bluuebunny/crossref_metadata_2025 huggingface dataset:
Expected Rates of Select Adverse Events following Immunization for COVID-19 Vaccine Safety Monitoring
Authors: Abara Winston E. , Gee Julianne , Mu Yi , Deloray Mark , Ye Tun , Shay David K. , Shimabukuro Tom
Published: September 2021

Background

Knowledge of expected rates of potential adverse events of special interest (AESI) that may occur coincidentally following COVID-19 vaccination is essential for vaccine safety surveillance and assessment. We calculated the expected rates of 21 potential AESI following COVID-19 vaccination among vaccinated persons within 1 day, 7 days, and 42 days of vaccination.

Methods

We used meta-analytic methods to estimate background rates of 21 medical conditions considered potential AESI and calculated expected rates of each potential AESI within 1 day, 7 days, and 42 days of vaccination.

Results

Background rates of three commonly monitored AESI, Guillain-Barre syndrome (GBS), myopericarditis, and all-cause deaths were 2.0 GBS cases/100,000 person-years, 1.3 myopericarditis cases/100,000 person-years, and 863.8 all-cause deaths/100,000 person-years, respectively. Based on these background rates, if 10,000,000 persons are vaccinated, we would expect 0.5, 3.7, and 22.5 GBS cases; 0.3, 2.4, and 14.3 myopericarditis cases; and 236.5, 1655.5, and 9932.8 all-cause deaths to occur in coincident temporal association (i.e., as a result of background incidence) within 1 day, 7 days, and 42 days of vaccination, respectively.

Conclusion

Knowledge of expected rates of potential AESI can help contextualize adverse health events associated temporally with immunization, aid in safety signal detection, guide COVID-19 vaccine public health communication, and inform benefit-risk assessments of COVID-19 vaccines.
Effects of Dipeptidyl Peptidase-4 Inhibitors and Sulfonylureas on Cognitive and Physical Function in Nursing Home Residents
Authors: Zullo Andrew R. , Duprey Matthew S. , Smith Robert J. , Gutman Roee , Berry Sarah D. , Munshi Medha N. , Dore David D.
Published: September 2021

Aims

Dipeptidyl peptidase-4 inhibitors (DPP4Is) may mitigate hypoglycemia-mediated declines in cognitive and physical functioning compared to sulfonylureas (SUs), yet comparative studies are unavailable among older adults, especially nursing home (NH) residents. We evaluated the effects of DPP4Is versus SUs on cognitive and physical functioning among NH residents.

Materials and Methods

This new-user cohort study included long-stay NH residents aged ≥65 years from the 2007-2010 national US Minimum Data Set (MDS) clinical assessments and linked Medicare claims. We measured cognitive decline from the validated 6-point MDS Cognitive Performance Scale, functional decline from the validated 28-point MDS Activities of Daily Living scale, and hospitalizations or emergency department visits for altered mental status from Medicare claims. We compared 180-day outcomes in residents who initiated a DPP4I versus SU after propensity score matching using Cox regression models.

Results

The cohort (N=1,784) had a mean (SD) age of 80 (8) years and was 73% female. Approximately 46% had no or mild cognitive impairment and 35% had no or mild functional impairment before treatment initiation. Compared to SU users, DPP4I users had statistically similar 180-day rates of cognitive decline (HR=0.61, 95%CI 0.31-1.19), altered mental status events (HR=0.71, 95%CI 0.39-1.27), and functional decline (HR=0.89, 95%CI 0.51-1.56).

Conclusions

Rates of cognitive and functional decline were not markedly reduced among DPP4I users compared to SU users, but the point estimates and lower 95% confidence bounds do not rule out the possibility that DPP4Is result in reduced rates. Larger studies with greater statistical power should resolve this remaining uncertainty.
Classification of Functional Movement Disorders with Resting State fMRI
Authors: Waugh Rebecca E. , Parker Jacob A. , Hallett Mark , Horovitz Silvina G.
Published: September 2021

Functional movement disorder (FMD) is a type of functional neurological disorder characterized by abnormal movements that patients do not recognize as self-generated. Prior imaging studies show a complex pattern of altered activity, linking regions of the brain involved in emotional responses, motor control, and agency. This study aimed to better characterize these relationships by building a classifier via support vector machine (SVM) to accurately classify 61 FMD patients from 59 healthy controls using features derived from resting state functional MRI (rs-fMRI). First, we selected 66 seed regions based on prior related studies, then calculated the full correlation matrix between them, before performing recursive feature elimination to winnow the feature set to the most predictive features and building the classifier. We identified 29 features of interest that were highly predictive of FMD condition, classifying patients from controls with 80% accuracy. The features selected by the model highlight the importance of the interconnected relationship between areas associated with emotion, reward and sensorimotor integration, potentially mediating relationships between regions associated with motor function, attention and executive function. Exploratory machine learning was able to identify this distinctive, abnormal pattern, suggesting that alterations in functional linkages between these regions may be a consistent feature of the condition in many FMD patients.
Taking a participatory research approach within workplace health promotion research to improve physical activity levels in office-based workers: a scoping review protocol
Authors: Buffey Aidan , Carson Brian P , Donnelly Alan , Salsberg Jon
Published: September 2021

Introduction

Physical activity (PA) workplace health promotion (WHP) interventions have traditionally utilised a top-down research approach at an individual level where participants are considered as passive subjects. Whereas participatory research involves the participants and relevant stakeholders within the research process utilising a bottom-up approach which focuses on the health priorities of the participants and allows the integration of the researcher’s expertise and the end-users lived experiences, which has been shown to aid in the acceptability and relevance of the research.

