title: Association between SARS-Cov-2 infection during pregnancy and adverse pregnancy outcomes: a re-analysis of data from Wei et al. (2021).

abstract:
BackgroundWei et al. have published a meta-analysis (MA) which aimed to "evaluate the association between SARS-CoV-2 infection during pregnancy and adverse pregnancy outcomes".

Using classical random-effects model, they found that SARS-CoV-2 infection was associated with preeclampsia, preterm birth and stillbirth.

Performing MA with low event rates or with few studies may be challenging as MA relies on several within and between study distributional assumptions.

Methodsto assess the robustness of the results provided by Wei et al., we performed a sensitivity analysis using several frequentist and Bayesian meta-analysis methods. We also estimated fragility indexes.

ResultsFor eclampsia (patients with Covid-19 vs without), the confidence intervals of most frequentist models contain 1. All beta-binomial models (Bayesian) lead to credible intervals containing 1. The prediction interval, based on DL method ranges from 0.75 to 2.38. The fragility index is 2 for the DL method.

For preterm, the confidence (credible) intervals exclude 1. The prediction interval is broad, ranging from 0.84 to 20.61. The fragility index ranges from 27 to 10.

For stillbirth, the confidence intervals of most frequentist models contain 1. Six Bayesian MA models lead to credible intervals containing 1.The prediction interval ranges from 0.52 to 8.49. The fragility index is 3.

InterpretationGiven the available data and the results of our broad sensitivity analysis, we can only suggest that SARS-CoV-2 infection during pregnancy is associated to preterm, and may be associated to preeclampsia. For stillbirth, more data are needed as none of the Bayesian analyses are conclusive.

category: obstetrics and gynecology


title: The Effectiveness of Telephone Intervention for Improving Patient Adherence to Medication among Diabetic Patients: A Systematic Review and Meta-analysis of Randomized Trials

abstract:
IntroductionDiabetes is one of the chronic diseases that requires adherence to prescribed medications. With the current pandemic, mobile technology plays a role in caring for patients remotely.

ObjectiveTo determine the effectiveness of telephone intervention (phone call and text message) on medication adherence among diabetic patients.

MethodologyRandomized controlled trials were searched in Cochrane Library, PubMed, Herdin, BMC Health Services Research using combination of terms through boolean operators ("phone message" OR "phone call" AND ("medication adherence" AND "diabetes") which compared telephone intervention vs usual care. mean, sample size and standard deviation of Medication Adherence in each study were extracted. Review Manager 5.4 software was used for statistical analysis.

ResultsThree trials met the inclusion criteria and were included in this study. The telephone intervention did not result in statistically significant improvement in medication adherence among diabetics (pooled mean difference: 0.05 95%CI -.08 to 0.17) Conclusion: The intervention was no more effective than the usual care. However, mobile use has potential application for remote care during this pandemic.

category: health systems and quality improvement


title: Thyroid function and the risk of Alzheimer's disease: A Mendelian Randomisation study

abstract:
BackgroundObservational epidemiological studies propose that variations in thyroid function are associated with the risk of dementia; however, there have been inconsistent findings regarding the direction of the association. It is still unclear whether these associations are causal or not. We aim to test whether genetically determined variation within the normal range of thyroid function and hypothyroidism are causally associated with the risk of Alzheimers disease (AD).

MethodsMendelian Randomisation (MR) analyses_using genetic instruments associated with normal range TSH and FT4 levels. Secondary analyses included investigation of the role of hypothyroidism. Bidirectional MR was conducted to address the presence of a potential reverse causal association. Summary statistics were obtained from the ThyroidOmics Consortium and the latest available GWAS meta-analyses.

ResultsMR analyses show a causal association between normal range TSH levels and decreased risk of AD (OR = 0.98, 95% CI=0.97-0.99, p = 0.01). There was no evidence for a causal association between FT4 or hypothyroidism and Alzheimers disease. Bidirectional MR did not show any effect of Alzheimers disease on TSH or FT4.

ConclusionsThis Mendelian Randomisation study shows for the first time a causal association between normal-range thyroid function and AD. Future studies should clarify the underlying pathophysiological mechanisms.

category: endocrinology


title: Susceptibility of zero community transmission regimes to new variants of SARS-CoV-2: a modelling study of Queensland

abstract: We used an agent-based model Covasim to assess the risk of sustained community transmission of SARS-CoV-2/COVID-19 in Queensland (Australia) in the presence of high-transmission variants of the virus. The model was calibrated using the demographics, policies, and interventions implemented in the state. Then, using the calibrated model, we simulated possible epidemic trajectories that could eventuate due to leakage of infected cases with high-transmission variants, during a period without recorded cases of locally acquired infections, known in Australian settings as "zero community transmission". We also examined how the threat of new variants reduces given a range of vaccination levels. Specifically, the model calibration covered the first-wave period from early March 2020 to May 2020. Predicted epidemic trajectories were simulated from early February 2021 to late March 2021. Our simulations showed that one infected agent with the ancestral (A.2.2) variant has a 14% chance of crossing a threshold of sustained community transmission (SCT) (i.e., > 5 infections per day, more than 3 days in a row), assuming no change in the prevailing preventative and counteracting policies. However, one agent carrying the alpha (B.1.1.7) variant has a 43% chance of crossing the same threshold; a threefold increase with respect to the ancestral strain; while, one agent carrying the delta (B.1.617.2) variant has a 60% chance of the same threshold, a fourfold increase with respect to the ancestral strain. The delta variant is 50% more likely to trigger SCT than the alpha variant. Doubling the average number of daily tests from [~] 6,000 to 12,000 results in a decrease of this SCT probability from 43% to 33% for the alpha variant. However, if the delta variant is circulating we would need an average of 100,000 daily tests to achieve a similar decrease in SCT risk. Further, achieving a full-vaccination coverage of 70% of the adult population, with a vaccine with 70% effectiveness against infection, would decrease the probability of SCT from a single seed of alpha from 43% to 20%, on par with the ancestral strain in a naive population. In contrast, for the same vaccine coverage and same effectiveness, the probability of SCT from a single seed of delta would decrease from 62% to 48%, a risk slightly above the alpha variant in a naive population. Our results demonstrate that the introduction of even a small number of people infected with high-transmission variants dramatically increases the probability of sustained community transmission in Queensland. Until very high vaccine coverage is achieved, a swift implementation of policies and interventions, together with high quarantine adherence rates, will be required to minimise the probability of sustained community transmission.

category: epidemiology


title: Risk of sustained SARS-CoV-2 transmission in Queensland, Australia


title: Automatic Electrophysiological Noise Reduction and Epileptic Seizure Detection for Stereoelectroencephalography

abstract: The objective of this study was to develop a computational algorithm capable of locating artifacts and identifying epileptic seizures, which specifically implementing in clinical stereoelectroencephalography (SEEG) recordings. Based on the nonstationary nature and broadband features of SEEG signals, a comprehensive strategy combined with the complex wavelet transform (CWT) and multi-layer thresholding method was implemented for both noise reduction and seizure detection. The artifacts removal pipeline integrated edge artifact removal, discrete spectrum analysis, and peak density evaluation. For automatic seizure detection, integrated power analysis and multi-dynamic thresholding were applied. The F1-score was applied to evaluate overall performance of the algorithm. The algorithm was tested using expert-marked, double-blinded, clinical SEEG data from seven patients undergoing presurgical evaluation. This approach achieved the F1 score of 0.86 for noise reduction and 0.88 for seizure detection. This offline-approach method with minimum parameter tuning procedures and no prior information required, proved to be a feasible and solid solution for clinical SEEG data evaluation. Moreover, the algorithm can be improved with additional tuning and implemented with machine learning postprocessing pipelines.

category: neurology


title: Potential environmental transmission routes of SARS-CoV-2 inside a large meat processing plant experiencing COVID-19 clusters

abstract:
Worldwide exceptionally many COVID-19 clusters were observed in meat processing plants. Many contributing factors, promoting transmission, were suggested, including climate conditions in cooled production rooms favorable for environmental transmission but actual sampling studies are lacking. We aimed to assess SARS-CoV-2 contamination of air and surfaces to gain insight in potential environmental transmission in a large Dutch meat processing plant experiencing COVID-19 clusters.

We performed SARS-CoV-2 screening of workers operating in cooled production rooms and intensive environmental sampling during a two-week study period in June 2020. Sampling of air (both stationary and personal), settling dust, ventilation systems, and sewage was performed. Swabs were collected from high-touch surfaces and workers hands. Screening of workers was done using oronasopharyngeal swabs. Samples were tested for presence of SARS-CoV-2 RNA by RT-qPCR.

Of the 76 (predominantly asymptomatic) workers tested, 27 (35.5%) were SARS-CoV-2 RNA positive with modest to low viral loads (Ct[≥]29.7). In total, 6 out of 203 surface swabs were positive (Ct [≥]38), being swabs taken from communal touchscreens/handles. One of the 12 personal air samples and one of the 4 sewage samples were positive, RNA levels were low (Ct[≥]38). All other environmental samples tested negative.

