bluuebunny/crossref_metadata_2025 huggingface dataset:
Unbiased identification of unknown cellular and environmental factors that mediate eQTLs using principal interaction component analysis
Authors: Vochteloo Martijn , Deelen Patrick , Vink Britt ,   BIOS Consortium, Tsai Ellen A. , Runz Heiko , Andreu-Sánchez Sergio , Fu Jingyuan , Zhernakova Alexandra , Westra Harm-Jan , Franke Lude
Published: July 2022

Expression quantitative trait loci (eQTL) can reveal the regulatory mechanisms of trait associated variants. eQTLs are highly cell-type and context-specific, but often these contexts are unknown or not measured. Here, we introduce PICALO (Principal Interaction Component Analysis through Likelihood Optimization), an unbiased method to identify known and hidden contexts that influence eQTLs. PICALO uses expectation maximization to identify latent components, referred to as Principal Interaction Components (PIC), that interact with genotypes to maximize explained eQTL effect-sizes.

We applied PICALO to bulk RNA-seq eQTL datasets in blood (n=2,932) and brain (n=2,440). We identify 31 PICs in blood, interacting with 4,169 (32%) unique cis-eQTLs (BH-FDR≤0.05). In brain, we identified 21 PICs, interacting with 4,058 (39%) unique cis-eQTLs (BH-FDR≤0.05). These PICs are associated with RNA quality, cell type composition or environmental influences. Furthermore, PICs clearly disentangle distinct eQTL contexts, for example technical from non-technical factors. Combined, 3,065 unique genes showed a cis-eQTL effect that is dependent on a cell type or other non-technical context, emphasizing the value of methods like PICALO. PICALO is robust, works well with heterogeneous datasets, yields reproducible interaction components, and identifies eQTL interactions and contexts that would have been missed when using cell counts or expression based principal components.

Since PICALO allows for the identification of many context-dependent eQTLs without any prior knowledge of such contexts, this method can help to reveal and quantify the influence of previously unknown environmental factors that play a role in common diseases.
Cryo-electron tomography suggests tubulin chaperones form a subset of microtubule lumenal particles with a role in maintaining neuronal microtubules
Authors: Chakraborty Saikat , Martinez-Sanchez Antonio , Beck Florian , Toro-Nahuelpan Mauricio , Hwang In-Young , Noh Kyung-Min , Baumeister Wolfgang , Mahamid Julia
Published: July 2022

The functional architecture of the long-lived neuronal microtubule (MT) cytoskeleton is maintained by various MT-associated proteins (MAPs), most of which are known to bind to the MT outer surface. However, electron microscopy (EM) has long ago revealed the presence of particles inside the lumens of neuronal MTs, of yet unknown identity and function. Here, we use cryogenic electron tomography (cryo-ET) to analyze the three-dimensional (3D) structures and organizations of MT lumenal particles in primary hippocampal neurons, human induced pluripotent stem cell-derived neurons and pluripotent P19 cells. We obtain in-cell 3D maps of several lumenal particles from the respective cells and detect structural features that are common to all cell-types, underscoring their potential overarching functions. Mass spectrometry-based proteomics combined with structural modeling suggests a subset of lumenal particles could be tubulin-binding cofactors (TBCs) bound to tubulin monomers. A different subset of smaller particles, which remains unidentified, exhibits densities that bridge across the MT protofilaments. We show that increased lumenal particle concentration within MTs is concomitant with neuronal differentiation and correlates with higher MT curvatures. Enrichment of lumenal particles around MT lattice defects and at freshly polymerized MT open-ends suggest a MT protective role. Together with the identified structural resemblance of a subset of particles to TBCs, these results hint at a role in local tubulin proteostasis for the maintenance of long-lived neuronal MTs.
Efficient base-catalysed Kemp elimination in an engineered ancestral enzyme
Authors: Gutierrez-Rus Luis I. , Alcalde Miguel , Risso Valeria A , Sanchez-Ruiz Jose M.
Published: July 2022

The routine generation of enzymes with completely new active sites is one of the major unsolved problems in protein engineering. Advances in this field have been so far modest, perhaps due, at least in part, to the widespread use of modern natural proteins as scaffolds for de novo engineering. Most modern proteins are highly evolved and specialized, and, consequently, difficult to repurpose for completely new functionalities. Conceivably, resurrected ancestral proteins with the biophysical properties that promote evolvability, such as high stability and conformational diversity, could provide better scaffolds for de novo enzyme generation. Kemp elimination, a non-natural reaction that provides a simple model of proton abstraction from carbon, has been extensively used as a benchmark in de novo enzyme engineering. Here, we present an engineered ancestral β-lactamase with a new active site capable of efficiently catalysing the Kemp elimination. Our Kemp eliminase is the outcome of a minimalist design based on a single function-generating mutation followed by sharply-focused, low-throughput library screening. Yet, its catalytic parameters (kcat/KM=2·105 M−1s−1, kcat=635 s−1) compare favourably with the average modern natural enzyme and with the best proton-abstraction de novo Kemp eliminases reported in the literature. General implications of our results for de novo enzyme engineering are discussed.
Network analysis applied to DASS-21: Emergence of a new dimension
Authors: Alvarenga Marco Antônio Silva , Bandeira Paulo Felipe Ribeiro , Guilhermino Carollina Souza , de Azevedo Tiago Geraldo , Olímpio Kelly Fernandes , Kersul Camila , da Cunha Glacithane Lins , Alves-Teodoro Juliana , Ribeiro Pricila Cristina Correa , Mansur-Alves Marcela , Teodoro Maycoln Lêoni Martins
Published: July 2022

