bluuebunny/crossref_metadata_2025 huggingface dataset:
Rolling With the Punches: A National Electronic Injury Surveillance System Database Study of Craniofacial Injuries in Boxing
Authors: Wolfe Erin M. , Pierrot Randall G. , Slavin Benjamin R. , Plotsker Ethan L. , Samaha Georges J. , Gishen Kriya , Thaller Seth R.
Published: March 2021

Introduction:

Boxing is a popular combat sport in which competitors may sustain high impact blows to the face. For this reason, they are at high risk for craniofacial injuries; however, data on facial injuries specific to boxing remains sparse. Studies on safety measures, such as headgear, to prevent such injuries in boxing have been inconclusive. Boxing is popular with a wide audience. However, there is no consensus on safety measures across different populations involved in boxing due to lack of data. The objective of this study is to characterize the demography and incidence of injury types of patients presenting to emergency departments with boxing-related craniofacial injuries on a national scale in order to facilitate the establishment of evidence-based safety guidelines for prevention of boxing-related injuries.

Methods:

The National Electronic Injury Surveillance System database was searched for boxing-related craniofacial injuries from the last 10 years (2010–2019). Injuries involving boxing were isolated and organized into 5-year age groups. Information on demographics and injury type was extracted from the National Electronic Injury Surveillance System database. Statistical analysis was performed between different age and gender groups.

Results:

A total of 749 boxing-related craniofacial injuries treated in US emergency departments between 2010 and 2019 were recorded. The 19 to 34-year-old age group had the highest number of cases (54%), followed by the 12 to 18-year-old age group (31%). The most common injury types within both of these age groups were concussions and lacerations. This difference was found to be significant when compared to other craniofacial injury types (P < 0.05). The majority of athletes in these age groups were male (93% and 91%, respectively). Analysis of sex differences demonstrated concussions were more common in females compared to other injury types, whereas lacerations in males were more common compared to other injury types; these differences were found to be significant (P < 0.05).

Conclusions:

The high incidence of boxing-related craniofacial injuries such as concussions and lacerations incurred in young adults (19–34 years) and adolescents (12–18 years) indicate that protective measures such as community-based safety interventions and revised guidelines for protective equipment may be indicated in these groups to protect against craniofacial injuries such as lacerations and concussions. Further studies are required to develop algorithms for management of boxing-related craniofacial injuries and to evaluate the safety and efficacy of protective equipment such as boxing headgear on concussions.
The Full Spectrum of COVID-19 Development and Recovery Among Kidney Transplant Recipients
Authors: Cristelli Marina P. , Viana Laila A. , Dantas Marcus T.C. , Martins Suelen B.S. , Fernandes Ruan , Nakamura Monica R. , Santos Daniel W.C.L. , Taddeo Julia B. , Azevedo Vega F. , Foresto Renato D. , Tedesco-Silva Helio , Medina-Pestana Jose
Published: March 2021

Background.

Coronavirus disease 2019 (COVID-19) fatality rate is high among kidney transplant recipients. Among survivors, kidney outcomes, seroconversion, and persistence of viral shedding are unexplored.

Methods.

Single-center prospective cohort study including data from kidney transplant recipients with confirmed COVID-19 between March 20, 2020 and July 31, 2020. Outcomes were adjudicated until August 31, 2020 or the date of death.

Results.

There were 491 patients with COVID-19 among the 11 875 recipients in follow-up. The majority were middle aged with ≥1 comorbidities. Thirty-one percent were treated at home, and 69% required hospitalization. Among the hospitalized, 61% needed intensive care, 75% presented allograft dysfunction, and 46% needed dialysis. The overall 28-day fatality rate was 22% and among hospitalized patients it was 41%. Age (odds ratio, 3.08; 95% confidence interval, 1.86-5.09), diabetes mellitus (odds ratio, 1.69; 95% confidence interval, 1.06-2.72), and cardiac disease (odds ratio, 2.00; 95% confidence interval, 1.09-3.68) were independent factors for death. Among the 351 survivors, 19% sustained renal graft dysfunction, and there were 13 (4%) graft losses. Biopsy (n = 20) findings were diverse but decisive to guide treatment and estimate prognosis. Seroconversion was observed in 79% of the survivors and was associated with disease severity. Persistence of viral shedding was observed in 21% of the patients without detectable clinical implications.

Conclusions.

This prospective cohort analysis confirms the high 28-day fatality rate of COVID-19, associated primarily with age and comorbidities. The high incidence of allograft dysfunction was associated with a wide range of specific histologic lesions and high rates of sequelae and graft loss. Seroconversion was high and the persistence of viral shedding deserves further studies.
The Magnitude and Functionality of SARS-CoV-2 Reactive Cellular and Humoral Immunity in Transplant Population Is Similar to the General Population Despite Immunosuppression
Authors: Thieme Constantin J. , Anft Moritz , Paniskaki Krystallenia , Blazquez-Navarro Arturo , Doevelaar Adrian , Seibert Felix S. , Hoelzer Bodo , Justine Konik Margarethe , Meister Toni L. , Pfaender Stephanie , Steinmann Eike , Moritz Berger Marc , Brenner Thorsten , Kölsch Uwe , Dolff Sebastian , Roch Toralf , Witzke Oliver , Schenker Peter , Viebahn Richard , Stervbo Ulrik , Westhoff Timm H. , Babel Nina
Published: March 2021

Background.