Although one-third of workers tested SARS-CoV-2 RT-PCR positive, environmental contamination was limited. Hence widespread transmission of SARS-CoV-2 via air and surfaces was considered unlikely within this plant at the time of investigation in the context of strict COVID-19 control measures in place.

category: infectious diseases


title: Pulmonary thromboembolism in patients after COVID-19 - predictive indicators for correct diagnosis

abstract: IntroductionInfection caused by SARS-CoV-2 has been shown to lead to significant procoagulant events, in some cases involving life-threatening pulmonary thromboembolism (PE). Additional conditions complicating the diagnosis are the presence of risk factors for PE in almost all patients with COVID-19, as well as the overlap of the clinical presentation between PE and COVID-19. Materials and Methods: [T]herefore we conducted a single-center study at the Heart and Brain Hospital, Pleven in the period December 2020-February 2021. It included 27 consecutively hospitalized patients with recent pneumonia caused by Covid-19 and clinical presentation referring to PE. The cohort was divided into two groups - with and without a definitive diagnosis of PE, proven by CT pulmoangiography. The aim was to find the indicators that predict the presence of PE in patients with acute or Post-acute COVID-19 conditions. Results: Our results show that part of the ECG criteria - S-wave over 1.5 mm in I lead and aVL (p = 0.007), Q-wave in III and aVF (p = 0.020), as well as the D-dimer as quantitative variable (p = 0.025) proved to be independent predictors of PE. The RV/ LV diameter ratios [≥]1.0 as well as right ventricular dysfunction showed sensitivity 62.5%, specificity 100%, positive predictive value 100% and negative such 86.4% to verify the PE diagnosis[Lcy] We suggest that the cut-off value of D-dimer of 1032 ng/ml has an optimal sensitivity (Se) of 87.5%, specificity (Sp) 57.9%, positive a predictive value (PPV) 46.7% and negative predictive value (NPV) of 91.7% for the diagnosis of PE (p = 0.021). Conclusion: Against the background of acute and Post-acute COVID-19 conditions ECG and EchoCG criteria remain predictive of PE. We suggest that a higher D-dimer cut-off value should be applied in COVID-19 and post-COVID-19 patients in order to confirm/dismiss the diagnosis PE.

category: cardiovascular medicine


title: Into the thirteenth Month: A Case Study on the Outbreak Analytics and Modeling the spread of SARS-CoV-2 Infection in Pune City, India

abstract: With more than 140 million people infected globally and 3 million deaths, the COVID 19 pandemic has left a lasting impact. A modern response to a pandemic of such proportions needs to focus on exploiting all available data to inform the response in real-time and allow evidence-based decision-making. The intermittent lockdowns in the last 13 months have created economic adversity to prevent anticipated large-scale mortality and relax the lockdowns have been an attempt at recovering and balancing economic needs and public health realities. This article is a comprehensive case study of the outbreak in the city limits of Pune, Maharashtra, India, to understand the evolution of the disease and transmission dynamics starting from the first case on March 9, 2020. A unique collaborative effort between the Pune Municipal Corporation (PMC), a government entity, and the Pune knowledge Cluster (PKC) allowed us to layout a context for outbreak response and intervention. We report here how access to granular data for a metropolitan city with pockets of very high-density populations will help analyze, in real-time, the dynamics of the pandemic and forecasts for better management and control of SARS-CoV-2. Outbreak data analytics resulted in a real-time data visualization dashboard for accurate information dissemination for public access on the epidemics progress. As government agencies craft testing and vaccination policies and implement intervention strategies to mitigate a second wave, our case study underscores the criticality of data quality and analytics to decode community transmission of COVID-19.


title: Impact of COVID-19 on deaths from respiratory diseases: Panel Data evidence from Chile.

abstract:
The COVID-19 pandemic has left other pathologies commonly present in the population in a secondary context. Therefore, it is necessary to study the evolution of these diseases in the presence or absence of COVID-19.

ObjectivesThe present study had the following objectives: 1. To evaluate the relationship between the COVID-19 epidemic and the possible decrease in deaths from respiratory diseases in Chile. 2 Study the relationship between meteorological variables and severity of COVID-19 with respect to deaths from respiratory diseases from January 2018 to February 2021.

MethodsThe variable number of deaths due to respiratory diseases in Chile was analyzed considering the monthly records of meteorological variables (temperature, precipitation and humidity) in each Region of Chile and severity of COVID-19, to evaluate the mortality trend before and after the pandemic. For this, different Non-Observable Heterogeneity Models for Panel Data were used

ResultsOur findings show that among the variables that affect the mortality rate from respiratory diseases, there are the number of deaths from COVID-19 that has a negative effect, the number of patients with COVID-19 in intensive care unit (ICU) that has a positive effect and the minimum temperature with a negative effect. These results are supported by the application of the panel regression with one-way random-effects models.

ConclusionThis study revealed that there is an unexpected reduction in deaths from respiratory diseases in Chile in the post-pandemic period. Therefore, it can be concluded that this variable decreased with the appearance of the COVID-19 pandemic.


title: Evaluating the role of common risk variation in the recurrence risk of schizophrenia in multiplex schizophrenia families

abstract: Multiplex families have higher recurrence risk of schizophrenia compared to the families of sporadic cases, but the source of this increased recurrence risk is unknown. We used schizophrenia genome-wide association study data (N=156,509) to construct polygenic risk scores (PRS) in 1,005 individuals from 257 multiplex schizophrenia families, 2,114 ancestry-matched sporadic cases, and 2,205 population controls, to evaluate whether increased PRS can explain the higher recurrence risk of schizophrenia in multiplex families compared to ancestry-matched sporadic cases. Using mixed-effects logistic regression with family structure modeled as a random effect, we show that SCZ PRS in familial cases does not differ significantly from sporadic cases either with, or without family history (FH) of psychotic disorders (All sporadic cases p = 0.92, FH+ cases p = 0.88, FH-cases p = 0.82). These results indicate that increased burden of common schizophrenia risk variation as indexed by current SCZ PRS, is unlikely to account for the higher recurrence risk of schizophrenia in multiplex families. In the absence of elevated PRS, segregation of rare risk variation or environmental influences unique to the families may explain the increased familial recurrence risk. These findings also further validate a genetically influenced psychosis spectrum, as shown by a continuous increase of common SCZ risk variation burden from unaffected relatives to schizophrenia cases in multiplex families. Finally, these results suggest that common risk variation loading are unlikely to be predictive of schizophrenia recurrence risk in the families of index probands, and additional components of genetic risk must be identified and included in order to improve recurrence risk prediction.

category: psychiatry and clinical psychology


title: A decade of Acceptability Research with Adolescents in Africa: Systematic review and evidence map

abstract:
Interventions aimed at improving adolescent developmental outcomes are more likely to be successful if the young people they target find them acceptable. However, no standard definitions or indicators exist to assess acceptability, acceptability research with adolescents in LMICs is still limited, and no known reviews synthesise the evidence from Africa.

We conducted a systematic review of peer-reviewed studies assessing intervention acceptability with young adults (aged 10-24) in Africa, published between January 2010 and June 2020. This paper maps and qualitatively synthesizes the scope, characteristics, and findings of these studies, including definitions of acceptability, methods used, the type and objectives of interventions assessed, and overall findings on adolescent acceptability.

The review was carried out in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Key word searches generated 4692 unique records and 55 final eligible studies, assessing 60 interventions. Most studies were conducted in Southern Africa, of which 32 jointly in South Africa and Uganda. The majority of interventions assessed for acceptability could be classified as HIV or HPV vaccine interventions (10), E-health (10), HIV testing interventions (8), support group interventions (7) and contraceptive interventions (6). The objectives of most interventions were linked to SDG3, specifically to HIV and sexual and reproductive health. Acceptability was overall high among these published studies. 22 studies provided reasons for acceptability or lack thereof, some specific to particular types of interventions and others common across intervention types.

Our review exposes considerable scope for future acceptability research and review work. This should include: extending acceptability research beyond the health (and particularly HIV) sector and to regions in Africa where this type of research is still scarce; including adolescents earlier, and potentially throughout the intervention process; further conceptualising the construct of acceptability among adolescents and beyond, and examining the relationship between acceptability and uptake.

Key QuestionsO_ST_ABSWhat is already known?C_ST_ABSO_LIAddressing the developmental needs of adolescents in African countries is critical if the continent is to achieve its sustainable development goals (SDGs).
C_LIO_LIMany interventions aimed at strengthening adolescent developmental outcomes have not achieved desired impact, and adolescent involvement is often poorly envisaged and implemented.
C_LIO_LIUptake and effectiveness of interventions is likely to be higher if these interventions are acceptable to adolescent end-users.
C_LI

What are the new findings?O_LIAcceptability of interventions assessed in Africa was generally high among adolescents.
C_LIO_LIUnderstanding of the intervention, ease of use, adequate emotional support, autonomy, confidentiality and protection from stigma were key overarching themes explaining why young people found interventions acceptable
C_LI

What do the new findings imply?O_LIIntervention developers and implementers across the continent should pay attention to these key aspects of interventions and their delivery.
C_LIO_LIIt is important to strengthen adolescents understanding of interventions, involve adolescents early on in intervention development, and engage with the broader context within which adolescent acceptability is shaped.
C_LIO_LIThere is a need for more acceptability research in important areas for adolescent development beyond (physical) health and, within the health sector, beyond HIV.
C_LI

category: public and global health


title: RGC-TBRS Personal Air Pollutant Exposure versus Health Condition and Perception Pilot Study for Young Asthmatics in Hong Kong (2019/2020)

abstract: This is a report of the RGC-TBRS funded observational pilot study which examines the effects of personal exposures to three types of air pollutants, namely, PM1.0, PM2.5, and PM10, on personal health condition and perception of young asthmatics (aged 12 - 15) in Hong Kong. This is the first study to investigate the relationship between PM1.0 and FEV1 and FVC of young asthmatics in Hong Kong, based on personal exposures obtained from portable sensors. Our preliminary results show that a higher level of PM1.0, PM2.5 and PM10 would deteriorate the health conditions of young asthmatics in HK. All correlations between particulates and lung functions are significant and negative, including PM1.0 exposure vs. FEV1 (R2=12%; p=0.023), PM1.0 exposure vs. FVC (R2=15%; p=0.010), PM2.5 exposure vs. FEV1 (R2=13%; p=0.019), PM2.5 exposure vs. FVC (R2=16%; p=0.008), PM10 exposure vs. FEV1 (R2=14%; p=0.012), and PM10 exposure vs. FVC (R2=18%; p=0.005). Moreover, after accounting for covariates, including age, gender, body mass index (BMI), temperature, and relative humidity, we found a significant relationship between PM1.0 exposure vs. FVC (Coefficient=-0.1224; p=0.032), PM2.5 exposure vs. FVC (Coefficient=-0.1177; p=0.021), PM10 exposure vs. FEV1 (Coefficient=-0.0703; p=0.019), and PM10 exposure vs. FVC (Coefficient=-0.1204; p=0.006). Further, using the pilot study data, we have performed a power analysis to estimate the sample size for our follow-up main study. Based on the primary null hypothesis that personal PM exposure would not change the FEV1 and FVC of young asthmatics in HK, the lowest sample size that gives 80% power at a 5% significance level is 107. Hence, the sample size (or the total number of participated asthma subjects) expected for the follow-up longitudinal clinical study should be 125 (after adjusting for the non-compliance and withdrawal of subjects). Our pilot study has demonstrated the feasibility of research into the effects of personal air pollutant exposure on health condition and health perception. Our follow-up study will address the challenges identified in the pilot study, based on the proposed follow-up actions for subject engagement, data collection, and data analysis.


title: Perceptions of immunity and vaccination certificates among the general population of Geneva, Switzerland.

abstract:
As of June 2021, the European Union (EU) and Switzerland have published information about the introduction of COVID certificates in order to facilitate the safe free movement of their citizens. With implementation underway, little is known about the public perception of such certificates with potential differences in acceptability among individuals.