The DASS-21 has been studied in different samples and cultures as a brief tool for screening and referral to specialized interventions, thus presenting the prerogative to be characterized as a complex system (CS). CS is a new approach to data analysis assumes that items on a scale are components integrated as a network. Despite this, to date network analysis has not been applied to verify the psychometric properties of the DASS-21. This was a non-clinical sample consisting of college students and professionals (N = 4017), aged 18 years or older (M = 31.16; SD = 10.308), from different Brazilian regions. The data collection was done through electronic forms composed by a sociodemographic questionnaire and DASS-21. Participants could forward the form to other potential respondents. Uni, bi, and multivariate analyses were used, and, among them, exploratory graph analysis (EGA) and boostrap EGA (BootEGA). EGA e BootEGA generated a model with four factors. The four-factor model from DASS-21 showed better fit rates compared to the others replicated in this research. The new four factor model has excellent composite reliability and is invariant regard to gender and type of activity performed. This research was composed of a non-probabilistic and convenience sample, without equitable geographical distribution of the participants and whose answers to this study were provided only by the web-based forms. The DASS-21 presented a new factor model composed of four distinct dimensions with excellent intrinsic features.
“I was scared dating… who would take me with my status?”- Living with HIV in the UTT era in Johannesburg, South Africa
Authors: Sineke Tembeka , Onoya Dorina , Mokhele Idah , Cele Refiloe , Sharma Shubhi , Sigasa Smangele , Dukashe Mandisa , Hansrod Laila , Inglis Robert , King Rachel , Bor Jacob
Published: July 2022

BACKGROUND

South Africa rolled out Universal Test-and-Treat (UTT) in 2016, extending treatment eligibility to all persons living with HIV (PLHIV). Through this study, we sought to understand the experience of people living with HIV in the UTT era in South Africa.

METHODS

In May 2021, we conducted in-depth interviews (IDI) (N = 27) with adult (≥ 18 years) PLHIV referred by HIV counsellors at three peri-urban primary healthcare clinics. We also conducted three focus group discussions (FGDs) (N = 27) with adult PLHIV recruited from clinics or from civil society organisations through snowball sampling. Follow-up interviews were conducted with 29 IDI and FGD participants, to gain a deeper understanding of their journey living with HIV. Participants were asked to reflect on their HIV diagnosis, what their HIV status meant to them in light of the UTT era and how, if at all, being HIV-positive affected their lives. Interviews and focus group discussions were audio-recorded, transcribed, translated to English, and analysed thematically.

RESULTS

The study included 4 men and 23 women recruited from clinics and 12 men and 16 women recruited from civil society (total N= 54). Participants reported that PLHIV could live a long life with antiretroviral therapy (ART) and that ART was widely accessible. However, they reported that HIV elicited feelings of guilt and shame as a sexually transmitted disease. Participants used the language of “blame” in discussing HIV transmission, citing their own reckless behaviour or blaming their partner for infecting them. Participants feared transmitting HIV to others and felt a responsibility to avoid transmission. To manage transmission anxieties, participants avoided sexual relationships, chose HIV-positive partners, and/or insisted on using condoms. Many participants feared – or had previously experienced – rejection by their partners due to their HIV status and reported hiding their medication, avoiding disclosure to their partners, or avoiding relationships altogether. Most participants also reported having low to no knowledge about treatment-as-prevention (TasP). Participants who were aware of TasP expressed less anxiety about transmitting HIV to others and greater confidence in having relationships.

CONCLUSION

Despite the normalization of HIV as a chronic disease, PLHIV still experience transmission anxiety and fears of rejection by their partners. Disseminating information on treatment-as-prevention could reduce the psychosocial burdens of living with HIV, encourage open communication with partners, and remove barriers to HIV testing and treatment adherence.
Sociodemographic factors affecting not receiving COVID-19 vaccine in Japan among people who originally intended to vaccinate: a prospective cohort study
Authors: Matsuyama Akiko , Mori Takahiro , Ogami Akira , Mafune Kosuke , Tateishi Seiichiro , Kuwamura Mami , Muramatsu Keiji , Fujino Yoshihisa , Mori Koji ,   the CORoNaWork project
Published: July 2022

Background

Vaccine hesitancy is a major issue for acquiring herd immunity. However, some individuals may go unvaccinated owing to inhibitory factors other than vaccine hesitancy. If there is even a small number of such people, support is needed for equitable vaccine distribution and acquiring herd immunity. We investigated sociodemographic factors that affected not undergoing COVID-19 vaccination in Japan among individuals who initially had strong intention to vaccinate.

Methods

We conducted this prospective cohort study on workers aged 20–65 years from December 2020 (baseline), to December 2021 using a self-administered questionnaire survey. There were 27,036 participants at baseline and 18,560 at follow-up. We included 6,955 participants who answered yes to this question at baseline: “Would you like to receive a COVID-19 vaccine as soon as it becomes available?” We applied multilevel logistic regression analyses to examine the association between sociodemographic factors and being unvaccinated at follow-up.

