bluuebunny/crossref_metadata_2025 huggingface dataset:
Mendelian randomization analysis identified potential genes pleiotropically associated with polycystic ovary syndrome
Authors: Sun Qian , Yuan Gao , Yang Jingyun , Lu Jiayi , Feng Wen , Yang Wen
Published: July 2021

Research question

Polycystic ovary syndrome (PCOS) is a common endocrine disorder with unclear etiology. Are there any genes that are pleiotropically or potentially causally associated with PCOS?

Design

We applied the summary data-based Mendelian randomization (SMR) method integrating genome-wide association study (GWAS) for PCOS and expression quantitative trait loci (eQTL) data to identify genes that were pleiotropically associated with PCOS. We performed separate SMR analysis using eQTL data in the ovary and whole blood.

Results

Although no genes showed significant pleiotropic association with PCOS after correction for multiple testing, some of the genes exhibited suggestive significance. RPS26 showed the strongest suggestive pleiotropic association with PCOS in both SMR analyses (β[SE]=0.10[0.03], PSMR=1.72×10−4 for ovary; β[SE]=0.11[0.03], PSMR=1.40×10−4 for whole blood). PM20D1 showed the second strongest suggestive pleiotropic association with PCOS in the SMR analysis using eQTL data for the whole blood, and was also among the top ten hit genes in the SMR analysis using eQTL data for the ovary. Two other genes, including CTC-457L16.2 and NEIL2, were among the top ten hit genes in both SMR analyses.

Conclusion

We identified multiple genes that were potentially involved in the pathogenesis of PCOS. Our findings provided helpful leads to a better understanding of the mechanisms underlying PCOS, and revealed potential therapeutic targets for the effective treatment of PCOS.

KEY MESSAGE

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, and its etiology can be multifaceted. We found that multiple genes were potentially involved in the pathogenesis of PCOS. The findings revealed the genetic mechanisms underlying PCOS and potential therapeutic targets for the effective treatment of PCOS.
Autonomic dysfunction after moderate-severe traumatic brain injury: symptom spectrum and clinical testing outcomes
Authors: Li Lucia M. , Vichayanrat Ekawat , Giovane Martina del , Lai Helen HL , Iodice Valeria
Published: July 2021

Background and Objective

Survivors of moderate-severe traumatic brain injury (msTBI) frequently experience chronic, debilitating somatic symptoms, which are largely unexplained. The phenomenon of paroxysmal sympathetic hyperactivity, reflecting hyperacute autonomic dysfunction, is well-documented after msTBI. Limited animal and human studies, using experimental measures, have found evidence for autonomic dysfunction after msTBI. However, no studies have investigated the range and type of autonomic symptoms and autonomic dysfunction existing in msTBI.

We set out to investigate the presence and type of subjective and objective autonomic dysfunction in msTBI.

Methods

We conducted two cohort studies. Cohort 1 comprises msTBI patients prospectively recruited from a national TBI outpatient clinic, in whom we assessed burden of autonomic symptoms using the Composite Autonomic Symptom Score (COMPASS31) autonomic symptom questionnaire. Cohort 2 comprises msTBI patients who had standard clinical autonomic function testing (supine/tilted catecholamine levels, head-up tilt, Valsalva manoeuvre, respiratory sinus arrhythmia assessment), retrospectively identified from the database of a regional clinical autonomic unit.

Results

Cohort 1 comprises 29 msTBI patients (6 females, median age 40 years, range 19-76), with a median time since injury of 19 months (range 4-105). There was multi-domain symptom burden, with all but 3 patients reporting symptoms on the COMPASS31 questionnaire, and 17/29 reporting symptoms in 3+ domains. The most commonly reported symptoms were gastrointestinal (22/29), followed by orthostatic (17/29), pupillomotor (14/29), secretomotor (14/29), bladder (12/29) and, least commonly, vasomotor (6/29). Cohort 2 comprises 18 msTBI patients (7 females, median age 44 years, range 21-64), with a median time between injury and testing of 57.5 months (range: 2-416). The majority of patients (15/18) had orthostatic symptoms as part of the reason for referral. Clinical autonomic function testing revealed a broad spectrum of autonomic dysfunction: 3/18 had evidence of sympathetic dysfunction, 10/18 had evidence of parasympathetic dysfunction, of which 6 also had evidence of mixed dysfunction.

Discussion

Our results provide evidence for clinically relevant autonomic dysfunction after moderate-severe TBI at the chronic stage. Our study advocates for routine enquiry about potential autonomic symptoms in this population, and the utility of formal clinical autonomic testing in providing diagnoses.
BNT162b2 mRNA Vaccine Effectiveness Given Confirmed Exposure; Analysis of Household Members of COVID-19 Patients
Authors: Gazit Sivan , Mizrahi Barak , Kalkstein Nir , Neuberger Ami , Peretz Asaf , Mizrahi-Reuveni Miri , Patalon Tal
Published: July 2021

Importance

While the mRNA BNT162b2 vaccine effectivness was demonstrated in general population, the question of effectiveness given confirmed exposure has yet been answered, though it has policy implications, as the need for self-quarantine when exposed and protective measures for vaccinated in high-risk areas.

Objective

Assessing the BNT162b2 vaccine effectiveness in preventing SARS-CoV-2 infection given high-risk exposure, through analysis of household members of confirmed cases.

Design

Retrospective cohort study. Data of household members of confirmed SARS-CoV-2 cases between 20/12/2020 and 17/03/2021 were collected.