The ability of transplant (Tx) patients to generate a protective antiviral response under immunosuppression is pivotal in COVID-19 infection. However, analysis of immunity against SARS-CoV-2 is currently lacking.

Methods.

Here, we analyzed T cell immunity directed against SARS-CoV-2 spike-, membrane-, and nucleocapsid-protein by flow cytometry and spike-specific neutralizing antibodies in 10 Tx in comparison to 26 nonimmunosuppressed (non-Tx) COVID-19 patients.

Results.

Tx patients (7 renal, 1 lung, and 2 combined pancreas-kidney Txs) were recruited in this study during the acute phase of COVID-19 with a median time after SARS-CoV-2-positivity of 3 and 4 d for non-Tx and Tx patients, respectively. Despite immunosuppression, we detected antiviral CD4+ T cell-response in 90% of Tx patients. SARS-CoV-2–reactive CD4+ T cells produced multiple proinflammatory cytokines, indicating their potential protective capacity. Neutralizing antibody titers did not differ between groups. SARS-CoV-2–reactive CD8+ T cells targeting membrane- and spike-protein were lower in Tx patients, albeit without statistical significance. However, frequencies of anti-nucleocapsid–protein-reactive, and anti-SARS-CoV-2 polyfunctional CD8+ T cells, were similar between patient cohorts. Tx patients showed features of a prematurely aged adaptive immune system, but equal frequencies of SARS-CoV-2–reactive memory T cells.

Conclusions.

In conclusion, a polyfunctional T cell immunity directed against SARS-CoV-2 proteins as well as neutralizing antibodies can be generated in Tx patients despite immunosuppression. In comparison to nonimmunosuppressed patients, no differences in humoral and cellular antiviral-immunity were found. Our data presenting the ability to generate SARS-CoV-2–specific immunity in immunosuppressed patients have implications for the handling of SARS-CoV-2–infected Tx patients and raise hopes for effective vaccination in this cohort.
Common Data Elements, Scalable Data Management Infrastructure and Analytics Workflows for Large-scale Neuroimaging Studies
Authors: Kuplicki Rayus , Touthang James , Zoubi Obada Al , Mayeli Ahmad , Misaki Masaya ,   NeuroMAP-Investigators, Aupperle Robin L , Teague T. Kent , McKinney Brett A. , Paulus Martin , Bodurka Jerzy
Published: March 2021

1.

Neuroscience studies require considerable bioinformatic support and expertise. Numerous high-dimensional and multimodal datasets must be preprocessed and integrated to create robust and reproducible analysis pipelines. We describe a common data elements and scalable data management infrastructure that allows multiple analytics workflows to facilitate preprocessing, analysis and sharing of large-scale multi-level data. The process uses the Brain Imaging Data Structure (BIDS) format and supports MRI, fMRI, EEG, clinical and laboratory data. The infrastructure provides support for other datasets such as Fitbit and flexibility for developers to customize the integration of new types of data. Exemplar results from 200+ participants and 11 different pipelines demonstrate the utility of the infrastructure.
Post-stroke reorganization of transient brain activity characterizes deficits and recovery of cognitive functions
Authors: Pirondini Elvira , Kinany Nawal , Le Sueur Cécile , Griffis Joseph C. , Shulman Gordon L. , Corbetta Maurizio , Van De Ville Dimitri
Published: March 2021

Functional magnetic resonance imaging (fMRI) has been widely employed to study stroke pathophysiology. In particular, analyses of fMRI signals at rest were directed at quantifying the impact of stroke on spatial features of brain networks. However, brain networks have intrinsic time features that were, so far, disregarded in these analyses. In consequence, standard fMRI analysis failed to capture temporal imbalance resulting from stroke lesions, hence restricting their ability to reveal the interdependent pathological changes in structural and temporal network features following stroke. Here, we longitudinally analyzed hemodynamic-informed transient activity in a large cohort of stroke patients (n = 103) to assess spatial and temporal changes of brain networks after stroke. While large-scale spatial patterns of these networks were preserved after stroke, their durations were altered, with stroke subjects exhibiting a varied pattern of longer and shorter network activations compared to healthy individuals. These temporal alterations were associated with white matter damage and were behavior-specific. Specifically, restoration of healthy brain dynamics paralleled recovery of cognitive functions, but was not significantly correlated to motor recovery. These findings underscore the critical importance of network temporal properties in dissecting the pathophysiology of brain changes after stroke, thus shedding new light on the clinical potential of time-resolved methods for fMRI analysis.