Results

In all, 289 participants (4.2%) went unvaccinated. The odds ratios (ORs) for being unvaccinated were significantly higher for participants aged 30–39 and 40–49 than those aged 60–65 years. Being divorced, widowed, or single, having low income, and having COVID-19 infection experience also had higher ORs.

Conclusions

We found that some participants who initially had strong intention to vaccinate may have gone unvaccinated owing to vaccine side effects and the financial impact of absenteeism due to side effects. It is necessary to provide information repeatedly about the need for vaccination as well as social support to ensure that those who intend to vaccinate are able to do so.
Protocol for the Tessa Jowell BRAIN MATRIX Platform Study
Authors: Watts Colin , Savage Joshua , Patel Amit , Mant Rhys , Wykes Victoria , Pohl Ute , Bulbeck Helen , Apps John , Sharpe Rowena , Thompson Gerard , Waldman Adam , Ansorge Olaf , Billingham Lucinda ,   the TJBM Investigators
Published: July 2022

Introduction

Gliomas are the most common primary tumour of the central nervous system (CNS), with an estimated annual incidence of 6.6 per 100,000 individuals in the USA and around 14 deaths per day from brain tumours in the UK. The genomic and biological landscape of brain tumours has been increasingly defined and, since 2016, the WHO classification of tumours of the CNS incorporates molecular data, along with morphology, to define tumour subtypes more accurately. The Tessa Jowell BRAIN MATRIX Platform (TJBM) study aims to create a transformative clinical research infrastructure that leverages UK NHS resources to support research that is patient centric and attractive to both academic and commercial investors.

Methods and analysis

The TJBM study is a programme of work with the principal purpose to improve the knowledge of glioma and treatment for glioma patients. The programme includes a platform study and subsequent interventional clinical trials (as separate protocols). The platform study described here is the backbone data-repository of disease, treatment and outcome data from clinical, imaging and pathology data being collected in glioma patients from secondary care hospitals. The primary outcome measure of the platform is time from biopsy to integrated histological-molecular diagnosis using whole genome sequencing and epigenomic classification. Secondary outcome measures include those that are process-centred, patient-centred and framework-based. Target recruitment for the study is 1000 patients with interim analyses at 100 and 500 patients.

Ethics and dissemination

The protocol was approved by West Midlands - Edgbaston Research Ethics Committee. Participants will be required to provide written informed consent. The results of this study will be disseminated through national and international presentations and peer-reviewed publications.

Trial registration number

ClinicalTrials.gov Identifier: NCT04274283; 18-Feb-2020

ISRCTN 14218060; 03-Feb-2020

Strengths and limitations of this study

The TJBM study is a programme of work, which will improve the knowledge of glioma, and treatment for glioma patients.

This platform study is a backbone data-repository of disease, treatment and outcome data from clinical, imaging and pathology data

The TJBM study will aim to provide rapid and accurate molecular diagnosis, a network of clinical hubs with robust protocols for the collection, processing, analysis and storage of tissue, images, and clinical and quality of life data

Gliomas occur at all ages and their specific subtype is difficult to predict preoperatively, therefore, the patient population eligible for the study is broad but currently excludes <16-year-old patients
Germline genomic and phenomic landscape of clonal hematopoiesis in 323,112 individuals
Authors: Uddin Md Mesbah , Yu Zhi , Weinstock Joshua S. , Nakao Tetsushi , Niroula Abhishek , Urbut Sarah M. , Koyama Satoshi , Zekavat Seyedeh M. , Paruchuri Kaavya , Silver Alexander J. , Mack Taralynn M. , Wong Megan Y. , Haidermota Sara M. , Bhattacharya Romit , Jorshery Saman Doroodgar , Raddatz Michael A. , Honigberg Michael C. , Hornsby Whitney E. , Zhang Martin Jinye , Sankaran Vijay G. , Griffin Gabriel K. , Gibson Christopher J. , Kresge Hailey A. , Ellinor Patrick T. ,   Veterans Affairs’ Million Veteran Program, Cho Kelly , Sun Yan V. , Wilson Peter W.F. , Pyarajan Saiju , Genovese Giulio , Xu Yaomin , Savona Michael R. , Reiner Alexander P. , Jaiswal Siddhartha , Ebert Benjamin L. , Bick Alexander G. , Natarajan Pradeep
Published: July 2022

With age, acquired mutations can cause clonal expansion of hematopoietic stem cells (HSC). This clonal hematopoiesis of indeterminate potential (CHIP) leads to an increased predisposition to numerous diseases including blood cancer and cardiovascular disease. Here, we report multi- ancestry genome-wide association meta-analyses of CHIP among 323,112 individuals (19.5% non-European; 5.3% have CHIP). We identify 15 genome-wide significant regions and nominate additional loci through multi-trait analyses, and highlight variants in genes involved in self- renewal and proliferation of HSC, telomere maintenance, and DNA damage response pathways. We then use Mendelian randomization to establish a causal relationship between CHIP and coronary artery disease. Next, we systematically profile consequences of CHIP across the phenome, which revealed strong associations with hematopoietic, neoplastic, and circulatory conditions corroborated by polygenic enrichment of CHIP loci in immune cells and cardiomyocytes. These findings expand the genomic and phenomic landscape of CHIP.
A new and efficient enrichment method for metagenomic sequencing of monkeypox virus
Authors: Aja-Macaya Pablo , Rumbo-Feal Soraya , Poza Margarita , Cañizares Angelina , Vallejo Juan A. , Bou Germán
Published: July 2022

Background

The methodology described in previous literature for monkeypox virus (MPXV) sequencing shows low efficiency when using metagenomic approaches. The aim of the present study was to evaluate a new fine-tuned method for extraction and enrichment of genomic MPXV DNA using clinical samples and to compare it to a non-enrichment metagenomic approach.