In March 2021, a self-administered online questionnaire was proposed to all individuals 18 years and older participating in the longitudinal follow-up of population-based seroprevalence studies in Geneva, Switzerland. The questionnaire covered aspects of individual and collective benefits, while allowing participants to select contexts in which vaccination certificates should be presented. Results were presented as the proportion of individuals agreeing or disagreeing with the implementation of vaccination certificates, selecting specific contexts where certificates should be presented, and agreeing or disagreeing with the potential risks related to certificates. Logistic regression was used to calculate odds ratios for factors associated with certificate non-acceptance.

Overall, 4,056 individuals completed the questionnaire (response rate 77.6%; mean age 53.3 {+/-} standard deviation 14.4 years; 56.1% were women). About 61.0% of participants agreed or strongly agreed that a vaccination certificate was necessary in certain contexts; and 21.6% believed there was no context where vaccination certificates should be presented. Contexts where a majority of participants perceived a vaccination certificate should be presented included jobs where others would be at risk of COVID-related complications (60.7%), jobs where employees would be at risk of getting infected (58.7%), or to be exempt from quarantine when traveling abroad (56.1%). Contexts where fewer individuals perceived the need for vaccination certificates to be presented were participation in large gatherings (36.9%), access to social venues (35.5%), or sharing the same workspace (21.5%). Younger age, an absence of willingness to get vaccinated, and an absence of belief in vaccination as an important step in surmounting the pandemic were factors associated with certificate non-acceptance.

This large population-based study showed that the general adult population in Geneva, Switzerland, agreed with the implementation of vaccination certificates in work-related and travel-related contexts. However, this solution was perceived as unnecessary for access to large gatherings or social venues, or to share the same workspace. Differences were seen with gender, age, education, socio-economic status, and vaccination willingness and perception, highlighting the importance of taking personal and sociodemographic variations into consideration when predicting acceptance of such certificates.


title: Temporal Analysis of Social Determinants Associated with COVID-19 Mortality

abstract:
This study examines how social determinants associated with COVID-19 mortality change over time. Using US county-level data from July 5 and December 28, 2020, the effect of 19 high-risk factors on COVID-19 mortality rate was quantified at each time point with negative binomial mixed models. Then, these high-risk factors were used as controls in two association studies between 40 social determinants and COVID-19 mortality rates using data from the same time points. The results indicate that counties with certain ethnic minorities and age groups, immigrants, prevalence of diseases like pediatric asthma and diabetes and cardiovascular disease, socioeconomic inequalities, and higher social association are associated with increased COVID-19 mortality rates. Meanwhile, more mental health providers, access to exercise, higher income, chronic lung disease in adults, suicide, and excessive drinking are associated with decreased mortality. Our temporal analysis also reveals a possible decreasing impact of socioeconomic disadvantage and air quality, and an increasing effect of factors like age, which suggests that public health policies may have been effective in protecting disadvantaged populations over time or that analysis utilizing earlier data may have exaggerated certain effects. Overall, we continue to recognize that social inequality still places disadvantaged groups at risk, and we identify possible relationships between lung disease, mental health, and COVID-19 that need to be explored on a clinical level.

CCS CONCEPTSO_LIApplied computing [->] Health informatics.
C_LI


title: Quantifying the Tradeoff Between Energy Consumption and the Risk of Airborne Disease Transmission for Building HVAC Systems

abstract: It has been established that combinations of increased ventilation, improved filtration, and other HVAC techniques can reduce the likelihood of airborne disease transmission in buildings. However, with only qualitative guidance, it is difficult for building managers to make informed decisions. Furthermore, the possible actions almost always require additional energy consumption, which is generally not well characterized. To address this knowledge gap, we propose simplified physics-based models that can be used to quantify both the expected transmission rate and the associated energy consumption that result from HVAC system operation. By formulating all disinfection mechanisms in terms of "equivalent outdoor air", a common basis is established for comparing and combining different strategies. The transmission rate can thus be modeled by considering the airborne concentration of infectious particles that would result from an infector in the space. Energy consumption is then estimated by considering the change in HVAC variables and applying standard analysis. To illustrate the insights provided by these models, we present examples of how the proposed analysis can be applied to specific spaces, highlighting the fact that underlying transmission risk and energy-optimal disinfection strategies can vary significantly based on space characteristics.


title: Network analysis shows decreased ipsilesional structural connectivity in glioma patients

abstract:
Gliomas that infiltrate networks and systems, such as the motor system, often lead to substantial functional impairment in multiple systems. Network-based statistics (NBS) allow to assess local network differences (1) and graph theoretical analyses (2) enable investigation of global and local network properties. Here, we used network measures to characterize glioma-related decreases in structural connectivity by comparing the ipsi- with the contralesional hemispheres of patients and correlated findings with neurological assessment.

We found that lesion location resulted in differential impairment of both short and long connectivity patterns. Network analysis showed reduced global and local efficiency in the ipsilesional hemisphere compared to the contralesional hemispheric networks. In network science, reduced global and local efficiency reflect the impairment of information transfer across different regions of a network.

One-Sentence SummaryNetwork analyses show glioma-related decreased ipsilesional structural connectivity and correlates with neurological status.


title: Prefrontal Cortex Definitions and Their Use in Distinguishing Pornography Addicted Juveniles

abstract:
Background and aimsIncreasing popularity of Internet has exposed our children pornography addiction. As in other types of addiction, it affects a brain region known as prefrontal cortex (PFC), which is important in executive functions and inhibitory control. However, this region was loosely defined, and there was no consensus for that definition. We aimed to use volumetric MRI in finding the defining region of PFC which would be suitable in distinguishing pornography addicted juveniles.

MethodsWe enrolled 30 juveniles (12-16 y.o.) consisting of 15 pornography addiction and 15 non-addiction subjects. We proposed several models of PFC definition from mix-and-matched subregions, consisting of orbitofrontal (OFC), inferior frontal gyrus (IFG; pars orbitalis, opercularis, and triangularis), dorsolateral PFC (DLPFC), and anterior cingulate (ACC). Suitable PFC definition was defined as models which volume statistically different between both groups. Brain volumetric was measured using 3D-T1 3T MRI images and analyzed using FreeSurfer(R) for automatic cortical reconstruction and brain segmentation (recon-all command).

ResultsWe found significant differences between groups in 6 models, which mainly included OFC, ACC, and DLPFC, with models devoid of DLPFC had lowest mean differences.

ConclusionThe most suitable definition of PFC for pornography addiction study should consist of OFC, ACC, and especially DLPFC. Inferior frontal gyrus pars orbitalis was not necessary for this purpose, but may increase effect size if it is included.


title: Ilioinguinal versus modified Stoppa approach for open reduction and internal fixation of displaced acetabular fractures: A Protocol for Systematic Review and Meta-Analysis

abstract:
BackgroundThe fracture of the acetabulum is one of the most challenging fractures to manage and operate for orthopaedic surgeons. To get a good surgical outcome, anatomical reduction of fractures and reconstruction of the joint is of utmost importance. To achieve a good postoperative outcome an appropriate surgical approach is necessary to achieve an anatomical reduction of fractures and fewer complications.

ObjectiveThe current review aims to compare the outcomes of the ilioinguinal versus modified Stoppa approach for open reduction and internal fixation (ORIF) of displaced acetabular fractures by analyzing the evidence from the current literature.

MethodsA systematic review of the literature will be conducted in accordance with the PRISMA guidelines. The primary searches will be conducted on the Medline (PubMed), Embase, Scopus, and Cochrane Library databases, using a pre-defined search strategy. The studies of any design in the English language will be included which compared the outcomes of the ilioinguinal and modified Stoppa approach for ORIF of displaced acetabular fractures and reported at least one outcome of interest. Studies that do not compare the outcomes of the ilioinguinal and modified Stoppa approach for the treatment of displaced acetabular fractures in adults (>18 years of age), case reports, conference abstracts, posters, book chapters, review articles, biomechanical studies, technical tips, cadaveric studies, and articles not in the English language will be excluded. Both qualitative and quantitative analyses will be done. Qualitative analysis will be done using appropriate tables and diagrams. Wherever feasible, quantitative analysis to be done with the appropriate software. The risk-of-bias assessment will be done using the MINORS tool for the non-randomized comparative studies, and The Cochrane Collaborations risk-of-bias tool will be used for randomized control trials.

category: orthopedics


title: Examining the epigenetic mechanisms of childhood adversity and sensitive periods: a gene set-based approach

abstract:
BackgroundSensitive periods are developmental stages of heightened plasticity when exposure to childhood adversity may exert lasting impacts. A few biological pathways are known to play key roles in regulating sensitive period plasticity across brain development. Epigenetic mechanisms including DNA methylation (DNAm) may provide a means through which life experiences during sensitive periods induce long-term biological changes. In the current study, we investigated the possibility that adversity during sensitive periods led to DNAm changes in genes that regulate the timing and duration of sensitive periods in development.

MethodsUsing childhood adversity data and genome-wide DNAm profiles from the Avon Longitudinal Study of Parents and Children (n=785), we summarized DNAm variation of CpG sites in the promoters of genes regulating sensitive periods with the first two principal components (PCs). DNAm summaries were calculated for genes regulating sensitive period opening (ngenes=15), closing (ngenes=36), and expression/duration (ngenes=8). We then performed linear discriminant analysis to test associations between these DNAm summaries and the timing of exposure to seven types of adversity.

ResultsSexual or physical abuse and financial hardship during middle childhood (6-7 years) were associated with DNAm of genes regulating the onset and duration of sensitive periods. Sensitivity analyses assessing the presence of any exposure before age 7 and a composite measure of adversity yielded fewer signals, highlighting the importance of accounting for timing and adversity type.