Significance Statement

Understanding the pathophysiology of a disorder is pivotal to design effective treatment. In this regard, recent advances in stroke research settled a new clinical concept:connectional diaschisis, which suggested that post-stroke impairments arise from both focal structural changes (tied to the injury) and widespread alterations in functional connectivity. fMRI time-resolved methods consider structural and temporal properties of brain networks as interdependent features. They are, thus, better suited to capture the intertwine between structural and functional changes. Here we leveraged a dynamic functional connectivity framework based on the clustering of hemodynamic-informed transients in a large and heterogeneous stroke population assessed longitudinally. We showed that lesions led to an unbalance in the brain dynamics that was associated with white matter fibers disruption and was restored as deficits recovered. Our work showed the potential of a time-resolved method to reveal clinically relevant dynamics of large-scale brain networks.
COVID-19 collateral damage: psychological distress and behavioral changes among older adults during the first outbreak in Stockholm, Sweden
Authors: Beridze Giorgi , Triolo Federico , Grande Giulia , Fratiglioni Laura , Calderón-Larrañaga Amaia
Published: March 2021

Introduction

During the first wave of the COVID-19 pandemic, Swedish public health authorities provided recommendations for 70+ year old people. They were strongly encouraged to self-isolate but remain physically active in a safe manner. This study aimed to explore the indirect, negative effects of COVID-19 restrictions (collateral damage) by exploring to what extent adherence to such recommendations might have impacted the lives and health of older adults living in central Stockholm.

Methods

An ad-hoc phone questionnaire was administered by trained staff between May and June 2020 to a random sample of older adults 68+ years old (n=1231), who had attended the regular follow-up assessment of the longitudinal Swedish National study on Aging and Care in Kungsholmen (SNAC-K) during 2016-2019. We explored three dimensions of collateral damage, namely psychological distress (feelings of worry, stress and loneliness), reductions in social and physical activities, and reductions in medical and social care use. Logistic regression models were used to test the association between age, sex, education and living arrangement, and the risk of collateral damage.

Results

Vast majority of participants adhered to the recommendations, with over three quarters practicing self-isolation (n=928). Half of the sample reported psychological distress, 55.3% reported reductions in social or physical activity, and 11.3% reported decreased medical or social care use. Over three quarters of participants were affected by at least one of the three collateral damage dimensions. Female sex was the strongest sociodemographic predictor of individual as well as co-occurring dimensions of collateral damage.

Conclusion

COVID-19 and its restrictions during the first half of 2020 have had a negative effect on the health and lives of a majority of elderly living in central Stockholm. Women were at a particularly higher risk of these negative consequences. We emphasize the need for predefined, evidence-based interventions to address these negative consequences.

STRENGTHS AND LIMITATIONS OF THIS STUDY

This study uses a large sample of older adults from a well-characterized population-based study (SNAC-K)

Several dimensions of the indirect, negative effects (collateral damage) of the COVID-19 pandemic are explored in this study

As Sweden’s response to COVID-19 differed from most countries, this study provides a unique opportunity of comparison with other settings

The cross-sectional design of this study does not allow to establish temporality between the onset of the pandemic and studied outcomes

The results of this study may not be generalisable to the entire elderly population in Sweden as participants are from an urban, affluent area in Stockholm
Assessing the utility of lymphocyte count to diagnose COVID-19
Authors: Fralick Michael , Bogler Orly , Tamming Daniel , Lapointe-Shaw Lauren , Kwan Janice , Tang Terence , Rawal Shail , Liu Jessica , Razak Farad , Verma Amol A
Published: March 2021

Background

COronaVirus Disease 2019 (COVID-19) can be challenging to diagnose, because symptoms are non-specific, clinical presentations are heterogeneous, and false negative tests can occur. Our objective was to assess the utility of lymphocyte count to differentiate COVID-19 from influenza or community-acquired pneumonia (CAP).

Methods

We conducted a cohort study of adults hospitalized with COVID-19 or another respiratory infection (i.e., influenza, CAP) at seven hospitals in Ontario, Canada.The first available lymphocyte count during the hospitalization was used. Standard test characteristics for lymphocyte count (×109/L) were calculated (i.e., sensitivity, specificity, area under the receiver operating curve [AUC]). All analyses were conducting using R.

Results

There were 869 hospitalizations for COVID-19, 669 for influenza, and 3009 for CAP. The mean age across the three groups was 67 and patients with pneumonia were older than those with influenza or COVID19, and approximately 46% were woman. The median lymphocyte count was nearly identical for the three groups of patients: 1.0 ×109/L (interquartile range [IQR]:0.7,2.0) for COVID-19, 0.9 ×109/L (IQR 0.6,1.0) for influenza, and 1.0 ×109/L (IQR 0.6,2.0) for CAP. At a lymphocyte threshold of less than 2.0 ×109/L, the sensitivity was 87% and the specificity was approximately 10%. As the lymphocyte threshold increased, the sensitivity of diagnosing COVID-19 increased while the specificity decreased. The AUC for lymphocyte count was approximately 50%.

Interpretation

Lymphocyte count has poor diagnostic discrimination to differentiate between COVID-19 and other respiratory illnesses. The lymphopenia we consistently observed across the three illnesses in our study may reflect a non-specific sign of illness severity. However, lymphocyte count above 2.0 ×109/L may be useful in ruling out COVID-19 (sensitivity = 87%).
Importation, circulation, and emergence of variants of SARS-CoV-2 in the South Indian State of Karnataka
Authors: Pattabiraman Chitra , Prasad Pramada , George Anson K , Sreenivas Darshan , Rasheed Risha , Reddy Nakka Vijay Kiran , Desai Anita , Vasanthapuram Ravi
Published: March 2021

