title: Boosters protect against SARS-CoV-2 infections in young adults during an Omicron-predominant period

abstract:
BackgroundWhile booster vaccinations clearly reduce the risk of severe COVID-19 and death, the impact of boosters on SARS-CoV-2 infection has not been fully characterized: doing so requires understanding their impact on asymptomatic and mildly symptomatic infections that often go unreported but nevertheless play an important role in spreading SARS-CoV-2. We sought to estimate the impact of COVID-19 booster doses on SARS-CoV-2 infection in a vaccinated and actively surveilled population of young adults during an Omicron-predominant period.

Methods and FindingsWe implemented a cohort study of young adults in a college environment (Cornell Universitys Ithaca campus) from December 5, 2021 through December 31, 2021 when Omicron was deemed the predominant SARS-CoV-2 variant on campus. Participants included 15,102 university students fully vaccinated with an FDA-authorized or approved vaccination (BNT162b2, mRNA-1273, or Ad26.COV2.S) who were enrolled in mandatory at-least-weekly surveillance PCR testing, and having no positive SARS-CoV-2 PCR test within 90 days before the start of the study period. Multivariable logistic regression considering those with full vaccination (a 2-dose series of BNT162b2 or mRNA-1273, or 1 dose of Ad26.COV2.S) with a booster dose versus those without a booster dose. 1,870 SARS-CoV-2 infections were identified in the study population. Controlling for gender, student group membership, full vaccination date and initial vaccine type, our analysis estimates that receiving a booster dose reduces the odds of having a PCR-detected SARS-CoV-2 infection relative to full vaccination by 52% (95% confidence interval [37%, 64%]). This result is robust to the choice of the delay over which a booster dose becomes effective (varied from 1 day to 14 days).

ConclusionsBoosters are effective, relative to full vaccination, in reducing the odds of SARS-CoV-2 infections in a college student population during a period when Omicron was predominant. Therefore, booster vaccinations for this age group can play an important role in reducing community and institutional transmission.


title: Sustained high prevalence of COVID-19 deaths from a systematic post-mortem study in Lusaka, Zambia: one year later

abstract:
BackgroundSparse data documenting the impact of COVID-19 in Africa has fostered the belief that COVID-19  skipped Africa. We previously published results from a systematic postmortem surveillance at a busy inner-city morgue in Lusaka, Zambia. Between June-October 2020, we detected COVID-19 in 15-19% of all deaths and concentrated in community settings where testing for COVID-19 was absent. Yet these conclusions rested on a small cohort of 70 COVID-19+ decedents. Subsequently, we conducted a longer and far larger follow-on survey using and expanding on the same methodology.

MethodsWe obtained a nasopharyngeal swab from each enrolled decedent and tested these using reverse transcriptase quantitative PCR (RT-qPCR). A subset of samples with a PCR cycle threshold <30 underwent genotyping to identify viral lineages. We weighted our results to adjust for enrolment ratios and stratified them by setting (facility vs. community), time of year, age, and location.

ResultsFrom 1,118 enrolled decedents, COVID-19 was detected among 32.0% (358/1,116). We observed three waves of transmission that peaked in July 2020, January 2021, and [~]June 2021 (end of surveillance). These were dominated by the AE.1 lineage and the Beta and Delta variants, respectively. During peak transmission, COVID-19 was detected in [~]90% of all deaths. Roughly four COVID-19 deaths occurred in the community for every facility death. Antemortem testing occurred for 52.6% (302/574) of facility deaths but only 1.8% (10/544) of community deaths and overall, only [~]10% of COVID-19+ deaths were identified in life.

ConclusionsCOVID-19 had a devastating impact in Lusaka. COVID-19+ deaths occurred in all age groups and was the leading cause of death during peak transmission periods. Testing was rarely done for the vast majority of COVID-19 deaths that occurred in the community, yielding a substantial undercount.

What is already known on this topicO_LIPreviously, we reported that COVID-19 was present among 15-19% of all decedents passing through a busy city morgue in Lusaka.
C_LIO_LIData documenting the mortal impact of COVID-19 in Africa remain sparse.
C_LIO_LISeveral modeling groups have also argued that COVID-19s impact in Africa has been underreported and hence underestimated.
C_LI

What this study addsO_LIAntemortem testing for COVID-19 captured only [~]10% of COVID-19 positive individuals indicating a substantial gap in surveillance.
C_LIO_LIDuring peak transmission periods, [~]90% of all deceased individuals tested positive for COVID-19.
C_LIO_LIMost COVID-19 positive deceased adults presented with symptoms typical of COVID-19, arguing that COVID-19 caused their deaths and was not a co-incidental finding.
C_LIO_LIDeaths occurred across the age spectrum, including among young children, indicating a different pattern of impact from what has been seen in high income country settings.
C_LIO_LIWe document three waves of transmission, attributable to the AE.1 lineage, and the Beta and Delta variants, respectively.
C_LI

category: infectious diseases


title: Mapping of cis-regulatory variants by differential allelic expression analysis identifies candidate risk variants and target genes of 27 breast cancer risk loci

abstract:
BackgroundBreast cancer (BC) genome-wide association studies (GWAS) have identified hundreds of risk-loci that require novel approaches to reveal the causal variants and target genes within them. As causal variants are most likely regulators of gene expression, we hypothesize that their identification is facilitated by pinpointing the variants with greater regulatory potential within risk-loci.

MethodsWe performed genome-wide differential allelic expression (DAE) analysis using microarrays data from 64 normal breast tissue samples. Then, we mapped the variants associated with DAE (daeQTLs) and intersected these with GWAS data to reveal candidate risk regulatory variants. Finally, we validated our approach by functionally analysing the 5q14.1 breast cancer risk-locus.

ResultsWe found widespread gene expression regulation by cis-acting variants in breast tissue, with 80% of coding and non-coding expressed genes displaying DAE (daeGenes). We identified over 23K daeQTLs for 2753 (16%) daeGenes, including at 154 known BC risk- loci. And in 31 of these risk-loci, we found risk-associated variant(s) and daeQTLs in strong linkage disequilibrium suggesting that the risk-causing variants are cis-regulatory, and in 27 risk-loci we propose 37 candidate target genes. As validation, we identified five candidate causal variants at the 5q14.1 risk-locus targeting the ATG10, RPS23, and ATP6AP1L genes, likely via modulation of miRNA binding, alternative transcription, and transcription factor binding.

ConclusionOur study shows the power of DAE analysis and daeQTL mapping to identify causal regulatory variants and target genes at BC risk loci, including those with complex regulatory landscapes, and provides a genome-wide resource of variants associated with DAE for future functional studies.

category: genetic and genomic medicine


title: Discrimination of sleep and wake periods from a hip-worn raw acceleration sensor using recurrent neural networks

abstract: The use of accelerometers has become an established method in population research. Accelerometers are small body-worn sensors that can monitor movement patterns and cycles over several days under free-living conditions. A key requirement for any accelerometer-based analysis is the reliable discrimination of sleep and wake episodes. However, many studies using hip-worn sensors either instruct the participants to remove the sensor over night or use algorithms developed for wrist placement which are known to perform poorly on hip data. Here we present a new algorithm to differentiate sleep from awake time in raw hip acceleration data using a machine learning approach. Validated on sleep estimates from a subset of the Tromso Study, the proposed algorithm outperformed the standard algorithms by discriminating sleep and wake correctly in 93.81% (95% CI: 0.72) of the time (F1 score = 0.93, 95% CI: 0.01). The value of our algorithm lies in the improved recognition of sleep and movement in large studies where manual scoring is unfeasible due to the amount of data. Even though the algorithm was developed to learn characteristic hip movements, it can easily be adapted for other sensor placements or study populations.

category: health informatics


title: Fed-GLMM: A Privacy-Preserving and Computation-Efficient Federated Algorithm for Generalized Linear Mixed Models to Analyze Correlated Electronic Health Records Data

abstract: Large collaborative research networks provide opportunities to jointly analyze multicenter electronic health record (EHR) data, which can improve the sample size, diversity of the study population, and generalizability of the results. However, there are challenges to analyzing multicenter EHR data including privacy protection, large-scale computation, heterogeneity across sites, and correlated observations. In this paper, we propose a federated algorithm for generalized linear mixed models (Fed-GLMM), which can flexibly model multicenter longitudinal or correlated data while accounting for site-level heterogeneity. Fed-GLMM can be applied to both federated and centralized research networks to enable privacy-preserving data integration and improve computational efficiency. By communicating only a limited amount of summary statistics, Fed-GLMM can achieve nearly identical results as the gold-standard method where the GLMM is directly fitted on the pooled dataset. We demonstrate the performance of Fed-GLMM in both numerical experiments and an application to longitudinal EHR data from multiple healthcare facilities.


title: Physical, psychological and cognitive profile of post-COVID condition in healthcare workers, Quebec, Canada

abstract:
ImportanceMost adults with COVID-19 do not require hospitalization, but the subsequent risk of post-COVID condition, including associated psychological and cognitive dysfunction, remains poorly understood among non-hospitalized versus hospitalized cases.

ObjectiveTo assess the prevalence and duration of post-COVID condition, including physical, psychological and cognitive symptoms.

DesignCase series and case-control study between December 2020 and May 2021

SettingHealthcare workers in Quebec, Canada

ParticipantsEligible cases were symptomatic healthcare workers with PCR-confirmed COVID-19 between July 2020 and May 2021. Among 17,717 contacted cases, 6061 (34%) participated. A random sample of symptomatic healthcare workers with negative PCR result between November 2020 and May 2021 served as controls. Among 11,498 contacted controls, 4390 (38%) participated.

ExposuresIn multivariable models, sociodemographic and clinical characteristics, as well as vaccine history, were evaluated as potential risk factors. Prevalence ratios compared self-reported cognitive dysfunctions (difficulty concentrating; difficulty organizing oneself; forgetfulness; loss of necessary items) among cases with post-COVID condition to controls, adjusting for psychological distress and fatigue.

OutcomesPost-COVID condition was defined by symptoms persisting [≥]4 weeks or [≥]12 weeks after COVID-19 onset.

ResultsFour-week and 12-week post-COVID condition prevalences of 46% (2,746/5,943) and 40% (653/1,746), respectively, were observed among non-hospitalized cases and 76% (90/118) and 68% (27/37), respectively, among hospitalized cases. Hospitalization, female sex and age were associated with higher risk.