Setting

Nationally centralized database of Maccabi Healthcare Services (MHS), the second largest Healthcare Maintenance Organization in Israel.

Participants

2.5 million MHS members were considered, of which we included only households with two adult members, given possible lower transmission and susceptibility among children. Households with no prior confirmed infections and a confirmed index case during the study period were included.

Exposure

Participants were classified into three vaccination groups in time of the index case (the confirmed exposure)-Unvaccinated; Fully Vaccinated(7 or more days post second dose) and a reference control group of Recently Vaccinated Once(0-7 days from the first dose, presumably still unprotected).

Main Outcomes and Measures

Assessing the probability of an additional SARS-CoV-2 infection in the household occurring within 10 days of an index case, calculated separately for the three vaccination groups. Main outcome was vaccine effectiveness given confirmed exposure. High testing rates among household members enabled us to estimate with a high degree of confidence effectiveness against asymptomatic SARS-CoV-2 infection as well.

Results

A total of 173,569 households were included, out of which 6,351 households had an index infection (mean [SD] age, 58.9 [13.5] years; 50% were women). Vaccine effectiveness of Fully Vaccinated compared to Unvaccinated participants was 80.0% [95% CI, 73.0-85.1] and 82.0% [95% CI, 75.5-86.7] compared to those Recently Vaccinated Once.

Conclusion and Relevance

The BNT162b2 vaccine is effective in a high-risk, real life, exposure scenario, but the protection rates afforded in these settings are lower than those previously described. Household members of COVID-19 patients and any individual with a confirmed exposure to COVID-19 are still at a considerable risk of being infected even if fully vaccinated.
The SARS-CoV-2 receptor-binding domain expressed in Pichia pastoris as a candidate vaccine antigen
Authors: Limonta-Fernández Miladys , Chinea-Santiago Glay , Martín-Dunn Alejandro Miguel , Gonzalez-Roche Diamile , Bequet-Romero Monica , Marquez-Perera Gabriel , González-Moya Isabel , Canaan-Haden-Ayala Camila , Cabrales-Rico Ania , Espinosa-Rodríguez Luis Ariel , Ramos-Gómez Yassel , Andujar-Martínez Ivan , González-López Luis Javier , de la Iglesia Mariela Perez , Zamora-Sanchez Jesus , Cruz-Sui Otto , Lemos-Pérez Gilda , Cabrera-Herrera Gleysin , Valdes-Hernández Jorge , Martinez-Diaz Eduardo , Pimentel-Vazquez Eulogio , Ayala-Avila Marta , Guillén-Nieto Gerardo
Published: July 2021

1.

The effort to develop vaccines based on economically accessible technological platforms available by developing countries vaccine manufacturers is essential to extend the immunization to the whole world population and to achieve the desired herd immunity, necessary to end the COVID-19 pandemic. Here we report on the development of a SARS-CoV-2 receptor-binding domain (RBD) protein, expressed in yeastPichia pastoris.The RBD was modified with addition of flexible N- and C-terminal amino acid extensions aimed to modulate the protein/protein interactions and facilitate protein purification. Fermentation with yeast extract culture medium yielded 30–40 mg/L. After purification by immobilized metal ion affinity chromatography and hydrophobic interaction chromatography, the RBD protein was characterized by mass-spectrometry, circular dichroism, and binding affinity to angiotensin-converting enzyme 2 (ACE2) receptor. The recombinant protein shows high antigenicity with convalescent human sera and also with sera from individuals vaccinated with the Pfizer-BioNTech mRNA or Sputnik V adenoviral-based vaccines. The RBD protein stimulates IFNγ, IL-2, IL-6, IL-4, and TNFα in mice secreting splenocytes from PBMC and lung CD3+ enriched cells. Immunogenicity studies with 50 µg of the recombinant RBD formulated with alum, induce high levels of binding antibodies in mice and non-human primates, assessed by ELISA plates covered with RBD protein expressed in HEK293T cells. The mouse sera inhibited the RBD binding to ACE2 receptor in anin-vitrotest and show neutralization of SARS-CoV-2 infection of Vero E6 cells. These data suggest that the RBD recombinant protein expressed in yeastP. pastorisis suitable as a vaccine candidate against COVID-19.

Highlights

The RBD protein (C-RBD-H6 PP) is expressed with high purity inP. pastoris.

Physico-chemical characterization confirms the right folding of the protein.

The recombinant protein shows high antigenicity with sera from convalescents.

The sera from animals inhibit the RBD-ACE2 binding and neutralize the virus.

The C-RBD-H6 protein stimulates IFNγ, IL-2, IL-6, IL-4, and TNFα in mice.
A Deep Learning Model for Screening Type 2 Diabetes from Retinal Photographs
Authors: Yun Jae-Seung , Kim Jaesik , Jung Sang-Hyuk , Cha Seon-Ah , Ko Seung-Hyun , Ahn Yu-Bae , Won Hong-Hee , Sohn Kyung-Ah , Kim Dokyoon
Published: July 2021

Objective

We aimed to develop and evaluate a non-invasive deep learning algorithm for screening type 2 diabetes in UK Biobank participants using retinal images.

Research Design and Methods

The deep learning model for prediction of type 2 diabetes was trained on retinal images from 50,077 UK Biobank participants and tested on 12,185 participants. We evaluated its performance in terms of predicting traditional risk factors (TRFs) and genetic risk for diabetes. Next, we compared the performance of three models in predicting type 2 diabetes using 1) an image-only deep learning algorithm, 2) TRFs, 3) the combination of the algorithm and TRFs. Assessing net reclassification improvement (NRI) allowed quantification of the improvement afforded by adding the algorithm to the TRF model.