As the pandemic of COVID-19 caused by the coronavirus SARS-CoV-2 continues, the selection of genomic variants which can influence how the pandemic progresses is of growing concern. Of particular concern, are those variants that carry mutations/amino acid changes conferring higher transmission, more severe disease, re-infection, and immune escape. These can broadly be classified as Variants of Concern (VOCs). VOCs have been reported from several parts of the world- UK (lineage B.1.1.7), South Africa (lineage B.1.351) and, Brazil (lineage P.1/B.1.1.28). The conditions that contribute to the emergence of VOCs are not well understood. International travel remains an important means of spread. To track importation, spread, and the emergence of variants locally; we sequenced whole genomes of SARS-CoV-2 from international travellers (n=75) entering Karnataka, a state in South India, between Dec 22, 2020- Jan 31, 2021, and from positive cases in the city of Bengaluru (n=108), between Nov 22, 2020- Jan 22, 2021. The resulting 176 SARS-CoV-2 genomes could be classified into 34 lineages, that were either imported (73/176) or circulating (103/176) in this time period. The lineage B.1.1.7 (a.k.a the UK variant) was the major lineage imported into the state (24/73, 32.9%), followed by B.1.36 (20/73, 27.4%) and B.1 (14/73, 19.2%). We identified B.1.36 (45/103; 43.7%), B.1 (26/103; 25.2%), B.1.1.74 (5/103; 4.9%) and B.1.468 (4/103; 3.9%) as the major variants circulating in Bengaluru city. A distinct clade within the B.1.36 lineage was associated with a local outbreak. Analysis of the complete genomes predicted multiple amino acid replacements in the Spike protein. In total, we identified nine amino acid changes (singly or in pairs) in the Receptor Binding Domain of the Spike protein. Of these, the amino acid replacement N440K was found in 37/65 (56.92%) sequences in the B.1.36 lineage. The E484K amino acid change which is present in both VOCs, B.1.351 and P.1/B.1.1.28, was found in a single circulating virus in the B.1.36 lineage. This study highlights the introduction of VOCs by travel and the local circulation of viruses with amino acid replacements in the Spike protein. These were spread across lineages, suggesting that multiple paths can lead to the emergence of VOCs, this, in turn, highlights the need to sequence and limit outbreaks of SARS-CoV-2 locally. Our data support the use of concentrated and continued genomic surveillance of SARS-CoV-2 to direct public health measures, suggest revisions to vaccines, and serve as an early warning system to prepare for a surge in COVID-19 cases.
Pulmonary Fibrosis after COVID-19 is Associated with Severity of Illness and Blood Leukocyte Telomere Length
Authors: McGroder Claire F. , Zhang David , Choudhury Mohammad A. , Salvatore Mary M. , D’Souza Belinda M. , Hoffman Eric A. , Wei Ying , Baldwin Matthew R. , Garcia Christine Kim
Published: March 2021

The risk factors for development of fibrotic interstitial lung abnormalities (ILA) after severe COVID-19 are incompletely described and the extent to which CT findings correlate with symptoms and physical function after hospitalization remain unclear. At 4 months after hospitalization, fibrotic ILA was more common in those who underwent mechanical ventilation (72%) than in those who did not (20%). We demonstrate that severity of initial illness, duration of mechanical ventilation, lactate dehydrogenase on admission, and leukocyte telomere length are independent risk factors for fibrotic ILA. These fibrotic changes correlate with lung function, cough and measures of frailty, but not with dyspnea.
Oral health inequality in people with severe mental illness: a cross-sectional study using National Health and Nutrition Examination Survey 1999-2016
Authors: Kang Jing , Wu Jianhua , Aggarwal Vishal , Shiers David , Doran Tim , Palmier-Claus Jasper
Published: March 2021

OBJECTIVE

To explore whether people with severe mental illness (SMI) experience worse oral health compared to the general population, and the risk factors for poor oral health in people with SMI.

METHOD

This study used cross-sectional data from the National Health and Nutrition Examination Survey (1999-2016) including on self-rated oral health, ache in mouth, tooth loss, periodontitis stage, and number of decayed, missing, and filled teeth. Candidate risk factors for poor oral health included demographic characteristics, lifestyle factors, physical health comorbidities, and dental hygiene behaviours. The authors used ordinal logistic regression and zero-inflated negative binomial models to explore predictors of oral health outcomes.

RESULTS

53,348 cases were included in the analysis, including 718 people with SMI. In the fully adjusted model, people with SMI were more likely to suffer from tooth loss (OR 1.40, 95% CI: 1.12-1.75). In people with SMI, the risk factors identified for poor oral health outcomes were older age, white ethnicity, lower income, smoking history, and diabetes. Engaging in physical activity and daily use of dental floss were associated with better oral health outcomes.

CONCLUSIONS

People with SMI experience higher rates of tooth loss than the general population, and certain subgroups are particularly at risk. Having a healthy lifestyle such as performing regular physical exercise and flossing may lower the risk of poor oral health. These findings suggest opportunities for targeted prevention and early intervention strategies to mitigate adverse oral health outcomes.

Significant outcomes (x3)

People with severe mental illness were at 40% higher risk of tooth loss when compared to the general population.

Older adults, smokers and people with diabetes were at particularly high risk of poor oral health.

Physical exercise and daily use of dental floss were associated with better oral health outcomes.

Limitations (x3)

The number of cases with data on periodontal disease was limited.