ConclusionsWith our novel gene set-based approach, we have uncovered suggestive evidence that epigenetic regulation of developmental plasticity may be affected by early life adversity. The complementarity of our gene-level view of the epigenome to the more common and granular epigenome-wide association study may yield novel mechanistic insights not only for adversity but also for other exposures and outcomes.

category: genetic and genomic medicine


title: Integrating a Polygenic Risk Score for Coronary Artery Disease as a Risk Enhancing Factor in the Pooled Cohort Equation is Cost-effective in a US Health System

abstract:
ImportanceThe pooled cohort equation (PCE) is used to determine an individuals 10-year risk (low, borderline, intermediate, or high) of atherosclerotic cardiovascular disease (ASCVD) but it fails to identify all individuals at high risk. Those with borderline or intermediate risk require additional risk enhancing factors to guide preventive therapy decisions. Including a polygenic risk score (PRS) for coronary artery disease as a risk enhancing factor improves precision in determining the risk of ASCVD and informs decisions for prevention therapy.

ObjectiveTo assess the cost-effectiveness of integrating PRS for coronary artery disease with the PCE to determine an individuals 10-year risk for ASCVD compared to the PCE-alone.

Design, setting, and populationA Markov model was developed on a hypothetical cohort of 40-year-old individuals in the US with borderline or intermediate PCE 10-year risk for ASCVD who fall in the top quintile of the PRS distribution and are not on preventive therapy (e.g., statins). Model transition probabilities and economic costs came from existing literature with costs reflecting a payer perspective and inflation-adjusted to 2019 US$.

InterventionsThe modeled strategies were: (1) the PCE-alone and (2) the PCE with PRS for coronary artery disease as a risk enhancing factor. Analyses were performed at 5 year, 10 year, and lifetime time horizons.

Main outcomes and measuresQuality-adjusted life-years (QALYs) gained, acute coronary syndromes and ischemic stroke events prevented, mean costs, and incremental cost-effectiveness ratios (ICER) were measured. One-way, two-way, and probabilistic sensitivity analyses were used to assess uncertainty in parameter estimates. Future costs and health benefits were discounted at an annual rate of 3%.

ResultsCompared to the PCE-alone, PCE+PRS was cost-saving, effective and cost-effective (dominant). A health system would save more than $500, $2,300, and $9,000 per additional high-risk individual identified using PCE+PRS and prevent 27, 47 and 83 acute CAD or ischemic stroke events per 1,000 persons in 5 year, 10 year, and lifetime time horizons, respectively.

Conclusions and relevanceImplementing PRS as a risk enhancing factor for CAD among individuals with borderline or intermediate 10-year risk reclassifies individuals as high-risk who would otherwise remain unidentified, prevents future acute CAD and ischemic stroke events, and both saves money and is cost-effective for health systems.

Key PointsO_ST_ABSQuestionC_ST_ABSIs it cost-effective to use polygenic risk scores (PRS) for coronary artery disease (CAD) among individuals with borderline or intermediate risk of atherosclerotic cardiovascular disease (ASCVD) to inform preventive therapy decisions?

FindingsWe modeled a hypothetical cohort of individuals with borderline or intermediate risk of ASCVD who fall in the top quintile of the CAD-PRS distribution but not on preventive therapy. Integrating CAD-PRS in the pooled cohort equation improved quality-adjusted life-years, saved money and was cost-effective.

MeaningIntegrating PRS as an enhancing factor in the pooled cohort equation risk assessment for ASCVD used in current clinical practice was cost-effective.

category: health economics


title: Using deep learning to predict brain age from brain magnetic resonance images and cognitive tests reveals that anatomical and functional brain aging are phenotypically and genetically distinct

abstract: With the world population aging, the prevalence of age-related brain diseases such as Alzheimers, Parkinsons, Lou Gehrigs, and cerebrovascular diseases. In the following, we built brain age predictors by leveraging 46,000 brain magnetic resonance images [MRIs] and cognitive tests from UK Biobank participants. We predicted age with a R-Squared [R2] of 76.4{+/-}1.0% and a root mean squared error of 3.58{+/-}0.05 years and identified the features driving the prediction using attention maps. We defined accelerated brain aging as the difference between brain age (predicted age) and age. Accelerated brain aging is partially heritable (h_g2=35.9{+/-}2.6%), and is associated with 219 single nucleotide polymorphisms [SNPs] in 25 genes (e.g CRHR1, involved in the hypothalamic-pituitary-adrenal pathway). Similarly, it is associated with biomarkers (e.g blood pressure), clinical phenotypes (e.g general health), diseases (e.g diabetes), environmental (e.g smoking) and socioeconomic variables (e.g income and education). We performed the same analysis, this time distinguishing between anatomical (MRI-based) and functional (cognitive tests-based) brain aging. We found the two accelerated aging phenotypes to be phenotypically .112{+/-}.006 correlated and genetically uncorrelated, with distinct SNPs and non-genetic factors associated with each. In conclusion, anatomical and functional brain aging are two distinct, complex phenotypes, which also differ in their genetic and non-genetic factors. Our brain predictors could be used to monitor the effects of emerging rejuvenating therapies on the brain.

category: health informatics


title: Telemedicine and Patient Satisfaction in Saudi Arabia

abstract:
ObjectivesPatients satisfaction with the healthcare system is a good indicator for measuring the quality of health services. This study aims to determine patients satisfaction with different types of telemedicine services (937 Call Center and Sehha Application) provided by the Ministry of Health in Saudi Arabia.

MethodsA cross-section study was conducted to evaluate consumers satisfaction toward telemedicine services in Saudi Arabia. A systematic random sampling method was used to collect consumers from each of the two telemedicine services including 937 medical call center and the Sehha application.

ResultsTwo hundred and forty-nine (249) randomly chosen consumers of 937 medical call center and the Sehha application have been answered the predesigned questionnaire about satisfaction towards different items of the two medical services. Among 249 consumers of telemedicine services, 83.14% of them were satisfied in general with medical services compared to 8.03% of consumers who were not satisfied. The satisfaction percentages toward physicians recommendations, communication skills, listening skills, and waiting time were 77.29%, 83.53%, 85.14%, and 67.87% respectively.

ConclusionTelemedicine applications are commonly used nowadays in most developed countries and some developing countries in order to maximize the delivery of healthcare to patients with different medical conditions. The overall satisfaction rates toward different telemedicine services in Saudi Arabia were high, and there was no significant difference in concern to the satisfaction rates between 937 medical call center and Sehha application. In general, consumers of telemedicine services were satisfied, and most of them considered advising other people to use them.


title: Identification of driver genes for severe forms of COVID-19 in a deeply phenotyped young patient cohort

abstract:
The etiopathogenesis of severe COVID-19 remains unknown. Indeed given major confounding factors (age and co-morbidities), true drivers of this condition have remained elusive. Here, we employ an unprecedented multi-omics analysis, combined with artificial intelligence, in a young patient cohort where major co-morbidities have been excluded at the onset. Here, we established a three-tier cohort of individuals younger than 50 years without major comorbidities. These included 47 "critical" (in the ICU under mechanical ventilation) and 25 "non-critical" (in a noncritical care ward) COVID-19 patients as well as 22 healthy individuals. The analyses included whole-genome sequencing, whole-blood RNA sequencing, plasma and blood mononuclear cells proteomics, cytokine profiling and high-throughput immunophenotyping. An ensemble of machine learning, deep learning, quantum annealing and structural causal modeling led to key findings. Critical patients were characterized by exacerbated inflammation, perturbed lymphoid/myeloid compartments, coagulation and viral cell biology. Within a unique gene signature that differentiated critical from noncritical patients, several driver genes promoted severe COVID-19 among which the upregulated metalloprotease ADAM9 was key. This gene signature was replicated in an independent cohort of 81 critical and 73 recovered COVID-19 patients, as were ADAM9 transcripts, soluble form and proteolytic activity. Ex vivo ADAM9 inhibition affected SARS-CoV-2 uptake and replication in human lung epithelial cells. In conclusion, within a young, otherwise healthy, COVID-19 cohort, we provide the landscape of biological perturbations in vivo where a unique gene signature differentiated critical from non-critical patients. The key driver, ADAM9, interfered with SARS-CoV-2 biology. A repositioning strategy for anti-ADAM9 therapeutic is feasible.

One sentence summaryEtiopathogenesis of severe COVID19 in a young patient population devoid of comorbidities.


title: Multi-centre post-implementation evaluation of SARS-CoV-2 antigen-based point of care tests used for asymptomatic screening of continuing care healthcare workers

abstract:
OBJECTIVESFrequent screening of SARS-CoV-2 among asymptomatic populations using antigen-based point of care tests (APOCT) is occurring globally with limited clinical performance data. The positive predictive value (PPV) of two APOCT used in the asymptomatic screening of SARS-CoV-2 among healthcare workers (HCW) at continuing care (CC) sites across Alberta, Canada was evaluated.

METHODSBetween February 22 and May 2, 2021, CC sites implemented SARS-CoV-2 voluntary screening of their asymptomatic HCW. Onsite testing with Abbott Panbio or BD Veritor occurred on a weekly or twice weekly basis. Positive APOCT were confirmed with a real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) reference method.

RESULTSA total of 71,847 APOCT (17,689 Veritor and 54,158 Panbio) were performed among 369 CC sites. Eighty-seven (0.12%) APOCT were positive, of which 39 (0.05%) confirmed as true positives using rRT-PCR. Use of the Veritor and Panbio resulted in a 76.6% and 30.0% false positive detection, respectively (p<0.001). This corresponded to a 23.4% and 70.0% PPV for the Veritor and Panbio, respectively.