This protocol describes a scoping review which will explore, identify and map participatory research techniques and their impact when utilised in office based WHP interventions designed to improve PA levels and/or decrease sitting time. Providing an overview of key characteristics of WHP interventions which took a participatory research approach.

Methods and analysis

This scoping review will follow the guidelines and framework from the PRISMA-ScR. Articles will be retrieved via five databases: Web of Science, PubMED, Scopus, Google Scholar and OpenGrey. A search strategy was piloted, and relevant review articles search strategies were explored, to identify appropriate key words and MeSH terms. Two independent reviewers will screen retrieved articles based on our inclusion and exclusion criteria by title and abstract first, followed by the full text. Any discrepancies will be discussed until a consensus is reached. Data will be extracted, charted and summarised via a narrative synthesis and qualitative analyses.

Ethics and dissemination

Ethical approval was not required or obtained for this scoping review. The completed scoping review findings will be disseminated in a peer-reviewed journal which has a research scope that encompasses participatory research and health promotion. The findings will be presented at appropriate academic conferences and to project partners to inform the design of a WHP intervention.

Strengths and limitations of this study

The proposed scoping review will explore and map the current participatory research techniques and approaches taken when completing an office-based workplace health promotion intervention designed to increase physical activity.

The scoping review by nature and the search strategy proposed will allow for a wide breadth of literature to be explored.

There is no critical appraisal or quality assessment of the included studies which is typical of a systematic review but not of a scoping review or the aim of this review article.

This scoping review has a narrow focus on physical activity and may limit/exclude articles aiming to improve psychological wellbeing or work performance.
Long-term Stored Platelets Coupled to Thrombospondin-1 Detection for Rapid and Accurate Identification of Pathogenic HIT Antibodies
Authors: Kanack A , Jones C , Singh B , Leger R , Heikal NM , Chen D , Pruthi RK , Padmanabhan A
Published: September 2021

Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening disorder characterized by antibodies to Platelet Factor 4 (PF4)-polyanion complexes which cause thrombocytopenia and thrombosis. Currently used technically-simple frontline assays such as the PF4-polyanion enzyme-linked immunosorbent assays (ELISAs) lack specificity, and more accurate functional assays such as the serotonin release assay (SRA) and PF4-dependent P-selectin expression assay (PEA) have long turnaround times due to technical complexity and availability only in the reference laboratory setting. There is a critical need for accurate near-patient functional testing to guide patient management, but a key barrier to attaining this goal is the short-term viability of platelets. Here, we detail a process of platelet cryopreservation that renders them viable for at least one year and show that PF4-treated cryopreserved platelets, when coupled with ELISA-based measurement of thrombospondin-1 release (a platelet α-granule protein), detects pathogenic HIT antibodies with high accuracy. Furthermore, testing of a cohort of non-pathogenic HIT antibodies that were strongly reactive in PF4/polyanion ELISA but negative in functional assays demonstrated negative results in the thrombospondin-1 release assay, confirming high specificity of this technique. These findings have the potential to transform the diagnostic testing paradigm in HIT by making in-hospital functional testing available for rapid and accurate diagnosis.
A Cross-sectional Study on Perceived Workplace Health Support and Health-Related Quality of Life
Authors: Kurogi Kazushirou , Ikegami Kazunori , Eguchi Hisashi , Tsuji Mayumi , Tateishi Seiichiro , Nagata Tomohisa , Matsuda Shinya , Fujino Yoshihisa , Ogami Akira ,   the CORoNaWork Project
Published: September 2021

Objective

Many companies in Japan have been increasingly interested in “health and productivity management (H&PM).” In terms of H&PM, we supposed that companies can enhance their employees’ perceived workplace health support (PWHS) by providing support for workers’ lively working and healthy living. This could then improve health-related QOL (HRQOL) by increasing PWHS. This study explored the relationship between PWHS and health-related quality of life (HRQOL).

Methods

During the COVID-19 pandemic in December 2020, we conducted an Internet-based nationwide health survey of Japanese workers (CORoNaWork study). A database of 27,036 participants was created. The question regarding the intensity of PWHS was measured using a four-point Likert scale. We used a linear mixed model (LMM) to analyze the relationship between the intensity of PWHS and the four domains of CDC HRQOL-4 (self-rated health, number of poor physical health days, number of poor mental-health days, and activity limitation days during the past 30 days).

Results

In the sex- and age-adjusted and multivariate models, the intensity of PWHS had a main effect on self-rated health and the three domains of unhealthy days (physical, mental, activity limitation). There was also a trend toward worse HRQOL scores as the PWHS decreased.