The study was cross-sectional so causation could not be inferred.

The analysis used prescriptions of antipsychotic and mood stabilising medication as a proxy measure of severe mental illness, as clinical diagnoses were not available in the dataset.

Data availability statement

The NHANES 1999-2016 data is available at CDC website: https://www.cdc.gov/nchs/nhanes/index.htm, and is accessible and free to download for everyone.
Serological response to COVID-19 vaccination in IBD patients receiving biologics
Authors: Wong Serre-Yu , Dixon Rebekah , Pazos Vicky Martinez ,   ICARUS-IBD Working Group, Gnjatic Sacha , Colombel Jean-Frederic , Cadwell Ken
Published: March 2021

Objective

The impact of medications on COVID-19 vaccine efficacy in IBD patients is unknown, as patients with immunosuppressed states and/or treated with immunosuppressants were excluded from vaccine trials. To address this, we evaluated serological responses to COVID-19 vaccination with the SARS-CoV-2 spike (S) mRNA BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (NIH-Moderna) vaccines in IBD patients enrolled in an ongoing SARS-CoV-2 sero-survey at the Icahn School of Medicine at Mount Sinai in New York City.

Design

We obtained sera from 48 patients who had undergone vaccination with one or two vaccine doses. Sera were tested for SARS-CoV-2 anti-RBD total immunoglobulins and IgG (Siemens COV2T and sCOVG assays), anti-Spike IgG (in-house ELISA), and anti-nucleocapsid antibodies (Roche).

Results

All IBD patients (15/15) who completed two-dose vaccine schedules achieved seroconversion to high levels. Two IBD patients with history of COVID-19 infections and who were seropositive at baseline seroconverted to high levels after the first dose. Concurrent biologic use was 85% (41/48), including 33% of patients (16) on TNF antagonist monotherapy, 42% (17) on vedolizumab monotherapy, 6% (3) on vedolizumab combination therapy with thiopurine, and 8% (4) ustekinumab; 1 patient was receiving guselkumab for psoriasis. Three patients (6%) were on oral steroids at the time of vaccination.

Conclusion

IBD patients receiving biologics can seroconvert with robust serological responses after complete Pfizer-BioNTech and NIH-Moderna COVID-19 vaccination. In IBD-patients with previous SARS-CoV-2 seroconversion, a single dose of either vaccine can induce high index values, mirroring findings from the general population.
Discrimination of non-nestmate early brood in ants: behavioural and chemical analyses
Authors: de Fouchier Arthur , Leroy Chloé , Khila Abderrahman , d’Ettorre Patrizia
Published: March 2021

Brood is critically important in social insect colonies. It carries the colony’s fitness through delivering future reproductive adults as well as workers that will increase the colony’s workforce. Adoption of non-nestmate brood can increase the colony workforce but entails the risk of rearing unrelated sexuals or social parasites. Thus, theory would predict that ant workers will evolve the ability to discriminate between nestmate and alien brood using the chemical cues displayed at the brood’s surface. This appears especially true for eggs and first instar (L1) larvae, which require more resources before becoming adult workers compared to older brood. However, the chemical signature of ant early brood stages and its recognition by workers remains understudied. To fill this gap, we investigated the chemical basis of early brood nestmate and cross-species recognition in six ant species. We also tested the discrimination behaviour of workers in brood retrieval trials. We observed species-level cues and discrimination against hetero-specific brood. We also found that eggs and most L1 larvae displayed a colony signature. However, only some species discriminated against non-nestmate early brood. Interestingly, these species belong to genera subject to brood parasitism. We hypothesize that non-nestmate brood discrimination could arise from species adaptations against brood parasitism.
Altered transcriptome-proteome coupling indicates aberrant proteostasis in Parkinson’s disease
Authors: Dick Fiona , Tysnes Ole-Bjørn , Alves Guido Werner , Nido Gonzalo S. , Tzoulis Charalampos
Published: March 2021

The correlation between mRNA and protein levels has been shown to decline in the ageing brain, possibly reflecting age-dependent changes in the proteostasis. It is thought that impaired proteostasis may be implicated in the pathogenesis of Parkinson’s disease (PD), but evidence derived from the patient brain is currently limited. Here, we hypothesized that if impaired proteostasis occurs in PD, this should be reflected in the form of altered correlation between transcriptome and proteome compared to healthy ageing.

To test this hypothesis, we integrated transcriptomic data with proteomics from prefrontal cortex tissue of 17 PD patients and 11 demographically matched healthy controls and assessed gene-specific correlations between RNA and protein level. To control for the effects of ageing, brain samples from 4 infants were included in the analyses.

In the healthy aged brain, we observed a genome-wide decreased correlation between mRNA and protein levels. Moreover, a group of genes encoding synaptic vesicle proteins exhibited inverse correlations. This phenomenon likely reflects the spatial separation of mRNA and protein into the neuronal soma and synapsis, respectively, commonly characterizing these genes. Most genes showed a significantly lower correlation between mRNA and protein levels in PD compared to neurologically healthy ageing, consistent with a proteome-wide decline in proteostasis. Genes showing an inverse correlation in PD were enriched for proteasome subunits, suggesting that these proteins show accentuated spatial separation of transcript and protein between the soma and axon/synapses in PD neurons. Moreover, the PD brain was characterized by increased positive mRNA-protein correlation for some genes encoding components of the mitochondrial respiratory chain, suggesting these may require tighter regulation in the face of mitochondrial pathology characterizing the PD brain.