Results

A new procedure that allows sample enrichment in MPXV DNA, avoiding wasting the sequencing quota in human DNA, was designed. This procedure consisted of host DNA depletion using a saponin/NaCl combination treatment and DNase. After typical quality control, samples using the enrichment method contained around 98 % of reads not classified as human DNA, while the non-enrichment protocol showed around 5-10 %. When reads not belonging to Orthopoxvirus were removed, enriched samples kept about 50 % of the original read counts, while non-enriched ones kept only 2-7 %.

Conclusions

Results showed a very significant improvement in sequencing efficiency, increasing the number of reads belonging to MPXV, the depth of coverage and the trustworthiness of the consensus sequences. This, in turn, would allow for more samples to be included in a single cartridge, reducing costs and time to diagnosis, which can be very important factors when dealing with a contagious disease.
Outlier expression of isoforms by targeted RNA sequencing as clinical markers of genomic variants in B lymphoblastic leukemia and other tumor types
Authors: Tsai Harrison K. , Gogakos Tasos , Lip Va , Tsai Jonathan , Li Yen-Der , Fisch Adam , Weiss Jonathan , Grimmett Leslie , Tran Thai Hoa , Caron Maxime , Langlois Sylvie , Sinnett Daniel , Pikman Yana , Kim Annette S. , Nardi Valentina , Silverman Lewis B. , Harris Marian H.
Published: July 2022

Recognition of aberrant gene isoforms indicative of underlying DNA events can impact molecular classification and risk stratification of B lymphoblastic leukemia (B-ALL). Aberrant ERG isoforms have been proposed as markers of the favorable-risk DUX4-rearranged (DUX4r) subtype while deletion-mediated IKZF1 isoforms are associated with adverse prognosis in non-DUX4r B-ALL. The high-risk IKZF1plus signature depends on gene deletions including PAX5 while intragenic PAX5 amplifications (PAX5amp) are recurrent in the provisional B-ALL with PAX5-alteration subtype. In this study, we screened for outlier expression of isoforms within targeted RNA sequencing assays designed for fusions. Outlier analysis of known and novel IKZF1, ERG, and PAX5 isoforms was 97.0% (32/33), 90% (9/10), and 100% (6/6) sensitive and 97.8% (226/231), 100% (35/35), and 88.5% (23/26) specific for IKZF1 intragenic or 3’ deletions, DUX4r, and PAX5 intragenic deletions respectively, where false positives were favored to represent low-level deletions below the limit of DNA-based detection. Outlier analysis also identified putative PAX5amp cases and revealed partial tandem duplication (PTD) spanning IKZF1 N159Y in the B-ALL with mutated N159Y subtype. To demonstrate utility in other tumor types, outlier analysis was 100% (9/9) sensitive and 100% (255/255) specific for KMT2A-PTD in hematologic samples and 100% (7/7) sensitive and 100% (79/79) specific for FGFR1 tyrosine kinase domain duplication in brain tumors. These findings support the use of aberrant isoform analysis in targeted RNA sequencing data as a robust strategy for the detection of clinically significant DNA events.
Monkeypox self-diagnosis abilities, determinants of vaccination intention and self-isolation intention after diagnosis among MSM in the Netherlands
Authors: Wang Haoyi , d’Abreu de Paulo Kennedy J.I. , Gültzow Thomas , Zimmermann Hanne M.L. , Jonas Kai. J.
Published: July 2022

Monkeypox is a zoonotic disease and leads to a smallpox-like disease in humans. The current epidemic in European countries requires informed responses. We investigated the ability to self-diagnose a potential monkeypox infection, and determinants of vaccination intention and self-isolation intention after exposure among MSM in the Netherlands. We found that about half were able to self-diagnose monkeypox, that 72% had a high intention to get vaccinated and 44% to self-isolate after monkeypox exposure. Determinants went beyond mere risk behaviour criteria.

Data availability

Data is available upon request.

Ethical statement

The study was assessed and approved by the ERCPN of Maastricht University (ref.188_11_02_2018_S32). Informed consent was provided by all participants.

Funding

There was no funding source for this study.

Authors’ contributions

All authors conceptualised this research; KJJ collected the data for this research; HW and KJIDDP analysed the data; all authors drafted the manuscript; all authors critically revised the manuscript for intellectual content; All authors read and approved the final version of the manuscript.
A power-based sliding window approach to evaluate the clinical impact of rare genetic variants
Authors: Cirulli Elizabeth T. , Schiabor Barrett Kelly M. , Bolze Alexandre , Grzymski Joseph J. , Lee William , Washington Nicole L.
Published: July 2022