Conclusions

This study aimed to document the relationship between PWHS and HRQOL. We found that the higher the PWHS of Japanese workers, the higher their self-rated health and the lower their unhealthy days. Companies need to assess workers’ PWHS and HRQOL and promote H&PM. H&PM is also necessary to maintain and promote the health of workers during the COVID-19 pandemic.
A Delay Differential Equation approach to model the COVID-19 pandemic
Authors: Kiselev I.N. , Akberdin I.R. , Kolpakov F.A.
Published: September 2021

SEIR (Susceptible - Exposed - Infected - Recovered) approach is a classic modeling method that has frequently been applied to the study of infectious disease epidemiology. However, in the vast majority of SEIR models and models derived from them transitions from one population group to another are described using the mass-action law which assumes population homogeneity. That causes some methodological limitations or even drawbacks, particularly inability to reproduce observable dynamics of key characteristics of infection such as, for example, the incubation period and progression of the disease’s symptoms which require considering different time scales as well as probabilities of different disease trajectories. In this paper, we propose an alternative approach to simulate the epidemic dynamics that is based on a system of differential equations with time delays to precisely reproduce a duration of infectious processes (e.g. incubation period of the virus) and competing processes like transition from infected state to the hospitalization or recovery. The suggested modeling approach is fundamental and can be applied to the study of many infectious disease epidemiology. However, due to the urgency of the COVID-19 pandemic we have developed and calibrated the delay-based model of the epidemic in Germany and France using the BioUML platform. Additionally, the stringency index was used as a generalized characteristic of the non-pharmaceutical government interventions implemented in corresponding countries to contain the virus spread. The numerical analysis of the calibrated model demonstrates that adequate simulation of each new wave of the SARS-CoV-2 virus spread requires dynamic changes in the parameter values during the epidemic like reduction of the population adherence to non-pharmaceutical interventions or enhancement of the infectivity parameter caused by an emergence of novel virus strains with higher contagiousness than original one. Both models may be accessed and simulated at https://gitlab.sirius-web.org/covid-19/dde-epidemiology-model utilizing visual representation as well as Jupyter Notebook.
Different B cell subpopulations show distinct patterns in their IgH repertoire metrics
Authors: Ghraichy Marie , von Niederhäusern Valentin , Kovaltsuk Aleksandr , Galson Jacob D. , Deane Charlotte M. , Trück Johannes
Published: September 2021

Background

Several human B-cell subpopulations are recognized in the peripheral blood, which play distinct roles in the humoral immune response. These cells undergo developmental and maturational changes involving VDJ recombination, somatic hypermutation and class switch recombination, altogether shaping their immunoglobulin heavy chain (IgH) repertoire.

Methods

Here, we sequenced the IgH repertoire of naïve, marginal zone, switched and plasma cells from 10 healthy adults along with matched unsorted and in silico separated CD19+ bulk B cells. We used advanced bioinformatic analysis and machine learning to thoroughly examine and compare these repertoires.

Results

We show that sorted B cell subpopulations are characterised by distinct repertoire characteristics on both the individual sequence and the repertoire level. Sorted subpopulations shared similar repertoire characteristics with their corresponding in silico separated subsets. Furthermore, certain IgH repertoire characteristics correlated with the position of the constant region on the IgH locus.

Conclusion

Overall, this study provides unprecedented insight over mechanisms of B cell repertoire control in peripherally circulating B cell subpopulations.
A third dose of inactivated vaccine augments the potency, breadth, and duration of anamnestic responses against SARS-CoV-2
Authors: Wang Kang , Cao Yunlong , Zhou Yunjiao , Wu Jiajing , Jia Zijing , Hu Yaling , Yisimayi Ayijiang , Fu Wangjun , Wang Lei , Liu Pan , Fan Kaiyue , Chen Ruihong , Wang Lin , Li Jing , Wang Yao , Ge Xiaoqin , Zhang Qianqian , Wu Jianbo , Wang Nan , Wu Wei , Gao Yidan , Miao Jingyun , Jiang Yinan , Qin Lili , Zhu Ling , Huang Weijin , Zhang Yanjun , Zhang Huan , Li Baisheng , Gao Qiang , Xie Xiaoliang Sunney , Wang Youchun , Wang Qiao , Wang Xiangxi
Published: September 2021

Emergence of variants of concern (VOC) with altered antigenic structures and waning humoral immunity to SARS-CoV-2 are harbingers of a long pandemic. Administration of a third dose of an inactivated virus vaccine can boost the immune response. Here, we have dissected the immunogenic profiles of antibodies from 3-dose vaccinees, 2-dose vaccinees and convalescents. Better neutralization breadth to VOCs, expeditious recall and long-lasting humoral response bolster 3-dose vaccinees in warding off COVID-19. Analysis of 171 complex structures of SARS-CoV-2 neutralizing antibodies identified structure-activity correlates, revealing ultrapotent, VOCs-resistant and broad-spectrum antigenic patches. Construction of immunogenic and mutational heat maps revealed a direct relationship between “hot” immunogenic sites and areas with high mutation frequencies. Ongoing antibody somatic mutation, memory B cell clonal turnover and antibody composition changes in B cell repertoire driven by prolonged and repeated antigen stimulation confer development of monoclonal antibodies with enhanced neutralizing potency and breadth. Our findings rationalize the use of 3-dose immunization regimens for inactivated vaccines.