Our results are highly consistent with a proteome-wide impairment of proteostasis in the PD brain and strongly support the hypothesis that aberrant proteasomal function is implicated in the pathogenesis of PD. Moreover, our findings have important implications for the correct interpretation of differential gene expression studies in PD. In the presence of disease-specific altered coupling of transcriptome and proteome, measured differences in mRNA levels cannot be used to infer changes at the protein-level and should be supplemented with direct determination of proteins nominated by the analyses.
Respiratory and Cardiovascular Health Effects of E-Cigarette Substitution: Protocol for Two Living Systematic Reviews
Authors: O’Leary Renée , Qureshi Maria Ahmed , La Rosa Giusy Rita Maria , Vernooij Robin W. M. , Odimegwu Damian Chukwu , Bertino Gaetano , Polosa Riccardo
Published: March 2021

Background

Despite the clear risks of tobacco use, millions of people continue to smoke. Electronic nicotine delivery systems (ENDS), commonly called e-cigarettes, have been proposed as a substitute for those who are unwilling or unable to quit. Current systematic and narrative reviews on the health effects of ENDS use, respiratory and cardiovascular effects in particular, have come to differing conclusions.

Objective

The purpose of our two systematic reviews is to critically assess and synthesize the available human studies on the respiratory and cardiovascular health effects of ENDS substitution for people who smoke. The primary goal is to provide clinicians with evidence on the health effects of ENDS substitution to inform their treatment recommendations and plans. The twin goal is to promote the health literacy of ENDS users with facts on the health effects of ENDS. A secondary goal is to develop policy briefs to provide governmental bodies with a preliminary assessment of the potential public health impacts of ENDS.

Methods

These two reviews will be living systematic reviews. The systematic reviews will be initiated with a baseline review. Studies will be evaluated with the JBI quality assessment tools and a checklist of biases drawn from the Centre for Evidence Based Medicine’s Catalogue of Bias. A narrative synthesis is planned due to the heterogeneity of data. A search for recently published studies will be conducted every three months, and an updated review published every six months for the duration of the project or possibly longer.

Results

The baseline and updated reviews will be published in a peer review journal. The review findings will be reported in a white paper for clinicians, a fact sheet for people who use ENDS, and country-specific policy briefs.

Conclusions

The substitution of ENDS for cigarettes is one of the ways to potentially reduce the risks of smoking. Clinicians and their patients need to understand the potential benefits and possible risks of substituting ENDS for cigarettes. Our living systematic reviews seek to highlight the best and most up-to-date evidence in this highly contentious and fast-moving field of research.
Temperature at conception and pregnancy loss in rural KwaZulu-Natal Province, South Africa: Implications for climate change policy in sub-Saharan African settings
Authors: Moodley Yoshan , Tanser Frank , Tomita Andrew
Published: March 2021

Background

Global warming is projected to cause a substantial rise in temperatures with serious health implications across sub-Saharan Africa. Although South African policy makers have drafted a climate change adaptation plan, potential health threats posed by increasing temperatures on women’s reproductive health are overlooked due to the lack of local population-based evidence. We sought to address the gap in the evidence around global warming and women’s reproductive health in sub-Saharan Africa by using one of the continent’s largest prospective cohorts from rural KwaZulu-Natal Province, South Africa to investigate the relationship between temperature at conception and pregnancy loss.

Methods

Our study sample consisted of 36341 pregnancies from 16765 women from the uMkhanyakude District of KwaZulu-Natal, South Africa between 2000-2017. Average monthly temperatures for the study locale during the study period were obtained from the South African Weather Services. An adjusted logistic regression model was used to investigate the relationship between temperature at conception and pregnancy loss (miscarriage or stillbirth).

Results

The rate of pregnancy loss in the study sample was 1.9 (95% Confidence interval [CI]: 1.7-2.0) per 100 pregnancies. We observed a 4% higher odds of pregnancy loss for each 1°C increase in temperature (Adjusted Odds Ratio: 1.04, 95% CI: 1.01-1.08).

Conclusion

There is a clear relationship between temperature and pregnancy loss in our sub-Saharan African setting. The effects of global warming will likely exacerbate the existing challenges for women’s reproductive health in this region. Pregnancy outcomes should be given adequate attention when sub-Saharan African governments draft policies in response to global warming.
COVID-19 Implications of the Physical Interaction of Artificial Fog on Respiratory Aerosols
Authors: Loss Matthew , Katchen Mark , Arvelo Ilan , Arnold Phil , Shum Mona
Published: March 2021

Introduction

Artificial fog is used in the film, television, and live entertainment industries to enhance lighting, as a visual effect, and to create a specific sense of mood or atmosphere. This study investigated whether the suspension time of respiratory aerosols spiked with tagged DNA tracers would change in the presence of glycerin- or glycol-containing artificial fogs.

Methods & Materials

Respiratory aerosols with tagged DNA tracers were sprayed into a closed environment without and with glycerin- or glycol-containing artificial fog, with air samples taken at regular intervals to determine the decay of tagged DNA tracer over time. The study treatments included Control (no fog), Glycerin Low (3 mg/m3), Glycerin High (∼15 mg/m3), Glycol Low (∼5 mg/m3), and Glycol High (∼40 mg/m3).