A substantial proportion of non-hospitalized cases with 4-week post-COVID condition often or very often reported cognitive dysfunction, including concentration (33%) or organizing (23%) difficulties, forgetfulness (20%) and loss of necessary items (10%), with no decline at 12 weeks. All four aspects of cognitive dysfunction were 2.2 to 3.0 times more prevalent among cases with post-COVID condition than in controls, but also independently associated with psychological distress and fatigue.

Conclusions and relevancePost-COVID condition may be a frequent sequela of ambulatory COVID-19 in working-age adults, with important effects on cognition. With so many healthcare workers infected since the beginning of the COVID-19 pandemic, the ongoing implications for quality healthcare delivery could be profound should cognitive dysfunction and other severe post-COVID symptoms persist in a professionally-disabling way over the longer term.

Key pointsO_ST_ABSQuestionC_ST_ABSHow common and long-lasting are the physical, psychological and cognitive effects of post-COVID condition in healthcare workers, both hospitalized and non-hospitalized?

FindingsThe prevalence of post-COVID condition was 46% at 4 weeks and 40% at 12 weeks among non-hospitalized cases and 76% and 68% among hospitalized cases. One third of non-hospitalized healthcare workers with post-COVID condition reported cognitive impairment, which was independently associated with persistent physical symptoms, but also psychological distress and fatigue.

MeaningPersistent cognitive and other professionally-disabling sequelae of COVID-19 in essential workers could have critical implications for quality healthcare delivery during and after the pandemic.


title: QUALITY CONTROL OF STAPHYLOCOCCUS AUREUS IN RIO GRANDE AND MENONITA CRIOLLO CHEESES FROM THE ALEJO CALATAYUD MARKET

abstract:
IntroductionThe Staphylococcus aureus count is one of the indicators of the microbiological quality of cheeses according to the parameters of the Bolivian Standard 32004, since this bacterium can cause food poisoning.

ObjectiveTo determine the presence and quantity of Staphylococcus aureus in Rio Grande and Menonita Creole cheeses in the Alejo Calatayud Market in the city of Cochabamba during the month of July 2019 according to parameters established by Bolivian Standard 32004.

MethodsEight samples taken from different cheeses randomly selected from the market were analyzed and subjected to quantitative analysis of CFU/g of Staphylococcus aureus in three different dilutions for each sample, giving a total of 24, 13 were discarded due to impossibility of counting and the remaining samples were subjected to confirmatory tests. The parameters established in the NB32004 were used for the qualification of the results of analysis and tests.

ResultsIn 100% of the samples (8 of 8), the presence of S. aureus bacteria was found in quantities higher than the acceptable CFU/g, determining as deficient the hygienic-sanitary quality of the ripened Creole cheeses sold in the Alejo Calatayud Market.

ConclusionCreole cheeses marketed in the Alejo Calatayud Market have a high degree of contamination by S. aureus and therefore do not comply with the parameters of NB32004 and the population is exposed to food poisoning.


title: Premature Cardiovascular Death and its Modifiable Risk Factors: Protocol of a Systematic Review and Meta-Analysis

abstract:
IntroductionThe burden of cardiovascular disease (CVDs), in the number of premature deaths, continues to increase globally and alarmingly, especially in almost all countries outside high-income countries. An accurate estimate of premature CVD death is of crucial importance for planning, implementing, and evaluating cardiovascular prevention and care interventions. However, existing literature reported the evidence on premature CVD death from selected regions, and there has been less evidence of systematic review with meta-analysis estimating the global premature death. This paper reports the protocol for a systematic review and meta-analysis to derive solid and updated estimates on global and setting-specific premature CVD death prevalence and its associated risk factors.

Methods and analysisPUBMED, EMBASE, Web of Science, CINAHL, and Cochrane Central Register of Controlled Trials (CENTRAL) will be used as the literature database. Retrieved records will be independently screened by two authors and relevant data will be extracted from studies that report data on premature mortality (death before the age of 70 years) related to CVD. Study selection and reporting will follow the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guideline. Pooled estimates of premature CVD mortality (based on standardised mortality ratio and years of life lost) and the effect size of modifiable risk factors will be computed applying random-effects meta-analysis. Heterogeneity among selected studies will be assessed using the I2 statistic and explored through meta-regression and subgroup analyses. Depending on data availability, we propose to conduct subgroup analyses by geographical area, CVD events, and socio-demographic variables of interest study. The risk of bias for the studies included in the systematic review or meta-analysis will be assessed by the Newcastle-Ottawa Quality Assessment Scale.

Ethics and disseminationEthics approval is not required as the data used in this systematic review will be extracted from published studies. The systematic review will focus on the premature CVD mortality rate and its associated factors. The findings of the final report will be disseminated to the scientific community through publication in a peer-reviewed journal and presentation at conferences.

PROSPERO registration numberCRD42021288415

category: cardiovascular medicine


title: Emergence and Spread of the SARS-CoV-2 Omicron Variant in Alberta Communities Revealed by Wastewater Monitoring

abstract: Wastewater monitoring of SARS-CoV-2 allows for early detection and monitoring of COVID-19 burden in communities and can track specific variants of concern. Targeted assays enabled relative proportions of SARS-CoV-2 Omicron and Delta variants to be determined across 30 municipalities covering >75% of the province of Alberta (pop. 4.5M) in Canada, from November 2021 to January 2022. Larger cities like Calgary and Edmonton exhibited a more rapid emergence of Omicron relative to smaller and more remote municipalities. Notable exceptions were Banff, a small international resort town, and Fort McMurray, a more remote northern city with a large fly-in worker population. The integrated wastewater signal revealed that the Omicron variant represented close to 100% of SARS-CoV-2 burden prior to the observed increase in newly diagnosed clinical cases throughout Alberta, which peaked two weeks later. These findings demonstrate that wastewater monitoring offers early and reliable population-level results for establishing the extent and spread of emerging pathogens including SARS-CoV-2 variants.

category: epidemiology


title: Evaluation of the Causal Relationship Between Smoking and Schizophrenia in Asia

abstract: Cigarette smoking has been suggested to be associated with the risk of schizophrenia (SCZ) in observational studies. A significant causal effect of smoking on SCZ has been reported in the European population using the Mendelian randomization (MR) approach; however, no evidence of causality was found in participants from East Asia (EAS). Using the Taiwan Biobank (TWBB, sample size up to 79,989), we conducted genome-wide association studies (GWAS) to identify susceptibility loci for smoking behavior, which included the initiation of smoking and the onset age. To maximize the power of genetic discovery in the EAS population, we meta-analyzed GWAS from the TWBB and Biobank Japan (BBJ, sample size up to 165,436) for smoking traits. The GWAS for SCZ was taken from the Asia Psychiatric Genomics Consortium, which included 22,778 cases and 35,362 controls. We performed a two-sample MR to estimate the causality of smoking behavior on SCZ in the EAS population. In TWBB, we identified one novel locus that met genome-wide significance for onset age. In a meta-analysis of TWBB and BBJ, we identified two novel loci for smoking initiation. In MR, a marginal significance was found for the causality of smoking initiation on SCZ (odds ratio (OR) = 4.00, 95% confidence interval (CI) = 0.89-18.01, P = 0.071). Later onset age for smoking was causally associated with a lower risk of SCZ (OR for a per-year increase in onset = 0.96, 95% CI = 0.91-1.01) with a marginal significance (P = 0.098).


title: Growth monitoring and promotion service utilization and associated factors among children under-two years of age in Samara-logia city of Afar Region, Northeast Ethiopia

abstract:
IntroductionUtilizing growth monitoring and promotion (GMP) during the first two years of birth helps to detect common childhood health problems (e.g., malnutrition and infections) at early stages and offers an opportunity for promoting education and nutritional counselling. However, no previously published study has investigated the level of GMP utilization and associated factors among pastoralist Ethiopian mothers including the Afar National and Regional State (ANRS), where under-nutrition is the major cause of childhood morbidity and mortality. This is the first study aimed to investigate the utilization and associated factors of GMP service for infants and young children in the ANRS of Ethiopia.

MethodsA community-based cross-sectional study was conducted from May to June 202 in the Samara-logia city administration. A total of 416 children aged two years were selected using a random sampling technique, and an interviewer-administered questionnaire was used to collect data. Multivariable logistic regression was applied to examine the influence of explanatory variables (including socio-demographic, obstetric and health service, and health literacy factors) on the utilization of GMP services.

ResultsThe overall utilization of GMP for infants and children was 15.9% with 95% confidence intervals (CI) from 12.0% to 19.5%. Children whose fathers attained college or higher schooling were more likely to utilize GMP services (AOR = 12.40; 95% CI: 4.15, 37.4). Children who resided in households with a higher number of children were less likely to utilize GMP services (AOR = 0.10; 95%CI: 0.03, 0.26 for households with 3-4 children and AOR = 0.16; 95% CI: 0.05, 0.48 for children with 4+). The odds for GMP service utilization was significantly higher among children who received postnatal care (AOR = 9.68; 95% CI: 3.57, 26.20).

ConclusionThe utilization of GMP services is lower to support the reduction of child morbidity and mortality attributed to malnutrition for infants and children in Ethiopia. A higher level of schooling and those who received postnatal care were more likely to utilize GMP, while those who were from households with a higher number of children were less likely to utilize GMP. Our findings suggest strengthening GMP service in Ethiopia, and focused efforts are required on the modifiable associated factors.


title: Trends, regional variation and clinical characteristics of recipients of antivirals and neutralising monoclonal antibodies for non-hospitalised COVID-19: a descriptive cohort study of 23.4 million people in OpenSAFELY

abstract:
BackgroundFrom December 16th 2021, antivirals and neutralising monoclonal antibodies (nMABs) were available to treat high-risk non-hospitalised patients with COVID-19 in England.

AimsTo develop a framework for detailed near real-time monitoring of treatment deployment, to ascertain eligibility status for patients and to describe trends and variation in coverage of treatment between geographic, clinical and demographic groups.

MethodsWith the approval of NHS England we conducted a retrospective cohort study using routine clinical data from 23.4m people in the OpenSAFELY-TPP database, approximately 40% of Englands population. We implemented national eligibility criteria and generated descriptive statistics with detailed clinical, demographic and geographic breakdowns for patients receiving an antiviral or nMAB.