CONCLUSIONSFrequent screening of SARS-CoV-2 among asymptomatic HCW in CC, using APOCT, resulted in a very low detection rate and a high detection of false positives. Careful assessment between the risks vs benefits of APOCT programs in this population needs to be thoroughly considered before implementation.


title: Stepwise evolution of carbapenem-resistance, captured in patient samples and evident in global genomics of Klebsiella pneumoniae

abstract:
The World Health Organization ranks Klebsiella pneumoniae as a priority antimicrobial-resistant (AMR) pathogen requiring urgent study. New strategies for diagnosis and treatment, particularly for those Klebsiella that are classified as carbapenem-resistant Enterobacteriaceae (CRE) need to recognize the increased prevalence of non-carbapenemase producing CRE (non-CP CRE). By integrating diverse Klebsiella genomes with known CRE phenotypes, we successfully identified a synchronized presence of CRE phenotype-related genes in plasmids and chromosomes in comparison to strains with carbapenem susceptible phenotypes. The data revealed a major contribution to CRE comes from the combined effect of chromosome and plasmid genes potentiated by modifications of outer membrane porins. Our computational workflow identified key gene contributors to the non-CP CRE phenotype, including those that lead to an increase of antibiotic expulsion by enhanced efflux pump activity and mobile elements that reduce antibiotic intake, such as IS1 and Tn3-like elements. These findings are consistent with a new model wherein a change to the balance in drug influx and efflux potentiates the ability of some beta-lactamases to enable survival in the presence of carbapenems. Analysis of the large numbers of documented CRE infections, as well as forensic analysis of a case study, showed that this potentiation can occur in short timeframes to deliver a non-CP CRE infection. Our results suggest that the multiple genes that function to build an AMR phenotype can be diagnosed, so that strains that will resist treatment with carbapenem treatment will be evident if a comprehensive genome-based diagnostic for CRE considers all of these sequence-accessible features.

SIGNIFICANCECarbapenem-resistant Enterobacteriaceae (CRE) has emerged as an important challenge in health-care settings, with Klebsiella pneumoniae playing a major role in the global burden of CRE infections. Through systematic characterisation of the chromosome and plasmid genes of K. pneumoniae strains and their antimicrobial traits we identified new CRE mechanisms that are important for accurate diagnosis of carbapenem-resistant AMR. The development of comprehensive genomics-based diagnostics for CRE will need to consider the multiple gene signatures that impact together to deliver non-carbapenemase, carbapenem-resistant infections.


title: Inflection in prevalence of SARS-CoV-2 infections missing the N501Y mutation as a marker of rapid Delta (B.1.617.2) lineage expansion in Ontario, Canada

abstract:
BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta lineage (B.1.617.2) was implicated in the SARS-CoV-2 surge in India. We sought to describe the rapid expansion of the Delta lineage in Ontario, Canada (population 15 million) using mutation profile information and confirmatory whole genome sequencing.

MethodsAll laboratory-confirmed SARS-CoV-2 cases reported to Public Health Ontario between April 1st and June 12th 2021, with cycle threshold values [≤]35, were eligible for screening for the N501Y and the E484K mutations. We classified cases via mutation screening as: (1) N501Y-/E484K- (wild-type/Delta), (2) Alpha (N501Y+/E484K-), (3) Beta/Gamma (N501Y+/E484K+), or (4) N501Y-/E484K+ (predominantly B.1.525, and B.1.1.318).

ResultsThe N501Y-/E484K- mutation profile went from having a 29% transmission deficit relative to Alpha (relative Re = 0.71, 95%CI: 0.64, 0.77) on April 1st to having a 50% transmission advantage on June 12th (relative Re = 1.50, 95%CI: 1.31, 1.71). Whole genome sequencing of N501Y-/E484K-cases (N=583) confirmed that the pattern of increasing relative reproduction number coincided with the replacement of wild-type with Delta variant (from 2.2% in early April, to 83% in late May).

DiscussionDelta is rapidly overtaking other SARS-CoV-2 variants in Ontario, and has a substantial transmission advantage. An inflection in the proportion of cases missing the N501Y mutation from rapidly decreasing to rapidly increasing,3 may be an early warning signal for Delta lineage expansion.


title: Unbiased sequencing of Mycobacterium tuberculosis urinary cell-free DNA reveals extremely short fragment lengths

abstract: Urine cell-free DNA (cfDNA) presents an attractive target for diagnosing pulmonary Mycobacterium tuberculosis (TB) infection but has not been thoroughly characterized. Here, we aimed to investigate the size and composition of TB-derived urine cfDNA with minimal bias using next-generation DNA sequencing (NGS). To enable analysis of highly fragmented urine cfDNA, we used a combination of DNA extraction (Q sepharose) and single-stranded sequence library preparation methods demonstrated to recover short, highly degraded cfDNA fragments. We examined urine cfDNA from ten HIV-positive patients with confirmed pulmonary TB (nine of which had TB cfDNA detectable by qPCR) and two TB-negative controls. TB-derived cfDNA was identifiable by NGS from all TB-positive patients. TB urine cfDNA was significantly shorter than human urine cfDNA, with median fragment lengths of [≤]19-52 bp and 42-92 bp, respectively. TB cfDNA abundance increased exponentially with decreased fragment length, with a peak fragment length of [≤]19 bp in most samples. Our methodology also revealed a larger fraction of short human genomic cfDNA than previously reported, with peak fragment lengths of 29-53 bp. Urine cfDNA fragments spanned the TB genome with relative uniformity, but nucleic acids derived from multicopy elements were proportionately overrepresented, providing regions of inherent signal amplification beneficial for molecular diagnosis. This study demonstrates the potential of urine cfDNA as a diagnostic biomarker for TB and will inform improved design of TB urine cfDNA assays. Methods capable of targeting the shortest cfDNA fragments possible will be critical to maximize TB urine cfDNA detection sensitivity.


title: A behavioural modelling approach to assess the impact of COVID-19 vaccine hesitancy

abstract: In this paper we introduce a compartmental epidemic model describing the transmission of the COVID-19 disease in presence of non-mandatory vaccination. The model takes into account the hesitancy and refusal of vaccination. To this aim, we employ the information index, which mimics the idea that individuals take their decision on vaccination based not only on the present but also on the past information about the spread of the disease. Theoretical analysis and simulations show clearly as a voluntary vaccination can certainly reduce the impact of the disease but it is unable to eliminate it. We also show how the information-related parameters affect the dynamics of the disease. In particular, the hesitancy and refusal of vaccination is better contained in case of large information coverage and small memory characteristic time. Finally, the possible influence of seasonality is also investigated.


title: Integrating PCR-free amplification and synergistic sensing for ultrasensitive and rapid CRISPR/Cas12a-based SARS-CoV-2 antigen detection

abstract: Antigen detection provides particularly valuable information for medical diagnoses; however, the current detection methods are less sensitive and accurate than nucleic acid analysis. The combination of CRISPR/Cas12a and aptamers provides a new detection paradigm, but sensitive sensing and stable amplification in antigen detection remain challenging. Here, we present a PCR-free multiple trigger dsDNA tandem-based signal amplification strategy and a de novo designed dual aptamer synergistic sensing strategy. Integration of these two strategies endowed the CRISPR/Cas12a and aptamer-based method with ultra-sensitive, fast, and stable antigen detection. In a demonstration of this method, the limit of detection was at the single virus level (0.17 fM, approximately two copies/L) in SARS-CoV-2 antigen nucleocapsid protein analysis of saliva or serum samples. The entire procedure required only 20 minutes. Given our systems simplicity and modular setup, we believe that it could be adapted reasonably easily for general applications in CRISPR/Cas12a-aptamer-based detection.


title: Report on Three Round COVID-19 Risk Blind Tests by Screening Eye-region Manifestations

abstract: The Coronavirus disease 2019 (COVID-19) has affected several million people since 2019. Despite various vaccines of COVID-19 protect million people in many countries, the worldwide situations of more the asymptomatic and mutated strain discovered are urging the more sensitive COVID-19 testing in this turnaround time. Unfortunately, it is still nontrivial to develop a new fast COVID-19 screening method with the easier access and lower cost, due to the technical and cost limitations of the current testing methods in the medical resource-poor districts. On the other hand, there are more and more ocular manifestations that have been reported in the COVID-19 patients as growing clinical evidence[1]. This inspired this project. We have conducted the joint clinical research since January 2021 at the ShiJiaZhuang City, Hebei province, China, which approved by the ethics committee of The fifth hospital of ShiJiaZhuang of Hebei Medical University. We undertake several blind tests of COVID-19 patients by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Meantime as an important part of the ongoing globally COVID-19 eye test program by AIMOMICS since February 2020, we propose a new fast screening method of analyzing the eye-region images, captured by common CCD and CMOS cameras. This could reliably make a rapid risk screening of COVID-19 with the sustainable stable high performance in different countries and races. For this clinical trial in ShiJiaZhuang, we compare and analyze 1194 eye-region images of 115 patients, including 66 COVID-19 positive patients, 44 rehabilitation patients (nucleic acid changed from positive to negative), 5 liver patients, as well as 117 healthy people. Remarkably, we consistently achieved very high testing results (> 0.94) in terms of both sensitivity and specificity in our blind test of COVID-19 patients. This confirms the viability of the COVID-19 fast screening by the eye-region manifestations. Particularly and impressively, the results have the similar conclusion as the other clinical trials of the globally COVID-19 eye test program[1]. Hopefully, this series of ongoing globally COVID-19 eye test study, and potential rapid solution of fully self-performed COVID risk screening method, can be inspiring and helpful to more researchers in the world soon. Our model for COVID-19 rapid prescreening have the merits of the lower cost, fully self-performed, non-invasive, importantly real-time, and thus enables the continuous health surveillance. We further implement it as the open accessible APIs, and provide public service to the world. Our pilot experiments show that our model is ready to be usable to all kinds of surveillance scenarios, such as infrared temperature measurement device at airports and stations, or directly pushing to the target people groups smartphones as a packaged application.


title: The tumor suppressor Adenomatous polyposis coli modulates T lymphocyte migration

abstract:
Adenomatous polyposis coli (APC) is a tumor suppressor whose mutations underlie familial adenomatous polyposis (FAP) and colorectal cancer. Although its role in intestinal epithelial cells is well characterized, APC importance for anti-tumor immunity is ill defined. APC regulates cytoskeleton organization, cell polarity and migration in various cells types. Here we address whether APC plays a role in T lymphocyte migration, a key step of anti-tumor immune responses.