Results

All artificial fog treatments had lower mean log reduction curves compared to the Control treatment. Compared to the Control and Glycerin Low treatments, the differences in mean log reduction for nearly all other artificial fog treatments were statistically significant (p<0.001); the difference between Control and Glycerin Low treatments was not statistically significant (p=0.087). The differences in mean log reduction between treatments using the same artificial fog type were not statistically significant.

Conclusion

Artificial fog use does not increase suspension time of respiratory aerosols, and therefore does not appear to increase the risk of airborne transmission of diseases from respiratory aerosols, such as COVID-19. Of the two types of artificial fogs investigated, that containing glycol decreased suspension time more than that containing glycerin. In practice, the additional reduction in suspension time provided by the physical interaction of respiratory aerosols with artificial fog does not suggest any practical benefit for using artificial fog as a control measure.
Development and validation of the long covid symptom and impact tools, a set of patient-reported instruments constructed from patients’ lived experience
Authors: Tran Viet-Thi , Riveros Caroline , Clepier Bérangère , Desvarieux Moïse , Collet Camille , Yordanov Youri , Ravaud Philippe
Published: March 2021

Objectives

To develop and validate patient-reported instruments, based on patients’ lived experiences, for monitoring the symptoms and impact of long covid.

Design

The long covid Symptom and Impact Tools (ST and IT) were constructed from the answers to a survey with open-ended questions to 492 patients with long covid. Validation of the tools involved adult patients with suspected or confirmed covid-19 and symptoms extending over three weeks after onset. Construct validity was assessed by examining the relations of the ST and IT scores with health related quality of life (EQ-5D-5L), function (PCFS, post-covid functional scale), and perceived health (MYMOP2). Reliability was determined by a test-retest. The “patient acceptable symptomatic state” (PASS) was determined by the percentile method.

Results

Validation involved 1022 participants (55% with confirmed covid-19, 79% female and 12.5% hospitalised for covid-19). The long covid ST and IT scores were strongly correlated with the EQ-5D-5L (rs = −0.45 and rs = −0.59 respectively), the PCFS (rs = −0.39 and rs = −0.55), and the MYMOP2 (rs = −0.40 and rs = −0.59). Reproducibility was excellent with an interclass correlation coefficient of 0.83 (95% confidence interval 0.80 to 0.86) for the ST score and 0.84 (0.80 to 0.87) for the IT score. In total, 793 (77.5%) patients reported an unacceptable symptomatic state, thereby setting the PASS for the long covid IT score at 30 (28 to 33).

Conclusions

The long covid ST and IT tools, constructed from patients’ lived experiences, provide the first validated and reliable instruments for monitoring the symptoms and impact of long covid.

Short summary

We developed the long covid Symptom and Impact Tools (ST and IT) from the experiences of 492 patients, captured during a survey with open-ended questions, and assessed their validity and reliability in a sample of 1022 patients with long covid.
Equitable Vaccine Access within an Age-Based Framework
Authors: Cobo-Lewis Alan B
Published: March 2021

Objectives

Several states have adopted age-based prioritization for COVID-19 vaccine eligibility (also prioritizing teachers and child care workers) because it is simple (especially when age is quantized by decade) and age is strongly associated with COVID-19 mortality. But this approach raises equity concerns based in law and ethics. This study proposes data-driven solutions for equitable policy that retains the advantages of an age-based approach.

Methods

Using data from CDC and U.S. Census Bureau, I analyzed 507,227 COVID-19 deaths in the U.S. by age and race-ethnicity and compared the risk ratios to published data on risk ratios for other conditions.

Results

COVID-19 mortality in the U.S. rose 2.59-fold per decade of life [95% confidence interval (2.52, 2.66)]. Down syndrome, organ transplantation, and intellectual/developmental disability have risk ratios for COVID-19 mortality that exceed that.

Conclusions

People with specific conditions (including certain disabilities and certain medical conditions) associated with a risk ratio of 2.59 or 6.71 should be granted vaccine eligibility along with people 10 or 20 years older, respectively. Along with additional recommendations on data collection and reporting, this could help address equity within an age-based framework.

3-Question Summary Box

Some states have adopted age-only prioritization for COVID-19 vaccine access, quantized by decade of life, because it is simple, and age has a strong association with COVID-19 mortality. But this raises concerns based in law and ethics.

This study quantifies the age effect and documents that COVID-19 mortality increases 2.59-fold per decade of life—a smaller increase than some conditions.

People with conditions associated with at least 2.59-fold COVID-19 mortality should be granted vaccine eligibility along with people at least 10 years older.
Depressive rumination is correlated with brain responses during self-related processing
Authors: Hsu Tzu-Yu , Liu Tzu-Ling , Cheng Paul Z. , Lee Hsin-Chien , Lane Timothy J. , Duncan Niall W.
Published: March 2021

Background

Rumination, a tendency to focus on negative self-related thoughts, is a central symptom of depression. Studying the self-related aspect of such symptoms is challenging due to the need to distinguish self effects per se from the emotional content of task stimuli. This study employs an emotionally neutral self-related paradigm to investigate possible altered self processing in depression and its link to rumination.