One sentence summary

A third booster dose of inactivated vaccine produces a highly sifted humoral immune response via a sustained evolution of antibodies capable of effectively neutralizing SARS-CoV-2 variants of concern.
Evaluation of Primary Prescription Nonadherence Post-discharge from an Inpatient Psychiatry Unit at a Large Urban Community Hospital – an Observational Study
Authors: Ganjam Meghana , Ruiz Ysatis , Allen Luis G. , Persaud Rosemary
Published: September 2021

Introduction

Here, we aimed to evaluate primary prescription nonadherence post-discharge from an acute inpatient psychiatric unit. Prescription nonadherence is a concern across all patient care settings, with primary nonadherence defined as not picking up prescribed medication from the pharmacy or not delivering prescriptions to the pharmacy. Secondary nonadherence, defined as filling a prescription but not taking the medication as prescribed, was not tracked in this study. The incidence of nonadherence can vary widely across settings and has been reported to range from 3– 86%. This is a particular concern in patients with a primary psychiatric diagnosis both in an outpatient and inpatient setting.

Design

The prescription fill rate of eligible patients was tracked on days 7 and 21 post-discharge from acute inpatient psychiatric units of an acute care multispecialty urban community teaching hospital.

Results

In total, 72 patients aged 18 and above (44%, women) were analyzed. A primary nonadherence incidence of 43% was found, which did not vary significantly across the analyzed variables of age, sex, or primary diagnosis.

Conclusion

Primary nonadherence is a significant issue in this population. Strategies, such as the implementation of “med-to-bed” programs and use of longer acting injectables when appropriate, would help in increasing adherence. Further research, including the evaluation of other variables that affect nonadherence, is needed to identify and develop steps to overcome the obstacles to adherence.
Large-scale proteome and metabolome analysis of CSF implicates altered glucose metabolism and succinylcarnitine in Alzheimer’s disease
Authors: Panyard Daniel J. , McKetney Justin , Deming Yuetiva K. , Morrow Autumn R. , Ennis Gilda E. , Jonaitis Erin M. , Van Hulle Carol A. , Yang Chengran , Sung Yun Ju , Ali Muhammad , Kollmorgen Gwendlyn , Suridjan Ivonne , Bayfield Anna , Bendlin Barbara B. , Zetterberg Henrik , Blennow Kaj , Cruchaga Carlos , Carlsson Cynthia M. , Johnson Sterling C. , Asthana Sanjay , Coon Joshua J. , Engelman Corinne D.
Published: September 2021

A major hallmark of Alzheimer’s disease (AD) is the aggregation of proteins (β-amyloid (A) and hyperphosphorylated tau (T)) in the brain, which makes the AD proteome in cerebrospinal fluid (CSF) of particular interest. Here, we conducted a CSF proteome-wide analysis among participants with and without AD pathology (n = 137 total participants: 56 A-T-, 39 A+T-, and 42 A+T+; 915 proteins analyzed), using a panel of 9 CSF biomarkers for neurodegeneration and neuroinflammation. We identified 61 proteins significantly associated with AT category (P < 5.46 x 10-5; strongest was SMOC1, P = 1.87 x 10-12) and 636 significant protein-biomarker associations (P < 6.07 x 10-6; strongest was a positive association between neurogranin and EPHA4, P = 2.42 x 10-25). Community network and pathway enrichment analyses highlighted three biomarker-associated protein networks centered around amyloid and tau measures, neurogranin, and the remaining biomarkers. Glucose metabolic pathways were enriched primarily among the amyloid- and tau-associated proteins, including malate dehydrogenase and aldolase A, both of which were associated with CSF phosphorylated tau levels in an independent replication cohort of 717 participants (P = 8.65 x 10-56and P = 1.35 x 10-45). Follow-up interrogation of related CSF metabolite levels in the same samples as the discovery proteomics analysis identified increasing levels of succinylcarnitine with ptau and numerous other CSF biomarkers (P < 0.00056) that were replicated in an independent sample of 363 participants. Together, these results implicate glucose metabolic dysregulation and increased CSF succinylcarnitine levels as amyloid and tau pathology emerge in AD.

One Sentence Summary:Combining cerebrospinal fluid proteomics data with neurodegeneration and neuroinflammation biomarkers, genomics, and cerebrospinal fluid metabolomics, we identify and replicate a theme of altered glucose metabolism proteins and the metabolite succinylcarnitine across amyloid and tau progression in Alzheimer’s disease.
Immunogenicity and Safety of the inactivated SARS-CoV-2 vaccine (BBIBP-CorV) in patients with malignancy
Authors: Ariamanesh Mona , Porouhan Pejman , PeyroShabany Babak , Fazilat-Panah Danial , Dehghani Mansoureh , Nabavifard Maryam , Hatami Farbod , Fereidouni Mohammad , Welsh James S. , Javadinia Seyed Alireza
Published: September 2021

Objective

Patients with malignancy suffer from a compromised immune system due to either the effects of malignancies or treatments. Cancer patients are at higher risk of different infections particularly SARS-CoV2 and usually produce weaker response to vaccines. The aim of this study was to evaluate the safety and immunogenicity of the inactivated SARS-CoV-2 vaccine (Sinopharm, BBIBP-CorV) in patients with malignancy.