Systematic determination of rare and novel variant pathogenicity remains a major challenge, even when there is an established association between a gene and phenotype. Here we present Power Window (PW), a novel sliding window technique that identifies the clinically impactful regions of a gene using population-scale clinico-genomic datasets. By sizing windows based on the number of variant carriers, rather than the number of variants or nucleotides, statistical power is held constant during analysis, enabling the localization of clinical impact as well as the removal of unassociated gene regions. This method can be used to focus on: specific variant types such as loss of function (LoF) or other coding; parts of a gene, such as those expressed in different tissues; or isolating gene regions with opposite directions of effect. Using a training set of 300K exomes from the UKBiobank (UKB), we developed PW-based LoF and coding models for well-established gene-disease associations and tested their accuracy in two additional cohorts (128k exomes from the UKB and 30k exomes from the Healthy Nevada Project (HNP)). The significant PW models retained a mean of 64% of the rare variant carriers in each gene (range 16-98%), with quantitative traits showing a mean effect size improvement of 48% compared to aggregating rare variants across the entire gene, and the odds ratios for binary traits improving by a mean of 2.4-fold. PW showcases that EHR-based statistical analyses can accurately distinguish between novel coding variants that will have high phenotypic penetrance in a population and those that will not, unlocking new potential for population genetic screening.
Hepatectomy combined with targeted and immunotherapy for CNLC stage IIIb hepatocellular carcinoma: a single-arm clinical trials protocol
Authors: Huang Jun-Tao , Zhong Jian-Hong , Zhang Jie , Gong Wen-Feng , Ma Liang , Li Le-Qun , Xiang Bang-De
Published: July 2022

Introduction

Current clinical guidelines recommend systematic antitumor therapy as the primary treatment option for patients with stage IIIb hepatocellular carcinoma (HCC) based on the China liver cancer staging (CNLC) criteria. Several different targeted therapeutics have been applied in combination with immunotherapeutic regimens to date in patients with advanced HCC. The present study was developed to evaluate the relative safety and efficacy of hepatectomy in combination with targeted apatinib treatment and immunotherapeutic camrelizumab treatment CNLC-IIIb stage HCC patients with the goal of providing evidence regarding the potential value of this therapeutic regimen in individuals diagnosed with advanced HCC.

Methods and analysis

This is a single-arm multicenter clinical trial in which patients undergo hepatectomy in combination with targeted treatment (apatinib) and immunotherapy (camrelizumab). Patients will undergo follow-up every 2-3 months following treatment initiation to record any evidence of disease progression and adverse event incidence for a minimum of 24 months following the discontinuation of treatment until reaching study endpoint events or trial termination. The primary endpoint for this study is patient mortality.

Ethics and dissemination

This study protocol was approved by the Ethics Committee of the Guangxi Medical University Cancer Hospital for Human Study (reference number KS2022[124]). The results of this study will be submitted for publication in a peer-reviewed journal.

Trial registration number

NCT05062837.

Strengths and limitations of this study

This study will be the first to assess the relative safety and efficacy of hepatectomy combined with targeted and immunotherapeutic treatment in CNLC-IIIb HCC patients.

As a multicenter study, the results of this analysis will be representative, generalizable, and reliable.

As this study will entail a prolonged follow-up period, it is critical that participants be thoroughly informed prior to enrollment, with individuals exhibiting high compliance being chosen for study inclusion.
Two years after lockdown: longitudinal trajectories of sleep disturbances and mental health over the COVID-19 pandemic and the effects of age, gender, and chronotype
Authors: Salfi Federico , Amicucci Giulia , Corigliano Domenico , Viselli Lorenzo , D’Atri Aurora , Tempesta Daniela , Gorgoni Maurizio , Scarpelli Serena , Alfonsi Valentina , Ferrara Michele
Published: July 2022

Since the first lockdown of Spring 2020, the COVID-19 contagion waves pervasively disrupted the sleep and mental health of the worldwide population. Notwithstanding the largest vaccination campaign in human history, the pandemic has continued to impact the everyday life of the general population for two years now. The present study provides the first evidence of the longitudinal trajectories of sleep disturbances and mental health throughout the pandemic in Italy, also describing the differential time course of age groups, genders, and chronotypes.

A total of 1062 Italians participated in a three-time points longitudinal study covering two critical stages of the emergency [the first lockdown (April 2020) and the second lockdown (December 2020)] and providing a long-term overview two years after the pandemic outbreak (April 2022). We administered validated questionnaires to evaluate sleep quality/habits, insomnia, depression, stress, and anxiety symptoms.

Analyses showed a gradual improvement in sleep disturbances, depression, and anxiety. Conversely, sleep duration progressively decreased, particularly in evening-type and younger people. Participants reported substantial earlier bedtime and get-up time. Stress levels increased during December 2020 and then stabilised. This effect was stronger in the population groups apparently more resilient during the first lockdown (older people, men, and morning-types).

Our results describe a promising scenario two years after the pandemic onset. However, the improvements were relatively small, the perceived stress increased, and the re-establishment of pre-existing social/working dynamics led to general sleep curtailment. Further long-term monitoring is required to claim the end of the COVID-19 emergency on Italians’ sleep and mental health.
Learning phenotypic patterns in genetic diseases by symptom interaction modeling
Authors: Yauy Kevin , Duforet-Frebourg Nicolas , Testard Quentin , Beaumeunier Sacha , Audoux Jerome , Simard Benoit , Larue Dimitri , Blum Michael G. B. , Bernard Virginie , Genevieve David , Bertrand Denis ,   PhenoGenius consortium, Philippe Nicolas , Thevenon Julien
Published: July 2022

Observing phenotyping practices from an international cohort of 1,686 cases revealed heterogeneity of phenotype reporting among clinicians. Heterogeneity limited their exploitation for diagnosis as only 43% of symptom-gene associations in the cohort were available in public databases. We developed a symptom interaction model that summarized 16,600 terms into 390 groups of interacting symptoms and detected 3,222,053 novel symptom-gene associations. By learning phenotypic patterns in genetic diseases, symptom interaction modeling handled heterogeneity in phenotyping, to the extent of covering 98% of our cohort’s symptom-gene associations. Using these symptom interactions improved the diagnostic performance in gene prioritization by 42% (median rank 80 to 41) compared to the best algorithms. Symptom interaction modeling will provide new discoveries in precision medicine by standardizing clinical descriptions.

