena Carlo , Triarico Antonio , Lilleri Daniele , Baldanti Fausto
Published: July 2021

Vaccine breakthrough SARS-CoV-2 infection has been monitored in 3720 healthcare workers receiving 2 doses of BNT162b2. SARS-CoV-2 infection is detected in 33 subjects, with a 100-day cumulative incidence of 0.93%. Vaccine protection against acquisition of SARS-CoV-2 infection is 83% (95%CI: 58-93%) in the overall population and 93% (95%CI: 69-99%) in SARS-CoV-2-experienced subjects, when compared with a non-vaccinated control group from the same Institution, in which SARS-CoV-2 infection occurs in 20/346 subjects (100-day cumulative incidence: 5.78%). The infection is symptomatic in 16 (48%) vaccinated subjects vs 17 (85%) controls (p=0.001). All analyzed patients, in whom the amount of viral RNA was sufficient for genome sequencing, results infected by the alpha variant. Antibody and T-cell responses are not reduced in subjects with breakthrough infection. Evidence of virus transmission, determined by contact tracing, is observed in two (6.1%) cases. This real-world data support the protective effect of BNT162b2 vaccine. A triple antigenic exposure, such as two-dose vaccine schedule in experienced subjects, may confer a higher protection.
Subgenomic and negative sense RNAs are not markers of active replication of SARS-CoV-2 in nasopharyngeal swabs
Authors: Chamings Anthony , Bhatta Tarka Raj , Alexandersen Soren
Published: July 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly in the global population since its emergence in humans in late 2019. Replication of SARS-CoV-2 is characterised by transcription and replication of genomic length RNA and shorter subgenomic RNAs to produce virus proteins and ultimately progeny virions. Here we explore the pattern of both genome-length and subgenomic RNAs and positive and negative strand SARS-CoV-2 RNAs in diagnostic nasopharyngeal swabs using sensitive probe based PCR assays as well as Ampliseq panels designed to target subgenomic RNAs. We successfully developed a multiplex PCR assay to simultaneously measure the relative amount of SARS-CoV-2 full length genomic RNA as well as subgenomic N gene and subgenomic ORF7a RNA. We found that subgenomic RNAs and both positive and negative strand RNA can be readily detected in swab samples taken up to 19 and 17 days post symptom onset respectively, and are strongly correlated with the amount of genomic length RNA present within a sample. Their detection and measurement is therefore unlikely to provide anymore insight into the stage of infection and potential infectivity of an individual beyond what can already be inferred from the total viral RNA load measured by routine diagnostic SARS-CoV-2 PCRs. Using both an original commercial and two custom SARS-CoV-2 Ampliseq mini-panels, we identified that both ORF7a and N gene subgenomic RNAs were consistently the most abundant subgenomic RNAs. We were also able to identify several non-canonical subgenomic RNAs, including one which could potentially be used to translate the ORF7b protein and others which could be used to translate ORF9b and the ORF N* which has arisen from a new transcription regulatory sequence recently created by mutations after SARS-CoV-2 jumped into people. SARS-CoV-2 genomic length and subgenomic length RNA’s were present in samples even if cellular RNA was degraded, further indicating that these molecules are likely protected from degradation by the membrane structures seen in SARS-CoV-2 infected cells.