ResultsWe identified 50,730 non-hospitalised patients with COVID-19 between 11th December 2021 and 23rd February 2022 who were potentially eligible for antiviral and/or nMAB treatment. 6420 (15%) received treatment (sotrovimab 3600 (56%); molnupiravir 2680 (42%); nirmatrelvir/ritonavir (Paxlovid) 80 (1%); casirivimab 50 (1%); and remdesivir <5). The proportion treated varied by risk group, with the lowest proportion treated in those with liver disease (10%; 95% CI 9-11). Treatment type also varied, with molnupiravir favoured over sotrovimab in only two high risk cohorts: Down syndrome (67%; 95% CI 59-74) and HIV/AIDS (63%; 95% CI 56-70). The proportion treated varied by ethnicity, from White (14%; 95% CI 13-14) or Asian (13%; 95% CI 12-14) to Black (9%; 95% CI 8-11); by NHS Regions (from 6% (95% CI 5-6) in Yorkshire and the Humber to 17% (95% CI 16-18) in the East of England); and by rurality from 16% (95% CI 14-17) in "Rural - village and dispersed" to 10% (95% CI 10-11) in "Urban - conurbation". There was also lower coverage among care home residents (4%; 95% CI 3-4), those with dementia (4%; 95% CI 3-5), those with sickle cell disease (7%; 95% CI 5-8), and in the most socioeconomically deprived areas (9%; 95% CI 8-9, vs least deprived: 15%; 95% CI 15-16). Patients who were housebound, or who had a severe mental illness had a slightly reduced chance of being treated (10%; 95% CI 8-11 and 10%; 95% CI 8-12, respectively). Unvaccinated patients were substantially less likely to receive treatment (5%; 95% CI 4-6).

ConclusionsUsing the OpenSAFELY platform we have developed and delivered a rapid, near real-time data-monitoring framework for the roll-out of antivirals and nMABs in England that can deliver detailed coverage reports in fine-grained clinical and demographic risk groups, using publicly auditable methods, using linked but pseudonymised patient-level NHS data in a highly secure Trusted Research Environment. Targeted activity may be needed to address apparent lower treatment coverage observed among certain groups, in particular (at present): different NHS regions, socioeconomically deprived areas, and care homes.

category: primary care research


title: Regional, circuit, and network heterogeneity of brain abnormalities in psychiatric disorders

abstract: The substantial individual heterogeneity that characterizes mental illness is often ignored by classical case-control designs that rely on group mean comparisons. Here, we present a comprehensive, multiscale characterization of individual heterogeneity of brain changes in 1294 cases diagnosed with one of six conditions and 1465 matched healthy controls. Normative models identified that person-specific deviations from population expectations for regional grey matter volume were highly heterogeneous, affecting the same area in <7% of people with the same diagnosis. However, these deviations were embedded within common functional circuits and networks in up to 56% of cases. The salience/ventral attention system was implicated transdiagnostically, with other systems selectively involved in depression, bipolar disorder, schizophrenia, and ADHD. Our findings indicate that while phenotypic differences between cases assigned the same diagnosis may arise from heterogeneity in the location of regional deviations, phenotypic similarities are attributable to dysfunction of common functional circuits and networks.

category: psychiatry and clinical psychology


title: Reconstructing subdistrict-level population denominators in Yemen after six years of armed conflict and forced displacement

abstract:
IntroductionYemen has experienced widespread insecurity since 2014, resulting in large-scale internal displacement. In the absence of reliable vital events registration, we tried to reconstruct the evolution of Yemens population between June 2014 and September 2021, at subdistrict (administrative level 3) resolution, while accounting for growth and internal migration.

MethodsWe reconstructed subdistrict-month populations starting from June 2014 WorldPop gridded estimates, as a function of assumed birth and death rates, estimated changes in population density, net internal displacement to and from the subdistrict and assumed overlap between internal displacement and WorldPop trends. Available displacement data from the Displacement Tracking Matrix (DTM) project were subjected to extensive cleaning and imputation to resolve missingness, including through machine learning models informed by predictors such as insecurity. We also modelled the evolution of displaced groups before and after assessment points. To represent parameter uncertainty, we complemented the main analysis with sensitivity scenarios.

ResultsWe estimated that Yemens population rose from about 26.3M to 31.1M during the seven-year analysis period, with considerable pattern differences at sub-national level. We found that some 10 to 14M Yemenis may have been internally displaced during 2015-2016, about five times United Nations estimates. By contrast, we estimated that the internally displaced population had declined to 1-2M by September 2021.

ConclusionsThis analysis illustrates approaches to analysing the dynamics of displacement, and the application of different models and data streams to supplement incomplete ground observations. Our findings are subject to limitations related to data quality, model inaccuracy and omission of migration outside Yemen. We recommend adaptations to the DTM project to enable more robust estimation.

category: public and global health


title: VinDr-Mammo: A large-scale benchmark dataset for computer-aided diagnosis in full-field digital mammography

abstract: Mammography, or breast X-ray, is the most widely used imaging modality to detect cancer and other breast diseases. Recent studies have shown that deep learning-based computer-assisted detection and diagnosis (CADe/x) tools have been developed to support physicians and improve the accuracy of interpreting mammography. However, most published datasets of mammography are either limited on sample size or digitalized from screen-film mammography (SFM), hindering the development of CADe/x tools which are developed based on full-field digital mammography (FFDM). To overcome this challenge, we introduce VinDr-Mammo - a new benchmark dataset of FFDM for detecting and diagnosing breast cancer and other diseases in mammography. The dataset consists of 5,000 mammography exams, each of which has four standard views and is double read with disagreement (if any) being resolved by arbitration. It is created for the assessment of Breast Imaging Reporting and Data System (BI-RADS) and density at the breast level. In addition, the dataset also provides the category, location, and BI-RADS assessment of non-benign findings. We make VinDr-Mammo publicly available on https://physionet.org/ as a new imaging resource to promote advances in developing CADe/x tools for breast cancer screening.

category: radiology and imaging


title: Predicting pneumothorax after lung biopsy from pre-operative imaging using a deep convolutional neural network

abstract:
BackgroundPneumothorax remains one of the most common complications after computed tomography (CT)-guided lung biopsies. Radiographic features including bullae and nodule size are possible markers for post-biopsy pneumothorax. We determine whether a convolutional neural network (CNN) can accurately predict a pneumothorax after lung biopsy based on pre-operative imaging alone.

MethodsWith institutional review board approval, we retrospectively evaluated 3,822 patients who underwent a CT-guided lung biopsy between 2011 to 2019. Two image sets were created with CT scout images (1300 patients, 650 pneumothoraces) and chest x-rays (CXR) taken within three months pre-procedure (884 patients, 140 pneumothoraces). Using pre-operative images, CNNs of varying layer depths were trained using transfer learning to predict the development of a pneumothorax post-biopsy. Performance against models were compared using sensitivity analysis and the McNemars test.

ResultsThe CNN models trained with CT scout images performed near chance. However, the models performed better with CXR radiographs taken within three months pre-biopsy. For the anterior-posterior view, sensitivity was 0.40, specificity was 0.89, PPV was 0.43, and NPV was 0.87 (AUC = 0.67). For the lateral view, sensitivity was 0.40, specificity was 0.80, PPV was 0.32, and NPV was 0.86 (AUC = 0.65). Increasing CNN layers did not affect performance (p > 0.05).

ConclusionChest radiographs taken within three months of lung biopsy may provide important radiographic information for CNNs to assess pneumothorax risk in patients prior to CT-guided lung biopsies. However, more baseline and standardized CXRs before biopsies are necessary to create a robust model for clinical application.


title: Effect of a Pilates exercise program on the flexion-relaxation rate in women with chronic low back pain

abstract:
PurposeTo evaluate the effect of a Pilates exercise program (PEP) on FRR and FRR asymmetry of the erector spinae (ES) muscle during standing maximal trunk flexion/extension in women with chronic low-back pain (LBP). A secondary goal was to investigate the effect of PEP on full trunk flexion ROM (TFRoM), pain intensity and functional capacity and analyse their relationship with the FRR.

Material and methodsThirty women with chronic LPB were randomly assigned to either PEP (EG, n=15) or control group (CG=15). EG followed an 8-week PEP while no specific intervention was carried out on the controls. Before and after this period all variables were recorded.

ResultsFRR did not show any significant changes between or within groups (p>0.05). EG showed a significant statistical difference in the FRR asymmetry pre- and post-intervention (p{square} 0.05). Full TFRoM did not show any significant changes between or within groups (p>0.05). EG showed a significant decrease of 30% on pain intensity and a significant increase of 13.4 % in functional capacity (P{square}0.001) from pre to post-intervention.

ConclusionsAn 8-week PEP does not affect FRR nor full trunk ROM, however yields improvements in pain intensity and functional capacity.Professionals should be aware of the negative effect on FRR asymmetry.

category: rehabilitation medicine and physical therapy


title: Factors Associated With Post-craniotomy Headache After Microvascular Decompression in Hemifacial Spasm? A Retrospective Study

abstract:
ObjectivePatients who undergo microvascular decompression (MVD) often experience post-craniotomy headache (PCH), while the PCH is always neglected. This study is aimed to describe the natural course and risk factors of PCH.

MethodsThe severity and duration of PCH in 87 patients who undergo MVD were recorded. Factors related to the severity and duration of PCH were analyzed.

ResultsMost patients (63.2%) had at least one assessment of moderate to severe PCH. Almost all patients (92%) would gradually decrease to disappear within 7 days. A small number of patients (25.5%) had PCH at the incision, and other patients had PCH inside the head. Younger age and gas in the prepontine cistern were the salient features of patients in the severe group. Younger, higher SAS, gas in the prepontine cistern area, and postoperative fever were independent risk factors that affect the duration of PCH.

ConclusionsPCH is the most common and self-limiting complication after MVD among patients with HFS. Young age, temperature > 38{degrees}C after MVD within 24h, and gas around the TN are associated may predict the severity and duration of PCH.