Material and Method

In total 364 patients with cancer (median age: 54 years old, F/M ratio: 217/147) who received two doses of Sinopharm vaccine were enrolled in this study. Vaccine related side effects was assessed by a questionnaire and the presence of SARS-CoV-2 anti-Spike protein (S) IgG and neutralizing antibody two months following vaccination were measured by immunological methods.

Results

Injection site pain and fever were the most common local and systemic side effects in vaccine receivers. Two months after the first dose, anti-S IgG and neutralizing antibody were detectable in 77.1% and 80.7% of all participants, respectively with an overall response to either or both measured in 86.9% of patients The rate of seroconversion was lower in older age, those with hematological malignancies and chemotherapy receivers.

Conclusion

The result of study confirmed the safety and short-term efficacy of Sinopharm inactivated vaccine (BBIBP-CorV) in patients with different type of malignancies.
MITIGATING THE 4th WAVE OF THE COVID-19 PANDEMIC IN ONTARIO
Authors: Cipriano Lauren E. , Haddara Wael M. R. , Sander Beate
Published: September 2021

Background

The goal of this study was to project the number of COVID-19 cases and demand for acute hospital resources for Fall of 2021 in a representative mid-sized community in southwestern Ontario. We sought to evaluate whether current levels of vaccine coverage and contact reduction could mitigate a potential 4th wave fueled by the Delta variant, or whether the reinstitution of more intense public health measures will be required.

Methods

We developed an age-stratified dynamic transmission model of COVID-19 in a mid-sized city (population 500,000) currently experiencing a relatively low, but increasing, infection rate in Step 3 of Ontario’s Wave 3 recovery. We parameterized the model using the medical literature, grey literature, and government reports. We estimated the current level of contact reduction by model calibration to cases and hospitalizations. We projected the number of infections, number of hospitalizations, and the time to re-instate high intensity public health measures over the fall of 2021 under different levels of vaccine coverage and contact reduction.

Results

Maintaining contact reductions at the current level, estimated to be a 17% reduction compared to pre-pandemic contact levels, results in COVID-related admissions exceeding 20% of pre-pandemic critical care capacity by late October, leading to cancellation of elective surgeries and other non-COVID health services. At high levels of vaccination and relatively high levels of mask wearing, a moderate additional effort to reduce contacts (30% reduction compared to pre-pandemic contact levels), is necessary to avoid re-instating intensive public health measures. Compared to prior waves, the age distribution of both cases and hospitalizations shifts younger and the estimated number of pediatric critical care hospitalizations may substantially exceed 20% of capacity.

Discussion

High rates of vaccination coverage in people over the age of 12 and mask wearing in public settings will not be sufficient to prevent an overwhelming resurgence of COVID-19 in the Fall of 2021. Our analysis indicates that immediate moderate public health measures can prevent the necessity for more intense and disruptive measures later.
Common and Disorders-Specific Cortical Thickness Alterations in Internalizing, Externalizing and Thought Disorders over a 2-year Period in the Preadolescents of the ABCD Study
Authors: Yu Gechang , Wu Xinran , Liu Zhaowen , Becker Benjamin , Zhang Kai , Kuang Nanyu , Kang Jujiao , Dong Guiying , Zhao Xing-Ming , Schumann Gunter , Feng Jianfeng , Sahakian Barbara J. , Robbins Trevor W. , Palaniyappan Lena , Zhang Jie
Published: September 2021

Overlap of brain changes across mental disorders has reinforced transdiagnostic models. However, the developmental basis for this overlap is unclear as are neural differences among internalizing, externalizing and thought disorders. These issues are critical to inform the theoretical framework for hierarchical transdiagnostic psychiatric taxonomy. We examined cortical thickness (CT) difference between healthy controls (n=4041) and patients with externalizing (n=1182), internalizing (n=1959) and thought (n=347) disorders in preadolescents (9-10 years) from the Adolescent Brain and Cognitive Development Study using linear mixed models. Genome-wide association analysis and cell type specificity analysis were performed on regional CT across 4,716 unrelated European youth. We found that youth with externalizing or internalizing disorders, but not thought disorders, exhibited significantly thicker cortex than controls. Externalizing and internalizing disorders shared thicker CT in left pars opercularis and caudal middle frontal gyrus related to lower cognitive performance. Somatosensory and primary auditory cortex were uniquely affected in externalizing disorders; primary motor cortex and higher-order visual association areas were uniquely affected in internalizing disorders. Only group of externalizing disorders demonstrated significant CT increase than controls at 2-year follow-up and decelerated cortical thinning from 10 to 12 years old. At genetic level, genes associated with CT in common and disorders-specific regions were also implicated in related diagnostic families. Microglia were the cell-type associated with CT for both externalizing/internalizing while dopaminergic/glutamatergic/GABAergic cells related only to externalizing-specific regions. These results showed that distinct anatomical trajectories relevant to internalizing/externalizing phenotypes may result from unique genetic and cell-type changes, but these occur in the background of significantly shared morphological variance.
Personal protective equipment does not sufficiently protect against virus aerosol unless combined with advanced air purification or ventilation techniques
Authors: Landry Shane A , Subedi Dinesh , Barr Jeremy J , MacDonald Martin I , Dix Samantha , Kutey Donna M , Mansfield Darren , Hamilton Garun S , Edwards Bradley A. , Joosten Simon A
Published: September 2021

Background

Healthcare workers (HCWs) are at risk from nosocomial transmission of SARS-CoV-2 from virus laden aerosols. This study aimed to: 1) quantify the degree of protection from virus aerosol provided by different types of mask (surgical, N95, fit-tested N95) and personal protective equipment (PPE); 2) determine if the use of a portable HEPA filter can enhance the effectiveness of PPE; 3) determine the effectiveness of a decontamination shower to remove virus aerosol contamination of a HCW.