Using a series of cell biology tools, we demonstrated that T cells from FAP patients carrying APC mutations display adhesion and migration defects. Concomitantly, they presented lower expression of the integrin VLA-4. To further dissect the cellular mechanisms underpinning these defects, we depleted APC in the CEM T cell line. We found that APC is critical not only for VLA-4-dependent adhesion but also for actomyosin and microtubule organization in migrating T cells. Finally, APC-silenced CEM cells preferentially adopt an ameboid-like migration featuring unstructured pseudopodia and blebbing.

These findings underscore a role of APC in T cell migration via modulation of integrin-dependent adhesion and cytoskeleton reorganization. Hence, APC mutations in FAP patients not only drive intestinal neoplasms, but also impair T cell migration, potentially leading to inefficient T cell-mediated anti-tumor immunity.

category: allergy and immunology


title: The tumor suppressor Adenomatous polyposis coli regulates T lymphocyte migration. Insights from familial polyposis patients


title: Can Auxiliary Indicators Improve COVID-19 Forecasting and Hotspot Prediction?

abstract: Short-term forecasts of traditional streams from public health reporting (such as cases, hospitalizations, and deaths) are a key input to public health decision-making during a pandemic. Since early 2020, our research group has worked with data partners to collect, curate, and make publicly available numerous real-time COVID-19 indicators, providing multiple views of pandemic activity in the U.S. This paper studies the utility of five such indicators--derived from de-identified medical insurance claims, self-reported symptoms from online surveys, and COVID-related Google search activity--from a forecasting perspective. For each indicator, we ask whether its inclusion in an autoregressive (AR) model leads to improved predictive accuracy relative to the same model excluding it. Such an AR model, without external features, is already competitive with many top COVID-19 forecasting models in use today. Our analysis reveals that (a) inclusion of each of these five indicators improves on the overall predictive accuracy of the AR model; (b) predictive gains are in general most pronounced during times in which COVID cases are trending in "flat" or "down" directions; (c) one indicator, based on Google searches, seems to be particularly helpful during "up" trends.


title: Acceptability, usability and performance of lateral flow immunoassay tests for SARS-CoV-2 antibodies: REACT-2 study of self-testing in non-healthcare key workers

abstract:
BackgroundSeroprevalence studies in key worker populations are essential to understand the epidemiology of SARS-CoV-2. Various technologies, including laboratory assays and point-of-care self-tests, are available for antibody testing. The interpretation of seroprevalence studies requires comparative data on the performance of antibody tests.

MethodsIn June 2020, current and former members of the UK Police forces and Fire service performed a self-test lateral flow immunoassay (LFIA) and provided a saliva sample, nasopharyngeal swab, venous blood samples for Abbott ELISA and had a nurse performed LFIA. We present the prevalence of PCR positivity and antibodies to SARS-CoV-2 in this cohort following the first wave of infection in England; the acceptability and usability of self-test LFIAs (defined as use of the LFIA kit and provision of a valid result, respectively); and determine the sensitivity and specificity of LFIAs compared to laboratory ELISAs.

ResultsIn this cohort of non-healthcare key workers, 7.4% (396/5,348; 95% CI, 6.7-8.1) were antibody positive. Seroprevalence was 8.9% (6.9-11.4) in those under 40 years, 11.5% (8.8-15.0) in those of non-white British ethnicity and 7.8% (7.1-8.7) in those currently working. The self-test LFIA had an acceptability of 97.7% and a usability of 90.0%. There was substantial agreement between within-participant LFIA results (kappa 0.80; 0.77-0.83). The LFIAs (self-test and nurse-performed) had a similar performance: compared to ELISA, sensitivity was 82.1% (77.7-86.0) self-test and 76.4% (71.9-80.5) nurse-performed with specificity of 97.8% (97.3-98.2) and 98.5% (98.1-98.8) respectively.

ConclusionA greater proportion of the non-healthcare key worker cohort showed evidence of previous infection with SARS-CoV-2 than the general population at 6.0% (5.8-6.1) following the first wave in England. The high acceptability and usability reported by participants and the similar performance of self-test and nurse-performed LFIAs indicate that the self-test LFIA is fit for purpose for home-testing in occupational and community prevalence studies.


title: MONITORING SARS-COV-2 TRANSMISSION AND PREVALENCE IN POPULATIONS UNDER REPEATED TESTING

abstract: We describe a repeat SARS-CoV-2 testing model for monitoring and containing outbreaks in a residential community. The analysis is motivated by the Ohio State University (OSU)s approach to monitoring disease at its Columbus, Ohio campus during the COVID-19 epidemic in autumn 2020. The model is simple, yet flexible enough to accommodate changes in behavior over time and to eliminate bias due to a nonrandom testing scheme. Model parameters are estimated from individual results of weekly SARS-CoV-2 testing of residents. Model output serves several purposes, including estimating the effective reproduction number and monitoring prevalence to help inform isolation and quarantine bed capacity. An extended version of the model is also considered where the residential population (on-campus students) is assumed to interact with another population for whom the testing regime is more relaxed and possibly less frequent (off-campus students or instructional faculty and staff). To illustrate the model application, we analyze both the synthetic data as well as the actual student SARS-CoV-2 testing data collected at OSU Columbus campus.


title: Covid-19 Incidence And Mortality By Age Strata And Comorbidities In Mexico City: A Focus In The Pediatric Population

abstract:
BackgroundSARS-COV2 appears less frequently and less severely in the pediatric population than in the older age groups. There is a need to precisely estimate the specific risks for each age group to design health and education policies suitable for each population

ObjectiveThis study aimed to describe the risk of death in SARS-COV2 infected subjects by age group and according to the presence of comorbidities.

MethodsWe analyzed data of confirmed SARS-COV2 infection cases where symptoms began between February 22th, 2020, and April 18th, 2021, as published by the General Epidemiology Direction (DGE) of the Mexican Ministry of Health. We calculated COVID-19 incidence and mortality by age group using population data from the Statistics and Population National Institute (INEGI), and estimated the association between risk of death and the presence of comorbidities.

ResultsMortality in SARS-COV2 infected people varied considerably, between 7 to 155 deaths per million per year in the under-20 age groups compared to 441 to 15,929 in the older age groups. Mortality in pediatric populations is strongly associated with comorbidities (OR: 4.6-47.9) compared to the milder association for older age groups (OR: 3.16-1.23).

ConclusionsThe risk of death from SARS-COV2 infection in children is low and is strongly associated with comorbidities.


title: A tool to distinguish viral from bacterial pneumonia

abstract:
Background and ObjectivesEstablishing the etiology of community-acquired pneumonia (CAP) in children at admission is challenging. As a result, most children receive antibiotics that do not need.

This study aims to build and validate a diagnostic tool combining clinical, analytical and radiographical features to sequentially differentiate viral from bacterial CAP, and among bacterial CAP, typical from atypical bacteria, to improve choice of treatment.

MethodsConsecutive hospitalized children between 1 month and 16 years of age with CAP were enrolled. An extensive microbiological workup was performed. A score was built with a training set of 70% patients, to first differentiate between viral and bacterial CAP and secondly, typical from atypical bacterial CAP. To select variables, a Ridge model was used. Optimal cut-off points were selected to maximize specificity setting a high sensitivity (80%). Weights of each variable were calculated with a multivariable logistic regression. The score was validated with the rest of the participants.

ResultsIn total, 262 (53%) children (median age, 2 years, 52.3% male) had an etiological diagnosis.

The step 1 discriminates viral from bacterial CAP. Bacterial CAPs were classified with a sensitivity=97%, a specificity=48%, and a ROCs area under the curve (AUC)=0.81. If a CAP was classificated as bacterial, it was assessed with step 2. The step 2 differentiates typical vs. atypical bacterial CAP. Typical bacteria were classified with a sensitivity=100%, a specificity=64%, and AUC=0.90.

ConclusionThis two-steps tool can facilitate the physicians decision to prescribe antibiotics without compromising patient safety.

Article summaryWe validated a clinical tool to predict the aetiology of CAP in children safely. This tool differentiates CAP into viral, atypical bacteria and typical bacteria.

"Whats Known on This Subject"Establishing the aetiology of community-acquired pneumonia (CAP) in children at admission is challenging. As a result, most admitted children with CAP receive antibiotics.

"What This Study Adds"We validated a clinical tool to predict the aetiology of pneumonia in children safely, differentiating among viral, atypical bacteria and typical bacteria.

category: pediatrics


title: Microsimulation based quantitative analysis of COVID-19 management strategies

abstract:
BackgroundPandemic management includes a variety of control measures, such as social distancing, testing/quarantining and vaccination applied to a population where the virus is circulating. The COVID-19 (SARS-CoV-2) pandemic is mitigated by several non-pharmaceutical interventions, but it is hard to predict which of these regulations are the most effective for a given population.

MethodsWe developed a computationally effective and scalable, agent-based microsimulation framework. This unified framework was fitted to realistic data to enable us to test control measures (closures, quarantining, testing, vaccination) in multiple infection waves caused by the spread of a new virus variant in a city-sized societal environment. Our framework is capable of simulating nine billion agent-steps per minute, allowing us to model interactions in populations with up to 90 million individuals.

FindingsWe show that vaccination strategies prioritising occupational risk groups minimise the number of infections but allow higher mortality while prioritising vulnerable groups minimises mortality but implies increased infection rate. We also found that intensive vaccination and non-pharmaceutical interventions can substantially suppress the spread of the virus, while low levels of vaccination and premature reopening may easily revert the epidemic to an uncontrolled state.

InterpretationOur analysis highlights that while vaccination protects the elderly from COVID-19, a large percentage of children will contract and spread the virus, and we also show the benefits and limitations of various quarantine and testing scenarios.

FundingThis work was carried out within the framework of the Hungarian National Development, Research, and Innovation (NKFIH) Fund 2020-2.1.1-ED-2020-00003.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe still do not have an effective medical treatment against COVID-19 (SARS-CoV-2), thus the majority of the efforts to stop the pandemic focuses on non-pharmaceutical interventions. Each country came up with a local solution to stop the spread of the virus by increased testing, quarantining, lock-down of various events and institutions or early vaccination. There is no clear way how these interventions can be compared, and it is especially challenging to predict how combinations of interventions could influence the pandemic. Various mathematical modelling approaches helped decision-makers to foresee the effects of their decisions. Most of these models rely on classical, deterministic compartmental "SEIR" models, which can be solved easily but cannot take into account spatial effects and most non-pharmaceutical interventions affect the same parameters, so there is no way to analyse their separate or joint effects. Agent-based microsimulations are harder to solve but can consider far more details. Several models were developed on these lines focusing on questions about ideal vaccination, lock-down or other specific problems, but none of these studies evaluated and compared the individual and mixed effects of a wide variety of control measures.