SignificanceThis is the first study to describe the severity, duration, location, and risk factors of PCH.

category: neurology


title: The clinical need for clustered AChR cell-based assay testing of seronegative MG

abstract: Trial eligibility in myasthenia gravis (MG) remains largely dependent on a positive autoantibody serostatus. This significantly hinders seronegative MG (SNMG) patients from receiving potentially beneficial new treatments. In a subset of SNMG patients, acetylcholine receptor (AChR) autoantibodies are detectable by a clustered AChR cell-based assay (CBA). Of 99 SNMG patients from two academic U.S. centers, 18 (18.2%) tested positive by this assay. Autoantibody positivity was further validated in 17/18 patients. In a complementary experiment, circulating AChR-specific B cells were identified in a CBA-positive SNMG patient. These findings corroborate the clinical need for clustered AChR CBA testing when evaluating SNMG patients.


title: Machine Learning for Real-Time Aggregated Prediction of Hospital Admission for Emergency Patients

abstract: Machine learning for hospital operations is under-studied. We present a prediction pipeline that uses live electronic health-records for patients in a UK teaching hospitals emergency department (ED) to generate short-term, probabilistic forecasts of emergency admissions. A set of XGBoost classifiers applied to 109,465 ED visits yielded AUROCs from 0.82 to 0.90 depending on elapsed visit-time at the point of prediction. Patient-level probabilities of admission were aggregated to forecast the number of admissions among current ED patients and, incorporating patients yet to arrive, total emergency admissions within specified time-windows. The pipeline gave a mean absolute error (MAE) of 4.0 admissions (mean percentage error of 17%) versus 6.5 (32%) for a benchmark metric. Models developed with 104,504 later visits during the Covid-19 pandemic gave AUROCs of 0.68-0.90 and MAE of 4.2 (30%) versus a 4.9 (33%) benchmark. We discuss how we surmounted challenges of designing and implementing models for real-time use, including temporal framing, data preparation, and changing operational conditions.

category: health systems and quality improvement


title: Gaps in mobility data and implications for modelling epidemic spread: a scoping review and simulation study

abstract:
Reliable estimates of human mobility are important for understanding the spatial spread of infectious diseases and the effective targeting of control measures. However, when modelling infectious disease dynamics, data on human mobility at an appropriate temporal or spatial resolution are not always available, leading to the common use of model-derived mobility proxies. In this study we reviewed the different data sources and mobility models that have been used to characterise human movement in Africa. We then conducted a simulation study to better understand the implications of using human mobility proxies when predicting the spatial spread and dynamics of infectious diseases.

We found major gaps in the availability of empirical measures of human mobility in Africa, leading to mobility proxies being used in place of data. Empirical data on subnational mobility were only available for 17/54 countries, and in most instances, these data characterised long-term movement patterns, which were unsuitable for modelling the spread of pathogens with short generation times (time between infection of a case and their infector). Results from our simulation study demonstrated that using mobility proxies can have a substantial impact on the predicted epidemic dynamics, with complex and non-intuitive biases. In particular, the predicted times and order of epidemic invasion, and the time of epidemic peak in different locations can be underestimated or overestimated, depending on the types of proxies used and the country of interest.

Our work underscores the need for regularly updated empirical measures of population movement within and between countries to aid the prevention and control of infectious disease outbreaks. At the same time, there is a need to establish an evidence base to help understand which types of mobility data are most appropriate for describing the spread of emerging infectious diseases in different settings.


title: Quantifying the vaccine-induced humoral immune response to spike-receptor binding domain as a surrogate for neutralization testing following mRNA-1273 (Spikevax) vaccination against COVID-19

abstract:
BackgroundThere is a need for automated, high throughput assays to quantify immune response after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study assessed the combined utility of the Roche assays, Elecsys(R) Anti-SARS-CoV-2 S (ACOV2S) and Elecsys Anti-SARS-CoV-2 (ACOV2N) using samples from the 2019-nCoV vaccine (mRNA-1273, Spikevax) phase 2 trial (NCT04405076).

MethodsSamples from 593 healthy participants in two age cohorts (18-54 years and [≥]55 years), who received two injections with either placebo (n=198) or mRNA-1273 at a dose of either 50 g (n=197) or 100 g (n=198), were collected at Days 1 (first vaccination), 15, 29 (second vaccination), 43 and 57. ACOV2S results were used to assess the humoral response to vaccination in different clinical trial subgroups and were compared to a live virus microneutralization assay. Sample panels from patients with evidence of previous or concomitant infection (as identified using ACOV2N) or with an inconsistent antibody response pattern were analyzed separately.

ResultsReceptor-binding domain (RBD)-specific antibodies were readily detectable by ACOV2S for the vast majority of participants (174/189 [50 g dose group] and 178/192 [100 g]) at the first time point of assessment, with non-converters predominantly older in age. Complete seroconversion for all participants was observed at the subsequent timepoint (Day 29) and before administration of the second dose of vaccine. Two weeks after the first vaccine dose (Day 15), geometric mean concentration (GMC) of antibody levels were 1.37-fold higher in the 100 g compared with the 50 g dose group; this difference reduced to 1.09-fold two weeks after the second dose (Day 43). In both the 50 g and 100 g dose groups, a more pronounced response was observed in the younger versus the older age group on Day 15 (2.49-fold and 3.94-fold higher GMC, respectively) and Day 43 (1.35-fold and 1.50-fold higher GMC). Few subjects had a previous or concomitant natural SARS-CoV-2-infection (n=8). Vaccination of pre-infected individuals boosted the immune response to very high ACOV2S results compared to infection-naive vaccine recipients. ACOV2S measurements were strongly correlated with those from the live microneutralization assay (Pearsons r=0.779; p<0.0001) and good qualitative agreement was achieved (100% positive and 91.8% negative percentage agreement; 90.0% positive and 100% negative predictive value).

ConclusionThe results from this study confirmed that ACOV2S is a highly valuable assay for the tracking of vaccine-related immune responses. Combined application with ACOV2N enables serologic monitoring for breakthrough infection or stratification of previous natively-infected individuals. The adaptive measuring range and high resolution of ACOV2S allows for the early identification of seroconversion as well as for resolution of very high titers and detection of longitudinal differences between age and dose groups. Additionally, good correlation of ACOV2S with live virus microneutralization indicates the utility of ACOV2S as a reliable estimate of neutralization capacity in routine diagnostic settings.


title: Short-term drop in antibody titer after the third dose of SARS-CoV-2 BNT162b2 vaccine in adults

abstract:
Little is known about the longevity of antibodies after a third dose of BNT162b2 (BioNTech/Pfizer). Therefore, the serum antibody levels were evaluated after the third dose of BNT162b2 which dropped significantly within 11 weeks from 4155.59 {+/-} 2373.65 BAU/ml to 2389.10 {+/-} 1433.90 BAU/ml, p-value <0.001 but remained higher than after the second dose.

These data underline the positive effect of third dose of BNT162b2 but shows a rapid and significant drop of antibodies within a short span of time.

Trial RegistrationThis trial was prospectively registered in the German Clinical Trial Register (DRKS00021270).


title: Ultrastructural characterisation of young and aged dental enamel by atomic force microscopy

abstract: Recent advances in atomic force microscopy (AFM) have allowed the characterisation of dental-associated biomaterials and biological surfaces with high-resolution and minimal sample preparation. In this context, the topography of dental enamel - the hardest mineralised tissue in the body - has been explored with AFM-based approaches at the micro-scale. With age, teeth are known to suffer changes that can impact their structural stability and function; however, changes in enamel structure because of ageing have not yet been explored with nanoscale resolution. Therefore, the aim of this exploratory work was to optimise an approach to characterise the ultrastructure of dental enamel and determine potential differences in topography, hydroxyapatite (HA) crystal size, and surface roughness at the nanoscale associated to ageing. For this, a total of six teeth were collected from human donors from which enamel specimens were prepared. By employing AC mode imaging, HA crystals were characterised in both transversal and longitudinal orientation with high-resolution in environmental conditions. Sound superficial enamel displayed the presence of a pellicle-like coating on its surface, that was not observable on cleaned specimens. Acidetching exposed crystals that were imaged and morphologically characterised in highresolution at the nanoscale in both the external and internal regions of enamel in older and younger specimens. Our results demonstrated important individual variations in HA crystal width and roughness parameters across the analysed specimens; however, an increase in surface roughness and decrease in HA width was observed for the pooled older external enamel group compared to younger specimens. Overall, high-resolution AFM was an effective approach for the qualitative and quantitative characterisation of human dental enamel ultrastructure at the nanometre range. Future work should focus on exploring the ageing of dental enamel with increased sample sizes to compensate for individual differences as well as other potential confounding factors such as behavioural habits and mechanical forces.

category: dentistry and oral medicine


title: Extending non-targeted exposure discovery of environmental chemical exposures during pregnancy and their association with pregnancy complications, a cross-sectional study

abstract:
BackgroundNon-targeted Analysis (NTA) methods can identify novel exposures in a variety of biological matrices, however, few have been assessed for relationships with pregnancy complications.

ObjectivesThis study characterizes levels of nine exogenous and endogenous chemicals including linear and branched isomers perfluorooctane sulfonate (PFOS); perfluorohexane sulfonate (PFHxS); monoethylhexyl phthalate; 4-nitrophenol; and tetraethylene glycol; the fatty acids: tridecanedioic acid and octadecanedioic acid, and the bile acid: deoxycholic acid. These chemicals were identified, selected, and confirmed in prior NTA steps and we evaluate their relationship with pregnancy complications in a diverse pregnancy cohort in San Francisco.

MethodsMatched maternal and cord serum samples were collected from 302 pregnant people at delivery from the Chemicals in Our Bodies cohort in San Francisco. Chemicals were identified via NTA and quantified using targeted approaches. We calculate distributions and Spearman correlation coefficients testing the relationship of chemicals within and between the maternal and cord blood matrices. Among the maternal samples we used logistic regression to calculate the odds of gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy associated with prenatal chemical exposures.

ResultsWe detected linear PFOS, PFHxS, tridecanedioic acid, and deoxycholic acid in at least 97% of maternal samples. We observed strong correlations between cord and maternal levels of PFHxS (coefficient = 0.9), linear PFOS (0.8), and branched PFOS (0.8). In maternal samples, branched PFOS was correlated with linear PFOS (0.8) and PFHxS (0.6). We found Linear PFOS and branched PFOS were positively associated with increased odds of GDM [OR (95%CI): 1.60 (0.94, 2.73) and 1.56 (1.00, 2.44) respectively] and tridecanedioic acid was positively associated with hypertensive disorders of pregnancy [1.71 (0.79, 3.82)].