One sentence summary

Learning phenotypic patterns in genetic disease by symptom interaction modeling addresses physicians’ heterogeneous phenotype reporting.
The Effect of the COVID-19 Pandemic on Mental Health in Low and Middle Income Countries
Authors: Aksunger Nursena , Vernot Corey , Littman Rebecca , Voors Maarten , Meriggi Niccolo , Abajobir Amanuel , Beber Bernd , Dai Katherine , Egger Dennis , Islam Asad , Kelley Jocelyn , Kharel Arjun , Matabaro Amani , Moya Andrés , Mwachofi Pheliciah , Nekesa Carolyn , Ochieng Eric , Rahman Tabassum , Scacco Alexandra , van Dalen Yvonne , Walker Michael , Janssens Wendy , Mobarak Ahmed Mushfiq
Published: July 2022

We track the effects of the COVID-19 pandemic on mental health in eight Low and Middle Income Countries (LMICs) in Asia, Africa, and South America utilizing repeated surveys of 21,162 individuals. Many respondents were interviewed over multiple rounds pre- and post-pandemic, allowing us to control for time trends and within-year seasonal variation in mental health. We demonstrate how mental health fluctuates with agricultural crop cycles, deteriorating during pre-harvest “lean” periods. Ignoring this seasonal variation leads to unreliable inferences about the effects of the pandemic. Controlling for seasonality, we document a large, significant, negative impact of the pandemic on mental health, especially during the early months of lockdown. In a random effects aggregation across samples, depression symptoms increased by around 0.3 standard deviations in the four months following the onset of the pandemic. The pandemic could leave a lasting legacy of depression. Absent policy interventions, this could have adverse long-term consequences, particularly in settings with limited mental health support services, which is characteristic of many LMICs.
Pregnancy-related complications and associated factors among women attending antenatal care at a specialised maternal and child health national referral hospital, in Uganda
Authors: Tamale Bridget Nagawa , Bulafu Douglas , Isunju John Bosco , Jamu Atuko Vicky , Baguma James Natweta , Tigaiza Arnold , Nalugya Aisha , Musitwa Rogers , Mugambe Richard K. , Ssekamatte Tonny , Lubogo David
Published: July 2022

Background

Although pregnancy and child birth-related complications remain a global public health concern, little is known about their prevalence and associated factors. Our study assessed pregnancy-related complications and associated factors among women attending antenatal care at a specialized maternal and child health national referral hospital in Uganda.

Methodology

A cross-sectional study was conducted among 285 pregnant women. Data were collected using the KoboCollect mobile application, and analysed using STATA 14. A modified poisson regression model was used for inferential statistics.

Findings

Out of the 285 women, 27.4% (78/285) had pregnancy-related complications. The most reported complications were anaemia, 10.9% (31/285); eclampsia, 8.1% (23/285); and still births, 4.9% (14/285). Having a higher gravidity of 4-6 (APR= 0.32, 95% CI: 0.17-0.57) and of more than 7 (APR= 0.32, 95% CI: 0.14-0.73) was negatively associated with pregnancy-related complications. Factors positively associated with pregnancy-related complications included; late first ANC (APR=1.85, 95% CI: 1.17-2.92), parity of ≥ 3 (APR= 3.69, 95% CI: 1.50-9.08) and induced abortion prior to current pregnancy (APR= 1.64, 95% CI: (1.08-2.47).

Conclusion

The prevalence of pregnancy-related complications was very high. Anaemia, eclampsia and still births were the most prevalent. A late first ANC, gravidity higher than 4, parity higher than 3, and history of an induced abortion prior to the current pregnancy were associated with having pregnancy-related complications. Interventions aimed at reducing maternal morbidity and mortality should aim at promoting early ANC attendance, and increasing access to safe abortion and family planning services.
SARS-CoV-2 IgG seroprevalence surveys in blood donors before the vaccination campaign, France 2020-2021
Authors: Gallian Pierre , Hozé Nathanaël , Brisbarre Nadège , Saba Villarroel Paola Mariela , Nurtop Elif , Isnard Christine , Pastorino Boris , Richard Pascale , Morel Pascal , Cauchemez Simon , de Lamballerie Xavier
Published: July 2022