Methods

Virus aerosol exposure experiments were conducted using bacteriophage PhiX174 (108copies/mL). A HCW wearing PPE (mask, gloves, gown, faceshield) was exposed to nebulised viruses for 40mins in a sealed clinical room. After exiting, the HCW doffed PPE. Virus exposure was quantified via skin swabs applied to the face and nostrils, forearms, neck, and forehead. Experiments were performed with and without the presence of a portable HEPA filter (set to 470m3/hr).

Findings

Swabs quantified significant virus exposure under the surgical and N95 mask. Only the fit-tested N95 resulted in lower virus counts compared to no mask control (p=0.027). Nasal swabs demonstrated very high virus exposure, which was not mitigated by the surgical or N95 masks, although there was a trend for the fit-tested N95 mask to reduce virus counts (p=0.058). The addition of HEPA filtration substantially reduced virus counts from all swab sites, and to near zero levels when combined with a fit-tested N95 mask, gloves, gown and faces shield. Virus counts were substantially reduced to near zero levels following a shower.

Interpretation

These data demonstrate that quantitatively fit tested N95 masks combined with a HEPA filter can offer protection against high virus aerosol loads at close range and for prolonged periods of time. Skin contamination from virus aerosol can be effectively by removed by showering.

Funding

Epworth Hospital Capacity Building Research Grant ID: EH2020-654
Effectiveness of inactive COVID-19 vaccines against severe illness in B.1.617.2 (Delta) variant-infected patients in Jiangsu, China
Authors: Hu Zhiliang , Tao Bilin , Li Zhongqi , Song Yan , Yi Changhua , Li Junwei , Zhu Meng , Yi Yongxiang , Huang Peng , Wang Jianming
Published: September 2021

The SARS-CoV-2 B.1.617.2 (Delta) variant has caused a new surge in the number of COVID-19 cases. The effectiveness of vaccines against this variant is not fully understood. Using data from a recent large-scale outbreak of COVID-19 in China, we conducted a real-world study to explore the effect of inactivated vaccine immunization on the course of disease in patients infected with Delta variants. We recruited 476 confirmed cases over the age of 18, of which 42 were severe. After adjusting for age, gender, and comorbidities, patients who received two doses of inactivated vaccine (fully vaccinated) had an 88% reduced risk in progressing to the severe stage (adjusted OR: 0.12, 95% CI: 0.02- 0.45). However, this protective effect was not observed in patients who only received only one dose of the vaccine(adjusted OR: 1.11, 95% CI: 0.51- 2.36). The full immunization offered 100% protection from a severe illness among women. The effect of the vaccine was potentially affected by underlying medical conditions (OR: 0.26, 95% CI: 0.03-1.23). This is the largest real-world study confirming the effectiveness of inactive COVID-19 vaccines against severe illness in Delta variant-infected patients in Jiangsu, China.
No difference in risk of hospitalisation between reported cases of the SARS-CoV-2 Delta variant and Alpha variant in Norway
Authors: Veneti Lamprini , Valcarcel Salamanca Beatriz , Seppälä Elina , Starrfelt Jostein , Storm Margrethe Larsdatter , Bragstad Karoline , Hungnes Olav , Bøås Håkon , Kvåle Reidar , Vold Line , Nygård Karin , Buanes Eirik Alnes , Whittaker Robert
Published: September 2021

Objectives

To estimate the risk of hospitalisation among reported cases of the Delta-variant of SARS-CoV-2 compared to the Alpha variant in Norway. We also estimated the risk of hospitalisation by vaccination status.

Methods

We conducted a cohort study on laboratory-confirmed cases of SARS-CoV-2 in Norway, diagnosed between 3 May and 15 August 2021. We calculated adjusted risk ratios (aRR) with 95% confidence intervals (CIs) using multivariable binomial regression, accounting for variant, vaccination status, demographic characteristics, week of sampling and underlying comorbidities.

Results

We included 7,977 cases of Delta and 12,078 cases of Alpha. Overall, 347 (1.7%) cases were hospitalised. The aRR of hospitalisation for Delta compared to Alpha was 0.97 (95%CI 0.76–1.23). Partially vaccinated cases had a 72% reduced risk of hospitalisation (95%CI 59%–82%), and fully vaccinated cases had a 76% reduced risk (95%CI 61%–85%), compared to unvaccinated cases.

Conclusions

We found no difference in the risk of hospitalisation for Delta cases compared to Alpha cases in Norway. Further research from a wide variety of settings is needed to better understand the association between the Delta variant and severe disease. Our results support the notion that partially and fully vaccinated persons are highly protected against hospitalisation with COVID-19.