DiscussionChemicals measured in this study were identified through NTA and targeted quantification. We identified endogenous and exogenous chemicals some of which have seldom been quantified in pregnant people.

category: endocrinology


title: SARS-CoV-2 genomic surveillance enables the identification of Delta/Omicron co-infections in Argentina.

abstract: Molecular surveillance of SARS-CoV-2 is crucial to early detect new variants and lineages. In addition, detection of coinfections with more than one SARS-CoV-2 lineage have been sporadically reported. In this work, surveillance of SARS-CoV-2 variants was performed on 2067 RNA samples (Ct>30) obtained during December 2021 and January 2022 from Cordoba province, Argentina, by real time RT-PCR specific for VOC/VOI relevant mutations (TaqMan SARS-CoV-2 Mutation Panel, Applied Biosystems). The following distribution of variants was obtained: Omicron (54.9%), Delta (44.2%) and Lambda (0.8%). Three samples (0.1%), obtained the last week of December, presented a profile compatible with a Delta/Omicron co-infection. One of them was sequenced by NGS-Illumina, obtaining reads for both VOCs. One of the studied patients presented severe symptoms, although he was not vaccinated and presented risk factors (older than 60 years, arterial hypertension). We describe for the first time in Argentina, the identification of cases of co-infection with two SARS-CoV-2 lineages, VOCs Delta and Omicron, during the third COVID-19 wave in the country (a high viral circulation period), when Delta and Omicron co-circulated. Our findings highlight the importance of continuing with molecular surveillance and co-detection studies of VOC/VOIs, in order to elucidate possible recombination events and the emergence of new variants.


title: Bioinfo-pharmacology: the example of therapeutic hypothermia

abstract:
Computer-aided drug discovery (CADD) is a widely used method for drug discovery with many successes. Meanwhile, CADD has the limitation of analyzing multi-level scores such as docking results of multiple proteins with multiple drugs. We propose a method of PageRank to solve the problem. This method can make a comprehensive ranking based on multi-level scores. Then we take an example of therapeutic hypothermia (TH). Three levels of TH data were used in the article: the log2 foldchange (logFC) of proteins, the relative expression values of mRNA, and the docking scores of proteins and molecules. After calculation, we get the comprehensive drug rank and drug combination rank of each group of TH, which means we can generate the rank of drug directly from bioinformatics. Based on this method, we raised the concept of bioinfo-pharmacology. Given the high rationality and compatibility of bioinfo-pharmacology, it can effectively enhance popular drug discovery techniques such as the docking or pharmacophore model. Besides, it could advance the application of precision medicine.

Keyword: computer-aided drug discovery (CADD); precision medicine; Therapeutic hypothermia; di-erential gene expression; virtual screening;

category: pharmacology and therapeutics


title: Phase Recognition in Contrast-Enhanced CT Scans based on Deep Learning and Random Sampling

abstract:
PurposeA fully automated system for interpreting abdominal computed tomography (CT) scans with multiple phases of contrast enhancement requires an accurate classification of the phases. Current approaches to classify the CT phases are commonly based on 3D convolutional neural network (CNN) approaches with high computational complexity and high latency. This work aims at developing and validating a precise, fast multi-phase classifier to recognize three main types of contrast phases in abdominal CT scans.

MethodsWe propose in this study a novel method that uses a random sampling mechanism on top of deep CNNs for the phase recognition of abdominal CT scans of four different phases: non-contrast, arterial, venous, and others. The CNNs work as a slice-wise phase prediction, while the random sampling selects input slices for the CNN models. Afterward, majority voting synthesizes the slice-wise results of the CNNs, to provide the final prediction at scan level.

ResultsOur classifier was trained on 271,426 slices from 830 phase-annotated CT scans, and when combined with majority voting on 30% of slices randomly chosen from each scan, achieved a mean F1-score of 92.09% on our internal test set of 358 scans. The proposed method was also evaluated on 2 external test sets: CTPAC-CCRCC (N = 242) and LiTS (N = 131), which were annotated by our experts. Although a drop in performance has been observed, the model performance remained at a high level of accuracy with a mean F1-score of 76.79% and 86.94% on CTPAC-CCRCC and LiTS datasets, respectively. Our experimental results also showed that the proposed method significantly outperformed the state-of-the-art 3D approaches while requiring less computation time for inference.

ConclusionsIn comparison to state-of-the-art classification methods, the proposed approach shows better accuracy with significantly reduced latency. Our study demonstrates the potential of a precise, fast multi-phase classifier based on a 2D deep learning approach combined with a random sampling method for contrast phase recognition, providing a valuable tool for extracting multi-phase abdomen studies from low veracity, real-world data.


title: Higher levels of myelin are associated with higher resistance against tau pathology in Alzheimer's disease

abstract: In Alzheimers disease (AD), pathologic tau gradually progresses from initially circumscribed predilection regions to closely connected cortical regions. The pattern of tau-deposition is of critical importance for the clinical expression of AD, but the factors that underlie region-dependent susceptibility and resistance to tau pathology remain elusive. Motivated by brain-autopsy findings suggesting late thinly myelinated regions are the first to develop tau pathology, we investigated whether the level of myelination in fiber-tracts and cortex is predictive of region-specific tau accumulation. To address this hypothesis, we combined MRI-derived template of normative myelin distribution with tau-PET imaging from two independent samples of AD-biomarker characterized participants. We found that higher myelinated cortical regions show lower tau-PET uptake in spatially corresponding areas and regions connected by highly myelinated fiber-tracts show lower rates of tau spreading. These findings were independent of amyloid-PET levels. Together, our findings suggest that higher myelination is an important resistance factor against tau pathology in AD.


title: Automated detection of axonal injury along white matter tracts in acute severe head trauma

abstract: New techniques for individualized assessment of white matter integrity are needed to detect traumatic axonal injury (TAI) and predict outcomes in critically ill patients with acute severe traumatic brain injury (TBI). Diffusion MRI tractography has the potential to quantify white matter microstructure in vivo and has been used to characterize tract-specific changes in TBI. However, tractography is not routinely used in the clinical setting to assess the extent of TAI, in part because focal lesions reduce the robustness of automated methods. In the present study, we propose an automated pipeline for individualized assessment of white matter damage in patients with acute severe TBI that is based on tractography reconstructions and multivariate analysis of along-tract diffusion metrics. We used the Mahalanobis distance to test for a deviation of diffusion metrics along 40 white matter tracts in 18 patients with acute severe TBI as compared to 33 healthy subjects. The automated pipeline successfully reconstructed white matter tracts in all patients with a successful FreeSurfer anatomical segmentation (17 of 18 patients), including 13 with focal lesions. In these 17 patients, a mean of 37.5 +/- 2.1 tracts were reconstructed without the need for manual intervention and a mean of 2.47 +/- 2.1 needed to be reinitialized upon visual inspection. The pipeline detected at least one injured tract in all patients (mean: 12.6, SD: 7.6). The number and neuroanatomic location of disrupted tracts varied across patients and levels of consciousness. The pre-motor, parietal, and temporal sections of the corpus callosum were the structures most frequently injured (in 10, 9, and 8 patients respectively), consistent with histological studies of TAI. Multivariate measures of TAI did not show a significant association with behavioral measures of consciousness, or subscales measuring basic language and motor function. In summary, we provide proof- of-principle evidence that an automated tractography pipeline can be used to detect and quantify TAI in patients with acute severe head trauma and could therefore assist in the clinical assessment of TAI.


title: The Acoustic Dissection of Cough: Diving into Machine Listening-based COVID-19 Analysis and Detection

abstract:
PurposeThe coronavirus disease 2019 (COVID-19) has caused a crisis worldwide. Amounts of efforts have been made to prevent and control COVID-19s transmission, from early screenings to vaccinations and treatments. Recently, due to the spring up of many automatic disease recognition applications based on machine listening techniques, it would be fast and cheap to detect COVID-19 from recordings of cough, a key symptom of COVID-19. To date, knowledge on the acoustic characteristics of COVID-19 cough sounds is limited, but would be essential for structuring effective and robust machine learning models. The present study aims to explore acoustic features for distinguishing COVID-19 positive individuals from COVID-19 negative ones based on their cough sounds.

MethodsWith the theory of computational paralinguistics, we analyse the acoustic correlates of COVID-19 cough sounds based on the COMPARE feature set, i. e., a standardised set of 6,373 acoustic higher-level features. Furthermore, we train automatic COVID-19 detection models with machine learning methods and explore the latent features by evaluating the contribution of all features to the COVID-19 status predictions.

ResultsThe experimental results demonstrate that a set of acoustic parameters of cough sounds, e. g., statistical functionals of the root mean square energy and Mel-frequency cepstral coefficients, are relevant for the differentiation between COVID-19 positive and COVID-19 negative cough samples. Our automatic COVID-19 detection model performs significantly above chance level, i. e., at an unweighted average recall (UAR) of 0.632, on a data set consisting of 1,411 cough samples (COVID-19 positive/negative: 210/1,201).

ConclusionsBased on the acoustic correlates analysis on the COMPARE feature set and the feature analysis in the effective COVID-19 detection model, we find that the machine learning method to a certain extent relies on acoustic features showing higher effects in conventional group difference testing.


title: Disparities in Knowledge, Attitude and Practices on Mental Health among Healthcare Workers and Community members in Meru County, Kenya

abstract:
BackgroundMental health (MH) remains a neglected priority in many low and middle-income countries. Currently, there is inadequate data on the prevalence of mental health in Kenya. This is compounded by huge inequity in the distribution of skilled human resources for mental health services. Inadequate knowledge about mental health and negative attitudes towards people with mental health disorders is widespread among the general public.

MethodsThis was a descriptive cross-sectional survey that utilised mixed methods for data collection. A total of 535 community members and 109 healthcare workers (HCWs) were targeted for the study. All cadres of healthcare workers in the selected health facilities who voluntarily consented to participate were recruited through simple random sampling. Data were collected using household surveys, Key Informant Interviews (KIIS) with facility in-charges; Focus Group Discussions (FGD) with community members particularly community Health Volunteers (CHVs) and youth; and In-depth Interviews (IDI) with community gate keepers such as religious leaders, Religious leader, Chiefs/sub-Chiefs, and traditional leaders. Data analysis included simple univariate frequencies of questions chosen to reflect the key concepts on mental health. Descriptive statistics were used to determine frequencies and percentages for the different variables under study. For qualitative data, thematic analysis was applied to generate themes through deductive and inductive methods. Triangulation of qualitative and quantitative data was conducted.