We conducted a cross-sectional study for SARS-CoV-2 anti-S1 IgG prevalence in French blood donors (n=32605), from May-2020 to January-2021. A mathematical model combined seroprevalence with daily number of hospital admissions to estimate the probability of hospitalization upon infection and determine the number of infections while correcting for antibody decay. There was an overall seroprevalence increase over the study period and we estimate that ∼15% of the French population had been infected by SARS-CoV-2 by January-2021. The infection/hospitalization ratio increased with age, from 0.56% (18-30yo) to 6.75% (61-70yo). Half of the IgG-S1 positive individuals had no detectable antibodies 4 to 5 months after infection. The seroprevalence in group O donors (7.43%) was lower (p=0.003) than in A, B and AB donors (8.90%). We conclude, based on seroprevalence data and mathematical modelling, that the overall immunity in the French population before the vaccination campaign started was too low to achieve herd immunity.
Has the pandemic enhanced and sustained digital health-seeking behaviour? A big data interrupted time-series analysis of Google Trends
Authors: van Kessel Robin , Kyriopoulos Ilias , Wong Brian Li Han , Mossialos Elias
Published: July 2022

Background

Due to the emergency responses early in the pandemic, the use of digital health in healthcare increased abruptly, yet it remains unclear whether this introduction was sustainable on the long term. We explore trends in digital health-seeking behaviour as proxy for readiness to adopt digital health as a mainstream form of healthcare.

Methods

We use weekly Google Trends data from February 2019 to August 2021 in Canada, United States, United Kingdom, New Zealand, Australia, and Ireland. We used five keywords to monitor online search interests in Google Trends: online doctor, telehealth, online health, telemedicine, and health app. Data are analysed using an interrupted time-series analysis with break-points on 11 March 2020 and 20 December 2020.

Results

Digital health searches immediately increased in all countries after the pandemic announcement. There was some variance in what keywords were used per country. However, searches declined after this immediate spike, sometimes towards pre-pandemic levels. The exception is the search volume of health app, which showed to either remain stable or gradually increase during the pandemic.

Interpretation

Our findings suggest that digital health-seeking behavioural patterns associated with the pandemic are currently not sustainable. Further building of digital health capacity and development of robust digital governance and literacy frameworks remain crucial to more structurally facilitate digital health transformation across countries.

Funding

Not applicable.
Results of the basic-VRS trial: clinical outcomes and cost-effectiveness of basic low vision rehabilitation in Portugal
Authors: Hernández-Moreno Laura , Senra Hugo , Marques Ana Patricia , Perdomo Natacha Moreno , Macedo Antonio Filipe
Published: July 2022

Purpose

The aim of this study was twofold: i) to investigate and characterize the clinical impact of vision rehabilitation in patients with vision impairment, and ii) to investigate the cost-effectiveness of a basic vision rehabilitation service in Portugal.

Methods

Patients diagnosed with age-related macular degeneration or diabetic retinopathy and visual acuity in the range 0.4 to 1.0 logMAR in the better-seeing eye were recruited. Participants were randomised to one of the study arms consisting of immediate intervention and delayed intervention. The intervention included: new refractive correction, optical reading aids, in-office training and advice about modifications at home. Visual ability, health-related quality-of-life and costs of the intervention were measured. Economic analysis was performed to evaluated if the intervention was cost-effective. The trial compared the outcomes 12-weeks after the start in both arms.

Results

Of the 46 participants, 34(74%) were diagnosed with diabetic retinopathy, 25(54%) were female and the mean age was 70.08 yrs (SD=8.74). In the immediate intervention arm visual ability was 0.28 logits (SD=1.14) at baseline and it increased to 0.91logits (SD=1.24) after the intervention (p<0.001). Changes in the delayed intervention arm were not statistically significant (mean improvement = 0.10 logits, SE=0.11, p=0.95). Acuity in the better seeing eye, near acuity and critical print size also improved during the study. The mean cost of the intervention was €118.79 (SD=24.37). Incremental cost-effectiveness ratio using the EQ-5D-5L index value was €3322/QALY and €1235/QALY when using near acuity.

Conclusions

The current study gives evidence of positive clinical impact of a basic vision rehabilitation intervention and that a basic vision rehabilitation service is cost-effective. These findings are important to clinical and rehabilitation practices and for planning vision rehabilitation services.
Retinal Vein Occlusion at the University of Gondar Tertiary Eye Care and Training Centre, North-West Ethiopia
Authors: Tilahun Matias , Tsegaw Asamere
Published: July 2022

Objective

Retinal vein occlusion (RVO) is the second most common retinal vascular diseases after diabetic retinopathy. Delay in detection and treatment can result in irreversible visual impairment and blindness. The aim of this study was to assess the magnitude and clinical pattern of patients with RVO presentedd to the retina clinic at University of Gondar Tertiary Eye Care and Training Centre

Methods

A hospital based Cross-sectional study was conducted from October 2017 – March 2018 and patients of all ages with RVO seen at our retina clinic during the study period were reviewed. Pertinent ophthalmic history, ophthalmic clinical examination and laboratory tests were done including detailed funducopy for each patient. Data were collected with structured questionnaire, entered to SPSS version 20 and analysed.

Result

A total of 38 eyes of 36 new patients with RVOs were seen during the six month study period and reviewed. Twenty four (66%) study patients were males and the mean age was 58 ± 10.87 years. Thirty four (94.4%) patients had unilateral disease. Nineteen (52.78%) had Central retinal vein occlusion (CRVO), 13 (36.11%) had branch retinal vein occlusion (BRVO) and 4 (11.11%) had hemispheric retinal vein occlusion (HRVO). Glaucoma was the commonest risk factor seen in 17 (47.22%) patients followed by systemic hypertension 10 (27.78%) and diabetes mellitus 8 (22%). The commonest complications encountered were macular edema, retinal or optic disc neovascularization and neovascular glaucoma seen in 15 (41.67%), 11 (30.5%) and 4 (11.11%) patients respectively. Over a third of patients 15 (41.67%) presented to our retina clinic after 6 months of onset of the illness and 15 (39.47%) eyes were blind at presentation.