Results

When predicting TRFs with the deep learning algorithm, the areas under the curve (AUCs) obtained with the validation set for age, sex, and HbA1c status were 0.931 (0.928-0.934), 0.933 (0.929-0.936), and 0.734 (0.715-0.752), respectively. When predicting type 2 diabetes, the AUC of the composite logistic model using non-invasive TRFs was 0.810 (0.790-0.830), and that for the deep learning model using only fundus images was 0.731 (0.707-0.756). Upon addition of TRFs to the deep learning algorithm, discriminative performance was improved to 0.844 (0.826-0.861). The addition of the algorithm to the TRFs model improved risk stratification with an overall NRI of 50.8%.

Conclusions

Our results demonstrate that this deep learning algorithm can be a useful tool for stratifying individuals at high risk of type 2 diabetes in the general population.
Multi-contrast magnetic resonance imaging of visual white matter pathways in glaucoma patients
Authors: Ogawa Shumpei , Takemura Hiromasa , Horiguchi Hiroshi , Miyazaki Atsushi , Matsumoto Kenji , Masuda Yoichiro , Yoshikawa Keiji , Nakano Tadashi
Published: July 2021

Purpose

Glaucoma is a disorder that involves visual field loss caused by retinal ganglion cell damage. Previous diffusion magnetic resonance imaging (dMRI) studies have demonstrated that retinal ganglion cell damage affects tissues in the optic tract (OT) and optic radiation (OR). However, because previous studies have used a simple diffusion tensor model to analyze dMRI data, the microstructural interpretation of white matter tissue changes remains uncertain. In this study, we used a multi-contrast MRI approach to further clarify the type of microstructural damage that occurs in glaucoma patients.

Methods

We collected multi-shell dMRI data from 17 glaucoma patients and 30 controls using 3T MRI. Using the dMRI data, we estimated three types of tissue property metrics: intracellular volume fraction (ICVF), orientation dispersion index (ODI), and isotropic volume fraction (IsoV). Quantitative T1 (qT1) data, which may be relatively specific to myelin, were collected from all subjects.

Results

In the OT, all four metrics showed significant differences between the glaucoma and control groups. In the OR, only the ICVF showed significant between-group differences. ICVF was significantly correlated with qT1 in the OR of glaucoma patients, although qT1 did not show any abnormality at the group level.

Conclusions

Our results suggest that at the group level, tissue changes in the glaucoma patients’ OR might be explained by axonal damage, which is reflected in the intracellular diffusion signals, rather than myelin damage. The significant correlation between ICVF and qT1 suggests that myelin damage might also occur in a smaller number of severe cases.
Neuropsychiatric disorders as risk factors and consequences of COVID-19: A Mendelian randomization study
Authors: Xiang Yong , Qiu Jinghong , Zhang Ruoyu , Chau Carlos Kwan-Long , Rao Shitao , So Hon-Cheong
Published: July 2021

Background

More than 180 million cases of COVID-19 have been reported worldwide. It has been proposed that neuropsychiatric disorders may be risk factors and/or consequences of COVID-19 infection. However, observational studies could be affected by confounding bias.

Methods

We performed bi-directional two-sample Mendelian randomization (MR) analysis to evaluate causal relationships between liability to COVID-19 (and severe/critical infection) and a wide range of neuropsychiatric disorders or traits. We employed GWAS summary statistics from the COVID-19 Host Genetics Initiative. A variety of MR methods including those accounting for horizontal pleiotropy were employed.

Results

Overall, we observed evidence that liability to COVID-19 or severe infection may be causally associated with higher risks of post-traumatic stress disorder (PTSD), bipolar disorder (BD) (especially BD II), schizophrenia (SCZ), attention deficit hyperactivity disorder (ADHD) and suicidal thought (ST) when compared to the general population. On the other hand, liability to a few psychiatric traits/disorders, for example ADHD, alcohol and opioid use disorders may be causally associated with higher risks of COVID-19 infection or severe disease. In genetic correlation analysis, cannabis use disorder, ADHD, and anxiety showed significant and positive genetic correlation with critical or hospitalized infection. All the above findings passed multiple testing correction at a false discovery rate (FDR)<0.05. For pneumonia, in general we observed a different pattern of causal associations. We observed bi-directional positive associations with depression- and anxiety-related phenotypes.

Conclusions

In summary, this study provides evidence for tentative bi-directional causal associations between liability to COVID-19 (and severe infection) and a number of neuropsychiatric disorders. Further replications and prospective studies are required to verify the findings.
Post-viral mental health sequelae in infected persons associated with COVID-19 and previous epidemics and pandemics: Systematic review and meta-analysis of prevalence estimates
Authors: Zürcher Simeon Joel , Banzer Céline , Adamus Christine , Lehmann Anja I. , Richter Dirk , Kerksieck Philipp
Published: July 2021

Aims

Post-viral mental health problems (MHP) in COVID-19 patients and survivors were anticipated already during early stages of this pandemic. We aimed to synthesize the prevalence of the anxiety, depression, post-traumatic and general distress domain associated with virus epidemics since 2002.