ResultsApproximately 39.1% of respondents reported to have had a family member with mental illness and 68% of HCWs reported to have diagnosed a patient with mental illness. 64% of respondents cited causes of mental disorders as witchcraft; generational curses in some families; genetic factors; drug and substance abuse especially marijuana; social and economic/financial pressures; and injuries from accidents. 93.3% of the HCWs reported to have referred patients to a mental health facility. Only 29.4% of the HCWs reported having counselling services in the facilities for patients with mental health needs. Majority (90.8% HCWs and 62.3% community members) reported that it is convenient for patients with MH needs and illness from the community to access the health care facilities and that MH services were available and mainly offered at the Meru Teaching and Referral Hospital (81.7% HCWs and 53.8% community members). Majority of HCWs (89.9%) reported that MH services were affordable to community members. On the contrary, only 44.4% of community members reported that MH services are affordable. The HCWs reported that the drugs were given for free at the health facilities while community members reported that sometimes stock-outs in drugs for MH existed in which case they would purchase drugs from pharmacies. Majority (96.4% HCWs and 62.5% community members) reported that patients with mental health1 needs and illness2 are treated with respect in the facilities. Aside from health facilities, community members also seek mental health services from: religious leaders; traditional healers including the Religious leader who were approached for cleansing if one believed that the mental health issues were a curse for committing certain offenses. It was also evident that some families did not seek any kind of help for their relatives with mental health illness and needs, with some even detaining them.

ConclusionThis study adds to the global knowledge on mental health among healthcare workers and community members providing vital data at service delivery level from an African developing country perspective. There is evidence of high burden of MH in the county with very few facilities offering MH services for patients. The existence of myths and misconceptions around the causes of MH is evident and needs to be addressed. There are also evident disparities in the perception of HCWs and Community members in MH with regards to availability and affordability of MH services and access to MH drugs. Communities still seek MH services from traditionalists and some people still neglect MH cases. Sustained poor mental health of individuals, families, the communities including healthcare workers has an enormous contribution towards negative health seeking behavior as well as social capital, an important determinant of health not just in Kenya but in many rural settings across the world. With this therefore, there is need to build the capacity of health care workers and create awareness to the community members as well as strengthen health systems to tackle MH.


title: Aerosolized Ad5-nCoV booster vaccination elicited potent immune response against the SARS-CoV-2 Omicron variant after inactivated COVID-19 vaccine priming

abstract: The SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant around the world and exhibits immune escape to current COVID-19 vaccines to some extent due to its numerous spike mutations. Here, we evaluated the immune responses to booster vaccination with intramuscular adenovirus-vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines 6 months prior. We found that the Ad5-nCoV booster induced potent neutralizing activity against the wild-type virus and Omicron variant, while aerosolized Ad5-nCoV generated the greatest neutralizing antibody responses against the Omicron variant at day 28 after booster vaccination, at 14.1-fold that of CoronaVac, 5.6-fold that of ZF2001 and 2.0-fold that of intramuscular Ad5-nCoV. Similarly, the aerosolized Ad5-nCoV booster produced the greatest IFN{gamma} T-cell response at day 14 after booster vaccination. The IFN{gamma} T-cell response to aerosolized Ad5-nCoV was 12.8-fold for CoronaVac, 16.5-fold for ZF2001, and 5.0-fold for intramuscular Ad5-nCoV. Aerosolized Ad5-nCoV booster also produced the greatest spike-specific B cell response. Our findings suggest that inactivated vaccine recipients should consider adenovirus-vectored vaccine boosters in China and that aerosolized Ad5-nCoV may provide a more efficient alternative in response to the spread of the Omicron variant.


title: Exposures associated with sporadic Cryptosporidium infection in industrialised countries: a systematic review

abstract:
Transmission of Cryptosporidium can occur via contaminated food or water, contact with animals or other people. Exposures are often identified from outbreak investigations, but sources for sporadic disease and pathways to infection are still unclear. The aim of this review is to consolidate the literature to describe exposures associated with human cryptosporidiosis in industrialised countries.

Methods followed the recommendations made in the Cochrane Handbook for Systematic Reviews of Interventions. Three steps were used to identify the literature including electronic database searching using PubMed, Scopus and Web Of Science; reference list trawling; and an exploration of the grey literature. Quality was assessed using the Newcastle-Ottawa Scale. Screening of results was undertaken by two reviewers and data extracted using a standardised form. A narrative summary presented. Papers were included if they reported on sporadic cases and were published between 2008 and 2018. Exposures were grouped into pathways.

After full-text screening, eight articles (comprising 11 studies) were included, and seven (comprising 10 studies) were suitable for further synthesis. None of the identified grey literature was included. Four studies described case-control methods, two were case-case studies and one cross-sectional. Study year ranged from 1999 to 2017 and the studies were conducted in five, large countries in three continents: Europe (UK and the Netherlands), North America (USA, Canada), and Australia.

Included papers investigated water and animal exposures most frequently. Recreational water was not a major source of sporadic illness in this review. The person-to-person pathway represented the most consistent finding, with all three studies reporting on contact with a symptomatic individual demonstrating correlations between exposure and disease. This applied particularly to the home environment, which is increasingly understood to be a significant setting for spread of Cryptosporidium infection. Further work on this would help support public health messaging on preventing spread of disease at home.

Systematic review registration: PROSPERO number CRD42017056589.


title: Self-injury, suicidal ideation and -attempt and eating disorders in young people following the initial and second COVID-19 lockdown

abstract:
BackgroundThe initial COVID-19 lockdowns have had negative effect on different mental health measures, especially in young women. However, the impact on self-injury, suicidality and eating disorder (ED) are less elucidated and remains inconsistent. We compare self-reported self-injury, suicide ideation and -attempt and symptoms of EDs from before through different pandemic periods until spring 2021.

MethodsYoung participants in the Danish National Birth Cohort reported these measures in an 18-year follow-up in 2015-2021 and in a COVID-19 survey in spring 2021 when participants were aged 19-24 years. Changes in measures from pre to post lockdown were estimated with longitudinal data (N=7,597) and with repeated cross-sectional data (N=24,625) by linear regression.

FindingsIn the longitudinal comparisons 14% of women and 7% of men reported self-injury pre lockdown, which decreased 6%-points (95% CI:-7%;-5%) for women and 3%-points (95% CI:-4%;-2%) for men during lockdown. For suicide ideation, the pre lockdown proportions were 25% and 18% for women and men respectively, and decreased 7%-points (95% CI:-8%;-6%) for women and 3%-points (95% CI:-5%;-1%) for men. For suicide attempt no change was observed. Pre lockdown 15% and 3% of women and men, respectively, had symptoms of EDs, which decreased 2%-points (95% CI:-3%;-1%) for women. We observed no changes in proportions of self-injury, suicide ideation or EDs in the repeated cross-sectional data.

InterpretationOur findings provide no support for increase in self-injury, suicidality and EDs following the lockdowns, and if anything, indicate a reduction in self-injury and suicide ideation as well as EDs in women.


title: Community Engagement to support COVID-19 Vaccine Uptake: A living systematic review protocol

abstract:
BackgroundWidespread vaccination against Coronavirus Disease 2019 (COVID-19) is one of the most effective ways to control, and ideally, end the global COVID-19 pandemic. Vaccine hesitancy and vaccine rates vary widely across countries and populations and are influenced by complex socio-cultural, political, economic, and psychological factors. Community engagement is an integral strategy within immunisation campaigns and has been shown to improve vaccine acceptance. As evidence on community engagement to support COVID-19 vaccine uptake is emerging, this review aims to lessen the knowledge-to-practice gap by providing regular evidence on current best-practice.

MethodologyA living systematic review will be conducted which includes an initial systematic review and bi-monthly review updates. Searching and screening for the review and subsequent updates will be done in four streams: a systematic search of six databases, grey literature review, preprint review, and citizen sourcing. All articles will be collated into Covidence, where screening will be done by a minimum of two reviewers at title/abstract and full-text. Data will be extracted across pre-defined data extraction tables, and synthesis will occur using the convergent integrated approach. Updates to the review resulting from the subsequent bi-monthly searches will be shared in an open-access platform. The protocol has been registered with PROSPERO: CRD42022301996.

DiscussionGiven the variation in vaccination rates across different contexts and the recognition that high vaccination coverage is required to reduce COVID-19 transmission and to stop the emergence of new variants, it is imperative the global community implements strategies that will improve uptake and that this work is widely shared and contextualised. Community engagement to promote vaccine uptake is highly encouraged, and recent studies highlight its potential to influence vaccine rates, particularly across populations that are marginalised. The high-priority research needed on this topic, and the rapidly changing evidence base, supports the conduct of a living systematic review.


title: The prevalence of female genital mutilation: a systematic review and meta-analysis of national, regional, facility and school-based studies.

abstract:
BackgroundFemale Genital Mutilation/Cutting (FGM/C) is a non-medical procedure entailing the modification of the external female genitalia. The Sustainable Development Goals aim to end FGM/C by 2030. This systematic review aimed to examine FGM/C prevalence and types, by World Health Organization (WHO) region and country.

Methods and FindingsA systematic search using MeSH headings and keywords from inception to March 2, 2020 was undertaken in MEDLINE, PsycINFO, Web of Science, and Embase to identify studies presenting FGM/C prevalence. Abstract and full-text screening, quality assessment, and data extraction were undertaken by two reviewers. Only nationally representative studies were included in the meta-analysis. Pooled FGM/C prevalence was estimated by meta-analysis using random effects models. FGM/C prevalence and types were presented separately by women aged 15-49 and girls aged 0-14. 3,205 articles were identified. 135 met the inclusion criteria and 28 were included in the meta-analysis. Across 27 countries, the pooled prevalence estimate of FGM/C in women aged 15-49 was 40% (95% CI: 26-55%; I2 =100%), and 15% (95% CI: 10-21%; I2 =100%) in girls aged 0-14 across 34 countries. The country with the highest FGM/C prevalence in women was Guinea (97%) and the lowest, Uganda (0{middle dot}3%). The highest prevalence in girls was in Mali (77%), and the lowest in Ghana (0%). The most common category of FGM/C was "flesh removed" at 69% (women) and 70% (girls). Limitations include that studies had heterogeneous terminology and relied on recall.