Added-value of this studyHere we present PanSim, a framework where we introduce a detailed infection event simulation step and the possibility to control specific workplaces individually (schools, hospitals, etc.), test various vaccination, testing and quarantine scenarios while considering preconditions, age, sex, residence and workplace of individuals and mutant viruses with various infectivity. The level of details and granularity of simulations allow our work to evaluate this wide range of scenarios and control measures accurately and directly compare them with one another to provide quantitative evidence to support decision-makers. Analysis of our simulations also provides emergent results on the risks children and non-vaccinated individuals face.

Implications of all the available evidenceThe agent-based microsimulation framework allows us to evaluate the risk and possible consequences of particular interventions precisely. Due to the outstanding efficiency of the computations, it is possible to apply scenario-based analysis and control design methods which require a high number of simulation runs to obtain results on a given confidence level. This will enable us to design and quantitatively assess control measures in case of new waves of COVID-19 or new pandemic outbreaks.


title: Dietary practices, physical activity and social determinants of non-communicable diseases in Nepal: a systemic analysis

abstract:
BackgroundThe objective of this paper was to describe the role of dietary practices and physical activity in the interaction of the social determinants of non-communicable diseases (NCDs) in Nepal.

MethodThe study was a qualitative study design guided by systemic intervention methodology. Qualitative data were collected through key informant interviews (n=63) and focus group discussions (n= 12), and case study-based thematic analysis was carried out. Causal loop diagram was utilised to illustrate the dynamic interactions of the social determinants based on the themes. The study also involved sense-making sessions with policy level and local stakeholders.

FindingsFour key interacting themes emerged from the study. Dietary and physical activity practices have shifted significantly at community level contributing to increased risk of NCDs. The practice of healthy and locally produced meals was gradually being displaced by junk food and linked to junk food availability and declining agricultural activities. Health system was ineffective in preventing unhealthy practices. Gender and social economic factors were driving the poor dietary practices and physical inactivity.

ConclusionWhile the current dietary and physical activity-related practices within communities were poor, the broader determinants such as socio-economic circumstances and gender further fuelled such practices. The health system has potential to play an effective role in the prevention of the behavioural and social determinants of NCDs.


title: TEleRehabilitation Nepal (TERN) to improve quality of life of people with spinal cord injury and acquired brain injury. A proof-of-concept study.

abstract:
BackgroundSpinal Cord Injury (SCI) and Acquired Brain Injury (ABI) lead to unemployment, poverty, increased mortality, and decreased quality of life in low-and middle-income countries (LMICs). Telemedicine is increasingly facilitating access to healthcare, in LMICs. This prospective cohort intervention study aims to investigate feasibility and acceptability of telerehabilitation to provide long-term follow-up of individuals with SCI and ABI, in Nepal, post-discharge from hospital.

MethodsTERN was delivered by Spinal Injury Rehabilitation Centre, Nepal, in collaboration with University of Leeds, UK. A home visit connected participants to the Multidisciplinary Team (MDT), through a specialised video conference system. The MDT performed a comprehensive assessment before recommending personalised interventions. Outcome measures assessed functional independence in performing activities of daily living, health-related quality of life and emotional disturbances using Modified Barthel Index, EuroQoL-5D, and Depression, Anxiety, Stress Scale, respectively. A subset of participants was interviewed, exploring acceptability of telerehabilitation.

FindingsBetween January and December 2020, 97 participants with SCI (n = 82) and ABI (n = 15) were enrolled. After receiving telerehabilitation, significant improvement to self-reported functional independence (p<.001) and quality of life were found, (p<.001). Self-reported severity of depression, anxiety and stress significantly decreased (p<.001). Qualitative interviews (n = 18) revealed participants accepted telerehabilitation, they valued regular contact with professionals without costly, difficult travel.

InterpretationThis is the first study to test telerehabilitation in Nepal. This approach can be safely delivered for long-term follow-up for individuals with SCI or ABI, overcoming geographical barriers to healthcare access. A larger-scale controlled study is required to further explore clinical and cost-effectiveness.

category: rehabilitation medicine and physical therapy


title: Identification of social engagement indicators associated with autism spectrum disorder using a game-based mobile application

abstract:
ObjectiveAutism spectrum disorder (ASD) is a widespread neurodevelopmental condition with a range of potential causes and symptoms. Children with ASD exhibit behavioral and social impairments, giving rise to the possibility of utilizing computational techniques to evaluate a childs social phenotype from home videos.

MethodsHere, we use a mobile health application to collect over 11 hours of video footage depicting 95 children engaged in gameplay in a natural home environment. We utilize automated dataset annotations to analyze two social indicators that have previously been shown to differ between children with ASD and their neurotypical (NT) peers: (1) gaze fixation patterns and (2) visual scanning methods. We compare the gaze fixation and visual scanning methods utilized by children during a 90-second gameplay video in order to identify statistically-significant differences between the two cohorts; we then train an LSTM neural network in order to determine if gaze indicators could be predictive of ASD.

ResultsOur work identifies one statistically significant region of fixation and one significant gaze transition pattern that differ between our two cohorts during gameplay. In addition, our deep learning model demonstrates mild predictive power in identifying ASD based on coarse annotations of gaze fixations.

DiscussionUltimately, our results demonstrate the utility of game-based mobile health platforms in quantifying visual patterns and providing insights into ASD. We also show the importance of automated labeling techniques in generating large-scale datasets while simultaneously preserving the privacy of participants. Our approaches can generalize to other healthcare needs.


title: Landscape of human gut antibiotic resistome and progression of diabetes

abstract:
ObjectiveTo investigate the association between human gut antibiotic resistome and the progression of type 2 diabetes (T2D) in a large cohort study.

DesignThe present study included 1210 participants from the Guangzhou Nutrition and Health Study. We depicted the landscape of human gut antibiotic resistome with shotgun metagenomic data and examined its association with T2D and cardiometabolic traits. The co-occurrence network analysis was used to explore the associations between T2D-related ARGs and gut microbial species. We also examined the associations between gut antibiotic resistome features and fecal metabolome.

ResultsThere was a significant overall shift in gut antibiotic resistome structure among healthy, prediabetes and T2D groups (p = 0.004). We found that larger ARG diversity was associated with a higher risk of T2D (all p < 0.05). Based on the association found between resistomes and T2D, we developed diabetes ARG score and demonstrated its creative use as a new predictor for T2D progression manifested by the change of insulin resistance. Further network analysis showed the co-occurrence association between T2D-related ARGs and gut microbial species, which indicated the potential bacterial hosts of these ARG biomarkers. Resistome-metabolome co-analysis suggests a potential link of ARGs with fecal metabolites, which may reflect the host-microbial metabolic adaptation.

ConclusionOur data depict the landscape of gut antibiotic resistome diversity and composition and uncover a close relationship between human gut antibiotic resistome and T2D progression.

O_TEXTBOXSignificance of this studyO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIHuman gut is the key reservoir of microbiota harboring both commensal and pathogenic bacteria.
C_LIO_LIGrowing evidence has revealed that the gut microbiota composition was associated with type 2 diabetes (T2D).
C_LIO_LIProspective cohort studies showed that self-reported long-term use of antibiotics was associated with higher T2D risk.
C_LI

What are the new findings?O_LIThere was a significant overall shift in gut antibiotic resistome structure among healthy, prediabetes and T2D groups.
C_LIO_LIWe found for the first time that higher gut ARG diversity was associated with a higher risk of T2D.
C_LIO_LIWe constructed a diabetes ARG score (DAS) using the identified T2D related ARGs, it was positively associated with glycemic traits.
C_LIO_LILongitudinal validation analysis confirmed that the DAS was associated with T2D progression, characterized by the change of insulin resistance.
C_LI

How might it impact on clinical practice in the foreseeable future?O_LIOur findings support a recommendation to avoid the abuse of antibiotics, and the identified antibiotic resistome markers could also be served as potential intervention target in future.
C_LI

C_TEXTBOX


title: Pre-existing anxiety, depression, and neurological disability are associated with long COVID: A prospective and longitudinal cohort study of the United Kingdom Multiple Sclerosis Register

abstract:
ObjectivesTo assess the prevalence of long COVID among people with multiple sclerosis (MS) and its predictors, including their pre-COVID-19 functional status.

DesignCommunity-based prospective and longitudinal cohort study

SettingThe United Kingdom (UK) MS Register (UKMSR) COVID-19 study

ParticipantsA national cohort of people with MS and COVID-19

Main outcome measuresParticipants used the online questionnaire-based platform of the UKMSR to update their COVID-19 symptoms, recovery status, and duration of symptoms for those who had fully recovered. Questionnaires were date-stamped for estimation of COVID-19 symptom duration for those who had not recovered at their last follow-up. The UKMSR holds demographic and up-to-date clinical data on participants as well as their web-based Expanded Disability Status Scale (a measure of physical disability in MS) and Hospital Anxiety and Depression Scale scores. The association between these factors and recovery from COVID-19 was assessed using multivariable Cox regression analysis.

ResultsOut of 7,977 people with MS who participated in the UKMSR COVID-19 study, 599 had COVID-19 and updated their recovery status prospectively. At least 181 participants (31.1%) had long-standing COVID-19 symptoms for [≥]4 weeks and 76 (13.1 %) for [≥]12 weeks. Participants with higher levels of pre-COVID-19 physical disability, participants with anxiety and/or depression prior to COVID-19 onset, and women were less likely to report recovery from COVID-19.

ConclusionsLong COVID appears to disproportionately affect people with pre-existing mental health problems or physical disabilities. As post-COVID-19 rehabilitation services are being developed, individualised pathways should be considered to accommodate the needs of these vulnerable populations.