Methods

In this systematic review and meta-analysis, we searched PubMed, PsycINFO, and Embase from 2002 until April 14, 2021 for peer-reviewed studies reporting prevalence of MHP in adults with laboratory-confirmed or suspected SARS-CoV-1, H1N1, MERS-CoV, H7N9, Ebolavirus, or SARS-CoV-2 infection. We included studies that assessed post-viral MHP with validated and frequently used scales. A three-level random-effects meta-analysis for dependent sizes was conducted to account for multiple outcome reporting. We pooled MHP across all domains and separately by severity (above mild or moderate-to-severe) and by acute (one month), ongoing (one to three months), and post-illness stages (longer than three months). A meta-regression was conducted to test for moderating effects, particularly for exploring estimate differences between SARS-Cov-2 and previous pandemics and epidemics. PROSPERO registration: CRD42020194535.

Results

We identified 59 studies including between 14 to 1002 participants and providing 187 prevalence estimates. MHP, in general, decreased from acute to post-illness from 46□3% to 38□8% and for mild and moderate-to-severe from 22□3% to 18□8%, respectively. We found no evidence of moderating effects except for non-random sampling and H1N1 showing higher prevalence. Pooled MHP differed somewhat between previous pandemics/ epidemics and SARS-CoV-2 but were in a comparable range.

Conclusions

MHP prevalence estimates decreased over time but were still on a substantial level at post-illness. Post-viral mental health problems caused by SARS-CoV-2 could have been expected much earlier, given the previous post-viral sequelae.
The Impact of Non-Pharmaceutical Interventions on the First COVID-19 Epidemic Wave in South Africa
Authors: Mabuka Thabo , Ncube Nesisa , Ross Michael , Silaji Andrea , Macharia Willie , Ndemera Tinashe , Lemeke Tlaleng
Published: July 2021

On the 5thof March 2020, South Africa reported its first cases of COVID-19. This signalled the onset of the first COVID-19 epidemic wave in South Africa. The response by the Government of South Africa to the COVID-19 epidemic in South Africa was the use of non-pharmaceutical interventions (NPIs). In this study, a semi-reactive COVID-19 model, the ARI COVID-19 SEIR model, was used to investigate the impact of NPIs in South Africa to understand their effectiveness in the reduction of COVID-19 transmission in the South African population. This study also investigated the COVID-19 testing, reporting, hospitalised cases and excess deaths in the first COVID-19 epidemic wave in South Africa. The results from this study show that the COVID-19 NPI policies implemented by the Government of South Africa played a significant role in the reduction of COVID-19 active, hospitalised cases and deaths in South Africa’s first COVID-19 epidemic wave.
Trends and Variation in Data Quality on the EU Clinical Trials Register: A Cross-Sectional Study
Authors: DeVito Nicholas J , Goldacre Ben
Published: July 2021

The EU Clinical Trial Register (EUCTR) is a public facing portal containing information on trials of medicinal products conducted in the European Union (EU) and European Economic Area (EEA). Today, the registry holds information on over 30,000 trials. Given its distinct regulatory purpose, and results reporting requirements, the EUCTR should be a valuable open-source hub for trial information. Past work examining the EUCTR has suggested that data quality on the registry may be lacking. Using the full EUCTR public dataset, we examined areas in which national regulators are expected to ensure data quality including the posting of registrations, updating trial completion information, and monitoring results posting in line with EU guidelines. We identified issues across all areas examined with notable research hubs like France, Spain, and The Netherlands lacking consistent and complete data on the registry. These deficiencies complicate the utility of the EUCTR for research, transparency, and accountability efforts.
Longitudinal testing for SARS-CoV-2 RNA in day care centers in Hesse, Germany, during increased local incidence and with VOC Alpha as dominant variant: Results of the SAFE KiDS 2 and SAFE KiDS 3 study
Authors: Schenk Barbara , Hoehl Sebastian , Rudych Olga , Menger Dominic , Farmand Samira , Wrobel Franziska , Kreutzer Emilie , Gebert Daniela , Flohr Melanie , Berger Franziska , Weigel Vanessa , Kortenbusch Marhild , Berger Annemarie , Ciesek Sandra
Published: July 2021

In the summer of 2020, we investigated the rate of inapparent shedding of SARS-CoV-2 in a representative sample of day care centers from Hesse, Germany, and found a low positivity rate during a period of low local community spread.

To investigate the influence of a high local incidence setting, we conducted the SAFE KiDS 2 study. 577 children and 334 staff members of 47 day care centers were tested for respiratory and gastrointestinal shedding of SARS-CoV-2, and three infections with SARS-CoV-2 in the infectious period were detected. We conclude that viral shedding occurred infrequently while the original “wild-type” variant was dominant.

The more transmissible SARS-CoV-2 variant Alpha (B.1.1.7) became the dominant strain after SAFE KiDS 2 was concluded. The SAFE KiDS 3 study investigated the impact of the Alpha variant of SARS-CoV-2 on inapparent viral shedding in the day care setting. In this study, 756 children and 226 staff members from 46 day care centers provided self-collected saliva swabs, the so-called “Lollipop” swabs, which were tested by RT-PCR. In the four-week study period, none of the participants tested positive for SARS-CoV-2 RNA, demonstrating that inapparent shedding of SARS-CoV-2 in the day care setting was also rare during the dominance of the Alpha variant.