ConclusionsThere is large variation in FGM/C prevalence, and the lower prevalence in the current generation of girls is encouraging. However, considerable policy and community-level interventions are required to meet the SDG. Future research should consider collecting data on the 15-19 age group in order to accurately assess generational differences in FGM prevalence. The study protocol is available: https://osf.io/ema9j/.

FundingNone

category: sexual and reproductive health


title: impaired bed mobility in prediagnostic and de novo Parkinson's disease

abstract:
BackgroundWearable technology research suggests that nocturnal movements are disturbed in early Parkinsons disease (PD). In this study, we investigate if patients also already experience impaired bed mobility before PD diagnosis. Furthermore, we explore its association with motor and nonmotor features and its value for phenoconversion and disease progression prediction.

MethodsPPMI data were downloaded for de novo PD subjects, subjects at-risk for developing a synucleinopathy (with isolated REM sleep behavior disorder, hyposmia or a pathogenic mutation) and controls. Impaired bed mobility was assessed with the MDS-UPDRS part 2 item 9. A frequency analysis was performed. Multivariable logistic regression analyses were used to investigate the association with other PD variables. Cox proportional-hazards models were used to test if difficulties with turning in bed could predict phenoconversion. Linear mixed models were used to evaluate if difficulties with turning in bed could predict disease progression.

ResultsOf the at-risk subjects, 9.2-12.5% experienced difficulties with turning in bed vs. 25.0% of de novo PD subjects and 2.5% of controls. Impaired turning ability was associated with MDS-UPDRS motorscore (axial signs in the at-risk group, bradykinesia in the de novo PD group) and SCOPA-AUT score (gastrointestinal symptoms). In addition, difficulties with turning in bed were a significant predictor for phenoconversion in the at-risk group and for development of motor complications in the de novo PD group.

ConclusionOur findings suggest that difficulties with turning in bed can be helpful as clinical symptom for a prodromal PD screening and for motor complication prediction in early PD.

HighlightsO_LISubjective difficulties with turning in bed are a prodromal PD symptom.
C_LIO_LIImpaired bed mobility predicts synucleinopathy phenoconversion in at-risk groups.
C_LIO_LIImpaired bed mobility predicts development of motor complications in de novo PD.
C_LI


title: A non-coding single nucleotide polymorphism at 8q24 drives IDH1-mutant glioma formation

abstract: Establishing causal links between inherited polymorphisms and cancer risk is challenging. Here, we focus on the single nucleotide polymorphism rs55705857 (A>G), which confers a 6-fold increased risk of IDH-mutant low-grade glioma (LGG) and is amongst the highest genetic associations with cancer. By fine-mapping the locus, we reveal that rs55705857 itself is the causal variant and is associated with molecular pathways that drive LGG. Mechanistically, we show that rs55705857 resides within a brain-specific enhancer, where the risk allele disrupts OCT2/4 binding, allowing increased interaction with the Myc promoter and increased Myc expression. To functionally test rs55705857, we generated an IDH1R132H-driven LGG mouse model and show that mutating the highly conserved, orthologous mouse rs55705857 locus dramatically accelerated tumor development from 463 to 172 days and increased penetrance from 30% to 75%. Overall, our work generates new LGG models and reveals mechanisms of the heritable predisposition to lethal glioma in [~]40% of LGG-patients.

category: oncology


title: Donor whole blood DNA methylation is not a strong predictor of acute graft versus host disease in unrelated donor allogeneic haematopoietic cell transplantation

abstract:
Allogeneic hematopoietic cell transplantation (HCT) is used to treat many blood-based disorders and malignancies. While this is an effective treatment, it can result in serious adverse events, such as the development of acute graft-versus-host disease (aGVHD). This study aimed to develop a donor-specific epigenetic classifier that could be used in donor selection in HCT to reduce the incidence of aGVHD.

The discovery cohort of the study consisted of 288 donors from a population receiving HLA-A, -B, -C and -DRB1 matched unrelated donor HCT with T cell replete peripheral blood stem cell grafts for treatment of acute leukaemia or myelodysplastic syndromes after myeloablative conditioning. Donors were selected based on recipient aGVHD outcome; this cohort consisted of 144 cases with aGVHD grades III-IV and 144 controls with no aGVHD that survived at least 100 days post-HCT matched for sex, age, disease and GVHD prophylaxis.

Genome-wide DNA methylation was assessed using the Infinium Methylation EPIC BeadChip (Illumina), measuring CpG methylation at >850,000 sites across the genome. Following quality control, pre-processing and exploratory analyses, we applied a machine learning algorithm (Random Forest) to identify CpG sites predictive of aGVHD. Receiver operating characteristic (ROC) curve analysis of these sites resulted in a classifier with an encouraging area under the ROC curve (AUC) of 0.91.

To test this classifier, we used an independent validation cohort (n=288) selected using the same criteria as the discovery cohort. Different attempts to validate the classifier using the independent validation cohort failed with the AUC falling to 0.51. These results indicate that donor DNA methylation may not be a suitable predictor of aGVHD in an HCT setting involving unrelated donors, despite the initial promising results in the discovery cohort.

Our work highlights the importance of independent validation of machine learning classifiers, particularly when developing classifiers intended for clinical use.


title: Sex differences in functional network topology over the course of aging in 37543 UK Biobank participants

abstract: Aging is a major risk factor for cardiovascular and neurodegenerative disorders, with considerable societal and economic implications. Healthy aging is accompanied by changes in connectivity between and within resting-state functional networks, however, there is no consensus on the impact of sex on these age-related alterations. Here, in a large cross-sectional sample of 37543 UK Biobank participants, we show that multilayer measures that capture the interaction between positive and negative connections provide crucial information on the impact of sex on age-related changes in network topology, being closely related to cognitive, structural, and cardiovascular risk factors that have been shown to differ between men and women. We also provide additional insights into the genetic influences on multilayer connectivity changes that occur during aging. Our findings indicate that multilayer measures contain previously unknown information on the relationship between sex and age, opening up new avenues for research into functional brain connectivity in aging.

category: geriatric medicine


title: Analysis of the metabolic syndrome and its association with cART in HIV positive individuals receiving various cART regimens with review of literature.

abstract:
ContextMany endocrine and metabolic disorders are seen in patients with HIV infection. Various comorbidities have been reported at a higher rate in HIV positive individuals, some at an earlier age. Since metabolic syndrome and its determinants are slowly developing, studies are needed in this regard.

AimsThe study aimed to analyze various parameters associated with the metabolic syndrome in HIV positive individuals and stratify subjects based on their treatment regimens, and present a brief comparison based on the same.

Settings and DesignA cross sectional study involving 155 participants was conducted at a tertiary care centre in Western India.

Materials and MethodsDetailed history and clinical examination was carried out. Routine investigations were done and parameters of interest to the study were then analysed based on AHA/NHLBI definitions.

Statistical Analysis usedUnivariate analysis of all parameters. Multiple logistic regression for statistically significant parameters.

Results and ConclusionDeranged HDL cholesterol was the most common component of the metabolic syndrome seen amongst all participants (53.8%) which was significantly higher in the treatment naive group (P = 0.001). The difference between the incidence of metabolic syndrome between the ART naive group and patients receiving ART was not significant. Males had a significantly higher prevalence of metabolic syndrome than females (26.3%>12.4%, P = 0.026). There was a significant difference in the incidence between the Zidovudine and Tenofovir treatment groups(P=0.02). Patients on the TLE (Tenofovir, Lamivudine, and Efavirenz) regimen had the lowest prevalence (4.2%) of metabolic syndrome.

category: hiv aids


title: The origin, epidemiology and phylodynamics of HIV-1 CRF47_BF

abstract: CRF47_BF is a circulating recombinant form (CRF) of the human immunodeficiency virus type 1 (HIV-1), the etiological agent of AIDS. CRF47_BF represents one of 19 CRFx_BFs and has a geographic focus in Spain, where it was first identified in 2010. Since its discovery, CRF47_BF has expanded considerably in Spain, predominantly through heterosexual contact ([~]56% of the infections). Little is known, however, about the origin and diversity of this CRF or its epidemiological correlates, as very few samples have been available so far. This study conducts a phylogenetic analysis with representatives of all CRFx_BF sequence types along with HIV-1 M Group subtypes to place the CRF47_BF sequences in a definitive phylogenetic context. The CRFx_BF sequences cluster into a single, not well supported, clade that includes their dominant parent subtypes (subtype B and subtype F). This clade also includes subtype D and excludes subsubtype F2. The CRF47_BF sequences all share a most recent common ancestor. Further analysis of this clade couples CRF47_BF protease-reverse transcriptase sequences and epidemiological data from an additional 87 samples collected throughout Spain, coupled with additional CRF47_BF database sequences from Brazil and Spain to investigate the origin and phylodynamics of CRF47_BF. The Spanish region with the highest proportion of CRF47_BF samples in the data set was the Basque Country (43.7%) with Navarre next highest at 19.5%. We include in our analysis epidemiological data on host sex, mode of transmission, time of collection, and geographic region. The phylodynamic analysis indicates that CRF47_BF originated in Brazil around 1993-1994 and spread to Spain from Brazil in approximately 1999-2000. The virus spread rapidly throughout Spain with increasing population sizes prior to 2010 and again between 2010 and 2017 with population declines to 2019 and a steady state through 2020. Three strongly supported clusters associated with Spanish regions (Basque Country, Navarre, and Aragon), together comprising 60.8% of the Spanish samples, were identified, one of which was also associated with transmission among men who have sex with men. The expansion in Spain of CRF47_BF, together with that of other CRFs and subtype variants of South American origin, previously reported, reflects the increasing relationship between the South American and European HIV-1 epidemics.