Highlights

The SARS-CoV-2 Delta variant has dominated in Norway since July 2021

There was no difference in the risk of hospitalisation for Delta cases compared to Alpha

Partially and fully vaccinated cases had >70% decreased risk of hospitalisation
Advanced analysis in epidemiological modeling: Detection of wave
Authors: Atangana Abdon , İğret Araz Seda
Published: September 2021

Some mathematical concepts have been used in the last decades to predict the behavior of spread of infectious diseases. Among them, the reproductive number concept has been used in several published papers for study the stability of the spread. Some conditions were suggested to predict there would be either stability or instability. An analysis was also suggested to determine conditions under which infectious classes will increase or die out. Some authors pointed out limitations of the reproductive number, as they presented its inability to fairly help understand the spread patterns. The concept of strength number and analysis of second derivatives of the mathematical models were suggested as additional tools to help detect waves. In this paper, we aim at applying these additional analyses in a simple model to predict the future.
The association between SARS-CoV-2 infection and neuronal damage: A population-based nested case-control study
Authors: Aziz N. Ahmad , Santos Marina L.S. , Breteler Monique M.B.
Published: September 2021

Objective

To assess whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with changes in plasma levels of neurofilament light chain (NfL), an extremely sensitive marker of neuroaxonal damage, in community-dwelling individuals.

Setting

This study was embedded within the Rhineland Study, an ongoing community-based cohort study in Bonn, Germany

Design

Cross-sectional nested case-control study.

Participants

Participants were selected based on results from a previously conducted seroprevalence survey within the framework of the Rhineland Study. Cases were defined as those individuals who had had two positive confirmatory test results, including a recombinant spike-based immunofluorescence assay and a plaque reduction neutralization test (N=21). As controls, a random sample of individuals with a negative ELISA test result (Controls I, N=1117), and those with a borderline or positive ELISA test result who failed confirmatory testing (Controls II, N=68), were selected.

Outcome measures

Plasma levels of NfL at the time of measurement, as well as change in plasma NfL levels compared to previously measured pre-pandemic levels

Results

After adjustment for age, sex and batch effects, serologically confirmed SARS-CoV-2 infection was neither associated with cross-sectional NfL levels, nor with the magnitude of change from pre-pandemic levels, compared to either of the two control groups. Similarly, after adjustment for age, sex and batch effects, self-reported neurological symptoms – including altered sense of smell or taste, headache, myalgia and fever – were not associated with changes in NfL levels in participants with a serologically confirmed SARS-CoV-2 infection (all p ≥ 0.56).

Conclusions

Our findings indicate that mild-to-moderate coronavirus disease-19 is unlikely to be associated with a clinically relevant degree of neuroaxonal damage, even in those cases associated with neurological symptoms.
Heterogeneity of recurrences in rectal cancer: application of population models facilitates personalized medicine
Authors: Nagtegaal Iris D. , van de Water Carlijn , Borst Dyogo , Marijnen Corrie A.M. , van de Velde Cornelis J.H. , Hugen Niek , Jongejans Eelke
Published: September 2021

Due to heterogeneity in presentation and outcome, patients with metastatic disease cannot be considered a single group. The timing, location and combinations of recurrences determine the feasibility of treatment of the individual patient in an era in which the options for local and systemic treatment have expanded. Studies investigating this complexity are hampered by the lack of both large cohorts and adequate methods.

In a well-defined cohort of rectal cancer patients from a randomized clinical trial, with long standardized follow-up, we applied spatial projection models derived from population ecology to overcome the complexity problem. We describe the recurrence patterns in detail and performed stochastic simulation experiments resulting in 1.5 million evaluable patients. The risk of subsequent recurrences was dependent on the presentation of the first recurrent event and decreased with increasing recurrence-free interval. The risk of local recurrence for the median patient (65.8 years, pT3 adenocarcinoma) was threefold increased after the development of rare metastases. The risk of development of rare metastases was increased after the development of other extrahepatic metastases.

Our cross-disciplinary approach delivers insights allowing for the development of personalized strategies for (local) treatment of recurrent disease, as well as for surveillance strategies that may potentially impact large patient cohorts. In this proofof-principle study we demonstrate the feasibility of spatial projection models for cancer research.
Artificial Intelligence in Dry Eye Disease
Authors: Storås Andrea M. , Strümke Inga , Riegler Michael A. , Grauslund Jakob , Hammer Hugo L. , Yazidi Anis , Halvorsen Pål , Gundersen Kjell G. , Utheim Tor P. , Jackson Catherine
Published: September 2021

Dry eye disease (DED) has a prevalence of between 5 and 50%, depending on the diagnostic criteria used and population under study. However, it remains one of the most underdiagnosed and undertreated conditions in ophthalmology. Many tests used in the diagnosis of DED rely on an experienced observer for image interpretation, which may be considered subjective and result in variation in diagnosis. Since artificial intelligence (AI) systems are capable of advanced problem solving, use of such techniques could lead to more objective diagnosis. Although the term ‘AI’ is commonly used, recent success in its applications to medicine is mainly due to advancements in the sub-field of machine learning, which has been used to automatically classify images and predict medical outcomes. Powerful machine learning techniques have been harnessed to understand nuances in patient data and medical images, aiming for consistent diagnosis and stratification of disease severity. This is the first literature review on the use of AI in DED. We provide a brief introduction to AI, report its current use in DED research and its potential for application in the clinic. Our review found that AI has been employed in a wide range of DED clinical tests and research applications, primarily for interpretation of interferometry, slit-lamp and meibography images. While initial results are promising, much work is still needed on model development, clinical testing and standardisation.
Using multivariate models to examine the impact of COVID-19 pandemic and gender differences on health and health care
Authors: Ye Jiancheng , Ren Zhimei
Published: September 2021

Objective

To examine the effect of the COVID-19 pandemic, the effect of sex, and the joint effect of sex and the COVID-19 pandemic in relation to health communication, physical activity, mental health, and behavioral health.