The influence of the variant of concern Delta on day care centers has yet to be studied.
Connection between two historical tuberculosis outbreak sites in Japan, Honshu, due to a new ancestral L2 sublineage
Authors: Guyeux Christophe , Senelle Gaetan , Refrégier Guislaine , Cambau Emmanuelle , Sola Christophe
Published: July 2021

By gathering an initial collection of 680 public Sequence Read Archives from the Mycobacterium tuberculosis complex (MTC) including 190 belonging to the lineage 2 Beijing, and using a new bioinformatical pipeline, TB-Annotator, that analyzes more than 50,000 characters, we characterized a phylogenetically significant L2 sublineage from isolates found in Tochigi province, that we designate as Asia Ancestral 5. These isolates harbor a number of specific criteria (42 specific SNPs) and their intra-cluster pairwise distance suggested historical and not epidemiological transmission. These isolates harbor a mutation in rpoC, and do not fulfill, either the Modern Beijing lineage criteria (L2.2.1.2.2) or the other currently known Ancestral Beijing lineages described so far. Asia Ancestral 5 isolates do not possess mutT2 58 and ogt 12 characteristics of Modern Beijing, but possess ancient evolutionary characteristics. By looking into the literature, we found in a reference isolate ID381, found in Kobe and Osaka, and defined as “G3”, 36 out of 42 shared and specific SNPs in the same sublineage. Using this study, we also confirmed the intermediate position of the Asia Ancestral 4 recently described in Thailand and suggest an improved classification of the L2 that now includes Asia Ancestral 4 and 5. Increasing the recruitment to around 3000 genomes (including 642 belonging to L2) confirmed our results and suggest new historical ancestral L2 phylogenetically relevant branches that remain to be investigated in detail. We discuss some anthropological and historical data from Japan history and its link to Korea and China. This study shows that the reconstruction of the early history of tuberculosis pandemia in Asia is likely to reveal complex patterns since its emergence.
Tuberculostearic acid, a potential parameter for scoring system construction for Tuberculous meningitis diagnosis
Authors: Fong Tsz Hei , Shi Wangpan , Li Siyi , Liu Guanghui , Ng Chung Lam , Jiang Haishan
Published: July 2021

This study aimed to validate the value of tuberculostearic acid (TBSA) whether it could implicate the existence of M. tuberculosis and assist for clinical diagnosis of Tuberculous Meningitis (TBM). Gas Chromatography/mass spectrometry was used to detect TBSA in the chemically pretreated cerebrospinal fluid of suspected TBM patients. In total, 140 patients were admitted for our study included 27 confirm TBM patients and 50 TBSA positive patients. Sensitivity of 0.7407 (CI 95%: 0.5372-0.8889) and specificity of 0.7345 (CI 95%: 0.6432-0.8132) were calculated. The Lancet consensus scoring system was also applied to evaluate the possibility of TBM in suspected patients, finding that TBSA positive patients showed a similar distributive grouping as the definite TBM patients. Our study implicates that the prospective use of TBSA is worth combining into a scoring system for characterizing the features of Mtb, showing a great potential of TBM diagnosis by TBSA in the future.
Prospective sero surveillance among healthcare workers vaccinated with ChAdOx1 nCoV-19 Corona vaccine in a tertiary hospital of Kerala, India
Authors: Njarekkattuvalappil Swathi Krishna , Bhaskaran Ramesh , V Sree Raj , Jose Ponnu , Rafi Aboobacker Mohammed , Thomas Joe , Innah Susheela J , Raphael Lucy , G Unnikrishnan U , Rajmohan Priyanka , Valsan Chithra , Kuttichira Praveenlal
Published: July 2021

Background

India started Covid-19 vaccination from January 16, 2021 after the approval of two candidate vaccines namely Covishield ™ and Covaxin ™. We report antibody responses among healthcare workers following two doses of Covishield ™ vaccination in a tertiary care setting.

Methods

This prospective serosurveillance study was done among healthcare workers of Jubilee Mission Medical College, vaccinated during January- March 2021. Blood samples were drawn from 170 participants after their 1st dose and from 156 participants after their 2nd dose of Covishield ™ to measure the specific Ig G antibodies against the recombinant S1 subunit of the S protein of SARS-CoV-2.

Results

The median level of anti SARS CoV-2 Ig G antibody 28 days after the first dose vaccination is 3.64 S/C (IQR=5.91) and 11.6 S/C (IQR= 5.97) after 14 days of second dose vaccination. Protective levels of anti SARS CoV-2 Ig G antibodies is developed by 25 participants (14.7%) after 28 days of first dose of vaccination and by 109 participants (69.9%) after 14 days of second dose. 18-44 years age group (p=0.027) and absence of comorbidities (p=0.079) are associated with protective IgG levels.

Conclusions

Rise in specific Ig G is observed after vaccination. Higher antibody response is observed with younger age group and absence of comorbidities, though statistically not significant. The influence of BMI is also not significant.
Gene and metabolite expression dependence on body mass index in human myocardium
Authors: Adebayo Adewale S , Roman Marius , Yusoff Syabira , Gulston Melanie , Joel-David Lathishia , Anthony Bony , Lai Florence Y , Murgia Antonio , Eagle-Hemming Bryony , Sheikh Sophia , Kumar Tracy , Aujla Hardeep , Dott Will , Griffin Julian L , Murphy Gavin J , Woźniak Marcin J
Published: July 2021