title: A Genomic Snapshot of Enterococcus faecalis within Public Hospital Environments in South Africa

abstract: Enterococci are among the most common opportunistic hospital pathogens. This study used whole-genome sequencing (WGS) and bioinformatics to determine the antibiotic resistome, genetic support, clones and phylogenetic relationship of Enterococcus faecalis isolated from hospital environments in South Africa. Isolates were recovered from 11 frequently touched sites by patients and healthcare workers in different wards at 4 levels of healthcare (A, B, C and D) in Durban, South Africa. Following microbial identification and antibiotic susceptibility tests. Of the 245 E. faecalis isolates identified, 38 were subjected to WGS on the Illumina MiSeq platform. The tet(M) (31/38, 82%) and erm(C) (16/38, 42%) genes were the most common antibiotic resistome found in isolates originating from the different hospital environments which corroborated with their antibiotic resistance phenotypes. The isolates harboured mobile genetic elements consisting of plasmids (n=11) and prophages (n=14), that were mostly clone-specific. Of note, a large number insertion sequence (IS) families were found with the IS3 (55%), IS5 (42%), IS1595 (40%) and Tn3 Transposon been the most predominate. Microbial typing using WGS data revealed 15 clones with 6 major sequence types (ST) belonging to ST16 (n =7), ST40 (n = 6), ST21 (n =5), ST126 (n = 3), ST23 (n =3) and ST386 (n=3). Phylogenomic analysis showed that the major clones were mostly conserved within specific hospital environments. However, further metadata insights revealed the complex intra-clonal spread of these E. faecalis major clones between the sampling sites within each specific hospital setting. The results of these genomic analyses will offer insights into E. faecalis in the hospital environments relevant in the design of optimal infection prevention strategies in hospital settings.

category: infectious diseases


title: Safety and immunogenicity of a hybrid-type vaccine booster in BBIBP-CorV recipients: a randomized controlled phase 2 trial

abstract: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with immune escape ability raises the urgent need for developing cross-neutralizing vaccines against the virus. NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluated the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in adults previously vaccinated with the inactivated vaccine BBIBP-CorV in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who had administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, were vaccinated with either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The primary outcome was immunogenicity and safety of booster vaccinations. The exploratory outcome was cross-reactive immunogenicity against multiple SARS-CoV-2 variants of concerns (VOCs). The incidence of adverse reactions was low in both booster vaccinations, and the overall safety profile of heterologous boost was quite similar to that of homologous boost. Heterologous NVSI-06-08 booster was immunogenically superior to homologous booster of BBIBP-CorV. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster were significantly higher than by the booster of BBIBP-CorV against not only SARS-CoV-2 prototype strain but also multiple VOCs. Especially, the neutralizing activity induced by NVSI-06-08 booster against the immune-evasive Beta variant was no less than that against the prototype strain, and a considerable level of neutralizing antibodies against Omicron (GMT: 367.67; 95%CI, 295.50-457.47) was induced by heterologous booster, which was substantially higher than that boosted by BBIBP-CorV (GMT: 45.03; 95%CI, 36.37-55.74). Our findings showed that NVSI-06-08 was safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which was immunogenically superior to homologous boost with another dose of BBIBP-CorV. Our study also indicated that the design of hybrid antigen may provide an effective strategy for broad-spectrum vaccine developments.


title: Impact of SARS-CoV-2 vaccination of children ages 5-11 years on COVID-19 disease burden and resilience to new variants in the United States, November 2021-March 2022: a multi-model study

abstract:
BackgroundSARS-CoV-2 vaccination of persons aged 12 years and older has reduced disease burden in the United States. The COVID-19 Scenario Modeling Hub convened multiple modeling teams in September 2021 to project the impact of expanding vaccine administration to children 5-11 years old on anticipated COVID-19 burden and resilience against variant strains.

MethodsNine modeling teams contributed state- and national-level projections for weekly counts of cases, hospitalizations, and deaths in the United States for the period September 12, 2021 to March 12, 2022. Four scenarios covered all combinations of: 1) presence vs. absence of vaccination of children ages 5-11 years starting on November 1, 2021; and 2) continued dominance of the Delta variant vs. emergence of a hypothetical more transmissible variant on November 15, 2021. Individual team projections were combined using linear pooling. The effect of childhood vaccination on overall and age-specific outcomes was estimated by meta-analysis approaches.

FindingsAbsent a new variant, COVID-19 cases, hospitalizations, and deaths among all ages were projected to decrease nationally through mid-March 2022. Under a set of specific assumptions, models projected that vaccination of children 5-11 years old was associated with reductions in all-age cumulative cases (7.2%, mean incidence ratio [IR] 0.928, 95% confidence interval [CI] 0.880-0.977), hospitalizations (8.7%, mean IR 0.913, 95% CI 0.834-0.992), and deaths (9.2%, mean IR 0.908, 95% CI 0.797-1.020) compared with scenarios where children were not vaccinated. This projected effect of vaccinating children 5-11 years old increased in the presence of a more transmissible variant, assuming no change in vaccine effectiveness by variant. Larger relative reductions in cumulative cases, hospitalizations, and deaths were observed for children than for the entire U.S. population. Substantial state-level variation was projected in epidemic trajectories, vaccine benefits, and variant impacts.

ConclusionsResults from this multi-model aggregation study suggest that, under a specific set of scenario assumptions, expanding vaccination to children 5-11 years old would provide measurable direct benefits to this age group and indirect benefits to the all-age U.S. population, including resilience to more transmissible variants.


title: Trends and factors associated with initiation of HIV treatment and uptake of viral load testing among PLHIV in Jamaica

abstract:
IntroductionJamaica did not achieve the UNAIDS 90-90-90 targets in 2020. This study aims to examine trends and factors associated with uptake of HIV treatment and viral load testing among people living with HIV (PLHIV) in Jamaica, to make recommendations for improving patient management and outcomes.

MethodsThis secondary analysis uses patient-level data from the National Treatment Service Information System. The baseline sample is PLHIV initiating anti-retroviral treatment (ART) between January 2015-December 2019. Descriptive statistics are used to summarize demographic and clinical variables. Multivariable logistic regression is used to assess factors associated with ART initiation (31+ days vs. same day) and viral load testing uptake (viral load test vs. no test), using categorical variables for age group, gender and regional health authority. Adjusted odds ratios and 95% confidence intervals are reported.

ResultsSame day ART initiation increased by 72% over 5 years. The coverage of 1st viral load test was 90% but declined to 79% for the 2nd test. Testing occurred mostly after 0-6 months on ART (n=3047, 55%) and uptake was highest in the South-East Region (n=2885, 53%). Those virally suppressed were significantly more likely to have same day ART initiation compared to those non-suppressed (aOR=1.58, CI=1.43-1.75). Males were significantly more likely to have same day ART initiation (aOR=1.46, CI=1.32-1.62) but no first viral load test (aOR=1.55, CI=1.27-1.90) compared to females.

ConclusionThe goal of immediate ART initiation is increasingly being met and is significantly associated with viral suppression at the first viral load test. Males were less likely to have a viral load test after ART initiation. A qualitative assessment should be conducted to understand important challenges faced to access routine viral load testing, followed by implementation of differentiated service care models, targeting males.


title: Integrated single-cell RNA sequencing analysis reveals alterations of ageing human lung endothelium heterogeneity in idiopathic pulmonary fibrosis

abstract: Increasing age is the main risk factor for chronic lung diseases (CLD) including idiopathic pulmonary fibrosis (IPF). Halting or reversing progression of IPF remains an unmet clinical need due to limited knowledge of underlying mechanisms. In particular, the contribution of the endothelium to ageing in human lung under physiological conditions and in IPF remains insufficiently understood. In this study, we analysed heterogeneity of endothelium in physiologically ageing human lung and its alterations in IPF. We conducted a comprehensive in silico analysis of scRNAseq profiles of human lung tissues from older healthy donors and age-matched IPF patients (n=9 for each group) by integrating datasets from two independent cohorts. We generated a single-cell map of the ageing human lung and identified 17 subpopulations of ageing endothelium (12 for blood and 5 for lymphatic vessels, including 4 "de-differentiated"), with distinct transcriptional profiles, specific gene expression signatures and percentage contributions, revealing previously underappreciated extent of heterogeneity. In IPF lung, the balance of different endothelial sub-types was significantly altered both in terms of cell numbers and gene expression patterns, identifying disease-relevant subpopulations and transcriptional changes associated with specific signalling pathways and cellular processes. These findings reveal a previously unrecognised phenomenon of ageing human lung endothelium re-programming towards an "IPF endothelium" state, suggesting potential avenues for therapeutic management or biomarker discovery for diagnostics or prognostics of IPF. Our study creates a conceptual framework for appreciating the heterogeneity of ageing endothelium and its alterations in CLDs and diseases associated with fibrosis in other organs, including lymphoedema and cancer.

category: respiratory medicine


title: Idetification of CACNA1B (p.K567R) mutation responsible for familiar AVNRT

abstract: Atrioventricular nodal reentry tachycardia (AVNRT) is the most common form of paroxysmal supraventricular tachycardia (PSVT). The exact cause of AVNRT has not yet been found. However, an increasing number of reports suggest that AVNRT is hereditary, but no precise pathogenic gene has been found so far. In our study, we found that a point mutation of CACNA1B (p.K567R) which encoded the 1 subunit of N-type calcium channel (Cav 2.2), was cosegregated with AVNRT in one family. Previous research showed that overexpression and point mutations of human CACNA1B in zebrafish embryos may be related to abnormal heart rate. Telemetric ECG recordings showed that rats with a CACNA1B point mutation displayed sporadic supraventricular tachycardia and altered QRS complex morphology. In addition, the CACNA1B (p.K567R) rats presented a double path phenomenon and AVNRT induction by intracardiac electrophysiological examination. Indexes of heart rate variance in CACNA1B mutation rats showed an in cardiac sympathetic activity and an imbalance of cardiac sympathetic and parasympathetic activity. Single-cell RNA sequencing indicated that the number of neurons in the superior cervical ganglion (SCG) of mutant rats was higher than in wild-type (WT) rats, accompanied by an increased expression of CACNA1B. Functional enrichment in SCG proteomics suggests that point mutant rats have abnormalities in synaptic function and ion transport, which could lead to the release of neurotransmitters. This could affect the cardiac autonomic neural activity and lead to an imbalance in sympathetic and parasympathetic activity and the subsequent occurrence of AVNRT. Our findings indicate that CACNA1B (p.K567R) is the pathogenic gene of AVNRT in familial AVNRT and confirm that CACNA1B is the first definitive AVNRT pathogenic gene that has been discovered.

category: pathology