Trial RegistrationClinicalTrials.gov: NCT04354519


title: Averting an outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in a university residence hall through wastewater surveillance

abstract: A wastewater surveillance program targeting a university residence hall was implemented during the spring semester 2021 as a proactive measure to avoid an outbreak of COVID-19 on campus. Over a period of 7 weeks from early February through late March 2021, wastewater originating from the residence hall was collected as grab samples 3 times per week. During this time, there was no detection of SARS-CoV-2 by RT-qPCR in the residence hall wastewater stream. Aiming to obtain a sample more representative of the residence hall community, a decision was made to use passive samplers beginning in late March onwards. Adopting a Moore Swab approach, SARS-CoV-2 was detected in wastewater samples on just two days after passive samplers were activated. These samples were also positive for the B.1.1.7 (Alpha) Variant of Concern (VOC) by RT-qPCR. The positive result triggered a public health case finding response including a mobile testing unit deployed to the residence hall the following day with testing of nearly 200 students and staff, which identified two laboratory-confirmed cases of B.1.1.7 variant COVID-19. These individuals were re-located to a separate quarantine facility averting an outbreak on campus. Aggregating wastewater and clinical data, the campus wastewater surveillance program has yielded the first estimates of fecal shedding rates of the B.1.1.7 VOC of SARS-CoV-2 in individuals from a non-clinical setting.


title: Metacognition in Functional Cognitive Disorder

abstract:
Functional cognitive disorder (FCD) is common but underlying mechanisms remain poorly understood. Metacognition, an individuals ability to reflect on and monitor cognitive processes, is likely to be relevant. Local metacognition refers to an ability to estimate confidence in cognitive performance on a moment-to-moment basis, whereas global metacognition refers to long-run self-evaluations of overall performance. Using a novel protocol comprising task-based measures and hierarchical Bayesian modelling, we compared local and global metacognitive performance in individuals with FCD and evaluated interactions between these levels of metacognition. We also investigated how local and global metacognition were related to the presence of affective symptomatology.

Eighteen participants with FCD were recruited to this cross-sectional study. Participants completed computerised tasks that enabled local metacognitive efficiency for perception and memory to be measured using the hierarchical meta-d (HMeta-d) model within a signal detection theory framework. Participants also completed the Multifactorial Memory Questionnaire (MMQ) measuring global metacognition (beliefs about memory performance), and questionnaires measuring anxiety and depression. Estimates of local metacognitive efficiency were compared to those estimated from two control groups who had undergone comparable metacognitive tasks. Global metacognition scores were compared to existing normative data. A hierarchical regression model was used to evaluate associations between global metacognition, depression and anxiety and local metacognitive efficiency, while simple linear regressions were used to evaluate whether affective symptomatology and local metacognitive confidence were associated with global metacognition.

Participants with FCD had intact local metacognition for perception and memory when compared to controls, with the 95% highest-density intervals for metacognitive efficiency overlapping with the two control groups in both cognitive domains. FCD participants had significantly lower global metacognition scores compared to normative data; MMQ-Ability (t=6.54, p<0.0001) and MMQ-Satisfaction (t=5.04, p<0.0001). Mood scores, global metacognitive measures and metacognitive bias were not significantly associated with local metacognitive efficiency. Increased local metacognitive bias ({beta}= -0.20 (SE=0.09), q= 0.01) and higher depression scores as measured by Patient Health Questionnaire-9 ({beta}= -1.40 (SE=2.56), q= 0.01) were associated with lower global metacognition scores.

We show that local metacognition is intact, whilst global metacognition is impaired, in FCD, suggesting a decoupling between the two metacognitive processes. In a Bayesian model, an aberrant prior (impaired global metacognition), may override bottom up sensory input (intact local metacognition), giving rise to the subjective experience of abnormal cognitive processing. Future work should further investigate the interplay between local and global metacognition in FCD and aim to identify a therapeutic target to recouple these processes.


title: Diet quality and risk and severity of COVID-19: a prospective cohort study

abstract:
ObjectivePoor metabolic health and certain lifestyle factors have been associated with risk and severity of coronavirus disease 2019 (COVID-19), but data for diet are lacking. We aimed to investigate the association of diet quality with risk and severity of COVID-19 and its intersection with socioeconomic deprivation.

DesignWe used data from 592,571 participants of the smartphone-based COVID Symptom Study. Diet quality was assessed using a healthful plant-based diet score, which emphasizes healthy plant foods such as fruits or vegetables. Multivariable Cox models were fitted to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for COVID-19 risk and severity defined using a validated symptom-based algorithm or hospitalization with oxygen support, respectively.

ResultsOver 3,886,274 person-months of follow-up, 31,815 COVID-19 cases were documented. Compared with individuals in the lowest quartile of the diet score, high diet quality was associated with lower risk of COVID-19 (HR, 0.91; 95% CI, 0.88-0.94) and severe COVID-19 (HR, 0.59; 95% CI, 0.47-0.74). The joint association of low diet quality and increased deprivation on COVID-19 risk was higher than the sum of the risk associated with each factor alone (Pinteraction=0.005). The corresponding absolute excess rate for lowest vs highest quartile of diet score was 22.5 (95% CI, 18.8-26.3) and 40.8 (95% CI, 31.7-49.8; 10,000 person-months) among persons living in areas with low and high deprivation, respectively.

ConclusionsA dietary pattern characterized by healthy plant-based foods was associated with lower risk and severity of COVID-19. These association may be particularly evident among individuals living in areas with higher socioeconomic deprivation.

category: nutrition


title: Interpretable Gender Classification from Retinal Fundus Images using BagNets

abstract: Deep neural networks (DNNs) are able to predict a persons gender from retinal fundus images with high accuracy, even though this task is usually considered hardly possible by ophthalmologists. Therefore, it has been an open question which features allow reliable discrimination between male and female fundus images. To study this question, we used a particular DNN architecture called BagNet, which extracts local features from small image patches and then averages the class evidence across all patches. The BagNet performed on par with the more sophisticated Inception-v3 model, showing that the gender information can be read out from local features alone. BagNets also naturally provide saliency maps, which we used to highlight the most informative patches in fundus images. We found that most evidence was provided by patches from the optic disc and the macula, with patches from the optic disc providing mostly male and patches from the macula providing mostly female evidence. Although further research is needed to clarify the exact nature of this evidence, our results suggest that there are localized structural differences in fundus images between genders. Overall, we believe that BagNets may provide a compelling alternative to the standard DNN architectures also in other medical image analysis tasks, as they do not require post-hoc explainability methods.

category: ophthalmology


title: Communication of pain intensity and unpleasantness through magnitude ratings: Influence of scale type, but not sex of the participant

abstract: A critical aspect for much human pain research is the ability of participants to communicate their first person, experiential perspective to a third person observer. This communication is frequently accomplished via pain ratings. The type of scale and how participants/patients may differentially use the scale has a major influence on the communication of pain experiences. The present study examined the role of sex on the pain rating process using both noxious and innocuous stimuli and two different types of rating scales. Participants underwent noxious heat, auditory and visual stimulation paradigms. Pain intensity and unpleasantness ratings were collected using the visual analog scale (VAS) and numerical rating scale (NRS) in a random order. For noxious heat stimuli, low (44-45{degrees}C) and high (47-48{degrees}C) intensity stimuli were delivered. To identify if one rating scale allows better discrimination between different stimulus intensities and if this is dependent on sex, discrimination thresholds were calculated. Significant effect for rating scale and intensity level of stimuli were found for all stimulus modalities (noxious heat, auditory and visual) indicating that higher intensity and unpleasantness ratings were found using the NRS compared to the VAS. No effect of sex or interaction with sex was found. No differences in rating scale and sex were found for the discrimination thresholds. Biases in rating scales usage exist with NRS yielding higher ratings to the same stimuli. However, this bias does not appear to contribute significantly to sex differences in pain.

category: pain medicine


title: Diagnosing pediatric mitochondrial disease: lessons from 2,000 exomes

abstract:
BackgroundThe spectrum of mitochondrial disease is genetically and phenotypically diverse, resulting from pathogenic variants in over 400 genes, with aerobic energy metabolism defects as a common denominator. Such heterogeneity poses a significant challenge in making an accurate diagnosis, critical for precision medicine.

MethodsIn an international collaboration initiated by the European Network for Mitochondrial Diseases (GENOMIT) we recruited 2,023 pediatric patients at 11 specialist referral centers between October 2010 and January 2021, accumulating exome sequencing and HPO-encoded phenotype data. An exome-wide search for variants in known and potential novel disease genes, complemented by functional studies, followed ACMG guidelines.

Results1,109 cases (55%) received a molecular diagnosis, of which one fifth have potential disease-modifying treatments (236/1,109, 21%). Functional studies enabled diagnostic uplift from 36% to 55% and discovery of 62 novel disease genes. Pathogenic variants were identified within genes encoding mitochondrial proteins or RNAs in 801 cases (72%), while, given extensive phenotype overlap, the remainder involved proteins targeted to other cellular compartments. To delineate genotype-phenotype associations, our data was complemented with registry and literature data to develop "GENOMITexplorer", an open access resource detailing patient- (n=3,940), gene- (n=427), and variant-level (n=1,492) associations (prokischlab.github.io/GENOMITexplorer/).

ConclusionsReaching a molecular diagnosis was essential for implementation of precision medicine and clinical trial eligibility, underlining the need for genome-wide screening given inability to accurately define mitochondrial diseases clinically. Key to diagnostic success were functional studies, encouraging early acquisition of patient- derived tissues and routine integration of high-throughput functional data to improve patient care by uplifting diagnostic rate.


title: Entitled to Property: Inheritance Laws, Female Bargaining Power, and Child Health in India

abstract: Child height is a significant predictor of human capital and economic status throughout adulthood. Moreover, non-unitary household models of family behavior posit that an increase in womens bargaining power can influence child health. We study the effects of an inheritance policy change, the Hindu Succession Act (HSA), which conferred enhanced inheritance rights to unmarried women in rural India, on child height. We find robust evidence that the HSA improved the height and weight of children. In addition, we find evidence consistent with a channel that the policy improved the womens intrahousehold bargaining power within the household, leading to improved parental investments for children. These study findings are also compatible with the notion that children do better when their mothers control a more significant fraction of the family. Therefore, policies that empower women can have additional positive spillovers for childrens human capital. (JEL D13, I12, I13, J13, J16, J18, K13, O12, O15, Z12, Z13)