We hypothesized that body mass index (BMI) dependent changes in myocardial gene expression and energy-related metabolites underlie the biphasic association between BMI and mortality (the obesity paradox) in cardiac surgery. We performed transcriptome profiling and measured a panel of 144 metabolites in 53 and 55, respectively, myocardial biopsies from a cohort of sixty-seven adult patients undergoing coronary artery bypass grafting (registration: NCT02908009). The initial analysis identified 239 transcripts with biphasic BMI dependence. 120 displayed u-shape and 119 n-shape expression patterns. The identified local minima or maxima peaked at BMI 28-29. Based on these results and to best fit the WHO classification, we grouped the patients into three groups: BMI<25, 25≤BMI≤32, and BMI>32. The group analysis indicated that protein translation-related pathways were downregulated in 25≤BMI≥32 compared with BMI<25 patients. Muscle contraction transcripts were upregulated in 25≤BMI≥32 patients, and cholesterol synthesis and innate immunity transcripts were upregulated in the BMI>32 group. Transcripts involved in translation, muscle contraction and lipid metabolism also formed distinct correlation networks with biphasic dependence on BMI. Metabolite analysis identified acylcarnitines and ribose-5-phosphate increasing in the BMI>32 group and α-ketoglutarate increasing in the BMI<25 group. Molecular differences in the myocardium mirror the biphasic relationship between BMI and mortality.
Characterizing parametric differences between the two waves of COVID-19 in India
Authors: Omprakash Arpit
Published: July 2021

The first case of COVID-19 in India was reported on January 30, 2020 [1]. The number of infections rose steeply and preventative measures such as lockdowns were implemented to slow down the spread of the disease. Infections peaked around mid-September the same year and the cases gradually started declining. Following the relaxation of lockdown and the appearance of mutant strains of the virus, a much severe second wave of COVID-19 emerged starting mid-February. For characterization and comparison of both the waves, a SIQR (Susceptible-Infected-Quarantined-Removed) model is used in this paper. The results indicate that a single patient can infect approximately 2.44 individuals in the population. The epidemic doubling time was calculated to be 11.8 days. It is predicted that the actual number of infected patients is grossly underestimated (by a factor of 16) by current testing methods.
A new model of unreported COVID-19 cases outperforms three known epidemic-growth models in describing data from Cuba and Spain
Authors: Ramirez-Torres Erick E. , Selva Castañeda Antonio R. , Randez Luis , Valdés García Luis E. , Cabrales Luis E. Bergues , Sisson Scott A. , Montijano Juan I.
Published: July 2021

Estimating the unreported cases of Covid-19 in a region/country is a complicated problem. We propose a new mathematical model that, combined with a deterministic model of the total growth of cases, describes the time evolution of the unreported cases for each reported Covid-19 case. The new model considers the growth of unreported cases in plateau periods and the decrease towards the end of an epidemic wave. We combined the new model with a Gompertz-growth model, a generalized logistic model, and a susceptible-infectious-removed (SIR) model; and fitted them via Bayesian methods to data from Cuba and Spain. The combined-model fits yielded better Bayesian-Information-Criterion values than the Gompertz, logistic, and SIR models alone. This suggests the new model can achieve improved descriptions of the evolution of a Covid-19 epidemic wave. The new model is also able to provide reliable predictions of the epidemic evolution in a short period of time. We include in the paper the steps that researchers should take to use the new model for predictions with other data.
Implementation of Individualised Polygenic Risk Score Analysis: A Test Case of a Family of Four
Authors: Corpas Manuel , Megy Karyn , Metastasio Antonio , Lehmann Edmund
Published: July 2021

Polygenic risk scores (PRS) have been widely applied in research studies, showing how population groups can be stratified into risk categories for many common conditions. As healthcare systems consider applying PRS to keep their populations healthy, little work has been carried out demonstrating their implementation at an individual level. We performed a systematic curation of PRS sources from established data repositories, selecting 27 phenotypes, comprising almost 40 million SNPs related to cancer, cardiovascular, metabolic and autoimmune diseases. We tested selected phenotypes using whole genome sequencing data for a family of four family related individuals, with the 1000 Genomes Project (1000G) Phase III participants as background populations. Over 98 billion allele effects were calculated in order to obtain the PRS for each of the individuals analysed here. PRS calculation for the 1000G cohort of 2,504 participants allows us to develop a methodology for risk inference and general PRS deployment. Our approach for PRS implementation advances the discussion on the adoption of PRS in a preventative healthcare setting.
Longitudinal Risk Factors For Developing Depression in Parkinson’s Disease
Authors: Antar Tarek , Morris Huw R , Faghri Faraz , Leonard Hampton , Nalls Mike , Singleton Andrew , Iwaki Hirotaka
Published: July 2021

Background

Despite the established importance of identifying depression in Parkinson’s disease, our understanding of the factors which place the Parkinson’s disease patient at future risk of depression is limited.

Methods

Our sample consisted of 874 patients from two longitudinal cohorts, PPMI and PDBP, with median follow-up durations of 7 and 3 years respectively. Risk factors for depression at baseline were determined using logistic regression. A Cox regression model was then used to identify baseline factors that predisposed the non-depressed patient to develop depressive symptoms that were sustained for at least one year, while adjusting for antidepressant use and cognitive impairment. Common predictors between the two cohorts were identified with a random-effects meta-analysis.

Results

We found in our analyses that the majority of baseline non-depressed patients would develop sustained depressive symptoms at least once during the course of the study. Probable REM sleep disorder (pRBD), age, duration of diagnosis, impairment in daily activities, mild constipation, and antidepressant use were among the baseline risk factors for depression in either cohort. Our Cox regression model indicated that pRBD, impairment in daily activities, hyposmia, and mild constipation could serve as longitudinal predictors of sustained depressive symptoms.