Conclusion

Glaucoma, hypertension and diabetes mellitus were the most common risk factors identified among study patients. A majority of patients had potentially blinding complications. There was also delay in presentation. Diagnostic and therapeutic facilities of the center should be improved to prevent vision loss from complications. People should be educated to seek health care immediately after the onset of visual symptoms.
Exploring the possible causal role of the immune response to varicella-zoster virus on multiple traits: a phenome-wide Mendelian randomization study
Authors: yu Xinzhu , Lophatananon Artitaya , Mekli Krisztina , Muir Kenneth R , Guo Hui
Published: July 2022

Background
The immune response to infections could be largely driven by the individuals genes, especially in the major histocompatibility complex (MHC) region. Varicella-zoster virus (VZV) is a highly communicable pathogen. In addition to infection, the re-activations of VZV can be a potential causal factor for multiple traits. Identification of VZV immune response-related health conditions can therefore help elucidate the aetiology of certain diseases.
Methods
A phenome-wide Mendelian randomization study (MR-PheWAS) of anti-VZV Immunoglobulin G (IgG) level with 1,370 traits was conducted to explore the potential causal role of VZV-specific immunity on multiple traits using the UK Biobank cohort. For each trait, we performed Mendelian randomization (MR) analyses using five methods with or without instrumental variables (IVs) in the MHC region.
Results
We identified 49 single nucleotide polymorphisms (SNPs) associated with anti-VZV IgG level as IVs, five of which were located in the MHC region. Statistical evidence for a causal effect of anti-VZV IgG level on 75 traits was found in at least three of the MR methods, 60 traits if IVs in the MHC region were removed from MR analysis. With or without the MHC IVs, we found that a higher anti-VZV IgG level led to increased risk of 14 diseases and lower risks of 9 diseases. In addition, anti-VZV IgG level was causally associated with 5 biomarker-related traits.
Conclusions
Anti-VZV IgG was causally associated with multiple traits. MHC IVs had a substantial impact on MR causal inference, and therefore, should not be neglected from analysis.
HIV care preferences among young people living with HIV in Lesotho: A secondary data analysis of the PEBRA cluster randomized trial
Authors: Seiler Olivia , Kopo Mathebe , Kao Mpho , Lejone Thabo Ishmael , Tschumi Nadine , Glass Tracy Renée , Brown Jennifer Anne , Labhardt Niklaus Daniel , Amstutz Alain
Published: July 2022

Sub-Saharan Africa is home to 89% of all young people living with HIV, a key population with specific challenges and needs. In-depth knowledge of service demands is needed to tailor and differentiate service delivery for this group. We evaluated HIV care preferences among young people living with HIV who were part of the PEBRA (Peer Educator Based Refill of ART) cluster-randomized trial.

The PEBRA trial evaluated a novel model of care at 20 health facilities in Lesotho, Southern Africa. In the PEBRA model, a peer educator regularly assessed participant preferences regarding antiretroviral therapy (ART) refill location, SMS notifications (for adherence, drug refill, viral load) and general care support options, and delivered services accordingly over a 12-month period. We present these preferences, their changes over time and how often it was not feasible to deliver them.

At enrolment, 41 of 123 (33.3%) chose ART refill outside the health facility, compared to 8 of 123 (6.5%) after 12 months. Among those selecting clinic-based ART refill, many collected ART during the peer educator led Saturday clinic club, 45 of 123 (36.5%) at the beginning and 55 of 123 (44.7%) at the end. SMS reminder for adherence and/or ART refill was chosen by 51 of 123 (41.5%) at enrolment and 54 of 123 (44.7%) at the last assessment. Support by the peer educator was popular at the beginning (110 of 123 (89.4%)) and lower but still high at the end (85 of 123 (69.1%)). 13 of 123 (10.6%) participants chose support by the nurse only at the first and 21 of 123 (17.1%) at the last assessment. The overarching trial was prospectively registered onClinicalTrials.gov(NCT03969030).

Our longitudinal preference assessment among young people living with HIV showed a sustained interest in SMS notifications for adherence and refill visits as well as in additional support by a peer educator. ART refill outside the health facility was not as popular as expected; instead, medication pick-up at the facility, especially during Saturday clinic clubs, was favoured.
Use of Machine Learning Techniques for Predicting Heart Disease Risk from Phone Enquiries Data
Authors: Martín-Rodríguez Fernando , Pájaro-Lorenzo Javier , Isasi-de-Vicente Fernando , Fernández-Barciela Mónica
Published: July 2022

This paper is about the application of known machine learning (ML) techniques for the prediction of heart disease risk. A public database is used to train and test the ML models. Results are evaluated using standard measures like precision, recall and F-score. ML models selected are well known techniques and they are based on different approaches. Chosen methods are: MLP (Multi-Layer Perceptron), SVM (Support Vector Machine) and Bagged Tree (Bootstrap Aggregated Trees). After evaluating techniques alone on their own, a new “triple voting method” (TVM) is tested applying the three individual methods and “adding” their results to improve accuracy.