Methods

We drew data from the National Cancer Institute’s 2020 Health Information National Trends Survey (HINTS). We described and compared the characteristics of social determinants of health, physical activity, mental health, alcohol use, patterns of social networking service use, and health information data sharing. Analyses were weighted to provide nationally representative estimates. Multivariate models (multiple linear regression, multiple logistic regression, and multinomial logistic model) were used to assess the sole and joint effect of sex and pandemic. In addition, we applied the Bonferroni correction to adjust p-values to decrease the risks of type I errors when making multiple statistical tests.

Results

Women are more likely to use mobile health and health communication technologies. The effect of sex after the COVID-19 pandemic is significant on mental health, and women are more possible to have depression or anxiety disorders. The effect of sex is also significant before and after the pandemic regarding seeking health or medical information. Women have a smaller quantity and intensity of physical activity, which has a negative effect on health.

Conclusion

Gender differences exist regardless of the COVID-19 pandemic and the pandemic amplifies the differences in some health and health care domains. Intersectional gender analyses are integral to addressing issues that arise and mitigating the exacerbation of inequities. Responses to the pandemic should consider diverse perspectives, including sex and gender.
Life course circumstances contribute to the acceleration of phenotypic and functional aging in Chinese middle-aged and older adults
Authors: Cao Xingqi , Ma Chao , Zheng Zhoutao , He Liu , Hao Meng , Chen Xi , Crimmins Eileen M. , Gill Thomas M. , Levine Morgan E. , Liu Zuyun
Published: September 2021

Accelerated aging implies health inequalities in late life and consequently, poses a huge challenge to society. With two well-validated aging measures, this study aimed to evaluate the relative contributions of life course circumstances to variance in these aging measures with policy implications. We assembled data for 6224 middle-aged and older adults (≥45 years) who participated in the 2014 life course survey, the 2015 biomarker collection, and the 2015 main survey of the China Health and Retirement Longitudinal Study (CHARLS). Two aging measures, including physiological dysregulation (PD) and frailty index (FI), were calculated. Life course circumstances, i.e., 70 circumstances variables involving childhood and adulthood circumstances, demographics, and behaviors, were categorized into 11 study domains for simplicity. The Shapley value decomposition, hierarchical clustering, and general linear regression models were performed. The Shapley value decomposition revealed that all 11 study domains accounted for about 6.3% and 29.7% of the variance in PD and FI, respectively. We then identified six subpopulations who shared similar patterns in terms of childhood and adulthood circumstances. One subpopulation (i.e., disadvantaged) who reported experiencing more childhood and adulthood adversity consistently exhibited accelerated aging indicated by the two aging measures. We conclude that life course circumstances contribute differently to the acceleration of phenotypic and functional aging in Chinese middle-aged and older adults. Special attention should be given to promoting health for the disadvantaged subpopulation and narrowing their health gap with advantaged counterparts. Our findings highlight the role of life course circumstances in ameliorating health inequalities in late life.
Generation of CD34+CD43+ hematopoietic progenitors to induce thymocytes from human pluripotent stem cells
Authors: Flippe Léa , Gaignerie Anne , Sérazin Céline , Baron Olivier , Saulquin Xavier , Anegon Ignacio , David Laurent , Guillonneau Carole
Published: September 2021

Immunotherapy using primary T cells has revolutionized medical care in some pathologies in recent years but limitations associated to challenging cell genome edition, insufficient cell number production, the use of only autologous cells and lack of product standardization have limited its uses in the clinic. The alternative use of T cells generated in vitro from human pluripotent stem cells (hPSCs) offers great advantages by providing a self-renewing source of T cells that can be readily genetically modified and facilitate the use of standardized universal off-the-shelf allogeneic cell products and rapid clinic access. However, despite their potential, the feasibility and functionality of T-cells differentiated from hPSCs needs better comprehension before moving to the clinic. In this study, we generated human induced pluripotent stem cells from T-cells (T-iPSCs) allowing preservation of already recombined TCR, with the same properties as human embryonic stem cells (hESCs). Based on these cells, we differentiated with high efficiency hematopoietic progenitor stem cells (HPSCs), capable of self-renewal and differentiation into any cell blood type, and then DN3a thymic progenitors from several T-iPSC lines. To better comprehend differentiation, we analyzed the transcriptomic profiles of the different cell types and demonstrated that HPSCs differentiated from hiPSCs had a very similar profile to cord blood hematopoietic stem cells (HSCs). Furthermore, differentiated T-cell progenitors had a similar profile to thymocytes at the DN3a stage of thymic lymphopoiesis. Therefore, with this approach, we were able to regenerate precursors of therapeutic human T cells to potentially treat a wide number of diseases.