Methods

People with unipolar depression (MDD; n = 25) and controls (n = 25) underwent task-based EEG recording. Late event-related potentials were studied along with low frequency oscillatory power. EEG metrics were compared between groups and correlated with depressive symptoms and reported rumination.

Results

The MDD group displayed a difference in late potentials across fronto-central electrodes between self-related and non-self-related conditions. No such difference was seen in controls. The magnitude of this difference was positively related with depressive symptoms and reported rumination. MDD also had elevated theta oscillation power at central electrodes in self-related conditions, which was not seen in controls.

Conclusions

Rumination appears linked to altered self-related processing in depression, independently of stimuli-related emotional confounds. This connection between self-related processing and depression may point to self-disorder being a core component of the condition.
Parthanatos-inducing zinc agent C010DS-Zn elicits anti-tumor immune responses involving T cells and macrophagesin vivo
Authors: Chung Jinhyuk Fred , Her Zhisheng , Kong Wai Mun , Chen Qingfeng
Published: March 2021

Immune checkpoint inhibitors opened a new horizon in cancer therapy by enabling durable and complete responses in patients, but their wider application against general solid cancers has been hampered by the lack of a broadly acting anti-cancer immune response initiating agents. Parthanatos is a previously unexplored immunogenic programmed necrosis mechanism that is triggered by the hyperactivation of PARP DNA repair and executed by an efficient DNA-fragmentation mechanism. We developed a proprietary macromolecular zinc complex agent C010DS-Zn that efficiently induced parthanatos against 4T1 murine cancer cellsin vitro, which was characterized as PARP-mediated necrotic death with massive DNA damages.Ex vivoscreening of its cytotoxicity against a panel of 53 low-passage human solid cancer PDX tumor fragments demonstrated its consistent delivery of characteristically DNA-damaging cell death that was unseen in the corresponding apoptosis positive controls. Further characterization of itsin vivotreatment effects versus the immunosuppressive 4T1-Balb/c and immunogenic CT26-Balb/c syngeneic cancer models showed that sufficiently high intravenous C010DS-Zn treatments led to robust initiation of the tumor-suppressed antitumor immune compartments such as T cells and macrophages. At lower non-anticancer doses, C010DS-Zn treatment still led to significantly reduced macrophage content and inflammation in the 4T1 tumor, suggesting its potential utility against macrophage-mediated inflammations such as those seen in MIS-C or COVID19. Given the observation of its low serum bioavailability in a rat pharmacokinetic study, these results suggest potential development opportunities for C010DS-Zn to become a widely applicable immune initiation agent with chemo-like broad applicability upon its pharmacokinetic improvements.
Single-cell proteo-genomic reference maps of the hematopoietic system enable the purification and massive profiling of precisely defined cell states
Authors: Triana Sergio H. , Vonficht Dominik , Jopp-Saile Lea , Raffel Simon , Lutz Raphael , Leonce Daniel , Antes Magdalena , Hernández-Malmierca Pablo , Ordoñez-Rueda Diana , Ramasz Beáta , Boch Tobias , Jann Johann-Christoph , Nowak Daniel , Hofmann Wolf-Karsten , Müller-Tidow Carsten , Hübschmann Daniel , Alexandrov Theodore , Benes Vladimir , Trumpp Andreas , Paulsen Malte , Velten Lars , Haas Simon
Published: March 2021

Single-cell genomics has transformed our understanding of complex cellular systems. However, excessive costs and a lack of strategies for the purification of newly identified cell types impede their functional characterization and large-scale profiling. Here, we have generated high content single-cell proteo-genomic reference maps of human blood and bone marrow that quantitatively link the expression of up to 197 surface markers to cellular identities and biological processes across all major hematopoietic cell types in healthy aging and leukemia. These reference maps enable the automatic design of cost-effective high-throughput cytometry schemes that outperform state-of-the-art approaches, accurately reflect complex topologies of cellular systems, and permit the purification of precisely defined cell states. The systematic integration of cytometry and proteo-genomic data enables measuring the functional capacities of precisely mapped cell states at the single-cell level. Our study serves as an accessible resource and paves the way for a data-driven era in cytometry.
Genomic taxonomic assignment of individual root-knot nematodes
Authors: Sellers Graham S , Jeffares Daniel C , Lawson Bex , Prior Tom , Lunt David H
Published: March 2021

Root-knot nematodes (RKN; genusMeloidogyne) are polyphagous plant pathogens of great economic importance to agriculturalists globally. These species are small, diverse, and can be challenging for accurate taxonomic identification. Many of the most important crop pests confound analysis with simple genetic marker loci as they are polyploids of likely hybrid origin. Here we take a low-coverage, long-read genome sequencing approach to characterisation of individual root-knot nematodes. We demonstrate library preparation for Oxford Nanopore Technologies Flongle sequencing of low input DNA from individual juveniles and immature females, multiplexing up to twelve samples per flow cell. Taxonomic identification with Kraken 2 (ak-mer-based taxonomic assignment tool) is shown to reliably identify individual nematodes to species level, even within the very closely relatedMeloidogyne incognitagroup. Our approach forms a robust, low-cost, and scalable method for accurate RKN species diagnostics.