Conclusions

We identified several potential risk factors to aid physicians in the early detection of depression in Parkinson’s disease patients. Our findings also underline the importance of adjusting for multiple covariates when analyzing risk factors for depression.
Characterization and Mitigation of Model Bias in Parametric Mapping of Dopamine Response to Behavioral Challenge
Authors: Levine Michael A. , Mandeville Joseph B. , Calabro Finnegan , Izquierdo-Garcia David , Price Julie C. , Luna Beatriz , Catana Ciprian
Published: July 2021

Abstract

Compartmental modeling of 11C-raclopride (RAC) is commonly used to measure dopamine response to intra-scan behavioral tasks. Bias in estimates of binding potential (BPND) and its dynamic changes (ΔBPND) can arise when the selected compartmental model deviates from the underlying biology. In this work, we characterize the bias associated with assuming a single target compartment and propose a model for reducing this bias by selectively discounting the contribution of the initial uptake period.

Methods

69 healthy young adult participants were scanned using RAC PET/MR while simultaneously performing a rewarded behavioral task. BPND and ΔBPND were estimated using an extension of the Multilinear Reference Tissue Model (MRTM2) with the task challenge encoded as a Heaviside step function. Bias was estimated using simulations designed to match the acquired data and was reduced by introducing a new model (DE-MRTM2) that reduces the biasing influence of the initial uptake period in the modeled estimation of BPND for both simulations and participant data.

Results

Bias in ΔBPND was observed to vary both spatially with BPND and with the assumed value of k4. At the most likely value of k4 (0.13 min-1), the average bias and the maximum voxel bias magnitude in the nucleus accumbens were estimated to be 1.2% and 3.9% respectively. Simulations estimated that debiasing the contribution of the first 27 minutes of acquired data reduced average bias and maximum voxel bias in the nucleus accumbens ΔBPND to -0.3% and 2.4% respectively. In the acquired participant data, DE-MRTM2 produced modest changes in the experimental estimates of striatal ΔBPND, while extrastriatal bias patterns were greatly reduced. DE-MRTM2 also considerably reduced the dependence of ΔBPND upon the first-pass selection of k2’.

Conclusion

Selectively discounting the contribution of the initial uptake period can help mitigate BPND- and k4-dependent bias in single compartment models of ΔBPND, while also reducing the dependence of ΔBPND on the first-pass estimation of k2’.
A national survey of attitudes towards and intentions to vaccinate against COVID-19: implications for communications
Authors: Stead Martine , Jessop Curtis , Angus Kathryn , Bedford Helen , Ussher Michael , Ford Allison , Eadie Douglas , MacGregor Andy , Hunt Kate , MacKintosh Anne Marie
Published: July 2021

Background

Hesitancy about COVID-19 vaccination threatens comprehensive vaccination. It is important to examine vaccination acceptance when people are making real rather than hypothetical decisions, to identify whether targeted support is needed, and to identify implications for communications.

Methods

Cross-sectional online and telephone survey with probability-based sample (n=4,978) of British adults, conducted January-February 2021. Measures: socio-demographic characteristics (age, gender, ethnicity, education, financial status), COVID-19 status, vaccine acceptance, trust in COVID-19 vaccination information sources, perceptions of vaccination priority groups, and perceptions of importance of second dose.

Findings

Among 5,931 individuals invited, survey response rate was 84%. COVID-19 vaccine acceptance (83%) was associated with increasing age, higher level of education and having been invited for vaccination. Acceptance decreased with unconfirmed past COVID-19, greater financial hardship, and non-White British ethnicity; Black/Black British participants had lowest acceptance. Overall, healthcare and scientific sources of information were most trusted. Compared with White British participants, other ethnicities had lower trust in healthcare and scientific sources. Those with lower educational attainment or financial hardship had lower trust in healthcare and scientific sources. Those with no qualifications had higher trust in media and family/friends. While trust was low overall in community or faith leaders it was higher among those with Asian/Asian British and Black/Black British ethnicity compared with White British participants. Views of vaccine prioritisation were mostly consistent with UK official policy but there was support for prioritising additional groups. There was high support for having the second vaccine dose.

Conclusions

Targeted engagement is needed to address COVID-19 vaccine hesitancy in non-White British ethnic groups, in younger adults, and among those with lower education, greater financial hardship and unconfirmed past infection. Healthcare professionals and scientific advisors should play a central role in communications and tailored messaging is needed for hesitant groups. Careful communication around vaccination prioritisation continues to be required.
Tracing and testing multiple generations of contacts to COVID-19 cases: cost-benefit tradeoffs
Authors: Kim Jungyeol , Chen Xingran , Nikpey Hesam , Rubin Harvey , Bidokhti Shirin Saeedi , Sarkar Saswati
Published: July 2021

Traditional contact tracing for COVID-19 tests the direct contacts of those who test positive even if the contacts do not show any symptom. But, by the time an infected individual is tested, the infection starting from the person may have infected a chain of individuals. Hence, why should the testing stop at direct contacts, and not test secondary, tertiary contacts or even contacts further down? One deterrent in testing long chains of individuals right away may be that it substantially increases the testing load, or does it? We investigate the costs and benefits of such multi-hop contact tracing for different number of hops. Considering a large number of contact topologies, spanning synthetic networks of divergent characteristics and those constructed from recorded interactions, we show that the cost-benefit tradeoff can be characterized in terms of a single measurable attribute, the initial epidemic growth rate. Once this growth rate crosses a threshold, multi-hop contact tracing substantially reduces the outbreak size compared to traditional contact tracing. Multi-hop even incurs a lower cost compared to the traditional contact tracing for a large range of values of the growth rate. The cost-benefit tradeoffs and the choice of the number of hops can be classified into three phases, with sharp transitions between them, depending on the value of the growth rate. The need for choosing a larger number of hops becomes greater as the growth rate increases or the environment becomes less conducive toward containing the disease.

Author summary

The COVID-19 pandemic has wrecked havoc on lives and livelihoods worldwide. Other epidemics may well emerge in future and one needs a preparedness to prevent their growth into another pandemic. During the early stages of a new epidemic, or even a mutated version of an earlier epidemic, pharmaceutical interventions may not be available but contact tracing and timely quarantine are among the few available control measures. We show that 1) traditional contact tracing may not successfully contain the outbreak depending on the rate of growth of the epidemic, but 2) the cost-benefit tradeoffs may be substantially enhanced through the deployment of a natural multi-hop generalization which tests contact chains starting from those who test positive.
Prominent Spatiotemporal Waves of COVID-19 Incidence in the United States: Implications for Causality, Forecasting, and Control
Authors: Jalal Hawre , Lee Kyueun , Burke Donald S.
Published: July 2021

Better understanding of the spatiotemporal structure of the COVID-19 epidemic in the USA may help inform more effective prevention and control strategies. By analyzing daily COVID-19 case data in the United States, Mexico and Canada, we found four continental-scale epidemic wave patterns, including travelling waves, that spanned multiple state and even international boundaries. These major epidemic patterns co-varied strongly with continental-scale seasonal temperature change patterns. Geo-contiguous states shared similar timing and amplitude of epidemic wave patterns irrespective of similarities or differences in state government political party affiliations. These analyses provide evidence that seasonal factors, probably weather changes, have exerted major effects on local COVID-19 incidence rates. Seasonal wave patterns observed during the first year of the epidemic may become repeated in the subsequent years.

One Sentence Summary

The COVID-19 epidemic in the United States has consisted of four continental-scale spatiotemporal waves of case incidence that have spanned multiple states and even international boundaries.
Uptake of SARS-CoV-2 workplace testing programs, March 2020 to March 2021
Authors: Duarte Nathan , D’Mello Sean , Duarte Natalie A , Rocco Simona , Van Wyk Jordan , Pillai Abhinav Arun , Liu Michael , Williamson Tyler , Arora Rahul K
Published: July 2021

Structured Abstract

Objective

To track uptake of workplace SARS-CoV-2 testing programs using publicly-available data (e.g., press releases), supplementing findings from employer surveys.

Methods

We tracked testing programs reported by 1,159 Canadian and 1,081 international employers across sectors from March 1, 2020 to March 31, 2021. We analyzed trends in uptake of testing programs, including over time and by workplace setting.

Results

9.5% (n=110) of Canadian employers and 24.6% (n=266) of international employers tracked reported testing. The prevalence of reported testing programs was less than 20% in some settings associated with high risk of transmission including retail and customer-facing environments, and indoor and mixed blue collar workplaces.

Conclusions

Publicly-available data suggest that fewer employers are testing than indicated by surveys. Workplace safety in high-risk workplaces could be further improved by implementing testing strategies that deploy both screening and diagnostic tests.
Temozolomide sensitivity of malignant glioma cell lines – a systematic review assessing consistencies between in vitro studies
Authors: Poon Michael TC , Bruce Morgan , Simpson Joanne E , Hannan Cathal J , Brennan Paul M
Published: July 2021

Malignant glioma cell line models are integral to pre-clinical testing of novel potential therapies. Accurate prediction of likely efficacy in the clinic requires that these models are reliable and consistent. We assessed this by examining the reporting of experimental conditions and sensitivity to temozolomide in glioma cells lines.

We searched Medline and Embase (Jan 1994-Jan 2021) for studies that evaluated the effect of temozolomide monotherapy on cell viability of at least one malignant glioma cell line. Studies using a drug-resistant cell line or a modified preparation of temozolomide were excluded. Key data items included type of cell lines, temozolomide exposure duration, and cell viability measure (IC50).

We included 212 eligible studies from 2,789 non-duplicate records that reported 248 distinct cell lines. The commonest cell line was U87 (60.4%). Only 10.4% studies used a patient-derived cell line. The proportion of studies not reporting each experimental condition ranged from 8.0-27.4%, including base medium (8.0%), serum supplementation (9.9%) and number of replicates (27.4%). In studies reporting IC50 the median value for U87 cell line at 24 hours, 48 hours and 72 hours was 123.9μM (IQR 75.3-277.7μM), 223.1μM (IQR 92.0-590.1μM) and 230.0μM (IQR 34.1-650.0μM), respectively (Figure 2A). The median IC50 at 72 hours for patient-derived cell lines was 220μM (IQR 81.1-800.0μM).

Temozolomide sensitivity reported in comparable studies was not consistent between and within individual malignant glioma cell lines. Drug discovery science performed on these models cannot reliably inform clinical translation. A consensus model of reporting can maximise reproducibility and consistency among in vitro studies.

Key points

There is a wide variety of study designs for malignant glioma cell line studies.

Reporting of experimental designs of cell line studies was suboptimal.

Temozolomide sensitivity was inconsistent between and within individual cell lines.

Importance of the study

There is a wide variety of experimental designs for malignant glioma cell line studies but the reporting of these is suboptimal.

Temozolomide sensitivity reported in comparable studies was not consistent between and within individual malignant glioma cell lines.

While there will be variations of opinion on what the optimal design is, a consensus model of a reporting structure is the only rational way to maximise the yield from in vitro studies to find novel therapies for our patients.